Caspase-3 gene expression in human luteinized granulosa cells is inversely correlated with the number of oocytes retrieved after controlled ovarian stimulation

Granulosa cells control oocyte maturation through paracrine signalling and changes to the microenvironment around the oocyte. Apoptosis occurs as a physiological mechanism of granulosa cell renewal, but how it relates with the ovarian response to induced ovulation is still unclear. Therefore, this study evaluated apoptosis-related gene expression levels in granulosa cells of patients undergoing controlled ovarian stimulation. We enrolled prospectively 59 consecutive IVF patients referred to a tertiary academic hospital for couple infertility treatment. Luteinized granulosa cells were isolated from follicular fluid and the RNA was extracted, reverse-transcribed and the gene expression of apoptosis inducers (caspase-3, caspase-8 and bax) and inhibitor (Bcl-2) was quantified by real-time polymerase chain reaction. Caspase-3 gene expression correlated negatively with the number of pre-ovulatory follicles (Spearman’s r?= ?0.308), the number of collected oocytes (r?= ?0.451), the number of mature oocytes (r?= ?0.526), the number of fertilized oocytes (r?= ?0.439) and the number of viable embryos (r?= ?0.443, all statistically significant at p?caspase-8, bax or bcl-2. These preliminary findings suggest that increased caspase-3 gene expression in granulosa cells is associated with a worse ovulatory response in humans.     

放疗联合安罗替尼对小细胞肺癌患者胱天蛋白酶3、多腺苷二磷酸核糖聚合酶表达的影响研究

目的探讨放疗联合安罗替尼对小细胞肺癌(SCLC)患者胱天蛋白酶3(caspase 3)、多腺苷二磷酸核糖聚合酶(PARP)表达的影响。方法将86例SCLC患者随机分为放疗组(n=42)和联合组(放疗联合安罗替尼,n=44),探索两组1年生存率、不良反应发生情况及对caspase 3、PARP表达的影响。结果治疗前两组患者血清caspase 3、PARP水平比较,差异均无统计学意义(P﹥0.05);治疗后联合组患者血清caspase 3水平明显高于放疗组,PARP水平明显低于放疗组,差异均有统计学意义(P﹤0.01)。两组患者白细胞减少、中性粒细胞减少发生率比较,差异均无统计学意义(P﹥0.05)。联合组患者1年生存率高于放疗组,差异有统计学意义(P﹤0.05)。结论放疗联合安罗替尼可以有效提高SCLC患者血清内caspase 3水平,降低PARP水平,延长患者的生存时间,值得临床进一步研究。     

甘木通乙酸乙酯提取物对低糖缺氧诱导的神经细胞的保护作用

目的 研究甘木通乙酸乙酯提取物对低糖缺氧诱导神经细胞凋亡的保护作用.方法 PC12细胞结合物理缺氧方式建立缺血性中风的细胞模型,CCK-8检测细胞活性,测定乳酸脱氢酶(LDH)漏出分析细胞膜完整性,流式细胞术和Hoechst 33258染色检测细胞凋亡,JC-1法测定细胞内线粒体膜电位,Western blot检测凋亡相关蛋白Bcl-2、Bax、cleaved caspase-3蛋白表达,检测SOD、MDA水平分析甘木通乙酸乙酯提取物的抗氧化能力.结果 与模型组比较,甘木通乙酸乙酯提取物可以有效提高缺氧PC12细胞的存活率(P<0.01),降低LDH漏出量(P<0.01),提高线粒体膜电位,增加细胞内SOD水平,降低MDA水平,增加Bcl-2蛋白表达,减少Bax,cleaved caspase-3蛋白的表达(P<0.05,P<0.01),降低细胞凋亡率.结论 甘木通乙酸乙酯提取物可抑制低糖缺氧诱导PC12细胞凋亡,该神经保护作用可能与细胞的线粒体凋亡途径有关.     

转录激活因子-4、第二个线粒体衍生的半胱氨酸蛋白酶激活剂在卵巢癌组织中的表达及临床意义

目的探讨卵巢癌组织中转录激活因子-4(ATF-4)、第二个线粒体衍生的半胱氨酸蛋白酶激活剂(SMAC)蛋白的表达情况及临床意义。方法收集90例卵巢癌患者的卵巢癌组织标本和90例卵巢良性肿瘤患者的良性肿瘤组织标本。采用免疫组化染色法检测两种组织中ATF-4、SMAC蛋白的表达情况,并对卵巢癌组织中ATF-4、SMAC蛋白表达与卵巢癌患者病理特征的关系进行分析。结果免疫组化染色结果显示,卵巢癌组织中ATF-4的阳性表达率明显高于卵巢良性肿瘤组织(P﹤0.01)。卵巢癌组织中SMAC蛋白的阳性表达率明显低于卵巢良性肿瘤组织(P﹤0.01)。FIGO分期为Ⅲ~Ⅳ期、有淋巴结转移、组织学分级为G3级的上皮性卵巢癌患者上皮性卵巢癌组织中ATF-4蛋白的阳性表达率均高于FIGO分期为Ⅰ~Ⅱ期、无淋巴结转移、组织学分级为G1~G2级的患者(P﹤0.05);FIGO分期为Ⅲ~Ⅳ期、有淋巴结转移、组织学分级为G3级的上皮性卵巢癌患者上皮性卵巢癌组织中SMAC蛋白的阳性表达率均明显低于FIGO分期为Ⅰ~Ⅱ期、无淋巴结转移、组织学分级为G1~G2级的患者(P﹤0.01);不同病灶直径的上皮性卵巢癌组织中ATF-4、SMAC蛋白的阳性表达率比较,差异均无统计学意义(P﹥0.05)。结论上皮性卵巢癌组织中ATF-4蛋白的表达上调,SMAC蛋白的表达下调,且ATF-4、SMAC蛋白表达可能与上皮性卵巢癌患者的病情进展有一定关系。     

Microbiota and caspase-1/caspase-8 regulate IL-1β-mediated bone disease

A leucine-to-proline missense mutation at residue 98 in the proline-serine-threonine phosphatase interacting protein 2 (Pstpip2) gene leads to autoinflammatory disease that is characterized by splenomegaly, necrosis, and spontaneous development of osteomyelitis in mice (Pstpip2^cmo). Disease progression in these mice resembles that of chronic recurrent multifocal osteomyelitis in humans. Our group and others have shown that disease progression in Pstpip2^cmo mice is mediated by the cytokine IL-1β, independently of inflammasomes or IL-1α. Our recent publication highlighted herein establishes that diet-induced changes in intestinal microbiota provide protection against the development of osteomyelitis in Pstpip2^cmo mice. Moreover, the proteases caspase-1 and caspase-8 have redundant roles in cleaving IL-1β and promoting disease. This addendum reviews the current literature on the Pstpip2^cmo murine disease model and the clinical significance of the role of PSTPIP2 in regulating autoinflammatory osteomyelitis, which is mediated by innate components of immune cells.     

Doxorubicin alters the mitochondrial dynamics machinery and mitophagy in the liver of treated animals

Doxorubicin (Dox) is an effective chemotherapeutic agent, but known to cause cardiac and hepatic toxicity. Mechanisms of toxicity have not been clearly identified, but shown to involve oxidative stress and mitochondrial dysfunction. However, antioxidant supplementation has only shown modest protection from Dox‐induced toxicity in clinical trials. Therefore, further research is required to discern alternative mechanisms that may also play an important role in Dox‐induced toxicity. Thus, we aimed to investigate the role of mitochondrial fusion and fission in Dox‐induced hepatic toxicity, which has not yet been investigated. Six‐week‐old male F344 rats were injected IP with 20 mg/kg of Dox or saline. Once administered, both groups of animals were fasted with no food or water until sacrifice 24 h later. Dox decreased content of primary regulators of mitochondrial fusion (OPA1, MFN1, and MFN2) with no effect on regulators of fission (DRP1 and FIS1), thus shifting the balance favoring mitochondrial fission. Moreover, it was determined that mitochondrial fission was likely not coupled to cell proliferation or cytochrome c release leading to the activation of mitochondrial‐mediated apoptotic signaling. Rather, mitochondrial fission may be coupled to mitophagy and may be an adaptive response to protect against Dox‐induced hepatic toxicity. This is the first study to report the role of altered mitochondrial dynamics and mitophagy machinery in Dox‐induced hepatic injury.     

Design,synthesis, biological evaluations,molecular docking,and in vivo studies of novel phthalimide analogs

A series of novel phthalimide analogs containing an indole or brominated indole moiety were synthesized and their antimicrobial activity was evaluated. Compound 8 showed a broad spectrum activity, revealing 53–67% of erythromycin activity on the tested bacteria and 60–70% of miconazole activity on the tested fungi. Anticancer activity was evaluated on the cell lines HepG2, MCF‐7, A549, H1299, and Caco2. The results revealed that the new phthalimide analog 8 has broad‐spectrum anticancer activity toward all the tested cancer cell lines, followed by compound 11 , which showed good activity toward all the tested cell lines except for MCF‐7. The ability of the promising analogs 5 , 8 , and 11 to bind to topoisomerase II DNA gyrase was investigated. Caspase‐3 activation and Bcl‐2 assay of the best active derivatives 8 , 11 in addition to compound 5 were evaluated. The antifibrotic activity was studied in an in vivo model and the histopathological studies revealed that treatment with the new compound 8 improved the fibrotic liver tissues to normality.

     

Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway

Glabridin, a flavonoid extracted from licorice (Glycyrrhiza glabra), possesses various biological properties, including anticancer activities. However, the effect of glabridin on oral cancer cell apoptosis and the underlying molecular mechanisms has not been elucidated. In this study, we demonstrated that glabridin treatment significantly inhibits cell proliferation in human oral cancer SCC‐9 and SAS cell lines. Flow cytometric assays demonstrated that glabridin induced several features of apoptosis, such as sub‐G1 phase cell increase and phosphatidylserine externalization. Furthermore, glabridin induced apoptosis dose‐dependently in SCC‐9 cells through caspase‐3, −8, and −9 activation and poly (ADP‐ribose) polymerase cleavage. Moreover, glabridin increased the phosphorylation of the extracellular signal–regulated kinase, p38, and c‐Jun N‐terminal kinase (JNK) pathways in a dose‐dependent manner. Moreover, the inhibition of the JNK1/2 inhibitor significantly reversed the glabridin‐induced activation of the caspase pathway. In conclusion, our findings suggest that glabridin induces oral cancer cell apoptosis through the JNK1/2 pathway and is a potential therapeutic agent for oral cancer.