Neuropathic pain,a debilitating condition caused by dysfunction of the somatosensory nervous system,remains difficult to treat due to limited understanding of its molecular mechanisms.Bioinformatics analysis identifie...Neuropathic pain,a debilitating condition caused by dysfunction of the somatosensory nervous system,remains difficult to treat due to limited understanding of its molecular mechanisms.Bioinformatics analysis identified cerebellin 2(CBLN2)as highly enriched in human and murine proprioceptive and nociceptive neurons.We found that CBLN2 expression is persistently upregulated in dorsal root ganglia(DRG)following spinal nerve ligation(SNL)in mice.In addition,transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription.SNL also induced SOX11 upregulation,with SOX11 and CBLN2 co-localized in nociceptive neurons.The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia.High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes,including upregulation of numerous NF-κB downstream targets.Consistently,CBLN2 activated NF-κB signaling,and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity,proinflammatory cytokines and chemokines production,and neuronal hyperexcitability.Together,these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.展开更多
BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in t...BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in the clinical features,response to treatment,and survival outcomes of adult patients with AML.METHODS This retrospective study enrolled 102 adults with AML.SOX11 gene expression in bone marrow samples was measured using real-time PCR.Data were correlated to the patients’clinical features,response to treatment,and survival rates.RESULTS Increased SOX11 expression was significantly associated with the presence of the FLT3-ITD mutation(P<0.001),the FAB-M2 subtype(P=0.008),and cytogenetic abnormalities(P=0.011).However,no significant association was found between SOX11 expression and other clinical laboratory parameters,complete remission,disease-free survival,or overall survival.CONCLUSION SOX11 expression may serve as a marker to identify specific subsets of AML patients who could benefit from intensive targeted chemotherapy.展开更多
Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate int...Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate into osteogenic cells.After transfection with relevant plasmids,cell proliferation,cell cycle progression,and apoptosis were assessed.Alizarin red staining was used to detect calcium nodules in the cells,alkaline phosphatase(ALP)staining was used to detect ALP activity in the cells,and quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine RUNX2 and Osterix expression levels.An OP rat model was established using ovariectomy and micro-computed tomography scanning.Hematoxylin and eosin staining and Masson’s trichrome staining were used to evaluate the pathological conditions of bone tissues,while immunohistochemistry was conducted to detect RUNX2 in bone tissues.Results AST promoted the osteogenic differentiation of BMSCs,reduced miR-181d-5p expression levels,and increased SOX11 expression levels.Restoring miR-181d-5p expression or reducing SOX11 expression levels reversed the effects of AST on the osteogenic differentiation of hBMSCs.miR-181d-5p was found to target SOX11 in hBMSCs.AST improved OP in rats,and miR-181d-5p overexpression or SOX11 inhibition reversed the therapeutic effects of AST on OP in rats.Conclusion AST promoted the osteogenic differentiation of hBMSCs and alleviated OP by targeting SOX11 via miR-181d-5p.展开更多
目的:探讨过表达SOX11(Sex determination region of Y chromosome 11)基因对人视网膜母细胞瘤Y79细胞增殖、凋亡的影响及参与该过程的细胞信号传到途径。方法:将用重组pc DNA3.1-SOX11质粒转染的Y79细胞作为实验组,以空载体pc-DNA3.1-m...目的:探讨过表达SOX11(Sex determination region of Y chromosome 11)基因对人视网膜母细胞瘤Y79细胞增殖、凋亡的影响及参与该过程的细胞信号传到途径。方法:将用重组pc DNA3.1-SOX11质粒转染的Y79细胞作为实验组,以空载体pc-DNA3.1-mock转染的细胞作为对照组。细胞增殖通过Edu细胞荧光染色法检测,细胞凋亡通过Hoechst 33342细胞染色法检测。PTEN、AKT及pAKT的表达采用westernblot法检测。结果:实验组中SOX11 mRNA的相对表达量显著高于对照组[(354±26.2)%vs(100±1.3)%,P<0.05]。实验组细胞在450nm吸光(OD)值低于对照组(2.8±0.3 vs4.5±0.3,P<0.05)。Edu免疫荧光染色结果证实,实验组细胞增殖比例较对照组低[(12.4±4.3)%vs(32.3±3.3)%,P<0.05]。Hoechst 33342细胞凋亡荧光染色结果表明,实验组细胞凋亡比例较对照组高[(10.3±2.3)%vs(5.3±1.4)%,P<0.05]。Western blot实验结果表明,实验组PTEN蛋白的相对表达量高于对照组(0.6±0.03 vs 0.3±0.03,P<0.05),磷酸化Akt的相对表达量低于对照组(0.4±0.02 vs 0.7±0.02,P<0.05)。结论:过表达SOX11基因显著抑制人视网膜母细胞Y79的增殖并促使细胞凋亡。PTEN/Akt信号通路的激活可能参与该过程。展开更多
基金supported by STI2030-Major Projects(2022ZD0204700)the National Natural Science Foundation of China(32030048,32200817,and 82271256).
文摘Neuropathic pain,a debilitating condition caused by dysfunction of the somatosensory nervous system,remains difficult to treat due to limited understanding of its molecular mechanisms.Bioinformatics analysis identified cerebellin 2(CBLN2)as highly enriched in human and murine proprioceptive and nociceptive neurons.We found that CBLN2 expression is persistently upregulated in dorsal root ganglia(DRG)following spinal nerve ligation(SNL)in mice.In addition,transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription.SNL also induced SOX11 upregulation,with SOX11 and CBLN2 co-localized in nociceptive neurons.The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia.High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes,including upregulation of numerous NF-κB downstream targets.Consistently,CBLN2 activated NF-κB signaling,and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity,proinflammatory cytokines and chemokines production,and neuronal hyperexcitability.Together,these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
文摘BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in the clinical features,response to treatment,and survival outcomes of adult patients with AML.METHODS This retrospective study enrolled 102 adults with AML.SOX11 gene expression in bone marrow samples was measured using real-time PCR.Data were correlated to the patients’clinical features,response to treatment,and survival rates.RESULTS Increased SOX11 expression was significantly associated with the presence of the FLT3-ITD mutation(P<0.001),the FAB-M2 subtype(P=0.008),and cytogenetic abnormalities(P=0.011).However,no significant association was found between SOX11 expression and other clinical laboratory parameters,complete remission,disease-free survival,or overall survival.CONCLUSION SOX11 expression may serve as a marker to identify specific subsets of AML patients who could benefit from intensive targeted chemotherapy.
基金supported by the National Natural Science Foundation of China(No.81700888).
文摘Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate into osteogenic cells.After transfection with relevant plasmids,cell proliferation,cell cycle progression,and apoptosis were assessed.Alizarin red staining was used to detect calcium nodules in the cells,alkaline phosphatase(ALP)staining was used to detect ALP activity in the cells,and quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine RUNX2 and Osterix expression levels.An OP rat model was established using ovariectomy and micro-computed tomography scanning.Hematoxylin and eosin staining and Masson’s trichrome staining were used to evaluate the pathological conditions of bone tissues,while immunohistochemistry was conducted to detect RUNX2 in bone tissues.Results AST promoted the osteogenic differentiation of BMSCs,reduced miR-181d-5p expression levels,and increased SOX11 expression levels.Restoring miR-181d-5p expression or reducing SOX11 expression levels reversed the effects of AST on the osteogenic differentiation of hBMSCs.miR-181d-5p was found to target SOX11 in hBMSCs.AST improved OP in rats,and miR-181d-5p overexpression or SOX11 inhibition reversed the therapeutic effects of AST on OP in rats.Conclusion AST promoted the osteogenic differentiation of hBMSCs and alleviated OP by targeting SOX11 via miR-181d-5p.
文摘目的:探讨过表达SOX11(Sex determination region of Y chromosome 11)基因对人视网膜母细胞瘤Y79细胞增殖、凋亡的影响及参与该过程的细胞信号传到途径。方法:将用重组pc DNA3.1-SOX11质粒转染的Y79细胞作为实验组,以空载体pc-DNA3.1-mock转染的细胞作为对照组。细胞增殖通过Edu细胞荧光染色法检测,细胞凋亡通过Hoechst 33342细胞染色法检测。PTEN、AKT及pAKT的表达采用westernblot法检测。结果:实验组中SOX11 mRNA的相对表达量显著高于对照组[(354±26.2)%vs(100±1.3)%,P<0.05]。实验组细胞在450nm吸光(OD)值低于对照组(2.8±0.3 vs4.5±0.3,P<0.05)。Edu免疫荧光染色结果证实,实验组细胞增殖比例较对照组低[(12.4±4.3)%vs(32.3±3.3)%,P<0.05]。Hoechst 33342细胞凋亡荧光染色结果表明,实验组细胞凋亡比例较对照组高[(10.3±2.3)%vs(5.3±1.4)%,P<0.05]。Western blot实验结果表明,实验组PTEN蛋白的相对表达量高于对照组(0.6±0.03 vs 0.3±0.03,P<0.05),磷酸化Akt的相对表达量低于对照组(0.4±0.02 vs 0.7±0.02,P<0.05)。结论:过表达SOX11基因显著抑制人视网膜母细胞Y79的增殖并促使细胞凋亡。PTEN/Akt信号通路的激活可能参与该过程。
