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Abstract Background and aim Recurrent pregnancy loss (RPL), also known as recurrent implantation failure (RIF), is a distressing condition affecting women characterized by two or more consecutive miscarriages or the inability to carry a pregnancy beyond 20 weeks. Immunological factors and genetic variations, particularly in Vit D Binding Protein (VDBP), have gained attention as potential contributors to RPL. This study aimed to provide insight into the immunological, genetic, and metabolic networks underlying RPL, placing a particular emphasis on the interactions between VDBP, HLA-G1, CTLA-4, ENTPD1, and adenosine-fetal-maternal conflict crosstalk. Methods A retrospective study included 198 women with three or more consecutive spontaneous abortions. Exclusion criteria comprised uterine abnormalities, endocrine disorders, parental chromosomal abnormalities, infectious factors, autoimmune diseases, or connective tissue diseases. Immunological interplay was investigated in 162 female participants, divided into two groups based on their Vit D levels: normal Vit D-RPL and low Vit D-RPL. Various laboratory techniques were employed, including LC/MS/MS for Vit D measurement, ELISA for protein detection, flow cytometry for immune function analysis, and molecular docking for protein–ligand interaction assessment. Results General characteristics between groups were significant regarding Vit D and glucose levels. Low Vit D levels were associated with decreased NK cell activity and downregulation of HLA-G1 and HLA-G5 proteins, while CTLA-4 revealed upregulation. VDBP was significantly downregulated in the low Vit D group. Our findings highlight the intricate relationship between Vit D status and adenosine metabolism by the downregulation of SGLT1, and NT5E, key components of adenosine metabolism, suggests that Vit D deficiency may disrupt the regulation of adenosine levels, leading to an impaired reproductive outcome. HNF1β, a negative regulator of VDBP, was upregulated, while HNF1α, a positive regulator, was downregulated in low Vit D women after RPL. Molecular docking analysis revealed crucial residues involved in the interaction between Vit D and HNF1β. Conclusion Collectively, these findings underscore the importance of Vit D in modulating immune function and molecular pathways relevant to pregnancy maintenance, highlighting the need for further research to elucidate the mechanisms and potential therapeutic interventions for improving pregnancy outcomes in individuals with Vit D deficiency and RPL.

Abstract Background and aim Metabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common liver condition globally. The FIB-4 test is used to detect fibrosis in fatty liver disease but has limited accuracy in predicting liver stiffness, resulting in high rates of false positives and negatives. The new BAST scoring system, incorporating waist circumference, AST, and BMI, has been developed to assess the presence of fibrosis in NAFLD patients. This study compares the effectiveness of BAST and FIB-4 in predicting liver fibrosis in MASLD patients. Patients and methods The study included 140 non-diabetic MASLD patients who underwent transient elastography measurement. BAST score and FIB-4 were calculated for each patient. Patients were grouped based on fibrosis severity; F1, F2, and F3–F4. The sensitivity and specificity of the BAST score and FIB-4 were assessed using receiver operating characteristic curves. Results The BAST score increased significantly with fibrosis progression from F1 to F3–F4. In differentiating advanced fibrosis (F2–F3) from mild/moderate fibrosis (F1–F2), the BAST score at cutoff ≤ − 0.451 showed better diagnostic performance with 90.70% sensitivity, 74.07% specificity, 84.8% PPV and 83.3% NPV compared to FIB-4 that had 60.47% sensitivity, 50.0% specificity, 65.8% PPV and 44.3% NPV. Similarly, for differentiating between F1 and F2 fibrosis, the BAST score at cutoff ≤ − 1.11 outperformed FIB-4, with 80.23% sensitivity, 79.49% specificity, 89.6% PPV and 64.6% NPV, while FIB-4 had 59.30% sensitivity, 51.28% specificity, 72.9% PPV and 36% NPV. Conclusions The BAST score is a better predictor of liver fibrosis in MASLD compared to FIB-4, especially in cases of advanced fibrosis or cirrhosis.

Abstract Background The neutrophil percentage-to-albumin ratio (NPAR) is a novel measure of systemic inflammation and infection. Low albumin levels increase the risk of infection, while high neutrophil counts indicate the presence of infection. Spontaneous bacterial peritonitis (SBP) is a serious infection in cirrhotic ascites, and the potential of NPAR in diagnosing SBP is not yet established. Objective The objective of this study is to determine the diagnostic value of NPAR in identifying SBP. Patients This prospective multicenter study included 465 patients diagnosed with cirrhotic ascites and SBP according to international guidelines. Demographic, clinical, and laboratory data were collected. The sensitivity and specificity of NPAR values for diagnosing SBP were assessed using the receiver operating characteristic curve. Results For SBP diagnosis in the total cohort, NPAR of > 17 had a sensitivity of 85.71%, specificity of 66.67%, and 95% CI (42.1–99.6). In culture-positive SBP, the NPAR at a cut-off > 5.2 had a sensitivity of 85.71%, specificity of 83.33%, and 95% CI (0.709 to 0.979), while in culture-negative SBP, the NPAR at a cut-off > 2.1 had a sensitivity of 92.86%, specificity of 33.33% and CI (0.367 to 0.764). The multivariate analysis revealed that albumin (OR = 2.78, [1.11;3.98], INR (OR = 0.198, [0.066;0.596], creatinine (OR = 0.292, [0.1; 0.81], CRP (OR = 3.18, [1.239;4.52] total leukocytic count (TLC) (OR = 1.97, [1.878; 2.07], platelets (OR = 2.09, [0.99; 2.31] and neutrophil (OR = 3.43, [1.04;3.89] were significantly associated with higher prediction rates for culture positive SBP. Conclusions NPAR could be a new, affordable, noninvasive test for diagnosing SBP.

Abstract Background Cytokines play a crucial role in regulating the function of the immune system by controlling the production, differentiation, and activity of immune cells. Occult hepatitis C virus (OHCV) infection can lead to liver damage, including cirrhosis and hepatocellular carcinoma. This study investigates the immunopathogenic impact of the cytokines IL-17 and IL-22 in OHCV infection compared to chronic hepatitis C (CHC) infection. Methods We studied three groups of patients: 35 with OHCV, 100 untreated patients with CHC, and 30 healthy control subjects. All subjects underwent physical examination and biochemical testing. We used the sandwich enzyme-linked immunosorbent assay method to measure serum IL-17 and IL-22 levels in all groups. Results Compared to the occult and control groups, the CHC group had significantly higher serum IL-17 levels (p

Abstract Background Sorafenib (Sor) is the only approved multikinase inhibitor indicated for the treatment of HCC. Previous studies have shown that amygdalin (Amy) possesses anticancer activities against several cancer cell lines; we suggested that these compounds might disrupt AMPK/mTOR and BCL-2. Therefore, the current study used integrated in vitro and in silico approaches to figure out Amy and Sor’s possible synergistic activity in targeting AMPK/mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death in HepG2 cells. Results Notably, Amy demonstrated exceptional cytotoxic selectivity against HepG2 cells in comparison to normal WI-38 cells (IC50 = 5.21 mg/ml; 141.25 mg/ml), respectively. In contrast, WI-38 cells were far more sensitive to the toxicity of Sor. A substantial synergistic interaction between Amy and Sor was observed (CI50 = 0.56), which was connected to cell cycle arrest at the S and G2/M stages and increased apoptosis and potential necroptosis. Amy and Sor cotreatment resulted in the highest glutathione levels and induction of pro-autophagic genes AMPK, HGMB1, ATG5, Beclin 1, and LC3, suppressed the mTOR and BCL2 anti-apoptotic gene. Finally, the docking studies proposed that Amy binds to the active site of the AMPK enzyme, thus inhibiting its activity. This inhibition of AMPK ultimately leads to inhibition of mTOR and thus induces apoptosis in the HepG2 cells. Conclusion Although more in vivo research using animal models is needed to confirm the findings, our findings contribute to the evidence supporting Amy’s potential anticancer effectiveness as an alternative therapeutic option for HCC.

Abstract Background and aim There is lack of 30-day hospital readmission prediction score in patients with liver cirrhosis and SBP. The aim of this study is to recognize factors capable of predicting 30-day readmission and to develop a readmission risk score in patients with SBP. Methods This study prospectively examined the 30-day hospital readmission for patients previously discharged with a diagnosis of SBP. Based on index hospitalization variables, a multivariable logistic regression model was implemented to recognize predictors of patient hospital readmission within 30 days. Consequently, Mousa readmission risk score was established to predict 30-day hospital readmission. Results Of 475 patients hospitalized with SBP, 400 patients were included in this study. The 30-day readmission rate was 26.5%, with 16.03% of patients readmitted with SBP. Age ≥ 60, MELD > 15, serum bilirubin > 1.5 mg/dL, creatinine > 1.2 mg/dL, INR > 1.4, albumin

Abstract Environmental contamination by phenol has been reported in both aquatic and atmospheric environments. This study aimed to separate and purify the peroxidase enzyme from bacteria that degrade phenol from wastewater sources. An enrichment culture of MSM was used to screen 25 bacterial isolates from different water samples for peroxidase production, six of the isolates exhibited high levels of peroxidase enzyme activity. Qualitative analysis of peroxidase revealed that isolate No. 4 had the highest halo zones (Poly-R478: 14.79 ± 0.78 mm, Azure B: 8.81 ± 0.61 mm). The promising isolate was identified as Bacillus aryabhattai B8W22 by 16S rRNA gene sequencing with accession number OP458197. As carbon and nitrogen sources, mannitol and sodium nitrate were utilized to achieve maximum peroxidase production. A 30-h incubation period was used with pH 6.0, 30 °C, mannitol, and sodium nitrate, respectively, for maximal production of peroxidase. Purified peroxidase enzyme showed 0.012 U/mg specific activity, and SDS-PAGE analysis indicated a molecular weight of 66 kDa. The purified enzyme exhibits maximum activity and thermal stability at pH values of 4.0 and 8.0, respectively, with maximum activity at 30 °C and complete thermal stability at 40 °C. In the purified enzyme, the Km value was 6.942 mg/ml and the Vmax value was 4.132 mol/ml/hr, respectively. The results demonstrated that Bacillus aryabhattai B8W22 has promising potential for degrading phenols from various phenol-polluted wastewater sources.

Abstract Background Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. Methods We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. Results Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. Conclusion This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.