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Backgroundː Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), within few months of being declared as a global pandemic by WHO, the number of confirmed cases has been over 75 million and over 1.6 million deaths since the start of the Pandemic and still counting, there is no consensus on factors that predict COVID-19 case progression despite the diversity of studies that reported sporadic laboratory predictive values predicting severe progression. We review different biomarkers to systematically analyzed these values to evaluate whether are they are correlated with the severity of COVID-19 disease and so their ability to be a predictor for progression. Methods The current meta-analysis was carried out to identify relevant articles using eight different databases regarding the values of biomarkers and risk factors of significance that predict progression of mild or moderate cases into severe and critical cases. We defined the eligibility criteria using a PICO model. Results Twenty-two relevant articles were selected for meta-analysis the following biomarkers C-reactive protein, interleukin-6, LDH, neutrophil, %PD-1 expression, D-dimer, creatinine, AST and Cortisol all recorded high cut-off values linked to severe and critical cases while low lymphocyte count, and low Albumin level were recorded. Also, we meta- analyzed age and comorbidities as a risk factors of progression as hypertension, Diabetes and chronic obstructive lung diseases which significantly correlated with cases progression (p Conclusions ː The current meta-analysis is the first step for analysing and getting cut-off references values of significance for prediction COVID-19 case progression. More studies are needed on patients infected with SARS-CoV-2 and on a larger scale to establish clearer threshold values that predict progression from mild to severe cases. In addition, more biomarkers testing also help in building a scoring system for the prediction and guiding for proper timely treatment.

Background: Screening of blood products is considered a mandatory protocol implemented in health care facilities in order to reduce the onset of transfusion-transmitted infections (TTIs). This study was aimed to determine the sero-prevalence of ABO and Rh blood groups and their associated TTIs among blood donors in the Central Region of Saudi Arabia. Methods: This was retrospective study performed on the blood donors’ records from March 2017 to December 2018 at Buraidah Central Hospital Blood Bank. Study was conducted on a total of 4590 blood donors. ABO and Rh typing was performed.The blood samples were also screened serologically for hepatitis B surface antigen (HBsAg), anti-hepatitis B core total antibodies (anti-HBc total), hepatitis C virus (HCV), human immunodeficiency viruses (HIV), human T-lymphotrophic virus-1 (HTLV-1) and veneral disease research laboratory test(VDRL) for syphilis. Results: Out of 4590 blood donors, O positive blood group was found to be highest (42%), followed by A positive (23.4%), B positive (20.9%), O negative (5.45%), AB positive (3.4%), A negative (2.8%), B negative (2.1%) and AB negative (0.5%). Moreover, total number of Rh-negative donors was significantly lowered as compared with Rh-positive. Seroreactive tests were found to be positive in only 1.002% of all studied donors and mainly found in male donors. Among TTI, anti-HBc total was the highest (0.784%), followed by HBsAg, HCV, VDRL and TPHA. Whereas all tested donors were found to be negative for HIV infections. Conclusions: The information collected for the frequency of ABO blood phenotypic groups has a vital significance in establishing a simple blood group database. This study clearly determined significantly lower rate of seropositive TTIs among the studied blood donors but still steps are needed to improve the knowledge and to prevent the seropositive occurrence of TTIs. Keywords: Blood group, TTIs, Anti-HBc total, HBsAg, HCV, VDRL, KSA

This study was undertaken to investigate an association between genetic variants of ERCC2 (Lys751Gln), ERCC2 (Asp312Asn) or XRCC1 (Arg399Gln) polymorphisms with the risk of prostate cancer (PC) in Saudi population. This is a case-control study conducted on 124 PC patients and 425 healthy human controls. Blood samples were used for DNA extraction and gene polymorphisms for ERCC2 (Lys751Gln), ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln). The risk of the associations was calculated by odds ratio (OR) and 95% confidence interval (CI). The data demonstrated no significant associations between ERCC2 (Lys751Gln) polymorphism and PC risk, whereas ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms were found to be significantly associated with PC risk (OR of 2.2, 95% CI, 1.1–4.1; p = 0.02) and (OR of 2.4, 95% CI, 1.3–4.5; p = 0.005), respectively. Likewise, recessive genotype models also showed significant association of ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms with PC risk (p = 0.009). Interestingly, these genetic associations were more pronounced in aged populations (p = 0.003) as well as in smokers (p

Inducible nitric oxide synthase (iNOS) expression is associated with the pathogenesis of osteoarthritis (OA). This study was undertaken to investigate whether interleukin-1β (IL-1β)-mediated induction of iNOS can be regulated by microRNA-26a-5p (hsa-miR-26a-5p) in OA. Bioinformatics approaches show that 3'UTR of iNOS mRNA contained the 'seed-matched-sequence' for hsa-miR-26a-5p. IL-1β-induced expression of iNOS correlated with the down-regulation of miR-26a-5p in human OA chondrocytes. hsa-miR-26a-5p directly suppressed the luciferase activity of 3'UTR-iNOS reporter clone. Transfection with pre-miR-26a-5p induced marked silencing of iNOS expression. Activation of NF-κB pathway down-regulated the expression of hsa-miR-26a-5p and induced iNOS expression. In short, this is the first report that shows hsa-miR-26a-5p is a direct regulator of iNOS expression in human chondrocytes. hsa-miR-26a-5p may be an important regulator of human cartilage homeostasis and a new target for OA therapy.

During first trimester of human pregnancy, the maternal system develops immunity against infection and to provide protection of allogeneic foetus from abortion. This study was undertaken to determine the role of trophoblast specific CD74 isoforms in first trimester trophoblast derived cells under normal and lipopolysaccharide (LPS) stimulated conditions.Gene and protein of CD74 were determined in first trimester trophoblast derived cells, JEG-3 and ACH-3 P and also in human placenta by PCR, western blotting and immunoprecipitation. Effect of LPS mediated infection on the regulation of CD74 isoforms was studied intracellularly and also on the cells surface by flow cytometry.Data demonstrated that JEG-3 and ACH-3 P cells under normal conditions have not expressed CD74 isoforms neither intracellularly or nor on the surface. These results were further validated directly in human placenta. However, treatment of these trophoblast cells with a bacterial LPS, significantly upregulated CD74 mRNA expression (p0.05). Furthermore, expression of CD74 on the surface was not detected even after stimulation with LPS. Interestingly, CD74 isoform at 35 kDa was significantly detected intracellularly upon stimulation with LPS (p0.05). These results were further confirmed by western blotting followed by immunoprecipitation.To the best of our knowledge, this is the first study concluded that the bacterial LPS induce infection in the first trimester trophoblasts via intracellular upregulation of CD74. Data indicated that the lack of cell surface expression of trophoblastic specific isoforms of CD74 may provide protection for human pregnancy in the first trimester.

Vitiligo is a common pigmentary disorder, the precise etiology of which remains obscure. Tyrosinase, a key enzyme involved in melanin synthesis, has now been implicated as an autoantigen for vitiligo patients, but it is not clear how this prevalent protein becomes antigenic in vitiligo.To investigate the status and contribution of oxidized tyrosinase in vitiligo and to explore whether oxidized tyrosinase has a role in disease progression.Tyrosinase was modified by reactive-oxygen-species (ROS). Binding characteristics of antibodies in vitiligo patients (n=25) with varying disease duration (DD) and disease severity were screened against ROS-modified tyrosinase (ROS-tyrosinase) by immunoassays and their results were compared with healthy controls (n=23).The ROS caused extensive alterations in conformation and function of tyrosinase. Protein-A purified IgGs from vitiligo patients (Vt-IgG) showed strong binding to ROS-tyrosinase in comparison with IgGs from healthy controls (p0.001). Interestingly, not only was there an increased number of subjects positive for anti-ROS-tyrosinase-IgGs, but also the levels of these IgGs were significantly higher among vitiligo patients, whose DD were ≥10 years as compared to patients with short DD (10 years). In addition, a significant correlation was observed between the levels of anti-ROS-tyrosinase-IgGs and the patients' ages or with disease severity. Experimentally induced anti-ROS-tyrosinase-IgGs show reactivity with tyrosinase from vitiligo patients. Furthermore, vitiligo patients had lower levels of tyrosinase activity compared with healthy controls. Not only these, levels of carbonylation were also higher among vitiligo patients whose DD were ≥10 years as compared to patients with DD10 years.This is the first study to demonstrate the role of oxidized tyrosinase in vitiligo. Our novel results support an association between oxidized tyrosinase and vitiligo autoimmunity. The stronger antibodies response to oxidized tyrosinase in vitiligo patients with higher DD or with severe patients suggests that oxidized tyrosinase may be a useful biomarker in evaluating the progression of vitiligo and in elucidating the mechanisms of disease pathogenesis.

Alopecia areata (AA) is a non-scarring hair loss disorder that ranges in severity from patchy loss of scalp hair (AA patchy persistent; AAP) to loss of all scalp and body hair (alopecia universalis; AU). The cause of AA is unknown but most evidences support that AA has an autoimmune etiology, where free radicals play an important role. This study was undertaken to investigate the role of nitric oxide (NO) modified erythrocytes superoxide dismutase (eSOD) in AA. Data revealed that NO-induced damage in eSOD caused alteration in hydrophobic or aromatic amino acids and protein carbonyl contents. NO-specific quencher, carboxyl-PTIO further reiterates NO-modifications. Specificity of antibodies from AA patients (n=26) was analyzed toward NO-modified eSOD (NO-eSOD) and their results were compared with healthy controls (n=30). Protein-A purified IgG of AA patients (AA-IgG) showed strong binding to NO-eSOD in comparison with IgG from controls. In addition, AA-IgG from patients with AU recognized NO-eSOD in a greater extent as compared to AA-IgG from patients with AAP. Furthermore, AU patients' sera contained higher levels of NO or carbonyl contents and lower levels of SOD activity compared with AAP patients' or control sera. In conclusion, this is the first study to demonstrate the role of NO-modified-eSOD in AA. Our novel results conclude that perturbations in SOD by NO presenting unique neo-epitopes that might be one of the factors for the antigen driven antibodies induction in AA. Preferential binding of NO-eSOD by AA-IgG pointed out the likely role of NO-eSOD in the initiation/progression of AA.

Protein modifications by 4-hydroxy-2-nonenals (HNE) are involved in various diseases. Histones are DNA protective nucleoprotein, which adopt different structures under oxidative stress. This study was undertaken to test the role of HNE-modified-histone-H2A (HNE-H2A) in systemic lupus erythematosus (SLE). Our data revealed that HNE-mediated-lipid peroxidation in histone-H2A caused alteration in histidine, lysine and cystein residues. In addition, protein carbonyl contents were also high in HNE-H2A. HNE-specific quencher, L-carnosine further reiterates HNE-modifications. Specificity of autoantibodies from SLE patients (n=48) were analyzed towards HNE-H2A and their results were compared with sex- and age-matched controls (n=36). SLE autoantibodies show preferential binding to HNE-H2A in comparison with histone-H2A (p

IntroductionDuring aging, advanced glycation end products (AGEs) accumulate in articular cartilage. In this study we determined whether AGEs induce endoplasmic reticulum (ER) stress and studied the ER stress-activated pathways that stimulate cyclooxygenase-2 (COX-2) expression in human chondrocytes.MethodsChondrocytes were stimulated with AGE-BSA. Gene expression was determined by quantitative PCR and protein expression was studied by immunoblotting. Studies to elucidate involved pathways were executed using siRNAs and specific inhibitors of eukaryotic initiation factor-2α (eIF2α), MAPKs and NF-κB.ResultsAGE-BSA induced expression of GRP78 with concomitant increase in COX-2 expression was observed in human chondrocytes. In addition, expression of Bag-1, an ER stress marker was also increased by AGE-BSA. RAGE knockdown inhibited AGE-BSA-induced expression of GRP78 and COX-2. Treatment with eIF2α inhibitor or eIF2α knockdown inhibited AGE-BSA-induced expression of GRP78 and COX-2 with decreased PGE2 production. Treatment with SB202190 inhibited AGE-BSA-induced expression of GRP78 and COX-2, while treatment with PD98051 inhibited AGE-BSA-induced GRP78 protein expression but had no effect on COX-2 protein expression. SP600125 had no effect on either GRP78 or COX-2 protein expression. Bay 11-7082 suppressed AGE-BSA-induced GRP78 and COX-2 expression. AGE-BSA-induced activation of NF-κB was inhibited by treatment with SB202190 and by eIF2α knockdown, but was not inhibited when chondrocytes were treated with SP600125 or PD98059.ConclusionThis study demonstrates that AGEs induce ER stress and stimulate the expression of COX-2 through eIF2α, p38-MAPK and NF-κB pathways in human chondrocytes. Our results provide important insights into cartilage degradation in osteoarthritis associated with latent ER stress.

Objectives The role of hydroxyl radical ( OH) damaged Immunoglobulin G (IgG) in rheumatoid arthritis (RA) has been investigated. Design and methods The study was hypothesized that oxidative by-products, like OH-damage IgG, help to initiate autoimmunity in RA. To test this hypothesis, IgG was modified by OH. Immunogenicity of native and modified IgG was probed by inducing polyclonal antibodies in rabbits. Autoantibodies from 77 RA sera were screened by direct binding and competition ELISA. Results The OH caused extensive damage to IgG. The OH-IgG was found to be highly immunogenic in rabbits as compare to native IgG. High degree of specific binding by 72.7% RA sera autoantibodies towards OH-IgG was observed, in comparison to its native analogue (p Conclusion The OH modification of IgG causes perturbations, resulting in the generation of neo-epitopes, and making it a potential immunogen. The IgG modified with the ·OH may be one of the factors for the induction of circulating RA autoantibodies.