Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the pr...Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.展开更多
Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as wate...Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as water or air,poses a significant challenge for delivering highly-controlled chemical flow to an animal subject.Moreover,contact-based cue manipulation and delivery easily shift the position of the animal subject,which is often undesirable for high-quality brain imaging.Additionally,more advanced interfacing tools that align with the diverse range of body part sizes of an animal,ranging from micrometer-scale neurons to meter-long limbs,are much needed.This is particularly crucial when dealing with dimensions that are beyond the reach of conventional experimental tools.展开更多
Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy,resulting in abnormal sensation in lower lip.It is generally believed that spontaneous sensory recovery in this...Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy,resulting in abnormal sensation in lower lip.It is generally believed that spontaneous sensory recovery in this nerve injury is difficult.However,during our follow-up,patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery.In this study,a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery.展开更多
After reconstructing the anterior cruciate ligament(ACL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing stage.With good biological features and high formability,M...After reconstructing the anterior cruciate ligament(ACL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing stage.With good biological features and high formability,Magnesium-Zinc-Gadolinium(ZG21)wires are developed to bunch the tendon graft for matching the bone tunnel during transplantation.Microstructure,tensile strength,degradation,and cytotoxicity of ZG21 wire are evaluated.The rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT,histology,and mechanical test.The SEM/EDS,immunochemistry,and in vitro assessments are performed to investigate the underlying mechanism.Material tests demonstrate the high formability of ZG21 wire as surgical suture.Micro-CT shows ZG21 wire degradation accelerates tunnel bone formation,and histologically with earlier and more fibrocartilage regeneration at the healing interface.The mechanical test shows higher ultimate load in the ZG21 group.The SEM/EDS presents ZG21 wire degradation triggered calcium phosphate(Ca-P)deposition.IHC results demonstrate upregulation of Wnt3a,BMP2,and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of healing.In vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a,βcatenin,ocn and opn to stimulate osteogenesis.Ex vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon tissue.In conclusion,the ZG21 wire is feasible for tendon graft bunching.Its degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction.展开更多
Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic ...Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC.However,even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC(EBVa GC),suggesting a predominant role of epigenetic abnormities,especially promoter Cp G methylation,in the pathogenesis of NPC and EBVa GC.High frequencies of promoter methylation of tumor suppressor genes(TSGs)have been frequently reported in NPC and EBVa GC,with several EBV-induced methylated TSGs identified.Further characterization of the epigenomes(genome-wide Cp G methylation profile—methylome)of NPC and EBVa GC shows that these EBV-associated tumors display a unique high Cp G methylation epigenotype with more extensive gene methylation accumulation,indicating that EBV acts as a direct epigenetic driver for these cancers.Mechanistically,oncogenic modulation of cellular Cp G methylation machinery,such as DNA methyltransferases(DNMTs),by EBV-encoded viral proteins accounts for the EBV-induced high Cp G methylation epigenotype in NPC and EBVa GC.Thus,uncovering the EBV-associated unique epigenotype of NPC and EBVa GC would provide new insight into the molecular pathogenesis of these unique EBVassociated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.展开更多
AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carc...AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.展开更多
AIM:To study the molecular mechanism of laterally spreading tumor (LST), a cell line [Laterally Spreading Tumor-Rectum 1 (LST-R1)] was derived and the characteristics of this cell line were investigated. METHODS:A new...AIM:To study the molecular mechanism of laterally spreading tumor (LST), a cell line [Laterally Spreading Tumor-Rectum 1 (LST-R1)] was derived and the characteristics of this cell line were investigated. METHODS:A new cell line (LST-R1) originated from laterally spreading tumor was established. Properties of the cell line were characterized using scanning and transmission electron microscopy, immunohistochemistry method, cytogenetic analysis and nude mice xenograft experiments. In vitro invasion assay, cDNA microarray and Western blotting were used to compare the difference between the LST-R1 and other colorectal cancer cell lines derived from prudent colon cancer. RESULTS:Our study demonstrated that both epithelial special antigen (ESA) and cytokeratin-20 (CK20) were expressed in LST-R1. The cells presented microvilli and tight junction with large nuclei. The karyotypic analysis showed hyperdiploid features with structural chromosome aberrations. The in vivo tumorigenicity was also demonstrated in nude mice xenograft experiments. The invasion assay suggested this cell line has a higher invasive ability. cDNA microarray and Western blotting show the loss of the expression of E-cadherin in LST-R1 cells.CONCLUSION:We established and characterized a colorectal cancer cell line, LST-R1 and LST-R1 has an obvious malignant tendency, which maybe partially attributed to the changes of the expression of some adhesion molecules, such as E-cadherin. It is also a versatile tool for exploring the original and progressive mechanisms of laterally spreading tumor and the early colon cancer genesis.展开更多
Skeletal tissue is highly innervated.Although different types of nerves have been recently identified in the bone,the crosstalk between bone and nerves remains unclear.In this review,we outline the role of the periphe...Skeletal tissue is highly innervated.Although different types of nerves have been recently identified in the bone,the crosstalk between bone and nerves remains unclear.In this review,we outline the role of the peripheral nervous system(PNS)in bone regeneration following injury.We first introduce the conserved role of nerves in tissue regeneration in species ranging from amphibians to mammals.We then present the distribution of the PNS in the skeletal system under physiological conditions,fractures,or regeneration.Furthermore,we summarize the ways in which the PNS communicates with bone-lineage cells,the vasculature,and immune cells in the bone microenvironment.Based on this comprehensive and timely review,we conclude that the PNS regulates bone regeneration through neuropeptides or neurotransmitters and cells in the peripheral nerves.An in-depth understanding of the roles of peripheral nerves in bone regeneration will inform the development of new strategies based on bone-nerve crosstalk in promoting bone repair and regeneration.展开更多
In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment.Medline,Excerpta Medica Database(EMBASE),O...In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment.Medline,Excerpta Medica Database(EMBASE),Ovid,and China National Knowledge Infrastructure(CNKI),were searched for the period from January 1990 to June 2021 using the keywords"male infertility,""medical therapy,""supplement/nutrient therapy,"and related terms.Randomized controlled trials(RCTs)investigating medicines(mainly follicle-stimulating hormone(FSH),androgen,and clomiphene/tamoxifen)or supplements(mainly zinc,selenium,vitamin C or E,carnitine,coenzyme Q10(CoQ10),or combined treatment)for idiopathic infertile men were selected for meta-analysis.Preferred reporting items for systematic reviews and meta-analysis(PRISMA)was used for data extraction,and a risk-of-bias tool and grades of recommendation,assessment,development,and evaluation(GRADE)system adapted to the NMA were employed to assess the quality of the evidence.The primary outcomes were live birth and spontaneous pregnancy rate(SPR).The secondary outcomes were sperm parameters(including concentration,progressive motility,and morphology)and side effects.In total,65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included.A total of 36 studies reported SPR but only three reported live birth rates.The quality of the included studies was found to be moderate to high.Compared with a placebo or being untreated,carnitine plus vitamins significantly improved SPR(relative risk(RR)=3.7,95%confidence interval(95%CI),1.6-8.5);fatty acids significantly increased sperm concentrations(mean difference(MD)=12.5×10^(6)mL-1,95%CI,3.1×10^(6)-22.0×10^(6));and selective estrogen receptor modulator(SERM)plus CoQ10 significantly improved sperm progressive motility(MD=11.0%,95%CI,0.1%-21.9%)and normal sperm morphology(MD=11.0%,95%CI,4.6%-17.4%).The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations,respectively,even after excluding trials at a high risk of bias.Compared with a placebo or being untreated,FSH(RR=4.9,95%CI,1.1-21.3)significantly increased SPR,whereas SERM plus kallikrein increased sperm concentration(MD=16.5×10^(6)mL^(-1),95%CI,1.6×10^(6)-31.4×10^(6)),and SERM plus CoQ10 significantly improved sperm progressive motility(MD=11.3%,95%CI,7.3%-15.4%)and normal morphology(MD=11.2%,95%CI,5.4%-16.9%)in men with oligoasthenozoospermia(OA).In terms of side effects,fatty acids and pentoxifylline were associated with foul breath and/or a bad taste(RR=8.1,95%CI,1.0-63.5)and vomiting(RR=8.0,95%CI,1.0-63.0),respectively.In conclusion,the optimal treatment for male infertility for live birth is still unknown.Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in cou ples with men with OA,respectively.The efficacy of other treatments on pregnancy outcomes warrants further verification.展开更多
Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal ...Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.展开更多
Although the Epstein-Barr virus(EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma(NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant trans...Although the Epstein-Barr virus(EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma(NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cells. These cancer stem-like cells(CSCs) have the ability to selfrenew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBVassociated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1(LMP1) and latent membrane protein 2A(LMP2A)], cellular microRNAs, and adenosine triphosphate(ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.展开更多
Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recen...Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.展开更多
@Yun Qian$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 3...@Yun Qian$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Chi-Chun Wong$Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong!Hong Kong, China@San-Chuan Lai$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Zheng-Hua Lin$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Wei-Liang Zheng$Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Hui Zhao$Emergency Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Kong-Han Pan$Department of Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Shu-Jie Chen$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Jian-Min Si$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province,展开更多
More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ,...More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZbinding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and micro RNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis.展开更多
基金supported by the GRF RGC&CRF,Hong Kong(Grant Nos.:475012 and C5045-20 EF)HMRF,Hong Kong(Grant No.:03141386)+3 种基金ITF,Hong Kong(Grant No.:ITS/209/12)UGC Direct Grant 2011,2012,2021.032HKOG Trust Fund 2011,2014,2019the National Natural Science Foundation of China(Grant Nos.:81974225 and 82201823)。
文摘Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.
基金funded by a Croucher Innovation Award(CIA20CU01)from the Croucher Foundationthe General Research Fund(14100122)+4 种基金the Collaborative Research Fund(C6027-19GF&C7074-21GF)the Area of Excellence Scheme(AoE/M-604/16)of the Research Grants Councilthe University Grants Committee of Hong Kong,Chinathe Excellent Young Scientists Fund(Hong Kong and Macao,China)(82122001)from the National Natural Science Foundation of Chinathe Lo’s Family Charity Fund Limited(all to HK).
文摘Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as water or air,poses a significant challenge for delivering highly-controlled chemical flow to an animal subject.Moreover,contact-based cue manipulation and delivery easily shift the position of the animal subject,which is often undesirable for high-quality brain imaging.Additionally,more advanced interfacing tools that align with the diverse range of body part sizes of an animal,ranging from micrometer-scale neurons to meter-long limbs,are much needed.This is particularly crucial when dealing with dimensions that are beyond the reach of conventional experimental tools.
基金supported by the Applied Basic Research Programs of the Sichuan Provincial Science and Technology Department(Grant number:2021YJ0129)Research Program of Science and Technology Department of Sichuan Province(Grant number:2021YFS0217)the National Natural Science Foundation of China(81870782)。
文摘Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy,resulting in abnormal sensation in lower lip.It is generally believed that spontaneous sensory recovery in this nerve injury is difficult.However,during our follow-up,patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery.In this study,a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery.
基金Theme-based research scheme of Hong Kong Research Grant Council(RGC Ref:T13-402/17-N)National Natural Science Foundation of China(No.U1804251)。
文摘After reconstructing the anterior cruciate ligament(ACL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing stage.With good biological features and high formability,Magnesium-Zinc-Gadolinium(ZG21)wires are developed to bunch the tendon graft for matching the bone tunnel during transplantation.Microstructure,tensile strength,degradation,and cytotoxicity of ZG21 wire are evaluated.The rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT,histology,and mechanical test.The SEM/EDS,immunochemistry,and in vitro assessments are performed to investigate the underlying mechanism.Material tests demonstrate the high formability of ZG21 wire as surgical suture.Micro-CT shows ZG21 wire degradation accelerates tunnel bone formation,and histologically with earlier and more fibrocartilage regeneration at the healing interface.The mechanical test shows higher ultimate load in the ZG21 group.The SEM/EDS presents ZG21 wire degradation triggered calcium phosphate(Ca-P)deposition.IHC results demonstrate upregulation of Wnt3a,BMP2,and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of healing.In vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a,βcatenin,ocn and opn to stimulate osteogenesis.Ex vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon tissue.In conclusion,the ZG21 wire is feasible for tendon graft bunching.Its degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction.
基金This paper is dedicated to the late Professor JS Chiao, who initiated the research in China for rifamycin production employing A. mediterranei more than 30 years ago and who continued the endeavor to resolve the mechanism of the 'nitrate stimulating effect' up to the last breath of his life. This work was supported by the National Natural Science Foundation of China (30830002), the National High Technology Research and Development Program of
China (2007AA021301, 2007AA021503), and the Research Unit Fund of Li Ka Shing Institute of Health Sciences (7103506).
基金Supported by grants from Health and Medical Research Fund(HMRF)(No.13120082)Hong Kong Research Grants Council(RGC)(No.474710 and T12-401/13R)+1 种基金National Natural Science Foundation of China(NSFC)(No.81372898 and 81172582)The Chinese University of Hong Kong
文摘Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC.However,even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC(EBVa GC),suggesting a predominant role of epigenetic abnormities,especially promoter Cp G methylation,in the pathogenesis of NPC and EBVa GC.High frequencies of promoter methylation of tumor suppressor genes(TSGs)have been frequently reported in NPC and EBVa GC,with several EBV-induced methylated TSGs identified.Further characterization of the epigenomes(genome-wide Cp G methylation profile—methylome)of NPC and EBVa GC shows that these EBV-associated tumors display a unique high Cp G methylation epigenotype with more extensive gene methylation accumulation,indicating that EBV acts as a direct epigenetic driver for these cancers.Mechanistically,oncogenic modulation of cellular Cp G methylation machinery,such as DNA methyltransferases(DNMTs),by EBV-encoded viral proteins accounts for the EBV-induced high Cp G methylation epigenotype in NPC and EBVa GC.Thus,uncovering the EBV-associated unique epigenotype of NPC and EBVa GC would provide new insight into the molecular pathogenesis of these unique EBVassociated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.
基金Supported by National Natural Science Foundation of China, No.81201963Inner Mongolia Natural Science Foundation of China,No.2010MS1123
文摘AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.
基金Supported by The South China National Research Centre for Integrated Biosciences, and has been conducted collaboratively between Zhongshan University (ZU)The Chinese University of Hong Kong
基金The Research Fund for the Doctoral Program of Higher Education, No. 20069981008
文摘AIM:To study the molecular mechanism of laterally spreading tumor (LST), a cell line [Laterally Spreading Tumor-Rectum 1 (LST-R1)] was derived and the characteristics of this cell line were investigated. METHODS:A new cell line (LST-R1) originated from laterally spreading tumor was established. Properties of the cell line were characterized using scanning and transmission electron microscopy, immunohistochemistry method, cytogenetic analysis and nude mice xenograft experiments. In vitro invasion assay, cDNA microarray and Western blotting were used to compare the difference between the LST-R1 and other colorectal cancer cell lines derived from prudent colon cancer. RESULTS:Our study demonstrated that both epithelial special antigen (ESA) and cytokeratin-20 (CK20) were expressed in LST-R1. The cells presented microvilli and tight junction with large nuclei. The karyotypic analysis showed hyperdiploid features with structural chromosome aberrations. The in vivo tumorigenicity was also demonstrated in nude mice xenograft experiments. The invasion assay suggested this cell line has a higher invasive ability. cDNA microarray and Western blotting show the loss of the expression of E-cadherin in LST-R1 cells.CONCLUSION:We established and characterized a colorectal cancer cell line, LST-R1 and LST-R1 has an obvious malignant tendency, which maybe partially attributed to the changes of the expression of some adhesion molecules, such as E-cadherin. It is also a versatile tool for exploring the original and progressive mechanisms of laterally spreading tumor and the early colon cancer genesis.
基金This project was supported by RGC-GRF Hong l(ong (766613, 14106145), the National Basic Research Program of China (2013CB531401), the National Natural Science Foundation of China (NSFC) (81201963, 81372600), the Shenzhen Municipal Science and Technology R&D fund (JCYJ20120619152326450), and the Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute.
基金National Science Foundation of China(No.82002313,No.82072444)National Key Research&Development Program of China(2021YFA1101503,2018YFC2001502 and 2018YFB1105705)+2 种基金Department of Science and Technology of Hubei Province(No.2020BCB004)University Grants Committee,Research Grants Council of the Hong Kong Special Administrative Region,China(14121721,14108720,C7030-18G,T13-402/17-N and Ao E/M-402/20)Wuhan Union Hospital“Pharmaceutical Technology nursing”special fund(No.2019xhyn021)。
文摘Skeletal tissue is highly innervated.Although different types of nerves have been recently identified in the bone,the crosstalk between bone and nerves remains unclear.In this review,we outline the role of the peripheral nervous system(PNS)in bone regeneration following injury.We first introduce the conserved role of nerves in tissue regeneration in species ranging from amphibians to mammals.We then present the distribution of the PNS in the skeletal system under physiological conditions,fractures,or regeneration.Furthermore,we summarize the ways in which the PNS communicates with bone-lineage cells,the vasculature,and immune cells in the bone microenvironment.Based on this comprehensive and timely review,we conclude that the PNS regulates bone regeneration through neuropeptides or neurotransmitters and cells in the peripheral nerves.An in-depth understanding of the roles of peripheral nerves in bone regeneration will inform the development of new strategies based on bone-nerve crosstalk in promoting bone repair and regeneration.
基金supported by the National Public Welfare Projects for Chinese Medicine(201507001)to Xiao Ke WuTheme-based Research Scheme(T13-602/21-N)from Research Grant Councilthe Health and Medical Research Fund(06170246)from Food and Health Bureau to Chi Chiu Wang。
文摘In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment.Medline,Excerpta Medica Database(EMBASE),Ovid,and China National Knowledge Infrastructure(CNKI),were searched for the period from January 1990 to June 2021 using the keywords"male infertility,""medical therapy,""supplement/nutrient therapy,"and related terms.Randomized controlled trials(RCTs)investigating medicines(mainly follicle-stimulating hormone(FSH),androgen,and clomiphene/tamoxifen)or supplements(mainly zinc,selenium,vitamin C or E,carnitine,coenzyme Q10(CoQ10),or combined treatment)for idiopathic infertile men were selected for meta-analysis.Preferred reporting items for systematic reviews and meta-analysis(PRISMA)was used for data extraction,and a risk-of-bias tool and grades of recommendation,assessment,development,and evaluation(GRADE)system adapted to the NMA were employed to assess the quality of the evidence.The primary outcomes were live birth and spontaneous pregnancy rate(SPR).The secondary outcomes were sperm parameters(including concentration,progressive motility,and morphology)and side effects.In total,65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included.A total of 36 studies reported SPR but only three reported live birth rates.The quality of the included studies was found to be moderate to high.Compared with a placebo or being untreated,carnitine plus vitamins significantly improved SPR(relative risk(RR)=3.7,95%confidence interval(95%CI),1.6-8.5);fatty acids significantly increased sperm concentrations(mean difference(MD)=12.5×10^(6)mL-1,95%CI,3.1×10^(6)-22.0×10^(6));and selective estrogen receptor modulator(SERM)plus CoQ10 significantly improved sperm progressive motility(MD=11.0%,95%CI,0.1%-21.9%)and normal sperm morphology(MD=11.0%,95%CI,4.6%-17.4%).The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations,respectively,even after excluding trials at a high risk of bias.Compared with a placebo or being untreated,FSH(RR=4.9,95%CI,1.1-21.3)significantly increased SPR,whereas SERM plus kallikrein increased sperm concentration(MD=16.5×10^(6)mL^(-1),95%CI,1.6×10^(6)-31.4×10^(6)),and SERM plus CoQ10 significantly improved sperm progressive motility(MD=11.3%,95%CI,7.3%-15.4%)and normal morphology(MD=11.2%,95%CI,5.4%-16.9%)in men with oligoasthenozoospermia(OA).In terms of side effects,fatty acids and pentoxifylline were associated with foul breath and/or a bad taste(RR=8.1,95%CI,1.0-63.5)and vomiting(RR=8.0,95%CI,1.0-63.0),respectively.In conclusion,the optimal treatment for male infertility for live birth is still unknown.Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in cou ples with men with OA,respectively.The efficacy of other treatments on pregnancy outcomes warrants further verification.
基金supported by Fujian Provincial Natural Science(2020J01122587)National Natural Science Foundation of China(82103355,82102255,and 82222901)+1 种基金RGC Theme-based Research Scheme(T12-703/19-R)Research grants Council-General Research Fund(14117422 and 14117123)。
文摘Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.
基金supported by funding from the Focus Investigation Scheme-A of The Chinese University of Hong Kongthe Research Grants Council of Hong Kong, GRF (471211, 470312), CRF (CUHK8/CRF/11R) and AoE NPC (AoE/M-06/08)the Theme-Based Research Scheme (T12-401/13-R)
文摘Although the Epstein-Barr virus(EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma(NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cells. These cancer stem-like cells(CSCs) have the ability to selfrenew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBVassociated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1(LMP1) and latent membrane protein 2A(LMP2A)], cellular microRNAs, and adenosine triphosphate(ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.
基金supported by NSFC Joint Research Fund for Hong Kong and Macao Young Scholars(No.30928012)National Natural Science Foundation of China(No.81071634,81172582,and 30801344)Shenzhen Science Fund for Distinguished Young Scholars(No.JC201005270328A)
文摘Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.
基金Supported by the National Natural Science Foundation of China,No.81372623the Zhejiang Province Key Science and Technology Innovation Team,No.2013TD13
文摘@Yun Qian$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Chi-Chun Wong$Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong!Hong Kong, China@San-Chuan Lai$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Zheng-Hua Lin$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Wei-Liang Zheng$Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Hui Zhao$Emergency Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Kong-Han Pan$Department of Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Shu-Jie Chen$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Jian-Min Si$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province,
基金General Research Fund(No.2140855RGC Reference No.CUHK14114414)from The Research Grants Council of Hong Kong+1 种基金National Natural Science Grant No.81201591 from ChinaDirect Grant for Research No.2014.2.002 from The Chinese University of Hong Kong
文摘More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZbinding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and micro RNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis.