Prevalence and relative factors of health anxiety of elders in community healthcare centers.

OBJECTIVE: The study's aims were (i) to identify the prevalence of health anxiety (HA) among the elderly in urban community healthcare centers and (ii) to determine whether HA is related to social, physical, or psychological factors. DESIGN: It is a population-based observational study. SETTING: Data were collected from urban community healthcare centers in Chengdu, China, from October 2016 to March 2017. PARTICIPANTS: A total of 893 participants aged ≥ 60 years. MEASUREMENTS: The Short HA Inventory was used for HA assessment. Mental health status was assessed using the Geriatric Depression Inventory and Mini-Mental State Examination. Other information was collected through face-to-face interviews. Data analysis was performed using SPSS 19.0. RESULTS: The point prevalence rate of HA was 9.53% (95%CI = 6.99%-12.07%). The number of chronic diseases was a positive factor associated with HA in a regression analysis. As compared with participants without chronic diseases, people with one (OR = 1.796; 95%CI = 0.546-5.909), two (OR = 2.922; 95%CI = 0.897-9.511), and three chronic diseases (OR = 6.448; 95%CI = 2.147-19.363) had higher odds of suffering from HA. CONCLUSIONS: The prevalence of HA was high in the elderly population. Certain physical conditions, such as having chronic diseases, were significant impact factors. More attention should be paid to the situation of HA in this population.

Ethanol promotes apoptosis in rat ovarian granulosa cells via the Bcl-2 family dependent intrinsic apoptotic pathway.

Excessive and indulgent alcohol consumption causes tremendous public health issues worldwide. Not only is ethanol associated with a broad spectrum of critical chronic diseases, ethanol is also demonstrated to exert striking reproductive toxicity for both males and females. Epidemiological investigations suggested that ethanol is closely related to fertility decrease in women. Animal studies showed that ethanol intake obstructed ovulation and reduced ovarian weight during gestation. However, cellular mechanism for this inhibitory effect of ethanol on female fertility is yet to be explored. This study recruited rat ovarian granulosa cells, the primary effector of ovary, to investigate the effects of ethanol on cell apoptosis and explore potential mechanism. Ovarian granulosa cells treated with ethanol for three hours manifested observable reduction in cell viability and apparent apoptosis. In the presence of 200 and 300 mmol/l of ethanol, the percentages of apoptotic cells increased to 33% and 36%, respectively. In addition, apoptosis related caspase-3 activity was elevated with increasing concentrations of ethanol, suggesting a dose dependent effect. Furthermore, high concentrations of ethanol significantly disturbed the transcriptional and translational regulation of anti-apoptotic Bcl-2 and pro-apoptotic Bax, which are the two key members of Bcl-2 family tightly involved in intrinsic apoptotic pathway. These results indicated that ethanol promotes apoptosis in rat ovarian granulosa cells, possibly via the intrinsic apoptotic pathway.

Comparative RNA-Seq transcriptome analysis on silica induced pulmonary inflammation and fibrosis in mice silicosis model.

Silicosis is a long-established public health issue in developing countries due to increasingly serious air pollution and poorly implemented occupational safety regulation. Inhalation of silica triggers cytotoxicity, oxidative stress, pulmonary inflammation and eventually silicosis. Current understanding in the pathogenesis and mechanism of silicosis is limited, and no effective cure is clinically available once silicosis is developed. A number of studies were conducted to investigate silica-induced alternate gene expressions in pulmonary cells. However, transcriptome analysis in a silicosis animal model is needed. This study was performed to evaluate the transcriptional alternations in silicotic mice using comparative RNA-Seq. A silicosis mice model was established by intratracheal instillation of silica suspensions, and validated by histological examinations. High-throughput sequencing and differential gene expression analysis revealed 749 upregulated genes and 70 downregulated genes in the silicosis model. Genes related to immune cell interactions, immune cell responses and inflammation were significantly enriched. Cytokine-cytokine receptor interaction and downstream JAK-STAT signaling pathways were the most significantly enriched KEGG pathways. Reverse transcription-polymerase chain reaction analysis and immunohistochemistry were performed to validate further the differential expression patterns of representative genes. The reported results in this study provide the basis for elucidating the molecular mechanisms for silica-induced pulmonary inflammation and fibrosis, and support the prevention and treatment of silicosis.

Evaluation on the thyroid disrupting mechanism of malathion in Fischer rat thyroid follicular cell line FRTL-5.

Thyroid hormones are involved in many important physiological activities including regulation of energy metabolism, development of nervous system, maintenance of cerebral functions, and so on. Endocrine-disrupting chemicals (EDCs) that interfere with thyroid functions raise serious concerns due to their frequent misuse in areas where regulations are poorly implemented. In addition, chemicals that are originally regarded safe may now be considered as toxic with the development of life sciences. Malathion is an organophosphate insecticide that is widely applied and distributed in agricultural and residential settings. Due to the low acute toxicity and rapid degradation, malathion is not listed as a primary thyroid disrupting chemical. However, emerging evidences reported that malathion affected thyroperoxidase catalyzed iodide oxidation which in turn influenced thyroid hormone transportation, and enhanced parathyroid hyperplasia prevalence. Nevertheless, direct effect of malathion on thyroid hormone biosynthesis remains to be elucidated. This study investigated the effects of thyroid disruption of malathion in Fischer rat thyroid follicular cell line, FRTL-5. Transcriptional and translational analyses on thyroglobulin demonstrated that both mRNA and protein expression levels were significantly inhibited by malathion. Cellular cAMP level and TSH receptor expression were distinctly reduced by malathion (6.0 µg/ml). These results suggested that malathion directly disrupted the biosynthesis of thyroid hormone and the mechanism involved down-regulation of TSH receptor and cellular cAMP. This subsequently led to the suppression of TSH dependent signal transduction, TG transcription inhibition, and obstruction of thyroid hormone biosynthesis.

Plasma levels of interleukin-6 and antidepressant response to Paroxetine in Chinese depressive patients.

This study aimed to investigate the correlation between interleukin-6 (IL-6) plasma levels and treatment outcomes of selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD). A total of 104 patients (33 males and 71 females), aged 18 to 72 years, were enrolled. Peripheral blood samples were collected before treatment initiation (baseline) and eight weeks after oral paroxetine treatment. The Hamilton Depression Rating Scale (HAMD)-17 was used to evaluate the efficacy of paroxetine. Baseline plasma IL-6 levels were found to be significantly lower in patients who responded to treatment than in non-responders. A negative correlation was found between the HAMD-17 reduction rate and baseline IL-6 levels. Furthermore, associations were examined between HAMD-17 reduction rate in patients and other factors, such as IL-6 levels, sex, age, and body mass index. Baseline IL-6 was the only factor showing a significant impact on the reduction rate of HAMD-17 at week 8. These results suggest that plasma IL-6 level may be a promising biological marker for predicting the likely treatment response to paroxetine in individual patients with MDD.

Trends in the prevalence of cognitive impairment in Chinese older adults: based on the Chinese Longitudinal Healthy Longevity Survey cohorts from 1998 to 2014.

In the context of a rapidly ageing Chinese population, this study aims to examine trends in the prevalence of cognitive impairment among people ≥65 y of age in China. Our sample is 72 821 adults aged 65-105 y from the seven waves of the Chinese Longitudinal Healthy Longevity Survey, a national mixed longitudinal cohort. The Chinese version of the Mini-Mental State Examination was used to measure CI. Risk factor-adjusted prevalence trend was examined using multilevel regression models. Age-standardized prevalence of cognitive impairment increased from 11.00% in 1998 to 11.84% in 2008 and decreased to 8.88% in 2014. Older age, female gender, less education, rural residence, not married, lack of physical and cognitive activities, suffering from stroke, vision and hearing impairment, and activities of daily living disability were negatively associated with cognitive impairment. Our study suggests a decreasing trend of cognitive impairment prevalence in China. However, whether decreasing prevalence will contribute to a reduced burden of cognitive impairment given the ageing of the population is unknown.

IGF-1 defends against chronic-stress induced depression in rat models of chronic unpredictable mild stress through the PI3K/Akt/FoxO3a pathway.

This study aims to investigate the role of IGF-1 in chronic-stress induced depression through the PI3K/Akt/FoxO3a pathway. A rat model of chronic unpredictable mild stress (CUMS) was established. In total, 48 rats were randomized into control (normal rats), CUMS (CUMS modeled rats) and CUMS + IGF-1 (injection of IGF-1 before CUMS modeling) groups. Body weight, horizontal (number of horizontal crossing) and vertical activity (rearing times), and sucrose consumption were identified one day before and after the open-field test. The mRNA and protein expression of PI3K, Akt, FoxO3a and Bim in the hippocampus was measured by RT-qPCR and Western blotting, respectively. Compared with the control group, a lower body weight, a decreased number of horizontal crossings, reduced rearing times and lower sucrose consumption were observed in the CUMS and CUMS + IGF-1 groups after the test. However, a higher body weight, number of horizontal crossings, rearing times and sucrose consumption were found in the CUMS + IGF-1 group than those in the CUMS group. Compared with the control group, mRNA and protein expression of PI3K, Akt and FoxO3a was decreased, and Bim mRNA and protein expression was increased in the CUMS + IGF-1 and CUMS groups. Meanwhile, in comparison to the CUMS group, mRNA and protein expression of PI3K, Akt and FoxO3a was elevated, and Bim mRNA and protein expression was reduced in the CUMS + IGF-1 group. The results suggested that IGF-1 exerted an antidepressant-like effect on chronic-stress induced depression through the PI3K/Akt/FoxO3a pathway.

MicroRNA-451a, microRNA-34a-5p, and microRNA-221-3p as predictors of response to antidepressant treatment.

Aberrant expression of microRNAs (miRNAs) has been shown to be involved in early observations of depression. The aim of this study was to determine if serum levels of miRNA-451a, miRNA-34a-5p, and miRNA-221-3p can serve as indicators of disease progression or therapeutic efficacy in depression. We collected data from 84 depressed patients and 78 control volunteers recruited from the medical staff at the West China Hospital. Depression severity was rated using the 24-item Hamilton Depression Scale (HAMD). Serum miRNA-451a, miRNA-34a-5p, and miRNA-221-3p levels were determined in samples from the depressed patients before and 8 weeks after antidepressant treatment as well as in samples from controls. Compared with the controls, the patients had lower miRNA-451a levels, higher miRNA-34a-5p and miRNA-221-3p levels, and increased HAMD scores whether they underwent antidepressant treatment or not. Eight weeks after antidepressant treatment, the patients exhibited increased miRNA-451a levels, decreased miRNA-34a-5p and miRNA-221-3p levels, and reduced HAMD scores. The serum level of miRNA-451a was negatively correlated with HAMD scores of the patients, while the serum levels of miRNA-34a-5p and miRNA-221-3p were positively correlated with HAMD scores whether the patients underwent antidepressant treatment or not. Paroxetine was markedly effective in 50 patients who also displayed an increased level of miRNA-451a but reduced levels of miRNA-34a-5p and miRNA-221-3p. In contrast, paroxetine was moderately effective or ineffective in 34 patients. In conclusion, depressed patients had lower serum miRNA-451a but higher serum miRNA-34a-5p and miRNA-221-3p, and these miRNAs are potential predictors of the efficacy of antidepressants.

Effects of escitalopram with a Chinese traditional compound Jiuweizhenxin-keli on mismatch negativity and P50 in patients with major depressive disorders.

OBJECTIVE: The objective of this study was to investigate the therapeutic effects of escitalopram in conjunction with Jiuweizhenxin-keli on neuroelectrophysiology in patients with major depressive disorders (MDD). PATIENTS AND METHODS: Patients with depressive episode of MDD according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were randomly assigned to Esc group (30 patients) receiving escitalopram treatment and JK group (30 patients) treated with a combination of escitalopram and Jiuweizhenxin-keli. The healthy control (HC) group (30 persons with normal health condition) served as control. All groups were subject to examination of 24-item Hamilton Depression Rating Scale and Hamilton Anxiety Scale, mismatch negativity (MMN), and sensory gating potential P50 (SG-P50) of event-related potentials. Data were collected at three different time points: baseline (before treatment) and week 2 and week 6 post treatment. RESULTS: At baseline, all electrophysiological parameters of patients with MDD were significantly higher than those of HCs. After treatment, in the Esc group, MMN latency, S2-P50 amplitude, and S2-P50/S1-P50 amplitude ratio decreased; however, the decrements were not statistically significant compared to either baseline or the HC group. Also, no significant changes were observed in the percentage of individuals whose S2-P50/S1-P50 ≥0.5 in the Esc group. On the other hand, in the JK group after a 6-week treatment, MMN latency (206.35±32.14 ms) was significantly shorter than that of the Esc group (219.57±36.51 ms), S2-P50 amplitude (7.27±4.85 µV) reduced significantly compared with the baseline level (10.21±4.10 µV), the percentage of individuals whose S2-P50/S1-P50 ≥0.5 in the JK group greatly decreased and this was not significantly different compared to that of the HC group (P≥0.05). CONCLUSION: Neuroplasticity of patients with MDD is apparently disturbed, characterized by aberrant MMN latency and SG-P50-related event-related potential parameters. A combination of escitalopram and Jiuweizhenxin-keli treatment can markedly restore these neuroelectrophysiological features, and thus, could be a novel therapeutic solution for improving the impaired neuroplasticity of MDD patients.

Pharmacokinetics of escin Ia in rats after intravenous administration.

ETHNOPHARMACOLOGICAL RELEVANCE: Escin, a natural mixture of triterpene saponins, is commonly utilized for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema. Escin Ia is the chief active ingredient in escin and plays key role in mediating its pharmacological effects. Adequate pharmacokinetic data are essential for proper application of escin agent in clinical practice. However, pharmacokinetic properties of escin Ia are still poorly understood and this conflicts with the growing use of escin agent over the years. The goal of this study is to investigate the pharmacokinetic behavior of escin Ia in rats after low, medium and high-dose intravenous administration. MATERIALS AND METHODS: Wistar rats were divided into 3 groups (n=6 per group) and escin Ia was administered via the caudal vein at doses of 0.5, 1.0 and 2.0 mg/kg, respectively. Subsequently, the concentrations of escin Ia and its metabolite isoescin Ia, a positional isomer of escin Ia, in rats׳ plasma were measured by an established liquid chromatography tandem mass spectrometry (LC-MS/MS) method at various time points following the administration of the drug. Main pharmacokinetic parameters were calculated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany). RESULTS: After intravenous administration, the Cmax and AUC of escin Ia increased in a dose-proportional manner at the dose of 0.5 mg/kg and 1.0 mg/kg, while increased in a more than dose-proportional manner at the doses of 1.0 mg/kg and 2.0 mg/kg. The t1/2 was significantly longer with increased intravenous doses, while other parameters such as CL and Vd also exhibit disagreement among three doses. Taken together, our data showed dose-dependent pharmacokinetic profile of escin Ia in rats after intravenous administration at the doses of 0.5-2.0 mg/kg. After intravenous administration, escin Ia was rapidly and extensively converted to isoescin Ia. CONCLUSIONS: The results suggested dose-dependent pharmacokinetics of escin Ia at the doses of 0.5-2.0 mg/kg after intravenous administration. Escin Ia is isomerized to isoescin Ia rapidly and extensively regardless of the doses.

MicroRNA-451a, microRNA-34a-5p, and microRNA-221-3p as predictors of response to antidepressant treatment

Aberrant expression of microRNAs (miRNAs) has been shown to be involved in early observations of depression. The aim of this study was to determine if serum levels of miRNA-451a, miRNA-34a-5p, and miRNA-221-3p can serve as indicators of disease progression or therapeutic efficacy in depression. We collected data from 84 depressed patients and 78 control volunteers recruited from the medical staff at the West China Hospital. Depression severity was rated using the 24-item Hamilton Depression Scale (HAMD). Serum miRNA-451a, miRNA-34a-5p, and miRNA-221-3p levels were determined in samples from the depressed patients before and 8 weeks after antidepressant treatment as well as in samples from controls. Compared with the controls, the patients had lower miRNA-451a levels, higher miRNA-34a-5p and miRNA-221-3p levels, and increased HAMD scores whether they underwent antidepressant treatment or not. Eight weeks after antidepressant treatment, the patients exhibited increased miRNA-451a levels, decreased miRNA-34a-5p and miRNA-221-3p levels, and reduced HAMD scores. The serum level of miRNA-451a was negatively correlated with HAMD scores of the patients, while the serum levels of miRNA-34a-5p and miRNA-221-3p were positively correlated with HAMD scores whether the patients underwent antidepressant treatment or not. Paroxetine was markedly effective in 50 patients who also displayed an increased level of miRNA-451a but reduced levels of miRNA-34a-5p and miRNA-221-3p. In contrast, paroxetine was moderately effective or ineffective in 34 patients. In conclusion, depressed patients had lower serum miRNA-451a but higher serum miRNA-34a-5p and miRNA-221-3p, and these miRNAs are potential predictors of the efficacy of antidepressants.

Functional domains of androgen receptor coactivator p44/Mep50/WDR77and its interaction with Smad1.

p44/MEP50/WDR77 has been identified as a coactivator of androgen receptor (AR), with distinct growth suppression and promotion function in gender specific endocrine organs and their malignancies. We dissected the functional domains of p44 for protein interaction with transcription factors, transcriptional activation, as well as the functional domains in p44 related to its growth inhibition in prostate cancer. Using a yeast two-hybrid screen, we identified a novel transcription complex AR-p44-Smad1, confirmed for physical interaction by co-immunoprecipitaion and functional interaction with luciferase assays in human prostate cancer cells. Yeast two-hybrid assay revealed that the N-terminal region of p44, instead of the traditional WD40 domain at the C-terminus, mediates the interaction among p44, N-terminus of AR and full length Smad1. Although both N and C terminal domains of p44 are necessary for maximum AR transcriptional activation, the N terminal fragment of p44 alone maintains the basic effect on AR transcriptional activation. Cell proliferation assays with N- and C- terminal deletion mutations indicated that the central portion of p44 is required for nuclear p44 mediated prostate cancer growth inhibition.

Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.

Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR) and estrogen receptor (ER) in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.

G protein coupling profile of mGluR6 and expression of G alpha proteins in retinal ON bipolar cells.

Metabotropic glutamate receptor 6 (mGluR6) is a group III, pertussis toxin (PTX)-sensitive G protein coupled mGluR that plays a specialized role in the retina. Retinal ON bipolar cells, which receive direct glutamatergic input from photoreceptor cells, express mGluR6 as their primary postsynaptic glutamate receptor. Activation of mGluR6 in these cells initiates an intracellular signaling cascade ultimately leading to inhibition of a cation channel and cell hyperpolarization. The primary mediator of this pathway in vivo is G alpha(o), but the potential roles of other G proteins from the G alpha(i/o) family in the regulation of this or other signaling pathways in ON bipolar cells are unclear. To determine which specific G proteins from the G alpha(i/o) family are able to couple to mGluR6, a G alpha reconstitution system was employed using PTX-insensitive G alpha mutants expressed with mGluR6 in PTX-treated sympathetic neurons from the rat superior cervical ganglion (SCG). The efficiency of coupling to mGluR6 was G(oa) > G(ob), G(i1) > G(i2), G(i3), whereas no coupling was observed with G alpha(z), nor with the retinal G alpha proteins, rod (GNAT2) or cone (GNAT1) transducin (G alpha(Tr-R), G alpha(Tr-C)). Finally, the expression of G alpha proteins determined to couple with mGluR6 was examined in rat ON bipolar cells using single cell RT-PCR. Co-expression of mGluR6 message was used to distinguish ON from OFF bipolar cells. Expression of G alpha(o) was detected in every ON bipolar cell examined. Message for G alpha(i1), which coupled moderately to mGluR6, was not detected in ON bipolar cells, nor was G alpha(i3), which coupled to mGluR6 in only a few cells but on average did not exhibit statistically significant coupling. Finally, though G alpha(i2) was detectable in ON bipolar cells, its coupling to mGluR6 in the SCG system was not significant. Together, these data indicate that signaling through mGluR6 in mammalian ON bipolar cells is highly focused, apparently acting through a single G alpha protein subtype.