LncRNA HULC induces the progression of osteosarcoma by regulating the miR-372-3p/HMGB1 signalling axis.

BACKGROUND: Osteosarcoma is a malignancy that normally affects children, adolescents, and young adults. Although accumulating evidence has demonstrated the importance of HULC in osteosarcoma, little is reported about its functional roles and molecular mechanisms. METHODS: The expression of HULC and miR-372-3p in osteosarcoma tissues was quantified by qRT-PCR. The regulatory roles of HULC and miR-372-3p on cell proliferation, apoptosis, migration and invasion were determined by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays, respectively. The bioinformatics prediction software RAID v2.0 was used to predict the putative binding sites. The interactions among HULC, miR-372-3p and HMGB1 were explored by luciferase assay and western blot assay. RESULTS: Our results revealed elevated HULC and decreased miR-372-3p expression in both osteosarcoma tissues and cell lines. Overexpression of HULC or knockdown of miR-372-3p promoted osteosarcoma cell proliferation, migration and invasion and induced cell apoptosis. Bioinformatics and luciferase assays verified that HULC directly interacted with miR-372-3p to attenuate miR-372-3p binding to the HMGB1 3'-UTR. Furthermore, mechanistic investigations confirmed that activation of the miR-372-3p/HMGB1 regulatory loop by knockdown of miR-372-3p or overexpression of HMGB1 reversed the in vitro roles of HULC in promoting osteosarcoma cell proliferation, migration and invasion. CONCLUSION: Our study is the first to demonstrate that HULC may act as a ceRNA to modulate HMGB1 expression by competitively sponging miR-372-3p, leading to the regulation of osteosarcoma progression, which provides new insight into osteosarcoma diagnosis and treatment.

SP1-induced ZFAS1 aggravates sepsis-induced cardiac dysfunction via miR-590-3p/NLRP3-mediated autophagy and pyroptosis.

BACKGROUND: Sepsis-induced cardiac dysfunction is one of the leading complications of sepsis, contributing to the high morbidity and mortality of septic patients. Several lines of evidence have demonstrated that autophagy and pyroptosis may be involved in septic cardiac dysfunction. In this study, we examined the impact of zinc finger antisense 1 (ZFAS1) on sepsis-induced myocardial dysfunction via regulating pyroptosis and autophagy. METHOD: Mice with cecal ligation and puncture (CLP)-induced sepsis was constructed in vivo. Myocardial injury was assessed by H&E staining, immunohistochemistry (IHC) for NLRP3, caspase 1, and interleukin (IL)-1ß, as well as ELISA assay for serum levels of creatine kinase (CK), CK-MB, tumor necrosis factor α (TNF-α), and IL-1ß. Primary cardiomyocytes exposed to lipopolysaccharide (LPS) were established to simulate sepsis-induced cardiac dysfunction in vitro. Cell viability was examined by MTT assay and concentration of TNF-α and IL-1ß was measured by ELISA. Flow cytometry, immunofluorescent staining and western blotting were performed to assess pyroptosis and autophagy. The transcriptional regulation of SP1 on ZFAS1 was determined using ChIP assay. Luciferase reporter assay was performed to verify the ZFAS1/miR-590-3p interaction. Besides, activation of AMPK/mTOR signaling was detected using western blotting. RESULTS: Highly expressed ZFAS1 was observed in sepsis-induced cardiac dysfunction in the in vivo and in vitro model. Knockdown of ZFAS1 robustly abolished LPS-induced pyroptosis and attenuated the inhibition of autophagy. SP1 was identified to be an essential transcription factor to positively regulate ZFAS1 expression. Moreover, miR-590-3p functioned as a downstream effector to reverse ZFAS1-mediated sepsis-induced cardiac dysfunction. AMPK/mTOR signaling was involved in miR-590-3p-regulated autophagy and pyroptosis of cardiomyocytes. Furthermore, the regulatory network of ZFAS1/miR-590-3p on AMPK/mTOR signaling was verified in vivo. CONCLUSION: ZFAS1, activated by SP1, aggravates the progression of sepsis-induced cardiac dysfunction via targeting miR-590-3p/AMPK/mTOR signaling-mediated autophagy and pyroptosis of cardiomyocytes.

Long noncoding RNA LINC01510 promotes the growth of colorectal cancer cells by modulating MET expression.

BACKGROUND: Abnormal expression of long non-coding RNA (lncRNAs) often facilitates unrestricted growth of cancer cells. Long intergenic non-protein coding RNA 1510, an enhancer lncRNA (LINC01510), a lncRNA enhancer is upregulated in colorectal cancer (CRC), and its expression might relate to MET as revealed by lncRNA microarray data. However, the potential biological role of LINC01510 and its regulatory mechanism in CRC remain unclear. Therefore, we investigated the involvement of LINC01510 in the proliferation of CRC cells. METHODS: Microarray analysis, In situ hybridization, colony formation assay, MTT assay, Western blotting, quantitative RT-PCR and flow cytometry were applied. The two-tailed Student's t test and analysis of variance or general linear model of single factor variable was used for statistical analyse. RESULTS: In the present study, we found that LINC01510 was significantly upregulated in CRC tissues and cell lines. The LINC01510 expression level were associated with the clinicopathological grade and stage. Meanwhile, gain- and loss-of-function assays demonstrated that LINC01510 overexpression increased CRC cell proliferation, and promoted cell cycle progression from the G1 phase to the S phase. Further study indicated that LINC01510 was positively correlated with the expression of MET, and its effects were most likely at the transcriptional level. CONCLUSIONS: Taken together, our findings suggested that upregulation of LINC01510 contributes to the proliferation of CRC cells, at least in part, through the regulation of MET protein. LINC01510 could be a candidate prognostic biomarker and a target for new therapies in CRC patients.

Investigating the validation of the Chinese Mandarin version of the Social Responsiveness Scale in a Mainland China child population.

BACKGROUND: Researchers from several different countries have found the Social Responsiveness Scale (SRS) to have good psychometric properties. However, to our knowledge, no studies on this subject have been reported in Mainland China. In this study, we investigated the psychometric properties of the Chinese Mandarin version of the SRS when used in Mainland China. METHODS: The reliability and validity of the parent-report SRS in a sample of 749 children of 4- to 14-year-olds: 411 typically developing and 338 clinical participants (202 with autism spectrum disorder (ASD)) were examined. RESULTS: Internal consistency for total scale (0.871-0.922), test-retest reliability (0.81-0.94), and convergent validity with the Autism Behavior Checklist (ABC) (0.302-0.647) were satisfactory. The SRS total score discriminated between the ASD and other developmental disorders. Receiver operating characteristic (ROC) analyses revealed that the SRS was predicted to accurately classify 69.2-97.2% of youth ASD. Exploratory factor analysis (EFA) supported a single-factor solution for the ASD subsample. Confirmatory factor analysis (CFA) did not confirm the theoretical construct of five factors model with inadequate fit in the ASD subsample. CONCLUSIONS: Overall, our findings supported the reliability and validity of the parent-report SRS as one ASD screening instrument. In addition, we also suggest that the use of separate cut-offs for screening purposes (optimizing sensitivity) vs. clinical confirmation (optimizing specificity) should be considered.

Combination of early Interleukin-6 and -18 levels predicts postoperative nosocomial infection.

Background: The inflammatory response plays a critical role in postoperative nosocomial infections, which are the most common postoperative complications causing adverse events and poor postoperative outcomes. This study aimed to explore the ability of early inflammation-related factor levels to predict the occurrence of nosocomial infections after abdominal surgery. Methods: The study included 146 patients with open abdominal surgery (a nosocomial infection group (NI group, n=42) and a no-nosocomial infection group (NNI group, n=104)). After 1:1 matching, the patients were divided into a matching nosocomial infection group (M-NI group, n=25) and a matching no-nosocomial infection group (M-NNI group, n=25). Serum levels of interleukin (IL)-6, IL-8, IL-10, IL-12, IL-18, macrophage migration inhibitory factor (MIF), and monocyte chemotactic protein (MCP-1) were tested at three time points (pre-operation, 0-hour post-operation (POD1) and 24-hour post-operation (POD2)). The area under the receiver operating characteristic curve (AUC-ROC) was used to test the predictive abilities. Results: There were significant differences in the levels of IL-6, IL-12, and IL-18 between the M-NI and M-NNI groups (p < 0.05), but not in the levels of other inflammatory factors. MIF, IL-8, and MCP-1 levels were higher in the M-NI group than in the M-NNI group at POD2 (p < 0.05). In the ROC analysis, the AUC for prediction of nosocomial infection using a combination of IL-6 and IL-18 at POD1 was 0.9616, while the AUCs for IL-6 alone and IL-12 alone were 0.8584 and 0.8256, respectively. Conclusions: The combination of the levels of inflammatory factors, IL-6 and IL-18, at the 0-hour postoperative time point, significantly improved the predictive ability to the development of postoperative infection during perioperative period. Our study suggests the importance of monitoring postoperative inflammatory markers.

Overexpression of circ PTK2 suppresses the progression of nonalcoholic fatty liver disease via the miR-200c/SIK2/PI3K/Akt axis.

Excessive hepatic lipid accumulation is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A previous study showed that the circular RNA (circRNA) PTK2 was significantly downregulated in NAFLD mice. However, the detailed function of circ PTK2 in NAFLD remains unclear. A high-fat diet (HFD) was used to establish a mouse model of NAFLD, and free fatty acid (FFA) treatment was used to establish an in vitro model of NAFLD. Oil red O staining was used to evaluate lipid accumulation. The pathological changes in mice were observed by HE staining. Western blotting and RT-qPCR were applied to assess protein and mRNA levels, respectively. A dual luciferase reporter assay and RIP were used to explore the relationship among circ PTK2, miR-200c and SIK2. Circ PTK2 and SIK2 were downregulated and miR-200c was upregulated in NAFLD. Upregulation of circ PTK2 reversed lipid accumulation in FFA-treated HepG2 cells. Moreover, circ PTK2 bound to miR-200c, and SIK2 was identified as the direct target of miR-200c. Moreover, the miR-200c inhibitor-induced decrease in lipid accumulation was reversed by SIK2 knockdown. Furthermore, the impact of circ PTK2 overexpression on PI3K/Akt signaling was partially reversed by SIK2 silencing. Circ PTK2 overexpression alleviates NAFLD development via the miR-200c/SIK2/PI3K/Akt axis. Thus, our work might provide new methods for NAFLD treatment.

Rare purulent pericarditis caused by carbapenem-resistant Acinetobacter baumannii: A case report.

BACKGROUND: Pericardial infection caused by Acinetobacter baumannii is rare, particularly that of carbapenem-resistant A baumannii (CRAB). CASE PRESENTATION: We describe a rare case of purulent pericarditis due to CRAB in a 76-year-old man with acute myocardial infarction and acute kidney injury. The man was admitted to the intensive care unit for a catheter-related bloodstream infection. Pericardial effusion was detected via the bedside X-ray and ultrasound, and pericardiocentesis was performed. Cultures of the pericardial fluid, catheter tip, and blood independently revealed the presence of CRAB. These findings confirmed a diagnosis of purulent pericarditis. CONCLUSIONS: Clinicians should be reminded that CRAB infection can lead to purulent pericarditis, particularly in patients with congestive heart failure or renal insufficiency.

Long non­coding RNA ENST00000547547 inhibits cell proliferation, invasion and migration in colorectal cancer cells.

Colorectal cancer (CRC) is one of the most common and lethal types of cancer worldwide. Multiple lines of evidence have illustrated that long non­coding RNAs (lncRNAs) are critical molecules in the regulation of CRC development and progression. The identification of new lncRNAs is expected to provide new biomarkers and potential therapeutic targets for CRC diagnosis and prevention. Previous research has revealed that, ENST00000547547, a 434­bp lncRNA on human chromosome12q15 (RP11­611E13.3­001), was found to be downregulated in CRC tissues from lncRNA microarray studies. However, its role in the development and progression of CRC remains largely unknown. In the present study, we demonstrated that the ENST00000547547 level is significantly downregulated in CRC tissues compared to normal tissues. Furthermore, the overexpression of ENST00000547547 inhibited the cell proliferation, invasion and migration of CRC cells in vitro and decreased tumorigenesis ability in vivo. Furthermore, we provided the first evidence that ENST00000547547 inhibited the proliferation of CRC cells by affecting the cell cycle and apoptosis. Finally, we demonstrated that the epithelial­mesenchymal transition (EMT) process was associated with the inhibitory effects of ENST00000547547 on the invasion and migration of CRC cells. In summary, the present study indicated that lncRNA ENST00000547547 acted as a tumor suppressor in CRC, which may provide us with a new biomarker for CRC prognosis and a potential therapeutic target for molecular cancer therapy.

The long non-coding RNA ENST00000547547 reduces 5-fluorouracil resistance of colorectal cancer cells via competitive binding to microRNA-31.

Colorectal cancer (CRC) is one of the most common cancers and the third leading cause of cancer-related deaths due to its rapid progression and poor prognosis. 5-Fluorouracil (5-FU)-based chemotherapies are the standard treatment for locally advanced CRC. However, a considerable percentage of CRCs have inherent or acquired 5-FU resistance, which critically impedes clinical outcomes. In the present study, we reported that the expression level ENST00000547547 was downregulated in 5-FU-resistant CRC cells in comparison with the parental cells, While rising with the treatment of 5-FU in parental cells. Overexpression of ENST00000547547 promoted 5-FU-induced cell apoptosis and reduced the chemoresistance of 5-FU in vitro. Moreover, we found that ENST00000547547 was a target of miR-31, as confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Notably, miR-31 was upregulated in 5-FU-resistant CRC cells, and knockdown of miR-31 increased the chemosensitivity of 5-FU-resistant CRC cells. Furthermore, we demonstrated that ENST00000547547 reduced the chemoresistance of 5-FU via competitive binding to miR-31 in 5-FU-resistant CRC cell lines. Collectively, our findings revealed that ENST00000547547 reduced chemoresistance in 5-FU of 5-FU-resistant CRC cells through competitive binding to miR-31 and has the potential to serve as a therapeutic target in CRC patients.

Post-receptor crosstalk between growth hormone and insulin signal in rats born small for gestational age with catch-up growth.

OBJECTIVE: Insulin resistance has been observed in individuals born small for gestational age (SGA) with catch-up growth (CUG), yet the mechanisms involved remain unclear. This study examined the role of GH and insulin signaling crosstalk in insulin resistance of SGA rats with CUG. DESIGN AND METHODS: SGA rats were developed by dietary restriction in pregnant rats. GH receptor inhibition was performed on four-week old CUG-SGA and AGA rats. Phosphorylation of IRS-1, AKT, and ERK, and expression of SOCS3 in the skeletal muscle were determined via immunoblot analysis at baseline and after insulin stimulation in CUG-SGA, NCUG-SGA and AGA groups. RESULTS: Compared to AGA controls, phosphorylation of IRS-1 and AKT in response to insulin stimulation in CUG-SGA rats was significantly blunted (P<0.05), and phosphorylation of ERK at baseline was dramatically activated (P<0.05). SOCS3 expression was significantly increased in CUG-SGA compared to AGA (P = 0.001) and NCUG-SGA (P = 0.006) rats, and was significantly suppressed following GHR inhibition (P<0.05). Furthermore, phosphorylation of IRS-1 and AKT in response to insulin stimulation increased after GHR inhibition (P<0.05). CONCLUSIONS: Insulin resistance in CUG-SGA rats is associated with impairment of IRS-1-PI3K-AKT signaling, which may result from GH signaling-induced up-regulation of SOCS3.