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1.
Mol Ther Nucleic Acids ; 26: 1270-1279, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34853726

RESUMO

YTHDF1 is the most versatile and powerful reader protein of N 6-methyladenosine (m6A)-modified RNA, and it can recognize both G(m6A)C and A(m6A)C RNAs as ligands without sequence selectivity. YTHDF1 regulates target gene expression by different mechanisms, such as promoting translation or regulating the stability of mRNA. Numerous studies have shown that YTHDF1 plays an important role in tumor biology and nontumor lesions by mediating the protein translation of important genes or by affecting the expression of key factors involved in many important cell signaling pathways. Therefore, in this review we focus on some of the roles of YTHDF1 in tumor biology and diseases.

2.
Sci China Life Sci ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34735681

RESUMO

Ulcerative colitis (UC) is a long-term, recurrent inflammatory bowel disease for which no effective cure is yet available in the clinical setting. Repairing the barrier dysfunction of the colon and reducing intestinal inflammation are considered key objectives to cure UC. Here we demonstrate a novel therapeutic strategy based on a C60 fullerene suspension (C60FS) to treat dinitrobenzene sulfonic acid-induced UC in an animal model. C60FS can repair the barrier dysfunction of UC and effectively promote the healing of ulcers; it also manifests better treatment effects compared with mesalazine enema. C60FS can reduce the numbers of basophils in the blood of UC rats and mast cells in the colorectal tissue, thereby effectively alleviating inflammation. The expression of H1R, H4R, and VEGFR2 receptors in colorectal tissues is inhibited by C60FS, and the levels of histamine and prostaglandin in the rat blood are reduced. This work presents a reliable strategy based on fullerene to cure UC and provides a novel guide for UC treatment.

3.
Front Med (Lausanne) ; 8: 754890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746191

RESUMO

Objective: To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy. Methods: Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated. Results: Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6-59.9], 74.2 95% CI: 65.6-81.4), and 45.8% (95% CI: 38.7-53.2), respectively. Conclusion: Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.

4.
Cancer Lett ; 523: 100-110, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34601022

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype among breast cancers with high recurrence and this condition is partly due to chemoresistance. Therefore, fully understanding the mechanism of TNBC-resistance is the key to overcoming chemoresistance, which will be an effective strategy for TNBC therapy. Various potential mechanisms involved in the chemoresistance of TNBC have been investigated and indicated that noncoding RNAs (ncRNAs) especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) take part in most TNBC resistance. The ncRNA-induced chemoresistance process is involved in the alteration of many activities. here, we mainly summarize the mechanisms of ncRNAs in the chemoresistance of TNBC and discuss the potential clinical application of ncRNAs in the treatment of TNBC, indicating that targeting ncRNAs might be a promising strategy for resensitization to chemotherapies.

5.
Nutr Metab (Lond) ; 18(1): 82, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496912

RESUMO

BACKGROUND: As a newly proposed diagnosis, data on the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rare. We aimed to assess the prevalence and risk factors of MAFLD using new definition in the contemporary South China population. METHODS: In this population based, cross sectional study, a total of 5377 participants aged 30-79 years old were recruited from the South China between 2018 and 2019. MAFLD was diagnosed in subjects who have both hepatic steatosis and metabolic disorders according to the newly international expert consensus. The total prevalence of MAFLD and prevalence by sex and age was estimated. Demographic characteristics, history of disease, and lifestyle were recorded by participants on a questionnaire. Abdominal ultrasonography was performed and evaluated by experienced sonographers. Multivariable logistic regression was used to calculate the odds ratios (ORs) of MAFLD. RESULTS: Overall prevalence of MAFLD was 29.2% (95% confidence interval [CI] 28.0% to 30.5%). Prevalence was higher in women (31.7%) than in men (25.5%; p < 0.001 for sex difference) and in subjects aged 50 years or older (30.7%) than in those aged 30-49 years (19.8%; p < 0.001 for age difference). In participants diagnosed with MAFLD, the prevalence of overweight/obesity was up to 90.5%, type 2 diabetes (T2DM) and metabolic dysregulation were 25.0% and 62.2%, respectively. Risk factors for MAFLD included overweight/obesity (OR = 4.67; 95% CI, 3.76-5.83), T2DM (OR = 2.41, 95% CI, 1.68-3.47), hypertriglyceridemia (OR = 2.42, 95% CI, 2.03-2.87), high school education (OR = 1.50, 95% CI, 1.23-1.82), high income (OR = 1.22, 95% CI, 1.05-1.42). A lower risk of MAFLD was associated with high physical activity equivalent (OR = 0.71, 95% CI, 0.60-0.85). A U-shaped association of frequency of soups and ORs of MAFLD was found, the adjusted ORs (95% CI) of lower and higher frequency of soups were 1.58 (1.32-1.89) and 1.36 (1.13-1.63), respectively. CONCLUSIONS: Our results showed a high prevalence of MAFLD in the general adult population in South China. Obesity has the greatest impact on MAFLD, physical activity and moderate consumption of soups might be the potential protective factors of MAFLD.

6.
Nat Commun ; 12(1): 5444, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521850

RESUMO

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although functional and phenotypic changes of immune cells have been reported, a global understanding of immune responses underlying acute KD is unclear. Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells from seven patients with acute KD before and after intravenous immunoglobulin therapy and from three age-matched healthy controls. The most differentially expressed genes are identified in monocytes, with high expression of pro-inflammatory mediators, immunoglobulin receptors and low expression of MHC class II genes in acute KD. Single-cell RNA sequencing and flow cytometry analyses, of cells from an additional 16 KD patients, show that although the percentage of total B cells is substantially decreased after therapy, the percentage of plasma cells among the B cells is significantly increased. The percentage of CD8+ T cells is decreased in acute KD, notably effector memory CD8+ T cells compared with healthy controls. Oligoclonal expansions of both B cell receptors and T cell receptors are observed after therapy. We identify biological processes potentially underlying the changes of each cell type. The single-cell landscape of both innate and adaptive immune responses provides insights into pathogenesis and therapy of KD.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Monócitos/imunologia , Síndrome de Linfonodos Mucocutâneos/genética , Plasmócitos/imunologia , Doença Aguda , Imunidade Adaptativa/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/patologia , Estudos de Casos e Controles , Proliferação de Células , Criança , Pré-Escolar , Células Clonais , Feminino , Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Imunoglobulinas Intravenosas/uso terapêutico , Imunofenotipagem , Masculino , Monócitos/efeitos dos fármacos , Monócitos/patologia , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/patologia , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologia , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Análise de Sequência de RNA , Análise de Célula Única
7.
BMC Pediatr ; 21(1): 409, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535106

RESUMO

BACKGROUND: The prevalence of allergic diseases (ADs), such as asthma and allergic rhinitis (AR), is increasing worldwide in both adults and children. Although ADs are common and frequently coexist in outpatient care, city-level data regarding the characteristics of childhood AD remain limited in China. This study aimed to assess the profile and characteristics of ADs in the city of Shanghai. METHODS: A multicenter retrospective study was designed to collect routine administrative data from outpatient and emergency departments from 66 hospitals in Shanghai, China, from 2016 to 2018. Children with asthma, AR, allergic conjunctivitis (AC), and allergic skin diseases were investigated. Demographic characteristics, patients visit pattern, spectrum of diagnosis, and comorbidities were analyzed. RESULTS: A total of 2,376,150 outpatient and emergency visits for ADs were included in the period from 2016 to 2018. Allergic skin diseases accounted for 38.9%, followed by asthma (34.8%), AR (22.9%), and AC (3.3%), with a male predominance in all four diseases. Asthma and allergic skin diseases were most frequent in the 1 to < 4 years of age group, while AR and AC were more common in the 4 to < 7 years of age group. Asthma accounted for the greatest number of annual and emergency visits. The most frequent comorbidity of asthma was lower respiratory tract infection (LRTI) (49.3%), followed by AR (20.5%) and upper respiratory tract infection (14.1%). The most common comorbidities of AR were otitis media (23.4%), adenoid hypertrophy/obstructive sleep apnea (22.1%), followed by LRTI (12.1%), asthma (9.4%) and chronic pharyngitis (8.9%). CONCLUSIONS: Asthma and allergic skin diseases were the most common ADs in outpatient and emergency departments in the study period. Respiratory tract infection was the most common comorbidity of asthma in children. More attention should be devoted to the treatment of comorbidities to improve childhood AD outcomes with a better understanding of the characteristics of ADs in outpatient care.


Assuntos
Pacientes Ambulatoriais , Rinite Alérgica , Adulto , Criança , China/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Retrospectivos , Rinite Alérgica/epidemiologia
8.
J Healthc Eng ; 2021: 9998947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422252

RESUMO

Social support refers to the subjective and (or) objective influence of various social relationships on individuals, which has a certain influence on the negative emotions of the kidney transplant patients. But there are still significant differences among various studies, so we performed a meta-analysis to analyze the social support degree of kidney transplant recipients. This article searched and selected the relevant cross-sectional surveys from PubMed, Embase, VIP, CNKI, Wanfang, and CBM databases according to the inclusion and exclusion criteria and used the STROBE list combined with the observational research quality evaluation tools of Sanderson to conduct the quality appraisal. The "meta" and "metaphor" packages of the R software version 3.5.1 were used for the meta-analysis. A total of 17 studies with 2697 patients were included. The total scores of the social support and objective support of the renal transplant patients were abundant after the operation, indicating that the economic, physical, and emotional supports from the family, society, and the official organization are accepted. But the subjective support and support utilization degree were general. The support utilization was different among different genders, and female patients were lower than the males. In particular, the female patients relatively presented autism and the social support utilization degree was low. Medical staffs are needed to join the family, hospital, and society to create favorable conditions and improve the social support system and the utilization degree of the social support, thereby promoting the physical and mental health development of the patients.

9.
CNS Neurosci Ther ; 27(11): 1327-1338, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34346561

RESUMO

AIMS: Secondary bleeding and further hematoma expansion (HE) aggravate brain injury after intracerebral hemorrhage (ICH). The majority of HE results from hypertensive ICH. Previous study reported higher iron content in the brains of hypertensive patients. Iron overload exacerbates the risk of hemorrhagic transformation in thromboembolic stroke mice. Whether iron overload during the process of hypertension participates in secondary bleeding of hypertensive ICH remains unclear. METHODS: Hypertension was induced by continuous infusion of angiotensin II (Ang II) with an osmotic pump into C57BL/6 mice. ICH was simulated by intrastriatal injection of the liquid polymer Onyx-18. Iron chelation and iron overload was achieved by deferoxamine mesylate or iron dextran injection. Secondary bleeding was quantified by measuring the hemoglobin content in the ipsilateral brain hemisphere. RESULTS: Ang II-induced hypertensive mice showed increased iron accumulation in the brain and expanded secondary hemorrhage after ICH modeling. Moreover, iron chelation suppressed while iron overload aggravated secondary bleeding. Mechanistically, iron exacerbated the loss of contractile cerebral vascular smooth muscle cells (VSMCs), aggravated blood-brain barrier (BBB) leakage in Ang II-induced hypertensive mice, and increased glial and MMP9 accumulation after ICH. CONCLUSION: Iron overload plays a key role in secondary bleeding after ICH in Ang II-induced hypertensive mice. Iron chelation during the process of Ang II-induced hypertension suppresses secondary bleeding after ICH.

10.
Turk J Gastroenterol ; 32(6): 532-542, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34405820

RESUMO

BACKGROUND: Previous studies have shown that miR-224 regulates the progression of liver cancer. The aim of this study was to investigate the underlying mechanisms. METHODS: The miR-224, p-STAT3 and SMAD4 expression levels were checked with tissue or/and serum samples of HCC patients by qRT-PCR or IHC methods. The regulatory role of IL-6 in p-STAT3 and SMAD4 was investigated by Western-blot. The targeted gene of miR-224 was verified by both Western-blot and luciferase reporter assay. Furthermore, the carcinogenesis of miR-224 in HCC was investigated by cell experiments in vitro and mouse xenograft model and in vivo imaging in vivo. RESULTS: It was found miR-224 was elevated in both tissue and serum of HCC patients. The p-STAT3 expression was higher but the SMAD4 was lower in the HCC tumor tissues. Moreover, IL-6 can induce the p-STAT3/STAT3 and miR-224 expression in HCC cells and STAT3 played the bridge role between IL-6 and miR-224. Target gene studies found miR-224 targeted the 3'UTR of SMAD4. Finally, the promoting roles of miR-224in the growth, proliferation, invasion and migration of HCC were discovered by in vitro and in vivo studies. CONCLUSION: It implies that miR-224 may potentially represent a new target for developing novel anti-HCC therapeutics.

11.
Soft Matter ; 17(28): 6688-6696, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34240085

RESUMO

Herein, we report a method of fabricating strong and thermosensitive double network (T-DN) poly(N-isopropyl acrylamide) (PNIPAM)-based hydrogels, i.e. rigid and brittle poly(2-acrylamido-2-methylpropanesulfonic acid sodium salt) (PNaAMPS) as the first and soft and ductile poly(N-isopropyl acrylamide-co-acrylamide) (P(NIPAM-co-AAm)) as the second interpenetrating each other. In particular, NIPAM was deliberately integrated into the double network as an adjustor of elastic modulus and hydrophilicity, besides thermosensitivity. Such double network construction strategy resulted in PNaAMPS/P(NIPAM-co-AAm) T-DN hydrogels of excellent mechanical properties (0.83-1.37 MPa) and desirable temperature-dependent swellabilities. Besides, T-DN hydrogels with various NIPAM contents exhibited good biocompatibility with high cell survival rates around normal body temperatures. Furthermore, crystal violet (CV) could be readily loaded to impart antibacterial functionality to the T-DN hydrogels against E. coli. The double network construction strategy could be adapted to fabricating high-strength antibacterial hydrogels for a broad range of biomedical applications.


Assuntos
Escherichia coli , Hidrogéis , Antibacterianos , Módulo de Elasticidade , Resistência à Tração
12.
Int J Hyg Environ Health ; 236: 113805, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34271373

RESUMO

BACKGROUND: Although ambient fine particulate matter (PM2.5) has been associated with adverse respiratory outcomes in children, few studies have examined PM2.5 constituents with respiratory diseases in children in China. OBJECTIVES: To investigate the associations of short-term exposure to PM2.5 and its constituents with pediatric emergency room visits (ERVs) for respiratory diseases in Shanghai, China. METHODS: We collected daily concentrations of PM2.5 and its constituents in urban Shanghai from January 1, 2016, to December 31, 2018. Daily pediatric ERVs for four major respiratory diseases, including upper respiratory tract infection, bronchitis, pneumonia, and asthma, were obtained from 66 hospitals in Shanghai during the same period. Associations of exposure to daily PM2.5 and constituents with respiratory ERVs were estimated using the over-dispersed generalized additive models. RESULT: Short-term exposure to PM2.5 and its constituents were associated with increased pediatric ERVs for respiratory diseases. Specifically, an interquartile range increase in the 3-day average PM2.5 level (31 µg/m3) was associated with 1.86% (95%CI: 0.52, 3.22), 1.53% (95%CI: 0.01, 3.08), 1.90% (95%CI: 0.30, 3.52), and 2.67% (95%CI: 0.70, 4.68) increase of upper respiratory tract infection, bronchitis, pneumonia, and asthma ERVs, respectively. As for PM2.5 constituents, we found organic carbon, ammonium, nitrate, selenium, and zinc were associated with higher risk of respiratory ERVs in the single constituent and the constituent-PM2.5 models. CONCLUSION: Short-term exposure to PM2.5 was associated with increased pediatric ERVs for respiratory diseases. Constituents related to anthropogenic combustion and traffic might be the dominant contributors of the observed associations.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Criança , China/epidemiologia , Serviço Hospitalar de Emergência , Exposição Ambiental , Humanos , Material Particulado/análise
13.
Chemosphere ; 282: 131091, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34119731

RESUMO

In this study, calcite was investigated as an activator for the norfloxacin (NOR) degradation by peroxymonosulfate (PMS). Under optimum conditions, the NOR removal percentage was 99.7% within 60 min, and the pseudo-first-order kinetics effectively described the two-stage oxidation process. The NOR removal percentage improved from 10.4% to 91.5% and the reaction rate constant elevated from 0.0010 to 0.1217 min-1 when 0.5 g/L calcite was added compared to that without calcite addition. Furthermore, the results of radical scavenger and electron spin resonance trapping indicated that the favorable alkaline environment and a proper level of carbonate in the Calcite/PMS system facilitated the activation of PMS to generate 1O2 for rapid NOR degradation. Compared with NaOH, calcite was able to maintain the pH (8-9) of the reaction system stable. Besides, the content of anions with buffering capacity and organic matter in the water matrix influenced the removal percentage of NOR. Seven intermediates were identified and the NOR degradation pathways were suggested. The findings of this research provided an environmentally friendly activator for remediation of organic wastewater and deepened the understanding of the interaction between calcium carbonate and PMS.


Assuntos
Carbonato de Cálcio , Norfloxacino , Peróxidos , Águas Residuárias
14.
Opt Express ; 29(11): 16652-16664, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34154223

RESUMO

A microwave photonics interrogation system for multiplexing fiber Fabry-Perot (FP) sensors is demonstrated in this paper. Different from previous FP demodulation schemes, this system aims at quasi-distributed sensing networks composed of FP sensors with a short effective cavity length less than 1 mm. With the help of a dispersion element, the superimposed reflected spectrum from FP sensors based on a hollow core fiber (HCF) can be converted into separate response passbands in the frequency domain simultaneously, whose center frequency will shift linearly with the variations of environment. The experimental results exhibit high linearity and interrogation ability for both the all-FP multiplexing system and hybrid multiplexing system. A strain interrogation sensitivity of 0.938 kHz/µÉ› and temperature sensitivity of -0.699 MHz/°C have been realized, corresponding to a FP cavity length demodulation sensitivity of 1.563 MHz/µm. Furthermore, numerical studies about the impacts of the HCF-FP spectrum envelope on the RF response passband, as well as the theoretical minimum detectable cavity length and multiplexing capacity of the system, are also carried out.

15.
Redox Biol ; 45: 102033, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34119876

RESUMO

S-adenosylhomocysteine (SAH) is hydrolyzed by SAH hydrolase (SAHH) to homocysteine and adenosine. Increased plasma SAH levels were associated with disturbed renal function in patients with diabetes. However, the role and mechanism of SAHH in diabetic nephropathy is still unknown. In the present study, we found that inhibition of SAHH by using its inhibitor adenosine dialdehyde (ADA) accumulates intracellular or plasma SAH levels and increases high glucose-induced podocyte injury and aggravates STZ-induced diabetic nephropathy, which is associated with Nod-like receptor protein 3 (NLRP3) inflammasome activation. Inhibition or knockout of NLRP3 attenuates SAHH inhibition-aggravated podocyte injury and diabetic nephropathy. Additionally, SAHH inhibition increases thioredoxin-interacting protein (TXNIP)-mediated oxidative stress and NLRP3 inflammasome activation, but these effects were not observed in TXNIP knockout mice. Mechanistically, SAHH inhibition increased TXNIP by inhibiting histone methyltransferase enhancer of zeste homolog 2 (EZH2) and reduced trimethylation of histone H3 lysine 27 and its enrichment at promoter of early growth response 1 (EGR1). Moreover, EGR1 is activated and enriched at promoters of TXNIP by SAHH inhibition and is essential for SAHH inhibition-induced TXNIP expression. Inhibition of EGR1 protected against SAHH inhibition-induced NLRP3 inflammasome activation and oxidative stress and diabetic nephropathy. Finally, the harmful effects of SAHH inhibition on inflammation and oxidative stress and diabetic nephropathy were also observed in heterozygote SAHH knockout mice. These findings suggest that EZH2/EGR1/TXNIP/NLRP3 signaling cascade contributes to SAHH inhibition-aggravated diabetic nephropathy. Our study firstly provides a novel insight into the role and mechanism of SAHH inhibition in diabetic nephropathy.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Animais , Proteínas de Transporte/genética , Nefropatias Diabéticas/genética , Epigênese Genética , Humanos , Inflamassomos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR , Estresse Oxidativo , Tiorredoxinas/genética
16.
Am J Clin Nutr ; 114(4): 1360-1370, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34192296

RESUMO

BACKGROUND: S-adenosylmethionine (SAM) as methyl donors participates in methylation and is converted into S-adenosylhomocysteine (SAH), which is a precursor of homocysteine. Increased plasma SAH and homocysteine are associated with increased risk of cardiovascular disease. However, the relation of plasma SAM with cardiovascular risk is still unclear. OBJECTIVES: To determine the relation between plasma SAM and risk of mortality among patients with coronary artery disease (CAD). METHODS: Baseline plasma SAM concentrations were measured in 1553 patients with CAD from the Guangdong Coronary Artery Disease Cohort between October 2008 and December 2011. Proportional hazards Cox analyses were performed to ascertain associations between SAM and risk of all-cause and cardiovascular mortality. RESULTS: After a median follow-up of 9.2 (IQR: 8.5-10.2) y, of 1553 participants, 321 had died, including 227 deaths from cardiovascular diseases. Patients in the lowest quartile of SAM concentrations had a higher risk of all-cause death (HR, 1.59; 95% CI: 1.14, 2.21) and cardiovascular death (HR, 2.14; 95% CI: 1.41, 3.27) than those in the highest quartile in multivariable adjusted analysis. Each 1-SD decrease in the SAM concentration remained associated with a 42% greater risk of total death (HR, 1.42; 95% CI: 1.23, 1.64) and a 66% higher risk of cardiovascular death (HR, 1.66; 95% CI: 1.37, 2.01) after fully adjusting for other cardiovascular risk factors. Furthermore, each 1-SD decrease in plasma SAM/SAH ratio, as the methylation index, was also inversely associated with the risk of all-cause (HR, 1.80; 95% CI: 1.42, 2.29) and cardiovascular mortality (HR, 1.68; 95% CI: 1.29, 2.19) in fully adjusted analyses. CONCLUSIONS: Our data show a significant inverse relation between plasma SAM and risk of mortality in patients with CAD after adjustment for homocysteine, SAH, and other cardiovascular disease risk factors.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , S-Adenosilmetionina/sangue , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , S-Adenosil-Homocisteína/sangue
17.
Cell Death Differ ; 28(10): 2900-2915, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33990776

RESUMO

Accumulating evidence has shown that long noncoding RNAs (lncRNAs) are involved in several biological processes, including immune responses. However, the role of lncRNAs in antiviral innate immune responses remains largely elusive. Here, we identify an uncharacterized human lncRNA AVAN from influenza A virus (IAV) infected patients, that is significantly upregulated following RNA virus infection. During IAV infection, AVAN play an indispensable role in antiviral immune responses. In vivo, we enforced the expression of AVAN in transgenic mice or adeno-associated virus encoding AVAN delivery system and found that AVAN significantly alleviated IAV virulence and virus replication. Mechanistically, nuclear AVAN positively regulates the transcription of forkhead box O3A (FOXO3a) by associating with its promoter and inducing chromatin remodeling to promote neutrophil chemotaxis. Meanwhile, cytoplasmic AVAN binds directly to the E3 ligase TRIM25 and enhances TRIM25-mediated K63-linked ubiquitination of RIG-I, thereby promoting TRIM25- and RIG-I-mediated antiviral innate immune responses, including the induction of type I interferon and ISGs. Moreover, AVAN binds to the B Box/CCD domain of TRIM25 and 1-200nt of AVAN were the functional moieties. Collectively, our findings highlight the potential clinical implications of human lncRNA AVAN as a key positive regulator of the antiviral innate immune response and a promising target for developing broad antiviral therapeutics.

18.
BMC Pregnancy Childbirth ; 21(1): 372, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975553

RESUMO

BACKGROUND: The gonadotrophin-releasing hormone (GnRH) antagonist protocol has some advantages, such as a simple method, short medication duration, and low incidence of ovarian hyperstimulation syndrome, but whether the GnRH antagonist protocol is suitable for normal ovarian responders has been controversial. We compared the clinical outcomes of fresh and frozen-thawed transfer cycles between the depot GnRH agonist protocol and GnRH antagonist protocol in normal ovarian responders. METHODS: Data of normal ovarian responders who underwent in vitro fertilization-embryo transfer (IVF-ET) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) between January 2017 and December 2018 in our hospital were retrospectively analysed. In this study, there were 1119 fresh transfer cycles, including 502 GnRH antagonist cycles (GnRH antagonist group) and 617 depot GnRH agonist cycles (depot GnRH agonist group), as well as 468 frozen-thawed transfer cycles, includng 191 GnRH antagonist cycles (GnRH antagonist group) and 277 depot GnRH agonist cycles (depot GnRH agonist group). The clinical outcomes were compared between the GnRH antagonist group and the depot GnRH agonist group. RESULTS: With the fresh transfer cycles, there were no statistically significant differences in the anti-Mullerian hormone level, number of transferred embryos or high-quality embryo rate between the two groups. The total dosage of gonadotropin (Gn), duration of Gn stimulation, number of oocytes retrieved, clinical pregnancy rate and incidences of moderate and severe ovarian hyperstimulation syndrome (OHSS) were significantly lower but the abortion rate was significantly higher in the GnRH antagonist group than in the depot GnRH agonist group (all P < 0.05). With the frozen-thawed transfer cycles, there were no statistically significant differences in the number of transferred embryos, clinical pregnancy rate or abortion rate between the two groups (all P > 0.05). CONCLUSIONS: With the fresh transfer cycles, the GnRH antagonist protocol had a lower clinical pregnancy rate and lower incidences of moderate and severe OHSS than the depot GnRH agonist protocol, but with the frozen-thawed transfer cycles, both protocols had similar clinical pregnancy rates. These results remain to be further confirmed through large-sample, prospective, randomized and controlled studies.


Assuntos
Fertilização In Vitro , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Indução da Ovulação/métodos , Adulto , Preparações de Ação Retardada , Transferência Embrionária , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/administração & dosagem , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas
19.
J Nutr Biochem ; 95: 108778, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34004342

RESUMO

Non-alcoholic fatty liver disease is a common metabolic disorder associated with insulin resistance and lacks a specific treatment. Our previous studies demonstrated that freeze-dried Saskatoon berry powder (SBp) reduced high fat-high sucrose (HFHS) diet-induced hyperglycemia and insulin resistance in mice. The present study examined the effect of SBp and one of its active components, cyanidin-3-glucoside (C3G), on hepatic steatosis in mice fed with HFHS diet for 10 weeks. HFHS diet significantly increased fasting plasma glucose, cholesterol, triglycerides, insulin resistance, inflammatory markers (tumor necrosis factor-α, monocyte chemotactic protein-1, plasminogen activator inbitor-1), alanine aminotransferase activity, and monocyte adhesion compared to control diet. In the liver, HFHS diet increased steatosis, lipid accumulation, collagen deposition, and the abundance of patatin-like phospholipase domain-containing 3, CCAAT-enhancer-binding protein homologous protein, toll-like receptor-4, and macrophage marker. Supplementation with SBp (5%) or C3G in an amount corresponding to that in 5% SBp to HFHS diet had similar effects to reduced fasting plasma glucose, liver steatosis, enzyme activity, lipid, collagen and macrophage deposition, hyperglycemia, hyperlipidemia, insulin resistance, monocyte adhesion, markers related to liver steatosis, inflammation, oxidative or endoplasmic reticulum stress in the peripheral circulation and/or liver compared to mice fed with HFHS diet alone. No significant difference in the studied variables was detected between mice treated with HFHS+SBp and C3G diet. The results suggest that SBp or C3G administration attenuates HFHS diet-induced liver steatosis in addition to insulin resistance and chronic inflammation in mice. C3G may contribute to the beneficial effects of SBp.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/efeitos adversos , Suplementos Nutricionais , Frutas/química , Obesidade/induzido quimicamente , Rosaceae/química , Adolescente , Animais , Glicemia , Sacarose na Dieta/administração & dosagem , Homeostase , Humanos , Insulina/genética , Insulina/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Pós
20.
J Cell Mol Med ; 25(9): 4316-4325, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33788378

RESUMO

Uromodulin (UMOD) can bind complement factor H (cFH) and inhibit the activation of complement alternative pathway (AP) by enhancing the cofactor activity of cFH on degeneration of C3b. UMOD, an N-glycans-rich glycoprotein, is expressed in thick ascending limb of Henle's loop where the epithelia need to adapt to gradient change of pH and ion concentration. ELISA-based cofactor activity of cFH and erythrocytes haemolytic assay was used to measure the impact of native and de-glycosylated UMOD on the functions of cFH. The binding assay was performed under different pH and ion concentrations, using ELISA. The levels of sialic acid on UMOD, from healthy controls and patients with chronic kidney disease (CKD), were also detected by lectin-ELISA. It was shown that removal of glycans decreased the binding between UMOD and cFH and abolished the ability of enhancing C3b degradation. In acidic condition, the binding became stronger, but it reduced as sodium concentration increased. A significant decrease of α-2,3 sialic acids on UMOD was observed in CKD patients compared with that of healthy individuals. The sialic acids on UMOD, local pH and sodium concentration could impact the binding capacity between UMOD and cFH and thus regulate the activation of complement AP.


Assuntos
Fator H do Complemento/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Insuficiência Renal Crônica/patologia , Uromodulina/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Hemólise , Humanos , Concentração de Íons de Hidrogênio , Masculino , Insuficiência Renal Crônica/metabolismo
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