BACKGROUND Circular RNAs(circRNAs)are critical regulators in tumorigenesis,functioning as microRNA sponges or protein decoys.Although numerous circRNAs have been implicated in gastric cancer progression,the role of hs...BACKGROUND Circular RNAs(circRNAs)are critical regulators in tumorigenesis,functioning as microRNA sponges or protein decoys.Although numerous circRNAs have been implicated in gastric cancer progression,the role of hsa_circRNA_101996 remains unclear.This study hypothesizes that hsa_circRNA_101996 promotes gastric cancer cell proliferation and apoptosis via the microRNA-577(miR-577)/high mobility group nucleosome binding domain 5(HMGN5)axis.AIM To investigate the role of hsa_circRNA_101996 in gastric cancer proliferation and apoptosis through the miR-577/HMGN5 axis.METHODS Forty-one paired gastric cancer tissues and adjacent non-cancerous tissues were analyzed.Differential circRNA expression was identified using GSE83521 and GSE89143 datasets.miR-577 and HMGN5 were predicted via CircInteractome and TargetScan.Functional experiments(MTT,colony formation,Western blot)and dual-luciferase reporter assays were performed in gastric cancer cell lines(OCUM-1,HSC-39).In vivo tumorigenesis was validated in nude mice.Statistical analysis included Student’s t-test and one-way ANOVA(P<0.05).RESULTS Hsa_circRNA_101996 was significantly upregulated in gastric cancer tissues and cell lines compared to adjacent non-cancerous tissues(P<0.05).Dual-luciferase reporter assays validated the interactions among hsa_circRNA_101996,miR-577,and HMGN5.In vitro,gastric cancer cells overexpressing hsa_circRNA_101996 showed significantly increased proliferation and decreased apoptosis compared to controls(P<0.05).Cells transfected with miR-577 mimics exhibited reduced proliferation and increased apoptosis(P<0.05).Co-transfection with hsa_circRNA_101996 or HMGN5 reversed the effects of miR-577 mimics.In vivo,hsa_circRNA_101996-overexpressing tumors showed increased volume and HMGN5 expression(P<0.05).CONCLUSION Hsa_circRNA_101996 promotes gastric cancer progression by sponging miR-577 to upregulate HMGN5,suggesting a novel therapeutic target for gastric cancer.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
目的观察渗漏点位于黄斑中心凹500µm范围之内的急性中心性浆液性脉络膜视网膜病变(CSC)患者行577 nm阈下微脉冲激光治疗(SML)后黄斑区结构及微循环的变化。方法回顾性病例研究。纳入2022年8月至2023年10月在苏北人民医院眼科确诊...目的观察渗漏点位于黄斑中心凹500µm范围之内的急性中心性浆液性脉络膜视网膜病变(CSC)患者行577 nm阈下微脉冲激光治疗(SML)后黄斑区结构及微循环的变化。方法回顾性病例研究。纳入2022年8月至2023年10月在苏北人民医院眼科确诊为急性CSC且渗漏点位于黄斑中心凹500µm范围之内的患者36例(36只眼)。患眼均行SML治疗,记录所有急性CSC患者行SML治疗前、治疗后1个月、3个月的最佳矫正视力(BCVA)、相干光层析成像术(OCT)及相干光层析血管成像术(OCTA)检查相关指标,对比研究急性CSC患眼经SML治疗前后黄斑区形态及微循环指标的变化。结果(1)本组急性CSC患眼在接受SML治疗后3个月的患眼视力显著提高(P<0.001)。接受SML治疗后1个月和3个月患眼的黄斑中心凹视网膜厚度(CMT)均显著降低(均P<0.05)。接受SML治疗后1个月和3个月患眼的黄斑中心凹下脉络膜厚度(SFCT)均明显降低(均P<0.05)。(2)本组急性CSC患眼经SML治疗后脉络膜毛细血管血流密度(CCVD)水平呈上升趋势,但仅治疗后3个月相比于治疗后1个月CCVD显著提升(P<0.05)。本组急性CSC患眼SML治疗后3个月,黄斑区浅层视网膜毛细血管血流密度(SCPVD)、黄斑区深层视网膜毛细血管血流密度(DCPVD)均较治疗前显著降低(均P<0.05)。(3)与治疗前相比,经SML治疗后1个月和3个月患眼的环绕黄斑无血管区面积(FAZ)区域300µm范围内的血流密度(vessel density around the FAZ-300,FD-300)均显著提高(均P<0.05)。结论对于渗漏点位于黄斑中心凹500µm之内的急性CSC患者,SML可快速降低患眼黄斑CMT及SFCT,逐步增加脉络膜毛细血管血流密度,降低中心凹浅层与深层视网膜毛细血管血流密度。展开更多
AIM:To evaluate the efficacy and safety of conbercept combined with 577 nm subthreshold micropulse laser(STML)for treatment of diabetic macular edema(DME).METHODS:A retrospective study was conducted.From October 2022 ...AIM:To evaluate the efficacy and safety of conbercept combined with 577 nm subthreshold micropulse laser(STML)for treatment of diabetic macular edema(DME).METHODS:A retrospective study was conducted.From October 2022 to March 2024,72 patients diagnosed with DME at the outpatient clinic were enrolled.The patients were divided into two groups:the simple group(treated with conbercept alone)and the combination group(treated with 577 nm STML combined with conbercept).The following itmes were compared between the two groups:best corrected visual acuity(BCVA),central macular thickness(CMT),foveal avascular zone(FAZ),vessel density of the superficial capillary plexus(SCP)and deep capillary plexus(DCP),retinal mean sensitivity(RMS),injection numbers,and the number of cases with adverse effects.RESULTS:The mean age of patients was 57.13±8.76(range 34-77)y with DR history of 0.89±0.55y.With the progression of treatment,both groups showed significant improvements in BCVA,CMT,DCP vessel density,and RMS compared to baselines(all,P<0.05).At 3 and 6mo after treatment,the combination group exhibited significantly better outcomes in BCVA,CMT,DCP vessel density,and RMS than the simple group(P<0.05).During the treatment period,neither group showed significant improvements in FAZ and SCP vessel density(P>0.05),and no significant differences in FAZ and SCP vessel density were observed between the two groups(P>0.05).The average number of injections required in the combination group was lower than that in the simple group(3.33±0.68 vs 4.06±0.96,P<0.05).No other serious ophthalmic adverse events were observed in either group.CONCLUSION:Conbercept combined with STML has better outcomes for treatment of DME and less intravitreal injections compared to conbercept monotherapy.展开更多
BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highl...BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.展开更多
文摘BACKGROUND Circular RNAs(circRNAs)are critical regulators in tumorigenesis,functioning as microRNA sponges or protein decoys.Although numerous circRNAs have been implicated in gastric cancer progression,the role of hsa_circRNA_101996 remains unclear.This study hypothesizes that hsa_circRNA_101996 promotes gastric cancer cell proliferation and apoptosis via the microRNA-577(miR-577)/high mobility group nucleosome binding domain 5(HMGN5)axis.AIM To investigate the role of hsa_circRNA_101996 in gastric cancer proliferation and apoptosis through the miR-577/HMGN5 axis.METHODS Forty-one paired gastric cancer tissues and adjacent non-cancerous tissues were analyzed.Differential circRNA expression was identified using GSE83521 and GSE89143 datasets.miR-577 and HMGN5 were predicted via CircInteractome and TargetScan.Functional experiments(MTT,colony formation,Western blot)and dual-luciferase reporter assays were performed in gastric cancer cell lines(OCUM-1,HSC-39).In vivo tumorigenesis was validated in nude mice.Statistical analysis included Student’s t-test and one-way ANOVA(P<0.05).RESULTS Hsa_circRNA_101996 was significantly upregulated in gastric cancer tissues and cell lines compared to adjacent non-cancerous tissues(P<0.05).Dual-luciferase reporter assays validated the interactions among hsa_circRNA_101996,miR-577,and HMGN5.In vitro,gastric cancer cells overexpressing hsa_circRNA_101996 showed significantly increased proliferation and decreased apoptosis compared to controls(P<0.05).Cells transfected with miR-577 mimics exhibited reduced proliferation and increased apoptosis(P<0.05).Co-transfection with hsa_circRNA_101996 or HMGN5 reversed the effects of miR-577 mimics.In vivo,hsa_circRNA_101996-overexpressing tumors showed increased volume and HMGN5 expression(P<0.05).CONCLUSION Hsa_circRNA_101996 promotes gastric cancer progression by sponging miR-577 to upregulate HMGN5,suggesting a novel therapeutic target for gastric cancer.
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
文摘目的观察渗漏点位于黄斑中心凹500µm范围之内的急性中心性浆液性脉络膜视网膜病变(CSC)患者行577 nm阈下微脉冲激光治疗(SML)后黄斑区结构及微循环的变化。方法回顾性病例研究。纳入2022年8月至2023年10月在苏北人民医院眼科确诊为急性CSC且渗漏点位于黄斑中心凹500µm范围之内的患者36例(36只眼)。患眼均行SML治疗,记录所有急性CSC患者行SML治疗前、治疗后1个月、3个月的最佳矫正视力(BCVA)、相干光层析成像术(OCT)及相干光层析血管成像术(OCTA)检查相关指标,对比研究急性CSC患眼经SML治疗前后黄斑区形态及微循环指标的变化。结果(1)本组急性CSC患眼在接受SML治疗后3个月的患眼视力显著提高(P<0.001)。接受SML治疗后1个月和3个月患眼的黄斑中心凹视网膜厚度(CMT)均显著降低(均P<0.05)。接受SML治疗后1个月和3个月患眼的黄斑中心凹下脉络膜厚度(SFCT)均明显降低(均P<0.05)。(2)本组急性CSC患眼经SML治疗后脉络膜毛细血管血流密度(CCVD)水平呈上升趋势,但仅治疗后3个月相比于治疗后1个月CCVD显著提升(P<0.05)。本组急性CSC患眼SML治疗后3个月,黄斑区浅层视网膜毛细血管血流密度(SCPVD)、黄斑区深层视网膜毛细血管血流密度(DCPVD)均较治疗前显著降低(均P<0.05)。(3)与治疗前相比,经SML治疗后1个月和3个月患眼的环绕黄斑无血管区面积(FAZ)区域300µm范围内的血流密度(vessel density around the FAZ-300,FD-300)均显著提高(均P<0.05)。结论对于渗漏点位于黄斑中心凹500µm之内的急性CSC患者,SML可快速降低患眼黄斑CMT及SFCT,逐步增加脉络膜毛细血管血流密度,降低中心凹浅层与深层视网膜毛细血管血流密度。
基金Supported by Henan Province Youth Health Science and Technology Innovation Talent Training Project(No.LJRC2023008)The Key Scientific Research Projects Plan of Universities in Henan Province(No.24A320040).
文摘AIM:To evaluate the efficacy and safety of conbercept combined with 577 nm subthreshold micropulse laser(STML)for treatment of diabetic macular edema(DME).METHODS:A retrospective study was conducted.From October 2022 to March 2024,72 patients diagnosed with DME at the outpatient clinic were enrolled.The patients were divided into two groups:the simple group(treated with conbercept alone)and the combination group(treated with 577 nm STML combined with conbercept).The following itmes were compared between the two groups:best corrected visual acuity(BCVA),central macular thickness(CMT),foveal avascular zone(FAZ),vessel density of the superficial capillary plexus(SCP)and deep capillary plexus(DCP),retinal mean sensitivity(RMS),injection numbers,and the number of cases with adverse effects.RESULTS:The mean age of patients was 57.13±8.76(range 34-77)y with DR history of 0.89±0.55y.With the progression of treatment,both groups showed significant improvements in BCVA,CMT,DCP vessel density,and RMS compared to baselines(all,P<0.05).At 3 and 6mo after treatment,the combination group exhibited significantly better outcomes in BCVA,CMT,DCP vessel density,and RMS than the simple group(P<0.05).During the treatment period,neither group showed significant improvements in FAZ and SCP vessel density(P>0.05),and no significant differences in FAZ and SCP vessel density were observed between the two groups(P>0.05).The average number of injections required in the combination group was lower than that in the simple group(3.33±0.68 vs 4.06±0.96,P<0.05).No other serious ophthalmic adverse events were observed in either group.CONCLUSION:Conbercept combined with STML has better outcomes for treatment of DME and less intravitreal injections compared to conbercept monotherapy.
基金Supported by the National Natural Science Foundation of China,No.82274528.
文摘BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.
