Heart failure(HF)represents one of the leading causes of morbidity and mortality in the modern world,which threatened approximately 1%~2%of adults’lives.HF is the end stage of multiple cardiovascular diseases charact...Heart failure(HF)represents one of the leading causes of morbidity and mortality in the modern world,which threatened approximately 1%~2%of adults’lives.HF is the end stage of multiple cardiovascular diseases characterized by cardiac hypertrophy and myocardial remodeling,and the pathophysiological processes of which include oxidative stress,endoplasmic reticulum homeostasis,apoptosis,autophagy,energy metabolism disorder,etc.The regulation of protein homeostasis intrinsically interrelates the above pathophysiological processes.Therefore,it is imperative to elucidate the molecular mechanism from the perspective of protein homeostasis to find new therapeutic targets for HF treatment.The dynamic regulation and post-translational modification of protein synthesis and degradation play a vital role in response of living organisms to physiological changes.The ubiquitin-proteasome system(UPS),which degrades 70-90%of endogenous proteins,plays an integral part in the pathophysiological processes of HF.The UPS can regulate oxidative stress,endoplasmic reticulum homeostasis,apoptosis and autophagy of cardiomyocytes(CMs),energy metabolism,targeting degradation signals and structural proteins,thus modulating cardiac hypertrophy,fibrosis and remodeling,finally contributing to the occurrence and progression of HF.Thus,regulating UPS is a promising effective strategy to treat HF.Increasing evidence indicates that traditional Chinese medicine(TCM)targeting the UPS is potential to ameliorate HF.This review will summarize the current knowledge focusing on the underlying mechanism and the important research advances related to UPS in treating HF,and the traditional Chinese medicine targeting UPS.展开更多
Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)have recently been identified to be closely related to the occurrence and development of atherosclerosis(AS).A growing body of evidence has suggested Chine...Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)have recently been identified to be closely related to the occurrence and development of atherosclerosis(AS).A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating As.In this review,the related research progress of AS and LOX-1 has been summarized.And the anti-As effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed.As a potential biomarker and target for intervention in AS,LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention andtreatment.展开更多
Inflammation and immune disorders are integral to the occurrence and progression of atherosclerosis(AS).With the role of regulatory T cells(Tregs)in immune regulation attracting attention,it has been widely accepted t...Inflammation and immune disorders are integral to the occurrence and progression of atherosclerosis(AS).With the role of regulatory T cells(Tregs)in immune regulation attracting attention,it has been widely accepted that Treg decrease and dysfunction are involved in AS pathogenesis.Chinese medicine(CM)has the advantages of being dual-directional,multi-targeted,and having minimal side effects in immune regulation.The anti-atherosclerosis effects of CM via Treg modulation have been revealed in clinical and animal studies.Therefore,this article reviews existing research on Tregs,the relationship between Tregs and AS,and the progress of CM for treating and prevention of atherosclerotic cardio-cerebrovascular diseases by regulating Tregs.Although the underlying mechanisms remain to be elucidated,CM treatment targeting Treg cells might provide a promising and novel future approach for prevention and treatment of AS.展开更多
BACKGROUND Both programmed cell death-1(PD-1)inhibitors and lenvatinib,which have a synergistic effect,are promising drugs for tumor treatment.It is generally believed that combination therapy with a PD-1 inhibitor an...BACKGROUND Both programmed cell death-1(PD-1)inhibitors and lenvatinib,which have a synergistic effect,are promising drugs for tumor treatment.It is generally believed that combination therapy with a PD-1 inhibitor and lenvatinib is safe and effective.However,we report a case of toxic epidermal necrolysis(TEN),a grade 4 toxicity,after this combination therapy.CASE SUMMARY A 39-year-old male presented with erythema,blisters and erosions on the face,neck,trunk and limbs 1 wk after receiving combination therapy with lenvatinib and toripalimab,a PD-1 inhibitor.The skin injury covered more than 70%of the body surface area.He was previously diagnosed with liver cancer with cervical vertebra metastasis.Histologically,prominent necrotic keratinocytes,hyperkeratosis,liquefaction of basal cells and acantholytic bullae were observed in the epidermis.Blood vessels in the dermis were infiltrated by lymphocytes and eosinophils.Direct immunofluorescence staining was negative.Thus,the diagnosis was confirmed to be TEN(associated with combination therapy with toripalimab and lenvatinib).Full-dose and long-term corticosteroids,high-dose intravenous immunoglobulin and targeted antibiotic drugs were administered.The rashes gradually faded;however,as expected,the tumor progressed.Therefore, sorafenib and regorafenib were given in succession, and the patient was still alive at the10-mo follow-up.CONCLUSIONCautious attention should be given to rashes that develop after combination therapy with PD-1inhibitors and lenvatinib. Large-dose and long-course glucocorticoids may be crucial for thetreatment of TEN associated with this combination treatment.展开更多
基金This work was supported by Beijing Natural Science Foundation(Grant No.JQ18026)the National Natural Science Foundation of China(NNSFC+2 种基金Grant Nos.82073978,81773589)Fundamental Research Funds for the Central Universities(2021-JYB-XJSJJ-053)Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases(No.2018B030322012,MB2020KF01).
文摘Heart failure(HF)represents one of the leading causes of morbidity and mortality in the modern world,which threatened approximately 1%~2%of adults’lives.HF is the end stage of multiple cardiovascular diseases characterized by cardiac hypertrophy and myocardial remodeling,and the pathophysiological processes of which include oxidative stress,endoplasmic reticulum homeostasis,apoptosis,autophagy,energy metabolism disorder,etc.The regulation of protein homeostasis intrinsically interrelates the above pathophysiological processes.Therefore,it is imperative to elucidate the molecular mechanism from the perspective of protein homeostasis to find new therapeutic targets for HF treatment.The dynamic regulation and post-translational modification of protein synthesis and degradation play a vital role in response of living organisms to physiological changes.The ubiquitin-proteasome system(UPS),which degrades 70-90%of endogenous proteins,plays an integral part in the pathophysiological processes of HF.The UPS can regulate oxidative stress,endoplasmic reticulum homeostasis,apoptosis and autophagy of cardiomyocytes(CMs),energy metabolism,targeting degradation signals and structural proteins,thus modulating cardiac hypertrophy,fibrosis and remodeling,finally contributing to the occurrence and progression of HF.Thus,regulating UPS is a promising effective strategy to treat HF.Increasing evidence indicates that traditional Chinese medicine(TCM)targeting the UPS is potential to ameliorate HF.This review will summarize the current knowledge focusing on the underlying mechanism and the important research advances related to UPS in treating HF,and the traditional Chinese medicine targeting UPS.
基金Supported by the National Natural Science Foundation of China(No.81874432 and No.82074369)Science and Technology Planning Project of Guangdong Province(No.2018B030322012)。
文摘Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)have recently been identified to be closely related to the occurrence and development of atherosclerosis(AS).A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating As.In this review,the related research progress of AS and LOX-1 has been summarized.And the anti-As effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed.As a potential biomarker and target for intervention in AS,LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention andtreatment.
基金Supported by Science and Technology Planning Project of Guangdong Province(No.2018B030322012)National Natural Science Foundation of China(No.81874432 and No.82074369)。
文摘Inflammation and immune disorders are integral to the occurrence and progression of atherosclerosis(AS).With the role of regulatory T cells(Tregs)in immune regulation attracting attention,it has been widely accepted that Treg decrease and dysfunction are involved in AS pathogenesis.Chinese medicine(CM)has the advantages of being dual-directional,multi-targeted,and having minimal side effects in immune regulation.The anti-atherosclerosis effects of CM via Treg modulation have been revealed in clinical and animal studies.Therefore,this article reviews existing research on Tregs,the relationship between Tregs and AS,and the progress of CM for treating and prevention of atherosclerotic cardio-cerebrovascular diseases by regulating Tregs.Although the underlying mechanisms remain to be elucidated,CM treatment targeting Treg cells might provide a promising and novel future approach for prevention and treatment of AS.
基金Supported by Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases,No. 2018B030322012
文摘BACKGROUND Both programmed cell death-1(PD-1)inhibitors and lenvatinib,which have a synergistic effect,are promising drugs for tumor treatment.It is generally believed that combination therapy with a PD-1 inhibitor and lenvatinib is safe and effective.However,we report a case of toxic epidermal necrolysis(TEN),a grade 4 toxicity,after this combination therapy.CASE SUMMARY A 39-year-old male presented with erythema,blisters and erosions on the face,neck,trunk and limbs 1 wk after receiving combination therapy with lenvatinib and toripalimab,a PD-1 inhibitor.The skin injury covered more than 70%of the body surface area.He was previously diagnosed with liver cancer with cervical vertebra metastasis.Histologically,prominent necrotic keratinocytes,hyperkeratosis,liquefaction of basal cells and acantholytic bullae were observed in the epidermis.Blood vessels in the dermis were infiltrated by lymphocytes and eosinophils.Direct immunofluorescence staining was negative.Thus,the diagnosis was confirmed to be TEN(associated with combination therapy with toripalimab and lenvatinib).Full-dose and long-term corticosteroids,high-dose intravenous immunoglobulin and targeted antibiotic drugs were administered.The rashes gradually faded;however,as expected,the tumor progressed.Therefore, sorafenib and regorafenib were given in succession, and the patient was still alive at the10-mo follow-up.CONCLUSIONCautious attention should be given to rashes that develop after combination therapy with PD-1inhibitors and lenvatinib. Large-dose and long-course glucocorticoids may be crucial for thetreatment of TEN associated with this combination treatment.
