Molecular Role of Asn680Ser and Asp37Glu Missense Variants in Saudi Women with Female Infertility and Polycystic Ovarian Syndrome.

Female infertility (FI) is a global health issue. Polycystic ovary syndrome (PCOS) is a common cause of FI. The renalase gene (RNLS) is associated with FI and other human diseases. Based on the documented missense variants, rs6166 and rs2296545 single-nucleotide polymorphisms (SNPs) were not identified in Saudi women with FI and PCOS. This study aimed to investigate the molecular role of the two SNPs in Saudi women with FI and PCOS. In this cross-sectional study, 96 healthy controls, 96 women with FI, and 96 women with PCOS were recruited. DNA was isolated, and polymerase chain reactions and Sanger sequencing analysis were performed using rs6166 and rs2296545 SNPs. The data obtained from the three groups were used to perform statistical analyses based on genotype, allele frequencies, regression models, and ANOVA analysis. Both rs6166 and rs2296545 had no role in FI or PCOS in Saudi women. A predicted reason for non-association in Saudi women could be the role of elderly women in the controls compared with women with FI and PCOS. Moreover, age, weight, and body mass index were higher in the control group than the FI and PCOS groups. In conclusion, rs6166 and rs2296545 SNPs were not associated with FI or PCOS in Saudi women.

Combined Supplementation of Clostridium butyricum and Bifidobacterium infantis Diminishes Chronic Unpredictable Mild Stress-Induced Intestinal Alterations via Activation of Nrf-2 Signaling Pathway in Rats.

Exposure to long-term chronic unpredictable mild stress (CUMS) can cause redox imbalance and inflammation, which may affect the integrity of the gut barrier. The present study was conducted to investigate the effects of a probiotics bacterium mixture, including Clostridium butyricum (C. butyricum) and Bifidobacterium infantis (B. infantis), on the intestinal homeostasis in rats exposed to multiple low-intensity stressors for 28 days. The mechanism of CUMS-induced altered intestinal homeostasis was evaluated by focusing on the nuclear factor-E2-related factor-2 (Nrf-2) pathway. In contrast to the CUMS group, probiotic mixture supplementation significantly (p < 0.01) reversed the stress-induced elevated corticosterone level, protein and lipid oxidation, and increased enzymatic and non-enzymatic antioxidant levels, as well as upregulated Nrf-2/HO-1 pathway. Probiotics supplementation further significantly (p < 0.01) decreased the CUMS-induced inflammation, altered T-lymphocyte levels, and suppressed the protein expression of nuclear factor kappa B (NF-κB) in rat intestines. Improvement in histological changes and intestinal barrier integrity further validate the beneficial effects of probiotic mixtures on CUMS-induced altered intestinal morphology. In conclusion, our results suggest that the combination of C. butyricum and B. infantis significantly attenuated CUMS-induced oxidative stress, inflammation, and T-lymphocyte modulation by upregulating Nrf-2/HO-1 signaling and inhibiting NF-κB expression in rat intestine.

Quantification of Methylisothiazolinone and Methylchloroisothiazolinone Preservatives by High-Performance Liquid Chromatography.

Isothiazolinone preservatives (methylisothiazolinone (MIT) and methylchloroisothiazolinone (CMIT) are commonly used in cosmetics, industrial and household products. However, these isothiazolinone derivatives are known to cause allergic contact dermatitis. Hence, a sensitive, accurate, and reliable method for the detection of these compounds is thus warranted. The study aims to analyze concentrations of MIT and CMIT by high performance liquid chromatography. The analytical method used for quantification of MIT and CMIT in cosmetic products (leave-on-baby wet wipes) complies with the validation acceptance criteria (international standards ISO 5725, EU25 European Union for cosmetic regulations). MIT and CMIT were extracted and analyzed in leave-on baby wet-wipes collected from different stores in Riyadh city. Extraction was performed by ultrasonication of the samples, solid-phase extraction, and liquid-liquid extraction. Ten (10) µL of the sample was injected into the HPLC system and samples were analyzed with a mixture of acetic acid and methanol (80:20 v/v) in an isocratic mode. The flow rate was maintained at 1 mL/min. UV detection was performed at 274 nm. The results demonstrated recoveries between 90 and 106%, measurement uncertainty of C +/- 0.4% for methylisothiazolinone and C +/- 0.03% for methylchloroisothiazolinone, repeatability limit (r = 0.2%) and intermediate precision limit; R = 2% and R2 of 0.9996.

Unleashing the power of anti-CD20 immunotherapy: Mitigating multiple sclerosis risk in Epstein-Barr virus latent infections.

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative connective tissue disease affecting the central nervous system (CNS). Recently, there has been a dramatic improvement in several vital concepts of immune pathophysiology underlying MS. Notably, one of the prerequisites to MS development is Epstein-Barr virus (EBV) infection. Greater attention has been drawn towards promising, innovative immunotherapies in the management and treatment of MS. Whilst there are numerous immunotherapies currently proposed for MS, the B cell depleting therapy that predominantly uses the anti-CD20 monoclonal antibodies (mAbs) such as rituximab, ocrelizumab, and ofatumumab have demonstrated promising clinical benefits by targeting the memory B cells, which are the primary reservoir of EBV latency. Although mAbs have proved beneficial in the treatment of MS, they pose the risk of potential adverse effects. The current systematic review was undertaken to explore the therapeutic role of anti-CD20 therapy and its downsides in the treatment of MS and EBV infection. Clinical trials and prospective and retrospective studies reporting anti-CD20 therapy were carefully reviewed. The initial sections discuss the clinical features of MS, the probable link between EBV and MS, and the role of B cells in MS pathogenesis. Here, we show the potential role of anti-CD20 therapy more of a boon than a bane as the therapy yields more promising results for MS treatment. Nevertheless, the adverse effects could be minimized following a planned therapeutic regimen for treating MS patients.

The Epidemiological Pattern, Resistance Characteristics and Clinical Outcome of Enterobacter cloacae: Recent Updates and Impact of COVID-19 Pandemic.

OBJECTIVES: E. cloacae is an opportunistic organism that causes serious infections, particularly in immuno-compromised and hospitalized patients, along with the emergence of resistance traits. The COVID-19 pandemic has impacted the epidemiological pattern and resistance traits of E. cloacae infections as well as those of other bacteria. The study aims to assess the epidemiological patterns, resistance characteristics and clinical outcomes of E. cloacae in Saudi Arabia and the impact of the COVID-19 pandemic. METHODS: King Fahad Medical City in Riyadh provided the data between January 2019 and December 2021 for the retrospective study of 638 isolates of E. cloacae. The clinical outcome of an E. cloacae infection was also determined by collecting and statistically analyzing the clinical records of 153 ICU patients. RESULTS: The total percentage of resistant E. cloacae isolates decreased from 48.36% in 2019 to 38% in 2020 and 37.6% in 2021. The overall mortality rate among ICU patients was 40.5%, with an adult age group having a substantial relative risk value of 1.37. CONCLUSION: E. cloacae is a prevalent nosocomial infection in which adult age is a significant risk factor for mortality. Moreover, this study emphasizes the importance of comparing E. cloacae resistance trends before and throughout the pandemic period in order to better understand the bacteria's behaviour.

Assessing the knowledge and attitude towards HIV/AIDS among the general population and health care professionals in MENA region.

INTRODUCTION: Human Immunodeficiency Virus infection continue to represent a global health concern influenced by various social, economic, and cultural factors. The MENA are among the top regions in the world with the fastest-growing HIV epidemic. Thus, adequate knowledge and a positive attitude of people toward HIV/AIDS are of utmost importance to prevent the spreading of the disease. Accordingly, this study aims to evaluate the knowledge and attitude of the public and healthcare population toward HIV/AIDs. METHODS: A cross-sectional analysis was conducted among residents within our population from October 2018 until August 2019. An anonymous online questionnaire was used to investigate the population's demographic characteristics, HIV/AIDS-related knowledge, and attitudes toward HIV-infected patients. Participants completed a 40-item questionnaire designed to measure their knowledge and attitude toward HIV/AIDS. The data was collected via surveys, administered through electronic tablets to the participants at public places (n = 5,757) and through an online version of the questionnaire on Google Forms (n = 2500), which was sent through social media platforms. Descriptive statistics were used to analyse the data using the R-statistical software program. RESULTS: A total of 8,257 participants were included in our analysis. Saudi Arabian citizens represented 79% of the participants, while participants from the MENA countries represented 11.7% and 3% from the other Gulf Cooperation Council countries. Fifty-nine (59%) knew that HIV is a contagious infection, and 13.8% were unaware that HIV could be transmitted sexually. A few healthcare professionals reported negative attitudes toward HIV infected patients. Many risk factors, including age, gender, nationality, and education, significantly affected the knowledge and attitude scores. In this survey, we found that social media is the primary source of participants' information. CONCLUSIONS: Overall correct knowledge score of individuals about HIV/AIDS was relatively low. This study showed that the general population was knowledgeable to a certain degree about HIV/AIDS and its modes of transmission. Nevertheless, they lack a detailed understanding of the disease's nature, modes of transmission, and existing treatment. Policymakers in the region should further eliminate social discrimination and stigma in HIV-infected patients.

A unique investigation of thallium, tellurium, osmium, and other heavy metals in recurrent pregnancy loss: A novel approach.

OBJECTIVE: To study the impact of heavy metals especially tellurium, thallium, and osmium, in recurrent pregnancy loss (RPL) and to study their association with antioxidant status and DNA damage. METHODS: This case-control study included women with RPL (n = 30) and healthy pregnant women as control (n = 30). Following blood collection, serum levels of thallium, tellurium, osmium, lead, mercury, and cadmium were estimated by inductively coupled plasma mass spectrophotometer. RESULTS: Women with RPL exhibited significantly higher levels of heavy metals (P < 0.001) when compared with control women. Intriguingly, increased levels of serum thallium, tellurium, osmium, and lead were negatively correlated with total antioxidant status (P < 0.05). Further, the RPL group demonstrated strong positive correlation between heavy metals (thallium, tellurium, osmium, lead) and DNA damage (P < 0.05). No significant correlation between other heavy metals and markers of cellular damage was noted. CONCLUSION: Enhanced levels of heavy metals in women with RPL and correlation of thallium, tellurium, osmium, and lead with markers of cellular damage reflect the role of heavy metal poisoning, especially thallium, tellurium, and osmium, as potential risk factor in the etiology underlying recurrent miscarriage.

The platinum coordination complex inhibits cell invasion-migration and epithelial-to-mesenchymal transition by altering the TGF-ß-SMAD pathway in colorectal cancer.

Introduction: There is a steady increase in colorectal cancer (CRC) incidences worldwide; at diagnosis, about 20 percent of cases show metastases. The transforming growth factor-beta (TGF-ß) signaling pathway is one of the critical pathways that influence the expression of cadherins allowing the epithelial-to-mesenchymal transition (EMT), which is involved in the progression of the normal colorectal epithelium to adenoma and metastatic carcinoma. The current study aimed to investigate the impact of a novel coordination complex of platinum (salicylaldiminato) PT(II) complex with dimethyl propylene linkage (PT-complex) on TGF-ß and EMT markers involved in the invasion and migration of the human HT-29 and SW620 CRC cell lines. Methods: Functional study and wound healing assay showed PT-complex significantly reduced cell motility and the migration and invasion of CRC cell lines compared to the untreated control. Western blot performed in the presence and absence of TGF-ß demonstrated that PT-complex significantly regulated the TGF-ß-mediated altered expressions of EMT markers. Results and Discussion: PT-complex attenuated the migration and invasion by upregulating the protein expression of EMT-suppressing factor E-cadherin and suppressing EMT-inducing factors such as N-Cadherin and Vimentin. Moreover, PT-complex significantly suppressed the activation of SMAD3 in both CRC cell lines. Further, the microarray data analysis revealed differential expression of genes related to invasion and migration. In conclusion, besides displaying antiproliferative activity, the PT complex can decrease the metastasis of CRC cell lines by modulating TGF-ß-regulated EMT markers. These findings provide new insight into TGF-ß/SMAD signaling as the molecular mechanism involved in the antitumoral properties of novel PT-complex.

Immune and Oxidative Response against Sonicated Antigen of Mycoplasma capricolum subspecies capripneumonia-A Causative Agent of Contagious Caprine Pleuropneumonia.

Vaccines are vital for prevention and control of mycoplasma diseases. The exploration of a vaccine candidate for the development of a vaccine is imperative. The present study envisages the evaluation of immune and oxidative response against an adjuvanted, sonicated antigen of Mycoplasma capricolum subsp. capripneumonia in male Angora rabbits (1 year old, 2 kg) divided in four groups, each having six animals. Group 1 was the healthy control and received 1 mL PBS via subcutaneous route. Group 2 was administered 1 mL of saponin-adjuvanted and -sonicated antigen, Group 3 was given 1 mL of montanide ISA 50-adjuvanted and-sonicated antigen, and Group 4 was given 1 mL of standard vaccine via subcutaneous route. Animals were evaluated for cellular and humoral immune response and oxidative parameters at 0, 7, 14, 21, and 28 days of the study. Total leukocytic, neutrophilic, and basophilic counts showed a significant (p < 0.05) increase in vaccinated groups compared to the healthy group on most of the intervals. TNF-α levels were significantly (p < 0.05) higher in the Group 2 than the Group 1 at all the time intervals and more comparable to Group 4 than Group 3. IL-10 levels were significantly (p < 0.05) higher in vaccinated groups compared to the healthy group on days 14, 21, and 28, but were lower in Group 3 than in Group 2 and Group 4. More hypersensitivity as inflammation and histopathological cellular infiltration in the ear was produced in Group 2 and Group 4 than in Group 3. IgG levels were significantly (p < 0.05) higher in Group 2 and Group 4 than in Group 3 on days 14 and 21. Antibody titers were comparatively higher in Group 4, followed by Group 2 and 3, than Group 1. Significantly (p < 0.05) higher oxidant and lower antioxidant values were noted in Group 2 and 4 compared to Group 3 and Group 1 on most of the intervals. The TLC and antibody titer showed increasing trend throughout the trial, whereas TNF-α, IgG, L, M and E started decreasing from day 14, and IL-10, N and B started decreasing from day 21. This study concludes that the saponin-adjuvanted and-sonicated antigen induces comparatively higher immune response than montanide but is associated with oxidative and inflammatory reactions.

Gene expression data analysis identifies multiple deregulated pathways in patients with asthma.

Asthma is a chronic inflammatory disorder associated with airway hyper-responsiveness. Although a number of studies have investigated asthma at the molecular level, the molecular immune signatures associated with asthma severity or with the response to corticosteroids are still being unraveled. The present study integrated four asthma-related gene expression datasets from the Gene Expression Omnibus and identified immune-gene signatures associated with asthma development, severity, or response to treatment. Normal and mild asthmatic patients clustered separately from the severe asthma group, suggesting substantial progression-related changes in gene expression. Pathway analysis of up-regulated severe asthma-related genes identified multiple cellular processes, such as polymorphism, T-cell development, and transforming growth factor-ß signaling. Comparing gene expression profiles of bronchoalveolar lavage cells in response to corticosteroid treatment, showed substantial reductions in genes related to the inflammatory response, including tumor necrosis factor signaling in the corticosteroid sensitive versus resistant patients, suggesting a defective immune response to corticosteroids. The data highlight the multifactorial nature of asthma, but revealed no significant overlap with the gene expression profiles from different datasets interrogated in current studies. The presented profile suggests that genes involved in asthma progression are different from those involved in the response to corticosteroids and this could affect the clinical management of different groups of patients with asthma.