1.Mechanisms of Huanglian Jiedutang and Its Major Active Constituents in Inhibiting LPS-induced M1 Polarisation of BV2 Microglia
Haojia ZHANG ; Kai WANG ; Kunjing LIU ; Xin LAN ; Zijin SUN ; Chunyu WANG ; Wenyuan MA ; Wei SHAO ; Jinhua HAN ; Liyang DONG ; Changxiang LI ; Xueqian WANG ; Youxiang CUI ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):44-55
ObjectiveTo investigate whether Huanglian Jiedutang (HLJD) and its major active constituents (geniposide, baicalin, and berberine) can inhibit the inflammatory response of BV2 cells under lipopolysaccharide (LPS) stimulation via the high-mobility group protein B1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, and to explore differences in therapeutic efficacy among the three monomers, their combined formula, and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 (CCK-8) method to examine the effects of different concentrations of dimethyl sulfoxide (DMSO, 0.8%, 0.4%, 0.2%, 0.1%, and 0.05%) on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD (200, 100, 50, 25, 12.5, 6.25 mg·L-1). Nitric oxide (NO) assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography (HPLC) determined the content of geniposide, baicalin, and berberine in HLJD, and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay (ELISA) measured levels of inflammatory factors (TNF-α, IL-1β, IL-6, IL-10) in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1, TLR4, and NF-κB-related proteins. ResultsCompared with the blank group, DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L-1 HLJD. Under stimulation with 2 mg·L-1 LPS, this concentration of HLJD effectively reduced NO release, and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide, 15 μg of baicalin, and 30 μg of berberine. Based on these ratios, experimental groups were blank, LPS (2 mg·L-1), HLJD (200 mg·L-1), monomer combination, geniposide (4.8 mg·L-1), baicalin (3 mg·L-1), and berberine (6 mg·L-1). The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α, IL-1β, IL-6, and IL-10 in the supernatant (P<0.01). HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01) while upregulating anti-inflammatory IL-10 (P<0.01), with the monomer combination showing the strongest effect (P<0.05, P<0.01). Compared with the blank group, LPS significantly increased the proportion of CD80⁺CD86⁺ (M1-type) BV2 cells (P<0.01). HLJD and its constituents partially inhibited M1 polarization (P<0.05, P<0.01), with the monomer combination exhibiting the most pronounced effect (P<0.05, P<0.01). Compared with the blank group, LPS upregulated HMGB1, TLR4, and NF-κB-related proteins (P<0.01), whereas HLJD and its active constituents significantly reduced their expression (P<0.05, P<0.01), with the monomer combination having the strongest regulatory effect (P<0.05, P<0.01). ConclusionHLJD and its major active constituents (geniposide, baicalin, berberine) can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect, significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.
2.Confirmatory analysis of HBsAg reactive samples from voluntary blood donors
Qiaolin ZHANG ; Fang WANG ; Dong LIU ; Fengjiao HAN ; Liu LI ; Xiaochuan ZHENG ; Xuelian DENG ; Dongyan YANG
Chinese Journal of Blood Transfusion 2026;39(4):452-457
Objective: To systematically analyze the confirmatory positivity of different combinations of HBsAg screening results in blood testing, providing data to support the optimization of blood donor eligibility management. Methods: A retrospective analysis was conducted on blood screening data from 174 266 voluntary blood donor samples at the Chongqing Blood Center between October 2021 and September 2022. Samples with inconsistent results between the two HBsAg enzymelinked immunosorbent assays (ELISA) and individual donor nucleic acid testing (NAT) were confirmed using an electrochemiluminescence immunoassay (ECLIA) and a neutralization test. The detection efficacy of four different HBsAg ELISA reagents was compared using the HBsAg-confirmed positive samples. Results: A total of 767(0.44%) HBV-reactive (HB-sAg and/or HBV DNA reactive) samples were detected. Among them, 344 samples with discordant serological and NAT results were collected, of which 64(18.6%) were confirmed positive by neutralization test. Additionally, 5 samples that were neutralization-negative but double-reactive for HBsAg and HBV DNA were confirmed as positive according to FDA guidance, resulting in a total of 69(20.1%) confirmed HBsAg-positive samples. There were significant differences in the neutralization test confirmation rates among different screening result categories (P<0.05): The group with dual HBsAg reagent reactivity (double reactive) & NAT-negative had the highest confirmation rate (96.9%, 31/32); the group reactive to only reagent 2 (single reactive) had a rate of 25.7% (29/113); while the confirmation rates for samples reactive to only reagent 1 and samples with isolated HBV DNA positivity were extremely low [0(0/34) and 2.4%(4/165), respectively]. The four commercial reagents showed significant differences in their ability to detect confirmed positive samples that were initially single reactive (P<0.05). Conclusion: Given the performance variations among HBsAg screening reagents, thorough performance verification is essential before implementation. When NAT is negative, dual HBsAg reactivity in screening can serve as a basis for confirming infection and directly deferring blood donors. However, confirming infection in donors with single HBsAg reactivity is more challenging, necessitating supplementary tests to rule out infection risk.
3.The feasibility of using high-definition thoracoscopy to identify sympathetic ganglia during thoracic sympathicotomy for primary palmar hyperhidrosis
Gang XU ; Chaoyue HU ; Cong CHEN ; Yuancai LIN ; Daolong ZHU ; Han LIU ; Dong WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(04):578-583
Objective To explore the feasibility of using high-definition thoracoscopy to identify sympathetic ganglia during thoracic sympathicotomy for primary palmar hyperhidrosis. Methods The clinical data of patients with primary palmar hyperhidrosis who underwent high-definition thoracoscopic sympathicotomy in Taikang Xianlin Drum Tower Hospital from June to July 2023 were retrospectively analyzed. Intraoperative visualization rates and anatomical variations of sympathetic ganglia were recorded, and the consistency between white-light thoracoscopy and near-infrared fluorescence imaging was compared. Additionally, surgical videos from previous fluorescence-guided procedures were reviewed. Results Finally 100 patients were collected, including 54 females and 46 males, with an average age of (21.92±6.56) years. All patients underwent endoscopic thoracic sympathicotomy at R3 level. The overall intraoperative ganglion visualization rate was 92.5% (740/800), with G2-G5 rates of 95.5% (191/200), 94.0% (188/200), 94.0% (188/200), and 86.5% (173/200), respectively. Ganglion variations occurred in 32.0% (237/740), predominantly at G3 (29.8%) and G4 (42.6%). In 5 indocyanine green-enhanced patients, the concordance rate between white-light and near-infrared fluorescence imaging was 100.0% (38/38). Video analysis of 14 near-infrared fluorescence-guided surgeries demonstrated a 99.1% (107/108) consistency rate. Postoperative palmar hyperhidrosis improvement reached 100.0% (100/100) with no Horner’s syndrome. Conclusion With the wide clinical application of high-definition thoracoscopy, accurate thoracic sympathicotomy has the feasibility of clinical application.
4.Analysis of knowledge, attitude, and practice levels regarding health protection against air pollution and related factors among Chinese primary school students
Chinese Journal of School Health 2026;47(7):958-961
Objective:
To assess the current status of knowledge, attitude, and practice (KAP) regarding health protection against air pollution among primary school students in China, and to analyze the impacts of fine particulate matter (PM 2.5 ) exposure, family, and individual factors on KAP levels, so as to provide empirical basis for implementing targeted interventions.
Methods:
Using stratified cluster random sampling method, a questionnaire survey was conducted among 19 297 primary school students from third to fifth grade across 30 provinces (autonomous regions and municipalities directly under the central government) in China in 2024. The questionnaire was developed based on the Technical Guidelines for the Assessment of Civic Environmental and Health Literacy (Trial), and encompasses three dimensions:knowledge, attitude, and practice. Spearman correlation analysis, Chi-square test, multivariate Logistic regression, and Bootstrap mediation effect test was applied for data analysis.
Results:
The overall mean KAP score for health protection against air pollution among primary school students was (79.73±13.53), with an adequacy rate of 80.47% ( n =15 528). The dimension scores for knowledge, attitude, and practice were (41.34±8.01, 16.43± 2.61 ), and (21.97±5.71), respectively. Knowledge was positively correlated with attitude and practice, and attitude was positively correlated with practice ( r =0.51, 0.35, 0.32, all P <0.01). Multivariate Logistic regression showed that the northeast region ( OR =2.36, 95% CI =2.02-2.75), having parents with a bachelor s degree or higher ( OR =4.76, 95% CI =2.71-8.37), living with both parents ( OR =1.33, 95% CI =1.15-1.55), being in the fifth grade ( OR =1.22, 95% CI =1.11-1.33), outdoor PM 2.5 level exceeding standard limits at the survey site ( OR =1.25, 95% CI =1.16-1.34), history of allergy ( OR =1.47, 95% CI =1.31-1.64), and wearing masks during heavily polluted weather ( OR =1.19, 95% CI =1.07-1.31) were promoting factors for KAP adequacy rate (all P <0.05). Conversely, obesity was a detrimental factor ( OR =0.78, 95% CI =0.69-0.88, all P <0.05).
Conclusions
Primary school students in China exhibit a favorable KAP level regarding health protection against air pollution, though regional, familial, and individual disparities persist. Exposure to PM 2.5 levels exceeding standard limits exerts a direct positive effect on enhancing health protection literacy. Future efforts should focus on the western region, families with lower educational attainment children to implement tailored, stratified interventions.
5.Effect of Modifed Huanglian Wendantang on Oxidative Stress in Metabolic Syndrome
Xinyu DONG ; Yi HAN ; Yubo HAN ; Li LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):153-161
ObjectiveTo observe the effect of modified Huanglian Wendantang on oxidative stress in metabolic syndrome. MethodsA total of 180 patients with metabolic syndrome treated in the outpatient clinics and wards of the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine from October 2023 to May 2025 were enrolled in this study. According to the randomized numerical table method, the patients were assigned into two groups (90 cases). The basic treatment of the two groups was the same, and the observation group was additionally treated with modified Huanglian Wendantang. The course of treatment was 3 months. The two groups were compared in terms of traditional Chinese medicine (TCM) efficacy, obesity degree [waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR)], blood pressure indicators [systolic blood pressure (SBP) and diastolic blood pressure (DBP)], lipids and glucose indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), fasting glucose (FPG), 2-hour postprandial glucose (2 h PG), and glycosylated hemoglobin (HbA1c)], insulin resistance indicators [homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride-glucose index (TYG index), triacylglycerol-to-high-density lipoprotein cholesterol (TG/HDL) ratio], oxidative stress indicators [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), catalase (CAT), and reactive oxygen species (ROS)], and the safety of treatment. ResultsIn terms of TCM efficacy, the treatment in the observation group was significantly effective in 46 cases, effective in 30 cases, and ineffective in 10 cases, with the total effective rate of 88.4%. The treatment in the control group was significantly effective in 33 cases, effective in 28 cases, and ineffective in 23 cases, with the total effective rate of 72.6%. The observation group had higher total effective rate than the control group (χ2=11.26,P<0.05). After treatment, both groups showed declined levels of WC, BMI, WHR, WHtR, SBP, DBP, TC, TG, LDL-C, FPG, FINS, 2 h PG, HbA1c, HOMA-IR, TG/HDL ratio, TYG index, MDA, and ROS and elevated levels of HDL-C, SOD, GSH, GSH-Px, and CAT (P<0.05). After treatment, the observation group showed lower levels of WC, BMI, WHR, WHtR, TC, TG, LDL-C, FPG, FINS, 2 h PG, HbA1c, HOMA-IR, TG/HDL ratio, TYG index, MDA, and ROS and higher levels of HDL-C, SOD, GSH, GSH-Px, and CAT than the control group (P<0.05). However, after treatment, there was no significant difference in SBP or DBP between the observation group and the control group. No significant adverse reactions were observed in either group. ConclusionModified Huanglian Wendantang can significantly alleviate metabolic syndrome symptoms and reduce oxidative stress, exhibiting antioxidant effects. Moreover, it does not induce adverse reactions, demonstrating safety.
6.Effect of Modifed Huanglian Wendantang on Oxidative Stress in Metabolic Syndrome
Xinyu DONG ; Yi HAN ; Yubo HAN ; Li LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):153-161
ObjectiveTo observe the effect of modified Huanglian Wendantang on oxidative stress in metabolic syndrome. MethodsA total of 180 patients with metabolic syndrome treated in the outpatient clinics and wards of the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine from October 2023 to May 2025 were enrolled in this study. According to the randomized numerical table method, the patients were assigned into two groups (90 cases). The basic treatment of the two groups was the same, and the observation group was additionally treated with modified Huanglian Wendantang. The course of treatment was 3 months. The two groups were compared in terms of traditional Chinese medicine (TCM) efficacy, obesity degree [waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR)], blood pressure indicators [systolic blood pressure (SBP) and diastolic blood pressure (DBP)], lipids and glucose indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), fasting glucose (FPG), 2-hour postprandial glucose (2 h PG), and glycosylated hemoglobin (HbA1c)], insulin resistance indicators [homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride-glucose index (TYG index), triacylglycerol-to-high-density lipoprotein cholesterol (TG/HDL) ratio], oxidative stress indicators [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), catalase (CAT), and reactive oxygen species (ROS)], and the safety of treatment. ResultsIn terms of TCM efficacy, the treatment in the observation group was significantly effective in 46 cases, effective in 30 cases, and ineffective in 10 cases, with the total effective rate of 88.4%. The treatment in the control group was significantly effective in 33 cases, effective in 28 cases, and ineffective in 23 cases, with the total effective rate of 72.6%. The observation group had higher total effective rate than the control group (χ2=11.26,P<0.05). After treatment, both groups showed declined levels of WC, BMI, WHR, WHtR, SBP, DBP, TC, TG, LDL-C, FPG, FINS, 2 h PG, HbA1c, HOMA-IR, TG/HDL ratio, TYG index, MDA, and ROS and elevated levels of HDL-C, SOD, GSH, GSH-Px, and CAT (P<0.05). After treatment, the observation group showed lower levels of WC, BMI, WHR, WHtR, TC, TG, LDL-C, FPG, FINS, 2 h PG, HbA1c, HOMA-IR, TG/HDL ratio, TYG index, MDA, and ROS and higher levels of HDL-C, SOD, GSH, GSH-Px, and CAT than the control group (P<0.05). However, after treatment, there was no significant difference in SBP or DBP between the observation group and the control group. No significant adverse reactions were observed in either group. ConclusionModified Huanglian Wendantang can significantly alleviate metabolic syndrome symptoms and reduce oxidative stress, exhibiting antioxidant effects. Moreover, it does not induce adverse reactions, demonstrating safety.
7.Development of the "Clinical Ethics" Course for the Eight-Year Clinical Medicine Program: Explorations and Practices by an Interdisciplinary Teaching Team
Jiangli HAN ; Yali CONG ; Qiong BAI ; Shu LI ; Guangkuan XIE ; Tongyan HAN ; Chuan MA ; Ying YAO ; Fei DONG ; Huilin LIU ; Rui WU ; Qinggang GE ; Liang WANG ; Yuxi XIA ; Shixian GU ; Xuan HE ; Ning SHEN
Medical Journal of Peking Union Medical College Hospital 2026;17(5):1223-1229
With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.
8.Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cells.
Han LIU ; Yujie HONG ; Hui CHEN ; Xianggui WANG ; Jiale DONG ; Xiaoqian LI ; Zihan SHI ; Qian ZHAO ; Longyuan ZHOU ; JiaXin WANG ; Qiuling ZENG ; Qinglin TANG ; Qi LIU ; Florian RIEDER ; Baili CHEN ; Minhu CHEN ; Rui WANG ; Yao ZHANG ; Ren MAO ; Xianxing JIANG
Acta Pharmaceutica Sinica B 2025;15(1):278-295
Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.
9.Dorsal CA1 NECTIN3 Reduction Mediates Early-Life Stress-Induced Object Recognition Memory Deficits in Adolescent Female Mice.
Yu-Nu MA ; Chen-Chen ZHANG ; Ya-Xin SUN ; Xiao LIU ; Xue-Xin LI ; Han WANG ; Ting WANG ; Xiao-Dong WANG ; Yun-Ai SU ; Ji-Tao LI ; Tian-Mei SI
Neuroscience Bulletin 2025;41(2):243-260
Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals
;
Female
;
Mice
;
CA1 Region, Hippocampal/metabolism*
;
Cell Adhesion Molecules/metabolism*
;
CRF Receptor, Type 1/metabolism*
;
Memory Disorders/etiology*
;
Mice, Inbred C57BL
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Nectins/genetics*
;
Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors*
;
Recognition, Psychology/physiology*
;
Stress, Psychological/complications*
10.Cardiomyocyte-specific long noncoding RNA Trdn-as induces mitochondrial calcium overload by promoting the m6A modification of calsequestrin 2 in diabetic cardiomyopathy.
Xiaohan LI ; Ling LIU ; Han LOU ; Xinxin DONG ; Shengxin HAO ; Zeqi SUN ; Zijia DOU ; Huimin LI ; Wenjie ZHAO ; Xiuxiu SUN ; Xin LIU ; Yong ZHANG ; Baofeng YANG
Frontiers of Medicine 2025;19(2):329-346
Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca2+ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca2+ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m6A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca2+ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals
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Diabetic Cardiomyopathies/pathology*
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RNA, Long Noncoding/genetics*
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Myocytes, Cardiac/metabolism*
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Mice
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Calsequestrin/genetics*
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Calcium/metabolism*
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Male
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Sarcoplasmic Reticulum/metabolism*
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Methyltransferases/metabolism*
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Mice, Inbred C57BL
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Mitochondria, Heart/metabolism*
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Disease Models, Animal
;
Mitochondria/metabolism*


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