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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

DNA methylation in inflammatory bowel disease and beyond

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World Journal of Gastroenterology 2013年第32期19卷 5238-5249页

作者： Daren Low Atsushi Mizoguchi Emiko Mizoguchi Gastrointestinal Unit Department of MedicineMassachusetts General HospitalHarvard Medical School Molecular Pathology Unit Department of PathologyMassachusetts General HospitalHarvard Medical School center for the Study of inflammatory bowel disease Massachusetts General HospitalHarvard Medical School

inflammatory bowel disease(IBD)is a consequence of the complex,dysregulated interplay between genetic predisposition,environmental factors,and microbial composition in the *** a great advancement in identifying host-susceptibility genes using genome-wide association studies(GWAS),the majority of IBD cases are still *** immediate challenge in post-GWAS era is to identify other causative genetic factors of *** methylation has received increasing attention for its mechanistical role in IBD *** stable,yet dynamic DNA modification,can directly affect gene expression that have important implications in IBD *** alterations in DNA methylation associated with IBD are likely to outset as early as embryogenesis all the way until *** this review,we will discuss the recent advancement in understanding how DNA methylation alterations can contribute to the development of IBD.

关键词： Intestinal inflammation Crohn’s disease Colitis DNA methyltransferase Epi-therapy

Stem cell therapy:light in the tunnel for penetrating Crohn’s disease

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Gastroenterology Report 2023年第1期11卷 78-87页

作者： Nan Lan Xianrui Wu Bo Shen center for inflammatory bowel disease Columbia University Irving Medical Center/NewYork Presbyterian HospitalNew YorkNYUSA Department of Colorectal Surgery The 6th Hospital of Sun Yat-Sen UniversityGuangzhouGuangdongP.R.China

Patients with Crohn’s disease frequently suffer from fistula resulting from adverse sequelae of persistent complicated active disease or surgical *** affects a patient’s quality of life and is directly associated with the need for surgical *** of fistula can be made through CT enterography,MR enterography,gastrograffin-based imaging,and transanal *** for fistula mainly consists of medication,endoscopic procedures,and *** are emerging approaches under current investigation,such as stem cell *** results showed a decent response in patients with perianal and rectovaginal fistula with minimal side *** investigation is still needed for other internal fistula.

关键词： Crohn’s disease fistula perianal disease stem cells therapy

Antibody markers in the diagnosis of inflammatory boweldisease

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World Journal of Gastroenterology 2016年第3期22卷 1304-1310页

作者： Keiichi Mitsuyama Mikio Niwa Hidetoshi Takedatsu Hiroshi Yamasaki Kotaro Kuwaki Shinichiro Yoshioka Ryosuke Yamauchi Shuhei Fukunaga Takuji Torimura inflammatory bowel disease center Kurume University School of MedicineKurume 830-0011Japan Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume 830-0011Japan Institute for Advanced Sciences Toagosei Co.Ltd.2 OhkuboTsukubaIbaraki 300-2611Japan

inflammatory bowel disease(IBD), including Crohn's disease and ulcerative colitis, is a chronic intestinal inflammation of unknown etiology. The diagnosis of IBD is based on endoscopic, radiologic and histopathologic criteria. Recently, the search for a noninvasive marker that could augment or replace part of this diagnostic process has become a focus of IBD research. In this review, antibody markers, including microbial antibodies, autoantibodies and peptide antibodies, will be described, focusing on their common features. At present, no single marker with qualities that are satisfactory for the diagnosis and treatment of IBD has been identified, although panels of some antibodies are being evaluated with keen interest. The discovery of novel IBD-specific and sensitive markers is anticipated. Such markers could minimize the use of endoscopic and radiologic examinations and could enable clinicians to implement individualized treatment plans designed to improve the long-term prognosis of patients with IBD.

关键词： Biomarker Crohn's disease Serologicalantibody Ulcerative colitis

Evaluating the effectiveness of infliximab on perianal fistulizing Crohn’s disease by magnetic resonance imaging

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Gastroenterology Report 2019年第1期7卷 50-56,I0002页

作者： Xiaohan Yan Mingming Zhu Qi Feng Yunqi Yan Jiangchen Peng Xitao Xu Antao Xu Zhihua Ran Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthShanghai Inflammatory Bowel Disease Research CenterRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Radiology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background and aim:Data on the radiologic evaluation of perianal fistulizing Crohn’s disease(PFCD)naive to anti-tumor necrosis factor therapy are scarce,especially in Asian *** assessed the effectiveness of infliximab(IFX)on PFCD and explored predictors of‘deep remission’based on clinical and radiologic ***:Patients with Crohn’s disease and active anal fistulas attending our care center for IFX therapy were prospectively *** patient underwent clinical examination according to the Fistula Drainage Assessment Index,endoscopy for assessment of Crohn’s disease Activity Index(CDAI)and Perianal Crohn’s disease Activity Index(PCDAI),magnetic resonance imaging(MRI)to determine Van Assche score and Ng score,and laboratory tests up to 2 weeks prior to the start of and up to 2 weeks after the sixth IFX therapy(Week 32).Results:Among 38 patients treated with IFX,52.6%achieved clinical remission based on the Fistula Drainage Assessment Index and 42.1%achieved deep remission based on Ng *** Assche score(from 14.5±4.26 to 7.36±7.53),CDAI(from 170±92 to 71±69)and PCDAI(from 7.45±2.65 to 2.44±3.20)decreased significantly after six IFX *** only predictor of deep remission was simple fistula(P=0.004,odds ratio=3.802,95%confidence interval:1.541–9.383).Conclusions:IFX has been shown to have appreciable effectiveness in Chinese patients with *** is the gold standard for evaluating PFCD,but Van Assche score has some limitations.

关键词： Crohn’s disease perianal fistula magnetic resonance imaging infliximab

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

Computed tomography-guided endoscopic needle knife therapy for ileal pouch sinus

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Gastroenterology Report 2016年第4期4卷 334-336,I0003页

作者： Custon T.Nyabanga Joseph Veniero Bo Shen Cleveland Clinic Lerner College of medicine of Case Western Reserve University ClevelandOHUSA Department of Diagnostic Radiology Cleveland ClinicClevelandOHUSA center for inflammatory bowel diseases Digestive Disease InstituteCleveland ClinicClevelandOHUSA

Ileal pouch-anal anastomosis surgery can be complicated by anastomotic leaks,leading to the formation of abscess and chronic sinus that have been routinely managed by a surgical *** developed the endoscopic needle knife sinusotomy(NKSi)technique,which has become a valid *** basic principle of endoscopic NKSi is dissection and drainage of the sinus through its orifice internally into the lumen of pouch *** success of NKSi requires an access to the sinus from the pouch *** of the most challenging situations for NKSi is a closed orifice of the sinus,which leaves an isolated chronic abscess *** we report a case of complicated presacral sinus with a closed orifice that was not amenable to NKSi,necessitating a CT-guided guide wire placement and subsequent NKSi.

关键词： endoscopic needle knife sinusotomy ileal pouch-anal anastomosis anastomotic leak presacral sinus computed tomography

Specific shRNA targeting of FAK influenced collagen metabolism in rat hepatic stellate cells

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World Journal of Gastroenterology 2010年第32期16卷 4100-4106页

作者： Zhi-Na Dun Xiao-Lan Zhang Jun-Yan An Li-Bo Zheng Robert Barrett Shu-Rui Xie Department of Gastroenterology The Second Hospital of Hebei Medical University Hebei Key Laboratory of Gastroenterology Hebei Institute of Gastroenterology Shijiazhuang Hebei Province China inflammatory bowel disease center and Immunobiology Research Institute Cedars-Sinai Medical center Los Angeles CA 90048 United States

AIM:To investigate the effects and mechanism of disruption of focal adhesion kinase(FAK) expression on collagen metabolism in rat hepatic stellate cells(HSC).METHODS:The plasmids expressing FAK short hairpin RNA(shRNA) were transfected into HSC-T6 cells,and the level of FAK expression was determined by both real-time quantitative polymerase chain reaction(QPCR) and Western blotting *** production of type collagen and type collagen in FAK-disrupted cells was analyzed by real-time *** level of collagen metabolism proteins,including matrix metalloproteinases-13(MMP-13) and tissue inhibitors of metalloproteinases-1(TIMP-1) was also determined by both real-time Q-PCR and Western blotting ***:The transfection of FAK shRNA plasmids into HSC resulted in disrupted FAK *** with the HK group,the levels of type collagen and type collagen mRNA transcripts in FAK shRNA plas-mid group were signif icantly decreased(0.69 ± 0.03 vs 1.96 ± 0.15,P = 0.000;0.59 ± 0.07 vs 1.62 ± 0.12,P = 0.020).The production of TIMP-1 in this cell type was also signif icantly reduced at both mRNA and protein levels(0.49 ± 0.02 vs 1.72 ± 0.10,P = 0.005;0.76 ± 0.08 vs 2.31 ± 0.24,P = 0.000).However,the expression of MMP-13 mRNA could be significantly up-regulated by the transfection of FAK shRNA plasmids into HSC(1.74 ± 0.20 vs 1.09 ± 0.09,P = 0.000).CONCLUSION:These data support the hypothesis that shRNA-mediated disruption of FAK expression could attenuate extracellular matrix(ECM) synthesis and promote ECM degradation,making FAK a potential target for novel anti-f ibrosis therapies.

关键词： Focal adhesion kinase Hepatic stellate cells Matrix metalloproteinases RNA interference Type collagen Tissue inhibitors of metallo-proteinases

Insights on the use of biosimilars in the treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2017年第11期23卷 1932-1943页

作者： Michael K Zheng David Q Shih Gary C Chen F.Widjaja Foundation Inflammatory Bowel and Immunobiology Research InstituteCedars-Sinai Medical Center Comprehensive Digestive Institute of Nevada

Biologic therapy, such as those that target tumor necrosis factor(TNF) signaling, has proven to be an efficacious method of treatment for patients with inflammatory bowel disease(IBD) with regards to symptom management and mucosal healing. However, the rising prevalence of IBD worldwide and the everincreasing burden of biologic pharmaceuticals in the health care industry is alarming for insurance companies, clinicians, and patients. The impending patent expiry and the relatively high costs of biologics, particularly anti-TNF agents, have paved the way for biosimilar development for IBD. The United States Food and Drug Administration defines a biosimilar as a biological product that is highly similar to its reference medicinal product, with no clinically meaningful differences in terms of safety, purity, and potency. The hope with biosimilars is that their entry into the market will be able to drive competition between pharmaceutical companies to reduce prices like that of the generic market, and that access to appropriate biologic treatments for IBD patients is increased in the long-term. Yet, there are challenging issues such as indication extrapolation and interchangeability that are still being debated in the field of IBD and must be addressed in future issued guidance. This review will discuss the issues and implications concerning the use of biosimilar therapy for IBD.

关键词： Biosimilar Biologic inflammatory bowel disease Ulcerative colitis Crohn’s disease Indication extrapolation Interchangeability