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1.
Journal for ImmunoTherapy of Cancer ; 10(Supplement 2):A958, 2022.
Article in English | EMBASE | ID: covidwho-2161949

ABSTRACT

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has demonstrated high transmissibility and possesses several spike protein mutations that allow for evasion of previously established immunity.1 mRNA vaccines against the spike protein of the ancestral strain of the virus have been reported to induce robust T cell immunity against the omicron variant when examined in healthy individuals. 2 However, the effectiveness of the booster vaccine doses in late-stage lung cancer patients undergoing active anti-PD-1/ PD-L1 agent immunotherapy has yet to be investigated.3 Methods To address this question, we assessed both CD8+ and CD4+ T cell responses using a modified activationinduced marker (AIM) assay that was performed on peripheral blood mononuclear cells (PBMCs), which was coupled with high dimension spectral flow cytometry analyses. The PBMCs were obtained using cryopreserved blood samples collected from The COVID-19 Vaccine Study of Infections and Immune REspoNse (SIIREN) trial, and a total of 51 patient samples (20 non-cancer patients and 31 lung cancer patients) were assessed. Results Our observations included that booster vaccines induced CD8+ T cell response in both non-cancer subjects and lung cancer patients against ancestral strain and omicron variant, while only marginal induction or trend was detected for CD4+ T cells in normal subjects. Pertinent results also consisted of identification of distinct subpopulation dynamics involving varying degrees of differentiation of antigen-specific CD8+ and CD4+ T cells in lung cancer patients compared to non-cancer subjects, thus demonstrating evidence of dysfunction. Another noteworthy finding included the observation of sex biased T cell responses with female lung cancer patients demonstrating more efficient antigen-specific T cell responses compared to males. Conclusions We conclude that lung cancer patients in our study cohort have substantial qualitative deviation in their T cell response to mRNA vaccine from the normal individuals. This altered response may be a consequence of altered T cell differentiation states, resulting in the high degree of heterogeneity of AIM+ T cells identified in booster vaccinated individuals. Moreover, the dampened T cell response to omicron in cancer patients could implicate that less protection was established by vaccination for lung cancer patients, especially given that humoral response is also reduced in cancer patients.4 This further highlights the need for heightened protective measures for cancer patients to minimize the risk of breakthrough infection with the omicron and other future variants of SARS-CoV-2.5.

2.
Stem Cells Translational Medicine ; 11(6):567-571, 2022.
Article in English | EMBASE | ID: covidwho-2161165
3.
Egyptian Pediatric Association Gazette ; 70(1) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2139797

ABSTRACT

Background: Vitamin D is classified as an immunomodulatory hormone that is synthesized because of skin exposure to sunlight. It is known to come into play during the regulation of hormone secretion, immune functions, cell proliferation, and differentiation. Its deficiency can cause many diseases and their associated pleiotropic effects. In addition, in relation to its eminent function as regards adaptive immune response and innate immune response, vitamin D level is associated with immune tolerance. Method(s): Literature search prior to May 2021 was conducted through selected websites, including the MEDLINE, Embase, Web of Science, Cochrane Central, www.ClinicalTrials.gov, PubMed, Science Direct, Google Scholar, and EFSA. Result(s): Vitamin D is found effective for the regulation of hormone secretion, immune functions, and cell proliferation along with differentiation. Its role as an immune modulator is based on the presence of receptors on many immune cells and the synthesis of its active metabolite from these cells. Vitamin D, an immune system modulator, inhibits cell proliferation and stimulates cell differentiation. A fair number of immune system diseases, encompassing autoimmune disorders alongside infectious diseases, can occur because of low serum vitamin D levels. Supplementation of vitamin D has positive effects in lessening the severity nature of disease activity;there exists no consensus on the dose to be used. Conclusion(s): It is figured out that a higher number of randomized controlled trials are essential to evaluate efficacy pertaining to clinical cases, treatment duration, type, and dose of supplementation and pathophysiology of diseases, immune system functioning, and the effect of vitamin D to be administered. Copyright © 2022, The Author(s).

4.
Tissue Engineering - Part A ; 28:391, 2022.
Article in English | EMBASE | ID: covidwho-2062830

ABSTRACT

Purpose/Objectives: Acute and chronic respiratory diseases constitute a substantial socioeconomic burden on a global scale, as made abundantly clear in the last two years with the rampant coronavirus disease 2019 (COVID-19) pandemic. Alas, the development of new therapies for pathological respiratory conditions has been hindered by the inadequacy of current preclinical models, which often fail to provide reliable predictions on drug safety and efficacy in humans. In particular, considerable anatomical and physiological differences between the respiratory systems of commonly used animal models and humans are one of the main issues leading to high drug attrition and clinical failure rates. Accordingly, the generation of physiologically relevant preclinical lung models for early drug development and pharmaceutical research is urgently needed. In this work, poly(ϵ-caprolactone) (PCL) and gelatin were used as raw materials to produce electrospun scaffolds for in vitro lung tissue engineering, in order to generate human biomimetic platforms for preclinical drug safety and efficacy testing. Methodology: PCL and gelatin were mixed at varying volume ratios: 1:0 (PP), 6:1 (PPG61), 4:1 (PPG41), and 2:1 (PPG21), so as to determine the optimal gelatin concentration for cell adhesion and growth. Poly(vinylpyrrolidone) (PVP) was added to every polymer mixture to facilitate the electrospinning process, and electrospun fibrous matrices were fabricated using a needleless electrospinning technique. Scaffold morphology, chemical composition, and wettability were characterized with scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and water contact angle analysis, respectively. Biocompatibility testing was performed using human bronchial (16HBE) and alveolar (A549) epithelial cell lines, consisting of cell metabolic activity, proliferation, and adhesion evaluation over two weeks of in vitro culture. Results: All polymer blends resulted in the formation of electrospun scaffolds with a nanofibrous structure. The addition of gelatin in PPG61 scaffolds improved fiber morphology compared to PP formulations, but increasing proportions of this polymer in PPG41 and PPG21 mats caused a larger number of defects, such as beading and branching. FTIR analysis confirmed the presence of PCL and PVP in PP scaffolds, as well as the addition of gelatin in all PPG blends. Moreover, as expected, all scaffolds were hydrophilic, with water contact angles below 90°, being suitable for protein adsorption and cell adhesion. Regarding 16HBE and A549 cell viability, surprisingly, no major differences were found between the different formulations over the two-week culture period, showing that all polymer blends were equally capable of promoting cell adhesion and growth. While PP scaffolds significantly outperformed PPG electrospun mats in early timepoints, no such differences were identified at the end of the experimental period. Conclusion/Significance: These results suggested that PCL, PVP, and/or gelatin blend electrospun scaffolds are conducive to lung epithelial cell adhesion and proliferation. Nevertheless, further studies investigating epithelial cell differentiation and function should be conducted to fully assess the suitability of these biomaterials as platforms for in vitro lung tissue engineering.

5.
Biochemistry (Mosc) ; 87(9): 916-931, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2038256

ABSTRACT

Endoplasmic reticulum (ER) is a multifunctional membrane-enclosed organelle. One of the major ER functions is cotranslational transport and processing of secretory, lysosomal, and transmembrane proteins. Impaired protein processing caused by disturbances in the ER homeostasis results in the ER stress. Restoration of normal ER functioning requires activation of an adaptive mechanism involving cell response to misfolded proteins, the so-called unfolded protein response (UPR). Besides controlling protein folding, UPR plays a key role in other physiological processes, in particular, differentiation of cells of connective, muscle, epithelial, and neural tissues. Cell differentiation is induced by the physiological levels of ER stress, while excessive ER stress suppresses differentiation and can result in cell death. So far, it remains unknown whether UPR activation induces cell differentiation or if UPR is initiated by the upregulated synthesis of secretory proteins during cell differentiation. Cell differentiation is an important stage in the development of multicellular organisms and is tightly controlled. Suppression or excessive activation of this process can lead to the development of various pathologies in an organism. In particular, impairments in the differentiation of connective tissue cells can result in the development of fibrosis, obesity, and osteoporosis. Recently, special attention has been paid to fibrosis as one of the major complications of COVID-19. Therefore, studying the role of UPR in the activation of cell differentiation is of both theoretical and practical interest, as it might result in the identification of molecular targets for selective regulation of cell differentiation stages and as well as the potential to modulate the mechanisms involved in the development of various pathological states.


Subject(s)
COVID-19 , Endoplasmic Reticulum Stress , Cell Differentiation , Fibrosis , Humans , Unfolded Protein Response
6.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2005865

ABSTRACT

Sparked by the development of genome sequencing technology, the quantity and quality of data handled in immunological research have been changing dramatically. Various data and database platforms are now driving the rapid progress of machine learning for immunological data analysis. Of various topics in immunology, T cell receptor repertoire analysis is one of the most important targets of machine learning for assessing the state and abnormalities of immune systems. In this paper, we review recent repertoire analysis methods based on machine learning and deep learning and discuss their prospects.

7.
Natural Product Communications ; 17(7), 2022.
Article in English | EMBASE | ID: covidwho-1956964

ABSTRACT

Objective: The Chinese herbal formula Huo-Xiang-Zheng-Qi (HXZQ) is effective in preventing and treating coronavirus disease 19 (COVID-19) infection;however, its mechanism remains unclear. This study used network pharmacology and molecular docking techniques to investigate the mechanism of action of HXZQ in preventing and treating COVID-19. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to search for the active ingredients and targets of the 10 traditional Chinese medicines (TCMs) of HXZQ prescription (HXZQP). GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledge Base (PharmGKB), Therapeutic Target Database (TTD), and DrugBank databases were used to screen COVID-19-related genes and intersect them with the targets of HXZQP to obtain the drug efficacy targets. Cytoscape 3.8 software was used to construct the drug-active ingredient–target interaction network of HXZQP and perform protein–protein interaction (PPI) network construction and topology analysis. R software was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, AutoDock Vina was utilized for molecular docking of the active ingredients of TCM and drug target proteins. Results: A total of 151 active ingredients and 250 HXZQP targets were identified. Among these, 136 active ingredients and 67 targets of HXZQP were found to be involved in the prevention and treatment of COVID-19. The core proteins identified in the PPI network were MAPK1, MAPK3, MAPK8, MAPK14, STAT3, and PTGS2. Using GO and KEGG pathway enrichment analysis, HXZQP was found to primarily participate in biological processes such as defense response to a virus, cellular response to biotic stimulus, response to lipopolysaccharide, PI3K-Akt signaling pathway, Th17 cell differentiation, HIF-1 signaling pathway, and other signaling pathways closely related to COVID-19. Molecular docking results reflected that the active ingredients of HXZQP have a reliable affinity toward EGFR, MAPK1, MAPK3, MAPK8, and STAT3 proteins. Conclusion: Our study elucidated the main targets and pathways of HXZQP in the prevention and treatment of COVID-19. The study findings provide a basis for further investigation of the pharmacological effects of HXZQP.

8.
Anti-Infective Agents ; 20(2), 2022.
Article in English | EMBASE | ID: covidwho-1938561

ABSTRACT

Coronavirus disease-2019 (COVID-19) has gained much popularity not only in the Wuhan city of China but internationally also;in January 2020, the corona rapidly spread to many countries like the USA, Italy, Russia, India, Singapore, Pakistan, Thailand, Canada, Australia, England, and so on through passengers traveling to other countries. Corona patients can be cured with synthetic drugs, traditional herbal medicines (THM), use of Vitamin D and the quarantine approach. Different allopathic medicines, herbal extracts, and vitamin D have been observed to be useful in the treatment of novel coronavirus, like Remdesivir, hydroxychloroquine, Teicoplanin, Lopinavir+ Ritonavir, Ribavirin + corticosteroids, Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. Various antiviral drugs are used to treat COVID-19, alone or in combination with other medications like Interferon-α, Lopinavir + Ritonavir, Arbidol, corticosteroids, etc., and some herbal extracts;also quarantine approach and Vitamin D are used that not only cure the infection but also boost up our immunity. For this review article, different papers were searched on Google Scholar, Scopus, WHO’s website, PubMed, clinicaltrials.gov and other relevant scientific research websites. In this review article, we have discussed the current strategies that are being used to treat COVID-19. Along with allopathic drugs, some herbal extracts can also be used to treat this novel coronavirus, like Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. and even vitamin D.

9.
Prescriber ; 33(6):13-16, 2022.
Article in English | EMBASE | ID: covidwho-1913876

ABSTRACT

CRISPR is a gene editing technique that has revolutionised research and has the potential to transform the treatment of many diseases. This article discusses the principles of the technique, its therapeutic applications and potential safety issues.

10.
Topics in Antiviral Medicine ; 30(1 SUPPL):116-117, 2022.
Article in English | EMBASE | ID: covidwho-1881009

ABSTRACT

Background: SARS-CoV-2 induces cytokine response dysregulation and immune dysfunction. What remains unclear is how cytokine signaling shapes immune responses during early SARS-CoV-2 infection when adaptive immunity is developing. Our goal is to identify immune pathways that shape the early development of adaptive immune responses in COVID-19 patients. We performed paired single-cell transcriptomic and epigenomic profiling at two time-points of early SARS-CoV-2 infection to determine immune signatures of acute infection and epigenetic drivers that underpin immune response dynamics. Methods: PBMC samples were collected from four moderate to severe COVID-19 patients at two early time-points (n = 3 for Week 1 and n = 3 for Week 2 after symptom onset, including 2 participants having paired blood sampling at both time points) and from two healthy controls (n = 2). Using paired scRNA-Seq and scATAC-Seq, we captured transcriptomic and epigenomic profiles in the same single cells to identify chromatin accessibility changes as a potential mechanism for the surge and decline of immune responses elicited during acute SARS-CoV-2 infection. Using bioinformatic approaches, we identified heterogeneous immune cell populations, modeled cell differentiation trajectories, determined dysregulated immune pathways through gene set enrichment analysis, and connected chromatin co-accessible landscapes. Results: We captured transcriptomic and epigenomic profiles of 43,726 single cells and identified paired transcriptional and epigenetic landscapes in six major immune cell types: CD4+ T cells, CD8+ T cells, B cells, dendritic cells, monocytes, and NK cells. We found that early SARS-CoV-2 infection induced a surge in IL-2, IL-6, IFN-α, IFN-γ, TNF-α, and NF-κB responses at Week 1 that declined at Week 2 in adaptive immune cells (CD4+ T, CD8+ T, and B cells). In contrast, TGF-β responses surged early at Week 1 and continued to increase at Week 2 in these cells. In B cells and plasmablasts, we found early surges of IGHA1 (encoding IgA heavy chain) and SOX4 (an essential transcription factor for B cell development) expressions that correlated with expression of SMAD-dependent TGF-β signaling pathway. Further, we found a notable increase in chromatin accessibility at the SMAD binding regulatory element 150 kb upstream of SOX4 in B cells of infected patients. Conclusion: Our data suggest a significant increase in TGF-β activity that instructs dynamic B cell-associated protective immunity during early SARS-CoV-2 infection.

11.
Molecules ; 27(10)2022 May 23.
Article in English | MEDLINE | ID: covidwho-1875718

ABSTRACT

(1) Background: A novel bioreactor platform of neuronal cell cultures using low-magnitude, low-frequency (LMLF) vibrational stimulation was designed to discover vibration influence and mimic the dynamic environment of the in vivo state. To better understand the impact of 40 Hz and 100 Hz vibration on cell differentiation, we join biotechnology and advanced medical technology to design the nano-vibration system. The influence of vibration on the development of nervous tissue on the selected cell line SH-SY5Y (experimental research model in Alzheimer's and Parkinson's) was investigated. (2) Methods: The vibration stimulation of cell differentiation and elongation of their neuritis were monitored. We measured how vibrations affect the morphology and differentiation of nerve cells in vitro. (3) Results: The highest average length of neurites was observed in response to the 40 Hz vibration on the collagen surface in the differentiating medium, but cells response did not increase with vibration frequency. Also, vibrations at a frequency of 40 Hz or 100 Hz did not affect the average density of neurites. 100 Hz vibration increased the neurites density significantly with time for cultures on collagen and non-collagen surfaces. The exposure of neuronal cells to 40 Hz and 100 Hz vibration enhanced cell differentiation. The 40 Hz vibration has the best impact on neuronal-like cell growth and differentiation. (4) Conclusions: The data demonstrated that exposure to neuronal cells to 40 Hz and 100 Hz vibration enhanced cell differentiation and proliferation. This positive impact of vibration can be used in tissue engineering and regenerative medicine. It is planned to optimize the processes and study its molecular mechanisms concerning carrying out the research.


Subject(s)
Neurons , Vibration , Cell Cycle , Cell Differentiation , Cell Proliferation
12.
British Journal of Haematology ; 197(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1856858

ABSTRACT

The proceedings contain 252 papers. The topics discussed include: immunogenicity of Covid-19 vaccination in patients with myelodysplastic syndromes;antibody responses to SARS-CoV-2 vaccination in patients with acute leukemia and high-risk MDS on active anti-cancer therapies;CD9 derepression drives cellular differentiation and restores immune recognition in pediatric acute myeloid leukemia;follow-up of patients with FLT3-mutated relapsed or refractory acute myeloid leukemia in the phase 3 ADMIRAL trial;efficacy and safety of Maribavir as a rescue treatment for investigator assigned therapy in transplant recipients with refractory or resistant cytomegalovirus infections in the SOLSTICE study: phase 3 trial results;long-term survival benefit of eculizumab treatment in patients with paroxysmal nocturnal hemoglobinuria: data from the international PNH registry;and analysis of anemia persistence and related adverse events in patients with paroxysmal nocturnal hemoglobinuria treated with pegcetacoplan.

13.
Front Cell Dev Biol ; 10: 818616, 2022.
Article in English | MEDLINE | ID: covidwho-1817932

ABSTRACT

Urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycosyl-phosphatidyl-inositol anchored (GPI) membrane protein. The uPAR primary ligand is the serine protease urokinase (uPA), converting plasminogen into plasmin, a broad spectrum protease, active on most extracellular matrix components. Besides uPA, the uPAR binds specifically also to the matrix protein vitronectin and, therefore, is regarded also as an adhesion receptor. Complex formation of the uPAR with diverse transmembrane proteins, including integrins, formyl peptide receptors, G protein-coupled receptors and epidermal growth factor receptor results in intracellular signalling. Thus, the uPAR is a multifunctional receptor coordinating surface-associated pericellular proteolysis and signal transduction, thereby affecting physiological and pathological mechanisms. The uPAR-initiated signalling leads to remarkable cellular effects, that include increased cell migration, adhesion, survival, proliferation and invasion. Although this is beyond the scope of this review, the uPA/uPAR system is of great interest to cancer research, as it is associated to aggressive cancers and poor patient survival. Increasing evidence links the uPA/uPAR axis to epithelial to mesenchymal transition, a highly dynamic process, by which epithelial cells can convert into a mesenchymal phenotype. Furthermore, many reports indicate that the uPAR is involved in the maintenance of the stem-like phenotype and in the differentiation process of different cell types. Moreover, the levels of anchor-less, soluble form of uPAR, respond to a variety of inflammatory stimuli, including tumorigenesis and viral infections. Finally, the role of uPAR in virus infection has received increasing attention, in view of the Covid-19 pandemics and new information is becoming available. In this review, we provide a mechanistic perspective, via the detailed examination of consolidated and recent studies on the cellular responses to the multiple uPAR activities.

14.
Science ; 373(6558):977.21-979, 2021.
Article in English | EMBASE | ID: covidwho-1769814
15.
Science ; 373(6558):977.19-979, 2021.
Article in English | EMBASE | ID: covidwho-1769813
16.
Science ; 373(6558):977.13-979, 2021.
Article in English | EMBASE | ID: covidwho-1769812
17.
Science ; 373(6558):977.12-979, 2021.
Article in English | EMBASE | ID: covidwho-1769811
18.
Science ; 373(6558):977.7-978, 2021.
Article in English | EMBASE | ID: covidwho-1769810
19.
Science ; 373(6558):977.6-978, 2021.
Article in English | EMBASE | ID: covidwho-1769809
20.
Science ; 373(6558):977.4-978, 2021.
Article in English | EMBASE | ID: covidwho-1769808
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