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Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer

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National Science Review 2024年第1期11卷 94-106页

作者： Yuqing Sun Haixin Yu Shaoqing Han Ruoxi Ran Ying Yang Yongling Tang Yuhao Wang Wenhao Zhang Heng Tang Boqiao Fu Boshi Fu Xiaocheng Weng Song-Mei liu Hexiang Deng Shuang Peng Xiang Zhou College of Chemistry and Molecular sciences Key Laboratory of Biomedical Polymers-Ministry of Education Wuhan University department of Digestive Surgical Oncology Union Hospital Tongji Medical College Huazhong University of Science and Technology Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and Technology department of clinical laboratory Center for Gene Diagnosis and Program of Clinical Laboratory Zhongnan Hospital of Wuhan University College of Chemistry and Materials Science Hubei Engineering University department of Pharmacology School of Pharmacy China Medical University Taikang Center for life and Medical sciences Wuhan University department of Hematology Zhongnan Hospital of Wuhan University

Cell-free RNA(cf RNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cf RNA isolation technologies due to the low abundance and instability of cf ***, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids(containing cf RNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework(MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cf RNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cf RNA in serum from patients with liver cancer was described and a cf RNA signature with six cf RNAs was identified to diagnose liver cancer with high diagnostic efficiency(area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.

关键词： MOF circulating cell-free RNA biomarker liver cancer diagnosis

Non-pancreatic hyperlipasemia:A puzzling clinical entity

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World Journal of Gastroenterology 2024年第19期30卷 2538-2552页

作者： Krisztina Eszter Feher David Tornai Zsuzsanna Vitalis laszlo Davida Nora Sipeki Maria Papp Division of Gastroenterology Department of Internal MedicineFaculty of MedicineUniversity of DebrecenDebrecen H-4032Hajdu-BiharHungary Kalman laki Doctoral School of biomedical and clinical sciences Faculty of MedicineUniversity of DebrecenDebrecen H-4032Hungary

BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic *** non-pancreatic hyperlipasemia(NPHl)is puzzling for attending physicians during the diagnostic procedure for *** would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it.A more precise description of the NPHl condition could potentially provide prognostic factors for adverse outcomes which is currently *** To perform a detailed clinical and laboratory characterization of NPHl in a large prospective patient cohort with an assessment of parameters determining disease *** A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal(UlN)was prospectively evaluated over 31 *** were identified using daily electronic laboratory reports developed to support an ongoing observational,multicenter,prospective cohort study called the EASY trial(ISRCTN10525246)to establish a simple,easy,and accurate clinical scoring system for early prognostication of *** of NPHl was established based on≥3×UlN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of *** A total of 808 patients[male,n=420(52%);median age(IQR):65(51-75)years]were diagnosed with≥3×UlN serum lipase levels.A total of 392 patients had AP,whereas 401 had NPHl with more than 20 different *** and acute kidney injury(AKI)were the most prevalent etiologies of NPHl(27.7%and 33.2%,respectively).The best discriminative cut-off value for lipase was≥666 U/l(sensitivity,71.4%;specificity,88.8%).The presence of AKI or sepsis negatively affected the diagnostic performance of *** w

关键词： Non-pancreatic hyperlipasemia Acute pancreatitis Glycoprotein 2 Acute kidney injury Sepsis Mortality

Prognostic role of intestinal ultrasound in Crohn’s disease

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World Journal of Gastroenterology 2023年第23期29卷 3595-3605页

作者： Cristina Manzotti Francesco Colombo Tommaso Zurleni Piergiorgio Danelli Giovanni Maconi Gastroenterology Unit Department of Biomedical and Clinical SciencesUniversity of MilanL.Sacco University HospitalMilano 20157Italy Division of General Surgery Department of Biomedical and Clinical SciencesUniversity of MilanL.Sacco University HospitalMilano 20157Italy

The majority of patients affected by Crohn’s disease(CD)develop a chronic condition with persistent inflammation and relapses that may cause progressive and irreversible damage to the bowel,resulting in stricturing or penetrating complications in around 50%of patients during the natural history of the *** is frequently needed to treat complicated disease when pharmacological therapy failes,with a high risk of repeated operations in *** ultrasound(IUS),a non-invasive,cost-effective,radiation free and reproducible method for the diagnosis and follow-up of CD,in expert hands,allow a precise assessment of all the disease manifestations:Bowel characteristics,retrodilation,wrapping fat,fistulas and ***,IUS is able to assess bowel wall thickness,bowel wall stratification(echo-pattern),vascularization and elasticity,as well as mesenteric hypertrophy,lymph-nodes and mesenteric blood *** role in the disease evaluation and behaviour description is well assessed in literature,but less is known about the potential space of IUS as predictor of prognostic factors suggesting response to a medical treatment or postoperative *** availability of a low cost exam as IUS,able to recognize which patients are more likely to respond to a specific therapy and which patients are at high risk of surgery or complications,could be a very useful instrument in the hands of IBD *** aim of this review is to present current evidence about the prognostic role that IUS can show in predicting response to treatment,disease progression,risk of surgery and risk of post-surgical recurrence in CD.

关键词： Intestinal ultrasound Crohn’s disease Postoperative recurrence Bowel wall thickness Remission Intestinal surgery

Detecting the filamentary structure of 3D point clouds:Proposal of a wavelet-based method

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International Journal of Modeling, Simulation, and Scientific Computing 2017年第3期8卷 311-336页

作者： Roberto D’Ercole department of biomedical and clinical sciences“l.sacco”university of milan Via G.B.Grassi 74 Milan 20157Italy

The analysis of the filamentary structure of the cosmo as well as that of the internal structure of the polar ice suggests the development of models based on three-dimensional(3D)point processes.A point process,regarded as a random measure,can be expressed as a sum of Delta Dirac measures concentrated at some random *** integration with respect to the point process leads the continuous wavelet transform of the process *** possible mother wavelets,we propose the application of the Mexican hat and the Morlet wavelet in order to implement the scale-angle energy density of the process,depending on the dilation parameter and on the three angles which define the direction in the Euclidean *** indicator proves to be a sensitive detector of any variation in the direction and it can be successfully implemented to study the isotropy or the filamentary structure in 3D point patterns.

关键词： 3D Continuous wavelet transform energy density scale-angle energy density Mexican hat Morlet mother wavelet random measure filamentary structure rotation matrix Euler angles isotropy anisotropy

Cerebral ultrasound abnormalities in offsprings of women with C677T homozygous mutation in the MTHFR gene:a prospective study

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World Journal of Pediatrics 2015年第2期11卷 134-140页

作者： laura Pogliani Chiara Cerini Francesca Penagini Piergiorgio Duca Chiara Mameli Gian Vincenzo Zuccotti department of Pediatrics L.Sacco HospitalUniversity of Milan74 GB GrassiMilanIT 20157Italy department of clinical sciences L.Sacco HospitalUniversity of Milan74 GB GrassiMilanIT 20157Italy

Background:Perinatal stroke is a common cause of neurologic *** clinically under-recognized,its true incidence is not *** thrombophilia is likely to be a predisposing *** date,a general consensus for evaluation of babies born to mothers with genetic thrombotic predisposition is *** study was undertaken to assess the frequency of cerebral abnormalities in the offspring of women with homozygous C677T mutation in the MTHFR gene,and to seek for association with additional maternal or pregnancy risk ***:Mother-infant pairs were consecutively recruited from October 2006 through February *** underwent a thorough physical examination at birth,and a cerebral ultrasound examination(cUS)was performed within 24 hours of their *** neonates with major cerebral lesions,a thrombophilia panel test was ***-up cUS was performed in babies with major or minor cerebral ***:Ninety-one neonates(47 males)were *** cUS,abnormalities were detected in 18(19.8%)*** neonates were diagnosed with a minor lesion;a major ischemic/hemorrhagic lesion was found in 6 *** were a neat male preponderance and significant associations with a history of suspected miscarriage,maternal coagulation factors gene mutations,and reduced protein S or protein C ***:Our data confirmed a high incidence of cerebral abnormalities in neonates born to women with C677T homozygous mutation in the MTHFR *** at birth proved to be an effective screening tool or a diagnostic test,that should be routinely performed in babies born to mothers with known thrombotic predisposition.

关键词： cerebral ultrasound maternal thrombophilia methylenetetrahydrofolatereductase polymorphism perinatal stroke

In vitro engineered models of neurodegenerative diseases

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BIOCEll 2024年第1期48卷 79-96页

作者： ZEHRA GÜl MORÇIMEN ŞEYMA TAŞDEMIR AYlIN ŞENDEMIR Bioengineering department Graduate School of Natural and Applied SciencesEge UniversityIzmir35040Türkiye Bioengineering department Faculty of Engineering and Natural ScienceCelal Bayar UniversityManisa45110Türkiye Bioengineering department Ege UniversityIzmir35040Türkiye department of biomedical Technologies Graduate School of Natural and Applied SciencesEge UniversityIzmir35040Türkiye

Neurodegeneration is a catastrophic process that develops progressive damage leading to functional andstructural loss of the cells of the nervous system and is among the biggest unavoidable problems of our *** do not reflect the pathophysiology observed in humans due to distinct differences between the neuralpathways,gene expression patterns,neuronal plasticity,and other disease-related mechanisms in animals *** in vitro cell culture models are also not sufficient for pre-clinical drug testing in reflecting thecomplex pathophysiology of neurodegenerative ***,modern,engineered techniques are applied to developmulticellular,intricate in vitro models and to create the closest microenvironment simulating biological,biochemical,and mechanical characteristics of the in vivo degenerating *** THIS review,the capabilities and shortcomings ofscaffold-based and scaffold-free techniques,organoids,and microfluidic models that best reflect neurodegeneration invitro in the biomimetic framework are discussed.

关键词： Neurodegenerative diseases In vitro models Scaffolds Organoids Microfluidic devices

Enigmatic origin of hepatitis B virus:An ancient travelling companion or a recent encounter?

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World Journal of Gastroenterology 2014年第24期20卷 7622-7634页

作者： Gianguglielmo Zehender Erika Ebranati Elena Gabanelli Chiara Sorrentino Alessra lo Presti Elisabetta Tanzi Massimo Ciccozzi Massimo Galli l.sacco department of biomedical and clinical sciences University of Milan20157 MilanItaly department of Infectious Parasitic and Immunomediated DiseasesNational Institute of Health00161 RomeItaly department of biomedical sciences for Health University of Milan20157 MilanItaly

Hepatitis B virus(HBV)is the leading cause of liver disease and infects an estimated 240 million people *** is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral *** ten genotypes(A-J)that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic *** A and D are ubiquitous and the most prevalent genotypes in Europe(mainly represented by subgenotypes D1-3 and A2);genotypes B and C are restricted to eastern Asia and Oceania;genotype E to central and western Africa;and genotypes H and F(classified into 4 subgenotypes)to latin America and *** review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes,particularly those concerning the origin and dispersion histories of genotypes A,D,E and F and their *** lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely *** is hypothesised that HBV evolutionary rates are time dependent,and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations.

关键词： Hepatitis B virus genotypes and subgenotypes Phylogeography Population dynamics and epidemics Molecular epidemiology Hepatitis B virus phylodynamics

TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1209-1220页

作者： Shuai Song Xiaokai Zhang Zihang Huang Yongchao Zhao Shuyang lu linqi Zeng Fengze Cai Tongyao Wang Zhiqiang Pei Xinyu Weng Wei luo Hao lu Zilun Wei Jian Wu Peng Yu li Shen Xiaochun Zhang Aijun Sun Junbo Ge department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiChina State Key laboratory of Cardiology Zhongshan HospitalFudan UniversityShanghaiChina Key laboratory of Viral Heart Diseases National Health CommissionShanghaiChina Key laboratory of Viral Heart Diseases Chinese Academy of Medical SciencesShanghaiChina National clinical Research Center for Interventional Medicine ShanghaiChina department of cardiac surgery Zhongshan HospitalFudan UniversityShanghaiChina Institutes of biomedical sciences Fudan UniversityShanghaiChina Shanghai Institute of Hypertension Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and ***,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely *** analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l *** investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure *** TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre *** and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac ***,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 ***1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 ***,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 *** conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

关键词： TEAD1 expression Wnt4

Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking lOXl2-mediated vascularization

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Bone Research 2024年第2期12卷 372-389页

作者： longqing Wang Wenhao Jiang Siyuan Zhao Dong Xie Qing Chen Qi Zhao Hao Wu Jian luo lili Yang Spine Center Department of OrthopaedicsShanghai Changzheng HospitalSecond Affiliated Hospital of Naval Medical UniversityShanghai 200003PR China Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center) Tongji University School of MedicineShanghaiPR China Shanghai Key laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiPR China department of Orthopaedics No.905 Hospital of PLA NavyShanghaiPR China

Ossification of the Posterior longitudinal ligament(OPll)is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone,resulting in limited spinal mobility and nerve *** both bulk and single-cell RNA sequencing,we elucidate the molecular characteristics,cellular components,and their evolution during the OPll process at a single-cell resolution,and validate these findings in clinical *** study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in ***,our study identifies lOXl2 as a key regulator in this *** gain-and loss-of-function studies,we elucidate the role of lOXl2 in the endothelial-like differentiation of ligament *** acts via the HIF1A pathway,promoting the secretion of downstream VEGFA and *** function is not related to the enzymatic activity of ***,we identify sorafenib,a broad-spectrum tyrosine kinase inhibitor,as an effective suppressor of lOXl2-mediated vascular *** disrupting the coupling between vascularization and osteogenesis,sorafenib demonstrates significant inhibition of OPll progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone *** findings underscore the potential of sorafenib as a therapeutic intervention for OPll.

关键词： lOXl2 ligament finding