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Dysregulated bidirectional epithelial-mesenchymal crosstalk:A core determinant of lung fibrosis progression

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 27-33页

作者： Liudi Yao Zijian Xu donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK Clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK

Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)***-ing of disease pathogenesis remains limited and has prevented the development of effective *** an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully *** human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory *** review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

关键词： Lung fibrosis Epithelial-mesenchymal transition(EMT) Crosstalk

LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

End-tidal capnometry during emergency department procedural sedation and analgesia： a randomized, controlled study

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World Journal of Emergency Medicine 2016年第1期7卷 13-18页

作者： Samuel G. Campbell Kirk D. Magee Peter J. Zed Patrick Froese Glenn Etsell Alan LaPierre donna warren Robert R. MacKinley Michael B. Butler George Kovacs David A. Petrie Department of Emergency Medicine and Anesthesia Dalhousie University Halifax Nova Scotia Canada Faculty of Pharmaceutical Sciences and Department of Emergency Medicine University of British Columbia Vancouver BC Canada Charles V. Keating Emergency and Trauma Centre Halifax Nova Scotia Canada Department of Emergency Medicine Anesthesia and Anatomy Dalhousie University Halifax Nova Scotia Canada

BACKGROUND:This prospective,randomized trial was undertaken to evaluate the utility of adding end-tidal capnometry(ETC)to pulse oximetry(PO)in patients undergoing procedural sedation and analgesia(PSA)in the emergency department(ED).METHODS:The patients were randomized to monitoring with or without ETC in addition to the current standard of *** endpoints included respiratory adverse events,with secondary endpoints of level of sedation,hypotension,other PSA-related adverse events and patient ***:Of 986 patients,501 were randomized to usual care and 485 to additional ETC *** this series,48%of the patients were female,with a mean age of 46 *** manipulations(71%),cardioversion(12%)and abscess incision and drainage(12%)were the most common procedures,and propofol and fentanyl were the sedative/analgesic combination used for most *** was no difference in patients experiencing de-saturation(Sa O2<90%)between the two groups;however,patients in the ETC group were more likely to require airway repositioning(12.9%vs.9.3%,P=0.003).Hypotension(SBP<100 mm Hg or<85 mm Hg if baseline<100 mm Hg)was observed in 16(3.3%)patients in the ETC group and 7(1.4%)in the control group(P=0.048).CONCLUSIONS:The addition of ETC does not appear to change any clinically significant *** found an increased incidence of the use of airway repositioning maneuvers and hypotension in cases where ETC was *** do not believe that ETC should be recommended as a standard of care for the monitoring of patients undergoing PSA.

关键词： Procedural sedation and analgesia Capnography Adverse events Emergency medicine

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The impact of aging on cardiac remodeling in chronic mitral regurgitation

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Journal of Geriatric Cardiology 2023年第10期20卷 748-755页

作者： David Leibowitz donna Zwas Ronen Beeri Ronny Alcalai Israel Gotsman Heart Institute Hadassah Medical Center and Faculty of MedicineHebrew University of JerusalemJerusalemIsrael

BACKGROUND Chronic mitral regurgitation(MR)is a volume overload state that causes dilatation of the left sided cardiac *** presence of significant dilatation is considered an indication for mitral valve intervention,however,aging may affect left ventricular(LV)remodeling independently of valvular *** objective of this study was to examine age-related changes in cardiac remodeling in a broad population of patients with chronic *** Consecutive subjects that underwent echocardiography examinations recorded in the echocardiography database of a university-affiliated laboratory were *** were categorized into none/mild,moderate or severe *** purposes of analysis of differences with aging,the population was divided into groups above and below 70 years of age and standard echocardiographic measurements were compared between the *** A total of 3492 subjects with at least moderate MR(mean age:76 years,52%female)were included in the study and compared to 18,250 subjects with none or mild *** patients had significantly smaller LV end-diastolic diameters and volumes and significantly larger left atrial(LA)volumes when compared to the younger *** volume index increased in both age groups as MR severity increased,while LV end-diastolic volume increased with increasing MR only in the younger *** Cardiac remodeling in chronic MR is significantly influenced by *** based recommendations of timing of mitral valve interventions in asymptomatic MR patients,based on assessment of LA and LV remodeling,may need to take age into account.

关键词： remodeling mitral cardiac

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Editorial

CCS Chemistry 2023年第11期5卷 1-4页

作者： Xi Zhang donna J.Minton CCS Beijing Peoples R China

“A journey of a thousand miles begins with a single step.”—Laozi,Chinese philosopher Welcome to the first issue of CCS Chemistry for 2023!We are excited to be starting on our fifth volume of the *** our launch in 2019,we have gained a lot of momentum,reviewed thousands ofmanuscripts,and published some of the best work in *** have been very fortunate during that time to have Prof.

关键词： chemistry. journal gained

The vanilloid receptor and hypertension

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Acta Pharmacologica Sinica 2005年第3期26卷 286-294页

作者： donna H WANG Department of Medicine College of Human Medicine East Lansing MI 48825 Michigan State University USA

Mammalian transient receptor potential (TRP) channels consist of six related pro-tein sub-families that are involved in a variety of pathophysiological function,anddisease *** TRPV 1 channel,a member of the TRPV sub-family,isidentified by expression cloning using the"hot"pepper-derived vanilloid com-pound capsaicin as a ***,TRPV1 is also referred as the vanilloidreceptor (VR1) or the capsaicin ***1 is mainly expressed in a subpopula-tion of primary afferent neurons that project to cardiovascular and renal *** capsaicin-sensitive primary afferent neurons are not only involved in theperception of somatic and visceral pain,but also have a"sensory-effector"*** the latter,these neurons release stored neuropeptides through a cal-cium-dependent mechanism via the binding of capsaicin to *** most studiedsensory neuropeptides are calcitonin gene-related peptide (CGRP) and substanceP (SP),which are potent vasodilators and natriuretic/diuretic *** evi-dence using the model of neonatal degeneration of capsaicin-sensitive sensorynerves revealed novel mechanisms that underlie increased salt sensitivity andseveralexperimental models of *** mechanisms include insuffi-cient suppression of plasma renin activity and plasma aldosterone levels subse-quent to salt loading,enhancement of sympathoexcitatory response in the face ofa salt challenge,activation of the endothelin-1 receptor,and impaired natriureticresponse to salt loading in capsaicin-pretreated *** data indicate thatsensory nerves counterbalance the prohypertensive effects of several neurohor-monal systems to maintain normal blood pressure when challenged with *** therapeutic utilities of vanilloid compounds,endogenous agonists,and sensory neuropeptides are also discussed.

关键词： TRP family afferent neurons capsaicin calcitonin gene-related peptide substance P vanilloid receptor renin-angiotensin-aldosterone system endothelin,sympathetic nervous system salt-sensitive hypertension

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Editorial

CCS Chemistry 2023年第12期5卷 2674-2678页

作者： Qilin Zhou Xi Zhang donna J.Minton 不详 CCS

“These two tetrahedra are symmetrical;they cannot be superimposed:they are in relation to each other what an image is,in a mirror,in relation to the real thing.”1—Louis Pasteur,on the Discovery of Chirality,1848.

关键词： mirror symmetrical Chiral

Neuroimmune actions in the brain and interactions with the effects of alcohol

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Neural Regeneration Research 2021年第9期16卷 1791-1792页

作者： donna L.Gruol Neuroscience Department The Scripps Research InstituteLa JollaCAUSA

The neuroimmune system of the brain:Early studies(1990’s)on the neurological consequences of human immunodeficiency virus-1(HIV-1)infection in the brain were instrumental in establishing that specific brain cell types can function as an innate immune system within the brain and in that role influence cognitive function(Kaul et al.,2005).

关键词： Neuroimmune actions in the brain and interactions with the effects of alcohol

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Increased salt sensitivity induced by sensory denervation: role of superoxide

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Acta Pharmacologica Sinica 2004年第12期25卷 60-66页

作者： Alex F CHEN,donna H WANG Department of Medicine and Pharmacology & Toxicology Michigan State University East Lansing MI 48824 USA Department of Medicine and Pharmacology & Toxicology Michigan State University East Lansing MI 48824 USA

AIM: To test the hypothesis that production of superoxide in mesenteric resistance arteries is increased and con- tributes to the development of hypertension induced by sensory denervation plus high salt intake. METHODS: Newborn Wistar rats were given capsaicin 50 mg/kg sc on the 1st and 2nd d of life. After weaning, male rats were grouped as follows and treated for 3 weeks with: capsaicin pretreatment plus normal sodium diet (0.5 %, CAP-NS), CAP plus high sodium diet (4 %, CAP-HS), control plus NS (CON-NS), or CON-HS. Both tail-cuff systolic blood pressure and mean arterial pressure (MAP) were measured in each of the groups. Western blot analysis was used for measurement of manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) in the mesenteric resistance arteries. Lucigenin chemiluminescence assay was used for superoxide production in the mesenteric resistance arteries. The Griess method was used for measurement of nitrite/nitrate levels in plasma. RESULTS: Both tail-cuff pressure and MAP were higher in CAP-HS compared with CAP-NS, CON-HS, and CON- NS rats (P<0.05). Both MnSOD and eNOS in the mesenteric resistance arteries were increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, nitrite/nitrate levels in plasma were not different among 4 groups. Acute iv administration of tempol, a membrane-permeable superoxide scavenger, de- creased MAP in both CAP-HS and CON-HS when compared with their respective controls. However, the de- creases of MAP between these two groups were not different. Chronic treatment with tempol failed to prevent the development of hypertension in CAP-HS rats. Superoxideproduction in the mesenteric resistance arteries was increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, chronic treatment with tempol did not prevent the increase of mesenteric superoxideproduction in CAP-HS rats. CONCLUSIONS: Regardless of increased vascular MnSOD levels, salt

关键词： superoxides tempol afferent neurons capsaicin denervation dietary sodium chloride nitric oxide