Search results for: breast cancer survivability

Authors: Selim M. Khan

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Indoor air quality is strongly influenced by the presence of radioactive radon (222Rn) gas. Indeed, exposure to high 222Rn concentrations is unequivocally linked to DNA damage and lung cancer and is a worsening issue in North American and European built environments, having increased over time within newer housing stocks as a function of as yet unclear variables. Indoor air radon concentration can be influenced by a wide range of environmental, structural, and behavioral factors. As some of these factors are quantitative while others are qualitative, no single statistical model can determine indoor radon level precisely while simultaneously considering all these variables across a complex and highly diverse dataset. The ability of AI- machine (deep) learning to simultaneously analyze multiple quantitative and qualitative features makes it suitable to predict radon with a high degree of precision. Using Canadian and Swedish long-term indoor air radon exposure data, we are using artificial deep neural network models with random weights and polynomial statistical models in MATLAB to assess and predict radon health risk to human as a function of geospatial, human behavioral, and built environmental metrics. Our initial artificial neural network with random weights model run by sigmoid activation tested different combinations of variables and showed the highest prediction accuracy (>96%) within the reasonable iterations. Here, we present details of these emerging methods and discuss strengths and weaknesses compared to the traditional artificial neural network and statistical methods commonly used to predict indoor air quality in different countries. We propose an artificial deep neural network with random weights as a highly effective method for assessing and predicting indoor radon.

Keywords: radon, radiation protection, lung cancer, aI-machine deep learnng, risk assessment, risk prediction, Europe, North America

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Authors: Misty Attwood, Helgi Schioth

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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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Authors: Fei Ye, Åsa Barrefelt, Manuchehr Abedi-Valugerdi, Khalid M. Abu-Salah, Salman A. Alrokayan, Mamoun Muhammed, Moustapha Hassan

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With appropriate encapsulation in functional nanoparticles drugs are more stable in physiological environment and the kinetics of the drug can be more carefully controlled and monitored. Furthermore, targeted drug delivery can be developed to improve chemotherapy in cancer treatment, not only by enhancing intracellular uptake by target cells but also by reducing the adverse effects in non-target organs. Inorganic imaging agents, delivered together with anti-cancer drugs, enhance the local imaging contrast and provide precise diagnosis as well as evaluation of therapy efficacy. We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bio-imaging and anticancer drug delivery. The poly (lactic-co-glycolic acid) PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (MN:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T2-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r2 relaxivity of approximately 523 s-1 mM-1 Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicles degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

Keywords: biodegradable polymers, multifunctional nanoparticles, quantum dots, anticancer drugs

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Authors: Husham Bayazed

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Purpose of Presentation: Obesity and overweight are among the biggest health challenges of the 21st century, according to the WHO. Obviously, obese individuals suffer different courses of disease – from infections and allergies to cancer- and even respond differently to some treatment options. Of note, obesity often seems to predispose and triggers several secondary diseases such as diabetes, arteriosclerosis, or heart attacks. Since decades it seems that immunological signals gear inflammatory processes among obese individuals with the aforementioned conditions. This review aims to shed light how obesity sparks or rewire the immune system and predisposes to such unpleasant health outcomes. Moreover, lessons from the Covid-19 pandemic ascertain that people living with pre-existing conditions such as obesity can develop severe acute respiratory syndrome (SARS), which needs to be elucidated how obesity and its adjuvant inflammatory process distortion contribute to enhancing severe COVID-19 consequences. Recent Findings: In recent clinical studies, obesity was linked to alter and sparks the immune system in different ways. Adipose tissue (AT) is considered as a secondary immune organ, which is a reservoir of tissue-resident of different immune cells with mediator release, making it a secondary immune organ. Adipocytes per se secrete several pro-inflammatory cytokines (IL-6, IL-4, MCP-1, and TNF-α ) involved in activation of macrophages resulting in chronic low-grade inflammation. The correlation between obesity and T cells dysregulation is pivotal in rewiring the immune system. Of note, autophagy occurrence in adipose tissues further rewire the immune system due to flush and outburst of leptin and adiponectin, which are cytokines and influencing pro-inflammatory immune functions. These immune alterations among obese individuals are collectively incriminated in triggering several metabolic disorders and playing role in increasing cancers incidence and susceptibility to different infections. During COVID-19 pandemic, it was verified that patients with pre-existing obesity being at greater risk of suffering severe and fatal clinical outcomes. Beside obese people suffer from increased airway resistance and reduced lung volume, ACE2 expression in adipose tissue seems to be high and even higher than that in lungs, which spike infection incidence. In essence, obesity with pre-existence of pro-inflammatory cytokines such as LI-6 is a risk factor for cytokine storm and coagulopathy among COVID-19 patients. Summary: It is well documented that obesity is associated with chronic systemic low-grade inflammation, which sparks and alter different pillars of the immune system and triggers different metabolic disorders, and increases susceptibility of infections and cancer incidence. The pre-existing chronic inflammation in obese patients with the augmented inflammatory response against the viral infection seems to increase the susceptibility of these patients to developing severe COVID-19. Although the new weight loss drugs and bariatric surgery are considered as breakthrough news for obesity treatment, but preventing is easier than treating it once it has taken hold. However, obesity and immune system link new insights dispute the role of immunotherapy and regulating immune cells treating diet-induced obesity.

Keywords: immunity, metabolic disorders, cancer, COVID-19

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Authors: Emad M.Abdullat, Hasan A. Ader-Rahman, Rayyan Al Ali, Arwa.A.Hudaib

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This retrospective study aims to determine the epidemiological features of such deaths in one of the general teaching hospitals in Jordan with a focus on weaning practices and its relation to sucking as major factors underlying the mechanism of choking in infants and young children. The study utilized a retrospective design to review the records of forensic cases due to foreign body aspiration examined at the forensic department at the Jordan University Hospital. A total of 27 cases of choking in the pediatric age group were retrieved from the reports of the autopsy cases dissected. All cases of children who died due to chocking by foreign bodies were under 11 years old. Choking by food materials constituted (44.4%) of cases under 3 years of age while choking by non-food material were less prevalent under 3 years of age and comprising 18.5% of the cases. Health care personnel and parents need to be aware that introduction of solid food, unlike exclusive breast or formula-milk feeding, can have serious consequences if occurring in inappropriate timing or consistency during early childhood physical and functional development. Parents need to be educated regarding the appropriate timing and process of weaning.

Keywords: chocking, infants, weaning practices, young children

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Authors: A. O. Ogunkeyede, D. Amuchi, A. A. Adebayo

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Heavy metal contaminations in soil have received great attention. Anthropogenic activities such as vehicular emission, industrial activities and constructions have resulted in elevated concentration of heavy metals in the surface soils. The metal particles can be free from the surface soil when they are disturbed and re-entrained in air, which necessitated the need to investigate surface soil at market environment where adults and children are present on daily basis. This study assesses concentration of heavy metal pollution, ecological and health risk factors in surface soil at Effurun market. 8 samples were collected at household material (EMH), fish (EMFs), fish and commodities (EMF-C), Abattoir (EMA 1 & 2), fruit sections (EMF 1 & 2) and lastly main road (EMMR). The samples were digested and analyzed in triplicate for contents of Lead (Pb), Nickel (Ni), Cadmium (Cd) and Copper (Cu). The mean concentration of the Pb mg/kg (112.27 ± 1.12) and Cu mg/kg (156.14 ± 1.10) were highest in the abattoir section (EMA 1). The mean concentrations of the heavy metal were then used to calculate the ecological and health risk for people within the market. Pb contamination at EMMR, EMF 2, EMFs were moderately while Pb shows considerable contamination at EMH, EMA 1, EMA 2 and EMF-C sections of the Effurun market. The ecological risk factor varies between low to moderate pollution for Pb and EMA 1 has the highest potential ecological risk that falls within moderate pollution. The hazard quotient results show that dermal exposure pathway is the possible means of heavy metal exposure to the traders while ingestion is the least sources of exposure to adult. The ingestion suggested that children around the EMA 1 have the highest possible exposure to children due to hand-to-mouth and object-to-mouth behaviour. The results further show that adults at the EMA1 will have the highest exposure to Pb due to inhalation during burning of cow with tyre that contained Pb and Cu. The carcinogenic risk values of most sections were higher than acceptable values, while Ni at EMMR, EMF 1 & 2, EMFs and EMF-C sections that were below the acceptable values. The cancer risk for inhalation exposure pathway for Pb (1.01E+17) shows a significant level of contamination than all the other sections of the market. It suggested that the people working at the Abattoir were very prone to cancer risk.

Keywords: carcinogenic, ecological, heavy metal, risk

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Authors: Mohamed Moussaoui, Mouna Baassi, Soukayna Baammi, Hatim Soufi, Mohammed Salah, Rachid Daoud, Achraf EL Allali, Mohammed Elalaoui Belghiti, Said Belaaouad

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The present study aims to investigate the quantitative structure-activity relationship (QSAR) of a series of Thiazole derivatives reported as anticancer agents (hepatocellular carcinoma), using principally the electronic descriptors calculated by the density functional theory (DFT) method and by applying the multiple linear regression method. The developed model showed good statistical parameters (R²= 0.725, R²ₐ𝒹ⱼ= 0.653, MSE = 0.060, R²ₜₑₛₜ= 0.827, Q²𝒸ᵥ = 0.536). The energy of the highest occupied molecular orbital (EHOMO) orbital, electronic energy (TE), shape coefficient (I), number of rotatable bonds (NROT), and index of refraction (n) were revealed to be the main descriptors influencing the anti-cancer activity. Additional Thiazole derivatives were then designed and their activities and pharmacokinetic properties were predicted using the validated QSAR model. These designed molecules underwent evaluation through molecular docking (MD) and molecular dynamic (MD) simulations, with binding affinity calculated using the MMPBSA script according to a 100 ns simulation trajectory. This process aimed to study both their affinity and stability towards Cyclin-Dependent Kinase 2 (CDK2), a target protein for cancer disease treatment. The research concluded by identifying four CDK2 inhibitors - A1, A3, A5, and A6 - displaying satisfactory pharmacokinetic properties. MDs results indicated that the designed compound A5 remained stable in the active center of the CDK2 protein, suggesting its potential as an effective inhibitor for the treatment of hepatocellular carcinoma. The findings of this study could contribute significantly to the development of effective CDK2 inhibitors.

Keywords: QSAR, ADMET, Thiazole, anticancer, molecular docking, molecular dynamic simulations, MMPBSA calculation

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Authors: Ashwani Kumar Aggarwal

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NIR Light is non-ionizing and can pass easily through living tissues such as breast without any harmful effects. Therefore, use of NIR light for imaging the biological tissue and to quantify its optical properties is a good choice over other invasive methods. Optical tomography involves two steps. One is the forward problem and the other is the reconstruction problem. The forward problem consists of finding the measurements of transmitted light through the tissue from source to detector, given the spatial distribution of absorption and scattering properties. The second step is the reconstruction problem. In X-ray tomography, there is standard method for reconstruction called filtered back projection method or the algebraic reconstruction methods. But this method cannot be applied as such, in optical tomography due to highly scattering nature of biological tissue. A hybrid algorithm for reconstruction has been implemented in this work which takes into account the highly scattered path taken by photons while back projecting the forward data obtained during Monte Carlo simulation. The reconstructed image suffers from blurring due to point spread function. This blurred reconstructed image has been enhanced using a digital filter which is optimal in mean square sense.

Keywords: least-squares optimization, filtering, tomography, laser interaction, light scattering

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Authors: Grâce Chidikofan, François Pinta, A. Benoist, G. Volle, J. Valette

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Statement of the Problem: biomass gasification systems may be relevant for decentralized power generation from recoverable agricultural and wood residues available in rural areas. In recent years, many systems have been implemented in all over the world as especially in Cambodgia, India. Although they have many positive effects, these systems can also affect the environment and human health. Indeed, during the process of biomass gasification, black wastewater containing tars are produced and generally discharged in the local environment either into the rivers or on soil. However, in most environmental assessment studies of biomass gasification systems, the impact of these releases are underestimated, due to the difficulty of identification of their chemical substances. This work deal with the analysis of the environmental impacts of tars from wood gasification in terms of human toxicity cancer effect, human toxicity non-cancer effect, and freshwater ecotoxicity. Methodology: A Life Cycle Assessment (LCA) approach was adopted. The inventory of tars chemicals substances was based on experimental data from a downdraft gasification system. The composition of six samples from two batches of raw materials: one batch made of tree wood species (oak+ plane tree +pine) at 25 % moisture content and the second batch made of oak at 11% moisture content. The tests were carried out for different gasifier load rates, respectively in the range 50-75% and 50-100%. To choose the environmental impacts assessment method, we compared the methods available in SIMAPRO tool (8.2.0) which are taking into account most of the chemical substances. The environmental impacts for 1kg of tars discharged were characterized by ILCD 2011+ method (V.1.08). Findings Experimental results revealed 38 important chemical substances in varying proportion from one test to another. Only 30 are characterized by ILCD 2011+ method, which is one of the best performing methods. The results show that wood species or moisture content have no significant impact on human toxicity noncancer effect (HTNCE) and freshwater ecotoxicity (FWE) for water release. For human toxicity cancer effect (HTCE), a small gap is observed between impact factors of the two batches, either 3.08E-7 CTUh/kg against 6.58E-7 CTUh/kg. On the other hand, it was found that the risk of negative effects is higher in case of tar release into water than on soil for all impact categories. Indeed, considering the set of samples, the average impact factor obtained for HTNCE varies respectively from 1.64 E-7 to 1.60E-8 CTUh/kg. For HTCE, the impact factor varies between 4.83E-07 CTUh/kg and 2.43E-08 CTUh/kg. The variability of those impact factors is relatively low for these two impact categories. Concerning FWE, the variability of impact factor is very high. It is 1.3E+03 CTUe/kg for tars release into water against 2.01E+01 CTUe/kg for tars release on soil. Statement concluding: The results of this study show that the environmental impacts of tars emission of biomass gasification systems can be consequent and it is important to investigate the ways to reduce them. For environmental research, these results represent an important step of a global environmental assessment of the studied systems. It could be used to better manage the wastewater containing tars to reduce as possible the impacts of numerous still running systems all over the world.

Keywords: biomass gasification, life cycle analysis, LCA, environmental impact, tars

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Authors: Witri Pratiwi, Shopa Nur Fauzah, Dini Norviatin

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WHO recommends breastfeeding exclusively for infants aged 0 to 6 months because breast milk is the best nutrition. There are several factors associated with the success of exclusive breastfeeding. This study aims to determine the factors associated with the success of exclusive breastfeeding. A cross-sectional study was conducted at 6 community health centers in Cirebon City, Indonesia. Primary data were obtained from a validated questionnaire given to mothers who have children aged 6 to 24 months. A total of 326 mothers participated in this study. Two hundred and eighteen (66.9%) mothers gave exclusive breastfeeding to their babies, and 108 (33.1%) did not give exclusive breastfeeding. The baby gender (p=0.240), birth weight (p=0.436), and place of birth (0.137) were not related to exclusive breastfeeding. Mode of delivery (p=0.029) and early initiation of breastfeeding (p=0.001) were significantly associated with exclusive breastfeeding. Infants with early initiation of breastfeeding are three times more likely to get exclusive breastfeeding compared to those who do not get breastfeeding early (p=0.001; OR=3.696 [95% CI 1.764 – 7.746]). Early initiation of breastfeeding is the most important factor in determining the success of exclusive breastfeeding. Promotion and education on the importance of early breastfeeding initiation to prospective mothers, families, and health workers are expected to be improved.

Keywords: early initiation of breastfeeding, exclusive breastfeeding, mode of delivery, Indonesia

Procedia PDF Downloads 138

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: Miceska Simona, Škof Erik, Frković Grazio Snježana, Jeričević Anja, Smrkolj Špela, Cvjetićanin Branko, Novaković Srdjan, Grčar Kuzmanov Biljana, Kloboves-Prevodnik Veronika

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Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by the dissemination of the tumor cells (TC) in the peritoneal cavity forming malignant ascites at the time of diagnosis or recurrence. Still, cytology itself has been underutilized as a modality for the diagnosis of HGSOC from ascites, and histological examination from the tumor tissue is yet the only validated method used. The objective of this study was to evaluate the reliability of cytology in the diagnosis of HGSOC in relation to the histopathological examination. Methods: The study included 42 patients with histologically confirmed HGSOC, accompanied by malignant ascites. To confirm the malignancy of the TC in the ascites and to define their immunophenotype, immunohistochemical reaction (IHC) of the following antigens: Calretinin, MOC, WT1, PAX8, p53, p16 & Ki-67 was evaluated on ascites cytospins and tissue blocks. For complete cytological determination of HGSOC, BRCA 1/2 gene mutation was determined from ascites, tissue block, and blood. BRCA1/2 mutation from blood was performed to define the type of mutation, somatic vs germline. Results: Among 42 patients, the immunophenotype of HGSOC from ascites was confirmed in 36 cases (86%). For more profound analysis, the patients were divided in 3 groups regarding the number of TC present in the ascites: patients with less than 10% TC, 10% TC, and more than 10% TC. From all included patients, in the group with less than 10% TC, there were 10 cases, and only 5 of them(50%) showed HGSOC phenotype; 12 cases had equally 10% of TC, and 11 cases (92%) showed HGSOC phenotype; 20 cases had more than 10% TC and all of them (100%) confirmed the HGSOC immunophenotype from ascites. Only 33 patients were eligible for further BRCA1/2 analysis. Eleven BRCA1/2 mutations were detected from thetissue block: 6 germline and 5 somatic. In 2 cases with less than 10% TC, BRCA1/2 mutation was not detected; 4 cases had 10% TC, and 2 of them (50%) confirmed the mutation; 4 cases had more than 10% TC, and all showed 100% reliability with the tumor tissue. Conclusions: Cytology is a highly reliable method for determining the immunophenotype of HGSOC and BRCA1/2 mutation if more than 10% of tumor cells are present in the ascites. This may present an additional non-invasive clinical approach for fast and effective diagnose in the future, especially in inoperable conditions or relapses.

Keywords: cytology, ascites, high-grade serous ovarian cancer, immunophenotype, BRCA1/2

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Authors: Khairy M. A. Zoheir, Nehma A. Ali, Ahmed M. Darwish, Mohamed S. Kishta, Ahmed A. Abd-Rabou, Mohamed A. Abdelhafez, Karima F. Mahrous

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The study comprehensively investigated the multifaceted therapeutic properties of the IQGAP1shRNA plasmid, encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of IQGAP1shRNA plasmid. Using this model, IQGAP1shRNA plasmid was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, heart, liver, ovaries, and kidneys, was reversed with IQGAP1shRNA plasmid treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers (ALT, AST, ALP, LPO) indicative of hepatocellular injury and oxidative stress were reduced with GST, highlighting its hepatoprotective and antioxidative effects. IQGAP1shRNA plasmid also restored depleted antioxidants (GSH and SOD), emphasizing its potent antioxidative and free radical scavenging capabilities. Molecular insights into immune dysregulation revealed downregulation of IQGAP1, IQGAP3 interleukin-2 (IL-2), and interleukin-4 (IL-4) mRNA expression in the liver of immunosuppressed rats. IL-2 and IL-4 play pivotal roles in immune regulation, T-cell activation, and B-cell differentiation. Notably, treatment with IQGAP1shRNA plasmid exhibited a significant upregulation of IL-2 and IL-4 mRNA expression, thereby accentuating its immunomodulatory potential in orchestrating immune homeostasis. Additionally, immune dysregulation was associated with increased levels of TNF-α. However, treatment with IQGAP1shRNA plasmid effectively decreased the levels of TNF-α, further underscoring its role in modulating inflammatory responses and restoring immune balance in immunosuppressed rats. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk assessment prediction suggest its potential as a pharmacologically favourable agent with no serious adverse effects. In conclusion, this study confirms the therapeutic potential of the IQGAP1shRNA plasmid, showcasing its effectiveness against hepatotoxicity, oxidative stress, immunosuppression, and its notable anticancer activity.

Keywords: IQGAP1, shRNA, cancer, liver, rat

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Authors: K. Rhea Devaiah, B. S. Premalatha

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Background: Tonsillar Lingual sulcus is the area between the tonsils and the base of the tongue. The surgical resection of the lesions in the head and neck results in changes in speech and swallowing functions. The severity of the speech and swallowing problem depends upon the site and extent of the lesion, types and extent of surgery and also the flexibility of the remaining structures. Need of the study: This paper focuses on the importance of speech and swallowing rehabilitation in an individual with the lesion in the Tonsillar Lingual Sulcus and post-operative functions. Aim: Evaluating the speech and swallow functions post-intensive speech and swallowing rehabilitation. The objectives are to evaluate the speech intelligibility and swallowing functions after intensive therapy and assess the quality of life. Method: The present study describes a report of an individual aged 47years male, with the diagnosis of basaloid squamous cell carcinoma, left tonsillar lingual sulcus (pT2n2M0) and underwent wide local excision with left radical neck dissection with PMMC flap reconstruction. Post-surgery the patient came with a complaint of reduced speech intelligibility, and difficulty in opening the mouth and swallowing. Detailed evaluation of the speech and swallowing functions were carried out such as OPME, articulation test, speech intelligibility, different phases of swallowing and trismus evaluation. Self-reported questionnaires such as SHI-E(Speech handicap Index- Indian English), DHI (Dysphagia handicap Index) and SESEQ -K (Self Evaluation of Swallowing Efficiency in Kannada) were also administered to know what the patient feels about his problem. Based on the evaluation, the patient was diagnosed with pharyngeal phase dysphagia associated with trismus and reduced speech intelligibility. Intensive speech and swallowing therapy was advised weekly twice for the duration of 1 hour. Results: Totally the patient attended 10 intensive speech and swallowing therapy sessions. Results indicated misarticulation of speech sounds such as lingua-palatal sounds. Mouth opening was restricted to one finger width with difficulty chewing, masticating, and swallowing the bolus. Intervention strategies included Oro motor exercise, Indirect swallowing therapy, usage of a trismus device to facilitate mouth opening, and change in the food consistency to help to swallow. A practice session was held with articulation drills to improve the production of speech sounds and also improve speech intelligibility. Significant changes in articulatory production and speech intelligibility and swallowing abilities were observed. The self-rated quality of life measures such as DHI, SHI and SESE Q-K revealed no speech handicap and near-normal swallowing ability indicating the improved QOL after the intensive speech and swallowing therapy. Conclusion: Speech and swallowing therapy post carcinoma in the tonsillar lingual sulcus is crucial as the tongue plays an important role in both speech and swallowing. The role of Speech-language and swallowing therapists in oral cancer should be highlighted in treating these patients and improving the overall quality of life. With intensive speech-language and swallowing therapy post-surgery for oral cancer, there can be a significant change in the speech outcome and swallowing functions depending on the site and extent of lesions which will thereby improve the individual’s QOL.

Keywords: oral cancer, speech and swallowing therapy, speech intelligibility, trismus, quality of life

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Authors: Mohamed Boubekri

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Daylight in general and sunlight in particular are vital to life on earth, and it is not difficult to believe that their absence fosters conditions that promote disease. Through photosynthesis and other processes, sunlight provides photochemical ingredients necessary for our lives. There are fundamental biological, hormonal, and physiological functions coordinated by cycles that are crucial to life for cells, plants, animals, and humans. Many plants and animals, including humans, develop abnormal behaviors when sunlight is absent because their diurnal cycle is disturbed. Building​ codes disregard this aspect of daylighting when promulgating windows for buildings. This paper discusses the health aspects of daylighting design.

Keywords: daylighting, health, sunlight, sleep, disorders, circadian rythm, cancer

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Authors: Hossein Rassi, Marjan Moradi Fard, Samaneh Niko

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Human papillomavirus type 16 and 18 are closely associated with the development of human cervical carcinoma, which is one of the most common causes of cancer death in women worldwide. At present, HPV type 18 accounts for about 34 % of all HPV infections in Iran and the most promising vaccine against HPV infection is based on the L1 major capsid protein. The L1 protein of HPV18 has the capacity to self-assemble into capsomers or virus-like particles (VLPs) that are non-infectious, highly immunogenic and allowing their use in vaccine production. The methylotrophic yeast Pichia pastoris is an efficient and inexpensive expression system used to produce high levels of heterologous proteins. In this study we expressed HPV18 L1 VLPs in P. pastoris. The gene encoding the major capsid protein L1 of the high-risk HPV type 18 was isolated from Iranian patient by PCR and inserted into pTG19-T vector to obtain the recombinant expression vector pTG19-HPV18-L1. Then, the pTG19-HPV18-L1 was transformed into E. coli strain DH5α and the recombinant protein HPV18 L1 was expressed under IPTG induction in soluble form. The HPV18 L1 gene was excised from recombinant plasmid with XhoI and EcoRI enzymes and ligated into the yeast expression vector pPICZα linearized with the same enzymes, and transformed into P. pastoris. Induction and expression of HPV18 L1 protein was demonstrated by BMGY/BMMY and RT PCR. The parameters for induced cultivation for strain in P. pastoris KM71 with HPV16L1 were investigated in shaking flask cultures. After induced cultivation BMMY (pH 7.0) medium supplemented with methanol to a final concentration of 1.0% every 24 h at 37 degrees C for 96 h, the recombinant produced 78.6 mg/L of L1 protein. This work offers the possibility for the production of prophylactic vaccine for cervical carcinoma by P. pastoris for HPV-18 L1 gene. The VLP-based HPV vaccines can prevent persistent HPV18 infections and cervical cancer in Iran. The HPV-18 L1 gene was expressed successfully in E.coli, which provides necessary basis for preparing HPV-18 L1 vaccine in human. Also, HPV type 6 L1 proteins expressed in Pichia pastoris will facilitate the HPV vaccine development and structure-function study.

Keywords: Pichia pastoris, L1 virus-like particles, human papillomavirus type 18, biotechnology

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Authors: Priyal Chikhaliwala, Sudeshna Chandra

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Liver cancer is one of the most common malignant tumors with poor prognosis. This is because liver cancer does not exhibit any symptoms in early stage of disease. Increased serum level of AFP is clinically considered as a diagnostic marker for liver malignancy. The present diagnostic modalities include various types of immunoassays, radiological studies, and biopsy. However, these tests undergo slow response times, require significant sample volumes, achieve limited sensitivity and ultimately become expensive and burdensome to patients. Considering all these aspects, electrochemical biosensors based on dendrimer-magnetic nanoparticles (MNPs) was designed. Dendrimers are novel nano-sized, three-dimensional molecules with monodispersed structures. Poly-amidoamine (PAMAM) dendrimers with eight –NH₂ groups using ethylenediamine as a core molecule were synthesized using Michael addition reaction. Dendrimers provide added the advantage of not only stabilizing Fe₃O₄ NPs but also displays capability of performing multiple electron redox events and binding multiple biological ligands to its dendritic end-surface. Fe₃O₄ NPs due to its superparamagnetic behavior can be exploited for magneto-separation process. Fe₃O₄ NPs were stabilized with PAMAM dendrimer by in situ co-precipitation method. The surface coating was examined by FT-IR, XRD, VSM, and TGA analysis. Electrochemical behavior and kinetic studies were evaluated using CV which revealed that the dendrimer-Fe₃O₄ NPs can be looked upon as electrochemically active materials. Electrochemical immunosensor was designed by immobilizing anti-AFP onto dendrimer-MNPs by gluteraldehyde conjugation reaction. The bioconjugates were then incubated with AFP antigen. The immunosensor was characterized electrochemically indicating successful immuno-binding events. The binding events were also further studied using magnetic particle imaging (MPI) which is a novel imaging modality in which Fe₃O₄ NPs are used as tracer molecules with positive contrast. Multicolor MPI was able to clearly localize AFP antigen and antibody and its binding successfully. Results demonstrate immense potential in terms of biosensing and enabling MPI of AFP in clinical diagnosis.

Keywords: alpha-fetoprotein, dendrimers, electrochemical biosensors, magnetic nanoparticles

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Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

Abstract:

In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

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Authors: L. Szymanski, Z. Kolacinski, Z. Kamiński, G. Raniszewski, J. Fraczyk, L. Pietrzak

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In the article the development and demonstration of method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nano containers. Methodology of the production carbon - ferromagnetic nanocontainers includes: the synthesis of carbon nanotubes, chemical and physical characterization, increasing the content of ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Folic acid is ligand of folate receptors which is overexpresion in tumor cells. The presence of ligand should ensure the specificity of the interaction between ferromagnetic nanocontainers and tumor cells. The chemical functionalization contains several step: oxidation reaction, transformation of carboxyl groups into more reactive ester or amide groups, incorporation of spacer molecule (linker), attaching folic acid. Activation of carboxylic groups was prepared with triazine coupling reagent (preparation of superactive ester attached on the nanocontainers). The spacer molecules were designed and synthesized. In order to ensure biocompatibillity of linkers they were built from amino acids or peptides. Spacer molecules were synthesized using the SPPS method. Synthesis was performed on 2-Chlorotrityl resin. The linker important feature is its length. Due to that fact synthesis of peptide linkers containing from 2 to 4 -Ala- residues was carried out. Independent synthesis of the conjugate of foilic acid with 6-aminocaproic acid was made. Final step of synthesis was connecting conjugat with spacer molecules and attaching it on the ferromagnetic nanocontainer surface. This article contains also information about special CVD and microvave plasma system to produce nanotubes and ferromagnetic nanocontainers. The first tests in the device for hyperthermal RF generator will be presented. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz.

Keywords: synthesis of carbon nanotubes, hyperthermia, ligands, carbon nanotubes

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Authors: Abdulkareem M. Hamid, Yaseen Elhebshi, Adam Daïch

Abstract:

Luotonins and its derivatives (Isoluotonins) are alkaloids from the aerial parts of Peganum nigellastrum Bunge that display three major skeleton types. Luotonins A, B, and E are pyrroloquinazolinoquinoline alkaloids. A few methods were known for the sysnthesis of Isoluotonin. All luotonins have shown promising cytotoxicities towards selected human cancer cell lines, especially against leukemia P-388 cells. Luotonin A is the most active one, with its activity stemming from topoisomerase I-dependent DNA-cleavage. Such intriguing biological activities and unique structures have led not only to the development of synthetic methods for the efficient synthesis of these compounds, but also to interest in structural modifications for improving the biological properties. Recent progress in the study of luotonins is covered.

Keywords: luotonin A, isoluotonin, pyrroloquiolines, alkaloids

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Authors: Alsulami H., Alghamdi N., Alasker A., Almohen N., Shome D.

Abstract:

Most conventional chemotherapeutic agents which are used for the treatment of cancers not only eradicate cancer cells but also affect normal hematopoietic Stem cells (HSCs) that leads to severe pancytopenia during treatment. Therefore, a need exists for novel approaches to treat cancer without or with minimum effect on normal HSCs. Parthenolide (PTL), a herbal product occurring naturally in the plant Feverfew, is a potential new chemotherapeutic agent for the treatment of many cancers such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In this study we investigated the effect of different PTL concentrations on the viability of normal HSCs and also on the ability of these cells to form colonies after they have been treated with PTL in vitro. Methods: In this study, 24 samples of bone marrow and cord blood were collected with consent, and mononuclear cells were separated using density gradient separation. These cells were then exposed to various concentrations of PTL for 24 hours. Cell viability after culture was determined using 7ADD in a flow cytometry test. Additionally, the impact of PTL on hematopoietic stem cells (HSCs) was evaluated using a colony forming unit assay (CFU). Furthermore, the levels of NFҝB expression were assessed by using a PE-labelled anti-pNFκBP65 antibody. Results: this study showed that there was no statistically significant difference in the percentage of cell death between untreated and PTL treated cells with 5 μM PTL (p = 0.7), 10 μM PTL (p = 0.4) and 25 μM (p = 0.09) respectively. However, at higher doses, PTL caused significant increase in the percentage of cell death. These results were significant when compared to untreated control (p < 0.001). The response of cord blood cells (n=4) on the other hand was slightly different from that for bone marrow cells in that the percentage of cell death was significant at 100 μM PTL. Therefore, cord blood cells seemed more resistant than bone marrow cells. Discussion &Conclusion: At concentrations ≤25 μM PTL has a minimum or no effect on HSCs in vitro. Cord blood HSCs are more resistant to PTL compared to bone marrow HSCs. This could be due to the higher percentage of T-lymphocytes, which are resistant to PTL, in CB samples (85% in CB vs. 56% in BM. Additionally, CB samples contained a higher proportion of CD34+ cells, with 14.5% of brightly CD34+ cells compared to only 1% in normal BM. These bright CD34+ cells in CB were mostly negative for early-stage stem cell maturation antigens, making them young and resilient to oxidative stress and high concentrations of PTL.

Keywords: stem cell, parthenolide, NFKB, CLL

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Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

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Authors: Su Chul Han, Seungwoo Park

Abstract:

As the increasing incidence of cancer, the technology and modality of radiotherapy have advanced and the importance of preclinical model is increasing in the cancer research. Furthermore, the small animal dosimetry is an essential part of the evaluation of the relationship between the absorbed dose in preclinical small animal and biological effect in preclinical study. In this study, we carried out realistic modeling of the preclinical small animal phantom possible to verify irradiated dose using commercial software. The small animal phantom was modeling from 4D Digital Mouse whole body phantom. To manipulate Moby phantom in commercial software (Mimics, Materialise, Leuven, Belgium), we converted Moby phantom to DICOM image file of CT by Matlab and two- dimensional of CT images were converted to the three-dimensional image and it is possible to segment and crop CT image in Sagittal, Coronal and axial view). The CT images of small animals were modeling following process. Based on the profile line value, the thresholding was carried out to make a mask that was connection of all the regions of the equal threshold range. Using thresholding method, we segmented into three part (bone, body (tissue). lung), to separate neighboring pixels between lung and body (tissue), we used region growing function of Mimics software. We acquired 3D object by 3D calculation in the segmented images. The generated 3D object was smoothing by remeshing operation and smoothing operation factor was 0.4, iteration value was 5. The edge mode was selected to perform triangle reduction. The parameters were that tolerance (0.1mm), edge angle (15 degrees) and the number of iteration (5). The image processing 3D object file was converted to an STL file to output with 3D printer. We modified 3D small animal file using 3- Matic research (Materialise, Leuven, Belgium) to make space for radiation dosimetry chips. We acquired 3D object of realistic small animal phantom. The width of small animal phantom was 2.631 cm, thickness was 2.361 cm, and length was 10.817. Mimics software supported efficiency about 3D object generation and usability of conversion to STL file for user. The development of small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study.

Keywords: mimics, preclinical small animal, segmentation, 3D printer

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Authors: Chen Wang, Jared Evans, Yan Asmann

Abstract:

With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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Authors: Enoch Kudoahor, Nan Zheng

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We describe the use of readily available self-doped TiO2 and visible light, under a mild condition to synthesize a class of monocyclic, bicyclic, and benzocyclobutene amino compounds containing the endoperoxide bridges; their derivatives and further test their effective clinical activities against malaria, cancer, and their resistances. Considering their stable under photooxidation conditions and recyclability, we use a self-doped TiO2 under a visible condition to synthesize these classes of amino endoperoxides. These amino endoperoxides are stable over a period compared to classes of endoperoxides.

Keywords: catalysis, endoperoxides, titanium dioxide, visible light

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Authors: Mariam Mojally, Randa Abdou, Wisal Bokhari, Sultan Sab, Mohammed Dawoud, Amjad Albohy

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Secondary metabolites produced by endophytes are an excellent source of biologically active compounds. In our current study, we evaluated terezine E and 14-hydroxyterezine D for binding to the active site of histone deacetylase (PDB ID: 4CBT) and matrix metalloproteinase 9 (PDB ID: 4H3X) by molecular docking using AutoDock Vina software after having tested their cytotoxic activities on three cell lines (human ductal breast epithelial tumor cells (T47D)-HCC1937), human hepatocarcinoma cell line (HepG2)-HB8065), and human colorectal carcinoma cells (HCT-116)-TCP1006, purchased from ATCC, USA)). Additionally, their antimicrobial activities were investigated, and their minimum inhibitory concentration (MIC) values were determined against P. notatum and S. aureus by the broth microdilution method. Higher cytotoxicity was observed for terezine E against all tested cell lines compared to 14-hydroxyterezine D. Molecular docking results supported the high cytotoxicity of terezine E and showed higher binding affinity with 4CBT with an energy score of 9 kcal/mol. Terezine E showed higher antibacterial and antifungal activities than 14-hydroxyrerezine D: MIC values were 15.45 and 21.73 mg/mL against S. aureus and 8.61 and 11.54 mg/mL against P. notatum, respectively

Keywords: Terezine E, 14-Hydroxyterezine D, cytotoxicity, antimicrobial activity, molecular docking

Procedia PDF Downloads 73

Authors: Christos E. Lampropoulos, Maria Konsta, Tamta Sirbilatze, Ifigenia Apostolou, Vicky Dradaki, Konstantina Panouria, Irini Dri, Christina Kordali, Vaggelis Lambas, Georgios Mavras

Abstract:

Objectives: Full Mini Nutritional Assessment (MNA) questionnaire is one of the most useful tools in diagnosis of malnutrition in hospitalized patients, which is related to increased morbidity and mortality. The purpose of our study was to assess the nutritional status of elderly, hospitalized patients and examine the hypothesis that MNA may predict mortality and extension of hospitalization. Methods: One hundred fifty patients (78 men, 72 women, mean age 80±8.2) were included in this cross-sectional study. The following data were taken into account in analysis: anthropometric and laboratory data, physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, dietary habits, cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were mortality (from admission until 6 months afterwards) and duration of admission. The latter was compared to national guidelines for closed consolidated medical expenses. Logistic regression and linear regression analysis were performed in order to identify independent predictors for mortality and extended hospitalization respectively. Results: According to MNA, nutrition was normal in 54/150 (36%) of patients, 46/150 (30.7%) of them were at risk of malnutrition and the rest 50/150 (33.3%) were malnourished. After performing multivariate logistic regression analysis we found that the odds of death decreased 20% per each unit increase of full MNA score (OR=0.8, 95% CI 0.74-0.89, p < 0.0001). Patients who admitted due to cancer were 23 times more likely to die, compared to those with infection (OR=23, 95% CI 3.8-141.6, p=0.001). Similarly, patients who admitted due to stroke were 7 times more likely to die (OR=7, 95% CI 1.4-34.5, p=0.02), while these with all other causes of admission were less likely (OR=0.2, 95% CI 0.06-0.8, p=0.03), compared to patients with infection. According to multivariate linear regression analysis, each increase of unit of full MNA, decreased the admission duration on average 0.3 days (b:-0.3, 95% CI -0.45 - -0.15, p < 0.0001). Patients admitted due to cancer had on average 6.8 days higher extension of hospitalization, compared to those admitted for infection (b:6.8, 95% CI 3.2-10.3, p < 0.0001). Conclusion: Mortality and extension of hospitalization is significantly increased in elderly, malnourished patients. Full MNA score is a useful diagnostic tool of malnutrition.

Keywords: duration of admission, malnutrition, mini nutritional assessment score, prognostic factors for mortality

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

Abstract:

Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.

Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus

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Authors: Darawan Augsornwan, Artitaya Sabangbal, Maneewan Srijan, Kanokarn Kongpitee, Lalida Petphai, Palakorn Surakunprapha

Abstract:

Background: Srinagarind Hospital, Ward 3C, has patients with head and neck cancer, congenital urology anomalies such as hypospadis, cleft lip and cleft palate and congenital megacolon who need surgery. Undergoing surgery is a difficult time for patients/ family; they feel fear and anxiety. Nurses work closely with patients and family for 24 hours in the process of patients care, so should have the good nursing ability, innovation and an efficient nursing care system to promote patients self-care ability reducing suffering and preventing complications. From previous nursing outcomes we found patients did not receive appropriate information, could not take care of their wound, not early ambulation after the operation and lost follow-up. Objective: to develop the nursing system for patients who were undergoing an operation. Method: this is a participation action research. The sample population was 11 nurses and 60 patients. This study was divided into 3 phase: Phase 1. Situation review In this phase we review the clinical outcomes, the process of care from documents such as nurses note and interview nurses, patients and family about the process of care by nurses. Phase 2: focus group with 11 nurses, searching guideline for specific care, nursing care system then establish the protocol. This phase we have the protocol for giving information, teaching protocol and teaching record, leaflet for all of top five diseases, make video media to convey information, ambulation package and protocol for patients with head and neck cancer, patients zoning, primary nurse, improved job description for each staff level. Program to record number of patients, kind of medical procedures for showing nurses activity each day. Phase 3 implementation and evaluation. Result: patients/family receive appropriate information about deep breathing exercise, cough, early ambulation after the operation, information during the stay in the hospital. Patients family satisfaction is 95.04 percent, appropriate job description for a practical nurse, nurse aid, and worker. Nurses satisfaction is 95 percent. The complications can be prevented. Conclusion: the nursing system is the dynamic process using evidence to develop nursing care. The appropriate system depends on context and needs to keep an eye on every event.

Keywords: development, nursing system, patients undergoing operation, 3C Ward

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