Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder associated with gut microbiota dysbiosis, intestinal barrier dysfunction, and low-grade inflammation. This study aimed to evaluate the effects of Akkermansia muciniphila Muc T (ATCC BAA-835) on gut microbiota composition, intestinal barrier integrity, and TLR4/NF-κB/NLRP2-mediated inflammatory signaling in a stress-induced rat model of IBS-D. IBS-D was induced in rats using combined chronic and acute stress paradigms. Animals received A. muciniphila supplementation during the experimental period. Serum inflammatory cytokines and tight junction–related proteins were quantified by ELISA. Protein expression levels of TLR4, NF-κB, and NLRP2 were assessed by Western blotting. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing of fecal samples. Histopathological and immunofluorescence analyses were performed to assess tissue inflammation and cellular damage. IBS-D rats exhibited increased inflammatory cytokine levels, impaired tight junction protein expression, activation of the TLR4/NF-κB/NLRP2 pathway, and significant alterations in gut microbiota diversity. A. muciniphila supplementation significantly attenuated inflammatory responses, restored intestinal barrier–associated proteins, and suppressed inflammatory signaling. Microbiota analysis revealed partial correction of dysbiosis, including increased abundance of beneficial taxa such as Faecalibacterium prausnitzii. A. muciniphila alleviates IBS-D–associated intestinal inflammation and barrier dysfunction by modulating gut microbiota composition and inflammatory signaling pathways, supporting its potential as a microbiota-based therapeutic strategy for IBS-D.

This study investigated the protective effects of zingerone (ZIN) against thioacetamide (TAA)-induced hepatic encephalopathy (HE) in rats (n = 10 per group). HE was induced by TAA (200 mg/kg, intraperitoneally (i.p.)) on days 1 and 3, and rats were treated with ZIN (25 or 50 mg/kg/day, intragastric gavage (i.g.)) for 14 days. Serum biochemistry, oxidative stress, inflammatory markers, ER stress-related proteins, apoptosis indicators, histopathology, and behavioral outcomes were evaluated TAA administration markedly increased whole-blood ammonia concentrations together with serum activities of the hepatic injury biomarkers ALT, AST, ALP, GGT, and LDH compared with the Control group, while ZIN treatment significantly improved these parameters. ZIN reduced malondialdehyde (MDA) levels and restored antioxidant defenses (SOD and GSH) in both liver and brain tissues. Pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were elevated after TAA exposure, whereas IL-10 was reduced; ZIN dose-dependently reversed these changes. In addition, TAA increased ER stress markers (GRP78, CHOP, ATF6, XBP1, IRE1, and PERK) and apoptosis-related Bax and caspase-3 expression, which were significantly suppressed by ZIN. In brain tissue, ZIN preserved BDNF expression and reduced GFAP immunoreactivity. Behavioral impairments, including anxiety-like behavior and locomotor deficits, were significantly improved at 50 mg/kg. Overall, ZIN exhibited dose-dependent hepatoprotective and neuroprotective effects in TAA-induced hepatic encephalopathy, as evidenced by attenuation of oxidative stress, inflammation, ER stress, and apoptosis. This study provides an integrated evaluation of ZIN in hepatic encephalopathy, extending prior findings in other hepatotoxicity models, including CCl₄ and cadmium-induced injury, as well as related phytochemical studies in HE.

Background/Objectives: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene. DMD is characterized by exon deletions in about 76% of cases, with common deletions in exons 47, 48, 51, and 52. We evaluated the effectiveness of an mRNA-based therapy targeting these exon deletions, which are frequently seen in DMD patients. Methods: The current study involved two protocols: 1. applying the therapy to cells from patients diagnosed with DMD, and 2. applying the therapy to genetically modified transgenic mdx/d2 mice. After treatment, dystro-phin was detected in all experimental groups. Results: Our study showed that, both in vitro and in vivo analyses demonstrated that the mRNA-based therapy successfully restored dystrophin expression in dystrophic muscle cells and tissues. Gene expression analysis, together with protein-level assessments, including Western blot, immunoflu-orescence (IF), ELISA, and immunohistochemistry (IHC), confirmed a significant in-crease in dystrophin levels in the treated groups compared with the control group. In addition to dystrophin restoration, other key sarcolemmal proteins involved in main-taining muscle membrane stability, such as γ-sarcoglycan, β-dystroglycan, and β-actin, were also highly expressed. These findings suggest an overall improvement in muscle cell membrane integrity. Consistent with the molecular results, behavioral analyses performed in the animal model revealed significant functional improvements, includ-ing enhanced mobility, motor coordination, longer walking and resting durations, and a reduced risk of falls. Overall, the results indicate that mRNA-mediated dystrophin replacement improves both muscle structural integrity and functional performance. Conclusions: Our study proved that the mRNA complex successfully produced func-tional dystrophin in transgenic mdx/d2 mice without causing allergic reactions or damage to the kidney, intestines, muscles, or brain.

Objectives:Sepsis-induced acute lung injury (ALI), driven by uncontrolled inflammation and oxidative stress, remains a major cause of mortality in critically ill patients. This study aimed to investigate the protective and mechanistic effects of syringic acid (SA), a natural phenolic compound, against lipopolysaccharide (LPS)-induced ALI in rats. Materials and Methods:Male Sprague-Dawley rats were allocated into five groups: control, SA80, LPS, SA40+LPS, and SA80+LPS. SA was orally administered (40 or 80 mg/kg/day) for 14 days before a single intraperitoneal injection of LPS (10 mg/kg). Lung tissues were collected 12 hr post-LPS for histopathological, biochemical, and molecular evaluations. In silico docking using Schrödinger Maestro (2025/1) assessed SA interaction with the KEAP1 Kelch domain (PDB: 5FZN). Results:LPS challenge caused severe pulmonary edema, inflammatory infiltration, elevated proinflammatory cytokines, lipid peroxidation, and reduced antioxidant enzyme activities. SA pretreatment, particularly at 80 mg/kg, significantly (P<0.05) alleviated these alterations. Mechanistically, SA down-regulated the HMGB1/TLR4/NF-κB signaling cascade and activated the Keap1/Nrf2/HO-1 antioxidant pathway. Reduced 8-OHdG and caspase-3 expression indicated mitigation of oxidative DNA damage and apoptosis. Docking analysis revealed strong binding affinity and favorable MM-GBSA scores for SA within the KEAP1 active pocket, suggesting direct modulation of Nrf2 activation. Conclusion:SA confers potent protection against LPS-induced ALI through coordinated anti-inflammatory and antioxidant mechanisms involving HMGB1/TLR4/NF-κB inhibition and Keap1/Nrf2/HO-1 activation. These findings highlight SA as a promising therapeutic candidate for sepsis-associated pulmonary injury.

Objectives:This study aimed to evaluate the protective effects of Gallic acid (GA) against (Doxorubicin) DOX-induced renal injury and to explore potential molecular interactions underlying its effects. Materials and Methods:Fifty male rats were randomly assigned to five groups: Control, DOX, GA50+DOX, GA100+DOX, and GA100. DOX was administered as a single intraperitoneal dose on day 8 (40 mg/kg), while GA was given orally at 50 or 100 mg/kg for 10 consecutive days. Renal tissues were collected on day 11 and analyzed for oxidative stress markers, pro- and anti-inflammatory cytokines, and the apoptotic marker caspase-3 via ELISA. Immunohistochemistry assessed Nrf-2 and HO-1 expression, and histopathology evaluated structural alterations. Molecular docking simulations were performed for DOX/topoisomerase IIα (PDB ID: 4FM9) and GA/TNF-α (PDB ID: 2AZ5). Results:GA significantly ameliorated DOX-induced oxidative stress, inflammatory cytokine imbalance, caspase-3 activation, and histological damage in a dose-dependent manner, while enhancing Nrf-2 and HO-1 expression. Docking analysis confirmed DOX binding to topoisomerase IIα and revealed strong GA-TNF-α binding affinity. Conclusion:GA exerts substantial renoprotective effects against DOX-induced nephrotoxicity by modulating oxidative, inflammatory, and apoptotic pathways. The agreement between in vivo findings and in silico modeling supports GA as a potential complementary agent to reduce chemotherapy-related renal injury.

(ACR)-induced neurotoxicity, focusing on oxidative stress, endoplasmic reticulum (ER) stress, neuroinflammation, and apoptosis mechanisms. Fifty male Sprague-Dawley rats were divided into five groups: Control, ACR, GA50 +ACR, GA100 +ACR, and GA100. GA (50 and µmg/kg) and ACR (50 mg/kg) were administered intraperitoneally for 14 days. ACR exposure significantly decreased antioxidant enzyme activities (SOD, GSH, GPx, CAT) and increased malondialdehyde (MDA) levels, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), neuronal nitric oxide synthase (nNOS), and apoptosis-related gene expression (Bax and caspase-3). Histopathological analysis revealed neuronal degeneration and vascular hyperemia, while BDNF, Nrf2, and HO-1 immunoreactivity decreased in the ACR group. GA treatment, particularly at 100 mg/kg, markedly ameliorated these biochemical, molecular, and histopathological alterations. These findings indicate that GA exerts significant neuroprotective effects against ACR-induced brain injury by modulating oxidative stress, ER stress, inflammatory, and apoptotic pathways.

Antibiotic resistance is one of the most important problems threatening global public health by complicating the treatment of infections worldwide. The increase in resistant microorganisms creates a serious economic and social burden on healthcare systems and increasingly limits treatment options. Conscious use of antibiotics, infection control measures and the development of alternative treatment strategies are vital to ensure sustainability in health. Klebsiella pneumoniae is the most common gram-negative bacterium among urinary tract infections. Treatment of infections has become difficult due to the resistance to beta-lactam antibiotics. Bee venom (BV) and nanovesicle fractions isolated from BV are bioactive compounds with antimicrobial and antibiofilm activity. The aim of this study was to determine the antimicrobial and antibiofilm effects of BVand bee venom-derived nanovesicle fractions against the nosocomial infection agent K. pneumoniae, and to evaluate CTX-M PCR band detection under the tested conditions. Minimum inhibitory concentration (MIC), antibiofilm activity, fractional inhibition concentrations (FIC), CTX-M PCR band detection, and viability rates in L929 cells were evaluated for both BVand the bee venom-derived nanovesicle fraction against K. pneumoniae. MIC value of nanovesicle fractions isolated from BVwas determined as 1.95 mg/L. In combination with piperacillin and tazobactam, a synergistic effect was detected with a value of 0.5. Antibiofilm activity was measured with the highest absorbance value of 0.163 and 0.094 for BV nanovesicle fractions. A detectable CTX-M PCR band was observed in the BVgroup at 0.5× MIC, whereas no detectable band was observed at both concentrations by day 4. In the bee venom-derived nanovesicle fraction group, no detectable CTX-M PCR band was observed at 2× MIC and 0.5× MIC under the tested conditions. In contrast, detectable CTX-M PCR bands were observed in the piperacillin-tazobactam group. It was reported that the combination groups decreased the viability rate in L929 cell lines. The bee venom-derived nanovesicle fraction showed antimicrobial, antibiofilm, and PCR-based detection findings under the tested conditions, supporting the need for further investigation in broader in vitro and in vivo models.

Diabetes mellitus (DM) is a global disease that directly affects many organs, including the brain and cerebellum. This study aims to evaluate the effects of zingerone (ZO) on neurotoxicity, a prevalent consequence of DM. Female Sprague–Dawley rats (n = 60) were divided into 6 groups. Experimental groups were established as Control, DM, DM + Metformin (MET), DM + ZO25, DM + ZO50, and ZO50. At the end of 28 days, the brain and cerebellum tissues were used for the analyses. To evaluate oxidative stress and oxidative DNA damage, neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), 8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and glutathione reductase (GR) levels were measured. Apoptosis was assessed by determining Caspase-3 expression levels. In addition, H2A.X, NeuN, and glial fibrillary acidic protein (GFAP) expression levels were analyzed to evaluate DNA damage, neuronal integrity, and glial activation, respectively.While nNOS, 8-OHdG, Caspase-3, H2A.X, NeuN, GFAP, MDA, and iNOS levels increased in the DM group, it was observed that tissue damage decreased in a dose-dependent manner in the ZO treatment groups. Also, while there was a decrease in SOD and GR activity and GSH levels in the DM group, ZO 50 mg/kg treatment caused an increase in these enzymes. This study suggests that ZO may exert neuroprotective effects by mitigating oxidative stress, suppressing inflammation, and modulating apoptosis in diabetes-induced neurotoxicity.

Mercury chloride (HgCl₂) is a well-known environmental toxicant that can induce neurotoxicity through oxidative stress, neuroinflammation, endoplasmic reticulum (ER) stress, dysregulated autophagy, and apoptosis. This study evaluated the potential neuroprotective effects of hesperidin (HES), a bioactive flavonoid with antioxidant and anti-inflammatory properties, against HgCl₂-induced brain injury in rats. Sixty male Sprague Dawley rats received 1.23 mg/kg HgCl₂ intraperitoneally for 7 days, while HES was administered orally at doses of 100, 200, or 400 mg/kg. HgCl₂ exposure resulted in elevated lipid peroxidation, impaired antioxidant status, increased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and reduced IL-10 levels. Upregulation of Bax and caspase-3, downregulation of Bcl-2 and BDNF, along with increased GFAP immunoreactivity, indicated enhanced neuronal apoptosis and astrocyte activation. Furthermore, increased Beclin-1, LC3A/B, and ER stress-related markers (GRP78, PERK, ATF4, XBP1, IRE1, CHOP) suggested disturbances in cellular homeostasis. HES treatment—most notably at 400 mg/kg—attenuated oxidative stress, improved antioxidant enzyme activities, reduced pro-inflammatory responses while partially restoring IL-10, and modulated apoptosis, autophagy, and ER stress-associated pathways. In addition, increased BDNF levels following HES administration may indicate improved neuronal plasticity. Collectively, these findings suggest that hesperidin may have therapeutic potential as a neuroprotective agent against HgCl₂-induced neurotoxicity by modulating multiple molecular pathways involved in oxidative damage, inflammation, apoptosis, autophagy, and ER stress.

This study investigates the protective effects of galangin (GAL) against doxorubicin (Dox)-induced hepatorenal toxicity in a rat model, focusing on oxidative stress, inflammation, and key markers, including interleukin-6 (IL-6), 8-hydroxydeoxyguanosine (8-OHdG), and aquaporin-1 (AQP-1). Male Sprague-Dawley rats were divided into four groups: Control, Dox, Dox+GAL 50 mg/kg, and Dox+GAL 100 mg/kg. GAL significantly attenuated Dox-induced damage by reducing IL-6 and 8-OHdG levels, restoring AQP-1 expression, and improving histopathological profiles. Biochemical analysis demonstrated GAL's antioxidant activity, evidenced by elevated levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), alongside decreased levels of malondialdehyde (MDA). These findings suggest GAL as a potential therapeutic agent for mitigating Dox-induced organ toxicity, with broader implications for conditions involving oxidative stress and inflammation.

OBJECTIVES:This study aimed to evaluate the efficacy of photobiomodulation therapy (PBMT), therapeutic ultrasound (TUS), boric acid (BA), and their combinations in preventing experimentally induced intra-abdominal adhesions in rats. MATERIALS AND METHODS:Ninety-six male Wistar rats (14 weeks old) were randomly assigned to eight groups (Control, Laparotomy, Physiological Saline, BA, PBMT, TUS, BA + PBMT, and BA + TUS; n = 12/group). Adhesions were surgically induced. Treatments were applied once daily for 7 consecutive days as follows: BA (8 mg/kg, intraperitoneal), PBMT (904 nm, 3 J/cm2 applied to the incision site), and TUS (1 MHz, 0.5 W/cm2 applied to the incision site). On Day 8, rats were euthanized, and peritoneal fluid and adhesion tissue samples were collected for macroscopic scoring, histopathology, biochemical assays, and gene expression analyses. RESULTS:PBMT alone significantly reduced adhesion scores compared with the control (p < 0.05) and showed the most pronounced antifibrotic effect, while BA and TUS, alone or in combination, had limited impact. BA treatment increased malondialdehyde (MDA) levels (p < 0.05), indicating higher oxidative stress, whereas PBMT enhanced antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT) (p < 0.05). Gene expression analysis revealed that PBMT modulated cytokines linked to inflammation, particularly tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). CONCLUSION:PBMT demonstrated significant potential in reducing intra-abdominal adhesions by alleviating inflammation, controlling oxidative stress, and promoting tissue repair. BA and TUS showed limited efficacy under the present experimental conditions, and BA in particular was associated with increased oxidative stress and inflammatory responses. Further research with optimized dosing, extended treatment durations, and combination strategies is warranted.

The present study evaluated Polygonum cognatum extract (PCE) as a therapeutic agent for diabetes treatment. The research used twenty-four Sprague–Dawley male rats which weighed between 250–300 g and were 90 days old. The researchers distributed the 24 rats into four groups which included Control and Diabetes Mellitus (DM) and PCE and DM + PCE. The DM and DM + PCE groups received streptozotocin (STZ) as a single dose to create diabetes in their animals. The solution of STZ required dissolution in a 0.1 M cold citrate buffer which had a pH of 4.5 before i.p. injection. The researchers administered PCE at a dose of 60 mg/kg. The researchers administered PCE through gavage at a daily dose of 10 mg/kg which patients received orally (p.o.) The rats received the treatment for 20 days. The researchers performed rat sacrifices to obtain blood samples and pancreas and liver tissue specimens. The diabetes group showed elevated liver enzyme levels and lipid profile parameters and malondialdehyde (MDA) compared to the Control and PCE groups. The diabetes group showed elevated MDA levels and decreased high-density lipoprotein cholesterol (HDL-C) and glutathione (GSH) concentrations together with reduced glutathione peroxidase (GPx) and superoxide dismutase (SOD) and catalase (CAT) enzyme activities. The combination of PCE with DM led to reduced glucose levels and decreased liver enzyme activity and lipid profile and MDA concentrations and elevated HDL-C and GSH levels and enhanced GPx and SOD and CAT activities. PCE downregulated the expression of caspase-3 and nuclear factor kappa B (NF-κB) and B-cell lymphoma 2 (Bcl-2) associated X-protein (Bax) and toll like receptor 4 (TLR-4) but it increased the expression of Bcl-2 and nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). The research showed that PCE treatment resulted in decreased blood sugar levels and better liver enzyme and lipid profile results and decreased lipid peroxidation and enhanced antioxidant enzyme activities and reduced oxidative stress in DM rats according to biochemical and histopathological results.

In this study we report the first identification of the therapeutic effects of pomiferin isolated from Maclura pomifera against acute liver and kidney injury induced by sepsis. These results were obtained using a rat model of sepsis. We focused on targeting the nuclear factor kappa B (NF-κB) activation cascade, oxidative stress, and cytochrome-c, three key components involved in the pathophysiology of sepsis-associated acute liver and kidney injury. This assessment was conducted using biochemical, histopathological, immunohistochemical, and immunofluorescence analyses to examine parameters in liver and kidney tissues. The cecal ligation and puncture technique, used to induce sepsis, consistently caused acute liver and kidney damage. This was evidenced by significant increases (p < 0.0001), relative to untreated control rats, in the abundance of Toll-like receptor 4, NF-κB p65, phospho-NF-κB p65, 8-hydroxydeoxyguanosine, cytochrome-c, and caspase-3, higher degeneration, lipid peroxidation, and necrosis. This technique also caused significant decreases (p < 0.001) in components of the cellular antioxidant system in the hepatic and renal tissues of septic rats. Pomiferin, particularly at a dose of 300 mg/kg, showed promising pharmacological effects by reversing these pathological changes. Overall, pomiferin appears to protect liver and kidney tissues during sepsis by suppressing the NF-κB activation cascade, reducing oxidative stress, and lowering cytochrome-c activity. These effects suggest that pomiferin may be useful for managing sepsis patients with acute liver and kidney injury.

The aim of this study was to investigate the potential effects of monosodium glutamate (MSG), a known flavour enhancer added to many ready-to-eat foods, as a feed additive in rainbow trout (Oncorhynchus mykiss). Evaluating the effects of MSG on aquatic organisms will fill the knowledge gap in this field by monitoring the haematological indices of O. mykiss with growth parameters and somatic indices, histomap mapping with histopathological observations and determination of antioxidant/cytokine enzyme levels via holistic/multi-biomarker approaches. Accordingly, rainbow trout feed was supplemented with MSG at different concentrations [(control (0% MSG), MSG-I (0.25% MSG), MSG-II (0.5% MSG), MSG-III (0.75% MSG) and MSG-IV (1% MSG)], and a 60-day feeding trial was conducted. Considering the weight gain, MSG-IV group showed an increase of 24.5% compared to the control and was determined as 61%. Exposure to different concentrations of MSG caused a decrease in erythrocyte, leukocyte, hemoglobin (Hg) and hematocrit (Hct) levels in O. mykiss. The effect of the same application on liver tissue, which is the detoxification organ, was determined as inhibition in antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and nuclear factor erythroid 2-related factor 2 (NRF-2) level, induction in Reactive oxygen species (ROS) -malondialdehyde (MDA) level, DNA damage, caspase-3, tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) activities. Histopathological examination of the liver and intestine revealed hydropic degeneration in a very small number of cells and mild hyperaemia of the blood vessels, with inflammation and DNA damage responses. With the reflection of this situation on histomap results, tissue damage profile and toxicity process differed based on dose and marker and manifested itself with mild-to-severe symptoms. These findings revealed that feeding with high concentrations of MSG was effective in NRF-2/ROS pathways of oxidative stress and showed strong haemato/hepatotoxic effects. Although all MSG concentrations applied were successful in terms of biomass measurements in terms of aquaculture, physiologically, the severity of toxic effects caused by MSG exposure was felt at a low level in liver tissues, and such pollutants should be considered in risk assessment.

This study examined the anti-ulcer potential of chicken feather protein hydrolysate (Hyd) against indomethacin (Ind)-induced gastric ulcer. Hyd was prepared from feathers by microbial fermentation technique using locally isolated Bacillus licheniformis EYT2 (GenBank accession number: PV612017). Hyd was orally administrated to the rats at the doses of 100 mg/kg BW (low-dose group, Hyd100) and 200 mg/kg BW (high-dose group, Hyd200) before Ind treatment. The effectiveness of Hyd was compared with Ranitidin (Ran). Six experimental groups were designed: Control, Ind, Ran+Ind, Hyd100 + Ind, Hyd200 + Ind, and Ran+Hyd200 + Ind. Hyd was determined to have a high protein content (81.6%) and exhibit high water solubility in a wide pH range from 1 to 10. Ind-treatment caused severe erosion, ulceration, and degeneration in gastric tissue, elevated the levels of malondialdehyde, pro-inflammatory cytokines, inducible nitric oxide synthase, 8 hydroxy-2'-deoxyguanosine, Bax, caspase-3, nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase-38 (MAPK-38) and reduced the levels of glutathione, antioxidant enzymes, anti-inflammatory cytokine IL-10, prostaglandin E2, anti-apoptotic gene Bcl-2 and nuclear factor erythroid 2-related factor 2 (Nrf2). Conversely, Hyd administration, especially high dose Hyd (Hyd200 + Ind group) reversed these alterations. Furthermore, a combination of Ran and high-dose Hyd (Ran+Hyd200 + Ind) completely prevented Ind toxicity. The protective effect of Hyd was attributed to its antioxidant, antiapoptotic and anti-inflammatory activites as well as prostaglandin synthesis-enhancing property. These results imply that Hyd may be used as a supplement with anti-ulcer activity in alternative medicine and/or as a protein source in animal and human nutrition. This is the first report on anti-ulcer potential of Hyd.

Candida albicans is a commensal fungus of the vaginal and reproductive tract microbiota, but its overgrowth contributes to mucosal infections and reproductive dysfunctions. The fungus secretes exosomes carrying virulence factors, including secreted aspartyl proteinase (SAP) genes, which are critical for tissue invasion and immune modulation. Acarbose, an alpha-glucosidase inhibitor, has been shown to suppress C. albicans biofilm formation and hyphal transition. This study is aimed at evaluating the effects of acarbose on the ovarian microbiota, gut-ovary axis, and SAP gene expression profile in a rat model following exposure to C. albicans exosomes. Rats were divided into two groups: the control group received intraperitoneal C. albicans exosomes (8 log(10) CFU/mL), whereas the acarbose group received the same exosomes followed by oral acarbose (25 mg/kg/day). Exosomes were characterized by NTA and SEM. Ovarian tissue gene expression (SAP1-10) was analyzed by qRT-PCR. Inflammatory cytokines and tight junction proteins were assessed via ELISA, and microbiota composition was determined using 16S rRNA sequencing. Acarbose significantly reduced IL-8 and TNF-alpha levels while increasing IL-10, ZO-1, claudin-5, and occludin expression compared with Candida-infected controls (p < 0.05). Gut microbiota diversity and classification success were higher in the acarbose group, indicating microbial balance restoration. Acarbose mitigated C. albicans exosome-induced inflammation and barrier dysfunction while enhancing microbial diversity, suggesting its potential role in modulating the ovarian-gut axis and reducing fungal virulence through SAP gene suppression.

AIM: To investigate the effects of zingerone (ZO) on the retina in diabetic rats. METHODS: A total of 70 rats were randomly selected and divided into seven groups [diabetic group (Dm+; n=10), diabetic+metformin group (Dm+Met; n=10), diabetic+ZO25 group (Dm+ZO25; n=10), diabetic+ZO50 group (Dm+ZO50; n=10), diabetic+metformin group+ZO 50 Group (Dm+Met+ZO50; n=10)]. Diabetes was induced by streptozotocin (STZ), and metformin and two different doses of ZO were administered via gavage. Retinal tissues were evaluated by histopathological and immunohistochemical analyses. RESULTS: In diabetic rats, severe retinal inflammation, tissue necrosis, and increased tumor necrosis factor-α (TNF-α) expression were observed. ZO administration reduced these effects in a dose-dependent manner. Protective effects of metformin alone were limited, and no synergistic benefit was observed in ZO+Met groups. Administration of 50 mg/kg ZO to non-diabetic rats caused no retinal toxicity. Additionally, elevated 8-OHdG and c-Jun N-terminal kinase (JNK) expressions in diabetic retinopathy models were significantly reduced by ZO treatment. CONCLUSION: ZO can markedly reduce the pathological effects of the retina in a diabetic rat model.

Gut microbiota plays a crucial role in maintaining host homeostasis by regulating metabolic processes and immune responses. Disruptions in microbial composition are closely associated with inflammatory diseases and are often linked to the activation of key signaling pathways such as Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa TLR4/MyD88/NF-κB and NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Natural bioactive compounds, particularly flavonoids, have gained attention due to their potential to modulate both gut microbiota and inflammation-related pathways. In this context, the present study aimed to evaluate the effects of gossypetin on gut microbiota composition and its regulatory role on TLR4, MyD88, NF-κB, and NLRP3 signaling pathways in a rat model. Adult female Wistar albino rats were divided into control and gossypetin-treated groups (50 mg/kg, oral gavage/56 days dose). Gut microbiota was analyzed by 16S rRNA sequencing, and protein expression levels were assessed using Western blot. Histopathological, immunohistochemical, and immunofluorescence analyses were also in liver, intestinal, and spleen tissue performed. Gossypetin administration reduced microbial diversity and altered microbiota composition, with increases in Mediterraneibacter spp., Blautia spp., and Lactobacillus spp. Western blot results showed significant decreases in NLRP3 (p ≤ 0.01) and NF-κB (p ≤ 0.05) levels, while TLR4 and MyD88 remained unchanged. Histological analyses revealed mild tissue alterations and increased oxidative stress markers. These results suggest that gossypetin modulates microbiota composition and exerts selective anti-inflammatory effects, highlighting its potential in microbiota-associated inflammatory regulation.

In this study, the potential protective effects of syringic acid (SA) on gastric tissue were investigated in an indomethacin (INDO)-induced gastric ulcer model. A total of 84 male Sprague–Dawley rats were randomly divided into seven groups. In the in vivo experiments, rats were administered SA at doses of 5, 50, and 100 mg/kg and omeprazole (OMP) at a dose of 5 mg/kg intragastrically (i.g.) for 14 days, and indomethacin (100 mg/kg, i.g.) was administered on the final day. Following INDO administration, the rats were sacrificed under anesthesia, and gastric tissues were carefully excised for further analyses. The collected gastric tissues were subjected to biochemical, histopathological, and immunofluorescence analyses. In addition, in silico analyses were performed to support the INDO-induced gastric ulcer model. Using the licensed Schrödinger Maestro 2025/1 software, the binding properties of INDO to the COX-1 receptor were evaluated through molecular docking, MM-GBSA, and pharmacophore matching analyses. INDO administration was associated with oxidative stress, inflammation, apoptosis, and histopathological damage in gastric tissue. SA treatment appeared to alleviate INDO-induced gastric injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties. SA treatment ameliorated histopathological alterations in ulcerated areas, particularly at doses of 50 and 100 mg/kg, whereas the 5 mg/kg dose did not show a significant protective effect. In addition, in silico analyses suggested that INDO may contribute to ulcer formation by inhibiting COX-1, thereby reducing prostaglandin production in the gastric mucosa. Overall, the findings of this study suggest that SA may reduce oxidative stress, suppress inflammatory responses, and inhibit apoptosis, thereby contributing to the protection of gastric tissue against INDO-induced injury. These results indicate that SA may have therapeutic potential for the prevention of NSAID-induced gastric injury; however, further experimental and clinical studies are needed to confirm these effects and clarify the underlying mechanisms.

Introduction: Sepsis is a dysregulated systemic immune response to infection which may result in mortality. It may also lead to organ injury, including injury to the lung. French maritime pine bark extract (MPBE) has been proposed to prevent/treat various inflammatory diseases due to its strong anti-inflammatory and antioxidant effects. This study evaluates the protective and therapeutic effects of MPBE on lung injury induced by intraperitoneal E. coli lipopolysaccharide (LPS) in rats. Materials and Methods: The study design was as follows: Control, MPBE20, MPBE50, LPS, LPS+MPBE20 and LPS+MPBE50. Blood and lung tissue samples were collected 6 h after the LPS induction following a 10-day administration of MPBE. Results: LPS-induced sepsis was confirmed by the overproduction of IL-1β and TNF-α in bloodstream compared to the Control (p < 0.001). Lung injury was determined by severe histopathological changes and neutrophil infiltration in the lung tissue following intraperitoneal LPS injection. In lung tissue, MPBE improved the levels of P2X7R, TLR4, NLRP3, IL-1β, TNF-α, JNK, H2AX, 8-OHdG, MDA, GSH, Caspase-1 and Caspase-3, and pathological changes in MPBE+LPS groups compared to the LPS group. Conclusions: MPBE appears to regulate P2X7R signaling and the inflammatory–apoptotic pathway by protecting the lung from oxidative cell damage in LPS-induced sepsis in vivo.