Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.S...Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.Skeletal muscle,as a major metabolic organ system,undergoes significant remodeling during ALI.However,its specific regulatory contributions remain largely uncharacterized.Methods:Partial(2/3)hepatectomy and acetaminophen were used to induce ALI in male mice.RNA-sequencing(RNA-seq),assay for transposase-accessible chromatin by sequencing(ATAC-seq),chromatin immunoprecipitation,luciferase assay,Western blotting,TUNEL assay,immunohistochemistry,and phase separation assays were performed to reveal the transcriptional axis involved.Serum fibroblast growth factor binding protein 1(FGFBP1)protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.Results:Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid(GC)signaling-mediated regulation of fibroblast growth factor 6(FGF6)in skeletal muscle metabolism.Muscle-specific knockdown of GC receptor(GR)exacerbates ALI and suppresses liver regeneration.Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration,with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown.Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling.Moreover,FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane.Circulating FGFBP1 subsequently interacts with hepatic FGF5 through LLPS mechanisms to regulate liver regeneration.Conclusion:Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis,providing a potential therapeutic target and treatment strategy for ALI.展开更多
The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval ...The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval at the B1 locus on chromosome 5A,which included the candidate gene encoding a zinc finger protein(TraesCS5A01G542800)as an awn length inhibitor(ALI).The Ali-A1 allele for the awnless trait showed abundant sequence differences in the promoter regions compared to the ali-A1 allele for the long-awn trait.The results of the swap experiment on the promoters from the two ALI-A1 alleles showed that the two promoters caused a difference in the protein level,indicating the gene was regulated at the transcript level.However,the ali-A1 allele contained an SNP that caused a premature stop codon in its coding region,resulting in a truncated protein compared to the functional Ali-A1 protein.The Ali-A1 protein contained two ethylene-responsive element binding factor-associated amphiphilic repression(EAR)motifs,one at the N terminus(EAR-N)and the other at the C terminus(EAR-C),and they were involved in interactions with the wheat co-repressor protein TOPLESS(TPL1).The ali-A1 protein retained the EAR-N motif but lost the EAR-C motif,resulting in the attenuated ability to interact with TPL1.The tpl1 mutant produced a longer awn compared to the wild type.Ali-A1 repressed the transcription of two downstream genes,TaLRP-A1 and TaARF-B1,involved in endogenous auxin concentrations and auxin responses in wheat.We concluded that the awn length is regulated not only by the ALI-A1 gene at transcript levels but also by Ali-A1 and TPL1 at the protein level in wheat.展开更多
BACKGROUND Herbal supplements are increasingly used to manage menopausal symptoms.Physta®is a commercial herbal ingredient containing Eurycoma longifolia standardized water extract,traditionally used for vitality...BACKGROUND Herbal supplements are increasingly used to manage menopausal symptoms.Physta®is a commercial herbal ingredient containing Eurycoma longifolia standardized water extract,traditionally used for vitality.Its adaptogenic and anti-inflammatory properties promote hormonal balance,physical function,and sexual health,supporting its potential benefits for menopausal health.AIM To investigate Physta®’s role in improving menopausal quality of life,mood states,and overall safety profile compared with placebo.METHODS In this 12-week,randomized,double-blind,placebo-controlled trial,138 females aged 40-55 with menopausal symptoms were randomly assigned to receive Physta®50 mg,Physta®100 mg,or placebo.MENQOL and POMS were assessed at baseline,week 6,and week 12.Safety outcomes were evaluated through biochemical tests,vital signs,and female reproductive hormonal profile.RESULTS Physta®100 mg significantly reduced total MENQOL scores by 33.9%from baseline to week 12(P=0.049)with notable improvements in the physical(-36.4%,P=0.046)and sexual(-36.3%,P=0.043)domains.Total mood disturbance also declined more in the Physta®100 mg group(-38.6%)compared with placebo(-30.1%),although not statistically significant.No significant changes were observed in the vital signs and biochemical parameters,indicating the safety and tolerability of Physta®.No significant alterations were found in the female reproductive hormone profile,supporting its hormonal neutrality.CONCLUSION Physta®100 mg improved menopausal quality of life and mood without adverse effects,supporting its potential as a safe herbal therapy.Further studies with higher doses and longer durations are needed.展开更多
[Objectives]To investigate the protective effects of xanthoxylin on acute lung injury induced by D-Galactosamine(D-GalN)and Lipopolysaccharide(LPS)in rats.[Methods]Sixty male SD rats were randomly divided into a norma...[Objectives]To investigate the protective effects of xanthoxylin on acute lung injury induced by D-Galactosamine(D-GalN)and Lipopolysaccharide(LPS)in rats.[Methods]Sixty male SD rats were randomly divided into a normal group,a model group,a silybin group(50 mg/kg),and three xanthoxylin groups(low-dose,medium-dose,high-dose as 60,120,and 240 mg/kg),10 rats per group.The rats were administered for 17 consecutive days,on day 14,all the rats except for the normal group were intraperitoneally injected with a D-GalN(400 mg/kg)/LPS(30μg/kg)mixture once to establish acute lung injury models.At 72 h after modeling,their serum MCP-1 levels,IL-1β,IL-6,PCT,CRP,TNF-αlevels in bronchoalveolar lavage fluid,and IL-1β,IL-6,TNF-αlevels in lung tissue were measured,and lung tissue histological examination were checked by HE staining.[Results]Compared with the model group,the serum MCP-1 levels,IL-1β,IL-6,PCT,CRP,TNF-αlevels in bronchoalveolar lavage fluid,and IL-1β,IL-6,TNF-αlevels in lung tissue in xanthoxylin groups were significantly decreased(P<0.05 or P<0.01),and lung tissue injury were alleviated.[Conclusions]Xanthoxylin has protective effects on acute lung injury in rats,and it may be related to the increase of anti-inflammatory capacity and the promotion of lung tissue self-healing.展开更多
Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure a...Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure and death.Despite significant advances in clinical care,ALI/ARDS remains the leading cause of death among intensive care unit patients.Sepsis is the primary risk factor for the development of ALI/ARDS,as excessive inflammatory responses contribute to organ injury and high mortality in critically ill patients.展开更多
Background:Sepsis is often accompanied by lactic acidemia and acute lung injury(ALI).Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients.We...Background:Sepsis is often accompanied by lactic acidemia and acute lung injury(ALI).Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients.We further observed a significant correlation between the levels of cold-inducible RNA-binding protein(CIRP)in plasma and bronchoalveolar lavage fluid(BALF),as well as lactate levels,and the severity of post-sepsis ALI.The underlying mechanism,however,remains elusive.Methods:C57BL/6 wild type(WT),Casp8^(-/-),Ripk3^(-/-),and Zbp1^(-/-)mice were subjected to the cecal ligation and puncture(CLP)sepsis model.In this model,we measured intra-macrophage CIRP lactylation and the subsequent release of CIRP.We also tracked the internalization of extracellular CIRP(eCIRP)in pulmonary vascular endothelial cells(PVECs)and its interaction with Z-DNA binding protein 1(ZBP1).Furthermore,we monitored changes in ZBP1 levels in PVECs and the consequent activation of cell death pathways.Results:In the current study,we demonstrate that lactate,accumulating during sepsis,promotes the lactylation of CIRP in macrophages,leading to the release of CIRP.Once eCIRP is internalized by PVEC through a Toll-like receptor 4(TLR4)-mediated endocytosis pathway,it competitively binds to ZBP1 and effectively blocks the interaction between ZBP1 and tripartite motif containing 32(TRIM32),an E3 ubiquitin ligase targeting ZBP1 for proteasomal degradation.This interference mechanism stabilizes ZBP1,thereby enhancing ZBP1-receptor-interacting protein kinase 3(RIPK3)-dependent PVEC PANoptosis,a form of cell death involving the simultaneous activation of multiple cell death pathways,thereby exacerbating ALI.Conclusions:These findings unveil a novel pathway by which lactic acidemia promotes macrophage-derived eCIRP release,which,in turn,mediates ZBP1-dependent PVEC PANoptosis in sepsis-induced ALI.This finding offers new insights into the molecular mechanisms driving sepsis-related pulmonary complications and provides potential new therapeutic strategies.展开更多
急性肺损伤(ALI)是一种具有高发病率和高死亡率的严重疾病,目前缺乏有效的治疗手段。近年来,干细胞治疗因其多能性和再生能力受到广泛关注。本综述总结了不同类型干细胞(如间充质干细胞、上皮祖细胞、内皮祖细胞等)在急性肺损伤中的治...急性肺损伤(ALI)是一种具有高发病率和高死亡率的严重疾病,目前缺乏有效的治疗手段。近年来,干细胞治疗因其多能性和再生能力受到广泛关注。本综述总结了不同类型干细胞(如间充质干细胞、上皮祖细胞、内皮祖细胞等)在急性肺损伤中的治疗潜力,重点阐述了其作用机制、实验研究进展以及临床应用的挑战和未来方向。Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality rates, for which effective treatment options remain elusive. In recent years, stem cell therapy has emerged as a promising approach due to the pluripotency and regenerative capabilities of stem cells. This review explores the therapeutic potential of various stem cell types, including mesenchymal stem cells (MSCs), epithelial progenitor cells, and endothelial progenitor cells, in the context of ALI. It highlights their mechanisms of action, recent advances in experimental studies, and the challenges associated with clinical translation, while providing insights into future research directions.展开更多
Coronavirus disease 2019(COVID-19)is a multi-system disease that can lead to various severe complications.Acute limb ischemia(ALI)has been increasingly recognized as a COVID-19-associated complication that often predi...Coronavirus disease 2019(COVID-19)is a multi-system disease that can lead to various severe complications.Acute limb ischemia(ALI)has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis.However,the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood.Hypercoagulability and thrombosis are considered important mechanisms,but we also emphasize the roles of vasospasm,hypoxia,and acidosis in the pathogenesis of the disease.The angiotensin-converting enzyme 2(ACE2)pathway,inflammation,and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19.Furthermore,we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic,age,and gender perspectives based on our analysis of molecular mechanisms.Additionally,we summarize therapeutic approaches such as use of the interleukin-6(IL-6)blocker tocilizumab,calcium channel blockers,and angiotensin-converting enzyme inhibitors,providing insights for the future treatment of coronavirus-associated limb ischemic diseases.展开更多
基金supported by the NSFC Distinguished Young Scholars Fund(82325010)the National Natural Science Foundation of China(82370874)+4 种基金the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212700)the Major Natural Science Project of the Scientific Research and Innovation Plan of Shanghai Municipal Commission of Education(2023ZKZD17)the Shanghai Research Center for Endocrine and Metabolic Diseases(2022ZZ01002)the Shanghai Key Discipline of Public Health Grants Award(GWVI-11.1-20)the Basic Scientific Research Project(General Cultivation Program)of Shanghai Sixth People’s Hospital(ynms202203).
文摘Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.Skeletal muscle,as a major metabolic organ system,undergoes significant remodeling during ALI.However,its specific regulatory contributions remain largely uncharacterized.Methods:Partial(2/3)hepatectomy and acetaminophen were used to induce ALI in male mice.RNA-sequencing(RNA-seq),assay for transposase-accessible chromatin by sequencing(ATAC-seq),chromatin immunoprecipitation,luciferase assay,Western blotting,TUNEL assay,immunohistochemistry,and phase separation assays were performed to reveal the transcriptional axis involved.Serum fibroblast growth factor binding protein 1(FGFBP1)protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.Results:Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid(GC)signaling-mediated regulation of fibroblast growth factor 6(FGF6)in skeletal muscle metabolism.Muscle-specific knockdown of GC receptor(GR)exacerbates ALI and suppresses liver regeneration.Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration,with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown.Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling.Moreover,FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane.Circulating FGFBP1 subsequently interacts with hepatic FGF5 through LLPS mechanisms to regulate liver regeneration.Conclusion:Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis,providing a potential therapeutic target and treatment strategy for ALI.
基金supported by the Grand Science and Technology Special Project in Shanxi Province(202201140601025-2)the National Natural Science Foundation of China(32201749)supported by the Agriculture and Food Research Initiative Competitive Grant 2022-68013-36439(WheatCAP)from the USDA National Institute of Food and Agriculture.
文摘The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval at the B1 locus on chromosome 5A,which included the candidate gene encoding a zinc finger protein(TraesCS5A01G542800)as an awn length inhibitor(ALI).The Ali-A1 allele for the awnless trait showed abundant sequence differences in the promoter regions compared to the ali-A1 allele for the long-awn trait.The results of the swap experiment on the promoters from the two ALI-A1 alleles showed that the two promoters caused a difference in the protein level,indicating the gene was regulated at the transcript level.However,the ali-A1 allele contained an SNP that caused a premature stop codon in its coding region,resulting in a truncated protein compared to the functional Ali-A1 protein.The Ali-A1 protein contained two ethylene-responsive element binding factor-associated amphiphilic repression(EAR)motifs,one at the N terminus(EAR-N)and the other at the C terminus(EAR-C),and they were involved in interactions with the wheat co-repressor protein TOPLESS(TPL1).The ali-A1 protein retained the EAR-N motif but lost the EAR-C motif,resulting in the attenuated ability to interact with TPL1.The tpl1 mutant produced a longer awn compared to the wild type.Ali-A1 repressed the transcription of two downstream genes,TaLRP-A1 and TaARF-B1,involved in endogenous auxin concentrations and auxin responses in wheat.We concluded that the awn length is regulated not only by the ALI-A1 gene at transcript levels but also by Ali-A1 and TPL1 at the protein level in wheat.
基金Supported by Biotropics Malaysia Berhad,Malaysia,NN-2021-016.
文摘BACKGROUND Herbal supplements are increasingly used to manage menopausal symptoms.Physta®is a commercial herbal ingredient containing Eurycoma longifolia standardized water extract,traditionally used for vitality.Its adaptogenic and anti-inflammatory properties promote hormonal balance,physical function,and sexual health,supporting its potential benefits for menopausal health.AIM To investigate Physta®’s role in improving menopausal quality of life,mood states,and overall safety profile compared with placebo.METHODS In this 12-week,randomized,double-blind,placebo-controlled trial,138 females aged 40-55 with menopausal symptoms were randomly assigned to receive Physta®50 mg,Physta®100 mg,or placebo.MENQOL and POMS were assessed at baseline,week 6,and week 12.Safety outcomes were evaluated through biochemical tests,vital signs,and female reproductive hormonal profile.RESULTS Physta®100 mg significantly reduced total MENQOL scores by 33.9%from baseline to week 12(P=0.049)with notable improvements in the physical(-36.4%,P=0.046)and sexual(-36.3%,P=0.043)domains.Total mood disturbance also declined more in the Physta®100 mg group(-38.6%)compared with placebo(-30.1%),although not statistically significant.No significant changes were observed in the vital signs and biochemical parameters,indicating the safety and tolerability of Physta®.No significant alterations were found in the female reproductive hormone profile,supporting its hormonal neutrality.CONCLUSION Physta®100 mg improved menopausal quality of life and mood without adverse effects,supporting its potential as a safe herbal therapy.Further studies with higher doses and longer durations are needed.
基金Supported by Scientific Research Start-up Fund for Introduced PhD.Talents of Guangxi University of Chinese Medicine,2023(2023BS024)Basic Research Ability Enhancement Project for Young and Middle-aged Teachers in Guangxi Universities(2022KY0286)+2 种基金Guangxi Key Research and Development Program(Guike AB21196016)Guangxi Science and Technology Base and Talent Special Project(Guike AD21238031)Guangxi Key Discipline of Zhuang Medicine in Chinese Medicine(GZXK-Z-20-64).
文摘[Objectives]To investigate the protective effects of xanthoxylin on acute lung injury induced by D-Galactosamine(D-GalN)and Lipopolysaccharide(LPS)in rats.[Methods]Sixty male SD rats were randomly divided into a normal group,a model group,a silybin group(50 mg/kg),and three xanthoxylin groups(low-dose,medium-dose,high-dose as 60,120,and 240 mg/kg),10 rats per group.The rats were administered for 17 consecutive days,on day 14,all the rats except for the normal group were intraperitoneally injected with a D-GalN(400 mg/kg)/LPS(30μg/kg)mixture once to establish acute lung injury models.At 72 h after modeling,their serum MCP-1 levels,IL-1β,IL-6,PCT,CRP,TNF-αlevels in bronchoalveolar lavage fluid,and IL-1β,IL-6,TNF-αlevels in lung tissue were measured,and lung tissue histological examination were checked by HE staining.[Results]Compared with the model group,the serum MCP-1 levels,IL-1β,IL-6,PCT,CRP,TNF-αlevels in bronchoalveolar lavage fluid,and IL-1β,IL-6,TNF-αlevels in lung tissue in xanthoxylin groups were significantly decreased(P<0.05 or P<0.01),and lung tissue injury were alleviated.[Conclusions]Xanthoxylin has protective effects on acute lung injury in rats,and it may be related to the increase of anti-inflammatory capacity and the promotion of lung tissue self-healing.
基金supported by National Natural Science Foundation of China(82471792,82270004,81870061,82202382,31770945)Beijing Municipal Natural Science Foundation(7242135)Zhejiang Provincial Natural Science Foundation(LY20H010003).
文摘Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure and death.Despite significant advances in clinical care,ALI/ARDS remains the leading cause of death among intensive care unit patients.Sepsis is the primary risk factor for the development of ALI/ARDS,as excessive inflammatory responses contribute to organ injury and high mortality in critically ill patients.
基金supported by grants from the USA VA(1I01BX004838 and IK6BX006297)the Shenzhen Science and Technology Program(JCYJ20230807142311024).
文摘Background:Sepsis is often accompanied by lactic acidemia and acute lung injury(ALI).Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients.We further observed a significant correlation between the levels of cold-inducible RNA-binding protein(CIRP)in plasma and bronchoalveolar lavage fluid(BALF),as well as lactate levels,and the severity of post-sepsis ALI.The underlying mechanism,however,remains elusive.Methods:C57BL/6 wild type(WT),Casp8^(-/-),Ripk3^(-/-),and Zbp1^(-/-)mice were subjected to the cecal ligation and puncture(CLP)sepsis model.In this model,we measured intra-macrophage CIRP lactylation and the subsequent release of CIRP.We also tracked the internalization of extracellular CIRP(eCIRP)in pulmonary vascular endothelial cells(PVECs)and its interaction with Z-DNA binding protein 1(ZBP1).Furthermore,we monitored changes in ZBP1 levels in PVECs and the consequent activation of cell death pathways.Results:In the current study,we demonstrate that lactate,accumulating during sepsis,promotes the lactylation of CIRP in macrophages,leading to the release of CIRP.Once eCIRP is internalized by PVEC through a Toll-like receptor 4(TLR4)-mediated endocytosis pathway,it competitively binds to ZBP1 and effectively blocks the interaction between ZBP1 and tripartite motif containing 32(TRIM32),an E3 ubiquitin ligase targeting ZBP1 for proteasomal degradation.This interference mechanism stabilizes ZBP1,thereby enhancing ZBP1-receptor-interacting protein kinase 3(RIPK3)-dependent PVEC PANoptosis,a form of cell death involving the simultaneous activation of multiple cell death pathways,thereby exacerbating ALI.Conclusions:These findings unveil a novel pathway by which lactic acidemia promotes macrophage-derived eCIRP release,which,in turn,mediates ZBP1-dependent PVEC PANoptosis in sepsis-induced ALI.This finding offers new insights into the molecular mechanisms driving sepsis-related pulmonary complications and provides potential new therapeutic strategies.
文摘急性肺损伤(ALI)是一种具有高发病率和高死亡率的严重疾病,目前缺乏有效的治疗手段。近年来,干细胞治疗因其多能性和再生能力受到广泛关注。本综述总结了不同类型干细胞(如间充质干细胞、上皮祖细胞、内皮祖细胞等)在急性肺损伤中的治疗潜力,重点阐述了其作用机制、实验研究进展以及临床应用的挑战和未来方向。Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality rates, for which effective treatment options remain elusive. In recent years, stem cell therapy has emerged as a promising approach due to the pluripotency and regenerative capabilities of stem cells. This review explores the therapeutic potential of various stem cell types, including mesenchymal stem cells (MSCs), epithelial progenitor cells, and endothelial progenitor cells, in the context of ALI. It highlights their mechanisms of action, recent advances in experimental studies, and the challenges associated with clinical translation, while providing insights into future research directions.
基金supported by the Zhejiang Provincial Medical Scientific Research Program(No.2022RC136),China.
文摘Coronavirus disease 2019(COVID-19)is a multi-system disease that can lead to various severe complications.Acute limb ischemia(ALI)has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis.However,the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood.Hypercoagulability and thrombosis are considered important mechanisms,but we also emphasize the roles of vasospasm,hypoxia,and acidosis in the pathogenesis of the disease.The angiotensin-converting enzyme 2(ACE2)pathway,inflammation,and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19.Furthermore,we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic,age,and gender perspectives based on our analysis of molecular mechanisms.Additionally,we summarize therapeutic approaches such as use of the interleukin-6(IL-6)blocker tocilizumab,calcium channel blockers,and angiotensin-converting enzyme inhibitors,providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
