简介:AbstractExtracellular vesicles (EVs) are anuclear particles composed of lipid bilayers that contain nucleic acids, proteins, lipids, and organelles. EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components, including lipids, proteins, messenger RNAs, DNA, microRNAs, organelles, etc, to nearby or distant target cells to activate and regulate the function and phenotype of target cells. Under physiological conditions, EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease, asthma, acute lung injury/acute respiratory distress syndrome, idiopathic pulmonary fibrosis (IPF), and pulmonary artery hypertension. In addition, in multiple preclinical studies, EVs derived from mesenchymal stem cells (EVs) have shown promising therapeutic effects on reducing and repairing lung injuries. Furthermore, in recent years, researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects. This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.
简介:AbstractBackground:Clinically amyopathic dermatomyositis (CADM) is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease (ILD). Poor prognosis of the patients was strongly associated with rapid progressive ILD. The aim of this study was to identify risk factors for prediction of different types of ILD in CADM.Methods:In this study, data of 108 inpatients with CADM were collected, including 87 with ILD. The baseline clinical data and laboratory parameters, including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis (A/SIP) and chronic interstitial pneumonitis (CIP).Results:In 87 patients with CADM-ILD, 39 (36.1%) were A/SIP, and 48 (44.4%) were CIP. There were 22 (20.4%) patients with asymptomatic ILD who were detected by routine high resolution computed tomography. Cytokeratin-19 fragment (CYFRA21-1) was significantly higher in CADM-ILD than that in CADM patients without ILD; carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP. Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5 (MDA5), while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52. Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD, higher titer of anti-MDA5 indicated increased likelihood for A/SIP, and higher titer of anti-Ro-52 was also clearly associated with CIP.Conclusions:This study indicated that the prevalence of ILD was high in CADM. Asymptomatic ILD has been previously underestimated. Anti-MDA5 was a risk factor for the presence of A/SIP, and CYFRA21-1 was a risk factor for ILD.
简介:Despitethehnpactofhighly-activemltiretroviraltherapy(HAART),manifestedasmarkedreductionsintheincidenceofopwrtunistieinfectionsinthelast5,years,respiratoryproblemsstillconstituteamajorburdenofdiseaseinthoseinfectedwithHIV.ReasonsforthisincludethelimitedavailabilityofHAART.worldwide,thefailureofsustainedviralsuppressioninupto50%ofpatientstakingHAART,failureofprophylaxisforspecificopportunisticinfectiorrs,andanincreasingnumberofpatientspresentingwithpreviouslymldiagnosedadvancedHIVinfection.
简介:无
简介:AbstractPurpose:To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury.Methods:Twenty female healthy goats were randomly divided into three groups by different driving pressures: 4.0 MPa group (n = 4), 4.5 MPa group (n = 12) and 5.0 MPa group (n = 4). The severe blast lung injury model of goats was established using a BST-I bio-shock tube. Vital signs (respiration, heart rate and blood pressure), lung ultrasound score (LUS), PO2/FiO2 and extravascular lung water (EVLW) were measured before injury (0 h) and at 0.5 h, 3 h, 6 h, 9 h, 12 h after injury. Computed tomography scan was performed before injury (0 h) and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume. The correlation of LUS with PaO2/FiO2, EVLW, and lung injury ratio (lesion volume/total lung volume*100%) was analyzed. All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination. Statistical analysis was performed by the SPSS 22.0 software. The measurement data were expressed as mean ± standard deviation. The means of two samples were compared using independent-sample t-test. Pearson correlation analysis was conducted.Results:(1) At 12 h after injury, the mortality of goats was 0, 41.67% and 100% in the 4.0 Mpa, 4.5 MPa and 5.0 MPa groups, respectively; the area of pulmonary hemorrhage was 20.00% ± 13.14% in the 4.0 Mpa group and 42.14% ± 15.33% in the 4.5 MPa group. A severe lung shock injury model was established under the driving pressure of 4.5 MPa. (2) The respiratory rate, heart rate, LUS and EVLW were significantly increased, while PaO2/FiO2 was significantly reduced immediately after injury, and then they gradually recovered and became stabilized at 3 h after injury. (3) LUS was positively correlated with EVLW (3 h: r = 0.597, 6 h: r = 0.698, 9 h: r = 0.729; p < 0.05) and lung injury ratio (12 h: r= 0.884, p < 0.05), negatively correlated with PaO2/FiO2 (3 h: r =-0.871, 6 h: r =-0.637, 9 h: r =-0.658; p < 0.05).Conclusion:We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.
简介:AbstractThe complement system plays a key role in the pathogenesis of autoimmune diseases, which usually injures the kidney. More and more studies have shown the pathogenic role and indicated that abnormal activation of the complement system was highly involved in the outbreak of autoimmune diseases. This review mainly introduced recent studies of complement system activation contributing to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, antiphospholipid syndrome, antineutrophil cytoplasmic antibody-associated vasculitides, and so on. Understanding the pathogenic roles of complement activation in various autoimmune diseases will identify potential novel therapeutic targets on complement systems.
简介:AbstractCardiovascular disease (CVD) remains the leading cause of death worldwide. Therefore, exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair, reversing cardiac remodeling, and reducing adverse cardiovascular events. Recently, significant progress has been made in understanding the function of protein kinases and their interactions with other regulatory proteins in myocardial biology. Protein kinases are positioned as critical regulators at the intersection of multiple signals and coordinate nearly every aspect of myocardial responses, regulating contractility, metabolism, transcription, and cellular death. Equally, reconstructing the disrupted protein kinases regulatory network will help reverse pathological progress and stimulate cardiac repair. This review summarizes recent researches concerning the function of protein kinases in CVDs, discusses their promising clinical applications, and explores potential targets for future treatments.
简介:Thearticlediscussestherelationshipbetweenepidemicsandinternationalsecurity.Itanalyzeshowhumaneconomicbehaviorshavebrokentheequilibriumofco-evolution,andexaminesthepossibledangerousimpactsofthisuponhumansociety.Finally,mechanismsofcooperationagainstpandemicsatthegovernmentalandgrassrootslevelarelisted.Theauthorsarguethatonlybyrevisingourconceptionofdevelopmentandestablishinganintegratedunderstandingofglobalprogresscanweachieveinternationalcooperationagainstepidemics.
简介:Background:Depressiondisordercoexistsinchronicdiseaseswithsomaticdiseasesandhashighmorbidity,disabilityandmortality.Currentresearcheshaveconfirmedthatdepressionmaybecausedbycoronaryheartdisease,hypertensionandheartfailure.Meanwhile,cardiovasculardiseasesmaycauseorworsendepression,leadingtoprolongedhospitalizationandcomplications.
简介:SincePresidentObamaannouncedthePrecisionMedicineInitiativeintheUnitedStates,moreandmoreattentionhasbeenpaidtoprecisionmedicine.However,clinicianshavealreadyusedittotreatconditionssuchascancer.Manycardiovasculardiseaseshaveafamilialpresentation,andgeneticvariantsareassociatedwiththeprevention,diagnosis,andtreatmentofcardiovasculardiseases,whicharethebasisforprovidingprecisecaretopatientswithcardiovasculardiseases.Large-scalecohortsandmultiomicsarecriticalcomponentsofprecisionmedicine.Herewesummarizetheapplicationofprecisionmedicinetocardiovasculardiseasesbasedoncohortandomicstudies,andhopetoelicitdiscussionaboutfuturehealthcare.
简介:Theprimarysymptomsofrespiratorydisordersarebreathlessness,chestpainandcough,whichmaybeassociatedwithsputumproduction.However,disordersofthelungscanproducedistantsymptoms(e.g.non-metastaticmanifestationsoflungcancer),andnon-respiratoryconditionssuchasanaemiaandmetabolicacidosscancauseberathlessness.Adequateassessmentofanypatientrequiresafullclinicalhistoryandexamination.Thiscontributionconsidersaspectsdirectlyrelevanttotherespiratorysystem.
简介:AbstractPrions are unconventional infectious agents that cause lethal transmissible neurodegenerative diseases in human and animals. Prions can be distinguished from other known pathogens by their lack of nucleic acids. The most essential process for prion propagation is conversion from normal cellular prion protein on the cell membrane to insoluble, limited protease digestion-resistant, pathogenic scrapie prion protein. For dozens of years, many pharmacological tools and interventions targeting different stages of disease progression have been developed and evaluated, and a few have been entered clinical trials. However, no approved prophylactic or therapeutic drugs for prion diseases are available. In this review, we summarize the current concepts in prion research and discuss advances in the research and development of drugs for the prevention and treatment of prion disease.
简介:Objective:Variousnanoparticleshavebeendesignedandtestedinordertoselectoptimalcarriersfortheinhalationdeliveryofanticancerdrugstothelungs.Methods:Thefollowingnanocarrierswerestudied:micelles,liposomes,mesoporoussilicananoparticles(MSNs),polypropyleneimine(PPI)dendrimer-siRNAcomplexesnanoparticles,quantumdots(QDs),andpoly(ethyleneglycol)polymers.Allparticleswerecharacterizedusingthefollowingmethods:dynamiclightscattering,zetapotential,atomicforcemicroscopy,invitrocyto-andgenotoxicity.Invivoorgandistributionofallnanoparticles,retentioninthelungs,andanticancereffectsofliposomesloadedwithdoxorubicinwereexaminedinnudemiceafterthepulmonaryorintravenousdelivery.Results:Significantdifferencesinlunguptakewerefoundaftertheinhalationdeliveryoflipid-basedandnon-lipid-basednanoparticles.Theaccumulationofliposomesandmicellesinlungsremainedrelativelyhigheven24hafterinhalationwhencomparedwithMSNs,QDs,andPPIdendrimers.Therewerenotabledifferencesbetweennanoparticleaccumulationinthelungsandotherorgans1and3hafterinhalationorintravenousadministrations,but24hafterintravenousinjectionallnanoparticlesweremainlyaccumulatedintheliver,kidneys,andspleen.Inhalationdeliveryofdoxorubicinbyliposomessignificantlyenhanceditsanticancereffectandpreventedsevereadversesideeffectsofthetreatmentinmicebearingtheorthotopicmodeloflungcancer.Conclusion:Theresultsofthestudydemonstratethatlipid-basednanocarriershadconsiderablyhigheraccumulationandlongerretentiontimeinthelungswhencomparedwithnon-lipid-basedcarriersaftertheinhalationdelivery.Theseparticlesaremostsuitableforeffectiveinhalationtreatmentoflungcancer.
简介:AbstractThis review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of "gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome." Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.
简介:因为他们的能力,B房间通常被认为是有免疫力的反应的积极管理者生产抗体,包括自身抗体。因为B房间用作介绍抗原的房间并且在有免疫力的回答施加另外的调节功能,抗体的生产便于最佳的CD4+T房间激活。然而,某些B房间能否定地也由生产规章的cytokines并且直接经由cell-to-cell接触与病原的T房间交往调整有免疫力的反应。B房间的这些类型被定义为规章的B(Breg)房间。Breg房间的规章的函数在发炎的鼠标模型被表明了,癌症,移植,并且特别地在autoimmunity。在这评论,我们集中于在人的自体免疫的疾病导致发展的理解和Breg房间的功能和B房间的含意的最近的进展。
简介:肝疾病包含许多肝条件,包括肝失败,肝肝硬化和尖锐、长期的肝炎的一个系列,例如酒鬼,丰满,药,病毒、长期的肝炎。肝损害是在肝疾病的一个主要原因的因素;通常,这些因素包括直接的肝损坏和调停免疫者的肝损害。Neutrophils(也作为neutrophilicgranulocytes或polymorphonuclear白血球(PMN)知道)是在人的最丰富的传播的白血房间类型,并且PMN是一个主要天生的有免疫力的房间子集。到微脉管系统的neutrophils的不恰当的激活和homing贡献肝疾病的许多类型的病理学的表明。这评论总结基于临床的电流和动物模型研究的嗜中性调停肝损害的新奇概念。