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1.
Acta Biomater ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513911

RESUMO

Gold nanoprisms (GNPs) have been broadly studied for the potential applications in both imaging and treatment on tumors due to their special characteristics. Herein we reported that a new nanoplatform GNPs@PSS/PDADMAC-siRNA (GNPs-siRNA) was designed and fabricated by sequentially coating the GNPs with poly (sodium 4-styrenesulfonate) (PSS) and poly (-diallyldimethylammonium chloride) (PDADMAC) to carry small interfering RNA (siRNA). Human program death-ligand 1 (PD-L1) was recently known to be crucial for cancer cell survival through the intrinsic signaling activities, besides serving as an important checkpoint gene in immune system. We successfully attached the human PD-L1 siRNA to the surface of GNPs@PSS/PDADMAC to obtain the GNPs-hPD-L1 siRNA nanoplatform. Real Time Cellular Analysis (RTCA) assay demonstrated that GNPs-hPD-L1 siRNA exhibited remarkable capacity to inhibit the proliferation of human lung cancer cells. Subsequent in vitro and in vivo experiments verified that the GNPs-hPD-L1 siRNA not only functioned as a carrier for siRNA delivery to down-regulate the hPD-L1 expression, but also served for photoacoustic (PA) imaging and photothermal agents for photothermal therapy (PTT) in both human lung cancer cells and human lung cancer cells-derived tumors. Our findings could be expected to provide an innovative direction for future clinical transformation application. STATEMENT OF SIGNIFICANCE: To our knowledge, this is the first paper related to the hPD-L1 siRNA delivery combined with the gold nanoparticles, especially the gold nanoprisms. The as-prepared GNPs-hPD-L1 siRNA nanoplatform not only functioned as a carrier for siRNA delivery to down-regulate the PD-L1 expression, but also acted as photothermal agents for theranostic effects in both human lung cancer cells and human lung cancer cells-derived tumors. The as-prepared GNPs-hPD-L1 siRNA nanoplatform could knock down human PD-L1 gene expression, which caused the inhibition on proliferation of human lung cancer cell in vitro or in vivo. The as-prepared GNPs-hPD-L1 siRNA nanoplatform possessed excellent photoacoustic imaging ability and photothermal therapy effects.

2.
Microbiome ; 7(1): 116, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439031

RESUMO

BACKGROUND: Inflammasomes have been found to interact with the gut microbiota, and this effect is associated with depression, but the mechanisms underlying this interaction have not been elucidated in detail. RESULTS: The locomotor activity of NLRP3 KO mice was significantly greater than that of their WT littermates, while cohousing and transplantation of the NLRP3 KO gut microbiota avoid the effects of NLRP3 KO on the general locomotor activity at baseline. Meanwhile, transplantation of the NLRP3 KO microbiota alleviated the CUS-induced depressive-like behaviors. The compositions of the gut microbiota in NLRP3 KO mice and WT mice were significantly different in terms of the relative abundance of Firmicutes, Proteobacteria, and Bacteroidetes. Fecal microbiota transplantation (FMT) from NLRP3 KO mice significantly ameliorated the depressive-like behavior induced by chronic unpredictable stress (CUS) in recipient mice. Given the correlation between circular RNA HIPK2 (circHIPK2) and depression and the observation that the level of circHIPK2 expression was significantly increased in CUS-treated mice compared with that in the control group, further experiments were performed. FMT significantly ameliorated astrocyte dysfunction in recipient mice treated with CUS via inhibition of circHIPK2 expression. CONCLUSIONS: Our study illustrates the involvement of the gut microbiota-circHIPK2-astrocyte axis in depression, providing translational evidence that transplantation of the gut microbiota from NLRP3 KO mice may serve as a novel therapeutic strategy for depression.

3.
Mar Drugs ; 17(7)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269758

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Chitosan oligosaccharide (COS) is widely known to have various biological effects, and in this study we aimed to evaluate the liver-protective effect in diet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly composed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome were performed to assess the effects of COS23 on lipids in plasma and the liver as well as on intestinal microbiota. Our results revealed that COS23 obviously attenuated hepatic steatosis and ameliorated liver injury in diet-induced obese mice. The hepatic toxic lipids-especially triglycerides (TGs) and free fatty acids (FFAs)-were decreased dramatically after COS23 treatment. COS23 regulated lipid-related pathways, especially inhibiting the expressions of FFA-synthesis-related genes and inflammation-related genes. Furthermore, COS23 could alter lipid profiles in plasma. More importantly, COS23 also decreased the abundance of Mucispirillum and increased the abundance of Coprococcus in gut microbiota and protected the intestinal barrier by up-regulating the expression of tight-junction-related genes. In conclusion, COS23, an enzymatically digested product of COS, might serve as a promising candidate in the clinical treatment of NAFLD.

4.
Proc Natl Acad Sci U S A ; 116(30): 15184-15193, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31289229

RESUMO

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates glucose, lipid, and energy homeostasis. While gene expression of FGF21 is regulated by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha in the fasted state, little is known about the regulation of trafficking and secretion of FGF21. We show that mice with a mutation in the Yip1 domain family, member 6 gene (Klein-Zschocher [KLZ]; Yipf6 KLZ/Y ) on a high-fat diet (HFD) have higher plasma levels of FGF21 than mice that do not carry this mutation (controls) and hepatocytes from Yipf6 KLZ/Y mice secrete more FGF21 than hepatocytes from wild-type mice. Consequently, Yipf6 KLZ/Y mice are resistant to HFD-induced features of the metabolic syndrome and have increased lipolysis, energy expenditure, and thermogenesis, with an increase in core body temperature. Yipf6 KLZ/Y mice with hepatocyte-specific deletion of FGF21 were no longer protected from diet-induced obesity. We show that YIPF6 binds FGF21 in the endoplasmic reticulum to limit its secretion and specifies packaging of FGF21 into coat protein complex II (COPII) vesicles during development of obesity in mice. Levels of YIPF6 protein in human liver correlate with hepatic steatosis and correlate inversely with levels of FGF21 in serum from patients with nonalcoholic fatty liver disease (NAFLD). YIPF6 is therefore a newly identified regulator of FGF21 secretion during development of obesity and could be a target for treatment of obesity and NAFLD.

5.
J Photochem Photobiol B ; 196: 111508, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31152936

RESUMO

Cardiovascular malady (CVM) isn't just the essential driver of death in created western nations, yet additionally, its sickness load is expanding in China. Oxidative pressure initiated free radicals assume a basic job in cell forms involved in atherosclerosis and numerous other heart illnesses. Quercetin (QC) is cancer prevention agents medicate which is demonstrated that successfully secures against CVMs. Encapsulations of medications in polymeric materials are generally utilized in creating continued and controllable medication discharge, or to keep away from the debasement of non-discharged medications. In this present work, a novel arrangement of polymeric superparamagnetic nano-silica (SiN)@poly(lactic-co-glycolic acid) (PLGA) (SiN@PLGA) stacked with QC was created by means of lyophilization method so as to improve poor watery solvency and steadiness of the medication with the point of preventing atherosclerosis. The aftereffects of SEM investigation and the checking, TEM affirmed the manufacture of the circular nanocomposite, smooth surface, and thin size dispersion. The discharge profile of QC from the particles was explored by deciding the medication sum discharged at explicit interims for by iridescence. The data got from this investigation encourages the structure and manufacture of nanocomposite as conceivable conveyance frameworks for epitome, assurance and controlled arrival of the flavonoid QC which is expecting to secure against CVMs.


Assuntos
Nanocompostos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Quercetina/química , Dióxido de Silício/química , Animais , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Nanocompostos/toxicidade , Quercetina/metabolismo , Quercetina/uso terapêutico
6.
Adv Healthc Mater ; 8(15): e1900192, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31197956

RESUMO

Emerging Fenton-like activity of copper ions has inspired great exploration for tumor microenvironment-activated tumor therapy due to the toxic ·OH production for chemodynamic therapy and extra oxygen generation for photodynamic therapy (PDT). Still, the ·OH produced by copper ions is not satisfied even when copper ions are placed in a low pH environment (pH ≈ 5.0). To amplify its Fenton-like activity, in this work, one kind of Cu2+ -protein self-assemblies (C-m-ABs) loaded with photosensitizer indocyanine green (ICG) is constructed, which can catalyze H2 O2 generating more amounts of ·OH under light irradiation once Cu2+ is reduced to Cu+ by glutathione. Such fantastic phenomena confirms that C-m-ABs can act as a photo-Fenton-like agent. Furthermore, C-m-ABs can dramatically accelerate O2 generation (catalase activity) to enhance the PDT of ICG. After loading with the anticancer drug doxorubicin, C-m-ABs are further self-assembled into novel nanobelts, which simultaneously exhibit superior photo-heat conversion effects, enhanced r1 relaxation (21.416 s-1 mm-1 ) and stimuli-responsive drug release behaviors. High cytotoxicity in vitro, effective tumor accumulation capacity observed by fluorescence/photoacoustic/magnetic resonance imaging, and enhanced chemo-/photodynamic/photothermal therapeutic performance are achieved. Based on these results, a photo-Fenton-like metal-protein self-assemblies demonstrate great potential for tumor theranostics.

7.
Gut Microbes ; : 1-11, 2019 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-30982395

RESUMO

Alcohol-induced liver disease is closely related to translocation of bacterial products and bacteria from the intestine to the liver. However, it is not known whether bacterial translocation to the liver depends on certain intestinal microbiota changes that would predispose bacteria to translocate to the liver. In this study, we investigated the microbiota in the jejunum, ileum, cecum, feces and liver of mice subjected to chronic ethanol feeding using a Lieber DeCarli diet model of chronic ethanol feeding for 8 weeks. We demonstrate that chronic ethanol administration changes alpha diversity in the ileum and the liver and leads to compositional changes especially in the ileum. This is largely driven by an increase in gram-negative phyla - the source of endotoxins. Moreover, gram-negative Prevotella not only increased in the mucus layer of the ileum but also in liver samples. These results suggest that bacterial translocation to the liver might be associated with microbiota changes in the distal gastrointestinal tract.

8.
Acta Histochem ; 121(4): 407-412, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30885384

RESUMO

Angiotensin II (AngII) regulates pigment synthesis by tyrosinase in melanocytes. To evaluate the association between AngII and coat color formation, we detected the expression distribution of AngII in white and black sheep skins by LC-ESI-MS/MS, western blot, quantitative real-time-PCR (qPCR) and distribution of AngII by immunohistochemistry.Liquid chromatography-electrospray ionization tandem MS (LC-ESI-MS/MS) results showed that AngII was found in white and black skin tissues of sheep. Western blot results verified the LC-ESI-MS/MS results and suggested that AngII was expressed at significantly higher levels in black sheep skins compared with the white sheep skins. Quantitative real time PCR (qRT-PCR) results also revealed that the expression level of AngII mRNA was higher in black sheep skins than that in white sheep skins. Immunohistochemical analysis further demonstrated that AngII protein was localized in the hair bulb and outer root sheath of hair follicle in sheep. In summary, protein and transcripts exhibited the same expression pattern in white and black sheep skins. Furthermore, the expressions of AngII in the hair bulb and outer root sheath of black sheep were stronger than those in white sheep. These results suggested that AngII functions in sheep coat color regulation and offer a novel insight for further investigation on the role of AngII in the coat color formation in sheep.

9.
J Biomed Nanotechnol ; 15(4): 779-789, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30841970

RESUMO

The widespread application of nanoparticles causes extensive public concern on their biological safety. However, up to date, few reports have been associated with the impact of metal nanoparticles on gut microbiota in vivo. In this study, gold nanoclusters (AuNCs) were orally administered to BALB/c mice for 7 days, and the dynamic effects of AuNCs on gut microbiota were investigated at 0 h, 4 h, 8 h, 1 d, 3 d and 7 d, respectively. Using high-throughput sequencing of V4-V5 regions of the 16S rRNA gene on the Illumina MiSeq platform, we found that gavage of AuNCs did not significantly change the gut microbiota diversity and community at the initial 3 days. Bacteroidetes, Firmicutes, Proteobacteria, Deferribacteres, Tenericutes and Actinobacteria were the six most abundant phylum in the control and AuNCs groups. However, the phylum Proteobacteria was significantly increased by AuNCs at 7 d (P < 0.05). At the genus level, Roseburia were notably decreased while Staphylococcus, Ureaplasma and Methylobacterium were dramatically increased by AuNCs at 7 d (P < 0.05). Taken together, gavage of AuNCs shifted the bacterial composition at 7 d. This is the first research to investigate the toxicity of AuNCs from the perspective of gut microbiota and opens up a new avenue for the safety or toxicity evaluation of AuNCs.


Assuntos
Microbioma Gastrointestinal , Animais , Bacteroidetes , Camundongos , Camundongos Endogâmicos BALB C , Proteobactérias , RNA Ribossômico 16S
10.
Acta Biomater ; 89: 289-299, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30851455

RESUMO

Nanotheranostics has gained increasing interest, as it offers a great potential to realize personalized diagnostics and therapy. In this work, we report a facile approach of the fabrication of gold nanostars (GNS) attached with matrix metalloproteinases (MMP2) polypeptides (Ac-GPLGIAGQ) and IR-780 iodide through bovine serum albumin (BSA) for targeted dual-modal photoacoustic (PA)/near-infrared (NIR) fluorescence imaging and enhanced photothermal therapy (PTT)/photodynamic therapy (PDT) for lung cancer. MMP2 polypeptides served as the targeting ligand, IR-780 iodide functioned as the NIR fluorescence imaging agent as well as PTT/PDT agent, and GNS acted as the carrier of IR-780 molecules and performed PA imaging and PTT. DLS and CCK-8 assay demonstrated that the nanoprobes (GNS@BSA/I-MMP2) exhibited excellent stability and biocompatibility under physiological conditions. Subsequent in vitro studies verified that GNS@BSA/I-MMP2 nanoparticles (NPs) were effectively internalized by A549 cancer cells and exhibited remarkable antitumor efficacy. Furthermore, GNS@BSA/I-MMP2 NPs could specifically target the tumor and significantly suppress the tumor growth, and their antitumor effects were mainly through the synergistic effects of PDT and PTT based on IR-780 and GNS. These findings imply the potential of GNS@BSA/I-MMP2 NPs as a targeting PA/NIR probe in tumor diagnosis and combined therapy with a single light source. STATEMENT OF SIGNIFICANCE: We reported a convenient and facile approach to load IR-780 iodides in gold nanostars (GNS). This material could simultaneously perform near-infrared imaging/photoacoustic imaging and thermotherapy/photodynamic therapy. MMP2 coating on the surface of GNS@BSA/IR-780 promoted the prepared nanoparticles (GNS@BSA/I-MMP2) to target the tumor region. The heat generated by the synergistic effect of the GNS and IR-780 molecules resulted in the high temperature of the GNS@BSA/I-MMP2 NPs, which efficiently suppressed the growth of tumor, and the tumor volume decreased by 93% compared with that in the PBS groups with laser irradiation.

11.
J Ethnopharmacol ; 235: 47-55, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30735766

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Gardenia (FG) is a widely used bitter and cold herb for clearing heat and detoxicating. Currently, toxicity of FG and its relative formula has been reported in many clinical and animal studies. However, no systematic research has been carried out on FG-related gastrointestinal (GI) injury which has been emphasized in China since the Ming Dynasty. AIM OF THE STUDY: The purpose of this article is to investigate whether FG could damage GI and explore the mechanisms involved. MATERIAL AND METHODS: FG was given to male mice by 7-day intragastric administration at average doses of 0.90 g (L group), 1.50 g (M group), and 3.00 g (H group) crude drug/kg FG. Comprehensive understanding of changes in weight, diarrhea degree, stool routine, histomorphology and inflammatory factors of stomach, small intestine, and colon for evaluating the effect of different doses of FG on GI injury. Moreover, metabolomics-based mechanisms exploration of FG on GI injury was carried out via HPLC-Q-TOF/MS analysis on mice urine. RESULTS: High dose FG caused GI injury with serious diarrhea, decreased weight, abnormal stool routine, sever alteration in histomorphology of small intestine and colon (mild change in stomach), and significant change in inflammatory factors. The results of metabolomics suggested that 55 endogenous metabolites dispersed in 21 significantly altered metabolic pathways in 3.00 g/kg crude FG treated mice. The hub metabolites of GI injury were mainly related with vitamin B6 metabolism, phenylalanine metabolism, arachidonic acid metabolism, and taurine and hypotaurine metabolism via correlated network analysis. CONCLUSION: FG affected the normal functions of GI via the regulating a variety of metabolic pathways to an abnormal state, and our results provided a research paradigm for the GI-injury of the relative bitter and cold traditional Chinese medicines.


Assuntos
Gardenia/química , Gastroenteropatias/induzido quimicamente , Inflamação/induzido quimicamente , Extratos Vegetais/toxicidade , Animais , Ácido Araquidônico/metabolismo , Cromatografia Líquida de Alta Pressão , Gastroenteropatias/patologia , Inflamação/patologia , Masculino , Espectrometria de Massas , Medicina Tradicional Chinesa/efeitos adversos , Metabolômica , Camundongos , Fenilalanina/metabolismo , Taurina/análogos & derivados , Taurina/metabolismo , Vitamina B 6/metabolismo
12.
BMC Nephrol ; 20(1): 16, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30634931

RESUMO

BACKGROUND: Recent researches indicate that the intestinal consequences of renal ischemia reperfusion (IR) would predispose to the translocation of gut-derived endotoxin. Here, we designed experiments to test the hypothesis that the gut-derived endotoxin has a potential role in mediating local inflammatory processes in the acutely injured kidney. METHODS: Rats were performed sham or renal IR surgery (60 min of bilateral renal ischemia, then 24 h of reperfusion) (n = 5). The intestinal structural and mucosa permeability were evaluated. Serum endotoxin and bacterial load in liver and mesenteric lymph nodes (MLN) were measured. Separate groups were pretreated with oral norfloxacin 20 mg/kg/day or saline for 4 weeks and divided into sham plus saline, sham plus norfloxacin, renal IR plus saline and renal IR plus norfloxacin group. Serum biochemistry and endotoxin were determined. Kidney pathological changes were scored. Protein or mRNA expression of toll-like receptor 4 (TLR4) and proinflammatory mediators were measured in kidney homogenate. RESULTS: Renal IR led to marked intestinal integrity disruption and increase in intestinal permeability. These are accompanied by low grade of endotoxemia as well as increased bacterial load in liver and MLN. The group pretreated with norfloxacin showed significant attenuation of the increase in serum urea, ALAT, ASAT and endotoxin. The increased renal protein or mRNA of TLR4 and proinflammatory mediators (IL-6 and MCP-1) in the unpretreated animals was significantly attenuated in the norfloxacin-pretreated animals. However, norfloxacin pretreatment did not produce any protective effects on renal tubular integrity. CONCLUSIONS: Our results show for the first time that gut-derived endotoxin, resulting from an increased intestinal permeability after severe renal IR, subsequently amplifies intrarenal inflammatory response by activation renal TLR4 signaling. Our study results do not establish that antibiotic administration was effective in improving the overall renal outcome. However, our findings may be the first step to understanding how to tailor therapies to mitigate intrarenal inflammation in select groups of patients.

13.
Eur J Pharm Sci ; 121: 243-250, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29860115

RESUMO

AIM: The potential mechanism of penehyclidine hydrochloride (PHC) against myocardial ischemia-reperfusion (I/R) injury has not been fully elucidated. The aim of the present study was to reveal whether mitochondrial dynamics, apoptosis, and MAPKs were involved in the cardioprotective effect of this drug on myocardial I/R injury. METHODS: Ninety healthy adult male Wistar rats were separately pretreated with normal saline (0.9%); PHC; and signal pathway blockers of MAPKs, Drp1, and Bcl-2. Coronary artery ligation and subsequent reperfusion were performed to induce myocardial I/R injury. Echocardiography was performed. Myocardial enzymes and oxidative stress markers were detected. Myocardial cell apoptotic rates and infarct sizes were measured. Mitochondrial function was evaluated. Expression levels of MAPKs, mitochondria regulatory proteins (Drp1, Mfn1/2), and apoptosis-related proteins (Bcl-2, Bax) were determined. RESULTS: PHC pretreatment improved myocardial abnormalities (dysfunction, injury, infarct size, and apoptotic rate), mitochondrial abnormalities (dysfunction and fission), and excessive oxidative stress and inhibited the activities of p38MAPK and JNK signal pathways in rats with myocardial I/R injury (P < 0.05). Additionally, p38MAPK and JNK blockers (SB239063 and SP600125, respectively) had an effect on rats same as that of PHC. Although Drp1 blocker (Mdivi-1) showed a similar cardioprotective effect (P < 0.05), it did not affect the expression of MAPKs and apoptosis-related proteins (P > 0.05). In addition, Bcl-2 blocker (ABT-737) caused a high expression of Drp1 and a low expression of Mfn1/2 (P < 0.05). CONCLUSION: PHC regulated mitochondrial dynamics and apoptosis through p38MAPK and JNK signal pathways and provided cardioprotection in rats with myocardial I/R injury.

14.
J Control Release ; 283: 113-125, 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-29857004

RESUMO

Liver fibrosis refers to excessive accumulation of hepatic collagen, which is primarily produced by activated hepatic stellate cells (HSCs). No effective drugs are clinically available to treat this condition, reflecting the fact that antifibrotic drugs do not specifically target activated HSCs. Here, we report the synthesis and evaluation of poly (lactide-co-glycolide)-polyspermine-poly (ethylene glycol)-vitamin A (PLGA-PSPE-PEG-VA), and activated HSC-targeted, biocompatible amphiphilic polymers for co-delivery of chemical (silibinin) and genetic (siCol1α1) drugs that synergistically suppress collagen I accumulation in fibrogenesis. PLGA-PSPE-PEG-VA self-assembled into core-shell polymeric micelles (PVMs) at low concentrations. After loading with silibinin and siCol1α1, the resulting chemical/genetic drug-loaded PVMs (CGPVMs) exhibited a small particle size and a slightly positive surface. CGPVMs had very low cytotoxicity and hemolytic activity in vitro and were well tolerated in mice, with no liver toxicity or inflammation. Importantly, CGPVMs effectively accumulated in fibrotic livers and specifically targeted activated HSCs. As expected CGPVMs more efficiently decreased collagen I production and ameliorated liver fibrosis compared with chemical drug (silibinin)-loaded PVMs (CPVMs) or genetic drug (siCol1α1)-loaded PVMs (GPVMs) only. These results indicate that CGPVMs are a promising tool for targeted delivery of chemogenes to activated HSCs in the treatment of liver fibrosis.

15.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 34(6): 942-948, 2018 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-29761992

RESUMO

Diagnosis of Parkinson's disease (PD) based on speech data has been proved to be an effective way in recent years. However, current researches just care about the feature extraction and classifier design, and do not consider the instance selection. Former research by authors showed that the instance selection can lead to improvement on classification accuracy. However, no attention is paid on the relationship between speech sample and feature until now. Therefore, a new diagnosis algorithm of PD is proposed in this paper by simultaneously selecting speech sample and feature based on relevant feature weighting algorithm and multiple kernel method, so as to find their synergy effects, thereby improving classification accuracy. Experimental results showed that this proposed algorithm obtained apparent improvement on classification accuracy. It can obtain mean classification accuracy of 82.5%, which was 30.5% higher than the relevant algorithm. Besides, the proposed algorithm detected the synergy effects of speech sample and feature, which is valuable for speech marker extraction.

16.
Theriogenology ; 116: 71-82, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29778923

RESUMO

The reproductive efficiency of Meishan pigs is higher than that of Duroc pigs, but the underlying molecular mechanism for this disparity remains unclear. No systematic quantitative proteomics studies, comparing global proteins in Meishan and Duroc boar spermatozoa have been reported. Therefore, we applied iTRAQ labeling coupled with mass spectrometry, and analyzed the differences in proteins between Meishan and Duroc sperm. In the present study, a total of 1597 proteins were quantified. Of these proteins, 190 showed statistically significant fold changes between Meishan and Duroc spermatozoa. Bioinformatics analysis revealed that these differentially abundant proteins were primarily involved in energy metabolism, sperm motility, capacitation and sperm-oocyte binding. Remarkably, SPAG6, ACR, LDHC, CALM, ACE and ENO1 which are positively related to high litter size, were more abundant in Meishan spermatozoa than in Duroc spermatozoa. Moreover, APOA1, NDUFS2 and RAB2A which are negatively related to farrowing rates, were less abundant in Meishan spermatozoa than in Duroc spermatozoa. Interestingly, essential enzymes in Glycolysis/Gluconeogenesis, such as HK1, ALDH2, LDHA and LDHC, were markedly up-regulated in Meishan spermatozoa compared to Duroc spermatozoa. In addition, we first demonstrated that the levels of protein phosphorylation in Meishan spermatozoa were higher than those in Duroc. Taken together, the physiologically and functionally differential proteins may be one main reason for explaining the high reproductive efficiency of Meishan boar.


Assuntos
Reprodução/genética , Espermatozoides/metabolismo , Suínos/genética , Animais , Cruzamentos Genéticos , Feminino , Perfilação da Expressão Gênica , Tamanho da Ninhada de Vivíparos/genética , Masculino , Proteômica , Reprodução/fisiologia , Espermatozoides/fisiologia , Suínos/fisiologia
17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(4): 327-331, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29663993

RESUMO

OBJECTIVE: To systematically evaluate the clinical effect of prone position mechanical ventilation on the improvement of oxygenation in patients with severe pneumonia. METHODS: Pubmed, Embase, Cochrane Library, CNKI, Wanfang Data and VIP database were searched from the time of database built up until December 10th, 2017. All the published randomized controlled trials (RCTs) about the effects of prone position ventilation on the oxygenation of severe pneumonia patients were screened, and were confirmed by the literature reference citation retrieval. Inclusion and exclusion criteria had been used to review and rank the literature. After evaluating the quality of included studies, the data was extracted from RCTs and given a Meta-analysis using RevMen 5.1. RESULTS: Twelve RCTs with 650 cases were included. Eleven of them were Chinese literature while 1 was in English. Ten studies showed that the prone position ventilation had a significant influence on improving partial pressure of oxygen [weighted mean difference (WMD) = 9.93, 95% confidence interval (95%CI) = 2.92-16.95, P = 0.006], publication bias was found in these studies. Seven studies showed that the prone position ventilation had a significant influence on partial pressure of carbon dioxide (WMD = 9.99, 95%CI = 1.81-18.18, P = 0.02), publication bias was found in these studies. Seven studies showed that the prone position ventilation had a significant influence on oxygenation index (WMD = 31.22, 95%CI = 26.06-36.39, P < 0.000 01), publication bias was found in these studies. Two studies showed that the prone position ventilation had a significant influence on oxygen saturation of blood (WMD = 2.12, 95%CI = 1.24-3.00, P < 0.000 01), no publication bias was found in these studies. CONCLUSIONS: Prone position ventilation can effectively improve the patients' oxygenation index, partial pressure of oxygen, and oxygen saturation of blood, and reduce the partial pressure of carbon dioxide.


Assuntos
Decúbito Ventral , Humanos , Oxigênio , Pneumonia Associada à Ventilação Mecânica , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Fenômenos Fisiológicos Respiratórios
18.
Toxicol Lett ; 291: 112-120, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29653258

RESUMO

The toxic effects of cadmium (Cd) in the reproductive system have been confirmed, and lysine acetylation and succinylation play important roles in spermatogenesis. However, little attention determined whether Cd could affect lysine acylation and how it might have an impact on the reproductive system. Therefore, with the goal of contributing to this subject, we have examined the effects of Cd on lysine acetylation and succinylation of proteins in the germ cells of male mice testes during different developmental stages. We adopted intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) in mice once every 5 days from postnatal day 5-60. The results showed that Cd could restrict GAPDH activity, ATP and cAMP levels of germ cells to inhibit lysine acetylation and succinylation in the testes, inducing reproductive injuries. Cd also restricts acetylation of histone H4K5 and H4K12, which could result in failure of spermiogenesis. Remarkably, polarized acetylation occurs in meiosis, and high-level acetylation occurs earlier than high-level succinylation during spermatogenesis. Moreover, Cd has a limited effect on body weight but reduces the weight of the testis and litter size. Our research may provide a new way to reveal the mechanisms of Cd reproductive toxicity related to lysine acetylation and succinylation.


Assuntos
Cloreto de Cádmio/toxicidade , Lisina/metabolismo , Doenças Testiculares/induzido quimicamente , Doenças Testiculares/metabolismo , Acetilação , Trifosfato de Adenosina/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , AMP Cíclico/metabolismo , Células Germinativas/efeitos dos fármacos , Células Germinativas/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Injeções Intraperitoneais , Masculino , Meiose/efeitos dos fármacos , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Succinatos/metabolismo , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
19.
Hepatol Commun ; 2(4): 393-406, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29619418

RESUMO

C-type regenerating islet derived-3 (Reg3) lectins defend against pathogens and keep commensal bacteria at a distance. Deficiency of Reg3g and Reg3b facilitates alcohol-induced bacterial translocation and alcoholic liver disease. Intestinal Reg3g is down-regulated in animal models of diet-induced obesity, but the functional consequences for nonalcoholic steatohepatitis (NASH) are unknown. The aim of this study was to investigate the role of Reg3 lectins in NASH. NASH was induced by a Western-style fast-food diet in mice deficient for Reg3g or Reg3b and in transgenic mice overexpressing Reg3g in intestinal epithelial cells (Reg3gTg). Glucose tolerance was assessed after 18 weeks and insulin resistance after 19 weeks of feeding. After 20 weeks, mice were assessed for features of the metabolic syndrome. Obesity was not different in genetically modified mice compared with their respective wild-type littermates. Glucose intolerance, liver injury, hepatic inflammation, steatosis, fibrosis, and bacterial translocation to mesenteric lymph nodes and to the liver were not different in Reg3g-deficient mice compared with wild-type littermates. Plasma endotoxin levels were higher in Reg3g-deficient mice. Reg3b deficiency protected against glucose intolerance, but liver disease, bacterial translocation, and plasma endotoxin levels were similar to wild-type littermates. Absence of either REG3G or REG3B protein in the ileum was not compensated for by up-regulation of the respective other REG3 protein. Transgenic Reg3g mice also developed liver injury, steatosis, and fibrosis similar to their wild-type littermates. Conclusion: In contrast to alcoholic liver disease, loss of intestinal Reg3 lectins is not sufficient to aggravate diet-induced obesity and NASH. This supports a multi-hit pathogenesis in NASH. Only glucose metabolism is affected by Reg3b deficiency. (Hepatology Communications 2018;2:393-406).

20.
Genes (Basel) ; 9(4)2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29642393

RESUMO

The giant panda was widely distributed in China and south-eastern Asia during the middle to late Pleistocene, prior to its habitat becoming rapidly reduced in the Holocene. While conservation reserves have been established and population numbers of the giant panda have recently increased, the interpretation of its genetic diversity remains controversial. Previous analyses, surprisingly, have indicated relatively high levels of genetic diversity raising issues concerning the efficiency and usefulness of reintroducing individuals from captive populations. However, due to a lack of DNA data from fossil specimens, it is unknown whether genetic diversity was even higher prior to the most recent population decline. We amplified complete cytb and 12s rRNA, partial 16s rRNA and ND1, and control region sequences from the mitochondrial genomes of two Holocene panda specimens. We estimated genetic diversity and population demography by analyzing the ancient mitochondrial DNA sequences alongside those from modern giant pandas, as well as from other members of the bear family (Ursidae). Phylogenetic analyses show that one of the ancient haplotypes is sister to all sampled modern pandas and the second ancient individual is nested among the modern haplotypes, suggesting that genetic diversity may indeed have been higher earlier during the Holocene. Bayesian skyline plot analysis supports this view and indicates a slight decline in female effective population size starting around 6000 years B.P., followed by a recovery around 2000 years ago. Therefore, while the genetic diversity of the giant panda has been affected by recent habitat contraction, it still harbors substantial genetic diversity. Moreover, while its still low population numbers require continued conservation efforts, there seem to be no immediate threats from the perspective of genetic evolutionary potential.

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