Chronic obstructive pulmonary disease(COPD)is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.The prevalence of COPD has increased over the last decade and the drugs ...Chronic obstructive pulmonary disease(COPD)is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it,such as glucocorticoids and bronchodilators,have significant therapeutic effects;however,they also cause side effects,including infection and immunosuppression.Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.Among these new drugs,we focussed on thioredoxin(Trx).Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance,blocking the NF-κB and MAPK signalling pathways,suppressing the activation and migration of inflammatory cells and the production of cytokines,inhibiting the synthesis and the activation of adhesion factors and growth factors,and controlling the cAMP-PKA and PI3K/Akt signalling pathways.The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.In addition,Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor(MIF).Taken together,these findings suggest that Trx may be the ideal drug for treating COPD.展开更多
To probe the scale inhibition mechanisms,calcium carbonate scale occurring before and after the ad- dition of scale inhibitors was collected.The results from scale SEM confirm that,without scale inhibitor, calcium car...To probe the scale inhibition mechanisms,calcium carbonate scale occurring before and after the ad- dition of scale inhibitors was collected.The results from scale SEM confirm that,without scale inhibitor, calcium carbonate scale shows rhombohedron and hexagon,which are the characteristic feathers of calcite.After addition of inhibitors,morphology of scale is changed,and the more efficient the scale inhibitor is,the more greatly the morphology is modified.To elucidate the scale constitute,they were further analyzed by FT-IR,XRD.Besides calcite,vaterite and aragonite occur in calcium carbonate scale after addition of inhibitors,and the higher scale inhibition efficiency is,the more vaterite presents in scale.It can be concluded that the alteration of morphology is ascribed to the change of crystal form. There are three stages in the crystallizing process including occurrence and disappearing of unstable phase,occurrence and disappearing of metastable phase,development of stable phase.Without scale inhibitors,metastable phases usually transform into stable phase,thus the main constitute of formed scale is calcite.When scale inhibitors are added,both formation and transformation of metastable phases are inhibited,which results in the occurrence of aragonite and vaterite.From the fact that more vaterite presents in scale with a more efficient scale inhibitor added,we can see that the function of scale inhibitor is realized mainly by controlling the crystallizing process at the second stage.展开更多
Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis(OA). Exosomes are detectable in the human...Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis(OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. In addition, exosomes from stem cells can protect the OA joint from damage by promoting cartilage repair, inhibiting synovitis, and mediating subchondral bone remodeling.This review summarizes the roles and therapeutic potential of exosomes in OA and discusses the perspectives and challenges related to exosome-based treatment for OA patients in the future.展开更多
Chronic hyperglycemia is one of the main characteristics of diabetes. Persistent exposure to elevated glucose levels has been recognized as one of the major causal factors of diabetic complications. In pathologies, li...Chronic hyperglycemia is one of the main characteristics of diabetes. Persistent exposure to elevated glucose levels has been recognized as one of the major causal factors of diabetic complications. In pathologies, like type 2 diabetes mellitus(T2DM), mechanical and biochemical stimuli activate profibrotic signaling cascades resulting in myocardial fibrosis and subsequent impaired cardiac performance due to ventricular stiffness. High levels of glucose nonenzymatically react with long-lived proteins, such as collagen, to form advanced glycation end products(AGEs). AGE-modified collagen increase matrix stiffness making it resistant to hydrolytic turnover, resulting in an accumulation of extracellular matrix(ECM) proteins. AGEs account for many of the diabetic cardiovascular complications through their engagement of the receptor for AGE(RAGE). AGE/RAGE activation stimulates the secretion of numerous profibrotic growth factors, promotes increased collagen deposition leading to tissue fibrosis, as well as increased RAGE expression. To date, the AGE/RAGE cascade is not fully understood. In this review, we willdiscuss one of the major fibrotic signaling pathways, the AGE/RAGE signaling cascade, as well as propose an alternate pathway via Rap1 a that may offer insight into cardiovascular ECM remodeling in T2 DM. In a series of studies, we demonstrate a role for Rap1 a in the regulation of fibrosis and myofibroblast differentiation in isolated diabetic and non-diabetic fibroblasts. While these studies are still in a preliminary stage, inhibiting Rap1 a protein expression appears to down-regulate the molecular switch used to activate the ζ isotype of protein kinase C thereby promote AGE/RAGE-mediated fibrosis.展开更多
tRNA-derived small RNAs(tsRNAs),including tRNA-derived fragments(tRFs)and tRNA halves(tiRNAs),are small regulatory RNAs processed from mature tRNAs or precursor tRNAs.tRFs and tiRNAs play biological roles through a va...tRNA-derived small RNAs(tsRNAs),including tRNA-derived fragments(tRFs)and tRNA halves(tiRNAs),are small regulatory RNAs processed from mature tRNAs or precursor tRNAs.tRFs and tiRNAs play biological roles through a variety of mechanisms by interacting with proteins or mRNA,inhibiting translation,and regulating gene expression,the cell cycle,and chromatin and epigenetic modifications.The establishment and application of research technologies are important in understanding the biological roles of tRFs and tiRNAs.To study the molecular mechanisms of tRFs and tiRNAs,researchers have used a variety of bioinformatics and molecular biology methods,such as microarray analysis,real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR);Northern blotting;RNA sequencing(RNA-seq);cross-linking,ligation and sequencing of hybrids(CLASH);and photoactivatable-ribonucleoside-enhanced cross-linking and immunoprecipitation(PAR-CLIP).This paper summarizes the classification,action mechanisms,and roles of tRFs and tiRNAs in human diseases and the related signal transduction pathways,targeted therapies,databases,and research methods associated with them.展开更多
There are still controversies about the roles of microRNA-26a（miR-26a）in human malignancies,as it is a tumor suppressor in breast cancer,gastric cancer,and hepatocellular carcinoma,but is an oncogene in glioma and c...There are still controversies about the roles of microRNA-26a（miR-26a）in human malignancies,as it is a tumor suppressor in breast cancer,gastric cancer,and hepatocellular carcinoma,but is an oncogene in glioma and cholangiocarcinoma.Until now,the function of miR-26a in osteosarcoma remains largely elusive.Here,we found that miR-26a was downregualted in osteosarcoma tissues.Using in vitro and in vivo assays,we confirmed that miR-26a could inhibit the abilities of in vitro proliferation and suppress in vivo tumor growth in mouse model.Furthermore,we identified insulin-like growth factor 1（IGF-1）as a novel and direct target of miR-26a and revealed that miR-26a exerted its tumor-suppressor function,at least in part,by inhibiting IGF-1expression.These findings contribute to our understanding of the functions of miR-26a in osteosarcoma.展开更多
文摘Chronic obstructive pulmonary disease(COPD)is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it,such as glucocorticoids and bronchodilators,have significant therapeutic effects;however,they also cause side effects,including infection and immunosuppression.Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.Among these new drugs,we focussed on thioredoxin(Trx).Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance,blocking the NF-κB and MAPK signalling pathways,suppressing the activation and migration of inflammatory cells and the production of cytokines,inhibiting the synthesis and the activation of adhesion factors and growth factors,and controlling the cAMP-PKA and PI3K/Akt signalling pathways.The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.In addition,Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor(MIF).Taken together,these findings suggest that Trx may be the ideal drug for treating COPD.
文摘To probe the scale inhibition mechanisms,calcium carbonate scale occurring before and after the ad- dition of scale inhibitors was collected.The results from scale SEM confirm that,without scale inhibitor, calcium carbonate scale shows rhombohedron and hexagon,which are the characteristic feathers of calcite.After addition of inhibitors,morphology of scale is changed,and the more efficient the scale inhibitor is,the more greatly the morphology is modified.To elucidate the scale constitute,they were further analyzed by FT-IR,XRD.Besides calcite,vaterite and aragonite occur in calcium carbonate scale after addition of inhibitors,and the higher scale inhibition efficiency is,the more vaterite presents in scale.It can be concluded that the alteration of morphology is ascribed to the change of crystal form. There are three stages in the crystallizing process including occurrence and disappearing of unstable phase,occurrence and disappearing of metastable phase,development of stable phase.Without scale inhibitors,metastable phases usually transform into stable phase,thus the main constitute of formed scale is calcite.When scale inhibitors are added,both formation and transformation of metastable phases are inhibited,which results in the occurrence of aragonite and vaterite.From the fact that more vaterite presents in scale with a more efficient scale inhibitor added,we can see that the function of scale inhibitor is realized mainly by controlling the crystallizing process at the second stage.
基金supported by the National Key Research and Development Program of China (2018YFA0800802)the National Natural Science Foundation of China (No. 81530071+5 种基金No. 31571382No. 81871817)the Key Project of Innovation Program in Military Medicine (16CXZ016)the Sports Scientific Research Project of Chongqing (B201801)the Basic and Advanced Research Project in Chongqing (cstc2017jcyjAX0148)the Project of the State Key Laboratory of Trauma, Burns and Combined Injury (No. SKLZZ(Ⅲ)201601)。
文摘Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis(OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. In addition, exosomes from stem cells can protect the OA joint from damage by promoting cartilage repair, inhibiting synovitis, and mediating subchondral bone remodeling.This review summarizes the roles and therapeutic potential of exosomes in OA and discusses the perspectives and challenges related to exosome-based treatment for OA patients in the future.
基金Supported by Grants from the American Heart Association,No.SDG5310006(JAS)and No.BGIA4150122(JAS)
文摘Chronic hyperglycemia is one of the main characteristics of diabetes. Persistent exposure to elevated glucose levels has been recognized as one of the major causal factors of diabetic complications. In pathologies, like type 2 diabetes mellitus(T2DM), mechanical and biochemical stimuli activate profibrotic signaling cascades resulting in myocardial fibrosis and subsequent impaired cardiac performance due to ventricular stiffness. High levels of glucose nonenzymatically react with long-lived proteins, such as collagen, to form advanced glycation end products(AGEs). AGE-modified collagen increase matrix stiffness making it resistant to hydrolytic turnover, resulting in an accumulation of extracellular matrix(ECM) proteins. AGEs account for many of the diabetic cardiovascular complications through their engagement of the receptor for AGE(RAGE). AGE/RAGE activation stimulates the secretion of numerous profibrotic growth factors, promotes increased collagen deposition leading to tissue fibrosis, as well as increased RAGE expression. To date, the AGE/RAGE cascade is not fully understood. In this review, we willdiscuss one of the major fibrotic signaling pathways, the AGE/RAGE signaling cascade, as well as propose an alternate pathway via Rap1 a that may offer insight into cardiovascular ECM remodeling in T2 DM. In a series of studies, we demonstrate a role for Rap1 a in the regulation of fibrosis and myofibroblast differentiation in isolated diabetic and non-diabetic fibroblasts. While these studies are still in a preliminary stage, inhibiting Rap1 a protein expression appears to down-regulate the molecular switch used to activate the ζ isotype of protein kinase C thereby promote AGE/RAGE-mediated fibrosis.
基金supported by grants from the National Natural Science Foundation of China(no.81974316)the Scientific Innovation Team Project of Ningbo(no.2017C110019)+1 种基金Zhejiang Key Laboratory of Pathophysiology(no.202001)the K.C.Wong Magna Fund in Ningbo University.
文摘tRNA-derived small RNAs(tsRNAs),including tRNA-derived fragments(tRFs)and tRNA halves(tiRNAs),are small regulatory RNAs processed from mature tRNAs or precursor tRNAs.tRFs and tiRNAs play biological roles through a variety of mechanisms by interacting with proteins or mRNA,inhibiting translation,and regulating gene expression,the cell cycle,and chromatin and epigenetic modifications.The establishment and application of research technologies are important in understanding the biological roles of tRFs and tiRNAs.To study the molecular mechanisms of tRFs and tiRNAs,researchers have used a variety of bioinformatics and molecular biology methods,such as microarray analysis,real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR);Northern blotting;RNA sequencing(RNA-seq);cross-linking,ligation and sequencing of hybrids(CLASH);and photoactivatable-ribonucleoside-enhanced cross-linking and immunoprecipitation(PAR-CLIP).This paper summarizes the classification,action mechanisms,and roles of tRFs and tiRNAs in human diseases and the related signal transduction pathways,targeted therapies,databases,and research methods associated with them.
文摘There are still controversies about the roles of microRNA-26a（miR-26a）in human malignancies,as it is a tumor suppressor in breast cancer,gastric cancer,and hepatocellular carcinoma,but is an oncogene in glioma and cholangiocarcinoma.Until now,the function of miR-26a in osteosarcoma remains largely elusive.Here,we found that miR-26a was downregualted in osteosarcoma tissues.Using in vitro and in vivo assays,we confirmed that miR-26a could inhibit the abilities of in vitro proliferation and suppress in vivo tumor growth in mouse model.Furthermore,we identified insulin-like growth factor 1（IGF-1）as a novel and direct target of miR-26a and revealed that miR-26a exerted its tumor-suppressor function,at least in part,by inhibiting IGF-1expression.These findings contribute to our understanding of the functions of miR-26a in osteosarcoma.
