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1.
Bioorg Med Chem ; 44: 116291, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34216986

RESUMO

Twelve double fatty chains and Aib8-Arg34-GLP-1 (7-37) were designed and obtained by microwave-assisted solid-phase synthesis. Then, twelve conjugates of Aib8-Arg34-GLP-1 (7-37) were synthesized in 1% triethylamine aqueous solution. Conjugates 2, 3, 6, 7, 10 and 11 showed better GLP-1 receptor activation potency than semaglutide. However, conjugates 2, 6 and 10 showed slightly worse glucose-lowering effects in vivo than semaglutide but better effects than conjugates 3, 7 and 11. The CD spectra of conjugates 2, 6 and 10 indicated that they had the same secondary structure as liraglutide and semaglutide. The receptor affinity results for conjugates 2, 6 and 10 measured by SPR (surface plasmon resonance) showed that conjugate 2 had higher receptor affinity than conjugates 6 and 10. In addition, albumin binding assays indicated that double fatty acid chains had obvious synergistic effects compared with single fatty acid chains. In conclusion, the structure-activity relationship of different side chains was summarized and one candidate, conjugate 2, was screened.

2.
JMIR Mhealth Uhealth ; 9(7): e26098, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269681

RESUMO

BACKGROUND: Breastfeeding is essential for maintaining the health of mothers and babies. Breastfeeding can reduce the infection rate and mortality in newborns, and can reduce the chances of overweight and obesity in children and adolescents. For mothers, a longer duration of breastfeeding can reduce the risk of breast cancer, ovarian cancer, and type 2 diabetes. Although breastfeeding has many benefits, the global breastfeeding rate is low. With the progress of time, the popularity of mobile devices has increased rapidly, and interventions based on mobile health (mHealth) may have the potential to facilitate the improvement of the breastfeeding status. OBJECTIVE: The main objective of this study was to analyze the existing evidence to determine whether mHealth-based interventions can improve the status of breastfeeding. METHODS: We systematically searched multiple electronic databases (PubMed, Web of Science, The Cochrane Library, Embase, CNKI, WanFang, and Vip ) to identify eligible studies published from 1966 to October 29, 2020. Included studies were randomized controlled trials (RCTs) studying the influence of mHealth on breastfeeding. The Cochrane Collaboration Risk of Bias tool was used to examine the risk of publication bias. RevMan 5.3 was used to analyze the data. RESULTS: A total of 15 RCTs with a total sample size of 4366 participates met the inclusion criteria. Compared with usual care, interventions based on mHealth significantly increased the postpartum exclusive breastfeeding rate (odds ratio [OR] 3.18, 95% CI 2.20-4.59; P<.001), enhanced breastfeeding self-efficacy (mean difference [MD] 8.15, 95% CI 3.79-12.51; P=.002; I2=88%), reduced health problems in infants (OR 0.62, 95% CI 0.43-0.90; P=.01; I2=0%), and improved participants' attitudes toward breastfeeding compared with usual care (MD 3.94, 95% CI 1.95-5.92; P<.001; I2=0%). There was no significant difference in the initiation of breastfeeding within an hour of birth between the intervention group and the usual care group (OR 1.26, 95% CI 0.55-2.90; P=.59). In addition, subgroup analysis was carried out according to different subjects and publication times. The results showed that the breastfeeding rate was not limited by the types of subjects. The breastfeeding rate based on mHealth at 1 month and 2 months after delivery did not change over the time of publication (2009 to 2020), and the breastfeeding rate based on mHealth at 3 months and 6 months after delivery gradually increased with time (2009 to 2020). CONCLUSIONS: Interventions based on mHealth can significantly improve the rate of postpartum exclusive breastfeeding, breastfeeding efficacy, and participants' attitudes toward breastfeeding, and reduce health problems in infants. Therefore, encouraging women to join the mHealth team is feasible, and breastfeeding-related information can be provided through simple measures, such as text messages, phone calls, and the internet, to improve the health of postpartum women and their babies.

3.
Mol Nutr Food Res ; : e2001065, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075695

RESUMO

SCOPE: Inflammatory bowel disease (IBD) is an inflammatory gastrointestinal disorder in which endoplasmic reticulum (ER) stress and dysbiosis of the intestinal microbiota are implicated. Glycine supplementation is reported to reduce inflammatory responses in experimental colitis. However, the underlying mechanisms responsible for the beneficial effects remain unclear. METHODS AND RESULTS: Female C57BL/6 mice are orally administered with glycine (3.5 or 5.2 g kg-1 body weight) for 14 continuous days. On day 8 post-glycine supplementation, the mice are orally inoculated with 2 × 109 CFU Citrobacter rodentium (C. rodentium). The results show that glycine alleviates C. rodentium-induced body weight loss, increased disease activity index and spleen weight, colon length shortening, and colonic hyperplasia. Glycine suppresses the activation and infiltration of inflammatory cells, and secretion of pro-inflammatory cytokines in the colon tissues. The apoptosis of colon epithelial cells is also abrogated by glycine, which is associated with the inactivation of activating transcription factor 6α (ATF6α)-C/EBP homologous protein (CHOP) signaling. In addition, glycine administration increases α diversity, restores ß diversity, and abolishes the reduction in Lactobacillus, Bifidobacterium, Alistipes, Turicibacter, and Alloprevotella in the colon. CONCLUSIONS: Glycine supplementation is a nutritional strategy that may ameliorate C. rodentium-induced colitis by regulating ATF6α-CHOP-mediated ER stress and enhancing the abundance of Lactobacillus.

4.
JMIR Mhealth Uhealth ; 9(6): e24116, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114961

RESUMO

BACKGROUND: Stroke is a common, harmful disease with high recurrence and mortality rates. Uncontrolled blood pressure is an important and changeable risk factor for stroke recurrence. Telemedicine and mobile health (mHealth) interventions may have the potential to facilitate the control of blood pressure among stroke survivors, but their effect has not been established. OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to estimate the effects of telemedicine and mHealth interventions on the control of systolic blood pressure among stroke survivors. METHODS: The research literature published up to June 28, 2020, and consisting of RCTs related to telemedicine and mHealth interventions was searched in PubMed, EMBASE, Web of Science, and the Cochrane Library. The Cochrane risk of bias tool (RoB 2.0) was used to evaluate the quality of the studies. The Cochran Q test and I2 statistic were used to assess heterogeneity. Data were meta-analyzed using a random-effects model. Mean difference (MD) with 95% CI and 95% prediction interval (PI) were calculated. RESULTS: In total, 9 RCTs with a total sample size of 1583 stroke survivors met the inclusion criteria. Compared with the usual care, telemedicine and mHealth had a significantly greater impact on the control of systolic blood pressure (MD -5.49; 95% CI -7.87 to -3.10; P<.001; 95% PI -10.46 to -0.51). A subgroup analysis showed that the intervention mode of telephone plus SMS text messaging (MD -9.09; 95% CI -12.71 to -5.46; P<.001) or only telephone (MD -4.34; 95% CI -6.55 to -2.13; P<.001; 95% PI -7.24 to -1.45) had a greater impact on the control of systolic blood pressure than usual care. Among the stroke survivors with an intervention interval ≤1 week (MD -6.51; 95% CI -9.36 to -3.66; P<.001; 95% PI -12.91 to -0.10) or a baseline systolic blood pressure ≥140 mm Hg (MD -6.15; 95% CI -9.44 to -2.86; P<.001; 95% PI -13.55 to 1.26), the control of systolic blood pressure using telemedicine and mHealth was better than that of usual care. CONCLUSIONS: In general, telemedicine and mHealth reduced the systolic blood pressure of stroke survivors by an average of 5.49 mm Hg compared with usual care. Telemedicine and mHealth are a relatively new intervention mode with potential applications for the control of systolic blood pressure among stroke survivors, especially those with hypertensive stroke.


Assuntos
Hipertensão , Acidente Vascular Cerebral , Telemedicina , Pressão Sanguínea , Humanos , Hipertensão/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/terapia
5.
JMIR Mhealth Uhealth ; 9(6): e26095, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114965

RESUMO

BACKGROUND: Low back pain is one of the most common health problems and a main cause of disability, which imposes a great burden on patients. Mobile health (mHealth) affects many aspects of people's lives, and it has progressed rapidly, showing promise as an effective intervention for patients with low back pain. However, the efficacy of mHealth interventions for patients with low back pain remains unclear; thus, further exploration is necessary. OBJECTIVE: The purpose of this study was to evaluate the efficacy of mHealth interventions in patients with low back pain compared to usual care. METHODS: This was a systematic review and meta-analysis of randomized controlled trials designed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) statement standard. We searched for studies published in English before October 2020 in the PubMed, EMBASE, Web of Science, and Cochrane Library databases. Two researchers independently scanned the literature, extracted data, and assessed the methodological quality of the included studies. Bias risks were assessed using the Cochrane Collaboration tool. We used RevMan 5.4 software to perform the meta-analysis. RESULTS: A total of 9 studies with 792 participants met the inclusion criteria. The simultaneous use of mHealth and usual care showed a better reduction in pain intensity than usual care alone, as measured by the numeric rating scale (mean difference [MD] -0.85, 95% CI -1.29 to -0.40; P<.001), and larger efficacy in reducing disability, as measured by the Rolland-Morris Disability Questionnaire (MD -1.54, 95% CI -2.35 to -0.73; P<.001). Subgroup analyses showed that compared with usual care, mHealth using telephone calls significantly reduced pain intensity (MD -1.12, 95% CI -1.71 to -0.53; P<.001) and disability score (MD -1.68, 95% CI -2.74 to -0.63; P<.001). However, without the use of telephone calls, mHealth had no obvious advantage over usual care in improving pain intensity (MD -0.48, 95% CI -1.16 to 0.20; P=.16) and the disability score (MD -0.41, 95% CI -1.88 to 1.05; P=.58). The group that received a more sensitive feedback intervention showed a significantly reduced disability score (MD -4.30, 95% CI -6.95 to -1.69; P=.001). CONCLUSIONS: The use of simultaneous mHealth and usual care interventions has better efficacy than usual care alone in reducing pain intensity and disability in patients with low back pain. Moreover, the results of subgroup analysis revealed that mHealth using telephone calls might play a positive role in improving pain intensity and disability in patients with low back pain.


Assuntos
Pessoas com Deficiência , Dor Lombar , Telemedicina , Humanos , Dor Lombar/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários
7.
Food Chem ; 363: 130337, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34147891

RESUMO

In order to solve inherent problems of traditional molecularly imprinted electrochemical sensors (MIECS), a novel platform of surface molecularly imprinted magnetic metal-organic frameworks (mMOFs@MIPs) was coupled with magneto electrode to establish magnetic MIECS for the recognition of oxytetracycline (OTC). mMOFs@MIPs were synthesized using layer-by-layer modification method for the recognition of OTC. With the help of magneto electrodes, mMOFs@MIPs can be magnetically modified on the electrode surface, forming the electrochemical sensing interface. The imprinted cavities of mMOFs@MIPs can act as the electron channel of the probe to realize label-free detection of OTC. A linear response was obtained within the OTC concentration range of 1.0 × 10-9 g mL-1-1.0 × 10-4 g mL-1. The applicability of the sensor was estimated using the spiking and recovery method in milk samples with the recoveries ranging from 89.0% to 103.1%. It has potential applications in food safety analysis with high throughput detection capability, high specificity and good stability.

8.
J Ethnopharmacol ; 279: 114373, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34181959

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Prunella vulgaris L. (P. vulgaris) is a medicinal plant belonging to the Labiatae family, and its dried spikes is called as Xiakucao in China, which is a common traditional Chinese medicine with the activities of clearing the liver and expelling fire, improving eyesight, dispersing nodules and detumescence. Modern pharmacological studies have proved that P. vulgaris has various pharmacological activities such as immunomodulatory, antiviral, antibacterial and anti-insomnia activities. AIMS OF THIS REVIEW: P. vulgaris have been reported to have anti-insomnia effects. Nevertheless, the pharmacodynamic substance basis of this anti-insomnia effect is still unclear. The aim of this study was to identify the active components responsible for evoking the anti-insomnia effect of P. vulgaris and to evaluate its anti-insomnia effect. MATERIALS AND METHODS: In this study, we proposed a method combined with pharmacodynamic experiments, extraction and enrichment of chemical components, and the plasma pharmacochemistry to screen out the anti-insomnia components of P. vulgaris. Firstly, the active eluted fraction of the ethanol extract was screened out based on pharmacodynamic tracing method, and then the chemical composition was analyzed systematically by UPLC-MS/MS. Thirdly, pharmacodynamic tracing method and silica gel column chromatography were employed to screen out the active fraction of 70% ethanol eluted fraction, and its bioactive components in vitro and in vivo were identified by UPLC-MS/MS. Finally, screening out the anti-insomnia components of P. vulgaris by comparing the difference between in vivo and in vitro components, and three potentially bioactive ingredients were validated experimentally. RESULTS: It was confirmed that the fraction eluted with 70% ethanol from macroporous adsorption resin column was responsible for the anti-insomnia efficacy, and 55 compounds were identified or preliminarily identified. Then totally 9 compounds in vitro and 12 compounds in vivo from the active fraction of 70% ethanol eluted fraction were tentatively identified. Among them, mangiferin, rosmarinic acid and salviaflaside were the prototype components of P. vulgaris, which indicated that the three compounds might play the key role in the anti-insomnia activities. In vivo, compared to blank control group, the three compounds significantly shortened the sleeping latency and prolonged the sleeping time produced by pentobarbital sodium. CONCLUSIONS: This study clarified that mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of P. vulgaris. This is the first study on screening out the active ingredients responsible for evoking the anti-insomnia effect of P. vulgaris. The three compounds of P. vulgaris may help develop one or more drugs to prevent or treat insomnia. Further investigations are recommended to define the mechanism of the anti-insomnia activity of P. vulgaris.

9.
PLoS Negl Trop Dis ; 15(6): e0008442, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34153060

RESUMO

Japanese encephalitis virus (JEV) is a pathogen that causes severe vector-borne zoonotic diseases, thereby posing a serious threat to human health. Although JEV is potentially neurotropic, its pathogenesis and distribution in the host have not been fully elucidated. In this study, an infected mouse model was established using a highly virulent P3 strain of JEV. Immunohistochemistry and in situ hybridization, combined with anatomical imaging of the mouse brain, were used to dynamically localize the virus and construct three-dimensional (3D) images. Consequently, onset of mild clinical signs occurred in some mice at 3.5 d post JEV infection, while most mice displayed typical neurological signs at 6 d post-infection (dpi). Moreover, brain pathology revealed typical changes associated with non-suppurative encephalitis, which lasted up to 8 d. The earliest detection of viral antigen was achieved at 3 dpi in the thalamus and medulla oblongata. At 6 dpi, the positive viral antigen signals were mainly distributed in the cerebral cortex, olfactory area, basal ganglia, thalamus, and brainstem regions in mice. At 8 dpi, the antigen signals gradually decreased, and the localization of JEV tended to concentrate in the cerebrum and thalamus, while no viral antigen was detected in the brain at 21 dpi. In this model, the viral antigen was first expressed in the reticular thalamic nucleus (Rt), and the virus content is relatively stable. The expression of the viral antigen in the hippocampal CA2 region, the anterior olfactory nucleus, and the deep mesencephalic nucleus was high and persistent. The 3D images showed that viral signals were mostly concentrated in the parietal cortex, occipital lobe, and hippocampus, near the mid-sagittal plane. In the early stages of infection in mice, a large number of viral antigens were detected in denatured and necrotic neurons, suggesting that JEV directly causes neuronal damage. From the time of its entry, JEV is widely distributed in the central nervous system thereby causing extensive damage.

10.
Front Public Health ; 9: 686870, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1247959

RESUMO

Background: This article studies the relationship between the COVID-19 epidemic, public sentiment, and the volatility of infectious disease equities from the perspective of the United States. We use weekly data from January 3, 2020 to March 7, 2021. This provides a sufficient dataset for empirical analysis. Granger causality test results prove the two-way relationship between the fluctuation of infectious disease equities and confirmed cases. In addition, confirmed cases will cause the public to search for COVID-19 tests, and COVID-19 tests will also cause fluctuations in infectious disease equities, but there is no reverse correlation. The results of this research are useful to investors and policy makers. Investors can use the number of confirmed cases to predict the volatility of infectious disease equities. Similarly, policy makers can use the intervention of retrieved information to stabilize public sentiment and equity market fluctuations, and integrate a variety of information to make more scientific judgments on the trends of the epidemic.


Assuntos
COVID-19 , Doenças Transmissíveis , Epidemias , Doenças Transmissíveis/epidemiologia , Humanos , SARS-CoV-2 , Estados Unidos/epidemiologia , Volatilização
11.
Front Public Health ; 9: 686870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055733

RESUMO

Background: This article studies the relationship between the COVID-19 epidemic, public sentiment, and the volatility of infectious disease equities from the perspective of the United States. We use weekly data from January 3, 2020 to March 7, 2021. This provides a sufficient dataset for empirical analysis. Granger causality test results prove the two-way relationship between the fluctuation of infectious disease equities and confirmed cases. In addition, confirmed cases will cause the public to search for COVID-19 tests, and COVID-19 tests will also cause fluctuations in infectious disease equities, but there is no reverse correlation. The results of this research are useful to investors and policy makers. Investors can use the number of confirmed cases to predict the volatility of infectious disease equities. Similarly, policy makers can use the intervention of retrieved information to stabilize public sentiment and equity market fluctuations, and integrate a variety of information to make more scientific judgments on the trends of the epidemic.


Assuntos
COVID-19 , Doenças Transmissíveis , Epidemias , Doenças Transmissíveis/epidemiologia , Humanos , SARS-CoV-2 , Estados Unidos/epidemiologia , Volatilização
12.
Cell Death Dis ; 12(6): 512, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011928

RESUMO

NLRP3, a decisive role in inflammation regulation, is obviously upregulated by oxidative stress in kidney injury. The NLRP3 upregulation leads to unsolved inflammation and other pathological effects, contributing to aggravation of kidney injury and even transition to chronic kidney disease (CKD). However, the mechanism for NLRP3 upregulation and further aggravation of kidney injury remains largely elusive. In this study, we found NLRP3 3'UTR was shortened in response to kidney injury in vivo and oxidative stress in vitro. Functionally, such NLRP3 3'UTR shortening upregulated NLRP3 expression and amplified inflammation, fibrogenesis, ROS production and apoptosis, depending on stabilizing NLRP3 mRNA. Mechanistically, FIP1 was found to bind to pPAS of NLRP3 mRNA via its arginine-rich domain and to induce NLRP3 3'UTR shortening. In addition, FIP1 was upregulated in CKD specimens and negatively associated with renal function of CKD patients. More importantly, we found FIP1 was upregulated by oxidative stress and required for oxidative stress-induced NLRP3 upregulation, inflammation activation, cell damage and apoptosis. Finally, we proved that FIP1 silencing attenuated the inflammation activation, fibrogenesis, ROS production and apoptosis induced by UUO or IRI. Taken together, our results demonstrated that oxidative stress-upregulated FIP1 amplified inflammation, fibrogenesis, ROS production and apoptosis via inducing 3'UTR shortening of NLRP3, highlighting the importance of crosstalk between oxidative stress and alternative polyadenylation in AKI-CKD transition, as well as the therapeutic potential of FIP1 in kidney injury treatment.

13.
Respir Med ; 182: 106424, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33932714

RESUMO

BACKGROUND: The relationship between air pollution and meteorological factors on diseases has become a research hotspot recently. Nevertheless, few studies have touched the inferences of nitrogen dioxide (NO2) and atmospheric pressure (AP) on hospitalization risk for chronic obstructive pulmonary disease (COPD). OBJECTIVES: To investigate the short-term impact of particulate air pollutants and meteorology factors on hospitalizations for COPD and quantify the corresponding risk burden of hospital admission. METHODS: In our study, COPD cases were collected from Guangzhou Panyu Central Hospital (n = 11,979) from Dec of 2013 to Jun 2019. The 24-h average temperature, relative humidity (RH), wind speed (V), AP and other meteorological data were obtained from Guangzhou Meteorological Bureau. Air pollution data were collected from Guangzhou Air Monitoring Station. The influence of different NO2 and AP values on COPD risk was quantified by a distributed lag nonlinear model (DLNM) combined with Poisson Regression and Time Series analysis. RESULTS: We found that NO2 had a non-linear relationship with the incidence of COPD, with an approximate "M" type, appearing at the peaks of 126 µg/m³ (RR = 1.32, 95%CI, 1.07 to 1.64) and 168 µg/m³ (RR = 1.21, 95%CI, 0.94 to 1.55), respectively. And the association between AP and COPD incidence exhibited an approximate J-shape with a peak occurring at 1035 hPa (RR = 1.16, 95% CI, 1.02 to 1.31). CONCLUSIONS: The nonlinear relationship of NO2 and AP on COPD admission risk in different periods of lag can be used to establish an early warning system for diseases and reduce the possible outbreaks and burdens of COPD in a sensitive population.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33929347

RESUMO

OBJECTIVE: Virtual reality (VR) technology has begun to be gradually applied to clinical stroke rehabilitation. The study aims to evaluate the effect of traditional plus VR rehabilitation on motor function recovery, balance, and activities of daily living in stroke patients. METHOD: Studies published in English prior to October 2020 were retrieved from PubMed, EMBASE, Web of Science, and the Cochrane Library. and used RevMan 5.3 software for meta-analysis. RESULT: A total of 21 randomized controlled trials (RCTs) were included, which enrolled 619 patients. Traditional plus VR rehabilitation is better than traditional rehabilitation in upper limb motor function recovery measured by Fugl-Meyer Assessment-Upper Extremity (mean difference [MD] 3.49; 95% CI [1.24, 5.73]; P=.002) and manual dexterity assessed by Box & Block Test (MD 6.59; 95% CI [3.45, 9.74]; P<.0001); However, there is no significant difference from traditional rehabilitation in activities of daily living assessed by Functional Independence Measure (MD 0.38; 95% CI [-0.26, 1.02]; P=.25) and balance assessed by Berg Balance Scale (MD 2.18; 95% CI [-0.35, 4.71]; P=.09). CONCLUSION: Traditional plus VR rehabilitation therapy is an effective method to improve the upper limb motor function and manual dexterity of patients with limb disorders after stroke, and immersive VR rehabilitation treatment may become a new option for rehabilitation after stroke.

16.
Biomed Res Int ; 2021: 5582648, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860036

RESUMO

Lung cancer remains the leading cause of cancer death worldwide. Late diagnosis, chemoresistance, and metastasis are the main reasons for the high mortality rate of lung cancer. Therefore, the development of other treatments is urgent. Cediranib (CED), a vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, shows promising antitumour activities in various cancers including lung cancer. Here, we explored the effects and the underlying molecular mechanism of CED on non-small-cell lung cancer (NSCLC) cell line A549 cells in vitro. Our results show that CED could inhibit A549 cell proliferation and cloning formation. Meanwhile, G1 phase cell cycle arrest was also found, as featured by the increased proportion of G1 phase cells as well as the reduction of G1 phase relative proteins CDK4/cyclin D1 and CDK2/cyclin E. Moreover, the ratio of LC3-II/LC3-I was elevated significantly in CED-treated groups compared with the controls. Furthermore, the expression of p-Akt, p-P38, p-Erk1/2, and p-mTOR proteins was decreased obviously in the treatment groups. These results suggest that CED could induce apoptosis and G1 phase cell cycle arrest in A549 cells. Meanwhile, CED may induce autophagy through MAPK/Erk1/2 and Akt/mTOR signal pathway in A549 cells.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Quinazolinas/farmacologia , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinazolinas/química , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ensaio Tumoral de Célula-Tronco
17.
BMC Gastroenterol ; 21(1): 131, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33743586

RESUMO

BACKGROUND: As a secreted adipokine, adipsin has been recently shown to play a pivotal role in metabolic disorders. However, information regarding the association of circulating adipsin with non-alcoholic fatty liver disease (NAFLD) in humans is scant. METHODS: We recruited 1163 obese adult subjects with waist circumference at least 90 cm in men and 80 cm in women from the community. Circulating adipsin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating adipsin levels of NAFLD subjects was decreased compared to those in non-NAFLD (p < 0.05). The prevalence of NAFLD with lower levels of serum adipsin was significantly higher than those with higher values (57.6% vs. 50.9%, p < 0.05). Circulating adipsin levels were significantly associated with decreasing levels of fasting glucose and postprandial glucose (both p < 0.001 for interaction) in NAFLD subjects but not in non-NAFLD subjects. The risk of NAFLD was significantly decreased by 21.7% [OR (95% CI): 0.783 (0.679-0.902), p < 0.001], adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, HOMA-IR, and body fat mass. Importantly, subjects in the lowest quartile of circulating adipsin were 1.88 times more likely to have NAFLD than those in the highest quartile in multivariable logistic regression analyses. However, such associations with circulating adipsin were not noted for metabolic syndrome, abnormal liver enzyme and significant liver fibrosis. CONCLUSIONS: These results demonstrate that circulating adipsin levels in Chinese obese adults are negatively associated with risk of NAFLD, implying that serum adipsin levels may be a potential protective factor in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Índice de Massa Corporal , Fator D do Complemento , Estudos Transversais , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Circunferência da Cintura
18.
Vascular ; : 17085381211003694, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33759649

RESUMO

BACKGROUND: The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) combined with antiplatelet drugs in patients with peripheral artery disease remain largely unknown. OBJECTIVE: The aim of this meta-analysis was to explore the effects of NOACs combined with antiplatelet drugs versus antiplatelet drugs alone in this population. METHODS: A comprehensive search of randomized controlled trials published in PubMed, EMBASE, Web of Science, and the Cochrane Library in 30 September 2020 and before. According to the I2 statistic, a random or fixed-effect model was used to analyze the safety and effectiveness of NOACs combined with antiplatelet drugs in peripheral artery disease patients. RESULTS: Three RCTs met the inclusion criteria, with a total sample size of 11,761 participants. Compared with antiplatelet drugs alone, NOACs combined with antiplatelet drugs resulted in lower risk of ischemic stroke events (OR = 0.75, 95%CI 0.57-0.98, p = 0.03), while other treatment effects were not worse than those of single antiplatelet drugs (p ≥ 0.05). In addition, although compared with single antiplatelet drugs alone, NOACs combined with antiplatelet drugs had a higher risk of major bleeding and clinically related nonmajor bleeding, their risk was not higher for intracranial hemorrhage, which may endanger the life of patients, or for fatal bleeding. CONCLUSIONS: In summary, for peripheral artery disease patients, a combination of NOACs plus antiplatelet drugs may offer additional benefit in reducing ischemic stroke outcome, yet it may increase the risk of bleeding.

19.
Clin Transl Med ; 11(3): e321, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33784014

RESUMO

BACKGROUND: The contributions of various types of cell populations in dialysis-related peritoneal fibrosis are poorly understood. Single-cell RNA sequencing brings single-cell level resolution to the analysis of cellular transcriptomics, which provides a new way to further characterize the distinct roles and functional states of each cell population during peritoneal fibrosis. METHODS: Single-cell transcriptomics from normal peritoneal tissues of six patients, from effluent of patients with short-term peritoneal dialysis (less than 2 weeks, n = 6), and from long-term peritoneal dialysis patients (more than 6 years, n = 4) were analyzed. RESULTS: We identified a distinct cell component between samples among different groups. Functional analysis of the differentially expressed genes identified cell type specific biological processes relevant to different fibrosis stages. Well-known key molecular mechanisms participating in the pathophysiology of peritoneal fibrosis were vitrified, and some of them were found to be restricted to specific cell types. Gradually growing enrichment of PI3K/AKT/mTOR pathway and impairment of oxidative phosphorylation in mesothelial cells and fibroblasts were found from healthy control, short-term dialysis, to long-term dialysis, respectively. The fibroblasts' population obtained from the patients, who received peritoneal dialysis, showed a functional characteristic of immune-chemotaxis and immune response, which was characterized by broadly significant increase in the expression of interleukins, chemokines, cytokines, and human leukocyte antigens. Furthermore, we described the intercellular crosstalk networks based on receptor-ligand interactions, and highlighted a central role of fibroblasts in regulating the key mechanisms of peritoneal fibrosis through crosstalk with other cells. CONCLUSIONS: In summary, despite describing information for fibrogenic molecular mechanisms in the resolution level of individual cell populations, this work identifies the significant functional evolution of fibroblasts during peritoneal fibrosis. This study also reveals the intercellular receptor-ligand interactions in which the fibroblasts serve as a major node, eventually providing new insights into the role of fibroblasts during disease pathogenesis.

20.
Bioconjug Chem ; 32(3): 615-625, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33656323

RESUMO

Human Interleukin 2 (IL-2) has already achieved impressive results as a therapeutic agent for cancer and autoimmune diseases. However, one of the limitations associated with the clinical application of IL-2 is its short half-life owing to rapid clearance by the kidneys. Modification with fatty acids, as an albumin noncovalent ligand with the advantage of deep penetration into tissues and high activity-to-mass ratio, is a commonly used approach to improve the half-life of native peptides and proteins. In this investigation, we attempted to extend the half-life of IL-2 through conjugation with a fatty acid using sortase A (srtA). We initially designed and optimized three IL-2 analogues with different peptide linkers between the C-terminus of IL-2 and srtA recognition sequence (LPETG). Among these, analogue A3 was validated as the optimal IL-2 analogue for further modification. Next, six fatty acid moieties with the same fatty acid and different hydrophilic spacers were conjugated to A3 through srtA. The six bioconjugates generated were screened for in vitro biological activity, among which bioconjugate B6 was identified as near-optimal to IL-2. Additionally, B6 could effectively bind albumin through the conjugated fatty acid, which contributed to a significant improvement in its pharmacokinetic properties in vivo. In summary, we have developed a novel IL-2 bioconjugate, B6, modified with fatty acids using srtA, which may effectively serve as a new-generation long-acting IL-2 immunotherapeutic agent.

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