Coagulation and Inflammation in COVID-19: Reciprocal Relationship between Inflammatory and Coagulation Markers.

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as 2019-nCoV. Numerous cellular and biochemical issues arise after COVID-19 infection. The severe inflammation that is caused by a number of cytokines appears to be one of the key hallmarks of COVID-19. Additionally, people with severe COVID-19 have coagulopathy and fulminant thrombotic events. We briefly reviewed the COVID-19 disease at the beginning of this paper. The inflammation and coagulation markers and their alterations in COVID-19 illness are briefly discussed in the parts that follow. Next, we talked about NETosis, which is a crucial relationship between coagulation and inflammation. In the end, we mentioned the two-way relationship between inflammation and coagulation, as well as the factors involved in it. We suggest that inflammation and coagulation are integrated systems in COVID-19 that act on each other in such a way that not only inflammation can activate coagulation but also coagulation can activate inflammation.

Atypical Polycystic Kidney Disease as defined by Imaging.

Using age- and height-adjusted total kidney volume, the Mayo Clinic Imaging Classification provides a validated approach to assess the risk of chronic kidney disease (CKD) progression in autosomal dominant polycystic kidney disease (ADPKD), but requires excluding patients with atypical imaging patterns, whose clinical characteristics have been poorly defined. We report an analysis of the prevalence, clinical and genetic characteristics of patients with atypical polycystic kidney disease by imaging. Patients from the extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease recruited between 2016 and 2018 completed a standardized clinical questionnaire, kidney function assessment, genetic testing, and kidney imaging by magnetic resonance or computed tomography. We compared the prevalence, clinical features, genetics, and renal prognosis of atypical versus typical polycystic kidney disease by imaging. Forty-six of the 523 (8.8%) patients displayed atypical polycystic kidney disease by imaging; they were older (55 vs. 43 years; P < 0.001), and less likely to have a family history of ADPKD (26.1% vs. 74.6%; P < 0.001), a detectable PKD1 or PKD2 mutation (9.2% vs. 80.4%; P < 0.001), or progression to CKD stage 3 or stage 5 (P < 0.001). Patients with atypical polycystic kidney disease by imaging represent a distinct prognostic group with a low likelihood of progression to CKD.

Association between gene polymorphisms of IL-12, IL-12 receptor and IL-27 and organ involvement in Iranian endometriosis patients.

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue, immune cell dysfunction and abnormal cytokine secretion. In addition to immunological factors, genetic variations that influence endometriosis severity and cytokine expression levels play important roles in the pathogenesis of this disease. Interleukin-12 (IL-12), specifically its p40 subunit encoded by IL-12B gene and the interleukin-12 receptor ß1 (IL-12Rß2) chain of its receptor, as well as interleukin-27 (IL-27) are important in the establishment of endometriosis. So, in this study, we measured IL-12 and IL-27 serum levels and investigated the possible links between IL-12B rs3212227, IL-12Rß2 rs3790565 and IL-27 rs153109 polymorphisms and the risk of developing endometriosis in a group of Iranian women. In this case-control study, 162 endometriosis patients and 151 healthy women were included and tested for the aforementioned polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay (ELISA) method was also used to measure IL-12 and IL-27 serum levels. Although there was no statistically significant association between the genotypes and alleles of the studied polymorphisms and the development of endometriosis in general, the AA genotype of IL-12B rs3212227 showed a significant association with uterine endometriosis when compared to AC+CC genotypes (p = .04, CI = 0.270-0.988, OR = 0.517). Indeed, the AA genotype of the IL-12B rs3212227 single nucleotide polymorphism (SNP) may be linked with a lower risk of developing uterine endometriosis. There was no significant difference in IL-27 levels between the two studied groups (p = .49), and IL-12 levels were undetectable in both groups. In conclusion, the AA genotype of IL-12B rs3212227 might be associated with a decreased risk of uterine involvement in endometriosis patients.

Efficacy of Mesenchymal Stem Cells Therapy in Parasitic Infections: Are Anti-parasitic Drugs Combined with MSCs More Effective?

PURPOSE: Mesenchymal stem cells (MSCs) are mesodermal-origin postnatal stem cells that are able to self-renew and differentiate into several cell lineages. MSCs possess anti-inflammatory and anti-apoptotic activity, immunomodulatory action, as well as regenerative properties. Since MSCs also have antimicrobial properties, it has been suggested that they should be utilized for treating infectious diseases. In this study, the last pre-clinical advances in the efficacy of MSCs' therapy against parasitic diseases were reviewed. METHODS: Data about the effects of MSCs' therapy on experimental and pre-clinical parasitic infections were collected by searching relevant articles and reviewing them. RESULTS: In the present study, empirical findings on the impacts of MSCs' therapy against parasitic diseases were recapitulated. Studies have reported that the administration of MSCs reduces the burden of the parasite and modulates the levels of inflammatory and anti-inflammatory cytokines in parasitic diseases, including schistosomiasis, malaria, cystic echinococcosis, toxocariasis, leishmaniasis, and trypanosomiasis. Also, the administration of MSCs combined with anti-parasitic drugs enhanced anti-parasitic effects and immunomodulatory actions. CONCLUSION: Based on this review, empirical studies have revealed the beneficial effects of MSCs against some parasitic infections. This new therapeutic strategy showed both anti-parasitic and immunomodulatory effects. Also, the combination of anti-parasitic drugs with MSCs' therapy promoted anti-parasitic and immunomodulatory activities against parasitic infections.

Are genetic variations in IL-1ß and IL-6 cytokines associated with the risk of pre-eclampsia? Evidence from a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis study was performed to assess the potential association between interleukin-1 beta (IL-1ß) single nucleotide polymorphisms (SNPs) (rs1143634 and rs16944) and interleukin-6 (IL-6) SNP (rs1800795) and pre-eclampsia (PE). METHODS: A comprehensive literature search was conducted in the international search engines and databases, including MEDLINE (via PubMed), Scopus, and Web of Science (ISI) up to 9 March 2021. After retrieving relevant articles, data extraction was performed by four authors independently. Pooled ORs and corresponding 95% CIs were used to evaluate the association between IL-1ß and IL-6 polymorphisms and PE risk. Cochran's Q test was used to check heterogeneity, and the I2 index was calculated for measuring the heterogeneity between the estimations of included studies. RESULTS: After reviewing fully published studies, 21 studies were included in this study based on the eligibility criteria. Our results showed that rs16944 and rs1143634 of IL-1ß were significantly associated with the risk of PE. Regarding rs16944, the minor C allele significantly decreased the risk of PE (C vs. T: OR = 0.79, 95% CI = 0.69-0.90). In contrast, the minor T allele of rs1143634 significantly increased the risk of PE (T vs. C: OR = 1. 28, 95% CI = 1.04-1.58). There was no significant association between IL-6 rs1800795 (C vs. G: OR = 1.04, 95% CI = 0.93-1.16) polymorphism and PE risk. CONCLUSIONS: In conclusion, this meta-analysis suggests rs1143634 and rs16944 polymorphisms of IL-1ß are related to the risk of PE.

Proteome Analysis of CD4+ T Cells Reveals Differentially Expressed Proteins in Infertile Polycystic Ovary Syndrome Patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder affecting 6-7% of premenopausal women. Recent studies revealed that the immune system, especially CD4+ T helper cells are important in the context PCOS. Proteome analysis of CD4+ T lymphocytes can provide valuable information regarding the biology of these cells in the context of PCOS. OBJECTIVE: To investigate immune dysregulation in CD4+ T lymphocytes at the protein level in the context of PCOS using two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). METHODS: In the present study, we applied two-dimensional gel electrophoresis / mass spectrometry to identify proteins differentially expressed by peripheral blood CD4+ T cells in ten PCOS women compared with ten healthy women. Western blot technique was used to confirm the identified proteins. RESULTS: Despite the overall proteome similarities, there were significant differences in the expression of seven spots between the two groups (P <0.05). Three proteins, namely phosphatidylethanolaminebinding protein 1, proteasome activator complex subunit 1 and triosephosphate isomerase 1 were successfully identified by Mass technique and confirmed by western blot. All characterized proteins were over-expressed in CD4+ T cells from patients compared to CD4+ T cells from controls (P <0.05). Insilico analysis suggested that the over-expressed proteins interact with other proteins involved in cellular metabolism, especially glycolysis and ferroptosis pathway. CONCLUSION: These findings suggest that metabolic adjustments in CD4+ T lymphocytes, which is in favor of increased glycolysis and Th2 differentiation are important in the context of PCOS.

The effect of probiotics, parabiotics, synbiotics, fermented foods and other microbial forms on immunoglobulin production: a systematic review and meta-analysis of clinical trials.

The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics, parabiotics, synbiotics, fermented foods and other microbial forms on immunoglobulin production. We searched PubMed, Scopus, Web of Science, National Institute of Health Clinical Trials Register, and Cochrane Central Register of Clinical Trials, up to February 2020. All clinical trials that investigated the effects of oral intake of probiotics, parabiotics, synbiotics, fermented foods and other microbial forms on immunoglobulin (Ig)A, IgE, Japanese cedar pollen (JCP)-specific IgE, IgG, and IgM, for a duration of >7 days were included. Fifty-nine studies met the inclusion criteria, of these 54 studies were included in the analysis. The results indicated a significant increase in salivary IgA secretion rate (SMD = 0.21, 95% CI 0.02-0.39), while no significant effect was observed on other Igs. In conclusion, mentioned supplementation induced a small but significant effect on salivary secretion rate of IgA.

Effect of probiotic and synbiotic supplementation on inflammatory markers in health and disease status: A systematic review and meta-analysis of clinical trials.

The current systematic review and meta-analysis investigated the effect of probiotic/synbiotic on a wide range of inflammatory and anti-inflammatory markers in healthy and various disease conditions. PubMed, SCOPUS and Web of Science databases were searched. All clinical trials which investigated the effect of oral administration of probiotic or synbiotic on inflammatory markers (C-reactive protein (CRP), interleukin (IL) 1ß, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF) α, interferon (IFN) γ and transforming growth factor (TGF) ß) for more than one week with concurrent control groups were included. One-hundred sixty seven publications was analysed. Results were as follows: CRP decreased in healthy, metabolic disorders, inflammatory bowel disease (IBD), arthritis and critically ill condition but not in renal failure. IL-1B: no change in healthy subjects and arthritis. TNF-α: decreased in healthy, fatty liver, IBD and hepatic cirrhosis, no change in diabetes, metabolic syndrome (MS) + PCOS (polycystic ovary syndrome) and arthritis. IL-6: no change in healthy, metabolic disorders and arthritis, increased in cirrhosis and renal failure, decreased in PCOS + MS. IL-10: no change in healthy, IBD and metabolic disorders, increased in arthritis. IL-4, IL-8, IL-12, IFN-g and TGF-b: no change in healthy subjects. In conclusion, probiotic/synbiotic decreased some of the inflammatory markers. The intervention was most effective in CRP and TNF-α reduction in healthy or disease state. Moreover, the intervention decreased inflammation most effectively in the following disease conditions, respectively: IBD, arthritis, fatty liver. PROSPERO REGISTRATION NUMBER: CRD42018088688.

T Helper Cells Profile and CD4+CD25+Foxp3+Regulatory T Cells in Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered as the most common cause of female infertility that affects 4-10% of women in the reproductive age. Previous studies have shown the role of a balanced immune response in a successful pregnancy and fertility. OBJECTIVE: To investigate the T helper cells type 1 (Th1) /Th2/Th17/Treg paradigms in peripheral blood of infertile PCOS compared with normal fertile women. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated at the late follicular phase from 10 PCOS and 10 fertile women. PBMCs were stimulated with PMA and ionomycin in the presence of Berefeldin A as Golgi stop agent to detect intracellular cytokine production (IFN-γ, IL-17, and IL-4) from CD3+CD4+T cells population indicating T helper (Th) cells subsets by flowcytometry. Moreover, regulatory T cells were enumerated using CD25 and Foxp3 markers. RESULTS: In this study, we report that the frequency of Th1 cells was increased compared to Th2 cells in infertile PCOS when considering Th1/Th2 ratio (P=0.05). Analysis of Th17/Th2 ratio showed a significant difference with a bias toward Th17 dominancy in PCOS (P=0.02). The proportion of CD4+CD25+Foxp3+ regulatory T cells was significantly lower in PCOS patients than that of healthy fertile women (P=0.02). CONCLUSION: In summary, Th1 and Th17 bias and reduction of Treg and Th2 cells as regulators of immune responses might be involved in the pathogenesis of PCOS. These results are suggestive of an altered immune response to inflammatory status in PCOS patients, likely causing some complications such as infertility in these patients.

Therapeutic Efficacy of Mesenchymal Stem Cells and Mesenchymal Stem Cells-derived Neural Progenitors in Experimental Autoimmune Encephalomyelitis.

BACKGROUND AND OBJECTIVES: The goal of treatment for MS is to reduce the inflammation and induce the regeneration of degenerated axons. Considering the anti-inflammatory and regenerative capacity of mesenchymal stem cell (MSCs), in this study the therapeutic efficacy of allogeneic MSCs and MSCs-derived neural progenitor cells (MSCs-NPs) was investigated in cellular therapy of chronic experimental autoimmune encephalomyelitis (EAE). METHODS AND RESULTS: MSCs, MSCs-NPs and MSCs＋MSCs-NP were administered intravenously to EAE mice on days 22, 29, and 36 post immunization. The levels of cytokines and PGE2 in sera or supernatant of in vitro cultured splenocytes derived from treated mice were measured by ELISA. The results of this study showed that in comparison to MSCs monotherapy, MSCs-NPs administration had a more profound capability of inhibiting the proliferation of pathogenic MOG35₋55-specific T cells, decreasing IFN-γ production and increasing anti-inflammatory IL-10 cytokine production. These findings could be explained by higher ability of in vitro cultured MSCs-NPs in production of PGE2 compared to MSCs. In line with these findings, while the administration of MSCs and MSCs-NPs significantly decreased the clinical scores of EAE in comparison with the untreated EAE group, MSCs-NPs were significantly more efficient in reducing clinical score compared to MSCs. Of interest, combined therapy with MSCs and MSCs-NPs did not provide any benefit over monotherapy with MSCs-NPs. CONCLUSIONS: In comparison to MSCs, allogenic MSCs-NPs are more potent in the attenuation of EAE.

The Expression of T-Helper Associated Transcription Factors and Cytokine Genes in Pre-Eclampsia.

BACKGROUND: Pre-eclampsia (PE) is known as a main factor contributing to fetomaternal mortality, which might affect 2-8% of all pregnancies after the twentieth week of gestation. The balance of T helper subsets is essential to sustain a normal pregnancy and preventing fetomaternal complications. OBJECTIVE: To investigate differences in the levels of transcription factors and cytokine gene expression of Th1/Th2/Th17/Treg subsets within decidual and chorionic layers of placentas from 15 PE-afflicted and 15 healthy Iranian women in their third trimester of pregnancy. METHODS: Using Quantitative real-time PCR (Q-PCR), the expression of T-BET, GATA-3, ROR-É£t, FOXP3, and cytokines, including IL-1, IL-6, TNF-α, IFN-γ, IL-4, IL-31, IL-17, IL-23, TGF-ß1, TGF-ß2, TGF-ß3, and IL-35 in the placenta were compared at mRNA levels between groups. RESULTS: FOXP3 and GATA-3 were significantly down-regulated, while T-BET was up-regulated in PE deciduae compared to the control group (p<0.0001, p<0.02, and p<0.01, respectively). Concerning the chorionic samples, FOXP3 significantly decreased, while ROR-γt increased in the PE placentas compared to the healthy ones (p<0.0006 and p<0.02, respectively). Besides, most inflammatory cytokines were up-regulated, while anti-inflammatory cytokines were down-regulated in the PE placentas. Additionally, TNF-α/IL-35, IFN-É£/IL-35, IL-6/IL-35, and IL-23/IL-35 ratios were significantly higher (p<0.01) and IL-35/IL-17 ratio was significantly lower (p<0.05) in the pre-eclamptic patients compared to the healthy controls. CONCLUSION: Our results shed more light on the contribution of Th1/Th2/Th17/Treg balance within placenta in the fate of a normal pregnancy. Moreover, regulatory T cells and IL-35 seem to play a notable role in pre-eclampsia.

Epidemiological aspects and clinical outcome of patients with Rhinocerebral zygomycosis: a survey in a referral hospital in Iran.

INTRODUCTION: No comprehensive reports have been published on epidemiological status of Rhinocerebral zygomycosis infections and its outcome in our population, Hence, the current study came to address epidemiological characteristics as well as clinical outcome of patients with Rhinocerebral zygomycosis infection referred to a referral hospital in Iran. METHODS: This retrospective study was performed at the Rasoul-e-Akram hospital, an 800-bed tertiary care teaching hospital in Tehran, Iran. The pathology recorded charts were reviewed to identify all cases of Rhinocerebral zygomycosis from patients admitted between April 2007 and March 2014. A diagnosis of Rhinocerebral zygomycosis was based on histopathological assessments. RESULTS: Sixty four patients with Rhinocerebral zygomycosis were assessed. The mean age of the patients was 46.07 ± 22.59 years and 51.6% were female. Among those, 67.2% were diabetic, 26.6% were hypertensive and 29.7% had history of cancer. Different sinuses were infected in 73.4% of the patients. Out of all the patients 26.6% underwent surgical procedures and 17.2% were controlled medically. Extensive debridement was carried out in 40.6%. Neutropenia (<1500 cell/ µl) was revealed in 12.5%. In-hospital mortality rate was 35.9% and prolonged hospital stay (> 14 days) was found in 60.9%. According to the Multivariable logistic regression analysis, the main predictors of in-hospital mortality included female gender, advanced age, the presence of sinus infection, and neutropenia, while higher dosages of amphotericin administered had a protective role in preventing early mortality. In a similar Multivariate model, history of cancer could predict prolonged hospital stay, whereas using higher dose of amphotericin could lead to shortening length of hospital stay. CONCLUSION: There is no difference in demographic characteristics between our patients with Rhinocerebral zygomycosis and other nations. The presence of diabetes mellitus is closely associated with the presence of this infection. Sinus involvement is very common in those with Rhinocerebral zygomycosis leading to high mortality and morbidity. Besides female gender, advanced age, and presence of neutropenia was a major risk factor for increasing early mortality. The use of higher doses of antifungal treatment such as amphotericin can prevent both mortality and prolonged hospital stay. The cancer patients may need longer hospital stay because of needing comprehensive in-hospital treatment.

Effect of DiD Carbocyanine Dye Labeling on Immunoregulatory Function and Differentiation of Mice Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have been used to treat a variety of degenerative disorders. Labeling of MSCs with an appropriate tracer is vital to demonstrate the in vivo engraftment and differentiation of transplanted MSCs. DiD is a lipophilic fluorescent dye with near infrared emission spectra that makes it suitable for in vivo tracing. Therefore, in the present study the consequences of DiD labeling on induction of oxidative stress and apoptosis as well as inhibition of biological functions of mesenchymal stem cells (MSCs) were investigated. DiD labeling did not provoke the production of ROS, induction of apoptosis, or inhibition of production of immunosuppressive factors (PGE2 and IL-10) by MSCs. In addition, there were no statistical differences between DiD-labeled and unlabeled MSCs in suppression of proliferation and cytokine production (IFN-γ and IL-17) by in vitro stimulated splenocytes or improvement of clinical score in EAE after in vivo administration. In addition, DiD labeling did not alter the differentiation capacity of MSCs. Taken together, DiD can be considered as a safe dye for in vivo tracking of MSCs.

Computed tomography findings of a patient with severe dysplasia of the inner ear and recurrent meningitis: a case report of gusher ear in a five-year old boy.

Communication between subarachnoid and perlymphatic spaces can be due to a deficiency of lamina cribrosa (stapes gusher). Recognition of the condition may alter the course of treatment that can avoid perilymph gushing. A five-year-old boy presented with a history of congenital hearing loss and recurrent meningitis. The computed tomography (CT) of the temporal bone showed severe bilateral dysplasia in the inner ears in favor of gusher disease.