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1.
J Nat Prod ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742403

RESUMO

Melongenaterpenes A-L (1-12), 12 new sesquiterpenoids with rare spiro[4.5]decane skeletons, were isolated from the roots of Solanum melongena. Their 2D structures and relative configurations were determined based on NMR and HRESIMS data. The absolute configuration of melongenaterpene A (1) was defined by X-ray crystallographic analysis. The absolute configurations of the remaining compounds were determined by comparison of their NMR data with 1 and consideration of the biosynthetic pathway. This is the first report of the crystal structure of a vetispirane-type sesquiterpenoid. None of the compounds exhibited cytotoxic activity against the three human cancer cell lines HepG2, HeLa, and MCF-7.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31742840

RESUMO

Photoresponsive materials that degrade, expand, change shape, or alter their microscopic topology in response to light have been studied for a wide range of applications. Such materials are typically in a metastable state during irradiation and return to their pre-irradiated state after removal of the light source. Strategies for the synthesis of materials that can reversibly photoswitch between two or more stable states, remaining in each state until a different stimulus is applied, could find applications as actuators, catalysts, and sensors. Here, we report a polymer gel comprising poly(ethylene glycol) star polymers linked by Cu 24 L 24 cuboctahedral metal-organic cages/polyhedra (MOCs) decorated with coumarin ligands. Upon exposure to long-wavelength UV light in the presence of a photosensitizer and a hydrogen donor, this "polyMOC" material can be reversibly switched between three oxidation states of copper (Cu(II), Cu(I), and Cu(0)). The instability of the MOC junctions of these materials in the Cu(I) and Cu(0) states leads to network disassembly, providing Cu(I)/Cu(0) solutions, respectively, that are stable until exposure to a second stimulus, oxygen, induces re-oxidation to Cu(II) and rapid supramolecular gelation. This reversible supramolecular disassembly of the Cu-based polyMOC network is shown to occur in the presence of a fixed covalent second network generated in situ by copper-catalyzed azide-alkyne cycloaddition (CuAAC), providing interpenetrating supramolecular and covalent double networks with spatiotemporally enhanced mechanical properties. This work demonstrates that reversible disassembly of multicomponent MOCs can be used to switch bulk material properties, enabling functions that are difficult to access in traditional supramolecular networks.

3.
Arq. bras. oftalmol ; 82(5): 363-371, Sept.-Oct. 2019. graf
Artigo em Inglês | LILACS-Express | ID: biblio-1019434

RESUMO

ABSTRACT Purpose: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. Methods: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. Results: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. Conclusions: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.


RESUMO Objetivos: Como uma classe de drogas psicoesti mulantes, as anfetaminas são amplamente usadas por suas propriedades estimulantes, eufóricas e alucinógenas. Muitos desses efeitos resultam de aumentos agudos na neurotransmissão da dopamina e da serotonina. Após o início desses efeitos, a 3,4-metilenedioximetanfetamina produz danos persistentes nos terminais nervosos de dopamina e serotonina, resultando em neurotoxicidade duradoura. O objetivo desta investigação foi avaliar os efeitos do tratamento baixa dose de metilenedioximetanfetamina na função da retina em camundongos C57BL/6 e seus mecanismos subjacentes. Métodos: Camundongos C57BL/6 foram divididos aleatoriamente em dois grupos (n=10): um grupo foi tratado com solução salina tamponada de fosfato por injeção intraperitoneal diária; o outro grupo foi tratado com 1 mg/kg de metilenedioximetanfetamina por injeção intraperitoneal diária durante 3 meses. Eletroretinografia foi utilizada para testar a função da retina a cada mês. A coloração H&E e análise com deoxinucleotidil terminal transferase foram utilizados para avaliar a morfologia e histologia da retina. Testes de imunoabsorção enzimática foram utilizados para medir marcadores de estresse oxidativo e fatores inflamatórios. A expressão de genes e proteínas foi detectada por PCR em tempo real e western blot. Resultados: O tratamento de três meses com metilenedioximetanfetamina induziu disfunção de retina significativa por apoptose de células fotorreceptoras por estresse oxidativo e resposta inflamatória. Conclusões: Estes resultados sugerem que o tratamento a longo prazo com metilenedioximetanfetamina aumenta as respostas inflamatórias em células fotorreceptoras, resultando em disfunção de retina em camundongos C57BL/6. Assim, a investigação foence uma justificação pré-clínica para os danos na retina causados pelo abuso de metilenedioximetanfetamina.

4.
J Phys Chem Lett ; 10(20): 6368-6374, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31578867

RESUMO

Recent developments in quantum embedding have offered an attractive approach to describing electron correlation in molecules. However, previous methods such as density matrix embedding theory (DMET) require rigid partitioning of the system into fragments, which creates significant ambiguity for molecules. Bootstrap embedding (BE) is more flexible because it allows overlapping fragments, but when done on an orbital-by-orbital basis, BE introduces ambiguity in defining the connectivity of the orbitals. In this Letter, we present an atom-based fragment definition that significantly augments BE's performance in molecules. The resulting method, which we term atom-based BE, is very effective at recovering valence electron correlation in moderate-sized bases and delivers near-chemical-accuracy results using extrapolation. We anticipate atom-based BE may lead to a low-scaling and highly accurate approach to electron correlation in large molecules.

6.
Inflamm Res ; 68(12): 1025-1034, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31531682

RESUMO

OBJECTIVE: Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity. METHODS: HepG2.2.15 cells were cultured at 37 â„ƒ in the presence of 1-40 µg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α. RESULTS: We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc's anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants. CONCLUSION: SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection.

7.
Asian Pac J Cancer Prev ; 20(8): 2415-2420, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450915

RESUMO

Objectives: The optimal combination of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and chemotherapy has helped to improve therapeutic effects in non-small-cell lung cancer (NSCLC). This study aimed to explore the progression free survival (PFS) of patients after sequential administration of TKI and pemetrexed chemotherapy. Methods: This study retrospectively screened treatment-naive advanced NSCLC patients harbouring EGFR mutations who were prescribed a TKI and salvaged with pemetrexed chemotherapy or vice versa. The total, initial and salvage PFS were collected. Results: The total PFS including both the initial and salvage PFS was 18.0 mon (95% CI: 14.1­21.9 mon), which was not influenced by the sequence of administration (TKI first: 18.0 mon, 95% CI: 15.8­20.2 mon, pemetrexed first: 16.1 mon, 95% CI: 9.1­23.1 mon, HR 0.92, P=0.748). A longer PFS was achieved for TKI over chemotherapy in both the initial (10.6 and 5.9 mon, HR 2.62, P=0.001) and salvage therapy (12.0 and 6.0 mon, HR 1.29, P=0.001). TKI remained effective either before (10.6 mon) or after (12.0 mon) chemotherapy (HR 0.96, P=0.853). The same trend was observed for chemotherapy (5.9 and 6.0 mon for initial and salvage therapy, respectively, HR 0.82, P=0.417). Conclusions: The sequential administration of TKI and pemetrexed chemotherapy achieved a long PFS and was a suitable treatment for advanced NSCLC.

8.
Int J Biol Macromol ; 140: 858-870, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31446105

RESUMO

One purified fraction from crude Fuzhuan brick tea polysaccharides (FBTPS), FBTPS-3, was obtained through column chromatography of DEAE Sepharose Fast Flow. The chemical properties and probiotic effects of FBTPS-3 were evaluated by fermentation in vitro. Moreover, the effects of FBTPS-3 on the function and metabolic pathway of gut microbiota were investigated by metagenomic sequencing. The results showed that FBTPS-3 was an heteropolysaccharide with molecular weight of 741 kDa, which was mainly composed of Man, Rha, GalA, Gal and Ara in molar ratio of 8.7:15.5:42.2:19.7:13.9. The contents of carbohydrates and uronic acid in FBTPS-3 were 44.78 ±â€¯2.85% and 40.4 ±â€¯2.11%, respectively. After fermentation, the molecular weight of FBTPS-3 and content of carbohydrates were significantly decreased, indicating that FBTPS-3 could be utilized by gut microbiota. Furthermore, the relative abundances of Bacteroides, Megasphaera and Prevotella were significantly increased by FBTPS-3. FBTPS-3 also significantly promoted the production of acetic, propionic and n-butyric acids. Based on the metagenomic sequencing, it was found that FBTPS-3 significantly enriched the metabolic pathway of starch and sucrose. All the results suggest that FBTPS-3 is expected to be developed as functional ingredients or foods to improve the host health through regulating the gut microbiota and physiological metabolic functions.

9.
Radiother Oncol ; 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31431371

RESUMO

BACKGROUND: High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/ß ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/ß ratio for NSCLC treated with SBRT using individual patient data. MATERIALS AND METHODS: We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/ß ratio based on the observed number of local recurrences and accounting for tumor size. RESULTS: A total of 109 local progressions were observed after a median of 17.7 months (range 0.6-76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/ß = 12.8 Gy, 14.9 Gy and 12-16 Gy (depending on the prior for α/ß), respectively, although with large uncertainties that did not rule out the conventional α/ß = 10 Gy. CONCLUSIONS: Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/ß = 10 Gy is not ruled out by our data, larger values in the range 12-16 Gy are more probable, consistent with recent meta-regression analyses.

10.
Mult Scler Relat Disord ; 35: 185-192, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398657

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) can coexist with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Patients with overlapping Aquaporin 4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD and anti-NMDAR encephalitis with positive NMDAR antibodies in the cerebrospinal fluid (CSF) are rare but should not be ignored. METHODS: A unique case of NMOSD coexisting with anti-NMDAR encephalitis is presented. Case reports of AQP4-IgG-seropositive NMOSD overlapping with anti-NMDAR encephalitis with positive NMDAR antibodies in the CSF were reviewed. RESULTS: A 61-year-old female presented with headache, blurred vision, dysuria, limb weakness, coma, respiratory failure, and hypotension. Brain magnetic resonance imaging (MRI) showed abnormal signals in the left temporal lobe, white matter around the bilateral ventricles, midbrain, medulla oblongata, cervical, and upper thoracic medulla. AQP4-IgG antibodies were positive in the serum and CSF. NMDAR antibodies were positive in the CSF. The patient's condition was stable following intravenous gamma globulin, corticosteroids, immunosuppressants, and symptomatic support treatments. Only a single met the criteria of NMOSD simultaneously coexisting with anti-NMDAR encephalitis in addition to our own case. CONCLUSIONS: This case provides further evidence for the occurrence of NMOSD with AQP4-IgG-seropositive overlapping anti-NMDAR encephalitis in a Chinese patient. The mechanisms underlying the occurrence of double positive antibodies remains elusive. When NMOSD patients show unusual symptoms (abnormal behavior, prominent psychiatric manifestations, cognitive dysfunction, autonomic dysfunction), or atypical supratentorial lesions, the coexistence of anti-NMDAR encephalitis should be considered.

11.
J Chem Theory Comput ; 15(8): 4497-4506, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31343878

RESUMO

Fragment embedding is one way to circumvent the high computational scaling of accurate electron correlation methods. The challenge of applying fragment embedding to molecular systems primarily lies in the strong entanglement and correlation that prevent accurate fragmentation across chemical bonds. Recently, Schmidt decomposition has been shown effective for embedding fragments that are strongly coupled to a bath in several model systems. In this work, we extend a recently developed quantum embedding scheme, bootstrap embedding (BE), to molecular systems. The resulting method utilizes the matching conditions naturally arising from using overlapping fragments to optimize the embedding. Numerical simulation suggests that the accuracy of the embedding improves rapidly with fragment size for small molecules, whereas larger fragments that include orbitals from different atoms may be needed for larger molecules. BE scales linearly with system size (apart from an integral transform) and hence can potentially be useful for large-scale calculations.

12.
Nat Immunol ; 20(8): 1023-1034, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31263278

RESUMO

Stroke is a multiphasic process in which initial cerebral ischemia is followed by secondary injury from immune responses to ischemic brain components. Here we demonstrate that peripheral CD11b+CD45+ myeloid cells magnify stroke injury via activation of triggering receptor expressed on myeloid cells 1 (TREM1), an amplifier of proinflammatory innate immune responses. TREM1 was induced within hours after stroke peripherally in CD11b+CD45+ cells trafficking to ischemic brain. TREM1 inhibition genetically or pharmacologically improved outcome via protective antioxidant and anti-inflammatory mechanisms. Positron electron tomography imaging using radiolabeled antibody recognizing TREM1 revealed elevated TREM1 expression in spleen and, unexpectedly, in intestine. In the lamina propria, noradrenergic-dependent increases in gut permeability induced TREM1 on inflammatory Ly6C+MHCII+ macrophages, further increasing epithelial permeability and facilitating bacterial translocation across the gut barrier. Thus, following stroke, peripheral TREM1 induction amplifies proinflammatory responses to both brain-derived and intestinal-derived immunogenic components. Critically, targeting this specific innate immune pathway reduces cerebral injury.


Assuntos
Encéfalo/imunologia , Mucosa Intestinal/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Acidente Vascular Cerebral/patologia , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Animais , Encéfalo/citologia , Linhagem Celular , Imunidade Inata/imunologia , Inflamação/patologia , Mucosa Intestinal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células RAW 264.7
13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 160-164, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250609

RESUMO

OBJECTIVE: To observe whether necroptosis was happened in high glucose (HG) - induced primary cardiomyocytes injury and to investigate the likely mechanism. METHODS: The primary cultured cardiomyocytes were divided into 4 groups (n=9): control group (the cardiomyocytes were incubated with 5.5 mmol/L glucose for 48 h), HG group (the cardiomyocytes were incubated with 30 mmol/L glucose for 48 h), HG + necrostatin-1 (Nec-1) group (the cardiomyocytes was co-incubated with necroptosis inhibitor Nec-1 at 100 µmol/L and HG for 48 h) and hypertonic pressure group (HPG, the cardiomyocytes was co-incubated with 5.5 mmol/L glucose and 24.5 mmol/L mannitol for 48 h). Cell viability was measured by MTT method, reactive oxygen species (ROS) generation was measured by DHE staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) were tested by ELISA method. The mRNA and protein expressions of necroptosis related genes receptor interacting serine/threonine protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) were tested by quantitative real-time PCR and Western blot. RESULTS: The results showed HG intervention decreased cardiomyocytes viability, increased ROS generation, up-regulated the levels of TNF-α, IL-6 and IL-1ß, increased RIP1, RIP3, MLKL expressions at mRNA and protein levels. Nec-1 treatment attenuated HG-induced increased cardiomyocytes viability, reduced ROS generation, down-regulated the levels of TNF-α, IL-6 and IL-1ß, decreased RIP1, RIP3, MLKL expressions at mRNA and protein levels. CONCLUSION: Necroptosis was happened in high glucose-induced primary cardiomyocytes injury. Inhibition of necroptosis can reduce high glucose-induced cardiomyocytes damage, may be related to inhibition of oxidative stress and depression of inflammative factors releasing.


Assuntos
Apoptose , Miócitos Cardíacos/citologia , Miócitos Cardíacos/patologia , Necrose , Células Cultivadas , Citocinas/metabolismo , Glucose/efeitos adversos , Humanos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
14.
Arq Bras Oftalmol ; 82(5): 363-371, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31166425

RESUMO

PURPOSE: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. METHODS: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. RESULTS: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. CONCLUSIONS: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.

15.
J Mol Endocrinol ; 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125976

RESUMO

Lactoferrin (LF) is an iron-binding glycoprotein that plays an important role in promoting bone formation and inhibiting bone resorption; however, its effects on senile osteoporosis remain unknown. This study aimed to investigate the effects and mechanism of LF intervention using a senile osteoporosis model (SAMP6 mice) and senescent osteoblasts. Micro-CT and hematoxylin and eosin staining demonstrated that the intragastric administration (2 g·kg-1·d-1 ) of LF could improve the bone mass and microstructure of SAMP6 mice. Furthermore, LF treatment improved bone metabolism and increased insulin-like growth factor 1 (Igf1) mRNA expression and activated phosphorylation status of AKT. Using osteoblasts passaged for 10 generations as an in vitro senescence model, various markers associated with osteoblast formation and differentiation, as well as related indices of oxidative stress were analyzed. Our results revealed that after multiple generations, osteoblasts entered senescence, in conjunction with increased oxidative stress damage, reduced bone metabolism, and enhanced expression of aging-related markers. While inhibiting oxidative stress, LF improved osteoblast proliferation by promoting the expression of osteogenesis markers, including alkaline phosphatase (ALP) activity, Igf1, bone gla protein (Bglap), and osteoprotegerin/receptor activator of nuclear factor-kB ligand (Opg/Rankl) mRNA, and delayed senescence by decreasing the level of p16 and p21 expression. RNAI-mediated downregulation of IGF1 attenuated the effect of LF on osteogenesis. Therefore, the findings of the present study indicate that LF may promote osteogenesis via IGF1 signaling, thereby preventing senile osteoporosis.

16.
Huan Jing Ke Xue ; 40(5): 2186-2193, 2019 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087855

RESUMO

In order to explore the effect of land use pattern on phosphorus distribution and the potential release capacity of stream sediment in the upper Minjiang River, this paper presented organic phosphorus forms and their spatial distribution characteristics of sediments in the upper Minjiang River by using the IVANOFF method and discussing the effects of physicochemical properties of sediments on the distribution of organic phosphorus forms. The results show that:①nitrogen and phosphorus contents of sediments in Jianxi and Shaxi catchments are higher than those in the Futunxi catchment, probably related to the large number of farmland runoff and municipal sewage near the Jianxi and Shaxi catchments and the large forest area around the Futunxi catchment;②contents in the sediments from three catchments and TP contents in the sediments from Jianxi and Futunxi catchments showed the order of upper reaches < middle reaches < lower reaches, which may be caused by the mountainous and forested areas in the upper reaches and the intensive human activities in the middle and lower reaches;③nitrogen phosphorus in sediments of the three catchments were mainly non-active organic phosphorus, which indicated that upper reaches of the Minjiang river were generally less affected by external pollution, and the relative proportion of organic phosphorus in the sediments of different catchments was relatively large, while the change in different sections of the same river was relatively small;④physicochemical properties of sediments had a significant impact on the morphology and distribution of organic phosphorus, among which the effects of organic matter, TP, and TN were the most obvious, but the effects on sediments in different river basins were different. Therefore, to protect the water quality of the upper Minjiang River, it is necessary to strengthen the control of the living and agricultural pollution sources near the catchments.

17.
Huan Jing Ke Xue ; 40(3): 1043-1051, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087950

RESUMO

An electrical low pressure impactor particle monitor was used to monitor typical industries in Sichuan Province, such as cement, glass, ceramic, brick-tile, coal-fired boiler, biomass boiler, power plant, and steel industry. Fine particulate matter source profiles of each industry were developed based on the laboratory analysis. The results showed that Si, Ca, and Mg were the major elements of building industry particulate matter emission. Sulfate emission from double sodium-calcium was higher than from other desulfurization technologies in the building industry. The main chemical components of PM2.5 from power plants were SO42-, Ca2+, NH4+, Mg, and Si, while OC, Al, Si, and Ca were the main chemical components of PM2.5 from coal-fired boilers. The content of OC was the most abundant in biomass briquette boiler particulate matter emissions, followed by K and EC. In term of the biomass fuel boiler PM2.5 source profile, OC, EC, and Cl- were the major chemical components. Ca was the largest component of PM2.5 from the steel industry, accounting for 18.11% of the total PM2.5 emission, followed by SO42-, Na+, and Fe.

18.
J Immunother Cancer ; 7(1): 119, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053174

RESUMO

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-driven disorder that causes substantial morbidity and can lead to fatal distal airway obstruction and post-obstructive pneumonias. Patients require frequent surgical debridement of disease, and no approved systemic adjuvant therapies exist. METHODS: A phase II study was conducted to investigate the clinical activity and safety of programmed death-ligand 1 (PD-L1) blockade with avelumab in patients with RRP. RESULTS: Twelve patients were treated. All patients with laryngeal RRP displayed improvement in disease burden, and 5 of 9 (56%) displayed partial responses. None of 4 patients with pulmonary RRP displayed a response. Using each patient's surgical history as their own control, patients required fewer surgical interventions after avelumab treatment (p = 0.008). A subset of partial responders developed HPV-specific reactivity in papilloma-infiltrating T-cells that correlated with reduced HPV viral load and an increased Tissue Inflammation Signature. CONCLUSIONS: Avelumab demonstrated safety and clinical activity in patients with laryngeal RRP. Further study of immune checkpoint blockade for RRP, possibly with longer treatment duration or in combination with other immunotherapies aimed at activating antiviral immunity, is warranted. TRIAL REGISTRATION: NCT, number NCT02859454 , registered August 9, 2016.

19.
Molecules ; 24(10)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31109015

RESUMO

Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide. Mangiferin is a natural glucosylxanthone with antioxidant and anti-inflammatory properties, which has been confirmed to protect cardiac cells from myocardial infarction and myocardial ischemia reperfusion injury (MIRI); however, the underlying mechanism is still unclear. As oxidative stress is a major pathogenesis of MIRI, an H9C2 cell injury induced by hydrogen peroxide (H2O2) was established to simulate MIRI in vitro. Herein, the protective effect of mangiferin against MIRI was evaluated and the isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics was applied to explore the underlying molecular mechanism. In this research, mangiferin markedly ameliorated the oxidative imbalance by increasing the antioxidative capacity of the H9C2 cell. Moreover, proteomics analysis revealed that mangiferin pretreatment brought twenty differently-expressed proteins back to normal, most of which were related to glucose and fatty acid metabolism. Glycolysis, citrate cycle, and fatty acid degradation pathways were highlighted by Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis. Western blot validation of six cardiac metabolism-related proteins were consistent with the proteomics analysis. Taken together, mangiferin protected the cardiomyocytes from MIRI by enhancing the antioxidant capacity and increasing the activities of glycolysis, citrate cycle, and fatty acid degradation pathways.


Assuntos
Cardiotônicos/farmacologia , Peróxido de Hidrogênio/efeitos adversos , Miócitos Cardíacos/citologia , Proteômica/métodos , Xantonas/farmacologia , Animais , Linhagem Celular , Ciclo do Ácido Cítrico/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos
20.
Eur J Obstet Gynecol Reprod Biol ; 237: 100-105, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035117

RESUMO

OBJECTIVES: Research suggests the efficacy of progesterone for luteal phase support in assisted reproduction cycles using gonadotropin-releasing hormone analogues. Our study objective was to compare the efficacy of two available preparations of progesterone, vaginal gel and intramuscular injection, for luteal phase support in assisted reproduction cycles. STUDY DESIGN: This study included data gathered from 18 reproductive centers in China. Subjects were randomly allocated to receive progesterone gel or intramuscular progesterone (IMP). The progesterone gel group received micronized progesterone in gel (8%, 90 mg) once daily; the IMP group received IMP (progesterone oil) once daily. The ongoing pregnancy rate was calculated (number of women with a viable pregnancy at 12 weeks divided by the number of women who had undergone an oocyte pickup cycle). RESULTS: A total of 1313 patients were enrolled in the study, 1248 of whom began treatment. The intention-to-treat set included 527 and 531 patients in the gel and IMP groups, respectively. The ongoing pregnancy rate in the progesterone gel group was non-inferior to that in the IMP group (48.4% [95% confidence interval (CI): 44.0, 52.8] vs. 46.3% [95% CI: 42.0, 50.7]); the between-group rate difference was 2.1% (-4.0, 8.1). There was no difference between the gel group and IMP group on most secondary endpoints, including implantation rate, biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, early abortion rate, and vaginal bleeding rate, but there was a between-group difference in luteal phase bleeding rate. The safety analysis showed no difference in the incidence of total adverse events. CONCLUSIONS: Progesterone gel showed good efficacy and safety outcomes and therefore provides an alternative method of luteal support in Chinese in vitro fertilization patients.

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