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The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens

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Infectious Microbes & Diseases 2024年第2期6卷 65-73页

作者： Alexandra Stream Ross Corriden Simon Döhrmann Richard L.Gallo Victor Nizet Ericka L.Anderson Division of Host-Microbe Systems and Therapeutics Department of PediatricsUniversity of California San Diego School of MedicineLa JollaCaliforniaUSA department of Dermatology University of California San Diego School of MedicineLa JollaCaliforniaUSA Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San DiegoLa JollaCaliforniaUSA

Vitamin A and its biologically active derivative,retinoic acid(RA),are important for many immune ***,in particular,is essential for the development of immune cells,including neutrophils,which serve as a front-line defense against *** vitamin A deficiency has been linked to higher susceptibility to infections,the precise role of vitamin A/RA in host-pathogen interactions remains poorly ***,we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus(MRSA).RA treatment stimulated primary human neutrophils to produce reactive oxygen species,neutrophil extracellular traps and the antimicrobial peptide cathelicidin(LL-37).Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection,we expanded our analysis to other infectious *** did not affect the growth of a number of common bacterial pathogens,including MRSA,Escherichia coli K1 and Pseudomonas aeruginosa;however,RA directly inhibited the growth of group A Streptococcus(GAS).This antimicrobial effect,likely in combination with RA-mediated neutrophil boosting,resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of ***,in a murine model of GAS skin infection,topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial *** findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.

关键词： retinoic acid neutrophil bacterial infection Staphylococcus aureus group A Streptococcus neutrophil extracellular traps antimicrobial peptide cathelicidin

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy department of Surgery Morehouse School of MedicineAtlantaGAUSA department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA department of pediatrics Emory UniversityAtlantaGAUSA department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Comments on 2018 CPCS guideline for diagnosis and treatment of syncopein children and adolescents

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Science Bulletin 2019年第5期64卷 291-292页

作者： Chunyan Tao Xueqin Liu Chunyu Zhang Yonghong Chen? Yaqian Huang? department of pediatrics Peking University First Hospital

Syncope is one kind of transient loss of consciousness,due to transient global cerebral *** is sometimes misunderstood with other causes of transient loss of consciousness,like epilepsy,metabolic disorders,head trauma,psychological factors,and so *** in children and adolescents is common and seriously impacts the quality of their ***,its pathogenesis,etiologies,diagnosis and management are *** studies on syncope attract great interest of pediatricians and great progress has been made in this interesting *** on the improvement achieved so far,Chinese Pediatric Cardiology Society(CPCS)successfully developed a guideline for the diagnosis and treatment of syncope in children and adolescents,which would greatly improve the level of clinical management of syncope.

关键词： Comments 2018 CPCS guideline children and adolescents

Pressure pain sensitivity: A new stress measure in children and adolescents with type 1 diabetes?

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World Journal of Clinical pediatrics 2024年第1期13卷 150-154页

作者： Annemarie Cecilie Grauslund Emilie Bundgaard Lindkvist Steffen Ullitz Thorsen Søren Ballegaard Jens Faber Jannet Svensson Anna Korsgaard Berg department of pediatrics Herlev and Gentofte HospitalHerlev 2730Denmark Copenhagen University Hospital Steno Diabetes Center CopenhagenHerlev 2730Denmark department of Clinical Immunology RigshospitaletUniversity of CopenhagenCopenhagen 2100Denmark department of Endocrinology Herlev and Gentofte HospitalHerlev 2730Denmark department of Clinical Medicine Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen 2200Denmark

Type 1 diabetes(T1D)is associated with general-and diabetes-specific stress which has multiple adverse *** measuring stress is of great *** algometer measuring pressure pain sensitivity(PPS)has been shown to correlate to certain stress measures in ***,it has never been investigated in children and *** aim of our study was to examine associations between PPS and glycated hemoglobin(HbA1c),salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with ***-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study *** cortisol,PPS and questionnaires were collected,measured,and answered on ***1c was collected from medical *** found correlations between PPS and HbA1c(rho=0.35,P=0.046),cortisol(rho=-0.25,P=0.02)and Perceived Stress Scale(rho=-0.44,P=0.02)in different subgroups based on *** scored higher in PPS than females(P<0.001).We found PPS to be correlated to HbA1c but otherwise inconsistent in *** PPS values indicated either measurement difficulties or hypersensibility towards pain.

关键词： Stress Children and adolescents Type 1 diabetes Autonomic dysfunction

APIR:Aggregating Universal Proteomics Database Search Algorithms for Peptide Identification with FDR Control

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 171-187页

作者： Yiling Elaine Chen Xinzhou Ge Kyla Woyshner MeiLu McDermott Antigoni Manousopoulou Scott B.Ficarro Jarrod A.Marto Kexin Li Leo David Wang Jingyi Jessica Li department of Statistics and Data Science University of CaliforniaLos AngelesCA 90095USA department of Immuno-Oncology Beckman Research InstituteCity of Hope National Medical CenterDuarteCA 91010USA department of Quantitative and Computational Biology University of Southern CaliforniaLos AngelesCA 90089USA department of Cancer Biology and Blais Proteomics Center Dana-Farber Cancer InstituteDepartment of PathologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA 02215USA department of pediatrics City of Hope National Medical CenterDuarteCA 91010USA Bioinformatics Interdepartmental Program University of CaliforniaLos AngelesCA 90095USA department of Human Genetics University of CaliforniaLos AngelesCA 90095USA department of Computational Medicine University of CaliforniaLos AngelesCA 90095USA department of Biostatistics University of CaliforniaLos AngelesCA 90095USA

Advances in mass spectrometry(MS)have enabled high-throughput analysis of proteomes in biological *** state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide–spectrum matches(PSMs),which convert mass spectra to peptide *** database search algorithms use distinct search strategies and thus may identify unique ***,no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and a control on the false discovery rate(FDR).To fill in this gap,we proposed a statistical framework,Aggregation of Peptide Identification Results(APIR),that is universally compatible with all database search ***,under an FDR threshold,APIR is guaranteed to identify at least as many,if not more,peptides as individual database search algorithms *** of APIR on a complex proteomics standard dataset showed that APIR outpowers individual database search algorithms and empirically controls the *** data studies showed that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search *** APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis,e.g.,differential gene expression analysis on RNA sequencing *** APIR R package is available at https://***/yiling0210/APIR.

关键词： Shotgun proteomics Peptide–spectrum match Peptide identification Aggregation of lists FDR control

A 63-Year-Old Male with D-Transposition of the Great Arteries Who Had an Early Form of the Arterial Switch Operation

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Congenital Heart Disease 2024年第1期19卷 65-68页

作者： Michael A.Rebolledo Jane S.Yao Jason N.Johnson Umar S.Boston Benjamin R.Waller III Division of Pediatric Cardiology Department of PediatricsThe University of Tennessee Health Science CenterThe Heart InstituteLe Bonheur Children’s HospitalMemphisUSA College of Medicine The University of Tennessee Health ScienceMemphisUSA Division of Pediatric Cardiothoracic Surgery Department of SurgeryThe University of Tennessee Health Science CenterHeart InstituteLe Bonheur Children’s HospitalMemphisUSA

We describe a 63-year-old male who appears to have undergone an early form of the arterial switch operation for D-transposition of the great arteries performed in the *** review the clinical and imaging data that support our *** had a diagnostic cardiac catheterization which demonstrated severe pulmonary hypertension responsive to epoprostenol and *** case may represent one example of the experimental surgical work done prior to *** Jatene’s description of theﬁrst successful arterial switch performed in 1975.

关键词： Adult congenital heart disease arterial switch operation great vessel anomaly imaging(all modalities)

Sport and exercise during viral acute respiratory illness——Time to revisit

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Journal of Sport and Health Science 2024年第5期13卷 663-665页

作者： Olli Ruuskanen Maarit Valtonen Matti Waris Raakel Luoto Olli JHeinonen department of pediatrics and Adolescent Medicine Turku University Hospital and University of TurkuTurku 20521Finland Finnish Institute of High Performance Sport KIHU Jyvaskyla 40700Finland Institute of Biomedicine University of Turku and Department of Clinical VirologyTurku University HospitalTurku 20520Finland Paavo Nurmi Centre and Unit for Health and Physical Activity University of TurkuTurku 20520Finland

Athletes are commonly advised not to compete or train during major symptoms of a viral acute respiratory illness(ARI),which most commonly is a common *** has been traditionally thought that heavy physical stress could induce the worsening of symptoms of ARI and possibly cause potentially severe complications like myocarditis or sudden cardiac death(SCD).In addition,viral ARI may decrease athlete's performance.1 These concerns have been recently stressed during the coronavirus disease 2019(COVID-19)pandemic.2 However,it is anecdotally well-known that athletes commonly compete while experiencing common colds,most commonly due to picornaviral *** this perspective,we discuss what is known or not known regarding the risks of exercising during the viral ARI.

关键词： traditionally illness tally

Evaluation of Clinician Training in Autism Screening, Care Management, and Patient Education

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Open Journal of pediatrics 2024年第3期14卷 488-513页

作者： Belinda O’Hagan Julie White Ilana Hardesty Rachel Amgott Candice Bangham Xinyang Liu Alyson Codner Amy Ursitti Alana Chandler Sarah Foster Marilyn Augustyn Jacey Greece Division of Developmental and Behavioral pediatrics Department of Pediatrics Boston Medical Center Boston United States of America Boston University Chobanian & Avedisian School of Medicine Boston United States of America department of Community Health Sciences Boston University School of Public Health Boston United States of America

Objective: The demand for pediatric developmental evaluations has far exceeded the workforce available to perform them, which creates long significant wait times for services. A year-long clinician training using the Extension for Community Healthcare Outcomes (ECHO®) model with monthly meetings was conducted and evaluated for its impact on primary care clinicians’ self-reported self-efficacy, ability to administer autism screening and counsel families, professional fulfillment, and burnout. Methods: Participants represented six community health centers and a hospital-based practice. Data collection was informed by participant feedback and the Normalization Process Theory via online surveys and focus groups/interviews. Twelve virtual monthly trainings were delivered between November 2020 and October 2021. Results: 30 clinicians participated in data collection. Matched analyses (n = 9) indicated statistically significant increase in self-rated ability to counsel families about autism (Pre-test Mean = 3.00, Post-test Mean = 3.89, p = 0.0313), manage autistic patients’ care (Pre-test Mean = 2.56, Post-test Mean = 4.11, p = 0.0078), empathy toward patients (Pre-test Mean = 2.11, Post-test Mean = 1.22, p = 0.0156) and colleagues (Pre-test Mean = 2.33, Post-test Mean = 1.22, respectively, p = 0.0391). Unmatched analysis revealed increases in participants confident about educating patients about autism (70.59%, post-test n = 12 vs. 3.33%, pre-test n = 1, p = 0.0019). Focus groups found increased confidence in using the term “autism”. Conclusion: Participants reported increases in ability and confidence to care for autistic patients, as well as empathy toward patients and colleagues. Future research should explore long-term outcomes in participants’ knowledge retention, confidence in practice, and improvements to autism evaluations and care.

关键词： Autism Spectrum Disorder Program Evaluation Case-Based Training Provider Burnout Continuing Medical Education

Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

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Bone Research 2024年第2期12卷 334-348页

作者： Ziqian Xiang Pengfei Zhang Chunwang Jia Rongkun Xu Dingren Cao Zhaoning Xu Tingting Lu Jingwei Liu Xiaoxiong Wang Cheng Qiu Wenyang Fu Weiwei Li Lei Cheng Qiang Yang Shiqing Feng Lianlei Wang Yunpeng Zhao Xinyu Liu department of Orthopaedics Qilu Hospital of Shandong UniversityJinan 250012China University of Health and Rehabilitation Sciences Qingdao 226000China Xiangya School of Medicine Central South UniversityChangsha 410013China School of Nursing and Rehabilitation Shandong UniversityJinan 250012China department of pediatrics Cangzhou Central HospitalCangzhou 061011China department of Pediatric Surgery Qilu Hospital of Shandong UniversityJinan 250012China department of Pathology Qilu Hospital of Shandong UniversityJinan 250012China department of Spine Surgery Tianjin HospitalTianjin UniversityTianjin 30021China The Second Hospital of Shandong University Cheeloo College of MedicineShandong UniversityJinan 250012China

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be ***,Piezo1 channel was identified as a key iron transporter in response to mechanical ***1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron ***,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical ***,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

关键词： stress overload channel