Drug-induced liver injury (DILI) from acetaminophen (APAP) overdose involves ER stress, oxidative damage, apoptosis, and inflammation. This study assesses Terminalia arjuna bark extract (TAE) against APAP-induced toxicity in rats, comparing its efficacy with N-acetylcysteine (NAC) through key signaling and inflammatory markers. Twenty-four Wistar rats were equally divided into four groups: Control Negative (CN, no treatment), Control Positive (CP, acetaminophen 350 mg/kg), N-acetylcysteine (NAC, 150 mg/kg), and Terminalia arjuna bark extract (TAE, ethanolic, 80 mg/kg). Over 14 days, liver injury was induced in the CP group via acetaminophen, while the NAC and TAE groups received their respective treatments. Animals were decapitated on day 15, and biological samples were collected for analysis. Biochemical assessments included liver function markers (ALT, AST) and oxidative stress parameters (SOD, TAC, TBARS, TOS). Gene expression studies were performed for oxidative stress regulators (Keap1, Nrf2) and ER stress signaling molecules (ERK, JNK, PPAR-α, AKT). Histopathological examination evaluated liver architecture and cellular integrity. Acetaminophen induced significant hepatotoxicity, as reflected by elevated liver enzymes, increased oxidative stress, altered gene expression, and disrupted liver histology. APAP toxicity resulted in elevated oxidative stress, apoptosis, inflammation, and ER stress, leading to significant hepatic damage (p < 0.0001 vs CN). NAC and TAE treatments mitigated these effects, with TAE demonstrating superior improvement in oxidative stress markers (p < 0.0001 vs CP). Gene expression analysis revealed a protective shift in the Keap1-Nrf2 pathways in the treated groups. Histopathology confirmed reduced necrosis and preserved hepatic architecture in the NAC and TAE groups. T. arjuna exhibits potent hepatoprotective effects, comparable to NAC, through modulation of oxidative stress, apoptosis, and ER stress pathways. Further studies are needed to explore its clinical applicability in acute liver injury management.

Seeds from Abelmoschus esculentus have strong anti-inflammatory properties and may effectively treat inflammatory diseases. This study explores the therapeutic potential of A. esculentus seed extract on bioactive components, hematological parameters, liver function tests, leukocytes, cytokines and histology in asthmatic mice. Mice were divided into six groups: The normal group, groups treated with A. esculentus (10, 15 and 20 mg/mL), a dexamethasone group (3 mg/mL) and an asthmatic control group. On days 1 and 14 after acclimation, all groups except the normal control received intraperitoneal injections of ovalbumin, followed by oral doses of A. esculentus (10, 15 and 20 mg/mL) or dexamethasone (3 mg/mL) during 15th to 26th day of the experiment. All treated groups were exposed to ovalbumin inhalation for three days afterward. The bioactive components in the acetonic extract were identified through Gas Chromatography-Mass Spectrometry (GC-MS) analysis. The primary bioactive compounds identified were fatty acids, flavonoids and phenolics. Mice given the extract showed improved liver enzyme levels, reduced leukocyte infiltration, alleviated airway constriction, lower cytokine levels (IgE, IL-4, IL-5, IL-10, IL-13 and IL-17A) and normalized blood indices. In conclusion, the seed extract of A. esculentus has significant potential to reduce asthma symptoms in the asthmatic mouse model.

Venous thrombosis is the main cause of incidence rate and mortality of cardiovascular diseases worldwide. The current thrombolytic therapy often faces systemic side effects, limited targeting, and adverse hypoxic microenvironment adjustments within the thrombus, which may impair efficacy. The goal is to investigate the thrombolytic effect of MnO2@pep'-Fuco needle on venous thrombosis in both in-vivo and in-vitro environments. In this study, we have injected rats with PBS, MnO2@pep-Fuco, free uPA, MnO2-COOH/uPA, MnO2/uPA@pep-Fuco and MnO2/uPA@pep'-Fuco and then we have measured their vascular occlusion rate, haemolysis, body weight and the biochemical profile of plasma. The study systematically evaluates the thrombolytic performance of MnO2@pep'-Fuco nanoparticles and it is observed that these flower-shaped nanoparticles have a pep-Fuco grafting rate of 3.87%. They can release 23.2% of dissolved oxygen within 25 minutes and achieve 90.5% drug release rate within 50 hours. The nanoparticles also exhibit excellent biocompatibility, with a cell death rate of 1.26% and red blood cell adhesion rate of 90%. In-vivo experiments, a complete thrombolysis (100%) has been achieved with a thrombus-to-vein fluorescence intensity ratio of 2:7. The study reveals excellent biosafety, with a hemolysis rate of 0.65 to 0.82% without any significant changes in body weight. These results indicate that the MnO2/uPA@pep-Fuco nanoparticle system is a promising novel therapeutic strategy for treating venous thrombosis with great efficacy.

Oral mucositis is an inflammatory condition of the oral mucosa and causes pain associated with oral mucositis, leading to impaired quality of life. Localized drug delivery systems may provide effective treatment while avoiding the drawbacks of systemic administration. The purpose of this study was to formulate a buccal patch of lidocaine, fentanyl, and cetylpyridinium chloride using chitosan (CS), glycerol (G) and propylene glycol (PPG) to treat oral mucositis as a safe alternative to systemic administration. Solvent casting was used to create mucoadhesive buccal patches. Several characteristics were evaluated to optimize the buccal patch, including folding endurance, thickness measurement, mucoadhesion study, drug release, cell viability, permeation study and pharmacokinetic study. In addition, physicochemical interaction between CS, G and PPG was examined using FTIR, DSC and TGA. The optimized buccal patch BP4 showed a swelling index of 70%. All of the bioadhesive patches showed surface pH ranging from 6.2 ± 0.18 to 7.2 ± 0.18. Further, the BP4 had an adhesion force of 69 ± 3.06 × 10-3 N. The in vitro release of cetylpyridinium chloride, fentanyl and lidocaine from BP4 was 85%, 65% and 75%, respectively, for 12 hours. Ex vivo penetration study revealed 70%, 58%, and 78% penetration from three drugs, lidocaine, fentanyl, and cetylpyridinium chloride, respectively, from optimized buccal patches (BP4). When compared to suspension, the buccal administration of fentanyl and lidocaine in rabbits verified a notable increase in the bioavailability of the drugs. The developed mucoadhesive buccal patch represents a promising and safe localized delivery system for analgesic and antiseptic agents in the treatment of oral mucositis, offering sustained drug release and improved bioavailability.

Hepatocarcinogenesis arising from liver cirrhosis is a major contributor to hepatocellular carcinoma (HCC), but effective interventions remain limited Objective: This study aimed to elucidate the molecular mechanism by which icariin suppresses cirrhosis-to-cancer progression through the ROS/NLRP3/miR-145 axis. Fifty Sprague-Dawley rats were randomly assigned to five groups: control, model, low-dose icariin (ICA-L), high-dose icariin (ICA-H), and positive control. In vitro, SMMC-7721 and HepG2 cells were treated with TGF-β1 and various concentrations of icariin to assess their effects on hepatocellular carcinoma cell activity. Compared with the model group, icariin significantly reduced the liver index, serum AFP levels, Ki-67 positivity, and hepatic ROS levels in rats, suppressed NLRP3 expression, upregulated miR-145, and effectively ameliorated liver fibrosis and dysplasia (P<0.05). In SMMC-7721 cells, icariin inhibited TGF-β1-induced proliferation, migration and invasion, promoted apoptosis and G0/G1 phase arrest, while concurrently increasing exosomal miR-145 levels (P<0.05). Further mechanism verification confirmed that miR-145 directly targets and inhibits NLRP3 expression. Icariin effectively inhibits cirrhosis-associated carcinogenesis by suppressing the ROS-NLRP3 pathway and upregulating miR-145, providing a theoretical basis for the prevention and treatment of cirrhosis and hepatocellular carcinoma.

Endometriosis is a hormone-related gynecological disease and characterized by the invasion of endometrial cells outside the uterine cavity. This study aimed to investigate the impact of goserelin acetate implants on hormone levels in patients with endometriosis using a systematic review methodology. A comprehensive search of databases including PubMed, VIP, CNKI and Wanfang was conducted for controlled trials from 2000 to 2025. 12 included trials (1,299 participants) showed that goserelin acetate implant treatment significantly improved endometriosis [OR: 5.82, 95% CI (3.20, 10.59), P<0.000001], increased luteinizing hormone [MD: -2.04, 95% CI (-2.26, -1.83), P<0.00001], follicle-stimulating hormone [MD: -2.34, 95% CI (-2.58, -2.10), P<0.00001] and estradiol levels [MD: -1.89, 95% CI (-2.11, -1.66), P<0.00001], while reducing Visual Analog Scale scores [MD: -0.41, 95% CI (-0.48, -0.34), P<0.000001], recurrence rates [OR: 0.15, 95% CI (0.09, 0.24), P<0.00001] and adverse reactions [OR: 0.19, 95% CI (0.06, 0.55), P<0.00001]. The funnel plot exhibited an inverted funnel shape with relative symmetry, indicating no significant publication bias. The study demonstrates that goserelin acetate implants can effectively enhance overall treatment outcomes and regulate hormone levels in endometriosis patients.

Subarachnoid hemorrhage (SAH) from Intracranial Aneurysms (IA) represents a leading cause of death and morbidity from neurological deficits. Emerging research has identified that variations in vascular anatomy may contribute to endothelial dysfunction, hemodynamic stress, and pharmacological responsiveness in cerebrovascular tissues. This study aimed to determine whether variations in the posterior circulation vascular system are associated with the development of aneurysms. Additionally, it was explored whether these variations could provide additional risk assessment for cerebrovascular diseases. A retrospective study of digital subtraction angiography (DSA) and computed tomography angiogram (CTA) of the posterior circulation vascular anatomy in 104 patients, from Jan 2019 to Sept 2022 was conducted. The variables recorded were posterior communicating artery grading, posterior cerebral artery dominance, vertebral artery caliber, persistent fetal type posterior circulation presence and aneurysm laterality. Hypoplastic vertebral arteries were defined as those ≤ 0.8 mm in diameter. According to the study involving 104 individuals (47 men and 57 women) left-sided posterior communicating artery (PCoA) dominance is frequently present. Right-sided aneurysm formation was higher after exclusion of bilateral and midline aneurysms from the analysis. Persistent fetal-type posterior circulation was noted in 26.9% of all cases with a predominance for formation of right-sided petrosal type. The presence of a vascular phenotype with left-sided PCoA dominance and contralateral vertebral artery hypoplasia increases the risk for formation of an IA in vascular patients with or without persistent fetal-type posterior circulation and therefore could be used to develop pharmacologically-based treatment strategies, including continued stabilizing of endothelial cells using Cilostazol.

The indole-3-butyric acid based hydrazones have gained attention due to their reported biological effectiveness; however, their in-vivo pharmacokinetic properties and metabolic pathways are yet inadequately investigated. Comprehending structure-dependent variations in absorption and metabolism is essential for the preliminary optimization of this scaffold. The aim of the study was to comparatively assess the pharmacokinetics and biotransformation of two IBA-based hydrazones-4-indole-3-butane-(thiophen-2-ylmethylene) hydrazone (TIBH) and 1-(4-amino-3,5-dichlorophenyl) ethylidene-4-indole-3-butane hydrazone (DIBH) and to clarify the impact of structural substitution on their metabolic pathways in-vivo. UV-VIS spectrophotometry under verified linear circumstances assessed serum concentrations over 24 hr in healthy rats after a single oral dosage (10 mg/kg). Metabolites and temporal profiles were identified using LC-ESI-MS/MS. Biotransformer 3.0 was used for cheminformatic prediction of metabolic pathways and enzyme participation. In exploratory analysis, data are presented descriptively (mean ± SD). TIBH demonstrated accelerated absorption with an earlier peak concentration (Cmax at 4 hr) and a reduced half-life, while DIBH exhibited a delayed peak exposure (Cmax at 8 hr) and extended systemic persistence. The LC-MS/MS study showed that both compounds went through a lot of Phase-I (hydrolysis, hydroxylation and deamination) and Phase-II (glucuronidation, sulfonation and acetylation) metabolism. This made them more polar and facilitating elimination. Different metabolite profiles showed how substitution changed metabolism. TIBH had faster oxidative and conjugative turnover, while DIBH was more stable with late stage dechlorination. The predicted routes and enzyme involvement aligned well with the experimental results. This research indicated that aromatic substitution significantly affects the pharmacokinetic and metabolic properties of IBA-based hydrazones. Despite its constraints due to an exploratory design and absence of pharmacological validation, the combined experimental and computational methodology offers mechanistic understanding of structure-metabolism connections and guides subsequent optimization and biological assessment of hydrazone scaffolds.

Myocardial ischemia-reperfusion (I/R) injury represents a critical complication in cardiovascular diseases, profoundly influencing patient prognosis. This study endeavors to elucidate the protective mechanisms and effects of Platycodin-D (PD) on myocardial ischemia-reperfusion injury (MIRI). A rat model of myocardial ischemia-reperfusion was employed to assess the impact of PD treatment on cardiac performance, myocardial injury biomarkers (CK-MB, LDH, cTnI), and infarct size. Further mechanistic insights were gained through Western blot and JC-1 staining, which analyzed the modulation of the HIF-1α/BNIP3 signaling pathway and mitochondrial autophagy by PD. PD treatment markedly improved cardiac function, decreased levels of myocardial injury biomarkers (CK-MB, LDH, cTnI), and reduced infarct size. Mechanistically, PD was found to regulate the HIF-1α/BNIP3 signaling pathway, inhibit mitochondrial autophagy, and enhance mitochondrial function. Western blot and JC-1 staining confirmed that PD increases mitochondrial membrane potential and reduces the number of damaged mitochondria in cardiomyocytes. This study underscores the significant protective effects of Platycodin-D against myocardial ischemia-reperfusion injury, presenting a promising therapeutic approach for cardiovascular disease management.

Alcoholic liver disease (ALD) poses a significant global health challenge by causing progressive damage due to excessive alcohol consumption, highlighting the urgent need for effective treatments. Jin Ge Fang (JGF) is a traditional formulation whose potential hepatoprotective mechanism remains to be fully elucidated. This study aimed to investigate the protective effects of JGF on ALD and explore its regulatory roles in oxidative stress, inflammatory cascades, and the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway. An ethanol-induced ALD rat model was established and assessed histopathologically. Serum levels of hepatic function markers [aspartate transaminase (AST) and alanine transaminase (ALT)] and oxidative stress indicators [malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)] were measured. Inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)] were quantified using enzyme-linked immunosorbent assay (ELISA). Protein expression related to the TLR4/NF-κB pathway was analyzed by Western blotting. JGF treatment significantly improved liver histology, reducing steatosis and inflammatory infiltration. It markedly decreased serum AST and ALT activities, suppressed lipid peroxidation (as evidenced by reduced MDA levels), and enhanced endogenous antioxidant defenses (elevated SOD and GSH-Px activities). Furthermore, JGF significantly inhibited the release of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and downregulated the protein expression of key mediators in the TLR4/NF-κB signaling pathway. JGF demonstrates significant hepatoprotective effects against ALD. Its benefits are likely mediated through a dual action of ameliorating oxidative damage and suppressing inflammatory activation, potentially via inhibition of the TLR4/NF-κB signaling cascade.