Bronchopulmonary dysplasia (BPD) is a heterogeneous developmental lung disorder resulting from the interaction between antenatal susceptibility and postnatal injury. Increasing evidence suggests that its biological origins may precede preterm birth, with placental dysfunction, fetal growth restriction, inflammation and oxidative stress influencing pulmonary developmental trajectories before exposure to the extrauterine environment. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression at the post-transcriptional level, are emerging as potential molecular mediators linking these fetal and neonatal processes. This educational review examines miRNA dysregulation across the fetal-neonatal continuum of BPD. We first discuss the role of miRNAs in physiological lung development and their disruption following premature birth. We then explore how placental dysfunction and fetal growth restriction may influence miRNA networks, including placenta-enriched C19MC miRNAs, thereby contributing to antenatal susceptibility to BPD. Particular attention is given to miRNA-mediated regulation of pulmonary angiogenesis and VEGF signaling and to the bidirectional relationship between miRNAs and oxidative stress, including modulation of NRF2-dependent antioxidant responses. Beyond their mechanistic relevance, miRNAs offer potential translational opportunities. Their stability and detectability across different biological compartments-including placenta, cord blood, peripheral blood, respiratory samples and extracellular vesicles-make them attractive candidates for longitudinal biomarker profiling, while experimental modulation using miRNA mimics and inhibitors provides proof of concept for future therapeutic approaches. However, heterogeneity in biological sampling, analytical methods, developmental timing and BPD phenotypes, together with challenges in tissue-specific delivery and off-target effects, currently limit clinical translation. Rather than identifying a single 'BPD miRNA', future research should focus on dynamic, multi-compartment miRNA networks integrating antenatal programming with postnatal exposures. Such an approach may improve molecular endotyping, early risk stratification and ultimately the development of individualized preventive and therapeutic strategies for BPD.

Severe asthma patients (SA) are more susceptible to respiratory infections with human rhinoviruses (HRV) than healthy subjects (H), causing exacerbations. In response to HRV, circulating immune cells are recruited to and activated at the local sites of infection. Hypothesis: The activation of circulating immune cells in response to HRV is impaired in severe asthma. We infected peripheral blood mononuclear cells (PBMC) of H (n = 20) and SA (n = 50) with RV-A16 ex vivo. Cytokines were measured in culture supernatants by ELISA. Data were compared between SA and H and correlated to asthma phenotype biomarkers. RV-A16 induced IFNα, IFNγ, CCL2, CCL5, TNFα, IL-1β, IL-6 and IL-8. Except for CCL2, these cytokine responses were reduced in SA versus H. In SA, IFNα, IL-6 and CCL5 responses correlated negatively, but IL-1β correlated positively to FeNO. IFNγ correlated positively to blood eosinophils and serum IL-33, and INFα correlated positively to serum total IgE. Cytokine responses of circulating immune cells to RV-A16 are reduced in SA. Cytokines are differentially affected in allergic, eosinophilic or T2 low asthma. This could help to explain the increased risk for exacerbations in HRV infections in severe asthma and differences between phenotypes. Circulating immune cells might be considered as drug targets to reduce exacerbation rates.

The regulatory role of bone marrow in systemic metabolic processes remains incompletely characterized. Myeloid-derived growth factor (MYDGF) is a myeloid cell-secreted factor with emerging metabolic functions, but its action in diabetes-associated non-alcoholic fatty liver disease (DM NAFLD) is undefined. To investigate the influence of myeloid cell-derived MYDGF on DM NAFLD, both loss- and gain-of-function approaches were applied in vivo. DM NAFLD models were established in Mydgf-knockout (KO) mice, Pparg[ΔLyz2] mice and Pparg[ΔLyz2]/KO (DKO) mice. For in vitro studies, primary Kupffer cells (KCs) were stimulated with high glucose and recombinant MYDGF (rMYDGF) and bone marrow cells (BMCs) were co-cultured with KCs via a transwell system. Protein levels related to DM NAFLD pathology and signalling pathways were quantified. In this study, we found that MYDGF was significantly downregulated in DM NAFLD mouse liver. Myeloid MYDGF deficiency exacerbated hepatic inflammation, lipogenesis, steatosis and macrophage infiltration, while reconstituting myeloid MYDGF reversed these phenotypes. rMYDGF attenuated inflammation, reduced macrophage foaming, decreased cholesterol content and increased efferocytosis. Mechanistically, MYDGF induced AMP-activated protein kinase (AMPK) phosphorylation, which subsequently activated the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) pathway in KCs and upregulated downstream ABCA1 and ABCG1 expression. These results identify the AMPK/PPARγ/LXRα-ABCA1/ABCG1 cascade as the core signalling axis mediating MYDGF's metabolic regulatory effects, which bridges the previously unrecognized functional linkage between myeloid cell function and hepatic lipid homeostasis, and explains the protective phenotype observed in MYDGF-reconstituted DM NAFLD mice. In conclusion, myeloid cell-derived MYDGF ameliorates DM NAFLD, decreases cholesterol content in macrophages and reduces lipid accumulation via the AMPK/PPARγ/LXRα pathway. MYDGF serves as a key mediator for bone marrow-liver metabolic crosstalk, indicating that the bone marrow may act as a potential endocrine target for the prevention and treatment of diabetes-related metabolic disorders.

Alcoholic cardiomyopathy (ACM) is a severe cardiovascular complication of chronic alcohol consumption, but its underlying mechanisms remain incompletely understood. Cuproptosis is a recently identified copper-dependent form of regulated cell death; however, its role in ACM remains unclear. In this study, male C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli liquid diet to establish an ACM model, and RNA sequencing combined with bioinformatics analysis was performed to identify cuproptosis-related genes. Among the candidate genes, dihydrolipoamide branched-chain transacylase E2 (DBT) showed a consistent trend of downregulation across both independent RNA-seq cohorts, and was further validated by qRT-PCR and Western blotting. ACM mice exhibited increased serum and cardiomyocyte copper content, altered cuproptosis-related markers and impaired cardiac function. In AC16 cells, DBT knockdown induced copper overload, cuproptosis-related molecular alterations and mitochondrial dysfunction, which were markedly alleviated by the copper chelator tetrathiomolybdate. Conversely, DBT overexpression attenuated EtOH-induced copper overload, cuproptosis-related molecular alterations and mitochondrial dysfunction, with effects similar to those of tetrathiomolybdate. These findings suggest that DBT regulates ACM-related cardiomyocyte injury through cuproptosis-associated processes at the cellular level and may represent a potential therapeutic target for alcohol-induced myocardial injury.

Systemic antibiotics are effective when used as adjunctive therapy in the treatment of periodontitis; however, their use must be balanced against antimicrobial resistance, which is a major threat to global public health. This review provides an expert synthesis of the literature and a field-level overview of antimicrobial resistance in periodontal therapy, highlighting current knowledge and emerging directions, while examining how adjunctive antibiotic protocols may contribute to resistance within the periodontal microbiome through emerging metagenomic insights. To provide this synthesis, the PubMed database was searched for English-language publications using combinations of the terms periodontitis, systemic antibiotics, antimicrobials, resistance, resistome, therapeutic adjuncts, resistance genes, susceptibility, antibacterial and drug resistance, and the findings are presented as a narrative review. The evidence indicates that a substantial proportion of patients with periodontitis harbour subgingival microbiota that are non-susceptible to at least one antibiotic used in periodontal therapy. Across the included studies, antimicrobial resistance was most frequently reported in Prevotella and Porphyromonas species, while some studies also identified virulence-associated factors in Staphylococcus aureus, a non-classical periodontal organism detected within the subgingival microbiota. Overall, current evidence indicates a high prevalence of antibiotic resistance genes in the subgingival microbiota of patients with periodontitis and highlights the ecological consequences of adjunctive antibiotic use. These findings reinforce the need to optimize antibiotic prescribing protocols within an antibiotic stewardship framework and support further metagenomic investigations to refine understanding of resistance patterns, gene-transfer mechanisms and microbiome disruption, with the aim of advancing precision-based periodontal care.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a condition marked by persistent inflammation of the prostate, whose underlying mechanisms remain poorly defined. This study aimed to investigate the role of prostaglandin-endoperoxide synthase 1 (PTGS1) in macrophages and in a mouse model of experimental autoimmune prostatitis (EAP). Using multiple experimental methods, we found that PTGS1 was induced during IL-4-mediated M2 macrophage polarization, whereas PTGS1 silencing further enhanced M2 polarization. Mechanistically, PTGS1 functioned as a feedback regulatory checkpoint by interacting with PPARγ in the cytoplasm and restraining its nuclear translocation; PTGS1 silencing released this constraint, enhanced PPARγ nuclear accumulation, and promoted M2 macrophage polarization. In EAP mice, PTGS1 knockdown alleviated disease progression and reduced oxidative stress injury, accompanied by increased M2 macrophage polarization and reduced iNOS-positive pro-inflammatory macrophage accumulation. Furthermore, PTGS1 silencing diminished the PTGS1-PPARγ interaction, thereby enhancing PPARγ nuclear translocation and strengthening the M2 polarization program. In summary, our findings show that PTGS1 knockdown attenuates F4/80[+]/iNOS[+] pro-inflammatory macrophage accumulation, mitigates prostatic inflammation and oxidative stress, and offers a potential immunomodulatory strategy for CP/CPPS.

Postmenopausal oestrogen deficiency is associated with skeletal muscle loss and functional decline, thereby increasing the risk of sarcopenia in women. Considering the safety risks linked to hormone replacement therapy (HRT), alternative strategies are needed to attenuate skeletal muscle decline after menopause. A total of 24 female C57BL/6J mice were randomly assigned to four groups (n = 6 per group): Sham-operated (SHAM), ovariectomized (OVX), OVX treated with estradiol valerate (OVX + E2) and OVX treated with Bazi Bushen (OVX + BZBS). Skeletal muscle mass and function were evaluated in four groups. RNA sequencing was applied to explore the molecular mechanisms and key signalling pathways underlying BZBS-induced muscle protection. We further examined the role of the FGFR1/ERK signalling pathway in mediating the effects of BZBS on myogenic differentiation in C2C12 myoblasts. The results showed that OVX mice had reduced grip strength and skeletal muscle mass, increased fat accumulation, reduced lean mass and impaired metabolic activity. These phenotypic alterations were accompanied by myofiber atrophy, increased collagen staining, endocrine perturbations and elevated expression of p16, p21, Atrogin-1 and MuRF1. BZBS ameliorated these abnormalities. RNA-seq suggested that FGF/MAPK signalling may be involved. In D-gal-treated C2C12 myoblasts, BZBS reduced Atrogin-1 and MuRF1 expression while restoring MYHC and MYOG expression. Mechanistically, BZBS suppressed FGFR1/ERK signalling activation and bFGF partially reversed the protective effects of BZBS. Taken together, these findings suggest that FGFR1/ERK signalling may contribute to the protective effects of BZBS. Our findings provide evidence for the beneficial effects of BZBS on skeletal muscle deterioration associated with oestrogen deficiency.

Extracellular vesicles (EVs) are nanoscale, membrane-enclosed particles that transfer proteins, nucleic acids, lipids, and other bioactive molecules between cells. Their cargo-bearing capacity supports applications in drug delivery, regenerative medicine, and biomarker development, but ex vivo handling can alter vesicle recovery and cargo readouts. Storage temperature, pH, freeze-thaw exposure, storage duration, and buffer composition differentially affect EV-associated proteins and nucleic acids. This review evaluates preservation studies using EVs from non-diseased cells, tissues, and biological fluids, with emphasis on the distinction between EV recovery, cargo abundance, molecular integrity, and functional preservation. Across the available literature, optimal conditions depend on EV source, biological matrix, isolation method, storage duration, cargo class, and analytical endpoint. Standardized protocols that separately measure vesicle recovery, cargo abundance, molecular integrity, and biological activity are required to define source- and application-specific preservation strategies and resolve the mechanisms of storage-associated cargo alteration.

Treating acute liver failure (ALF) relies on rescuing dying hepatocytes and restoring liver regeneration. Ferroptosis contributes to ALF development, so regulating iron homeostasis or lipid peroxide production may be an effective treatment strategy. Ubiquitination can modify ferroptosis and is involved in liver diseases. The study aims to explore the mechanism of E3 ubiquitin ligase Smurf1 regulating ferroptosis in acute liver failure. Screened using proteomics, bioinformatics and experimental verification, we identified Smurf1, a ubiquitin-related protein associated with ferroptosis. Functional experiments were used to verify that Smurf1 regulates hepatocyte ferroptosis and acute liver failure. Furthermore, ubiquitination assays, western blotting and Co-IP experiments were applied to identify Ulk1 as a substrate of Smurf1. Further, we constructed the cell and animal models with silencing or overexpression of Smurf1 and Ulk1 to clarify the potential mechanism of Smurf1 on ferroptosis in ALF. Knockdown or overexpression of Smurf1 promoted or inhibited hepatocyte ferroptosis, respectively. In the animal model, knockdown of Smurf1 significantly aggravated the progression of ALF, suggesting that Smurf1 knockdown exacerbated liver failure by promoting hepatocyte ferroptosis. In conclusion, Smurf1 interacted with the new substrate Ulk1 and promoted its ubiquitin-mediated degradation at the post-translational level, and Smurf1 knockdown promotes ferroptosis in hepatocytes in a manner dependent on Ulk1-mediated autophagy activation.

After undergoing ADT treatment, drug resistance has emerged as a major hindrance in the treatment of prostate cancer, with enzalutamide resistance being the most notable. Our objective was to identify a new drug-resistance mechanism present in post-ADT-treatment patients. Utilizing proteomic sequencing, we discovered abnormal increases in IGF1R levels. Subsequent sequencing and bioinformatic analyses showed that IGF1R could cause abnormal changes in the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation. This phenomenon may be due to IGF1R's influence on the distribution of mitochondrial Ca[2+] and the production of reactive oxygen species (ROS). Our CHIP and dual-luciferase experiments confirmed the regulatory relationship between IGF1R and MICU1. The fluorescent results of Ca[2+] and ROS also confirmed that IGF1R could regulate mitochondrial Ca[2+] distribution and ROS production. Our team validated the relationship between IGF1R and drug resistance through cell phenotype experiments, and explored its potential as a therapeutic target through a fa-ci curve. Finally, we verified the effectiveness of the mechanisms we found through a xenograft assay. Our study confirms the potential for IGF1R as a clinical therapeutic target.

Autophagy plays complex, context-dependent roles in lung adenocarcinoma (LUAD), but the upstream molecular drivers that govern this process remain elusive. NLRC4 is classically defined as a pyroptosis-inducing inflammasome sensor, yet its non-canonical, tumour-intrinsic function in LUAD progression remains largely unexplored. Through multi-omics screening and prognostic modelling across TCGA and GEO datasets, we identified NLRC4 as a critical autophagy-associated protective factor, which was validated in an institutional cohort of paired LUAD tissues. In vitro and in vivo assays, autophagic flux monitoring, reciprocal co-immunoprecipitation and genetic rescue experiments were employed to elucidate the underlying mechanism. NLRC4 protein was markedly downregulated in LUAD tissues alongside the tumour suppressor PTEN, correlating with advanced TNM stage and poor overall survival. Functionally, restoring NLRC4 expression inhibited LUAD cell proliferation, motility, invasion and epithelial-mesenchymal transition in vitro, whereas NLRC4 depletion accelerated xenograft tumour growth in vivo. Crucially, NLRC4 selectively stimulated complete autophagic flux without triggering Caspase-1/Gasdermin cleavage or lytic pyroptotic death. Mechanistically, NLRC4 physically interacted with NFKB1 (p105/p50) in a tumour-selective manner, relieving NF-κB-mediated transcriptional repression of PTEN. This restored PTEN expression, thereby tonically dampening the PI3K/AKT/mTOR signalling cascade. Genetic blockade of autophagy (siATG5) or PTEN ablation largely reversed the tumour-suppressive effects of NLRC4, confirming the functional dependency on the PTEN-autophagy axis. Our study establishes a non-canonical, tumour-intrinsic role for NLRC4 in restraining LUAD progression via the PI3K/AKT/mTOR axis to induce protective autophagy, positioning it as a promising prognostic biomarker and potential therapeutic target.

Postpartum depression (PPD) affects approximately 17.2% of women giving birth globally, but current pharmacotherapies face significant limitations including invasive intravenous delivery (brexanolone) and high costs Bergamot essential oil (BEO) has demonstrated efficacy in aromatherapy for depression, yet its role in PPD remains unexplored. This study investigated whether prophylactic or therapeutic inhalation of nebulized BEO ameliorates PPD-like phenotypes in a rat model of hormone-simulated pseudopregnancy (HSP) with abrupt withdrawal, and explored potential mechanisms involving hippocampal synaptic plasticity and neuroinflammation. The main components of BEO were characterized using gas chromatography-mass spectrometry (GC-MS). A rat model of PPD was constructed using the HSP post-withdrawal method, and animals were randomly divided into control group (Ctrl), sham surgery group (Sham), model group (PPD), fluoxetine group (Flu; 10 mg/kg, i.p., post-modelling) as a positive control representing first-line SSRI therapy (brexanolone, though FDA-approved for PPD, requires costly intravenous administration and specialized medical supervision, and was therefore not used as a comparator), therapeutic BEO group (BEO; 2.5% v/v inhalation post-modelling) and prophylactic BEO group (P-BEO; 2.5% v/v inhalation during HSP modelling). The sucrose preference test (SPT), open field test (OFT) and elevated plus maze (EPM) were used to evaluate the depressive-like behaviours, and HE staining was used to observe the effects of BEO on the thymus and spleen of immune organs. Nissl staining was utilized to quantify the Nissl bodies in the hippocampus (HIPP) of PPD model rats. Additionally, immunohistochemistry and Western blotting were conducted to detect alterations in postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) within the hippocampus of the rats. Enzyme-linked immunosorbent assay (ELISA) was employed to further analyse the levels of insulin-like growth factor-1 (IGF-1, a neurotrophic factor linked to synaptic plasticity), interleukin-1β (IL-1β, a pro-inflammatory cytokine implicated in PPD pathogenesis) and interleukin-10 (IL-10, an anti-inflammatory cytokine implicated in PPD pathogenesis) in serum, cerebrospinal fluid (CSF) and HIPP. Molecular docking was performed to predict interactions between BEO's core constituents (limonene, γ-terpinene, α-pinene, β-pinene, α-phellandrene) and target proteins (PSD-95, SYP, IL-1β, IGF-1, IL-10). Both therapeutic and prophylactic BEO inhalation significantly increased sucrose preference (from 78.78% ± 17.25% to 96.44% ± 2.60% [BEO] and 97.33% ± 0.87% [P-BEO], p < 0.05), total distance travelled in the OFT (from 900.07 ± 523.07 to 1932.64 ± 665.88 cm [BEO] and 1671.51 ± 544.36 cm [P-BEO]; p < 0.05) and open arm time in the EPM (from 16.34 ± 15.44 to 49.91 ± 24.99 s [BEO] and 50.81 ± 16.12 s [P-BEO]; p < 0.05). Both BEO groups exhibited increased Nissl body counts in hippocampal CA1 (from 7.44 ± 1.59 to 18.44 ± 2.60 [BEO] and 19.56 ± 2.07 [P-BEO]; p < 0.05), CA2, CA3 and DG subregions (p < 0.05 vs. PPD), as well as increased PSD-95/SYP protein abundance. Both BEO regimens increased IGF-1 levels in serum and CSF (p < 0.05 vs. PPD), with the P-BEO group showing a significantly higher serum IGF-1 levels compared to the Flu group (p < 0.05). Additionally, both P-BEO and BEO groups decreased IL-1β levels in serum and HIPP, while increasing IL-10 levels in the CSF (p < 0.05 vs. PPD for all). Molecular docking revealed favourable binding affinities (binding energy < -5.0 kcal/mol) between BEO constituents and all five target proteins. No significant histopathological alterations were observed in thymus or spleen following BEO exposure. Collectively, these findings suggest that BEO inhalation may attenuate PPD-like phenotypes in this rat model, potentially through modulation of hippocampal synaptic plasticity and neuroinflammation via regulation of IGF-1, IL-1β and IL-10. While these results are preliminary, the non-invasive delivery and observed dual-phase efficacy suggest that BEO inhalation may represent a more accessible approach worthy of further investigation for PPD management, particularly in resource-limited settings where current FDA-approved treatments are unavailable.

Myocardial ischemia-reperfusion injury (MIRI) is a major cause of cardiovascular morbidity and mortality. Reperfusion, although essential for myocardial restoration, can paradoxically exacerbate injury through oxidative stress, calcium overload, mitochondrial permeability transition pore opening and inflammatory infiltration. The vulnerability to MIRI is substantially amplified in subjects with diabetes mellitus, where chronic hyperglycemia, insulin resistance, and the resulting oxidative stress and low-grade inflammation impair endogenous cardioprotective mechanisms and worsen postinfarction outcomes. Ischemic conditioning strategies, including preconditioning and postconditioning, serve as powerful innate methods to mitigate MIRI by exposing the myocardium to brief, sublethal ischemic episodes that activate crucial prosurvival signalling pathways. Among these pathways, the survivor activating factor enhancement pathway, which is mediated predominantly by signal transducer and activator of transcription 3 (STAT3), and the reperfusion injury salvage kinase pathway, which involves AKT and ERK, are particularly important. However, in many models of diabetes, diabetes-induced STAT3 dysfunction may disrupt these protective pathways, often making conditioning stimuli less effective. The precise mechanisms underlying this impairment remain incompletely understood. Additionally, paradoxical changes in STAT3 expression have been reported, and key posttranslational modifications of STAT3 have not yet been investigated in the context of diabetic MIRI. This review provides a critical appraisal of the role, regulatory mechanisms and therapeutic potential of STAT3 in ischemic conditioning in patients with diabetes and discusses strategies aimed at restoring cardioprotection in this high-risk population.

Iron is an essential micronutrient whose ability to cycle between ferric (Fe[3+]) and ferrous (Fe[2+]) states makes it crucial for physiological processes, including oxygen transport, DNA synthesis, and oxidative phosphorylation. However, because both deficiency and excess can cause severe pathology, precise regulation is critical. The liver plays a central role in systemic iron metabolism, and growing evidence identifies hepatic iron dyshomeostasis as a key catalyst in diverse liver disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD/MASH), alcoholic liver disease, liver fibrosis, and hepatocellular carcinoma (HCC). Hepatic iron accumulation promotes liver injury primarily through oxidative stress, mitochondrial dysfunction, and ferroptosis. In this review, we synthesize the multi-layered regulatory landscape of hepatic iron homeostasis, encompassing systemic coordination, cellular fine-tuning, and epigenetic modifications. We thoroughly dissect the pathogenic impact of iron overload and critically evaluate emerging therapeutic strategies aimed at restoring iron balance, such as hepcidin mimetics and ferroptosis modulators. Finally, we discuss current literature gaps-including preclinical model limitations, the lack of standardized non-invasive biomarkers, and drug delivery bottlenecks-providing a clear roadmap for future translational research in iron-related liver pathologies.