Myocardial fibrosis (MF) is a pivotal pathological process implicated in various cardiovascular diseases, particularly heart failure. Astragaloside IV (AS-IV), a natural compound derived from Astragalus membranaceus, possesses potent cardioprotective properties. However, the precise molecular mechanisms underlying its anti-MF effects, particularly in relation to senescence, remain elusive. Thus, this study aimed to investigate the therapeutic potential and underlying molecular mechanisms of AS-IV in treating ISO-induced MF in mice, employing transcriptomics, proteomics, in vitro, and in vivo experiments. We assessed the positive effects of AS-IV on ISO-induced MF using HE staining, Masson staining, ELISA, immunohistochemical staining, transthoracic echocardiography, transmission electron microscopy, and DHE fluorescence staining. Additionally, we elucidated the regulatory role of AS-IV in MF through comprehensive transcriptomics and proteomics analyses, complemented by Western blotting and RT-qPCR validation of pertinent molecular pathways. Our findings demonstrated that AS-IV treatment markedly attenuated ISO-induced myocardial injury and oxidative stress, concomitantly inhibiting the release of SASPs. Furthermore, integrated transcriptomics and proteomics analyses revealed that the anti-MF mechanism of AS-IV was associated with regulating cellular senescence and the p53 signaling pathway. These results highlight AS-IV exerts its anti-MF effects not only by inhibiting oxidative stress but also by modulating senescence through the p53 signaling pathway.

Background: Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited treatment options. Premature senescence of alveolar epithelial type II cells (AT2 cells) plays a critical role in PF pathogenesis. This study aimed to identify natural compounds targeting senescence-related pathways for PF treatment. Methods: An integrated approach was implemented, combining bioinformatics, artificial intelligence (AI)-assisted molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling, and experimental validation. Core targets associated with aging-related pulmonary fibrosis (PF) were identified via database mining (GeneCards and AgingAtlas) and protein-protein interaction (PPI) network analysis. Natural compounds were screened using the HERB database, and resveratrol (RES) was selected due to its multi-target activity and favorable ADMET characteristics. The efficacy of RES was evaluated through in vitro experiments using bleomycin (BLM)-induced senescent A549 alveolar epithelial cells and in vivo studies in a BLM-induced PF mouse model (C57BL/6J). Molecular docking simulations were performed to predict the binding affinity between RES and key targets, including SERPINE1, MMP2, and IL-6. Results: Bioinformatics identified 322 aging-related PF targets, with TP53, AKT1, STAT3, JUN, and NFKB1 as core regulators. Resveratrol was selected as a top candidate modulating all five core targets and exhibiting optimal drug-likeness. Molecular docking and dynamics simulations confirmed strong binding affinity between RES and key senescence-associated proteins (SERPINE1: −8 kcal/mol; MMP2: −7.5 kcal/mol; IL-6: −7.1 kcal/mol). In vitro , RES (10–40 μM) significantly suppressed bleomycin-induced senescence in A549 cells, reducing SA-β-Gal activity and downregulating SERPINE1, MMP2, and IL6 expression. In vivo , RES treatment (20–80 mg/kg, 21 days) attenuated bleomycin-induced PF in mice, improving weight loss, reducing alveolar damage, inflammation, and collagen deposition (Masson’s trichrome) in a dose-dependent manner. Conclusion: Resveratrol effectively inhibits alveolar epithelial cell senescence and ameliorates pulmonary fibrosis, likely by targeting key senescence-associated pathways (e.g., SERPINE1, MMP2, IL-6). This study provides a promising transdisciplinary strategy for anti-fibrotic drug discovery and highlights RES as a potential therapeutic candidate for PF.

Background: The inflammatory response is the main pathophysiological basis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and is a key factor leading to frequent exacerbations and disease progression. Suppressing the inflammatory response can improve pulmonary function, prognosis, and quality of life in AECOPD patients.Purpose: To evaluate the effect of Qingjin Huatan decoction (QHD) on pulmonary function and inflammatory mediators in AECOPD patients.Methods: Randomized controlled trials (RCTs) on the treatment of AECOPD with QHD were retrieved from eight Chinese and English electronic databases up to 31 May 2024. The quality of the studies was assessed using the Cochrane Risk of Bias Tool and the modified Jadad scale. Statistical analysis, sensitivity analysis, and publication bias assessment were performed using Stata 17.0 software.Results: A total of 40 RCTs involving 3,475 AECOPD patients were included. Compared to conventional treatment, QHD significantly improved pulmonary function, with increases in FEV1 (MD = 0.30, 95% CI: 0.26 to 0.34, p = 0.000), FVC (MD = 0.34, 95% CI: 0.27 to 0.41, p = 0.000), FEV1/FVC (MD = 6.07, 95% CI: 5.55 to 6.58, p = 0.000), and PaO₂ (MD = 7.20, 95% CI: 4.94 to 9.47, p = 0.000), and a decrease in PaCO₂ (MD = −5.37, 95% CI: 7.99 to −2.74, p = 0.000). QHD also significantly suppressed the expression of inflammatory mediators, including TNF-α (MD = −10.87, 95% CI: 12.51 to −9.23, p = 0.000), IL-1β (MD = −13.63, 95% CI: −16.31 to −10.95, p = 0.000), IL-6 (MD = −7.58, 95% CI: −10.10 to −5.06, p = 0.000), IL-8 (MD = −9.45, 95% CI: −12.05 to −6.85, p = 0.000), CRP (MD = −5.62, 95% CI: −6.60 to −4.65, p = 0.000), and PCT (MD = −0.84, 95% CI: −1.07 to −0.62, p = 0.000). Additionally, QHD improved clinical efficacy (RR = 4.16, 95% CI: 3.26 to 5.30, p = 0.000) without increasing the incidence of adverse reactions (RR = 1.04, 95% CI: 0.68 to 1.61, p = 0.000).Conclusion: Existing evidence suggests that QHD can significantly improve pulmonary function, suppress the expression of inflammatory mediators, and enhance clinical efficacy in AECOPD patients, with a good safety profile. Given the limitations of this study, more high-quality studies are needed to provide reliable evidence.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=559436, identifier CRD42024559436

Background: Heart failure with reduced ejection fraction (HFrEF) affects a substantial portion of the global population, with left ventricular remodeling (LVR) and inflammation identified as key contributors to disease progression. Standardized Rhodiola rosea Injection (SRRI) is a pharmacopoeia-based botanical drug preparation derived from Rhodiola rosea, widely used in China for heart failure treatment. It is standardized in composition and quality control, with known antioxidant, anti-inflammatory, and anti-fibrotic properties. However, comprehensive evaluations of SRRI’s effects on LVR and inflammatory mediators in HFrEF patients are limited.Purpose: To evaluate the effects of SRRI on LVR and inflammatory mediators in patients with HFrEF.Methods: A systematic review and meta-analysis were conducted following PRISMA and Cochrane guidelines. Eight databases were searched for randomized controlled trials (RCTs) on SRRI in HFrEF treatment with studies identified from inception to 31 October 2024. Quality assessment of the included studies was conducted using the Cochrane Collaboration’s risk of bias tool and the modified Jadad scale. Statistical analysis was performed using Stata version 17.0, with sensitivity analyses conducted by sequentially excluding studies to assess the robustness of findings. Publication bias was evaluated using Egger’s test.Results: Twenty-five RCTs with 2,325 participants were included. SRRI significantly improved LVR, indicated by increased LVEF (MD = 6.81, 95% CI: 5.71 to 7.91, P < 0.00001), reduced LVEDD (MD = −4.37, 95% CI: −5.42 to −3.33, P < 0.00001), and decreased LVESD (MD = −4.48, 95% CI: −5.42 to −3.58, P < 0.00001). Additionally, SRRI effectively reduced inflammatory mediators, including TNF-α (MD = −10.37, 95% CI: −12.96 to −7.78, P < 0.00001), IL-6 (MD = −6.99, 95% CI: −8.88 to −5.11, P < 0.00001), and hs-CRP (MD = −2.58, 95% CI: −3.37 to −1.79, P < 0.00001). SRRI also significantly reduced BNP (MD = −105.10, 95% CI: −132.29 to −77.90, P < 0.00001) and NT-pro BNP (MD = −415.95, 95% CI: −553.00 to −278.89, P < 0.00001). Clinical effectiveness was improved, with no significant increase in adverse reactions (RR = 0.86, 95% CI: 0.59 to 1.25, P = 0.44). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected.Conclusion: SRRI appears to effectively enhance LVR, reduce inflammatory mediators, and improve clinical effectiveness in HFrEF patients while maintaining a favorable safety profile. However, the current evidence is limited by methodological shortcomings, and further well-designed, multicenter RCTs are needed to validate these findings, especially in diverse populations and over long-term treatment durations.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=603884, Identifier CRD42024603884.

Epstein-Barr virus (EBV) infection can trigger life-threatening complications, including hemophagocytic lymphohistiocytosis (HLH) and septic shock. The overlapping clinical manifestations of these conditions pose significant diagnostic and therapeutic challenges. This article reports the case of a previously healthy 19-year-old female who presented with persistent high fever (40.1°C), tachycardia, tachypnea, and hypotension, along with markedly elevated inflammatory markers, meeting the diagnostic criteria for septic shock. Laboratory investigations revealed rapid, significant decreases in white blood cell (WBC) count and platelet count. A positive serum EBV viral capsid antigen (VCA) IgM test led to a suspicion of EBV-associated HLH (EBV-HLH). Prior to a definitive diagnosis of EBV-HLH, the patient was initiated on early and adequate combination therapy with corticosteroids and antivirals. This intervention resulted in rapid clinical and laboratory improvement: body temperature normalized by day 3, and peripheral blood counts gradually returned to normal. The subsequent bone marrow aspiration confirmed the HLH diagnosis, supported by elevated serum ferritin and soluble interleukin-2 receptor (sCD25) levels, fulfilling the diagnostic criteria for HLH. The patient was discharged on a tapering regimen of oral methylprednisolone and achieved complete recovery without relapse during follow-up. This case suggests that rapidly progressive and significant leukopenia and thrombocytopenia are key early indicators for distinguishing EBV-HLH from sepsis alone. Early recognition of EBV-HLH and timely initiation of combined corticosteroid and antiviral therapy can effectively control cytokine storm and improve clinical outcomes in patients with favorable treatment responses, providing valuable clinical insights for managing similar severe cases.