ABSTRACT
Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.
ABSTRACT
Background: Severe infection with SARS-CoV-2 induces systemic autoreactive antibodies with specificity to Type I IFN, phospholipids, nuclear or tissue specific targets. The wide breadth of targets suggests a system-wide defect in B cell tolerance during viral infection and that the source of autoreactive antibodies is likely a heterogenous subset of B cells. BND cells are mature naïve B cells that do not express IgM but do express IgD and are enriched in autoreactive specificities. BND cells are held in an anergic state in healthy humans as a mechanism of peripheral tolerance, although in vitro evidence suggests anergy can be broken with strong inflammation. We hypothesized that robust inflammation associated with viral infection from SARS-CoV2 may relax peripheral tolerance and promote breakage of BND cell anergy. Methods: Plasma and PBMCs were collected from healthy controls (N=10), subjects immunized with Pfizer BNT162b2-mRNA/Moderna mRNA-1273 (N=10), subjects with mild (N=11) or severe SARS-CoV-2 infection (N=14). BND cells were examined ex vivo for markers of activation by flow cytometry. Phosphorylation of signaling proteins downstream of the BCR were measured in vitro with or without BCR crosslinking. Inflammatory cytokines were measured in plasma by multiplex. For statistical analysis, unpaired t test between populations or paired t test between unstimulated and BCR stimulated conditions were performed. Results: BND cells from severe SARS-CoV-2 infection have lower expression of CD21, associated with loss of anergy, higher expression of activation markers CD68 and CD86 with lower expression of inhibitory receptors CD22 and CD72 when compared to BND cells from other subjects, suggesting a phenotypical breach of anergy. Upon BCR crosslinking, BND cells have higher levels of downstream signaling components of the BCR (pPLCγ2, pBlnk, and pSyk) when compared to healthy controls and immunized subjects, suggesting a functional breach in anergy with infection. Examination of plasma from severe SARS-CoV-2 infection showed higher levels of inflammatory cytokines (IFNγ, TNFα, IL-6 and CRP) where TNFα and CRP correlated with enhanced BCR signaling in BND cells. Conclusion: We demonstrate that SARS-CoV-2 viral infection relaxes peripheral tolerance of BND cells, likely through strong systemic inflammation produced during infection. These autoreactive cells overcome anergy and become activated with increased BCR signaling. Thus BND cells could be a source of autoreactive antibodies during viral infection.
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Relevance: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. The prevalence rates of PCOS depend on the diagnostic criteria used and the characteristics of the population sample, and in the general population of women of reproductive age, the prevalence of the syndrome ranges from 6-9% to 19.9% [1,2]. According to modern criteria adopted by the consensus in Rotterdam, then systematically updated by ESHRE / ASRM (2014), the presence of two of the three criteria in a patient simultaneously allows to diagnose PCOS if other pathological conditions are excluded (thyroid pathology, congenital adrenal hyperplasia, adrenogenitalsyndrome, androgen-secreting tumors, Itsenko-Cushing syndrome). Modern international diagnostic criteria include the following signs: (1) signs of polycystic ovaries according to information from pelvic ultrasound investigation (the presence of more than 10 follicles in each ovary);(2) oligo-anovulation;(3) clinical (presence of hirsutism) or biochemical (increased androgen levels) development of ovarian hyperandrogenism [3, 4]. Polycystic ovary syndrome is closely related to many diseases, including metabolic syndrome. Although insulin resistance is an important risk factor for metabolic syndrome and other diseases associated with PCOS, hyperandrogenismmay also be an independent risk factor for type 2 diabetes, obesity, cardiovascular disease (CVD), and metabolic syndrome in female patients. Obesity is the most common symptom in PCOS patients (33-88%), which has a large impact on fertility and can lead to adverse effects such as menstrual irregularities, anovulation, infertility and abortion. Therefore, weight management in early PCOS is essential to improve fertility and quality of life. Hyperandrogenism plays a decisive role in abdominal obesity in obese women during adolescence, adulthood and menopause [5]. Although some studies have shown a negative association between plasma androgen levels (A4, DHEA and DHEAS) and obesity [6,7]. But the mechanism of how androgens affect fat cells in women is poorly understood. A number of observations show that among obese women with PCOS, metabolic disorders associated with insulin resistance and obesity, in many cases, play a more important role in the mechanism of anovulation in PCOS than excess androgens. In recent years, it has been established that in PCOS there is a frequent combination of hyperandrogenism and insulin resistance. With insulin resistance, there is a decrease in the response of insulin-sensitive tissues to the hormone insulin with its sufficient level in the blood. Insulin resistance is found in 30-70% of patients with PCOS who are overweight or obese, and in patients with normal body weight it occurs in 20-25% of cases. The above facts, as well as our own observations, prompted us to analyze the studied women of fertile age with impaired reproductive system against the background of overweight and obesity. Considering the above, the aim of this study was to identify the relationship between insulin resistance and reproductive disorders in women with overweight and obesity. Material and research methods. The study included 123 women with clinical development of HA and impaired reproductive function, who consulted the consultative clinic of the RSSPMC of Obstetrics and Gynecology of the Ministry of Health of the Republic of Uzbekistan. The criteria for inclusion in the main group were: age of women from 18 to 35 years (average age was 25.8 .. 3.28 years), absence of pregnancy, body mass index over 25 kg / m2. Exclusion criteria from the main group: type 1 and 2 diabetes, pituitary tumors, hypogonadotropichypogonadism, congenital adrenal hyperplasia, hypothyroidism, severe somatic pathology. All patients who applied for the consultation underwent: (1) Collection of anamnestic information. (2) Measurement of anthropometric indicators (height, weight, waist and hip circumference) and assessment of body hair growth using the Ferriman-Hallway scale. (3) Body mass index was
ABSTRACT
Since its inception in 2019 from China, the novel Coronavirus has caused an unprecedented havoc in the economic and public health sector. Many countries were forced to close their borders and cross-border interactions in order to limit the spread of the disease. Furthermore, many economic and commercial activities were adversely affected as many businesses had to close. The only ones that the pandemic spared were the ones providing essential services. By March 2020, many public healthcare facilities had already been overrun. Other governments devised alternative means of managing significant cases of COVID-19, such as introducing home-based care to give room for more critical cases to be taken care of in intensive care units. It is imperative to identify the disease's risk factors to mitigate the unexpected devastation caused by the SARS-CoV-2. Global epidemiological results indicate that men, especially the elderly, are more susceptible to Coronavirus infection. The number of reported Coronavirus cases varies by gender, and this disparity continues to grow in favor of male participants until they reach the age of 60. Other studies have also established that men more than women are susceptible to coronavirus infection. Further, male patients diagnosed with coronavirus infection were shown to have an elevated mortality rate. SARS-CoV-2 is the Covid-19 pathogen that is transmitted via respiratory globules, through indirect or direct interaction. Evaluation of the genome has revealed that SARS-CoV-2 is 79% similar to SARS-CoV-2;they employ ACE2 receptors to attack cells, meanwhile it has been established that TMPRSS2 promotes ACE2, therefore causing more severe reactions in comparison to the other types of coronaviruses. Studies describe ACE2 as a gateway for viruses to enter cells. It is directly associated with the COVID-19 clinical symptoms. Research has shown that TMPRSS2 and ACE2 are expressed in the male reproductive system tract and testis and are controlled by testosterone. Thus, the male reproductive system has all the mechanism needed to bid SARs-CoV-2, and these possibilities raise the capability of ACE2 and TMPRSS2 as potential vectors of COVID-19. This review examines how the novel Coronavirus find its way into the human cells through known receptors such as ACE2, antibody Fcy R, etc. The examination is also done on the mechanisms of its spike proteins transition with the help of proteases such as cathepsins, Furin, and TMPRSS2. The study reviewed six articles selected based on PRISMA criteria.
ABSTRACT
Since covid-19 has been shown to cause infertility in male patients, this study evaluated the sexual level of covid19 patients using sperm and reproductive hormones. For the covid-19 patients, the semen volume was 2.1 ml smaller than the healthy ones, while the sperm count was 67 ml lower than non-covid-19. A substantial difference in total sperm number was found (36 for covid-19 patients and 103 for non-covid-19), with total sperm numbers of 125.33 for patients and 447.21 x106 for healthy. In other words, the percentage of motile sperm was 21.42 for sick and 55.26 for healthy. We discovered that covid-19 sperm have less than 33.84% overall motility than healthy sperm, while the normal morphology revealed for covid-19 patients showed 8.87 per cent less than non-covid-19. The difference between covid-19 and non-covid-19 testosterone is 130.2NG/DL, while the covid-19 patients had 3.7mIU/mL less FSH than non-covid-19 individuals, indicating that covid-19 reduces FSH. LH in covid-19 patients was 3.48UI/L lower than the non-covid-19 patients. As a result, we compared covid-19 and non-covid-19 patients' sex hormone profiles. Therefore, covid-19 has a deleterious effect on sperm properties. Finally, the study adds to the expanding clinical evidence on covid19's influence on male reproductive health. Future research should focus on the effect of covid-19 on female fertility.
ABSTRACT
Background: The two FDA approved mRNA-based SARS-CoV2 vaccines have shown >90% efficacy at preventing COVID and eliciting protective immunity in nearly all healthy individuals. However, the extent of vaccine induced antibody and T cell immunity in immunocompromised patients is not well known. Our study objective is to determine if patients with hematologic malignancies treated with B-cell targeting chimeric antigen receptor (CAR) T cell therapies can mount antibody and T cell immune responses to SARS-CoV2 vaccines. A prospective single-center study to evaluate the SARS-CoV2 immune responses in immunocompromised individuals (COVAX Study) was initiated at University of Pennsylvania following the IRB guidelines. The study enrolled 8 healthy adults,12 patients are in remission after treatment (average of 40.6 months) with CART cells targeting either CD19 or CD19+CD22 and received both doses of SARS-CoV2 vaccine. Methods and Results: Serology to SARS-CoV2 spike-receptor binding domain (RBD) IgG, RBD-IgA, RBD-IgM and spike-specific T cell responses were measured prior to vaccination and serially up to 28 days after booster vaccination. RBD-IgG and RBD-IgA were detected in 8/8 and 7/8 healthy subjects compared to 5/12 and 2/12 CART patients, respectively (Figure A). In the CART cohort, several patients who demonstrated an induction of RBD-IgG (57.2/uL +/- 20.2) compared to those who were RBD-IgG-negative (9/uL +/- 10.1, ANOVA with multiple comparisons test p=0.017) have higher level of circulating B cells. No association was found with time since CART infusion, age, disease type, or vaccine manufacturer. All 8 healthy subjects demonstrated induction of SARS-Cov2 spike-specific CD4 + T cell immunity compared to 7 out of 11 CART patients (Figure B). RBD-IgG responses were not correlated with CD4 + T cell activation (Pearson correlation, R=0.21, p=0.53). Indeed, 3 CART patients demonstrated robust CD4 + T cell activation despite absence of antibody induction. Overall, 8/12 CART patients demonstrated induction of either or both humoral and T cell immune responses. Conclusions: We show that immune responses to SARS-CoV2 mRNA vaccines are induced in majority of patients who have been treated with CART therapies targeting B-cell lineage antigens. Induction of vaccine-specific antibody was strongly associated with the level of circulating B cells. However, in CART cohort patients despite severe humoral immune deficiency, strong CD4 + T cell responses were observed suggestive of a sufficient protective immunity. [Formula presented] Disclosures: Frey: Novartis: Research Funding;Sana Biotechnology: Consultancy;Kite Pharma: Consultancy;Syndax Pharmaceuticals: Consultancy. Garfall: Amgen: Honoraria;CRISPR Therapeutics: Research Funding;GlaxoSmithKline: Honoraria;Janssen: Honoraria, Research Funding;Novartis: Research Funding;Tmunity: Research Funding. Porter: American Society for Transplantation and Cellular Therapy: Honoraria;Genentech: Current equity holder in publicly-traded company, Ended employment in the past 24 months;ASH: Membership on an entity's Board of Directors or advisory committees;DeCart: Membership on an entity's Board of Directors or advisory committees;Incyte: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Kite/Gilead: Membership on an entity's Board of Directors or advisory committees;National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding;Tmunity: Patents & Royalties;Wiley and Sons Publishing: Honoraria. June: AC Immune, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm: Consultancy;Tmunity, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm: Current equity holder in publicly-traded company;Novartis: Patents & Royalties.