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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

lncRNA ZNF593-AS inhibits cardiac hypertrophy and myocardial remodeling by upregulating Mfn2 expression

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Frontiers of Medicine 2024年第3期18卷 484-498页

作者： Xiang Nie Jiahui Fan Yanwen Wang Rong Xie Chen Chen Huaping Li Dao Wen Wang Division of Cardiology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders Wuhan430030China

lncRNA ZNF593 antisense(ZNF593-AS)transcripts have been implicated in heart failure through the regulation of myocardial *** decreased transcriptional activity of ZNF593-AS has also been detected in cardiac ***,the function of ZNF593-AS in cardiac hypertrophy remains ***,we report that the expression of ZNF593-AS reduced in a mouse model of left ventricular hypertrophy and cardiomyocytes in response to treatment with the hypertrophic agonist phenylephrine(PE).In vivo,ZNF593-AS aggravated pressure overload–induced cardiac hypertrophy in knockout *** contrast,cardiomyocyte-specific transgenic mice(ZNF593-AS MHC-Tg)exhibited attenuated TAC-induced cardiac *** vitro,vector-based overexpression using murine or human ZNF593-AS alleviated PE-induced myocyte hypertrophy,whereas GapmeR-induced inhibition aggravated hypertrophic *** using RNA-seq and gene set enrichment analyses,we identified a link between ZNF593-AS and oxidative phosphorylation and found that mitofusin 2(Mfn2)is a direct target of ***593-AS exerts an antihypertrophic effect by upregulating Mfn2 expression and improving mitochondrial ***,it represents a promising therapeutic target for combating pathological cardiac remodeling.

关键词： lncRNA ZNF593-AS cardiac hypertrophy Mfn2 oxidative phosphorylation

Causal associations between gastroesophageal reflux disease and essential hypertension: A bidirectional Mendelian randomization study

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World Journal of Clinical Cases 2024年第5期12卷 880-890页

作者： Ning Wei Ming-Hui Liu Yu-Hu Song department of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022Hubei ProvinceChina

BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of *** To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential *** Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and *** MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers *** MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental *** IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD *** the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD ***,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension *** We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.

关键词： Gastroesophageal reflux disease Essential hypertension Hypertensive heart disease Mendelian randomization study

STAT3 ameliorates truncated tau-induced cognitive deficits

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Neural Regeneration Research 2024年第4期19卷 915-922页

作者： Bingge Zhang Huali Wan Maimaitijiang Maierwufu Qian Liu Ting Li Ye He Xin Wang Gongping Liu Xiaoyue Hong Qiong Feng department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and Technology department of Laboratory Medicine Guangdong ProvincialPeople's Hospital(Guangdong Academy of Medical Sciences)Southern Medical University department of Laboratory Medicine Zhongnan Hospital of Wuhan University department of Pathology Wuhan Children's HospitalTongji Medical CollegeHuazhong University of Science and Technology

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease ***,the molecular mechanisms of truncated tau-induced cognitive deficits remain *** suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive *** luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the *** of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 ***,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by *** together,STAT3 plays a critical role in truncated tau-related neuropathological *** indicates a new mechanism behind the effect of tau-N368 on synapses and memory ***3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

关键词： Alzheimer’s disease apoptosis cognitive deficit memory neurodegenerative disease neuron loss N-methyl-D-aspartic acid receptor STAT3 synapse tau-N368

Cell polarization in ischemic stroke: molecular mechanisms and advances

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Neural Regeneration Research 2025年第3期20卷 632-645页

作者： Yuanwei Li Xiaoxiao Xu Xuan Wu Jiarui Li Shiling Chen Danyang Chen Gaigai Li Zhouping Tang department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

关键词： astrocyte polarization immune regulation inflammation ischemic injury microglia polarization neutrophil polarization signaling pathways stroke

Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model

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Neural Regeneration Research 2024年第3期19卷 687-696页

作者： Longqing Zhang Xi Tan Fanhe Song Danyang Li Jiayi Wu Shaojie Gao Jia Sun Daiqiang Liu Yaqun Zhou Wei Mei department of Anesthesiology Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Healthand Wuhan Clinical Research Center for Geriatric AnesthesiaTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains *** this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated *** injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated *** changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1α*** together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.

关键词： G-protein-coupled receptor 39(GPR39) neuroinflammation neuropathic pain nuclear respiratory factor 1(NRF1) peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α) sirtuin 1(SIRT1) spinal cord mitochondrial transcription factor A(TFAM)

Transforming Adolescent Smiles:Correcting Skeletal Mandibular Retrusion and Bimaxillary Protrusion with Clear Aligners

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Current medical science 2024年第3期44卷 657-666页

作者： Wen-jie FAN Jia-qi ZHANG Jia-qi ZHAN Li HU Li-li CHEN department of Stomatology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China School of Stomatology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Wuhan National High Magnetic Field Center Wuhan430074China The affiliated Lianyungang hospital of Xuzhou medical university/The First People’s hospital of Lianyungang Lianyungang222000China The First affiliated hospital of Kangda college of Nanjing medical university/The First People’s hospital of Lianyungang Lianyungang222000China

Maxillary protrusion combined with mandibular retraction is a highly prevalent but extremely complex maxillofacial deformity that can have a serious negative impact on patients’facial aesthetics and mental *** traditional orthodontic treatment strategy often involves extracting 4 first premolars and conventional fixed techniques,combined with mini-implant screws,to retract the anterior teeth and improve facial *** recent years,an invisible orthodontic technique,without brackets,has become increasingly ***,while an invisible aligner has been used in some cases with reasonable results,there remain significant challenges in achieving a perfect *** case report presents an adolescent patient with bimaxillary protrusion and mandibular *** on the characteristics of the invisible aligners and the growth characteristics of the adolescent’s teeth and jawbone,we designed precise three-dimensional tooth movement and corresponding resistance/over-correction for each tooth,while utilizing the patient’s jawbone growth potential to promote rapid development of the mandible,accurately and efficiently correcting bimaxillary protrusion and skeletal mandibular *** patient’s facial aesthetics,especially the lateral morphology,have been greatly improved,and various aesthetic indicators have also shown significant changes,and to the patient’s great benefit,invasive mini-implant screws were not used during the *** case highlights the advantages of using invisible aligners in adolescent maxillary protrusion combined with mandibular retraction ***,comprehensive and accurate design combined with good application of growth potential can also enable invisible orthodontic technology to achieve perfect treatment effects in tooth extractions,providing clinical guidance for orthodontists.

关键词： mandibular retrusion esthetic orthodontic treatment clear aligners growth potential

The generation and use of animal models of osteosarcoma in cancer research

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Genes & Diseases 2024年第2期11卷 664-674页

作者： Feifei Pu Haoyu Guo Deyao Shi Fengxia Chen Yizhong Peng Xin Huang Jianxiang Liu Zhicai Zhang Zengwu Shao department of Orthopedics Wuhan Hospital of Traditional Chinese and Western Medicine (Wuhan No.1 Hospital)Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of Radiation and medical Oncology Zhongnan HospitalWuhan UniversityWuhanHubei 430071China Hubei Cancer Clinical Study Center Zhongnan HospitalWuhan UniversityWuhanHubei 430071China

Osteosarcoma is the most common malignant bone tumor affecting children and ***,the most common treatment is surgery combined with neoadjuvant *** the survival rate of patients with osteosarcoma has improved in recent years,it remains poor when the tumor(s)progress and distant metastases ***,better animal models that more accurately replicate the natural progression of the disease are needed to develop improved prognostic and diagnostic markers,as well as targeted therapies for both primary and metastatic *** present review described animal models currently being used in research investigating osteosarcoma,and their characteristics,advantages,and *** models may help elucidate the pathogenic mechanism(s)of osteosarcoma and provide evidence to support and develop clinical treatment strategies.

关键词： Animal model Cancer Osteosarcoma Pathogenic mechanism Translational research

Predictive Value of High Mobility Group Box-1 and miR-146b in Septic Shock Patients

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Wuhan university Journal of Natural sciences 2024年第1期29卷 85-94页

作者： FENG Jun SHAO Shasha LIU Junya PAN Yongjun YIN Huimei WANG Junshuai department of Emergency Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030HubeiChina department of Critical Care Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030HubeiChina department of Critical Care Medicine Southern University of Science and Technology HospitalShenzhen 518055GuangdongChina department of Emergency Medicine People's Hospital of Bortala Mongol Autonomous PrefectureBole 833400XinjiangChina

In the face of the elevated incidence and mortality rate of septic shock in the ICU,this retrospective study seeks to investigate the indicative and predictive value of high-mobility group box 1(HMGB1)and miR-146b in patients with septic *** RTPCR was employed in this study to quantify the HMGB1 and miR-146b levels in plasma samples obtained from the patient group and healthy *** investigation involved the comparison between the two groups and tracking changes in the patient group over *** finding revealed that upon admission,the patient group exhibited markedly elevated relative expression levels of HMGB1,which subsequently decreased over ***,the patient group displayed significantly reduced relative expression levels of miR-146b upon admission,which subsequently increased over time compared to the control *** operating characteristic(ROC)curves showed good predictive value for HMGB1 and *** experimental results suggest that HMGB1 and miR-146b serve as valuable and convenient biomarkers for evaluating the severity of septic shock and predicting ***,it is proposed that serum miR-146b may be inducible and potentially exerts a negative regulatory effect on the expression of HMGB1.

关键词： septic shock feedback loop high mobility group box-1 miR-146b disease severity