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1.
BMC Cardiovasc Disord ; 21(1): 472, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598675

RESUMO

BACKGROUND: High blood pressure is a well-recognized risk factor for cardiovascular events, and the incidence of hypertension is increasing among young people. This study investigated the relationship between ALT and AST levels and hypertension among freshmen in China. METHODS: This cross-sectional study was conducted in the Anhui Province from September to November 2018. A total of 3114 freshmen underwent a physical examination including testing of biochemical indicators and a standardized questionnaire. RESULTS: The overall prevalence of elevated ALT and AST were 6.8% and 2.3% among freshmen. The mean ALT and AST levels were higher in males (22.59 ± 21.98 vs.12.62 ± 10.30 U/L; 23.55 ± 12.24 vs. 20.02 ± 5.75 U/L, respectively). The prevalence of hypertension was significantly higher in men (16.1%) than in women (1.9%). The mean values of BMI, SBP, DBP, TC, TG, and LDL-C were found to be increased with elevated levels of serum ALT and AST in the quartiles (P for trend < 0.05). After adjusting for covariates, the risk of hypertension was significantly higher in the highest ALT quartile than in the lowest quartile (OR (95% CI) of 1.681 (1.028, 2.751) in males; 2.802 (1.102, 7.124) in females). A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders only in total population and females (P for trend < 0.05). CONCLUSIONS: These findings suggest that ALT level is significantly associated with hypertension both in male and female freshmen.

2.
Biol Pharm Bull ; 44(10): 1536-1547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34602563

RESUMO

This study aimed to investigate the effect of norisopoldine (NOR) on acute lung injury in septic mice. Lipopolysaccharide (LPS) was used to establish sepsis induced acute lung injury (ALI) in mice. The dry and wet weight of mice lung was detected, and the pathological changes of lung were observed by hematoxylin and eosin (H&E) staining. Bronchoalveolar lavage fluid (BALF) was detected. Inflammatory factors in BALF were detected by enzyme-linked immunosorbent assay (ELISA). The polarization of macrophages in lung tissue was detected by flow cytometry. The markers of M1 and M2 macrophages were detected by RT-PCR. LPS induced RAW264.7 cells were treated with NOR. Inflammatory response, macrophage polarization, glycolysis, and M2 pyruvate kinase (PKM2)/hypoxia inducible factor-1α (HIF-1α)/peroxisome proliferator activated receptor-γ co-activator 1-α (PGC-1α) signaling pathway were detected. NOR could effectively alleviate sepsis induced ALI, and reduce the number of total cells, total protein concentration, neutrophils, macrophages in BALF. NOR decreased the level of inflammatory factors and promoted macrophages from M1 to M2 type in vivo and vitro. Moreover, NOR could activated PKM2, and inhibited PKM2 from cytoplasm to nuclear, attenuated HIF-1α expression, and increased PGC-1α and peroxisome proliferator-activated receptor (PPAR)-γ expression. In addition, NOR inhibited glycolysis and promoted oxidative phosphorylation in RAW264.7 cells. Furthermore, PKM2 inhibitors could reverse the effect of NOR on PKM2/HIF-1α/PGC-1α signaling pathway in RAW264.7 cells. NOR alleviated sepsis induced AIL in mice, inhibited the inflammatory response, promote M2 polarization of macrophages through regulating PKM2/HIF-1α/PGC-1α signaling pathway.

3.
Arq Bras Cardiol ; 2021 Sep 20.
Artigo em Português, Inglês | MEDLINE | ID: mdl-34550168

RESUMO

BACKGROUND: Recent epidemiological studies have shown that alterations in microbiota and its metabolites are associated with systemic arterial hypertension. Helicobacter pylori (H. pylori) is one of the most common bacterial pathogens, and the potential association between H. pylori infection and hypertension are controversial. OBJECTIVE: This study aimed to clarify their association and provide a new theoretical basis for uncovering the pathogenesis of hypertension. METHODS: Case-control and cross-sectional studies on the association between H. pylori and hypertension published from 1996 to 2019 indexed in PubMed, Google Scholar, Chinese Wan Fang Data, and Chinese National Knowledge Infrastructure (CNKI). The pooled odds ratios (OR) and 95% confidence interval (CI) were estimated. I2 was performed to evaluate the statistical heterogeneity. Publication bias was evaluated using Begg's and Egger's test. The extracted data was analyzed in Stata 12.0. Statistical significance was defined as p-value < 0.05. RESULTS: A total of 17 studies involving 6,376 cases of hypertension and 10,850 controls were enrolled. H. pylori infection rate in hypertension patients and controls were 64.9% and 56.3%, respectively. A significantly positive association was shown between H. pylori infection and hypertension with an overall OR of 2.07 (95% CI: 1.46-2.94; p < 0.05). Subgroup analysis revealed that the prevalence of H. pylori infection was associated with hypertension in the region of Asia and the case-control group, ORs (95% CI) were 2.26 (1.51-3.38) and 2.53 (1.72-3.72), respectively. After stratifying by detection methods, differences still existed in subgroups (all p < 0.05). CONCLUSION: This meta-analysis indicated that H. pylori infection is positively associated with hypertension.

4.
Kidney Blood Press Res ; : 1-8, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34515147

RESUMO

BACKGROUND: Previous studies have reported that disturbance of endogenous circadian rhythms enhances the chance of hypertension and suggested that circadian clock genes could have a crucial function in the onset of the disease. This case-control study was aimed to investigate the association of the mRNA expression of aryl hydrocarbon receptor nuclear translocator like (Arntl), clock circadian regulator (Clock), and period circadian regulators 1 and 2 (Per1 and Per2) with hypertension and blood pressure levels. METHODS: A total of 172 subjects were recruited in this study, including 86 hypertension and 86 nonhypertension controls. The mRNA expression levels in peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction. The differences in Arntl, Clock, Per1, and Per2 mRNA expression were compared between the 2 groups, and the relationship between mRNA expression and cardiometabolic risk profiles was also assessed. RESULTS: We found that the mRNA expression of Arntl was downregulated in the hypertension cases compared with controls in women (1.10 [0.66, 1.71] vs. 1.30 [0.99, 2.06], p = 0.031). There was a significant negative correlation between the Arntl mRNA expression and SBP (r = -0.301, p = 0.004) and DBP (r = -0.222, p = 0.034) in women. In men, a negative correlation between the Per1 mRNA expression and SBP (r = -0.247, p = 0.026) was found. CONCLUSIONS: The Arntl mRNA expression may play an important role in progression of hypertension in women.

5.
Free Radic Biol Med ; 175: 216-225, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474106

RESUMO

Nitric oxide (NO) plays an important role in cardiovascular and immune systems. Quantification of blood nitrite and nitrate, two relatively stable metabolites of NO (generally as NOx), has been acknowledged, in part, representing NO bioactivity. Dysregulation of NOx had been reported in SARS-CoV-2 infected populations, but whether patients recovered from COVID-19 disease present with restored NOx is unknown. In this study, serum NO2- and NO3- were quantified and analyzed among 109 recovered adults in comparison to a control group of 166 uninfected adults. Nitrite or nitrate levels were not significantly different among mild-, common-, severe- and critical-type patients. However, these recovered patients had dramatically lower NO2- and NO2-/NO3- than the uninfected group (p < 0.0001), with significantly higher NO3- levels (p = 0.0023) than the uninfected group. Nitrate and nitrite/nitrate were positively and negatively correlated with patient age, respectively, with age 65 being a turning point among recovered patients. These results indicate that low NO2-, low NO2-/NO3- and high NO3- may be potential biomarkers of long-term poor or irreversible outcomes after SARS-CoV-2 infection. It suggests that NO metabolites might serve as a predictor to track the health status of recovered COVID-19 patients, highlighting the need to elucidate the role of NO after SARS-CoV-2 infection.


Assuntos
COVID-19 , Nitritos , Adulto , Idoso , Biomarcadores , Humanos , Nitratos , Óxido Nítrico , SARS-CoV-2
6.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2678-2687, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472288

RESUMO

Fluorescence imaging has been widely used in the fields of biomedicine and clinical diagnosis. Compared with traditional fluorescence imaging in the visible spectral region (400-760 nm), near-infrared (NIR, 700-1 700 nm) fluorescence imaging is more helpful to improve the signal-to-noise ratio and the sensitivity of imaging. Highly-sensitive fluorescent probes are required for high-quality fluorescence imaging, and the rapid development of nanotechnology has led to the emergence of organic dyes with excellent fluorescent properties. Among them, organic fluorescent probes with the advantages of high safety, good biocompatibility, and high optical stability, are more favorable than inorganic fluorescent probes. Therefore, NIR fluorescence imaging assisted with organic fluorescent probes can provide more structural and dynamic information of biological samples to the researchers, which becomes a hot spot in the interdisciplinary research field of optics, chemistry and biomedicine. This review summarizes the application of NIR organic fluorescent probes in cervical cancer imaging. Several typical organic fluorescent probes (such as indocyanine green, heptamethine cyanine dye, rhodamine and polymer fluorescent nanoparticles) assisted NIR fluorescence imaging and their applications in cervical cancer diagnosis were introduced, and the future development and application of these techniques were discussed.


Assuntos
Nanopartículas , Neoplasias do Colo do Útero , Feminino , Corantes Fluorescentes , Humanos , Imagem Óptica , Polímeros , Neoplasias do Colo do Útero/diagnóstico por imagem
7.
Artigo em Inglês | MEDLINE | ID: mdl-34416242

RESUMO

BACKGROUND: Investigations have revealed the association between inflammation and post-stroke depression (PSD). However, whether the C-reactive protein (CRP) level, a biomarker of inflammation, would affect the development of PSD is still controversial. METHODS: A systematic search of databases was performed for eligible studies. Standardized Mean Difference (SMD) with 95% Confidence Interval (CI) was used to assess the association between the CRP level in the acute phase of stroke and the risk of PSD. RESULTS: 13 cohort studies that involved 3536 participants were included. Combined results showed that compared with non-PSD patients, the CRP level of PSD patients was significantly higher on admission (SMD = 0.19, 95% CI: 0.12-0.27). A subgroup analysis by classifying the assessment time of depression showed obvious differences of the CRP levels between the PSD patients who were diagnosed more than 1 month after stroke and the non-PSD (1-3 months: SMD = 0.16, 95% CI: 0.06-0.25; >3months: SMD = 0.34, 95% CI: 0.18-0.51). CONCLUSION: A higher level of CRP in the acute phase of stroke suggests an increased risk for PSD.

8.
Int J Obes (Lond) ; 45(10): 2269-2273, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34267325

RESUMO

BACKGROUND AND OBJECTIVES: COVID-19-related school closures may increase the prevalence of childhood obesity, which has aroused public concerns. We aimed to analyze the weight and height changes in Chinese preschool children during the COVID-19-related school closures period. METHODS: A total of 124,603 children from multi-city kindergartens in China were included in this study. We evaluated the prevalence of overweight and obese in preschool children experienced school closures, and compared the changes in BMI, weight, and height of preschool children among COVID-19 school closures period, the same period last year and the same period the year before last. RESULTS: After the school closures, childhood obesity prevalence increased, whereas overweight prevalence decreased. During school closures, the average increase in height was about 1 cm less as compared with the same period last year and the year before last, but no noteworthy difference in the weight change was observed among the three periods. CONCLUSIONS: During COVID-19 school closures, children's height increase seemed to be more affected than weight change. Innovative, robust, and highly adaptable strategies should be taken to increase physical activity, reduce sedentary time and promote healthy diets, to minimize the adverse impact of school closures.


Assuntos
Estatura/fisiologia , Peso Corporal/fisiologia , COVID-19 , Obesidade Pediátrica/epidemiologia , Pré-Escolar , Controle de Doenças Transmissíveis , Feminino , Humanos , Masculino , Sobrepeso/epidemiologia , Estudos Retrospectivos , Instituições Acadêmicas
9.
Cell Death Dis ; 12(7): 683, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234118

RESUMO

Ribonucleotide reductase (RR) is a unique enzyme for the reduction of NDPs to dNDPs, the building blocks for DNA synthesis and thus essential for cell proliferation. Pan-cancer profiling studies showed that RRM2, the small subunit M2 of RR, is abnormally overexpressed in multiple types of cancers; however, the underlying regulatory mechanisms in cancers are still unclear. In this study, through searching in cancer-omics databases and immunohistochemistry validation with clinical samples, we showed that the expression of MYBL2, a key oncogenic transcriptional factor, was significantly upregulated correlatively with RRM2 in colorectal cancer (CRC). Ectopic expression and knockdown experiments indicated that MYBL2 was essential for CRC cell proliferation, DNA synthesis, and cell cycle progression in an RRM2-dependent manner. Mechanistically, MYBL2 directly bound to the promoter of RRM2 gene and promoted its transcription during S-phase together with TAF15 and MuvB components. Notably, knockdown of MYBL2 sensitized CRC cells to treatment with MK-1775, a clinical trial drug for inhibition of WEE1, which is involved in a degradation pathway of RRM2. Finally, mouse xenograft experiments showed that the combined suppression of MYBL2 and WEE1 synergistically inhibited CRC growth with a low systemic toxicity in vivo. Therefore, we propose a new regulatory mechanism for RRM2 transcription for CRC proliferation, in which MYBL2 functions by constituting a dynamic S-phase transcription complex following the G1/early S-phase E2Fs complex. Doubly targeting the transcription and degradation machines of RRM2 could produce a synthetic inhibitory effect on RRM2 level with a novel potential for CRC treatment.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorretais/enzimologia , Inibidores Enzimáticos/farmacologia , Técnicas de Silenciamento de Genes , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Pirimidinonas/farmacologia , Ribonucleosídeo Difosfato Redutase/metabolismo , Transativadores/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Tirosina Quinases/metabolismo , Ribonucleosídeo Difosfato Redutase/genética , Transdução de Sinais , Transativadores/genética , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Int J Nanomedicine ; 16: 4847-4861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305398

RESUMO

Purpose: Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform. Methods: In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation. Results: The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice. Conclusion: To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.


Assuntos
Nanopartículas , Neoplasias do Colo do Útero , Animais , Doxorrubicina , Feminino , Fluorescência , Humanos , Hipertermia Induzida , Verde de Indocianina , Camundongos , Camundongos Nus , Fototerapia , Terapia Fototérmica , Medicina de Precisão , Nanomedicina Teranóstica , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia
11.
J Biophotonics ; : e202100117, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34331509

RESUMO

Photothermal therapy (PTT) has attracted wide attention due to its noninvasiveness and its thermal ablation ability. As photothermal agents are crucial factor in PTT, those with the characteristics of biocompatibility, non-toxicity and high photothermal stability have attracted great interest. In this work, new indocyanine green (IR-820) was utilized as a photothermal agent and near-infrared (NIR) fluorescence imaging nanoprobe. To improve the biocompatibility, poly(styrene-co-maleic anhydride) (PSMA) was utilized to encapsulate the IR-820 molecules to form novel IR-820@PSMA nanoparticles (NPs). Then, the optical and thermal properties of IR-820@PSMA NPs were studied in detail. The IR-820@PSMA NPs showed excellent photothermal stability and biocompatibility. The cellular uptaking ability of the IR-820@PSMA NPs was further confirmed in HeLa cells by the NIR fluorescent confocal microscopic imaging technique. The IR-820@PSMA NPs assisted PTT of living HeLa cells was conducted under 793 nm laser excitation, and a high PTT efficiency of 73.3% was obtained.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34199578

RESUMO

Individual and meteorological factors are associated with cognitive function in older adults. However, how these two factors interact with each other to affect cognitive function in older adults is still unclear. We used mixed effects models to assess the association of individual and meteorological factors with cognitive function among older adults. Individual data in this study were from the database of China Family Panel Studies. A total of 3448 older adults from 25 provinces were included in our analysis. Cognitive functions were measured using a memory test and a logical sequence test. We used the meteorological data in the daily climate dataset of China's surface international exchange stations, and two meteorological factors (i.e., average temperature and relative humidity) were assessed. The empty model showed significant differences in the cognitive scores of the older adults across different provinces. The results showed a main impact of residence (i.e., urban or rural) and a significant humidity-residence interaction on memory performance in older adults. Specifically, the negative association between humidity and memory performance was more pronounced in urban areas. This study suggested that meteorological factors may, in concert with individual factors, be associated with differences in memory function in older adults.


Assuntos
Clima , Conceitos Meteorológicos , Idoso , China/epidemiologia , Cognição , Humanos , Umidade , Temperatura
13.
Tour Manag ; 87: 104393, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34276119

RESUMO

Public health interventions to combat COVID-19 can be viewed as an exogenous shock to the economy, especially for industries-such as leisure, recreation, and tourism-that rely heavily on human mobility. This study investigates whether and how exactly the economic impact of government public health policies varies over time. Focusing on the leisure and recreation industry, we use data for 131 countries/regions from February to May 2020 and employ generalized difference-in-differences models to investigate the short- and longer-term effects of public health policies. We find that stricter policies lead, on average, to an immediate 9.2-percentage-point drop in leisure and recreation participation. Even so, that industry recovers in about seven weeks after a COVID-19 outbreak in countries/regions that undertake active interventions. After thirteen weeks, leisure and recreation involvement recovers to 70% of pre-pandemic levels in a place that actively intervened but stagnates at about 40% in one that did not.

14.
Front Psychiatry ; 12: 653245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262488

RESUMO

Objective: To investigate the prevalence of suicidal ideation among the first batch of students returning to a college during the COVID-19 epidemic, and to explore the correlation of suicidal ideation with family characteristics and social support. Methods: A cluster sampling survey with a self-designed questionnaire was conducted among the first batch of students returning to a college in Wuhu, China. The Positive and Negative Suicidal ideation (PANSI) and Social Support Scale (SSRS) were used to define students' suicidal ideation and social support, respectively. The influence of family characteristics and social support on the students' suicidal ideation was investigated using multivariate unconditional logistic regression analysis. Results: Two thousand seven hundred valid questionnaires were collected, including 673 males (24.9%) and 2,027 females (75.1%), in this study. A total of 146 students (5.4%) showed suicidal ideation. Male respondents reported higher rates (7.9%) than females (4.6%). Multivariate logistic regression analysis showed that a higher risk level of residence before returning to school and lower objective support were the risk factors for suicidal ideation in males. In contrast, a higher level of maternal education, a poorer relationship with the mother, and lower scores for subjective support and support availability had significant effects on females' suicidal ideation. Limitations: This is a cross-sectional study, and lacks comparison to the time point unaffected by COVID-19. Moreover, it was limited by COVID-19 epidemic prevention and control restrictions, and the differences in returning to school in different regions. Only one college was investigated in this study, and all of the respondents were sophomores, so there may be some limitations in the representativeness of the sample and extrapolation of the results. Conclusion: Family characteristics and social support have had an important influence on suicidal ideation among students returning to school during the COVID-19 epidemic. Some gender differences were identified. Targeted interventions are needed for early prevention and control.

15.
Am J Cancer Res ; 11(6): 2975-2989, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249439

RESUMO

Hepatocellular carcinoma (HCC), one of the most deadly diseases all around the world. HBV infection is a causative factor of HCC and closely associated with HCC development. Ribonucleotide reductase (RR) is a key enzyme for cellular DNA synthesis and RR small subunit M2 (RRM2) is highly upregulated in HCC with poor survival rates. We have previously shown that HBV can activate the expression of RRM2 and the activity of RR enzyme for the viral DNA replication in host liver cells. Thus, RRM2 may be an important therapeutic target for HCC and HBV-related HCC. Pterostilbene, a natural plant component, potently inhibited in vitro RR enzyme activity with the IC50 of about 0.62 µM through interacting with RRM2 protein, which was much higher than current RRM2 inhibitory drugs. Pterostilbine inhibited cell proliferation with an MTT IC50 of about 20-40 µM in various HCC cell lines, causing DNA synthesis inhibition, cell cycle arrest at S phase, and accordingly apoptosis. On the other hand, the compound significantly inhibited HBV DNA replication in HBV genome integrated and newly transfected HCC cells, and the EC50 for inhibiting HBV replication was significantly lower than the IC50 for inhibiting HCC proliferation. Notably, pterostilbene possessed a similar inhibitory activity in sorafenib and lamivudine resistant HCC cells. Moreover, the inhibitory effects of pterostilbine against HCC proliferation and HBV replication were significantly reversed by addition of dNTP precursors, suggesting that RR was the intracellular target of the compound. Finally, pterostilbine effectively inhibited HCC xenograft growth with a relatively low toxicity in nude mouse experiments. This study demonstrates that pterostilbene is a novel potent RR inhibitor by targeting RRM2. It can simultaneously inhibit HCC proliferation and HBV replication with a potential new use for treatment of HCC and HBV-related HCC.

16.
Eur J Pharm Sci ; 166: 105931, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34256100

RESUMO

At present, oral chemotherapy showing the advantages of non-invasiveness, convenience, and high patient compliance, is gradually replacing traditional intravenous chemotherapy to treat patients with cancer. RA-XII, a unique natural cyclopeptide, exhibits various biological activities, such as anti-tumor, anti-angiogenic, and anti-metastatic activities. Designing an orally available formulation of RA-XII is of great importance in the development of clinically useful anticancer agents. However, RA-XII shows low oral bioavailability in rats due to its poor solubility and low permeability. To overcome these limitations, in this work, a natural deep eutectic solvent (NADES) was designed to efficiently deliver RA-XII by oral administration. A novel NADES composed of betaine and mandelic acid in the molar ratio of 1:1 (Bet-Man NADES) was successfully prepared based on a binary phase diagram of Bet and Man. Acute toxicity studies indicated that Bet-Man NADES was well tolerated with acceptable toxicity. In Bet-Man NADES solutions, the solubility of RA-XII was increased by up to 17.54-fold, and the diffusion and permeability of RA-XII carried out in a Franz cell was also significantly improved 10.35 times. In terms of biopharmaceutical classification this is translated into a change for RA-XII from class IV to class II systems. More importantly, Bet-Man NADES was transferred into the solid formulation by the inclusion of a polymer, and amorphous solid dispersions based on Bet-Man NADES (PVP K30/NADES/RA-XII, ASDs) were successfully prepared to improve uniformity, apparent solubility, dissolution, and cytotoxicity in vitro. Consequently, the oral bioavailability of RA-XII in NADES solutions and ASDs was enhanced by approximately 11.58 and 7.56 times compared with that of pure RA-XII in 0.5% CMCNa. Thus, it can be seen that a natural deep eutectic solvent and its modified amorphous solid dispersions are appropriate novel strategies for improving dissolution rate and bioavailability of poor soluble natural products such as RA-XII.


Assuntos
Neoplasias , Peptídeos Cíclicos , Administração Oral , Animais , Humanos , Ratos , Solventes
17.
Arq Bras Cardiol ; 116(6): 1072-1078, 2021 06.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34133589

RESUMO

BACKGROUND: Uric acid (UA), the end product of purine nucleotide metabolism, participates in the processes of metabolic and cardiovascular diseases. Experimental evidence suggests it is an important mediator in the physiological response to blood pressure increase. OBJECTIVE: To evaluate the association between serum UA levels and pre-hypertension and hypertension in a Chinese population. METHODS: A cross-sectional study was conducted from March to September 2017, and 1,138 participants aged 35 to 75 were enrolled in this study, where 223 normotensive, 316 pre-hypertensive, and 599 hypertensive subjects were selected to evaluate the association between serum UA levels and hypertension. A p-value <0.05 was considered statistically significant. RESULTS: Serum UA levels were significantly higher in the pre-hypertension and hypertension group compared to the control group in the entire population (p<0.05 for all). Quantitative trait analysis indicated that serum UA levels were (2.92±0.81, 3.06±0.85, 3.22±0.98 mg/d) linearly increased in normotensive, pre-hypertensive and hypertensive females, with a p value of 0.008. Serum UA levels in the quartiles were positively correlated with DBP (p<0.05), particularly in females. After adjusting for age, gender, body mass index (BMI), glucose (GLU), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-hypertension from the lowest (referent) to the highest levels of serum UA were 1.718 (1.028-2.872), 1.018 (0.627-1.654) and 1.738 (1.003-3.010). Additionally, the second quartile of serum UA levels were significantly associated with hypertension, with an OR (95% CI) of 2.036 (1.256-3.298). CONCLUSIONS: This study suggests that higher serum UA levels are positively associated with pre-hypertension and hypertension among Chinese adults.


Assuntos
Hipertensão , Pré-Hipertensão , Adulto , China , Estudos Transversais , Feminino , Humanos , Fatores de Risco , Ácido Úrico
18.
BMC Endocr Disord ; 21(1): 130, 2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34176482

RESUMO

BACKGROUND: Hypertension and overweight are independent risk factors for cardiovascular disease, and overweight increase the risk of developing high blood pressure. ERBB3( also known as HER3) plays a considerable role in the development of cardiovascular diseases. However, the effect of ERBB3 levels in hypertensive overweight patients is unknown. The aim of this study was to assess the association between ERBB3 levels and hypertension in overweight Chinese patients. METHODS: We evaluated the height,weight, blood pressure, biochemical indicators, and ERBB3 levels in 128 Chinese adults aged 33-79 years. Plasma ERBB3 levels were assessed by the enzyme-linked immunosorbent assay, and body mass index(BMI) was calculated as body weight divided by height squared. Participants were allocated into three groups according to blood pressure and BMI: healthy control (CNT, n = 31; normotensive and non-overweight), hypertension (HT, n = 33; hypertension and non-overweight), and hypertension with overweight (HTO, n = 64; hypertension and overweight). Statistical significance was defined as a two-tailed P < 0.05. RESULTS: There was no significant difference in mean ERBB3 levels among the three groups, although a linear decrease from CNT (1.13 ± 0.36), HT (1.03 ± 0.36), to HTO (0.84 ± 0.26 ng/mL) was observed in men (P = 0.007). Among the drinking population, the ERBB3 level was significantly reduced in the HTO group as compared with those of the CNT and HT groups (0.76 ± 0.23 versus 1.18 ± 0.37 and 1.20 ± 0.30, respectively). ERBB3 levels were negatively correlated with diastolic blood pressure in men (r= - 0.293, P = 0.012), smoking (r= - 0.47, P = 0.004), and drinking (r = - 0.387, P = 0.008). BMI in men and among drinkers, and uric acid among drinkers were negatively correlated with ERBB3 levels. Multivariate conditional logistic regression showed that plasma ERBB3 levels were associated with a reduced risk of HTO in men [odds ratio (OR) 0.054; 95 % confidence interval (CI): 0.007-0.412) and drinkers (OR 0.002; 95 % CI: 0.000-0.101). CONCLUSIONS: ERBB3 may contribute to the pathogenesis of hypertension in overweight patients, with BMI, gender, and drinking all potentially modulating the process.

19.
Aging Cell ; 20(7): e13425, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34157207

RESUMO

Liver ageing not only damages liver function but also harms systemic metabolism. To better understand the mechanisms underlying liver ageing, we transplanted the livers of young rats to young and old rats and performed untargeted metabolomics to detect changes in the metabolites in the liver tissues and sera. A total of 153 metabolites in the livers and 83 metabolites in the sera were different between the old and young rats that did not undergo liver transplantation; among these metabolites, 7 different metabolites were observed in both the livers and sera. Five weeks after liver transplantation, the levels of 25 metabolites in the young donor livers were similar to those in the old rats, and this result probably occurred due to the effect of the whole-body environment of the older recipients on the young livers. The 25 altered metabolites included organic acids and derivatives, lipids and lipid-like molecules, etc. In the sera, the differences in 78 metabolites, which were significant between the young and old rats, were insignificant in the old recipient rats and made the metabolic profile of the old recipients more similar to that of the young recipients. Finally, combining the above metabolomic data with the transcriptomic data from the GEO, we found that the altered metabolites and genes in the liver were enriched in 9 metabolic pathways, including glycerophospholipid, arachidonic acid, histidine and linoleate. Thus, this study revealed important age-related metabolites and potential pathways as well as the interaction between the liver and the whole-body environment.

20.
Arq. bras. cardiol ; 116(6): 1072-1078, Jun. 2021. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1278335

RESUMO

Resumo Fundamento O ácido úrico , produto final do metabolismo dos nucleotídeos das purinas, participa dos processos de doenças metabólicas e cardiovasculares. Evidências experimentais sugerem que o ácido úrico é um mediador importante na resposta fisiológica ao aumento da pressão arterial. Objetivo Avaliar a associação entre os níveis séricos de AU e pré-hipertensão e hipertensão em uma população chinesa. Métodos Conduziu-se um estudo transversal entre março e setembro de 2017, e 1.138 participantes com idades entre 35 e 75 anos foram incluídos neste estudo, onde 223 normotensos, 316 pré-hipertensos e 599 hipertensos foram selecionados para avaliar a associação entre níveis séricos de AU e hipertensão. Considerou-se um valor de p<0,05 estatisticamente significativo. Resultados Os níveis séricos de AU foram significativamente maiores no grupo pré-hipertensão e hipertensão em comparação com o grupo controle em toda a população (p<0,05 para todos). A análise quantitativa das características indicou níveis séricos de AU (2,92±0,81, 3,06±0,85, 3,22±0,98 mg/d) linearmente aumentados em mulheres normotensas, pré-hipertensas e hipertensas, com um valor de p de 0,008. Os níveis séricos de AU nos quartis correlacionaram-se positivamente com a PAD (p<0,05), principalmente em mulheres. Após o ajuste para idade, sexo, índice de massa corporal (IMC), glicose (GLI), colesterol total (CT), triglicerídeos (TG), colesterol HDL (lipoproteína de alta densidade), as razões de chances ( odds ratios — ORs) e intervalos de confiança (IC) de 95% da pré-hipertensão, dos níveis séricos de AU mais baixos (referentes) aos mais altos foram 1,718 (1,028-2,872), 1,018 (0,627-1,654) e 1,738 (1,003-3,010). Além disso, o segundo quartil dos níveis séricos de AU esteve significativamente associado à hipertensão, com uma OR (IC 95%) de 2,036 (1,256-3,298). Conclusões O presente estudo sugere que níveis séricos mais elevados de AU estão positivamente associados à pré-hipertensão e hipertensão entre adultos chineses.


Abstract Background Uric acid (UA), the end product of purine nucleotide metabolism, participates in the processes of metabolic and cardiovascular diseases. Experimental evidence suggests it is an important mediator in the physiological response to blood pressure increase. Objective To evaluate the association between serum UA levels and pre-hypertension and hypertension in a Chinese population. Methods A cross-sectional study was conducted from March to September 2017, and 1,138 participants aged 35 to 75 were enrolled in this study, where 223 normotensive, 316 pre-hypertensive, and 599 hypertensive subjects were selected to evaluate the association between serum UA levels and hypertension. A p-value <0.05 was considered statistically significant. Results Serum UA levels were significantly higher in the pre-hypertension and hypertension group compared to the control group in the entire population (p<0.05 for all). Quantitative trait analysis indicated that serum UA levels were (2.92±0.81, 3.06±0.85, 3.22±0.98 mg/d) linearly increased in normotensive, pre-hypertensive and hypertensive females, with a p value of 0.008. Serum UA levels in the quartiles were positively correlated with DBP (p<0.05), particularly in females. After adjusting for age, gender, body mass index (BMI), glucose (GLU), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-hypertension from the lowest (referent) to the highest levels of serum UA were 1.718 (1.028-2.872), 1.018 (0.627-1.654) and 1.738 (1.003-3.010). Additionally, the second quartile of serum UA levels were significantly associated with hypertension, with an OR (95% CI) of 2.036 (1.256-3.298). Conclusions This study suggests that higher serum UA levels are positively associated with pre-hypertension and hypertension among Chinese adults.

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