The aim of the current study was to investigate luteolin-induced apoptosis and the molecular mechanisms underlying it in HT29 cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the cytotoxicity of luteolin on HT29 cells, and a dichloro-dihydro-fluorescein diacetate assay was used to measure cellular levels of reactive oxygen species (ROS). The effects of luteolin on the mitochondrial membrane potential were also evaluated. Bax and Bcl-2 mRNA expression were determined using reverse transcription-quantitative PCR. Additionally, western blot analysis was performed to assess changes in cytochrome c and caspase-3 protein expression. Localization of nuclear factor erythroid 2-related factor 2 (Nrf2) in the nucleus was also assessed using immunofluorescence. Luteolin exhibited cytotoxicity on HT29 cells in a time-and concentration-dependent manner. Additionally, ROS production was indicated to be increased and ROS scavenging was decreased, which resulted in a significant increase in the levels of ROS in the cells. The mitochondrial membrane potential was indicated to decrease following luteolin treatment. At the molecular level, luteolin significantly increased the mRNA expression of Bax and the protein expression of cytochrome c, caspase-3, p47 phox and p22 phox . The results revealed that luteolin decreased Bcl-2 protein expression and inhibited the nuclear localization of Nrf2. In conclusion, the current study indicated that luteolin inhibited HT29 cell proliferation and induced apoptosis via the mitochondrial pathway.

Gastric cancer is one of the most common malignant tumors. MicroRNA-196b (miR-196b) has been demonstrated to play important roles in human cancers. However, its functions in gastric cancer progression were still largely unknown. In this study, the expression of miR-196b was determined by quantitative real-time PCR. Esophageal cancer-related gene 4 (ECRG4) level was examined by western blot assay and immunohistochemistry staining assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell migration and invasion were analyzed by transwell assay. The association between miR-196b and ECRG4 was analyzed by dual-luciferase reporter assay. The functional role of miR-196b in vivo was analyzed by murine xenograft assay. As a result, we found the expression of miR-196b was elevated and the protein expression of ECRG4 was reduced in gastric cancer tissues and cells. MiR-196b inhibition suppressed gastric cancer cell proliferation, migration and invasion. ECRG4 was a target of miR-196b and its protein expression was negatively regulated by miR-196b. Moreover, ECRG4 overexpression showed similar effects with miR-196b inhibition on the malignant behaviors of GC cells and ECRG4 knockdown reversed the effects of miR-196b inhibition on gastric cancer cell proliferation, migration and invasion. In addition, miR-196b inhibition suppressed tumor volume and weight in vivo. In conclusion, downregulation of miR-196b inhibited gastric cancer progression by modulating ECRG4 expression, indicating that miR-196b might be a potential therapeutic target for gastric cancer.

LncRNA maternally expressed gene 3 (MEG3) is a potential prognostic and diagnostic biomarker in colorectal carcinoma (CC). However, its cellular functions and mechanism remain not fully uncovered. Relative expression of MEG3, miRNA (miR)-103a-3p, and pyruvate dehydrogenase E1 subunit beta (PDHB) was detected by RT-qPCR and western blotting. Cell proliferation was measured by CCK-8 assay, colony formation assay, and flow cytometry, as well as xenograft tumor assay. Transwell assay examined cell invasion. Endoplasmic reticulum (ER) stress was eva luated by western blotting. Dual-luciferase reporter assay and RNA immunoprecipitation determined the relationship between miR-103a-3p and MEG3 or PDHB. Expression of MEG3 was downregulated in human CC tumor tissues and cells (SW620 and HCT116), accompanied by higher miR-103a-3p and lower PDHB. Restoring MEG3 suppressed cell viability, colony formation ability, and invasion, 2 arrested cell cycle, and induced apoptosis rate in SW620 and HCT116 cells, as well as promoted expression of ER stress-related proteins (GRP78, ATF6, CHOP, caspase-3, and caspase-9). Furthermore, MEG3 overexpression hindered tumor growth and facilitated ER stress in vivo. Molecularly, miR-103a-3p was a target of MEG3, and further targeted PDHB. Similarly, in function, blocking miR-103a-3p suppressed CC in vitro by affecting proliferation, invasion, and ER stress; in addition, restoring miR-103a-3p partially counteracted the suppressive role of MEG3 in CC cells. MEG3 sponged miR-103a-3p to suppress CC malignancy by inducing ER stress and inhibiting cell proliferation and invasion via upregulating PDHB, suggesting a novel MEG3/miR-103a-3p/PDHB ceRNA pathway. Key words : MEG3; ER stress; miR-103a-3p; pyruvate dehydrogenase E1 subunit beta (PDHB); colorectal carcinoma Endoplasmic reticulum (ER) stress, caused by the accumulation of unfolded or misfolded proteins, plays a dual role in tumorigenesis and development [1], by linking to fundamental biological processes, such as proliferation, apoptosis, migration, invasion and autophagy [2-4]. In response to ER stress, unfolded protein response (UPR) is activated to promote tumor-survival response or anti-tumor response [5, 6]. Not surprisingly, ER stress and UPR are associated with intestinal diseases, including colorectal carcinoma (CC) [7, 8]. CC is the third most common cancer according to global cancer statistics 2018 of the International Agency for Research on Cancer [9], and its incidence and mortality are expected to be rapidly increasing in many low-income and middle-income countries [10]. The survival of CC patients is closely related to the stage of CC [11], thus it is essential to identify more efficient mole cular targets for better understanding of the mechanism underlying CC progression, as well as seeking early diagnostic markers. Recently, it has been well-documented that long noncoding RNAs (lncRNAs) as key regulators mediate competing endogenous RNA (ceRNA) network to regulate carcinogenesis, progression and treatment of CC [12, 13]. LncRNA...

Background Abundant studies have identified the association between childhood maltreatment and self-harm (SH), but little has been discussed with regard to the role of resilience in SH behaviors of adolescents who had experienced childhood maltreatment. In this study, we investigated if resilience, as well as its five dimensions, could present negative associations with presence, repetition, and severity of SH among maltreated and neglected adolescents in China. Methods A cross-sectional survey including 2,084 maltreated teenagers aged from 10 to 17 years was conducted in southwest China Yunnan province. The Childhood Trauma Questionnaire (CTQ), The Resilience Scale for Chinese Adolescents (RSCA), and the Modified version of Adolescents Self-Harm Scale (MASHS) were adopted to measure childhood maltreatment experiences, psychological resilience, and SH behaviors of the respondents, respectively. Binary univariate and multivariate logistic regression models were employed to discuss the associations between resilience and occurrence, repetition, severity of SH. Results Among the participants who met the criteria of CTQ, the prevalence rates of SH were 63.83%, 73.94%, 71.50%, 55.53%, and 58.21% for physical abuse (PA), emotional abuse (EA), sexual abuse (SA), physical neglect (PN), and emotional neglect (EN). Final regression model demonstrated that resilience was in general inversely associated with SH, repeated SH, and severe SH for all types of childhood maltreatment, with adjusted odds ratios (aORs) ranging from 0.29 (95% CI: 0.19-0.44) to 0.46 (95% CI: 0.26-0.81). Of the five dimensions of resilience, emotion regulation served as the strongest associated factor of SH among abused youths, regardless of maltreatment types. Besides, compared with those who had lower level of goal concentration and interpersonal assistance, subjects with higher resilience level reported significantly decreased risks of SH occurrence, SH repetition, and more severe SH, in adolescents who had experienced EA and PN. Conclusions Resilience showed inverse association with childhood maltreatment related SH in Chinese adolescents. These findings preliminarily indicated that interventions targeting on building up resilience, especially enhancing emotion regulation ability, improving goal concentration, and consolidating interpersonal assistance, could be effective in reducing SH risk, repetition, and severity in maltreated Chinese teenagers.

Salusin-α and salusin-β are newly identified bioactive peptides of 28 and 20 amino acids, respectively, that were initially predicted using in silico analyses and are widely distributed in the endocrine system, hematopoietic system, and central nervous system. The goal of our study was to investigate the cardiovascular effect of salusin-β microinjections into the rostral ventrolateral medulla (RVLM) in anesthetized rats and study their mechanism of action. Microinjection of the artificial cerebrospinal fluid (aCSF) into the RVLM did not affect the blood pressure (BP) or heart rate (HR) in anesthetized rats. Topical application of salusin-β into the RVLM produced a dose-dependently increase of BP in anesthetized rats. Microinjection of higher dose salusin-β produced significant tachycardia. Prior application of the L-NAME into the RVLM of rats did not alter the hypertension and tachycardia induced by intra-RVLM salusin-β. Notable, the cardiovascular functions elicited by intra-RVLM salusin-β were significantly decreased by pretreatment with Nic, KYN and atropine. In conclusion, the present study shows that the hypertension and tachycardia induced by intra-RVLM salusin-β might be partly mediated, at least in our opinion, by muscarinic receptors, glutamate receptors or L-type calcium channels.