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Vibration-reduced anxiety-like behavior relies on ameliorating abnormalities of the somatosensory cortex and medial prefrontal cortex

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Neural Regeneration Research 2024年第6期19卷 1351-1359页

作者： Afzal Misrani Sidra Tabassum Tintin Wang Huixian Huang Jinxiang Jiang Hongjun Diao Yanping Zhao Zhen Huang Shaohua Tan Cheng Long Li Yang South China Normal University-Panyu Central Hospital Joint Laboratory of translational Medical Research Panyu Central Hospital School of Life Sciences Guangzhou University School of Life Sciences South China Normal University Guangzhou Hongai Cultural Development Inc. 5. Yinguo Health Management Team College of Biophotonics South China Normal University

Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping. The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety. However, the underlying mechanism remains unclear. In this study, we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors. We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion. We found that unlike in humans, the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice, while individual vibration components did. Additionally, the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice, decreased the level of γ-aminobutyric acid A(GABA) receptor α 1 subtype, reduced the level of CaMKII in the prefrontal cortex, and increased the number of GABAergic interneurons. At the same time, electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation. Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.

关键词： anxiety medial prefrontal cortex parvalbumin interneuron pressure somatosensory cortex Tibetan singing bowl vibration

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Imprinting at the KBTBD6 locus involves species-specific m ternal methylation and monoallelic expression in livestock animals

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Journal of Animal Science and Biotechnology 2024年第1期15卷 127-145页

作者： Jinsoo Ahn In-Sul Hwang Mi-Ryung Park Seongsoo Hwang Kichoon Lee Department of Animal Sciences The Ohio State UniversityColumbusOH 43210USA Animal Biotechnology Division Rural Development AdministrationNational Institute of Animal ScienceJeonbuk 55365Republic of Korea Columbia Center for translational Immunology Columbia University Irving Medical CenterColumbia UniversityNew YorkNY 10032USA Animal Welfare Research team National Institute of Animal ScienceRDA1500Kongjwipatjwi‑roJeollabuk‑do 55365Republic of Korea

Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.

关键词： Differentially methylated region Domesticated mammal Imprinting KBTBD6 Parthenogenetic

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Participant Heterogeneity of Systemic Scleroderma Interventional Trials Worldwide

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International Journal of Dermatology And Venereology 2024年第2期7卷 99-107页

作者： Shi Li-Qing Zhou Shi-Hang Ruan Ping-Lang Zhang Bo Xin Yue Zhao Cheng Yao Xu Tian Jing-Ru Lu Qian-Jin Hospital for Skin Diseases (Institute of Dermatology) Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing Jiangsu China Key Laboratory of Basic and translational Research on Immune-Mediated Skin Diseases Chinese Academy of Medical Sciences Nanjing Jiangsu China Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs Nanjing Jiangsu China Department of Dermatology Hunan Key Laboratory of Medical Epigenomics the Second Xiangya Hospital Central South University Changsha Hunan China.

Objective: Heterogeneity of participants in clinical trials distorts intervention efficacy. However, factors associated with participant heterogeneity in randomized clinical trials (RCTs) focusing on systemic sclerosis (SSc) are not clear. We conducted this systematic review to establish normative standards for future research and help develop management guidelines.Methods: Three databases and 4 registries were searched to identify characteristics of SSc RCTs across different countries. Risk of bias was assessed by the Cochrane Collaboration’s tool and logistic regression was performed to calculate crude and adjusted odds ratios.Results: In total, 261 trials met our inclusion criteria. The quality of SSc RCTs worldwide was relatively poor, with no trend of improvement in recent years, and only 12.2% were ranked as having a low risk of bias. Trials with a low risk of bias as well as single-center, single-country, or open-label trials tended to have better participant adherence than trials with a high risk of bias and multiple-center, multiple-country, or double-blind trials. Interestingly, trial registration and primary outcome definition contributed to high withdrawal. National income was also relevant; participant adherence in high-income countries, but not in upper- and lower-middle-income countries, was significantly altered by different variables.Conclusion: Overall, the risk of bias, national income, and trial design may lead to participant heterogeneity of SSc RCTs and ultimately confound the general clinical utility of the results. Trials with a rigorous design and transparent conduction protocol are crucial for obtaining unbiased data that can serve as a reference and for maintaining the fundamental repeatability of SSc RCTs.

关键词： systemic sclerosis randomized clinical trials heterogeneity participant adherence national income risk of bias

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Advances in the treatment of IgA nephropathy with biological agents

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Chronic Diseases and translational Medicine 2024年第1期10卷 1-11页

作者： Yongze Zhuang Hailing Lu Junxia Li Department of Nephrology 900 Hospital of the Joint Logistics TeamPLAFuzhou General Clinical Medical CollegeFujian Medical UniversityFuzhouFujianChina

Immunoglobulin A nephropathy(IgAN)is the most common primary glomerular disease,and the“four-hit”theory represents its currently accepted pathogenic mechanism.Mucosal immunity triggered by infections in the respiratory tract,intestines,or other areas leads to antigen presentation,T cell stimulation,B cell maturation,and the production of IgA-producing plasma cells.The proteins B-lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL)are involved in this process,and alternative complement and lectin pathway activation are also part of the pathogenic mechanism.Kidney Disease Improving Global Outcomes guidelines indicate that a specific effective treatment for IgAN is lacking,with renin-angiotensin-aldosterone system inhibitors being the primary therapy.Recent research shows that biological agents can significantly reduce proteinuria,stabilize the estimated glomerular filtration rate,and reverse some pathological changes,such as endocapillary proliferation and crescent formation.There are four main categories of biological agents used to treat IgA nephropathy,specifically anti-CD20 monoclonal antibodies,anti-BLyS or APRIL monoclonal antibodies,monoclonal antibodies targeting both BLyS and APRIL(telitacicept and atacicept),and monoclonal antibodies inhibiting complement system activation(narsoplimab and eculizumab).However,further research on the dosages,treatment duration,long-term efficacy,and safety of these biological agents is required.

关键词： anti-CD20 monoclonal antibodies APRIL biological agents BLyS complement IgAnephropathy

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Protein neddylation and its role in health and diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1869-1904页

作者： Shizhen Zhang Qing Yu Zhijian Li Yongchao Zhao Yi Sun Department of Breast Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Institute of translational Medicine Zhejiang University School of MedicineHangzhou 310029China Department of Thyroid Surgery Zhejiang Cancer HospitalInstitute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Key Laboratory of Head&Neck Cancer translational Research of Zhejiang Province Hangzhou 310022China Department of Hepatobiliary and Pancreatic Surgery Zhejiang University School of MedicineHangzhou 310029China Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Zhejiang University Cancer Center Hangzhou 310029China Leading Innovative and Entrepreneur team Introduction Program of Zhejiang Hangzhou 310024China Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

NEDD8(Neural precursor cell expressed developmentally downregulated protein 8)is an ubiquitin-like protein that is covalently attached to a lysine residue of a protein substrate through a process known as neddylation,catalyzed by the enzyme cascade,namely NEDD8 activating enzyme(E1),NEDD8 conjugating enzyme(E2),and NEDD8 ligase(E3).The substrates of neddylation are categorized into cullins and non-cullin proteins.Neddylation of cullins activates CRLs(cullin RING ligases),the largest family of E3 ligases,whereas neddylation of non-cullin substrates alters their stability and activity,as well as subcellular localization.Significantly,the neddylation pathway and/or many neddylation substrates are abnormally activated or over-expressed in various human diseases,such as metabolic disorders,liver dysfunction,neurodegenerative disorders,and cancers,among others.Thus,targeting neddylation becomes an attractive strategy for the treatment of these diseases.In this review,we first provide a general introduction on the neddylation cascade,its biochemical process and regulation,and the crystal structures of neddylation enzymes in complex with cullin substrates;then discuss how neddylation governs various key biological processes via the modification of cullins and non-cullin substrates.We further review the literature data on dysregulated neddylation in several human diseases,particularly cancer,followed by an outline of current efforts in the discovery of small molecule inhibitors of neddylation as a promising therapeutic approach.Finally,few perspectives were proposed for extensive future investigations.

关键词： NEDD8 attached attractive

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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of Medicine 2024年第2期18卷 327-343页

作者： Niu Qiao Yizhu Lyu Feng Liu Yuliang Zhang Xiaolin Ma Xiaojing Lin Junyu Wang Yinyin Xie Ruihong Zhang Jing Qiao Hongming Zhu Li Chen Hai Fang Tong Yin Zhu Chen Qiang Tian Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine research.Though an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly understood.Here,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy.Our study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma composition.One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA.Furthermore,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins.Overall,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

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EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1187-1203页

作者： Yongyun Li Tianyu Zhu Jie Yang Qianqian Zhang Shiqiong Xu Shengfang Ge Renbing Jia Jianming Zhang Xianqun Fan Department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology Shanghai 200001China National Research Center for translational Medicine(Shanghai) State Key Laboratory of Medical GenomicsShanghai Institute of HematologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of translational Medicine Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai 200240China

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma(UM).Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular functions.In search of genetic vulnerability for UM,we found that inhibition of euchromatic histone lysine methyltransferase 2(EHMT2)expression or activity significantly reduced the proliferation and migration capacity of cancer cells.Notably,elevated expression of EHMT2 had been validated in UM samples.Furthermore,Kaplan-Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T stage.Chromatin immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of EHMT2.Its transcription was suppressed by EHMT2 in a methyltransferasedependent pattern in GNAQ/11-mutant UM cells,leading to elevated RhoA activity.Rescuing constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic phenotypes.Simultaneously blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth,suggesting the driver role of these two key molecules.In summary,our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

关键词： Uveal melanoma EHMT2 RhoA pathway ARHGAP29 G protein GNAQ GNA11

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Game-changing insights on vertebral skeletal stem cells in bone metastasis and therapeutic horizons

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Oncology Research 2024年第1期32卷 95-98页

作者： QIUQIANG CHEN XIAOLEI ZHAO WENXUE MA Key Laboratory for translational Medicine The First Affiliated HospitalHuzhou University School of MedicineHuzhou313000China Department of Urology Huaihe Hospital of Henan UniversityKaifeng475004China Department of Medicine Moores Cancer CenterSanford Stem Cell InstituteUniversity of California San DiegoLa Jolla92093USA

Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.

关键词： Vertebral skeletal stem cells(vSSCs) Stem cell research Metastasis Breast prostate and lung cancers Spinal metastasis Matthew Greenblatt Genetic expressions

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Identification of TMEM217 as a novel prognostic biomarker and potential therapeutic target in acute myeloid leukemia

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Genes & Diseases 2024年第4期11卷 90-93页

作者： Yunying Yao Zhizhou Xi Min Wu Bo Jiao Jiaming Gao Donghe Li Xi Xie Pengfei Xu Jiaoyang Li Lei Yan Ruibao Ren Ping Liu Shanghai Institute of Hematology State Key Laboratory for Medical GenomicsNational Research Center for Translational MedicineCollaborative Innovation Center of HematologyRuijin Hospital affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China International Center for Aging and Cancer Hainan Medical UniversityHaikouHainan 570102China

Despite remarkable advances in molecular and cell biology of acute myeloid leukemia(AML),AML patients still frequently relapse and have low 5-year overall survival(OS)rates.1 It is worth noting that a recent study from the registry or clinical trial compilation has reported an improvement in the OS of adult AML patients,especially those under 60 years of age.

关键词： acute myeloid leukemia

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Childhood sleep:physical,cognitive,and behavioral consequences and implications

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World Journal of Pediatrics 2024年第2期20卷 122-132页

作者： Jianghong Liu Xiaopeng Ji Susannah Pitt Guanghai Wang Elizabeth Rovit Terri Lipman Fan Jiang School of Nursing University of Pennsylvania418 Curie Blvd.Room 424Claire M.Fagin HallPhiladelphiaPA 19104USA College of Health Sciences University of DelawareNewarkDE 19716USA Geisinger Commonwealth School of Medicine ScrantonPA 18510USA Pediatric translational Medicine Institute Department of Developmental and Behavioral PediatricsSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background Sleep problems in children have been increasingly recognized as a major public health issue.Previous research has extensively studied and presented many risk factors and potential mechanisms for children’s sleep problems.In this paper,we aimed to identify and summarize the consequences and implications of child sleep problems.Data sources A comprehensive search for relevant English language full-text,peer-reviewed publications was performed focusing on pediatric sleep studies from prenatal to childhood and adolescence in a variety of indexes in PubMed,SCOPUS,and Psych Info published in the past two decades.Both relevant data-based articles and systematic reviews are included.Results Many adverse consequences are associated with child sleep deficiency and other sleep problems,including physical outcomes(e.g.,obesity),neurocognitive outcomes(e.g.,memory and attention,intelligence,academic performance),and emotional and behavioral outcomes(e.g.,internalizing/externalizing behaviors,behavioral disorders).Current prevention and intervention approaches to address childhood sleep problems include nutrition,exercise,cognitive–behavioral therapy for insomnia,aromatherapy,acupressure,and mindfulness.These interventions may be particularly important in the context of coronavirus disease 2019.Specific research and policy strategies can target the risk factors of child sleep as well as the efficacy and accessibility of treatments.Conclusions Given the increasing prevalence of child sleep problems,which have been shown to affect children’s physical and neurobehavioral wellbeing,understanding the multi-aspect consequences and intervention programs for childhood sleep is important to inform future research direction as well as a public health practice for sleep screening and intervention,thus improving sleep-related child development and health.

关键词： Behavior Child sleep Consequences Implications Neurocognitive Physical Prevention/intervention

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