Objective To investigate the relationship between very long chain saturated fatty acids(VLCSFAs)levels in the serum of American adults and chronic kidney disease(CKD),thereby providing new insights for the prevention and treatment of CKD.Methods Using data from the 2011-2014 National Health and Nutrition Examination Survey(NHANES),individuals under 20 years of age and those lacking serum creatinine,blood urea nitrogen,urine albumin-to-creatinine ratio(uACR),or other covariate data were excluded.Estimated glomerular filtration rate(eGFR)was calculated using the CKD-EPI(2009)equation.The independent relationship between VLCSFAs and CKD was examined using weighted multivariate logistic regression,the XGBoost machine learning model,and subgroup analyses.Restricted cubic splines(RCS)were used to test for nonlinear associations.Results A total of 4 164 participants were analyzed.Serum VLCSFAs levels differed significantly between the CKD and non-CKD groups(P<0.05).In fully adjusted models,weighted multivariate logistic regression revealed a decreasing trend in CKD risk with increasing serum VLCSFAs levels,particularly for docosanoic acid,tricosanoic acid,and lignoceric acid,which significantly reduced CKD risk(docosanoic acid:odds ratio[OR]=0.17,95%CI:0.06-0.43,P<0.001;tricosanoic acid:OR=0.02,95%CI:0.002-0.15,P<0.001;lignoceric acid:OR=0.13,95%CI:0.04-0.40,P<0.001).RCS analysis showed no nonlinear association between VLCSFAs and CKD.The XGBoost machine learning model identified triacontanoic acid as the most important factor for CKD risk.Subgroup analysis indicated that docosanoic acid,tricosanoic acid,and lignoceric acid exerted protective effects only in CKD participants with concomitant hypertension,while showing no impact on those with diabetes,coronary heart disease,or stroke.Conclusion Elevated circulating VLCSFAs levels in US adults are associated with reduced CKD risk.Further large-scale prospective studies are needed to validate these findings.

ABSTRACT The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) lacks effective therapies. Using a murine aristolochic acid I model (AAI), followed by a 2 week remodeling phase, we mapped macrophage states across the AKI to CKD transition. Single‐cell RNA sequencing of kidneys from control, acute, and remodeling stages profiled 39 345 cells spanning 18 clusters. Macrophage subclustering and trajectories revealed emergence of scar‐associated macrophages (SMs) marked by high Acp5 (encoding tartrate‐resistant acid phosphatase 5 (TRAP5)) and enriched during the remodeling phase. Cell–cell communication highlighted a dominant Spp1–Cd44 axis driving SM activation. Immunofluorescence confirmed TRAP5+CD68+ macrophage accumulation in multiple murine CKD and human CKD biopsies. Functionally, pharmacological TRAP5 inhibition conferred robust protection against AKI–CKD transition. TRAP5 blockade initiated in the AKI phase markedly attenuated fibrosis, inflammation, and renal dysfunction in both AAI and ischemia‐reperfusion injury (IRI) models; while preinhibition similarly mitigated unilateral ureteral obstruction (UUO)‐induced fibrosis. In bone marrow‐derived macrophages (BMDMs), TRAP5 blockade abrogated osteopontin (Spp1)‐driven metabolic and profibrotic reprogramming. In conclusion, TRAP5+ scar‐associated macrophages are disease‐promoting effectors of maladaptive remodeling in AKI–CKD transition. Targeting TRAP5 not only suppresses profibrotic macrophage activation but also protects renal structure and function across multiple models, establishing TRAP5 inhibition as a promising therapeutic strategy to halt CKD progression.

Urinary extracellular vesicles (uEVs) have emerged as promising non-invasive molecular carriers for biomarker discovery, yet the physiological variability and tissue-associated characteristics of uEV RNA cargo in healthy individuals remain poorly defined. This knowledge gap limits the interpretation, normalization, and clinical translation of uEV-based transcriptomic studies. Here, we performed a longitudinal RNA-sequencing analysis of uEVs from 12 healthy donors, of whom six contributed complete longitudinal sample sets, to establish a molecular reference framework for physiological uEV transcriptomes. We systematically characterized inter- and intra-individual variation in uEV RNA cargo and found substantial transcriptomic heterogeneity despite relatively stable extracellular vesicle secretion levels over time. A conserved set of highly expressed genes was significantly enriched in ribosomal function and oxidative phosphorylation, indicating their role in fundamental cellular maintenance. Importantly, we identified 12 protein-coding genes that showed consistently low expression variance both across individuals and within individuals over time. Cross-dataset analyses using independent external and pan-cancer datasets further supported their potential utility as candidate reference transcripts for uEV RNA studies. Computational tissue deconvolution inferred predominant kidney- and bladder-associated transcriptomic signatures, while cell-type enrichment analysis showed relatively high enrichment scores for smooth muscle cells and mesenchymal stem cells. Together, this study defines the physiological landscape of healthy uEV transcriptomes, delineates key sources of biological variation, and provides candidate reference transcripts and tissue-associated molecular profiles to support the standardization and translational application of uEV-based molecular biomarker research.

Recombinant human erythropoietin (rhEPO) fused with human immunoglobulin G (IgG) Fc fragment (rhEPO-Fc) is a novel erythropoiesis-stimulating agent designed to extend plasma half-life and enhance biological activity. However, data on the efficacy and safety of rhEPO-Fc in hemodialysis patients with chronic kidney disease (CKD)-related anemia remain limited. This phase 3 trial enrolled patients from 45 Chinese hospitals. Participants were randomized (2:1) to receive either rhEPO-Fc or rhEPO (Chinese hamster ovary cell-derived) for 28 weeks. The rhEPO-Fc responders were eligible for a 24-week extension period. The primary endpoint was the least square mean (LSM) change in hemoglobin (Hb) levels from baseline between weeks 21 and 28. Among 356 rhEPO-Fc and 178 rhEPO recipients, patients receiving rhEPO-Fc demonstrated non-inferiority Hb maintenance compared with rhEPO. The inter-group LSM differences in the full analysis set and per-protocol set were 3.96 g/L (95% CI: 3.02-4.89; p < 0.001) and 2.27 g/L (95% CI: 0.60-3.95; p = 0.008), respectively. Adverse drug reaction rates were comparable (rhEPO-Fc: 39.2% vs. rhEPO: 40.2%). Dose adjustments due to treatment-emergent adverse events were significantly lower with rhEPO-Fc (0.0% vs. 2.2%; p < 0.05). Deaths unrelated to the study drugs occurred in two rhEPO-Fc and four rhEPO patients. These findings indicated that rhEPO-Fc effectively maintained Hb levels in patients with CKD anemia undergoing hemodialysis, showing comparable efficacy to rhEPO with reduced dosing frequency and a similar safety profile.

Psoriasis is a chronic systemic inflammatory skin disease characterized by complex pathogenic mechanisms involving various cellular interactions. The nervous system significantly influences the development and exacerbation of psoriatic lesions, particularly in innervated regions. Despite the recognized importance of these interactions, a comprehensive understanding of the underlying mechanisms between different cell types and the nervous system in psoriasis is still lacking. This review systematically explores the intricate regulatory interactions between multiple cellular components and the nervous system in psoriasis. We aim to identify potential therapeutic targets and propose innovative strategies to improve clinical outcomes of patients with psoriasis.

OBJECTIVE:Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS:Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS:Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION:Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.

BACKGROUND:Esophageal hypersensitivity is an important cause of refractory gastroesophageal reflux disease, in which patients do not respond to standard acid-suppressive therapy and suffer from continuous noncardiac chest pain and regurgitation. The N-methyl-D-aspartate receptor (NMDAR) may play a crucial role in the development of visceral hypersensitivity in functional gastrointestinal disorders. However, the specific mechanisms of visceral hypersensitivity in upper digestive tract diseases remain poorly understood. AIM:To investigate the role of the NMDAR2B/protein kinase A (PKA)/cAMP-response element binding protein (CREB) signaling pathway in the development of esophageal neuropathic pain associated with gastroesophageal reflux disease (GERD). METHODS:Thirty-six 6-week-old specific pathogen free rats were randomly assigned to six groups: the control, model, model + NMDAR agonist, model + NMDAR antagonist, model + PKA antagonist, and model + NMDAR antagonist + PKA agonist groups, with six rats in each group. The model was induced via an intraperitoneal injection of ovalbumin for sensitization along with local esophageal stimulation. Immunohistochemistry and Western blotting were utilized to assess the expression levels of NMDAR2B signaling pathway-related proteins in the cingulate gyrus, dorsal thalamus, spinal dorsal horn, and peripheral esophageal tissues. RT-PCR was used to measure the corresponding mRNA expression, and ELISA was used to determine the serum brain-derived neurotrophic factor (BDNF) concentration. Behavioral scoring was performed during balloon distention and acid perfusion of the lower esophagus. RESULTS:Compared with the control group, the model group presented significantly increased expression levels of the NMDAR2B, PKA, CREB, BDNF, substance P, and calcitonin gene-related peptide proteins and mRNAs in the cingulate gyrus, dorsal thalamus, spinal dorsal horn, and lower esophagus (P < 0.05). Compared with the model group, the model + NMDAR agonist group exhibited even higher expression levels of these proteins and mRNAs (P < 0.05), whereas the model + NMDAR antagonist and model + PKA antagonist groups presented lower expression levels (P < 0.05). The model + NMDAR antagonist + PKA agonist group presented higher expression levels than did the model + NMDAR antagonist group (P < 0.05). The changes in the serum BDNF concentration and behavioral score during balloon distention and acid perfusion were consistent with these changes in expression. CONCLUSION:The NMDAR2B signaling pathway plays a critical role in the development of neuropathic pain in GERD through the PKA/CREB/BDNF pathway.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.

BACKGROUND:The relationship between cancer development and alterations in IgG N-glycosylation has been well-established. However, comprehensive profiling of the N-glycome and N-glycoproteome in gastric cancer (GC) remains limited. Furthermore, the prognostic potential of IgG N-glycan patterns in identifying precursors to GC has yet to be fully elucidated. METHODS:The IgG N-glycome in GC was characterized using a custom high-throughput orthogonal mass spectrometry approach. Multivariate analysis was employed to identify and assess glycomic alterations. A comprehensive bioinformatics analysis was also conducted to investigate the differential expression of N-glycosylation-related genes and their potential roles in GC pathogenesis. Additionally, interleukin-11 (IL-11) levels were quantified using a standardized enzyme-linked immunosorbent assay (ELISA). RESULTS:Galactosylation and sialylation of IgG decreased mainly in the IgG1 and IgG2 subclasses in GC, with subclass-specific changes in IgG3 and IgG4 galactosylation. These glycan modifications were represented by unique glycopeptides (IgG1_H5N5, IgG2_H4N3F1, IgG2_H4N4, IgG2_H4N4F1S1, IgG3/4_H4N4F1, IgG3/4_H4N4F1S1), which outperformed CA72-4 for GC diagnosis. Analysis of key glycogenes revealed differential expression patterns, implicating a functional role for IgG N-glycosylation in GC. Notably, the abundance of specific IgG glycosylation exhibited a significant correlation with serum level of IL-11. CONCLUSIONS:Alterations in subclass-specific IgG N-glycosylation represent promising biomarkers for the detection and monitoring of GC progression, potentially influenced by cytokine-driven inflammation. Understanding these changes could improve our knowledge of molecular mechanisms, aiding in diagnostic improvements and therapeutic development.

OBJECTIVES:Observational studies suggest a potential link between Hepatitis C virus (HCV) infection and extrahepatic cancers, but the causal relationship remains unclear. METHODS:We applied a two-sample Mendelian randomization (MR) approach to evaluate the causal relationships between HCV infection and various extrahepatic cancers. A two-step MR was used to identify potential mediators, followed by colocalization analysis to identify HCV-associated susceptibility genes (HSGs). A pan-cancer analysis using TCGA data was conducted, and a prognostic model based on HSGs was developed using least absolute shrinkage and selection operator (LASSO) regression and Cox models. Genetic risk score (GRS) analysis from the UK Biobank validated our findings. RESULTS:We identified a causal link between genetic susceptibility to HCV infection and kidney cancer, both in univariable and multivariable MR analyses. The two-step MR identified five mediators in the causal pathway. IRF5 was highlighted as a key HSG in both the colocalization and pan-cancer analyses. Our prognostic model incorporating three HSGs predicted overall survival (OS) in kidney cancer patients. GRS analysis confirmed the association. CONCLUSIONS:The present study provides evidence supporting a causal link between HCV infection and the development of kidney cancer.

Aim:Cyclophosphamide (CTX), a cornerstone in breast cancer combination chemotherapy, frequently induces adverse effects including myelosuppression, gastrointestinal disturbances, hepatic impairment, and alopecia. Chemotherapy-induced alopecia severely impacts patients' quality of life and psychological well-being. Modified Huanjingjian (MHJJ), a traditional Chinese herbal formula, demonstrates clinical efficacy in alleviating chemotherapy-related side effects, yet its mechanisms against CTX-induced alopecia remain uncharacterized. And our main aim was to explore the efficacy and the mechanism of MHJJ in mice. Methods:UPLC-QE-Orbitrap-MS characterized MHJJ's chemical composition. A CTX-induced alopecia murine model was established. Systemic toxicity was evaluated through body weight monitoring, automated biochemical analysis (ALT/AST levels), and hematological profiling (WBC/PLT counts). Hair follicle histopathology was assessed via H&E staining. IHC and IF staining quantified proliferation markers and hair follicle stem cell (HFSC) biomarkers. Reduced representation bisulfite sequencing (RRBS) was used to map DNA methylation patterns. Wnt pathway dynamics were analyzed through qRT-PCR and IF staining. Results:We identified 110 bioactive compounds in MHJJ. MHJJ intervention attenuated alopecia severity, restored follicular architecture, and increased follicular density compared to CTX monotherapy (p<0.05). HFSC proliferation markers (Ki67/CD34) showed significant upregulation, while apoptosis markers (Caspase-3) were suppressed. RRBS revealed MHJJ-mediated hypomethylation in differentially methylated regions, with gene body methylation constituting 60% of total methylation changes. Methylation-modulated genes predominantly localized to Wnt signaling pathways: MHJJ enhanced Wnt3/Wnt10a expression while suppressing Cer1/Axin1. Corresponding methylation reductions at promoter and gene body regions were confirmed at mRNA and protein levels. Conclusion:MHJJ mitigates CTX-induced alopecia through epigenetic regulation of HFSCs, specifically via DNA hypomethylation-mediated activation of Wnt3/Wnt10a and suppression of Cer1/Axin1. This mechanism promotes follicular regeneration by restoring Wnt signaling homeostasis, positioning MHJJ as a promising adjuvant for chemotherapy-induced alopecia management.

Previous studies have suggested a potential role of estrogen in the pathophysiology of chronic kidney disease (CKD); however, the association and causality between estrogen and kidney function remain unclear. The cross-sectional correlation between serum estradiol concentration and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) was analyzed using data from the National Health and Nutrition Examination Survey 2013–2016. Causality was tested using mutual bidirectional Mendelian randomization (MR) approaches based on six large-scale GWAS studies. Weighted generalized multivariate linear regression was employed to estimate the association between estradiol and eGFR and ACR, and a restricted cubic spline analysis was utilized to investigate potential nonlinear relationships. A total of 8932 participants were included. Serum estradiol concentration was positively associated with eGFR after adjusting for potential covariates (β, 0.76; 95

Chronic kidney disease (CKD) imposes a substantial global health burden. Emerging evidence implicates respiratory sarcopenia as a potential mortality accelerator. This dual-cohort study aimed to clarify the correlation between respiratory sarcopenia and all-cause mortality in CKD populations and evaluate prognostic impacts of longitudinal transitions. We analyzed 1,300 CKD participants without preexisting chronic respiratory conditions from the China Health and Retirement Longitudinal Study (CHARLS) and 1,346 from the U.S. Health and Retirement Study (HRS). Respiratory sarcopenia was defined using surrogate measures, including peak expiratory flow rate for respiratory muscle strength and appendicular skeletal muscle mass index for muscle mass. Multivariable Cox proportional hazards models were employed to assess the associations between respiratory sarcopenia and all-cause mortality. Over median follow-ups of 88 and 96 months, respiratory sarcopenia was associated with a significantly elevated risk of mortality (CHARLS: Hazard Ratio [HR] = 1.61, 95% Confidence Interval [CI] 1.17-2.22; HRS: HR = 1.48, 95% CI 1.07-2.04). Longitudinal progression from non-sarcopenic to respiratory sarcopenic status was associated with an increased risk of mortality (CHARLS: HR = 1.94, 95% CI 1.01-3.76; HRS: HR = 1.82, 95% CI 1.02-3.28), while reversion was associated with a reduced risk of death in the HRS cohort (HR = 0.15, 95% CI 0.03-0.94). Respiratory sarcopenia was independently associated with an increased risk of all-cause mortality in CKD populations using multivariable-adjusted analyses, and reversion from respiratory sarcopenia was associated with a lower risk of mortality. The multi-cohort design strengthens the clinical relevance of these findings, despite limitations from the indirect diagnosis and potential confounding.

Focal segmental glomerulosclerosis (FSGS) is a common chronic glomerular disease characterized by podocyte injury. The aim of the present study was to investigate autophagy-related characteristics in FSGS. GSE200828, GSE99340, GSE47183, GSE108109, and GSE104948 were used as training sets, and GSE129973 was used as the validation set. 222 autophagy-related genes (ARGs) were incorporated. Autophagy-related differentially expressed genes (ARDEGs) were obtained and then analyzed using violin plots, PPI network analysis, functional enrichment analysis, gene set enrichment analysis, immune cell infiltration and cMAP. Two machine learning methods were applied to select candidate ARGs. Nomogram and receiving operating curve were conducted to assess diagnostic value and screen out core genes. An in vivo rat model of FSGS was established to verify expression of core genes via WB and qRT-PCR. The results indicated that nine ARDEGs were identified. PPI network contained nine nodes and 30 edges, and TP53 had the highest degree value. ARDEGs were significantly enriched in physiological processes and pathways related to autophagy and immunity. Patients with FSGS had higher levels of resting natural killer cells, monocytes and activated dendritic cells, and lower levels of plasma cells, follicular helper T cells, resting dendritic cells and resting mast cells. Through cMAP analysis, 10 small molecule compounds were identified which might work as potential therapeutic drugs in FSGS. Next, three candidate ARGs were obtained which were further evaluated by nomogram and diagnostic value. Among them, TP53 and RELA had high diagnostic values. In vivo, TP53 and RELA were at higher levels in FSGS than in the control group. In conclusion, TP53 and RELA are promising autophagy-related diagnostic and therapeutic markers in FSGS.

Stellera chamaejasme L., a traditional Chinese medicinal herb used for treating skin disorders such as psoriasis, was investigated to identify its bioactive antipsoriatic components and elucidate its underlying mechanisms of action. In an imiquimod (IMQ)-induced psoriasis-like skin lesion mouse model, the ethyl acetate (Et) fraction exhibited the most significant therapeutic effect among various solvent-partitioned extracts, as demonstrated by hematoxylin-eosin (H&E), immunohistochemistry (IHC), and immunofluorescence (IF) analyses. The bioassay-guided fractionation of the Et extract led to the isolation of eleven compounds (1-11), whose structures were characterized using nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography. Among them, wikstroelide J (WJ, compound 11) exhibited the most potent activity, inhibiting M5-induced hyperproliferation of HaCaT keratinocytes (IC₅₀ = 9.4 μM) and alleviating psoriasis-like skin lesions in vivo. Mechanistically, WJ modulated T-cell subsets and downregulated the JAK2/PI3K/AKT signaling pathway, with pathway involvement further supported by the use of the JAK2 inhibitor AG490. These findings highlight WJ as a promising antipsoriatic agent that targets the JAK2/PI3K/AKT pathway. Future studies will aim to improve its pharmacological properties and assess its efficacy in clinical settings, although current limitations, such as a lack of pharmacokinetic and clinical data, remain to be addressed.

Studies examining the relationship between fine particulate matter (PM2.5) exposure and cancer risk is inconclusive, with an evident scarcity of comprehensive data on the overall cancer risk. Given the emergence of new evidence, updated meta-analyses is essential. A search was performed on multiple databases including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library up to Jan 2025. Hazard ratios (HRs), relative risks (RRs), or incidence rate ratios (IRRs) with their 95 % confidence intervals (CIs) were extracted and pooled. Moreover, a comprehensive and detailed quality assessment of the included studies was conducted to validate the plausibility of the findings. Overall, 57 original studies were included, covering 36 cancer categories and including overall cancer and malignancies specific to particular anatomical sites. For each increase of 10 μg per cubic meter in PM2.5 concentration, there was an observed pooled HR of 1.07 for overall cancer (95 %CI:1.02-1.13). In the case of site-specific cancers, the pooled HRs were 1.11 (95 %CI:1.07-1.15), 1.06 (95 %CI:1.02-1.11), 1.17 (95 %CI:1.07-1.28), and 1.14 (95 %CI:1.03-1.26) for lung, breast, liver and esophageal cancers, respectively. Furthermore, PM2.5 exposure may potentially correlate with the risk of cancers at other anatomical locations including upper aerodigestive tract, oral cavity, kidney, skin, as well as digestive organs. In light of available evidence, it is inferred that PM2.5 exposure could potentially raise overall cancer risk with moderate certainty. As for site-specific malignancies, there is very low certainty evidence for lung cancer, low certainty evidence for breast cancer, and moderate certainty evidence for both liver and esophageal cancers.

Objective Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. Methods For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. Results Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. Conclusion Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment.Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320–332.

Photoacoustic imaging (PAI), renowned for its high spatial resolution and deep tissue penetration, holds great promise for disease diagnosis and molecular detection. However, the performance of commercially available PAI contrast agent is often hindered by intrinsic fluorescence, which reduces photoacoustic (PA) signal intensity and contrast, thereby limiting their applications. Herein, we rationally designed and synthesized a class of PAI contrast agents based on a phenothiazine core. By precise molecular engineering, we introduced a twisted intramolecular charge transfer (TICT) effect to suppress fluorescence, minimize radiative decay, and facilitate nonradiative energy dissipation, thereby enhancing photothermal conversion efficiency and significantly improving PA signal intensity and imaging contrast-to-noise ratio both in vitro and in vivo. Moreover, the structure facilitates the convenient incorporation of derivatization sites, allowing for further structural expansion and modification. Building upon this platform, we developed a hypochlorous acid (HOCl)-responsive PA probe, DHU-PAOCl-1, to further explore the biomedical imaging potential of these designed contrast agents. DHU-PAOCl-1 exhibited high selectivity and pH stability, with a detection limit of 11.88 nM. In a dermatitis animal model, DHU-PAOCl-1 enabled precise in situ visualization of endogenously generated HOCl at inflammatory sites, offering a powerful imaging tool for the early diagnosis and real-time monitoring of inflammation-related diseases. Collectively, this study provides an effective molecular design strategy for high-performance PAI contrast agents and expands the application potential of PAI technology in molecular diagnostics and therapeutic monitoring.

Introduction Limited by the specific location of atopic facial dermatitis, treatment options for atopic dermatitis are limited. Our previous research confirms that BiShengZhiYan cream (BSZY cream) can reconstruct the damaged skin barrier and strengthen the repair ability of skin. However, little evidence of its efficacy and safety for the treatment of atopic facial dermatitis is available.Methods and analysis A protocol for a randomised, double-blind, controlled trial of BSZY cream is designed for patients with mild-to-moderate atopic facial dermatitis. We will recruit 130 patients with mild-to-moderate atopic facial dermatitis from the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine. The participants will be assigned to the BSZY cream group (treatment group) or the emulsion matrix group (control group) randomly. The intervention period will be 4 weeks, once daily in the morning and once in the evening. The primary outcome is the Scoring Atopic Dermatitis Scale. The Clinical Dermatologist Evaluation Form, Patient Self-Assessment Questionnaire and Safety Indicators will be evaluated as secondary outcomes. The follow-up will be conducted at week 8±3 days. The skin condition is assessed by a clinical dermatologist at week 0±3 days, week 2±3 days and week 4±3 days.Ethics and dissemination The protocol has been approved by Shanghai University of Traditional Chinese Medicine’s Yueyang Hospital ethics committee (No. 2023-024). All participants will be asked to sign an informed consent in compliance with the Declaration of Helsinki. On completion of the trial, we plan to disseminate the results through peer-reviewed publications and present the findings at relevant scientific conferences. Data will be provided on reasonable request under participant confidentiality and data privacy regulations.Trial registration number NCT05792826.