Increased hypertension risk for the elderly with high blood levels of strontium and lead.

Hypertension has long been recognized as the global health burden. Heavy metal pollution may be one of the environmental risk factors of hypertension. However, the association remains unclear. We studied the levels of aluminum (Al), vanadium (V), manganese (Mn), arsenic (As), selenium (Se), strontium (Sr), barium (Ba), titanium (Ti), lead (Pb) and cobalt (Co) in whole blood, and the relationship between trace element exposure and hypertension in the elderly community-based Chinese population. A total of 1013 participants from the west of Anhui Province in China were consecutively enrolled in this study in 2016. The general sociodemographic characteristics, lifestyles, disease history and physical examination information were collected by face-to-face survey and physical examination. The levels of ten trace elements were determined by inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic regression model was used to assess the association of trace element exposure with the risk of hypertension. Results showed that the odds ratio of hypertension in the highest quartile was 1.811 (95% CI 1.175-2.790, P trend = 0.005) and 1.772 (95% CI 1.121-2.800, P trend = 0.022), respectively, after adjusting for potential confounders, as compared with the lowest quartile of blood Pb and Sr levels.

Limited polymorphism in k13 gene of Plasmodium falciparum and k12 of Plasmodium vivax isolates imported from African and Asian countries between 2014 and 2019 in Hangzhou city, China.

BACKGROUND: Malaria causes major public health problems globally and drug resistance hinders its control and elimination. Molecular markers associated with drug resistance are considered as a beneficial tool to monitor the disease trends, evolution and distribution so as to help improve drug policy. METHODS: We collected 148 Plasmodium falciparum and 20 Plasmodium vivax isolates imported into Hangzhou city, China between 2014 and 2019. k13 gene of P. falciparum and k12 of P. vivax were sequenced. Polymorphisms and prevalence of k13 and k12 were analyzed. RESULTS: Most (98.65%, 146/148) P. falciparum infections were imported from Africa, and half P. vivax cases came from Africa and the other half from Asia. Nucleotide mutation prevalence was 2.03% (3/148) and the proportion of amino acid mutations was 0.68% (1/148). The amino acid mutation, A676S, was observed in an isolate from Nigeria. No mutation of k12 was observed from the parasites from African and Asian countries. CONCLUSIONS: Limited polymorphism in k13 gene of P. falciparum isolates imported from African countries, but no evidence for the polymorphism of k12 in P. vivax samples from African and Asian countries was found. These results provide information for drug policy update in study region.

Swainsonine represses glioma cell proliferation, migration and invasion by reduction of miR-92a expression.

BACKGROUND: Swainsonine is a natural indolizidine alkaloid, its anti-tumor activity has been widely reported in varied cancers. This study aimed to investigate whether Swainsonine exerted anti-tumor impact on glioma cells, likewise uncovered the relative molecular mechanisms. METHODS: After administration with diverse concentrations of Swainsonine, cell growth, migration and invasion in U251 and LN444 cells were appraised by the common-used CCK-8, BrdU, flow cytometry and Transwell assays. MiR-92a mimic, inhibitor and the correlative NC were transfected into U251 and LN444 cells, and assessment of miR-92a expression was by utilizing qRT-PCR. Functions of miR-92a in above-mentioned cell biological processes were analyzed again in Swainsonine-treated cells. The momentous proteins of cell cycle, apoptosis and PI3K/AKT/mTOR pathway were ultimately examined by western blot. RESULTS: Swainsonine significantly hindered cell proliferation through decreasing cell viability, declining the percentage of BrdU cells, down-regulating CyclinD1 and up-regulating p16 expression. Enhancement of percentage of apoptotic cells was presented in Swainsonine-treated cells via activating cleaved-Caspase-3 and cleaved-Caspase-9. Additionally, Swainsonine impeded the abilities of migration and invasion by decreasing MMP-2, MMP-9, Vimentin and E-cadherin. Repression of miR-92a was observed in Swainsonine-treated cells, and miR-92a overexpression overturned the anti-tumor activity of Swainsonine in glioma cells. Finally, western blot assay displayed that Swainsonine hindered PI3K/AKT/mTOR pathway via regulating miR-92a. CONCLUSIONS: These discoveries corroborated that Swainsonine exerted anti-tumor impacts on glioma cells via repression of miR-92a, and inactivation of PI3K/AKT/mTOR signaling pathway.

MicroRNA-374a Inhibits Aggressive Tumor Biological Behavior in Bladder Carcinoma by Suppressing Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: microRNA (miR)-374a plays a crucial role in cancer progression by promoting the metastasis and proliferation of various types of malignant tumors. Because its role in bladder cancer is unknown, we investigated whether miR-374a affects the progression of bladder cancer and studied the underlying mechanism. METHODS: The Cancer Genome Atlas was used to analyze the clinical relevance of miR-374a. Quantitative PCR, western blotting, and luciferase and immunofluorescence assays were used to detect the expression patterns, downstream targets, and function of miR-374a in bladder cancer cells. Apoptosis was evaluated by flow cytometry after cisplatin treatment. RESULTS: Via in silico analysis, low levels of miR-374a were associated with poor prognosis in bladder cancer patients with distant metastasis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. miR-374a mimic abrogated the metastatic potential and invasiveness of bladder cancer cells via WNT5A downregulation in both T24 and TCCSUP human bladder cancer cells; the opposite was observed with miR-374a inhibitor. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of ß-catenin. Cisplatin treatment significantly increased the apoptosis rate. Expression levels of cancer stemness-related proteins were reduced in miR-374a mimic-pretreated cells. CONCLUSION: Lower expression of miR-374a is associated with poor prognosis and miR-374a improves tumor biological behavior in bladder cancer cells, suggesting that miR-374a might be a novel small-molecule therapeutic target.

Oxidized low-density lipoprotein suppresses mouse granulosa cell differentiation through disruption of the hypoxia-inducible factor 1 pathway.

Obesity predisposes women to reproductive disorders. One symptom of obesity in women is higher levels of oxidized Low-density lipoprotein (oxLDL) in serum and preovulatory follicles. The present study was designed to test the hypothesis that oxLDL might impair follicle differentiation and luteinization. Given that Hypoxia-inducible factor 1 (HIF1) plays crucial roles in supporting follicle differentiation and luteinization in mammals, we focused on oxLDL-mediated events that may affect the HIF1 pathway. We report that exposure to oxLDL diminished the expression of HIF1α and its target genes and suppressed the differentiation of mouse luteinized granulosa cells following induction by human Chorionic gonadotophin (hCG) under hypoxic conditions (1% oxygen). Significantly, the proteasome inhibitor MG-132 prevented this oxLDL-attenuation differentiation phenotype by blocking HIF1α degradation. Together, these findings suggest that suppression of granulosa cell differentiation by oxLDL, via HIF1α down-regulation, may contribute the negative effects of obesity on female fertility.

[Toxoplasma gondii infection in pet dogs and owners in Hangzhou].

Sixty pet feeding families were obtained by random sampling in Hangzhou. The positive rate of IgG antibodies to Toxoplasma gondii in pet owners was 3.3% (4/120). The rate in males and females was 8.6% (3/35) and 1.2% (1/85) (χ2=4.207, P<0.05). The positive rate in pet dogs was 13.3% (8/60). The positive rate in dogs fed with a raw-meat diet (33.3%, 4/12) were significantly higher than that of others (4.2%, 2/48) (χ2=6.123, P<0.05).

Deciphering glycosylation-driven prognostic insights and therapeutic prospects in glioblastoma through a comprehensive regulatory model.

The oncogenesis and development of glioblastoma multiforme have been linked to glycosylation modifications, which are common post-translational protein modifications. Abnormal glycosyltransferase development leads to irregular glycosylation patterns, which hold clinical significance for GB prognosis. By utilizing both single-cell and bulk data, we developed a scoring system to assess glycosylation levels in GB. Moreover, a glycosylation-based signature was created to predict GB outcomes and therapy responsiveness. The study led to the development of an glyco-model incorporating nine key genes. This risk assessment tool effectively stratified GB patients into two distinct groups. Extensive validation through ROC analysis, RMST, and Kaplan-Meier (KM) survival analysis emphasized the model's robust predictive capabilities. Additionally, a nomogram was constructed to predict survival rates at specific time intervals. The research revealed substantial disparities in immune cell infiltration between low-risk and high-risk groups, characterized by differences in immune cell abundance and elevated immune scores. Notably, the glyco-model predicted diverse responses to immune checkpoint inhibitors and drug therapies, with high-risk groups exhibiting a preference for immune checkpoint inhibitors and demonstrated superior responses to drug treatments. Furthermore, the study identified two potential drug targets and utilized Connectivity Map analysis to pinpoint promising therapeutic agents. Clofarabine and YM155 were identified as potent candidates for the treatment of high-risk GB. Our well-crafted glyco-model effectively discriminates patients by calculating the risk score, accurately predicting GB outcomes, and significantly enhancing prognostic assessment while identifying novel immunotherapeutic and chemotherapeutic strategies for GB treatment.

Cuproptosis in glioblastoma: unveiling a novel prognostic model and therapeutic potential.

Glioblastoma, a notably aggressive brain tumor, is characterized by a brief survival period and resistance to conventional therapeutic approaches. With the recent identification of "Cuproptosis," a copper-dependent apoptosis mechanism, this study aimed to explore its role in glioblastoma prognosis and potential therapeutic implications. A comprehensive methodology was employed, starting with the identification and analysis of 65 cuproptosis-related genes. These genes were subjected to differential expression analyses between glioblastoma tissues and normal counterparts. A novel metric, the "CP-score," was devised to quantify the cuproptosis response in glioblastoma patients. Building on this, a prognostic model, the CP-model, was developed using Cox regression techniques, designed to operate on both bulk and single-cell data. The differential expression analysis revealed 31 genes with distinct expression patterns in glioblastoma. The CP-score was markedly elevated in glioblastoma patients, suggesting an intensified cuproptosis response. The CP-model adeptly stratified patients into distinct risk categories, unveiling intricate associations between glioblastoma prognosis, immune response pathways, and the tumor's immunological environment. Further analyses indicated that high-risk patients, as per the CP-model, exhibited heightened expression of certain immune checkpoints, suggesting potential therapeutic targets. Additionally, the model hinted at the possibility of personalized therapeutic strategies, with certain drugs showing increased efficacy in high-risk patients. The CP-model offers a promising tool for glioblastoma prognosis and therapeutic strategy development, emphasizing the potential of Cuproptosis in cancer treatment.

Eating behavior during pregnancy mediates the association between depression and diet quality--a new strategy for intervention in pregnancy.

Background: Depression can result in changes in eating behavior and decrease the quality of eating. It has been shown that maternal depression during pregnancy can result in malnutrition, which can have adverse effects on the pregnancy and the offspring. There is currently no clear association between depression and diet. Methods: Five hundred and forty-nine pregnant women recruited from Danyang Maternal and Child Health Hospital in Jiangsu Province participated in this study and were administered the Intuitive Eating Scale-2 (IES-2), Edinburgh Post-natal Depression Scale (EPDS), Pregnancy Stress Scale (PPS), Self-rating Anxiety Scale (SAS), and Dietary Guidelines Adherence Index for Pregnant Women during Pregnancy (CDGCI-PW). The nutritional software collected dietary records for three consecutive days in mid-pregnancy to calculate dietary intake and nutrients that support energy production. The mediation analyses were conducted using SPSS 24.0 macro PROCESS. Results: The relationship between depressive symptoms during pregnancy and diet quality was moderated primarily by two aspects of eating behavior, "Reliance on Hunger and Satiety Cues" (RHS) and "Body-Food Choice Congruence" (BFC). Depressive symptoms (EPDS scores) showed a negative correlation with RHS, BFC, and RHS, and BFC showed a positive correlation with diet quality, yielding a significant specific indirect effect. The multiple mediation model explained 14.7% of the variance in the diet quality. Conclusion: This study highlights the important role of eating behaviors during pregnancy in the relationship between depressive symptoms (EPDS scores) and diet quality, and provides preliminary evidence for feasible ways pregnant women with depressive symptoms can improve diet quality, promote maternal and child health, and reduce depression.

Selenium May Be Involved in Esophageal Squamous Cancer Prevention by Affecting GPx3 and FABP1 Expression: A Case-Control Study Based on Bioinformatic Analysis.

The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai'an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect myocardial infarction through FABP1, which remains to be further studied.

Using a new phase-locked visual feedback protocol to affirm simpler models for alpha dynamics.

Alpha band oscillations are the most prominent rhythmic oscillations in EEG, which are related to various types of mental diseases, such as attention deficit hyperactivity disorder, anxiety, and depression. However, the dynamics of alpha oscillations, especially how the endogenous alpha oscillations be entrained by exogenous stimulus, are still unclear. Recently, a newly-developed phase-locked visual feedback (PLVF) protocol has shown effectiveness in modulating alpha rhythm, which provides empirical evidence for the further investigation of the neural mechanism of alpha dynamics. In this work, extensive numerical simulations based on four well-studied models were used to investigate the questions that (1) What kind of dynamic model exhibits a modulation phenomenon of PLVF? (2) What is the dynamic mechanism of PLVF for alpha modulation? (3) Which factors affect the modulation effects in PLVF? The result indicates that the dynamics of endogenous alpha oscillations are close to a simpler dynamic structure, like fixed-point attractor or limit-cycle attractor, which shows a global consistent dynamic behavior at different phases of the alpha oscillation. The further analysis explains the dynamic mechanism of PLVF for amplitude and frequency modulation of the alpha rhythm, as well as the influence of parameter settings in the modulation. All these findings provide a deeper understanding of the endogenous alpha oscillations entrained by exogenous phased locked visual stimulus and lead in turn to the refinement of a control strategy for alpha modulation, which could potentially be used in developing new neural modulation methods for cognitive enhancement and mental diseases treatment.

Continuous supplementation of folic acid in pregnancy and the risk of perinatal depression-A meta-analysis.

BACKGROUND: The blood folic acid1(FA) level of depressed patients seems to be lower than that of normal, and pregnant women are at greater risk of FA deficiency. The relationship between FA and perinatal depression has not been well described. METHODS: We conducted a meta-analysis of the evidence for the association between the two, using current FA supplementation behavior during pregnancy and blood FA levels as exposures, and the incidence of perinatal depressive symptoms and mean Edinburgh Postnatal Depression Scale2 (EPDS) scores as outcomes. The present study was recorded in PROSPERO (2019 CRD: 42,020,211,509). RESULTS: Fifteen studies were identified, covering a total of 26,275 women from eleven observational studies and four randomized controlled trials. For the primary outcome of folic acid supplementation behavior and risk of perinatal depression, the overall odds ratio was 0.742 (95% CI: (0.647-0.852)), with a combined effect value of 0.84 (95% CI: (0.76, 0.93)) for studies in which an OR could be extracted. A negative association was observed between blood folate levels and depressive symptoms (Standardized mean difference (SMD) =-0.127, 95% CI:(-0.183,-0.071)). No association was observed between folic acid intervention and EPDS score. Continuous supplementation of folic acid during pregnancy may reduce the incidence of perinatal depressive symptoms (R = 0.017, (95 CI%:(0.014, 0.021)). LIMITATIONS: Lack of rigorous randomized controlled trials due to ethical issues, and the research is heterogeneous and does not consider the influence of genetic factors. CONCLUSIONS: Continuous use of FA during pregnancy may reduce the incidence of perinatal depressive symptoms.

Usefulness of four surrogate indexes of insulin resistance in middle-aged population in Hefei, China.

OBJECTIVE: Previous study have shown that lipid accumulation product (LAP), visceral adiposity index (VAI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C) and triglycerides/glucose index (TyG index) could be simple clinical indicators of insulin resistance (IR) based on anthropometric and/or biochemical parameters. However, the rational and preferred surrogate marker of IR in different population has yet to be validated. The aim of this study was evaluating the practicability of the LAP, VAI, TG/HDL-C, and TyG in predicting IR in middle-aged Chinese population. METHODS: A cross-sectional study was conducted in 569 Chinese participants (mean age was 48.5; man 67.7%), and each participant completed a questionnaire survey, anthropometric measurement, and biochemical testing. One-way ANOVAs, Chi-squared test, Pearson's correlation, and multiple logistic regression were used to evaluate the association between VAI, LAP, TG/HDL-C, and TyG with IR. To correctly discriminate individuals with insulin resistance, a receiver operating characteristic (ROC) analysis was conducted for each evaluated variable and the overall diagnostic accuracy was quantified using the area under the ROC curve (AUC). The AUC of evaluated variables were compared using a nonparametric approach. The optimal cut-off points were determined by the Youden's index, and the corresponding sensitivity and specificity were provided. RESULTS: Significant positive correlation was identified between HOMA-IR with TG/HDL-C (r = 0.306), VAI (r = 0.217), LAP (r = 0.381), and TyG (r = 0.371), respectively (all p < .001). After adjustment for potential confounders of IR, compared with the lowest tertiles, odds ratio (95% CI) having IR in the highest tertiles of TG/HDL-C, VAI, LAP and TyG were 6.07 (2.89-12.71), 10.89 (4.37-27.13), 4.68 (2.00-10.92), and 12.20 (5.04-29.56). The area under ROC curves to predict HOMA-diagnosed IR was 0.773 for TG/HDL-C, 0.767 for VAI, 0.806 for LAP, and 0.800 for TyG, respectively. Among those, LAP showed the greatest value of AUC [0.806 (0.763-0.850)] and highest specificity (0.804). CONCLUSION: Compared with other indicators, the LAP and TyG are simple, relatively accurate, clinically available surrogate markers of insulin resistance in middle-aged population in Hefei, China. Among 4 evaluated parameters, the LAP have the highest specificity and the TyG have the highest sensitivity.Key MessagesLAP and TyG could be used as simple and alternative methods to identify the individuals at risk for insulin resistance.LAP and TyG have relatively high predictive ability in diagnosis of IR compared with VAI and TG/HDL-C.No significant difference is observed between LAP and TyG in the ability of predicting insulin resistance.

Trimester- and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals.

OBJECTIVE: The importance of diagnosis and treatment of thyroid dysfunction during pregnancy has been widely recognized. We therefore established trimester- and method-specific reference intervals for thyroid testing in pregnant women according to the NACB recommended criteria. Several factors can affect the setting of reference intervals, in particular manufacturer's methodology, euthyroid definition and iodine status. DESIGN: Cross-sectional dataset analysis. SUBJECTS: Five hundred and five normal pregnant women at different stages of gestation were rigorously selected for setting reference intervals. All were healthy, iodine sufficient, euthyroid and negative for both serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). MEASUREMENTS: Thyrotrophin (TSH), total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3) and anti-TPOAb and anti-TgAb were measured using the Bayer ADVIA Centaur system. Iodine content in drinking water, salt and urine was determined by national standard methods. The 2·5th and 97·5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. RESULTS: All participants had long-term consumption of iodized salt and median urinary iodine of 150-200 µg/l during each three trimester. The reference intervals for the first, second and third trimesters were, respectively, TSH 0·03-4·51, 0·05-4·50 and 0·47-4·54 mIU/l and FT4 11·8-21·0, 10·6-17·6 and 9·2-16·7 pmol/l. The manufacturer's method, euthyroid definition and iodine status may influence TSH and FT4 reference intervals. Alterations in thyroid hormone concentrations during pregnancy differed at different stage of gestation and to those of a nonpregnant state. CONCLUSIONS: The trimester- and method-based reference intervals for thyroid tests during pregnancy are clinically appropriate. Some variables should be controlled when establishing reference intervals.

Optimized Propofol Anesthesia Increases Power of Subthalamic Neuronal Activity in Patients with Parkinson's Disease Undergoing Deep Brain Stimulation.

INTRODUCTION: Propofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS. METHODS: This retrospective study enrolled 68 PD patients undergoing bilateral STN-DBS surgery. All patients received local scalp anesthesia, with (asleep group, n = 35) or without (awake group, n = 33) propofol-remifentanil general anesthesia by target-controlled infusion under electroencephalogram monitoring. The primary outcome was subthalamic neuronal spiking characterization during microelectrode recording. The secondary outcomes were clinical outcomes including motor, cognition, mind, sleep, and quality of life at 6 months. RESULTS: Significantly increased delta and theta power were obtained under propofol anesthesia (awake vs. asleep group, mean ± standard deviation; delta: 31.97 ± 9.87 vs. 39.77 ± 10.56, p < 0.01; theta: 21.09 ± 5.55 vs. 24.82 ± 6.63, p = 0.01). After excluding the influence of confounding factors of age and preoperative motor scores, there was a statistically significant influence on the delta, theta, and alpha power of STN neuronal activity under different anesthesia regimens (delta: ß = 2.64, p < 0.01; theta: ß = 2.11, p < 0.01; alpha: ß = 1.42, p = 0.01). There were no differences in modified burst index, firing rate, tract numbers of microelectrode recording, and other clinical outcomes between the two groups. CONCLUSION: Optimized propofol anesthesia enhanced the delta, theta, and alpha power in STN compared with the awake technique and likely contributed to target recognition under propofol anesthesia. These results demonstrate that propofol is suitable, but needs to be optimized, for asleep STN-DBS. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identification number: ChiCTR2100045942. Registered 29 April 2021-Retrospectively registered.

Increased invasive phenotype of CSF-1R expression in glioma cells via the ERK1/2 signaling pathway.

Glioma is a common malignant tumor of the central nervous system (CNS) that has no effective treatment. In this study, we report that colony-stimulating factor-1 receptor (CSF-1R) is a key mediator of malignant features in glioma via modulation of the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In general, CSF-1R upregulation in glioma is associated with poor histologic grade and sursvival. Enforced expression of CSF-1R is sufficient to enhance cell growth, migration, invasion, and epithelial-mesenchymal transition, while CSF-1R silencing suppresses the above-described malignant phenotypes. Mechanistic investigations show that CSF-1R promotes activation of the ERK1/2 signaling pathway. Inhibition of the ERK1/2 pathway by SCH772984 reduces CSF-1R-induced migration, invasion, and lung metastasis of glioma cells, thus establishing a role of the ERK1/2 signaling pathway in mediating the CSF-1R effect. In summary, our results suggest that CSF-1R overexpression in gliomas contributes to the malignant behaviors of cancer cells.

MicroRNA-1225-5p behaves as a tumor suppressor in human glioblastoma via targeting of IRS1.

BACKGROUND: MicroRNAs (miRNAs) play an important role in cancer initiation, progression, and metastasis by directly regulating their target genes. MATERIALS AND METHODS: In this study, we observed that the miR-1225-5p expression level in glioblastoma tissues was significantly lower as compared with that in normal brain tissues, and its low expression was significantly associated with histopathological grade and poor patient prognosis. RESULTS: Through establishing a miR-1225-5p overexpression glioblastoma cell line, we found that ectopic overexpression of miR-1225-5p inhibited the proliferation, migration, and invasion of glioblastoma cells in vitro. Moreover, the growth of a glioblastoma xenograft tumor was attenuated by overexpression of miR-1225-5p. Further integrative studies suggested that the insulin receptor substrate 1 (IRS1) was a direct functional target of miR-1225-5p in glioblastoma, and the mRNA and protein levels of IRS1 in six human glioblastoma cell lines (A172, SW1783, U87, LN-229, SW1088, and T98G) were significantly higher as compared with normal human astrocytes. CONCLUSION: These results suggest that miR-1225-5p may be a novel candidate for glioblastoma therapy.

Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via induction of PUMA-mediated apoptosis.

BACKGROUND: Glioblastoma is one of the most aggressive and common malignancies of the central nervous system in humans. Owing to the correlation of high Hsp90 expression with prognosis and clinical pathology features of diverse types of cancer, targeting Hsp90 with small-molecule inhibitors has become a promising anticancer strategy. PURPOSE: In this study, we aimed to explore the possibility of anticancer effect of NMS-E973 in giloblastoma and elucidate the mechanism. METHODS: Cell based MTT assay and colony formation assay were used to detect cell viability. Apoptosis was analyzed by nuclear staining with Hoechst 33258 and Annexin V/propidium iodide staining followed by flow cytometry. Western-blot and RT-PCR were used to detect gene expression. Xenograft assay was used to explore the anticancer effect of NMS-E973 in vivo. RESULTS: We found that NMS-E973 induces apoptosis and inhibits cell growth in glioblastoma cells in cell culture and xenograft models. As a proapoptotic Bcl-2 member, PUMA was induced by NMS-E973 in a p53-dependent manner in glioblastoma in cell culture, thereby inducing apoptosis in glioblastoma cells. Furthermore, PUMA was induced by NMS-E973 treatment in xenograft tumors, and deficiency in PUMA significantly suppressed the antitumor effects of NMS-E973. CONCLUSION: Our study suggests that PUMA-mediated apoptosis is important for the therapeutic responses of NMS-E973. Induction of PUMA might be a potential biomarker for predicting NMS-E973 responses.

Vitexin induces G2/M­phase arrest and apoptosis via Akt/mTOR signaling pathway in human glioblastoma cells.

Glioblastoma is a common primary brain tumor with aggressive malignancy, which results in poor outcomes, short survival time and high mortality. Vitexin, an active ingredient from natural products, has been reported to inhibit cell growth and induce cell apoptosis in various cancer cell lines including hepatocellular carcinoma, oral and esophageal cancer. To the best of the authors knowledge, the present study was the first to investigate anticancer effects of vitexin on human glioblastoma cells and potential underlying mechanisms. The present study demonstrated that vitexin inhibited cell viability in a dose­ and time­dependent manner. In the present study, vitexin induced G2/M cell cycle arrest, as demonstrated by flow cytometry. Induction of cell apoptosis following vitexin treatment, was further indicated by observation of morphological alterations, flow cytometry analysis and detection of cleaved­poly (ADP­ribose) polymerase. The present study also demonstrated that vitexin inhibited RAC­alpha serine/threonine­protein kinase (Akt)/mechanistic target of rapamycin kinase (mTOR) signaling in human glioblastoma cells. Collectively, the results of the present study demonstrated that vitexin induced G2/M cell cycle arrest and apoptosis by inhibiting Akt/mTOR signaling in human glioblastoma cells. Vitexin may in the future be used as a therapeutic agent for treatment of malignant glioblastoma.