1.Improvement of myocardial injury by traditional Chinese medicine:mitochondrial calcium homeostasis mediates macrophage autophagy and pyroptosis pathway
Lingyun LIU ; Guixin HE ; Weibin QIN ; Hui SONG ; Liwen ZHANG ; Weizhi TANG ; Feifei YANG ; Ziyi ZHU ; Yangbin OU
Chinese Journal of Tissue Engineering Research 2025;29(6):1276-1284
BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.
2.Efficacy of Fufang Lingjiao Jiangya Pills with Different Proportions of Goat Horn Replacing Antelope Horn on Spontaneous Hypertensive Rats
Tengjian WANG ; Wanlu ZHAO ; Yang YU ; Yan LIU ; Kun CAO ; Zheyuan LIN ; Yue WU ; Lilan LUO ; Weizhi LAI ; Zhaohuan LOU ; Qiaoyan ZHANG ; Quanlong ZHANG ; Luping QIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):68-78
ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats (SHR). In this experiment, 50 SHR rats were randomly grouped as follows: model (n=8), captopril (0.01 g·kg-1) (n=6), low-dose blank Fufang Lingjiao Jiangya pills (0.342 g·kg-1) (n=6), high-dose blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1) (n=6), low-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), high-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6), low-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), and high-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6). Additionally, 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration, 3 h post administration, and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions, 48 SHR rats were randomly grouped as follows: model, blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1), antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1), 2× goat horn-containing Fufang Lingjiao Jiangya pills (0.824 g·kg-1), 4× goat horn Fufang Lingjiao Jiangya pills (0.969 g·kg-1), and 6× goat horn Fufang Lingjiao Jiangya pills (1.112 g·kg-1). The normal group included 8 WKY rats, and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks, and blood pressure was recorded at various time points (pre-administration, 3 h post administration, and on days 4, 7, 10, and 14 of administration). Serum levels of angiotensin-converting enzyme (ACE), angiotensin Ⅱ(Ang Ⅱ), renin, and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart, kidney, and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2, angiotensin Ⅱ type 1 receptor (AT1R), and angiotensinogen (AGT) in the kidney tissue were determined by Western blot, while the expression of nuclear factor (NF)-κB p65 and Toll-like receptor 4 (TLR4) in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group, all treatment groups showed lowered blood pressure (P<0.05, P<0.01), and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group, the model group showed elevated serum levels of ACE, Ang Ⅱ, renin, and IL-6, while the elevations were declined in the Fufang Lingjiao Jiangya pills groups (P<0.05, P<0.01). Pathological changes in the heart, kidney, and thoracic aorta were alleviated in all the treatment groups, with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R, AGT, NF-κB p65, and TLR4 and up-regulated protein levels of ACE2 (P<0.05, P<0.01) compared with model group, with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system (RAAS) and TLR4/NF-κB signaling pathways.
3.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
4.Unveiling the role of Pafah1b3 in liver fibrosis: A novel mechanism revealed.
Lifan LIN ; Shouzhang YANG ; Xinmiao LI ; Weizhi ZHANG ; Jianjian ZHENG
Journal of Pharmaceutical Analysis 2025;15(1):101158-101158
Liver fibrosis is a common outcome of various chronic hepatic insults, characterized by excessive extracellular matrix (ECM) deposition. The precise mechanisms, however, remain largely undefined. This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3 (Pafah1b3) in liver tissues from both carbon tetrachloride (CCl4)-treated mice and patients with cirrhosis. Deletion of Pafah1b3 significantly attenuated CCl4-induced fibrosis, hepatic stellate cell (HSC) activation, and activation of transforming growth factor-β (TGF-β) signaling. Mechanistically, PAFAH1B3 binds to mothers against decapentaplegic homolog 7 (SMAD7), disrupting SMAD7's interaction with TGF-β receptor 1 (TβR1), which subsequently decreases TβR1 ubiquitination and degradation. Pharmacological inhibition using 3-IN-P11, a specific Pafah1b3 inhibitor, conferred protective effects against CCl4-induced fibrosis in mice. Furthermore, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.
5.Polyphyllin VII promotes hepatic stellate cell ferroptosis via the HIC1/CX3CL1/GPX4 axis.
Feng JIANG ; Xinmiao LI ; Mengyuan LI ; Weizhi ZHANG ; Yifei LI ; Lifan LIN ; Lufan HE ; Jianjian ZHENG
Journal of Pharmaceutical Analysis 2025;15(5):101147-101147
Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.
6.Effect of stigma on symptoms of post-traumatic stress disorder in college students:a propensity score matching analysis
Li ZHANG ; Weizhi LIU ; Qianlan YIN
Academic Journal of Naval Medical University 2025;46(7):950-955
Objective To examine the relationship between stigma and post-traumatic stress disorder(PTSD)symptoms among college students.Methods With cluster random sampling method,1 312 college students were surveyed from various types of higher education institutions.Propensity score matching was employed to control potential confounding variables such as gender,age,and education level.Stigma were compared between the PTSD and non-PTSD groups.Results After matching,the students in the PTSD group(n=139)exhibited significantly higher levels of stigma compared to the non-PTSD group(n=139,P<0.01).Further analysis revealed that stigma significantly affected all PTSD symptom clusters,with the strongest association found for hyperarousal and reactivity symptoms.Conclusion Individuals with PTSD may experience more severe stigma,which in turn may exacerbate their PTSD symptoms.Greater attention should be given to the potential impact of stigma on PTSD symptoms in college students,and effective interventions are needed to address this issue.
7.Establishment of UPLC characteristic spectrum of Liushenqu standard decoction and determination of related index components
Jiahui XIE ; Jiabao WEI ; Shuangyan TANG ; Kaiwei HUANG ; Weizhi ZHAO ; Yu HU ; Hui ZHANG
International Journal of Traditional Chinese Medicine 2025;47(5):669-675
Objective:To establish the characteristic spectrum of Liushenqu standard decoction using ultra-high performance liquid chromatography (UPLC); To determine the contents of related index components; To evaluate the quality of Liushenqu standard decoction.Methods:UPLC method was used to establish characteristic spectrum of Liushenqu standard decoction. Chromatographic Fingerprint Similarity Evaluation System (2012 edition) was used for similarity analysis, the characteristic peak was assigned, and the content of its index components was determined.Results:The characteristic peaks of Liushenqu standard decoction were calibrated and 8 components were identified, namely uridine, adenosine, guanosine, 5-hydroxymethylfurfural, tryptophan, vanillic acid, ferulic acid and shaftaside. The contents of uridine, adenosine, tryptophan ferulic acid and shaftaside in 10 batches of Liushenqu standard decoction were simultaneously determined, and ranged from 0.036 1~0.383 9 mg/g, 0.030 7~0.170 2 mg/g, 0.007 0~0.060 2 mg/g, 0.001 0~0.005 0 mg/g, 0.000 8~0.013 8 mg/g, respectively. The transfer rates ranged from 44.2% to 50.8%, 60.1% to 67.7%, 60.4% to 76.4%, 62.7% to 77.4%, 50.7% to 61.4%, respectively.Conclusion:The established UPLC characteristic spectrum and content determination method are accurate and repeatable, which can provide references for quality control of Liushenqu standard granules.
8.Study on quality standard of wine-processed Coptidis Rhizoma standard decoction
Huilin YANG ; Kaiwei HUANG ; Yanghua LI ; Suqin CAI ; Shuping XU ; Jiabao WEI ; Hui ZHANG ; Weizhi ZHAO ; Pei TAN
International Journal of Traditional Chinese Medicine 2025;47(9):1285-1292
Objective:To establish the quality standard of the standard decoction of wine-processed Coptidis Rhizoma by studying the extraction rate, fingerprint and component quantitative analysis.Methods:ccording to the Technical Requirements for Quality Control and Standard Formulation of Chinese Medicine Formula Granules, 15 batches of the standard decoction of wine-processed Coptidis Rhizoma were prepared, and the paste rate was determined; HPLC fingerprints of 15 batches of standard decoction of wine-processed Coptidis Rhizoma were established, and evaluated by combining similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis; the contents of berberine, epiberberine, pamadine, and safranine in the samples of the 15 batches were determined and analyzed their transfer rates.Results:A total of 15 batches of standard decoction samples were calibrated with 11 common peaks, referring to the recognition of 8 components. The similarity between the samples and the control product was greater than 0.900; the clustering analysis could cluster the 15 batches of samples into 2 classes; the results of the principal component analysis showed that the cumulative variance contribution rate of the 3 principal component factors was 89.388%; the OPLS-DA screened out the 3 components of the quality difference; the 15 batches of samples out of the paste rate was 15.7% -20.8%, and the mass fractions of berberine, epiberberine, safranine, and palmatine were 18.47%-24.38%, 2.82%-3.49%, 5.08%-6.69%, and 4.84%-6.68%, respectively, with transfer rates of 41.7%-61.7%, 46.9%-68.7%, 39.8%-61.5%, and 43.8%-65.2%.Conclusion:The fingerprint and content determination method established in this study is accurate, stable, simple, and can be used for the quality control and evaluation of the standard decoction of wine-processed Coptidis Rhizoma.
9.Norms and research progress of anatomic liver resection for hepatocellular carcinoma
Chinese Journal of Hepatobiliary Surgery 2024;30(2):151-155
Hepatectomy is the most important curative treatment for liver neoplasms, and its deve-lopment has experienced such concepts as local resection, irregular resection, regular resection and anatomic resection. With the enhanced understanding of hepatic anatomy, the progression of hepatic parenchymal dissection devices and the implementation of controlled low central venous pressure strategies, both open and minimally invasive hepatectomy have gained great popularity and development. Under the guidance of the concept of precision surgery, anatomic resection has garnered increasing attention, yet a contentious debate persists regarding the selection between anatomic and non-anatomic liver resection. In clinical practice, it is imperative to conduct a comprehensive evaluation of the tumor's location, size, biological characteristics, and hepatic function. This evaluation should consider the safety and thoroughness of the surgical procedure, as well as the potential for tumor recurrence and the subsequent follow-up treatment. Ultimately, the selection of surgical methods should be based on maximizing the patient's benefits. This paper reviews and discusses the published literatures, both domestic and abroad, on the norms and research progress of anatomic liver resection for hepatocellular carcinoma.
10.Establishment of a high-throughput sequencing platform for the whole genome of Chikungunya virus based on a multiplex-PCR method
Wenzhe SU ; Yan LI ; Weizhi LU ; Huaping XIE ; Kuibiao LI ; Biao DI ; Kai NIE ; Huanyu WANG ; Zhoubin ZHANG ; Songtao XU
Chinese Journal of Preventive Medicine 2024;58(4):489-496
Objective:To establish a rapid pipeline for whole genome sequencing of Chikungunya virus (CHIKV) by combining imbricated multiplex-PCR amplification and Illumina high-throughput sequencing platform.Methods:The primary reference sequences of CHIKV were downloaded from the National Center for Biotechnology Information (NCBI) database, covering all genotypes of CHIKV. After multiple alignments using the Mafft software and phylogenetic analysis, the 20 CHIKV references were selected for primer design. The Primal Scheme tool and Geneious Prime software were used to design, evaluate and optimize the primer panel. Finally, seven CHIKV-positive samples were involved in the validation of the primer panel.Results:All the amplicons of the designed panel were generated successfully. The consensuses generated from the mapping results could cover 100.00% of the coding region of the CHIKV genome when the Ct-value of the sample was less than 33, as the percentage would decrease to 99.38% when the Ct-value reached 35. The mapping percentage could be increased by 5.70%-25.43% when using the stepwise correction mapping strategy.Conclusion:The multiplex-PCR amplification method for CHIKV whole genome sequencing is relatively simple and convenient, which only requires two tubes of PCR amplification and performs well on CHIKV-positive clinical samples with different concentration levels of virus.

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