IL-32是一种兼具促炎与抗炎特性的多功能细胞因子,其表达已被证明会随胃黏膜疾病进展和胃癌(GC)严重程度而升高,从而参与胃“炎-癌”转化进程。但IL-32究竟如何影响胃“炎-癌”恶性转化并最终导致GC侵袭和迁移的不良结局仍存在较大争议...IL-32是一种兼具促炎与抗炎特性的多功能细胞因子,其表达已被证明会随胃黏膜疾病进展和胃癌(GC)严重程度而升高,从而参与胃“炎-癌”转化进程。但IL-32究竟如何影响胃“炎-癌”恶性转化并最终导致GC侵袭和迁移的不良结局仍存在较大争议。为更好地阐明IL-32异常表达对胃“炎-癌”转化不同组织病理学阶段的调节作用及可能影响机制,探寻早期截断及治疗胃癌前病变(GPL)分子机制的新方向和突破口,本文对Pubmed、Web of Science、中国知网等6个国内外权威数据库近30年与IL-32相关的文献进行检索,发现IL-32在胃“炎-癌”转化不同组织病理学阶段发挥的致病性或保护性作用取决于其不同亚型、分泌形式、周围细胞因子环境、疾病状态和遗传因素。IL-32可能通过NF-κB、MAPK、COX2、PR3、IDO、NOD、PKCδ、FAK及STAT3等多信号途径调控巨噬细胞极化,放大或抑制胃黏膜慢性炎症刺激,从而参与胃“炎-癌”转化进程。本文对IL-32在Correa级联反应不同阶段作用的新认识可能有助于细胞因子导向治疗发展,旨在调节IL-32不同选择性剪接亚型及靶向IL-32信号的治疗手段可作为未来医学治疗GPL和GC的新策略。展开更多
Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,whic...Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,which is further related to successful embryo implantation or conception,either naturally or after assisted reproductive technology.Moreover,this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells(EECs),which results in altered signaling biomolecule secretion,including exosome content.In the context of endometrium regeneration,mesenchymal stromal cells(MSCs)and umbilical cord(UC)-derived stem cells have been applied in clinical trials with promising results.It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs.Specifically,microRNAs in exosomes secreted by the hypoxic damaged EECs,such as miR-214-5p and miR-21-5p,play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3(STAT3)signaling pathway.Taking into consideration the above information,UC-MSCs may be considered as a modern intervention for endometrial regeneration.展开更多
BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel ...BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel of circulating microRNAs(miRNAs)independently or in combination with other tumor biomarkers and evaluate their sensitivity and specificity in classifying breast cancer patients by grade.METHODS In the present study,we analyzed the aberrant expression of miR-21,miR-221,miR-1246,miR-145,and miR-382,in addition to the tumor biomarkers cancer antigen 15-3(CA15-3)and 8-hydroxy-2′-deoxyguanosine(8-OHdG)in breast cancer patients with varying grades.RESULTS Our results revealed distinct expression patterns of these miRNAs between grade II and III patients.Specifically,miR-21,miR-221,and miR-1246 were significantly elevated, while miR-145 and miR-382 were downregulated. Elevated serum levels of CA15-3 and 8-OHdG wereobserved in breast cancer patients compared to healthy controls, with CA15-3 showing greater diagnostic efficacyin differentiating between grades. Our study revealed strong correlations among evaluated miRNAs, suggestingtheir interconnected roles in breast cancer progression. Receiver operating characteristic curve analysisdemonstrated high diagnostic accuracy for all investigated miRNAs, with miR-21 and miR-1246 showing thehighest diagnostic power for differentiating patients from healthy individuals and distinguishing breast cancergrades. Moreover, the combination of multiple miRNAs and conventional tumor biomarkers revealed enhanceddiagnostic accuracy and sensitivity.CONCLUSIONThese findings suggest that circulating miRNAs may play a significant role in distinguishing breast cancer patientsbased on tumor grade, with superior diagnostic performance over some tumor biomarkers, supporting thedevelopment of multi-analyte liquid biopsy approaches in the diagnostic process and personalized management ofbreast cancer patients.展开更多
文摘IL-32是一种兼具促炎与抗炎特性的多功能细胞因子,其表达已被证明会随胃黏膜疾病进展和胃癌(GC)严重程度而升高,从而参与胃“炎-癌”转化进程。但IL-32究竟如何影响胃“炎-癌”恶性转化并最终导致GC侵袭和迁移的不良结局仍存在较大争议。为更好地阐明IL-32异常表达对胃“炎-癌”转化不同组织病理学阶段的调节作用及可能影响机制,探寻早期截断及治疗胃癌前病变(GPL)分子机制的新方向和突破口,本文对Pubmed、Web of Science、中国知网等6个国内外权威数据库近30年与IL-32相关的文献进行检索,发现IL-32在胃“炎-癌”转化不同组织病理学阶段发挥的致病性或保护性作用取决于其不同亚型、分泌形式、周围细胞因子环境、疾病状态和遗传因素。IL-32可能通过NF-κB、MAPK、COX2、PR3、IDO、NOD、PKCδ、FAK及STAT3等多信号途径调控巨噬细胞极化,放大或抑制胃黏膜慢性炎症刺激,从而参与胃“炎-癌”转化进程。本文对IL-32在Correa级联反应不同阶段作用的新认识可能有助于细胞因子导向治疗发展,旨在调节IL-32不同选择性剪接亚型及靶向IL-32信号的治疗手段可作为未来医学治疗GPL和GC的新策略。
文摘Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,which is further related to successful embryo implantation or conception,either naturally or after assisted reproductive technology.Moreover,this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells(EECs),which results in altered signaling biomolecule secretion,including exosome content.In the context of endometrium regeneration,mesenchymal stromal cells(MSCs)and umbilical cord(UC)-derived stem cells have been applied in clinical trials with promising results.It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs.Specifically,microRNAs in exosomes secreted by the hypoxic damaged EECs,such as miR-214-5p and miR-21-5p,play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3(STAT3)signaling pathway.Taking into consideration the above information,UC-MSCs may be considered as a modern intervention for endometrial regeneration.
基金Supported by National Research Centre,Egypt,No.E120504.
文摘BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel of circulating microRNAs(miRNAs)independently or in combination with other tumor biomarkers and evaluate their sensitivity and specificity in classifying breast cancer patients by grade.METHODS In the present study,we analyzed the aberrant expression of miR-21,miR-221,miR-1246,miR-145,and miR-382,in addition to the tumor biomarkers cancer antigen 15-3(CA15-3)and 8-hydroxy-2′-deoxyguanosine(8-OHdG)in breast cancer patients with varying grades.RESULTS Our results revealed distinct expression patterns of these miRNAs between grade II and III patients.Specifically,miR-21,miR-221,and miR-1246 were significantly elevated, while miR-145 and miR-382 were downregulated. Elevated serum levels of CA15-3 and 8-OHdG wereobserved in breast cancer patients compared to healthy controls, with CA15-3 showing greater diagnostic efficacyin differentiating between grades. Our study revealed strong correlations among evaluated miRNAs, suggestingtheir interconnected roles in breast cancer progression. Receiver operating characteristic curve analysisdemonstrated high diagnostic accuracy for all investigated miRNAs, with miR-21 and miR-1246 showing thehighest diagnostic power for differentiating patients from healthy individuals and distinguishing breast cancergrades. Moreover, the combination of multiple miRNAs and conventional tumor biomarkers revealed enhanceddiagnostic accuracy and sensitivity.CONCLUSIONThese findings suggest that circulating miRNAs may play a significant role in distinguishing breast cancer patientsbased on tumor grade, with superior diagnostic performance over some tumor biomarkers, supporting thedevelopment of multi-analyte liquid biopsy approaches in the diagnostic process and personalized management ofbreast cancer patients.
