Integrinβ1和MMP-9在结直肠癌组织中的表达及其与临床预后的关系

目的探究整合素β_1(Integrinβ_1)和基质金属蛋白酶9(MMP-9)在结直肠癌组织中的表达情况及其与临床预后之间的关系。方法选取2008年3月-2011年3月经该院确诊为结直肠癌的52例患者的病理标本及31例正常肠黏膜组织标本,通过免疫组织化学链霉亲和素过氧化物酶连接方法(Immunohistochemical SP)测定Integrinβ_1及MMP-9蛋白的分布和表达情况,分析其表达与结直肠癌的部分病理特征参数之间的关系。依据患者病变情况的不同采用相应的手术治疗后进行随访,评价其术后复发情况及5年生存率。结果免疫组织化学结果显示Integrinβ_1蛋白在结直肠癌组织、癌旁组织及正常肠黏膜组织中的阳性表达率分别为82.69%、14.29%及6.45%。MMP-9在结直肠癌组织、癌旁组织及正常肠黏膜组织中的阳性表达率分别为80.77%、16.67%及9.68%。Integrinβ_1及MMP-9在结直肠中的表达水平均与患者Dukes分期、肝转移相关(P<0.05)。两者在结直肠癌组织中的表达呈正相关,同时结直肠癌患者Integrinβ_1及MMP-9的蛋白表达与术后复发率、术后生存时间均呈负相关。结论 Integrinβ_1及MMP-9在结直肠癌组织中表达升高,两者皆与结直肠癌的病理特征和肿瘤的侵袭转移密切相关,同时影响结直肠癌患者的术后复发及生存,此外在结直肠癌发病的过程中两者的高表达可能具有协同作用,所以Integrinβ_1及MMP-9可以作为今后治疗和预后结直肠癌的新靶点。

Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications

Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery.However,transplanted stem cells show a high death percentage,creating challenges to successful transplantation and prognosis.Thus,it is necessary to investigate the mechanisms underlying stem cell death,such as apoptotic cascade activation,excessive autophagy,inflammatory response,reactive oxygen species,excitotoxicity,and ischemia/hypoxia.Targeting the molecular pathways involved may be an efficient strategy to enhance stem cell viability and maximize transplantation success.Notably,a more complex network of cell death receives more attention than one crucial pathway in determining stem cell fate,highlighting the challenges in exploring mechanisms and therapeutic targets.In this review,we focus on programmed cell death in transplanted stem cells.We also discuss some promising strategies and challenges in promoting survival for further study.

Evaluation of retinal and choroidal changes in patients with Alzheimer’s type dementia using optical coherence tomography angiography

AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and to explore changes in retinal function.METHODS:Twenty-nine patients with ATD and 26 age-matched normal subjects were enrolled.All subjects underwent OCTA scans to analyse the superficial retinal vessel parameters in the macular area,including the vessel length density,the vessel perfusion density and the area of foveal avascular zone(FAZ),as well as the choroidal thickness.The differences between the patients with ATD and the normal control group were compared and explored the relevant factors affecting vessel parameters.We also recorded the flash ERGs using the RETeval system and intended to explore changes in retinal function by analysing the ERG image amplitude in patients with ATD.RESULTS:The vessel parameters[Pvessel length density=0.005 and Pvessel perfusion density=0.006]and average choroid thickness(P<0.001)in the macular area of the ATD group was less than the control group.The FAZ area was statistically significantly enlarged in the ATD group(P<0.001).These parameters were correlated with the Mini-Mental State Examination(MMSE)score and the Montreal Cognitive Assessment(MoCA).CONCLUSION:Patients with ATD exhibit decreases in the parameters associated with fundus.In addition,these indicators significantly correlate with the MMSE score and the MoCA score.OCTA may be an adjunct tool with strong potential to track changes in the diagnosis and monitoring the progression of the disease.

Vascular wall microenvironment:Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner

Vascular calcification and vascular ageing are“silent”diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes,as well as in the ageing population.Melatonin(MT)has been shown to induce cardiovascular protection effects.However,the role of MT on vascular calcification and ageing has not been well-identified.In this study,the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells(ECs)and vascular smooth muscle cells(VSMCs)in vascular calcification and vascular ageing.Furthermore,we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs.The exosomes secreted from melatonin-treated ECs(MT-ECs-Exos)inhibited calcification and senescence of VSMCs.Mechanistically,miR-302d-5p was highly enriched in MT-ECs-Exos,while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence.Notably,Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence.Furthermore,we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N^(6)-methyladenosine(m^(6)A)-dependent manner.Interestingly,MT alleviated vascular calcification and ageing in 5/6-nephrectomy(5/6 NTP)mice,a chronic kidney disease(CKD)induced vascular calcification and vascular ageing mouse model.MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice.ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice.Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway,dependent on m^(6)A methylation.

Epigenetic regulation in metabolic diseases:mechanisms and advances in clinical study

Epigenetics regulates gene expression and has been confirmed to play a critical role in a variety of metabolic diseases,such as diabetes,obesity,non-alcoholic fatty liver disease(NAFLD),osteoporosis,gout,hyperthyroidism,hypothyroidism and others.The term‘epigenetics’was firstly proposed in 1942 and with the development of technologies,the exploration of epigenetics has made great progresses.There are four main epigenetic mechanisms,including DNA methylation,histone modification,chromatin remodelling,and noncoding RNA(ncRNA),which exert different effects on metabolic diseases.Genetic and non-genetic factors,including ageing,diet,and exercise,interact with epigenetics and jointly affect the formation of a phenotype.Understanding epigenetics could be applied to diagnosing and treating metabolic diseases in the clinic,including epigenetic biomarkers,epigenetic drugs,and epigenetic editing.In this review,we introduce the brief history of epigenetics as well as the milestone events since the proposal of the term‘epigenetics’.Moreover,we summarise the research methods of epigenetics and introduce four main general mechanisms of epigenetic modulation.Furthermore,we summarise epigenetic mechanisms in metabolic diseases and introduce the interaction between epigenetics and genetic or non-genetic factors.Finally,we introduce the clinical trials and applications of epigenetics in metabolic diseases.