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In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells

World Journal of Gastroenterology 2025年第3期31卷 84-102页

作者： Patricia de la Cruz-Ojeda Ester Parras-Martínez Raquel Rey-Pérez Jordi Muntané Functional Genomics of Solid Tumors Laboratory Centre de Recherche des CordeliersParis 75006France department of Oncology Surgery Cell Therapy and Organ TransplantationInstitute of Biomedicine of SevilleVirgen del Rocio University HospitalSeville 41013Spain Biomedical Research Center for Hepatic and Digestive Diseases CIBERehdMadrid 28029Spain department of Medical Physiology and Biophysics University of SevilleSeville 41009Spain

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology *** is still a recommended treatment for a large proportion of patients with advanced *** patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 *** To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 *** available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 *** HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 *** RNA,including small and long RNA,was extracted with a commercial miRNeasy *** was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory *** MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 ***12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 *** axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib *** Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关键词： Cell culture Hepatocellular carcinoma Non-coding RNA RNAseq Sorafenib

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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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Antioxidant biocompatible composite collagen dressing for diabetic wound healing in rat model

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Regenerative Biomaterials 2021年第2期8卷 74-84页

作者： Bei Qian Jialun Li Ke Guo Nengqiang Guo Aimei Zhong Jie Yang Jiecong Wang Peng Xiao Jiaming Sun Lingyun Xiong department of Plastic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and Technology1277 Jiefang AvenueWuhan 430022China Wuhan Clinical Research Center for Superficial organ reconstruction Wuhan 430022China

Associated with persistent oxidative stress,altered inflammatory responses,poor angiogenesis and epithelization,wound healing in diabetic patients is impaired.N-acetylcysteine(NAC)is reported to resist excess reactive oxygen species(ROS)production,prompt angiogenesis and maturation of the *** have revealed that graphene oxide(GO)can regulate cellular behavior and form cross-links with naturally biodegradable polymers such as collagen(COL)to construct composite ***,we reported a COL-based implantable scaffold containing a mixture of GO capable of the sustained delivery of NAC to evaluate the wound healing in diabetic *** morphological,physical characteristics,biocompatibility and NAC release profile of the GO-COL-NAC(GCN)scaffold were evaluated in *** healing studies were performed on a 20mm dorsal full-skin defect of streptozotocin(STZ)-induced diabetic *** injured skin tissue was removed at the 18th day post-surgery for histological analysis and determination of glutathione peroxidase(GPx),catalase(CAT)and superoxide dismutase(SOD)*** diabetic rats,we confirmed that the GCN scaffold presented a beneficial effect in enhancing the wound healing ***,due to the sustained release of NAC,the scaffold may potentially induce the antioxidant defense system,upregulating the expression levels of the antioxidant enzymes in the wound *** findings revealed that the antioxidant biocompatible composite collagen dressing could not only deliver NAC in situ for ROS inhibition but also promote the wound healing *** scaffold with valuable therapy potential might enrich the approaches for surgeon in diabetic wound treatment in the future.

关键词： collagen graphene oxide N-acetylcysteine sustained release diabetic wound healing

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Alendronate loaded graphene oxide functionalized collagen sponge for the dual effects of osteogenesis and anti-osteoclastogenesis in osteoporotic rats

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Bioactive Materials 2020年第4期5卷 859-870页

作者： Yuyang Zeng Muran Zhou Lifeng Chen Huimin Fang Shaokai Liu Chuchao Zhou Jiaming Sun Zhenxing Wang department of Plastic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Wuhan Clinical Research Center for Superficial organ reconstruction Wuhan430022China

Graphene Oxide(GO)-related hydrogels have been extensively studied in hard tissue repair,because GO can not only enhance the mechanical properties of polymers but also promote osteogenic differentiation of mesenchymal stem ***,simple GO-related hydrogels are not ideal for the repair of osteoporotic bone defects as the overactive osteoclasts in ***(Aln)is known to inhibit osteoclasts and may bind to GO through covalent ***,delivering Aln in GO-related hydrogels may be effective to repair osteoporotic bone ***,we developed a control-released system which is constructed by collagen(Col)-GO sponges loaded with Aln(Col-GO-Aln)for osteoporotic bone defect *** vitro,Col-GO-Aln sponges prolonged the release period of Aln,and the sponge containing 0.05%(w/v)GO released Aln faster than sponge with 0.2%***,tartrate-resistant acid phosphatase(TRAP)and F-actin staining demonstrated that Col-GO-Aln sponges effectively inhibited osteoclastogenesis of *** vivo,micro-CT scan showed that the volume of newborn bone in defect site by 0.05%GO sponge was nearly three times larger than that of other ***,the CT and histological examinations of rat femur proved that Col-GO-Aln sponges decreased the number of osteoclasts and suppressed the systemic bone loss in osteoporotic *** findings reveal that the application of GO as carriers of anti-osteoporosis drugs is a viable treatment for *** results also underscore the potential of GO-related hydrogels with Aln-releasing capacity for bone regeneration in osteoporosis.

关键词： Osteoporosis Osteoporotic bone defect Graphene oxide Osteoclast Alendronate

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Simple application of adipose-derived stem cell-derived extracellular vesicles coating enhances cytocompatibility and osteoinductivity of titanium implant

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Regenerative Biomaterials 2021年第1期8卷 64-72页

作者： Lifeng Chen Shan Mou Jinfei Hou Huimin Fang Yuyang Zeng Jiaming Sun Zhenxing Wang department of Plastic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Wuhan Clinical Research Center for Superficial organ reconstruction Wuhan Union Hos pitalHuazhong University of Science and Technology1277 Jiefang AvenueWuhan 430022China

Surface modification using bioactive molecules is frequently performed to improve the biological properties of medical metal biomaterial titanium(Ti)*** evidence suggests that mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)served as potent bioactive *** a subset of MSC EV,adipose-derived stem cel-derived extracellular vesicles(ADSC-EVs)could be obtained from abundant adipose ***,it possesses multiple re-generative properties and might be used to endow biological activities to medical Ti ***,we present a simple ADSC-EV coating strategy based on physisorption of *** ADSC-EV functionalized Ti implants(EV-Ti)revealed enhanced osteoblast compatibility and osteoinduc-tive *** spreading area of EV-Ti group was 1.62-and 1.48-fold larger than that of Ti group after 6 and 12 h of cell seeding,***,EV-Ti promoted alkaline phosphatase,col-lagen 1 and osteocalcin gene expression in osteoblast by 1.51-,1.68-and 1.82-fold compared with pristine Ti,***,the MSC-EVs modification method reported here provide a clinically translatable strategy to promote the bioactivity of Ti implants.

关键词： adipose-derived stem cll-derived extraellular vesicles titanium surface modification fibronectin osteoinductivity

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May the assessment of baseline mucosal molecular pattern predict the development of gluten related disorders among microscopic enteritis?

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World Journal of Gastroenterology 2016年第35期22卷 8017-8025页

作者： Giuseppe Losurdo Floriana Giorgio Domenico Piscitelli Lucia Montenegro Claudia Covelli Maria Grazia Fiore Antonio Giangaspero Andrea Iannone Mariabeatrice Principi Annacinzia Amoruso Michele Barone Alfredo Di Leo Enzo Ierardi Section of Gastroenterology Department of Emergency and Organ Transplantation University of Bari Section of Pathology Department of Emergency and Organ Transplantation University of Bari

AIM To evaluate mucosal baseline m RNA expression of tissue transglutaminase 2(t TG2), interferon gamma(IFNγ), toll-like receptor 2(TLR2) and Myeloid Differentiation factor 88(MyD 88) in patients with microscopic enteritis(ME).METHODS We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count(IELs). ME was defined according to the criteria of Bucharest Consensus Conference. For each patient, formalin embedded biopsy samples of the duodenum referred to the period of ME diagnosis were retrieved. Real-time polymerase chain reaction(RT-PCR) was used to detect the amount of mR NA coding for tT G2, IFNγ, TLR2 and My D88, and the quantity was expressed as fold change compared to controls. Control group was represented by duodenal normal specimens from 15 healthy subjects undergoing endoscopy for functional symptoms. Comparisons among continuous variables were performed by One way analysis of variance(ANOVA) and Bonferroni’s test. The χ~2 test was used for categorical variables. Pearson’s test was used to evaluate correlations. Receiver operating curves were drawn for all four markers to estimate sensitivity and specificity in discriminating the development of CD and *** After a period of follow up of 21.7 ± 11.7 mo, the following diagnoses were achieved: gluten related disorders in 48 subjects(31 CD; 17 GS) and non-gluten related ones in 41(29 Irritable Bowel Syndrome- IBS; 12 Others). CD patients had the highest tT G2 levels(8.3 ± 4.5). The ANOVA plus Bonferroni analysis showed that CD > Other ME > GS = IBS > negative controls. A cut off value of 2.258 was able to discriminate between CD and GS with a sensitivity of 52.94% and a specificity of 87.1%. Additionally, CD patients had the highest IFNγ levels(8.5 ± 4.1). ANOVA plus

关键词： Celiac disease MyD 88 Microscopic enteritis Gluten sensitivity Tissue transglutaminase Interferon gamma Toll-like receptor 2

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Global transplantation:Lessons from organ transplantation organizations worldwide

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World Journal of Transplantation 2025年第1期15卷 44-56页

作者： Solonas Symeou Eleni Avramidou Vassilios Papalois Georgios Tsoulfas Medical School University of IoanninaIoannina 45110Greece department of Transplantation Surgery Center for Research and Innovation in Solid Organ TransplantationSchool of MedicineAristotle University of ThessalonikiThessaloniki 54642Greece Imperial College Renal and Transplant Centre Imperial College Healthcare NHS TrustHammersmith HospitalLondon W120HSUnited Kingdom department of Surgery and Cancer Imperial College LondonLondon SW72AZUnited Kingdom

Although national transplant organizations share common visions and goals,the creation of a unified global organization remains *** in ethnicity,culture,religion,and education shape local practices and infrastructure,making the establishment of a single global entity *** with these social disparities aside,logistical factors such as time and distance between organ procurement and transplantation sites pose significant *** technological advancements have extended organ preservation times,they have yet to support the demands of transcontinental transplantations *** review presents a comparative analysis of the structures,operational frameworks,policies,and legislation governing various transplant organizations around the *** differences pertain to the administration of these organizations,trends in organ donation,and organ allocation policies,which reflect the financial,cultural,and religious diversity across different *** a global transplant organization may be out of reach,agreeing on best practices for the benefit of patients is essential.

关键词： organ transplantation National transplant organizations organ donation Global transplantation Transplant systems

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Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism

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World Journal of Gastroenterology 2013年第23期19卷 3583-3595页

作者： Zhong-Yang Shen Jing Zhang Hong-Li Song Wei-Ping Zheng department of organ Transplantation Tianjin First Central Hospital

AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent ***: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.

关键词： Bone marrow mesenchymal stem cells Zona occludens 1 Ischemia-reperfusion injury Intestinal mucosa Tumor necrosis factor-α

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Noninvasive molecular analysis of Helicobacter pylori : Is it time for tailored first-line therapy?

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World Journal of Gastroenterology 2017年第14期23卷 2453-2458页

作者： Enzo Ierardi Floriana Giorgio Andrea Iannone Giuseppe Losurdo Mariabeatrice Principi Michele Barone Antonio Pisani Alfredo Di Leo Gastroenterology Section Department of Emergency and Organ Transplantation University of Bari

The main problem of Helicobacter pylori(H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction(PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin su

关键词： Helicobacter pylori Antibiotic resistance Noninvasive molecular test Tailored therapy Stool

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Unexpected me diastinal mass in a liver transplanted patient

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 199-201页

作者： Giuseppe Losurdo Giuseppe Ingravallo Antonio Mongelli Nicola Maurizio Castellaneta Antonio Pisani Section of Gastroenterology Department of Emergency and Organ Transplantation University "Aldo Moro" Section of Pathology Department of Emergency and Organ Transplantation University "Aldo Moro"

To the Editor:The risk of de novo cancer increases by 2 to 7-fold after liver transplantation[1].The most common de novo cancers are both solid(non-melanoma skin cancers,colorectal carcinoma,genito-urinary and head-neck cancer)[2,3]as well as hematologic malignancies,in particular the so-called post-transplant lymphoproliferative disorder[4].

关键词： mediastinal mass liver transplanted patient post-transplant

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