Background:It is well recognized that developing new animal models,refining the existing mouse models,and thoroughly characterizing their features are essential for gaining a deeper understanding of rosacea pathogenes...Background:It is well recognized that developing new animal models,refining the existing mouse models,and thoroughly characterizing their features are essential for gaining a deeper understanding of rosacea pathogenesis and for advancing therapeutic strategies in this direction.Accordingly,we aimed to characterize the pathological features of a long-term LL-37-induced mouse model of rosacea and to compare the disease manifestations and pathophysiological characteristics between short-term and long-term LL-37-induced models.A key focus was to investigate differential gene expression and the underlying mechanisms of immune system dysregulation in these models.Methods:We comparatively assessed skin lesion manifestations,the extent of inflammatory infiltration,sebaceous gland alterations,fibrosis,and angiogenesis in both models.Assessments were performed using photographic documentation,hematoxylin-eosin(HE)staining,Van Gieson's(VG)staining,immunohistochemistry,and Western blotting.Furthermore,we employed RNA sequencing to analyze differential gene expression in mouse skin.The RNA sequencing data were validated using immunofluorescence staining and Western blotting,with a specific focus on gene variations and mechanisms related to immune system dysregulation.Results:Mice subjected to long-term LL-37 induction developed rosacea-like pathological features,including angiogenesis,thickened skin tissue,and sebaceous gland hypertrophy.In the short-term LL-37-induced model,immune dysregulation primarily involved the innate immune response.However,long-term LL-37 induction resulted in significant activation of both innate and adaptive immune responses.Conclusion:The long-term LL-37-induced mouse model offers a valuable animal model for the detailed investigation of the pathological mechanisms driving moderate-to-severe rosacea with prolonged disease duration.Importantly,this model provides a significant experimental foundation for exploring the potential role of immune system dysregulation in rosacea pathogenesis.展开更多
Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs ...Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs can function as effectors,facilitating infection via effector-triggered susceptibility(ETS).Mechanisms of Avr-mediated ETS remain largely unexplored.Here we report that the Magnaporthe oryzae effector Avr-PikD enters rice cells via the canonical cytoplasmic secretion pathway and suppresses rice basal defense.Avr-PikD interacts with an LSD1-like transcriptional activator AKIP30 of rice,and AKIP30 is also a positive regulator of rice immunity,whereas Avr-PikD impedes its nuclear localization and suppresses its transcriptional activity.In summary,M.oryzae delivers Avr-PikD into rice cells to facilitate ETS by inhibiting AKIP30-mediated transcriptional regulation of immune response against M.oryzae.展开更多
The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown...The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC pro- liferation, accompanied with the reduction of proliferating cell nuclear antigen （PCNA） expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF recep- tor [~ （PDGFR~）-extracellular signal-regulated kinase 1/2 （ERK1/2） signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFR^-ERK1/2 signaling cascade.展开更多
Lianhua Qingwen capsule/granule is an innovative Chinese medicine developed under the guidance of the traditional Chinese medicine(TCM)collateral disease theory.It has the effect of“clearing heat and removing toxin,v...Lianhua Qingwen capsule/granule is an innovative Chinese medicine developed under the guidance of the traditional Chinese medicine(TCM)collateral disease theory.It has the effect of“clearing heat and removing toxin,ventilating the lungs and discharging heat”.In 2003,it was approved as a new drug by the China National Medical Products Administration,through expedited approval during severe acute respiratory syndrome,and now,it has become a representative proprietary Chinese medicine for the treatment of infectious diseases of the respiratory system.Pharmacodynamic studies have revealed that Lianhua Qingwen has broad-spectrum antiviral,antibacterial and anti-inflammatory,antipyretic,coughrelieving,and immunoregulation effects.Clinically it has been used in the treatment of communicable and infectious respiratory diseases such as Coronavirus Disease 2019,influenza,colds,pulmonary infections,etc.and has achieved remarkable curative effects,showing the important clinical guidance of the TCM collateral disease theory.展开更多
According to the self-discipline of traditional Chinese medicine,vessel-collateral theory was constructed systematically,which was important to improving prevention and treatment level of vasculopathy.The hypothesis o...According to the self-discipline of traditional Chinese medicine,vessel-collateral theory was constructed systematically,which was important to improving prevention and treatment level of vasculopathy.The hypothesis of“homeostasis(Cheng),compensatory auto-adaptation(Zhi),regulation(Tiao)and equilibrium(Ping)”based on the“qi–yin-yang–five elements”coupled with the ying(nutrients)-wei(defense)theory,has become the core content of the vessel-collateral theory.Clinical and laboratory trials have been developed to further confirm the scientific connotations of the hypothesis,such as Tong Xin Luo capsule,as the representative drugs of vessel collateral theory,showed good efficacy in protecting the vascular endothelium,stabilizing the vulnerable plaque and reducing the blood vessel spasm.“Sou,ti,shu,tong”was the characteristics of Tong Xin Luo capsule in treating“microvascular damage”as the core mechanism of acute myocardial infarction,cerebral infarction and microvascular complications of diabetes.Shen Song Yang Xin capsules in the treatment of arrhythmia have made integrated adjustment advantage.Qi Li Qiang Xin capsules have been made treating both manifestation and root cause of chronic heart failure.These research have improved prevention and treatment level of major vascular system diseases.展开更多
Aging,a complex and multisystem process,has increasingly become a hot issue of global concern.Traditional Chinese medicine has accumulated rich understanding of aging during thousands of years of development,which pro...Aging,a complex and multisystem process,has increasingly become a hot issue of global concern.Traditional Chinese medicine has accumulated rich understanding of aging during thousands of years of development,which provides valuable references for the in-depth study of overall aging.According to the Qi-collateral theory in traditional Chinese medicine,essence is the origin of life;Qi is the driving force of life;and spirit is the embodiment of life.This theory interprets key scientific issues such as the formation of life,the driving force of life,the function of Zang-Fu organs,and the spirit and consciousness.Furthermore,it reveals the key mechanism of aging.That is,the deficiency of kidney essence is the root of aging;the loss of vitality is the key of aging;and the depletion of body and spirit is the manifestation of aging.Based on the experience of medical practitioners in the past dynasties,such as nourishing essence,black food tonifying the kidney,and supplementing essence with flesh-blood products,the treatment method of invigorating kidney and supplementing essence,harmonizing Yin and Yang,reinforcing the vitality,and nourishing the body and spirit was proposed.Furthermore,an innovative Chinese patent medicine,Bazi Bushen capsules,is developed,which exerts the antiaging effect by replenishing Qi,invigorating the spirit,and nourishing the body and spirit.Pharmacological and clinical studies have confirmed that this preparation has antiaging effects and are effective in the prevention and treatment of age-related diseases.Experimental studies have shown that Bazi Bushen capsules can delay the overall aging,reduce the DNAmethylation and extend the healthy life of naturally aging mice,mitigate the age-related cognitive dysfunction,improve neurological function,maintain redox homeostasis and telomere integrity,and inhibit apoptosis.Moreover,Bazi Bushen capsules can increase the dermal thickness and the collagen fiber and elastic fiber content to prevent skin aging.In addition,Bazi Bushen capsules can correct the lipid metabolism disorders and ameliorate multisystem age-related diseases such as osteoporosis in surgically induced menopausal rats.This article discusses the pathogenesis,treatment,and prescription of aging and the antiaging theory,aiming to provide a basis for delaying aging and preventing related diseases.展开更多
基金The National Natural Science Foundation of China,Grant/Award Number:82204006Science and Technology Project of Hebei Education Department,Grant/Award Number:QN2022009+1 种基金Medical Science Research Project of Hebei,Grant/Award Number:20221534National Natural Science Foundation of Hebei Province,Grant/Award Number:H2024209038。
文摘Background:It is well recognized that developing new animal models,refining the existing mouse models,and thoroughly characterizing their features are essential for gaining a deeper understanding of rosacea pathogenesis and for advancing therapeutic strategies in this direction.Accordingly,we aimed to characterize the pathological features of a long-term LL-37-induced mouse model of rosacea and to compare the disease manifestations and pathophysiological characteristics between short-term and long-term LL-37-induced models.A key focus was to investigate differential gene expression and the underlying mechanisms of immune system dysregulation in these models.Methods:We comparatively assessed skin lesion manifestations,the extent of inflammatory infiltration,sebaceous gland alterations,fibrosis,and angiogenesis in both models.Assessments were performed using photographic documentation,hematoxylin-eosin(HE)staining,Van Gieson's(VG)staining,immunohistochemistry,and Western blotting.Furthermore,we employed RNA sequencing to analyze differential gene expression in mouse skin.The RNA sequencing data were validated using immunofluorescence staining and Western blotting,with a specific focus on gene variations and mechanisms related to immune system dysregulation.Results:Mice subjected to long-term LL-37 induction developed rosacea-like pathological features,including angiogenesis,thickened skin tissue,and sebaceous gland hypertrophy.In the short-term LL-37-induced model,immune dysregulation primarily involved the innate immune response.However,long-term LL-37 induction resulted in significant activation of both innate and adaptive immune responses.Conclusion:The long-term LL-37-induced mouse model offers a valuable animal model for the detailed investigation of the pathological mechanisms driving moderate-to-severe rosacea with prolonged disease duration.Importantly,this model provides a significant experimental foundation for exploring the potential role of immune system dysregulation in rosacea pathogenesis.
基金supported by grants from the National Natural Science Foundation of China(31401692,31901960,32272513,32001976)the Natural Science Foundation of Fujian Province(2019J01766,2023J011418,2020J05177)+3 种基金Fujian Provincial Science and Technology Key Project(2022NZ030014)External Cooperation Program of Fujian Academy of Agricultural Sciences(DWHZ-2024-23)State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crop Opening Project(SKL2019005)Project of Fujian Provincial Department of Education(JAT190627)。
文摘Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs can function as effectors,facilitating infection via effector-triggered susceptibility(ETS).Mechanisms of Avr-mediated ETS remain largely unexplored.Here we report that the Magnaporthe oryzae effector Avr-PikD enters rice cells via the canonical cytoplasmic secretion pathway and suppresses rice basal defense.Avr-PikD interacts with an LSD1-like transcriptional activator AKIP30 of rice,and AKIP30 is also a positive regulator of rice immunity,whereas Avr-PikD impedes its nuclear localization and suppresses its transcriptional activity.In summary,M.oryzae delivers Avr-PikD into rice cells to facilitate ETS by inhibiting AKIP30-mediated transcriptional regulation of immune response against M.oryzae.
基金We are grateful to Dr Guan KL （Moore＇s Cancer Center, La Jolla, CA, USA） for the gift of pCMV-MEKca. This study was supported by the National Natural Science Foundation of China （30770787 and 90919035）, the National Basic Research Program of China （2005CB523301）, and the International Cooperation in Science and Technology Projects （2006DFB32460） and the Hebei Province Natural Science Foundation （C2007000831）.
文摘The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC pro- liferation, accompanied with the reduction of proliferating cell nuclear antigen （PCNA） expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF recep- tor [~ （PDGFR~）-extracellular signal-regulated kinase 1/2 （ERK1/2） signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFR^-ERK1/2 signaling cascade.
基金This study was supported by special major project for technologies of innovative manufacturing of major new drugs(2018ZX09737002)。
文摘Lianhua Qingwen capsule/granule is an innovative Chinese medicine developed under the guidance of the traditional Chinese medicine(TCM)collateral disease theory.It has the effect of“clearing heat and removing toxin,ventilating the lungs and discharging heat”.In 2003,it was approved as a new drug by the China National Medical Products Administration,through expedited approval during severe acute respiratory syndrome,and now,it has become a representative proprietary Chinese medicine for the treatment of infectious diseases of the respiratory system.Pharmacodynamic studies have revealed that Lianhua Qingwen has broad-spectrum antiviral,antibacterial and anti-inflammatory,antipyretic,coughrelieving,and immunoregulation effects.Clinically it has been used in the treatment of communicable and infectious respiratory diseases such as Coronavirus Disease 2019,influenza,colds,pulmonary infections,etc.and has achieved remarkable curative effects,showing the important clinical guidance of the TCM collateral disease theory.
基金supported by National Basic Research Program of China(973 Program)(No.2005CB523301)Major Creation of New Drugs during the 11th Five-Year Plan Period(No.2009ZX09313-003).
文摘According to the self-discipline of traditional Chinese medicine,vessel-collateral theory was constructed systematically,which was important to improving prevention and treatment level of vasculopathy.The hypothesis of“homeostasis(Cheng),compensatory auto-adaptation(Zhi),regulation(Tiao)and equilibrium(Ping)”based on the“qi–yin-yang–five elements”coupled with the ying(nutrients)-wei(defense)theory,has become the core content of the vessel-collateral theory.Clinical and laboratory trials have been developed to further confirm the scientific connotations of the hypothesis,such as Tong Xin Luo capsule,as the representative drugs of vessel collateral theory,showed good efficacy in protecting the vascular endothelium,stabilizing the vulnerable plaque and reducing the blood vessel spasm.“Sou,ti,shu,tong”was the characteristics of Tong Xin Luo capsule in treating“microvascular damage”as the core mechanism of acute myocardial infarction,cerebral infarction and microvascular complications of diabetes.Shen Song Yang Xin capsules in the treatment of arrhythmia have made integrated adjustment advantage.Qi Li Qiang Xin capsules have been made treating both manifestation and root cause of chronic heart failure.These research have improved prevention and treatment level of major vascular system diseases.
基金This study was supported by the Strategic Consulting Project of the Chinese Academy of Engineering-Strategic Research on Anti-aging Effects of Traditional Chinese Medicine(2022-XY-45)the Natural Science Foundation of Hebei Province of China(no.H2022106065)+1 种基金the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine(no.2023172)the Scientific Research Project of Traditional Chinese Medicine Administration of Hebei Province(no.2023391).
文摘Aging,a complex and multisystem process,has increasingly become a hot issue of global concern.Traditional Chinese medicine has accumulated rich understanding of aging during thousands of years of development,which provides valuable references for the in-depth study of overall aging.According to the Qi-collateral theory in traditional Chinese medicine,essence is the origin of life;Qi is the driving force of life;and spirit is the embodiment of life.This theory interprets key scientific issues such as the formation of life,the driving force of life,the function of Zang-Fu organs,and the spirit and consciousness.Furthermore,it reveals the key mechanism of aging.That is,the deficiency of kidney essence is the root of aging;the loss of vitality is the key of aging;and the depletion of body and spirit is the manifestation of aging.Based on the experience of medical practitioners in the past dynasties,such as nourishing essence,black food tonifying the kidney,and supplementing essence with flesh-blood products,the treatment method of invigorating kidney and supplementing essence,harmonizing Yin and Yang,reinforcing the vitality,and nourishing the body and spirit was proposed.Furthermore,an innovative Chinese patent medicine,Bazi Bushen capsules,is developed,which exerts the antiaging effect by replenishing Qi,invigorating the spirit,and nourishing the body and spirit.Pharmacological and clinical studies have confirmed that this preparation has antiaging effects and are effective in the prevention and treatment of age-related diseases.Experimental studies have shown that Bazi Bushen capsules can delay the overall aging,reduce the DNAmethylation and extend the healthy life of naturally aging mice,mitigate the age-related cognitive dysfunction,improve neurological function,maintain redox homeostasis and telomere integrity,and inhibit apoptosis.Moreover,Bazi Bushen capsules can increase the dermal thickness and the collagen fiber and elastic fiber content to prevent skin aging.In addition,Bazi Bushen capsules can correct the lipid metabolism disorders and ameliorate multisystem age-related diseases such as osteoporosis in surgically induced menopausal rats.This article discusses the pathogenesis,treatment,and prescription of aging and the antiaging theory,aiming to provide a basis for delaying aging and preventing related diseases.
