Showing papers in "Immunological Investigations in 2021"

NLR: A Cost-effective Nomogram to Guide Therapeutic Interventions in COVID-19.

Abstract: COVID-19 exhibits a non-yet elucidated heterogeneity dominated by mild form of the illness. Nevertheless, mortality is frequent among patients with a delayed innate immune response that suddenly exacerbates during the second week after admission leading to a lethal over inflammation. Therefore, this rapid and unpredictable deterioration requires timely prediction of COVID-19 refractoriness and critical illness. The two biomarkers readily available in routine laboratories, blood lymphocytes and neutrophil counts, are expected to provide an accurate clinical tool to incline reasonable medication and care because lymphopenia marks immune exhaustion while neutrophilia demonstrates the immunological exuberation. Meanwhile, combining the two parameters as a Neutrophil-to-lymphocyte ratio (NLR) helps to constitute a powerful predictive and prognostic nomogram. This scoring tool allows clinicians to stratify COVID-19 severities on admission and guide early interventions to accelerate recovery and shorten the course of disease in order to alleviate the shortage of medical resources and reduce mortality.

Overexpression of lncRNA HULC Attenuates Myocardial Ischemia/reperfusion Injury in Rat Models and Apoptosis of Hypoxia/reoxygenation Cardiomyocytes via Targeting miR-377-5p through NLRP3/Caspase‑1/IL‑1β Signaling Pathway Inhibition.

Abstract: Objective Acute myocardial infarction (AMI) is characterized by myocardial tissue necrosis and activation of inflammatory response. This study aims to elucidate the potential mechanism underlying the protective effects of long non-coding RNA (lncRNA) highly up-regulated in liver cancer (HULC) against myocardial ischemia/reperfusion (I/R) injury in rat models and apoptosis of cardiomyocytes. Methods We firstly established rat models of myocardial I/R injury and rat cardiomyocyte (H9c2 cells) models of hypoxia/reoxygenation (H/R) injury. Sprague-Dawley (SD) neonatal rats were randomized into four groups: sham, I/R, I/R+ microRNA (miR) -377-5p mimic, and I/R+ miR-377-5p antagomir, respectively. Then, histopathological examination was applied. Apoptosis was evaluated by transferase-mediated dUTP nick end labeling (TUNEL) staining. Cell vitality was measured using MTT assay. The concentrations of creatine kinase MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL) -6 (IL-6), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The expression of Cleaved-Caspase-3, Caspase-3, NOD-like receptor P3 (NLRP3), Caspase-1, and IL-1β was analyzed by immunohistochemical (IHC) or Western blot analysis. Results We found that HULC was downregulated and miR-377-5p was upregulated in IR-injured myocardial tissue and the H/R-induced H9c2 cell. Overexpression of miR-377-5p increased myocardial dysfunction and apoptosis and activated formation and secretion of IL-6 and TNF-α. The preprocessing of miR-377-5p silencing emerged opposite results. Strikingly, dual luciferase reporter assay showed that HULC was a sponge of miR-377-5p. Subsequently, mechanism experiments revealed that NLRP3/Caspase‑1/IL‑1β was a target axis of miR-377-5p. In vitro, the protective effect of HULC overexpression on H9c2 cell viability and inflammation was offset by miR-377-5p silencing. Finally, rescue assay suggested that HULC-miR-377-5p -NLRP3/Caspase‑1/IL‑1β axis regulated the apoptosis and inflammation of H/R-induced H9c2 cells. Conclusions Overall, these results indicate that the protective effect of HULC against myocardial I/R injury and H/R cardiomyocyte apoptosis partially relies on the inhibition of NLRP3/Caspase‑1/IL‑1β signaling pathway.

Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.

Abstract: Background Biological agents are commonly used for the treatment of ulcerative colitis (UC). As new treatments, tofacitinib, and fecal microbiota transplantation (FMT) have demonstrated efficacy in treating UC. This network meta-analysis aims to determine the efficacy and safety of biological agents, tofacitinib, and FMT. Methods A network meta-analysis was conducted by systematically searching the PubMed, Embase, and Cochrane Libraries. According to strict inclusion and exclusion criteria, we included randomized controlled trials (RCTs) of biological agents, tofacitinib, and FMT in UC. A random-effect model was chosen by the network meta-analysis and sensitivity analysis. Heterogeneity test and publication bias test were performed to determine the efficacy of treatments. Results Data were extracted from 16 RCTs and we found that all treatments were more effective than the placebos. A total of 21 comparisons were made to determine efficiency. We found that infliximab, vedolizumab, and FMT performed better curative effect in terms of absolute effects and relative ranks. Furthermore, there was no statistical difference in the efficacy of biological agents, tofacitinib, and FMT. Moreover, no treatments were found to increase the occurrence of adverse events when compared with placebos, except infliximab. However, vedolizumab seemed to reduce the occurrence of adverse events compared with infliximab. Conclusion Of the biological agents, vedolizumab and infliximab were the most effective, suggesting that biological agents are still a better choice. Nevertheless, tofacitinib and FMT may be promising alternatives with high efficacies. However, more safety and maintenance studies need to be conducted in future for the acquisition of more accurate results.Abbreviations: FMT: Fecal microbiota transplantation; UC: Ulcerative colitis; RCTs: Randomized controlled trials; IBD: Inflammatory bowel disease; CD: Crohn's disease; IBS: Irritable bowel syndrome; CDI: Clostridium difficile infections; ITT: Intention-to-treat; RR: Relative risk; CI: Confidence interval; CrI: Credible intervals; IFX: Infliximab; ADA: Adalimumab; TFB: Tofacitinib; GLM: Golimumab; VDZ: Vedolizumab; PBO: Placebo; wk: week; F: Female; M: Male; AEs: Adverse events; SAEs: Serious adverse events; anti-TNF: Anti-tumor necrosis factors.

Neutrophil Extracellular Trapping Network Promotes the Pathogenesis of Neutrophil-associated Asthma through Macrophages

Abstract: Asthma is a complex airway inflammatory disease that can be roughly classified into eosinophilic phenotype and non-eosinophilic phenotype Most of the latter manifested as airway inflammation dominated by neutrophil infiltration, namely neutrophil-dominated asthma (NA) Neutrophil extracellular trapping (NETs) is a newly discovered antimicrobial mechanism of neutrophils; however, NETs can not only resist killing pathogenic microorganisms, but also promote tissue damage and autoimmune response In the present study, we successfully established NA model in C57BL/6 mice and observed the increased formation of NETs In NA mice, the free DNA abundance, the airway resistance, the cell numbers (total cell number, macrophage number, and neutrophil number), and inflammatory cytokine levels were significantly increased while the lung dynamic compliance was significantly reduced After DNase I treatment, the above indexes in NA mice were all improved In NA mice, either treatment with macrophage scavenger or IL-1β neutralizing antibody also improved the above-described indexes In vitro, in human peripheral blood-derived neutrophils, PMA treatment significantly increased the formation of NETs Furthermore, in macrophages differentiated from THP-1 monocytes, LPS or isolated NETs both significantly increased the levels of cytokines In conclusion, NETs can stimulate macrophages to secrete IL-1β, which promotes neutrophils infiltration in the airway; infiltrated neutrophils, in turn, generates NETs, which can amplify the tissue damage caused by NETs and macrophages, inducing and aggravating NA

Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients

Abstract: Objectives: Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement caused by homozygous or compound heterozygous mutations in the ataxia telan...

A Review of Immunomodulatory Effects of Fluoroquinolones.

Abstract: Past researches indicate that some types of antibiotics, apart from their antimicrobial effects, have some other important effects which indirectly are exerted by modulating and regulating the immune system's mediators. Among the compounds with antimicrobial effects, fluoroquinolones (FQs) are known as synthetic antibiotics, which exhibit the property of decomposing of DNA and prevent bacterial growth by inactivating the enzymes involved in DNA twisting, including topoisomerase II (DNA gyrase) and IV. Interestingly, immune responses are indirectly modulated by FQs through suppressing pro-inflammatory cytokines, such as interleukin 1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α), and super-inducing IL-2, which tend to increase both the growth and activity of T and B lymphocytes. In addition, they affect the development of immune responses by influencing of expression of other cytokines and mediators. This study aims to review past research on the immunomodulatory effects of FQs on the expression of cytokines, especially IL-2 and to discuss controversial investigations.

Application of Emerging Plant-Derived Nanoparticles as a Novel Approach for Nano-Drug Delivery Systems.

Abstract: Nanotechnology has enabled the delivery of small molecular drugs packaged in nanosized vesicles to the target tissues. Plant-Derived Nanoparticles (PDNPs) are vesicles with natural origin and unique properties. These nanoparticles have several advantages over synthetic exosomes and liposomes. They provide bioavailability and biodistribution of therapeutic agents when delivered into different tissues. These nanoparticles can be modified according to the specificity of their functions in target tissues. When PDNPs are internalized, they can induce stem cells proliferation, reduce colitis injury, activate intrinsic and extrinsic apoptosis pathways, and inhibit tumor growth and progression. These properties make them potential drug delivery systems in targeting diseased tissues, such as inflammatory regions and different cancers.

Wharton’s Jelly Mesenchymal Stem Cells Exosomes and Conditioned Media Increased Neutrophil Lifespan and Phagocytosis Capacity

Abstract: Neutrophils are the first cells involved in inflammation and pathogen elimination, but they have a short lifespan. So, strategies for enhancing neutrophil lifespan and activities can be useful in many situations such as patients with immunodeficiencies. Previous researches demonstrated that mesenchymal stem cell (MSC) has anti-apoptotic effects on neutrophils. These multipotent cells have immunomodulatory properties and can be isolated from different tissues. MSCs isolated from Wharton's jelly (WJ-MSCs), a mucosal connective tissue of the umbilical cord, may be better candidates than MSCs obtained from bone marrow or adipose tissue, because WJ-MSCs are younger and protected from damages that are resulted from aging, environmental toxins, and diseases. In addition, they have high proliferative capacity, easier accessibility, and more abundance. It was shown that following in vitro expansion, they are more effective than other sources of MSCs. Cell to cell contact or secretion of soluble factors and exosomes are the main approaches of MSCs in applying their effects. Exosomes and conditioned media (CM) were prepared from WJ-MSCs. Then, neutrophils were isolated and cultured with medium, CM, or exosomes. Then, neutrophil respiratory burst, apoptosis, and phagocytosis capacity were assessed by NBT assay, Annexin V-PI method, and Giemsa staining, respectively. Both treatments improved neutrophil lifespan and phagocytosis. Only MSC-CM could enhance neutrophil respiratory burst. This research demonstrated that MSC-exosomes and CM have protective effects on neutrophil function and lifespan. It can be concluded that MSC mediators can be responsible factors for protective functions of MSCs on neutrophils.

Immunological role of IgG subclasses

Abstract: The loss of tolerance to self-antigens is the unequivocal "red line" of autoimmunity: both development of autoreactive T and B cells and production of polyclonal autoantibodies represent seminal keys to the pathogenesis of protean autoimmune diseases. Most of these autoantibodies are immunoglobulins G (IgG), functionally distinguished in four subclasses named IgG1, IgG2, IgG3, and IgG4, due to structural differences in the hinge and heavy chain constant regions. Different studies analyzed serum levels of IgG subclasses in the course of different disorders, showing that they might have a pathogenic role by regulating interactions among immunoglobulins, Fc-gamma receptors, and complement. To date, the mechanisms promoting different IgG subclasses distribution during the natural history of most autoimmune diseases remain somewhat unclear. Evidence from the medical literature shows that the serum IgG profile is peculiar for many autoimmune diseases, suggesting that different subclasses could be specific for the underlying driving autoantigens. A better knowledge of IgG subsets may probably help to elucidate their pathological task, but also to define their relevance for diagnostic purposes, patients' personalized management, and prognosis assessment.

Intranodal Administration of Neoantigen Peptide-loaded Dendritic Cell Vaccine Elicits Epitope-specific T Cell Responses and Clinical Effects in a Patient with Chemorefractory Ovarian Cancer with Malignant Ascites

Abstract: Chemorefractory ovarian cancer has limited therapeutic options. Hence, new types of treatment including neoantigen-specific immunotherapy need to be investigated. Neoantigens represent promising ta...

Upregulation of TIGIT and PD-1 in Colorectal Cancer with Mismatch-repair Deficiency

Abstract: Background: The role of T cell Ig and ITIM domain (TIGIT) and programmed cell death-1 (PD-1) in colorectal cancer (CRC) with mismatch repair deficiency is unknown.Methods: This was a study of 60 CR...

Activated γδ T Cells Promote Dendritic Cell Maturation and Exacerbate the Development of Experimental Autoimmune Uveitis (EAU) in Mice.

Abstract: Our previous study reveals that gamma delta (γδ) T cells were activated and dendritic cells (DCs) underwent maturation during the inflammation phase in experimental autoimmune uveitis (EAU) mice, and the interaction between DCs and γδ T cells may significantly exacerbate the development of EAU. However, the interactions between DCs and γδ T cells that can affect DCs maturation to influence EAU development must be further addressed. In this study we showed that mature DC numbers in TCR-δ-/- (KO) EAU mice were lower than those in wild-type (WT) C57BL/6 (B6) mice. The γδ T cells harvested from WT EAU mice secreted more interferon-γ (IFN-γ), however, after blocking IFN-γ, the maturation of DCs was significantly downregulated. By contrast, the percentage of IFN-γ- and IL-17-producing CD4+ T cells in KO EAU mice decreased to a greater extent than that in WT EAU mice during the inflammatory phase. Additionally, the levels of IFN-γ/IL-17 in serum were in agreement with those of CD4+ T cells. Furthermore, after activated γδ T cells injection, the inflammatory symptoms of EAU mice were more aggravated. In vitro co-cultures of both cell types showed that activated γδ T cells may induce DCs to generate higher levels of intracellular cell adhesion molecule-1 (ICAM-1/CD54), CD80, CD83, and CD86. Moreover, co-culture of the two cells may induce the activation of CD4+ T cells. Taken together, our results demonstrated that activated γδ T cells may promote DCs maturation and further enhance the generation of Th1/Th17 cells in EAU mice, resulting in exacerbated EAU.

B Cell Response to Vaccination.

Abstract: As one of the most important weapons against infectious diseases, vaccines have saved countless lives since their first use in the late eighteenth century. Antibodies produced by effector B cells upon vaccination play a critical role in mediating protection. The past several decades of research have led to a revolution in our understanding of B cell response to vaccination. Vaccines against SARS-CoV-2 coronavirus were developed at an unprecedented speed to power our global fight against COVID-19 pandemic. Nevertheless, we still face many challenges in the development of vaccines against many other deadly viruses, such as human immunodeficiency virus (HIV) and influenza virus. In this review, we summarize the latest findings on B cell response to vaccination and pathogen infection. We also discuss the current challenges in the field and the potential strategies targeting B cell response to improve vaccine efficacy.Key abbreviations box: BCR: B cell receptor; bNAb: broadly neutralizing antibody; DC: dendritic cells; DZ: dark zone; EF response: extrafollicular response; FDC: follicular dendritic cell; GC: germinal center; HIV: human immunodeficiency virus; IC: immune complex; LLPC: long-lived plasma cell; LZ: light zone; MBC: memory B cell; SLPB: short-lived plasmablast; TFH: T follicular helper cells; TLR: Toll-like receptor.

Successful Treatment of Covid-19 Associated Cytokine Release Syndrome with Colchicine. A Case Report and Review of Literature.

Abstract: We describe the case of a 42 year old, healthy patient with Covid-19 who despite improvement in his respiratory symptoms developed a mild to moderate cytokine release syndrome (CRS) and an associated monoarticular gout flare. Since the patient refused admission to the hospital and had stable vital signs, we chose to treat him with a safe anti-inflammatory and non-immunosuppressive therapy. To hit two birds with one stone, we considered colchicine, as it has systemic anti-inflammatory effects and is also effective in gout flare. Unexpectedly, 48 hours after treatment, not only did his ongoing fever and toe pain disappear, he also had significant improvements in his general state of health and all his inflammatory markers including fibrinogen, ferritin, D-dimer, and IL-6 levels normalized. To our knowledge, the use of colchicine in Covid-19 and CRS has not been reported. This observation merits the consideration of colchicine as a safe, inexpensive and oral medication for the treatment of mild to moderate CRS in Covid-19 patients. More importantly, in Covid-19 patients with early lung involvement colchicine may be an appropriate candidate to prevent CRS in adjunction with routine antiviral agents. Indeed, multicenter, randomized controlled studies are required to evaluate the benefits of this therapy.

Endometriosis: What is the Influence of Immune Cells?

Abstract: Background: Endometriosis does not have a well-established physiopathology. It has been addressed that endometriosis is an inflammatory disease, where endocrine-immunological interactions are probably involved in the pathogenesis of the disease. The role of the immune system in endometriosis has been suggested to play an important role in both initiation and progression of the disease.Methods: A search for the following keywords was performed in the PubMed database: "endometriosis", "endometriosis and ovarian cancer", "endometriosis and immunology", and "endometriosis and cytokines".Results: The articles identified were published in English between 1921 and 2020. We selected 100 articles for further analysis.Conclusion: The recognition of the direct involvement of these two important physiological mechanisms causes a change in the pathophysiological focus of the disease. Researching the activities of numerous cells involved in immune reactions may offer new therapeutic targets.

Pharmaceutical Aspects and Clinical Evaluation of COVID-19 Vaccines

Abstract: COVID-19, the disease caused by the novel severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), was first detected in December 2019 and has since morphed into a global pandemic claiming over 2.4 million human lives and severely impacting global economy. The race for a safe and efficacious vaccine was thus initiated with government agencies as well as major pharmaceutical companies as frontrunners. An ideal vaccine would activate multiple arms of the adaptive immune system to generate cytotoxic T cell responses as well as neutralizing antibody responses, while avoiding pathological or deleterious immune responses that result in tissue damage or exacerbation of the disease. Developing an effective vaccine requires an inter-disciplinary effort involving virology, protein biology, biotechnology, immunology and pharmaceutical sciences. In this review, we provide a brief overview of the pathology and immune responses to SARS-CoV-2, which are fundamental to vaccine development. We then summarize the rationale for developing COVID-19 vaccines and provide novel insights into vaccine development from a pharmaceutical science perspective, such as selection of different antigens, adjuvants, delivery platforms and formulations. Finally, we review multiple clinical trial outcomes of novel vaccines in terms of safety and efficacy.

Fibroblast-like Synoviocytes-derived Exosomal PCGEM1 Accelerates IL-1β-induced Apoptosis and Cartilage Matrix Degradation by miR-142-5p/RUNX2 in Chondrocytes.

Abstract: Background: Long non-coding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) has been revealed to participate in the pathogenesis of osteoarthritis (OA). However, the molecular mechanism of PCGEM1 regulating OA progression has not been fully elucidated.Methods: Fibroblast-like synoviocytes (FLSs) were isolated from synovium tissues of OA patients (OA-FLSs) and trauma donors (Normal-FLSs). The size and morphology of the isolated exosomes were analyzed by transmission electron microscopy and nanoparticle tracking analysis. Protein levels were analyzed by western blotting. Expression levels of PCGEM1, microRNA-142-5p (miR-142-5p), runt-related transcription factor 2 (RUNX2) mRNA, and OA related genes were assessed by qRT-PCR. Cell proliferation, viability, and apoptosis were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide or flow cytometry assays. The relationship between miR-142-5p and PCGEM1 or RUNX2 was verified by dual-luciferase reporter and/or RNA pull down assays.Results: PCGEM1 was overexpressed in OA cartilages and exosomes from OA-FLSs. Exosomal PCGEM1 from OA-FLSs facilitated IL-1β-induced apoptosis and cartilage matrix degradation in chondrocytes. MiR-142-5p was downregulated while RUNX2 was upregulated in OA cartilages. Exosomal PCGEM1 from OA-FLSs regulated RUNX2 expression by sponging miR-142-5p in IL-1β-induced chondrocytes. MiR-142-5p inhibitor offset exosomal PCGEM1 knockdown-mediated effects on the apoptosis and cartilage matrix degradation of IL-1β-induced chondrocytes. RUNX2 overexpression counteracted the suppressive effect of miR-142-5p mimic on apoptosis and cartilage matrix degradation of IL-1β-induced chondrocytes.Conclusion: Exosomal PCGEM1 from OA-FLSs facilitated IL-1β-induced apoptosis and cartilage matrix degradation in chondrocytes by sequestering miR-142-5p and upregulating RUNX2, which offered new insights into the pathogenesis of OA.

Associations between Gene Polymorphisms in Pro-inflammatory Cytokines and the Risk of Inflammatory Bowel Disease: A Meta-analysis.

Abstract: The relationships between polymorphisms in pro-inflammatory cytokines and the risk of inflammatory bowel disease (IBD) remain discrepant. Therefore, the authors conducted a meta-analysis to robustly explore relationships between polymorphisms in pro-inflammatory cytokines and the risk of IBD by integrating the results of previous works. Medline, Embase, Wanfang, VIP and CNKI were searched throughly for eligible studies, and 35 genetic association studies were finally included in this meta-analysis. We noticed that genotypic frequencies of IL-1B rs1143627, IL-6 rs1800795 and IL-8 rs4073 polymorphisms among cases with IBD and population-based controls differed significantly. Moreover, we found that genotypic frequencies of IL-1B rs1143627 and IL-6 rs1800795 polymorphisms among cases with IBD and population-based controls of Caucasian origin differed significantly, whereas genotypic frequency of IL-8 rs4073 and IL-18 rs187238 polymorphisms among cases with IBD and population-based controls of Asian origin also differed significantly. Furthermore, we also noticed that genotypic frequency of IL-18 rs187238 polymorphism among cases with Crohn's disease (CD) and population-based controls differed significantly. In conclusion, this meta-analysis demonstrated that IL-1B rs1143627 and IL-6 rs1800795 polymorphisms were significantly associated with the risk of IBD in overall population and Caucasians. Moreover, IL-8 rs4073 polymorphism was significantly associated with the risk of IBD in overall population and Asians. In addition, we also noticed that IL-18 rs187238 polymorphism was significantly associated with the risk of CD, and IL-18 rs1946518 polymorphism was significantly associated with the risk of IBD in Asians.

Association between IFN-λ 3 Gene Polymorphisms and Outcome of Treatment with Direct Acting Antivirals in Chronic HCV-Infected Egyptian Patients.

Abstract: Background: Single nucleotide polymorphisms (SNPs) of the interferon lambda 3 (IFN-λ 3) gene are associated with viral clearance and treatment response in chronic hepatitis C virus (HCV) infection. Aim: to assess whether specific IFN-λ 3 gene SNP, known as rs12979860 (C > T), could predict the outcome of treatment with direct acting antivirals (DAAs) among Egyptian patients with chronic HCV genotype 4 infection. Methods: Tetra-primer (ARMS-PCR) and PCR-RFLP methods were used for SNP genotyping in 100 chronic HCV-infected patients and 50 healthy subjects as control group. Results: The CC (wild type) genotype of rs12979860 was identified in 20 patients, 50% of them achieved sustained virological response (SVR). SNP genotype TT was found in 17 patients and only 2 of them (11.76%) were responders. The frequency of CT genotypes was significantly higher in responders than in non-responders (p= .021). In contrast, the frequency of TT genotypes was significantly higher in non-responders (42.85%, p< .001). On univariate and multivariate logistic regression analyses of the significant predictors of SVR, there were six predictive factors (Age, diabetes mellitus, AST, albumin, type of therapy and IFN-λ 3 genotype). Conclusion: The TT genotype and T allele were significantly associated with failure to achieve SVR. However, CT genotype of IFN-λ 3 (rs12979860) may be considered as a predictor for SVR in patients who received DAAs.

SARS-CoV-2: Unique Challenges of the Virus and Vaccines.

Abstract: In November 2019, the highly infectious coronavirus SARS-CoV-2 emerged in Wuhan, China, and has since spread to almost all countries worldwide. Since its emergence, the COVID-19 infection has led to significant public health, economic and social problems. The current pandemic has inspired researchers to make every effort to design and develop an effective COVID-19 vaccine to provide sufficient protection against the virus and control the infection. In December 2020, the Pfizer vaccine was the first COVID-19 vaccine given Emergency Use Authorization (EUA), and the second FDA so-approved vaccine was the Moderna mRNA-1273 vaccine, which was introduced a week later. Both Pfizer and Moderna vaccines are mRNA-based vaccines, and are estimated to have an efficacy rate of more than 94%. The aim of this article is to provide a review of the attempts made to develop safe SARS-CoV-2 vaccines, highlighting potential challenges and concerns, such as disease enhancement, virus mutations, and public acceptance of the vaccine.

Antioxidant and Immunomodulatory Properties of Partially purified Exopolysaccharide from Lactobacillus Casei Isolated from Chinese Northeast Sauerkraut

Abstract: Background: Exopolysaccharides (EPS) from Lactobacillus spp. have been found to have biological activities. Our previous work demonstrated the antibiofilm activity of EPS from Lactobacillus casei N...

Association of Polymorphisms in Cytokine genes with susceptibility to Precancerous Lesions and Cervical Cancer: A systematic review with meta-analysis.

Abstract: Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical canc...

TIGIT and CD155 as Immune-Modulator Receptor and Ligand on CD4 + T cells in Preeclampsia Patients.

Abstract: One of the main characteristics of preeclampsia (PE) is systemic inflammation. CD4+ FoxP3+ cells play a critical role in both fetomaternal tolerance and successful pregnancy. T-cell immunoglobulin,...

Serum Levels of Hepcidin in Rheumatoid Arthritis and Its Correlation with Disease Activity and Anemia: A Meta-analysis

Abstract: Present studies on serum hepcidin levels in patients with rheumatoid arthritis (RA) are inconsistent. We aimed to synthetically evaluate the relationship between hepcidin and RA, and the correlation of serum hepcidin levels and RA disease activity as well as anemia associated with RA. Multiple electronic databases were searched. Pooled standard mean difference (SMD) with 95% confidence interval (CI) and correlation coefficients between hepcidin levels and rheumatoid factor (RF), disease activity for 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) were calculated. Totally, 13 articles were available for this meta-analysis. The results revealed that serum levels of hepcidin were higher in RA patients compared to healthy controls (SMD = 0.573, 95% CI = 0.317 to 0.829, p < .001); RA patients with anemia had higher serum hepcidin levels than RA patients without anemia (SMD = 0.400, 95% CI = 0.080 to 0.720, p = .014); RA patients with pure ACD had higher serum hepcidin levels than RA patients with ACD and IDA (SMD = 0.658, 95% CI = 0.018 to 1.299, p = .044). Moreover, the result of correlation coefficients identified a significant positive correlation between hepcidin levels and RF, DAS28 as well as ESR. Serum hepcidin levels may be closely associated with the development of RA.

Modulation of Th17 Proliferation and IL-17A Gene Expression by Acetylated Form of Apigenin in Patients with Multiple Sclerosis

Abstract: The presence of Th17 cells in CNS lesion of MS patients due to their inflammatory cytokines secretion is in line with the deterioration of the disease. Currently, the use of natural compounds with ...

Dendritic Cells Currently under the Spotlight; Classification and Subset Based upon New Markers.

Abstract: Dendritic cells (DCs) are considered as a subset of mononuclear phagocytes that composed of multiple subsets with distinct phenotypic features DCs play crucial roles in the initiation and modulation of immune responses to both allo- and auto-antigens during pathogenic settings, encompassing infectious diseases, cancer, autoimmunity, transplantation, as well as vaccination DCs play a role in preventing autoimmunity via inducing tolerance to self-antigens This review focus on the most common subsets of DCs in human Owing to the low frequencies of DC cells in blood and tissues and also the lack of specific DC markers, studies of DCs have been greatly hindered Human DCs arise by a dedicated pathway of lympho-myeloid hematopoiesis and give rise into specialized subtypes under the influence of transcription factors that are specific for each linage In humans, the classification of DCs has been generally separated into the blood and cutaneous subsets, mainly because these parts are more comfortable to examine in humans

Better, Faster, Stronger: mRNA Vaccines Show Promise for Influenza Vaccination in Older Adults.

Abstract: Older adults have diminished immune responses that lead to increased susceptibility and severity of infectious diseases. Influenza is a leading killer of older adults despite the availability of seasonal influenza vaccination. Influenza vaccines are strain specific, and their efficacy varies greatly year to year based on how well the vaccine virus matches the circulating strains. Additionally, older adults have reduced vaccination responses. The COVID-19 pandemic highlighted the increased mortality rate in older adults for infectious disease, and brought vaccine development to the forefront. The speed of vaccine development was met with an equally impressive vaccine efficacy. Interestingly, both mRNA-based COVID-19 vaccines currently available have shown similar efficacy in both young and older adults. mRNA vaccine production has significantly reduced the production timeline compared to current influenza vaccines, making them particularly attractive for influenza vaccine development. Faster production coupled with improved efficacy would be a tremendous advancement in protecting older adults from influenza morbidity and mortality.

Fetomaternal Immune Tolerance: Crucial Mechanisms of Tolerance for Successful Pregnancy in Humans

Abstract: For many years, the question of how the maternal immune system tolerates the foreign fetus has remained unanswered, and numerous studies have considerably attempted to elucidate underlying mechanisms for fetomaternal tolerance. This review aimed at discussing various significant mechanisms in fetomaternal compatibility. At the fetomaternal interface, in addition to having efficient control against infections, innate and adaptive maternal immune systems selectively prevent fetal rejection. In general, understanding the complex mechanisms of fetomaternal tolerance is critical for immunologic tolerance induction and spontaneous abortion prevention in high-risk populations. Different cells and molecules, such as regulatory T-cells, dendritic cells, decidua cells, IDO, Class I HLA molecules, TGF-β, and IL-10, induce maternal immune tolerance in the fetus in numerous ways. The findings on fetomaternal immune tolerance have remained controversial and require further research.

Prevalence of SARS-CoV-2 Specific Antibodies in Asymptomatic Hemodialysis Patients.

Abstract: Background: Since the outbreak of the new coronavirus pandemic, the importance of carrying out an infection check to prevent acquisition and transmission among end-stage renal disease patients (ESRD) under maintenance hemodialysis (MHD) has become a major concern in the health care system. Applying serology screening tests could enlighten the view with regards to disease prevalence in dialysis wards.Methods: We subjected 328 end-stage renal disease patients to maintenance hemodialysis. After dividing patients into suspicious and non-suspicious groups for COVID-19 infection based on their clinical manifestation, they were investigated for SARS-CoV-2 specific IgM and IgG screening against nucleoprotein (NP), spike protein (SP), and receptor-binding domain (RBD), utilizing our recently developed ELISA tests.Results: We found that approximately 10.1% of asymptomatically tested cases were antibody positive. Although IgG positivity showed a higher prevalence than IgM across all three virus antigen subunits, there were no significant differences among mentioned immunoglobulins of the studied groups. The most prevalent antibody was from the IgG subtype against virus nucleoprotein (NP), while the lowest prevalence was attributed to receptor-binding domain (RBD) IgM.Conclusion: High seropositive rate among asymptomatic end-stage renal disease patients, as a sample of high-risk population, reflected the importance of considering SARS-CoV-2 specific antibody screening for disease containment.

Impact of IL-17F 7488T/C Functional Polymorphism on Progressive Rheumatoid Arthritis: Novel Insight from the Molecular Dynamic Simulations.

Abstract: Resorption of bones and cartilage coupled with structural changes in the inflamed joints are the major hallmark of rheumatoid arthritis (RA). Genetic polymorphisms in pro-inflammatory interleukins ...