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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)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While 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 explained.Within 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 properties.This 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

High day and night temperatures impact on cotton yield and quality——current status and future research direction

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棉花研究(英文) 2023年第3期6卷 209-225页

作者： SAINI Dinesh K. IMPA S.M. mccallister donna PATIL Gunvant B. ABIDI Noureddine RITCHIE Glen JACONIS S.Y. JAGADISH Krishna S.V. Department of Plant and Soil Science Texas Tech UniversityLubbockTX 79410USA Department of Agricultural and Applied Economics Texas Tech UniversityLubbockTX 79410USA Institute of Genomics for Crop Abiotic Stress Tolerance Texas Tech UniversityLubbockTX 79410USA Fiber and Biopolymer Research Institute Texas Tech UniversityLubbockTX 79410USA Cotton Incorporated CaryNC 27513USA

Heat waves,and an increased number of warm days and nights,have become more prevalent in major agricultural regions of the world.Although well adapted to semi-arid regions,cotton is vulnerable to high temperatures,particularly during flowering and boll development.To maintain lint yield potential without compromising its quality under high-temperature stress,it is essential to understand the effects of heat stress on various stages of plant growth and development,and associated tolerance mechanisms.Despite ongoing efforts to gather data on the effects of heat stress on cotton growth and development,there remains a critical gap in understanding the distinct influence of high temperatures during the day and night on cotton yield and quality.Also,identifying mechanisms and target traits that induce greater high day and night temperature tolerance is essential for breeding climate-resilient cotton for future uncertain climates.To bridge these knowledge gaps,we embarked on a rigorous and comprehensive review of published literature,delving into the impact of heat stress on cotton yields and the consequential losses in fiber quality.This review encompasses information on the effects of heat stress on growth,physiological,and biochemical responses,fertilization,cotton yield,and quality.Additionally,we discuss management options for minimizing heat stress-induced damage,and the benefits of integrating conventional and genomics-assisted breeding for developing heat-tolerant cotton cultivars.Finally,future research areas that need to be addressed to develop heat-resilient cotton are proposed.

关键词： Controlled environment Cotton Fiber yield and quality Heat stress Heat tents Reproductive failure

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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 unknown.We 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 signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a conse-quence.In 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 differentiation.Together,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

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 chambers.The presence of significant dilatation is considered an indication for mitral valve intervention,however,aging may affect left ventricular(LV)remodeling independently of valvular disease.The objective of this study was to examine age-related changes in cardiac remodeling in a broad population of patients with chronic MR.METHODS Consecutive subjects that underwent echocardiography examinations recorded in the echocardiography database of a university-affiliated laboratory were retrieved.Subjects were categorized into none/mild,moderate or severe MR.For 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 groups.RESULTS 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 MR.Older patients had significantly smaller LV end-diastolic diameters and volumes and significantly larger left atrial(LA)volumes when compared to the younger group.LA volume index increased in both age groups as MR severity increased,while LV end-diastolic volume increased with increasing MR only in the younger population.CONCLUSIONS Cardiac remodeling in chronic MR is significantly influenced by age.Guideline 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9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 journal.Since our launch in 2019,we have gained a lot of momentum,reviewed thousands ofmanuscripts,and published some of the best work in chemistry.We 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 development.The 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 ligand.Therefore,TRPV1 is also referred as the vanilloidreceptor (VR1) or the capsaicin receptor.VR1 is mainly expressed in a subpopula-tion of primary afferent neurons that project to cardiovascular and renal tissues.These capsaicin-sensitive primary afferent neurons are not only involved in theperception of somatic and visceral pain,but also have a"sensory-effector"function.Regarding the latter,these neurons release stored neuropeptides through a cal-cium-dependent mechanism via the binding of capsaicin to VR1.The most studiedsensory neuropeptides are calcitonin gene-related peptide (CGRP) and substanceP (SP),which are potent vasodilators and natriuretic/diuretic factors.Recent evi-dence using the model of neonatal degeneration of capsaicin-sensitive sensorynerves revealed novel mechanisms that underlie increased salt sensitivity andseveralexperimental models of hypertension.These 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 rats.These data indicate thatsensory nerves counterbalance the prohypertensive effects of several neurohor-monal systems to maintain normal blood pressure when challenged with saltloading.The 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

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 USA 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

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 sensitive hypertension induced by sensory degen

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

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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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