BACKGROUND In the recent years, there has been increasing interest in traditional Chinese medicine as a neuroprotective nutrient in the management of chronic neurodegenerative disease, such as diabetic cognitive decline. Astragalus polysacharin (APS), a Chinese herb extract, is a biologically active treatment for neurodegenerative diseases. Therefore, in the present study, we investigated the neuroprotective effects of APS (20 mg/kg) on diabetes-induced memory impairments in Sprague-Dawley (SD) rats and explored its underlying mechanisms of action. MATERIAL AND METHODS Thirty SD rats were randomly divided into a control group (CON group, n=10), a diabetic model (DM) group (n=10), and an APS group (n=10). We administered 55 mg/kg streptozotocin (STZ, Sigma) by intraperitoneal injection to induce a diabetic model. Food and water intake, body weight, and blood fasting plasma glucose (FPG) were measured. The Morris water maze test (MWM) was used to assess learning and memory ability, and we measured levels of N-methyl-D-aspartate receptor (NMDA), calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element-binding protein (CREB) in the hippocampus. RESULTS APS (20 mg/kg) administration decreased the rats' fasting plasma glucose (FPG) levels and body weight. APS (20 mg/kg) administration improved the cognitive performance of diabetes-induced rats in the Morris water maze test. APS (20 mg/kg) administration reduced the number of dead cells in the CA1 region of the hippocampus. Furthermore, APS (20 mg/kg) administration obviously upregulated the phosphorylation levels CREB, NMDA, and CaMK II. CONCLUSIONS These results suggest that APS has the neuroprotective effects, and it may be a candidate for treatment of neurodegenerative diseases such as diabetic cognitive impairment.

BACKGROUND Using regional homogeneity (ReHo) blood oxygen level-dependent functional MR (BOLD-fMRI), we investigated the structural and functional alterations of brain regions among patients with methamphetamine-associated psychosis (MAP). MATERIAL AND METHODS This retrospective study included 17 MAP patients, 16 schizophrenia (SCZ) patients, and 18 healthy controls. Informed consent was obtained from all patients before the clinical assessment, the severity of clinical symptoms was evaluated prior to the fMRI scanning, and then images were acquired and preprocessed after each participant received 6-min fRMI scanning. The participants all underwent BOLD-fMRI scanning. Voxel-based morphometry was used to measure gray matter density (GMD). Resting-state fMRI (rs-fMRI) was conducted to analyze functional MR, ReHo, and functional connectivity (FC). RESULTS GMD analysis results suggest that MAP patients, SCZ patients, and healthy volunteers show different GMDs within different brain regions. Similarly, the ReHo analysis results suggest that MAP patients, SCZ patients, and healthy volunteers have different GMDs within different brain regions. Negative correlations were found between ReHo- and the PANSS-positive scores within the left orbital interior frontal gyrus (L-orb-IFG) of MAP patients. ReHo- and PANSS-negative scores of R-SFG were negatively correlated among SCZ patients. The abnormal FC of R-MFG showed a negative correlation with the PANSS score among MAP patients. CONCLUSIONS The abnormalities in brain structure and FC were associated with the development of MAP.

BACKGROUND Long noncoding RNA (lncRNA) acts as key regulator in human cancers, including retinoblastoma. However, the function of LINC00152 remains largely unknown in retinoblastoma. Thus, this study aimed to explore the role and molecular mechanisms of LINC00152 in retinoblastoma. MATERIAL AND METHODS The real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify the expression levels of LINC00152, miR-613 and yes-associated protein 1 (YAP1). The target genes of LINC00152 and miR-613 were identified by dual-luciferase reporter analysis, RNA immunoprecipitation (RIP) and RNA pulldown assays. The viability, apoptosis, and invasion of retinoblastoma cells were assessed by Cell Counting Kit-8, flow cytometry, and Transwell assays, respectively. In addition, western blot was used to test the protein expression in retinoblastoma cells or tissues. Cell sensitivity to carboplatin and adriamycin was analyzed by computing IC₅₀ value. The effects of LINC00152 silencing in vivo were measured by a xenograft experiment. RESULTS LINC00152 was obviously upregulated, while miR-613 was decreased in retinoblastoma tissues and cells. MiR-613, a target of LINC00152, was negatively regulated by LINC00152. Functional experiment further illustrated that silencing of LINC00152 evidently repressed proliferation, invasion, and autophagy while reinforced apoptosis of retinoblastoma cells, besides, retinoblastoma cells were more sensitive to carboplatin and adriamycin after knockdown of LINC00152. Importantly, knockdown of LINC00152-induced effects on retinoblastoma cells could be overturned by introducing miR-613 inhibitor. Downregulation of miR-613 abolished silencing of YAP1-effects on proliferation, apoptosis, invasion, autophagy, and chemoresistance of retinoblastoma cells. The results of the xenograft experiment indicated that LINC00152 silencing impeded tumor growth in vivo. CONCLUSIONS Mechanistically, LINC00152 enhanced the aggressiveness of retinoblastoma and boosted carboplatin and adriamycin resistance by regulating YAP1 by sponging miR-613 in human retinoblastoma.

BACKGROUND Circadian disruption is a potential cancer risk factor in humans. However, the role of the clock gene, cryptochrome 2 (CRY2), in osteosarcoma (OS) is still not clear. MATERIAL AND METHODS To evaluate the potential role of CRY2 in HOS osteosarcoma cells, CRY2-silenced cell lines were established. Furthermore, we investigated the effect of CRY2 knockdown on HOS cells by CCK-8, colony formation, migration assay, and flow cytometry, in vitro. RESULTS CRY2 knockdown promoted HOS OS cell proliferation and migration. We used a cell cycle assay to show that CRY2 knockdown increased the S phase cell population and reduced the G1 phase cell population. Western blot analyses showed that CRY2 knockdown decreased P53 expression and increased expression of c-myc and cyclin D1. Simultaneously, CRY2 knockdown increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, but did not change the phosphorylation of c-Jun N terminal kinase (JNK) and P38. CRY2 knockdown also increased the expression of matrix metalloproteinase (MMP)-2 and β-catenin, and increased OS cell proliferation and migration by inducing cell cycle progression and promoting mitogen-activated protein kinase (MAPK) and Wnt/β-catenin signaling pathways. Although it has previously been unclear whether the expression of CRY2 affects the expression of other clock genes in the clock gene network, our results show that knockdown of CRY2 significantly increased the mRNA expression of CRY1, Period (PER) 1, PER2, BMAL1, and CLOCK. CONCLUSIONS Our results suggest that CRY2 may be an anti-oncogene in OS, whose functions involve both downstream genes and other circadian genes.

BACKGROUND The aim of this study was to explore the influence of mitofusin-2 (Mfn-2) on phosphatidylinositol transfer protein 3 (PITPNM3) and tumor growth and the potential mechanism behind the regulation of Mfn-2 on PITPNM3 in hepatic carcinoma cell line SMMC-7721. MATERIAL AND METHODS We obtained promoter sequence of PITPNM3 gene from University of Santa Cruz (UCSC) genomic database, and we predict transcriptional factor of PITPNM3 genes by JASPAR database. Target transcription factor was determined by comparison of binding sites number for promoter. SMMC-7721 cells were transfected with expression plasmid containing Mfn-2, transcription factor gene and PITPNM3. The cells transfected with empty vector were used as control. Real-time polymerase chain reaction was used to determine the mRNA level of target genes. Co-immunoprecipitation (Co-IP) assay was used to determine the interaction between Mfn-2 and target transcription factor. Chromatin immunoprecipitation assay (ChIP) assay was used to determine the binding of transcription factor with PITPNM3 promoter. Tumorigenicity assay was used to compare the effect of Mfn-2, SP1, and PITPNM3 on tumor development. RESULTS SP1 was selected as the target transcriptional factor. In the Co-IP assay, Mfn-2 was shown to interact with SP1. In the ChIP assay Mfn-2 transfection resulted in decreased binding number of SP1 with PITPNM3 promoter. Furthermore, PITPNM3 mRNA levels were significantly increased in SMMC-7721 cells transfected with SP1 but were decreased after transfection with Mfn-2. In nude mice, PITPNM3 and SP1 upregulation lead to larger tumor lump and conversely Mfn-2 upregulation lead to smaller tumor lump. CONCLUSIONS Mfn-2 could suppress expression of PITPNM3 through interaction with transcription factor SP1; Mfn-2 may have anti-tumor activity; SP1 and PITPNM3 may promote tumor development.

BACKGROUND Colorectal cancer (CRC) is one of the most common malignancies worldwide, with high morbidity and mortality rates. The purpose of this study was to identify potential biomarkers in the progression of CRC. MATERIAL AND METHODS Gene and isoform expression datasets of CRC was downloaded from The Cancer Genome Atlas (TCGA). EBSeq of R was used for the normalization of gene and isoform expression, as well as the identification of differential expression genes (DEGs) and isoforms (DEIs) of CRC samples compared with normal samples. The enriched functions of DEGs and DEIs were obtained based on the Database for Annotation, Visualization and Integrated Discovery (DAVID). An independent dataset, GSE38832, was downloaded from the Gene Expression Omnibus (GEO) database for survival analysis of genes with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC. RESULTS A total of 2301 genes and 4241 isoforms were found to be significantly differentially expressed in stage I-IV CRC samples. They are closely associated with muscle or cell system activity. Sixteen genes were screened out with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC. Aberrant CBX8 and CD96 expressions were found to be significantly associated with CRC survival. CONCLUSIONS Through combined analysis of gene and isoform expression profiles, we identified several potential biomarkers that may play an important role in the development of CRC and could be helpful in its early diagnosis and treatment.

BACKGROUND Long non-coding RNA differentiation antagonizing nonprotein coding RNA (lncRNA DANCR) has been reported to act as an oncogene in various human cancers. The role of DANCR in development of pancreatic cancer (PC) is unknown. The aim of our research was to investigate the biological role of DANCR in PC. MATERIAL AND METHODS Expressions of DANCR, miR-214-5p, and E2F2 mRNA in PC tissues and cell lines were examined by qRT-PCR. Western blotting was carried out for detection of E2F2 protein expression in PC cells. Transwell assays were used to examine the metastatic ability of PC cells, while CCK-8 and colony formation assay were applied to evaluate cell proliferation. The effects of DANCR on PC cells were assessed by knockdown in vitro and in vivo. The regulatory mechanism of competitive endogenous RNAs were obtained from bioinformatics prediction and luciferase reporter assay. RESULTS DANCR was markedly upregulated in clinical tissues and cell lines of PC. High DANCR expression exhibited a significant correlation with poor prognosis. DANCR knockdown inhibited growth and metastasis of PC cells. Furthermore, DANCR acted as sponge to regulate miR-214-5p, and miR-214-5p inhibitor reversed the effects of DANCR knockdown on PC cells. Moreover, DANCR positively modulated E2F2 expression through miR-214-5p in PC cells. CONCLUSIONS Collectively, our findings demonstrated that lncRNA DANCR/miR-214-5p/E2F2 axis acts as an oncogene in PC development, which might provide a potential target for PC therapy.

BACKGROUND The purpose of this study was to determine whether cofilin-2 could serve as a protein marker for predicting radiotherapy response and as a potential therapeutic target in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS Cofilin-2 protein levels in serum and tissue samples from patients with NPC were assessed by sandwich ELISA and IHC. In vitro, cofilin-2 levels in CNE-2R cells were significantly higher than those of CNE-2 cells. Meanwhile, CNE-2R cells were silenced for cofilin-2 to obtain a stable cofilin-2-RNAi-LV3 cell line. Then, cell proliferation, radiosensitivity, invasion and migration abilities, cell cycle, and apoptosis were evaluated by Cell Counting Kit 8 assay (CCK-8), flow cytometry (FCM), clone formation assay, and in vitro. RESULTS The secreted levels of the cofilin-2 protein in radioresistant NPC patients were significantly higher than those of radiosensitive cases. After cofilin-2 knockdown in nasopharyngeal carcinoma CNE-2R cells, proliferation was decreased, while apoptosis and radiosensitivity were enhanced; cell cycle distribution was altered, and the transplanted tumors in nude mice grew significantly less. CONCLUSIONS Overall, our findings suggest that cofilin-2 acts as a marker for predicting radiotherapy response and is a potential therapeutic target in nasopharyngeal carcinoma.

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) has gained popularity as a minimally invasive surgery for treating lumbar disc herniation. However, there is limited research focusing on the reoperation rate and its associated factors. This study aims to investigate the rate of reoperation and identify the causes and risk factors for reoperation after PELD. MATERIAL AND METHODS We conducted a retrospective analysis of patients who underwent PELD (interlaminar and transforaminal approaches) at our hospital from November 2016 to May 2020. A matched case-control design was employed to identify relevant risk factors for reoperation, with a matching ratio of 1:3. Clinical characteristics and radiological parameters were compared, and univariate analysis was performed using independent samples t-test and chi-squared test. RESULTS Among the 435 patients included in the study, the reoperation rate for those with a minimum 2-year follow-up was 6.2% (27/435). The causes of reoperation and their respective rates were as follows: recurrence of lumbar disc herniation (3.2%, 14/435), incomplete decompression (1.8%, 8/435), persistent low back pain (0.7%, 3/435), and postoperative infection (0.5%, 2/435). Univariate analysis revealed that age (P=0.015), Pfirrmann grade IV-V (P=0.017), and lack of active straight leg raise exercises (P=0.026) were significantly associated with reoperation. Multiple logistic regression analysis indicated that age (P=0.001), Pfirrmann grade IV-V (P=0.033), and lack of active straight leg raise exercises postoperatively (P=0.003) were independent risk factors for reoperation after PELD. CONCLUSIONS The primary cause of reoperation in lumbar disc herniation patients after PELD was recurrence of the herniation. Additionally, severe disc degeneration, older age, and lack of active straight leg raise exercises were identified as significant risk factors associated with an increased reoperation rate.

BACKGROUND We aimed to investigate the prevalence trends and explore the influencing factors of post-stroke depression based on the National Health and Nutrition Examination Survey (NHANES) database, including data from 2005 to 2018. MATERIAL AND METHODS A total of 1298 patients with stroke were included in this study. Multivariate logistic regression analysis was performed to select influencing factors. Subgroup analysis was conducted based on different populations. The odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS The prevalence of post-stroke depression was 16.35% in 2005 and 23.29% in 2018, and presented a linear upward trend by year (F=195.00, P<0.001) from 2005 to 2018. Age (≥60 years vs <60 years; OR=0.40; 95% CI, 0.30-0.54), sex (female vs male; OR=1.37; 95% CI, 1.02-1.84), education level (junior middle school or below vs college or above; OR=0.64; 95% CI, 0.46-0.90), annual household income (≥$20,000 vs <$20,000; OR=0.60; 95% CI, 0.45-0.80), and sleep disorders (sleep disorders vs no sleep disorders; OR=4.07; 95% CI, 3.01-5.49) were associated with the risk of post-stroke depression. The age-based subgroup analysis showed that sex and education level were not influencing factors of post-stroke depression in patients ≥60 years, and education level was not related to the risk of post-stroke depression among men in the sex-based analysis. CONCLUSIONS Stroke patients with sleep disorders, age <60 years, and female sex may have an increased risk of post-stroke depression.