SEC61G Promotes Cervical Cancer Proliferation by Activating MAPK Signaling Pathway.

Objective: The abnormal expression of SEC61G plays an important role in the development of various tumors. This study explored the effects of SEC61G on MAPK signaling pathway and proliferation of cervical cancer (CC) cells. Methods: shRNA was used to inhibit the expression of SEC61G and EdU to observe its effect on the proliferation of CC cell SiHa. The effect of SEC61G on invasion was evaluated by Transwell assay. TCGA database was used to analyze the influence of high or low SEC61G expression level on the overall survival of CC patients. Western blot was used to detect the expressions of SEC61G, p-RAF1, Raf1, p-MEK1/2, MEK1/2, and p-ERK1/2 in cells. SiHa cells overexpressing SEC61G (SiHa-SEC61G) and control group (SiHa-mock) were subcutaneously implanted in nude mice. The tumor growth curve was measured at the specified time points between SiHa-SEC61G and SiHa-mock. The inhibitory effect of gefitinib on SEC61G was further evaluated. Results: In patients with CC, high SEC61G expression predicted poor prognosis. Silencing SEC61G inhibited proliferation and invasion of CC cells in vitro. Overexpression of SEC61G can promote the proliferation and invasion of CC cells in vitro. Meanwhile, overexpression of SEC61G promoted the proliferation of CC xenografts. Knocking down SEC61G can inhibit MAPK signaling pathway. Gefitinib can inhibit CC proliferation and tumor growth by SEC61G. Conclusion: SEC61G is highly expressed in CC and has poor prognosis. Inhibition of SEC61G expression can effectively inhibit the growth and proliferation of human CC cells. The mechanism may be related to the inhibition of MAPK signaling pathway.

LRSAM1 E3 Ubiquitin Ligase Promotes Choriocarcinoma Progression and Metastasis via p53/p21 Signaling Impediment.

Objective: The E3 ubiquitin ligase LRSAM1 (LRSAM1) was involved in many cancers, but whether it exerts anti- or protumor efficacies on choriocarcinoma cellular structures remains unknown. We wanted to explore the efficacies of aberrant LRSAM1 expression on human choriocarcinoma cellular structures and the underlying mechanisms. Methods: LRSAM1 mRNA expressions in choriocarcinoma lines of cells JEG-3 and JAR cellular structures, as well as HTR8/sev8 human trophoblastic cell line cellular structures, were assessed using assay analysis of quantitative real-time polymerase chain reactions. We compared cell proliferation, migratory flow, invasive force, adhesion, and apoptotic process between cellular structures infected with si-LRSAM1 plasmids versus negative controls using CCK-8, clone formation, Transwell, adhesion, and flow cytometry assays. Protein expressions of LRSAM1, E-cadherin, and N-cadherin (indicators of epithelial-mesenchymal transformation) and p53/p21 pathway components were quantitated using a Western blot assay. The morphology of tumor lesions was observed in xenografted nude mice using immunohistochemistry (IHC) analyses. Results: LRSAM1 was markedly overexpressed within JEG-3 and JAR choriocarcinoma cellular structures compared to HTR8/sev8 trophoblast cellular structures. Compared to si-NC, LRSAM1 knockdown robustly restricted cell proliferating, migratory flow, invasive force, and adhesion and fueled apoptotic cell process in JEG-3 as well as JAR cellular structures and suppressed tumor growth, as evidenced by the reduction in tumor volume and weight in naked mice inoculated with transfected cellular structures. Compared to si-negative control (si-NC), si-LRSAM1 significantly decreased Ki67 (a proliferating indicator) and N-cadherin expressions but reduced E-cadherin expression in JEG-3 and JAR cellular structures. Blocking the p53/p21 pathway by pifithrin-a (a p53 restrictor) successfully reversed the anti-inhibitory effect of LRSAM1 depletion, resulting in enhanced proliferating and metastasis in JEG-3 and JAR cellular structures. Conclusion: LRSAM1 exerts tumorigenic roles in choriocarcinoma. Via the activating of the p53/p21 pathway of signaling and impediment of choriocarcinoma cell proliferating, migratory flow, and invasive force, LRSAM1 knockdown slows the course of the disease. For choriocarcinoma diagnosis and treatment, it serves as a new therapeutic target.

Metformin in Combination with Progesterone Improves the Pregnancy Rate for Patients with Early Endometrial Cancer.

Objective. To study the therapeutic effects of metformin in combination with medroxyprogesterone in the early endometrial cancer patients with fertility requirements. A total of 120 patients with early endometrial cancer admitted to and treated in our hospital were enrolled and evenly assigned into two groups according to different therapeutic regimens, namely, metformin group (metformin combined with medroxyprogesterone acetate) and control group (medroxyprogesterone acetate alone). The objective response rate (ORR) and disease control rate (DCR) were 71.7% (43/60) and 90.0% (54/60) in the metformin group and 53.3% (32/60) and 78.3% (47/60) in the control group, respectively. Adverse reactions such as gastrointestinal reaction, headache, and insomnia were mainly observed in patients. The body mass index (BMI) declined from (34.43 ± 4.34) kg/m2 to (24.77 ± 2.39) kg/m2 in the metformin group and from (33.37 ± 4.49) kg/m2 to (31.28 ± 3.55) kg/m2 in the control group after treatment. After treatment, serum levels of vascular endothelial growth factor (VEGF), angiotensin-2 (Ang-2), carbohydrate antigen 125 (CA125), and CA19-9 in the metformin group were significantly lower than those in the control group (P = 0.005, P < 0.001, P = 0.002, and P < 0.001). During follow-up, the pregnancy rate was 81.7% (49/60) in the metformin group and 61.7% (37/60) in the control group, and the former was prominently higher than the latter (P = 0.025). Metformin in combination with progesterone is effective in treating early endometrial cancer patients with fertility requirements, which significantly reduced the BMI of patients and increased the pregnancy rate after treatment.

Pectic polysaccharides ameliorate the pathology of ulcerative colitis in mice by reducing pyroptosis.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease which seriously affects the quality of life of patients. There has been an increasing amount of research related to the therapeutic effects and mechanisms of natural plant substances in the treatment of recurrent UC. Rauwolfia verticillata var. Hainanensis is a medicinal plant that is native to Hainan Island, China. Some studies have documented that pectic polysaccharides (PPs) from Rauvolfia inhibited the progression of colon ulcers. However, their mechanisms of action have not been established. Studies have revealed that suppressing pyroptosis can attenuate the damage of experimental colitis. However, it is unclear whether PPs from Rauvolfia verticillata inhibit inflammation through pyroptosis. This study investigated the effects and potential mechanisms of PPs extracted from Rauvolfia verticillata on experimental UC in mice. Methods: Male C57 mice (6-8 weeks old) were allocated into the control group, the dextran sulfate sodium (DSS)-induced UC model group (DSS group), or the DSS with pectic polysaccharides treatment group (DSS + PP group). The body weights, rectal bleeding, and stool consistencies in the mice were observed, and the disease activity index (DAI) score was calculated. Colon tissues were collected for pathological analysis by histological hematoxylin and eosin (H&E) staining. The levels of caspase-1 and interleukin (IL)-1ß were detected by immunohistochemistry. Pyroptosis was assessed by transmission electron microscopy. Results: UC in mice induced by DSS resulted in decreased general physical activity and body weight, increased DAI score, significant histological changes, inhibited caspase-1 and IL-1ß expression, and promoted pyroptosis. These DSS-induced changes could be partially ameliorated by administration of PP. Conclusions: PPs exerted an ameliorative effect on DSS-induced UC in mice by reducing pyroptosis.

Mechanism of M2 macrophage-derived extracellular vesicles carrying lncRNA MEG3 in inflammatory responses in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. M2 macrophages possess certain anti-inflammation activity. Accordingly, the current study set out to investigate the potential mechanism of M2 macrophage-derived extracellular vesicles (M2-EVs) in UC inflammation. Firstly, mouse peritoneal macrophages were induced to M2 phenotype, and M2-EVs were isolated. , the murine model of UC was established, and the length and weight of the colon, disease activity index (DAI), apoptosis, and inflammatory response of UC mice were measured. Young adult mouse colon (YAMC) cells were induced with the help of lipopolysaccharide. LncRNA maternally expressed 3 (LncRNA MEG3), miR-20b-5p, and cAMP responsive element binding protein 1 (CREB1) expression patterns were detected in UC models. In addition, we analyzed the binding relationship among MEG3, miR-20b-5p, and CREB1. UC mice presented with shortened colon length, lightened weight, increased DAI score, enhanced apoptosis, and significant inflammatory cell infiltration, while M2-EVs reversed these trends. In vitro, M2-EVs increased UC cell viability and reduced inflammation. Mechanistic experimentation revealed that M2-EVs transferred MEG3 into YAMC cells to up-regulate MEG3 expression and promote CREB1 transcription by competitively binding to miR-20b-5p. Moreover, up-regulation of MEG3 in M2-EVs enhanced the protective effect of M2-EVs on UC cells, while over-expression of miR-20b-5p attenuated the aforementioned protective effect of M2-EVs on UC mice and cells. Collectively, our findings revealed that M2-EVs carrying MEG3 enhanced UC cell viability and reduced inflammatory responses via the miR-20b-5p/CREB1 axis, thus alleviating UC inflammation.

Rauwolfia vomitoria Extract Represses Colorectal Cancer Cell Autophagy and Promotes Apoptosis.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent digestive tract tumors in the world with an increasing incidence. Currently, surgical resection and chemotherapy are the main therapeutic options; however, their effects are limited by various adverse reactions. Rauwolfia vomitoria extract (Rau) has been shown to repress the progression of multiple human cancers; however, whether Rau plays a role in CRC remains undetermined. METHODS: Influences of Rau treatment on HCT-116 and LoVo cells were estimated via MTT and colony formation experiments. Flow cytometry analysis was adopted to evaluate the apoptosis rate of HCT-116 and LoVo cells. Apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and autophagy-related proteins (LC3 and P62) were assessed by Western blotting. Effects of Rau on autophagy of HCT-116 and LoVo cell were evaluated through GFP-LC3 analysis. In vivo xenograft tumor assay was conducted to further examine the role of Rau in CRC tumor growth. RESULTS: Rau remarkably repressed HCT-116 and LoVo cell viability and promoted HCT-116 and LoVo cell apoptosis in vitro in a dose-dependent manner. Rau increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2 in HCT-116 and LoVo cells. Moreover, Rau was demonstrated to decrease the LC3||/LC3| ratio and increase the level of P62 in HCT-116 and LoVo cells. In addition, we found that Rau repressed xenograft tumor growth and also repressed autophagy in vivo. CONCLUSION: Our findings revealed that Rau repressed CRC cell viability and autophagy in vitro and in vivo, suggesting that Rau might be a potent therapeutic agent of CRC.

Screening of a microbial consortium for selective degradation of lignin from tree trimmings.

To acquire microbial consortia with effectively precedent degradation of lignin, samples obtained from rotten trunks, rotten stumps and soil near it were screened and isolated after generations of subculture. The dynamic change illustrated that their community structures were affected by pH and tended to be stable after 6 days' cultivation. The desired one, named DM-1, was gained through successive cultivation for over 5 generations, whose high selectivity in lignin degradation was observed within 16 days' cultivation (SV = 2.78). Meanwhile, a remarkable reduction in the fiber crystallinity of tree trimmings (10.35%) resulted from the bio-degradation of DM-1, displayed a greater exposure of cellulose by selective removal of lignin. The diversity analysis of DM-1 was investigated by PCR amplification and 16S rDNA sequencing, indicated that mesorhizobium, cellulosimicrobium, pandoraea, achromobacter and stenotrophomones were the predominant genera. Furthermore, fungi (3 strains), bacteria (4 strains) and actinomycetes (5 strains) constituted 12 strains in total were gained by plate isolation from DM-1.

Spatiotemporal dynamics of bacterial and archaeal communities in household biogas digesters from tropical and subtropical regions of Yunnan Province, China.

A combination of 16S rRNA gene PCR-based techniques and the determination of abiotic factors were used to study community composition, richness, and evenness and the correlation between biotic and abiotic factors in 19 household biogas digesters in tropical and subtropical regions of Yunnan Province, China. The results revealed that both bacterial and archaeal community composition differed between regions and archaeal community composition was more affected by season than bacterial; regardless of sampling location, the dominant bacterial phyla included Chloroflexi, Bacteroidetes, Firmicutes, and Proteobacteria, and the most dominant archaeal phylum was Euryarchaeota; in digesters from both regions, Chloroflexi as the first or second most dominant bacteria accounted for 21.50-26.10 % of bacterial library sequences, and the phylum Crenarchaeota as the second most dominant archaea accounted for 17.65-19.77 % of archaeal library sequences; the species Methanosaeta concilii as the most dominant archaeal species accounted for 67.80-72.80 % of the sequences. This study found that most of the abundant microbial communities in 19 biogas digesters are similar, and this result will provide enlightenment for finding the universal nature in rural biogas digesters at tropical and subtropical regions in China.

Investigation of methanogenic community structures in rural biogas digesters from different climatic regions in Yunnan, southwest China.

Understanding of the microbial community structures of the biogas digesters in different climatic regions can help improve the methane production in the fermentation process. The methanogenic archaeal diversity in four rural biogas digesters (BNA, JSA, LJA, and XGA) was investigated by a culture-independent rRNA approach in different climatic regions in Yunnan. Community structure composed of 711 clones in the all libraries. A total of 33 operational taxonomic units (OTUs) were detected, and major groups of methanogens were the orders Methanosarcinales and Methanomicrobiales. 63.2 % of all archaeal OTUs belong to the order Methanosarcinales which mostly contain acetotrophic methanogens. Methanomicrobiales (19.5 % in all OTUs) were detected in considerable number. Additionally, there were minor rates of uncultured archaea. The principal component analysis indicated that the genus Methanosaeta was mainly affected by the fermentation temperatures.