Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the Cochrane Handbook for Systematic Reviews of Interventions. Twenty-four studies were eligible. We identified strong evidence of two microbial markers Fusobacterium and Porphyromonas for ADA vs. CRC, and nine microbial markers Lachnospiraceae-Lachnoclostridium, Ruminococcaceae-Ruminococcus, Parvimonas spp., Parvimonas micra, Enterobacteriaceae, Fusobacterium spp., Bacteroides, Peptostreptococcus-Peptostreptococcus stomatis, Clostridia spp.-Clostridium hylemonae, Clostridium symbiosum, and Porphyromonas-Porphyromonas asaccharolytica for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.

Background: End-stage renal disease (ESRD) is a growing global health concern, and hemodialysis (HD) remains the most common life-sustaining therapy for patients with advanced kidney failure. Both humoral and cellular immunity are impaired post hemodialysis, leading to immune system dysfunction. Methods: We utilized flow cytometry to quantify cell populations based on surface markers, including CD3 (total T lymphocytes), CD4 (helper T-cells), CD8 (cytotoxic T-cells), CD19 (B lymphocytes), and CD16/CD56 (natural killer (NK) cells). EDTA-blood samples were collected intravenously immediately before and after dialysis. Results: A consistent decline in CD3⁺ T lymphocytes was observed post hemodialysis. This reduction occurred across both male and female cohorts: p = 0.0342 and p = 0.0002, respectively. CD8⁺ cytotoxic T-cells decreased significantly post HD, p = 0.0003. Conversely, CD4⁺ helper T-cells exhibited a paradoxical increase, p = 0.0321. The divergent trends in CD4⁺ and CD8⁺ cells led to a statistically significant increase in the CD4/CD8 ratio post dialysis, p = 0.0005. Notably, stratification by gender uncovered that the post-HD changes in CD4⁺ and CD8⁺ T-cells were exclusive to female patients. Females demonstrated a pronounced increase in CD4⁺ cells and a sharper decline in CD8⁺ cells compared to males. CD19⁺ B lymphocytes showed a statistically significant decline post hemodialysis (p < 0.0001). While both genders exhibited reduced B-cell percentages, female patients experienced a more pronounced reduction than males. NK cells were severely depleted post dialysis in both male and female cohorts. Conclusions: Overall, the immune alterations observed in HD patients, including T-cell reduction, B-cell lymphopenia, and changes in NK cell populations, contribute to the increased risk of infections, malignancy, and cardiovascular disease in this population.

Obesity is a growing healthcare problem globally. In Saudi Arabia, 24% of adults aged 15 years and above have been living with Obesity. It is considered a chronic inflammatory condition that is linked to a wide range of disorders including type 2 diabetes mellitus, insulin resistance and cardiovascular diseases. In this study, we aimed to assess the influence of obesity on the proportion of Th17 cells among healthy, overweight, and obese women in Saudi Arabia. Additionally, we aimed to explore potential ligands targeting the master transcription factor of Th17 cells: RORγt. A cross-sectional study was conducted, wherein their body mass index (BMI) and waist circumference (WC) were measured. The proportion of peripheral Th17 cells was determined using flow cytometry. We found a decrease in the proportion of peripheral Th17 among women with central obesity, though this was observed among overweight and obese participants. Interestingly, both BMI and WC were inversely correlated with the proportion of peripheral Th17 cells in women experiencing overweight or obesity, while no change was observed among healthy participants. Notably, the analysis revealed a significant moderate negative correlation between the proportion of Th17 cells and HbA1c levels, observed only among the overweight and obese participants. In this study, we identified three potential binding sites on RORγt molecules of Th17 cells, bound to 58 chemical ligands. The majority of the chemical structures (72.4%) were targeted binding pocket 1 of the RORγt molecule. These findings could provide a new insight to develop new pharmaceutical molecules targeting immune cells to combat obesity and related metabolic disorders.

BACKGROUND: Invariant natural killer T (iNKT) cells are an immune subset that purportedly link the adaptive and the innate arms of the immune system. Importantly, iNKT cells contribute to anti-cancer immunity in different types of hematological and solid malignancies by secreting pro-inflammatory cytokines. Therefore, using such cells in treating different type of tumors would be an ideal candidate for cancer immunotherapy. OBJECTIVE: To assess the prognostic effect of iNKT cells across different types of solid and hematological tumors. METHODS: In systematic review and meta-analysis, articles assessed the prognostic effect of iNKT cells were systemically searched using the scientific databases including Google Scholar, ScienceDirect, PubMed, Cochrane Central, and Scopus. RESULTS: Strikingly, the analysis showed the positive impact of intratumoral or circulating iNKT cells on the survival rate in patients with all studied tumors with overall effect of a pooled hazard ratio of 0.89 (95% CI 0.81 to 0.98; p = 0.01). A highly statistical heterogeneity was noted between studied tumor with I2 = 87%; p = 0.00001. CONCLUSIONS: Taken together, this study would present a new insight into the impact of iNKT cells correlate with caner patients’ survival rate and how such cells would be used as a therapeutic target in these patients.

Men have limited options for contraception, despite the widely accepted public health benefits of it, placing the contraceptive burden solely on women. The current study focuses on inhibiting the PP1γ2 enzyme, which plays a role in sperm maturation and motility. The study considered three top compounds based on the findings of molecular docking. The three compounds exhibited a good interaction profile with a binding affinity score of D751-0223 (−8.7 kcal/mol), D751-014 (−8.1 kcal/mol), and N117-0087 (−8 kcal/mol) measured in kcal/mol. Molecular dynamics simulation (MDS) were performed on the PP1γ2–ligand complexes along with the Apo form. The results suggested that all the complexes were stable with no major deviations observed compared to Apo. The average RMSDs for PP1γ2-D751-0223, D751-014, and Apo were 1.27 Å, 1.73 Å, 1.39 Å, and 1.69 Å, respectively. The PP1γ2–ligand complexes were observed with unique salt bridge interactions such as Glu133-Arg137, Asp4-Lys107, Asp188-Arg116, and Glu120-Arg90. The principal component analysis (PCA) findings indicated that every complex had a distinctive motion state. Furthermore, the net MM/PBSA scores for D751-0223, D751-0143, and N117-0087 were −80.01 kcal/mol, −72.18 kcal/mol, and −64.26 kcal/mol, respectively, while the MM/GBSA and MM/PBSA values were −82, −73.07,−67.26 and −80.01, −72.18, −64.26, measured in kcal/mol, respectively. The WaterSwap energy estimation was performed to validate the former technique, and the findings demonstrated that PP1γ2-D751-0223 is a stable complex, with a value of −51.05 kcal/mol. This work provides a baseline to researchers for the identification of novel therapeutic approaches for non-hormonal male contraceptives.

Background/Objectives: SARS-CoV-2 continues to generate antigenically divergent variants that reduce the breadth of existing vaccine-induced antibody responses. Fc-fusion subunit vaccines offer advantages in stability, antigen display, and Fc-mediated immune engagement. This study aimed to design and evaluate a tetravalent RBD–Fc fusion construct incorporating RBDs from Wuhan-Hu-1 and Omicron BA.4/BA.5 and to determine whether this configuration can induce broad antibody recognition across SARS-CoV-2 variants. The objective was to assess its feasibility, biochemical properties, and initial immunogenicity. Methods: Immune responses to the construct were first assessed using the C-ImmSim simulation platform. The full-length fusion was synthesized, subcloned into pcDNA3.1(+), expressed in HEK293 cells, and purified by Protein G affinity chromatography. Protein integrity was evaluated by reducing SDS–PAGE. BALB/c mice (female, 8 weeks) were immunized with a prime–boost–boost schedule, and sera were analyzed by ELISA, considering binding to Wuhan-Hu-1, Omicron BA.4/BA.5, and a panel of RBD variants. Results: In silico analysis predicted coordinated antigen clearance, class switching, memory B- and CD4⁺ T-cell formation, and transient cytokine induction. The recombinant protein was expressed efficiently, yielding a major ~56 kDa band and a ~23 kDa RBD fragment. Vaccinated mice generated strong IgG responses to Wuhan-Hu-1 and BA.4/BA.5 RBDs and showed broad binding to major variant RBDs. Conclusions: The tetravalent RBD–Fc fusion vaccine was successfully produced and elicited broad antibody binding across SARS-CoV-2 variants, supporting its potential as a versatile protein-based vaccine platform.