Electroencephalography Microstate Class D is a Brain Marker of Subjective Sleep Quality for College Students with High Habitual Sleep Efficiency.

Subjective sleep quality is an individual's subjective sleep feeling, and its effective evaluation is the premise of improving sleep quality. However, people with autism or mental disorders often experience difficulties in verbally expressing their subjective sleep quality. To solve the above problem, this study provides a non-verbal and convenient brain feature to assess subjective sleep quality. Reportedly, microstates are often used to characterize the patterns of functional brain activity in humans. The occurrence frequency of microstate class D is an important feature in the insomnia population. We therefore hypothesize that the occurrence frequency of microstate class D is a physiological indicator of subjective sleep quality. To test this hypothesis, we recruited college students from China as participants [N = 61, mean age = 20.84 years]. The Chinese version of the Pittsburgh Sleep Quality Index scale was used to measure subjective sleep quality and habitual sleep efficiency, and the state characteristics of the brain at this time were assessed using closed eyes resting-state brain microstate class D. The occurrence frequency of EEG microstate class D was positively associated with subjective sleep quality (r = 0.32, p < 0.05). Further analysis of the moderating effect showed that the occurrence frequency of microstate class D was significantly and positively correlated with subjective sleep quality in the high habitual sleep efficiency group. However, the relationship was not significant in the low sleep efficiency group (ßsimple = 0.63, p < 0.001). This study shows that the occurrence frequency of microstate class D is a physiological indicator of assessing subjective sleep quality levels in the high sleep efficiency group. This study provides brain features for assessing subjective sleep quality of people with autism and mental disorders who cannot effectively describe their subjective feelings.

[Retracted] Inhibition of δ­opioid receptors induces brain glioma cell apoptosis through the mitochondrial and protein kinase C pathways.

[This retracts the article DOI: 10.3892/ol.2013.1546.].

Atp8a1 deletion increases the proliferative activity of hematopoietic stem cells by impairing PTEN function.

PURPOSE: The eukaryotic cell plasma membrane contains several asymmetrically distributed phospholipids, which is maintained by the P4-ATPase flippase complex. Herein, we demonstrated the biological effects and mechanisms of asymmetrical loss in hematopoietic stem cells (HSCs). METHODS: An Atp8a1 knockout mouse model was employed, from which the HSC (long-term HSCs and short-term HSCs) population was analyzed to assess their abundance and function. Additionally, competitive bone marrow transplantation and 5-FU stress assays were performed. RNA sequencing was performed on Hematopoietic Stem and Progenitor Cells, and DNA damage was assayed using immunofluorescence staining and comet electrophoresis. The protein abundance for members of key signaling pathways was confirmed using western blotting. RESULTS: Atp8a1 deletion resulted in slight hyperleukocytosis, associated with the high proliferation of HSCs and BCR/ABL1 transformed leukemia stem cells (LSCs). Atp8a1 deletion increased the repopulation capability of HSCs with a competitive advantage in reconstitution assay. HSCs without Atp8a1 were more sensitive to 5-FU-induced apoptosis. Moreover, Atp8a1 deletion prevented HSC DNA damage and facilitated DNA repair processes. Genes involved in PI3K-AKT-mTORC1, DNA repair, and AP-1 complex signaling were enriched and elevated in HSCs with Atp8a1 deletion. Furthermore, Atp8a1 deletion caused decreased PTEN protein levels, resulting in the activation of PI3K-AKT-mTORC1 signaling, further increasing the activity of JNK/AP-1 signaling and YAP1 phosphorylation. CONCLUSION: We identified the role of Atp8a1 on hematopoiesis and HSCs. Atp8a1 deletion resulted in the loss of phosphatidylserine asymmetry and intracellular signal transduction chaos.

[Clinical study of double plate system in the treatment of complex proximal humeral fractures in the elderly].

OBJECTIVE: To explore the clinical outcomes of anteromedial combined with lateral locking plate for complex proximal humeral fractures in the eldery. METHODS: From June 2018 to October 2020, 30 patients who underwent surgical treatment for Neer grade 3 to 4 proximal humeral fractures, including 8 males and 22 females, aged from 51 to 78 years old with an average of (61.5±7.5) years old. Of them, 15 patients had fractures fixed with anteromedial combined with lateral locking plate(ALLP group), whereas 15 received internal fixation with proximal humerus locking plate only(PHLP group). The clinical data, simple shoulder test (SST), humeral head height loss, varus angle and shoulder range of motion were compared between the two groups. RESULTS: All fractures were healed. The follow-up time ranged from 12 to 24 months, with an average of(14.3±2.9) months. The operation time of ALLP group was longer than that of PHLP group (P<0.05). There was no significant difference in intraoperative blood loss between the two groups (P>0.05). There was no significant difference in SST score between the two groups at 1, 3 and 12 months after operation (P>0.05). In terms of radiographic measurement, there was no significant difference in humeral head height loss and varus angle between the two groups at 1 and 3 months after operation (P>0.05). At 12 months after operation, the height loss and varus angle of humeral head in ALLP group were lower than those in PHLP group (P<0.05). In shoulder range of motion, the range of forward elevation in ALLP group was larger than that in PHLP group 1 year after operation(P<0.05). There was no significant difference in external rotation between the two groups. CONCLUSION: Anteromedial combined with lateral locking plate in the treatment of complex proximal humeral fractures in the elderly can increase the stability of the medial column and obtain a good fracture prognosis. But there are also disadvantages such as longer operation time, so it should be individualized according to the fracture type of the patient.

Low-dose cyclophosphamide combined with IL-2 inhibits tumor growth by decreasing regulatory T cells and increasing CD8+ T cells and natural killer cells in mice.

Interleukin-2 (IL-2) benefits some cancer patients by promoting the proliferation of cytotoxic effector T cells, but this process is limited by the expansion of regulatory T cells (Tregs). Low-dose cyclophosphamide (CTX) can inhibit the number and function of Tregs. We treated carcinoma-bearing mice with Vehicle, CTX, IL-2 and CTX + IL-2 to investigate the effects of low-dose CTX combined with IL-2 in antitumor treatment. In comparison to monotherapy, CTX + IL-2 significantly limited tumor growth, via tumor cell proliferation inhibition and increased apoptosis. The infiltration of CD8+ T cells in tumor tissues was significantly increased in the CTX + IL-2 group. CTX + IL-2 safely increased CD8+ T and natural killer cells in the spleen, lymph nodes and peripheral blood, and CTX attenuated the increase in Tregs induced by IL-2 in the spleen.

Exploring the Relationship Between Trait Mindfulness and Interpersonal Sensitivity for Chinese College Students: The Mediating Role of Negative Emotions and Moderating Role of Effectiveness/Authenticity.

Background: Interpersonal sensitivity is a prominent mental health problem facing college students today. Trait mindfulness is a potential positive factor that may influence interpersonal relationships. However, the precise relationship between trait mindfulness and interpersonal sensitivity remains elusive, which limits the optimization and further application of mindfulness-based intervention schemes targeting interpersonal sensitivity. This study aimed to explore (a) whether negative emotions mediate the relationship between trait mindfulness and interpersonal sensitivity and (b) whether the relationship among trait mindfulness, negative emotions, and interpersonal sensitivity is moderated by effectiveness/authenticity. We hypothesize that (a) negative emotions mediate the relationship between trait mindfulness and interpersonal sensitivity, and (b) effectiveness/authenticity moderates the indirect association between trait mindfulness and interpersonal sensitivity through negative emotions. Methods: One thousand four hundred nineteen Chinese college students (1,023 females, 396 males), aged from 17 to 23 (SD = 0.86, mean = 18.38), participated in this study. Their trait mindfulness, negative emotions, the effectiveness/authenticity, and interpersonal sensitivity were measured using well-validated self-report questionnaires. Results: Correlational analyses indicated that both trait mindfulness and effectiveness/authenticity were significantly and negatively associated with interpersonal sensitivity. Mediation analyses uncovered a partial mediating role of negative emotions in the relationship between trait mindfulness and interpersonal sensitivity. Moderated mediation analyses showed that in college students with high effectiveness/authenticity, the relationship between trait mindfulness and negative emotions was stronger, whereas the relationship between negative emotions and interpersonal sensitivity was weaker. Conclusion: Negative emotion is a mediator of the relationship between trait mindfulness and interpersonal sensitivity, which in turn is moderated by effectiveness/authenticity. These findings suggest a potential mechanism through which trait mindfulness influences interpersonal sensitivity. Mindfulness-based interventions have the potential to decrease interpersonal sensitivity and offer a basis for predicting individual differences in response to mindfulness-based interventions among individuals.

Relationship Between Trait Mindfulness and Sleep Quality in College Students: A Conditional Process Model.

Sleep quality can affect the physical and mental health, as well as the personal development of college students. Mindfulness practices are known to ameliorate sleep disorder and improve sleep quality. Trait mindfulness, an innate capacity often enhanced by mindfulness training, has been shown to relate to better sleep quality and different aspects of psychological well-being. However, how individual difference factors such as trait mindfulness relate to sleep quality remains largely unclear, which limits the optimization and further application of mindfulness-based intervention schemes targeting the improvement of sleep quality. In this study, we aimed to investigate how negative emotions and neuroticism may influence the relationship between trait mindfulness and sleep quality. A conditional process model was built to examine these relationships in 1,423 Chinese young adults. Specifically, the conditional process model was constructed with trait mindfulness as the independent variable, sleep quality as the dependent variable, negative emotions as the mediating variable, and neuroticism as the moderating variable. Our results showed that negative emotions mediated the link between mindfulness and sleep quality and that neuroticism had a moderating effect on the relationship between mindfulness and sleep quality. Together, these findings suggested a potential mechanism of how trait mindfulness influences sleep quality, provided a therapeutic target for which mindfulness-based interventions may act upon to improve sleep quality, and offered a basis for prediction of different intervention effects among individuals.

miR-424-5p Regulates Hepatoma Cell Proliferation and Apoptosis.

OBJECTIVE: Yes-associated protein (Yes-associated protein 1 [YAP1]) is an important oncogene that is related to the pathogenesis and progression of liver cancer. It was found that miR-424-5p expression was significantly decreased in liver cancer tissues, revealing its anticancer effect. Bioinformatic analysis demonstrated the targeted relationship between miR-424-5p and the 3' untranslated region of YAP1. This study investigated the role of miR-424-5p in regulating YAP1 expression and affecting hepatoma cell proliferation and apoptosis. MATERIALS AND METHODS: Tumors and normal liver tissues adjacent to tumors were collected from patients to detect the expression of miR-424-5p and YAP1. A dual-luciferase reporter gene assay was adopted to explore the targeted regulation between miR-424-5p and YAP1. Liver cancer HCCLM3 and MHCC97-L cells and normal liver HL-7702 cells were cultured in vitro to compare expression levels of miR-424-5p and YAP1. HCCLM3 and MHCC97-L cells were divided into the miR-NC group and miR-424-5p mimic group. Cell apoptosis was detected by flow cytometry. Cell proliferation was determined by EdU staining. RESULTS: Compared with normal liver tissue, miR-424-5p expression was significantly decreased, while YAP1 mRNA and protein levels were obviously upregulated in liver cancer tissues, which were related to the clinical stage. A negative correlation was found between miR-424-5p and YAP1 mRNA levels in liver cancer tissues. Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-424-5p and YAP1. miR-424-5p expression in HCCLM3 and MHCC97-L cells decreased compared with L20 cells, which correlated with malignancy. YAP1 level in HCCLM3 and MHCC97-L cells was significantly enhanced, which correlated with malignancy. miR-424-5p mimic transfection significantly downregulated YAP1 expression in HCCLM3 and MHCC97-L cells, resulting in enhanced apoptosis and attenuated cell proliferation. CONCLUSIONS: Decreased miR-424-5p expression and increased YAP1 expression are found in patients with liver cancer. Increased miR-424-5p can inhibit YAP1 expression, attenuate hepatoma cell proliferation, and induce cell apoptosis.

[Identification and preparation of a glycol-protein fraction AN from tea extracts and its in vivo and in vitro anti-hyperglycosemia activity].

The present study compared active ingredients of tea from different sources to select tea type and the fraction of tea extracts for the highest anti-hyperglycemic activity, and to verify anti-hyperglycemic activity of the selected tea extract. Tea extracts were separated and enriched by molecular weight using ultra-filtration technology. The extracts were first screened by α-glucosidase inhibition assay, followed by using a rat inverted intestine sac system to measure the effect on glucose transport. Both alloxan-induced diabetic rat model and high-fat diet combined with streptozotocin-induced rat diabetes mellitus model were used to study the effects of active components on blood glucose, body weight, insulin resistance. The experimental results showed that the different kinds of tea extracts had different inhibitory effects on α-glucosidase, and the inhibitory effect of tea extract E on α-glucosidase was stronger. The effects of different components of tea extract E also varied greatly, of which Fraction AN protein had stronger inhibitory effect on α-glucosidase than other fragments, and Fraction AN protein had a strong inhibitory effect on glucose transport, reduced blood sugar and normalized insulin secretion in diabetic rats. The results suggest that a glycol-protein fraction(AN) from the extracts might be responsible for the anti-hyperglycemic activity of tea polysaccharides. The AN glycol-protein fraction has strong inhibitory effects on both α-glucosidase activity and glucose transport by the small intestine. It also reduced blood glucose level and normalized insulin secretion in diabetic rats, and has a protective effect on diabetic rats.

Silencing of FRAT1 by siRNA inhibits the proliferation of SGC7901 human gastric adenocarcinoma cells.

Frequently rearranged in advanced T cell lymphomas-1 (FRAT1) positively regulates the Wnt/ß-catenin signaling pathway by inhibiting glycogen synthase kinase-3 mediated phosphorylation of ß-catenin. FRAT1 is a proto-oncogene, implicated in tumorigenesis. The present study aimed to investigate the effects of FRAT1 silencing on the proliferation and apoptosis of SGC7901 cells. FRAT1 in SGC7901 cells was silenced by RNA interference. Reverse transcription-quantitative polymerase chain reaction was used for the analysis of FRAT1 mRNA and western blotting was used to evaluate FRAT1 and ß-catenin protein levels. Cell proliferation was analyzed by the MTT assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression of FRAT1 mRNA, FRAT1 and ß-catenin protein in FRAT1-silenced SGC7901 cells were reduced significantly compared to untreated cells. The proliferation of FRAT1 silenced SGC7901 cells decreased significantly The FRAT1 silenced SGC7901 cells were arrested at G0/G1 stage to a greater degree, and apoptosis was increased. In summary, silencing of FRAT1 inhibits SGC7901 cell proliferation and induces apoptosis, possible through a reduction in ß-catenin expression. FRAT1 may serve as a prognostic biomarker and therapeutic target for gastric cancer.

Synergistic antitumor effect of puerarin combined with 5-fluorouracil on gastric carcinoma.

Combination chemotherapy is a crucial method in the treatment of gastric cancer. The aim of the present study was to investigate the inhibitory effects of puerarin and 5­fluorouracil (5­FU) on BGC­823 gastric cancer cells in vitro and in vivo. The in vitro growth inhibition of puerarin or 5­FU alone or combined on BGC­823 cells was determined using a cell counting kit 8 (CCK­8) on living cells. Apoptotic morphological features and proteins expression levels were detected by Hoechst 33258 staining, an Annexin V/propidium iodide apoptosis kit and western blot analysis, respectively. Tumor xenografts were established in nude mice and the inhibitory effects and side effects were detected. Results of the CCK­8, Hoechst 33258 staining and flow cytometry revealed that the combined treatment was more effective than the separate treatments. The tumor volume was 90.65% of that of the controls and the mean tumor weight was only 0.125 g at the end of the experiment in the combination group compared with the control group (0.822 g). In addition, it was determined that liver and renal toxicity did not increase in combined treatment. These findings showed that puerarin and 5­FU produced a significant synergic effect on gastric cancer cells, while there was no increase in side effects.

Synergistic effect of puerarin and 5-fluorouracil on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common types of human malignancy worldwide, which is becoming increasingly resistant to traditional drug treatments. Puerarin combined with 5-fluorouracil (5-FU) may be a useful treatment for liver cancer. The primary aim of the present study was to determine whether combined treatment with 5-FU and puerarin is more effective against the hepatocellular carcinoma (HCC) cell line, SMMC7721, than treatment with 5-FU or puerarin alone. The growth inhibition of SMMC7721 cells by puerarin or 5-FU alone or in combination was determined by the Cell Counting Kit-8 assay, in vitro. Apoptotic morphological features and the percentage of apoptotic cells were detected using Hoechst 33258 staining and an Annexin V/PI apoptosis kit, respectively. In addition, a tumor xenograft model was established in nude mice using SMMC7721 cells. Puerarin and 5-FU alone or in combination were injected into the mice, and the inhibition of tumor growth was evaluated by monitoring tumor volume and weight. Treatment with 6,400 or 640 µM 5-FU resulted in growth inhibition of 95.56±0.81 and 75.91±3.54%, respectively. The combination index values were <1 when the fraction of affected cells was between 0.2555 and 0.7420. Furthermore, the percentage of apoptotic cells was markedly increased in the combined treatment group when compared with that of the individual treatment groups, in vitro and in vivo. Individual treatment with puerarin resulted in a tumor volume inhibition rate (IR) of 70.58% and a tumor weight IR of 46.20%. Treatment with 5-FU was found to decrease the tumor volume by 76.26% and tumor weight by 49.86%. In the combined treatment group, the tumor volume and weight IRs were 93.11 and 75.21%, respectively. A marked increase in the inhibition of tumor growth and the number of apoptotic cells in response to combined treatment with puerarin and 5-FU was identified with no observed liver or renal toxicity. These results suggest that puerarin and 5-FU exhibit a synergistic treatment effect on the HCC SMMC7721 cell line.

Synergistic effects of puerarin combined with 5-fluorouracil on esophageal cancer.

Puerarin is an isoflavone derived from kudzu roots with a wide range of biological and medicinal properties. The aim of the present study was to investigate the inhibitive effects of puerarin combined with 5­fluorouracil (5­FU) on Eca­109 esophageal cancer cells in vitro and in vivo. Inhibitive effects of the treatments on Eca­109 cells were detected by cell counting kit­8, Hoechst 33258 staining and flow cytometry. A tumor xenograft model was established in nude mice. Puerarin and 5­FU, administered either in combination or individually, were injected into mice and the inhibitive effects along with any side effects were observed. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Puerarin and 5­FU, administered as combined treatment or individual drugs, significantly inhibited proliferation and induced marked apoptosis. The mean growth inhibition rate (± standard deviation) reached 87.27±5.37% and the apoptotic rate at 48 h reached 36.18±1.24% in the combined treatment group. The percentages of apoptotic cells induced by puerarin and 5­FU (combined or alone) were significantly higher than those of the control group (P<0.05). Puerarin or 5­FU alone significantly inhibited the growth of xenograft tumors in comparison to the control group (P<0.05), with inhibition rates of 76.93 and 72.21%, respectively. The drugs combined exhibited a significantly greater effect than either drug alone (P<0.05), with the tumor inhibition rate reaching 89.06%. During the course of chemotherapy, no evident side effects were observed. The results suggested that the combined inhibitive effects of puerarin and 5­FU were greater than the effects of the agents used individually. In addition, puerarin combined with 5­FU exhibited synergistic effects at lower concentrations and promoted apoptosis, but did not increase the side effects of chemotherapy, which indicated that puerarin may be a safe and effective chemosensitive agent in the treatment of human esophageal cancer.

Suppressive effect of sinomenine combined with 5-fluorouracil on colon carcinoma cell growth.

It is reported that sinomenine (SIN) and 5-fluorouracil (5-FU) both are effective for colon cancer, but their cooperative suppressive effects and toxicity remain to be clarified in detail. This study aimed to determine suppressive effects and toxicity of sinomenine (SIN) plus 5-fluorouracil (5-FU) on LoVo colon carcinoma cells in vitro and in vivo. CCK-8, Hoechst 33258 staining and an annexin V-FITC/PI apoptosis kit were used to detect suppressive effects. Western blotting was applied to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis. SIN or 5-FU or both were injected into nude mice, and then suppressive effects and side effects were observed. SIN plus 5-FU apparently inhibited the proliferation of LoVo cells and induced apoptosis. Moreover the united effects were stronger than individually (p<0.05). The results of annexin V-FITC /PI staining and Hoechst 33258 staining showed that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone was significantly higher than the control group (p<0.05). Expression of Bax and Bcl-2 was up-regulated and down-regulated respectively. SIN or 5-FU significantly inhibited effects on the volume of tumour xenografts and their combined suppressive effects were stronger (p<0.05). No obvious side effects were observed. It was apparent that the united effects of SIN and 5-FU on the growth of colorectal carcinoma LoVo cells in vitro and in vivo were superior to those using them individually, and it did not markedly increase the side effects of chemotherapy.

Potential effects of Mina53 on tumor growth in human pancreatic cancer.

Myc-induced nuclear antigen (Mina53) is a protein with a molecular weight of 53 kDa expression of which is induced by c-Myc. Increased expression of Mina53 is documented in some human carcinomas. In this study, we found markedly increased Mina53 expression in pancreatic cancer tissue specimens. This expression did not correlate with clinicopathological characteristics, such as sex, age, and presence of distant metastasis. However, there was a statistically significant association with histological differentiation, TNM stage, and lymph node metastases. To study functional role of Mina53, we silenced its expression by siRNA in PANC-1 cells. These cells were arrested in the G2/M phase, and apoptosis rates were increased. In conclusion, increased expression of Mina53 may play an important role in the development of human pancreatic cancer. Mina53 can be used as a marker for pancreatic cancer and may potentially be exploited as a target for treatment of pancreatic cancer.

Cooperative inhibitory effect of sinomenine combined with 5-fluorouracil on esophageal carcinoma.

AIM: To investigate the inhibitory effects of sinomenine (SIN) combined with 5-fluorouracil (5-FU) on esophageal carcinoma in vitro and in vivo. METHODS: Esophageal carcinoma (Eca-109) cells were cultured in DMEM. The single or combined growth inhibition effects of SIN and 5-FU on the Eca-109 cells were examined by measuring the absorbance of CCK-8 dye in living cells. Hoechst 33258 staining and an Annexin V/PI apoptosis kit were used to detect the percentage of cells undergoing apoptosis. Western blotting was used to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis. SIN at 25 mg/kg and 5-FU at 12 mg/kg every 3 d, either combined or alone, was injected into nude mice and tumor growth inhibition and side effects of the drug treatment were observed. RESULTS: SIN and 5-FU, both in combination and individually, significantly inhibited the proliferation of Eca-109 cells and induced obvious apoptosis. Furthermore, the combined effects were greater than those of the individual agents (P < 0.05). Annexin V/PI staining and Hoechst 33258 staining both indicated that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone were significantly different from the control (P < 0.05). The up-regulation of Bax and down-regulation of Bcl-2 showed that the essential mechanism of apoptosis induced by SIN and 5-FU occurs via the mitochondrial pathway. SIN and 5-FU alone significantly inhibited the growth of tumor xenografts in vivo, and the combined inhibition rate was even higher (P < 0.05). During the course of chemotherapy, no obvious side effects were observed in the liver or kidneys. CONCLUSION: The combined effects of SIN and 5-FU on esophageal carcinoma were superior to those of the individual compounds, and the drug combination did not increase the side effects of chemotherapy.

Proton pump inhibitor for non-erosive reflux disease: a meta-analysis.

AIM: To evaluate the efficacy, safety and influential factors of proton pump inhibitor (PPI) treatment for non-erosive reflux disease (NERD). METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Library were searched up to April 2013 to identify eligible randomized controlled trials (RCTs) that probed into the efficacy, safety and influential factors of PPI treatment for NERD. The rates of symptomatic relief and adverse events were measured as the outcomes. After RCT selection, assessment and data collection, the pooled RRs and 95%CI were calculated. This meta-analysis was performed using the Stata 12.0 software (Stata Corporation, College Station, Texas, United States). The level of evidence was estimated by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Seventeen RCTs including 6072 patients met the inclusion criteria. The results of the meta-analysis showed that PPI treatment was significantly superior to H2 receptor antagonists (H2RA) treatment (RR = 1.629, 95%CI: 1.422-1.867, P = 0.000) and placebo (RR = 1.903, 95%CI: 1.573-2.302, P = 0.000) for the symptomatic relief of NERD. However, there were no obvious differences between PPI and H2RA (RR = 0.928, 95%CI: 0.776-1.110, P = 0.414) or PPI and the placebo (RR = 1.000, 95%CI: 0.896-1.116, P = 0.997) regarding the rate of adverse events. The overall rate of symptomatic relief of PPI against NERD was 51.4% (95%CI: 0.433-0.595, P = 0.000), and relief was influenced by hiatal hernia (P = 0.030). The adverse rate of PPI against NERD was 21.0% (95%CI: 0.152-0.208, P = 0.000), and was affected by hiatal hernia (P = 0.081) and drinking (P = 0.053). CONCLUSION: PPI overmatched H2RA on symptomatic relief rate but not on adverse rate for NERD. Its relief rate and adverse rate were influenced by hiatal hernia and drinking.

Inhibition of δ-opioid receptors induces brain glioma cell apoptosis through the mitochondrial and protein kinase C pathways.

Brain glioma is a malignant tumor with a high incidence rate and poor prognosis that has become a focus of studies of central nervous system diseases. Previous studies have suggested that δ-opioid receptors may affect the proliferation and apoptosis of numerous types of tumor cells. However, to date, their precise mechanism(s) of action have not been elucidated. The present study aimed to investigate the effects of inhibiting δ-opioid receptors in brain glioma cell proliferation and apoptosis and their relevant molecular mechanisms. Various doses of naltrindole were supplied to treat brain glioma cells using the MTT method to assess the proliferation index. Flow cytometry was used to investigate the changes in cell apoptosis and mitochondrial membrane potential. The expression levels of Bax, Bcl-2, Bcl-xL, cytochrome c, caspase-9, caspase-3 and protein kinase C (PKC) were measured using western blotting. Naltrindole was observed to inhibit brain glioma cell proliferation and promote apoptosis in a dose- and time-dependent manner. Furthermore, the addition of naltrindole lead to changes in the brain glioma cell membrane potential and regulated Bax translocation to the mitochondrial membrane, consequently promoting the release of cytochrome c into the cytoplasm, followed by the activation of caspase-9 and -3, which caused cell apoptosis. In addition, naltrindole was able to regulate the expression levels of the cellular internal phosphorylated PKC proteins, which are closely associated with the inhibition of cell proliferation. In conclusion, the inhibition of δ-opioid receptors may inhibit brain glioma cell proliferation and lead to apoptosis, which is closely associated with the mitochondrial and PKC pathways.

Sinomenine sensitizes gastric cancer cells to 5-fluorouracil in vitro and in vivo.

Sinomenine (SIN) has been reported to exert antitumor effects in various types of human cancer. The present study aimed to investigate the effects of SIN on gastric cancer and to briefly address its mechanism of action. In this study, the single and combined effects of SIN with 5-fluorouracil (5-FU) on human gastric cancer cells were assessed using an MTT assay, a combination index method and an MKN-28 xenograft mice model. Levels of apoptosis were determined using Hoechst 33258 staining and flow cytometry. Expression levels of certain apoptosis-related proteins were examined by western blotting. mRNA levels of the 5-FU-associated gene, thymidylate synthase (TS), were measured by RT-PCR. The results showed that SIN enhances 5-FU-mediated cellular growth inhibition and apoptosis in gastric cancer cells, reduces TS mRNA accumulation and activates the mitochondrial apoptotic pathway. The same chemotherapy sensitizer effect of SIN was confirmed in vivo. SIN is a promising chemotherapy sensitizer for 5-FU. Our results indicate that this may be a potential combination chemotherapeutic strategy for gastric cancer.

Tumor suppressor function of ezrin-radixin-moesin-binding phosphoprotein-50 through ß-catenin/E-cadherin pathway in human hepatocellular cancer.

AIM: To determine the effect and molecular mechanism of ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) in hepatocellular carcinoma (HCC). METHODS: Three human HCC cell lines, i.e., SM-MC7721, HepG2 and Hep3B, were used. We transfected the Pbk-CMV-HA-EBP50 plasmid into SMMC7721 cells with Lipofectamine 2000 to overexpress EBP50. Western blotting were performed to determine the effects of the plasmid on EBP50 expression and to detect the expression of ß-catenin and E-cadherin before and after the transfection of the plasmid into SMMC7721 cells. In vitro cell proliferation was assessed with a Cell Counting Kit-8 (CCK-8) assay. Cell cycle distribution was assessed with flow cytometry. Invasion and migration ability of before and after the transfection were determined with a transwell assay. Cell apoptosis was demonstrated with Annexin V-FITC. The effect of EBP50 overexpressing on tumor growth in vivo was performed with a xenograft tumor model in nude mice. RESULTS: The transfection efficiency was confirmed with Western blotting (1.36 ± 0.07 vs 0.81 ± 0.09, P < 0.01). The CCK8 assay demonstrated that the growth of cells overexpressing EBP50 was significantly lower than control cells (P < 0.01). Cell cycle distribution showed there was a G0/G1 cell cycle arrest in cells overexpressing EBP50 (61.3% ± 3.1% vs 54.0% ± 2.4%, P < 0.05). The transwell assay showed that cell invasion and migration were significantly inhibited in cells overexpressing EBP50 compared with control cells (5.8 ± 0.8 vs 21.6 ± 1.3, P < 0.01). Annexin V-FITC revealed that apoptosis was significantly increased in cells overexpressing EBP50 compared with control cells (14.8% ± 2.7% vs 3.4% ± 1.3%, P < 0.05). The expression of ß-catenin was downregulated and E-cadherin was upregulated in cells overexpressing EBP50 compared with control cells (0.28 ± 0.07 vs 0.56 ± 0.12, P < 0.05; 0.55 ± 0.08 vs 0.39 ± 0.07, P < 0.05). In vivo tumor growth assay confirmed that up-regulation of EBP50 could obviously slow the growth of HCC derived from SMMC7721 cells (28.9 ± 7.2 vs 70.1 ± 7.2, P < 0.01). CONCLUSION: The overexpression of EBP50 could inhibit the growth of SMMC7721 cells and promote apoptosis by modulating ß-catenin, E-cadherin. EBP50 may serve as a potential therapeutic target in HCC.