Increasing public concern on insomnia during the COVID-19 outbreak in China: An info-demiology study.

Background: Since December 2019, an unexplained pneumonia has broken out in Wuhan, Hubei Province, China. In order to prevent the rapid spread of this disease, quarantine or lockdown measures were taken by the Chinese government. These measures turned out to be effective in containing the contagious disease. In spite of that, social distancing measures, together with disease itself, would potentially cause certain health risks among the affected population, such as sleep disorder. We herein conducted this web search analysis so as to examine the temporal and spatial changes of public search volume of the mental health topic of "insomnia" during COVID-19 pandemic in China. Methods: The data sources included Baidu Index (BDI) to analyze related search terms and the official website of the National Health Commission of the People's Republic of China to collect the daily number of newly confirmed COVID-19 cases. Following a descriptive analysis of the overall search situation, Spearman's correlation analysis was used to analyze the relationship between the daily insomnia-related search values and the daily newly confirmed cases. The means of search volume for insomnia-related terms during the COVID-19 outbreak period (January 23rd, 2020 to April 8th, 2020) were compared with those during 2016-2019 using Student's t test. Finally, by analyzing the overall daily mean of insomnia in various provinces, we further evaluated whether there existed regional differences in searching for insomnia during the COVID-19 outbreak period. Results: During the COVID-19 outbreak period, the number of insomnia-related searches increased significantly, especially the average daily the BDI for the term "1 min to fall asleep immediately". Spearman's correlation analysis showed that 6 out of the 10 insomnia-related keywords were significantly positively related to the daily newly confirmed cases. Compared with the same period in the past four years, a significantly increased search volume was found in 60.0% (6/10) insomnia-related terms during the COVID-19 outbreak period. We also found that Guangdong province had the highest number of searches for insomnia-related during the pandemic. Conclusions: The surge in the number of confirmed cases during the COVID-19 pandemic has led to an increase in concern and online searches on this topic of insomnia. Further studies are needed to determine whether the search behavior truly reflect the real-time prevalence profile of relevant mental disorders, and further to establish a risk prediction model to determine the prevalence risk of psychopathological disorders, including insomnia, using insomnia-related BDI and other well-established risk factors.

Analysis of the resilience level and associated factors among patients with lumbar disc herniation.

This study aims to determine the resilience level and its influence on anxiety among Chinese lumbar disc herniation (LDH) patients, and to determine the critical psychological and non-psychological predictors of resilience among LDH patients. Twenty hundred and fifty LDH patients from a tertiary hospital in Jinzhou, China were included in this survey to answer the Resilience Scale-14 (RS-14), Zung Self-Rating Anxiety Scale (SAS), Herth Hope Index (HHI), Revised Life Orientation Test (LOT-R), Multidimensional Scale of Perceived Social Support (MSPSS), Perceived Stress Scale-10 (PSS-10). The mean resilience level of LDH patients was 61.96 ± 12.37. Resilience was negatively correlated with anxiety (χ2 = 32.603, p < 0.001), accompanied by a significant linear trend (χ2 = 28.567, p < 0.001). Hope, stress, social support, and medical payment type accounted for 48.7% resilience variance. This study reveals that Chinese LDH patients had low resilience level, and that lower level of resilience was closely associated with higher anxiety level. The predictors for resilience among LDH patients include hope, stress, social support, as well as medical payment types. These findings provide local government and related health-care professionals with a basis for development of targeted mental health management of Chinese LDH patients, and will also help to devise appropriate health intervention strategies for promoting the mental health status of LDH patients.

Psychometric evaluation of the Chinese version of social anxiety scale for social media users and cross-sectional investigation into this disorder among college students.

BACKGROUND: Recent years have seen an increased incidence of social anxiety due to increasing intensive use of social media, especially among young adults. OBJECTIVE: The present study aimed to translate the original English version of Social Anxiety Scale for Social Media Users (SAS-SMU) into Chinese, examine its applicability among Chinese College students via reliability and validity indexes, and investigate the influencing factors contributing to SAS-SMU. METHODS: A cross-sectional study was conducted among a cohort of 1307 Chinese college students, 486 males and 821 females, aged 20.75 ± 3.13 years old. The original version of SAS-SMU was translated into Chinese using the backward and forward translation procedure. An exploratory factor analysis (EFA) and a confirmatory factor (CFA) analysis were used for construction of underlying factor structure. Criterion-related validity was assessed using Interaction anxiousness scale (IAS) and the "extraversion" domain of Eysenck Personality Short Scale (EPQ-R-S). Cronbach's alpha coefficient was computed for evaluation of internal consistency. A multivariate stepwise linear regression analysis was conducted for determining the potential correlates of SMU-related social anxiety. RESULTS: The final Chinese version of SAS-SMU had 21 items. Item analysis, exploratory factor, EFA, and CFA jointly supported a three-factor structure of the translated version, defined as social recognition anxiety, interaction anxiety, and privacy concern anxiety, respectively. The three-factor structure of this scale showed configural, metric, scalar measurement invariance across gender. Cronbach's alpha coefficient of the scale and its three subscales were 0.96, 0.93, 0.94, and 0.91, respectively. The mean SAS-SMU overall score for each college student was 51.63 ± 16.32, with 21.64 ± 7.24 (recognition anxiety), 17.10 ± 6.30 (interaction anxiety), 12.90 ± 4.61 (privacy concern anxiety) for each subscale, respectively. IAS score, mobile phone addiction index (MPAI) score, EPQ-E score, time spent on social media per week, relationship with parents, childhood life status, whether being an only child, and cyber bullying experience can explain 51.1% of the variance of SMU related social anxiety. CONCLUSION: Based on the data, the Chinese version of SAS-SMU has shown to be satisfactory in psychometric properties. Subjects prone to interaction anxiousness, addictive smartphone use, extraversion personality trait, bad relationship with parents, unfortunate childhood life, only-child status, and having cyberbullying experience tend to have a higher level of SMU related social anxiety.

MiR-410-3p facilitates Angiotensin II-induced cardiac hypertrophy by targeting Smad7.

MicroRNAs (miRNAs) have emerged as important regulators in the development of cardiovascular diseases. miR-410-3p was shown to play a protective or detrimental role in the progression in cardiovascular events. However, the exact role and the underlying mechanism of miR-410-3p in cardiac hypertrophy have not been documented. The current work was aimed to determine the role and underlying mechanism of miR-410-3p on Angiotensin II (Ang II) induced cardiac hypertrophy. FITC-phalloidin staining was used for determination of cardiomyocyte surface area. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to identify mRNA expression level of hypertrophic markers. Smad7 protein expression level was analyzed using Western blot. Dual-luciferase reporter assay was used to examine the regulatory function of miR-410-3p on Smad7. MiR-410-3p was found significantly up-regulated in Ang II-induced cardiac hypertrophy. MiR-410-3p inhibitor remarkably alleviated cardiomyocyte hypertrophic changes. Dual-luciferase reporter assay result indicated that miR-410-3p directly targeted Smad7 and miR-410-3p inhibitor effectively prevented Ang II triggered down-regulation of Smad7. Moreover, Smad7 overexpression significantly reversed the pro-hypertrophic effect of miR-410-3p. In summary, our findings revealed that miR-410-3p mediated Ang II-induced cardiac hypertrophy via targeting inhibition of Smad7.

LNCAROD enhances hepatocellular carcinoma malignancy by activating glycolysis through induction of pyruvate kinase isoform PKM2.

BACKGROUND: Mounting evidence has suggested the essential role of long non-coding RNAs (lncRNAs) in a plethora of malignant tumors, including hepatocellular carcinoma. However, the underlyling mechanisms of lncRNAs remain unidentified in HCC. The present work was aimed to explore the regulatory functions and mechanisms of LncRNA LNCAROD in HCC progression and chemotherapeutic response. METHODS: The expression of LNCAROD in HCC tissues and cell lines were detected by quantitative reverse transcription PCR (qPCR). Cancer cell proliferation, migration, invasion, and chemoresistance were evaluated by cell counting kit 8 (CCK8), colony formation, transwell, and chemosensitivity assays. Methylated RNA immunoprecipitation qRCR (MeRIP-qPCR) was used to determine N6-methyladenosine (m6A) modification level. RNA immunoprecipitation (RIP) and RNA pull down were applied to identify the molecular sponge role of LNCAROD for modulation of miR-145-5p via the competing endogenous RNA (ceRNA) mechanism, as well as the interaction between LNCAROD and serine-and arginine-rich splicing factor 3 (SRSF3). The interaction between insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and LNCAROD was also identified by RIP assay. Gain- or-loss-of-function assays were used to identify the function and underlying mechanisms of LNCAROD in HCC. RESULTS: We found that LNCAROD was significantly upregulated and predicted a poorer prognosis in HCC patients. LNCAROD upregulation was maintained by increased m6A methylation-mediated RNA stability. LNCAROD significantly promoted HCC cell proliferation, migration, invasion, and chemoresistance both in vitro and in vivo. Furthermore, mechanistic studies revealed that pyruvate kinase isoform M2 (PKM2)-mediated glycolysis enhancement is critical for the role of LNACROD in HCC. According to bioinformatics prediction and our experimental data, LNCAROD directly binds to SRSF3 to induce PKM switching towards PKM2 and maintains PKM2 levels in HCC by acting as a ceRNA against miR-145-5p. The oncogenic effects of LNCAROD in HCC were more prominent under hypoxia than normoxia due to the upregulation of hypoxia-triggered hypoxia-inducible factor 1α. CONCLUSIONS: In summary, our present study suggests that LNCAROD induces PKM2 upregulation via simultaneously enhancing SRSF3-mediated PKM switching to PKM2 and sponging miR-145-5p to increase PKM2 level, eventually increasing cancer cell aerobic glycolysis to participate in tumor malignancy and chemoresistance, especially under hypoxic microenvironment. This study provides a promising diagnostic marker and therapeutic target for HCC patients.

Nicotine induces cardiac toxicity through blocking mitophagic clearance in young adult rat.

Since an outbreak of vaping-related deaths in the US has been reported as a public health crisis, the cardiovascular safety of nicotine nowadays receives increasing attention due to use of tobacco cigarette alternatives, such as electronic cigarettes. However, whether and how nicotine contributes to cardiac detrimental effects are in great controversy, especially less understood in young adult population. We report that chronic nicotine exposure, a major component of Electronic cigarettes, resulted in directly inhibited cardiomyocytes viability, increased cardiac fibrosis, and markedly suppressed cardiac function compared with sham. Gene array combined with bioinformatics analysis identified cardiac apoptosis and mitophagy were the key signals responsible for nicotine induced cardiac detrimental effect. Mechanistically, nicotine exposure markedly increased cleaved Caspase 3 and cleaved Caspase 9 indicating the involvement of intrinsic apoptotic pathway (mitochondrial cell death pathway). Meanwhile, nicotine-induced ROS outbreak promoted lysomal alkalization, furthermore blocked mitophagic degradation, thereby disrupted mitophagic flux promoted mitochondrial cell death cascade. Taken together, these findings indicate that nicotine confers cardiotoxicity via ROS-induced mitophagic flux blockage and provide the first demonstration of a causative link between nicotine and cardiac toxicity in young adult rat which may suggest nicotine induces cardiomyocytes impairment leading to cardiotoxicity in young adult population.

Activation of Protein Kinase Cδ Contributes to the Induction of Src/EGF Receptor/ERK Signaling in Ammonia-treated Astrocytes.

Previously, we showed that Src-mediated EGF receptor transactivation/ERK activation mediates ammonia-induced astrocyte swelling, which represents a major component of brain edema in hyperammonemic disorders. Here, we tested the role of PKC in the induction of this signaling pathway and its involvement in ammonia-mediated cell swelling. We found that incubating astrocytes with bisindolylmaleimide (BIM, an inhibitor of classical and novel PKC isoforms) or rottlerin, a PKCδ-specific inhibitor, attenuated the ammonia-induced phosphorylation of EGFR, while GF109203X had no effect on this pathway. We further found that BIM or rottlerin pretreatment inhibited the ammonia-induced phosphorylation of Src and that ammonia significantly increased the level of PKCδ pulled down by a Src antibody. AG1478, a specific EGFR kinase activity inhibitor, effectively inhibited phosphorylation at Tyr1068 but had no discernable effect on phosphorylation at Tyr845. Moreover, BIM or rottlerin abrogated ammonia-induced ERK phosphorylation. BIM-, rottlerin-, or GF109203X-treated astrocytes showed a significant reduction in cell swelling compared to that observed after treatment with ammonia alone. Finally, it was found that AG1478 attenuated ammonia-induced PKCα translocation to the particulate fraction. Taken together, our results indicate that PKCδ mediates ammonia-induced astrocyte swelling by activating Src and downstream EGF receptor/ERK signaling, which may contribute to the pathogenesis of neuropsychiatric disorders associated with hyperammonemia.

Translation of the Chinese Version of the Nomophobia Questionnaire and Its Validation Among College Students: Factor Analysis.

BACKGROUND: Nomophobia or phobia of no mobile phone is the fear of being without a mobile phone or being unable to contact others via a mobile phone. It is a newly emerging psychiatric disorder among mobile phone users. OBJECTIVE: There are no psychometric scales available in China for examining nomophobia, although China has become the largest mobile phone handset consumer market in the world. Therefore, this study aimed to translate the original English version of a psychometric scale into Chinese and further examine its reliability and validity among Chinese college students. METHODS: The original version of the Nomophobia Questionnaire (NMP-Q) was first translated into Chinese using the backward and forward translation procedure. An exploratory factor analysis (a principal component analysis plus varimax rotation) and a confirmatory factor analysis (CFA) were performed to examine the underlying factor structure of the translated questionnaire. The internal consistency reliability of the scale was determined by computing the Cronbach alpha coefficient, the test-retest reliability, and the corrected item-total correlation. A multivariate regression analysis was used for examining associations between nomophobia and independent variables among the college students. RESULTS: A total of 2000 participants were included in the study. Their ages ranged from 16 to 25 years, with 51.95% (1039/2000) being male participants. The Chinese version of NMP-Q retained 18 items. The eigenvalues, total variance explained, and scree plot jointly support a 4-factor structure of the translated questionnaire. The CFA reached the adaptive standard, and the discriminant validity of the scale was good. The Cronbach alpha coefficient of this scale was .925, and the Cronbach alpha coefficients of the subscales were .882, .843, .895, and .818. The test-retest reliability was 0.947. Corrected item-total correlation ranged from 0.539 to 0.663. The significant predictors for each of the dimensions of nomophobia and total score of the questionnaire were the average number of hours spent on a mobile phone daily and gender. CONCLUSIONS: The Chinese version of the NMP-Q exhibited satisfactory psychometric properties.

Neuroprotective role of icariin in experimental spinal cord injury via its antioxidant, anti­neuroinflammatory and anti­apoptotic properties.

Icariin is a type of flavonoid derived from the Chinese herbal plant Epimedium sagittatum Maxim. Mounting evidence has confirmed the beneficial effects of icariin in neurological diseases, including spinal cord injury (SCI). The aim of the present study was to investigate the neuroprotective effects of icariin in SCI and the precise underlying mechanism. The weight­drop injury technique was applied to construct an SCI model in Sprague­Dawley rats. Icariin (35 µmol/kg) was administered orally once daily for 7 consecutive days to examine its neuroprotective effects. The Basso, Beattie and Bresnahan scoring system was used for neurobehavioral evaluation. The water content of the injured spinal cord was measured via the dry­wet weight method. Biochemical indices were examined by colorimetric assay using commercially available kits. Western blot analysis was used to detect protein expression. Icariin significantly accelerated the recovery of the locomotor function of SCI rats and decreased spinal cord water content. Icariin also attenuated SCI­induced pro­apoptotic protein expression and activity, while it increased anti­apoptotic protein levels. In addition, icariin alleviated oxidative stress in SCI rats and decreased the levels of inflammatory molecules, including interleukin (IL)­1ß, IL­6, tumor necrosis factor­α, nitric oxide, nuclear factor­κB and inducible nitric oxide synthase, and increased the expression of anti­inflammatory proteins, including NADPH­quinone oxidoreductase­1, heme oxygenase­1 and nuclear factor erythroid 2­related factor 2 in the injured spinal cord. Therefore, icariin treatment accelerated locomotor function recovery in SCI, and its protective effects may be mediated via its antioxidant, anti­inflammatory and anti­apoptotic bioactivity.

Inhibition of cardiotrophin­1 overexpression is involved in the anti­fibrotic effect of Astrogaloside IV.

Astragaloside IV (AsIV), one of the major active ingredients in Astragalus membranaceus, has demonstrated remarkable antifibrotic effects via its antioxidative activity. Cardiac fibrosis is an important pathological mechanism during cardiac remodelling associated with heart failure. In the present study, the mechanism underlying the antifibrotic effect of AsIV upon isoprenaline (ISO) stimulation was investigated. AsIV significantly improved cardiac fibrosis in vivo and dose­dependently inhibited ISO­induced CF proliferation in vitro. The ISO­triggered elevation in reactive oxygen species (ROS) levels was remarkably inhibited by AsIV, as well as ROS scavenger N­acetylcysteine (NAC), and not affected by cardiotrophin­1 (CT­1) knockdown. In addition, AsIV effectively reversed ISO­induced upregulation of CT­1 expression, which was blunted by pretreatment with NAC. Cardiac fibroblast (CF) proliferation and collagen Ι overexpression induced by ISO stimulation were effectively abrogated by AsIV, NAC, and CT­1 small interfering RNA transfection. Taken together, these results demonstrated that AsIV was able to effectively inhibit ISO­induced CF proliferation and collagen production through negative regulation of ROS­mediated CT­1 upregulation.

Epidermal growth factor receptor transactivation is involved in the induction of human hepatoma SMMC7721 cell proliferation by insufficient radiofrequency ablation.

Our previous study revealed that insufficient radiofrequency ablation (RFA) promotes the malignancy of human hepatocellular carcinoma (HCC) SMMC7721 cells via the Ca2+/calmodulin-dependent protein kinase II (CaMKII)/extracellular signal-regulated kinase (ERK)-induced overexpression of vascular endothelial growth factor (VEGF). The aims of the present study were to address the involvement of epidermal growth factor receptor (EGFR) transactivation in the enhanced SMMC7721 cell proliferation induced by insufficient RFA, in addition to its association with the CaMKII/ERK/VEGF signaling cascade. SMMC7721 cells were subjected to a 47°C treatment regimen to simulate insufficient RFA. Cell proliferation was determined using MTT and colony formation assays. The expression levels of VEGF, CaMKII, phosphorylated (phospho)-CaMKII, ERK, phospho-ERK, EGFR and phospho-EGFR were analyzed using western blotting. The results demonstrated that the enhancement of SMMC7721 cell proliferation by the 47°C treatment regimen was significantly inhibited by exposure of the cells to AG178 (a specific inhibitor of EGFR). Furthermore, AG1478 exposure prevented the overexpression of VEGF and phosphorylation of ERK, but had no significant effects on CaMKII phosphorylation. By contrast, 47°C treatment-induced EGFR phosphorylation was inhibited by treatment with KN93 (a specific inhibitor of CaMKII). Overall, the results of the present study have suggested a role for EGFR transactivation in the RFA-promoted growth of residual HCC. Thus, targeting EGFR may represent a useful preventive and therapeutic strategy for RFA-induced HCC progression and recurrence.

Astragaloside IV inhibits isoprenaline­induced cardiac fibrosis by targeting the reactive oxygen species/mitogen­activated protein kinase signaling axis.

Cardiac fibrosis is considered an important pathological mechanism in the progression of cardiac remodeling and heart failure. Astragaloside IV (AsIV) is a major active ingredient in Astragalus membranaceus. In a preliminary experiment, it was demonstrated that this naturally occurring substance exhibited cardioprotective effects via preventing cardiomyocyte hypertrophy and apoptosis. The present study aimed to investigate the effects of AsIV on ß­adrenergic receptor (ß­AR)­mediated cardiac fibrosis, and the associated mechanism. Cell Counting Kit­8 (CCK­8) assay was used to examine the proliferation of rat cardiac fibroblast (CF) cultures. Collagen I secretion was detected by ELISA. Dihydroethidium was used to determine intracellular ROS levels. Western blotting was used to examine the expression level of total and phosphorylated mitogen­activated protein kinases (MAPKs). In the present study, the effects of AsIV on ß­adrenergic receptor (ß­AR) ­mediated cardiac fibrosis were investigated, and the associated mechanism was revealed. Isoprenaline (ISO) is a selective ß­AR agonist, and treatment with AsIV significantly inhibited (ISO)­triggered cardiac fibroblast proliferation and type I collagen synthesis. In addition, ISO resulted in a significant elevation of reactive oxygen species (ROS) levels and phosphorylation of the three profibrotic MAPKs, namely extracellular signal­regulated kinase, p38MAPK and c­Jun N­terminal kinase. AsIV effectively reversed the aforementioned ISO­induced alterations. In addition, N­acetylcysteine, a typical ROS scavenger, mimicked the inhibitory effects of AsIV on MAPK activation. The present study demonstrated that AsIV may inhibit ISO­induced cardiac fibrosis by suppressing ROS­mediated MAPK activation.

Genistein inhibited ammonia induced astrocyte swelling by inhibiting NF-κB activation-mediated nitric oxide formation.

Our previous study has indicated the involvement of epidermal growth factor receptor (EGFR) transactivation in ammonia-induced astrocyte swelling, which represents a major pathogenesis of brain edema in hepatic encephalopathy. In this study, we examined the effect of genistein, a naturally occurred broad-spectrum protein tyrosine kinase (PTK) inhibitor, on ammonia-induced cell swelling. We found that genistein pretreatment significantly prevented ammonia-induced astrocyte swelling. Mechanistically, ammonia triggered EGFR/extracellular signal-regulated kinase (ERK) association and subsequent ERK phosphorylation were alleviated by genistein pretreatment. Moreover, ammonia-induced NF-κB nuclear location, iNOS expression, and consequent NO production were all prevented by AG1478 and genistein pretreatment. This study suggested that genistein could alleviate ammonia-induced astrocyte swelling, which may be, at least partly, related to its PTK-inhibiting activity and repression of NF-κB mediated iNOS-derived NO accumulation.

Feeble Antipyretic, Analgesic, and Anti-inflammatory Activities were Found with Regular Dose 4'-O-ß-D-Glucosyl-5-O-Methylvisamminol, One of the Conventional Marker Compounds for Quality Evaluation of Radix Saposhnikoviae.

INTRODUCTION: 4'-O-ß-D-glucosyl-5-O-methylvisamminol (GML) is a conventional marker compound for quality control of Radix Saposhnikoviae. Despite that, neither pharmacodynamic or pharmacokinetic information is available with regard to GML. As such, the aim of thisstudy was to assess the conventional evaluation indices for the quality of Radix Saposhnikoviae. MATERIALS AND METHODS: Pyretic animal model, hot plate test, and ear edema model were established to evaluate and compare the antipyretic, analgesic, and anti-inflammatory effect of the chromone derivativescimifugin, prime-O-glucosylcimifugin (PGCN), and GML in Radix Saposhnikoviae. High performance liquid chromatography separation and analysis was used to obtain pharmacokinetic parameters. Simulated gastric fluid and simulated intestinal fluid was used to investigate the metabolite profiles of PGCN and GML in gastrointestinal tract. RESULTS: Cimifugin exerted a marked dose-dependent antipyretic, analgesic, and anti-inflammatory effect, whereas the effects of PGCN were relatively lower. GML had feeble pharmacodynamic effects. Pharmacokinetic study showed that only cimifugin was detected in the plasma sample of cimifugin and PGCN-treated animals, with drug concentration in the former much higher than the latter. No components were traced in the plasma samples from GML-treated rats. Stability study showed that PGCN and GML was predominantly biotransformed into cimifugin and 5-O-methyvisammiol, respectively. The latter was proven to be extremely unstable in liver tissue homogenate and plasma. CONCLUSIONS: A feeble antipyretic, analgesic, and anti-inflammatory activities was observed when GML was orally delivered. Given that Radix Saposhnikoviae extract is generally administered orally, we speculate that this compound might be a nonpharmacolagically active agent in real usage. Thus, it might be unscientific to evaluate the quality of Radix Saposhnikoviae based on the content of GML. SUMMARY: GML-derived cimifugin, which represents the potential pharma codynamic component of Radix Saposhnikoviae chromones, in plasma was almost nil in contrast to cimifugin and PGCN. And thus, feeble antipyretic, analgesic, and anti-inflammatory activities were found with GML. Abbreviations used: AUC:area under concentration-time curve, DNP:2,4-Dinitrophenol, HPLC:high performance liquid chromatography, HPLC-MS:high performance liquid chromatography- mass spectrography, GML:4'-O-ß-D-glucosyl-5-O-methylvisamminol, MVL:5-O-methyvisammiol, PGCN:prime-O-glucosylcimifugin, SGF:alkaline phosphatase. SIF:simulated intestinal fluid.

Polysaccharide enhances Radix Saposhnikoviae efficacy through inhibiting chromones decomposition in intestinal tract.

Vegetative but not reproductive stage of Saposhnikovia divaricate (Turxz.) schischk possesses pharmacological activities. However, our recent study showed that reproductive S. divaricate supplemented with polysaccharide showed evidently elevated pharmacological activities and increased cimifugin content in rat serum. The aims of present study were to assess the influence of polysaccharides on the chromones pharmacological activities in Radix Saposhnikoviae (RS), the dried root of vegetative stage of S. divaricate, and to explore the underlying mechanisms. Only cimifugin was detected in the plasma of chromone treated animals and RS polysaccharide significantly increased the plasma content of cimifugin. It was shown that neither cimifugin absorption nor glycoside components transformation in simulated digestive fluid was affected by RS polysaccharide. However, a significant promotion of transformation of cimifugin to more stable prime-O-glucosylcimifugin (PGCN) by RS polysaccharide, and a protective effect of polysaccharide on chromone components were observed in small intestine solutions. Meanwhile, RS polysaccharide produced a significant elevation of cimifugin and PGCN concentration in vivo. Based on these findings, we concluded that RS polysaccharide could greatly increase the content of cimifugin, which might be related to its degradation-proof effect on cimifugin, via transforming cimifugin to comparatively more stable PGCN and spatial structure protection.

Total glycosides of Ranunculus japonius prevent hypertrophy in cardiomyocytes via alleviating chronic Ca(2+) overload.

OBJECTIVE: To evaluate the in vitro anti-hypertrophic effect of total Glycosides of Ranunculus Japonius (TGRJ). METHODS: Neonatal rat cardiomyocytes were cultured and hypertrophy was induced by administrating isoproterenol (ISO, 10 µmol/L) or angiotensin 2 (Ang 2, 1 µmol/L) for 48 hours. In the treatment groups, cells were pretreated with TGRJ (0.3 g/L) for 30 minutes prior to hypertrophic stimuli. The anti-hypertrophic effects of TGRJ were examined by measuring cell size, total protein content, and protein synthesis. Intracellular free Ca(2+) concentration ([Ca(2+)]i) was evaluated using fluorescence dye Fura-2/AM. Sacroplasmic/endoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a), atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and beta-myosin heavy chain (ß-MHC) protein expression levels were measured by Western blotting . SERCA2a activity was assayed by p-nitrophenal phosphate disodium salt hexahydrate method. RESULTS: Increased cell size, total protein content, and protein synthesis following ISO or Ang 2 stimulation were significantly inhibited by pretreatment with TGRJ (all P<0.05). This anti-hypertrophic effect of TGRJ was confirmed by its suppressing effect on elevated expression of the three hypertrophic related genetic markers, ANP, BNP, and ß-MHC. In addition, TGRJ inhibited ISO or Ang 2 induced up-regulation of [Ca(2+)]i under chronic but not acute conditions. And ISO or Ang 2 induced down-regulation of SERCA2a expression and activity was also effectively rectified by TGRJ pretreatment. CONCLUSIONS: The results of present study suggested that TGRJ could prevent ISO or Ang 2 induced cardiac hypertrophy through improving chronic [Ca(2+)]i disorder, might via normalizing SERCA2a expression and activity.

Insufficient radiofrequency ablation promotes human hepatoma SMMC7721 cell proliferation by stimulating vascular endothelial growth factor overexpression.

The aims of the current study were to investigate the influence of insufficient radiofrequency ablation (RFA) on the cell proliferation of the human hepatocellular carcinoma (HCC) cells, SMMC7721, and to elucidate the underlying mechanism. SMMC7721 cells were subjected to a 47°C treatment regimen to simulate insufficient RFA, in the presence or absence of KN93 [a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII)], PD98059 [a specific inhibitor of extracellular signal-regulated kinase (ERK)], or axitinib (a specific inhibitor of vascular endothelial growth factor (VEGF) receptor]. Cell proliferation was determined using a thiazolyl terazolium assay (MTT). The levels of CaMKII, phospho-CaMKII, ERK, phospho-ERK and VEGF were observed by western blot analysis. The results demonstrated that the 47°C treatment regimen: i) Triggered upregulation of VEGF expression in the SMMC7721 cells, which was reduced by CaMKII or ERK inhibition; ii) induced ERK activation was prevented by KN93; and iii) promoted SMMC7721 cell proliferation, which was greatly inhibited by axitinib, KN93 and PD98059. In conclusion, the results indicated that insufficient RFA promotes SMMC7721 cell proliferation by activating CaMKII/ERK-dependent VEGF overexpression.

Astragalus polysaccharide inhibits isoprenaline-induced cardiac hypertrophy via suppressing Ca²âº-mediated calcineurin/NFATc3 and CaMKII signaling cascades.

Pathological cardiac hypertrophy induced by increased sympathetic drive can subsequently lead to congestive heart failure, which represents the major cause of morbidity and mortality worldwide. Astragalus polysaccharide (APS) is an active compound extracted from Chinese herb Astragalus membranaceus (AM), a frequently used "Qi-invigorating" herbal medicine in traditional medicine broadly used for the treatment of cardiovascular and other diseases. Currently, little is known about the effect of APS on cardiac hypertrophy. In the present study, we aimed to investigate its effect on cardiac hypertrophy and to clarify its possible mechanisms. In vitro cardiac hypertrophic model induced by isoprenaline (ISO) was employed to explore the anti-hypertrophic action of APS. We found that 10 µM ISO treatment for 48 h caused cultured cardiomyocytes to undergo significant increases in cell surface area, total protein content, protein synthesis as well as the expression of hypertrophic markers, including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which were effectively inhibited by APS in a dose dependent manner. Moreover, we found that APS pretreatment alleviated the augment of intracellular free calcium during cardiac hypertrophy induced by ISO. Our further study revealed that the upregulated expression of calcineurin, translocation of nuclear factor of activated T cells, cytoplasmic 3 (NFATc3) into nucleus and activation of calmodulin kinase II (reflected by p-CaMKII) were dose dependently suppressed by the application of APS. According to this research, APS exerted its anti-hypertrophic action via inhibiting Ca(2+)-mediated calcineurin/NFATc3 and CaMKII signaling cascades, which provided new insights into the application of APS to the therapy of heart diseases.

Activation of Wnt signaling inhibits the pro-apoptotic role of Notch in gastric cancer cells.

Notch and Wnt signaling play critical roles in the regulation of development and diseases. Several studies have previously reported that Notch may be a therapeutic target in the treatment of various types of human cancer. In this study, we report that activation of Notch1 inhibits the proliferation of BGC-823 gastric cancer cells. However, the activation of the Wnt/ß­catenin signaling pathway promotes the growth of BGC-823 cells. Furthermore, the combinational activation of the two signaling pathways promotes the proliferation of BGC-823 cells. These data suggest that the activation of Wnt signaling overcomes the pro-apoptotic role of Notch in BGC-823 gastric cancer cells.