1.Dual Targeting of TBK1 and JAK-STAT1 Pathways by (-)-epigallocatechin-3-gallate Suppresses Type I Interferon-driven Inflammation
Liang LI ; Qi-Huan SHENG ; Huan LIU ; Wen-Hao YANG ; Jia-Lin SHI ; Ying-Jie SUN ; Rui JING ; Wei-Hua MAI ; Zhi-Min LI ; Xiao-Li XIE
Progress in Biochemistry and Biophysics 2026;53(7):1969-1983
ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.
2.The evolution of ventricular assist devices and future perspectives
Sheng-hua LI ; Mei LIU ; Han-luo LI ; Ya-lan LEI ; Xiao-ke SHANG
Chinese Journal of Interventional Cardiology 2025;33(3):170-175
Ventricular assist devices(VADs)have emerged as a pivotal therapeutic option for end-stage heart failure,undergoing significant technological advancements from pneumatic membrane pumps to continuous-flow centrifugal pumps.This review provides a detailed overview of several VAD models,including HeartMate Ⅲ,EVAHEART 2,and Heart Con.The initial generation of VADs established a foundation for subsequent developments,despite the occurrence of frequent complications.The second generation of VADs demonstrated a notable improvement in patient prognosis but carried the risk of ventricular collapse.The third generation of VADs represents a further reduction in size,incorporating magnetic levitation technology to enhance durability and blood compatibility.In the future,the development of VADs will focus on better emulating the physiological function of the native heart,improving pulsatility,and extending device longevity.As technology advances,VADs are expected to offer heart failure patients with a greater range of treatment options and a higher quality of life.
3.Application of mechanical circulatory support devices in heart failure
Ya-lan LEI ; Mei LIU ; Han-luo LI ; Sheng-hua LI ; Xiao-ke SHANG
Chinese Journal of Interventional Cardiology 2025;33(5):288-294
Following extensive interdisciplinary research and development over several years,mechanical circulatory support devices(MCSD),including ventricular assist device(VAD)and total artificial heart(TAH),are now established as vital treatment options for patients with advanced heart failure.These devices have proven to be crucial in assisting or replacing a failing heart,offering patients a new lease of life and improving their quality of life.Currently,mechanical circulatory support(MCS)has become a well-recognised,long-term treatment option for patients who are unable to undergo heart transplantation due to donor organ shortages or contraindications.Given their continuous availability independent of donor organ limitations,these devices are poised to play an increasingly vital role in the future of medicine.This article aims to summarize the evolution,clinical applications,categorization,and potential complications of MCSD.
4.Study on mechanism of Jiawei Shaofu Zhuyu decoction in treatment of endometriosis fibrosis based on mitophagy
Can-can HUANG ; Wen-wen WAN ; Xiu-jia JI ; Bin YUE ; Yu-gui ZHANG ; Xiao-hua ZHANG ; Li LIANG ; Guo-lian CHEN ; Quan-sheng WU ; Hai-yan MAO
Chinese Pharmacological Bulletin 2025;41(6):1177-1185
Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.
5.Comparison of the therapeutic efficacy of different methods of anesthesia in microscopic varicocelectomy for the treatment of varicocele
Qun-sheng LI ; Ning-hua LI ; Lei ZHOU ; Dong-run LI ; Jie LU ; Chun-yan HE ; Yu-nu ZHOU ; Jian-mo CHEN ; Wen-tao YANG
National Journal of Andrology 2025;31(8):692-697
Objective:To compare the therapeutic efficacy and safety of local anesthesia and spinal anesthesia for the patients with varicocele(VC)who underwent microsurgical varicocelectomy(MV).Methods:We retrospectively analyzed the data of VC patients who underwent MV treatment at the Andrology Department of the Affiliated Ruikang Hospital of Guangxi University of Chinese Medicine from May 2020 to March 2023.Cases with complete clinical data and follow-up evaluation were selected and divided into a control group(spinal anesthesia)and an observation group(local anesthesia)according to different anesthesia methods.The surgical time(including anesthesia time),visual analogue scale(VAS)score for pain,hospital stay,treatment cost,sperm concentration,for-ward motile sperm rate,and normal sperm morphology rate after three months of surgery,as well as postoperative complications and re-currence rate were compared between the two groups.Results:A total of 107 eligible cases were included,with 56 cases in the con-trol group and 51 cases in the observation group.There was no significant difference in the VAS score for pain during and after four hours of surgery,as well as postoperative complications,and recurrence rate between the two groups(P>0.05).There was an signif-icant increase in sperm concentration,forward motile sperm rate,and normal sperm morphology rate in both of two groups after three months of surgery(P<0.05).However,there was no significant difference between the two groups three months after surgery(P>0.05).The surgical time and hospital stay were shorter than those of the control group(P<0.05).And the treatment cost in observa-tion group was lower than that of the control group(P<0.05).Conclusion:Both local anesthesia and lumbar anesthesia for MV treatment of VC have good efficacy and safety.However,patients treated with MV under local anesthesia for VC have obvious advanta-ges in terms of operation time(including anesthesia time),hospital stay,and treatment cost,which is worthy of clinical promotion and application.
6.Application of mechanical circulatory support devices in heart failure
Ya-lan LEI ; Mei LIU ; Han-luo LI ; Sheng-hua LI ; Xiao-ke SHANG
Chinese Journal of Interventional Cardiology 2025;33(5):288-294
Following extensive interdisciplinary research and development over several years,mechanical circulatory support devices(MCSD),including ventricular assist device(VAD)and total artificial heart(TAH),are now established as vital treatment options for patients with advanced heart failure.These devices have proven to be crucial in assisting or replacing a failing heart,offering patients a new lease of life and improving their quality of life.Currently,mechanical circulatory support(MCS)has become a well-recognised,long-term treatment option for patients who are unable to undergo heart transplantation due to donor organ shortages or contraindications.Given their continuous availability independent of donor organ limitations,these devices are poised to play an increasingly vital role in the future of medicine.This article aims to summarize the evolution,clinical applications,categorization,and potential complications of MCSD.
7.Study on mechanism of Jiawei Shaofu Zhuyu decoction in treatment of endometriosis fibrosis based on mitophagy
Can-can HUANG ; Wen-wen WAN ; Xiu-jia JI ; Bin YUE ; Yu-gui ZHANG ; Xiao-hua ZHANG ; Li LIANG ; Guo-lian CHEN ; Quan-sheng WU ; Hai-yan MAO
Chinese Pharmacological Bulletin 2025;41(6):1177-1185
Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.
8.Establishment of a rapid fluorescence immunochromatographic assay for avian influenza virus subtype H5N6
Hui LI ; Li LIU ; Yi-sheng ZHOU ; Zhi-hong ZHANG ; Qian-qian SI ; Ru-xia WANG ; Zhi-qiang DENG ; Yi-bing FAN ; Liang JIN ; Jie SUN ; Chun-hua YANG
Chinese Journal of Zoonoses 2025;41(3):243-248,283
In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.
9.Diagnosis and Treatment of a Case of Spironolactone-Associated Asymptomatic Hyperuricemia After Renal Transplantation
Yun XIAO ; Xiaoyu HAN ; Chao ZHENG ; Yu FU ; Hanbin XIONG ; Bin ZOU ; Baolin WANG ; Hua ZOU ; Chenglong YIN ; Zhengyao JIANG ; Sheng ZOU ; Anle DU ; Guohui LI ; Xiaohui GUO ; Lin ZHONG ; Jiake HE
Herald of Medicine 2025;44(10):1562-1565
Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.
10.The evolution of ventricular assist devices and future perspectives
Sheng-hua LI ; Mei LIU ; Han-luo LI ; Ya-lan LEI ; Xiao-ke SHANG
Chinese Journal of Interventional Cardiology 2025;33(3):170-175
Ventricular assist devices(VADs)have emerged as a pivotal therapeutic option for end-stage heart failure,undergoing significant technological advancements from pneumatic membrane pumps to continuous-flow centrifugal pumps.This review provides a detailed overview of several VAD models,including HeartMate Ⅲ,EVAHEART 2,and Heart Con.The initial generation of VADs established a foundation for subsequent developments,despite the occurrence of frequent complications.The second generation of VADs demonstrated a notable improvement in patient prognosis but carried the risk of ventricular collapse.The third generation of VADs represents a further reduction in size,incorporating magnetic levitation technology to enhance durability and blood compatibility.In the future,the development of VADs will focus on better emulating the physiological function of the native heart,improving pulsatility,and extending device longevity.As technology advances,VADs are expected to offer heart failure patients with a greater range of treatment options and a higher quality of life.

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