There are three homologous proteins (α, β and γ) in the growth arrest and DNA damage 45 (Gadd45) family. These proteins act as cellular responders to physiological and environmental stimuli. Gadd45β plays a significant role in the pathogenesis of liver diseases. Liver injury and growth stimulation increase expression of Gadd45β, which promotes cell survival, growth and proliferation in normal liver cells. By contrast, Gadd45β plays a role in promoting apoptosis and inhibiting tumour function in hepatocellular carcinoma (HCC). Currently, it is believed that Gadd45β benefits the liver through two different pathways: binding to MAPK kinase 6 (MKK6) to increase PCD induced by p38 (inhibiting tumours) or binding to constitutive androstane receptor (CAR) to jointly activate transcription of liver synthesis metabolism (promoting liver regeneration). This article aims to systematically review the role of Gadd45β in liver diseases, including its regulatory mechanism on expression and involvement in liver cell damage, inflammation, fibrosis and HCC. In conclusion, we explore the potential of targeting Gadd45β as a therapeutic strategy for liver diseases.

Purpose: To systematically analysis the burden and trends of blindness and vision loss for those aged ≥55 years from 1990 to 2019 and to predict trends over the next few years. Methods: The data were extracted from the Global Burden of Disease Study (GBD) 2019. Trends from 1990 to 2019 were calculated using average annual percentage change (AAPC) by joinpoint regression analysis. Bayesian age-period-cohort (BAPC) models were used to predict future trends. Results: In 2019, the global prevalence of blindness and vision loss was 471.1 million with 15.9 million disability-adjusted life-years (DALYs) for those aged ≥55 years. These numbers will reach 640.3 million cases and 18.9 million DALYs in 2030. The prevalence rate (per 100,000 population) increased from 32,137.8 (95% uncertainty interval [UI], 26,307.9–39,246.3) in 1990 to 33,509 (95% UI, 27,435.5–40,996.2) in 2019, with an AAPC of 0.143 (95% confidence interval [CI], 0.125–0.161; P  < 0.001). The DALY rate (per 100,000 population) decreased from 632.9 (95% UI, 447.7–870.9) in 1990 to 579.3 (95% UI, 405.2–803.4) in 2019, with an AAPC of −0.293 (95% CI, −0.323–[-]0.263). Although the prevalence rates of cataracts, age-related macular degeneration, glaucoma, and near vision loss showed increasing trends from 1990 to 2019, the DALY rates indicated a downward trend for all blindness-causing diseases. The burden is heavier for women and in low Socio-demographic Index (SDI) regions. Conclusions: Despite a decline from 2001 to 2019, the burden of blindness and vision loss, measured by prevalence and DALYs, continues to rise after adjusting for population growth and aging. Blindness and vision loss are significant public health burdens, especially for women and in low-SDI regions.

The pathogenesis of inflammatory bowel disease (IBD) is driven by an interplay among intestinal dysbiosis and aberrant mucosal immune responses. This review centers on the microbiota as a pivotal pathogenic hub, systematically dissecting how three hallmark features of dysbiosis—reduced microbial alpha diversity, depletion of immunomodulatory commensals, and expansion of pro-inflammatory pathobionts—collectively compromise epithelial barrier function, promote bacterial translocation, and sustain chronic mucosal inflammation. We further integrate emerging evidence implicating bidirectional gut-brain axis communication in amplifying both peripheral inflammation and central nervous system (CNS)-mediated behavioral comorbidities. Building on this mechanistic framework, we critically evaluate next-generation microbiota-targeted interventions: standardized fecal microbiota transplantation (FMT), rationally designed live biotherapeutic products (LBPs), precision phage cocktails targeting defined pathobionts, and microbiome-informed dietary strategies. Collectively, these approaches represent a paradigm shift—from broad-spectrum immunosuppression toward mechanism-guided, ecosystem-level modulation—thereby advancing the goal of precision medicine in IBD.

Opioid-induced constipation (OIC) represents a prevalent adverse effect of opioid analgesics, affecting 60–90% of patients and significantly compromising quality of life. This review delineates the multifactorial pathogenesis of OIC. Peripheral μ-opioid receptor (MOR) activation suppresses enteric neuronal excitability, inhibits intestinal motility and secretion, and impairs rectoanal function. Notably, the colon appears to exhibit a distinctive lack of tolerance to opioids. Enteric glial cell activation has been implicated in neuroinflammation, while interstitial cells of Cajal show impaired pacemaker function. Central mechanisms are increasingly recognized to involve the brain–gut axis. Furthermore, opioid-induced barrier disruption, microbiota dysbiosis, and LPS/TLR4-mediated inflammation are proposed to interact and may contribute to a self-reinforcing cycle. Animal models have been instrumental in dissecting these mechanisms. However, they present limitations in reproducibility, clinical phenotype fidelity, and translational validity, particularly regarding microbiome composition and neuroimmune responses. Future research should prioritize the development of standardized, physiologically relevant animal models incorporating multi-omics approaches, and validate mechanism-based therapeutic strategies, including peripherally acting MOR antagonists and microbiota-targeted interventions, for precision management of OIC.

Fused in sarcoma (FUS), a DNA–RNA binding protein, affects gene transcription, while its role in non-alcoholic steatohepatitis (NASH)-fibrosis is not well understood. In this study, immunohistochemistry and western blot analysis were used to detect the expression of FUS in liver samples from patients with NASH and in LX-2 cells. Immunofluorescence staining showed that FUS co-localized with growth arrest and DNA damage 45β (GADD45B) in hepatic stellate cells (HSCs). Chromatin immunoprecipitation combined with quantitative PCR and luciferase reporter assays were performed to validate the binding sites and transcriptional activity of FUS to the TGFB1 and COL1A1 promoters. Gadd45b knockout (Gadd45b KO) and wild-type mice with the NASH-fibrosis model validated the role of GADD45B in NASH-fibrosis. Downregulation of GADD45B reduced HSC activation triggered by TGFB1 stimulation or FUS overexpression. Ameliorated collagen deposition and decreased nuclear FUS content in HSCs were detected in Gadd45b KO mice. Overall, this study suggests that FUS and GADD45B could be potential treatment targets for NASH-fibrosis.