Search results for: innate immune

Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

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Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

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Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: Wen-Yu Lin, Yi-Ching Chung, Tzyy-Rong Jinn

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It is well known that enterovirus 71 (EV71) causes recurring outbreaks of hand, foot and mouth disease (HFMD) and encephalitis leading to complications or death in young children. And, several HFMD of EV71 with high mortalities occurred in Asia countries, such as Malaysia (1997), Taiwan (1998) and China (2008). Thus, more effective antiviral drugs are needed to prevent or reduce EV71-related complications. As reported, interferon-α protects mice from lethal EV71 challenge by the modulation of innate immunity and then degrade enterovirus protease 3Cᵖʳᵒ. On the other side, pleconaril by targeting enterovirus VP1 protein and then block virus entry and attachment. Thus, the aim of this study was to evaluate the synergistic antiviral activity of interferon-α and pleconaril against enterovirus 71 infection. In a preliminary study showed that pleconaril at concentrations of 50, 100 and 300 µg/mL reduced EV71-induced CPE to 52.0 ± 2.5%, 40.2 ± 3.5% and 26.5 ± 1.5%, respectively, of that of the EV71-infected RD control cells (taken as 100%). Notably, 1000 IU/mL of interferon-α in combination with pleconaril at concentrations of 50, 100 and 300µg/mL suppressed EV71-induced CPE by 30.2 ± 3.8%, 16.5 ± 1.3% and 2.8 ± 2.0%, respectively, of that of the pleconaril alone treated with the infected RD cells. These results indicated that interferon-α 1000 IU/mL combination with pleconaril (50, 100 and 300µg/mL) inhibited EV71-induced CPE more effectively than treated with pleconaril alone in the infected RD cells.

Keywords: enterovirus 71, interferon-α, pleconaril, RD cells

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Authors: Khalid Mahmoud Gaafar

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In human diets , ω-6 and ω-3 are important essential fatty acids for immunity and health. However, considerable alteration in dietary patterns and contents has resulted in change of the consumption of such fatty acids ,with subsequent increase in the consumption of ω-6 fatty acids and a marked decrease in the consumption of ω-3 fatty acids. This dietary alteration has led to an imbalance in the ratio for ω-6/ω-3, which at 20:1 now differs considerably from the original ratio (1:1). Therefore, dietary supplements such as eggs and meat enriched with omega 3 are necessary to increase the consumption of ω-3 to meet the recommended need for ω-3. Foods that supply ω-6 fatty acids include soybean, palm , sunflower, and rapeseed oils, whereas foods that supply ω-3 fatty acids such as linseed and fish oils. Lin seed oils contain Alpha – linolenic acid (ALA), which can be converted to DHA and EPA in the birds body, with linseed oil containing more than 50% ALA. On the other hand, high doses of omega 6 sources in the diet may have deleterious effects on humans. Maintaining an optimum ratio of ω-3 and ω-6fatty acids not only improves performance but also prevents these health risks. The ratio of n-6:ω-3 fatty acids also plays an important role in the immune response, production performance of broilers and designing meat enriched with ω-3 polyunsaturated fatty acids (PUFAs). Birds of three experimental groups fed on basal starter (0-2nd weeks), grower (3rd -4th weeks) and finisher (5th week) rations. The first is control group fed during the grower-finisher periods on basic diet with two replicate (one fed on basic diet contain vegetable oil and the other don’t) without any additives. The three experimental groups (T1 – T2 –T3) fed during the grower- finisher periods on diets free from vegetable oils and contain of 5% of extruded mixture of soybean and linseed (60%:40%). The second (T2) and third (T3) experimental groups supplemented with vitamin B12 and enzyme mixture. The first experimental groups don’t receive vitamins or enzymes. The obtained results showed a significant increased growth performance, immune response, highest antioxidant activity and serum HDL with lowest serum LDL and triglycerides levels in all experimental groups compared with control group, which was highly significant in group fed on vitamin B6.

Keywords: omega fatty acids, broiler, feeding, human health, growth performance, immunity

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Authors: Rohit Rutka

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The aim of the present paper is to reveal the importance of music as an indispensable aspect in education of art, with regard to every single culture which serves as indisputable support to sustainable development in India. Indian system of education is one of the oldest systems of the world. Both secular and sacred education was handed over systematically by formalizing the system of education. We have found significant growth in the system of education in our country since ancient times. It is a veritable avenue which enables societies to transmit music and musical skills from one generation to the upcoming ones. The research is based on a comprehensive literature review on the impact of music to sustainable development. This paper contextualized that music education is imperative to Sustainable Development, to the adult. It is a vital force of self-expression, communication and empowerment economically, in growing children, involvement in music education will promote their creative ability, thereby contribute to the full development of intellectual capacities, apt emotional development that gives the right values and feelings to various events and happenings, music helps to develop skills, innate and instinctive talent in human being and recommend that the informal music teaching should be incorporated into school system so as to transmit and preserve the cultural music and that the study of music should be made compulsory at all levels of the Indian educational system.

Keywords: sustainable development, music education, culture, music as a pillar to sustainable development

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: Ravinder Singh, Ankita Gurao, Saroj Bandhan, Sudhir Kumar Kashyap

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The Bos taurus Beta defensin 3 is a defensin peptide secreted by neutrophils and epithelial that exhibits anti-microbial activity. It is one of the crucial components forming an innate defense against intra mammary infections in livestock. The beta defensin 3 by virtue of its anti-microbial activity inhibits major mastitis pathogens including Staphylococcus aureus and Pseudomonas aeruginosa etc, which are also responsible for biofilm formation leading to antibiotic resistance phenomenon. Therefore, the defensin may prove as a non-conventional option to treat mastitis. In this study, computational analysis has been performed including sequence comparison among species and homology modeling of Bos taurus beta defensin 3 protein. The assessments of protein structure were done using the protein structure and model assessment tools integrated in Swiss Model server, which employs various local and global quality evaluation parameters. Further, molecular docking was also carried out between the defensin peptide and the components of biofilm to gain insight into various interactions and structural differences crucial for functionality of this protein.

Keywords: beta defensin 3, bos taurus, docking, homology modeling

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Authors: Jessica P. Fiorotti, Maria C. Freitas, Caio J. B. Coutinho-Rodrigues, Mariana G. Camargo, Emily S. Mesquita, Amanda R. C. Corval, Ricardo O. B. Bitencourt, Allan F. Marciano, Diva D. Spadacci-Morena, Patricia S. Golo, Isabele C. Angelo, Vania R. E. P. Bittencourt

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The bovine tick, Rhipicephalus microplus, is an arthropod of great importance in veterinary medicine leading to anemia, weight loss, animals' leather depreciation and also acting as a vector of many pathogens. In this way, the parasitism causes a loss of 3.24 billion dollars per year in Brazil. Knowingly, entomopathogenic fungi act as natural controller of some arthropods, acting mainly by active penetration through the cuticle. However, it can also act on the hemolymph and through the production of mycotoxins. Hemocytes are responsible for the cellular immune response and participate in the processes of phagocytosis, nodulation and encapsulation and may undergo changes when challenged by pathogens. The aim of the present study was to evaluate changes in R. microplus hemocytes after inoculation of Metarhizium robertsii using transmission electron microscopy. The isolate ARSEF 2575 and 200 engorged R. microplus females were used. The groups were divided into control, in which the females were inoculated with 5 μL of sterile distilled water solution and 0.1% Tween 80, and a group inoculated with 5 μL of fungal suspension at the concentration of 10⁷ conidia mL⁻¹. The experiment was performed in duplicate and each group contained 50 females. Twenty-four hours after fungal inoculation, hemolymph was collected through the cuticle dorsal surface perforation of the tick females. After collection, the hemolymph samples were centrifuged at 500 x g for 3 minutes at 4 °C, the plasma was discarded and the hemocyte pellet was resuspended in 50 μl PBS. The suspension material was fixed in 2% glutaraldehyde in Millonig buffer for three hours. After fixation, the material was centrifuged at 500 x g for 3 minutes, the supernatant was discarded and the cells were resuspended in a wash solution. Subsequently, the cells were post-fixed with 1% osmium tetroxide in phosphate buffer for one hour at room temperature and dehydrated in increasing concentrations of ethanol, and then embedded in Epon resin. The ultrathin sections were examined under the LEO EM 906E transmission electron microscopy at 80kV. The ultrastructural results revealed that.in control group, the cells were considered intact, in which the granulocytes were observed with granules of different electrodensities, intact mitochondria and cytoplasm without vacuolization. In addition, granulocytes showed plasma membrane projections similar to pseudopodia. Plasmatocytes presented as irregularly shaped cells, with the eccentric nucleus, agranular cytoplasm and some cells presented pseudopodia. Nevertheless, in the group exposed to the fungus, most of the cells presented in degeneration. The granulocytes found had fewer granules in the cytoplasm and more vacuoles. Plasmatocytes, after treatment, presented many vacuoles also in the cytoplasm and the lysosomes presented great amount of electrodense material in their interior. Thus, the results suggest that the fungus has a depressant action in the immune system of the tick, not only by the cell degranulation, but also suggesting that this leads to morphological changes in the hemocytes and may even trigger processes such as phagocytosis.

Keywords: bovine tick, cellular defense, entomopathogenic fungi, immune response

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Authors: Philip Friedlander, John Rutledge, Jason Suh

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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

Procedia PDF Downloads 54

Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

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The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.

Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1

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Authors: Mustafa M. Donma, Orkide Donma

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A growing list of cancers might be influenced by obesity. Obesity is associated with an increased risk for the occurrence and development of some cancers. Inflammation can lead to cancer. It is one of the characteristic features of cancer and plays a critical role in cancer development. C-reactive protein (CRP) is under evaluation related to the new and simple prognostic factors in patients with metastatic renal cell cancer. Obesity can predict and promote systemic inflammation in healthy adults. BMI is correlated with hs-CRP. In this study, SII index and CRP values were evaluated in children with normal BMI and those within the range of different obesity grades to detect the tendency towards cancer in pediatric obesity. A total of one hundred and ninety-four children; thirty-five children with normal BMI, twenty overweight (OW), forty-seven obese (OB) and ninety-two morbid obese (MO) participated in the study. Age- and sex-matched groups were constituted using BMI-for age percentiles. Informed consent was obtained. Ethical Committee approval was taken. Weight, height, waist circumference (C), hip C, head C and neck C of the children were measured. The complete blood count test was performed. C-reactive protein analysis was performed. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. SII index values were progressively increasing starting from normal weight (NW) to MO children. There is a statistically significant difference between NW and OB as well as MO children. No significant difference was observed between NW and OW children, however, a correlation was observed between NW and OW children. MO constitutes the only group, which exhibited a statistically significant correlation between SII index and CRP. Obesity-related bladder, kidney, cervical, liver, colorectal, endometrial cancers are still being investigated. Obesity, characterized as a chronic low-grade inflammation, is a crucial risk factor for colon cancer. Elevated childhood BMI values may be indicative of processes leading to cancer, initiated early in life. Prevention of childhood adiposity may decrease the cancer incidence in adults. To authors’ best knowledge, this study is the first to introduce SII index values during obesity of varying degrees of severity. It is suggested that this index seems to affect all stages of obesity with an increasing tendency and may point out the concomitant status of obesity and cancer starting from very early periods of life.

Keywords: children, C-reactive protein, systemic immune-inflammation index, obesity

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Authors: Jiwon Lee, Si-hwan Jang, Sanghyun Joo

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The popularity of emoticons are on the rise since the mobile messengers are generalized. At the same time, few problems of emoticons are also occurred due to innate characteristics of emoticons. Too many emoticons make difficult people to select one which is well-suited for user's intention. On the contrary to this, sometimes user cannot find the emoticon which expresses user's exact intention. Poor information delivery of emoticon is another problem due to a major part of current emoticons are focused on emotion delivery. In this situation, we propose a new concept of emoticons, editable emoticons, to solve above drawbacks of emoticons. User can edit the components inside the proposed editable emoticon and send it to express his exact intention. By doing so, the number of editable emoticons can be maintained reasonable, and it can express user's exact intention. Further, editable emoticons can be used as information deliverer according to user's intention and editing skills. In this paper, we propose the concept of editable emoticons and schema based editable emoticon description method. The proposed description method is 200 times superior to the compared screen capturing method in the view of transmission bandwidth. Further, the description method is designed to have compatibility since it follows MPEG-UD international standard. The proposed editable emoticons can be exploited not only mobile applications, but also various fields such as education and medical field.

Keywords: description schema, editable emoticon, emoticon transmission, mobile applications

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Authors: Rohan Shinde, Shreya Chugh

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Imagine a world where innovation is natural and not unusual. Imagine a world that works on inner wisdom rather than just information. Children live in such a world which is full of possibilities. If they learn to listen to their own intuition, genius would be common. We all are born with a natural intuitive ability to perceive beyond our senses. This is especially visible in children whose minds are still fresh, less obsessive and more in tune with nature. As we grow older, our modern lifestyle overloads with information and stresses our mind which obscures this innate intuitive capacity. The Art of Living Prajñā Yoga (Intuition Process), a 2-day program introduced for kids and teenagers between 5-18 years of age helps to kindle this intuitive ability and build confidence to act on their gut feeling. This program helps them to tap into the intuitive abilities of the mind, which is demonstrated by them seeing colors, reading text and identifying pictures with eyes closed. To make these faculties blossom and get more established, the mind needs proper nurturing and nourishment which is done in the Intuition Process. A research study has been conducted to measure these abilities manifested in students who have this program on different parameters such as confidence level, clarity of mind, problem solving skills, focus, increase in overall performance etc. The results have been plotted on the graph and conclusions are made on effectiveness of intuition process. Experience of few students with special abilities have also been documented.

Keywords: Abilities, Art of Living, Intuition, Mind

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Christine Alvarez, Rio Gojar, Hannah Jimala

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The Philippines is a large country composed of geographic islands and distinct cultural groups. But what makes such a diverse country connect and communicate with one another? This case study examines the narrative of lived experiences expressed by the selected indigenous peoples through an in-depth interview. Based on the results, some indigenous peoples feel that they are motivated to engage in interethnic discussions that concern their ethnic identity and such cultural misconceptions about them. Their experiences in being involved in indigenous people centered and community/academic organizations helped them in every interethnic communication. After all, some indigenous peoples expressed that they find their own communities as a safe space. Although indigenous peoples present less interethnic communication apprehension, its existence is still manifested in their experiences in verbal communication, non-verbal communication, and mediated communication. Lastly, their Interethnic Communication Apprehension manifested on their innate and learned personality whenever there is a large crowd, and is affected by their socioeconomic status. This study mainly focuses on what are the interethnic communication apprehension experiences of indigenous peoples in the country. Concepts are applied from the Contextual Theory of Interethnic Communication theory, Interethnic Communication Apprehension, and other types of communication. Meanwhile, the participants are determined through a purposive sampling with the criteria as indigenous people who stays in Manila in pursuit of higher education.

Keywords: ethnic identity, interethnic relation, intercultural communication, indigenous people community

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Authors: Aminul Islam

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The issue of aging is now an emerging aspect of all over the world. Both the rural and urban societies of our country are not immune from this problem. This study mainly explored the influence of wealth on the enjoyment of role and status of the elderly in rural Bangladesh. It is based on empirical findings from the four villages of Gopalnagar union of Dhunat upazila of Bogra district. The study depicted that wealth has much influence regarding the enjoyment of role and status. Mixed approach has been given priority in this study. Survey, observation, case study and life history methods and focus group discussion technique have also been used in this study. Data have been collected from both primary and secondary sources. Simple random sampling procedure has also been followed in this study.

Keywords: wealth, role status, elderly

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Authors: Jung–Min Yang

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In this paper, fault recovery for parallel interconnected asynchronous sequential machines is studied. An adversarial input can infiltrate into one of two submachines comprising parallel composition of the considered asynchronous sequential machine, causing an unauthorized state transition. The control objective is to elucidate the condition for the existence of a corrective controller that makes the closed-loop system immune against any occurrence of adversarial inputs. In particular, an efficient existence condition is presented that does not need the complete modeling of the interconnected asynchronous sequential machine.

Keywords: asynchronous sequential machines, parallel composi-tion, corrective control, fault tolerance

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Authors: Shahla Afshar Paiman, Sedigheh Madani, Zahra Hosseininezhad

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Introduction: The most common causes of appendix luminal obstruction are fecaliths and lymphoid follicle hyperplasia. Appendicitis is a very rare Gastrointestinal complication of varicella zosterand it is mostly observed in immune-compromised patient. Case presentation: Here we reported a case of varicella zoster-related perforated appendicitis with synchronous encephalopathy as a first presentation of chickenpox in a 10-year-old boy. He had no history of immunodeficiency or predisposing factors and his diagnosis is confirmed by both serological lab tests and abdominal fluid (peritoneal secretion) PCR. Conclusion: Varicella zoster could cause appendicitis as first presentation, along with other critical complications look likes encephalopathy.

Keywords: Varicella zoster, appendicitis, encephalitis, children

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Authors: S. Buloyan, V. Mamikonyan, H. Hakobyan, H. Harutyunyan, H. Gasparyan

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The liver is the strongest regenerating organ of the organism, and even with 2/3 surgically removed, it can regenerate completely. Hence, liver cirrhosis may only develop when the regenerating system is off. We present the results of a comparative study of structural and functional characteristics of rat liver tissue under the conditions of toxic liver cirrhosis development, induced by carbon tetrachloride, and its prevention/treatment by natural compounds with antioxidant and immune stimulating action. Studies were made on Wister rats, weighing 120~140 g. Grape seeds extracts, separately and in combination with well known anticirrhotic drug ursodeoxycholic acid (ursodiol) have demonstrated effectiveness in prevention of liver cirrhosis development and its treatment.

Keywords: carbon tetrachloride, GSE, liver cirrhosis, prevention, treatment

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Authors: Marina Kljaković-Gašpić Batinjan, Tea Petrović, Frano Vučković, Irzal Hadžibegović, Barbara Radovani, Ivana Jurin, Lovorka Đerek, Eva Huljev, Alemka Markotić, Ivica Lukšić, Irena Trbojević-Akmačić, Gordan Lauc, Ivan Gudelj, Rok Čivljak

Abstract:

Immunoglobulin G has essential role in defense against infectious diseases, but its role cannot be fully recognized without understanding of changes in its N-glycans attached to the Fc domain. We analyzed and compared total IgG glycome in plasma samples of patients with influenza, patients with COVID-19 and healthy controls. We found similarities in IgG glycosylation changes in COVID-19 survivors and influenza patients that could be the consequence of adequate immune response to enveloped viruses, while observed changes in deceased COVID-19 patients may indicate its deviation.

Keywords: COVID-19, glycosylation, immunoglobulin G, influenza, pneumonia, viral infection

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Authors: Valeria T. Dilcheva, Svetlozara L. Petkova, Ivelin Vladov

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Trichinellosis is a food-borne parasitic disease caused by nematodes of the genus Trichinella which are zoonotic parasites with cosmopolitan distribution and major socio-economic importance. Human infection is acquired through consumption of undercooked meat from domestic or wild animal. Penetration of Trichinella larvae into striated skeletal muscle cells results in ultrastructural and metabolic changes. Migration of larvae causes the typical symptoms and signs of the disease. The severity of the symptoms depends on the number of ingested Trichinella larvae and the immune response of the host. Eosinophilia is present, with few exceptions, in most cases of human trichinellosis, inasmuch as it is the earliest and most important host response. Even in human asymptomatic cases, increases in eosinophilia of up to 15% have been observed. Eosinophilia appears at an early stage of infection between the second and fifth weeks of infection. By 2005 it was considered that only two species of Trichinella genus were found in the country. After routine trichinelloscopy procedure disseminated single muscle larvae in samples of wild boars and badger were PCR-identified as T. pseudospiralis. The study aimed to observed hematological changes occurring during experimentally induced infection with Trichinella spiralis, T. britovi and T. pseudospiralis in mice. We performed hematological blood profile, tracking 15 blood indicators. In statistical analysis made by Two-way ANOVA, there were significant differences of HGB, MCHC, PLT, Lymph%, Gran% in all three types of trichinellosis compared to control animals. Capsule-forming T. spiralis showed statistically significant differences in HGB, MCHC, Lymph% and PLT compared to the other two species. Non capsule-forming T. pseudospiralis showed statistically significant differences in Lymph%, Gran% relative to the control and in Gran% relative to T. spiralis. It appears rather substantial the process of capsule formation for prolonged immune response and retention of high content of percentage of lymphocytes(Lymph%) and low of granulocyte(Gran%) in T. pseudospiralis, which is contrary to studies for T. spiralis and eosinophilia. Studies and analyzes of some specific blood profile parameters can provide additional data in favor of early diagnosis and adequate treatment as well as provide a better understanding of acute and chronic trichinosis.

Keywords: hematological test, T. britovi, T. spiralis, T. pseudospiralis

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Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

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Introduction: Serum Sickness-Like Reaction (SSLR) is an inflammatory immune response characterized by a rash, polyarthralgias, and fever. SSLR usually occurs in response to a new medication (most commonly antibiotics, anticonvulsants, or antiinflammatory agents) and is believed to involve the formation of drug-specific immune complexes. Here we present a case of a 16-year-old female patient who developed an SSLR in response to the D-mannose-containing over-the-counter supplement, Uqora, used to promote bladder health. Methodology: The methodology for this study included a thorough literature search for other cases of SSLR associated with D-Mannose containing products. Data collection was performed through a review of the patient’s medical record, including history, physical examination, relevant laboratory results, and treatment plan. Findings: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. Her CBC, basic metabolic panel, liver function panel, lyme titers, and urinalysis were all within normal limits. The patient was referred to an allergist, who diagnosed her with SSLR. All medications were discontinued, and she was treated with a 7-day course of prednisone and cetirizine. Her symptoms resolved, and her medications were slowly resumed sequentially over several months. However, UQora triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. Conclusion: This case report describes the first documented case of SSLR caused by UQora (active ingredient D-mannose). D-Mannose is a monosaccharide found in many plants and fruits, and it is commonly used to prevent urinary tract infections. While the clinical features and timeline, in this case, were typical of SSLR, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of SSLR and the importance of prompt identification and management to enhance patient safety. It is possible D-mannose was not the trigger, and further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Keywords: serum sickness-like reaction, d-mannose, hypersensitivity reaction, urticaria

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Authors: Mohammad Asadpour

Abstract:

Cryptosporidium spp. is zoonotic pathogens transmissible from a variety of animals to humans and is a considerable public health concern. Calves have been identified in numerous reports as a major source of environmental contamination with this pathogen. Parasite has a different species that are the cases of zoonotic disease in immunodeficient people and neonatal calves. Cryptosporidium oocysts are extremely resistant to chlorine and other physical cases that commonly used in drinking water. Reproduction of resistant oocytes is a way for this monoxenous parasite to remain in the environment. Cryptosporidium parvum is the most important species that has human and cattle genotypes. Cryptosporidium is one of the most important causes of diarrhea in neonatal calves and also, one of the four causes of diarrhea symptoms in pre-weaned calves. Because of the incompetent immune system in calves, Cryptosporidium infection is the cause of a lot of problems in raising farms.

Keywords: Cryptosporidium spp, dairy calves, importance, veterinary medicine

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Authors: Aydin M. Torkabadi, Ehsan Pourjavad

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A decade after the introduction of Lean in Saskatchewan’s public healthcare system, its effectiveness remains a controversial subject among health researchers, workers, managers, and politicians. Therefore, developing a framework to quantitatively assess the Lean achievements is significant. This study investigates the success of initiatives across Saskatchewan health regions by recognizing the Lean healthcare criteria, measuring the success levels, comparing the regions, and identifying the areas for improvements. This study proposes an integrated intelligent computing approach by applying Fuzzy Inference System (FIS) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). FIS is used as an efficient approach to assess the Lean healthcare criteria, and TOPSIS is applied for ranking the values in regards to the level of leanness. Due to the innate uncertainty in decision maker judgments on criteria, principals of the fuzzy theory are applied. Finally, FIS-TOPSIS was established as an efficient technique in determining the lean merit in healthcare systems.

Keywords: lean healthcare, intelligent computing, fuzzy inference system, healthcare evaluation, technique for order of preference by similarity to ideal solution, multi-criteria decision making, MCDM

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Authors: Hanjun Zhao, Ke Zhang, Bojian Zheng

Abstract:

Background: So far, there is no universal antiviral agent which can inhibit multiple viral infections. More and more drug-resistant viral strains emerge after the antiviral drug application for treatment. Defensins are the front line of host innate immunity and have broad spectrum antibacterial and antiviral effects. However, there is limited data to show if these defensins have good antiviral activity in vivo and what the antiviral mechanism is. Subjects: To investigate a peptide with widespread antivirus activity in vitro and in vivo and illustrate the antiviral mechanism. Methods: Antiviral peptide library designed from mouse beta defensins was synthesized by the company. Recombinant beta defensin was obtained from E. coli. Antiviral activity in vitro was assayed by plaque assay, qPCR. Antiviral activity in vivo was detected by animal challenge with 2009 pandemic H1N1 influenza A virus. The antiviral mechanism was assayed by western blot, ELISA, and qPCR. Conclusions: We identify a new peptide which has widespread effects against multiple viruses (H1N1, H5N1, H7N9, MERS-CoV) in vitro and has efficient antivirus activity in vivo. This peptide inhibits viral entry into target cells and subsequently blocks viral replication. The in vivo study of the antiviral peptide against other viral infections and the investigation of its more detail antiviral mechanism are ongoing.

Keywords: antiviral peptide, defensin, Influenza A virus, mechanism

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Authors: Shraddha Rane, Richard Warren, Stephen Eyre

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L-23 is a pro-inflammatory molecule that signals T cells to release cytokines such as IL-17A and IL-22. Psoriasis is driven by a dysregulated immune response, within which IL-23 is now thought to play a key role. Genome-wide association studies (GWAS) have identified a number of genetic risk loci that support the involvement of IL-23 signalling in psoriasis; in particular a robust susceptibility locus at a gene encoding a subunit of the IL-23 receptor (IL23R) (Stuart et al., 2015; Tsoi et al., 2012). The lead psoriasis-associated SNP rs9988642 is located approximately 500 bp downstream of IL23R but is in tight linkage disequilibrium (LD) with a missense SNP rs11209026 (R381Q) within IL23R (r2 = 0.85). The minor (G) allele of rs11209026 is present in approximately 7% of the population and is protective for psoriasis and several other autoimmune diseases including IBD, ankylosing spondylitis, RA and asthma. The psoriasis-associated missense SNP R381Q causes an arginine to glutamine substitution in a region of the IL23R protein between the transmembrane domain and the putative JAK2 binding site in the cytoplasmic portion. This substitution is expected to affect the receptor’s surface localisation or signalling ability, rather than IL23R expression. Recent studies have also identified a psoriatic arthritis (PsA)-specific signal at IL23R; thought to be independent from the psoriasis association (Bowes et al., 2015; Budu-Aggrey et al., 2016). The lead PsA-associated SNP rs12044149 is intronic to IL23R and is in LD with likely causal SNPs intersecting promoter and enhancer marks in memory CD8+ T cells (Budu-Aggrey et al., 2016). It is therefore likely that the PsA-specific SNPs affect IL23R function via a different mechanism compared with the psoriasis-specific SNPs. It could be hypothesised that the risk allele for PsA located within the IL23R promoter causes an increase IL23R expression, relative to the protective allele. An increased expression of IL23R might then lead to an exaggerated immune response. The independent genetic signals identified for psoriasis and PsA in this locus indicate that different mechanisms underlie these two conditions; although likely both affecting the function of IL23R. It is very important to further characterise these mechanisms in order to better understand how the IL-23 receptor and its downstream signalling is affected in both diseases. This will help to determine how psoriasis and PsA patients might differentially respond to therapies, particularly IL-23 biologics. To investigate this further we have developed an in vitro model using CD4 T cells which express either wild type IL23R and IL12Rβ1 or mutant IL23R (R381Q) and IL12Rβ1. Model expressing different isotypes of IL23R is also underway to investigate the effects on IL23R expression. We propose to further investigate the variants for Ps and PsA and characterise key intracellular processes related to the variants.

Keywords: IL23R, psoriasis, psoriatic arthritis, SNP

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Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

Abstract:

Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

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Authors: Sonal Purohit, Animesh Dubey

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Corporate governance deals with the entire network of formal and informal relationship with the management of the company and company’s stakeholders including employees, customers, creditors, local communities, and society in general. The recent financial crisis was truly a global crisis in its nature and effects. The Indian financial markets were not immune to this global financial crisis. It is believed that corporate governance also had a major role to play in staggering the effect of this crisis. The objective of this paper is to examine the failure of prevailing corporate governance practice in India during financial crisis. Lack of appropriate implementation of the corporate government norms was a reason behind the phenomenon of money being pulled-out by FIIs, which constitute major investors and influencers of the Indian financial market.

Keywords: corporate governance, FII, financial market, financial crisis

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Authors: Ren-Jye Lin, Li-Hsiung Lin, Bing-Cheng Liu, Ching-Len Liao

Abstract:

The human zinc finger protein 36-like protein family, containing zinc finger protein 36-like 1 (ZFP36L1) and zinc finger protein 36-like 2 (ZFP36L2), belongs to CCCH-type zinc-finger protein identified as an RNA-binding protein that participates in controlling posttranscriptional regulation via RNA decay pathways. Recently, we demonstrated that human ZFP36L1 showed potent antiviral activity against flavivirus Infection by both 5´-3´ XRN1 and 3´-5´RNA-exosome RNA decay pathways (Journal of Virology 2022 Jan 12;96(1): e0166521). However, another zinc finger protein 36-like protein member, ZFP36L2, in the host defense response against flaviviruses has yet to be addressed. Here, we also demonstrate that ZFP36L2 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L2 reduced JEV and DENV infection, and ZFP36L2 knockdown significantly promoted viral replication. Distinct from the antiviral mechanism of ZFP36L1, ZFP36L2 inhibits flavivirus infection by only a 5´-3´ XRN1-mediated RNA decay pathway but not the 3´-5´RNA-exosome RNA decay pathway. Human ZFP36L1 and ZFP36L2 can restrict flavivirus replication by directly binding and destabilizing viral RNA. Thus, for the first time, human zinc finger protein 36-like family members, ZFP36L1 and ZFP36L2, are identified as host antiviral factors that can bind and degrade flavivirus viral RNA by diverse antiviral mechanisms.

Keywords: ZFP36L1, ZFP36L2, 5'-3' exonuclease XRN1, antiviral mechansim

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Authors: Sadaf Ilyas, Saba Riaz

Abstract:

The extensive use of antibiotics has led to increases emergence of antibiotic-resistant organisms. Pseudomonas is a notorious opportunistic pathogen involoved in nosocomial infections and exhibit innate resistance to many antibiotics. The present study was conducted to assess the prevalence, levels of antimicrobial susceptibility and resistance mechanisms of Pseudomonas. A total of thirty clinical strains of Pseudomonas were isolated from different clinical sites of infection. All clinical specimens were collected from Chughtais Lahore Lab. Jail road, during 8-07-2010 to 11-01-2011. Biochemical characterization was done using routine biochemical tests. Antimicrobial susceptibility was determined by Kirby-Baeur method. The plasmids were isolated from all the strains and digested with restriction enzyme PstI and EcoRI. Transfer of Multi-resistance plasmid was checked via transformation and conjugation to confirm the plasmid mediated resistance to antibiotics. The prevalence of Pseudomonas in clinical specimens was found out to be 14% of all bacterial infections. IPM has shown to be the most effective drug against Pseudomonas followed by CES, PTB and meropenem, wheareas most of the Pseudomonas strains have developed significant resistance against Penicillins and some Cephalasporins. Antibiotic resistance determinants were carried by plasmids, as they conferred resistance to transformed K1 strains. The isolates readily undergo conjugation, transferring the resistant genes to other strains, illustrating the high rates of cross infection and nosocomial infection in the immunocompromised patients.

Keywords: pseudomonas, antibiotics, drug resistance, horizontal gene transfer

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