Paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) display a distinct and severe histopathology. Maternal metabolic status may program offspring susceptibility to MASLD. This study investigated if maternal dyslipidaemia and low vitamin C (VitC) status influence offspring MASLD using a validated guinea pig model. Thirty female guinea pigs received a low-fat (LF) diet until pregnancy was confirmed, then remained on LF or switched to a high-fat (HF) diet with or without reduced VitC. Offspring were evaluated at birth and after 10 weeks on postweaning HF or LF diets. In dams, HF diet induced dyslipidaemia and elevated hepatic triglycerides and alanine aminotransferase (ALT) compared to LF dams, without causing obesity. Newborns exposed to maternal HF diet showed increased hepatic triglycerides, liver-to-body weight ratio and ALT. By 10 weeks, liver fibrosis and MASLD activity scores were higher in offspring maintained on a postnatal HF diet compared to LF. Notably, offspring viability was markedly reduced on maternal HF diet with low VitC. These findings demonstrate that even short exposure to maternal HF diet, independent of obesity, can adversely affect offspring MASLD risk and highlight the need for early prevention. Additionally, findings support the need to investigate interactions between maternal diet, VitC status and offspring survival.

Angiotensin II (Ang II), a potent profibrotic stimulus, exhibits pleiotropic effects on cardiac cells. The fate of c-Kit[+] cells in an Ang II-elevated injured myocardium remains poorly defined. This study investigated, in vitro, the effect of Ang II on the phenotype of non-hematopoietic non-endothelial c-Kit[+] cardiac interstitial cells (CICs), expressing OCT4. Our findings demonstrate that Ang II directly drives the phenotypic transition of c-Kit[+] CICs into α-SMA-expressing myofibroblasts, accompanied by significant upregulation of prominent myofibroblast markers, SM22-α, collagen type IA, and its crosslinking enzyme, lysyl oxidase. Through targeted silencing experiments, we confirmed that Ang II-mediated phenotypic transition occurs via activation of the ERK1/2 MAPK pathway, triggered by collagen receptor Discoidin domain receptor 2 (DDR2), and involves the transcription factor, serum response factor (SRF). These results indicate that c-Kit[+] CICs are susceptible to myofibroblast transition in the infarcted myocardium, and may serve as an additional source of myofibroblasts contributing to repair and remodeling alongside resident fibroblasts. Additionally, we observed that overexpression of c-Kit attenuated Ang II-induced α-SMA upregulation by downregulating DDR2-ERK1/2-SRF signaling in c-Kit[+] CICs, highlighting the pivotal role of c-Kit expression levels in regulating cell fate. Furthermore, overexpression of c-Kit in Ang II-treated cardiac fibroblasts significantly reduced the expression of myofibroblast proteins, α-SMA, SM22-α, periostin, collagen type IA, collagen receptor DDR2, and lysyl oxidase, and resembled c-Kit[+] CICs in morphology. Collectively, these results suggest that c-Kit expression in myofibroblasts may potentially mitigate the adverse effects of cardiac fibrosis and promote favorable remodeling in the long term.

Proliferative vitreoretinal diseases (PVDs) encompass severe ocular disorders such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and epiretinal membranes (ERM), characterized by the formation of fibrovascular membranes that often lead to retinal detachment and vision loss. A central mechanism driving these conditions is the epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, orchestrated by a network of transcription factors (TFs). Among these, zinc finger E-box binding homeobox 1 (ZEB1) emerges as a pivotal regulator by repressing epithelial markers like E-cadherin and inducing mesenchymal markers such as N-cadherin and vimentin, thereby promoting cell migration and fibrotic membrane formation. nuclear factor of activated T cells 5 (NFAT5) contributes to this process by mediating osmotic stress responses and upregulating inflammatory cytokines, which further act upon EMT and fibrosis. activator protein 1 (AP-1) and hypoxia inducible factor 1 subunit alpha (HIF-1α) participate in driving inflammation, extracellular matrix (ECM) remodeling, and angiogenesis. While HIF-1α triggers vascular endothelial growth factor (VEGF) expression under hypoxic conditions, AP-1 modulates matrix metalloproteinases (MMPs) essential for ECM degradation and remodeling. Additional TFs, including Kruppel-like factor 4 (KLF4) and microphthalmia-associated transcription factor (MITF), are vital in maintaining RPE cell identity. Their downregulation under pathological conditions disrupts epithelial integrity and predisposes cells to undergo EMT. Moreover, β-catenin, through its role in the wingless-related integration site (Wnt) signaling pathway, reinforces EMT and ECM remodeling, further enhancing fibrotic progression. Adipocyte enhancer-binding protein 1 (AEBP1) and ZFP36 ring finger protein like 1 (ZFP36L1) also regulate inflammatory responses and ECM dynamics, providing novel post-transcriptional targets for therapeutic intervention. Overall, the synergistic interactions among these TFs create complex feedback loops that amplify pathological changes in PVDs. Targeting these molecular pathways offers promising avenues for developing multi-targeted therapies aimed at saving vision-threatening disease while reducing invasive surgical interventions.

Chronic hepatitis B (CHB) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) are important contributors to the growing worldwide burden of liver disease. There is limited understanding regarding the interaction between CHB and MASLD. This is a consequence of the changing terminology for liver disease, inconsistent application of diagnostic tools, and poor understanding of global populations. In this review, we collate data on the use of diagnostic tests for identifying MASLD and associated liver inflammation or fibrosis in people living with CHB. We advocate for improved consensus on diagnosis, evidence-based monitoring and risk stratification, enhanced access to interventions and reduced health inequity.

Bladder outlet obstruction (BOO) induces urinary bladder wall remodeling. However, the function of exosomal miRNAs from bladder smooth muscle cells (BSMCs) in BOO development remains unclear. Differentially expressed miRNA profiles in BSMC-derived exosomes from BOO rat models and normal rats were analyzed using miRNA sequencing. LPS-induced BSMCs were treated with exosomes from BOO-extracted BSMCs. The uptake of exosomes in BSMCs was assessed by PKH26 fuorescent dye. The protein levels of MCP-1, IL-1β, TNF-α, α-SMA, and collagen I were detected by western blotting and qPCR analysis. Cell proliferation and apoptosis were assessed by CCK-8, EdU, and flow cytometry, respectively. The interaction between miR-200b-3p and zonula occludens-1 (ZO-1) 3'UTR was analyzed by luciferase reporter gene assay. Results indicated that miRNA-200b-3p was upregulated in BSMC-derived exosomes from BOO rats compared with the sham group. Treatment with exosomes from BOO-extracted BSMCs further aggravated LPS-induced BSMC proliferation, inflammation, and fibrosis. Inhibition of miR-200b-3p attenuated these effects, which were restored by silencing ZO-1 expression in BSMCs. We identified upregulation of exosomal miR-200b-3p from BSMCs in BOO rats and demonstrated that BSMC-derived exosomes enhanced proliferation, inflammation, and fibrosis of BSMCs via miR-200b-3p/ZO-1 axis. Our work identifies a potential target for diagnosis and therapy in BOO.

Liver fibrosis is a progressive pathological process triggered by chronic liver disorders, which may progress to hepatocellular carcinoma (HCC) if left untreated. Currently, there are no specific therapeutic agents for liver fibrosis, highlighting an urgent need for novel pharmacological strategies. Tomatidine (TD), a major steroidal glycoal-kaloid abundant in immature tomato fruits, leaves, and stems, exhibits diverse biological activities including anti-inflammation, anti-tumor effects, and autophagy regulation. However, its role in liver fibrosis and the underlying molecular mechanisms remain incompletely understood. In this study, we combined network pharmacology, molecular docking, and experimental validation to investigate the potential effects of TD against liver fibrosis and its associated mechanism of action. In vitro experiments using the human hepatic stellate cell (HSC) line LX-2 demonstrated that TD inhibited HSC proliferation in a dose- and time-dependent manner, and downregulated the expression of fibrosis-related markers α-smooth muscle actin (α-SMA) and collagen type I α1 chain (COL1A1) at the gene, protein, and cellular levels. Network pharmacology analysis identified 18 common targets between TD and liver fibrosis, with core targets including MAPK3, RELA, and MAPK1 involved in intracellular signal transduction and stress-activated MAPK cascade. Although no autophagy-related targets were identified in the current database among these common targets, pharmacological evidence and experimental validation confirmed that TD promoted autophagy in LX-2 cells, as indicated by reduced P62 expression, increased LC3-II/LC3-I ratio and Beclin-1 levels, and enhanced autophagic flux. Further mechanism exploration revealed that TD exerted its autophagy-promoting effect by regulating the ERK/MAPK-mTOR-ULK1 signaling pathway: TD suppressed the phosphorylation of ERK and mTOR, while activating ULK1 phosphorylation. Molecular docking verified stable binding affinity between TD and key proteins in this pathway (ERK, MAPK, mTOR, ULK1) as well as autophagy-related proteins (P62, Beclin-1, LC3) and fibrosis-related protein COL1A1, with specific amino acid residues mediating hydrogen bond formation. Collectively, our findings demonstrate that TD modulates fibrosis-related markers in hepatic stellate cells by promoting autophagy in HSCs via the ERK/MAPK-mTOR-ULK1 pathway. This study enriches the biological function research of TD and provides a novel potential candidate and theoretical basis for the development of anti-liver fibrosis therapeutics.

Idiopathic pulmonary fibrosis is the most common and aggressive form of interstitial lung disease. Despite extensive research on the pathomechanisms of fibrogenesis, little is known about the mechanisms of fibrosis resolution. Here, lineage tracing of alveolar fibroblasts was carried out during fibrosis development and delayed resolution in aged mice. Histological analyses, single-cell transcriptomics, and ex vivo models including alveolar organoids and precision-cut lung slice cultures were employed. The data reveal that lipofibroblasts contribute to myofibroblast formation during fibrogenesis, with the reverse differentiation trajectory occurring during fibrosis resolution. Importantly, delayed resolution is associated with the persistence of ADAM metallopeptidase with thrombospondin type 1 motif 4-positive (ADAMTS4+) cells. Investigation of human lung transplant tissues, single-cell and spatial transcriptomic datasets, and functional ex vivo interventions reveal strong clinical relevance. Our study underscores the significance of the lipofibroblast-to-myofibroblast reversible switch in fibrosis development and resolution and identifies ADAM metallopeptidase with thrombospondin type 1 motif 4 as a potential therapeutic target in human lung fibrosis.

Against the backdrop of escalating global plastic pollution, there is an urgent need to elucidate the systemic health risks posed by nanoplastics (NPs) as emerging environmental contaminants that enter higher organisms through the food chain. This study employed a three-level trophic transfer model, examining the pathway from polystyrene nanoparticles to Tenebrio molitor larvae and subsequently to mice, offering a comprehensive elucidation of the mechanisms behind the multiorgan toxicity associated with food chain-transferred nanoplastics (FCT-NPs). Our results demonstrated extensive accumulation of FCT-NPs across multiple organs via systemic circulation. Integrative multiorgan omics analysis revealed that FCT-NPs primarily induced two major categories of multiorgan comorbidities: cardiovascular diseases and metabolic disorders, with the liver identified as a central metabolic hub that potentially regulates other organs through bile acid-mediated metabolic crosstalk. Mechanistically, dysregulation of key genes, such as MTOR and FN1, activated Wnt and TGF-β signaling pathways, which in turn promoted organ fibrosis. Additionally, aberrant expression of critical regulators─including CAT, LPL, NQO1, and APOE─was found to drive oxidative stress and disrupt lipid metabolism. These findings provide crucial scientific evidence for FCT-NPs risk assessment and underscore the imperative for enhanced plastic pollution control and further investigation into long-term exposure effects.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease triggered by sensitization to Aspergillus fumigatus or other Aspergillus species, with 1.0%-3.5% incidence in asthma patients and 7%-15% incidence in cystic fibrosis patients. It is more common in patients with asthma or cystic fibrosis. Clinical manifestations include recurrent bronchial obstruction, cough, pulmonary infiltrates, and bronchiectasis. However, its actual incidence is likely underestimated due to complex diagnostic criteria and insufficient clinical awareness. To standardize the integrated traditional Chinese and western medicine practice for ABPA, exert the advantage of synergistic efficacy of Chinese and western medicine, and improve the comprehensive diagnostic and therapeutic level, the Professional Committee of Allergy of the Chinese Association of Integrated Traditional and western Medicine organized multidisciplinary experts to formulate this consensus. This consensus defines diagnostic criteria, clinical classification and long-term management plans of ABPA, emphasizes the importance of environmental control and screening in high-risk populations, and systematically outlines an integrated diagnosis and treatment strategy combining western and traditional Chinese medicine. Western medicine is based on corticosteroids and antifungal agents, with biologics such as omalizumab representing an emerging option, while traditional Chinese medicine contributes through syndrome differentiation and treatment-addressing patterns such as "wind invading the lung" and "phlegm-stasis binding"-combined with proprietary Chinese medicines and acupuncture to enhance efficacy, with the aim of providing standardized guidance for clinical practice.