To study the central pharmacological effect of the water and chloroform-extract compounds from C. chinese in mice.The independent activity test and the hypnotic synergism test by sub-threshold hypnotic dosage of pentobarbital were employed to evaluate the central pharmacological effect of the extract-compounds, and the minimal neurotoxicity was evaluated by the rotorod test.the extract-compounds exhibited significant dose-related inhibition effect of the spontaneous motor activity in mice after intraperitoneal administration. And the two extract-compounds promoted the hypnotic effect by sub-threshold hypnotic dosage administration of pentobarbital, and produced ED50 value of 2.36 g kg (-1) and 0.75 g kg(-1), respectively. Also, both extract-compounds showed no neurotoxicity in the experiment.The extract compounds from C. chinese showed inhibitional effect on CNS.
Accumulating evidence has demonstrated the pivotal role of long noncoding RNAs (lncRNAs) in competing endogenous RNA (ceRNA) networks for predicting survival and evaluating prognosis in cancer patients. However, the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains unclear, and prognostic biomarkers for HNSCC are still lacking.A total of 546 RNA sequencing profiles of HNSCC patients with clinical outcome data were obtained from the Cancer Genome Atlas (TCGA) database, providing a large sample of RNA sequencing data. From these, 71 Long noncoding RNAs lncRNAs, 8 microRNAs (miRNAs), and 16 messenger RNAs (mRNAs) were identified to construct a HNSCC-specific ceRNA network (fold change >2, P < 0.05). Univariate and multivariate Cox proportional regression models were used to assess independent indicators of prognosis. Then the expression of lncRNAs harboring prognostic value was validated in human HNSCC cell lines and tumor samples from our cohort and another two datasets from GEO (Gene Expression Omnibus) databases.As a result, a 3-mRNA signature and 6-lncRNA signature were identified. The six-lncRNA signature exhibited the highest prognostic value. Notably, in the six lncRNAs, HOTTIP showed the greatest prognostic value and was significantly correlated with clinical stage and histological grade of HNSCC patients. Furthermore, it was proved that HOTTIP was upregulated in HNSCC cell lines and cancerous tissues compared with corresponding normal cell lines and normal tissues. Functional assessment analysis revealed that HOTTIP might play a key role in the oncogenesis and progression of HNSCC.The present study deepened our understanding of the ceRNA-related regulatory mechanism in the pathogenesis of HNSCC and identified candidate prognostic biomarkers for clinical outcome prediction in HNSCC. HOTTIP may function as a key candidate biomarker in HNSCC and serve as a prognostic marker for HNSCC patients.
Oral squamous cell carcinoma (OSCC) is a common type of malignant tumor worldwide. Claudin-7 (CLDN7) has been reported to exhibit low expression in tissues of patients with OSCC; however, the underlying mechanisms of CLDN7 remain to be elucidated. The present study aimed to investigate the effects of CLDN7 on the progression of OSCC and identify its potential regulatory mechanisms. CLDN7 and interferon regulatory factor-2 (IRF2) expression in several OSCC cell lines were detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Following CLDN7 overexpression, cell proliferation, invasion and migration were determined using a Cell Counting Kit-8, colony formation, Transwell and wound healing assays, respectively. The potential binding sites of IRF2 on the CLDN7 promoter were analyzed using the PROMO and JASPAR databases, which were verified via chromatin immunoprecipitation and RT-qPCR assays. The effects of IRF2 and CLDN7 on the biological functions of OSCC cells were examined by transfection with short hairpin RNA (shRNA) against CLDN7 (sh-CLDN7), or IRF2 and CLDN7 overexpression plasmids. The results revealed that CLDN7 and IRF2 expression were significantly downregulated in OSCC cell lines, and CLDN7 overexpression reduced the proliferation, invasion and migration of OSCC cells. Additionally, IRF2 was confirmed to combine with the CLDN7 promoter. CLDN7 silencing reversed the inhibitory effects of IRF2 overexpression on the proliferation, invasion and migration of OSCC cells. Taken together, these findings demonstrated that IRF2-induced CLDN7 upregulation suppressed the proliferation, invasion and migration of OSCC cells, suggesting the possibility of CLDN7 and IRF2 as novel targets for the treatment of OSCC.
The present study aimed to examine the expression of interleukin-6 receptor (IL-6R) mRNA and protein in pulp tissues, blood and saliva from patients with pulpitis. It also investigated the association between IL-6R and microRNA (miR)-30b, as well as their effects on pulpitis. A total of 28 patients with pulpitis were recruited into the experimental group and 16 subjects with no pulpitis who also underwent tooth extraction were recruited into the control group. Pulp tissues, plasma and saliva were collected from all participants. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of IL-6R mRNA and miR-30b in all sample types. Western blot analysis was performed to examine the protein expression of IL-6R in pulp tissues, while ELISA was used to determine the contents of IL-6R protein in the plasma and saliva samples. A dual luciferase reporter assay was performed to verify the interactions between IL-6R and miR-30b. The expression of IL-6R mRNA in the pulp tissues, plasma and saliva was significantly increased in patients with pulpitis compared with the control group. Similarly, the IL-6R protein expression in the samples from patients with pulpitis were also significantly increased compared with the control group. Conversely, the expression of miR-30b was significantly reduced in the samples from patients with pulpitis compared with the control group. The dual luciferase reporter assay revealed that miR-30b may bind with the 3'-untranslated seed region of IL-6R mRNA to regulate its expression. The present study demonstrated that the upregulated expression of IL-6R in pulp tissues, plasma and saliva from patients with pulpitis was associated with the downregulation of miR-30b expression. In addition, miR-30b may affect the progression of pulpitis via IL-6R and may be a potential genetic marker for the diagnosis of pulpitis.
Oral carcinoma (OC) is one of the most common malignant tumors in the Chinese population, and cancer metastasis is one of the leading causes of death in OC patients.This study is designed to investigate the correlation between miR-10a-5p and OC cell metastasis.MiR-10a-5p expression was detected by real-time fluorescence quantitative polymerase chain reaction in 93 pairs of OC and adjacent normal tissues, while protein expression was detected using western blot.Transwell assay was performed to assess the metastatic ability of OC cells.In this study, we found that miR-10a-5p expression was low in OC tissues, and the expression level decreased with the increase of histological grade and tumor node metastasis (TNM) stage.Compared with OC tissues without lymph node metastasis, miR-10a-5p was expressed less in OC tissues with lymph node metastasis.OC patients with low miR-10a-5p expression have a shorter 5-year overall survival after surgery.The luciferase gene reporter system confirmed that miR-10a-5p targeted inhibition of PIK3CA expression in OC cells.In addition, miR-10a-5p negatively regulated PI3K, P-AKT/AKT and P-mTOR/mTOR expression and inhibited the invasion and migration of SAS cells in vitro.All in all, the present study indicated that miR-10a-5p was lowly expressed as a tumor suppressor gene in OC tissues and suppressed the metastasis of OC cells in vitro by targeting PIK3CA via the PI3K/AKT/mTOR pathway.
Adult rats chronic unpredictable stress model of depression (CUS) was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract (licorice flavonoids, LF) from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids (300 mg x kg(-1), 100 mg x kg(-1) and 30 mg x kg(-1)) for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5'-Bromo-2'-deoxyuridine (BrdU) labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids (300 mg x kg(-1)) can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone (SGZ) of dentate gyrus (DG) region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti-depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.
The stark discrepancy in the prognosis of epilepsy is closely related to brain damage features and underlying mechanisms, which have not yet been unraveled. In this study, differences in the epileptic brain functional connectivity states were explored through a network-based connectivity analysis between intractable mesial temporal lobe epilepsy (MTLE) patients and benign epilepsy with centrotemporal spikes (BECT). Resting state fMRI imaging data were collected for 14 MTLE patients, 12 BECT patients and 16 healthy controls (HCs). Independent component analysis (ICA) was performed to identify the cortical functional networks. Subcortical nuclei of interest were extracted from the Harvard-Oxford probability atlas. Network-based statistics were used to detect functional connectivity (FC) alterations across intranetworks and internetworks, including the connectivity between cortical networks and subcortical nuclei. Compared with HCs, MTLE patients showed significant lower activity between the connectivity of cortical networks and subcortical nuclei (especially hippocampus) and lower internetwork FC involving the lateral temporal lobe; BECT patients showed normal cortical-subcortical FC with hyperconnectivity between cortical networks. Together, cortical-subcortical hypoconnectivity in MTLE suggested a low efficiency and collaborative network pattern, and this might be relevant to the final decompensatory state and the intractable prognosis. Conversely, cortical-subcortical region with normal connectivity remained well in global cooperativity, and compensatory internetwork hyperconnectivity caused by widespread cortical abnormal discharge, which might account for the self-limited clinical outcome in BECT. Based on the fMRI functional network study, different brain network patterns might provide a better explanation of mechanisms in different types of epilepsy.
The aim of this paper was to learn the effect of long-term intake of Y3+ in drinking water on learning-memory function and growth-development of rats.The rats were fed with water dissolved different level Y3+ (0, 0.534, 53.4, 5340 mg/L) for 6 months, pregnant rate, survive rate, bear rate, variety in weight were calculated, the learning-memory function was observed by step-down test.The results showed that a significantly decrease in electric shock period and an increase in incubation period were observed for the low dose group, in contrast, a significantly increase in electric shock period and error times, and an decreases in weight and survive rate were observed for the high dose group.Y3+ in 0.534 mg/L might improve the function of learning and memory in rats, and that Y3+ in 5340mg/L could restrain both the function of learning-memory functions and growth-development in rats.
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