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1.
JMIR Mhealth Uhealth ; 8(5): e14826, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32383684

RESUMO

BACKGROUND: As representatives of health information communication platforms accessed through mobile phones and mobile terminals, health-related WeChat public accounts (HWPAs) have a large consumer base in the Chinese-speaking world. However, there is still a lack of general understanding of the status quo of HWPAs and the quality of the articles they release. OBJECTIVE: The aims of this study were to assess the conformity of HWPAs to the Health on the Net Foundation Code of Conduct (HONcode) and to evaluate the suitability of articles disseminated by HWPAs. METHODS: The survey was conducted from April 23 to May 5, 2019. Based on the monthly (March 1-31, 2019) WeChat Index provided by Qingbo Big Data, the top 100 HWPAs were examined to evaluate their HONcode compliance. The first four articles published by each HWPA on the survey dates were selected as samples to evaluate their suitability. All materials were assessed by three raters. The materials were assessed using the HONcode checklist and the Suitability Assessment of Materials (SAM) score sheet. Data analysis was performed with SPSS version 17.0 (SPSS Inc, Chicago, IL, USA) and Excel version 2013 (Microsoft Inc, Washington DC, USA). RESULTS: A total of 93 HWPAs and 210 of their released articles were included in this study. For six of the eight principles, the 93 HWPAs nearly consistently did not meet the requirements of the HONcode. The HWPAs certified by Tencent Corporation (66/93, 71%) were generally slightly superior to those without such certification (27/93, 29%) in terms of compliance with HONcode principles. The mean SAM score for the 210 articles was 67.72 (SD 10.930), which indicated "adequate" suitability. There was no significant difference between the SAM scores of the articles published by certified and uncertified HWPAs (P=.07), except in the literacy requirements dimension (tdf=97=-2.418, P=.02). CONCLUSIONS: The HWPAs had low HONcode conformity. Although the suitability of health information released by HWPAs was at a moderate level, there were still problems identified, such as difficulty in tracing information sources, excessive implicit advertisements, and irregular usage of charts. In addition, the low approval requirements of HWPAs were not conducive to improvement of their service quality.

2.
Nat Commun ; 11(1): 1769, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286295

RESUMO

Our current understanding of how sugar metabolism affects inflammatory pathways in macrophages is incomplete. Here, we show that glycogen metabolism is an important event that controls macrophage-mediated inflammatory responses. IFN-γ/LPS treatment stimulates macrophages to synthesize glycogen, which is then channeled through glycogenolysis to generate G6P and further through the pentose phosphate pathway to yield abundant NADPH, ensuring high levels of reduced glutathione for inflammatory macrophage survival. Meanwhile, glycogen metabolism also increases UDPG levels and the receptor P2Y14 in macrophages. The UDPG/P2Y14 signaling pathway not only upregulates the expression of STAT1 via activating RARß but also promotes STAT1 phosphorylation by downregulating phosphatase TC45. Blockade of this glycogen metabolic pathway disrupts acute inflammatory responses in multiple mouse models. Glycogen metabolism also regulates inflammatory responses in patients with sepsis. These findings show that glycogen metabolism in macrophages is an important regulator and indicate strategies that might be used to treat acute inflammatory diseases.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32233392

RESUMO

Two-dimensional (2D)-structured photocatalysts with atomically thin layers not only have the potential to enhance hydrogen generation efficiency but also allow more direct investigations of the effects of surface terminations on photocatalytic activity. Taking 2D Bi2WO6 as a model, we found that the configuration of bilayer Bi2O2 sandwiched by alternating WO4 layers enabled the thermodynamic driving potential for photocatalytic hydrogen evolution. Without Pt deposition, the H2 generation efficiency can reach to 56.9 µmol/g/h by 2D Bi2WO6 as compared with no activity of Bi2WO6 nanocrystals under simulated solar light. This configuration is easily functionalized by adsorption of Cl-/Br- to form Bi-Cl/Bi-Br bonds, which leads to the decrease of recombination in photogenerated charge carriers and narrower band gaps. This work highlights an effective way to design photocatalysts with efficient hydrogen evolution by tuning the surface terminations.

4.
Arthritis Res Ther ; 22(1): 61, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32216830

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, and the damage of cartilage as well as bone. Resolvin D1 (RvD1) can promote inflammation resolution in acute inflammatory diseases, and recently, effects of RvD1 on chronic inflammatory diseases also attracted attention. This study aimed to examine the effect of RvD1 on pannus formation in RA and the underlying mechanism. METHODS: Serum levels of RvD1 and CTGF were determined in RA patients and healthy persons by UPLC-MS/MS and ELISA respectively. The levels of CTGF and inflammatory factors were assessed by qRT-PCR and ELISA. MicroRNA expression profile was determined by miRNA microarray. The effects of CTGF, RvD1, and miR-146a-5p on angiogenesis were evaluated with tube formation and chick chorioallantoic membrane (CAM) assays. Collagen-induced arthritis (CIA) mice were constructed to detect the effects of RvD1 and miR146a-5p on RA. STAT3 activation was determined by Western blotting. RESULTS: RvD1 levels decreased while CTGF levels increased in RA patients' serum, and an inverse correlation of the concentrations of RvD1 and CTGF in the serum of RA patients was synchronously observed. In CIA mice, RvD1 suppressed angiopoiesis and decreased the expression of CTGF. Simultaneously, RvD1 significantly decreased CTGF and pro-inflammation cytokines levels in RA FLS. Furthermore, CTGF suppressed angiopoiesis and RvD1 inhibited the proliferation and migration of RA FLS and angiopoiesis. MiRNA microarray and qRT-PCR results showed that RvD1 upregulated miRNA-146a-5p. The transfection experiments demonstrated that miRNA-146a-5p could decrease inflammatory factors and CTGF levels. Moreover, miRNA-146a-5p decreased the proliferation of FLS and angiogenesis in vivo. MiRNA-146a-5p also suppressed angiogenesis and downregulated the expression of CTGF in CIA mice. Finally, Western blot results revealed that miRNA-146a-5p inhibited the activation of STAT3. CONCLUSION: RvD1 is prone to alleviate RA progression through the upregulation of miRNA-146a-5p to suppress the expression of CTGF and inflammatory mediators, thereby decreasing pannus formation and cartilage damage.

5.
J Gene Med ; : e3185, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166861

RESUMO

BACKGROUND: Sitosterolemia (STSL), also known as phytosterolemia, is a rare autosomal recessive hereditary disease caused by mutations in the ABCG5 or ABCG8 genes. The disease is a result of disorders in lipoprotein metabolism, and is characterized by tendinous and tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, and thrombocytopenia and hemolytic anemia in several patients. The manifestations of STSL are diverse and can easily be misdiagnosed. In recent years, cases of this disease in children have been reported in succession. There is therefore a need for clinicians to improve identification of STSL and perform early intervention. METHODS: We evaluated four children with STSL caused by genetic mutations in ABCG5 or ABCG8, as well as their family members, by analyzing their clinical characteristics and performing Trio-whole exome sequencing. The biological consequences of the mutations were analyzed using various bioinformatics software. We also analyzed the consequences of a mutation commonly observed in STSL patients on the structure of the protein involved. RESULTS: We identified five previously unreported pathogenic mutations of different phenotypes of STSL: ABCG5 NM_022436:c.1337G>A; ABCG8 NM_022437:c.965-1G>A, c.323-1G>C, c.1418C>G and c.1534G>A. We also report the structural changes brought about by a mutation common in STSL patients, as well as the possible consequences of these changes. CONCLUSIONS: Our findings further broaden the genotypic and phenotypic profiles of the onset of STSL in the pediatric population and provide information for the diagnosis and treatment of this disease.

6.
Sci Rep ; 10(1): 4701, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170127

RESUMO

Humans and rodents with Comparative Gene Identification-58 (CGI-58) mutations manifest nonalcoholic fatty liver disease (NAFLD). Here we show that liver CGI-58 knockout (LivKO) mice fed a Western diet rapidly develop advanced NAFLD, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. After 14 weeks of diet challenge, starting at 6 weeks of age, LivKO mice showed increased inflammatory cell infiltration and proinflammatory gene expression in the liver, which was associated with elevated plasma levels of aminotransferases. Hepatic ductular reactions, pericellular fibrosis, and bridging fibrosis were observed only in the LivKO mice. Consistently, the KO mice had a significant increase in hepatic mRNAs for fibrogenic genes. In addition, LivKO mice displayed massive accumulation of lipid droplets (LDs) in hepatocytes. LDs were also observed in the cholangiocytes of the LivKO mice, but not the floxed controls. Four of the five LD coat proteins, including perilipins 2, 3, 4, and 5, were increased in the CGI-58 KO liver. CRISPR/Cas9-mediated knockout of CGI-58 in Huh7 human hepatoma cells induced LD deposition and perilipin expression, suggesting a cell autonomous effect. Our findings establish the Western diet-fed LivKO mice as an animal model of NASH and hepatic fibrosis. These animals may facilitate preclinical screening of therapeutic agents that counter against NAFLD progression.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32201120

RESUMO

BACKGROUND: The aim of this study was to estimate the attributable risk for all-cause mortality in hypertensive adults living in Beijing, China. METHODS: We conducted a prospective cohort study on the basis of the disease risk prediction model, which included 3006 hypertensive patients aged 50 and over who participated in the annual health examination from thirty-eight community health centers were randomly selected from all 53 community health centers in Dongcheng district of Beijing in China. This cohort study was conducted from January 1, 2013 to June 31, 2018 in these community health centers. Data included age, gender, education level, BMI, smoking and drinking status, renal function, diabetes mellitus (DM), coronary heart disease, levels of blood pressure, use of medications, and blood lipid levels. RESULTS: the follow-up time was 4.90±0.51 years. There were significant survival differences by gender, renal function (eGFR>90 vs. 60-90 vs. <60mL/min per 1.73m2), smoking (smoking vs. No smoking), hypertension severity (SBP≥140 or DBP≥r vs. SBP/DBP<140/90mmHg), education level (<6 vs. 6-12 vs. >12 years), coronary heart disease (CHD) (CHD vs. NO CHD). In the multivariate Cox proportional hazard analysis, the prognostic factors of all-cause mortality in hypertensive patients were male [HR 1.662, 95% CI 1.110-2.489, p=0.014], educational level<6 years [HR 2.044, 95% CI 1.164-3.591, p 0.013], age ≥65 years [HR 3.092, 95% CI 1.717-5.571, p<0.001], smoking [HR 1.885, 95% CI 1.170-3.309, p=0.009], eGFR<60mL/min per 1.73m2 [HR 3.591, 95% CI 2.023-6.371, p<0.001]. CONCLUSIONS: we conclude that decreasing eGFR, increasing age, smoking, low education and gender (male) are significant and independent risk factor for mortality in hypertension for this urban cohort. Recommendations may include protecting renal function, providing patient education, and cessation of smoking. It highlights that early preventive measures are needed to detect kidney impairment and protect renal function. It also suggests that earlier smoking cessation may be important for hypertensive patients.

8.
Chin J Integr Med ; 26(2): 92-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31997236

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility. METHODS: A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment. RESULTS: (1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05). CONCLUSION: Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).

9.
Life Sci ; 245: 117356, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31991181

RESUMO

AIMS: NPY-Y1R plays an important role in dietary regulation. Although germline knockdown of NPY-Y1R in mice alleviates high-fat-diet-induced obesity and increases CPT1α levels in the liver, the role of the Y1 receptor in specific tissues has not been studied. MAIN METHODS: MCD diet is the most widely used method to establish a model of lean NASH in a short time. We therefore evaluated the role of liver NPY-Y1R in NASH progression. KEY FINDINGS: In mice with liver-specific knockout of NPY-Y1R (LivKO) and wild-type control littermates fed MCD diet for 4 weeks, NPY-Y1R deficiency significantly decreased body and liver weight. Moreover, NPY-Y1R deletion protected mice against hepatic steatosis and injury. LivKO decreased TG, TC, and FFA levels in the liver and alanine aminotransferase activity in plasma. To clarify the mechanism, we evaluated the key enzymes involved in triglyceride hydrolase and fatty-acid oxidase. Expression of ATGL, CPT1α, and ACO was significantly increased in LivKO mice, whereas expression of fatty-acid synthase was significantly decreased. mRNA expression analysis revealed a marked reduction of genes involved in de-novo lipogenesis and monosaturated fatty-acid synthesis, including sterol-regulatory element-binding protein 1c and fatty-acid synthase. Moreover, liver injury-related factors were significantly decreased in LivKO mice, such as TNF-α, inducible nitric oxide synthase, and MCP-1. Thus, NPY-Y1R deficiency in the liver alleviates lipid deposition and injury. However, NPY-Y1R did not affect inflammation and fibrosis. SIGNIFICANCE: NPY-Y1R deficiency in the liver directly suppresses not only hepatic steatosis, but also liver injury, and thus provides a treatment option for NASH.


Assuntos
Deficiência de Colina/metabolismo , Fígado/metabolismo , Metionina/deficiência , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/patologia , Reação em Cadeia da Polimerase em Tempo Real , Triglicerídeos/metabolismo
10.
Chin J Integr Med ; 26(2): 88-91, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31111425

RESUMO

Endometriosis (EM), a refractory, highly recurrent and life-threatening chronic disease, requires long-term management and long-term drug treatment. Our previous studies showed that Chinese medicine (CM) can inhibit the postoperative recurrence of EM, improve quality of life, shorten the time to conception and increase pregnancy rates. CM produces few adverse reactions with high safety. These characteristics might be associated with the mechanism of CM's inhibition of recurrence. Therefore, we believe that CM may represent a good choice for long-term drug treatment and is worthy of clinical application.

11.
Cancer Med ; 9(4): 1562-1571, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31873982

RESUMO

BACKGROUND: With the rapid development of the socioeconomic status, the mortality of several cancers has been changed in China during the past 30 years. We aimed to estimate the trends of mortality and years of life lost (YLLs) of various cancers in urban and rural areas of China from 1990 to 2017. METHODS: The mortality data were collected from Chinese yearbooks and the age structure of population from the Chinese sixth population census were used as reference to calculate age-standardized mortality rates (ASMRs) and YLLs rates. Joinpoint regression analysis was implemented to calculate the annual percent change (APC) of mortality rates and YLL rates for cancers. YLLs owing to premature death were calculated as age-specific cancer deaths multiplied by the reference life expectancy at birth of 80 years for male and 82.5 years for female. RESULTS: The ASMRs of all cancers showed significant decreasing trends for urban residents from 1990 to 2017, such downward trend without significance was also observed among rural residents. Interestingly, ASMRs of lung cancer and breast cancer have raised continuously in rural areas since 1990. The age-standardized YYL rates for urban and rural residents decreased with 1.02% and 0.85% per year, respectively. YLLs in rural areas were higher than those in urban areas, whereas YLLs of urban outstripped those of rural finally with the increasing in YLLs of urban areas (216.71% for men and 207.87% for women). CONCLUSION: The ASMRs and YLL rates of all cancers have declined in urban and rural areas from 1990 to 2017. YLLs increased in urban areas and remained higher level in rural areas after 2014 year. Preventive measures should be strengthened to against cancer, especially for lung cancer.

12.
ACS Nano ; 13(12): 14252-14261, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31794178

RESUMO

In order to fulfill the increasing demand for renewable energy, besides the lithium-ion batteries, other alkali (Na, K)-ion batteries are extensively investigated. However, the difficulty to find universal and environmentally benign electrodes for these alkali (Na, K)-ion batteries still severely restricts their development. Promising characteristics, including molecular diversity, low cost, and operation safety, endow the organic electrodes more advantages for applications in alkali-ion batteries. However, organic electrodes usually deliver a reversible capacity smaller than that of their inorganic counterparts due to sluggish ion/electron diffusion and possible dissolution in organic electrolytes. This work introduces fluorine atoms into the covalent triazine frameworks (CTF) to obtain two-dimensional layered fluorinated CTF (FCTF) and its exfoliated few-layered product (E-FCTF) and uses them as anodes of Li, Na, and K organic batteries. Exfoliated E-FCTF electrode delivers high reversible capacities, as well as excellent cycle life for alkali organic batteries (1035 mAh g-1 at 100 mA g-1 after 300 cycles and 581 mAh g-1 at 2 A g-1 after 1000 cycles for lithium organic batteries). In view of the experimental probing and the theoretical calculation, the Li storage mechanism for the E-FCTF can be determined to be an intriguing multielectronic redox reaction originated from lithium storage on the benzene ring and triazine ring units.

13.
mBio ; 10(6)2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848275

RESUMO

Multiple cellular metabolic pathways are altered by HIV-1 infection, with an impact on immune activation, inflammation, and acquisition of non-AIDS comorbid diseases. The dysfunction of tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the underlying mechanism remains unknown. In this study, we demonstrated that the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, is activated by Trp metabolites to promote HIV-1 infection and reactivation. AHR directly binds to the HIV-1 5' long terminal repeat (5'-LTR) at the molecular level to activate viral transcription and infection, and AHR activation by Trp metabolites increases its nuclear translocation and association with the HIV 5'-LTR; moreover, the binding of AHR with HIV-1 Tat facilitates the recruitment of positive transcription factors to viral promoters. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection.IMPORTANCE Cellular metabolic pathways that are altered by HIV-1 infection may accelerate disease progression. Dysfunction in tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the mechanism responsible was not known. This study demonstrates that Trp metabolites augment the activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, to promote HIV-1 infection and transcription. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection.


Assuntos
Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Triptofano/metabolismo , Ativação Viral , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Regulação Viral da Expressão Gênica , Infecções por HIV/tratamento farmacológico , Repetição Terminal Longa de HIV/genética , Humanos , Modelos Biológicos , Ativação Transcricional , Triptofano/sangue , Carga Viral , Produtos do Gene tat do Vírus da Imunodeficiência Humana
14.
Virol Sin ; 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31863357

RESUMO

Suitable animal models for human immunodeficiency virus type 1 (HIV-1) infection are important for elucidating viral pathogenesis and evaluating antiviral strategies in vivo. The B-NSG (NOD-PrkdcscidIl2rgtm1/Bcge) mice that have severe immune defect phenotype are examined for the suitability of such a model in this study. Human peripheral blood mononuclear cells (PBMCs) were engrafted into B-NSG mice via mouse tail vein injection, and the repopulated human T-lymphocytes were observed at as early as 3-weeks post-transplantation in mouse peripheral blood and several tissues. The humanized mice could be infected by HIV-1, and the infection recapitulated features of T-lymphocyte dynamic observed in HIV-1 infected humans, meanwhile the administration of combination antiretroviral therapy (cART) suppressed viral replication and restored T lymphocyte abnormalities. The establishment of HIV-1 infected humanized B-NSG mice not only provides a model to study virus and T cell interplays, but also can be a useful tool to evaluate antiviral strategies.

15.
ACS Nano ; 13(10): 12137-12147, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31593436

RESUMO

Rationally constructing inexpensive sulfur hosts that have high electronic conductivity, large void space for sulfur, strong chemisorption, and rapid redox kinetics to polysulfides is critically important for their practical use in lithium-sulfur (Li-S) batteries. Herein, we have designed a multifunctional sulfur host based on yolk-shelled Fe2N@C nanoboxes (Fe2N@C NBs) through a strategy of etching combined with nitridation for high-rate and ultralong Li-S batteries. The highly conductive carbon shell physically confines the active material and provides efficient pathways for fast electron/ion transport. Meanwhile, the polar Fe2N core provides strong chemical bonding and effective catalytic activity for polysulfides, which is proved by density functional theory calculations and electrochemical analysis techniques. Benefiting from these merits, the S/Fe2N@C NBs electrode with a high sulfur content manifests a high specific capacity, superior rate capability, and long-term cycling stability. Specifically, even after 600 cycles at 1 C, a capacity of 881 mAh g-1 with an average fading rate of only 0.036% can be retained, which is among the best cycling performances reported. The strategy in this study provides an approach to the design and construction of yolk-shelled iron-based compounds@carbon nanoarchitectures as inexpensive and efficient sulfur hosts for realizing practically usable Li-S batteries.

16.
Int J Biol Sci ; 15(11): 2448-2460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595162

RESUMO

The mTOR complex 2 (mTORC2) is recognized as a promising target for breast cancer treatment. As mTORC2-specific inhibitors do not yet exist, studies into the role of mTORC2 in cancer are performed by deleting Rictor or by RNAi-mediated Rictor silencing. The purpose of this study was to explore the effects of Rictor ablation in bone mesenchymal stromal cells (BMSCs) on bone metastasis of breast cancer. First, female mice with the genotype of Prx1-Cre;Rictorf/f (hereafter RiCKO) or Rictorf/f (as control) were injected intratibially with cells of the breast cancer cell line (TM40D) at 4 months of age. Three weeks later, osteolytic bone destruction was detected in metastatic legs by X-ray and micro-CT. We found that Rictor ablation in BMSCs inhibited TM40D-induced osteolytic bone destruction and resulted in greater bone volume maintenance in vivo. Lower CTX-I serum level, a decreased number of TRAP+ osteoclasts and lower Cathepsin-K expression observed at the tumor-bone interface indicated that osteoclastogenesis was inhibited in RiCKO mice. Additionally, co-culture experiments confirmed that Rictor deletion in BMSCs diminished osteoclast differentiation partly via down regulation of RANKL expression. Furthermore, Rictor deficiency was found to reduce the transition of BMSCs to CAFs coupled with decreased secretion of cytokines (IL-6, RANKL, TGFß), which resulted in lower chemotaxis and less proliferation in TM40D cells. These results suggest that Rictor ablation in BMSCs plays dual roles in breast cancer bone metastasis: (1) repression of osteolytic bone destruction; (2) inhibition of tumor growth.

17.
Cardiovasc J Afr ; 30: 1-8, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31647492

RESUMO

OBJECTIVE: To investigate whether salidroside (Sal) protected the rat heart from exhaustive exercise-induced injury by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. METHODS: Forty-eight male Sprague-Dawley rats were divided into four groups (n = 12 rats per group): the control, the exhaustive swimming (ES) group, the low-dose Sal plus acute exhaustive swimming (SLE) group, and the high-dose Sal plus acute exhaustive swimming (SHE) group. In the SLE and SHE groups, 15 and 30 mg/kg Sal were administered, respectively, once a day. The rats in the control and ES groups were administered the same amount of physiological saline, respectively, once a day. On the 14th day, the rats in the ES, SLE and SHE groups underwent exhaustive swimming training once. Then cardiac function parameters and electrocardiograms were recorded. Biomarkers of myocardial injury in the serum and oxidative stress factors in the myocardial tissue were evaluated using ELISA tests. The levels of Nrf2, nuclear Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) messenger RNA and proteins were assessed in the myocardium using q-PCR and Western blotting, respectively. RESULTS: Compared to the control group, the ES group showed remarkable increases in serum brain natriuretic peptide (BNP), cardiac troponin I (cTnI) and reactive oxygen species levels, but significant decreases in catalase and glutathione levels (p < 0.05). Compared to the ES group, the Sal treatment decreased serum BNP and cTnI levels and alleviated the changes in levels of oxidative stress-related factors. After treatment with Sal, nuclear and intracellular levels of Nrf2 protein were increased in the myocardial cells, while the level of Keap1 protein was decreased (p < 0.05). CONCLUSIONS: Sal protected the heart from exhaustive exercise induced injury, and it may improve cardiac function and cardiac bioelectricity in exhausted rats by inducing Nrf2 expression.

18.
Cell Mol Immunol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649305

RESUMO

Despite their mutual antagonism, inflammation and immunosuppression coexist in tumor microenvironments due to tumor and immune cell interactions, but the underlying mechanism remains unclear. Previously, we showed that tumor cell-derived microparticles induce an M2 phenotype characterized by immunosuppression in tumor-infiltrating macrophages. Here, we further showed that lung cancer microparticles (L-MPs) induce macrophages to release a key proinflammatory cytokine, IL-1ß, thus promoting lung cancer development. The underlying mechanism involves the activation of TLR3 and the NLRP3 inflammasome by L-MPs. More importantly, tyrosine kinase inhibitor treatment-induced L-MPs also induce human macrophages to release IL-1ß, leading to a tumor-promoting effect in a humanized mouse model. These findings demonstrated that in addition to their anti-inflammatory effect, L-MPs induce a proinflammatory phenotype in tumor-infiltrating macrophages, promoting the development of inflammatory and immunosuppressive tumor microenvironments.

19.
Cancer Genomics Proteomics ; 16(6): 465-479, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31659101

RESUMO

BACKGROUND: Hyperactivity of the mechanistic target of rapamycin complex 1 (mTORC1) is implicated in a variety of diseases such as cancer and diabetes. Treatment may benefit from effective mTORC1 inhibition, which can be achieved by preventing arginine from disrupting the cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1)-GTPase-activating proteins toward RAGS subcomplex 2 (GATOR2) complex through binding with CASTOR1. An attractive idea is to determine analogues of arginine that are as competent as arginine in binding with CASTOR1, but without disrupting the CASTOR1-GATOR2 interaction. MATERIALS AND METHODS: Molecular dynamics simulations were performed for binding of arginine analogues with CASTOR1 and binding free energy, hydrogen bond formation, and root mean squared deviation and root mean square fluctuation kinetics were then calculated. RESULTS: The binding free energy calculations revealed that Nα-acetyl-arginine, citrulline, and norarginine have sufficient binding affinity with CASTOR1 to compete with arginine. The hydrogen bond analysis revealed that norarginine, Nα-acetyl-arginine and D-arginine have proficient H-bonds that can facilitate their entering the narrow binding pocket. CONCLUSION: Norarginine and Nα-acetyl-arginine are the top drug candidates for mTORC1 inhibition, with Nα-acetyl-arginine being the best choice.

20.
BMJ Open ; 9(9): e030919, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511292

RESUMO

OBJECTIVES: This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, EMbase, Cochrane Library, Web of Science, Clinical trials, SinoMed, Chinese Biomedicine, CNKI, WanFang and Chongqing VIP Information databases were comprehensively searched until February 2018. ELIGIBILITY CRITERIA: Randomised clinical trials (RCTs) comparing the effects of different immunosuppressive treatments in adult patients with IMN and nephrotic syndrome were included, and all included RCTs had a study-duration of at least 6 months. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened articles, extracted data and assessed study quality. Standard pairwise meta-analysis was performed using DerSimonian-Laird random-effects model. RESULTS: This study ultimately included 48 RCTs with 2736 patients and 13 immunosuppressive agents. The network meta-analysis results showed that most regimens, except for leflunomide (LEF), mizoribine (MZB) and steroids (STE), showed significantly higher probabilities of total remission (TR) when compared with non-immunosuppressive therapies (the control group),with risk ratios (RRs) of 2.71 (95% CI) 1.81 to 4.06)for tacrolimus+tripterygium wilfordii (TAC+TW), 2.16 (1.27 to 3.69) foradrenocorticotropic hormone, 2.02 (1.64 to 2.49) for TAC, 2.03 (1.13 to3.64) for azathioprine (AZA), 1.91 (1.46 to 2.50) for cyclosporine (CsA), 1.86 (1.44 to2.42) for mycophenolate mofetil (MMF), 1.85 (1.52 to 2.25) for cyclophosphamide (CTX),1.81 (1.10 to 2.98) for rituximab (RIT), 1.80 (1.38 to 2.33) for TW, 1.72 (1.35 to 2.19) for chlorambucil. As for 24 hours UTP, the direct andindirect comparisons showed that AZA (standard mean difference (SMD), -1.02(95% CI -1.90 to -0.15)), CsA (SMD, -0.70 (95% CI -1.33 to -0.08)),CTX (SMD, -1.01 (95% CI -1.44 to -0.58)), MMF (SMD, -0.98 (95% CI -1.64 to -0.32)), MZB (SMD, -0.97 (95% CI -1.90 to-0.04]), TAC (SMD, -1.16 (95% CI -1.72 to -0.60)) and TAC+TW(SMD, -2.03 (95% CI -2.94 to -1.12)) could significantly superior thancontrol, except for chlorambucil, LEF, RIT and STE. Thechanges of serum creatinine (Scr) was not significantly different between eachtreatments of immunosuppressive agents and the control, except for STE whichhas the possibility of increasing Scr (SMD, 1.00 (95% CI 0.36 to 1.64)).Comparisons among all treatments of immunosuppressive agents showed nostatistical significance in the outcome of relapse. A drenocorticotropichormone (85.1%) showed the lowest probability of relapse under the cumulativeranking curve values among all immunosuppressants. Infection,gastrointestinal symptoms, and bone marrow suppression were the common adverseevents associated with most of the immunosuppressive therapies. CONCLUSIONS: This study demonstrates that TAC+TW, TAC and CTX are superior to other immunosuppressive agents in terms of TR and 24 hours UTP. Moreover, they are all at risk of infection, gastrointestinal symptoms, and myelosuppression. Furthermore, TAC could increase the risk of glucose intolerance or new-onset diabetes mellitus. Conversely, STE alone, LEF and MZB seem to have little advantage in clinical treatment of IMN. PROSPERO REGISTRATION NUMBER: CRD42018094228.

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