Background:Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with limited therapeutic options and poor survival. Resistance to standard temozolomide (TMZ) therapy remains a major challenge, necessitating novel agents. Tropolone derivatives, particularly the synthetic trichlorotropolone JO-122(2), have shown broad preclinical antitumor activity. This study aimed to determine whether JO-122(2), alone or combined with TMZ, can suppress GBM growth in vivo and to define the accompanying changes in the p53/MDM2/Bcl-2 apoptotic axis. Methods:JO-122(2), as monotherapy or combined with TMZ, was evaluated in a U87 MG GBM xenograft model in BALB/c nude mice (n = 8 per group). Tumor volumes were monitored over 25 days, and tumor growth inhibition (TGI) was calculated. Molecular mechanisms were investigated by RT-qPCR and ELISA, assessing gene expression and protein levels of the apoptotic regulators TP53, MDM2, BAX, BCL2, and CASP9. Results:JO-122(2) and TMZ monotherapy inhibited tumor growth (TGI = 42.08% and 61.44%, respectively). The combination therapy reduced tumor volume 4.9-fold compared to the vehicle control and achieved a TGI of 79.88% (p = 4.20 × 10⁻⁸ vs. control; p = 1.66 × 10⁻³ vs. TMZ; p = 5.97 × 10⁻⁵ vs. JO-122(2)). It also increased p53, Bax, and caspase-9 protein levels and decreased MDM2 and Bcl-2, with concordant upregulation of TP53 and BAX and downregulation of MDM2 and BCL2 mRNA, indicating modulation of the p53/MDM2/Bcl-2 axis. Conclusion:JO-122(2) exerts potent antitumor effects in GBM, particularly when combined with TMZ, by promoting mitochondrial apoptosis through the coordinated regulation of p53 and its downstream effectors.
Background:1,2-Dimethylhydrazine (DMH) induces pancreatic oxidative stress via reactive oxygen species overproduction and antioxidant depletion. Given the rich phytochemical and antioxidant properties of Vernonia amygdalina, this study investigated its therapeutic effects in inhibiting oxidative stress and histopathological damage induced by DMH in Wistar rats. Methods:Adult male Wistar rats were divided into different groups and exposed to DMH via the intraperitoneal route. Animals received oral administration of V. amygdalina ethanol extract at low (200 mg/kg) and high (400 mg/kg) doses, both before and after DMH exposure. The pancreatic tissues were then subjected to biochemical analysis and histopathological examination using standardized protocols. Results:The administration of V. amygdalina significantly attenuated body weight loss in both the pre- and post-treatment groups. Furthermore, it significantly improved (p < 0.05) the levels of total protein, amylase, nitric oxide, catalase, superoxide dismutase, malondialdehyde, glutathione peroxidase, glutathione (GSH), and glutathione reductase and reduced GSH percentages compared to the DMH group. The pancreatic tissues from DMH-induced rats treated with V. amygdalina showed a significant reduction (p < 0.05) in organ weight compared to the DMH group. Histological studies revealed the protective and regenerative effects of V. amygdalina on pancreatic tissues. Conclusion:This study indicates that V. amygdalina can effectively suppress irregularities in pancreatic function and oxidative stress induced by DMH toxicity due to its antioxidant properties. This observation implies that V. amygdalina holds promise as a novel therapeutic strategy for improving DMH systemic toxicity in animal models and could serve as a benchmark for future clinical trials.
Background:The emergence of mecC-carrying Staphylococcus aureus strains is a serious concern in public health. Our study investigated the clonal diversity, genetic characteristics, antimicrobial resistance, virulence determinants, biofilm-forming ability, and molecular epidemiology of mecC-positive Staphylococcus aureus isolates obtained from hospitalized patients in Iran. Methods:We analyzed 45 mecC-carrying S. aureus strains isolated from 1,590 S. aureus samples collected from different clinical sources. The characterization included antimicrobial susceptibility tests, assessment of biofilm formation, spa typing, multilocus sequence typing (MLST), and PCR analysis to detect resistance, biofilm-related, and virulence genes. Results:Our results showed that 17.8%, 17.8%, and 64.4% of the isolates were classified as weak, intermediate, and strong biofilm producers, respectively. The prevalence of the ant(4΄)-Ia and tet(M) was found in 80% and 73.3% of the isolates, respectively. MLST revealed that the 45 isolates belonged to four clonal complexes: CC8 (44.4%), CC130 (24.5%), CC121 (17.8%), and CC425 (13.3%). The majority of S. aureus isolates belonged to the CC8/ST239 lineage (44.4%). Also, tst-positive strains belonged to CC121/ST599/t5930 (17.8%) and CC8/ST239/t037 (11.1%), while eta-positive isolates belonged to CC/ST130/t843 (15.6%). Fusidic acid-resistant S. aureus isolates primarily belonged to CC8/ST239/t037 lineage (11.1%), followed by CC8/ST239/t7688 (6.7%), both carrying the fusB gene. Vancomycin-intermediate S. aureus strains were classified into CC/ST599/t5930 (6.7%) and CC/ST130/t843 (4.4%) clones. Conclusion:This study highlights the need for close and continuous monitoring of the genetic diversity and characteristics of the mecC-carrying S. aureus strains. Besides, urgent measures are required to prevent the transmission of these strains and to effectively treat associated infections.
Rabies is a fatal zoonotic disease, responsible for approximately 59,000 human deaths annually; the majority occur in developing regions of Asia and Africa. This review explores worldwide efforts to prevent and control rabies during 2016-2025, using the evolving themes of World Rabies Day (WRD) as a framework. The research objective is to assess epidemiological trends, intervention strategies, challenges, and innovations related to the World Health Organization's target of zero human rabies deaths by 2030. The findings highlight a significant reduction in global rabies occurrence, with mass vaccination campaigns for dogs achieving 70% coverage in Guinea and a 95% decrease in human cases in Latin America. However, gaps in surveillance, vaccine shortages, and poor public education persist. Low-cost intradermal prophylaxis, monoclonal antibodies, and AI-driven surveillance systems are promising approaches but remain constrained by socioeconomic inequalities and insufficient investment. Achieving "Zero by 30" requires stronger collaboration, equitable resource distribution, and sustained community mobilization.
Background:Mitochondrial dysfunction and impaired cellular energy metabolism are increasingly recognized as key contributing factors in depression. This study evaluated the amino acid L-arginine as a potential agent for behavioral rescue and bioenergetic restoration using a corticosterone-induced rat model of depression. Methods:Male rats were randomly assigned to four groups (n = 10): control (DMSO intraperitoneally [i.p.] + water oral gavage), corticosterone-induced depression (20 mg/kg, i.p. for 14 days), L-arginine treatment (150 mg/kg, oral gavage for 14 days), and fluoxetine (10 mg/kg, oral gavage for 14 days). To ensure handling equivalence, all oral administrations were performed via gavage (1.0 mL/100 g). Behavioral rescue was assessed via open field, forced swim (FST), and tail suspension (TST) tests. Hippocampal energy metabolism and PI3K/Akt/mTOR pathway activation were analyzed. Results:L-arginine significantly improved the hippocampal bioenergetic profile, demonstrating efficacy comparable to the positive control fluoxetine. It led to a significant reduction in immobility time during FST and TST, alongside restoring glycolysis, the tricarboxylic acid cycle, and mitochondrial respiratory chain activities. Concurrently, L-arginine enhanced the activation state of the PI3K/Akt/mTOR signaling pathway (phosphorylated Akt/Akt and p-mTOR/mTOR ratios) and improved the functional state of the mitochondrial permeability transition pore. These metabolic and signaling improvements strongly correlated with the rescue of depressive-like behaviors. Concludion:Our findings demonstrate that L-arginine possesses potent antidepressant-like potential, mediated through bioenergetic restoration and signaling pathway modulation. By activating key metabolic processes in the hippocampus, L-arginine effectively restores impaired cellular energy homeostasis, suggesting its promise as a metabolic modulator for alleviating neurobiological disturbances associated with depressive conditions.
