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Cuproptosis: copper-induced regulated cell death

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Science China(Life Sciences) 2022年第8期65卷 1680-1682页

作者： Wen-Jun Duan rong-rong he Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility Jinan UniversityGuangzhou 510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) Jinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research Jinan UniversityGuangzhou 510632China School of Traditional Chinese Medicine Jinan UniversityGuangzhou 510632China

“Life is pleasant. Death is peaceful. It's the transition that's troublesome.”——Isaac Asimov Copper is an essential trace element central to cardiovascular, neuronal, and immune functions. While copper deficiency ... 详细信息

关键词： functions copper peace

An endogenous neuropeptide hormone assists cancer cells in escaping from immune surveillance

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Science China(Life Sciences) 2023年第6期66卷 1451-1453页

作者： Chang-Yu Yan Yan-Ping Wu Yi-Fang Li rong-rong he Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility Jinan UniversityGuangzhou510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhou510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou510632China School of Traditional Chinese Medicine Jinan UniversityGuangzhou510632China

Unlike tumor chemotherapy,tumor immunotherapy relies heavily on the immune system of the *** recent years,immunotherapeutic approaches that target the immune checkpoint(ICT)pathways,have shown promise in cancer treatment,though resistance due to tumor-induced immunosuppression remains a major hurdle in some patients(Saleh and Elkord,2020).

关键词： endogenous cancer chemotherapy

Predator stress-induced depression is associated with inhibition of hippocampal neurogenesis in adult male mice

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Neural Regeneration Research 2019年第2期14卷 298-305页

作者： Yan-Ping Wu Hua-Ying Gao Shu-Hua Ouyang Hiroshi Kurihara rong-rong he Yi-Fang Li Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of Pharmacy Jinan University Anti-Stress and health Research Center College of Pharmacy Jinan University

Stress has been suggested to disturb the 5-hydroxytryptamine system and decrease neurogenesis, which contribute to the development of depression. Few studies have investigated the effect of predator stress, a type of psychological stress, on depression and hippocampal neurogenesis in adult mice; we therefore investigated this in the present study. A total of 35 adult male Kunming mice were allocated to a cat stress group, cat odor stress group, cat stress + fluoxetine group, cat odor stress + fluoxetine group, or a control group(no stress/treatment). After 12 days of cat stress or cat odor stress, behavioral correlates of depression were measured using the open field test, elevated plus maze test, and dark-avoidance test. The concentrations of hippocampal 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were measured using high-performance liquid chromatography-electrochemical detection. Neurogenesis was also analyzed using a bromodeoxyuridine and doublecortin double-immunostaining method. Cat stress and cat odor stress induced depression-like behaviors; this effect was stronger in the cat stress model. Furthermore, compared with the control group, cat stress mice exhibited lower 5-hydroxytryptamine concentrations, higher 5-hydroxyindoleacetic acid concentrations, and significantly fewer bromodeoxyuridine+/doublecortin+-labeled cells in the dentate gyrus, which was indicative of less neurogenesis. The changes observed in the cat stress group were not seen in the cat stress + fluoxetine group, which suggests that the effects of predator stress on depression and neurogenesis were reversed by fluoxetine. Taken together, our results indicate that depression-like behaviors induced by predator stress are associated with the inhibition of hippocampal neurogenesis.

关键词： nerve regeneration depressive disorder cat stress cat odor stress behavioral evaluation open field test elevated plus maze test dark-avoidance test 5-hydroxytryptamine 5-hydroxyindoleacetic acid hippocampal neurogenesis neural regeneration

Disturbed Yin-Yang balance:stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1

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Acta Pharmaceutica Sinica B 2020年第3期10卷 383-398页

作者： Chang Yan Zhuo Luo Wen Li Xue Li Robert Dallmann Hiroshi Kurihara Yi-Fang Li rong-rong he Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility Jinan University Guangzhou 510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) School of PharmacyJinan UniversityGuangzhou 510632China Institute of Atmospheric Environmental Safety and Pollution Control Jinan UniversityGuangzhou 510632China Warwick Medical School University of WarwickCoventry CV47ALUK

herpes simplex virus type 1(HSV-1),a neurotropic herpes virus,is able to establish a lifelong latent infection in the human *** primary replication in mucosal epithelial cells,the virus can enter sensory neurons innervating peripheral tissues via nerve *** viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny,and thus latency is established in the ***-Yang balance is an essential concept in traditional Chinese medicine(TCM)*** represents stable and inhibitory factors,and Yang represents the active and aggressive *** the organism is exposed to stress,especially psychological stress caused by emotional stimulation,the Yin-Yang balance is disturbed and the virus can re-engage in productive replication,resulting in recurrent ***,a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of *** we reviewed the recent advances in the studies of HSV-1 susceptibility,latency and *** included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.

关键词： herpes simplex virus type 1 HSV-1 Susceptibility Latency Reactivation Stress

Commentary: A nearly forgotten class of anti-inflammatory lipid molecules in central nervous system

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Acta Pharmaceutica Sinica B 2023年第6期13卷 2809-2811页

作者： Nan Ru Wan-Yang Sun Hua-Jun Wang Yan-Ping Wu Xiao-Fei Zheng rong-rong he The First Affiliated Hospital/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE)/Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research Jinan UniversityGuangzhou 510632China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacaoChina

Lipids are the major components of cells in the central nervous system(CNS) and are essential for the brain development and homeostasis. Several studies have demonstrated that impaired lipid metabolism is closely related to neurological diseases among the elderly^(1). Lipidomics can serve us well in identifying and quantifying lipid molecules in cells, tissues, and organisms at the system level. However, finding out biologically meaningful lipids from the massive lipidomics data is not straightforward.

关键词： Lipidomics Aging 3-Sulfogalactosyl diacylglycerols Anti-inflammation Central nervous system

New functions of oxylipins released by pyroptotic cells

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Acta Pharmaceutica Sinica B 2024年第12期14卷 5509-5511页

作者： Hui Xu Hong-Li Tan Hua-Jun Wang Xiao-Fei Zheng Yan-Ping Wu rong-rong he The First Affiliated Hospital Guangdong Engineering Research Center of Traditional Chinese Medicine&Disease SusceptibilityGuangzhou Key Laboratory of Traditional Chinese Medicine&Disease SusceptibilityGuangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese MedicineGuangdong Engineering Research Center of Traditional Chinese Medicine&Health ProductsInternational Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE)Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchState Key Laboratory of Bioactive Molecules and Druggability AssessmentGuangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative DrugsJinan UniversityGuangzhou 510632China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacaoChina

Pyroptosis typically features the perforation of cell membranes,a process triggered by the exposure of active N-terminal domain of Gasdermin D(GSDMD).This pivotal event subsequently leads to the release of pro-inflammatory cytokines,notably IL-1a and IL-1b,thereby fostering tissue inflammation and impeding the repair process ***,the question of whether small molecule metabolites expelled through these pyroptotic pores possess specific physiological functions has consistently captivated the scientific community’s curiosity.A recent study published in Nature by Mehrotra et al.2 unveiled a novel paradigm,suggesting that oxygenated polyunsaturated fatty acids(oxylipins),released from pyroptotic cells,can paradoxically promote wound *** research demonstrates,as the famous saying goes,“From death comes rebirth”,innovatively revealing the interdependent relationship between cell death,inflammation,and repair.

关键词： Programmed cell death Pyroptosis Oxylipins PGE2 Tissue repair

The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages

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Acta Pharmaceutica Sinica B 2022年第1期12卷 197-209页

作者： Yanping Wu Xiang Luo Qingqing Zhou Haibiao Gong Huaying Gao Tongzheng Liu Jiaxu Chen Lei Liang Hiroshi Kurihara Yi-Fang Li rong-rong he Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility Jinan UniversityGuangzhou 510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education College of PharmacyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China Formula-pattern Research Center School of Traditional Chinese MedicineJinan UniversityGuangzhou 510632China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Institute of Tumor Pharmacology College of PharmacyJinan UniversityGuangzhou 510632China

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stressevoked tumor susceptibility, and the stress hormone glucocorticoid(GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor(low-density lipoprotein receptor-related protein-1, LRP1) and the "don’t eat me" signal receptor(signal regulatory protein alpha, SIRPa). Further analysis revealed that GC led to a direct, glucocorticoid receptor(GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevatedgene level of SIRPa by down-regulating mi RNA-4695-3 p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPa axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPa axis may serve as a potential therapeutic strategy for tumor treatment.

关键词： Psychological stress Tumorigenesis Macrophages Phagocytosis LRP1 SIRPa Therapeutic target

Inhibitory effects of baicalein against herpes simplex virus type 1

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2323-2338页

作者： Zhuo Luo Xiu-Ping Kuang Qing-Qing Zhou Chang-Yu Yan Wen Li Hai-Biao Gong Hiroshi Kurihara Wei-Xi Li Yi-Fang Li rong-rong he Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility College of PharmacyCollege of PharmacyJinan UniversityGuangzhou 612505China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhou 612505China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou 612505China Yunnan University of Traditional Chinese Medicine Kunming 650550China

herpes simplex virus type 1(HSV-1)is a ubiquitous and widespread human pathogen,which gives rise to a range of diseases,including cold sores,corneal blindness,and ***,the use of nucleoside analogs,such as acyclovir and penciclovir,in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance ***,new anti-herpetic drugs and strategies should be urgently ***,we reported that baicalein,a naturally derived compound widely used in Asian countries,strongly inhibited HSV-1 replication in several *** was effective against the replication of both HSV-1/F and HSV-1/Blue(an acyclovir-resistant strain)in *** the ocular inoculation mice model,baicalein markedly reduced in vivo HSV-1/F replication,receded inflammatory storm and attenuated histological changes in the ***,baicalein was found to reduce the mortality of mice,viral loads both in nose and trigeminal ganglia in HSV-1 intranasal infection ***,an ex vivo HSV-1-EGFP infection model established in isolated murine epidermal sheets confirmed that baicalein suppressed HSV-1 *** investigations unraveled that dual mechanisms,inactivating viral particles and inhibiting IκB kinase beta(IKK-β)phosphorylation,were involved in the anti-HSV-1 effect of ***,our findings identified baicalein as a promising therapy candidate against the infection of HSV-1,especially acyclovir-resistant strain.

关键词： Anti-HSV-1 Baicalein Viral inactivation IKK-βphosphorylation NF-kβactivation HSV-1 infection

ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3523-3535页

作者： Xiao-Hui Ma Jiang-Han-Zi Liu Chun-Yu Liu Wan-Yang Sun Wen-Jun Duan Guan Wang Hiroshi Kuriara rong-rong he Yi-Fang Li Yang Chen Hongcai Shang Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibilty Jinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China international Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) Jinan UniversityGuangzhou 510632China institute of Traditional Chinese Medicine Xinjiang Medical UniversityUrumqi 830054China Sinnovation Center of Nursing Research Nursing Key Laboratory of Sichuan ProvinceState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China College of Pharmacy Guangzhou University of Chinese Medicine Guangzhou 510405China Key Laboratory of Chinese Internal Medicine of Ministry of Education Dongzhimen HospitalBeijing University of Chinese Medicine100700 BeijingChina

Myocardial ischemia/reperfusion(/R)injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell *** is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion *** we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids(PUFA)-phospholipids in myocardial cells,which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion *** animal and in vitro models,the crucial lipid species in I/R injury were identifed to be oxidized PUFAs enriched *** multi-omics,arachidonic acid 15-lipoxygenase-1(ALOx15)was identified as the primary mediator of ischemia-provoked phospholipid peroxidation,which was further confirmed using chemogenetic ***,our results reveal that ALOx15 induction in the ischemia phase acts as a"burning point"to ignite phospholipid oxidization into ferroptotic *** finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of V/R injury.

关键词： peroxidation ischemia damage