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1.
J Ethnopharmacol ; 247: 112273, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31586692

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Luohanguo (LHG), a traditional Chinese medicine, could clear heat, moisten the lung, soothe the throat, restore the voice, and lubricate intestine and open the bowels. LHG has been utilized for the treatment of sore throats and hyperglycemia in folk medicine as a homology of medicine and food. The hypoglycemic pharmacology of LHG has attracted considerable attention, and mogrosides have been considered to be active ingredients against diabetes mellitus. We have found that these mogrosides could be metabolized into their secondary glycosides containing 1-3 glucose residues in type 2 diabetes mellitus (T2DM) rats in previous studies. These metabolites may be the antidiabetic components of LHG in vivo. Thus far, no reports have been found on reducing blood glucose of mogrosides containing 1-3 glucose residues. AIMS OF THE STUDY: The aim of this study was to confirm that mogrosides containing 1-3 glucose residues were the active components of LHG for antidiabetic effects and to understand their potential mechanisms of action. MATERIALS AND METHODS: First, the special fraction of mogrosides containing 1-3 glucose residues was separated from a 50% ethanol extract of LHG, and the chemical components were identified by ultra-performance liquid chromatography (UPLC) and named low-polar Siraitia grosvenorii glycosides (L-SGgly). Second, the antidiabetic effects of L-SGgly were evaluated by HFD/STZ-induced (high-fat diet and streptozocin) obese T2DM rats by indexing fasting blood glucose (FBG), fasting insulin (FINS), and insulin resistance, and then compared with other fractions in the separation process. The changes in serum lipid levels were also detected. Finally, possible mechanisms of antidiabetic activity of L-SGgly were identified as increasing GLP-1 levels and activating liver AMPK in T2DM rats. RESULTS: The chemical analysis of L-SGgly showed that they contain 11-oxomogroside V, mogroside V, mogroside III, mogroside IIE, mogroside IIIA1, mogroside IIA1, and mogroside IA1, respectively. The total content of the mogrosides in L-SGgly was 54.4%, including 15.7% mogroside IIA1 and 12.6% mogroside IA1. L-SGgly showed excellent effects on obese T2DM rats compared with the other fractions of LHG extract, including significantly reducing the levels of FBG (p < 0.001) and modifying insulin resistance (p < 0.05). Meanwhile, they could significantly decrease the content of triglyceride (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and free fatty acid (p < 0.001) and increase the content of high-density lipoprotein cholesterol (p < 0.001) in serum of T2DM rats. Moreover, L-SGgly can significantly increase (p < 0.01) GLP-1 levels and decrease (p < 0.01) IL-6 levels in T2DM rat serum. AMPK-activating activity in T2DM rats was also upregulated by L-SGgly, but no statistical significance was shown. CONCLUSION: L-SGgly, fractions separated from LHG extract, were verified to have obvious anti-hyperglycemic and anti-hyperlipidemic effects on T2DM rats. Furthermore, L-SGgly regulated insulin secretion in T2DM rats by increasing GLP-1 levels. These findings provide an explanation for the antidiabetic role of LHG.

2.
Endocrine ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591683

RESUMO

PURPOSE: As the treatment regimens such as metformin could confound the correlation between type 2 diabetes (T2D) and gut microbiome, we should revisit the relationship between gut microbiota and T2D patients who are not currently treated with metformin. METHODS: The study recruited 65 T2D patients: 49 with and 16 without diabetic complications, and 35 healthy controls. We sequenced the 16S rRNA V3-V4 region of gut microbiota and detected metabolites based on liquid chromatography mass spectrometry (LC/MS) and gas chromatography mass spectrometry (GC/MS) in faecal samples. RESULTS: The composition of both the gut microbiota and faecal metabolites changed significantly with T2D patients. The abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes were higher in T2D patients than healthy subjects, and the short chain fatty acids (SCFAs), bile acids and lipids of T2D patients were significantly disordered. Moreover, the abundances of certain SCFA-producing bacteria (Lachnospiraceae and Ruminococcaceae etc.) were significantly increased in T2D patients, while the faecal SCFAs concentrations were significantly decreased. It's suggested that the role of SCFA-producing bacteria was not simply to produce SCFAs. Then we identified 44 microbial modules to explore the correlations between the gut microbiota and metabolic traits. Specially, most modules including certain SCFA-producing bacteria were comprehensively correlated to body mass index, the levels of blood glucose, blood pressure, blood cholesterol and faecal bile acids and lipids. CONCLUSIONS: Our study identified the relationships between the gut microbiota and faecal metabolites, and provided a resource for future studies to understand host-gut microbiota interactions in T2D.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31615166

RESUMO

In order to investigate the issues of the recycling and remanufacturing of construction and demolition waste (C&D waste), this paper develops a closed-loop supply chain (CLSC) consisting of a manufacturer, a retailer, and a recycler, considering both the retailer's fairness concern psychology and governmental regulations. Four mathematical models are developed for the calculations, and the models are solved through game theory. In both the decentralized and centralized scenarios, the members' strategies are discussed and the optimal values of decision variables are determined. A numerical study is carried out for sensitivity analyses to verify the accuracy of the theoretical conclusions. The results reveal that retailer fairness concerns lead to a decrease in the wholesale price of building materials and negatively affect manufacturers' profits. Additionally, governmental regulations can effectively increase the recycling amount and improve the utilization rate of C&D waste, and promote a virtuous cycle of the recycling and remanufacturing of C&D waste.

4.
Sci Rep ; 9(1): 14342, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586102

RESUMO

The interest in thermoelectrics (TE) for an electrical output power by converting any kind of heat has flourished in recent years, but questions about the efficiency at the ambient temperature and safety remain unanswered. With the possibility of integration in the technology of semiconductors based on silicon, highly harvested power density, abundant on earth, nontoxicity, and cost-efficiency, Si1-x-yGexSny ternary alloy film has been investigated to highlight its efficiency through ion implantation and high-temperature rapid thermal annealing (RTA) process. Significant improvement of the ambient-temperature TE performance has been achieved in a boron-implanted Si0.864Ge0.108Sn0.028 thin film after a short time RTA process at 1100 °C for 15 seconds, the power factor achieves to 11.3 µWcm-1 K-2 at room temperature. The introduction of Sn into Si1-xGex dose not only significantly improve the conductivity of Si1-xGex thermoelectric materials but also achieves a relatively high Seebeck coefficient at room temperature. This work manifests emerging opportunities for modulation Si integration thermoelectrics as wearable devices charger by body temperature.

5.
Theranostics ; 9(23): 6962-6975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31660080

RESUMO

Purpose: Positron emission tomography (PET) imaging of apoptosis is very important for early evaluation of tumor therapeutic efficacy. A stimuli-responsive probe based on the peptide sequence Asp-Glu-Val-Asp (DEVD), [18F]DEVD-Cys(StBu)-PPG(CBT)-AmBF3 ([18F]1), for PET imaging of tumor apoptosis was designed and prepared. This study aimed to develop a novel smart probe using a convenient radiosynthesis method and to fully examine the sensitivity and specificity of the probe response to the tumor treatment. Methods: The radiolabelling precursor DEVD-Cys(StBu)-PPG(CBT)-AmBF3 (1) was synthesized through multistep reactions. The reduction together with caspase-controlled macrocyclization and self-assembly of 1 was characterized and validated in vitro. After [18F]fluorination in the buffer (pH= 2.5), the radiolabelling yield (RLY), radiochemical purity (RCP) and stability of the probe [18F]1 in PBS and mouse serum were investigated by radio-HPLC. The sensitivity and specificity of [18F]1 for detecting the drug-induced apoptosis was fully evaluated in vitro and in vivo. The effect of cold precursor 1 on the cell uptake and tumor imaging of [18F]1 was also assessed. The level of activated caspase-3 in Hela cells and tumors with or without apoptosis induction was analyzed and compared by western blotting and histological staining. Results: The whole radiosynthesis process of [18F]1 was around 25 min with RLY of 50%, RCP of over 99% and specific activity of 1.45 ± 0.4 Ci/µmol. The probe was very stable in both PBS and mouse serum within 4 h. It can be activated by caspase-3 and then undergo an intermolecular cyclization to form nanosized particles. The retained [18F]1 in DOX-treated HeLa cells was 2.2 folds of that in untreated cells. Within 1 h microPET imaging of the untreated Hela-bearing mice, the injection of [18F]1 resulted in the increase of the uptake ratio of tumor to muscle (T/M) only from 1.74 to 2.18, while in the DOX-treated Hela-bearing mice T/M increased from 1.88 to 10.52 and the co-injection of [18F]1 and 1 even led to the increase of T/M from 3.08 to 14.81. Conclusions: A caspase-responsive smart PET probe [18F]1 was designed and prepared in a kit-like manner. Co-injection of [18F]1 and 1 generated remarkably enhanced tumor uptake and signal-to-noise ratio in the tumor-bearing mice with drug-induced apoptosis, which correlated well with the expression level of activated caspase-3. This early readout of treatment response ensured that the probe [18F]1 could serve as a promising PET imaging probe for timely and noninvasive evaluation of tumor therapy.

6.
Genes (Basel) ; 10(10)2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615047

RESUMO

Adipose tissue is one of the main organs for the energy storage and supply of organisms. Adipose deposition and metabolism are controlled by a cascade of transcription factors and epigenetic regulatory mechanisms. Previous studies have also shown that miR-106a plays a considerable role in the development of organisms. The regulatory mechanism of miR-106a on porcine preadipocytes is still not clear. In this study, preadipocytes were isolated from the neck subcutaneous deposits of 3-5-day old Chinese native Guanzhong black pigs using 5-ethynyl-20-deoxyuridine (EdU) staining and a CCK-8 assay to detect the number of proliferous cells and real-time qPCR (RT-qPCR) and western blot analysis to detect gene expression, as well as Oil Red O and BODIPY staining dye lipid droplets and flow cytometry (FCM) to detect cell cycles. We also used the double luciferase method to detect the relative luciferase activities. Upregulated miR-106a increased the number of proliferous cells and enhanced the expression of cell proliferation-related genes in porcine adipocytes. The double luciferase reporter vector confirmed that p21 was a target gene of miR-106a in the cell proliferation phase. miR-106a upregulation increased the number of lipid droplets and the expression of lipogenic genes and directly targeted BMP and activin membrane-bound inhibitor (BAMBI) in the process of differentiation. Our results indicated that miR-106a promotes porcine preadipocyte proliferation and differentiation by targeting p21 and BAMBI.

7.
Chemosphere ; 236: 124392, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545195

RESUMO

Uranium (U) contamination of soil has become a major concern with respect to its toxicity, accumulation in the food chain, and persistence in the environment. Anthropogenic activities like mining and processing of U ores has become pressing issues throughout the world. The aim of the work is to understand the chemical fractionation of U in polluted soil and the mechanism involved. U-free soils samples of eluvial (E), illuvial (B), and parent-material (C) horizons from a hydrometallurgical factory area were used. The experimental results showed that the U adsorption capacity decreased with depth, and its mobility in the upper soil is better than the lower. It was closely related to distribution coefficient (Kd), pH, organic-matter (OM), and carbonate content of soil horizons. The chemical fractionation of U was studied using the BCR sequential extraction scheme for soils after saturated adsorption. It was noted that the U reducible and oxidizable fraction in the E and B horizons can vertically transfer to the C horizon and occurs a significant rearrangement of U in different horizons. BET, SEM, XRD, and FT-IR analyses showed that different U distribution and migration in soil profile is mainly affected by specific surface area, soil particle size, mineral composition, and active groups. The XPS data further indicated that U (VI) is gradually converted to U (IV) with decreased depth and fixed in deeper soil becoming insoluble and immobile. It is the first step to investigate potential migration and plan U mining and milling area long-term management.

8.
J Neurophysiol ; 122(5): 1874-1883, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483699

RESUMO

In neonates, catecholamine (CA) secretion from adrenal medullary chromaffin cells (AMC) is an important mechanism for maintaining homeostasis during hypoxia. Nearly 90% of premature infants experience chronic intermittent hypoxia (IH) because of high incidence of apnea of prematurity, which is characterized by periodic stoppage of breathing. The present study examined the effects of repetitive hypoxia, designed to mimic apnea of prematurity, on CA release from AMC of neonatal rats. Neonatal rats were exposed to either control conditions or chronic intermittent hypoxia (IH) from ages postnatal days 0-5 (P0-P5), and CA release from adrenal medullary slices was measured after challenge with repetitive hypoxia (5 episodes of 30-s hypoxia, Po2 ~35 mmHg). In response to repetitive hypoxia, chronic IH-treated AMC exhibited sustained CA release, and this phenotype was not seen in control AMC. The sustained CA release was associated with long-lasting elevation of intracellular Ca2+ concentration ([Ca2+]i), which was due to store-operated Ca2+ entry (SOCE). 2-Aminoethoxydiphenyl borate, an inhibitor of SOCE, prevented the long-lasting [Ca2+]i elevation and CA release. Repetitive hypoxia increased H2O2 abundance, and polyethylene glycol (PEG)-catalase, a scavenger of H2O2 blocked this effect. PEG-catalase also prevented repetitive hypoxia-induced SOCE activation, sustained [Ca2+]i elevation, and CA release. These results demonstrate that repetitive hypoxia induces long-term facilitation of CA release in chronic IH-treated neonatal rat AMC through sustained Ca2+ influx mediated by SOCE.NEW & NOTEWORTHY Apnea of prematurity and the resulting chronic intermittent hypoxia are major clinical problems in neonates born preterm. Catecholamine release from adrenal medullary chromaffin cells maintains homeostasis during hypoxia in neonates. Our results demonstrate that chronic intermittent hypoxia induces a hitherto uncharacterized long-term facilitation of catecholamine secretion from neonatal rat chromaffin cells in response to repetitive hypoxia, simulating hypoxic episodes encountered during apnea of prematurity. The sustained catecholamine secretion might contribute to cardiovascular morbidities in infants with apnea of prematurity.

9.
Drug Metab Dispos ; 47(11): 1281-1290, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31484654

RESUMO

Benzbromarone (BBR), a uricosuric agent, has been known to induce hepatotoxicity, and its toxicity has a close relation to cytochrome P450-mediated metabolic activation. An oxidative debromination metabolite of BBR has been reported in microsomal incubations. The present study attempted to define the oxidative debromination pathway of BBR in vivo. One urinary mercapturic acid (M1) and one glutathione (GSH) conjugate (M2) derived from the oxidative debromination metabolite were detected in BBR-treated mice after solid phase extraction. M1 and M2 shared the same chromatographic behavior and mass spectral identities as those detected in N-acetylcysteine/GSH- and BBR-fortified microsomal incubations. The structure of M1 was characterized by chemical synthesis, along with mass spectrometry analysis. In addition, hepatic protein modification that occurs at cysteine residues (M'3) was observed in mice given BBR. The observed protein adduction reached its peak 4 hours after administration and occurred in a dose-dependent manner. A GSH conjugate derived from oxidative debromination of BBR was detected in livers of mice treated with BBR, and the formation of the GSH conjugate apparently took place earlier than the protein adduction. In summary, our in vivo work provided strong evidence for the proposed oxidative debromination pathway of BBR, which facilitates the understanding of the mechanisms of BBR-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This study investigated the oxidative debromination pathway of benzbromarone (BBR) in vivo. One urinary mercapturic acid (M1) and one glutathione (GSH) conjugate (M2) derived from the oxidative debromination metabolite were detected in BBR-treated mice. M1 and M2 were also observed in microsomal incubations. The structure of M1 was characterized by chemical synthesis followed by mass spectrometry analyses. More importantly, protein adduction derived from oxidative debromination of BBR (M'3) was observed in mice given BBR, and occurred in dose- and time-dependent manners. The success in detection of GSH conjugate, urinary N-acetylcysteine conjugate, and hepatic protein adduction in mice given BBR provided solid evidence for in vivo oxidative debromination of BBR. The studies allowed a better understanding of the metabolic activation of BBR.

10.
Brain Behav ; 9(10): e01398, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31532082

RESUMO

OBJECTIVES: Approximately, half of the acute stroke patients with minor symptoms were excluded from thrombolysis in some randomized controlled trials (RCTs). There is little evidence on treating minor strokes with rt-PA. Here, we performed a systematic review and meta-analysis to assess the safety and efficacy of thrombolysis in these patients. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched in July 2018. All available RCTs and retrospective comparative studies that compared thrombolysis with nonthrombolysis' for acute minor stroke (NIHSS ≤ 5) with quantitative outcomes were included. RESULTS: Ten studies, including a total of 4,333 patients, were identified. The risk of intracranial hemorrhage (ICH) was higher in the rt-PA group as compared with that in the non-rt-PA group (3.8% vs. 0.6%; p = .0001). However, there is no significant difference in the rate of mortality between the two groups (p = .96). The pooled rate of a good outcome in 90 days was 67.8% in those with rt-PA and 63.3% in those without rt-PA (p = .07). Heterogeneity was 43% between the studies (p = .08). After adjusting for the heterogeneity, thrombolysis was associated with good outcome (68.3% vs. 63.0%, OR 1.47; 95% CI 1.14-1.89; p = .003). In post hoc analyses, including only RCTs, the pooled rate of good outcome had no significant differences between the two groups (86.6% vs. 85.7%, 95% CI 0.44-3.17, p = .74; 87.4% vs. 91.9%, 95% CI 0.35-1.41, p = .32; before and after adjusting separately). CONCLUSIONS: Although thrombolysis might increase the risk of ICH based on existing studies, patients with acute minor ischemic stroke could still benefit from thrombolysis at 3 months from the onset.

11.
Chem Res Toxicol ; 32(9): 1791-1800, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31414593

RESUMO

Tofacitinib (TFT) is an oral JAK inhibitor which has been approved for the treatment of moderately and severely active rheumatoid arthritis. TFT was found to show concentration-, time-, and NADPH-dependent inhibition of CYP3A4, and irreversibility of the inactivation was also observed. Incubation (40 min, 37 °C) of recombinant CYP3A4 with TFT at 200 µM resulted in >70% loss of CYP3A4 activity. Estimated kinact and KI were 0.037 min-1 and 93.2 µM, respectively. GSH and superoxide dismutase/catalase revealed minor or little protection against the CYP3A4 inactivation. Furthermore, ketoconazole attenuated TFT-mediated CYP3A4 inactivation. Epoxide and α-keto-aldehyde intermediates of TFT were trapped and characterized in microsomal incubations, respectively. The aldehyde intermediate is believed to be the key for the enzyme inactivation. Multiple P450 enzymes, including CYPs2C19, 3A4, 2D6, and 1A2, participated in the metabolism of TFT to the epoxide, while the formation of the aldehyde was mainly catalyzed by CYP3A4. In conclusion, TFT was proven to be a mechanism-based inactivator of CYP3A4.

12.
Eur J Med Chem ; 181: 111582, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398615

RESUMO

5-Aminolevulinic acid (5-ALA) and its two ester derivatives (5-ALA-OMe and 5-ALA-OHex) have been approved for photodiagnosis and photodynamic therapy (PDT) of tumors in the clinical. However, their pharmacological activities are limited by their instability under physiological conditions and lack of tumor selectivity. With the aim to overcome these shortcomings, a glutathione-responsive 5-ALA derivative (SA) was designed based on the fact that many types of tumor cells have higher intracellular glutathione level than normal cells. SA was synthesized by masking the 5-amion group of 5-ALA methyl ester (5-ALA-OMe) with a self-immolative disulfide linker. Compared with 5-ALA and 5-ALA-OMe, SA exhibited higher stability under physiological conditions, and it can efficiently release the parent compound 5-ALA-OMe in response to glutathione. In tumor cells, SA displayed excellent protoporphyrin IX (PpIX) production activity at low concentrations while 5-ALA and 5-ALA-OMe were ineffective at the same concentration. The SA-induced PpIX production was positively correlated with the intracellular glutathione level, and SA exhibited enhanced phototoxicity due to its excellent PpIX generation activity. This study indicates that modification of the amino group in 5-ALA derivatives with a self-immolative disulfide linker is an effective strategy to improve their chemical stability and pharmacological activities, and SA is a potential photosensitizer for photodiagnosis and PDT of tumors.

13.
Oncogene ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427735

RESUMO

MicroRNAs (miRNAs) have been shown to be involved in the progression and tumor microenvironment of glioblastoma multiforme (GBM). Our previous research has indicated that miR-340-5p has an antitumor effect in vitro. However, the role of miR-340-5p in GBM has not been fully elucidated. Here, we show that downregulation of miR-340-5p in GBM is correlated with tumor size, recurrence, and poor survival. Moreover, we found that miR-340-5p levels are correlated with the density of tumor-associated macrophages (TAMs) and M2-polarized TAMs in GBM. Biofunctional investigations revealed that downregulation of miR-340-5p promoted TAM recruitment and M2-TAMs polarization in vitro and in vivo. In addition, we found that upregulation of miR-340-5p inhibited tumor growth and was associated with good prognosis in vivo. Through gene expression profiles and bioinformatics analysis, we showed that miR-340-5p directly targets POSTN, which recruited TAMs through integrin αvß3. Downregulation of miR-340-5p in GBM did not induce the differentiation of TAMs into polarized M2 cells but was able to promote the M2 polarization of TAMs through directly targeting LTBP-1. Furthermore, we found that M2-TAMs promoted tumorigenesis and were associated with a poor prognosis in vivo. In an in vitro study, we demonstrated that M2-TAMs inhibited miR-340-5p expression in GBM cells by upregulation of TGFß-1, which increased HMGA-2 expression in GBM. A ChIP assay confirmed that HMGA-2 transcriptionally suppressed miR-340-5p expression. Patients with low-miR-340-5p expression, high CD163, high POSTN, high LIBP1 levels, and high HMGA-2 had a poor prognosis with shorter overall survival, confirming data from the TCGA database. These findings suggest that an miR-340-5p-macrophage feedback loop modulates the progression and tumor microenvironment of GBM and may represent a prognostic biomarker and therapeutic strategy for GBM.

14.
Int J Biol Macromol ; 140: 727-735, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31437498

RESUMO

The osteoimmune environment plays indispensable roles in bone regeneration because it determines subsequent osteogenesis and osseointegration. Eucommia ulmoides polysaccharide (EUP) was proved to be an effective biomaterial that has immunomodulatory effects for improving the biomechanical quality of bone. Strontium is a trace element that inhibits inflammation and promotes bone growth. To develop a novel EUP-based osteoimmunomodulatory biomaterial with potentially enhanced bone regeneration, we synthesized strontium Eucommia ulmoides polysaccharides (EUP-Sr) and evaluated its morphology, structure and thermal stability. The materials characterization results confirmed that strontium was successfully introduced into the EUP and formed a new complex with thermal-stable property. The cytocompatibility evaluation of different concentrations of EUP-Sr by CCK8 assay suggested that EUP-Sr is beneficial to the macrophages proliferation. We further evaluated the gene expressions of RAW 264.7 cells treated with EUP-Sr. It was found that EUP-Sr could suppress inflammatory factors and osteoclastogenesis, and enhance the expressions of osteogenic factors of RAW 264.7 cells. Therefore, EUP-Sr should be a promising bioactive compound with the capability to create a positive pro-regenerative environment for skeleton tissue engineering.

15.
Int J Infect Dis ; 88: 34-40, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31374346

RESUMO

BACKGROUND: Tuberculosis (TB) is a critical global public threat, and limited epidemiology studies have been performed to explore the efficacy of active TB screening. METHODS: Three sites located in eastern China were chosen in 2013, and three rounds of systematic screenings were performed in permanent residents aged older than 15 years. RESULTS: The TB incidence showed a downtrend after several rounds of active screening at the three sites, and a significant change was observed at site A in the overall population. In the target population at sites A and B, both the elderly and people with a history of TB had a remarkable decline through the first or second round of screening. The implementation of active case-finding identified 2.36 [1.47,3.81] (2013 vs. 2012) and 1.49 [1.1,2.03] (2013-2015 vs. 2010-2012) more potential cases than the passive case-finding by the surveillance system at site A. CONCLUSIONS: Active case-finding of tuberculosis might be effective in high prevalence area with a low economic level, particularly among the elderly and people with a history of TB. Additionally, new rapid diagnosis technology should be considered to decrease the prevalence among people with a history of TB. Ultimately, active screening identified more active TB cases than passive case-finding, particularly in high prevalence area with underdeveloped economics.

16.
Brain Behav Immun ; 82: 63-75, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376498

RESUMO

Chronic excessive drinking leads to a wide spectrum of neurological disorders, including cognitive deficits, such as learning and memory impairment. However, the neurobiological mechanisms underlying these deleterious changes are still poorly understood. We conducted a comprehensive study to investigate the role and mechanism of autophagy in alcohol-induced memory impairment. To establish an ethanol-induced memory impairment mouse model, we allowed C57BL/6J mice intermittent access to 20% ethanol (four-bottle choice) to escalate ethanol drinking levels. Memory impairment was confirmed by a Morris water maze test. We found that mice exposed to EtOH (ethanol) and EtOH combined with the autophagy inhibitor 3-methyladenine (3-MA) showed high alcohol intake and blood alcohol concentration. We confirmed that the EtOH group exhibited notable memory impairment. Inhibition of autophagy by 3-MA worsened ethanol-induced memory impairment. Ethanol induced autophagy in the hippocampus of mice as indicated by western blotting, electron microscopy, RT-qPCR, and fluorescence confocal microscopy. We determined that the mTOR/BECN1 (S14) pathway is involved in ethanol-induced autophagy in vivo. Further, ethanol-induced autophagy suppressed the NLRP3 inflammatory and apoptosis pathways in the hippocampus in mice and in vitro. These findings suggest that autophagy activation in hippocampal cells alleviates ethanol-induced memory impairment in association with anti-apoptotic and anti-inflammatory pathways.

17.
ACS Appl Mater Interfaces ; 11(31): 27503-27511, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31291088

RESUMO

Poly(ether ether ketone) (PEEK) is a promising material in biomedical engineering due to its suitable mechanical properties and excellent chemical resistance and biocompatibility. However, the biological inertness of PEEK limits its applications. In this study, we developed a facile approach of immersion to generate a biocompatible and bioactive PEEK that induced osteodifferentiation. First, micropores on the surface of PEEK were introduced by concentrated sulfuric acid and subsequent water immersion, followed by the hydrothermal treatment to reduce residual sulfuric acid. Subsequently, the sulfonated PEEK surface was activated by the oxygen plasma treatment and then coated with a poly(dopamine) (PDA) layer by immersion into the dopamine solution. Finally, the tripeptide Arg-Gly-Asp (RGD) was integrated onto the PDA-coated surface of PEEK by immersion into the RGD peptide solution. The surface characteristics (physical chemistry and biological properties) and the ability to form bonelike apatite were systematically investigated by scanning electron microscopy, X-ray photoelectron spectroscopy, water contact angle analysis, the Archimedes' fluid saturation method, ellipsometry, a quartz crystal microbalance with dissipation monitoring, cell proliferation, real-time reverse transcription polymerase chain reaction analysis, alizarin red staining, immunocytochemistry staining, and simulated body fluid immersion. Collectively, the modified PEEK showed a significantly improved ability to promote cell proliferation, osteogenic differentiation, and bonelike apatite formation in vitro as compared to the PEEK control. These results demonstrate that combined facile surface modifications for PEEK enhance its bioactivity and biocompatibility, and induce osteodifferentiation. This study presents a strategy for broadening the use of PEEK in the application of orthopedic implants and could be industrially scalable in future.

18.
Environ Int ; 130: 104952, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31260929

RESUMO

Numerous studies have reported bioaccumulation of halogenated flame retardants (HFRs) and polychlorinated biphenyls (PCBs) in wildlife from electronic waste (e-waste) recycling sites. However, the concentrations and hazards of HFRs and PCBs in wildlife from non-e-waste sites which were not involved in any known e-waste recycling activities in the e-waste-impacted region are still unclear. Polybrominated diphenyl ethers (PBDEs), alternative HFRs (AHFRs; including dechlorane plus, decabromodiphenyl ethane, and 1,2-bis(2,4,6-tribromophenoxy) ethane), and PCBs were quantified in common kingfishers (Alcedo atthis) from a region affected by e-waste recycling in South China, and potential adverse effects were evaluated. Concentrations of ∑PBDEs and ∑PCBs in kingfishers ranged from 2.1 × 103-1.3 × 105 ng/g lipid mass (lm) and 2.1 × 103-1.5 × 106 ng/g lm, respectively. At e-waste recycling sites, these concentrations were 100- to 1000-fold greater than those in kingfishers from non-e-waste areas, where concentrations of ∑PBDEs and ∑PCBs were 16-1.2 × 103 and 39-3.0 × 103 ng/g lm, respectively. Concentrations of ∑AHFRs in kingfishers from e-waste sites and non-e-waste sites ranged from 8.5 to 3.6 × 102 and 0.8-2.9 × 102 ng/g lm, respectively. The greatest concentrations of PCBs in kingfishers were measured from the e-waste sites. Additionally, kingfishers from four non-e-waste sites in the vicinity of e-waste sites had greater PCB concentrations compared to the other six non-e-waste sites. Concentrations of AHFRs were negatively and significantly correlated with distance from an e-waste site, which indicated that AHFRs from non-e-waste sites might be influenced by point sources. Further, a significant (r2 = 0.53, p = 0.02) positive correlation between human population density and concentrations of ∑PBDEs in kingfishers from non-e-waste sites was observed. Concentrations of either PBDEs or PCBs from e-waste sites might pose severe, adverse reproductive effects to kingfishers, while the potential for adverse effects of PBDEs and PCBs to kingfishers from most non-e-waste sites seemed minimal.

19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 704-707, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302916

RESUMO

OBJECTIVE: To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy. METHODS: Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed. RESULTS: The karyotype of the child was determined as 46, XX; SNP array: arr [19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo. CONCLUSION: A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.


Assuntos
Deficiências do Desenvolvimento/genética , Epilepsia/genética , Deficiência Intelectual/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Deleção de Sequência , Criança , Estudos de Associação Genética , Humanos , Cariotipagem
20.
BMC Psychiatry ; 19(1): 220, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299940

RESUMO

BACKGROUND: Among patients with treatment-resistant schizophrenia (TRS), some exhibited further clozapine resistance (CR). This study aimed to investigate whether greater severity of treatment resistance in schizophrenia is associated with greater impairments in sustained attention. METHODS: Patients with a DSM-IV-defined schizophrenia were recruited from a psychiatric center in northern Taiwan (April 2010 to October 2010). Both TRS and CR were determined retrospectively from participants' medical records following the consensus guidelines. The patients were divided into three groups: 102 non-TRS, 48 TRS without CR, and 54 TRS with CR. They underwent both undegraded and degraded Continuous Performance Tests (CPT), and their performance scores (d') were standardized against a community sample to derive age-, sex-, and education-adjusted z scores. RESULTS: The TRS with CR group had significantly lower adjusted z scores of d' on both undegraded and degraded CPTs than the other two groups. Meanwhile, the differences between the TRS without CR group and the non-TRS group were not significant. Multivariable linear regression analyses with adjustment for covariates revealed a trend of gradient impairments on the degraded CPT from non-TRS to TRS without CR and to TRS with CR. The proportions of attentional deficits (an adjusted z score of ≤ - 2.5) on the degraded CPT also exhibited a significant trend, from 36.3% in the non-TRS group to 62.5% in the TRS without CR group and to 83.3% in the TRS with CR group. CONCLUSIONS: Greater severity of treatment resistance in schizophrenia was associated with greater impairments in sustained attention, indicating some common vulnerability.

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