Amina A. Abdelhadi

Obesity is associated with metabolic dysregulation and impaired male reproductive capacity, where the gut microbiota affects male reproductive function through diverse mechanisms that warrant further elucidation. This study aims to evaluate the effects of ketogenic and vegan dietary interventions in attenuating obesity-associated testicular injury and to examine the extent to which specific gut microbiota profiles mediate their impact. Forty-nine male adult albino rats were assigned to seven groups: control group, obese group (HFD), obese group + modified microbiota, obese group + ketogenic diet, obese group + ketogenic diet + modified microbiota, obese group + vegan diet, and obese group + vegan diet + modified microbiota. Metabolic markers (glucose, insulin, leptin, and HOMA-IR), reproductive hormones (testosterone, FSH, and LH), and testicular gene expression (IL-6, eNOS, and androgen receptor) were analyzed over five months. Gut microbiota composition (qPCR) and testicular histology/immunohistochemistry were assessed. HFD-fed rats exhibited hyperglycemia, insulin resistance, hypogonadism, and testicular degeneration. Both diets improved metabolic and hormonal profiles, restored testicular architecture, and downregulated inflammatory genes. Microbiota modification additively enhanced these effects, increasing the abundance of Lactobacillus and Akkermansia while reducing inflammation. The vegan diet showed superior efficacy in improving metabolic parameters, modulating pituitary–gonadal hormones, and attenuating testicular structural and functional alterations. Our findings demonstrate that ketogenic and vegan diets alleviate obesity-induced testicular dysfunction and that microbiota modulation amplifies these benefits by regulating the gut–testicular axis. Integrating dietary and microbial interventions may provide a basis for a promising approach to managing obesity-related male infertility.

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. To explore its pathophysiology, we investigated the association between neonatal allergic exposure and behavioral changes. Adult female C57BL/6J mice were immunized with adjuvant (aluminum hydroxide) or ovalbumin emulsified with adjuvant. After immunization, the mice were mated, and offspring were born at full term. The postnatal dams and infants were then simultaneously exposed to an allergen (ovalbumin) or vehicle via inhalation. After weaning, behavioral testing and histopathological analyses were conducted on male offspring. Compared with the vehicle-exposed offspring, the ovalbumin-exposed offspring had decreased sociability and increased repetitive behavior, thus representing an ASD-like phenotype in mice. Moreover, histopathological analyses revealed that the ovalbumin-exposed mice had increased astroglial, microglial, and eosinophilic infiltration in the olfactory bulb, as well as increased eosinophils in the nasal mucosa. The ovalbumin-exposed mice also had decreased dendritic spine density and a lower proportion of mature spines, suggesting the impairment of stimulus-induced synaptogenesis. In conclusion, postnatal allergic exposure induced an ASD-like phenotype, as well as allergic rhinitis, which was followed by glial inflammation in the olfactory bulb parenchyma.

Cancer immunotherapy is a promising strategy in cancer management, including hepatocellular carcinoma (HCC). This experimental study aimed to evaluate interleukin-10 (IL-10) as a biomarker for monitoring the response of tumor-derived autophagosomes vaccine in inducing antitumor immunity in HCC induced mice. It was conducted on 56 BALB/c mice; divided into 20 normal and 36, cancer induced with human liver cancer cell line (HepG2) cells. The latter group was subdivided into a positive control group (n=6) and a treated group (n=30), that was subdivided into 3 subgroups: (A) treated with dendritic cells (DC) vaccine only, (B) treated with vaccine named Dribbles only, and (C) treated with DC plus Dribbles. Serum IL-10 was assessed after immunotherapy. The mean percentage of tumor volume reduction in mice vaccinated by DC plus Dribbles was significantly superior to DC and Dribbles groups (p= 0.013, and p= 0.043, respectively). There was a statistically significant difference in IL-10 levels between different immunotherapy groups (p= 0.0003). As the mean IL-10 level was 19.50 pg/ml for the positive control group, 13 pg/ml for Dribbles group, 10 pg/ml for DCs group and 3.50 pg/ml for DCs plus Dribbles group. We conclude that DC-Dribbles vaccine has a remarkable efficacy superior to either Dribbles alone or DC alone in the decline of HCC development and survival improvement. IL-10 is a predictive biomarker for response after immunotherapy.

Aging enhances numerous processes that compromise homeostasis and pathophysiological processes. Among these, activated HSCs play a pivotal role in advancing liver fibrosis. This research delved into how aging impacts liver fibrosis mechanisms. The study involved 32 albino rats categorized into four groups: Group I (young controls), Group II (young with liver fibrosis), Group III (old controls), and Group IV (old with liver fibrosis). Various parameters including serum ALT, adiponectin, leptin, and cholesterol levels were evaluated. Histopathological analysis was performed, alongside assessments of TGF-β, FOXP3, and CD133 gene expressions. Markers of fibrosis and apoptosis were the highest in group IV. Adiponectin levels significantly decreased in Group IV compared to all other groups except Group II, while cholesterol levels were significantly higher in liver fibrosis groups than their respective control groups. Group III displayed high hepatic expression of desmin, α-SMA, GFAP and TGF- β and in contrast to Group I. Increased TGF-β and FOXP3 gene expressions were observed in Group IV relative to Group II, while CD133 gene expression decreased in Group IV compared to Group II. In conclusion, aging modulates immune responses, impairs regenerative capacities via HSC activation, and influences adipokine and cholesterol levels, elevating the susceptibility to liver fibrosis.

Background: Rheumatoid arthritis (RA) leads to joint deformities or permanent disability. The erratic expression of various micro-RNAs (miRNAs) is strongly associated with RA. This research assessed the significance of miRNA-146a and miRNA-155 as predictors of RA development. We also assessed their promising application as biomarkers of RA disease activity.Methods: This case-control study included 62 subjects (31 RA patients and 31 healthy controls). Participants' sera were used for laboratory tests and measuring miRNA-146a and miRNA-155 gene expression.Results: In RA patients, miRNA-146a and miRNA-155 expressions were significantly higher than in controls (P<0.001). The receiver operating characteristic (ROC) curve analysis showed that miRNA-146a could predict RA with area under curve (AUC) 0.857, sensitivity 77.4%, and specificity 80.6% (P<0.001) at 95% confidence interval (CI). MiRNA-155 could predict RA with AUC 0.829, sensitivity 77.4% and specificity 67.7% (P<0.001) at 95% CI. Active RA patients expressed more miRNA-146a and miRNA-155 than the inactive group. There was a significant positive correlation (P<0.05) among miRNAs-146a and155 expression levels and DAS-28 score in RA patients. MiRNA -146a increased the risk of active RA significantly independently by 2.023 folds. The ROC curve showed that miRNA -146a is useful for predicting RA disease activity with AUC 0.905, sensitivity 91.3% and specificity 87.5% (P<0.001) at 95% CI .Conclusion: MiRNA-146a and miRNA-155 expressions were remarkable in RA patients and were recognized as potential biomarkers for early RA diagnosis. MiRNA- 146a expression is an independent risk for active RA and could be a valuable biomarker to predict RA disease activity.

Background: Coagulase-negative Staphylococci (CoNS) are opportunistic pathogens causing severe hospital-acquired infections. This study aimed to determine the frequency of linezolid-resistant CoNS (LRCoNS) in intensive care unit (ICU) infected patients and the related resistance genes. Methods: Seventy CoNS were isolated from 254 different clinical samples from ICU patients. They were identified by conventional methods; species were identified by API. Antimicrobial susceptibility test (AST) by disc diffusion method was performed for CoNS isolates. Methicillin resistance was identified by resistance to cefoxitin (30 μg) disc. Linezolid resistance was confirmed by measuring the minimal inhibitory concentration (MIC) using E-test strips (0.016-256 μg/ml). Three resistance genes (cfr, optrA and poxtA) were tested for the LRCoNS by PCR. Results: Among the 70 CoNS isolates, three LRCoNS were detected by disc diffusion method and confirmed by MIC (>256 μg/ml). Approximately 71.4% of the isolated CoNS were multi-drug resistant (MDR) and 68.6% were methicillin-resistant (MR). The three LRCoNS isolates (2 Staphylococcus (S.) epidermidis and one S. haemolyticus) were positive for cfr gene and negative for optrA and poxtA genes. Conclusion: The presence of cfr gene in the three LRCoNS isolates could explain the MDR of the three strains. This is considered an alarm for the antimicrobial resistance to the last resort antibiotics in hospital settings. So far, the situation is not threatening. Yet, continuous monitoring is essentially required.

Background: Acinetobacter baumannii (A. baumannii) is a Gram-negative, aerobic coccobacillus. It causes life-threatening nosocomial infections, particularly in immunocompromised patients. Carbapenem-resistant A. baumannii are prevalent worldwide mostly caused by carbapenemase synthesis. Metallo β-lactamases (MBLs) include imipenemase (IMP), New Delhi metallo- β-lactamases (NDM) and Verona integrin metallo- β-lactamase (VIM). We aimed to investigate the prevalence of MBLs genes expression in carbapenem-resistant A. baumannii isolated from ICU patients as a reliable method for reducing the morbidity & mortality of these patients. Methods: Using conventional methods, 87 A. baumannii isolates were identified from 103 ICU patient specimens. Metallo β-lactamases were detected phenotypically in imipenem-resistant strains using a combined disc test (CDT). Real-time PCR was used to quantitate the expression of the blaIPM, blaNDM & blaVIM genes. Results: Imipenem resistance was identified in 82.8% of patients. Combined disc test was positive in 44.4% of imipenem-resistant isolates. For metallo-lactamases gene expression, blaVIM had a higher median value than blaNDM and blaIPM (0.5, 0.1 and 0 respectively). Combined disc test was found to have a statistically significant relationship with both NDM and VIM gene expression, which was considerably higher in isolates with positive CDT. Both NDM and VIM gene expression had a statistically non-significant correlation with CDT value, but their expression had a statistically significant negative correlation with CD zone of inhibition value. Conclusion: The expression of blaVIM and blaNDM genes is directly correlated with the level of MBLs production and the level of these enzymes can be detected phenotypically depending on its negative correlation with the CD zone of inhibition diameter.

H. pylori infection causes peptic ulcer, chronic gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric carcinoma. It has several virulence factors such as cytotoxin-associated gene A(cagA) and the induced by contact with epithelium antigen (iceA). We aimed to explore the relationship between cagA and iceA of H. pylori and gastrointestinal diseases. One hundred and eighteen patients who attended Gastrointestinal Endoscopy Unit at Zagazig University Hospitals, Egypt, were included in this study. Two gastric biopsies were collected and evaluated by rapid urease test (RUT) and PCR. cagA and iceA genes were amplified by PCR. We found that 54 patients (45.76%) were positive by both RUT and PCR. cagA and iceA genes were present in 57.4% and 46.29% of the studied patients, respectively. cagA was the most prevalent gene in gastritis (33.3%) and peptic ulcer (68.7%). iceA1/iceA2 positive genes were the most prevalent in gastric cancer (75%). iceA1 gene was present in 38.7% of cagA positive cases, but iceA2 gene was present in 45.2% of cagA positive cases. iceA1/iceA2 positive genes were present in 29% of cagA positive cases. In conclusion, cagA and iceA genes could be used as markers for severe gastrointestinal diseases. iceA gene was strongly related to cagA gene.