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Congenital Heart Disease 2024年第2期19卷 185-195页

作者： Camden L.Hebson Kyle Bliton Amr Y.Hammouda Kaitlyn Barr W.Hampton Gray Mohini Gunnett Waldemar F.Carlo Department of Pediatrics Division of Pediatric CardiologyUniversity of Alabama BirminghamBirmingham35233USA Department of Pediatrics Division of Pediatric PulmonologyUniversity of Alabama BirminghamBirmingham35233USA Department of Pediatrics University of Alabama BirminghamBirmingham35233USA Department of Surgery Division of Cardiothoracic SurgeryUniversity of Alabama BirminghamBirmingham35233USA

D-transposition of the great arteries(d-TGA)is surgically repaired with the arterial switch operation(ASO)with excellent results,however short and long-term morbidities still develop including neurocognitive *** significant central sleep apnea is uncommon in non-premature infants,but when present indicates immature autonomic control of respiration likely due to a neurologic *** report the unanticipatedfinding of central sleep apnea in four-term neonates with d-TGA after uncomplicated ASO,with the short-term complication of delayed hospital discharge and long-term concerns regarding this early marker of brain immaturity and its hindrance to normal *** this report,we will review each patient’s clinical course and then examine the literature on pediatric central sleep apnea,neurodevelopmental outcomes after ASO,and the important overlap of these entities in the care of patients going forward.

关键词： Transposition congenital heart disease sleep apnea polysomnography

Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： Peter H.King Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA birmingham Veterans Affairs Medical Center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary *** progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease *** on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom *** 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for *** Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the *** muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal *** accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real *** advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and *** technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of *** are two major goals of this *** first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activi

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

Two-stage corrective operation for the treatment of pes cavovarus in patients with spina bifida

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World Journal of Orthopedics 2024年第7期15卷 618-626页

作者： Anthony Mack Padgett Ezan Kothari Michael J Conklin Department of Orthopedics Indiana UniversityIndianapolisIN 46202United States Department of Orthopaedic Surgery University of Alabama at BirminghamBirminghamAL 35233United States Department of Orthopedic Surgery Children’s of AlabamaBirminghamAL 35233United States

BACKGROUND Pes cavovarus has an estimated incidence of 8%-17%in patients with spina bifida(SB).The majority of the current literature on surgical treatment of cavovarus feet in children and adolescents includes a variety of *** are currently no case series describing a treatment algorithm for deformity correction in this specific patient *** authors of this study present the results of a retrospective case series performed to assess the radiographic outcomes of two-stage corrective surgery in patients with *** Retrospective chart review was performed on patients with SB with a diagnosis of pes cavovarus at a freestanding children’s hospital who underwent surgical correction of the *** were excluded for lack of two-stage corrective operation,nonambulatory status,lack of at least six months follow-up,and age>18 years at the time of *** resulted in a cohort of 19 *** analysis was performed on 11 feet that had a complete series of preoperative and postoperative weightbearing *** and postoperative radiographic outcome measurements were compared using a two-sample *** Significant changes between the preoperative and postoperative measurements were seen in Meary’s angle,the anteroposterior talo-first metatarsal(AP TMT1)angle,and the talonavicular *** values of Meary’s angle were 17.9±13.1 preoperatively and 4.7±10.3 postoperatively(P=0.016).Mean AP TMT1 angle was 20.6±15.1 preoperatively and 9.3±5.5 postoperatively(P=0.011).Mean talonavicular coverage values were-10.3±9.6 preoperatively and-3.8±10.1 postoperatively(P=0.025).CONCLUSION The two-stage corrective procedure demonstrated efficacy in correcting cavovarus deformity in patients with *** should strongly consider employing the staged surgical algorithm presented in this manuscript for management of these patients.

关键词： Cavovarus Spina bifida Osteotomy Plantar release Radiographs Pediatrics

Nature’s Pharmacy under Siege: Investigating Antibiotic Resistance Pattern in Endophytic Bacteria of Medicinal Plants

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Advances in Microbiology 2024年第4期14卷 183-208页

作者： Bonoshree Sarkar Afroza Sultana Nabila Nawar Binti Farhana Tasnim Chowdhury Sadia Afrin Mohammad Fahim Taibur Rahman Atiqur Rahman Infection Biology Laboratory Department of Biochemistry and Molecular Biology University of Dhaka Dhaka Bangladesh Department of Pathology University of Alabama at Birmingham Birmingham USA

Antibiotic resistance poses a significant global health threat, necessitating a thorough understanding of its prevalence in various ecological contexts. Medicinal plants, renowned for their therapeutic properties, host endophytic bacteria that produce bioactive compounds. Understanding antibiotic resistance dynamics in these bacteria is vital for human health and antibiotic efficacy preservation. In this study, we investigated antibiotic resistance profiles in endophytic bacteria from five medicinal plants: Thankuni, Neem, Aparajita, Joba, and Snake plant. We isolated and characterized 113 endophytic bacteria, with varying resistance patterns observed against multiple antibiotics. Notably, 53 strains were multidrug-resistant (MDR), with 14 exhibiting extensive drug resistance (XDR). Thankuni-associated bacteria displayed 44% MDR and 11% XDR, while Neem-associated bacteria showed higher resistance (60% MDR, 13% XDR). Aparajita-associated bacteria had lower resistance (22% MDR, 6% XDR), whereas Joba-associated bacteria exhibited substantial resistance (54% MDR, 14% XDR). Snake plant-associated bacteria showed 7% MDR and 4% XDR. Genus-specific distribution revealed Bacillus (47%), Staphylococcus (21%), and Klebsiella (11%) as major contributors to MDR. Our findings highlight diverse drug resistance patterns among plant-associated bacteria and underscore the complexity of antibiotic resistance dynamics in diverse plant environments. Identification of XDR strains emphasizes the severity of the antibiotic resistance problem, warranting further investigation into contributing factors.

关键词： Antibiotic Resistance Endophytic Bacteria Medicinal Plants Drug Resistance

Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis

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Research 2024年第2期2023卷 123-137页

作者： Di Xiang Lei Jiang Qiong Yuan Yang Yu Ruiming Liu Meiting Chen Zheng Kuai Wendy Zhang Fan Yang Tingting Wu Zhiyu He Zuhui Ke Wanzi Hong Pengcheng He Ning Tan Yeying Sun Zhen Shi Xuebiao Wei Jianfang Luo Xiaoqiu Tan Yuqing Huo Gangjian Qin Chunxiang Zhang Department of Cardiology Key Laboratory of Medical ElectrophysiologyMinistry of EducationInstitute of Cardiovascular ResearchThe Affiliated Hospital of Southwest Medical UniversitySouthwest Medical UniversityLuzhouSichuan 646000China Department of Biomedical Engineering School of Medicine The University of Alabama at BirminghamBirminghamAL 35233USA Department of Cardiology.Guangdong Cardiovascular Institute Guangdong Provincial Key Laboratory of Coronary Heart Disease PreventionGuangdong Provincial Institute of Geriatric MedicineGuangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510100China Vascular Biology Center Medical College of GeorgiaAugusta UniversityAugustaGA 30912USA

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including *** non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still *** study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and *** identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with *** cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage *** differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid ***,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage *** role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout *** identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage *** provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in *** results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in *** results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.

关键词： inhibited Mor markedly

Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now

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World Journal of Diabetes 2024年第5期15卷 797-809页

作者： Joseph M Pappachan Cornelius James Fernandez Ambika P Ashraf Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology&Metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Division of Pediatric Endocrinology and Diabetes Department of PediatricsUniversity of Alabama at BirminghamBirminghamAL 35233United States

Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic *** has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and *** looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most *** there is a collective global effort to curb the devastation caused by the situation,the impact is poised to be pro-found.A multifaceted research effort,governmental legislation,and effective social action are crucial in attaining this *** article delves into the current epidemiological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based management strategies for diabesity.

关键词： Childhood obesity Diabesity Type 2 diabetes mellitus Adolescence Cardiovascular disease Pharmacotherapy

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2022年第2期12卷 511-531页

作者： Steven N.Austad Scott Ballinger Thomas W.Buford Christy S.Carter Daniel L.Smith Jr Victor Darley-Usmar Jianhua Zhang Department of Biology University of Alabama at BirminghamBirminghamAL 35294USA Department of Pathology University of Alabama at BirminghamBirminghamAL 35294USA Department of Medicine University of Alabama at BirminghamBirminghamAL 35294USA Department of Nutrition Sciences University of Alabama at BirminghamBirminghamAL 35294USA

Aging is by far the most prominent risk factor for Alzheimer’s disease(AD),and both aging and AD are associated with apparent metabolic *** developing effective therapeutic interventions to treat AD is clearly in urgent need,the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients,on disease pathogenesis,have been *** is also an increasing awareness of differential risk and potential targeting strategies related to biological sex,microbiome,and circadian *** a major part of intracellular metabolism,mitochondrial bioenergetics,mitochondrial quality-control mechanisms,and mitochondria-linked inflammatory responses have been considered for AD therapeutic *** review summarizes and highlights these efforts.

关键词： Mitochondrial DNA Mitochondrial electron transport chain Mitochondrial quality control Reactive species DAMPs Hexokinase biosynthesis pathway Diabetes Circadian regulation Microbiome

Cathepsin D overexpression in the nervous system rescues lethality and Aβ42 accumulation of cathepsin D systemic knockout in vivo

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4172-4184页

作者： Xiaosen Ouyang Willayat Y.Wani Gloria A.Benavides Matthew J.Redmann Hai Vo Thomas van Groen Victor M.Darley-Usmar Jianhua Zhang Department of Pathology University of Alabama at BirminghamBirminghamAL 35294USA Department of Cell Developmental and Integrative BiologyUniversity of Alabama at BirminghamBirminghamAL 35294USA birmingham VA Medical Center University of Alabama at BirminghamBirminghamAL 35294USA

The lysosome is responsible for protein and organelle degradation and homeostasis and the cathepsins play a key role in maintaining protein quality *** D(CTSD),is one such lysosomal protease,which when deficient in humans lead to neurolipofuscinosis(NCL)and is important in removing toxic protein *** studies demonstrated that CTSD germ-line knockout-CtsdKO(CDKO)resulted in accumulation of protein aggregates,decreased proteasomal activities,and postnatal lethality on Day 26±*** of wildtype CTSD,but not cathepsin B,L or mutant CTSD,decreased a-synuclein toxicity in worms and mammalian *** this study we generated a mouse line expressing human CTSD with a floxed STOP cassette between the ubiquitous CAG promoter and the *** crossing with Nestin-cre,the STOP cassette is deleted in NESTIN+cells to allow CTSD overexpression-CTSDtg(CDtg).The CDtg mice exhibited normal behavior and similar sensitivity to subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)induced *** breeding CDtg mice with CDKO mice,we found that over-expression of CTSD extended the lifespan of the CDKO mice,partially rescued proteasomal deficits and the accumulation of Aβ42 in the *** new transgenic mouse provides supports for the key role of CTSD in protecting against proteotoxicity and offers a new model to study the role of CTSD enhancement in vivo.

关键词： Cathepsin D transgenic mouse Mitochondrial bioenergetics Apoptosis Cathepsin D knockout mice Dopamine Autophagy Lysosome Life expectancy Behavior

IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling

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Cellular & Molecular Immunology 2023年第6期20卷 651-665页

作者： Holly Bachus Erin McLaughlin Crystal Lewis Amber M.Papillion Etty N.Benveniste Dave Durell Hill Alexander F.Rosenberg AndréBallesteros-Tato Beatriz León Department of Medicine Division of Clinical Immunology and RheumatologyUniversity of Alabama at BirminghamBirminghamALUSA Department of Microbiology University of Alabama at BirminghamBirminghamALUSA Department of Cell Developmental and Integrative BiologyUniversity of Alabama at BirminghamBirminghamALUSA informatics Institute University of Alabama at BirminghamBirminghamALUSA Alexion Pharmaceuticals Inc.New HavenCTUSA

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming. Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.

关键词： Th2 cell polarization IL-6 IL-2 SOCS3 JAK1 inhibitor

Protein-based profiling of the human IgA1 clonal repertoire revealed shared clones of serum polymeric IgA1 and milk secretory IgA1

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Cellular & Molecular Immunology 2023年第3期20卷 305-307页

作者： Jan Novak Matthew B.Renfrow R.Glenn King Colin Reily Todd J.Green Department of Microbiology University of Alabama at BirminghamBirminghamALUSA Department of Biochemistry and Molecular Genetics University of Alabama at BirminghamBirminghamALUSA

Human adaptive immunity involves the production and secretion of antibodies by differentiated B cells(ie.,antibody-secreting cells,also called plasma cells)in response to *** secreted antigen-specific antibodies are immunoglobulins that are present at substantial concentrations in blood,mucosal secretions,and breast ***,human immunoglobulins consist of two identical heavy(H)chains and two identical light(L)chains that are connected by disulfide bridges to form a homodimer of heterodimers(ie.,H+Ll2).Each heterodimer consists of one H chain linked with one L chain,whereas the homodimer is formed by linking two H chains *** genes for both the L and H chains are encoded by ligated gene segments that are genetically rearranged during V(D)J recombination,a process that endows each B cell with a unique receptor,giving rise to the enormous diversity of the B-cell antigen receptor repertoire.

关键词： IgA1 immunity chains