Apelin alleviated neuroinflammation and promoted endogenous neural stem cell proliferation and differentiation after spinal cord injury in rats.

BACKGROUND: Spinal cord injury (SCI) causes devastating neurological damage, including secondary injuries dominated by neuroinflammation. The role of Apelin, an endogenous ligand that binds the G protein-coupled receptor angiotensin-like receptor 1, in SCI remains unclear. Thus, our aim was to investigate the effects of Apelin in inflammatory responses and activation of endogenous neural stem cells (NSCs) after SCI. METHODS: Apelin expression was detected in normal and injured rats, and roles of Apelin in primary NSCs were examined. In addition, we used induced pluripotent stem cells (iPSCs) as a carrier to prolong the effective duration of Apelin and evaluate its effects in a rat model of SCI. RESULTS: Co-immunofluorescence staining suggested that Apelin was expressed in both astrocytes, neurons and microglia. Following SCI, Apelin expression decreased from 1 to 14 d and re-upregulated at 28 d. In vitro, Apelin promoted NSCs proliferation and differentiation into neurons. In vivo, lentiviral-transfected iPSCs were used as a carrier to prolong the effective duration of Apelin. Transplantation of transfected iPSCs in situ immediately after SCI reduced polarization of M1 microglia and A1 astrocytes, facilitated recovery of motor function, and promoted the proliferation and differentiation of endogenous NSCs in rats. CONCLUSION: Apelin alleviated neuroinflammation and promoted the proliferation and differentiation of endogenous NSCs after SCI, suggesting that it might be a promising target for treatment of SCI.

Overexpression of Epithelial Splicing Regulatory Protein 1 in Metastatic Lesions of Serous Ovarian Carcinoma Correlates with Poor Patient Prognosis.

Background: Epithelial splicing regulatory proteins (ESRPs) can regulate alternative splicing of RNA and play roles in tumorigenesis and development of various malignancies. In this study, bioinformatic analyses and immunohistochemistry (IHC) were used to investigate the function of ESPRs in serous ovarian carcinoma (SOC) oncogenesis and metastasis. Materials and Methods: The mRNA levels of ESRPs were analyzed by Oncomine and gene expression profiling interactive analysis (GEPIA). Prognostic values of ESRPs were analyzed by GEPIA and the UALCAN website. Genetic variations of ESRPs were analyzed by cBioPortal. ESRP1 was selected for further research. The relationship between ESRP1 and immunoregulatory molecules was studied by using the TISIDB database. ESRP1 protein expression in OC was investigated via IHC assays. Results: ESRP1 and ESRP2 mRNA were significantly upregulated in SOC (p < 0.05). The prognostic value of ESRP1 mRNA in SOC was inconsistent, and ESRP2 mRNA level did not relate to prognosis for OC patients. The IHC results showed higher ESRP1 expression in OC tissues than in normal ovarian tissues (p = 0.002), and ESRP1 expression in metastatic lesions of OC patients was higher than in paired primary OC tissues (p = 0.035). The ESRP1 expression was related to FIGO stage, differentiation, and peritoneal metastasis (p = 0.016; 0.031; 0.038, respectively). The ESRP1 switch (the differential expression of ESRP1 between metastatic and primary tumor of ovarian carcinoma) was significantly associated with E-cadherin expression in metastatic OC tumors (p = 0.012). The ESRP1 expression in both metastasis and ESRP1 switch significantly correlated with poor prognosis of OC patients (p = 0.045; 0.038, respectively), and ESRP1 switch and FIGO stage were independent risk factors for OC patient prognosis (p = 0.033; 0.009, respectively). Conclusions: The ESRP1 may promote OC metastasis by promoting OC cell colonization via the mesenchymal-epithelial transition (MET) process. The ESRP1 expression in metastatic lesions of OC patients may be a biomarker for predicting prognosis and a potential therapeutic target in OC.

Application of the original site point method in determining a baseline for two different types of sites in northern China.

Determining an ecological and environment damage baseline is the foundation of natural resource damage assessment. In complex damage assessment, the importance of a baseline is often underestimated or ignored. Existing baseline determination methods are insufficiently accurate and poorly available in practical application, which affect the damage assessment work. Based on the definition of baseline and the shortcomings of existing baseline-determination methods, this paper suggests the original site point (OSP) method as a determination principle. The baseline calculation area can be directly determined according to the site conditions in a sludge storage site with clear pollution distribution, and the OSP method has the advantage of determining the baseline rapidly. For a waste oil sludge storage site with unclear pollution distribution, the baseline calculation area should be determined according to preliminary and detailed sampling data. The calculation results of the two sites indicate that the baseline determined using the OSP method and the reference point (RP) method are similar, and the results of the environmental standard (ES) method are superior to those of the other two methods. The order of accuracy of baseline determination methods is the historical data (HD) method > the OSP method > the RP method > the model calculation (MC) method > the ES method. Through two application cases, this paper discusses the applicability of the OSP method and finally establishes the determination steps of the method. The OSP method has proven effective in determining the baseline, and the fast and accurate baseline determination method is more helpful for damage assessment. Integr Environ Assess Manag 2021;17:1263-1273. © 2021 SETAC.

The clinical significance and biological function of lncRNA SOCAR in serous ovarian carcinoma.

BACKGROUND: Ovarian cancer (OvCa) is one of the most lethal gynecologic malignancies worldwide. Pelvic and abdominal metastasis is a leading cause for the poor prognosis of OvCa patients. The relationship between long non-coding RNAs (lncRNAs) and OvCa remains unclear. Identifying key lncRNAs related with OvCa metastasis is crucial for research on the mechanism of OvCa metastasis. This study was designed to investigate the role of a novel lncRNA, which we named SOCAR, in serous OvCa. METHODS: LncRNA microarray and Real-time PCR were used to examine SOCAR expression in high grade serous ovarian cancer (HGSOC) and normal ovary tissues. The proliferation, migration and invasion of OvCa cell lines SKOV-3 and OVCAR-3 were analyzed by CCK-8, Transwell and Scratch wound healing assays. Western blotting was used to detect the expression of Wnt/ß-catenin pathway-related proteins. RESULTS: A novel serous OvCa-related lncRNA, SOCAR, was identified via microarray. SOCAR was overexpressed in primary HGSOC tumors compared with normal ovary tissues, and the expression of SOCAR correlated with progression in HGSOC patients. SOCAR also had higher expression in metastatic HGSOC tissues compared with primary cancer tissues. Moreover, upregulation of SOCAR promoted proliferation, migration and invasion in OvCa cells. Expression of Wnt1, ß-catenin and MMP-9 were all increased by SOCAR overexpression. CONCLUSION: SOCAR is related with HGSOC oncogenesis and progression. It may promote proliferation, migration and invasion in OvCa cells partially by upregulating MMP-9 through the Wnt/ß-catenin pathway.

CTD-2020K17.1, a Novel Long Non-Coding RNA, Promotes Migration, Invasion, and Proliferation of Serous Ovarian Cancer Cells In Vitro.

BACKGROUND Ovarian cancer is the most lethal malignant tumor of the female reproductive system, and the metastasis is one of the major factors that contribute to the poor outcome of patients with OC. Accumulating evidence indicates that lncRNAs are expressed and play important regulatory roles in ovarian cancer. MATERIAL AND METHODS Aberrant lncRNAs in primary ovarian cancer tissues (POCTs) and paired omental metastasis tissues (OMTs) of patients with HGSOC were studied via lncRNA microarray. Real-time PCR was performed to examine CTD-2020K17.1 expression in HGSOC tissues from 38 patients, a normal ovarian surface epithelium cell line, and 4 ovarian cancer cell lines. Additionally, Transwell assays, wound healing assays, CCK-8 proliferation assays, and flow cytometry were used to explore the biological function of CTD-2020K17.1 in ovarian cancer cells. Finally, Western blot analysis was used to verify the potential target gene of CTD-2020K17.1. RESULTS A novel lncRNA named CTD-2020K17.1 was identified via microarray analysis. Expression of CTD-2020K17.1 was significantly increased in OMTs and in 4 ovarian cancer cell lines compared with POCTs (P<0.05) or normal ovarian surface epithelial cell line (P<0.05). Moreover, CTD-2020K17.1 overexpression promoted migration, invasion, and proliferation of ovarian cancer cells, and CTD-2020K17.1 regulated the expression of CARD11. CONCLUSIONS CTD-2020K17.1 is significantly upregulated in OMTs and ovarian cancer cell lines. It can promote the migration, invasion, and proliferation of ovarian cancer cells, and CARD11 is regulated by CTD-2020K17.1.

The eIF3 complex of Trypanosoma brucei: composition conservation does not imply the conservation of structural assembly and subunits function.

The multisubunit eukaryotic initiation factor 3 (eIF3) plays multiple roles in translation but is poorly understood in trypanosomes. The putative subunits eIF3a and eIF3f of Trypanosoma brucei (TbIF3a and TbIF3f) were overexpressed and purified, and 11 subunits were identified, TbIF3a through l minus j, which form a tight complex. Both TbIF3a and TbIF3f are essential for the viability of T. brucei RNAi knockdown of either of them severely reduced total translation and the ratio of the polysome/80S peak area. TbIF3f and TbIF3a RNAi cell lines were modified to express tagged-TbIF3a and -TbIF3f, respectively. RNAi in combination with affinity purification assays indicated that both subunits are variably required for TbIF3 stability and integrity. The relative abundance of other subunits in the TbIF3f-tag complex changed little upon TbIF3a depletion; while only subunits TbIF3b, i, and e copurified comparably with TbIF3a-tag upon TbIF3f depletion. A genome-wide UV-crosslinking assay showed that several TbIF3 subunits have direct RNA-binding activity, with TbIF3c showing the strongest signal. In addition, CrPV IRES, but neither EMCV IRES nor HCV IRES, was found to mediate translation in T. brucei These results together imply that the structure of TbIF3 and the subunits function have trypanosome-specific features, although the composition is evolutionarily conserved.