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1.
Phytomedicine ; 67: 153158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31999981

RESUMO

Background Shengui Sansheng Pulvis (SSP) has about 300 years history used for stroke treatment, and evidences suggest it has beneficial effects on neuro-angiogenesis and cerebral energy metabolic amelioration post-stroke. However, its protective action and mechanisms on blood-brain barrier (BBB) is still unknown. Purpose Based on multiple neuroprotective properties of vasoactive intestinal peptide (VIP) in neurological disorders, we investigate if SSP maintaining BBB integrity is associated with VIP pathway in rat permanent middle cerebral artery occlusion (MCAo) model. Methods Three doses of SSP extraction were administered orally. Evaluations of motor and balance abilities and detection of brain edema were performed, and BBB permeability were assessed by Evans blue (EB) staining. Primary brain microvascular endothelial cells (BMECs) were subjected to oxygen-glucose deprivation, and incubated with high dose SSP drug-containing serum and VIP-antagonist respectively. Transendothelial electrical resistance (TEER) assay and Tetramethylrhodamine isothiocyanate (TRITC)-dextran (4.4 kDa) and fluorescein isothiocyanate (FITC)-dextran (70 kDa) were used to evaluate the features of paracellular junction. Western blot detected the expressions of Claudin-5, ZO-1, Occludin and VE-cadherin, matrix metalloproteinase (MMP) 2/9 and VIP receptors 1/2, and immunofluorescence staining tested VIP and Claudin-5 expressions. Results Our results show that SSP significantly reduces EB infiltration in dose-dependent manner in vivo and attenuates TRITC- dextran and FITC-dextran diffusion in vitro, and strengthens endothelial junctional complexes as represented by decreasing Claudin-5, ZO-1, Occludin and VE-cadherin degradations and MMP 2/9 expression, as well as promoting TEER in BMECs after ischemia. Moreover, it suggests that SSP notably enhances VIP and its receptors 1/2 expressions. VIP-antagonist exacerbates paracellular barrier of BMECs, while the result is reversed after incubation with high dose SSP drug-containing serum. Additionally, SSP also improve brain edema and motor and balance abilities after ischemic stroke. Conclusions we firstly demonstrate that the ameliorated efficacy of SSP on BBB permeability is related to the enhancements of VIP and its receptors, suggesting SSP might be an effective therapeutic agent on maintaining BBB integrity post-stroke.

2.
FASEB J ; 34(1): 95-106, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914697

RESUMO

Diabetic nephropathy (DN) is one of the leading causes of mortality in diabetic patients, but its pathogenesis is unclear. We aimed to study the role of the pro-ANP convertase Corin in the pathogenesis of DN. Corin and ANP expression in DN rat kidneys and high-glucose-treated HK-2 cells was analyzed by real-time PCR, western blotting, and immunohistochemical staining. The effect of Corin-siRNA or ANP-siRNA HK-2 cells on EA.hy926 cell migration was determined by scratch-wound healing assay. The expression of mitogen-activated protein kinase (MAPK) and endothelial NO synthase (eNOS) in EA.hy926 cells treated with conditioned medium from Corin-siRNA- or ANP-siRNA-transfected HK-2 cells was determined by western blotting. We found a significant reduction in Corin and ANP expression in DN rat kidneys. These results were recapitulated in HK-2 cells treated with high glucose. EA.hy926 cells treated with conditioned medium from Corin-deficient HK-2 cells had inhibited migration, increased MAPK activity, and decreased eNOS activity. Similar effects were observed with ANP-siRNA transfection. Finally, adding ANP to the Corin-deficient HK-2 conditioned medium rescued the above defects, indicating that Corin mediates its effects through ANP. In conclusion, Corin plays a renoprotective role through pro-ANP processing, and defects in Corin cause endothelial dysfunction through MAPK and eNOS signaling in DN.

3.
Chemosphere ; 240: 124902, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563721

RESUMO

Eisenia fetida earthworm is an ecotoxicologically important test species to monitor various pollutants. However, there is a little knowledge about the effects of cadmium (Cd) on earthworms at the transcriptional level. Firstly, we exposed E. fetida to soils supplemented with different concentrations (10, 30, 60 mg/kg soil) of Cd. Moreover, we depicted the characterization of gene expressions with E. fetida using high-throughput profiling of gene expression. In addition, a comparison of the gene expression profiles between each Cd treatment group and the control group suggested that differential expressional genes (DEGs) mainly enriched in enzyme activity, metabolism, oxidative stress, regeneration and apoptosis pathways. 8 DEGs from these pathways had been selected randomly to confirm the data of RNA-seq. Among these DEGs, six genes (metallothionein-2, phytochelatin synthase 1a, CuZn superoxide dismutase, sex determining region Y-box 2, sex determining region Y-box 4b, TP53-regulated inhibitor of apoptosis 1-like) up-regulated and 2 genes (beta-1,4-endoglucanase, apoptosis-stimulating of p53 protein 2-like) down-regulated in response to Cd exposure. The alteration of them indicated that earthworms could reduce the toxicity and bioavailability of Cd in polluted soil ecosystems through different pathways. This work lays an important foundation for linking earthworm transcriptional level with the ecological risk of Cd in soil ecosystem.


Assuntos
Cádmio/toxicidade , Oligoquetos/fisiologia , Poluentes do Solo/toxicidade , Aminoaciltransferases , Animais , Disponibilidade Biológica , Cádmio/análise , Ecossistema , Perfilação da Expressão Gênica , Metalotioneína/genética , Metalotioneína/metabolismo , Oligoquetos/efeitos dos fármacos , Oligoquetos/genética , Estresse Oxidativo/efeitos dos fármacos , Solo , Poluentes do Solo/análise , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
4.
Chin J Integr Med ; 25(10): 723-727, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31782008

RESUMO

Ischemic stroke accounts for the majority of all strokes and has been primary causes of long-term disability and mortality in worldwide. Mesenchymal stem cell (MSC) therapy suggests significantly improved effects on neurological functional outcome, neurogenesis, angiogenesis, blood-brain barrier permeability, inflammatory injury, neuroprotection and so on, following stroke. However, the occurrence of adverse effects results in restriction of the therapy. Chinese medicine accumulates abundant clinical experiences on stroke for over two thousand years, and some formulae and active ingredients of Chinese medicines have presented obvious efficacies in clinical treatment. Therefore, based on Chinese medicine theory, we provide some ideas of screening agents for combination treatment of Chinese medicines and MSC for ischemic stroke, and summarize the potentials of Chinese medicines in MSC treatment and analyze the feasibilities of Chinese medicines against side effects of MSC therapy. Consequently, we propose Chinese medicines combing with MSC should be a promising approach to clinical stroke treatment in future.

5.
Chin Med ; 14: 32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31548850

RESUMO

Background: Acupoint catgut embedding therapy characterized by acupoint, needle and catgut are superior to traditional acupuncture, due to exerting more comprehensive therapeutic efficacy. However, it is still deficient in clinical evidence for polyglycolic acid sutures, a novel biodegradable material instead of catgut, embedded for the treatment of simple obesity. In our study, we investigate the efficacy and related mechanism of polyglycolic acid sutures embedded in abdominal acupoints on simple obese persons by a randomized control trial. Methods: A total of 51 eligible participators were randomly allocated to a polyglycolic acid sutures embedding therapy (PASET) group (n = 28) or control group (n = 23). Participators in PASET group received polyglycolic acid sutures alternatively embedded in abdominal I group and II group acupoints in odd and even number therapeutic courses, and participators in control group were required to perform lifestyle modification. The duration of the study was 10 weeks. Results: It suggested that PASET significantly reduced weight, body mass index, hip circumference, waist circumference, waist/hip ratio, waist-to-height ratio and thickness of abdominal subcutaneous fat tissue compared with those before treatment (p < 0.01), but lifestyle modification only illustrated downward trend of weight (p < 0.05). Moreover, PASET group also improved the evaluated scores in aspects of physical function, self-esteem, public distress and sexual life, as well as decreased blood pressure, glycemia, low density lipoprotein, uric acid and the levels of tumor necrosis factor-alpha, interleukin-1ß, and increased high density lipoprotein in comparison with those before treatment (p < 0.05), whose efficacies are superior to control group. Additionally, our results also indicate PASET is relative safe and its pain and discomfort can be tolerable. Conclusions: PASET distinctly ameliorates anthropometric data and quality of life in obese population, which associates with improvements of metabolic profile and inflammatory response. Based on the advantageous actions, we think PASET is an effective therapeutic approach to simple obesity treatment.Trial registration ChiCTR, ChiCTR1800015591. Registered 10 April 2018, http://www.chictr.org.cn/showproj.aspx?proj=23258.

6.
Front Neurosci ; 13: 515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191223

RESUMO

Background: The traditional Chinese medicine Ginseng-Angelica-Shanseng-Pulvis (GASP) has been used to treat stroke for 300 years. This present study investigated if it can induce increases in neurogenesis following cerebral ischemic injury. Methods: Rats following middle cerebral artery occlusion were orally treated with high, medium, and low doses of a standardized GASP extract. Results: After 14 days, treatment with GASP improved regional blood flow and infarction volume by magnetic resonance imaging scanning, enhanced Ki67+ expression in the subventricular zone, increased brain-derived neurotrophic factor (BDNF) secretion, Nestin, and bone morphogenetic protein (BMP) 2/4 expressions in the hippocampus in a dose-dependent manner. Interestingly, low-dose treatment with GASP downregulated doublecortin and Notch1 expressions in the hippocampus, as well as upregulated glial fibrillary acidic protein expression in the subgranular zone and hairy and enhancer of split (Hes) 5 expression in the hippocampus, while treatment with middle and high doses of GASP reversed these results. Meanwhile, the consumed time was shortened in the basket test and the adhesive removal test and the spending time on exploring novel objects was prolonged by GASP treatment whose effects were more obvious at day 14 post-ischemia. Conclusion: Our study demonstrates that treatment with GASP increases neurogenesis and ameliorates sensorimotor functions and recognition memory. We hypothesize that these effects are thought be mediated by an effect on the BMP2/4 pathway and Notch1/Hes5 signal. Due to its beneficial efficacy, GASP can be recognized as an alternative therapeutic agent for ischemic stroke.

7.
Curr Vasc Pharmacol ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31060489

RESUMO

Aging has become a worldwide problem. During this process, incidence of related diseases such as diabetes and atherosclerosis increases dramatically. Studies within most recent two decades suggest pivotal role of advanced glycation end products (AGEs) in aging process. This review aims to systemically summarize effects and potential mechanism of Chinese Medicines on inhibiting AGEs-related aging diseases.

8.
Front Pharmacol ; 10: 386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31065240

RESUMO

Cerebral energy deficiency is a key pathophysiologic cascade that results in neuronal injury and necrosis after ischemic stroke. Shengui Sansheng San (SSS) has been used to treat stroke for more than 300 years. In present study, we investigated the therapeutic efficacy and mechanism of SSS extraction on cerebral energy deficiency post-stroke. In permanent middle cerebral artery occlusion (pMCAo) model of rats, it suggested that SSS extraction in dose-dependent manner improved neurological function, cerebral blood flow (CBF), 18F-2-deoxy-glucose uptake and the density and diameter of alpha smooth muscle actin (α-SMA) positive vasculature in ipsilateral area, as well as decreased infarcted volume. Meanwhile, the metabolomics study in cerebrospinal fluid (CSF) was performed by using 5-(diisopropylamino)amylamine (DIAAA) derivatization-UHPLC-Q-TOF/MS approach. Eighty-eight endogenous metabolites were identified, and mainly involved in citrate cycle, fatty acid biosynthesis, aminoacyl-tRNA biosynthesis, amino acids metabolism and biosynthesis, etc. The remarkable increase of citrate in CSF after treatment with three dosages indicated that the therapeutic mechanism of SSS extraction might be related with citrate cycle. Simultaneously, it showed that high dosage group significantly increased peripheral blood glucose level, the expressions of glucose transporter (GLUT) 1, GLUT3, and monocarboxylic acid transporter 1 (MCT1), which contributed to the transportation of glucose and lactate. By the regulations of phosphorylated pyruvate dehydrogenase E1-alpha (p-PDHA1), acetyl CoA synthetase and citrate synthetase (CS), the levels of citrate and its upstream molecules (pyruvate and acetyl CoA) in peri-infarction zone further enhanced, which ultimately caused the massive yield of adenosine triphosphate (ATP). Our study first demonstrated that SSS extraction could ameliorate cerebral energy deficiency after ischemia by citrate cycle, which is characterized by the enhancements of glucose supply, transportation, utilization, and metabolism.

9.
Acta Pharmacol Sin ; 40(10): 1279-1291, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31000769

RESUMO

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of ß-amyloid (Aß) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aß clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. In the present study, we established a platform to discover autophagy stimulator and screened the lab in-house FDA-approved drug library. We found that anti-parasitic drug nitazoxanide (NTZ) was an autophagy activator and could efficiently improve learning and memory impairments in APP/PS1 transgenic mice. In BV2 cells and primary cortical astrocytes, NTZ stimulated autophagy and promoted Aß clearance by inhibiting both PI3K/AKT/mTOR/ULK1 and NQO1/mTOR/ULK1 signaling pathways; NTZ treatment attenuated LPS-induced inflammation by inhibiting PI3K/AKT/IκB/NFκB signaling. In SH-SY5Y cells and primary cortical neurons, NTZ treatment restrained tau hyperphosphorylation through inhibition of PI3K/AKT/GSK3ß pathway. The beneficial effects and related signaling mechanisms from the in vitro studies were also observed in APP/PS1 transgenic mice following administration of NTZ (90 mg·kg-1·d-1, ig) for 100 days. Furthermore, NTZ administration decreased Aß level and senile plaque formation in the hippocampus and cerebral cortex of APP/PS1 transgenic mice, and improved learning and memory impairments in Morris water maze assay. In conclusion, our results highlight the potential of NTZ in the treatment of AD.

10.
Acta Pharmacol Sin ; 40(9): 1193-1204, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30833709

RESUMO

Gluconeogenesis is a major source of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), thus targeting gluconeogenesis to suppress glucose production is a promising strategy for anti-T2DM drug discovery. In our preliminary in vitro studies, we found that a small-molecule (E)-3-(2-(quinoline-4-yl)vinyl)-1H-indol-6-ol (QVO) inhibited the hepatic glucose production (HGP) in primary hepatocytes. We further revealed that QVO suppressed hepatic gluconeogenesis involving calmodulin-dependent protein kinase kinase ß- and liver kinase B1-adenosine monophosphate-activated protein kinase (AMPK) pathways as well as AMPK-independent mitochondrial function-related signaling pathway. To evaluate QVO's anti-T2DM activity in vivo, which was impeded by the complicated synthesis route of QVO with a low yield, we designed and synthesized 4-[2-(1H-indol-3-yl)vinyl]quinoline (IVQ) as a prodrug with easier synthesis route and higher yield. IVQ did not inhibit the HGP in primary hepatocytes in vitro. Pharmacokinetic studies demonstrated that IVQ was quickly converted to QVO in mice and rats following administration. In both db/db and ob/ob mice, oral administration of IVQ hydrochloride (IVQ-HCl) (23 and 46 mg/kg every day, for 5 weeks) ameliorated hyperglycemia, and suppressed hepatic gluconeogenesis and activated AMPK signaling pathway in the liver tissues. Furthermore, IVQ caused neither cardiovascular system dysfunction nor genotoxicity. The good druggability of IVQ has highlighted its potential in the treatment of T2DM and the prodrug design for anti-T2DM drug development.

11.
J Cell Mol Med ; 23(1): 126-142, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30421523

RESUMO

The remodelling of structural and functional neurovascular unit (NVU) becomes a central therapeutic strategy after cerebral ischaemic stroke. In the present study, we investigated the effect of combined therapy of sodium ferulate (SF), n-butylidenephthalide (BP) and adipose-derived stromal cells (ADSCs) to ameliorate the injured NVU in the photochemically induced thrombotic stroke in rats. After solely or combined treatment, the neovascularization, activation of astrocytes, neurogenesis, expressions of vascular endothelial growth factor (VEGF) and claudin-5 were assessed by immunohistochemical or immunofluorescence staining. In order to uncover the underlying mechanism of therapeutic effect, signalling of protein kinase B/mammalian target of rapamycin (AKT/mTOR), extracellular signal-regulated kinase 1/2 (ERK1/2), and Notch1 in infarct zone were analysed by western blot. 18 F-2-deoxy-glucose/positron emission tomography, magnetic resonance imaging, Evans blue staining were employed to evaluate the glucose metabolism, cerebral blood flow (CBF), and brain-blood barrier (BBB) permeability, respectively. The results showed that combined treatment increased the neovascularization, neurogenesis, and VEGF secretion, modulated the astrocyte activation, enhanced the regional CBF, and glucose metabolism, as well as reduced BBB permeability and promoted claudin-5 expression, indicating the restoration of structure and function of NVU. The activation of ERK1/2 and Notch1 pathways and inhibition of AKT/mTOR pathway might be involved in the therapeutic mechanism. In summary, we have demonstrated that combined ADSCs with SF and BP, targeting the NVU remodelling, is a potential treatment for ischaemic stroke. These results may provide valuable information for developing future combined cellular and pharmacological therapeutic strategy for ischaemic stroke.

12.
Am J Chin Med ; 46(8): 1727-1741, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30525898

RESUMO

Cardio/cerebral-vascular diseases seriously threaten human health and are the leading cause of death. As such, there is great interest in identifying a potential mechanism that controls the development process of cardio/cerebral vascular diseases. Present studies demonstrate that inflammasomes play an important role in the process of ischemic cardio/cerebral vascular diseases (ICCVDs). Among the pathological process of ICCVDs, inflammasomes activated the sterile inflammatory response that accelerated the development of diseases and aggravated the acute lesion of tissue. As the most thoroughly studied inflammasome, the NLRP3 inflammasome has been proven to be a potential therapeutic target for ICCVDs. In this review, we summarized the mechanisms of Chinese herbal medicine which can affect ICCVDs via the regulation of the NLRP3 inflammasome. Our study discovers that active compounds of Chinese medicines have a negative effect on NLRP3 in different ICCVDs models. Astragaloside IV may influence the receptor of the cell membrane to inhibit NLRP3 activation. Resveratrol, colchicinesis, salvianolic acid B, chrysophanol and sulforaphane may directly damage the formation of NLRP3 by inhibiting ASC or Caspase-1. Most of the active natural compounds can negatively regulate the downstream products of NLRP3 inflammasome such as IL-18 and IL1 ß . In addition, Chinese medicines such as sinomenine, ruscogenin, resveratrol, arctigenin and cepharanthineas may downregulate NLRP3 inflammasome by inducing autophagy activation. Due to the advantages of multi-target effects, Chinese herbal medicine can be treated as a splendid therapy for ICCVDs by inhibiting NLRP3 inflammasome.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Transtornos Cerebrovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/genética , Medicamentos de Ervas Chinesas/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamassomos/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Terapia de Alvo Molecular , Morfinanos/farmacologia , Morfinanos/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Espirostanos/farmacologia , Espirostanos/uso terapêutico
13.
Ecotoxicol Environ Saf ; 166: 242-250, 2018 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-30273847

RESUMO

The aim of the current study was to determine the potential developmental and metabolic abnormalities caused by Cr (VI) exposure on Bufo gargarizans (B. gargarizans) embryos. B. gargarizans embryos were treated with different concentrations of Cr (VI) (13, 52, 104, 208, and 416 µg Cr6+ L-1) for 6 days. Morphological abnormalities, total length, weight and developmental stage were monitored. Malformations of embryos were also examined using scanning electron microscopy (SEM). In addition, the transcript levels of several genes associated with lipid metabolism, oxidative stress, and thyroid hormones signaling pathways were also determined. Our results showed a time-dependent inhibitory effect of Cr (VI) on the growth and development of B. gargarizans embryos. On day 4, total length, weight, and developmental stage were significantly lower at 416 µg Cr6+ L-1 relative to control embryos. On day 6, significant reductions in total length, weight, and developmental stage were observed at 104, 208, and 416 µg Cr6+ L-1. Malformed embryos were found in all Cr (VI) treatments, which were characterized by axial flexures, yolk sac edema and rupture, surface tissue hyperplasia, stunted growth, wavy fin and fin flexure. RT-qPCR results showed that exposure to Cr (VI) down-regulated TRß and Dio2 mRNA expression and up-regulated Dio3 mRNA level at 416 µg Cr6+ L-1. The transcript levels of SOD and GPx were upregulated at 52, 208, and 416 µg Cr6+ L-1, while the transcript level of HSP90 was downregulated at 52, 208, and 416 µg Cr6+ L-1. Also, mRNA expression of lipid synthesis-related genes (FAE and ACC) were significantly downregulated in embryos treated with 208 and 416 µg Cr6+ L-1, but mRNA expression of fatty acid ß-oxidation-related genes (ACOX, CPT, and SCP) was significantly upregulated at 416 µg Cr6+ L-1. Therefore, our results suggested that Cr (VI) could disrupt thyroid endocrine pathways and lipid synthesis, leading to the inhibition of growth and development in B. gargarizans embryos. Furthermore, the decreased ability of scavenging ROS induced by Cr (VI) might be responsible for the teratogenic effects of Cr (VI).


Assuntos
Bufonidae/embriologia , Cromo/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Bufonidae/crescimento & desenvolvimento , Disruptores Endócrinos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , RNA Mensageiro/metabolismo , Superóxido Dismutase/metabolismo , Hormônios Tireóideos/metabolismo
14.
Zhongguo Fei Ai Za Zhi ; 21(8): 571-577, 2018 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-30172262

RESUMO

BACKGROUND: Cisplatin acquired resistance is a vital problem in the chemotherapy of non-small cell lung cancer, which needs to be further addressed. In recent years, obtaining drug resistant cells from cell cultivation and serving for metabolomics research to find differential metabolites and get potential biomarkers, is a good reference for clinical research and cancer treatment. This study aimed to obtain metabolite information related to cisplatin resistance through metabolomics analysis. METHODS: Metabolites were extracted from A549 cells and cisplatin resistant A549/DDP cells, and ultraperformance liquid chromatography coupled with time of flight mass spectrometry was used to perform metabolomic analysis of endogenous molecules of the two cells and obtain metabolic differences. RESULTS: Through data analysis, 40 metabolites were identified as differential metabolites, mainly involving phospholipids, fatty acids, amino acids and metabolites related to energy metabolism. CONCLUSIONS: The drug resistance of A549/DDP cells may be caused by the changes of cell membrane structure and related metabolic pathways.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Metabolômica/métodos , Células A549 , Cromatografia Líquida de Alta Pressão , Resistencia a Medicamentos Antineoplásicos , Humanos , Espectrometria de Massas
15.
Bull Environ Contam Toxicol ; 101(2): 178-184, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29947911

RESUMO

Mining is considered to be one of the most significant sources of environmental pollution with regard to heavy metals. Mineral mining causes large quantities of mercury, cadmium, and other elements to be released into the environment and naturally poses a serious threat to environment. This paper will analyze the pollution status of agricultural soil caused by the mining of heavy metals in various mining areas in the Xunyang County in the Shaanxi Province of China, an area in famous for its resource mining. Equally, it will look at the potential ecological risk assessment process that is used to analyze the ecological risks of mining heavy metals in agricultural soil located in the surrounding areas. Based on the soil investigation, As pose a moderate ecological risk on the Au mining area. In addition, the Hg metals pose a significantly high potential ecological risk and Cd metals pose a considerable potential ecological risk on the Hg mining area. In the Pb-Zn mining area, a significantly high potential ecological risk was mainly posed by Cd. These results suggest that many heavy metals pose a high potential ecological risk on the agricultural soil in these three mining areas in the Xunyang County, and may cause elevated heavy metal contents in crops, eventually jeopardizing the health of local residents who consume food grown in polluted soil.


Assuntos
Metais Pesados/análise , Poluentes do Solo/análise , Agricultura , China , Produtos Agrícolas , Monitoramento Ambiental/métodos , Poluição Ambiental/análise , Mineração , Medição de Risco
16.
Phytomedicine ; 44: 20-31, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29895489

RESUMO

BACKGROUND: As a traditional Chinese herbal formula, Shengui Sansheng San (SSS) has been employed for stroke treatment more than 300 years. PURPOSE: We hypothesize that SSS extraction is an angiogenic switch in penumbra post-stroke, and corresponding mechanisms are investigated. METHODS: In present study, rats were subjected to permanent middle cerebral artery occlusion model (MCAo) and were treated with low, middle and high doses of SSS extraction. We assessed neurological function and survival rate, and measured infarct volume by 2,3,5-triphenyltetrazolium chloride staining on day 7 after ischemia. von Willebrand factor (vWF), stromal cell-derived factor-1 alpha (SDF-1α) /chemokine (C-X-C motif) receptor 4 (CXCR4) axis, vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) as well as protein kinase B (AKT)/mammalian target of rapamycin (mTOR) /hypoxia-inducible factor-1 alpha (HIF-1α), extracellular signal-regulated kinase 1/2 (ERK1/2) and Notch1 signaling pathways were respectively investigated by immunofluorescence assay or western blotting in vivo and oxygen-glucose-deprived (OGD) brain microvascular endothelial cells (BMECs); simultaneously, wound healing of BMECs and tube formation assay were administrated. RESULTS: Compared to MCAo group, SSS extraction could significantly improve neurological functional scores, survival rate and cerebral infarct volume, enhance vWF+ vascular density and perimeter, SDF-1α/CXCR4 axis, VEGF expression, as well as activate AKT/mTOR/HIF-1α and ERK1/2 and inhibit Notch1 pathways in penumbra. In vitro, containing SSS extraction serum increased BMEC migration, capillary formation and VEGF expression via up-regulations of AKT/mTOR and ERK1/2 pathways in OGD BMECs, but ERK inhibitor (U0126) reversed the result of VEGF expression in high dose of SSS group. Additionally, VEGFR2 and Notch1 expressions were suppressed by containing SSS extraction serum. All results were in dose dependent manner. CONCLUSION: Our study firstly demonstrates that SSS extraction is an angiogenic switch. Due to suppressed VEGFR2/Notch1 cascades and activated AKT/mTOR and ERK1/2 signals in BMECs, a feedback loop of angiogenic homeostasis is established. Furthermore, the comprehensive mediations of SDF-1α/CXCR4 axis, AKT/mTOR/HIF-α, ERK1/2 and Notch1 pathways in penumbra contribute to the improvements of neurological function, survival rate and infarct volume post-stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Isquemia Encefálica/metabolismo , Células Cultivadas , Quimiocina CXCL12/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Endotélio Vascular/citologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Infarto da Artéria Cerebral Média , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptor Notch1/metabolismo , Receptores CXCR4/metabolismo , Acidente Vascular Cerebral/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
17.
PLoS One ; 13(6): e0198669, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29883469

RESUMO

BACKGROUND: Obesity paradox refers to lower mortality in subjects with higher body mass index (BMI), and has been documented under a variety of condition. However, whether obesity paradox exists in adults requiring mechanical ventilation in intensive critical units (ICU) remains controversial. METHODS: MEDLINE, EMBASE, China Biology Medicine disc (CBM) and CINAHL electronic databases were searched from the earliest available date to July 2017, using the following search terms: "body weight", "body mass index", "overweight" or "obesity" and "ventilator", "mechanically ventilated", "mechanical ventilation", without language restriction. Subjects were divided into the following categories based on BMI (kg/m2): underweight, < 18.5 kg/m2; normal, 18.5-24.9 kg/m2; overweight, BMI 25-29.9 kg/m2; obese, 30-39.9 kg/m2; and severely obese > 40 kg/m2. The primary outcome was mortality, and included ICU mortality, hospital mortality, short-term mortality (<6 months), and long-term mortality (6 months or beyond). Secondary outcomes included duration of mechanical ventilation, length of stay (LOS) in ICU and hospital. A random-effects model was used for data analyses. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 15,729 articles were screened. The final analysis included 23 articles (199,421 subjects). In comparison to non-obese patients, obese patients had lower ICU mortality (odds ratio (OR) 0.88, 95% CI 0.0.84-0.92, I2 = 0%), hospital mortality (OR 0.83, 95% CI 0.74-0.93, I2 = 52%), short-term mortality (OR 0.81, 95% CI 0.74-0.88, I2 = 0%) as well as long-term mortality (OR 0.69, 95% CI 0.60-0.79, I2 = 0%). In comparison to subjects with normal BMI, obese patients had lower ICU mortality (OR 0.88, 95% CI 0.82-0.93, I2 = 5%). Hospital mortality was lower in severely obese and obese subjects (OR 0.71, 95% CI 0.53-0.94, I2 = 74%, and OR 0.80, 95% CI 0.73-0.89, I2 = 30%). Short-term mortality was lower in overweight and obese subjects (OR 0.82, 95% CI 0.75-0.90, I2 = 0%, and, OR 0.75, 95% CI 0.66-0.84, I2 = 8%, respectively). Long-term mortality was lower in severely obese, obese and overweight subjects (OR 0.39, 95% CI 0.18-0.83, and OR 0.63, 95% CI 0.46-0.86, I2 = 56%, and OR 0.66, 95% CI 0.57-0.77, I2 = 0%). All 4 mortality measures were higher in underweight subjects than in subjects with normal BMI. Obese subjects had significantly longer duration on mechanical ventilation than non-obese group (mean difference (MD) 0.48, 95% CI 0.16-0.80, I2 = 37%), In comparison to subjects with normal BMI, severely obese BMI had significantly longer time in mechanical ventilation (MD 1.10, 95% CI 0.38-1.83, I2 = 47%). Hospital LOS did not differ between obese and non-obese patients (MD 0.05, 95% CI -0.52 to 0.50, I2 = 80%). Obese patients had longer ICU LOS than non-obese patients (MD 0.38, 95% CI 0.17-0.59, I2 = 70%). Hospital LOS and ICU LOS did not differ significantly in subjects with different BMI status. CONCLUSIONS: In ICU patients receiving mechanical ventilation, higher BMI is associated with lower mortality and longer duration on mechanical ventilation.


Assuntos
Índice de Massa Corporal , Estado Terminal/mortalidade , Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Adulto , Estado Terminal/terapia , Humanos , Fatores de Tempo
18.
Zhongguo Zhen Jiu ; 38(3): 319-23, 2018 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-29701053

RESUMO

To explore the mechanism of acupoint embedding for obesity based on the western pathological mechanism of chronic low inflammatory response inducing the imbalance between"promoting inflammation"and"anti-inflammation"in immune reaction, and the pathological nature of deficient healthy qi and state of evil domination in the TCM theory induced by the"stagnation heat, phlegm heat, dampness heat, stasis heat"on the basis of qi deficiency. The mechanism may be improving the secretory disorder of adipose tissue and metabolic inflammatory response by the enhanced anti-inflammatory phagocytosis clearance ability in the immune system which is caused by the new inflammatory reaction under the stimulation of innate immune response pattern. The model of"inhibiting chronic low inflammation reaction through the innate immunity"may be an important mechanism of acupoint embedding for obesity.


Assuntos
Pontos de Acupuntura , Inflamação/terapia , Obesidade/terapia , Tecido Adiposo/fisiopatologia , Humanos , Imunidade Inata , Medicina Tradicional Chinesa
19.
J Hazard Mater ; 349: 215-223, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29427972

RESUMO

Few studies have explored the long-term effects of elevated atmospheric CO2 combined with lead (Pb) contamination on plants. The objective of this study was to examine the effects of 3 years of elevated CO2 (700 ±â€¯23 µmol mol-1) on Pb accumulation and plant defenses in leaves of Robinia pseudoacacia L. seedlings in exposed to Pb (500 mg kg-1 soil). Elevated CO2 increased Pb accumulation in leaves and Pb removal rate in soils. In plants exposed to Pb stress, total chlorophyll and carotenoid contents in leaves were lower under elevated CO2 than under ambient CO2, but seedling height and width increased under elevated CO2 relative to ambient CO2. Elevated CO2 significantly (p < .01) stimulated malondialdehyde content in leaves under Pb exposure. Superoxide dismutase and catalase activity increased significantly (p < .01), peroxidase activity decreased significantly (p < .01), and glutathione, cystine, and phytochelatin contents increased under elevated CO2 + Pb relative to Pb alone. Elevated CO2 stimulated the production of soluble sugars, proline, flavonoids, saponins, and phenolics in plants exposed to Pb stress. Ove rall, long-term elevation of CO2 increased Pb-induced oxidative damage in seedlings, but enhanced the phytoextraction of Pb from contaminated soils.


Assuntos
Dióxido de Carbono/toxicidade , Chumbo/toxicidade , Robinia/efeitos dos fármacos , Poluentes do Solo/toxicidade , Carotenoides/metabolismo , Catalase/metabolismo , Clorofila/metabolismo , Glutationa/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Fitoquelatinas/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Robinia/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Superóxido Dismutase/metabolismo
20.
Sci Rep ; 8(1): 3656, 2018 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-29483565

RESUMO

There are several publications related to the soil organic carbon (SOC) on the Qinghai-Tibetan Plateau (QTP). However, most of these reports were from different parts of the plateau with various sampling depth. Here, we present the results from a systematic sampling and analysis of 200 soil pits. Most of the pits were deeper than 2 m from an east-west transect across the plateau. The SOC and total nitrogen (TN) pools of the 148 × 104 km2, the area of the permafrost zone, for the upper 2 m soils calculated from the vegetation map were estimated to be 17.07 Pg (interquartile range: 11.34-25.33 Pg) and 1.72 Pg (interquartile range: 1.08-2.06 Pg), respectively. We also predicted the distribution of land cover types in 2050 and 2070 using decision tree rules and climate scenarios, and then predicted SOC and TN pools of this region. The results suggested that the SOC and TN pools will decrease in the future. The results not only contribute to the carbon and nitrogen storage and stocks in the permafrost regions as a whole but most importantly, to our knowledge of the possible changes of C and N storage on the QTP in the future.

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