Search results for: sepsis immune modulation

Authors: Andleeb Zahra, Itrat Rubab, Sumaira Malik, Amina Khan, Muhammad Jawad Khan, M. Qaiser Fatmi

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Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use in an early diagnostic tool. miRNAs are small, double stranded, non-coding RNAs that regulate gene expression by deregulating mRNAs. miRNAs play important roles in modifying various cellular processes such as cell growth, differentiation, apoptosis, and immune response. Dis-regulated expression of miRNAs is known to affect the cell growth, and this may function as tumor suppressors or oncogenes in various cancers. Objectives: The main objectives of this study were to characterize the extracellular miRNAs involved in oral cancer (OC) to assist early detection of cancer as well as to propose a list of genes that can potentially be used as biomarkers of OC. We used gene expression data by microarrays already available in literature. Materials and Methods: In the first step, a total of 318 miRNAs involved in oral carcinoma were shortlisted followed by the prediction of their target genes. Simultaneously, the differentially expressed genes (DEGs) of oral carcinoma from all experiments were identified. The common genes between lists of DEGs of OC based on experimentally proven data and target genes of each miRNA were identified. These common genes are the targets of specific miRNA, which is involved in OC. Finally, a list of genes was generated which may be used as biomarker of OC. Results and Conclusion: In results, we included some of pathways in cancer to show the change in gene expression under the control of specific miRNA. Ingenuity pathway analysis (IPA) provided a list of major biomarkers like CDH2, CDK7 and functional enrichment analysis identified the role of miRNA in major pathways like cell adhesion molecules pathway affected by cancer. We observed that at least 25 genes are regulated by maximum number of miRNAs, and thereby, they can be used as biomarkers of OC. To better understand the role of miRNA with respect to their target genes further experiments are required, and our study provides a platform to better understand the miRNA-OC relationship at genomics level.

Keywords: biomarkers, gene expression, miRNA, oral carcinoma

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Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

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The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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Authors: O. Eso, M. Mohammadi, J. Darkwa, J. Calautit

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Residential buildings are responsible for 22% of the global end-use energy demand and 17% of global CO₂ emissions. Tropical climates particularly present higher latent heat gains, leading to more cooling loads. However, the cooling processes are all based on conventional mechanical air conditioning systems which are energy and carbon intensive technologies. Passive cooling systems have in the past been considered as alternative technologies for minimizing energy consumption in buildings. Nevertheless, replacing mechanical cooling systems with passive ones will require a careful assessment of the passive cooling system heat transfer to determine if suitable to outperform their conventional counterparts. This is because internal heat gains, indoor-outdoor heat transfer, and heat transfer through envelope affects the performance of passive cooling systems. While many studies have investigated sensible heat transfer in passive cooling systems, not many studies have focused on their latent heat transfer capabilities. Furthermore, combining heat prevention, heat modulation and heat dissipation to passively cool indoor spaces in the tropical climates is critical to achieve thermal comfort. Since passive cooling systems use only one of these three approaches at a time, integrating more than one passive cooling system for effective indoor latent heat removal while still saving energy is studied. This study is a systematic review of recently published peer review journals on integrated passive cooling systems for tropical residential buildings. The missing links in the experimental and numerical studies with regards to latent heat reduction interventions are presented. Energy simulation studies of integrated passive cooling systems in tropical residential buildings are also discussed. The review has shown that comfortable indoor environment is attainable when two or more passive cooling systems are integrated in tropical residential buildings. Improvement occurs in the heat transfer rate and cooling performance of the passive cooling systems when thermal energy storage systems like phase change materials are included. Integrating passive cooling systems in tropical residential buildings can reduce energy consumption by 6-87% while achieving up to 17.55% reduction in indoor heat flux. The review has highlighted a lack of numerical studies regarding passive cooling system performance in tropical savannah climates. In addition, detailed studies are required to establish suitable latent heat transfer rate in passive cooling ventilation devices under this climate category. This should be considered in subsequent studies. The conclusions and outcomes of this study will help researchers understand the overall energy performance of integrated passive cooling systems in tropical climates and help them identify and design suitable climate specific options for residential buildings.

Keywords: energy savings, latent heat, passive cooling systems, residential buildings, tropical residential buildings

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Carlos Teodoro, Oscar Bautista

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In this work, we analyze theoretically the mass transport in a time-periodic electroosmotic flow through a parallel flat plate microchannel under different periodic functions of the applied external electric field. The microchannel connects two reservoirs having different constant concentrations of an electro-neutral solute, and the zeta potential of the microchannel walls are assumed to be uniform. The governing equations that allow determining the mass transport in the microchannel are given by the Poisson-Boltzmann equation, the modified Navier-Stokes equations, where the Debye-Hückel approximation is considered (the zeta potential is less than 25 mV), and the species conservation. These equations are nondimensionalized and four dimensionless parameters appear which control the mass transport phenomenon. In this sense, these parameters are an angular Reynolds, the Schmidt and the Péclet numbers, and an electrokinetic parameter representing the ratio of the half-height of the microchannel to the Debye length. To solve the mathematical model, first, the electric potential is determined from the Poisson-Boltzmann equation, which allows determining the electric force for various periodic functions of the external electric field expressed as Fourier series. In particular, three different excitation wave forms of the external electric field are assumed, a) sawteeth, b) step, and c) a periodic irregular functions. The periodic electric forces are substituted in the modified Navier-Stokes equations, and the hydrodynamic field is derived for each case of the electric force. From the obtained velocity fields, the species conservation equation is solved and the concentration fields are found. Numerical calculations were done by considering several binary systems where two dilute species are transported in the presence of a carrier. It is observed that there are different angular frequencies of the imposed external electric signal where the total mass transport of each species is the same, independently of the molecular diffusion coefficient. These frequencies are called crossover frequencies and are obtained graphically at the intersection when the total mass transport is plotted against the imposed frequency. The crossover frequencies are different depending on the Schmidt number, the electrokinetic parameter, the angular Reynolds number, and on the type of signal of the external electric field. It is demonstrated that the mass transport through the microchannel is strongly dependent on the modulation frequency of the applied particular alternating electric field. Possible extensions of the analysis to more complicated pulsation profiles are also outlined.

Keywords: electroosmotic flow, mass transport, oscillatory flow, species separation

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Authors: Lito M. Amit, Venecio U. Ultra, Young-Woong Song

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The business process outsourcing (BPO) in the Philippines is expanding rapidly attracting more than 2% of total employment. Currently, the BPO industry is confronted with several issues pertaining to sustainable productivity such as meeting the staffing gap, high rate of employees’ turnover and workforce retention, and the occupational health and safety (OHS) of call center agents. We conducted a survey of OHS programs and health concerns among call center agents in the Philippines and determined the sociocultural factors that affect the vulnerability of call center agents to occupational health risks and hazards. The majority of the agents affirmed that OHS are implemented and OHS orientation and emergency procedures were conducted at employment initiations, perceived favorable and convenient working environment except for occasional noise disturbances and acoustic shock, visual, and voice fatigues. Male agents can easily adjust to the demands and changes in their work environment and flexible work schedules than female agents. Female agents have a higher tendency to be pressured and humiliated by low work performance, experience a higher incidence of emotional abuse, psychological abuse, and experience more physical stress than male agents. The majority of the call center agents had a night-shift schedule and regardless of other factors, night shift work brings higher stress to agents. While working in a call center, higher incidence of headaches and insomnia, burnout, suppressed anger, anxiety, and depressions were experienced by female, younger (21-25 years old) and those at night shift than their counterpart. Most common musculoskeletal disorders include body pain in the neck, shoulders and back; and hand and wrist disorders and these are commonly experienced by female and younger workers. About 30% experienced symptoms of cardiovascular and gastrointestinal disorders and weakened immune systems. Overall, these findings have shown the variable vulnerability by a different subpopulation of call center agents and are important in the occupational health risk prevention and management towards a sustainable human resource for BPO industry in the Philippines.

Keywords: business process outsourcing industry, health risk of call center agents, socio-cultural determinants, Philippines

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Authors: Susan Scott, Dina Hanna, Bassel Zebian, Gary Ruiz, Sreena Das

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Although the number of cases of TB in England has fallen over the last 4 years, it remains an important public health burden with 1 in 20 cases dying annually. The vast majority of cases present in non-UK born individuals with social risk factors. We present a case of non-pulmonary TB presenting in a healthy child born in the UK to professional parents. We present a case of a healthy 10 year old boy who developed acute back pain during school PE. Over the next 5 months, he was seen by various health and allied professionals with worsening back pain and kyphosis. He became increasing unsteady and for the 10 days prior to admission to our hospital, he developed fevers. He was admitted to his local hospital for tonsillitis where he suffered two falls on account of his leg weakness. A spinal X-ray revealed a pathological fracture and gibbus formation. He was transferred to our unit for further management. On arrival, the patient had lower motor neurone signs of his left leg. He underwent spinal fixture, laminectomy and decompression. Microbiology samples taken intra-operatively confirmed Mycobacterium Tuberculosis. He had a positive Mantoux and T-spot and treatment were commenced. There was no evidence of immune compromise. The patient was born in the UK, had a BCG scar and his only travel history had been two years prior to presentation when he travelled to the Phillipines for a short holiday. The patient continues to have issues around neuropathic pain, mobility, pill burden and mild liver side effects from treatment. Discussion: There is a paucity of case reports on spinal TB in paediatrics and diagnosis is often difficult due to the non-specific symptomatology. Although prognosis on treatment is good, a delayed diagnosis can have devastating consequences. This case highlights the continued need for higher index of suspicion and diagnosis in a world with changing patterns of migration and increase global travel. Surgical intervention is limited to the most serious cases to minimise further neurological damage and improve prognosis. There remains the need for a multi-disciplinary approach to deal with challenges of treatment and rehabilitation.

Keywords: tuberculosis, non-pulmonary TB, public health burden, diagnostic challenge

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Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

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Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

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Authors: Amean A. Yasir, Zainab Kh. A. Al-Mahdi Al-Amean

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In both developed and developing countries, obesity among women is increasing, but in different patterns and at very different speeds. It may have a negative effect on health, leading to reduced life expectancy and/or increased health problems. This research studied the age distribution among obese women, the types of overweight and obesity, and the extent of the problem of overweight/obesity and the obesity etiological factors among women in Hillah city in central Iraq. A total of 322 overweight and obese women were included in the study, those women were randomly selected. The Body Mass Index was used as indicator for overweight/ obesity. The incidence of overweight/obesity among age groups were estimated, the etiology factors included genetic, environmental, genetic/environmental and endocrine disease. The overweight and obese women were screened for incidence of infection and/or diseases. The study found that the prevalence of 322 overweight and obese women in Hillah city in central Iraq was 19.25% and 80.78%, respectively. The obese women types were recorded based on BMI and WHO classification as class-1 obesity (29.81%), class-2 obesity (24.22%) and class-3 obesity (26.70%), the result was discrepancy non-significant, P value < 0.05. The incidence of overweight in women was high among those aged 20-29 years (90.32%), 6.45% aged 30-39 years old and 3.22% among ≥ 60 years old, while the incidence of obesity was 20.38% for those in the age group 20-29 years, 17.30% were 30-39 years, 23.84% were 40-49 years, 16.92% were 50-59 years group and 21.53% were ≥ 60 years age group. These results confirm that the age can be considered as a significant factor for obesity types (P value < 0.0001). The result also showed that the both genetic factors and environmental factors were responsible for incidents of overweight or obesity (84.78%) p value < 0.0001. The results also recorded cases of different repeated infections (skin infection, recurrent UTI and influenza), cancer, gallstones, high blood pressure, type 2 diabetes, and infertility. Weight stigma and bias generally refers to negative attitudes; Obesity can affect quality of life, and the results of this study recorded depression among overweight or obese women. This can lead to sexual problems, shame and guilt, social isolation and reduced work performance. Overweight and Obesity are real problems among women of all age groups and is associated with the risk of diseases and infection and negatively affects quality of life. This result warrants further studies into the prevalence of obesity among women in Hillah City in central Iraq and the immune response of obese women.

Keywords: obesity, overweight, Iraq, body mass index

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Authors: Hsiao-Lan Wang, Chun-Han Chiang, I-Chen Chen

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In Chinese Mandarin, lexical tones play an important role to provide contrasts in word meaning. They are pitch patterns and can be quantified as the fundamental frequency (F0), expressed in Hertz (Hz). In this study, we aim to investigate the influence of frequency discrimination on Chinese children’s performance of reading abilities. Fifty participants from 3rd to 4th grades, including 24 children with reading difficulties and 26 age-matched children, were examined. A serial of cognitive, language, reading and psychoacoustic tests were administrated. Magnetoencephalography (MEG) was also employed to study children’s auditory sensitivity. In the present study, auditory frequency was measured through slide-up pitch, slide-down pitch and frequency-modulated tone. The results showed that children with Chinese reading difficulties were significantly poor at phonological awareness and auditory discrimination for the identification of frequency-modulated tone. Chinese children’s character reading performance was significantly related to lexical tone awareness and auditory perception of frequency-modulated tone. In our MEG measure, we compared the mismatch negativity (MMNm), from 100 to 200 ms, in two groups. There were no significant differences between groups during the perceptual discrimination of standard sounds, fast-up and fast-down frequencies. However, the data revealed significant cluster differences between groups in the slow-up and slow-down frequencies discrimination. In the slow-up stimulus, the cluster demonstrated an upward field map at 106-151 ms (p < .001) with a strong peak time at 127ms. The source analyses of two dipole model and localization resolution model (CLARA) from 100 to 200 ms both indicated a strong source from the left temporal area with 45.845% residual variance. Similar results were found in the slow-down stimulus with a larger upward current at 110-142 ms (p < 0.05) and a peak time at 117 ms in the left temporal area (47.857% residual variance). In short, we found a significant group difference in the MMNm while children processed frequency-modulated tones with slow temporal changes. The findings may imply that perception of sound frequency signals with slower temporal modulations was related to reading and language development in Chinese. Our study may also support the recent hypothesis of underlying non-verbal auditory temporal deficits accounting for the difficulties in literacy development seen developmental dyslexia.

Keywords: Chinese Mandarin, frequency modulation sweeps, magnetoencephalography, mismatch negativity, reading difficulties

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Authors: Sara A. Ben Lashihar

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The heritage building information modelling (HBIM) of the historical masonry buildings has expanded lately to meet the urgent needs for conservation and structural analysis. The masonry structures are unique features for ancient building architectures worldwide that have special cultural, spiritual, and historical significance. However, there is a research gap regarding the reliability of the HBIM modeling process of these structures. The HBIM modeling process of the masonry structures faces significant challenges due to the inherent complexity and uniqueness of their structural systems. Most of these processes are based on tracing the point clouds and rarely follow documents, archival records, or direct observation. The results of these techniques are highly abstracted models where the accuracy does not exceed LOD 200. The masonry assemblages, especially curved elements such as arches, vaults, and domes, are generally modeled with standard BIM components or in-place models, and the brick textures are graphically input. Hence, future investigation is necessary to establish a methodology to generate automatically parametric masonry components. These components are developed algorithmically according to mathematical and geometric accuracy and the validity of the survey data. The main aim of this paper is to provide a comprehensive review of the state of the art of the existing researches and papers that have been conducted on the HBIM modeling of the masonry structural elements and the latest approaches to achieve parametric models that have both the visual fidelity and high geometric accuracy. The paper reviewed more than 800 articles, proceedings papers, and book chapters focused on "HBIM and Masonry" keywords from 2017 to 2021. The studies were downloaded from well-known, trusted bibliographic databases such as Web of Science, Scopus, Dimensions, and Lens. As a starting point, a scientometric analysis was carried out using VOSViewer software. This software extracts the main keywords in these studies to retrieve the relevant works. It also calculates the strength of the relationships between these keywords. Subsequently, an in-depth qualitative review followed the studies with the highest frequency of occurrence and the strongest links with the topic, according to the VOSViewer's results. The qualitative review focused on the latest approaches and the future suggestions proposed in these researches. The findings of this paper can serve as a valuable reference for researchers, and BIM specialists, to make more accurate and reliable HBIM models for historic masonry buildings.

Keywords: HBIM, masonry, structure, modeling, automatic, approach, parametric

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Authors: Danilo A. F. Fontes, Magaly A. M.Lyra, Maria L. C. Moura, Leslie R. M. Ferraz, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim, Giovanna C. R. M. Schver, Ping I. Lee, Severino Alves-Júnior, José L. Soares-Sobrinho, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a first-choice drug in antiretroviral therapy with high efficacy in the treatment of infection by Human Immunodeficiency Virus, which causes Acquired Immune Deficiency Syndrome (AIDS). EFV has low solubility in water resulting in a decrease in the dissolution rate and, consequently, in its bioavailability. Among the technological alternatives to increase solubility, the Lamellar Double Hydroxides (LDH) have been applied in the development of systems with poorly water-soluble drugs. The use of analytical techniques such as X-Ray Diffraction (XRD), Infrared Spectroscopy (IR) and Differential Scanning Calorimetry (DSC) allowed the elucidation of drug interaction with the lamellar compounds. The objective of this work was to characterize and develop the binary systems with EFV and LDH in order to increase the solubility of the drug. The LDH-CaAl was synthesized by the method of co-precipitation from salt solutions of calcium nitrate and aluminum nitrate in basic medium. The systems EFV-LDH and their physical mixtures (PM) were obtained at different concentrations (5-60% of EFV) using the solvent technique described by Takahashi & Yamaguchi (1991). The characterization of the systems and the PM’s was performed by XRD techniques, IR, DSC and dissolution test under non-sink conditions. The results showed improvements in the solubility of EFV when associated with LDH, due to a possible change in its crystal structure and formation of an amorphous material. From the DSC results, one could see that the endothermic peak at 173°C, temperature that correspond to the melting process of EFZ in the crystal form, was present in the PM results. For the EFZ-LDH systems (with 5, 10 and 30% of drug loading), this peak was not observed. XRD profiles of the PM showed well-defined peaks for EFV. Analyzing the XRD patterns of the systems, it was found that the XRD profiles of all the systems showed complete attenuation of the characteristic peaks of the crystalline form of EFZ. The IR technique showed that, in the results of the PM, there was the appearance of one band and overlap of other bands, while the IR results of the systems with 5, 10 and 30% drug loading showed the disappearance of bands and a few others with reduced intensity. The dissolution test under non-sink conditions showed that systems with 5, 10 and 30% drug loading promoted a great increase in the solubility of EFV, but the system with 10% of drug loading was the only one that could keep substantial amount of drug in solution at different pHs.

Keywords: Efavirenz, Lamellar Double Hydroxides, Pharmaceutical Techonology, Solubility

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Authors: Yuan-Hao Lee, Chia-Wei Lee, Ming-Fang Lin, Tzu-Huei Wu, Chih-Hsiang Ko, Wing P. Chan

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Computed tomography (CT) scan of the head is a good method for investigating cranial lesions. However, radiation-induced oxidative stress can be accumulated in the eyes and promote carcinogenesis and cataract. In this regard, we aimed to protect the eyes with barium sulfate shield(s) during CT scans and investigate the resultant image quality and radiation dose to the eye. Patients who underwent health examinations were selectively enrolled in this study in compliance with the protocol approved by the Ethics Committee of the Joint Institutional Review Board at Taipei Medical University. Participants’ brains were scanned with a water-based marker simultaneously by a multislice CT scanner (SOMATON Definition Flash) under a fixed tube current-time setting or automatic tube current modulation (TCM). The lens dose was measured by Gafchromic films, whose dose response curve was previously fitted using thermoluminescent dosimeters, with or without barium sulfate or bismuth-antimony shield laid above. For the assessment of image quality CT images at slice planes that exhibit the interested regions on the zygomatic, orbital and nasal bones of the head phantom as well as the water-based marker were used for calculating the signal-to-noise and contrast-to-noise ratios. The application of barium sulfate and bismuth-antimony shields decreased 24% and 47% of the lens dose on average, respectively. Under topogram-based TCM, the dose saving power of bismuth-antimony shield was mitigated whereas that of barium sulfate shield was enhanced. On the other hand, the signal-to-noise and contrast-to-noise ratios of DSCT images were decreased separately by barium sulfate and bismuth-antimony shield, resulting in an overall reduction of the CNR. In contrast, the integration of topogram-based TCM elevated signal difference between the ROIs on the zygomatic bones and eyeballs while preferentially decreasing the signal-to-noise ratios upon the use of barium sulfate shield. The results of this study indicate that the balance between eye exposure and image quality can be optimized by combining eye shields with topogram-based TCM on the multislice scanner. Eye shielding could change the photon attenuation characteristics of tissues that are close to the shield. The application of both shields on eye protection hence is not recommended for seeking intraorbital lesions.

Keywords: computed tomography, barium sulfate shield, dose saving, image quality

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Authors: Keith T. S. Tung, H. W. Tsang, Rosa S. Wong, Frederick K. Ho, Patrick Ip

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Objectives: Atopic diseases are increasingly prevalent among children and adolescents, both locally and internationally. One of the possible contributing factors could be the hypercholesterolemia which leads to cholesterol accumulation in macrophages and other immune cells that would eventually promote inflammatory responses, including augmentation of toll-like receptor (TLR). Meanwhile, physical activity is well known for its beneficial effects against the condition of hypercholesterolemia and incidence of atopic diseases. This study, therefore, explored whether atopic diseases were associated with increased cholesterol levels and whether physical activity habit influenced this association. Methods: This is a sub-study derived from the longitudinal cohort study which recruited a group of children at five years of age in Kindergarten 3 (K3) to investigate the long-term impact of family socioeconomic status on child development. In 2018/19, adolescents (average age: 13 years old) were asked to report their physical activity habit and history of any atopic diseases. During health assessment, peripheral blood samples were collected from the adolescents to study their lipid profile [total cholesterol, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol]. Regression analyses were performed to test the relationships between variables of interest. Results: Among the 315 adolescents, 99 (31.4%) reported to have allergic rhinitis. There were 45 (14.3%) with eczema, 17 (5.4%) with a food allergy, and 12 (3.8%) with asthma. Regression analyses showed that adolescents with a history of any type of atopic diseases had significantly higher total cholesterol (B=13.3, p < 0.01) and LDL cholesterol (B=7.9, p < 0.05) levels. Further subgroup analyses were conducted to examine the effect of physical activity level on the association between atopic diseases and cholesterol levels. We found stronger associations among those who did not meet the World Health Organization recommendation of at least 60 minutes of moderate-to-vigorous activities each day (total cholesterol: B=15.5, p < 0.01; LDL cholesterol: B=10.4, p < 0.05). For those who met this recommendation, the associations between atopic diseases and cholesterol levels became insignificant. Conclusion: Our study results support the current research evidence on the relationship between an elevated level of cholesterol and atopic diseases. More importantly, our results provide preliminary support for the protective effect of regular exercises against elevated cholesterol level due to atopic diseases. The findings highlight the importance of a healthy lifestyle for keeping cholesterol levels in the normal range, which can bring benefits to both physical and mental health.

Keywords: atopic diseases, Chinese adolescents, cholesterol level, physical activity

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Authors: Hanbyul Kim, Hye-Jin Kin, Taehun Park, Woo Jun Sul, Susun An

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Skin is the largest organ of the human body and can provide the diverse habitat for various microorganisms. The ecology of the skin surface selects distinctive sets of microorganisms and is influenced by both endogenous intrinsic factors and exogenous environmental factors. The diversity of the bacterial community in the skin also depends on multiple host factors: gender, age, health status, location. Among them, age-related changes in skin structure and function are attributable to combinations of endogenous intrinsic factors and exogenous environmental factors. Skin aging is characterized by a decrease in sweat, sebum and the immune functions thus resulting in significant alterations in skin surface physiology including pH, lipid composition, and sebum secretion. The present study gives a comprehensive clue on the variation of skin microbiota and the correlations between ages by analyzing and comparing the metagenome of skin microbiome using Next Generation Sequencing method. Skin bacterial diversity and composition were characterized and compared between two different age groups: younger (20 – 30y) and older (60 - 70y) Xian, Chinese women. A total of 73 healthy women meet two conditions: (I) living in Xian, China; (II) maintaining healthy skin status during the period of this study. Based on Ribosomal Database Project (RDP) database, skin samples of 73 participants were enclosed with ten most abundant genera: Chryseobacterium, Propionibacterium, Enhydrobacter, Staphylococcus and so on. Although these genera are the most predominant genus overall, each genus showed different proportion in each group. The most dominant genus, Chryseobacterium was more present relatively in Young group than in an old group. Similarly, Propionibacterium and Enhydrobacter occupied a higher proportion of skin bacterial composition of the young group. Staphylococcus, in contrast, inhabited more in the old group. The beta diversity that represents the ratio between regional and local species diversity showed significantly different between two age groups. Likewise, The Principal Coordinate Analysis (PCoA) values representing each phylogenetic distance in the two-dimensional framework using the OTU (Operational taxonomic unit) values of the samples also showed differences between the two groups. Thus, our data suggested that the composition and diversification of skin microbiomes in adult women were largely affected by chronological and physiological skin aging.

Keywords: next generation sequencing, age, Xian, skin microbiome

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Authors: Anna Rudzińska, Katarzyna Szklener, Pola Juchaniuk, Anna Rodzajweska, Katarzyna Machulska-Ciuraj, Monika Rychlik- Grabowska, Michał łOziński, Agnieszka Kolak-Bruks, SłAwomir Mańdziuk

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Introduction: Immune checkpoint inhibition (ICI) belongs to the modern forms of anti-cancer treatment. Due to the constant development and continuous research in the field of ICI, many aspects of the treatment are yet to be discovered. One of the less researched aspects of ICI treatment is the influence of the adverse effects on the treatment success rate. It is suspected that adverse events in the course of the ICI treatment indicate a better response rate and correlate with longer progression-free- survival. Methodology: The research was conducted with the usage of the documentation of the Department of Clinical Oncology and Chemotherapy. Data of the patients with a lung cancer diagnosis who were treated between 2019-2022 and received ICI treatment were analyzed. Results: Out of over 133 patients whose data was analyzed, the vast majority were diagnosed with non-small cell lung cancer. The majority of the patients did not experience adverse effects. Most adverse effects reported were classified as grade 1 or grade 2 according to CTCAE classification. Most adverse effects involved skin, thyroid and liver toxicity. Statistical significance was found for the adverse effect incidence and overall survival (OS) and progression-free survival (PFS) (p=0,0263) and for the time of toxicity onset and OS and PFS (p<0,001). The number of toxicity sites was statistically significant for prolonged PFS (p=0.0315). The highest OS was noted in the group presenting grade 1 and grade 2 adverse effects. Conclusions: Obtained results confirm the existence of the prolonged OS and PFS in the adverse-effects-charged patients, mostly in the group presenting mild to intermediate (Grade 1 and Grade 2) adverse effects and late toxicity onset. Simultaneously our results suggest a correlation between treatment response rate and the toxicity grade of the adverse effects and the time of the toxicity onset. Similar results were obtained in several similar research conducted - with the proven tendency of better survival in mild and moderate toxicity; meanwhile, other studies in the area suggested an advantage in patients with any toxicity regardless of the grade. The contradictory results strongly suggest the need for further research on this topic, with a focus on additional factors influencing the course of the treatment.

Keywords: adverse effects, immunotherapy, lung cancer, PD-1/PD-L1 inhibitors

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Elene Zhuravliova, Tamar Barbakadze, Irina Kalandadze, Elnari Zaalishvili, Lali Shanshiashvili, David Mikeladze

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Background: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease, which is accompanied by demyelination and autoimmune response to myelin proteins. Among post-translational modifications, which mediate the modulation of inflammatory pathways during MS, methylation is the main one. The methylation of DNA, also amino acids lysine and arginine, occurs in the cell. It was found that decreased trans-methylation is associated with neuroinflammatory diseases. Therefore, abnormal regulation of the methyl cycle could induce demyelination through the action on PAD (peptidyl-arginine-deiminase) gene promoter. PAD takes part in protein citrullination and targets myelin basic protein (MBP), which is affected during demyelination. To determine whether MBP charge isomers are changing the methyl cycle, we have estimated the concentrations of methyl cycle metabolites in MBP-activated primary astrocytes and oligodendrocytes. For this purpose, the action of the citrullinated MBP- C8 and the most cationic MBP-C1 isomers on the primary cells were investigated. Methods: Primary oligodendrocyte and astrocyte cell cultures were prepared from whole brains of 2-day-old Wistar rats. The methyl cycle metabolites, including homocysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH), were estimated by HPLC analysis using fluorescence detection and prior derivatization. Results: We found that the action of MBP-C8 and MBP-C1 induces a decrease in the concentration of both methyl cycle metabolites, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), in astrocytes compared to the control cells. As for oligodendrocytes, the concentration of SAM was increased by the addition of MBP-C1, while MBP-C8 has no significant effect. As for SAH, its concentration was increased compared to the control cells by the action of both MBP-C1 and MBP-C8. A significant increase in homocysteine concentration was observed by the action of the MBP-C8 isomer in both oligodendrocytes and astrocytes. Conclusion: These data suggest that MBP charge isomers change the concentration of methyl cycle metabolites. MBP-C8 citrullinated isomer causes elevation of homocysteine in astrocytes and oligodendrocytes, which may be the reason for decreased astrocyte proliferation and increased oligodendrocyte cell death which takes place in neurodegenerative processes. Elevated homocysteine levels and subsequent abnormal regulation of methyl cycles in oligodendrocytes possibly change the methylation of DNA that activates PAD gene promoter and induces the synthesis of PAD, which in turn provokes the process of citrullination, which is the accompanying process of demyelination. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, astrocytes, methyl cycle metabolites, homocysteine, oligodendrocytes

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Authors: Pierre-Louis Lucas, Corinne Loutelier-Bourhis, Narimane Mati-Baouche, Philippe Chan Tchi-Song, Patrice Lerouge, Elodie Mathieu-Rivet, Muriel Bardor

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N-glycosylation is a post-translational modification taking place in the Endoplasmic Reticulum and the Golgi apparatus where defined glycan features are added on protein in a very specific sequence Asn-X-Thr/Ser/Cys were X can be any amino acid except proline. Because it is well-established that those N-glycans play a critical role in protein biological activity, protein half-life and that a different N-glycan structure may induce an immune response, they are very important in Biopharmaceuticals which are mainly glycoproteins bearing N-glycans. From now, most of the biopharmaceuticals are produced by mammalian cells like Chinese Hamster Ovary cells (CHO) for their N-glycosylation similar to the human, but due to the high production costs, several other species are investigated as the possible alternative system. In this purpose, the green microalgae Chlamydomonas reinhardtii was investigated as the potential production system for Biopharmaceuticals. This choice was influenced by the facts that C. reinhardtii is a well-study microalgae which is growing fast with a lot of molecular biology tools available. This organism is also producing N-glycan on its endogenous proteins. However, the analysis of the N-glycan structure of this microalgae has revealed some differences as compared to the human. Rather than in Human where the glycans are processed by key enzymes called N-acetylglucosaminyltransferase I and II (GnTI and GnTII) adding GlcNAc residue to form a GlcNAc₂Man₃GlcNAc₂ core N-glycan, C. reinhardtii lacks those two enzymes and possess a GnTI independent glycosylation pathway. Moreover, some enzymes like xylosyltransferases and methyltransferases not present in human are supposed to act on the glycans of C. reinhardtii. Furthermore, the recent structural study by mass spectrometry shows that the N-glycosylation precursor supposed to be conserved in almost all eukaryotic cells results in a linear Man₅GlcNAc₂ rather than a branched one in C. reinhardtii. In this work, we will discuss the new released MS information upon C. reinhardtii N-glycan structure and their impact on our attempt to modify the glycan in a Human manner. Two strategies will be discussed. The first one consisted in the study of Xylosyltransferase insertional mutants from the CLIP library in order to remove xyloses from the N-glycans. The second will go further in the humanization by transforming the microalgae with the exogenous gene from Toxoplasma gondii having an activity similar to GnTI and GnTII with the aim to synthesize GlcNAc₂Man₃GlcNAc₂ in C. reinhardtii.

Keywords: Chlamydomonas reinhardtii, N-glycosylation, glycosyltransferase, mass spectrometry, humanization

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: Ashima Sharma, Tapan K. Chaudhuri

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Human Serum Albumin (HSA) is one of the most demanded therapeutic protein with immense biotechnological applications. The current source of HSA is human blood plasma. Blood is a limited and an unsafe source as it possesses the risk of contamination by various blood derived pathogens. This issue led to exploitation of various hosts with the aim to obtain an alternative source for the production of the rHSA. But, till now no host has been proven to be effective commercially for rHSA production because of their respective limitations. Thus, there exists an indispensable need to promote non-animal derived rHSA production. Of all the host systems, Escherichia coli is one of the most convenient hosts which has contributed in the production of more than 30% of the FDA approved recombinant pharmaceuticals. E. coli grows rapidly and its culture reaches high cell density using inexpensive and simple substrates. The fermentation batch turnaround number for E. coli culture is 300 per year, which is far greater than any of the host systems available. Therefore, E. coli derived recombinant products have more economical potential as fermentation processes are cheaper compared to the other expression hosts available. Despite of all the mentioned advantages, E. coli had not been successfully adopted as a host for rHSA production. The major bottleneck in exploiting E. coli as a host for rHSA production was aggregation i.e. majority of the expressed recombinant protein was forming inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA form inclusion body is not preferred because it is tedious, time consuming, laborious and expensive. Because of this limitation, E. coli host system was neglected for rHSA production for last few decades. Considering the advantages of E. coli as a host, the present work has targeted E. coli as an alternate host for rHSA production through resolving the major issue of inclusion body formation associated with it. In the present study, we have developed a novel and innovative method for enhanced soluble and functional production of rHSA in E.coli (~60% of the total expressed rHSA in the soluble fraction) through modulation of the cellular growth, folding and environmental parameters, thereby leading to significantly improved and enhanced -expression levels as well as the functional and soluble proportion of the total expressed rHSA in the cytosolic fraction of the host. Therefore, in the present case we have filled in the gap in the literature, by exploiting the most well studied host system Escherichia coli which is of low cost, fast growing, scalable and ‘yet neglected’, for the enhancement of functional production of HSA- one of the most crucial biomolecule for clinical and biotechnological applications.

Keywords: enhanced functional production of rHSA in E. coli, recombinant human serum albumin, recombinant protein expression, recombinant protein processing

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Authors: Sung-Hee Nam, Kwang-Gill Lee, You-Young Jo, HaeYong Kweon

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Entomopathogenic fungi is a Cordyceps species that is isolated from dead silkworm and cicada. Fungi on cicadas were described in old Chinese medicinal books and From ancient times, vegetable wasps and plant worms were widely known to have active substance and have been studied for pharmacological use. Among many fungi belonging to the genus Cordyceps, Cordyceps sinensis have been demonstrated to yield natural products possessing various biological activities and many bioactive components. Generally, It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. Due to their commercial and economic importance, the demand for Cordyceps has been rapidly increased. However, a supply of Cordyceps specimen could not meet the increasing demand because of their sole dependence on field collection and habitat destruction. Because it is difficult to obtain many insect hosts in nature and the edibility of host insect needs to be verified in a pharmacological aspect. Recently, this setback was overcome that P. tenuipes was able to be cultivated in a large scale using silkworm as host. Pharmacological effects of P. tenuipes cultured on silkworm such as strengthening immune function, anti-fatigue, anti-tumor activity and controlling liver etc have been proved. They are widely commercialized. In this study, we attempted to establish a method for stable growth inhibition of P. tenuipes on silkworm hosts and an optimal condition for synnemata formation. To determine optimum culturing conditions, temperature and light conditions were varied. The length and number of synnemata was highest at 25℃ temperature and 100~300 lux illumination. On an average, the synnemata of wild P. tenuipes measures 70 ㎜ in length and 20 in number; those of the cultured strain were relatively shorter and more in number. The number of synnemata may have increased as a result of inoculating the host with highly concentrated conidia, while the length may have decreased due to limited nutrition per individual. It is not able that changes in light illumination cause morphological variations in the synnemata. However, regulation of only light and temperature could not produce stromata like perithecia, asci, and ascospores. Yamanaka reported that although a complete fruiting body can be produced under optimal culture conditions, it should be regarded as synnemata because it does not develop into an ascoma bearing ascospores.

Keywords: paecilomyces tenuipes, entomopathogenic fungi, silkworm larva, bombyx mori

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Authors: Marissa Dallara, Amalia Ardeljan, Lexi Frankel, Nadia Obaed, Naureen Rashid, Omar Rashid

Abstract:

Human Cytomegalovirus (HCMV) is a ubiquitous virus that remains latent in approximately 60% of individuals in developed countries. Viral load is kept at a minimum due to a robust immune response that is produced in most individuals who remain asymptomatic. HCMV has been recently implicated in cancer research because it may impose oncomodulatory effects on tumor cells of which it infects, which could have an impact on the progression of cancer. HCMV has been implicated in increased pathogenicity of certain cancers such as gliomas, but in contrast, it can also exhibit anti-tumor activity. HCMV seropositivity has been recorded in tumor cells, but this may also have implications in decreased pathogenesis of certain forms of cancer such as leukemia as well as increased pathogenesis in others. This study aimed to investigate the correlation between cytomegalovirus and the incidence of breast cancer. Methods The data used in this project was extracted from a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to analyze the patients infected versus patients not infection with cytomegalovirus using ICD-10, ICD-9 codes. Permission to utilize the database was given by Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Data analysis was conducted using standard statistical methods. Results The query was analyzed for dates ranging from January 2010 to December 2019, which resulted in 14,309 patients in both the infected and control groups, respectively. The two groups were matched by age range and CCI score. The incidence of breast cancer was 1.642% and 235 patients in the cytomegalovirus group compared to 4.752% and 680 patients in the control group. The difference was statistically significant by a p-value of less than 2.2x 10^-16 with an odds ratio of 0.43 (0.4 to 0.48) with a 95% confidence interval. Investigation into the effects of HCMV treatment modalities, including Valganciclovir, Cidofovir, and Foscarnet, on breast cancer in both groups was conducted, but the numbers were insufficient to yield any statistically significant correlations. Conclusion This study demonstrates a statistically significant correlation between cytomegalovirus and a reduced incidence of breast cancer. If HCMV can exert anti-tumor effects on breast cancer and inhibit growth, it could potentially be used to formulate immunotherapy that targets various types of breast cancer. Further evaluation is warranted to assess the implications of cytomegalovirus in reducing the incidence of breast cancer.

Keywords: human cytomegalovirus, breast cancer, immunotherapy, anti-tumor

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Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

Procedia PDF Downloads 47

Authors: Muhammad Arif Jalil, Xaythavay Luangvilay, Montree Bunruangses, Somchat Sonasang, Preecha Yupapin

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Black and white holes form the entangled pair⟨BH│WH⟩, where a white hole occurs when the particle moves at the same speed as light. The entangled black-white hole pair is at the center with the radian between the gap. When the speed of particle motion is slower than light, the black hole is gravitational (positive gravity), where the white hole is smaller than the black hole. On the downstream side, the entangled pair appears to have a black hole outside the gap increases until the white holes disappear, which is the emptiness paradox. On the upstream side, when moving faster than light, white holes form times tunnels, with black holes becoming smaller. It will continue to move faster and further when the black hole disappears and becomes a wormhole (Singularity) that is only a white hole in emptiness (Emptiness). This research studies use of black and white holes generated by a two-level circuit for communication transmission carriers, in which high ability and capacity of data transmission can be obtained. The black and white hole pair can be generated by the two-level system circuit when the speech of a particle on the circuit is equal to the speed of light. The black hole forms when the particle speed has increased from slower to equal to the light speed, while the white hole is established when the particle comes down faster than light. They are bound by the entangled pair, signal and idler, ⟨Signal│Idler⟩, and the virtual ones for the white hole, which has an angular displacement of half of π radian. A two-level system is made from an electronic circuit to create black and white holes bound by the entangled bits that are immune or cloning-free from thieves. Start by creating a wave-particle behavior when its speed is equal to light black hole is in the middle of the entangled pair, which is the two bit gate. The required information can be input into the system and wrapped by the black hole carrier. A timeline (Tunnel) occurs when the wave-particle speed is faster than light, from which the entangle pair is collapsed. The transmitted information is safely in the time tunnel. The required time and space can be modulated via the input for the downlink operation. The downlink is established when the particle speed is given by a frequency(energy) form is down and entered into the entangled gap, where this time the white hole is established. The information with the required destination is wrapped by the white hole and retrieved by the clients at the destination. The black and white holes are disappeared, and the information can be recovered and used.

Keywords: cloning free, time machine, teleportation, two-level system

Procedia PDF Downloads 36

Authors: Alvin Han, Reema Shafi, Alishba Afaq, Jennifer Gommerman, Valeria Ramaglia, Shannon E. Dunn

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Adolescents engaged in contact-sports can suffer from recurrent brain concussions with no loss of consciousness and no need for hospitalization, yet they face the possibility of long-term neurocognitive problems. Recent studies suggest that head concussive injuries during adolescence can also predispose individuals to multiple sclerosis (MS). The underlying mechanisms of how brain concussions predispose to MS is not understood. Here, we hypothesize that: (1) recurrent brain concussions prime microglial cells, the tissue resident myeloid cells of the brain, setting them up for exacerbated responses when exposed to additional challenges later in life; and (2) brain concussions lead to the sensitization of myelin-specific T cells in the peripheral lymphoid organs. Towards addressing these hypotheses, we implemented a mouse model of closed head injury that uses a weight-drop device. First, we calibrated the model in male 12 week-old mice and established that a weight drop from a 3 cm height induced mild neurological symptoms (mean neurological score of 1.6+0.4 at 1 hour post-injury) from which the mice fully recovered by 72 hours post-trauma. Then, we performed immunohistochemistry on the brain of concussed mice at 72 hours post-trauma. Despite mice having recovered from all neurological symptoms, immunostaining for leukocytes (CD45) and IBA-1 revealed no peripheral immune infiltration, but an increase in the intensity of IBA1+ staining compared to uninjured controls, suggesting that resident microglia had acquired a more active phenotype. This microglia activation was most apparent in the white matter tracts in the brain and in the olfactory bulb. Immunostaining for the microglia-specific homeostatic marker TMEM119, showed a reduction in TMEM119+ area in the brain of concussed mice compared to uninjured controls, confirming a loss of this homeostatic signal by microglia after injury. Future studies will test whether single or repetitive concussive injury can worsen or accelerate autoimmunity in male and female mice. Understanding these mechanisms will guide the development of timed and targeted therapies to prevent MS from getting started in people at risk.

Keywords: concussion, microglia, microglial priming, multiple sclerosis

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Authors: Siti Hajar Muhamad Rosli, Xin Yi Lim, Terence Yew Chin Tan, Muhammad nor Farhan Sa’At, Syazwani Sirdar Ali, Ami Fazlin Syed Mohamed

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A growing interest on therapeutic benefits of hemp (Cannabis sativa subsp. sativa) is evident in the pharmaceutical market, attributed to its lower levels of psychoactive constituent delta-9-tetrahydronannabidiol (THC). Deemed as a legal and safer alternative to its counterpart marijuana, the use of medicinal hemp is highly debatable as current scientific evidence on the efficacy for clinical use is yet to be established This study was aimed to provide an overview of the current landscape of hemp research, through recent clinical findings specific to the pharmacological properties of the hemp plant and its derived compounds. A systematic search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis-ScR (PRISMA) checklist on electronic databases (MEDLINE, OVID, Cochrane Library Central, and Clinicaltrials.gov) for articles published from 2009 to 2019. With predetermined inclusion criteria, all human trials with hemp intervention were included. A total of 18 human trials were identified, investigating therapeutic effects on the neuronal, gastrointestinal, musculoskeletal and immune system, with sample sizes ranging from one to 194 subjects. Three randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) consumption significantly improved spontaneous bowel movement in functional constipation. The use of commercial cannabidiol (CBD) sourced from hemp suggested benefits in cannabis dependence, epilepsy, and anxiety disorders. However, there was insufficient evidence to suggest analgesic or anxiolytics effects of hemp being equivalent to marijuana. All clinical trials reviewed varied in terms of test item formulation and standardisation, which made it challenging to confirm overall efficacy for a specific disease or condition. Published efficacy data on hemp are still at a preliminary level, with limited high quality clinical evidence for any specific therapeutic indication. With multiple variants of this plant having different phytochemical and bioactive compounds, future empirical research should focus on uniformity in experimental designs to further strengthen the notion of using medicinal hemp.

Keywords: cannabis, complementary medicine, hemp, herbal medicine.

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Authors: Alexandra Emmanuelle Membangbi, Jacky Njiki Bikoï, Esther Del-florence Moni Ndedi, Marie Joseph Nkodo Mindimi, Donatien Serge Mbaga, Elsa Nguiffo Makue, André Chris Mikangue Mbongue, Martha Mesembe, George Ikomey Mondinde, Eric Walter Perfura-yone, Sara Honorine Riwom Essama

Abstract:

Background: Tuberculosis (TB) is one of the top lethal infectious diseases worldwide. In recent years, interferon-γ (INF-γ) release assays (IGRAs) have been established as routine tests for diagnosing TB infection. However, produced INF-γ assessment failed to distinguish active TB (ATB) from latent TB infection (LTBI), especially in TB epidemic areas. In addition to IFN-γ, interleukin-2 (IL-2), another cytokine secreted by activated T cells, is also involved in immune response against Mycobacterium tuberculosis. The aim of the study was to assess the capacity of IFN-γ and IL2 to evaluate the therapeutic response of patients on anti-tuberculosis treatment. Material and Methods: We conducted a cross-sectional study in the Pneumonology Departments of the Jamot Hospital in Yaoundé between May and August 2021. After signed the informed consent, the sociodemographic data, as well as 5 mL of blood, were collected in the crook of the elbow of each participant. Sixty-one subjects were selected (n= 61) and divided into 4 groups as followed: group 1: resistant tuberculosis (n=13), group 2: active tuberculosis (n=19), group 3 cured tuberculosis (n=16), and group 4: presumed healthy persons (n=13). The cytokines of interest were determined using an indirect Enzyme-linked Immuno-Sorbent Assay (ELISA) according to the manufacturer's recommendations. P-values < 0.05 were interpreted as statistically significant. All statistical calculations were performed using SPSS version 22.0 Results: The results showed that men were more 14/61 infected (31,8%) with a high presence in active and resistant TB groups. The mean age was 41.3±13.1 years with a 95% CI = [38.2-44.7], the age group with the highest infection rate was ranged between 31 and 40 years. The IL-2 and INF-γ means were respectively 327.6±160.6 pg/mL and 26.6±13.0 pg/mL in active tuberculosis patients, 251.1±30.9 pg/mL and 21.4±9.2 pg/mL in patients with resistant tuberculosis, while it was 149.3±93.3 pg/mL and 17.9±9.4 pg/mL in cured patients, 15.1±8.4 pg/mL and 5.3±2.6 pg/mL in participants presumed healthy (p <0.0001). Significant differences in IFN-γ and IL-2 rates were observed between the different groups. Conclusion: Monitoring the serum levels of INF-γ and IL-2 would be useful to evaluate the therapeutic response of anti-tuberculosis patients, particularly in the both cytokines association case, that could improve the accuracy of routine examinations.

Keywords: antibiotic therapy, interferon gamma, interleukin 2, tuberculosis

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Authors: Apoorva D. R.

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INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a severe, potentially fatal syndrome in which there is excessive immune activation. The disease is seen in children and people of all ages, but infants from birth to 18 months are most frequently affected. HLH is a sporadic or familial condition that can be triggered by various events that disturb immunological homeostasis. In cases with a genetic predisposition and sporadic occurrences, infection is a frequent trigger. Because of the rarity of this disease, the diverse clinical presentation, and the lack of specificity in the clinical and laboratory results, prompt treatment is essential, but the biggest obstacle to a favorable outcome is frequently a delay in identification. CASE REPORT: Here we report a case of a 6-month-old male infant who presented to the dermatology outpatient with disseminated skin lesions present over the face, abdomen, scalp, and bilateral upper and lower limbs for the past month. The lesions were insidious in onset, initially started over the abdomen, and gradually progressed to involve other body parts. The patient also had a history of fever which was moderate in grade, on and off in nature for 1 month. There were no significant complaints in the past, family, or drug history. There was no history of feeding difficulties in the baby. Parents gave a history of developmental milestones appropriate for age. Examination findings include multiple well-defined monomorphic erythematous papules with a central crater present over bilateral cheeks. Few lichenoid shiny papules present over bilateral arms, legs, and abdomen. Ultrasound of the abdomen and pelvis showed mild degree hepatosplenomegaly, intraabdominal lymphadenopathy, and bilateral inguinal lymphadenopathy. Routine blood investigations showed anemia and lymphopenia. Multiple X-rays of the skull, chest, and bilateral upper and lower limbs were done and were normal. Histopathology features were suggestive of non-Langerhans cell cutaneous histiocytosis. CONCLUSION: HLH is a fatal and rare disease. A high level of suspicion and an interdisciplinary approach among experienced clinicians, pathologists, and microbiologists to define the diagnosis and causative disease are key to diagnosing this case. Early detection and treatment can reduce patient morbidity and mortality.

Keywords: histiocytosis, non langerhans cell, case report, fatal, rare

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Authors: Sophie Baudel, Aline Duplaa, Jean Muller, Stephan Lauriol, Yann Bernard

Abstract:

Argos is the main satellite telemetry system used by the wildlife research community, since its creation in 1978, for animal tracking and scientific data collection all around the world, to analyze and understand animal migrations and behavior. The marine mammals' biology is one of the major disciplines which had benefited from Argos telemetry, and conversely, marine mammals biologists’ community has contributed a lot to the growth and development of Argos use cases. The Argos constellation with 6 satellites in orbit in 2017 (Argos 2 payload on NOAA 15, NOAA 18, Argos 3 payload on NOAA 19, SARAL, METOP A and METOP B) is being extended in the following years with Argos 3 payload on METOP C (launch in October 2018), and Argos 4 payloads on Oceansat 3 (launch in 2019), CDARS in December 2021 (to be confirmed), METOP SG B1 in December 2022, and METOP-SG-B2 in 2029. Argos 4 will allow more frequency bands (600 kHz for Argos4NG, instead of 110 kHz for Argos 3), new modulation dedicated to animal (sea turtle) tracking allowing very low transmission power transmitters (50 to 100mW), with very low data rates (124 bps), enhancement of high data rates (1200-4800 bps), and downlink performance, at the whole contribution to enhance the system capacity (50,000 active beacons per month instead of 20,000 today). In parallel of this ‘institutional Argos’ constellation, in the context of a miniaturization trend in the spatial industry in order to reduce the costs and multiply the satellites to serve more and more societal needs, the French Space Agency CNES, which designs the Argos payloads, is innovating and launching the Argos ANGELS project (Argos NEO Generic Economic Light Satellites). ANGELS will lead to a nanosatellite prototype with an Argos NEO instrument (30 cm x 30 cm x 20cm) that will be launched in 2019. In the meantime, the design of the renewal of the Argos constellation, called Argos For Next Generations (Argos4NG), is on track and will be operational in 2022. Based on Argos 4 and benefitting of the feedback from ANGELS project, this constellation will allow revisiting time of fewer than 20 minutes in average between two satellite passes, and will also bring more frequency bands to improve the overall capacity of the system. The presentation will then be an overview of the Argos system, present and future and new capacities coming with it. On top of that, use cases of two Argos hardware modules will be presented: the goniometer pathfinder allowing recovering Argos beacons at sea or on the ground in a 100 km radius horizon-free circle around the beacon location and the new Argos 4 chipset called ‘Artic’, already available and tested by several manufacturers.

Keywords: Argos satellite telemetry, marine protected areas, oceanography, maritime services

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