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4.
Front Vet Sci ; 10: 1259760, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026674

RESUMO

This study aimed to investigate the effects of the combination of selenium and Bacillus subtilis (Se-BS) on the quality and flavor of meat and slaughter performance of broilers. A total of 240 one-day-old Arbor Acres broilers were randomly allotted to four treatments of a basal diet supplemented with no selenium (control), sodium selenite (SS), BS, or Se-BS and raised for 42 days. Compared with the control group, Se-BS significantly increased the carcass weight, the half-eviscerated weight, the completely eviscerated weight, the carcass rate, and redness in broiler muscles; improved the antioxidant state by increasing glutathione peroxidase (GPx) and glutathione S-transferase activities, the total antioxidant capacity, and GPx-1 and thioredoxin reductase 1 messenger RNA (mRNA) levels; promoted biological activity by increasing the contents of glutamate, phenylalanine, lysine, and tyrosine; and increased Se and five types of nitrogenous volatile substances in muscles. On the other hand, Se-BS treatment decreased the shear force, drip loss, and the malondialdehyde, glutathione, and lead contents in muscles. Se-BS exerted a better effect on slaughter performance, the physicochemical quality of meat, the redox status, the amino acid contents, the trace element contents, and volatile substances compared with SS and BS. In conclusion, Se-BS had a positive effect on the quality and flavor of meat and slaughter performance of broilers, suggesting that Se-BS may be a beneficial feed additive.

5.
Innovation (Camb) ; 4(4): 100450, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37485083

RESUMO

Hyperglycemia is a key risk factor for death and disability worldwide. To better inform prevention strategies, we aimed to delineate and predict the temporal, spatial, and demographic patterns in mean fasting plasma glucose (FPG) levels and their related disease burden globally. Based on the Global Burden of Disease Study 2019, we estimated the distributions of mean FPG levels and high FPG-related disease burden by age, sex, year, socioeconomic status (SES), and geographical region from 1990 to 2050. We also investigated the possible associations of demographic, behavioral, dietary, metabolic, and environmental factors with FPG levels and high FPG-related disease burden. In 2019, the global mean FPG level was 5.40 mmol/L (95% uncertainty interval [UI]: 4.86-6.00), and high FPG contributed to 83.0 deaths (95% UI, 64.5-107.1) and 2,104.3 DALYs (95% UI: 1,740.7-2,520.7) per 100,000 people. For both historical (1990-2019) and future (2020-2050) periods, the mean FPG levels and the high FPG-related disease burden increased globally, with greater increases among the middle-aged and elderly, and people in low-to-middle SES countries, relative to their counterparts. Aging, unhealthy lifestyles, elevated body mass index, and lower air temperatures were potential risk factors for high FPG levels and the high FPG-related disease burden. This study demonstrates that high FPG continues to contribute to the global disease burden and is expected to do so for at least the next 30 years. Older people and those living in low-to-middle SES countries should receive more attention in glycemic management health interventions. In addition, effective interventions that target identified risk factors should be adopted to handle the increasingly large disease burden of high FPG.

6.
Biol Trace Elem Res ; 201(12): 5756-5763, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36862247

RESUMO

This study aimed to investigate the effects of selenium (Se)-enriched Bacillus subtilis (Se-BS) on growth performance, antioxidant capacity, immune status, and gut health in broilers. A total of 240 one-day-old Arbor Acres broilers were randomly allotted to four groups and fed with basal diet (control group), 0.30 mg/kg Se (SS group), 3 × 109 CFU/g B. subtilis (BS group), and 0.30 mg/kg Se + 3 × 109 CFU/g B. subtilis (Se-BS group) for 42 days. The results showed that Se-BS supplementation increased body weight (BW), average daily gain, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and peroxidase (POD), total antioxidant capacity (T-AOC), and the contents of interleukin (IL)-2, IL-4, and immunoglobulin (Ig) G in plasma, the index and wall thickness of the duodenum, the villus height and crypt depth of the jejunum, and GPx-1 and thioredoxin reductase 1 mRNA levels in liver and intestine and decreased feed conversion ratio (FCR) and plasma malondialdehyde (MDA) content compared with the control group on day 42 (P < 0.05). Compared with groups SS and BS, Se-BS supplementation increased BW, the activities of GPx, CAT, and POD, and the contents of IL-2, IL-4, and IgG in plasma, the index and wall thickness of the duodenum, the crypt depth and secretory IgA content of the jejunum, and GPx-1 mRNA levels in liver and intestine and decreased FCR and plasma MDA content on day 42 (P < 0.05). In conclusion, Se-BS supplementation effectively improved the growth performance antioxidant capacity, immune status, and gut health of broilers.


Assuntos
Antioxidantes , Selênio , Animais , Selênio/farmacologia , Galinhas , Bacillus subtilis , Suplementos Nutricionais , Interleucina-4 , Dieta/veterinária , Glutationa Peroxidase , RNA Mensageiro/genética , Ração Animal/análise
7.
Sci Total Environ ; 871: 161975, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36740066

RESUMO

BACKGROUND: Maternal exposure to fine particular matter (PM2.5) during pregnancy, including ambient and household PM2.5, has been linked with increased risk of preterm birth (PTB). However, the global spatio-temporal distribution of PTB-related deaths and disability-adjusted life years (DALYs) attributable to PM2.5 is not well documented. We estimated the global, regional, and national patterns and trends of PTB burden attributable to both ambient and household PM2.5 from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study (GBD) 2019 database, we obtained the numbers of deaths and DALYs as well as age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) of PTB attributable to total, ambient, and household PM2.5 by socio-demographic index (SDI) and sex during 1990-2019. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of attributable burdens. RESULTS: In 2019, 126,752 deaths and 11.3 million DALYs related to PTB worldwide (two-thirds in Western Sub-Saharan Africa and South Asia) could be caused by excess PM2.5 above the theoretical minimum-risk exposure level (TMREL), of which 39 % and 61 % were attributable to ambient PM2.5 and household PM2.5, respectively. From 1990 to 2019, the global ASMR due to ambient PM2.5 increased slightly by 7.08 % whereas that due to household PM2.5 decreased substantially by 58.81 %, although the latter still dominated the attributable PTB burden, especially in low and low-middle SDI regions. Similar results were also observed for ASDRs. In addition, PTB burden due to PM2.5 was higher in male infants and in lower SDI regions. CONCLUSIONS: Globally in 2019, PM2.5 remains a great concern on the PTB burden, especially in Western Sub-Saharan Africa and South Asia. Between 1990 and 2019, age-standardized burden of PTB due to ambient PM2.5 increased globally, while that due to household PM2.5 decreased markedly but still dominated in low and low-middle SDI regions.


Assuntos
Nascimento Prematuro , Lactente , Feminino , Humanos , Masculino , Recém-Nascido , Anos de Vida Ajustados por Qualidade de Vida , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/induzido quimicamente , Carga Global da Doença , Material Particulado/toxicidade , Ásia Meridional
8.
Bioresour Technol ; 372: 128564, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36592867

RESUMO

The potentials of using endogenous free ammonia (FA) and free nitrous acid (FNA) as nitrous oxide (N2O) mitigators were investigated in treatment of both mainstream and sidestream wastewater. Although the N2O emission factor of a sidestream partial-nitritation (PN) reactor (averaged 1.70 % ± 0.39 %, n = 30) was about 2.4 times higher than a mainstream full-nitrification (FN) reactor (averaged 0.72 % ± 0.24 %, n = 30) (P < 0.01), one-hour exposure of PN sludge to 1.5 mg HNO2-N/L FNA could virtually abolish N2O emission. As for FN sludge, both 45 mg NH3-N/L FA and 0.015 mg HNO2-N/L FNA successfully mitigated N2O production at varying dissolved oxygen (DO) levels (50 % vs 61 %), while 1.5 mg HNO2-N/L FNA not only reduced more N2O (92 %) but also altered the N2O dependency on DO. Both FNA and FA sludge treatment were effective N2O mitigation strategies with FNA toward the end of carbon neutrality and FA being more economically appealing (2 % cost saving).


Assuntos
Amônia , Ácido Nitroso , Nitrificação , Esgotos , Óxido Nitroso/análise , Reatores Biológicos , Oxigênio/análise , Nitritos
9.
Glob Health Res Policy ; 7(1): 48, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36474302

RESUMO

BACKGROUND: Identifying factors associated with cardiovascular disease (CVD) is critical for its prevention, but this topic is scarcely investigated in Kashgar prefecture, Xinjiang, northwestern China. We thus explored the CVD epidemiology and identified prominent factors associated with CVD in this region. METHODS: A total of 1,887,710 adults at baseline (in 2017) of the Kashgar Prospective Cohort Study were included in the analysis. Sixteen candidate factors, including seven demographic factors, 4 lifestyle factors, and 5 clinical factors, were collected from a questionnaire and health examination records. CVD was defined according to International Clinical Diagnosis (ICD-10) codes. We first used logistic regression models to investigate the association between each of the candidate factors and CVD. Then, we employed 3 machine learning methods-Random Forest, Random Ferns, and Extreme Gradient Boosting-to rank and identify prominent factors associated with CVD. Stratification analyses by sex, ethnicity, education level, economic status, and residential setting were also performed to test the consistency of the ranking. RESULTS: The prevalence of CVD in Kashgar prefecture was 8.1%. All the 16 candidate factors were confirmed to be significantly associated with CVD (odds ratios ranged from 1.03 to 2.99, all p values < 0.05) in logistic regression models. Further machine learning-based analysis suggested that age, occupation, hypertension, exercise frequency, and dietary pattern were the five most prominent factors associated with CVD. The ranking of relative importance for prominent factors in stratification analyses showed that the factor importance generally followed the same pattern as that in the overall sample. CONCLUSIONS: CVD is a major public health concern in Kashgar prefecture. Age, occupation, hypertension, exercise frequency, and dietary pattern might be the prominent factors associated with CVD in this region.In the future, these factors should be given priority in preventing CVD in future.


Assuntos
Doenças Cardiovasculares , Hipertensão , Humanos , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Fatores Socioeconômicos , Aprendizado de Máquina
10.
Front Vet Sci ; 9: 993039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36176699

RESUMO

The research evaluated the effects of Aflatoxin B1 on growth performance, antioxidant status, immune response, and pro-inflammatory cytokine mRNA expression in ISA chicks. In total, 240 7-day-old ISA chicks were randomly assigned to four treatment groups. The control group comprised chicks fed a basal diet. The aflatoxin (AFB1)-treatment groups (T1, T2, and T3) comprised chicks fed the basal diet supplemented with AFB1 at concentrations of 5, 8, and 10 µg/kg, respectively. The growth performance, antioxidant status, immune responses, and pro-inflammatory cytokine mRNA expression in all groups were measured. In the T1 treatment group (receiving the lowest AFB1 dose), a reduction in the Newcastle disease virus antibody (NDV-Ab) titer, and increases in interleukin 2 (IL-2), IL-6, and interferon γ (IFN-γ) mRNA levels were observed on days 21 and 42 (P < 0.05). Treatment with the higher AFB1 doses (groups T2 and T3) reduced the chicks' growth performance on days 21 and 42, measured as reductions in body weight (BW) and average daily gain (ADG) compared with the control group. In the T2 and T3 groups, the total antioxidant capacity (T-AOC), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, serum immunoglobulin A (IgA) and IgG levels, and IL-2, IL-6, and IFN-γ levels were also lower than in the control group. On days 21 and 42, these two groups also showed increased malondialdehyde (MDA) content, higher feed to gain ratio (F/G), and higher IL-2, IL-6, and IFN-γ mRNA levels than the control group (P < 0.05). The T2 and T3 groups also showed reduced T-AOC, NDV-Ab titer, IL-2 content, and GPx-1 mRNA levels on days 21 and 42 (P < 0.05), increased IL-6 and IFN-γ mRNA levels on day 21, and increased F/G and MDA content on day 42 (P < 0.05) compared with group (T1). Increased MDA content and IL-6 mRNA levels in the liver and ileum were observed in group T3 compared with group T2 on day 21, and lower IgM and IL-6 levels were observed on days 21 and 42 (P < 0.05). In conclusion, our data showed that AFB1 exposure resulted in dose-dependent oxidative and inflammatory damage, immunosuppression, and a decline in the growth performance of chicks.

11.
Mol Cell Biochem ; 477(4): 1295-1308, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35137328

RESUMO

Previous studies have reported that exosomes bearing certain microRNAs (miRNAs) are related to the physiological functions of different types of cancer cells. Our study aimed to elucidate the role of miR-200a in esophageal squamous cell carcinoma (ESCC). We observed that miR-200a expression is higher in esophageal carcinoma cells, tissues, and exosomes than in normal cells and healthy tissues. We showed that exosome-shuttled miR-200a promotes the proliferation, migration, and invasion of esophageal cells and inhibits apoptosis, thereby leading to the progression of ESCC. We showed that miR-200a exerts its effects through its interaction with Keap1, thus altering the Keap1/Nrf2 signaling pathway. Our results suggest that exosome-shuttled miR-200a might be useful as a biomarker for prognosis in patients with ESCC.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína 1 Associada a ECH Semelhante a Kelch/biossíntese , MicroRNAs/metabolismo , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/metabolismo , Idoso , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Exossomos/genética , Feminino , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , RNA Neoplásico/genética
12.
Biol Trace Elem Res ; 200(8): 3798-3807, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34757520

RESUMO

Chicken hepatocytes were cultured in vitro and 240 specific pathogen-free (SPF) white leghorns chickens (7 days old) were obtained. The hepatocytes and chickens were randomly allocated to one of six treatment groups: control group; chitosan (COS) group; sodium selenite (Na2SeO3) group; selenide chitosan (COS-Se) group; chitosan sulfate (LS-COS) group; and selenide chitosan sulfate (LS-COS-Se) group. Our results showed that LS-COS-Se increased (P < 0.05) the activities of thioredoxin reductase (TXNRD), anti-superoxide anion radical (antiO2-), and superoxide dismutase (SOD), the mRNA levels of thioredoxin reductase 1 (TXNRD1) and thioredoxin reductase 3 (TXNRD3), and the chicken body weight, but reduced (P < 0.05) the malondialdehyde (MDA) content and the lactate dehydrogenase (LDH) activity. Compared with COS and LS-COS, the LS-COS-Se treatment increased (P < 0.05) the activities of TXNRD, SOD, catalase (CAT), and the mRNA levels of TXNRD1 and TXNRD3, but reduced (P < 0.05) the MDA content in vitro, whereas, in vivo, it increased (P < 0.05) body weight on day 28; the activities of TXNRD, antiO2-, and SOD; and the mRNA levels of TXNRD1 and TXNRD3. Compared with Na2SeO3 and COS-Se, the LS-COS-Se treatment increased (P < 0.05) the TXNRD and SOD activities, the mRNA levels of TXNRD1 and TXNRD3 in vitro, increased (P < 0.05) the chicken body weight on day 28, and the TXNRD, antiO2-, and SOD activities, but reduced (P < 0.05) the MDA content. These results indicated that LS-COS-Se was a useful antioxidant that improved hepatocyte activity, growth performance, and anti-oxidation capacity in hepatocytes (in vitro) and SPF chicken (in vivo) by activating the TXNRD system.


Assuntos
Quitosana , Selênio , Animais , Antioxidantes , Peso Corporal , Galinhas/genética , Quitosana/farmacologia , Hepatócitos , RNA Mensageiro/genética , Selênio/farmacologia , Superóxido Dismutase , Tiorredoxina Redutase 1/genética
13.
Poult Sci ; 99(11): 6045-6054, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33142523

RESUMO

The aim of this study was to investigate the effects of selenium (Se)-enriched Saccharomyces cerevisiae (SSC) on meat quality and to elucidate the underlying mechanisms in broilers. A total of 200 one-day-old Arbor Acres broiler chickens were randomly allocated to one of four treatments with 5 replications of 10 chickens each. Group 1 served as a control and was fed a basal diet without Se supplementation, while groups 2, 3, and 4 were fed the basal diet supplemented with S. cerevisiae (SC), sodium selenite (SS), and SSC, respectively. Breast muscle samples were collected to evaluate meat quality, selenium concentration, oxidative stability, and the mRNA levels of antioxidant enzyme genes on day 42. As compared with groups 1 and 2, SS and SSC supplementation increased Se concentration, glutathione peroxidase (GPx) and thioredoxin reductase (TR) activities, total antioxidant capacity, and the mRNA levels of GPx-1, GPx-4, TR-1, and TR-3 (P < 0.05) and decreased drip loss and malondialdehyde (MDA) content (P < 0.05). As compared with group 3, SSC supplementation increased pH, lightness, yellowness, Se concentration, GPx and superoxide dismutase activities, and the mRNA levels of GPx-1 and GPx-4 (P < 0.05) but decreased drip loss and MDA content (P < 0.05). Thus, SSC improved meat quality and oxidative stability by activating the glutathione and thioredoxin systems, which should be attributed to the combined roles of Se and SC.


Assuntos
Suplementos Nutricionais , Microbiologia de Alimentos , Glutationa , Carne , Saccharomyces cerevisiae , Selênio , Tiorredoxinas , Ração Animal/análise , Animais , Galinhas/microbiologia , Dieta/veterinária , Glutationa/genética , Glutationa Peroxidase/genética , Carne/microbiologia , Carne/normas , Distribuição Aleatória , Saccharomyces cerevisiae/metabolismo , Tiorredoxinas/genética
14.
Poult Sci ; 99(8): 3979-3986, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731985

RESUMO

This study aimed to investigate the effects of selenide chitosan sulfate (Se-CTS-S) on glutathione (GSH) system in hepatocytes and chickens. Chitosan, sodium selenite (Na2SeO3), selenide chitosan, chitosan sulfate (CTS-S), and Se-CTS-S were added to the culture medium and the basal diets; glutathione peroxidase (GSH-Px) activity, GSH content, total antioxidant capacity (T-AOC), and mRNA levels of cellular GPx (GPx-1) and phospholipid hydroperoxide GPx (GPx-4) in vivo and in vitro were determined. The results showed that Se-CTS-S increased (P < 0.05) GPx-1 and GPx-4 mRNA levels in hepatocytes and livers, and GSH-Px activity, GSH content, and T-AOC in the medium, hepatocytes, plasma, and livers compared with the control and chitosan treatments. Compared with CTS-S, Se-CTS-S treatments increased (P < 0.05) GPx-1 and GPx-4 mRNA levels in hepatocytes and livers, and GSH-Px activity, GSH content, and T-AOC capacity in the medium, hepatocytes, and livers. Compared with Na2SeO3 and CTS-Se, Se-CTS-S increased (P < 0.05) GPx-1 mRNA levels in hepatocytes and livers, GPx-4 mRNA levels in hepatocytes and livers, GSH-Px activity in the medium, hepatocytes, and livers, GSH contents in plasma and livers, and T-AOC in the medium, plasma, and livers. Thus, Se-CTS-S showed better biological activity that mainly benefited from the synergistic effects of Se and sulfate on GSH system.


Assuntos
Galinhas , Quitosana , Hepatócitos , Selênio , Animais , Quitosana/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/genética , Hepatócitos/efeitos dos fármacos , Organismos Livres de Patógenos Específicos
15.
Am J Transl Res ; 12(5): 1553-1568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509161

RESUMO

Esophageal cancer (EC) causes hundreds of thousands of deaths a year worldwide, especially the major subtype esophageal squamous cell carcinoma (ESCC). With the advent of next-generation sequencing and the availability of commercial microarrays, abnormities in genetic levels have been revealed in various independent researches. High frequencies of structure variations (SVs), single nucleotide variations (SNVs) and copy-number alterations (CNAs) in ESCCs are uncovered, and ESCC shows high levels of inter- and intratumor heterogeneity, implying diverse evolutionary trajectories. This review tries to explain the pathogenesis of ESCC on the scope of most often mutated genes based on prior studies, hopes to offer some hints for diagnosis and therapy in clinic.

16.
Artigo em Inglês | MEDLINE | ID: mdl-29946461

RESUMO

BACKGROUND: The goat (Caprahircus) is one of the most important livestock animals. Goat milk fat is an important component in the nutritional quality of goat milk. Growing evidence points to the critical roles of microRNAs (miRNAs) in lipid metabolism. RESULTS: Using a highly sensitive method of S-poly(T) plus for miRNAs detection, we analyze the expression patterns of 715 miRNAs in goat mammary gland tissues at different stages of lactation. We observed that miR-25 expression had an inverse relationship with milk production. Overexpression of miR-25 significantly repressed triacylglycerol synthesis and lipid droplet accumulation. To explore the regulatory mechanism of miR-25 in milk lipid metabolism, we analyzed its putative target genes with bioinformatics analysis followed by 3'-UTR assays. Peroxisome proliferative activated receptor gamma coactivator 1 beta (PGC-1beta), a key regulator of lipogenics was identified as a direct target of miR-25 with three specific sites within its 3'-UTR. In addition, miR-25 mimics in goat mammary epithelial cells reduced the expressions of genes involved in lipid metabolism. CONCLUSIONS: Taken together, our results show miR-25 is potentially involved in lipid metabolism and we reveal the function of the miR-25/PGC-1beta regulatory axis during lactation.

17.
Nanoscale ; 10(24): 11430-11440, 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29882950

RESUMO

Despite drug delivery systems (DDSs) receiving ever-increasing attention, development of a simple, effective, sensitive and clearable drug delivery and multifunctional theranostic nanoplatform for cancer therapy is still highly desirable and remains a challenge. Herein, using a one-step solvothermal method, hollow acanthosphere-like CuS superstructures assembled from ∼10 nm nanoparticles (NPs) were successfully obtained and used as an efficient drug delivery and theranostic platform for photoacoustic (PA) and infrared (IR) thermal imaging-guided cancer combination therapy. The special hollow characteristic of CuS superstructures with mesoporous shells and large cavities grants them high drug loading capacity; they demonstrate near-infrared (NIR)/pH stimuli-sensitive drug release and pronounced synergetic effects of chemo-photothermal therapy both in vitro and in vivo. In particular, our as-fabricated hollow loose CuS superstructures, with easily breakable characteristic, are biodegradable and able to be cleared from the body when their therapy task is completed. This CuS-superstructure-based clearable drug delivery and "all-in-one" cancer theranostic platform might provide possibilities for improving therapeutic efficacy and minimizing adverse effects.


Assuntos
Cobre/química , Sistemas de Liberação de Medicamentos , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia , Nanomedicina Teranóstica , Animais , Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Células HeLa , Humanos , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas , Técnicas Fotoacústicas , Espectrofotometria Infravermelho
18.
Mol Med Rep ; 17(1): 1289-1296, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115480

RESUMO

Oxidized low-density lipoprotein (Ox-LDL), as a strong oxidant, results in renal injury through multiple mechanisms. The aim of the present study was to determine the injury effects of Ox­LDL and the potential protective effects of the antioxidant reagent probucol on epithelial­mesenchymal transition (EMT) in human renal proximal tubular epithelial cells (HK­2) and to further explore the role and interrelation of lectin­like oxidized low­density lipoprotein receptor­1 (LOX­1), reactive oxygen species (ROS) and mitogen­activated protein kinase (MAPK) pathway. In the present study, concentrations of 0­100 µg/ml Ox­LDL were used to induce HK­2 cell EMT. Then, probucol (20 µmol/l) and the LOX­1 inhibitor, polyinosinic acid (250 µg/ml), were also used to pretreat HK­2 cells. Intracellular ROS activity was evaluated using the specific probe 2',7'­dichlorodihydrofluorescein diacetate (DCFH­DA). Concentration of nitric oxide (NO) was determined using a biochemical colorimetric method. Expression of E­cadherin, α­smooth muscle actin (SMA), LOX­1, NADPH oxidase 4 (NOX4), cytochrome b­245 α chain (p22phox), extracellular signal­regulated kinase (ERK), and p38 MAPK protein levels were examined by western blotting. The results revealed that Ox­LDL induced the expression of LOX­1 and α­SMA and reduced the expression of E­cadherin in a dose­dependent manner, and these effects were inhibited by polyinosinic acid or probucol pretreatment. Stimulation with 50 µg/ml Ox­LDL induced the expression of NOX4 and p22phox and increased intracellular ROS activity, but NO production in the cell supernatants was not affected. The Ox­LDL­mediated increases in Nox4 and p22phox expression and in ROS activity were inhibited by probucol pretreatment. Further investigations into the underlying molecular pathways demonstrated that ERK and p38 MAPK were activated by Ox­LDL stimulation and then inhibited by probucol pretreatment. The findings of the present study therefore suggest that Ox­LDL induced EMT in HK­2 cells, the mechanism of which may be associated with LOX­1­related oxidative stress via the ERK and p38 MAPK pathways. Notably, pretreatment with probucol inhibited the Ox­LDL­induced oxidative stress by reducing the expression of LOX­1, and blocked the progression of EMT.


Assuntos
Antioxidantes/farmacologia , Transição Epitelial-Mesenquimal , Lipoproteínas LDL/metabolismo , Probucol/farmacologia , Antígenos CD , Caderinas/metabolismo , Linhagem Celular , Sobrevivência Celular , Avaliação Pré-Clínica de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Túbulos Renais Proximais/citologia , Sistema de Sinalização das MAP Quinases , NADPH Oxidase 4/metabolismo , NADPH Oxidases/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores Depuradores Classe E/metabolismo
19.
Int J Mol Sci ; 18(4)2017 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-28362317

RESUMO

Myogenic differentiation, which occurs during muscle development, is a highly ordered process that can be regulated by E2F transcription factors. Available data show that E2F3b, but not E2F3a, is upregulated and required for myogenic differentiation. However, the regulation of E2F3b expression in myogenic differentiation is not well understood. To investigate whether E2Fb expression is controlled by miRNAs, we used bioinformatics to combine the database of microRNAs downregulated during myogenesis and those predicted to target E2F3. This identified miR-17 and miR-20a as miRNAs potentially involved in E2F3 regulation. We found that miR-17-92 controls the expression of E2F3b in C2C12 cells during myogenic differentiation. Moreover, we confirmed that miR-20a regulates the expression of E2F3b proteins in vivo using a muscle regeneration model.


Assuntos
Fator de Transcrição E2F3/genética , MicroRNAs/genética , Desenvolvimento Muscular/genética , Mioblastos/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Cardiotoxinas , Diferenciação Celular/genética , Linhagem Celular , Fator de Transcrição E2F3/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Células HEK293 , Humanos , Immunoblotting , Masculino , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Desenvolvimento Muscular/fisiologia , Doenças Musculares/induzido quimicamente , Doenças Musculares/fisiopatologia , Mioblastos/citologia , Regeneração/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
J Cell Biochem ; 118(12): 4285-4295, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28422320

RESUMO

Myogenesis involves myoblast proliferation and differentiation to myocytes, followed by fusion and hypertrophy to form myotubes during muscle development. Increasing evidence showed that microRNAs (miRNAs) play important roles in the regulation of myogenesis. We have previously revealed that miR-34b is steadily increased during this process. This miRNA regulates differentiation in various cell types, though its function in myogenesis remains to be elucidated. In this study, we show that miR-34b represses muscle cell proliferation and promotes myotube formation. Our quantitative iTRAQ-based proteomic analysis reveals 97 proteins are regulated by miR-34b in mouse myoblast C2C12. We identified that miR-34b targets 14-3-3 protein gamma, adenosylhomocysteinase and nucleolin by binding to their 3'UTR. Further analysis of these proteins expression patterns show that nucleolin is a cognate target of miR-34b during myogenic differentiation. Here, we proved that a moderate reduction of nucleolin in cells enhanced the myotube formation. However, nucleolin is required for myogenesis, as cells with low levels of nucleolin reduced cell proliferation rate and are unable to differentiate. Our data demonstrated that nucleolin regulates myogenesis in a protein-abundance-dependent manner. J. Cell. Biochem. 118: 4285-4295, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
MicroRNAs/metabolismo , Desenvolvimento Muscular , Músculo Esquelético/fisiologia , Mioblastos/fisiologia , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Regiões 3' não Traduzidas , Adenosil-Homocisteinase/genética , Adenosil-Homocisteinase/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Regulação da Expressão Gênica , Humanos , Camundongos , MicroRNAs/fisiologia , Modelos Animais , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/fisiologia , Proteômica , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/fisiologia , Nucleolina
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