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Background: Cadmium (Cd) is a heavy metal environmental pollutant that can cause serious health problems. Cd can cause structural changes in the testes and exposure to this heavy metal is associated with the loss of sperms and male infertility. The role of oxidative stress and inflammation in Cd toxicity has been acknowledged. Diallyl disulfide (DADS), an organo-sulfur compound found in garlic, possesses antioxidant, anti-inflammatory, and cytoprotective effects. This study evaluated the protective effect of DADS against Cd reproductive toxicity in male rats, emphasizing the involvement of redox imbalance, TLR-4/NF-κB and JAK1/STAT3 signaling, and SIRT1., Methods: DADS (10 mg/kg body weight) was administered orally to rats for 14 days and a single dose of Cd (1.2 mg/kg) was injected intraperitoneally on day 7. Blood and samples from the testes were collected for analysis., Results: Cd caused testicular injury manifested by multiple histopathological changes and loss of sperms from seminiferous tubules. Circulating levels of gonadotropins and testosterone were decreased in Cd-administered rats. DADS prevented Cd-induced testicular injury and ameliorated serum levels of gonadotropins and testosterone. Cd increased testicular reactive oxygen species (ROS) and malondialdehyde (MDA) and upregulated TLR-4, NF-κB, pro-inflammatory cytokines, JAK1 and STAT3 phosphorylation, Bax and caspase-3, while decreased antioxidants and Bcl-2. DADS effectively decreased ROS and MDA, downregulated TLR-4, NF-κB, JAK1, STAT3, pro-inflammatory cytokines and pro-apoptosis markers in Cd-administered rats. In addition, DADS enhanced antioxidants, Bcl-2, SIRT1 and cytoglobin in the testis of Cd-administered rats., Conclusion: DADS prevents Cd-induced testicular injury by attenuating oxidative stress, apoptosis, and TLR-4/NF-κB and JAK1/STAT3 signaling, and upregulating SIRT1 and antioxidants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Farnesol (FAR) is a sesquiterpene alcohol that exists in many fruits and vegetables and possesses promising anti-inflammatory and antioxidant activities. Cadmium (Cd) is an environmental pollutant known for its serious health effects. Liver injury associated with oxidative stress is a hazardous consequence of exposure to Cd. This study evaluated the effect of FAR on Cd-induced oxidative stress, inflammation, and hepatocyte injury, pinpointing the involvement of NF-κB/NLRP3 inflammasome axis, TGF-β/Smad3 signaling and PPARγ. FAR was supplemented for 14 days and rats received Cd on day 7. Elevated serum transaminases, ALP and LDH, decreased albumin, and multiple histopathological alterations were observed in Cd-administered rats. Cd increased liver MDA and NO, decreased GSH and antioxidant enzymes, and upregulated NF-κB p65, IL-6, TNF-α, iNOS, NLRP3, ASC, caspase-1, IL-1β, and cleaved caspase-3. TGF-β, Smad3 phosphorylation and α-SMA were upregulated, and collagen deposition was increased in Cd-administered rats. FAR ameliorated liver injury markers and tissue alterations, attenuated oxidative stress, suppressed NF-κB/NLRP3 inflammasome axis and TGF-β/Smad3 signaling, and enhanced antioxidants. In addition, FAR downregulated caspase-3 and pro-inflammatory cytokines and increased liver PPARγ in Cd-administered rats. In silico , FAR showed affinity to bind ASC and NLRP3 PYD domains, TGF-β, and PPARγ. In conclusion, FAR protects the liver against Cd toxicity by suppressing oxidative stress, inflammatory response and cell death, effects linked to modulation of NF-κB/NLRP3 inflammasome axis, TGF-β/Smad3 signaling and PPARγ., (Copyright © 2024 Alruhaimi et al.)

Background: Heavy metals can cause serious health problems that affect different organs. Cadmium (Cd) is an environmental contaminant known for its toxicological consequences on different organs. Hepatotoxicity is a serious effect of exposure to Cd with oxidative stress (OS) and inflammation playing a central role. Diallyl disulfide (DADS), an organo-sulfur compound found in garlic, is known for its cytoprotective and antioxidant effects. In this study, the effect of DADS on Cd-induced inflammation, oxidative stress and liver injury was investigated., Methods: DADS was supplemented for 14 days via oral gavage, and a single intraperitoneal dose of Cd (1.2 mg/kg body weight) was administered to rats on day 7. Blood and liver samples were collected at the end of the experiment for analyses., Results: Cd administration resulted in remarkable hepatic dysfunction, degenerative changes, necrosis, infiltration of inflammatory cells, collagen deposition and other histopathological alterations. Cd increased liver malondialdehyde (MDA) and nitric oxide (NO) ( p < 0.001), upregulated toll-like receptor (TLR)-4, nuclear factor-kappaB (NF-κB), pro-inflammatory mediators, and caspase-3 ( p < 0.001) whereas decreased glutathione (GSH) and antioxidant enzymes ( p < 0.001). Cd downregulated peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in inflammation and OS suppression ( p < 0.001). DADS ameliorated liver injury and tissue alterations, attenuated OS and apoptosis, suppressed TLR-4/NF-κB signaling, and enhanced antioxidants. In addition, DADS upregulated PPARγ in the liver of Cd-administered rats., Conclusions: DADS is effective against Cd-induced hepatotoxicity and its beneficial effects are linked to suppression of inflammation, OS and apoptosis and upregulation of PPARγ. DADS could be valuable to protect the liver in individuals at risk of Cd exposure, pending further studies to elucidate other underlying mechanism(s)., (© 2024 The Author(s). Published by IMR Press.)

Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli . In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Meloxicam has shown significant neuroprotection in experimental models of stroke, Alzheimer's disease, and Parkinson's disease. However, the potential of meloxicam to treat depression-like neuropathology in a chronic restraint stress (CRS) model and the associated molecular changes has been insufficiently explored. The current work aimed to explore the potential neuroprotective actions of meloxicam against CRS-evoked depression in rats. In the current experiments, animals received meloxicam (10 mg/kg/day; i.p.) for 21 days, and CRS was instigated by restraining the animals for 6 h/day during the same period. The sucrose preference test and the forced swimming test were used to explore the depression-linked anhedonia/despair, whereas the open-field test examined the animals' locomotor activity. The current findings revealed that CRS elicited typical depression behavioral anomalies in the animals, including anhedonia, despair, and diminished locomotor activity; these findings were reinforced with Z-normalization scores. These observations were corroborated by brain histopathological changes and increased damage scores. In CRS-exposed animals, serum corticosterone spiked, and the hippocampi revealed decreased monoamine neurotransmitter levels (norepinephrine, serotonin, and dopamine). Mechanistically, neuroinflammation was evident in stressed animals, as shown by elevated hippocampal TNF-α and IL-1β cytokines. Moreover, the hippocampal COX-2/PGE 2 axis was activated in the rats, confirming the escalation of neuroinflammatory events. In tandem, the pro-oxidant milieu was augmented, as seen by increased hippocampal 8-hydroxy-2'-deoxyguanosine alongside increased protein expression of the pro-oxidants NOX1 and NOX4 in the hippocampi of stressed animals. In addition, the antioxidant/cytoprotective Nrf2/HO-1 cascade was dampened, as evidenced by the lowered hippocampal protein expression of Nrf2 and HO-1 signals. Interestingly, meloxicam administration mitigated depression manifestations and brain histopathological anomalies in the rats. These beneficial effects were elicited by meloxicam's ability to counteract the corticosterone spike and hippocampal neurotransmitter decrease while also inhibiting COX-2/NOX1/NOX4 axis and stimulating Nrf2/HO-1 antioxidant pathway. Together, the present findings prove the neuroprotective/antidepressant actions of meloxicam in CRS-induced depression by ameliorating hippocampal neuroinflammation and pro-oxidant changes, likely by modulating COX-2/NOX1/NOX4/Nrf2 axis.

Background: Bariatric surgery offers long-term weight loss and maintenance for patients with obesity. Several factors may be associated with patients' inability to achieve successful excess weight loss (EWL) after the surgery. The purpose of this study was to identify factors associated with improved or in-progress EWL among patients who had undergone laparoscopic sleeve gastrectomy (LSG)., Methods: This original clinical investigation was conducted at the Outpatient Surgical Department-Medical Research Institute Hospital at Alexandria University in Egypt. A sample size of 100 adult surgical patients who had undergone LSG was selected from patients who attended follow-up in the study setting. Group A had an EWL% ≥50 and group B had an EWL <50. Body Mass Index (BMI) classes were defined as 25-30 kg/m 2 , >30-35 kg/m 2 , >35-40 kg/m 2 , >40 ≥ 45 kg/m 2 ., Results: Post-operatively, after six months, 100% of the patients in group A had a BMI between 25 and 30 mg/m2, compared to 0% in group B. Nevertheless, patients in group EWL<50 (group B) who had pre-operatively BMI class ≥45 mg/m2, had a reduction in weight of 89.5% post-operatively, (n = 2 still had a BMI >45 kg/m 2 post operatively), In total, 63.9% of the patients in group B managed to get towards a BMI of 30-35 kg/m 2 post-operatively. The main factors associated with group B (less %EWL after 6 months) were found to be related to higher preoperative BMI, the onset of obesity started in childhood, less preoperative weight loss, longer postoperative duration towards weight reduction, and lower postoperative compliance to dietary instructions (P = 0.0001, 0.048, 0.0001, 0.017, and 0.016, respectively)., Conclusion: Routine cross-sectional surveying can help clinicians in understanding patients' post-operative follow-up routines. Special attention to pre-operative BMI, weight-loss regimens, and childhood-onset as well as post-operative duration, low responders, and compliance with clinical assessment can improve weight loss outcomes., (© 2022 The Author(s).)