Small-molecule exhibits anti-tumor activity by targeting the RNA m6A reader IGF2BP3 in ovarian cancer.

Based on its absence in normal tissues and its role in tumorigenesis and tumor progression, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of N6-methyladenosine (M6A) on RNA, represents a putative valuable and specific target for some cancer therapy. In this study, we performed bioinformatic analysis and immunohistochemistry (IHC) to find that IGF2BP3 was highly expressed in tumor epithelial cells and fibroblasts of ovarian cancer (OC), and was associated with poor prognosis, metastasis, and chemosensitivity in OC patients. In particular, we discovered that knockdown IGF2BP3 expression inhibited the malignant phenotype of OC cell lines by decreasing the protein levels of c-MYC, VEGF, CDK2, CDK6, and STAT1. To explore the feasibility of IGF2BP3 as a therapeutic target for OC, a small molecular AE-848 was designed and screened by molecular operating environment (MOE), which not only could duplicate the above results of knockdown assay but also reduced the expression of c-MYC in M2 macrophages and tumor-associated macrophages and promoted the cytokine IFN-γ and TNF-α secretion. The pharmacodynamic models of two kinds of OC bearing animals were suggested that systemic therapy with AE-848 significantly inhibited tumor growth by reducing the expression of tumor-associated antigen (c-MYC/VEGF/Ki67/CDK2) and improving the anti-tumor effect of macrophages. These results suggest that AE-848 can inhibit the growth and progression of OC cells by disrupting the stability of the targeted mRNAs of IGF2BP3 and may be a targeted drug for OC treatment.

Molecular characterization and immune efficacy of fructose-1,6-bisphosphate aldolase from Haemaphysalis longicornis (Acari: Ixodidae).

BACKGROUND: Ticks are obligate hematophagous ectoparasites that transmit a variety of pathogens to humans, wildlife and domestic animals. Vaccination is an effective and environmentally friendly method for tick control. Fructose-1,6-bisphosphate aldolase (FBA) is an important glycometabolism enzyme that is a candidate vaccine against parasites. However, the immune protection of FBA in ticks is unclear. METHODS AND RESULTS: The 1092-bp open reading frame (ORF) of FBA from Haemaphysalis longicornis (HlFBA), encoding a 363-amino acid protein, was cloned using PCR methodology. The prokaryotic expression vector pET32a(+)-HlFBA was constructed and transformed into cells of Escherichia coli BL21(DE3) strain for protein expression. The recombinant HlFBA protein (rHlFBA) was purified by affinity chromatography, and the western blot results suggested that the rHlFBA protein was immunogenic. RESULTS: Results of the enzyme-linked immunosorbent assay showed that rabbits immunized with rHlFBA produced a humoral immune response specific to rHlFBA. A tick infestation trial indicated that, compared to the ticks in the histidine-tagged thioredoxin (Trx) group, the engorged tick weight and oviposition of female ticks and egg hatching rate of those in the rHlFBA group was reduced by 22.6%, 45.6% and 24.1%, respectively. Based on the cumulative effect of the these three parameters, the overall immune efficacy of rHlFBA was estimated to be 68.4%. CONCLUSIONS: FBA is a candidate anti-tick vaccine that can significantly reduce the engorged tick weight, oviposition, and egg hatching rate. The use of enzymes involved in glucose metabolism is a new strategy in the development of anti-tick vaccines.

Ferroelectric artificial synapse for neuromorphic computing and flexible applications.

Research of artificial synapses is increasing in popularity with the development of bioelectronics and the appearance of wearable devices. Because the high-temperature treatment process of inorganic materials is not compatible with flexible substrates, organic ferroelectric materials that are easier to process have emerged as alternatives. An organic synaptic device based on P(VDF-TrFE) was prepared in this study. The device showed reliable P/E endurance over 104 cycles and a data storage retention capability at 80 °C over 104 s. Simultaneously, it possessed excellent synaptic functions, including short-term/ long-term synaptic plasticity and spike-timing-dependent plasticity. In addition, the ferroelectric performance of the device remained stable even under bending (7 mm bending radius) or after 500 bending cycles. This work shows that low-temperature processed organic ferroelectric materials can provide new ideas for the future development of wearable electronics and flexible artificial synapses.

Increased Urinary CD163 Levels in Systemic Vasculitis with Renal Involvement.

OBJECTIVES: Systemic vasculitis includes a group of disorders characterized by inflammation of the vessel wall, involving multiple systems, and can cause malignant hypertension. CD163 is a specific marker of anti-inflammatory macrophages. This study is aimed at evaluating the CD163 levels in relation to systemic vasculitis and renal involvements. METHODS: Urinary CD163 levels were retrospectively measured by enzyme-linked immunosorbent assay (ELISA) in 51 patients with systemic vasculitis, 42 essential hypertensions, and 36 healthy volunteers. The associations between urinary CD163 levels and clinical indicators were analyzed. RESULTS: Urinary CD163 levels were significantly higher in patients with systemic vasculitis [68.20 (38.25~158.78) (pg/ml)] compared to essential hypertension [43.86 (23.30-60.71) (pg/ml)] (p = 0.003) and the healthy volunteers [30.76 (9.30-54.16) (pg/ml)] (p < 0.001). Furthermore, systemic vasculitis patients with renal involvement had significantly higher urinary CD163 levels relative to patients without renal involvement [86.95 (47.61 and 192.38) pg/ml] vs. [41.99 (17.70 and 71.95) pg/ml, p = 0.005]. After control factors age, sex, and BMI, urinary CD163 levels in systemic vasculitis patients were positively correlated with serum creatinine, blood urea nitrogen, and ß-2 microglobulin (r = 0.45, 0.48, and 0.46; p = 0.001, 0.001, and 0.002, respectively). In addition, we found the level of urinary CD163 in granulomatous vasculitis (including TA, GPA, and EGPA) was significantly higher than that in necrotizing vasculitis (including PAN) [86.95 (41.99 and 184.82) pg/ml] vs. [45.73 (21.43 and 74.43) pg/ml, p = 0.016]. CONCLUSION: Urinary CD163 levels were significantly higher in patients with systemic vasculitis, especially in patients with renal involvement. Thus, urinary CD163 has the potential to be a biomarker for systemic vasculitis with renal involvement.

SPOCK1 promotes the proliferation and migration of colon cancer cells by regulating the NF-κB pathway and inducing EMT.

Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) has been shown to promote various tumors, but its role in colon cancer (CRC) has not been clearly illuminated. The aim of this study was to investigate the effects of SPOCK1 interference on the proliferation, migration, and EMT of CRC cells. First, we analyzed the expression of SPOCK1 in various CRC datasets. Then, we investigated the correlation between SPOCK1 and prognosis in CRC patients. We overexpressed SPOCK1 and knocked down SPOCK1 expression in HCT-116 and SW480 cells, respectively. Then, cell proliferation was assayed with a CCK-8 assay, and cell migration was evaluated with a Transwell migration assay. NF-κB and EMT-related proteins were studied by western blotting. The results indicated that the mRNA levels of SPOCK1 were relatively high in CRC tissues and that high expression of SPOCK1 was negatively correlated with patient prognosis. With SPOCK1 overexpression in HCT-116 cells, cell proliferation and migration were increased, while SPOCK1 knockdown had the opposite effects. With SPOCK1 overexpression in HCT-116 cells, the expression levels of NF-κB and EMT-related proteins were elevated, while SPOCK1 knockdown produced the opposite results. In conclusion, our study demonstrates that SPOCK1 may activate the NF-κB/Snail signaling cascade to promote the proliferation and migration of CRC cells. SPOCK1 may serve as a new prognostic indicator and potential therapeutic target in CRC.

Huntingtin-associated protein 1 plays an essential role in the pathogenesis of type 2 diabetes by regulating the translocation of GLUT4 in mouse adipocytes.

OBJECTIVE: Glucose disposal by insulin-responsive tissues maintains the body glucose homeostasis and insulin resistance leads to a risk of developing type 2 diabetes (T2DM). Insulin stimulates the translocation of glucose transporter isoform 4 (GLUT4) vesicles from intracellular compartments to the plasma membrane to facilitate glucose uptake. However, the underlying mechanisms of GLUT4 vesicle translocation are not well defined. Here we show the role of huntingtin-associated protein 1 (HAP1) in GLUT4 translocation in adipocytes and the pathogenesis of T2DM. RESEARCH DESIGN AND METHODS: The parameters for glucose metabolism including body weight, glucose tolerance and insulin tolerance were assessed in wild-type (WT) and Hap1+/- mice. HAP1 protein expression was verified in adipose tissue. Hap1 mRNA and protein expression was monitored in adipose tissue of high-fat diet (HFD)-induced diabetic mice. Insulin-stimulated GLUT4 vesicle translocation and glucose uptake were detected using immunofluorescence techniques and quantified in primary adipocytes from Hap1-/- mice. The interaction between HAP1 and GLUT4 was assessed by immunofluorescence colocalization and co-immunoprecipitation in HEK293 cells and adipose tissue. The role of sortilin in HAP1 and GLUT4 interaction was approved by co-immunoprecipitation and RNA interference. RESULTS: The expression of Hap1 mRNA and protein was detected in WT mouse adipose tissue and downregulated in adipose tissue of HFD-induced diabetic mice. Hap1+/- mice exhibited increased body weight, pronounced glucose tolerance and significant insulin intolerance compared with the WT mice. HAP1 colocalized with GLUT4 in mouse adipocytes and cotransfected HEK293 cells. Furthermore, the insulin-stimulated GLUT4 vesicle translocation and glucose uptake were defective in Hap1-/- adipocytes. Finally, sortilin mediated the interaction of HAP1 and GLUT4. CONCLUSIONS: Our study showed that HAP1 formed a protein complex with GLUT4 and sortilin, and played a critical role in insulin-stimulated GLUT4 translocation in adipocytes. Its downregulation may contribute to the pathogenesis of diabetes.

Evaluating the implementation of rapid diagnostic tests in a malaria elimination setting.

BACKGROUND: It was recommended that malaria rapid diagnostic tests (RDTs) should be available in all epidemiological situations. But evidence was limited on the implementation of RDTs and its effectiveness in malaria elimination settings. This study examined the implementation of RDTs and how it affected the diagnosis of imported malaria patients in Jiangsu Province, China. METHODS: To scale up RDTs, this study developed an intervention package with four major elements covering the supply of RDT test, the training on RDTs, the monitoring and management of RDT use, and the advocacy of RDTs. By using a pretest-posttest control group design, we implemented the interventions in 4 cities in Jiangsu Province with the rest nine cities as controlled areas, from January 2017 to January 2018. Difference-in-Difference approach was used to evaluate the impact of the scale-up of RDTs on the identification of malaria cases. Three binary outcome measures were included to indicate delayed malaria diagnosis, malaria cases with confirmed malaria diagnosis at township-level institutions, and severe malaria cases, respectively. Linear probability regression was performed with time and group fixed effects and the interaction term between time and group. RESULTS: Intervention areas received sufficient RDT test supply, regular professional training programs, monthly tracking and management of RDT supply and use, and health education to targeted population. The implementation of interventions was associated with 10.8% (P = 0.021) fewer patients with delayed diagnosis. But intervention areas did not see a higher likelihood of having confirmed diagnosis from township-level institutions (coefficient = -0.038, P = 0.185) or reduced severe malaria cases (coef. = 0.040, P = 0.592). CONCLUSIONS: The comprehensive package of RDT implementation in this study is promising in scaling up RDT use and improving access to care among malaria patients, especially in malaria elimination settings.

Regulatory effects of Prohibitin 1 on proliferation and apoptosis of pulmonary arterial smooth muscle cells in monocrotaline-induced PAH rats.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by unbalanced proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Prohibitin 1 (PHB1) is known for its significant anti-proliferative activity. However, the role of PHB1 in PASMCs and PAH have not been elucidated. METHODS: Monocrotaline (MCT 60 mg/kg) was used to build a PAH model in SD rats. Right ventricular systolic pressure (RVSP) and right ventricle (RV) hypertrophy were measured. Morphology of pulmonary vessels was observed by Hematoxylin-Eosin (HE) staining. Expression of PHB1 in pulmonary arteries and PASMCs was determinated by immunoblot and immunofluorescence. Cell proliferation was detected by CCK8 and EDU when PASMCs were stimulated by PDGF-BB (20 ng/mL). Furthermore, siRNA for PHB1 and Akt inhibitor were conducted to investigate the mechanism behind the role of PHB1 and AKT signaling pathway in PASMCs proliferation and apoptosis. RESULTS: The protein expression of PHB1 in PAH rats lung tissue was significantly up-regulated accompanied by elevated RVSP and enhanced RV hypertrophy. Immunohistochemistry showed that PHB1 was mainly localized in the pulmonary vascular smooth muscle layer. PDGF-BB significantly up-regulated the expression of PHB1 in rat primary PASMCs in a time- and dose-dependent manner. After PHB1 knock down, PASMCs proliferation was significantly suppressed while apoptosis was significantly recovered. Meanwhile the level of proliferating cell nuclear antigen (PCNA) and P-Akt were significantly down-regulated. Perifosine (Akt inhibitor) also significantly inhibit proliferation of PASMCs. CONCLUSION: PHB1 contributes to pulmonary vascular remodeling by accelerating proliferation of PASMCs which involves AKT phosphorylation.

Dendrobium candidum aqueous extract attenuates isoproterenol-induced cardiac hypertrophy through the ERK signalling pathway.

CONTEXT: The pharmacological functions of Dendrobium candidum Wall. ex Lindl. (Orchidaceae) in cardiac hypertrophy remains unclear. OBJECTIVE: To evaluate whether D. candidum aqueous extract (DCAE) can attenuate experimental cardiac hypertrophy. MATERIALS AND METHODS: Cardiac hypertrophy in SD rats was induced by subcutaneously injection of isoproterenol (2 mg/kg), once a day for ten days. Rats were gavaged with DCAE (0.13 and 0.78 g/kg) daily for one month. At the end of treatment, measurement of left ventricular systolic pressure (LVSP), heart-to-body weight ratio (HW/BW), left ventricular/tibia length (LV/TL), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) levels, haematoxylin-eosin staining, and Masson's trichrome staining were conducted. In cultured H9c2 cells, DCAE (2 mg/mL) and U0126 (10 µM) were added 2 h before the isoproterenol (10 µM) stimulus. Phalloidin staining was used to evaluate cellular hypertrophy. The mRNA expression of ANP and BNP was measured by qRT-PCR. The expression of p-ERK was determined by immunoblotting. RESULTS: DCAE treatment significantly reduced the following indicators in vivo: (1) the LVSP (16%); (2) HW/BW (13%); (3) LV/TL (6%); (4) ANP (39%); (5) BNP (32%). In cultured H9c2 cells, phalloidin staining showed that DCAE relieved cellular hypertrophy (53% reduction). Furthermore, immunoblotting showed that DCAE can significantly inhibit p-ERK protein expression in vivo and in vitro (39% and 27% reduction, respectively). DISCUSSION AND CONCLUSIONS: DCAE prevents cardiac hypertrophy via ERK signalling pathway and has the potential for treatment of cardiac hypertrophy.

[Effect of Huntingtin-associated Protein 1 Gene on Proliferation of Mouse Fibroblasts].

OBJECTIVE: To determine the effect of Huntingtin-associated protein 1 ( Hap1) on fibroblast proliferation. METHODS: Hap1 knockout ( Hap1 -/-) primary fibroblasts were isolated and cultured in vitro. The proliferation of Hap1 -/- fibroblasts was detected by EdU proliferation assay and cell flow assay. Transcriptome sequencing of the wild-type and Hap1 -/- fibroblasts was screened for proliferation-related genes. Real-time quantitative PCR (qPCR) was performed to verify changes in expressions of related genes. Skin repair was examined in Hap1 knockdown mice with skin wounds. The proliferation of fibroblasts during wound repair was detected by PCNA immunohistochemical staining. RESULTS: Hap1 -/- fibroblasts were successfully cultured. Compared with WT, EdU-positive fibroblasts decreased in Hap1 -/-,with less cells entering the S phase. Transcriptome sequencing of primary fibroblasts identified genes of Cdc25C, E2f7, E2f8 and Ccl5. qPCR confirmed that Hap1 knockout increased E2f7 expression. Hap1 +/- mice had larger skin lesions, slower healing and lower positive density of fibroblast proliferation than those of wild type mice. CONCLUSION: Hap1 may positively regulate fibroblast proliferation by inhibiting the expression of cell cycle negative regulator E2f7.Its deletion inhibits fibroblasts entering the S phase, thereby reducing cell proliferation and affecting wound repair.

HMGB1/TLR4 promotes hypoxic pulmonary hypertension via suppressing BMPR2 signaling.

High mobility group box 1 (HMGB1), a critical nonclassical inflammatory cytokine, has been found up-regulated in patients with idiopathic pulmonary arterial hypertension (IPAH), but its role in vascular remodeling of pulmonary hypertension (PH) is still unknown. In present study, we demonstrated that the plasma level of inflammatory cytokine including HMGB1, interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were elevated in hypoxia-induced pulmonary hypertension rats model. Moreover, expressions of HMGB1 and Toll like receptor-4 (TLR4) in pulmonary arteries were obviously up-regulated accompanied with down-regulation of bone morphogenetic protein receptor 2 (BMPR2) signaling, characterized by decline of phosphorylated Smad1/5/8 (p-Smsd1/5/8) and inhibitor of differention 1 (Id1) expression. In cultured primary pulmonary arterial smooth muscle cells (PASMCs), we found that HMGB1 incubation significantly promoted proliferation and migration of PASMCs, down-regulated p-Smsd1/5/8 and Id1 expression, which can be abrogated by HMGB1 inhibitors saquinavir, glycyrrhizn and TLR4 inhibitors TAK-242. Furthermore, saquinavir, glycyrrhizn and TAK-242 treatment significantly attenuated the development of PH in rats by recovering homodynamic parameters, pulmonary vascular remodeling and BMPR2 signaling pathway. In summary, our results suggest that HMGB1/TLR4 signaling promotes hypoxia-induced pulmonary hypertension via suppressing BMPR2 signaling.

Cost-effectiveness analysis of malaria rapid diagnostic tests: a systematic review.

BACKGROUND: Rapid diagnostic tests (RDT) can effectively manage malaria cases and reduce excess costs brought by misdiagnosis. However, few studies have evaluated the economic value of this technology. The purpose of this study is to systematically review the economic value of RDT in malaria diagnosis. MAIN TEXT: A detailed search strategy was developed to identify published economic evaluations that provide evidence regarding the cost-effectiveness of malaria RDT. Electronic databases including MEDLINE, EMBASE, Biosis Previews, Web of Science and Cochrane Library were searched from Jan 2007 to July 2018. Two researchers screened studies independently based on pre-specified inclusion and exclusion criteria. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was applied to evaluate the quality of the studies. Then cost and effectiveness data were extracted and summarized in a narrative way. Fifteen economic evaluations of RDT compared to other diagnostic methods were identified. The overall quality of studies varied greatly but most of them were scored to be of high or moderate quality. Ten of the fifteen studies reported that RDT was likely to be a cost-effective approach compared to its comparisons, but the results could be influenced by the alternatives, study perspectives, malaria prevalence, and the types of RDT. CONCLUSIONS: Based on available evidence, RDT had the potential to be more cost-effective than either microscopy or presumptive diagnosis. Further research is also required to draw a more robust conclusion.

[Protective effect of Dendrobium candidum on isoproterenol induced cardiac hypertrophy in rats].

To study the effect and mechanism of Dendrobium candidum on isoproterenol-induced myocardial hypertrophy in rats, 60 healthy SD rats(30 males and 30 females) were randomly divided into 5 groups(12 in each group): normal group, model group, three D. candidum preventive administration groups(0.09, 0.18, 1.1 g·kg⁻¹). Except for the normal group, rats of other groups were injected back subcutaneously with ISO(5 mg·kg⁻¹) for 10 consecutive days. At the same time, preventive administration groups began to give different doses of the sample for 30 days and model group began to give normal saline. Left ventricular systolic pressure(LVSP) was measured in each group by common carotid artery cannulation, and the left ventricle(LW)/tibia length, heart weight index(HWI) and myocardial hydroxyproline(Hydro) content were calculated. Myocardial tissue HE staining and Masson staining were used to observe the myocardial structure and the degree of myocardial fibrosis respectively. Atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), and cardiac troponin I(cTN-I) concentration were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that as compared with the normal group, the levels of ANP, BNP and cTN-I in plasma were significantly increased in ISO-induced hypertrophic rats; as compared with the model group, D. candidumcan inhibit ISO-induced ventricular pressure and ventricular hypertrophy, reduce myocardial collagen synthesis, improve myocardial fibrosis and ventricular remodeling, and significantly down-regulate ANP, BNP and cTN-I levels in plasma. This study shows that D. candidum has a protective effect on isoproterenol-induced cardiac hypertrophy.

Mucilaginibacter rubeus sp. nov., isolated from rhizosphere soil.

A Gram-stain-negative, aerobic, non-motile, rod-shaped and non-spore-forming bacterium, designated EF23T, was isolated from rhizosphere soil of watermelon. Growth of strain EF23T was observed at 10-37 °C, at pH 5.0-9.0 and in the presence of 0-0.5 % (w/v) NaCl. Strain EF23T contained menaquinone 7 (MK-7) as the major isoprenoid quinone, and summed feature 3 (C16:1ω7c and/or iso-C15 : 0 2-OH), iso-C15 : 0, C16 : 0 and iso-C17 : 0 3-OH as the major fatty acids. Phosphatidylethanolamine was identified as the major polar lipid. The genomic DNA G+C content of strain EF23T was 43.7 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain EF23T was most closely related to Mucilaginibacter gossypii Gh-67T (98.9 % similarity) and Mucilaginibacter gossypiicola Gh-48T (97.6 %). DNA-DNA relatedness values between strain EF23T and M. gossypii KCTC 22380T and M. gossypiicola KCTC 22379T were 31.6 and 53.7 %. On the basis of the evidence presented in this polyphasic taxonomic study, strain EF23T is considered to represent a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter rubeus sp. nov. is proposed. The type strain is EF23T (=CGMCC 1.15913T=KCTC 52516T).

Establishment of a Novel Mouse Model of Coronary Microembolization.

BACKGROUND: Coronary microembolization (CME) has been frequently seen in acute coronary syndromes and percutaneous coronary intervention. Small animal models are required for further studies of CME related to severe prognosis. This study aimed to explore a new mouse model of CME. METHODS: The mouse model of CME was established by injecting polystyrene microspheres into the left ventricular chamber during 15-s occlusion of the ascending aorta. Based on the average diameter and dosage used, 30 C57BL/6 male mice were randomly divided into five groups (n = 6 in each): 9 µm/500,000, 9 µm/800,000, 17 µm/200,000, 17 µm/500,000, and sham groups. The postoperative survival and performance of the mice were recorded. The mice were sacrificed 3 or 10 days after the surgery. The heart tissues were harvested for hematoxylin and eosin staining and Masson trichrome staining to compare the extent of inflammatory cellular infiltration and fibrin deposition among groups and for scanning transmission electron microscopic examinations to see the ultrastructural changes after CME. RESULTS: Survival analysis demonstrated that the cumulative survival rate of the 17 µm/500,000 group was significantly lower than that of the sham group (0/6 vs. 6/6, P = 0.001). The cumulative survival rate of the 17 µm/200,000 group was lower than those of the sham and 9 µm groups with no statistical difference (cumulative survival rate of the 17 µm/200,000, 9 µm/800,000, 9 µm/500,000, and sham groups was 4/6, 5/6, 6/6, and 6/6, respectively). The pathological alterations were similar between the 9 µm/500,000 and 9 µm/800,000 groups. The extent of inflammatory cellular infiltration and fibrin deposition was more severe in the 17 µm/200,000 group than in the 9 µm/500,000 and 9 µm/800,000 groups 3 and 10 days after the surgery. Scanning transmission electron microscopic examinations revealed platelet aggregation and adhesion, microthrombi formation, and changes in cardiomyocytes. CONCLUSION: The injection of 500,000 polystyrene microspheres at an average diameter of 9 µm is proved to be appropriate for the mouse model of CME based on the general conditions, postoperative survival rates, and pathological changes.

Suppression of Bim by microRNA-19a may protect cardiomyocytes against hypoxia-induced cell death via autophagy activation.

Microvascular obstruction (MO), one of unfavorable complications of percutaneous coronary intervention (PCI), is responsible for the lost benefit of reperfusion therapy. Determination of microRNA-19a, a member of the miR-17-92 cluster, using quantitative real-time polymerase chain reaction (PCR) revealed notably down-regulated microRNA-19a, in myocardium with MO. Nonetheless, the role of miR-19a in MO and the underlying mechanism remains to be elucidated. To this end, an in vitro microembolization model in cardiomyocytes was used. Our data revealed that hypoxic exposure prompted cardiomyocyte apoptosis in a time-dependent manner accompanied by reduced miR-19a. miR-19a overexpression clearly ameliorated hypoxia-induced cell death (necrosis and apoptosis), at least in part, through switching on autophagy. Further dual-luciferase reporter assay and immunoblotting studies demonstrated that miR-19a-induced cytoprotection might be achieved in part through modulation of the specific target Bcl-2 interacting mediator of cell death, Bim, an apoptotic activator. Bim sufficiently interfered with miR-19a-induced LC3 conversion and increased cardiomyocyte apoptosis under hypoxia. Moreover, cardiomyocytes pretreated with 3-methyladenine conferred resistance to the cytoprotective effect of miR-19a and displayed notably increased TUNEL staining and caspase-3 activity. In conclusion, miR-19a protected cardiomyocytes against hypoxia-induced lethality at least in part via Bim suppression and subsequently autophagy activation.

Factors associated with decreased bone mineral density in postmenopausal women with schizophrenia.

OBJECTIVE: This study examined the risk factors for decreased bone mineral density (BMD) in postmenopausal women with schizophrenia. METHODS: Cluster sampling method was adopted in this large-sample, cross-sectional study. A total of 219 postmenopausal female inpatients with schizophrenia were selected and interviewed in Beijing. The average age of the patients was 60.4±7.0 years. Clinical assessment instruments included the Positive and Negative Syndrome Scale (PANSS) and a questionnaire with detailed general information and disease-related investigations. Laboratory measurements included prolactin (PRL), estradiol, progesterone, thyroid stimulating hormone, FT3, and FT4. BMD testing was performed by dual-energy X-ray absorptiometry. RESULTS: The prevalence of osteoporosis or osteopenia was 66.2% (n=145). Decreased BMD was associated with age, illness duration, therapeutic dose (equivalent chlorpromazine dose), treatment duration, PANSS-negative scores, body mass index (BMI), daily exercises (min/d), drinking (unit/wk), PRL, and estradiol. Multiple logistic regression analysis revealed that age, treatment duration, PANSS-negative score, BMI, and PRL were significantly associated with decreased BMD. CONCLUSION: Prevalence of BMD loss was higher in Chinese postmenopausal women with schizophrenia compared to the normal BMD group. A combination of demographic and clinical factors play important roles in determining decreased BMD, including older age, longer treatment duration, more PANSS-negative scores, higher BMI, and higher PRL level.

The tumor suppressor PTEN has a critical role in antiviral innate immunity.

The gene encoding PTEN is one of the most frequently mutated tumor suppressor-encoding genes in human cancer. While PTEN's function in tumor suppression is well established, its relationship to anti-microbial immunity remains unknown. Here we found a pivotal role for PTEN in the induction of type I interferon, the hallmark of antiviral innate immunity, that was independent of the pathway of the kinases PI(3)K and Akt. PTEN controlled the import of IRF3, a master transcription factor responsible for IFN-ß production, into the nucleus. We further identified a PTEN-controlled negative phosphorylation site at Ser97 of IRF3 and found that release from this negative regulation via the phosphatase activity of PTEN was essential for the activation of IRF3 and its import into the nucleus. Our study identifies crosstalk between PTEN and IRF3 in tumor suppression and innate immunity.

[Effects of rice-duck mutualistic organic farming on rice quality in the Yellow River Delta, China.] / ç¨»é¸­å ±ç”Ÿæœ‰æœºæ ½åŸ¹æ¨¡å¼å¯¹é»„æ²³ä¸‰è§’æ´²ç¨»ç±³å“è´¨çš„å½±å“.

Three cultivation models including rice-duck mutualistic, manual weeding and conventional rice farming were designed in the Yellow River Delta area to study the effects on rice milling quality, appearance quality, cooking and eating quality, and sanitation quality. The results showed that compared to conventional rice farming, the rice-duckmutualistic treatment increased grain width and brown rice rate, milled rice rate, head rice rate and reduced the chalkiness. This was mainly due to the increase of panicle numbers and grain mass and the decrease of the inferior grains. Due to the application of organic manure, the gel consistency increased, amylose and protein contents decreased, and the rice taste improved under rice-duck mutualistic and manual weeding cultivation treatments. As no chemical fertilizers and pesticides were applied under rice-duck mutualistic and manual weeding treatments, pesticide residues were greatly reduced or even not detected. Rice duck farming could improve the quality of rice and protect the environment, which would be a good ecological technology for high quality rice production.

Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction.

BACKGROUND: Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro. METHODS: Isolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups. RESULTS: Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures. CONCLUSION: These results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function.