Objective To investigate whether 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside(TSG)ameliorated polycystic ovary syndrome(PCOS)-like characteristics by inhibiting inflammation.Methods PCOS models were established ...Objective To investigate whether 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside(TSG)ameliorated polycystic ovary syndrome(PCOS)-like characteristics by inhibiting inflammation.Methods PCOS models were established by injecting subcutaneously with dehydroepiandrosterone into female Sprague-Dawley rats,followed by receiving intraperitoneal injection of TSG.The granular cells(GCs)KGN were transfected with small interfering RNAs(si-NC and si-CYP19A1).The cells were preincubated with lipopolysaccharide(LPS)and then treated with or without TSG.The estrous cycle was monitored using vaginal exfoliated cells.The morphology of ovarian follicles was analyzed by H&E staining.ELISA was used to analyze estradiol(E2),testosterone(T),follicle stimulating hormone(FSH),luteinizing hormone(LH),IL-6,TNF-α,AGEs,CRP and Omentin-1 levels in serum.Immunohistochemistry was performed to analyze PCNA and CYP19A1 expressions in the GCs of ovaries.Tunel staining was executed to detect the apoptosis of GCs.Quantitative polymerase chain reaction(qPCR)and Western blot were implemented to measure the expression of CYP19A1 in the ovaries and transfected cells.qPCR was used to analyze the expression of IL-6 and TNF-αin the transfected cells treated with LPS and TSG.Results The estrous cycles were restored in TSG group.Compared with model group,the sinus follicles were reduced and corpus luteums were increased in TSG group.TSG group showed increased E2,and decreased T and LH,compared with model group.Pro-inflammatory factors(IL-6,TNF-α,CRP and AGEs)were decreased,and anti-inflammatory factor(Omentin-1)was increased in TSG group compared with those in model group.TSG could partially inhibit decrease of PNCA-positive GCs and increase of Tunel-positive GCs caused by PCOS.The CYP19A1 expression of GCs in TSG group was upregulated compared with model group.The expressions of IL-6 and TNFαin si-CYP19A1 cells were increased compared with si-NC cells.Compared with cells(si-NC and si-CYP19A1)treated without LPS,the expressions of IL-6 and TNF-αcells were increased,and the expression of CYP19A1 was downregulated in LPS-preincubated cells.Compared with cells treated with LPS,the expression of IL-6 and TNF-αwere decreased,and the expression of CYP19A1 was increased in cells treated with LPS and TSG.Compared with si-NC cells treated with LPS and TSG,the expressions of IL-6 and TNF-αcells were increased in the si-CYP19A1 cells treated with LPS and TSG.Conclusion TSG could alleviate PCOS-like characteristics by increasing the expression of CYP19A1 in GCs to inhibit inflammatory response.展开更多
Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(E...Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(ER)stress plays a pivotal role in the pathogenesis and progression of GC.Therefore,this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.Methods:A novel ER stress-related risk score signature was developed employingmachine learning techniques.Then,a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature.The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored.Furthermore,through the single-cell RNA sequencing(scRNA-seq)analysis,the study highlightedCytochrome P450 Family 19 SubfamilyAMember 1(CYP19A1)as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide(MTT)and the expression of ER stress-related genes by RT-qPCR in STAD.Results:Based on the evaluation of five screened key ER stressrelated genes(AKR1B1,SERPINE1,ADCYAP1,MATN3,CYP19A1),our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards.The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD.Furthermore,the expression of CYP19A1 is significantly higher in STAD tissues than in normal tissues.High expression of CYP19A1 was related to a poor survival outcome for patients with STAD.Besides,compared to normal gastric epithelial cells,the expression of CYP19A1 was significantly higher in STAD cell lines.Silencing the expression of CYP19A1 significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes,including ATF4,DDIT3 and XBP1 in STAD.Conclusions:In conclusion,our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.展开更多
消化道肿瘤是我国最常见的恶性肿瘤,发病率和死亡率均居高位,严重威胁人们的身体健康,亟需寻找有效的诊断方法和治疗靶点。CYP19A1属于细胞色素P450家族的成员,定位于内质网,是将雄激素构化为雌激素的关键限速酶,在不同组织中发挥不同...消化道肿瘤是我国最常见的恶性肿瘤,发病率和死亡率均居高位,严重威胁人们的身体健康,亟需寻找有效的诊断方法和治疗靶点。CYP19A1属于细胞色素P450家族的成员,定位于内质网,是将雄激素构化为雌激素的关键限速酶,在不同组织中发挥不同的作用以维持重要的组织特异性功能。近年来的研究发现,CYP19A1在胃癌、结直肠癌等恶性消化道肿瘤中异常表达并促进肿瘤的进展。然而,CYP19A1在消化道肿瘤中的具体调控机制尚不明确。因此,本文对近年相关研究进行综述,以表明CYP19A1在消化道肿瘤生长过程中存在潜在的研究价值,对于靶向CYP19A1诠释消化道肿瘤的生长机制、预后预测以及靶向治疗等方面具有重要意义。Gastrointestinal tumors are the most prevalent malignant tumors in China, featuring high morbidity and mortality rates, seriously threatening people’s physical health. There is an urgent need to discover effective diagnostic approaches and therapeutic targets. Aromatase (CYP19A1), a member of the cytochrome P450 family, is located in the endoplasmic reticulum and serves as the key rate-limiting enzyme that converts androgens into estrogens, exerting diverse functions in different tissues to maintain crucial tissue-specific functions. Recent studies have revealed that CYP19A1 is aberrantly expressed in malignant gastrointestinal tumors such as gastric cancer and colorectal cancer and promotes tumor progression. Nevertheless, the specific mechanism underlying CYP19A1 in gastrointestinal tumors remains unclear. Thus, this article conducts a review of the relevant research in recent years to indicate the potential research value of CYP19A1 in the growth process of gastrointestinal tumors, which is of significant importance for interpreting the growth mechanism, prognosis prediction, and targeted therapy of gastrointestinal tumors by targeting CYP19A1.展开更多
[目的]研究CYP19A1基因的rs4646和rs10046位点多态性与晚期乳腺癌阿那曲唑治疗疗效的相关性。[方法]本研究共纳入272例激素受体阳性晚期乳腺癌患者,接受阿那曲唑治疗后抽取患者外周静脉血,提取DNA,多重PCR获取目的基因片段后,采用直接...[目的]研究CYP19A1基因的rs4646和rs10046位点多态性与晚期乳腺癌阿那曲唑治疗疗效的相关性。[方法]本研究共纳入272例激素受体阳性晚期乳腺癌患者,接受阿那曲唑治疗后抽取患者外周静脉血,提取DNA,多重PCR获取目的基因片段后,采用直接测序法分析CYP19A1基因多态性。对比等位基因分布频率在突变型和野生型两组患者中的差异。[结果]被检测的rs4646和rs10046符合Hardy-Weinberg平衡检验;比较rs4646突变型和野生型两组阿那曲唑疗效,32例完全缓解的患者中24例是rs4646突变型,76例疾病进展者中有60例是rs4646野生型,P<0.005,经过Bonferroni矫正P值仍有统计学意义。与rs4646野生型相比,携带rs4646突变型患者的中位生存期(median survival time,MST)显著延长(Log-rank检验P=0.007)。携带rs4646突变型患者的疾病进展时间(time to progression,TTP)显著延长(Log-rank检验P=0.049)。[结论]rs4646多态性位点可能会成为预测晚期乳腺癌阿那曲唑治疗疗效和预后的预测因子。展开更多
文摘Objective To investigate whether 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside(TSG)ameliorated polycystic ovary syndrome(PCOS)-like characteristics by inhibiting inflammation.Methods PCOS models were established by injecting subcutaneously with dehydroepiandrosterone into female Sprague-Dawley rats,followed by receiving intraperitoneal injection of TSG.The granular cells(GCs)KGN were transfected with small interfering RNAs(si-NC and si-CYP19A1).The cells were preincubated with lipopolysaccharide(LPS)and then treated with or without TSG.The estrous cycle was monitored using vaginal exfoliated cells.The morphology of ovarian follicles was analyzed by H&E staining.ELISA was used to analyze estradiol(E2),testosterone(T),follicle stimulating hormone(FSH),luteinizing hormone(LH),IL-6,TNF-α,AGEs,CRP and Omentin-1 levels in serum.Immunohistochemistry was performed to analyze PCNA and CYP19A1 expressions in the GCs of ovaries.Tunel staining was executed to detect the apoptosis of GCs.Quantitative polymerase chain reaction(qPCR)and Western blot were implemented to measure the expression of CYP19A1 in the ovaries and transfected cells.qPCR was used to analyze the expression of IL-6 and TNF-αin the transfected cells treated with LPS and TSG.Results The estrous cycles were restored in TSG group.Compared with model group,the sinus follicles were reduced and corpus luteums were increased in TSG group.TSG group showed increased E2,and decreased T and LH,compared with model group.Pro-inflammatory factors(IL-6,TNF-α,CRP and AGEs)were decreased,and anti-inflammatory factor(Omentin-1)was increased in TSG group compared with those in model group.TSG could partially inhibit decrease of PNCA-positive GCs and increase of Tunel-positive GCs caused by PCOS.The CYP19A1 expression of GCs in TSG group was upregulated compared with model group.The expressions of IL-6 and TNFαin si-CYP19A1 cells were increased compared with si-NC cells.Compared with cells(si-NC and si-CYP19A1)treated without LPS,the expressions of IL-6 and TNF-αcells were increased,and the expression of CYP19A1 was downregulated in LPS-preincubated cells.Compared with cells treated with LPS,the expression of IL-6 and TNF-αwere decreased,and the expression of CYP19A1 was increased in cells treated with LPS and TSG.Compared with si-NC cells treated with LPS and TSG,the expressions of IL-6 and TNF-αcells were increased in the si-CYP19A1 cells treated with LPS and TSG.Conclusion TSG could alleviate PCOS-like characteristics by increasing the expression of CYP19A1 in GCs to inhibit inflammatory response.
基金Natural Science Foundation of Liaoning Province(2022-MS-083)Application Basic Research Plan of Liaoning Province(2023JH2/101300084).
文摘Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(ER)stress plays a pivotal role in the pathogenesis and progression of GC.Therefore,this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.Methods:A novel ER stress-related risk score signature was developed employingmachine learning techniques.Then,a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature.The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored.Furthermore,through the single-cell RNA sequencing(scRNA-seq)analysis,the study highlightedCytochrome P450 Family 19 SubfamilyAMember 1(CYP19A1)as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide(MTT)and the expression of ER stress-related genes by RT-qPCR in STAD.Results:Based on the evaluation of five screened key ER stressrelated genes(AKR1B1,SERPINE1,ADCYAP1,MATN3,CYP19A1),our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards.The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD.Furthermore,the expression of CYP19A1 is significantly higher in STAD tissues than in normal tissues.High expression of CYP19A1 was related to a poor survival outcome for patients with STAD.Besides,compared to normal gastric epithelial cells,the expression of CYP19A1 was significantly higher in STAD cell lines.Silencing the expression of CYP19A1 significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes,including ATF4,DDIT3 and XBP1 in STAD.Conclusions:In conclusion,our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.
文摘消化道肿瘤是我国最常见的恶性肿瘤,发病率和死亡率均居高位,严重威胁人们的身体健康,亟需寻找有效的诊断方法和治疗靶点。CYP19A1属于细胞色素P450家族的成员,定位于内质网,是将雄激素构化为雌激素的关键限速酶,在不同组织中发挥不同的作用以维持重要的组织特异性功能。近年来的研究发现,CYP19A1在胃癌、结直肠癌等恶性消化道肿瘤中异常表达并促进肿瘤的进展。然而,CYP19A1在消化道肿瘤中的具体调控机制尚不明确。因此,本文对近年相关研究进行综述,以表明CYP19A1在消化道肿瘤生长过程中存在潜在的研究价值,对于靶向CYP19A1诠释消化道肿瘤的生长机制、预后预测以及靶向治疗等方面具有重要意义。Gastrointestinal tumors are the most prevalent malignant tumors in China, featuring high morbidity and mortality rates, seriously threatening people’s physical health. There is an urgent need to discover effective diagnostic approaches and therapeutic targets. Aromatase (CYP19A1), a member of the cytochrome P450 family, is located in the endoplasmic reticulum and serves as the key rate-limiting enzyme that converts androgens into estrogens, exerting diverse functions in different tissues to maintain crucial tissue-specific functions. Recent studies have revealed that CYP19A1 is aberrantly expressed in malignant gastrointestinal tumors such as gastric cancer and colorectal cancer and promotes tumor progression. Nevertheless, the specific mechanism underlying CYP19A1 in gastrointestinal tumors remains unclear. Thus, this article conducts a review of the relevant research in recent years to indicate the potential research value of CYP19A1 in the growth process of gastrointestinal tumors, which is of significant importance for interpreting the growth mechanism, prognosis prediction, and targeted therapy of gastrointestinal tumors by targeting CYP19A1.
文摘[目的]研究CYP19A1基因的rs4646和rs10046位点多态性与晚期乳腺癌阿那曲唑治疗疗效的相关性。[方法]本研究共纳入272例激素受体阳性晚期乳腺癌患者,接受阿那曲唑治疗后抽取患者外周静脉血,提取DNA,多重PCR获取目的基因片段后,采用直接测序法分析CYP19A1基因多态性。对比等位基因分布频率在突变型和野生型两组患者中的差异。[结果]被检测的rs4646和rs10046符合Hardy-Weinberg平衡检验;比较rs4646突变型和野生型两组阿那曲唑疗效,32例完全缓解的患者中24例是rs4646突变型,76例疾病进展者中有60例是rs4646野生型,P<0.005,经过Bonferroni矫正P值仍有统计学意义。与rs4646野生型相比,携带rs4646突变型患者的中位生存期(median survival time,MST)显著延长(Log-rank检验P=0.007)。携带rs4646突变型患者的疾病进展时间(time to progression,TTP)显著延长(Log-rank检验P=0.049)。[结论]rs4646多态性位点可能会成为预测晚期乳腺癌阿那曲唑治疗疗效和预后的预测因子。
