Background: Chronic stress can hinder wound healing as it suppresses both the cellular and innate immune responses. Objectives: The study aims to assess the effectiveness of the administration of topical and oral Cucurbita pepo L. (CP) ethanolic extract in prompting excisional wound healing in rats exposed to chronic stress, and to explain how it works. Materials and methods: Fifty albino rats assigned to five groups (n = 10) were utilized in this study. The chronic unpredictable mild stress (CUMS) model was used for 4 weeks to induce depressive-like behavior in rats, and a forced swim test and corticosterone were assessed to confirm its occurrence. During the experiment, an excisional wound was induced in the rats and followed. Oxidant/antioxidants status and pro-inflammatory cytokines levels were measured in the serum and wound area. Gene expression of pro-inflammatory cytokines was also assessed using RT-PCR. Wound closure histopathological changes and immunohistochemical expression of CD68, CD3, and CD4 at the wound area was assessed. Results: The administration of CP, both orally and topically, significantly reduced (p < 0.001) the depressive-like behavior and corticosterone and pro-inflammatory cytokines levels, while it significantly up-regulated the antioxidant activity compared to the untreated and topically CP-treated groups. Both topically CP-treated and combined CP-treated groups showed complete re-epithelialization, reduced inflammatory cells infiltration, collagen fibers deposition, and significantly increased CD3, CD4 positive T cells count, with a superior effect in the combined CP-treated groups. Conclusion: Cucurbita pepo L., administrated both topically and orally, can enhance the wound healing process in rats with depressive-like behavior mostly through the antioxidant, anti-inflammatory, and antidepressant activities observed in this study.

Purpose: Alzheimer's disease (AD) appears as a result of an increase in the accumulation of amyloid beta peptide (Aβ) and a decrease in neurotransmitters (Acetylcholine) within the brain cells which may be due to increase in acetylcholinesterase (AchE) activity and change in expression of Apolipoprotein E4 (ApoE4) and Clusterin (Clu) genes. The aim of the present study was using natural products such as Ginkgo biloba (G. biloba) extract that has the potential to reduce Aβ formation and increase AchE inhibition with its ability to save neuronal DNA from damage. Methods: Sixty male aged rats were divided into six experimental groups exposed to AlCl₃ to induce AD model and were treated with G. biloba extract. Collected brain tissues were used to assess the apoptosis rate, reactive oxygen species (ROS) generation, AchE inhibitory activity, expression alteration in ApoE4 and Clu genes, DNA fragmentations and gutathione peroxidase (GPx) activity. Results: The results exhibited that rats exposed to AlCl₃ increased significantly rate of apoptosis, ROS formation, DNA fragmentation, up-regulation of ApoE4 and Clu genes as well as decrease of AchE inhibitory activity and GPx activity compared with those in control rats. However, treatment of AlCl₃-rats with G. biloba extract improved the above neurotoxicity results induced by AlCl₃ exposure. Conclusion: It is therefore likely that G. biloba extract's protective properties against AD are due to its ability to activate the response against oxidative stress.

Objectives: Recently, increased attention has been given to pumpkin due to its proved nutritional components, which include antioxidant, antifatigue, and anti-inflammatory effects. The aim of the present work was to assess the impact of Cucurbita pepo L. (CP) on chronic unpredictable mild stress (CUMS)-induced changes in lymphoid organs through evaluating its effect on the histological structure of spleen, thymus gland, and lymph nodes compared to the antidepressant fluoxetine (FLU). Materials and Methods: Fifty male albino rats equally distributed into five groups that included control, control + CP, CUMS-exposed, FLU-treated, and CP-treated groups were used in this study. Rats were exposed to CUMS for 4 weeks, and treatment (either with FLU or CP) was started after 14 days of exposure. Behavior of the rats, serum corticosterone, oxidants/antioxidants profile, proinflammatory cytokines, and gene expression of glucocorticoid receptor (GR) and β-adrenergic receptor (β2-AR) were assessed after 28 days. Spleen, thymus gland, and lymph nodes were histopathologically assessed. Results: CP administration significantly reduced the CUMS-induced behavioural changes evident by the significant reduction in immobility time (p = 0.02) and corticosterone level (p < 0.001). Biochemically, CP reduced TNF-α and IL-6 (p < 0.001) and markedly alleviated the changes in oxidants/antioxidants in the serum and lymphoid organs compared to fluoxetine. CP significantly (p < 0.001) reduced CUMS-induced changes in GR and (β2-AR). Histopathologically, CP alleviated changes observed in the spleen, lymph nodes, and thymus gland. It significantly reduced the number of CD4, CD8, CD68, CD20, and caspase-3 immunopositive cells in the studied organs. Conclusions: This study proved the potential efficacy of CP in alleviating depression-associated immunodysregulation either alone or in combination with antidepressant therapy.

Background/Objectives: Loss of phosphatase and tensin homolog (PTEN) activity is a frequent feature of non-small-cell lung cancer (NSCLC), and epigenetic repression may contribute to its reduced expression. This study investigated the effects of 5-aza-2′-deoxycytidine (5-aza-dC) on PTEN, DNA methyltransferase 1 (DNMT1), PTEN promoter methylation-specific amplification patterns, and miR-148a-3p expression in NSCLC models. Methods: Publicly available cancer-genomics datasets were analyzed to compare PTEN and DNMT1 transcript abundance and to assess the association between PTEN methylation and transcript abundance in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). A549 and H460 cells were exposed to 2.5 or 5 µM 5-aza-dC for 72 h. Reverse-transcription quantitative PCR (RT-qPCR), Western blotting, methylation-specific PCR (MSP-PCR), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to evaluate RNA expression, protein abundance, methylation-specific amplification, and metabolic activity, respectively. Results: Bioinformatic analyses showed lower PTEN and higher DNMT1 expression in both NSCLC subtypes, together with inverse associations between PTEN methylation and transcript abundance. In both cell lines, 5-aza-dC reduced MTT metabolic activity and DNMT1 expression. PTEN mRNA and protein abundance increased significantly at 5 µM, whereas no significant changes were detected at 2.5 µM. MSP-PCR revealed persistent heterogeneous PTEN methylation-specific amplification patterns without clear evidence of progressive promoter demethylation. miR-148a-3p exhibited a biphasic response in A549 cells but remained unchanged in H460 cells. Conclusions: These findings support an association between 5-aza-dC exposure, increased PTEN expression, and reduced DNMT1 expression in NSCLC cells. Quantitative methylation analysis and mechanistic validation are required to clarify the contribution of miR-148a-3p to this regulatory association.

Fibromyalgia (FM) is a complex, chronic disorder characterized by widespread pain, fatigue, cognitive impairment, and sleep disturbances, and it is considered the second most prevalent rheumatic condition. Current pharmacological therapies are often associated with undesirable side effects, underscoring the need for safer, natural therapeutic alternatives. Moringa oleifera leaves are rich in nutrients and bioactive antioxidants and have demonstrated therapeutic potential in inflammatory and immune-related disorders. This study investigated the therapeutic effects of M. oleifera leaf extract in a reserpine-induced fibromyalgia model using multiple treatment groups of male mice. Behavioral, histological, and neurochemical assessments were conducted. Mice with reserpine-induced FM exhibited reduced body weight, decreased paw withdrawal threshold and thermal latency, diminished locomotor activity and grooming behavior, impaired spontaneous alternation, and prolonged immobility time. Histopathological examination revealed marked structural disruption of hippocampal tissue, accompanied by reduced serotonin levels and elevated concentrations of IL-1β, TNF-α, and NO compared with control animals. Treatment with M. oleifera significantly attenuated these alterations by improving behavioral performance, restoring hippocampal architecture, and normalizing serotonin levels and pro-inflammatory markers. These findings indicate that M. oleifera exerts a protective effect against reserpine-induced fibromyalgia, likely through modulation of serotonergic activity and suppression of inflammatory cytokine signaling pathways.

Fibromyalgia syndrome (FMS) is a chronic disorder marked by widespread musculoskeletal pain, fatigue, mood disturbances, and cognitive impairments. Current treatments primarily focus on symptom management. Ashwagandha (Withania somnifera), a traditional Ayurvedic herb, is known for its adaptogenic and neuroprotective properties. This study evaluated the protective effects of the methanolic root extract of Ashwagandha (ARE) in a reserpine-induced fibromyalgia model in male Swiss albino mice. Mice received oral ARE (100 mg/kg) for 17 days and reserpine (0.5 mg/kg, subcutaneously) for three consecutive days to induce fibromyalgia-like symptoms. Behavioral assessments included Von Frey, tail suspension, rotarod, and Y-maze tests. Histological analysis was conducted on the hippocampus and thalamus; however, neurochemical analysis focused on markers such as serotonin, norepinephrine, IL-1β, TNFα, MDA, and NO. Results indicated that ARE significantly reduced pain and depressive-like behavior and improved motor function (p < 0.0001); however, no significant changes were observed in open-field locomotion. Histological examination revealed protection of Ashwagandha against neurodegeneration and improved hippocampal integrity, accompanied by increased serotonin and norepinephrine levels and decreased pro-inflammatory cytokines. These findings suggest that Ashwagandha root extract may offer therapeutic benefits for managing fibromyalgia symptoms.