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
BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal ...BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal biopsies is challenging due to histomorphological overlaps,variability in pathological diagnosis consistency,and limited reproducibility.AIM To evaluate the diagnostic utility of P53,Ki67,P504S,and IMP3 in gastric cancer and its precancerous lesions,focusing on their effectiveness in distinguishing AH,LGD,HGD,and AC.METHODS From January 2018 to September 2020,a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors(2019).The specimens were categorized into four groups:AH,LGD,HGD,and AC.Immunohistochemistry was employed to assess the expression status of P53,Ki67,P504S,and IMP3.Intergroup comparisons were performed using theχ^(2)test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.RESULTS The expression rate of P504S was highest in the LGD group(53.3%,16/30),while IMP3 expression was highest in the AC group(41.9%,26/62),followed by the HGD group(33.3%).Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups(P<0.001).Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD,HGD,and AC groups(P<0.001),as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups,and between the LGD group and the HGD and AC groups(P<0.001).Additionally,significant correlations were found between P504S and the polarity expression pattern of Ki67,and between IMP3 and the mutation expression pattern of P53(P<0.001).The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67“polarity”expression pattern.IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern.The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.The rational use of P504S,Ki67,IMP3,and p53 can help distinguish gastric cancer and precancerous lesions,improving the early cancer diagnosis rate.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
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.
基金Supported by The Science and Technology Research Project of Anyang,No.2022C01SF074。
文摘BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal biopsies is challenging due to histomorphological overlaps,variability in pathological diagnosis consistency,and limited reproducibility.AIM To evaluate the diagnostic utility of P53,Ki67,P504S,and IMP3 in gastric cancer and its precancerous lesions,focusing on their effectiveness in distinguishing AH,LGD,HGD,and AC.METHODS From January 2018 to September 2020,a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors(2019).The specimens were categorized into four groups:AH,LGD,HGD,and AC.Immunohistochemistry was employed to assess the expression status of P53,Ki67,P504S,and IMP3.Intergroup comparisons were performed using theχ^(2)test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.RESULTS The expression rate of P504S was highest in the LGD group(53.3%,16/30),while IMP3 expression was highest in the AC group(41.9%,26/62),followed by the HGD group(33.3%).Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups(P<0.001).Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD,HGD,and AC groups(P<0.001),as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups,and between the LGD group and the HGD and AC groups(P<0.001).Additionally,significant correlations were found between P504S and the polarity expression pattern of Ki67,and between IMP3 and the mutation expression pattern of P53(P<0.001).The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67“polarity”expression pattern.IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern.The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.The rational use of P504S,Ki67,IMP3,and p53 can help distinguish gastric cancer and precancerous lesions,improving the early cancer diagnosis rate.
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.
