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Primary subarachnoid hemorrhage (SAH) is a type of acute stroke, accounting for approximately 10% of cases, with high disability and mortality rate. Early brain injury (EBI) is a critical factor in determining SAH mortality; however, there are no effective treatment interventions for EBI. Based on our results, the transmission of cyclic GMP-AMP (cGAMP) from neurons to microglia is a key molecular event that triggers type I interferon response, amplifies neuroinflammation, and leads to neuronal apoptosis. Abnormal intracytoplasmic mitochondrial DNA (mtDNA) is the initiating factor of the cGAS-cGAMP-STING signaling axis. Overall, the cGAS-cGAMP-STING signaling axis is closely associated with neuroinflammation after subarachnoid hemorrhage. Targeting cGAS triggered by cytoplasmic mtDNA may be useful for comprehensive clinical treatment of patients after SAH. Further studies targeting cGAS-specific antagonists for treating SAH are warranted. Video Abstract.
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Interferón Tipo I , Hemorragia Subaracnoidea , Humanos , Microglía , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Nucleotidiltransferasas/genética , ADN Mitocondrial , NeuronasRESUMEN
Intraductal papillomas have been mostly described in minor salivary glands but are extremely rare in the parotid gland. Consequently, limited information is available to guide otolaryngologists and pathologists in managing intraductal papillomas, specifically in the parotid gland. Diagnosing intraductal papillomas in this location poses significant challenges. In this report, the authors present a new case and first conduct a systematic literature review of the intraductal papillomas originating from the parotid gland. This study contributes valuable insights that can improve diagnostic accuracy, providing more precise treatments, and patient outcomes in cases of intraductal papillomas in the parotid gland.
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Neoplasias de la Parótida , Humanos , Diagnóstico Diferencial , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/diagnóstico , Neoplasias de la Parótida/cirugíaRESUMEN
In this study, a sensitive high-performance liquid chromatography detector was established and validated for the simultaneous determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang Capsules. The analysis was achieved on CHANIN 100-5-C18-H column (5µm, 250 mm×4.6 mm) with the temperature of 30oC. Gradient elution was applied using 0.1% phosphoric acid solution-methanol-acetonitrile (50:50) as mobile phase at the flow rate of 1.0 mL/min. The determination was performed at the wavelength of 225 nm (detecting geniposide), 254 nm (detecting ellagic acid), 343 nm (detecting piperine) and 225 nm (detecting costunolide and dehydrocostuslactone) along with the sample volume of 10µL. The linear ranges of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone demonstrated good linear relationships within their respective determination ranges. The average recoveries were 100.04%, 99.86%, 99.79%, 100.17% and 100.41%, respectively. RSD% was 1.3%, 1.2%, 1.2%, 1.2%, 1.5%, respectively. The developed method was proved to be simple, accurate and sensitive, which can provide a quantitative analysis method for the content determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang capsules.
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Alcaloides , Benzodioxoles , Cápsulas , Medicamentos Herbarios Chinos , Ácido Elágico , Iridoides , Lactonas , Piperidinas , Alcamidas Poliinsaturadas , Cromatografía Líquida de Alta Presión/métodos , Benzodioxoles/análisis , Alcamidas Poliinsaturadas/análisis , Piperidinas/análisis , Piperidinas/química , Alcaloides/análisis , Lactonas/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Iridoides/análisis , Ácido Elágico/análisis , Reproducibilidad de los Resultados , Sesquiterpenos/análisisRESUMEN
OBJECTIVE: To investigate the potential causal link between genetic variants associated with gut microbiome and risk of intracranial aneurysm (IA) using two-sample mendelian randomization (MR). METHODS: We performed two sets of MR analyses. At first, we selected the genome-wide statistical significant(P < 5 × 10-8) single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, we selected the locus-wide significant (P < 1 × 10-5) SNPs as IVs for the other set of analyses to obtain more comprehensive conclusions. Gut microbiome genetic association estimates were derived from a genome-wide association study (GWAS) of 18,473 individuals. Summary-level statistics for IA were obtained from 79,429 individuals, which included 7,495 cases and 71,934 controls. RESULTS: On the basis of locus-wide significance level, inverse variance weighted(IVW) showed that Clostridia [(odds ratio (OR): 2.60; 95% confidence interval (CI): 1.00-6.72, P = 0.049)], Adlercreutzia (OR: 1.81; 95% CI: 1.10-2.99, P = 0.021) and Victivallis (OR: 1.38; 95% CI: 1.01-1.88, P = 0.044) were positively related with the risk of unruptured intracranial aneurysm(UIA); Weighted median results of MR showed Oscillospira (OR: 0.37; 95% CI: 0.17-0.84, P = 0.018) was negatively with the risk of UIA and Sutterella (OR: 1.84; 95% CI: 1.04-3.23, P = 0.035) was positively related with the risk of UIA; MR-Egger method analysis indicated that Paraprevotella (OR: 0.32; 95% CI: 0.13-0.80, P = 0.035) was negatively with the risk of UIA and Rhodospirillaceae (OR: 13.39; 95% CI: 1.44-124.47, P = 0.048) was positively related with the risk of UIA. The results suggest that Streptococcus (OR: 5.19; 95% CI: 1.25-21.56; P = 0.024) and Peptostreptococcaceae (OR: 4.92; 95% CI: 1.32-18.32; P = 0.018) may increase the risk of UIA according to genome-wide statistical significance thresholds. CONCLUSION: This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on IAs.
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Microbioma Gastrointestinal , Aneurisma Intracraneal , Humanos , Microbioma Gastrointestinal/genética , Estudio de Asociación del Genoma Completo , Aneurisma Intracraneal/genética , Análisis de la Aleatorización Mendeliana , Oportunidad Relativa , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
The simultaneous utilization of electrons and holes to couple photocatalytic H2 production with selective biomass transformation has attracted immense interest toward achieving sustainability in the fields of energy and chemical industry. In this study, by assembling highly dispersed Ni(OH)2 onto ZnIn2S4 (ZIS), efficient H2 evolution along with highly selective photocatalytic oxidation of furfuryl alcohol (FA) to furfural (FF) in pure water was achieved under anaerobic conditions. The H2 production and FA conversion rates over the optimal Ni-ZIS sample reached about 686 and 583 µmol g-1 h-1, respectively, about 4.9 and 1.7 folds as those of pure ZIS. Moreover, the formation of by-products with C-C coupling was dramatically suppressed over Ni-ZIS, resulting in higher selectivity for FF (97%), which is about 2.7-fold that of pure ZIS (36%). Deep mechanistic studies were conducted to reveal the structural evolution and cocatalyst effects of Ni(OH)2. This study not only offers a feasible paradigm for modifying the surface of catalysts to tune the photoactivity and selectivity for product-oriented alcohol oxidation coupled with efficient H2 production in water but also reveals the working mechanism of the deposited Ni(OH)2 over ZIS toward coupling reactions.
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In the dairy industry, glucose (Glu) is used as bioactive substance to increase milk yield. However, the molecular regulation underneath needs further clarification. Here, the regulation and its molecular mechanism of Glu on cell growth and casein synthesis of dairy cow mammary epithelial cells (DCMECs) were investigated. When Glu was added from DCMECs, both cell growth, ß-casein expression and the mechanistic target of rapamycin complex 1 (mTORC1) pathway were increased. Overexpression and silencing of mTOR revealed that Glu promoted cell growth and ß-casein expression through the mTORC1 pathway. When Glu was added from DCMECs, both Adenosine 5'-monophosphate-activated protein kinase α (AMPKα) and Sestrin2 (SESN2) expression were decreased. Overexpression and silencing of AMPKα or SESN2 uncovered that AMPKα suppressed cell growth and ß-casein synthesis through inhibiting mTORC1 pathway, and SESN2 suppressed cell growth and ß-casein synthesis through activating AMPK pathway. When Glu was depleted from DCMECs, both activating transcription factor 4 (ATF4) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression were increased. Overexpression or silencing of ATF4 or Nrf2 demonstrated that Glu depletion promoted SESN2 expression through ATF4 and Nrf2. Together, these results indicate that in DCMECs, Glu promoted cell growth and casein synthesis via ATF4/Nrf2-SESN2-AMPK-mTORC1 pathway.
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Factor de Transcripción Activador 4 , Caseínas , Femenino , Bovinos , Animales , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Factor de Transcripción Activador 4/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Glucosa/farmacología , Glucosa/metabolismo , Glándulas Mamarias Animales/metabolismo , Células Epiteliales/metabolismoRESUMEN
Continuous variable quantum key distribution (CVQKD) can be potentially implemented through seawater channels, whereas the involved oceanic turbulence has a negative effect on the maximal transmission distance of quantum communication systems. Here, we demonstrate the effects of the oceanic turbulence on the performance of the CVQKD system and suggest an implementation feasibility of the passive CVQKD through the oceanic turbulence-based channel. We achieve the channel transmittance characterized by the transmission distance and depth of the seawater. Moreover, a non-Gaussian approach is used for performance improvement while counteracting the effects of excess noises on the oceanic channel. Numerical simulations show that the photon operation (PO) unit can bring reductions of excess noise when taking into account the oceanic turbulence, and hence results in performance improvement in terms of transmission distance and depth as well. The passive CVQKD explores the intrinsic field fluctuations of a thermal source without using an active scheme and hence has a promising application in chip integration for portable quantum communications.
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Studies have demonstrated the detrimental effects of overt hyperthyroidism on sexual functioning.Here,we comprehensively reviewed the studies that focused on the association between overt hyperthyroidism and erectile dysfunction (ED).After the systematic searching for relevant studies,we find that overt hyperthyroidism is significantly associated with the high risk of ED.The prevalence of ED in patients with hyperthyroidism ranges from 3.05% to 85%,while that in general population is 2.16% to 33.8%.A study reported that the erectile functioning of the hyperthyroidism patients was improved (International Index of Erectile Function:22.1±6.9 vs. 25.2±5.1) after the achievement of euthyroidism.The underlying mechanism of the increase in the risk of ED by overt hyperthyroidism might be correlated to the dysfunction of hypothalamus-pituitary-thyroid axis,dysregulation of sex hormones,abnormal expression of thyroid hormone receptors,and psychiatric or psychological disturbances (e.g.,depression,anxiety,and irritability).Since limited clinical trials have been conducted,additional well-designed cohorts with sizable samples are warranted to elucidate the evidence and mechanism of hyperthyroidism predisposing to ED.The present review indicates that overt hyperthyroidism and the risk of ED are associated,which reminds the clinicians should assess the thyroid stimulating hormone in hyperthyroidism patients presenting with ED,especially in those without positive conventional laboratory findings for causing ED.
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Disfunción Eréctil , Hipertiroidismo , Masculino , Humanos , Disfunción Eréctil/etiología , Ansiedad , Hipertiroidismo/complicaciones , TirotropinaRESUMEN
OBJECTIVES: To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis. METHODS: The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis. RESULTS: ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05). CONCLUSIONS: Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.
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Hormona Adrenocorticotrópica , Espasmos Infantiles , Niño , Humanos , Lactante , Hormona Adrenocorticotrópica/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Resultado del Tratamiento , Convulsiones , Electroencefalografía/efectos adversos , Espasmo/complicaciones , Espasmo/tratamiento farmacológicoRESUMEN
BACKGROUND: Circular RNAs (circRNAs) regulate various biological activities and have been shown to play crucial roles in hepatocellular carcinoma (HCC) progression. However, only a few coding circRNAs have been identified in cancers, and their roles in HCC remain elusive. This study aimed to identify coding circRNAs and explore their function in HCC. METHODS: CircMAP3K4 was selected from the CIRCpedia database. We performed a series of experiments to determine the characteristics and coding capacity of circMAP3K4. We then used in vivo and in vitro assays to investigate the biological function and mechanism of circMAP3K4 and its protein product, circMAP3K4-455aa, in HCC. RESULTS: We found circMAP3K4 to be an upregulated circRNA with coding potential in HCC. IGF2BP1 recognized the circMAP3K4 N6-methyladenosine modification and promoted its translation into circMAP3K4-455aa. Functionally, circMAP3K4-455aa prevented cisplatin-induced apoptosis in HCC cells by interacting with AIF, thus protecting AIF from cleavage and decreasing its nuclear distribution. Moreover, circMAP3K4-455aa was degraded through the ubiquitin-proteasome E3 ligase MIB1 pathway. Clinically, a high level of circMAP3K4 is an independent prognostic factor for adverse overall survival and adverse disease-free survival of HCC patients. CONCLUSIONS: CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, circMAP3K4 encoded circMAP3K4-455aa, protected HCC cells from cisplatin exposure, and predicted worse prognosis of HCC patients. Targeting circMAP3K4-455aa may provide a new therapeutic strategy for HCC patients, especially for those with chemoresistance. CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, IGF2BP1 facilitates circMAP3K4 peptide translation, then the circMAP3K4 peptide inhibits AIF cleavage and nuclear distribution, preventing HCC cells from cell death under stress and promoting HCC progression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Adenosina/análogos & derivados , Apoptosis , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , PéptidosRESUMEN
The relationship between SFA consumption and the risk of overweight/obesity remains unclear. Epidemiological evidence is lacking among Chinese population. This study aimed to investigate the association between individual dietary SFA intake and the risk of overweight/obesity in Chinese adults. Data from 8465 adults with BMI < 24 kg/m2 at entry in the China Health and Nutrition Survey (1989-2011) were analysed. Three-day 24-h dietary records were used to collect dietary data. Cox proportional hazards regression models were constructed to estimate hazard ratios (HR) and 95 % CI for the risk of developing overweight or obesity. A total of 3171 incident cases of overweight/obesity were identified (1649 for women and 1522 for men) during a median of 11 years of follow-up. Compared with the lowest category, the intake of total SFA (TSFA) showed no significant association with the risk of overweight/obesity. However, an increased risk of overweight/obesity was observed with a higher intake of medium chain SFA (MCSFA) (Ptrend = 0·004), especially decanoic acid (10:0) (HR was 1·25 (95 % CI 1·10, 1·42) comparing the highest category with the reference group; Ptrend < 0·001), whereas an inverse relationship was observed for hexanoic acid (6:0) consumption; compared with non-consumers, 6:0 intake was associated with 32 % lower risk of overweight/obesity (HR: 0·68 (95 % CI 0·56, 0·84); Ptrend < 0·001). Overall, the intake of subtypes of MCSFA but not TSFA was associated with the risk of overweight/obesity. Increasing hexanoic acid (6:0) and limiting decanoic acid (10:0) consumption may be protective for overweight/obesity among Chinese population.
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Obesidad , Sobrepeso , Adulto , Masculino , Humanos , Femenino , Sobrepeso/epidemiología , Estudios de Cohortes , Factores de Riesgo , Estudios Prospectivos , Índice de Masa Corporal , Obesidad/epidemiología , China/epidemiologíaRESUMEN
Enzymes of the matrixin family could be seen as a critical determinant in the breakdown of the extracellular matrix, cell membrane, and tissue regeneration and are interned in the process of brain bleeding. On the other hand, coagulation factor XIII deficiency is a sporadic hemorrhagic disease with an estimated prevalence of 1 in 1-2 million people. Cerebral hemorrhage is the leading cause of death in these patients. This study investigated the relationship between the expression of matrix metalloproteinase 9 and 2 genes with cerebral hemorrhage in these patients. For this purpose, in this case-control study, by examining the clinical and general findings of the studied patients, the Q-Real-time RT-PCR method was used to quantitatively examine the mRNA levels of matrix metalloproteinase 9 and 2 in 42 patients with hereditary deficiency of coagulation factor XIII, including two groups with and without a history of cerebral hemorrhage (case and control groups, respectively). A comparative method (2-ΔΔCT) was used to check the expression level of the target genes. The GAPDH gene expression levels were used to standardize the expression of the measured matrix metalloproteinase genes. The results showed that bleeding from the umbilical cord was the most common clinical symptom among all patients. High levels of MMP-9 gene expression were observed in 13 patients of the case group (69.99%) and three patients of the control group (11.9%). which showed a significant difference (CI: 2.77-95.3, P=0.001) Patients with coagulation factor XIII deficiency show a wide range of clinical symptoms crucial in screening and diagnosing this group of patients. Based on the results of this study, it seems that the increased expression of the MMP-9 gene is due to polymorphism or inflammation related to the pathogenesis of cerebral hemorrhage in this category of patients. It may be conceivable to diminish this impact by utilizing MMP-9 inhibitors and offering assistance to diminishes these patients' hospitalization and passing rates.
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Deficiencia del Factor XIII , Metaloproteinasa 9 de la Matriz , Humanos , Metaloproteinasa 9 de la Matriz/genética , Factor XIII/genética , Factor XIII/metabolismo , Estudios de Casos y Controles , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/genética , Deficiencia del Factor XIII/complicaciones , Deficiencia del Factor XIII/genética , Expresión GénicaRESUMEN
BACKGROUND: To investigate the effect of superficial temporal artery-middle cerebral artery (STA-MCA) bypass in the treatment of MCA stenosis or occlusion. METHODS: The clinical and imaging data of 31 MCA stenosis or occlusion patients with STA-MCA bypass were analyzed retrospectively. The operation was performed by STA-MCA M4 segment bypass via the frontotemporal approach. Modified Rankin Scale (mRS) was used to evaluate the neurological function of patients. RESULTS: After operation, head computed tomography (CT) showed that there was no new infarction or hemorrhage in the operation area. CTA and CTP showed that the bypass vessel was unobstructed in 29 cases and the cerebral perfusion was improved in 31 cases. Among the 31 patients, 7 patients had postoperative complications and 13 patients had improvement of clinical symptoms. The other patients had no complications and the clinical symptoms remained unchanged. The mRs score of 31 patients after operation indicated that the neurological function was significantly improved than pre-operation. Of the 31 patients, 23 cases were followed up. The mRs score showed that the neurological function of these 23 patients was further improved than that at discharge. In addition, DSA (or CTA) and CTP showed that the bypass vessel was unobstructed and the cerebral perfusion was further improved. CONCLUSION: STA-MCA bypass was an effective method for the treatment of MCA stenosis or occlusion. However, the results should be further verified by large sample, multi-center and long-term follow-up.
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Revascularización Cerebral , Arteria Cerebral Media , Revascularización Cerebral/métodos , Constricción Patológica/cirugía , Humanos , Arteria Cerebral Media/cirugía , Estudios Retrospectivos , Arterias Temporales/cirugíaRESUMEN
BACKGROUND: Whether consumption of egg and cholesterol is detrimental to cardiovascular health and longevity is highly debated. Data from large-scale cohort studies are scarce. This study aimed to examine the associations of egg and cholesterol intakes with mortality from all causes, cardiovascular disease (CVD), and other causes in a US population. METHODS AND FINDINGS: Overall, 521,120 participants (aged 50-71 years, mean age = 62.2 years, 41.2% women, and 91.8% non-Hispanic white) were recruited from 6 states and 2 additional cities in the US between 1995 and 1996 and prospectively followed up until the end of 2011. Intakes of whole eggs, egg whites/substitutes, and cholesterol were assessed by a validated food frequency questionnaire. Cause-specific hazard models considering competing risks were used, with the lowest quintile of energy-adjusted intake (per 2,000 kcal per day) as the reference. There were 129,328 deaths including 38,747 deaths from CVD during a median follow-up of 16 years. Whole egg and cholesterol intakes were both positively associated with all-cause, CVD, and cancer mortality. In multivariable-adjusted models, the hazard ratios (95% confidence intervals) associated with each intake of an additional half of a whole egg per day were 1.07 (1.06-1.08) for all-cause mortality, 1.07 (1.06-1.09) for CVD mortality, and 1.07 (1.06-1.09) for cancer mortality. Each intake of an additional 300 mg of dietary cholesterol per day was associated with 19%, 16%, and 24% higher all-cause, CVD, and cancer mortality, respectively. Mediation models estimated that cholesterol intake contributed to 63.2% (95% CI 49.6%-75.0%), 62.3% (95% CI 39.5%-80.7%), and 49.6% (95% CI 31.9%-67.4%) of all-cause, CVD, and cancer mortality associated with whole egg consumption, respectively. Egg white/substitute consumers had lower all-cause mortality and mortality from stroke, cancer, respiratory disease, and Alzheimer disease compared with non-consumers. Hypothetically, replacing half a whole egg with equivalent amounts of egg whites/substitutes, poultry, fish, dairy products, or nuts/legumes was related to lower all-cause, CVD, cancer, and respiratory disease mortality. Study limitations include its observational nature, reliance on participant self-report, and residual confounding despite extensive adjustment for acknowledged dietary and lifestyle risk factors. CONCLUSIONS: In this study, intakes of eggs and cholesterol were associated with higher all-cause, CVD, and cancer mortality. The increased mortality associated with egg consumption was largely influenced by cholesterol intake. Our findings suggest limiting cholesterol intake and replacing whole eggs with egg whites/substitutes or other alternative protein sources for facilitating cardiovascular health and long-term survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT00340015.
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Enfermedades Cardiovasculares/mortalidad , Colesterol/sangre , Dieta , Huevos , Anciano , Estudios de Cohortes , Huevos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Estados UnidosRESUMEN
BACKGROUND: Increasing evidence highlights healthy dietary patterns and links daily cooking oil intake with chronic diseases including cardiovascular disease (CVD) and diabetes. However, food-based evidence supporting the consumption of cooking oils in relation to total and cardiometabolic mortality remains largely absent. We aim to prospectively evaluate the relations of cooking oils with death from cardiometabolic (CVD and diabetes) and other causes. METHODS: We identified and prospectively followed 521,120 participants aged 50-71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Individual cooking oil/fat consumption was assessed by a validated food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for mortality through the end of 2011. RESULTS: Overall, 129,328 deaths were documented during a median follow-up of 16 years. Intakes of butter and margarine were associated with higher total mortality while intakes of canola oil and olive oil were related to lower total mortality. After multivariate adjustment for major risk factors, the HRs of cardiometabolic mortality for each 1-tablespoon/day increment were 1.08 (95% CI 1.05-1.10) for butter, 1.06 (1.05-1.08) for margarine, 0.99 (0.95-1.03) for corn oil, 0.98 (0.94-1.02) for canola oil, and 0.96 (0.92-0.99) for olive oil. Besides, butter consumption was positively associated with cancer mortality. Substituting corn oil, canola oil, or olive oil for equal amounts of butter and margarine was related to lower all-cause mortality and mortality from certain causes, including CVD, diabetes, cancer, respiratory disease, and Alzheimer's disease. CONCLUSIONS: Consumption of butter and margarine was associated with higher total and cardiometabolic mortality. Replacing butter and margarine with canola oil, corn oil, or olive oil was related to lower total and cardiometabolic mortality. Our findings support shifting the intake from solid fats to non-hydrogenated vegetable oils for cardiometabolic health and longevity.
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Enfermedades Cardiovasculares , Margarina , Mantequilla , Culinaria , Grasas de la Dieta , Humanos , Aceite de Oliva , Aceites de PlantasRESUMEN
RATIONALE: Evidence linking saturated fat intake with cardiovascular health is controversial. The associations of unsaturated fats with total and cardiovascular disease (CVD) mortality remain inconsistent, and data about non-CVD mortality are limited. OBJECTIVE: To assess dietary fat intake in relation to total and cause-specific mortality. METHODS AND RESULTS: We analyzed data of 521 120 participants aged 50 to 71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study with 16 years of follow-up. Intakes of saturated fatty acids (SFAs), trans-fatty acids, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were assessed via food frequency questionnaires. Hazard ratios and 95%CIs were estimated using the Cox proportional hazards model. Overall, 129 328 deaths were documented during 7.3 million person-years of follow-up. In the replacement of carbohydrates, multivariable-adjusted hazard ratios of total mortality comparing extreme quintiles were 1.29 (95% CI, 1.25-1.33) for SFAs, 1.03 (1.00-1.05) for trans-fatty acids, 0.98 (0.94-1.02) for MUFAs, 1.09 (1.06-1.13) for animal MUFAs, 0.94 (0.91-0.97) for plant MUFAs, 0.93 (0.91-0.95) for PUFAs, 0.92 (0.90-0.94) for marine omega-3 PUFAs, 1.06 (1.03-1.09) for α-linolenic acid, 0.88 (0.86-0.91) for linoleic acid, and 1.10 (1.08-1.13) for arachidonic acid. CVD mortality was inversely associated with marine omega-3 PUFA intake ( P trend <0.0001), whereas it was positively associated with SFA, trans-fatty acid, and arachidonic acid intake. Isocalorically replacing 5% of the energy from SFAs with plant MUFAs was associated with 15%, 10%, 11%, and 30% lower total mortality, CVD, cancer, and respiratory disease mortality, respectively. Isocaloric replacement of SFA with linoleic acid (2%) was associated with lower total (8%), CVD (6%), cancer (8%), respiratory disease (11%), and diabetes mellitus (9%) mortality. CONCLUSIONS: Intakes of SFAs, trans-fatty acids, animal MUFAs, α-linolenic acid, and arachidonic acid were associated with higher mortality. Dietary intake of marine omega-3 PUFAs and replacing SFAs with plant MUFAs or linoleic acid were associated with lower total, CVD, and certain cause-specific mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00340015.
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Enfermedades Cardiovasculares/mortalidad , Grasas de la Dieta/efectos adversos , Ácidos Grasos/efectos adversos , Anciano , Ácido Araquidónico/administración & dosificación , Ácido Araquidónico/efectos adversos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Causas de Muerte , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/administración & dosificación , Ácidos Grasos Monoinsaturados/administración & dosificación , Ácidos Grasos Monoinsaturados/efectos adversos , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Ácidos Grasos trans/administración & dosificación , Ácidos Grasos trans/efectos adversos , Estados Unidos/epidemiología , Ácido alfa-Linolénico/administración & dosificación , Ácido alfa-Linolénico/efectos adversosRESUMEN
BACKGROUND: Metabolic syndrome (MS) can promote the development of cardiovascular disease (CVD). The objective of this study was to examine the association of MS and its components with CVD, to further prevent and control CVD in Kazakhs. METHODS: In the cohort study, a total of 2644 participants completed the baseline survey between April 2010 and December 2012.The follow-up survey was conducted from April 2016 to December 2016 and was completed by 2286 participants (86.46% follow-up rate). Cox regression was used to evaluate the association of each component and the number of combinations of MS components on the development of CVD. RESULTS: A total of 278 CVD patients were enrolled from rural residents of Xinjiang. The average age of the MS and non-MS groups was 46.33 and 38.71 years, respectively. Independent associations with CVD were found for elevated blood pressure (BP) (adjusted hazard ratio (HR) [aHR] = 1.50,95%confidence interval [CI]: 1.08-2.08), elevated waist circumference (WC) (aHR = 1.60, 95%CI: 1.19-2.15), and elevated triglycerides (TG) (aHR = 1.44, 95%CI: 1.04-2.01). Participants with one to 5 MS components had an increased HR for developing CVD, from 1.82to 8.59 (P for trend < 0.001), compared with those with no MS components. The risk of developing CVD increased when TG and WC coexisted (aHR = 2.16, 95%CI: 1.54-3.04)), when TG and BP coexisted ((aHR = 1.92, 95%CI: 1.32-2.79), and when WC and BP coexisted (aHR = 1.93, 95%CI: 1.33-2.82)). However, no significant interactions were found between BP, WC, and TG. CONCLUSIONS: Elevations of BP, WC, and TG were independent risk factors for CVD in Kazakhs. Control of these factors is important to prevent CVD in this population.
Asunto(s)
Enfermedades Cardiovasculares , Síndrome Metabólico , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Estudios de Cohortes , Humanos , Síndrome Metabólico/epidemiología , Factores de Riesgo , Circunferencia de la CinturaRESUMEN
Purpose: This study aimed to investigate the protective effects of quercetin on the tight junction proteins of human retinal pigment epithelial cells (ARPE-19 cells) suffering from oxidative stress injury and explore the possible mechanism.Methods: H2O2 (300 µM) was used to establish an oxidative stress model of ARPE-19 cells. ARPE-19 cells were pretreated with different concentrations (0-80 µM) of quercetin before H2O2 exposure. The expression and distribution of tight junction proteins and autophagy-related proteins were detected by Western blot and immunostaining. ARPE-19 cells were pretreated with 5 mM 3-methyladenine (3-MA).Results: The cell viability weakened in the H2O2 group compared with the control group. However, it was preserved after pretreatment with quercetin. It was observed that the expression levels of occludin, claudin-1 were decreased in the H2O2 group. Quercetin treatment significantly enhanced the expression levels of them as compared to the H2O2 group. H2O2 alone strongly decreased the Zonula occludens protein 1 (ZO-1) expression in the cytomembrane. Quercetin supplementation enhanced the accumulation of ZO-1 in ARPE-19 cells. The expression levels of Beclin-1 and Microtubule associated protein light chain 3 II (LC-3II) increased, and that of P62 decreased in the quercetin protection group. The appearance of LC-3II, which examined by immunofluorescence experiments, enhanced in the quercetin protection group as compared with the control group. The expression levels of beclin-1 and LC-3II increased, and that of P62 increased in the autophagy-inhibited group compared with the quercetin protection group. The levels of occludin and claudin-1 also decreased.Conclusion: Quercetin prevents the loss of tight junction proteins by upregulating autophagy after oxidative stress in ARPE-19 cells.
Asunto(s)
Autofagia/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Degeneración Macular/prevención & control , Sustancias Protectoras/farmacología , Quercetina/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Humanos , Degeneración Macular/patología , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Quercetina/uso terapéutico , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/patología , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/patologíaRESUMEN
OBJECTIVE: To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens. METHODS: A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group (n=19) and a recurrence group (n=22). According to whether preventive treatment for recurrence was given, the children with recurrence were further divided into a preventive treatment group and a non-preventive treatment group. The clinical features were analyzed for all groups, and the annualized relapse rate (ARR) was compared before and after treatment with prevention regimens. RESULTS: For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% vs 32%; P < 0.05). There was no significant difference in the ARR between the preventive treatment and non-preventive treatment groups (P > 0.05). The assessment of preventive treatment regimens for 32 cases showed that the children treated with rituximab or azathioprine had a significant reduction in the ARR during treatment (P < 0.05). CONCLUSIONS: More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.
Asunto(s)
Autoanticuerpos , Neuritis Óptica , Niño , Humanos , Glicoproteína Mielina-Oligodendrócito , Recurrencia , Estudios RetrospectivosRESUMEN
Aberrant fibrogenesis impairs the architectural and functional homeostasis of the kidneys. It also predicts poor diagnosis in patients with end-stage renal disease (ESRD). Renal tubular epithelial cells (RTEC) can trans-differentiate into myofibroblasts to produce extracellular matrix proteins and contribute to renal fibrosis. Connective tissue growth factor (CTGF) is a cytokine upregulated in RTECs during renal fibrosis. In the present study, we investigated the regulation of CTGF transcription by megakaryocytic leukemia 1 (MKL1). Genetic deletion or pharmaceutical inhibition of MKL1 in mice mitigated renal fibrosis following the unilateral ureteral obstruction procedure. Notably, MKL1 deficiency in mice downregulated CTGF expression in the kidneys. Likewise, MKL1 knockdown or inhibition in RTEs blunted TGF-ß induced CTGF expression. Further, it was discovered that MKL1 bound directly to the CTGF promoter by interacting with SMAD3 to activate CTGF transcription. In addition, MKL1 mediated the interplay between p300 and WDR5 to regulate CTGF transcription. CTGF knockdown dampened TGF-ß induced pro-fibrogenic response in RTEs. MKL1 activity was reciprocally regulated by CTGF. In conclusion, we propose that targeting the MKL1-CTGF axis may generate novel therapeutic solutions against aberrant renal fibrogenesis.