Search results for: skin tumor

Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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Authors: Maya de Vries Kedem, Abir Jubran, Diana Baron

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Employment in Israel offers Palestinian workers an income double what they can earn in the West Bank. The need to support their families leads many educated Palestinians to forgo finding work in their profession in the Palestinian Authority and instead look for employment in those sectors open to them in Israel, particularly the construction, agriculture, and industry sectors. The International Labor Organization estimated that about 1,200 workers in Israel die every year because of occupational diseases (diseases caused by working conditions). Construction workers in Israel are constantly exposed to dust, noise, chemical materials, and work in awkward postures, which require prolonged bending, repetitive motion, and other risk factors that can lead to illnesses and death. Occupational health is vastly neglected in Israel and construction workers are particularly at risk . As of June 2022, the Israeli quota in the construction sector for Palestinian workers stood at 80,000. Kav LaOved released a new study on the state of occupational health among Palestinian workers employed in construction in Israel. The study Roadmap to Health: Palestinian Workers in Israel's Construction Sector reviews the extent to which the health of Palestinian workers is protected at work in Israel. The report includes analysis of a survey administered to 256 workers as well as interviews with 10 workers and with 5 Israeli occupational health experts. Report highlights: • Among survey respondents, 63.9% stated that safety procedures to protect their health are rarely followed in their workplace (e.g., taking breaks, using protective gear, following restrictions on lifting heavy items, and having inspectors regularly on site to monitor safety). • All 256 Palestinian workers who participated to the survey said that their health has been directly or indirectly harmed by working in Israel and reported suffering from the following problems: orthopedic problems such as joint, hand, leg or knee problems (100%); headaches (75%); back problems (36.3%); eye problems (23.8%); breathing problems (17.6%); chronic pain (14.8%); heart problems (7.8%); and skin problems (3.5%). • Workers who are injured or do not feel well often continue working for fear of losing their payment for that day. About half of the 256 survey respondents reported that they pay brokerage fees to find an employer with a work permit, often paying between 2,000 and 3,000 NIS per month. “I have an obligation—I pay about NIS 120 a day for my permit, [and] I have to pay for it whether I work or not" a worker said. • Most Palestinian construction workers suffer from stress and mental health problems. Workers pointed to several issues that greatly affect their mood and mental state: daily crossings at crowded checkpoints where workers stand for hours; lack of sleep due to leaving home daily at 3:00-3:30 am; commuting two to four hours to work in each direction; and abusive work environments. A worker told KLO that the sight of thousands of workers standing together at the checkpoint causes “high blood pressure and the feeling that you are going to be squeezed.” Another said, “I felt that my bones would break.” In the survey workers reported suffering from insomnia (70.1%), breathing difficulties (35.8%), chest pressure (27.6%), or rapid pulse rate (12.2%).

Keywords: construction sector, palestinian workers, occupational health, Israel, occupation

Procedia PDF Downloads 63

Authors: Luci V. Hyett

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The criminal law of England and Wales currently deems that a person cannot consent to the infliction of injury upon their own body, where the level of harm is considered to be Actual or Grevious. This renders the defence of consent of the victim as being unavailable to those persons carrying out an Alternative Body Modification procedure. However, the criminalization of consensual injury is more appropriately deemed as being categorized as an offense against public morality and not one against the person, which renders the State’s involvement in the autonomous choices of a consenting adult, when determining what can be done to one’s own body, an arbitrary one. Furthermore, to recognise in law that a person is capable of giving a valid consent to socially acceptable cosmetic interventions that largely consist of procedures designed to aesthetically please men and, not those of people who want to modify their bodies for other reasons means that patriarchal attitudes are continuing to underpin public repulsion and inhibit social acceptance of such practices. Theoretical analysis will begin with a juridical examination of R v M(B) [2019] QB 1 where the High Court determined that Alternative Body Modification was not a special category exempting a person so performing from liability for Grevious Bodily Harm using the defence of consent. It will draw from its reasoning which considered that ‘the removal of body parts were medical procedures being carried out for no medical reason by someone not qualified to carry them out’ which will form the basis of this enquiry. It will consider the philosophical work of Georgio Agamben when analysing whether the biopolitical climate in the UK, which places the optimization of the perfect, healthy body at the centre of political concern can explain why those persons who wish to engage in Alternative Body Modification are treated as the ‘Exception’ to that which is normal using the ‘no medical reason’ canon to justify criminalisation, rather than legitimising the industry through regulation. It will consider, through a feminist lens, the current conflict in law between traditional cosmetic interventions which alter one’s physical appearance for socially accepted aesthetic purposes such as those to the breast, lip and buttock and, modifications described as more outlandish such as earlobe stretching, tooth filing and transdermal implants to create horns and spikes under the skin. It will assert that ethical principles relating to the psychological impact of body modification described as ‘alternative’ is used as a means to exclude person’s seeking such a procedure from receiving safe and competent treatment via a registered cosmetic surgeon which leads to these increasingly popular surgery’s being performed in Tattoo parlours throughout the UK as an extension to other socially acceptable forms of self-modification such as piercings. It will contend that only by ‘inclusive exclusion’ will those ‘othered’ through ostracisation be welcomed into the fold of normality and this can only be achieved through recognition of alternative body modification as a legitimate cosmetic intervention, subject to the same regulatory framework as existing practice. This would assist in refocusing the political landscape by erring on the side of liberty rather than that of biology.

Keywords: biopolitics, body modification, consent, criminal law

Procedia PDF Downloads 89

Authors: Flavia Oliveira de A. M. Cruz, Edison Tostes Faria, Paula Elaine D. Reis

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When the breast is submitted to radiation therapy (RT), the most common effects are pain, skin changes, mobility restrictions, local sensory alteration, and fatigue. These effects, if not managed properly, may reduce the quality of life of cancer patients and may lead to the treatment discontinuation. Therefore, promoting knowledge and guidelines for symptom management remain a high priority for patients and a challenge for health professionals, due to the need to handle side effects in a population with a life-threatening disease. Printed materials are important strategies for supporting educative activities since they help the individual to assimilate and understand the amount of information transmitted. Nurses' behavior can be systematized through the use of an educative manual, which may be effective in promoting information regarding the treatment, self-care and how to control the effects of RT at home. In view of the importance of guaranteeing the validity of the material before its use, the objective of this research was to validate the content and appearance of an educative manual for breast cancer patients undergoing RT. The Theory of Psychometrics was used for the validation process in this descriptive methodological research. A minimum agreement rate (AR) of 80% was considered to guarantee the validity of the material. The data were collected from October to December 2017, by means of two assessments tools, constructed in the form of a Likert scale, with five levels of understanding. These instruments addressed different aspects of the evaluation, in view of two different groups of participants; 17 experts in the theme area of the educative manual, and 12 women that received RT previously to treat breast cancer. The manual was titled 'Orientation Manual: radiation therapy in breast', and was focused on breast cancer patients attended at the Department of Oncology of the Brasília University Hospital (UNACON/HUB). The research project was submitted to the Research Ethics Committee at the School of Health Sciences of the University of Brasília (CAAE: 24592213.1.0000.0030). Only two items of the assessment tool for the experts, one related to the manual's ability to promote behavioral and attitude changes and the other related to the extent of its use for other health services, obtained AR < 80% and were reformulated based on the participants' suggestions and in the literature. All other items were considered appropriate and/or complete appropriate in the three blocks proposed for the experts: objectives - 89%, structure and form - 93%, and relevance - 93%; and good and/or very good in the five blocks of analysis proposed for patients: objectives - 100%, organization - 100%, writing style - 100%, appearance - 100%, and motivation. The appearance and content validation of the educative manual proposed were attended to. The educative manual was considered relevant and pertinent and may contribute to the understanding of the therapeutic process by breast cancer patients during RT, as well as support clinical practice through the nursing consultation.

Keywords: oncology nursing, nursing care, validation studies, educational technology

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Authors: Langhit Kurar, Loren Charles

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Introduction: In light of recent BOAST 12 (August 2016) published guidance on management of ankle fractures, the project aimed to highlight key discrepancies throughout the care trajectory from admission to point of discharge at a district general hospital. Wide breadth of data covering three key domains: accident and emergency, radiology, and orthopaedic surgery were subsequently stratified and recommendations on note documentation, and outpatient follow up were made. Methods: A retrospective twelve month audit was conducted reviewing results of ankle fracture management in 37 patients. Inclusion criterion involved all patients seen at Darent Valley Hospital (DVH) emergency department with radiographic evidence of an ankle fracture. Exclusion criterion involved all patients managed solely by nursing staff or having sustained purely ligamentous injury. Medical notes, including discharge summaries and the PACS online radiographic tool were used for data extraction. Results: Cross-examination of the A & E domain revealed limited awareness of the BOAST 12 recent publication including requirements to document skin integrity and neurovascular assessment. This had direct implications as this would have changed the surgical plan for acutely compromised patients. The majority of results obtained from the radiographic domain were satisfactory with appropriate X-rays taken in over 95% of cases. However, due to time pressures within A & E, patients were often left without a post manipulation XRAY in a backslab. Poorly reduced fractures were subsequently left for a long period resulting in swollen ankles and a time-dependent lag to surgical intervention. This had knocked on implications for prolonged inpatient stay resulting in hospital-acquired co-morbidity including pressure sores. Discussion: The audit has highlighted several areas of improvement throughout the disease trajectory from review in the emergency department to follow up as an outpatient. This has prompted the creation of an algorithm to ensure patients with significant fractures presenting to the emergency department are seen promptly and treatment expedited as per recent guidance. This includes timing for X-rays taken in A & E. Re-audit has shown significant improvement in both documentation at time of presentation and appropriate follow-up strategies. Within the orthopedic domain, we are in the process of creating an ankle fracture pathway to ensure imaging and weight bearing status are made clear to the consulting clinicians in an outpatient setting. Significance/Clinical Relevance: As a result of the ankle fracture algorithm we have adapted the BOAST 12 guidance to shape an intrinsic pathway to not only improve patient management within the emergency department but also create a standardised format for follow up.

Keywords: ankle, fracture, BOAST, radiology

Procedia PDF Downloads 158

Authors: Faris Mohsin Alabeedi

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Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by the presence of autoantibodies directed against the epidermis's surface proteins. There are two forms of PV, mucocutaneous and mucosal-dominant PV. Disruption of the cell junctions is a hallmark of PV due to the autoantibodies targeting the desmosomal cadherins, desmoglein-3 (Dsg3) and desmoglein-1, leading to acantholysis in the skin and mucous membrane. Although the pathogenesis of PV is known, the detailed molecular events remain not fully understood. Our recent study has shown that both the PV sera and pathogenic anti-Dsg3 antibody AK23 can induce ROS and cause oxidative stress in cultured keratinocytes. In line with our finding, other independent studies also demonstrate oxidative stress in PV. Since Nrf2 plays a crucial role in cellular anti-oxidative stress response, we hypothesize that the expression of Nrf2 may alter in PV. Thus, treatment of cells with PV sera or AK23 may cause changes in Nrf2 expression and distribution. The purpose of this study was to examine the effect of AK23 and PV sera on Nrf2 in a normal human keratinocyte cell line, such as NTERT cells. Both a time-course and dose-dependent experiments with AK23, alongside the matched isotype control IgG, were performed in keratinocyte cultures and analysed by immunofluorescence for Nrf2 and Dsg3. Additionally, the same approach was conducted with the sera from PV patients and healthy individuals that served as a control in this study. All the fluorescent images were analysed using ImageJ software. Each experiment was repeated twice. In general, variations were observed throughout this study. In the dose-response experiments, although enhanced Dsg3 expression was consistently detected in AK23 treated cells, the expression of Nrf2 showed no consistent findings between the experiments, although changes in its expression were noticeable in cells treated with AK23. In the time-course study, a trend with induction of Nrf2 over time was shown in control cells treated with mouse isotype IgG. Treatment with AK23 showed a reduction of Nrf2 in a time-dependent manner, especially at the 24-hour time point. However, the earlier time points, such as 2 hours and 6 hours with AK23 treatments, detected somewhat variations. Finally, PV sera caused a decrease of Dsg3, but on the other hand, variations were observed in Nrf2 expression in PV sera treated cells. In general, PV sera seemed to cause a reduction of Nrf2 in the majority of PV sera treated samples. In addition, more pronounced cytoplasmic expression of Nrf2 has been observed in PV sera treated cells than those treated with AK23, suggesting that polyclonal and monoclonal IgG might induce a different effect on Nrf2 expression and distribution. Further experimental studies are crucial to obtain a more coincide global view of Nrf2-mediated gene regulation. In particular, Pemphigus Voulgaris studies assessing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into disease mechanisms and perhaps initiate further treatment approaches.

Keywords: pemphigus vulgaris, monoclonal antibody against desmoglein-3, Nrf2 oxidative stress, keratinocyte cultures

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Authors: Jiaying Zhang, Xin Mu, Chang Ni, Jeff L. Zhang

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Magnetic resonance elastography (MRE) non-invasively assesses tissue elastic properties, such as shear modulus, by measuring tissue’s displacement in response to mechanical waves. The estimated metrics on tissue elasticity or stiffness have been shown to be valuable for monitoring physiologic or pathophysiologic status of tissue, such as a tumor or fatty liver. To quantify tissue shear modulus from MRE-acquired displacements (essentially an inverse problem), multiple approaches have been proposed, including Local Frequency Estimation (LFE) and Direct Inversion (DI). However, one common problem with these methods is that the estimates are severely noise-sensitive due to either the inverse-problem nature or noise propagation in the pixel-by-pixel process. With the advent of deep learning (DL) and its promise in solving inverse problems, a few groups in the field of MRE have explored the feasibility of using DL methods for quantifying shear modulus from MRE data. Most of the groups chose to use real MRE data for DL model training and to cut training images into smaller patches, which enriches feature characteristics of training data but inevitably increases computation time and results in outcomes with patched patterns. In this study, simulated wave images generated by Finite Differential Time Domain (FDTD) simulation are used for network training, and U-Net is used to extract features from each training image without cutting it into patches. The use of simulated data for model training has the flexibility of customizing training datasets to match specific applications. The proposed method aimed to estimate tissue shear modulus from MRE data with high robustness to noise and high model-training efficiency. Specifically, a set of 3000 maps of shear modulus (with a range of 1 kPa to 15 kPa) containing randomly positioned objects were simulated, and their corresponding wave images were generated. The two types of data were fed into the training of a U-Net model as its output and input, respectively. For an independently simulated set of 1000 images, the performance of the proposed method against DI and LFE was compared by the relative errors (root mean square error or RMSE divided by averaged shear modulus) between the true shear modulus map and the estimated ones. The results showed that the estimated shear modulus by the proposed method achieved a relative error of 4.91%±0.66%, substantially lower than 78.20%±1.11% by LFE. Using simulated data, the proposed method significantly outperformed LFE and DI in resilience to increasing noise levels and in resolving fine changes of shear modulus. The feasibility of the proposed method was also tested on MRE data acquired from phantoms and from human calf muscles, resulting in maps of shear modulus with low noise. In future work, the method’s performance on phantom and its repeatability on human data will be tested in a more quantitative manner. In conclusion, the proposed method showed much promise in quantifying tissue shear modulus from MRE with high robustness and efficiency.

Keywords: deep learning, magnetic resonance elastography, magnetic resonance imaging, shear modulus estimation

Procedia PDF Downloads 37

Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

Procedia PDF Downloads 128

Authors: Vanessa G. P. Severino, Eliangela Cristina Candida Costa, Nubia Alves Mariano Teixeira Pires Gomides, Lucilia Kato, Afif Felix Monteiro, Maria Anita Lemos Vasconcelos Ambrosio, Carlos Henrique Gomes Martins

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One of the biomes present in Brazil is known as Cerrado, which is a vast tropical savanna ecoregion, particularly in the states of Goiás, Mato Grosso do Sul, Mato Grosso, Tocantins and Minas Gerais. Many species of plants are characterized as endemic and they have therapeutic value for a large part of the population, especially to the rural communities. Given that, the southeastern region of the state of Goiás contains about 21 rural communities, which present a form of organization based on the use of natural resources available. One of these rural communities is named of Coqueiros, where the knowledge about the medicinal plants was very important to this research. Thus, this study focuses on the ethnobotanical survey of this community on the use of Kielmeyera coriacea to treat diseases. From the 37 members interviewed, 76% indicated this species for the treatment of intestinal infection, leukemia, anemia, gastritis, gum pain, toothache, cavity, arthritis, arthrosis, healing, vermifuge, rheumatism, antibiotic, skin problems, mycoses and all kinds of infections. The medicinal properties attributed during the interviews were framed in the body system (disease categories), adapted from ICD 10; thus, 20 indications of use were obtained, among five body systems. Therefore, the root of this species was select to chemical and biological (antioxidant and antimicrobial) studies. From the liquid-liquid extraction of ethanolic extract of root (EER), the hexane (FH), ethyl acetate (FAE), and hydro alcoholic (FHA) fractions were obtained. The chemical profile study of these fractions was performed by LC-MS, identifying major compounds such as δ-tocotrienol, prenylated acylphoroglucinol, 2-hydroxy-1-methoxyxanthone and quercitrin. EER, FH, FAE and FHA were submitted to biological tests. FHA presented the best antioxidant action (EC50 201.53 μg mL-1). EER inhibited the bacterial growth of Streptococcus pyogenes and Pseudomonas aeruginosa, microorganisms associated with rheumatism, at Minimum Inhibitory Concentration (MIC) of 6.25 μg mL-1. In addition, the FH-10 subfraction, obtained from FH fractionation, presented MIC of 1.56 μg mL-1 against S. pneumoniae; EER also inhibited the fungus Candida glabrata (MIC 7.81 μg mL- 1). The FAE-4.7.3 fraction, from the fractionation of FAE, presented MIC of 200 μg mL-1 against Lactobacillus casei, which is one of the causes of caries and oral infections. By the correlation of the chemical and biological data, it is possible to note that the FAE-4.7.3 and FH-10 are constituted 4-hydroxy-2,3-methylenedioxy xanthone, 3-hydroxy-1,2-dimethoxy xanthone, lupeol, prenylated acylphoroglucinol and quercitrin, which could be associated with the biological potential found. Therefore, this study provides an important basis for further investigations regarding the compounds present in the active fractions of K. coriacea, which will permit the establishment of a correlation between ethnobotanical survey and bioactivity.

Keywords: biological activity, ethnobotanical survey, Kielmeyera coriacea Mart., LC-MS profile

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Authors: Boudjelal Amel

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Arisarum vulgare, a member of the Araceae family, is an herbaceous perennial widely distributed in the Mediterranean region. A. vulgare is recognized for its medicinal properties and holds significant traditional importance in Algeria for the treatment of various human ailments, including pain, infections, inflammation, digestive disorders, skin problems, eczema, cancer, wounds, burns and gynecological diseases. Despite its extensive traditional use, scientific exploration of A. vulgare remains limited. The study aims to investigate for the first time the therapeutic potential of A. vulgare ethanolic extract obtained by ultrasound-assisted extraction. The chemical composition of the extract was determined by LC-MS/MS analysis. For in vitro phytopharmacological evaluation, several assays, including DPPH, ABTS, FRAP and reducing power, were employed to evaluate the antioxidant activity. The antibacterial activity was assessed againt Escherichia coli, Salmonella typhimurium, Staphylococus aureus, Enterococcus feacium by disk diffusion and microdilution methods. The possible inhibitory activity of ethanolic extract was analyzed against the cholinesterases enzymes (AChE and BChE). The DNA protection activity of A. vulgare ethanolic extract was estimated using the agarose gel electrophoresis method. The capacities of the extract to protect plasmid DNA (pBR322) from the oxidizing effects of H2O2 and UV treatment were evaluated by their DNA-breaking forms. The in vivo wound healing potential of a traditional ointment containing 5% of A. vulgare ethanolic extract was also investigated. The LC-MS/MS profiling of the extract revealed the presence of various bioactive compounds, including naringenin, chlorogenic, vanillic, cafeic, coumaric acids, trans-cinnamic and trans ferrulic acids. The plant extract presented considerable antioxidant potential, being the most active for Reducing power (0,07326±0.001 mg/ml) and DPPH (0.14±0.004 mg/ml). The extract showed the highest inhibition zone diameter against Enterococcus feacium (36±0.1 mm). The ethanolic extract of A. vulgare suppressed the growth of Staphylococus aureus, Escherichia coli and Salmonella typhimurium according to the MIC values. The extract of the plant significantly inhibited both AChE and BChE enzymes. DNA protection activity of the A. vulgare extract was determined as 90.41% for form I and 51.92% for form II. The in vivo experiments showed that 5% ethanolic extract ointment accelerated the wound healing process. The topical application of the traditional formulation enhanced wound closure (95,36±0,6 %) and improved histological parameters in the treated group compared to the control groups. The promising biological properties of Arisarum vulgare revealed that the plant could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.

Keywords: arisarum vulgare, LC-MS/MS, antioxidant activity, antimicrobial activity, cholinesterases enzymes inhibition, dna-damage activity, in vivo wound healing

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Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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Authors: Megan L. Srinivas

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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

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Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay

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Rice milling is an important activity in agricultural economy of India, particularly the Burdwan district. However, the environmental impact of rice mills is frequently underestimated. The environmental impact of rice mills in the Burdwan district is a major source of concern, given the importance of rice milling in the local economy and food supply. In the Burdwan district, more than fifty (50) rice mills are in operation. The goal of this study is to investigate the effects of rice mills on several environmental components, with a particular emphasis on groundwater, surface water, soil, and vegetation. The research comprises a thorough review of numerous rice mills located around the district, utilising both qualitative and quantitative approaches. Water samples taken from wells near rice mills will be tested for groundwater quality, with an emphasis on factors such as heavy metal pollution and pollutant concentrations. Monitoring rice mill discharge into neighbouring bodies of water and studying the potential impact on aquatic ecosystems will be part of surface water evaluations. Furthermore, soil samples from the surrounding areas will be taken to examine changes in soil characteristics, nutrient content, and potential contamination from milling waste disposal. Vegetation studies will be conducted to investigate the effects of emissions and effluents on plant health and biodiversity in the region. The findings will provide light on the extent of environmental degradation caused by rice mills in the Burdwan district, as well as valuable insight into the effects of such operations on water, soil, and vegetation. The findings will aid in the development of appropriate legislation and regulations to reduce negative environmental repercussions and promote sustainable practises in the rice milling business. In some cases, heavy metals have been related to health problems. Heavy metals (As, Cd, Cu, Pb, Cr, Hg) are linked to skin, lung, brain, kidney, liver, metabolic, spleen, cardiovascular, haematological, immunological, gastrointestinal, testes, pancreatic, metabolic, and bone problems. As a result, this study contributes to a better knowledge of industrial environmental impacts and establishes the framework for future studies aimed at developing a more ecologically balanced and resilient Burdwan district. The following recommendations are offered for reducing the rice mill's environmental impact: To keep untreated effluents out of bodies of water, adequate waste management systems must be established. Use environmentally friendly rice milling processes to reduce pollution. To avoid soil pollution, rice mill by-products should be used as fertiliser in a controlled and appropriate manner. Groundwater, surface water, soil, and vegetation are all regularly monitored in order to study and adapt to environmental changes. By adhering to these principles, the rice milling industry of Burdwan district may achieve long-term growth while lowering its environmental effect and safeguarding the environment for future generations.

Keywords: groundwater, environmental analysis, biodiversity, rice mill, waste management, diseases, industrial impact

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Authors: Vishnu Asokan, Zaid M. Paloba

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Flow over cavities is an important area of research due to the significant change in flow physics caused by cavity aspect ratio, free stream Mach number and the nature of upstream boundary layer approaching the cavity leading edge. Cavity flow finds application in aircraft wheel well, weapons bay, combustion chamber of scramjet engines, etc. These flows are highly unsteady, compressible and turbulent and it involves mass entrainment coupled with acoustics phenomenon. Variation of flow dynamics in an angled cavity with a heated and cooled pylon upstream to the cavity with spatial combinations of heat flux addition and removal to the wall studied numerically. The goal of study is to investigate the effect of energy addition, removal to the cavity walls and pylon cavity flow dynamics. Preliminary steady state numerical simulations on inclined cavities with heat addition have shown that wall pressure profiles, as well as the recirculation, are influenced by heat transfer to the compressible fluid medium. Such a hybrid control of cavity flow dynamics in the form of heat transfer and pylon geometry can open out greater opportunities in enhancement of mixing and flame holding requirements of supersonic combustors. Addition of pylon upstream to the cavity reduces the acoustic oscillations emanating from the geometry. A numerical unsteady analysis of supersonic flow past cavities exposed to cavity wall heating and cooling with heated and cooled pylon helps to get a clear idea about the oscillation suppression in the cavity. A Cavity of L/D 4 and aft wall angle 22 degree with an upstream pylon of h/D=1.5 mm with a wall angle 29 degree exposed to supersonic flow of Mach number 2 and heat flux of 40 W/cm² and -40 W/cm² modeled for the above study. In the preliminary study, the domain is modeled and validated numerically with a turbulence model of SST k-ω using an HLLC implicit scheme. Both qualitative and quantitative flow data extracted and analyzed using advanced CFD tools. Flow visualization is done using numerical Schlieren method as the fluid medium gives the density variation. The heat flux addition to the wall increases the secondary vortex size of the cavity and removal of energy leads to the reduction in vortex size. The flow field turbulence seems to be increasing at higher heat flux. The shear layer thickness increases as heat flux increases. The steady state analysis of wall pressure shows that there is variation on wall pressure as heat flux increases. Shift in frequency of unsteady wall pressure analysis is an interesting observation for the above study. The time averaged skin friction seems to be reducing at higher heat flux due to the variation in viscosity of fluid inside the cavity.

Keywords: energy addition, frequency shift, Numerical Schlieren, shear layer, vortex evolution

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Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

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This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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Authors: Anna Höfer, Johannes Herrmann, Patrick Meybohm, Christopher Lotz

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Mitochondria are pivotal for energy supply and regulation of cellular functions. Deficiencies of mitochondrial metabolism have been implicated in diverse stressful conditions including infections. Platelets are key mediators for thrombo-inflammation during development and resolution of acute respiratory distress syndrome (ARDS). Previous data point to an exhausted platelet phenotype in critically-ill patients with coronavirus 19 disease (COVID-19) impacting the course of disease. The objective of this work was to characterize platelet mitochondrial metabolism in patients suffering from COVID-19 ARDSA longitudinal analysis of platelet mitochondrial metabolism in 24 patients with COVID-19 induced ARDS compared to 35 healthy controls (ctrl) was performed. Blood samples were analyzed at two time points (t1=day 1; t2=day 5-7 after study inclusion). The activity of mitochondrial citrate synthase was photometrically measured. The impact of oxidative stress on mitochondrial permeability was assessed by a photometric calcium-induced swelling assay and the activity of superoxide dismutase (SOD) by a SOD assay kit. The amount of protein carbonylation and the activity of mitochondria complexes I-IV were photometrically determined. Levels of interleukins (IL)-1α, IL-1β and tumor necrosis factor (TNF-) α were measured by a Multiplex assay kit. Median age was 54 years, 63 % were male and BMI was 29.8 kg/m2. SOFA (12; IQR: 10-15) and APACHE II (27; IQR: 24-30) indicated critical illness. Median Murray Score was 3.4 (IQR: 2.8-3.4), 21/24 (88%) required mechanical ventilation and V-V ECMO support in 14/24 (58%). Platelet counts in ARDS did not change during ICU stay (t1: 212 vs. t2: 209 x109/L). However, mean platelet volume (MPV) significantly increased (t1: 10.6 vs. t2: 11.9 fL; p<0.0001). Citrate synthase activity showed no significant differences between ctrl and ARDS patients. Calcium induced swelling was more pronounced in patients at t1 compared to t2 and to ctrl (50µM; t1: 0.006 vs. ctrl: 0.016 ΔOD; p=0.001). The amount of protein carbonylation as marker for irreversible proteomic modification constantly increased during ICU stay and compared to ctrl., without reaching significance. In parallel, superoxid dismutase activity gradually declined during ICU treatment vs. ctrl (t2: - 29 vs. ctrl.: - 17 %; p=0.0464). Complex I analysis revealed significantly stronger activity in ARDS vs. ctrl. (t1: 0.633 vs. ctrl.: 0.415 ΔOD; p=0.0086). There were no significant differences in complex II, III or IV activity in platelets from ARDS patients compared to ctrl. IL-18 constantly increased during the observation period without reaching significance. IL-1α and TNF-α did not differ from ctrl. However, IL-1β levels were significantly elevated in ARDS (t1: 16.8; t2: 16.6 vs. ctrl.: 12.4 pg/mL; p1=0.0335, p2=0.0032). This study reveals new insights in platelet mitochondrial metabolism during COVID-19 caused ARDS. it data point towards enhanced platelet activity with a pronounced turnover rate. We found increased activity of mitochondria complex I and evidence for enhanced oxidative stress. In parallel, protective mechanisms against oxidative stress were narrowed with elevated levels of IL-1β likely causing a pro-apoptotic environment. These mechanisms may contribute to platelet exhaustion in ARDS.

Keywords: acute respiratory distress syndrome (ARDS), coronavirus 19 disease (COVID-19), oxidative stress, platelet mitochondrial metabolism

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Authors: Mikyung Bak

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The dokkaebi, a beloved icon of Korean culture, is represented as an elf, goblin, monster, dwarf, or any similar creature in different media, such as animated shows, comics, soap operas, and movies. It is often described as a mythical creature with a horn or horns and long teeth, wearing tiger-skin pants or a grass skirt, and carrying a magic stick. Many Korean researchers agree on the similarity of the image of the Korean dokkaebi with that of the Japanese oni, a view that is regard as negative from an anti-colonial or nationalistic standpoint. They cite such similarity between the two mythical creatures as evidence that Japanese colonialism persists in Korea. The debate on the originality of dokkaebi’s visual representation is an issue that must be addressed urgently. This research demonstrates through a diagram the plurality of interpretations of dokkaebi’s visual representations in what are considered ‘authentic’ images of dokkaebi in Korean art and culture. This diagram presents the opinions of four major groups in the debate, namely, the scholars of Korean literature and folklore, art historians, authors, and artists. It also shows the creation of new dokkaebi visual representations in popular media, including those influenced by the debate. The diagram further proves that dokkaebi’s representations varied, which include the typical persons or invisible characters found in Korean literature, original Korean folk characters in traditional art, and even universal spirit characters. They are also visually represented by completely new creatures as well as oni-based mythical beings and the actual oni itself. The earlier dokkaebi representations were driven by the creation of a national ideology or national cultural paradigm and, thus, were more uniform and protected. In contrast, the more recent representations are influenced by the Korean industrial strategy of ‘cultural economics,’ which is concerned with the international rather than the domestic market. This recent Korean cultural strategy emphasizes diversity and commonality with the global culture rather than originality and locality. It employs traditional cultural resources to construct a global image. Consequently, dokkaebi’s recent representations have become more common and diverse, thereby incorporating even oni’s characteristics. This argument has rendered the grounds of the debate irrelevant. The dokkaebi has been used recently for tourist marketing purposes, particularly in revitalizing interest in regions considered the cradle of various traditional dokkaebi tales. These campaign strategies include the Jeju-do Dokkaebi Park, Koksung Dokkaebi Land, as well as the Taebaek and Sokri-san Dokkaebi Festivals. Almost dokkaebi characters are identical to the Japanese oni in tourist marketing. However, the pursuit for dokkaebi’s authentic visual representation is less interesting and fruitful than the appreciation of the entire spectrum of dokkaebi images that have been created. Thus, scholars and stakeholders must not exclude the possibilities for a variety of potentials within the visual culture. The same sentiment applies to traditional art and craft. This study aims to contribute to a new visualization of the dokkaebi that embraces the possibilities of both folk craft and art, which continue to be uncovered by diverse and careful researchers in a still-developing field.

Keywords: Dokkaebi, post-colonial period, representation, tourist marketing

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Authors: N. Perini, M. C. Thaller, F. Mercuri, S. Orlanducci, A. Rubechini, L. Migliore

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The preservation of cultural heritage is one of the major challenges of today’s society, because of the fundamental right of future generations to inherit it as the continuity with their historical and cultural identity. Parchments, consisting of a semi-solid matrix of collagen produced from animal skin (i.e., sheep or goats), are a significant part of the cultural heritage, being used as writing material for many centuries. Due to their animal origin, parchments easily undergo biodeterioration. The most common biological damage is characterized by isolated or coalescent purple spots that often leads to the detachment of the superficial layer and the loss of the written historical content of the document. Although many parchments with the same biodegradative features were analyzed, no common causative agent has been found so far. Very recently, a study was performed on a purple-damaged parchment roll dated back 1244 A.D, the A.A. Arm. I-XVIII 3328, belonging to the oldest collection of the Vatican Secret Archive (Fondo 'Archivum Arcis'), by comparing uncolored undamaged and purple damaged areas of the same document. As a whole, the study gave interesting results to hypothesize a model of biodeterioration, consisting of a microbial succession acting in two main phases: the first one, common to all the damaged parchments, is characterized by halophilic and halotolerant bacteria fostered by the salty environment within the parchment maybe induced by bringing of the hides; the second one, changing with the individual history of each parchment, determines the identity of its colonizers. The design of this model was pivotal to this study, performed by different labs of the Tor Vergata University (Rome, Italy), in collaboration with the Vatican Secret Archive. Three documents, belonging to a collection of dramatically damaged parchments archived as 'Faldone Patrizi A 19' (dated back XVII century A.D.), were analyzed through a multidisciplinary approach, including three updated technologies: (i) Next Generation Sequencing (NGS, Illumina) to describe the microbial communities colonizing the damaged and undamaged areas, (ii) RAMAN spectroscopy to analyze the purple pigments, (iii) Light Transmitted Analysis (LTA) to evaluate the kind and entity of the damage to native collagen. The metagenomic analysis obtained from NGS revealed DNA sequences belonging to Halobacterium salinarum mainly in the undamaged areas. RAMAN spectroscopy detected pigments within the purple spots, mainly bacteriorhodopsine/rhodopsin-like pigments, a purple transmembrane protein containing retinal and present in Halobacteria. The LTA technique revealed extremely damaged collagen structures in both damaged and undamaged areas of the parchments. In the light of these data, the study represents a first confirmation of the microbial succession model described above. The demonstration of this model is pivotal to start any possible new restoration strategy to bring back historical parchments to their original beauty, but also to open opportunities for intervention on a huge amount of documents.

Keywords: biodeterioration, parchments, purple spots, ecological succession

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Authors: Alla Ovsyannikova, Oksana Rymar, Elena Shakhtshneider, Mikhail Voevoda

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In Siberia endocrinologists increasingly noted young patients with the course of diabetes mellitus differing from 1 and 2 types. Therefore we did a molecular genetic study for this group of patients to verify the monogenic forms of diabetes mellitus in them and researched the characteristics of this pathology. When confirming the monogenic form of diabetes, we performed a correction therapy for many patients (transfer from insulin to tablets), prevented specific complications, examined relatives and diagnosed their diabetes at the preclinical stage, revealed phenotypic characteristics of the pathology which led to the high significance of this work. Materials and Methods: We observed 5 patients (4 families). We diagnosed MODY (Maturity Onset Diabetes of the Young) during the molecular genetic testing (direct automatic sequencing). All patients had a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b-cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist. Results: We diagnosed 3 rare types of MODY: two women had MODY8, one man – MODY6 and man and his mother - MODY12. Patients with types 8 and 12 had clinical features. Age of onset hyperglycemia ranged from 26 to 34 years. In a patient with MODY6 fasting hyperglycemia was detected during a routine examination. Clinical symptoms, complications were not diagnosed. The patient observes a diet. In the first patient MODY8 was detected during first pregnancy, she had itchy skin and mostly postprandial hyperglycemia. Upon examination we determined glycated hemoglobin 7.5%, retinopathy, non-proliferative stage, peripheral neuropathy. She uses a basic bolus insulin therapy. The second patient with MODY8 also had clinical manifestations of hyperglycemia (pruritus, thirst), postprandial hyperglycemia and diabetic nephropathy, a stage of microalbuminuria. The patient was diagnosed autoimmune thyroiditis. She used inhibitors of DPP-4. The patient with MODY12 had an aggressive course. In the detection of hyperglycemia he had complaints of visual impairment, intense headaches, leg cramps. The patient had a history of childhood convulsive seizures of non-epileptic genesis, without organic pathology, which themselves were stopped at the age of 12 years. When we diagnosed diabetes a patient was 28 years, he had hypertriglyceridemia, atherosclerotic plaque in the carotid artery, proliferative retinopathy (lacerocoagulation). Diabetes and early myocardial infarction were observed in three cases in family. We prescribe therapy with sulfonylureas and SGLT-2 inhibitors with a positive effect. At the patient's mother diabetes began at a later age (30 years) and a less aggressive course was observed. She also has hypertriglyceridemia and uses oral hypoglycemic drugs. Conclusions: 1) When young patients with hyperglycemia have extrapancreatic pathologies and diabetic complications with a short duration of diabetes we can assume they have one of type of MODY diabetes. 2) In patients with monogenic forms of diabetes mellitus, the clinical manifestations of hyperglycemia in each succeeding generation are revealed at an earlier age. Research had increased our knowledge of the monogenic forms of diabetes. The reported study was supported by RSCF, research project No. 14-15-00496-P.

Keywords: diabetes mellitus, MODY diabetes, monogenic forms, young patients

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Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid

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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.

Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk

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Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

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One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

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Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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Authors: Alondra Balbuena Medina, Carlos Diaz Delgado, Aleida Yadira Vilchis Fránces

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In Mexico, each year news is disseminated about the ravages of floods, such as the total loss of housing, damage to the fields; the increase of the costs of the food, derived from the losses of the harvests, coupled with health problems such as skin infection, etc. In addition to social problems such as delinquency, damage in education institutions and the population in general. The flooding is a consequence of heavy rains, tropical storms and or hurricanes that generate excess water in drainage systems that exceed its capacity. In urban areas, heavy rains can be one of the main factors in causing flooding, in addition to excessive precipitation, dam breakage, and human activities, for example, excessive garbage in the strainers. In agricultural areas, these can hardly achieve large areas of cultivation. It should be mentioned that for both areas, one of the significant impacts of floods is that they can permanently affect the livelihoods of many families, cause damage, for example in their workplaces such as farmlands, commercial or industry areas and where services are provided. In recent years, Information and Communication Technologies (ICT) have had an accelerated development, being reflected in the growth and the exponential evolution of the innovation giving; as a result, the daily generation of new technologies, updates, and applications. Innovation in the development of Information Technology applications has impacted on all areas of human activity. They influence all the orders of life of individuals, reconfiguring the way of perceiving and analyzing the world such as, for instance, interrelating with people as individuals and as a society, in the economic, political, social, cultural, educational, environmental, etc. Therefore the present work describes the creation of a system of calculation of flood costs for housing areas, retail establishments and agricultural areas from the Mexican Republic, based on the use and application of geotechnical tools being able to be useful for the benefit of the sectors of public, education and private. To generate analysis of hydrometereologic affections and with the obtained results to realize the Geoinformatics tool was constructed from two different points of view: the geoinformatic (design and development of GIS software) and the methodology of flood damage validation in order to integrate a tool that provides the user the monetary estimate of the effects caused by the floods. With information from the period 2000-2014, the functionality of the application was corroborated. For the years 2000 to 2009 only the analysis of the agricultural and housing areas was carried out, incorporating for the commercial establishment's information of the period 2010 - 2014. The method proposed for the resolution of this research project is a fundamental contribution to society, in addition to the tool itself. Therefore, it can be summarized that the problems that are in the physical-geographical environment, conceiving them from the point of view of the spatial analysis, allow to offer different alternatives of solution and also to open up slopes towards academia and research.

Keywords: floods, technological innovation, monetary estimation, spatial analysis

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Authors: G. Magalhães-Mota, C. Magro, S. Sério, E. Mateus, P. A. Ribeiro, A. B. Ribeiro, M. Raposo

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Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol], belonging to the class of Pharmaceuticals and Personal Care Products (PPCPs), is a broad-spectrum antimicrobial agent and bactericide. Because of its antimicrobial efficacy, it is widely used in personal health and skin care products, such as soaps, detergents, hand cleansers, cosmetics, toothpastes, etc. However, it has been considered to disrupt the endocrine system, for instance, thyroid hormone homeostasis and possibly the reproductive system. Considering the widespread use of triclosan, it is expected that environmental and food safety problems regarding triclosan will increase dramatically. Triclosan has been found in river water samples in both North America and Europe and is likely widely distributed wherever triclosan-containing products are used. Although significant amounts are removed in sewage plants, considerable quantities remain in the sewage effluent, initiating widespread environmental contamination. Triclosan undergoes bioconversion to methyl-triclosan, which has been demonstrated to bio accumulate in fish. In addition, triclosan has been found in human urine samples from persons with no known industrial exposure and in significant amounts in samples of mother's milk, demonstrating its presence in humans. The action of sunlight in river water is known to turn triclosan into dioxin derivatives and raises the possibility of pharmacological dangers not envisioned when the compound was originally utilized. The aim of this work is to detect low concentrations of triclosan in an aqueous complex matrix through the use of a sensor array system, following the electronic tongue concept based on impedance spectroscopy. To achieve this goal, we selected the appropriate molecules to the sensor so that there is a high affinity for triclosan and whose sensitivity ensures the detection of concentrations of at least nano-molar. Thin films of organic molecules and oxides have been produced by the layer-by-layer (LbL) technique and sputtered onto glass solid supports already covered by gold interdigitated electrodes. By submerging the films in complex aqueous solutions with different concentrations of triclosan, resistance and capacitance values were obtained at different frequencies. The preliminary results showed that an array of interdigitated electrodes sensor coated or uncoated with different LbL and films, can be used to detect TCS traces in aqueous solutions in a wide range concentration, from 10⁻¹² to 10⁻⁶ M. The PCA method was applied to the measured data, in order to differentiate the solutions with different concentrations of TCS. Moreover, was also possible to trace a curve, the plot of the logarithm of resistance versus the logarithm of concentration, which allowed us to fit the plotted data points with a decreasing straight line with a slope of 0.022 ± 0.006 which corresponds to the best sensitivity of our sensor. To find the sensor resolution near of the smallest concentration (Cs) used, 1pM, the minimum measured value which can be measured with resolution is 0.006, so the ∆logC =0.006/0.022=0.273, and, therefore, C-Cs~0.9 pM. This leads to a sensor resolution of 0.9 pM for the smallest concentration used, 1pM. This attained detection limit is lower than the values obtained in the literature.

Keywords: triclosan, layer-by-layer, impedance spectroscopy, electronic tongue

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Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

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Authors: C. Sancho Salvatierra, J. M. Martinez Nieto, R. García Gonzalez-Gordon, M. I. Martinez Bellido

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Introduction: Nature could act as an asset for human health protecting against possible diseases and promoting the state of both physical and mental health. Goals: This paper aims to determine which natural elements present evidence that show positive influence on human health, on which particular aspects and how. It also aims to determine the best biomarkers to measure such influence. Method: A systematic literature review was carried out. First, a general free text search was performed in databases, such as Scopus, PubMed or PsychInfo. Secondly, a specific search was performed combining keywords in order of increasing complexity. Also the Snowballing technique was used and it was consulted in the CSIC’s (The Spanish National Research Council). Databases: Of the 130 articles obtained and reviewed, 80 referred to natural elements that influenced health. These 80 articles were classified and tabulated according to the nature elements found, the health aspects studied, the health measurement parameters used and the measurement techniques used. In this classification the results of the studies were codified according to whether they were positive, negative or neutral both for the elements of nature and for the aspects of health studied. Finally, the results of the 80 selected studies were summarized and categorized according to the elements of nature that showed the greatest positive influence on health and the biomarkers that had shown greater reliability to measure said influence. Results: Of the 80 articles studied, 24 (30.0%) were reviews and 56 (70.0%) were original research articles. Among the 24 reviews, 18 (75%) found positive results of natural elements on health, and 6 (25%) both positive and negative effects. Of the 56 original articles, 47 (83.9%) showed positive results, 3 (5.4%) both positive and negative, 4 (7.1%) negative effects, and 2 (3.6%) found no effects. The results reflect positive effects of different elements of nature on the following pathologies: diabetes, high blood pressure, stress, attention deficit hyperactivity disorder, psychotic, anxiety and affective disorders. They also show positive effects on the following areas: immune system, social interaction, recovery after illness, mood, decreased aggressiveness, concentrated attention, cognitive performance, restful sleep, vitality and sense of well-being. Among the elements of nature studied, those that show the greatest positive influence on health are forest immersion, natural views, daylight, outdoor physical activity, active transport, vegetation biodiversity, natural sounds and the green residences. As for the biomarkers used that show greater reliability to measure the effects of natural elements are the levels of cortisol (both in blood and saliva), vitamin D levels, serotonin and melatonin, blood pressure, heart rate, muscle tension and skin conductance. Conclusions: Nature is an asset for health, well-being and quality of life. Awareness programs, education and health promotion are needed based on the elements that nature brings us, which in turn generate proactive attitudes in the population towards the protection and conservation of nature. The studies related to this subject in Spain are very scarce. Aknowledgements. This study has been promoted and partially financed by the Environmental Foundation Jaime González-Gordon.

Keywords: health, green areas, nature, well-being

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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Authors: Thiago E. Goto, Carla C. Lopes, Helena B. Nader, Anielle C. A. Silva, Noelio O. Dantas, José R. Siqueira Jr., Luciano Caseli

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Quantum dots (QD) are semiconductor nanocrystals that can be employed in biological research as a tool for fluorescence imagings, having the potential to expand in vivo and in vitro analysis as cancerous cell biomarkers. Particularly, cadmium selenide (CdSe) magic-sized quantum dots (MSQDs) exhibit stable luminescence that is feasible for biological applications, especially for imaging of tumor cells. For these facts, it is interesting to know the mechanisms of action of how such QDs mark biological cells. For that, simplified models are a suitable strategy. Among these models, Langmuir films of lipids formed at the air-water interface seem to be adequate since they can mimic half a membrane. They are monomolecular films formed at liquid-gas interfaces that can spontaneously form when organic solutions of amphiphilic compounds are spread on the liquid-gas interface. After solvent evaporation, the monomolecular film is formed, and a variety of techniques, including tensiometric, spectroscopic and optic can be applied. When the monolayer is formed by membrane lipids at the air-water interface, a model for half a membrane can be inferred where the aqueous subphase serve as a model for external or internal compartment of the cell. These films can be transferred to solid supports forming the so-called Langmuir-Blodgett (LB) films, and an ampler variety of techniques can be additionally used to characterize the film, allowing for the formation of devices and sensors. With these ideas in mind, the objective of this work was to investigate the specific interactions of CdSe MSQDs with tumorigenic and non-tumorigenic cells using Langmuir monolayers and LB films of lipids and specific cell extracts as membrane models for diagnosis of cancerous cells. Surface pressure-area isotherms and polarization modulation reflection-absorption spectroscopy (PM-IRRAS) showed an intrinsic interaction between the quantum dots, inserted in the aqueous subphase, and Langmuir monolayers, constructed either of selected lipids or of non-tumorigenic and tumorigenic cells extracts. The quantum dots expanded the monolayers and changed the PM-IRRAS spectra for the lipid monolayers. The mixed films were then compressed to high surface pressures and transferred from the floating monolayer to solid supports by using the LB technique. Images of the films were then obtained with atomic force microscopy (AFM) and confocal microscopy, which provided information about the morphology of the films. Similarities and differences between films with different composition representing cell membranes, with or without CdSe MSQDs, was analyzed. The results indicated that the interaction of quantum dots with the bioinspired films is modulated by the lipid composition. The properties of the normal cell monolayer were not significantly altered, whereas for the tumorigenic cell monolayer models, the films presented significant alteration. The images therefore exhibited a stronger effect of CdSe MSQDs on the models representing cancerous cells. As important implication of these findings, one may envisage for new bioinspired surfaces based on molecular recognition for biomedical applications.

Keywords: biomembrane, langmuir monolayers, quantum dots, surfaces

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Authors: Aurora Sheehy, Caitlin Prince

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Within current orthodox medical protocols, trauma and mental health issues are deemed to reside within the realm of cognitive or psychological therapists and are marginalised in these areas, in part due to limited drugs option available, mostly manipulating neurotransmitters or sedating patients to reduce symptoms. By contrast, this research presents examples from the clinical practice of how trauma can be assessed and treated physiologically. Adverse Childhood Experiences (ACEs) are a tally of different types of abuse and neglect. It has been used as a measurable and reliable predictor of the likelihood of the development of autoimmune disease. It is a direct way to demonstrate reliably the health impact of traumatic life experiences. A second assessment tool is Allostatic Load, which refers to the cumulative effects that chronic stress has on mental and physical health. It records the decline of an individual’s physiological capacity to cope with their experience. It uses a specific grouping of serum testing and physical measures. It includes an assessment of neuroendocrine, cardiovascular, immune and metabolic systems. Allostatic load demonstrates the health impact that trauma has throughout the body. It forms part of an initial intake assessment in clinical practice and could also be used in research to evaluate treatment. Examining medicinal plants for their physiological, neurological and somatic effects through the lens of Polyvagal theory offers new opportunities for trauma treatments. In situations where Polyvagal theory recommends activities and exercises to enable parasympathetic activation, many herbs that affect Effector Memory T (TEM) cells also enact these responses. Traditional or Indigenous European herbs show the potential to support the polyvagal tone, through multiple mechanisms. As the ventral vagal nerve reaches almost every major organ, plants that have actions on these tissues can be understood via their polyvagal actions, such as monoterpenes as agents to improve respiratory vagal tone, cyanogenic glycosides to reset polyvagal tone, volatile oils rich in phenyl methyl esters improve both sympathetic and parasympathetic tone, bitters activate gut function and can strongly promote parasympathetic regulation. Auricular Acupuncture uses a system of somatotopic mapping of the auricular surface overlaid with an image of an inverted foetus with each body organ and system featured. Given that the concha of the auricle is the only place on the body where the Vagus Nerve neurons reach the surface of the skin, several investigators have evaluated non-invasive, transcutaneous electrical nerve stimulation (TENS) at auricular points. Drawn from an interdisciplinary evidence base and developed through clinical practice, these assessment and treatment tools are examples of practitioners in the field innovating out of necessity for the best outcomes for patients. This paper draws on case studies to direct future research.

Keywords: polyvagal, auricular acupuncture, trauma, herbs

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