Unraveling IL-17 and IL-22 role in occult hepatitis C versus chronic hepatitis C virus infection.

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 < 0.001). The occult group also had higher serum IL-17 levels compared to the control group (p < 0.0001). There were no significant differences in IL-22 levels across the research groups. In the OHCV group, individuals with moderate inflammation (A2-A3) had significantly higher serum IL-17 levels than those with minimal inflammation (A0-A1), while in the CHC group, this difference was not statistically significant (p = 0.601). Neither the occult nor the CHC groups showed a correlation between serum IL-22 and inflammatory activity. There was no significant correlation between the levels of IL-17 or IL-22 and the stage of fibrosis/cirrhosis in either group. ROC curves were calculated for serum IL-17 and IL-22 levels and occult HCV infection, with cut-off values set at ≤ 32.1 pg/ml and < 14.3 pg/ml for IL-17 and IL-22, respectively. The AUROC (95%CI) was significantly higher for IL-17 than IL-22 (0.829 (0.732-0.902) vs. 0.504 (0.393-0.614), p < 0.001), suggesting that IL-17 has a stronger correlation with infection risk than IL-22. CONCLUSION: This study suggests that IL-17 may be involved in the immunopathogenesis of OHCV infection, especially in patients with moderate inflammation.

Evaluation of Bacillus aryabhattai B8W22 peroxidase for phenol removal in waste water effluents.

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.

Aerobic exercise as a non-pharmacological intervention for improving metabolic and hemodynamic profiles in type 2 diabetes.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a global health concern associated with numerous complications. Aerobic exercise is recognized as a crucial non-pharmacological intervention for T2DM management, but its specific effects on key health parameters warrant further investigation. OBJECTIVE: This study aimed to evaluate the impact of a structured 8-week aerobic exercise program on fasting blood glucose (FBG), glycated haemoglobin (HbA1c), body mass index (BMI), blood pressure (BP), and resting heart rate (RHR) in individuals with T2DM. METHODS: A prospective study was conducted with 100 participants diagnosed with T2DM. The intervention group (n = 50) underwent a supervised aerobic exercise program for eight weeks, while the control group (n = 50) received no structured exercise intervention. Pre- and post-intervention assessments were conducted to measure FBG, HbA1c, BMI, BP, RHR, and VO2 max were taken. RESULTS: The aerobic group exhibited a significant reduction in FBG, declining from 141 to 132 mg/dl. Correspondingly, HbA1c decreased from 7.93 to 7.15%. Additionally, the aerobic group demonstrated a notable decrease in RHR from 72 to 66 bpm, indicating improved cardiovascular fitness. Concurrently, VO2 max increased from 22 to 26 mL/kg/min, further supporting the enhancement of cardiorespiratory capacity. Trends toward improvement were also observed in SBP and DBP. Correlation analysis revealed significant relationships between various health parameters, highlighting the interconnectedness of these variables in T2DM management. CONCLUSIONS: This study provides robust evidence supporting the benefits of aerobic exercise in individuals with T2DM. The improvements in glycemic control, blood pressure, and cardiorespiratory fitness underscore the importance of incorporating structured exercise programs into diabetes management protocols. The results emphasize the importance of incorporating regular physical activity into diabetes management strategies to optimize health outcomes and reduce the risk of complications.

Perceptions of medicinal herbal products during the COVID-19 pandemic period among Saudi patients: a cross-sectional study.

A wide variety of health benefits have been demonstrated by medicinal plants, including potent antiviral properties. Additionally, many herbal remedies are known to reduce inflammation and boost immunity, making them an effective preventive measure against viral infections. The study aims to evaluate the perception of medicinal herbs and healthy foods during the pandemic period among Saudi patients. Furthermore, the study seeks to understand how people view medicinal herbs and healthy foods as a means of mitigating the effects of the pandemic and how that perception varies across different demographics. It will also assess the availability of these options in the country and how they have been utilized by the population. A cross-sectional online study was conducted among COVID-19-infected Saudi population at the University of Tabuk, Saudi Arabia. The perception of the use of medicinal herbs and the effect of healthy foods on the treatment or reduction of symptoms of COVID-19 was evaluated. The efficacy of 23 herbal products was evaluated. A total of 909 participants with COVID-19 infection were surveyed; 86.14% were women, 93.73% were between the ages of 18-60, 51.05% were unemployed, 57.43% had a bachelor's degree, and 90.64% were non-smokers. Study participants used medicinal herbs, slime drinks, and medicinal herb tea to reduce coronavirus infection risk by 67.11, 43.56, and 7.18%, respectively. Gender, education, consuming healthy food, and drinking medicinal herbs displayed significant variation among the studied participants (p < 0.001). The study revealed a prevalence of ginger (62.9%), lemon (51.1%), mint (46.8%), honey (45.7%), and anise (43.0%) as commonly used medicinal herb products. To conclude, the survey found a link between gender, education, consuming healthy foods, and drinking medicinal herbs to reduce infection symptoms among Saudi Arabians. Accordingly, lifestyle choices can have a positive impact on health, even in the face of a challenging environment.

Cadmium exposure and its association with oxidative stress, MT1A methylation, and idiopathic male infertility in Egypt: A case-control study.

Idiopathic male infertility, a significant health concern, lacks a clear etiology. Cadmium (Cd), a widespread environmental pollutant known to impact male reproductive health negatively, can accumulate in mussels, a common food source in Egypt. This study investigated the link between ecological Cd exposure, oxidative stress, MT1A methylation, and idiopathic male infertility in two regions of Alexandria. Thirty-three infertile men and 33 fertile controls were included. Cd levels were measured in mussels from the study sites and in participants' blood and semen. Biomarkers reflecting Cd exposure and its effects were assessed. Mussel Cd levels exceeded regulatory limits. Infertile men revealed significantly higher blood and semen Cd levels, reduced semen quality, increased oxidative stress, and elevated MT1A methylation compared to controls. MT1A methylation was inversely correlated with sperm count and is the strongest predictor of idiopathic male infertility, demonstrating the lowest p-value and considerable effect size. This study suggests that environmental Cd exposure, potentially through mussel consumption, may contribute to idiopathic male infertility in Egypt by increasing oxidative stress, inducing epigenetic modifications, and impairing semen quality. These findings underscore the need for further research into the mechanisms underlying Cd-induced male infertility and the development of preventative strategies.

Gingerol and/or sorafenib attenuates the DAB-induced HCC and hepatic portal vein dilatation via ATG4/CASP3 and COIIV/COX-2/NF-κB expression.

Ginger (Gin) has numerous therapeutic properties. One of Gin's most potent components is 6-gingerol, a naturally occurring phenol. This study aimed to investigate the therapeutic impact of gingerol and/or sorafenib on the ATG4/CASP3 and COIIV/COX-2/NF-B Expression as a potential therapy for DAB-induced HCC. Gin was administered to HCC mice induced by p-Dimethylaminoazobenzene (DAB) alone or combined with sorafenib (Sor). Superoxide dismutase (SOD), catalase (CAT), and oxidative stress malondialdehyde (MDA), as well as biochemical markers including AST, ALT, ALP, Albumin, and Bilirubin, were examined. The expression of oncogenes (COIIV, COX-2, NF-κB, and survivin) and tumor suppressor genes (ATG4 and CASP3) was evaluated using qPCR. According to the results, the levels of MDA have been markedly decreased, while SOD and CAT have been increased. Further, the expression levels of tumor suppressor genes were upregulated, whereas the expression levels of oncogene genes were downregulated. Furthermore, in a dose-dependent manner, gingerol has shown the potential to alleviate hepatic portal vein (PV) dilatation and could offer a reliable therapy for HCC. This suggests combining the two compounds may be more effective than alone and that Gin could be a promising therapeutic option for HCC. The binding of Gin and Sor to the active sites of the target genes prevents them from functioning normally, which in turn stops the pathways from carrying out their oncogenic functions. Additionally, COX-2 inhibition reduces the production of certain pro-inflammatory compounds, which further averts oncogenesis. Conclusively, this study indicated that Gin has cytoprotective properties and anti-cancer activity that may be related to controlling oxidative stress. This effect may be achieved by suppressing the COIIV/COX-2/NF-κB pathway and upregulating the ATG4 /CASP3 pathways.

Probiotic-derived silver nanoparticles target mTOR/MMP-9/BCL-2/dependent AMPK activation for hepatic cancer treatment.

Recent advances in nanotechnology have offered novel ways to combat cancer. By utilizing the reducing capabilities of Lactobacillus acidophilus, silver nanoparticles (AgNPs) are synthesized. The anti-cancer properties of AgNPs have been demonstrated in previous studies against several cancer cell lines; it has been hypothesized that these compounds might inhibit AMPK/mTOR signalling and BCL-2 expression. Consequently, the current research used both in vitro and in silico approaches to study whether Lactobacillus acidophilus AgNPs could inhibit cell proliferation autophagy and promote apoptosis in HepG2 cells. The isolated strain was identified as Lactobacillus acidophilus strain RBIM based on 16 s rRNA gene analysis. Based on our research findings, it has been observed that this particular strain can generate increased quantities of AgNPs when subjected to optimal growing conditions. The presence of silanols, carboxylates, phosphonates, and siloxanes on the surface of AgNPs was confirmed using FTIR analysis. AgNPs were configured using UV-visible spectroscopy at 425 nm. In contrast, it was observed that apoptotic cells exhibited orange-coloured bodies due to cellular shrinkage and blebbing initiated by AgNP treatment, compared to non-apoptotic cells. It is worth mentioning that AgNPs exhibited remarkable selectivity in inducing cell death, specifically in HepG2 cells, unlike normal WI-38 cells. The half-maximum inhibitory concentration (IC50) values for HepG2 and WI-38 cells were 4.217 µg/ml and 154.1 µg/ml, respectively. AgNPs induce an upregulation in the synthesis of inflammation-associated cytokines, including (TNF-α and IL-33), within HepG2 cells. AgNPs co-treatment led to higher glutathione levels and activating pro-autophagic genes such as AMPK.Additionally, it resulted in the suppression of mTOR, MMP-9, BCL-2, and α-SMA gene expression. The docking experiments suggest that the binding of AgNPs to the active site of the AMPK enzyme leads to inhibiting its activity. The inhibition of AMPK ultimately results in the suppression of the mechanistic mTOR and triggers apoptosis in HepG2 cells. In conclusion, the results of our study indicate that the utilization of AgNPs may represent a viable strategy for the eradication of liver cancerous cells through the activation of apoptosis and the enhancement of immune system reactions.

Diagnostic performance of new BAST score versus FIB-4 index in predicating of the liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease.

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.

Neutrophil percentage-to-albumin ratio is a new diagnostic marker for spontaneous bacterial peritonitis: a prospective multicenter study.

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.

Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death.

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.