Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to ...Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.展开更多
Background:Chronic obstructive pulmonary disease(COPD)is a progressive chronic inflammatory disease characterized by irreversible airflow limitation.Fritillaria thunbergii Miq.Zhebeimu(ZBM)has a long history in treati...Background:Chronic obstructive pulmonary disease(COPD)is a progressive chronic inflammatory disease characterized by irreversible airflow limitation.Fritillaria thunbergii Miq.Zhebeimu(ZBM)has a long history in treating COPD,but the underlying mechanism is still unclear.Methods:This study explored the pathological mechanism of COPD through RNA-Seq analysis and single-cell sequencing data analysis.And the mechanism of ZBM and blood entering sRNAs for COPD was verified with network pharmacology analysis and in vitro experiments.Results:The results showed that inflammation and oxidative stress exacerbated the progression of COPD,and the expression of HSP90AA1,PTGS2,and AGRN genes significantly increased in the lung tissue of patients.Network pharmacology analysis suggests that the natural products contained in ZBM may directly target HSP90AA1,PTGS2,and AGRN for the treatment of COPD.Analysis of the blood entering sRNA contained in the decoction of ZBM revealed its excellent antioxidant and anti-macrophage polarization effects.Meanwhile,ZBM decoction,sRNA2,and sRNA5 reduce oxidative stress and inflammation by acting on prostaglandin-endoperoxide synthase 2(PTGS2),nitric oxide synthase 2(NOS2),ATP-binding cassette,subfamily C member 1(ABCC1),and xeroderma pigmentosum complementation group C(XPC)genes.Conclusion:Our study demonstrated that ZBM extract and ZBM derived sRNA2 and sRNA5 can relieve COPD by regulating PTGS2-NOS2-XPC-ABCC1 axis.展开更多
BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymph...BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymphangiomas can give rise to complications such as abdominal pain,bleeding,volvulus,and intussusception.Here,we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult.CASE SUMMARY A 66-year-old man presented with intermittent melena,fatigue and refractory anemia nine months prior.Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding.Conservative management,including transfusion,hemostasis,gastric acid secretion inhibition and symptomatic treatment,was performed,but the lesions tended to recur shortly after surgery.Ultimately,the patient underwent capsule endoscopy,which revealed a more than 10 cm lesion accompanied by active bleeding.After singleballoon enteroscopy and biopsy,a diagnosis of jejunal cavernous lymphangioma was confirmed,and the patient underwent surgical resection.No complications or recurrences were observed postoperatively.CONCLUSION Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding.Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis.Surgical resection is an effective management method.展开更多
文摘Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.
文摘Background:Chronic obstructive pulmonary disease(COPD)is a progressive chronic inflammatory disease characterized by irreversible airflow limitation.Fritillaria thunbergii Miq.Zhebeimu(ZBM)has a long history in treating COPD,but the underlying mechanism is still unclear.Methods:This study explored the pathological mechanism of COPD through RNA-Seq analysis and single-cell sequencing data analysis.And the mechanism of ZBM and blood entering sRNAs for COPD was verified with network pharmacology analysis and in vitro experiments.Results:The results showed that inflammation and oxidative stress exacerbated the progression of COPD,and the expression of HSP90AA1,PTGS2,and AGRN genes significantly increased in the lung tissue of patients.Network pharmacology analysis suggests that the natural products contained in ZBM may directly target HSP90AA1,PTGS2,and AGRN for the treatment of COPD.Analysis of the blood entering sRNA contained in the decoction of ZBM revealed its excellent antioxidant and anti-macrophage polarization effects.Meanwhile,ZBM decoction,sRNA2,and sRNA5 reduce oxidative stress and inflammation by acting on prostaglandin-endoperoxide synthase 2(PTGS2),nitric oxide synthase 2(NOS2),ATP-binding cassette,subfamily C member 1(ABCC1),and xeroderma pigmentosum complementation group C(XPC)genes.Conclusion:Our study demonstrated that ZBM extract and ZBM derived sRNA2 and sRNA5 can relieve COPD by regulating PTGS2-NOS2-XPC-ABCC1 axis.
文摘BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymphangiomas can give rise to complications such as abdominal pain,bleeding,volvulus,and intussusception.Here,we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult.CASE SUMMARY A 66-year-old man presented with intermittent melena,fatigue and refractory anemia nine months prior.Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding.Conservative management,including transfusion,hemostasis,gastric acid secretion inhibition and symptomatic treatment,was performed,but the lesions tended to recur shortly after surgery.Ultimately,the patient underwent capsule endoscopy,which revealed a more than 10 cm lesion accompanied by active bleeding.After singleballoon enteroscopy and biopsy,a diagnosis of jejunal cavernous lymphangioma was confirmed,and the patient underwent surgical resection.No complications or recurrences were observed postoperatively.CONCLUSION Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding.Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis.Surgical resection is an effective management method.
