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1.
ObjectiveSwyer syndrome, or 46, XY complete gonadal dysgenesis, is a disorder of human sexual development which present with female external genitalia, lack of female reproductive organs, and a 46, XY karyotype. Many genes that participate in human sexual development have been implicated in the pathogenesis of 46, XY gonadal dysgenesis.Case reportA 18-year-old phenotypically female was presented with primary amenorrhea. Surveillance revealed hypergonadotropic hypogonadism, a normal male 46, XY karyotype and absent of functional gonad, which was confirmed by pathological examination of the streak gonad. Whole exome sequencing showed germline mutations of a novel missense variant, c.570G > C, p.Lys190Asn, in exon 2 of MAP3K1 gene.ConclusionGiven evolutionary conservation of lysine residue at position 190, the amino acid substitution may interfere with interaction between MAP3K1 and RHOA, and contributes to complete gonadal dysgenesis in the context of 46,XY.  相似文献   
2.
《Saudi Dental Journal》2022,34(7):565-571
PurposeThis study aimed to evaluate the neuroprotective ability of the conditioned medium of stem cells from human exfoliated deciduous teeth (CM-SHED) to prevent glutamate-induced apoptosis of neural progenitors.Materials and methodsNeural progenitors were isolated from two-day-old rat brains, and the conditioned medium was obtained from a mesenchymal stem cell SHED. Four groups were examined: neural progenitor cells cultured in neurobasal medium with (N + ) and without (N-) glutamate and glycine, and neural progenitor cells cultured in CM-SHED with (K + ) and without (K-) glutamate and glycine.ResultsThe expression of GABA A1 receptor (GABAAR1) messenger RNA (mRNA) in neural progenitor measured by real-time quantitative PCR. GABA contents were measured by enzyme-linked immunosorbent assay, whereas the apoptosis markers caspase-3 and 7-aminoactinomycin D were analysed with a Muse® cell analyzer. The viability of neural progenitor cells in the K + group (78.05 %) was higher than the control group N- (73.22 %) and lower in the N + group (68.90 %) than in the control group. The K + group showed the highest GABA content, which significantly differed from that in the other groups, whereas the lowest content was observed in the N + group. The expression level of GABAAR1 mRNA in the K + group was the highest compared to that in the other groups. CM-SHED potently protected the neural progenitors from apoptosis.ConclusionsCM-SHED may effectively prevent glutamate-induced apoptosis of neural progenitors.  相似文献   
3.
目的探讨血小板衍生生长因子D(PDGF-D)对人肺癌H1299细胞增殖、迁移和侵袭的影响,并阐明其可能的作用机制。  相似文献   
4.
目的探讨肾周脂肪梅奥粘连概率评分系统(MAP)在肾癌后腹腔镜肾部分切除术中的临床应用价值。 方法回顾性分析2015年1月至2020年6月徐州医科大学附属淮安医院泌尿外科收治的行后腹腔镜肾部分切除术的153例肾癌患者的临床病例资料。依据MAP评分系统将其分为低度复杂组、中度复杂组和高度复杂组三组。比较各组间的手术时间、术中出血量、术中及术后并发症、术中热缺血时间、术后住院时间及术后血肌酐变化情况。 结果在153例患者中,低度复杂组68例,中度复杂组58例和高度复杂组27例。三组患者在年龄、性别、术前血肌酐水平、肿瘤最大径、肿瘤位置、BMI、RENAL评分等方面差异无统计学意义(P>0.05)。随着复杂程度的提高,手术时间、术中出血量也在不断增加(P<0.05);而术中热缺血时间、术后住院时间及术后血肌酐水平无明显变化(P>0.05)。在术中并发症方面,随着复杂程度的提高,术中并发症的发生率也在增加(P<0.05),且高度复杂组的术后并发症发生风险是低度复杂组的13.895倍(P=0.002),MAP评分系统预测术中并发症发生的精度较高(AUC=0.757,P=0.002)。但是术后并发症各组比较差异无统计学意义(P>0.05)。 结论MAP评分系统在肾癌后腹腔镜肾部分切除术中,对预估手术难度及术中并发症发生风险有较好的临床应用价值。  相似文献   
5.
目的 牙周炎和非酒精性脂肪性肝病(NAFLD)的发生发展与活性氧(ROS)的大量积累密切相关。ROS参与调控c-Jun氨基末端激酶(JNK)/核因子-κB(NF-κB)信号分子的激活,当该信号分子被ROS过度激活后可引发机体内环境紊乱。因此,本研究旨在探究ROS/JNK/NF-κB信号分子在牙周炎诱导肝损伤中的作用机制。 方法 将12只SPF级雄性Wistar大鼠随机分为对照组和牙周炎组,在牙周炎组大鼠双侧上颌第一磨牙颈部进行钢丝结扎构建牙周炎模型,8周后检查大鼠牙周临床指标并处死,Micro-CT重建牙槽骨三维结构并分析牙槽骨吸收情况,组织病理学分析牙周及肝组织的病理改变,MitoSOX red试剂检测肝组织中ROS含量,生化试剂盒检测肝功指标和氧化应激生物标志物,实时荧光定量聚合酶链反应(qRT-PCR)检测肝组织中NF-κB、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、BCL2-Associated X的蛋白质(Bax)和B淋巴细胞瘤-2基因(Bcl-2)mRNA表达水平,蛋白免疫印迹(Western blot)法检测肝组织中磷酸化c-Jun氨基末端激酶(P-JNK)、JNK、NF-κB、Bax、Bcl-2和半胱氨酸天冬氨酸蛋白酶3(Caspase-3)蛋白表达水平,末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)染色法检测肝细胞凋亡。 结果 Micro-CT结果显示,牙周炎组大鼠牙槽骨骨质吸收明显,且釉牙骨质界到牙槽嵴顶的距离明显大于对照组。组织病理学结果显示,牙周炎组大鼠牙周组织内可见大量炎症细胞浸润和牙槽骨明显吸收;肝组织结构破坏,可见大量气球样变和红色脂滴形成。MitoSOX red染色结果显示牙周炎组肝组织中ROS含量明显升高。生化检测结果显示,牙周炎组血清中谷草转氨酶(AST)和谷丙转氨酶(ALT)含量升高;肝组织中超氧化物歧化酶(SOD)和谷胱甘肽(GSH)含量降低,丙二醛(MDA)含量升高。qRT-PCR和Western blot结果显示,牙周炎组肝组织中IL-6、TNF-α、Bax和NF-κB mRNA及P-JNK/JNK、NF-κB、Caspase-3和Bax蛋白表达水平较对照组显著上升,而Bcl-2 mRNA和蛋白表达水平下降。TUNEL染色结果显示牙周炎组肝组织中凋亡细胞数量明显增多。 结论 ROS/JNK/ NF-κB信号分子通过调控细胞凋亡参与牙周炎诱导肝损伤。  相似文献   
6.
《药学学报(英文版)》2020,10(5):799-811
Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.  相似文献   
7.
丝裂原活化蛋白激酶(MAPKs)是一组包括细胞外信号调节激酶1/2、c-Jun氨基端激酶1/2/3、p38亚型(α,β,γ和δ)和细胞外信号调节激酶5的丝/苏氨酸蛋白激酶,能够介导增殖、分化、凋亡、免疫、炎症等一系列细胞活动。痛觉敏化是一种中枢和外周伤害性感受器的重塑机制。大量研究显示,MAPKs在糖尿病动物模型的脊髓和背根神经节中广泛激活,在糖尿病神经病理性疼痛(DNP)中枢敏化和外周敏化中发挥了重要的作用。此外,一些药物也可通过抑制中枢和外周神经系统中MAPKs的激活来缓解DNP。本文主要总结了MAPKs在DNP中枢和外周敏化中作用的研究进展。  相似文献   
8.
目的 探讨微小RNA-148a-3p(miR-148a-3p)对丝裂原活化蛋白激酶激酶激酶9(MAP3K9)的靶向调控作用及对胃癌细胞增殖和凋亡的影响。方法 向对数生长期胃癌细胞株MGC-803转染miR-148a-3p模拟物(mimics组)和阴性对照(NC组),以未转染的MGC-803细胞为对照组;采用实时定量PCR(QPCR)检测各组miR-148a-3p水平以评价转染效率,MTT法检测各组细胞增殖能力,流式细胞术检测各组细胞凋亡情况,分别采用QPCR和Western blotting检测Bcl-2、Bax、caspase-3及MAP3K9 mRNA和蛋白水平,同时采用双荧光素酶报告实验验证miR-148a-3p与MAP3K9的靶向作用关系。结果 QPCR结果显示,对照组、NC组和mimics组的miR-148a-3p水平分别为1.021±0.123、1.087±0.196和2.854±0.368,与对照组和NC组比较,mimics组的miR-148a-3p水平升高(P<0.05)。mimics组MGC-803细胞的增殖活力较其余两组减弱(P<0.05)。mimics组MGC-803细胞凋亡率为(15.2±1.6)%,高于对照组的(3.5±0.9%)%和NC组的(4.5±1.1)%,差异具有统计学意义(P<0.05)。与对照组和NC组比较,mimics组的MAP3K9和Bcl-2的mRNA和蛋白水平均下调,而Bax和caspase-3的mRNA和蛋白水平均上调(P<0.05);双荧光素酶报告实验证实MAP3K9是miR-148a-3p的直接作用靶点。结论 MiR-148a-3p可抑制胃癌细胞MGC-803的增殖并诱导其凋亡,可能通过靶向MAP3K9来发挥抑癌作用,调控miR-148a-3p/MAP3K9轴在胃癌防治中有一定应用前景。  相似文献   
9.
BackgroundAdherent perinephric fat (APF) contributes to surgical complexity and can be associated with adverse perioperative outcomes for partial nephrectomy (PN). The Mayo Adhesive Probability (MAP) score accurately predicts the presence of APF during robotic-assisted partial nephrectomy (RAPN). Our primary aim is to validate MAP score as a predictor of APF in open partial nephrectomy (OPNx).MethodsWe reviewed 105 consecutive OPNx (100 patients) performed by a single surgeon with intraoperative determination of APF. We evaluated the ability of the MAP score to discriminate between those with APF and those without APF by estimating the area under the receiver operating characteristic curve (AUROCC). The association of perioperative outcomes with APF was evaluated as well.ResultsForty-three patients [49%; 95% confidence interval (CI), 39–59%] had intraoperative identification of APF. The MAP score had excellent ability to predict APF in OPNx (AUROCC, 0.82; 95% CI, 0.74–0.92). APF was observed in 6% of patients with a MAP score of 0-1, 27% with score 2, 52% with score 3, 75% with score 4, and 90% with score 5. The presence of APF was associated with longer operative times (P=0.004) and higher estimated blood loss (EBL) (P=0.003). Although not statistically significant, our study did suggest that APF may be associated with postoperative complications and prolonged length of stay (LOS) (>3 days).ConclusionsMAP score accurately predicts the presence of APF in patients undergoing OPNx. APF is associated with longer operative time and higher blood loss in OPNx.  相似文献   
10.
PurposeHepatoblastoma is the most common primary liver cancer of childhood and has few prognostic indicators. We have previously shown that Proviral Integration site for Moloney murine leukemia virus (PIM3) kinase decreased hepatoblastoma tumorigenicity. We sought to determine the effect of PIM3 overexpression on hepatoblastoma cells and whether expression of PIM3 correlated with patient/tumor characteristics or survival.MethodsThe hepatoblastoma cell line, HuH6, and patient-derived xenograft, COA67, were utilized. Viability, proliferation, migration, sphere formation, and tumor growth in mice were assessed in PIM3-overexpressing cells. Immunohistochemistry was performed for PIM3 on patient samples. Correlation between stain score and clinical/pathologic characteristics was assessed.ResultsPIM3 overexpression rescued the anti-proliferative effect observed with PIM3 knockdown. Sphere formation was increased in PIM3 overexpressing cells. Cells with PIM3 overexpression yielded larger tumors than those with empty vector. Seventy-four percent of samples expressed PIM3. There was no statistical difference in patient characteristics between subjects with strong versus weak PIM3 staining, but patients with strong PIM3 staining had decreased survival.ConclusionsPIM3 expression plays a role in hepatoblastoma tumorigenesis. PIM3 was present in the majority of hepatoblastomas and higher PIM3 expression correlated with decreased survival. PIM3 warrants investigation as a therapeutic target and prognostic marker for hepatoblastoma.  相似文献   
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