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

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

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Apolipoprotein A-I binding protein-mediated neuroprotection in glaucomatous neuroinflammation and neurodegeneration

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Neural Regeneration Research 2025年第5期20卷 1414-1415页

作者： Sinwoo Hwang Seunghwan Choi Soo-Ho Choi Keun-Young Kim Yury I.Miller Won-Kyu Ju Hamilton Glaucoma Center and Shiley Eye Institute The Viterbi Family Department of OphthalmologyUniversity of California San DiegoLa JollaCAUSA Department of Medicine University of California San DiegoLa JollaCAUSA National Center for Microscopy and Imaging Research Department of NeurosciencesUniversity of California San DiegoLa JollaCAUSA

Glaucoma is a multifactorial eye disorder that can cause vision loss and irreversible blindness,affecting individ uals aged 40 to 80 yea rs *** to the aging population,it is expected that the number of people affected by glaucoma will surpass 111 million by 2040 as the disease becomes more *** primarily contributes to optic nerve axon loss and the progressive degeneration of retinal ganglion cells (RGCs),subsequently leading to vision impairment.

关键词： irreversible pass primarily

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Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

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Genes & Diseases 2024年第3期11卷 338-350页

作者： Xin Xu Yuan Fang Somaira Nowsheen Ye-Xiong Li Zhenkun Lou Min Deng State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Department of General Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of dermatology University of California San DiegoSan DiegoCA 92093USA Department of Oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor *** is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy *** studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic *** this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)*** found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM *** regulation of AMPK requires the Hippo kinases but not LKB1/*** kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM ***,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival *** activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC ***,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

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Precision N-glycoproteomics reveals the essential role of the extracellular matrix in tropomyosin allergy in a mouse model

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Food Science and Human Wellness 2024年

作者： Guirong Liu Qianwei Wang Yibo Luo Lijuan Sun Ruolin Song Huilian Che Changqi Liu Xiaohui Guo College of Food Science and Nutritional Engineering， China Agricultural University Department of dermatology and Venereology， West China Hospital， Sichuan University School of Exercise and Nutritional Sciences， College of Health and Human Services， san diego State University

Approximately 2.5% of the global population experiences allergic reactions to seafood， making it one of the most prevalent and life-threatening allergies. Seafood allergy can lead to the disruption of the intestinal barrier， possibly due to abnormalities in intestinal glycosylation. In this study， the mechanisms underlying seafood allergy were explored through the lens of intestinal glycobiology. Mice were first sensitized with tropomyosin， resulting in significant increases in allergy symptom scores and specific antibody and Th2 cytokine levels. Intestinal damage was confirmed by histopathology assessments and levels of diamine oxidase and claudin-1. Moreover， alterations in glycosylated proteins within the jejunum were analyzed using high-throughput mass spectrometry and the pGlyco3.0 search engine， yielding 2283 glycosylation peptides corresponding to 655 unique glycosylation sites on 399 proteins in precision N-glycoproteomics. Differential expression and enrichment analyses revealed that differentially expressed glycoproteins play significant roles in the extracellular matrix (ECM)-receptor interaction pathway and focal adhesion pathway. In conclusion， tropomyosin sensitization leads to intestinal glycome changes， accompanied by remodeling of the intestinal ECM. Our research establishes an essential theoretical basis for targeting the intestinal glycome and ECM remodeling in a precise and fine-tuned manner for the treatment of food allergies.

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Current status of cognition and skin care behavior in adolescent patients with acne:A survey in China

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Chinese Medical Journal 2024年第4期137卷 476-477页

作者： Jing Tian Hong Shu Qiufang Qian Zhong Shen Chunyu Zhao Li Song Ping Li Xiuping Han Hua Qian Jinping Chen Hua Wang Lin Ma Yuan Liang Department of dermatology Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China Department of dermatology Kunming Children’s HospitalKunmingYunnan 650034China Department of dermatology Children’s Hospital of ShanghaiChildren’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Loreal China Co. LtdShanghai 200040China Department of dermatology Henan Children’s HospitalChildren’s Hospital Affiliated to Zhengzhou UniversityZhengzhou Hospital Beijing Children’s HospitalZhengzhou Children’s HospitalZhengzhouHenan 450052China Department of dermatology Shenzhen Children’s HospitalShenzhenGuangdong 518026China Department of dermatology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110004China Department of dermatology Children’s Hospital of Soochow UniversitySuzhouJiangsu 215025China Department of dermatology Guangzhou Women and Children's Medical CenterGuangzhouGuangdong 510623China Department of dermatology Children’s Hospital of Chongqing Medical UniversityChongqing 400014China

To the Editor:Acne vulgaris(AV)is a common inflammatory skin ***-based epidemiological studies have reported associations between dietary habits,lifestyle factors,family history,and the occurrence and development of acne.^([1–4])This study investigated the skincare behavior and cognition of patients with AV regarding predisposing factors using a designed electronic questionnaire.

关键词： patients dietary behavior

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Nociceptors and Macrophages in Bacterial Meningitis:Partners in Crime?

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Neuroscience Bulletin 2024年第3期40卷 418-420页

作者： Fang Gao Hongzhen Hu The Kimberly and Eric J.Waldman Department of dermatology Icahn School of Medicine at Mount SinaiNew York NY10029USA The Nash family Department of Neuroscience Icahn School of Medicine at Mount SinaiNew York NY10029USA The Mark Lebwohl Center for Neuroinfammation and Sensation Icahn School of Medicine at Mount SinaiNew York NY10029USA Friedman Brain Institute Icahn School of Medicine at Mount SinaiNew York NY10029USA

Bacterial meningitis is a serious and potentially life-threatening infection that affects the protective layers surrounding the brain and spinal cord,known as the *** types of bacteria,including Streptococcus pneumoniae,Neisseria meningitidis,and Haemophilus influenzae,can cause this *** populations,such as infants,children,immunocompromised adults,and the elderly,are particularly vulnerable to these *** of bacterial meningitis can manifest suddenly and may include high fever,severe and persistent headache,stiff neck,vomiting,sensitivity to light,and confusion or changes in mental state[1,2].Identifying these symptoms in infants can be more challenging and may lead to long-term disability or death[3].Despite the effectiveness of vaccines,it is crucial to understand how bacteria invade the brain and how our innate immune system responds to infection(Fig.1).

关键词： protective infection suddenly

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Paclitaxel-associated reticulate hyperpigmentation:Report and review of chemotherapy-induced reticulate hyperpigmentation

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World Journal of Clinical Cases 2016年第12期4卷 390-400页

作者： Philip R Cohen Department of dermatology University of California San Diego

Drug-induced reticulate hyperpigmentation is uncommon. Including the patient described in this report, chemotherapy-associated reticulate hyperpigmentation has only been described in ten individuals. This paper describes the features of a woman with recurrent and metastatic breast cancer who developed paclitaxelinduced reticulate hyperpigmentation and reviews the characteristics of other oncology patients who developed reticulate hyperpigmentation from their antineoplastic treatment. A 55-year-old Taiwan Residents woman who developed reticulate hyperpigmentation on her abdomen, back and extremities after receiving her initial treatment for metastatic breast cancer with paclitaxel is described. The hyperpigmentation became darker with each subsequent administration of paclitaxel. The drug was discontinued after five courses and the pigment faded within two months. Pub Med was searched with the key words: Breast, cancer, chemotherapy, hyperpigmentation, neoplasm, reticulate, tumor, paclitaxel, taxol. The papers generated by the search, and their references, were reviewed. Chemotherapy-induced reticulate hyperpigmentation has been described in four men and six women. Bleomycin, cytoxan, 5-fluorouracil, idarubacin, and paclitaxel caused the hyperpigmentation. The hyperpigmentation faded in 83% of the patients between two to six months after the associated antineoplastic agent was discontinued. In conclusion, chemotherapy-induced reticulate hyperpigmentation is a rare reaction that may occur during treatment with various antineoplastic agents. The hyperpigmentation fades in most individuals once thetreatment is discontinued. Therefore, cancer treatment with the associated drug can be continued in patients who experience this cutaneous adverse event.

关键词： Breast Cancer Chemotherapy Hyperpigmentation Neoplasm Reticulate Tumor Paclitaxel Taxol

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Orchard Sports Injury and Illness Classification System (OSIICS) Version 15

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Journal of Sport and Health Science 2024年第4期13卷 599-604页

作者： John W.Orchard Ebonie Rio Kay M.Crossley Jessica J.Orchard Margo Mountjoy School of Public Health University of SydneySydneyNSW 2006Australia La Trobe Sport and Exercise Medicine Research Centre La Trobe UniversityMelbourneVIC 3083Australia Department of family Medicine McMaster UniversityHamilton L8S 4L8Canada

Background:Sports medicine(injury and illnesses)requires distinct coding systems because the International Classification of Diseases is insuf-ficient for sports medicine *** Orchard Sports Injury and Illness Classification System(OSIICS)is one of two sports medicine coding systems recommended by the International Olympic *** updates of coding systems are ***:For Version 15,updates for mental health conditions in athletes,sports cardiology,concussion sub-types,infectious diseases,and skin and eye conditions were considered particularly ***:Recommended codes were added from a recent International Olympic Committee consensus statement on mental health conditions in *** landmark sports cardiology papers were used to update a more comprehensive list of sports cardiology *** union protocols on head injury assessment were used to create additional concussion ***:It is planned that OSIICS Version 15 will be translated into multiple new languages in a timely fashion to facilitate international *** large number of recently published sport-specific and discipline-specific consensus statements on athlete surveillance warrant regular updating of OSIICS.

关键词： Sports cardiology dermatology Eye injuries Concussion Infectious diseases Sports injury classification

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Ultraviolet light exposure and its penetrance through the eye in a porcine model

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International Journal of Ophthalmology(English edition) 2023年第2期16卷 172-177页

作者： Hideki Fukuoka Helena E.Gali Jennifer J.Bu Ruti Sella Natalie A.Afshari Shiley Eye Institute Viterbi Family Department of OphthalmologyUniversity of California San DiegoLa JollaCA 92093USA

AIM:To determine the amount of ultraviolet(UV)light irradiance that various layers of the eye receive as sunlight passes through the eye,and to investigate the protective benefits of UV light-blocking contact ***:Twenty-four porcine eyes were prepared in one of three ways:isolated cornea,cornea and lens together,or whole eye *** light irradiance was measured with a UV-A/B light meter before and after the eye preparations were placed over the meter to measure UV light penetration in each eye *** the whole eye preparation,a hole was placed in the fovea to measure light as it passed through the ***,UVprotective contact lenses were placed over the structures,and UV light penetrance was *** of UV light exposure were taken outdoors at various locations and ***:Cornea absorbed 63.56%of UV light that reached the *** and lens absorbed 99.34%of UV *** eye absorbed 99.77%of UV *** UV-protective contact lenses were placed,absorption was 98.90%,99.55%,and 99.87%,*** light exposure was dependent on directionality and time of day,and was greatest in areas of high albedo that reflect significant amounts of light,such as a ***:Cornea absorbs the majority of UV light that reaches the eye in this ***-protective contact lenses reduce UV exposure to the *** with high albedo expose the eye to higher levels of UV light.

关键词： ultraviolet light penetrance contact lens cornea lens

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Tests for paired count outcomes

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General Psychiatry 2018年第4期31卷 48-53页

作者： James A Proudfoot Tuo Lin Bokai Wang Xin M Tu Clinical and Translational Research Institute University of California San Diego Departments of Biostatistics& Computational Biology and Anesthesiology University of Rochester Department of family Medicine and Public Health University of California San Diego

Paired t-tests are widely used to compare differences in paired continuous outcomes. This test, however, does not apply to non-continuous outcomes. For binary outcomes,McNemar's test is the de facto method for comparing differences in paired binary variables. For count or frequency outcomes, there is not much discussion in the literature. The Wilcoxon signed-rank test is often used to assess differences in paired count outcomes. However, like the Mann-Whitney U test, or Wilcoxon rank-sum test for comparing two independent groups, the Wilcoxon signedrank test is generally not efficient(powerful). In this essay,we consider some alternative methods for comparing paired count outcomes and compare them with the Wilcoxon signed-rank test using Monte Carlo simulations.

关键词： Tests for paired count outcomes

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