Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits and repetitive behaviours. Emerging evidence highlights neuroinflammation, oxidative stress and mitochondrial dysfunction in its pathogenesis. Propionic acid (PPA), an enteric short-chain fatty acid, is frequently utilized to replicate ASD-like phenotypes in rodents. This study investigated the therapeutic efficacy of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist known for its neuroprotective and anti-inflammatory properties, in a PPA-induced rat model of ASD. Thirty male Wistar rats were randomly assigned to control, PPA + saline or PPA + pioglitazone (15 mg/kg/day, orally) groups. Neurobehavioural profiling utilized the sociability, open-field and passive avoidance learning tests. Furthermore, cerebral tissues were analysed for tumour necrosis factor-alpha (TNF-α), brain-derived neurotrophic factor (BDNF), sirtuin-1 (SIRT1), galectin-3 and malondialdehyde (MDA), alongside comprehensive histopathological evaluations of the hippocampus and cerebellum. Pioglitazone significantly improved social interaction, associative memory retention and spontaneous locomotor activity. Biochemically, the treatment significantly suppressed inflammatory and oxidative stress markers (TNF-α, galectin-3 and MDA) while increasing cerebral BDNF and SIRT1 levels. Histological assessments confirmed these neuroprotective benefits, demonstrating preserved neuronal architecture and decreased glial fibrillary acidic protein (GFAP) immunoreactivity, indicative of reduced reactive astrogliosis. These findings indicate that pioglitazone ameliorates behavioural, biochemical and histopathological alterations in the PPA-induced rat model of ASD. The concurrent restoration of cerebral SIRT1 levels suggests that SIRT1-related signalling may contribute to the observed neuroprotective effects.

Tuberculosis (TB) remains a major global health burden, and diabetes mellitus increases the risk of active TB. Thiazolidinediones (TZDs) have immunomodulatory effects, but their association with TB remains unclear. This study investigated the associations between TZD use and TB-related events in patients with type 2 diabetes (T2D), including TB requiring anti-TB treatment, pulmonary TB, and TB-related hospitalization. Using Taiwan's National Health Insurance Research Database, adults with newly diagnosed T2D between 2000 and 2017 were identified. Propensity score matching and Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for TB requiring anti-TB treatment, pulmonary TB, and TB-related hospitalization. After 1:1 matching, 44,095 TZD user-nonuser pairs and 9225 rosiglitazone user-nonuser pairs were identified. Overall, TZD use was not significantly associated with TB-related outcomes. However, rosiglitazone use was associated with lower risks of TB requiring anti-TB treatment (aHR, 0.56; 95% CI, 0.36-0.86), pulmonary TB (aHR, 0.79; 95% CI, 0.68-0.92), and TB-related hospitalization (aHR, 0.59; 95% CI, 0.43-0.81). Rosiglitazone use was associated with lower risks of TB-related outcomes in the primary Cox analyses; however, these associations were attenuated in time-dependent analyses and were no longer statistically significant after accounting for death as a competing event. These observational findings should therefore be considered hypothesis-generating rather than evidence of a causal or protective effect and require confirmation using more robust causal-inference approaches.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has become one of the most common chronic liver diseases worldwide, representing a major global health challenge closely linked to metabolic syndrome, obesity, and type 2 diabetes mellitus (TD2M). The condition is characterized by a multisystem nature driven by complex multifactorial mechanisms, including insulin resistance, lipotoxicity, mitochondrial dysfunction, genetic predispositions, and gut-liver axis alterations. Although liver biopsy remains the gold standard, non-invasive markers and advanced imaging methods are of key importance for early risk stratification. Furthermore, while liver-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) are significant, cardiovascular disease remains the leading cause of mortality in patients with MASLD. Current management relies primarily on lifestyle modifications, targeted pharmacotherapy (such as pioglitazone, GLP-1 receptor agonists, SGLT-2 inhibitors), and novel experimental therapies. Consequently, MASLD requires a multidisciplinary approach emphasizing early diagnosis, risk stratification, and comprehensive treatment of both hepatic and extrahepatic manifestations.

Hepatic fibrosis is a progressive liver disorder driven largely by inflammation and oxidative stress. AMP-activated protein kinase (AMPK) plays a pivotal role in regulating hepatic fibrogenesis and represents a promising therapeutic target. Therefore, this study aimed to investigate the hepatoprotective effects of pioglitazone (PIO) and to evaluate whether AMPK activation contributes to its protective actions against thioacetamide (TAA)-induced hepatic injury and fibrosis. Liver injury was induced by intraperitoneal administration of TAA (150 mg/kg, twice weekly) for 9 weeks. During the last 3 weeks, mice received PIO (3 mg/kg/day, orally). Hepatic injury and fibrosis were assessed using biochemical, histopathological, and molecular analyses. PIO treatment significantly attenuated TAA-induced hepatic injury and fibrosis, as demonstrated by improved liver histology, reduced plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and gamma-glutamyl transferase (GGT) activity, restoration of plasma albumin, and decreased α-smooth muscle actin (α-SMA) expression. These beneficial effects were associated with increased hepatic p-AMPK expression and reduced oxidative stress, evidenced by decreased malondialdehyde (MDA) and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) levels and restoration of reduced glutathione (GSH) content, as well as suppression of the transforming growth factor-β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) signaling pathway. PIO mitigates TAA-induced hepatic fibrosis, potentially through AMPK activation and subsequent suppression of the TGF-β/Smad signaling pathway, highlighting its potential as a promising antifibrotic agent.

Temporomandibular joint osteoarthritis (TMJOA) causes cartilage degeneration and jaw dysfunction, yet current treatments mainly provide symptomatic relief rather than restore the diseased joint microenvironment. Although suppressing ROS-driven oxidative stress is essential for limiting inflammatory injury, impaired clearance of accumulated apoptotic cells may perpetuate local inflammation and hinder regenerative repair. Here, single-cell RNA sequencing identifies macrophages as the dominant immune population in TMJOA and reveals a redox-inflammatory phenotype accompanied by elevated apoptotic burden but insufficient macrophage efferocytosis, indicating a pathological mismatch between oxidative stress and efferocytic clearance. To correct this mismatch, this study develops MCP@CD-MOF, a macrophage-targeting cyclodextrin metal-organic framework nanoplatform co-loaded with curcumin and pioglitazone. In vitro, MCP@CD-MOF reduces macrophage ROS accumulation and inflammatory cytokine production, enhances efferocytic uptake of apoptotic chondrocytes, and promotes matrix-regenerative macrophage-chondrocyte crosstalk. In vivo, intra-articular administration of MCP@CD-MOF preferentially accumulates in synovial macrophages, alleviates local inflammation, reduces apoptotic burden, and preserves osteochondral architecture without detectable systemic toxicity. Mechanistically, MCP@CD-MOF coordinates the FOXO1-GPX4/ERK1/2-NOX2 redox network with the FAK-DOCK1-PAK1 efferocytosis pathway. Collectively, MCP@CD-MOF integrates redox regulation with efferocytosis-driven macrophage reprogramming, providing a disease-modifying biomaterial strategy that couples inflammation resolution with osteochondral repair in TMJOA.