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Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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OBJECTIVE: To investigate the expressions of peripheral blood microRNA-21(miR-21) and transforming growth factor-beta(TNF-beta)/Smad signaling transduction pathway in patients with bronchial asthma complicated with respiratory virus infection. METHODS: Totally 109 patients with asthma complicated with respiratory virus infection(study group) and 104 patients without virus infection(control group) in the Third People's Hospital of Gansu Province between Feb.2019 and Feb.2021 were selected for the cross-sectional study. The basic data of the two groups were collected, and parameters including vital signs, lung function, peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins were measured. According to the guidelines, the patients of the two groups were divided into acute exacerbation phase and stable phase. The examination results of each group were compared and the levels of peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins expression of patients with asthma complicated with respiratory virus infection were analyzed. RESULTS: In study group, the proportion of respiratory virus infection among 109 patients was 33.94% for influenza virus, 23.85% for human rhinovirus, 19.27% for respiratory syncytial virus, 10.09% for parainfluenza virus, 6.42% for adenovirus, 4.59% for human coronavirus and 1.83% for human metapneumovirus respectively. The proportion of patients with acute exacerbation phase in the study group was higher than that in the control group, and the levels of peripheral blood miR-21, TGF-beta1, Smad7, pSmad2 and pSmad3 were higher than those in control group(P<0.05). The levels of miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 in peripheral blood of patients with acute exacerbation phase of asthma were higher than those of patients with stable phase of asthma(P<0.05). There were no statistical differences in peripheral blood miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 levels in asthma patients with different virus infections. CONCLUSION: Early respiratory virus infections might lead to increased expression of peripheral blood miR-21 and increased activation of TGF-beta/Smad signaling pathway in patients with asthma, which played an important role in acute attack of asthma.
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BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http://genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope:1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*15:02 and HLA-DRB1*15:03 alleles, whereas the IEDB_epitope:1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*07:01, HLA-DRB1*03:01, HLA-DRB3*01:01, and HLA-DRB4*01:01 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*15:02Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*15:03Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*07:01Allergy, hypersensitivity (Caucasian)HLA-DRB1*03:01Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*01:01Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*01:01Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-D343. doi: 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https://doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9):108454. doi: 10.1016/j.celrep.2020.108454.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Over the past century, synthetic polymers have had a transformative impact on human life, replacing nature-derived materials in many areas. Yet, despite their many advantages, the structure and function of synthetic polymers still appear rudimentary compared to biological matter: cells use dynamic self-assembly to construct complex materials and operate sophisticated macromolecular devices. The field of DNA nanotechnology has demonstrated that synthetic DNA molecules can be programmed to undergo predictable self-assembly, offering unparalleled control over the formation and dynamic properties of artificial nanostructures. Intriguingly, the principles of DNA nanotechnology can be applied to the engineering of soft programmable materials, bringing the abilities of synthetic polymers closer to their biological counterparts. In this perspective, we discuss the unique features of DNA-functionalized polymer materials. We describe design principles that allow researchers to build complex supramolecular architectures with predictable and dynamically adjustable material properties. Finally, we highlight two key application areas where this biologically inspired material class offers particularly promising opportunities: (1) as dynamic matrices for 3D cell and organoid culture and (2) as smart materials for nucleic acid sequencing and pathogen detection.
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Nanofibers are a type of nanomaterial with a diameter ranging from ten to a few hundred nanometers with a high surface-to-volume ratio and porosity. They can build a network of high-porosity material with excellent connectivity within the pores, making them a preferred option for numerous applications. This review explores nanofibers from the synthesis techniques to fabricate nanofibers, with an emphasis on the technological applications of nanofibers like water and air filtration, photovoltaics, batteries and fuel cells, gas sensing, photocatalysis, and biomedical applications like wound dressing and drug delivery. The nanofiber production market has an expected compound annual growth rate (CAGR) of 6% and should reach around 26 million US $ in 2026. The limitations and potential opportunities for large-scale applications of nano-fibrous membranes are also discussed. We expect this review could provide enriched information to better understand Electrospun Polymer Nanofiber Technology and recent advances in this field. © 2023 Bentham Science Publishers.
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BackgroundAnti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) is a rare autoimmune disease associated with a high mortality rate due to rapid-progressive interstitial lung disease (RP-ILD), particularly in East Asia[1]. MDA5, acts as a cytoplasmic sensor of viral RNA, thus activating antiviral responses including the type I interferon (IFN) signaling pathway[2]. The involvement of type 1 IFN in the pathogenesis of MDA5+DM has been proposed based on the significantly elevated expression of its downstream stimulated genes(ISG) in muscle, skin, lung, and peripheral blood[3;4]. Janus kinase inhibitor, which targets the IFN pathway, combined with glucocorticoid could improve the survival of early-stage MDA5+DM-ILD patients[5]. In clinical practice, there is still an urgent demand for sensitive biomarkers to facilitate clinical risk assessment and precise treatment.ObjectivesThis study aimed to investigate the clinical significance of interferon score, especially IFN-I score, in patients with anti-MDA5+DM.MethodsDifferent subtypes of idiopathic inflammatory myopathy, including anti-MDA5+DM(n=61), anti-MDA5-DM(n=20), antisynthetase syndrome(ASS,n=22),polymyositis(PM,n=6) and immune-mediated necrotizing myopathy(IMNM,n=9), and 58 healthy controls were enrolled.. A multiplex quantitative real-time PCR(RT-qPCR) assay using four TaqMan probes was utilized to evaluate two type I ISGs (IFI44, MX1, which are used for IFN-I score), one type II ISG (IRF1), and one housekeeping gene (HRPT1). Clinical features and disease activity index were compared between high and low IFN-I score groups in 61 anti-MDA5+DM patients. The association between laboratory findings and the predictive value of baseline IFN-I score level for mortality was analyzed.ResultsThe IFN scores were significantly higher in patients with anti-MDA5+DM than in HC (Figure 1A). The IFN-I score correlated positively with serum IFN α(r = 0.335, P =0.008), ferritin (r = 0.302, P = 0.018), and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score(r=0.426, P=0.001). Compared with patients with low IFN-I scores, patients with high IFN-I scores showed increased MYOACT score, CRP, AST, ferritin, and the percentages of plasma cells (PC%) but decreased lymphocyte count, natural killer cell count, and monocyte count. The 3-month survival rate was significantly lower in patients with IFN-I score > 4.9 than in those with IFN-I score ≤ 4.9(72.9% vs. 100%, P=0.044)(Figure 1B).ConclusionIFN score, especially IFN-I score, detected by multiplex RT-qPCR, can be a valuable biomarker for monitoring disease activity and predicting mortality in anti-MDA5+DM patients.References[1]I.E. Lundberg, M. Fujimoto, J. Vencovsky, R. Aggarwal, M. Holmqvist, L. Christopher-Stine, A.L. Mammen, and F.W. Miller, Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7 (2021) 86.[2]G. Liu, J.H. Lee, Z.M. Parker, D. Acharya, J.J. Chiang, M. van Gent, W. Riedl, M.E. Davis-Gardner, E. Wies, C. Chiang, and M.U. Gack, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 6 (2021) 467-478.[3]G.M. Moneta, D. Pires Marafon, E. Marasco, S. Rosina, M. Verardo, C. Fiorillo, C. Minetti, L. Bracci-Laudiero, A. Ravelli, F. De Benedetti, and R. Nicolai, Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features. Arthritis Rheumatol 71 (2019) 1011-1021.[4]Y. Ye, Z. Chen, S. Jiang, F. Jia, T. Li, X. Lu, J. Xue, X. Lian, J. Ma, P. Hao, L. Lu, S. Ye, N. Shen, C. Bao, Q. Fu, and X. Zhang, Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13 (2022) 6458.[5]Z. Chen, X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. New England Journal of Medicine 381 (2019) 291-293.AcknowledgementsThis work was supported by the National Natural Science Foundation of China [81974251], and Shanghai Hospital Develop ent Center, Joint Research of New Advanced Technology Project [SHDC12018106]Disclosure of InterestsNone Declared.
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Background & Aim: Adoptive T cell immunotherapy holds great promise for the treatment of viral complications. Our group has been developing and trialling virus-specific T cell therapies for more than 20 years. Recently, we have generated a repository of multi-virus-specific T cells for our clinical trials. Unfortunately, for many patients with viral complications, there is no suitable trial through which to access these therapies. In Australia, the Therapeutic Goods Administration has a Special Access Scheme (SAS) to enable provision of unapproved therapies for compassionate use. Our research group is now a leading Australian provider of "off-the-shelf" and custom-grown allogeneic virus-specific T cells to hospitals for patients with no other treatment options. Methods, Results & Conclusion(s): We have generated a repository of multi-virus-specific T cells from 20 healthy donors, with up to 150 doses of T cells per donor generated from a single blood sample. Each product batch is thoroughly characterised in terms of viral antigen specificity, HLA restriction and alloreactivity. These T cells target a combination of Epstein-Barr virus, cytomegalovirus, BK polyomavirus, John Cunningham virus and adenovirus epitopes. We have also generated a repository of SARS-CoV-2-specific T cells and occasionally grow custom patient-specific batches of T cells from nominated donors, on request. Since 2008, we have provided virus-specific T cells to 15 hospitals across Australia, and the volume of supply requests has significantly increased in recent years, as clinicians have gained interest in adoptive immunotherapy. In 2022, we provided T cells for 26 patients via the SAS. The majority were experiencing post-transplant complications, including cytomegalovirus disease, BK virus-associated haemorrhagic cystitis and post-transplant lymphoproliferative disorder. Through our clinical trials, we have developed rigorous processes for T cell therapy manufacture and characterisation, in addition to a computer-based selection algorithm, which we apply to SAS cases. As these cases are not part of a clinical trial, concomitant therapy varies, and monitoring is not uniform. However, we have received reports of clinical benefit from adoptive T cell therapy. These include cases of reduction in viral load, improvement in symptoms, and complete resolution of infection. We believe that these promising T cell therapies should be available to hospitals through a nationally funded centre for cellular therapies for critically ill patients.Copyright © 2023 International Society for Cell & Gene Therapy
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Hospitals were overburdened during peak periods of Coronavirus disease 2019 (COVID-19) pandemic, and bed occupancy was full. The ability to predict and plan patients' hospital length of stay allows predictability in terms of the free capacity of hospital facilities. The purpose of this article is to evaluate the factors that influence the hospital length of stay among discharged (recovered) from COVID-19 patients. This will allow the prediction of the likely number of bed days in the conditions of intensive workload of medical facilities for hospital care. A total of 441 discharged after hospital treatment for COVID-19 patients are followed up. Factors for prolonged hospital length of stay are searched among the indicators recorded at admission. Median hospital length of stay of the patients discharged from COVID-19 ward is 9 days (IQR 6-12) and in the COVID-19 intensive care unit 12 days (IQR 9.75-18.75). The median length of stay assessed by a survival analysis is 35 days in the COVID-19 unit and only 8 days in intensive care, due to the high mortality in the intensive care unit. The longer hospital length of stay of patients discharged from the COVID-19 wards is associated with the presence of hypertension (median 10 vs. 8 days for patients without the disease, p=0.006), ischemic heart disease (10 vs. 8 days, p<0.001), cerebrovascular disease (10 vs. 8 days, p=0.061 - did not reach significance), peripheral arterial disease (12 vs. 8 days, p=0.024), chronic renal failure or chroniodialysis (14 vs. 8 days, p<0.001), oncological illness (11 vs. 8 days, p=0.024), presence of at least one comorbidity (9 vs. 8 days, p=0.006), arrival at the hospital by ambulance vs. the patient's own transport (11 vs. 8 days, p=0.003), severe lung involvement shown on X-ray (10 vs. 8 days, p=0.030) or CT (18 vs. 10 days, p=0.045). Prolonged hospital length of stay is associated with older age (Spearman's rho=0.185, p<0.001), greater number of comorbidities (Spearman's rho=0.200, p<0.001), lower oxygen saturation on admission (Spearman's rho=- 0.294, p<0.001) and lower lymphocytes count (Spearman's rho=-0.209, p<0.001), as well as higher CRP (Spearman's rho=0.168, p<0.001), LDH (Spearman's rho=0.140, p=0.004), ferritin (Spearman's rho=0.143, p=0.004) and d-dimer (Spearman's rho=0.207, p<0.001). The multiple linear regression model found that the increase in the number of bed days of discharged from COVID-19 unit patients depends on the way the patient arrived at the Emergency Department (by ambulance instead of on their own transportation) and the presence of an accompanying oncological disease (R2=0.628, p<0.001). The hospital length of stay of patients discharged from COVID-19 intensive care unit is associated with the presence of hypertension (median 14 vs. 9 days for patients without the disease, p=0.067 - significance not reached) and at least one comorbidity (14 vs. 9 days, p=0.067 - significance not reached). The number of bed days is higher when recorded more comorbidities (Spearman's rho=0.818, p=0.004), lower oxygen saturation (Spearman's rho=-0.605, p=0.067 - significance not reached) and higher leukocytes count (Spearman's rho=0.546, p=0.102 - significance not reached). A multiple linear regression model demonstrated the hospital length of stay of patients in the COVID-19 intensive care unit as an outcome of the number of comorbidities only (R2=0.826, p=0.003). The ability to estimate and forecast quickly the number of bed-days based on a small number of variables would help reduce the burden on the healthcare system during a pandemic.
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SARS-CoV-2 is a new threat to public health due to its increased transmissibility and immune evasion. Angiotensin-converting enzyme 2 (ACE2) plays a critical role in SARS-CoV-2 infection as its serve as the virus's major entry receptor in humans. Vaccines have been authorized for emergency use to control the current pandemic and they have greatly reduced the spread of SARS-CoV-2 and mortality rates, nevertheless this coronavirus has shown the ability to endure crucial mutations that increases its infectivity which makes it likely that the virus will continue to mutate and disseminate. There is a need to find and introduce alternative and effective methods of controlling SARS-CoV-2. Notably, low-level laser therapy (LLLT) is a method of exposing cells or tissue to low levels of red and near infrared light which has a high success rate for treatment of other ailments. The aim of the study is to determine for the first time, the effects of LLLT on SARS-CoV-2 infected HEK293/ACE2 cells and compare them to uninfected ones. Both infected and uninfected HEK293/ACE2 cells were irradiated at a wavelength of 640 nm, at different doses. Then, the effects of laser irradiation on the cells and the virus were evaluated using luciferase, cytotoxicity, and cell viability assays. Preliminary results showed that irradiated uninfected cells had no changes in cell viability and cytotoxicity, while there were changes in irradiated infected cells. In addition, laser irradiation caused cell membrane damage in infected cells. Lastly, uninfected irradiated cells showed no luciferase activity while laser irradiation reduced luciferase activity in infected cells. © 2023 SPIE.
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The article describes the world's experience in developing the solar industry. It discusses the mechanisms of state support for developing renewable energy sources in the cases of five countries that are the most successful in this area—China, the United States, Japan, India, and Germany. Furthermore, it contains a brief review of state policy in producing electricity by renewable energy facilities in Kazakhstan. This paper uses statistical information from the International Renewable Energy Agency (IRENA), the International Energy Agency (IEA), British Petroleum (BP), and the Renewable Energy Network (REN21), and peer-reviewed sources. The research methodology includes analytical research and evaluation methods to examine the current state of solar energy policy, its motivators and incentives, as well as the prospects for its development in Kazakhstan and in the world. Research shows that solar energy has a huge development potential worldwide and is sure to take its place in gross electricity production. This paper focuses on the selected economic policies of the top five countries and Kazakhstan, in what may be considered a specific research limitation. Future research suggestions for the expansion of Renewable Energy (RE) in Kazakhstan could include analysing the impact of introducing dedicated policies and incentives for solar systems and exploring the benefits and challenges of implementing large RE zones with government–business collaboration.
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Previous studies have revealed that developmental regulated brain protein (Drebrin) is involved in cell- to-cell communication, nerve transmission, tumor metastasis, spermatogenesis and other life activities, but there are few studies on viruses. The aim of the current research was therefore, to study the function of Drebrin and its effect on the proliferation of porcine epidemic diarrhea virus (PEDV). The Drebrin gene was cloned according to the Drebrin gene sequence (XM_008015438.2) of Chlorocebus sabaeus registered by GenBank, and the phylogenetic tree was constructed to analyze its homology. The results showed that the CDS region of Vero cells Drebrin gene was 2088 bp long, encoding 695 amino acids, and was relatively conserved and had high homology with all species. To investigate the effect of Drebrin on the proliferation of PEDV in Vero cells, the eukaryotic expression vector pcDNA3.1-Drebrin-Flag was constructed. After transfection of Vero cells with different concentrations of pcDNA3.1-Drebrin-Flag, cells were infected with PEDV. Our results showed that overexpression of Drebrin in Vero cells could significantly inhibit the intracellular PEDV mRNA level and N protein expression, reduce the extracellular virus titer and inhibit the proliferation of PEDV. Further study on the interaction between Drebrin and PEDV S proteins by laser confocal technique was also performed. The results showed that Drebrin and S protein were co-located in the cytoplasm, suggesting that the two proteins may interact with each other. This study demonstrated for the first time that Drebrin can inhibit PEDV proliferation in Vero cells, laying a foundation for further research in to Drebrin function and provides a valuable information for anti-PEDV research.
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[] Atherosclerosis (As) is the pathological basis of coronary heart disease, and vascular endothelial injury is the initiating factor of coronary atherosclerosis. Vascular endothelial cells are a single layer of cells located in the inner layer of blood vessels and regulates exchanges between the blood stream and the surrounding tissues, and their integrity is very important. Many active monomers and the derivatives in natural products of traditional Chinese medicine modulate the function of endothelial cells by intervening oxidative stress, regulating the release of vasoactive substances, reducing inflammation, and equilibrating coagulation and anticoagulant system. They have the advantages of multi-pathway, multi-link and multi-target regulation in protecting from endothelial injury and attenuating atherogenesis. They have also been used to protect against corona virus disease 2019 (COVID-19) induced endothelial injury and atheroslerosis. This article reviews the research progress of the above issues in this field. © 2023, Editorial Office of Chinese Journal of Arteriosclerosis. All rights reserved.
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Purpose: Today, coronavirus disease-19 (COVID-19) treatment is an evolving process, and synbiotic administration has been suggested as a new therapeutic strategy. This study aims to investigate the effect of synbiotic supplementation in COVID-19 patients. Design/methodology/approach: In this placebo-controlled trial, 80 patients were randomized to receive oral synbiotic capsule (containing fructooligosaccharide and seven bacterial strains;Lactobacillus (L) casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, Bifidobacterium longum, L. bulgaricus, each one 109 colony-forming units) or placebo for two months. Inflammatory markers (Interleukin-6 [IL-6], C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) and white blood cell (WBC) count were evaluated at two timepoints (baseline, two months later). The measured variables were adjusted for confounders and analyzed by SPSS v21.0. Findings: All 80 enrolled patients completed the study. The study adherence was good (approximately 70%). The mean changes for IL-6 were not significant ( = -0.6 +or- 10.4 pg/mL vs = +11.2 +or- 50.3 pg/mL, p > 0.05). There were no significant improvements for CRP, ESR and WBC. Originality/value: Administration of synbiotics for two months did not improve inflammatory markers in COVID-19 patients.
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When it comes to supplying oxygen, current standard hospitals in Iran have proven inadequate in the face of the COVID-19 pandemic, particularly during infection peaks. Power disruptions drastically reduce the oxygen pressure in hospitals, putting patients' health at risk. The present study is the first to attempt to power an oxygen concentrator with a solar-energy-based system. The HOMER 2.81 package was used for technical–economic–environmental–energy analysis. The most notable aspects of this work include evaluating different available solar trackers, using up-to-date equipment price data and up-to-date inflation rate, considering the temperature effects on solar cell performance, sensitivity analysis for the best scenario, considering pollution penalties, and using a three-time tariff system with price incentives for renewable power. The study has been carried out at Hajar Hospital, Shahrekord, Chaharmahal and Bakhtiari Province, Iran. The study showed that, by supplying 60% of the power demand, the dual-axis solar tracking system offered the highest annual power output (47,478 kWh). Furthermore, generating power at—$0.008/kWh due to selling power to the grid, the vertical-axis tracker was found to be the most economical design. Comparing the configuration with a vertical-axis tracker with the conventional scenario (relying on the power distribution grid), the investment is estimated to be recovered in three years with $234,300 in savings by the end of the 25th year. In the best economic scenario, 6137 kg CO2 is produced, and the analysis revealed the negative impact of a temperature rise on the performance and solar power output.
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BACKGROUND This review is devoted to the analysis of the features of the immune response in COVID-19. The review indicates the clinical manifestations of COVID-19, modern data on the immunopathogenesis of the disease and its complications are considered. AIM OF STUDY To clarify some pathogenetic mechanisms of the immune response in COVID-19, which can help in creating an algorithm for examining patients for early prognosis and prevention of severe course and complications of the disease. MATERIAL AND METHODS To achieve this goal, the results of domestic and foreign scientific studies on the pathogenesis, diagnosis and treatment of COVID-19 were analyzed. The literature search was carried out in electronic search engines Scopus and PubMed. For the analysis, scientific articles published in the period from 2019 to 2021 were selected;88% of analyzed works are not older than 5 years. CONCLUSION The late production of type I IFN, an increase in the level of pro-inflammatory monocytes, a decrease in the expression of HLA-DR on monocytes, violation of the presentation of the virus and the formation of specific lymphocytes, the death of T-lymphocytes and profound immunosuppression are of greatest importance for the development of a severe form of COVID-19. © 2023 Sklifosovsky Research Institute for Emergency Medicine. All rights reserved.
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BackgroundVaccine-induced immunity is very important for controlling the COVID-19 infection. The vaccination supports humoral and cellular immunity, and this is one of the main strategy for us. Various vaccines approved in the countries have been shown to reduce infection rates, severity, and mortality.ObjectivesWe aimed to compare humoral and cellular immune responses after homologous or heterologous vaccination among patients with aiRMDs at their third vaccination with BNT162b2 or with two vaccinations followed by COVID-19 infection. We detected the anti-SARS-CoV2 antibody levels and measured the SARS-CoV-2 reactive B-, or T-cell mediated immunity in aiRMDs receiving homologous (Hom.), heterologous (Het.) vaccines or became infected (Inf.).MethodsA single center observational study evaluated immunogenicity and safety of the third dose vaccines or after two-dose regimen of vaccine and COVID infection in patients with aiRMDs. Neutralizing anti-RBD antibodies and specific T-cell response were measured.ResultsWe showed that following 4 months of the booster vaccination with the third dose of mRNA-based vaccine or after COVID infection, the positive (>21.8 BAU/mL) neutralizing anti-RBD IgG antibody response was outstanding in all three patient groups, 95.5%, 100% and 100% of the homologous and heterologous as well as the SARS-CoV-2 infected groups. Taken together booster vaccinations or SARS-CoV-2 infection after completing 2 doses of the vaccination can lead to the production of neutralizing antibodies still protective in RMD cases after 4 months of the third antigen exposition. The booster vaccination reduces the frequency of hospital admissions and mortality with ai RMDs. The vaccinations are effective independently from the type of vaccine, the SARS-CoV-2 specific memory B-cell populations showed a statistically not significant but lower frequency in the infection group. Clinical activity of aiRMDs was not increased following booster vaccination.ConclusionPatients, who received a heterologous booster vaccine had a higher level of peripheral memory B-cells compared to those who had COVID-19 infection. Biologic therapy decreased the level of B-cells. Patients with a disease duration of more than 10 years had higher level of CD8+TNF-α+ and CD8+IFN-γ+ T-cells compared to patients who were diagnosed less than 10 years ago. The third booster mRNA-based vaccine was as much effective as in the homologous and heterologous patients groups compared who had COVID infection.References[1] Szebeni, G.J.;Gemes, N.;Honfi, D.;Szabo, E.;Neuperger, P.;Balog, J.A.;Nagy, L.I.;Szekanecz, Z.;Puskas, L.G.;Toldi, G.;et al. Humoral and Cellular Immunogenicity and Safety of Five Different SARS-CoV-2 Vaccines in Patients With Autoimmune Rheumatic and Musculoskeletal Diseases in Remission or With Low Disease Activity and in Healthy Controls: A Single Center Study. Front. Immunol. 2022, 13, 846248.[2]Honfi, D.;Gémes, N.;Szabó, E.;Neuperger, P.;Balog, J.Á.;Nagy, L.I.;Toldi, G.;Puskás, L.G.;Szebeni, G.J.;Balog, A. Comparison of Homologous and Heterologous Booster SARS-CoV-2 Vaccination in Autoimmune Rheumatic and Musculoskeletal Patients. Int. J. Mol. Sci. 2022, 23, 11411Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Background & Aim: Despite the successful implementation of vaccines worldwide, COVID-19 remains a risk in patients with a compromised immune system. Emerging viral variants have also reduced the effectiveness of monoclonal antibody therapies in these patients. New treatment options are therefore required to improve clinical outcomes. Methods, Results & Conclusion(s): T cell immunotherapy has proven effective for the treatment of a number of refractory viral diseases in patients with a compromised immune system. We have now completed the manufacture of a bank of SARS-CoV-2 specific T cells and commenced an open-label phase I clinical trial at the Royal Brisbane and Women's Hospital, Australia. Patients enrolled in the study receive two doses of partially HLA-matched allogeneic T cells at a fortnightly interval. We have thus far recruited and treated three immune compromised patients with SARS-CoV-2 T cells. In two of the three patients treated thus far, the administration of T cell therapy was coincident with the clearance of viral load after 28 days. Viral clearance in these patients was also associated with an increase in circulating SARS-CoV-2 specific T cells. Our preliminary observations suggest that SARS-CoV-2 specific T cell therapy is well tolerated and has the potential to impact viral control in immune compromised patients.Copyright © 2023 International Society for Cell & Gene Therapy
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Introduction: Currently, isolated from SARS-CoV-2 virus exceed 600 million cases in the world. Objective(s): Isolation and characterization of the SARS-CoV-2 virus causing COVID-19 at the beginning of the pandemic in Peru. Method(s): Twenty nasal and pharyngeal swab samples were isolated from SARS-CoV-2 using two cell lines, Vero ATCC CCL-81 and Vero E-6;virus identification was performed by RT-PCR and the onset of cytopathic effect (CPE) was evaluated by indirect immunofluorescence and subsequent identification by genomic sequencing. One of the most widely circulating isolates were selected and named the prototype strain (PE/B.1.1/28549/2020). Then 10 successive passages were performed on Vero ATCC CCL-81 cells to assess mutation dynamics. Result(s): Results detected 11 virus isolates by cytopathic effect, and subsequently confirmed by RT-PCR and indirect immunofluorescence. Of these, six were sequenced and identified as the lineages B.1, B.1.1, B.1.1.1, and B.1.205 according to the Pango lineage nomenclature. The prototype strain corresponded to lineage B.1.1. The analysis of the strains from the successive passages showed mutations mainly at in the spike (S) protein of the virus without variation in the identity of the lineage. Conclusion(s): Four lineages were isolated in the Vero ATCC CCL-81 cell line. Subcultures in the same cell line showed mutations in the spike protein indicating greater adaptability to the host cell and variation in pathogenicity in vitro, a behavior that allows it to have more survival success.Copyright © 2023 Anales de la Facultad de Medicina. All rights reserved.
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Breast cancer is the most commonly diagnosed cancer globally and is among the leading causes of cancer deaths worldwide. Breast cancer mortality rates are increasing due to delays in diagnosis, prognosis, and treatment caused by the coronavirus disease 2019 (COVID-19) pandemic. Identification and validation of blood-based breast cancer biomarkers for early detection is a top priority worldwide. MicroRNAs (miRNAs) show the potential to serve as breast cancer biomarkers. miRNAs are small, endogenously produced RNAs that regulate growth and development. However, oncogenic miRNAs also play a major role in tumor growth and can alter the tumor microenvironment (TME) in favor of cancer metastasis. The TME represents a complex network of diverse cancerous and noncancerous cell types, secretory proteins, growth factors, and miRNAs. Complex interactions within the TME can promote cancer progression and metastasis via multiple mechanisms, including oxidative stress, hypoxia, angiogenesis, lymphangiogenesis, and cancer stem cell regulation. Here, we decipher the mechanisms of miRNA regulating the TME, intending to use that knowledge to identify miRNAs as therapeutic targets in breast cancer and use miRNAs as blood-based biomarkers. © Springer Nature Singapore Pte Ltd. 2022.
ABSTRACT
The year 2019 ended with the official report of an unknown pneumonia outbreak in Wuhan, Hubei Province, China. Subsequently, this novel pneumonia was named COVID-19, which mainly attacks the respiratory system, causing severe damage. Although vaccination has relieved the stress of combating pandemics around the world after one year, there are still unknowns and challenges that come with hope. In this regard, stem cell therapy has been proposed as an effective approach to treating COVID-19. Mesenchymal stem cells (MSCs) can potentially be used as a hopeful tool in the cell-based therapy due to their ability to regenerate and regulate immune response. Although research and clinical results have shown encouraging achievement in patients who were treated with MSCs, drawbacks and challenges still exist in the face of new opportunities. This review aims to introduce the challenges of the COVID-19 vaccine and the possible clinical use of MSC-based therapy. Through analysis of COVID-19 and MSC-based therapy, the author aims to find the possibilities and feasibility of using MSCs to treat acute respiratory diseases, such as COVID. As a result, the author finds that MSC treatment is very practical, and it shows significant potential to treat COVID-19. © 2023 SPIE.