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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder characterized by fat accumulation in the liver. This leads to aggravated hepatocyte inflammation due to impaired mitochondrial function, mitochondrial double-stranded RNA (mt-dsRNA) release, elevated oxidative stress, and reactive oxygen species (ROS) production. MicroRNA-29a (miR-29a) is used to reduce hepatic fibrosis in cases of cholestatic liver damage and lessen the severity of non-alcoholic steatohepatitis in animal studies by influencing mitochondrial protein balance. However, the effectiveness of miR-29a in diminishing mt-dsRNA-induced exacerbation of NAFLD remains poorly understood, particularly in the context of a Western diet (WD). Our results have found that mice with increased miR-29a levels and fed a WD showed notably decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, and low-density lipoprotein cholesterol levels. They also experienced less weight gain and lower final body and liver weights. In addition, overexpression of miR-29a reduced the severity of fibrosis, alleviated hepatic oxidative stress, misfolded protein aggregates, and the release of mt-dsRNA. Moreover, miR-29a attenuated the innate immune mitochondrial antiviral-signaling protein (MAVS) pathway response. In vitro, the research using HepG2 cells confirmed that miR-29a reduces MAVS expression and decreases the release of mt-dsRNA and superoxide initiated by palmitic acid (PA). Analysis of luciferase activity further established that the specific binding of miR-29a to the 3'UTR of MAVS led to a repression of its expression. In conclusion, these groundbreaking findings underscore the potential of miR-29a in improving the treatment of NAFLD and liver steatofibrosis by inhibiting the MAVS signaling pathway.
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MicroRNA-29a (miR-29a) has been suggested to serve a potential protective function against Parkinson's disease (PD); however, the exact molecular mechanisms remain elusive. This study explored the protective role of miR-29a in a cellular model of PD using SH-SY5Y cell lines through iTRAQ-based quantitative proteomic and biochemistry analysis. The findings showed that using a miR-29a mimic in SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+) significantly decreased cell death and increased mitochondrial membrane potential. It also reduced mitochondrial reactive oxygen species (ROS) and the production of α-synuclein. Subsequent heatmap analysis using iTRAQ-based quantitative proteomics revealed remarkably contrasting protein expression profiles for 882 genes when comparing the groups treated with miR-29a mimic plus MPP + against the control group treated solely with MPP+. The KEGG pathway analysis of these 882 genes indicated the substantial role of miR-29a in the PD pathway (P = 1.58x10-5) and highlighted its function in mitochondrial genes. Furthermore, treatment with a miR-29a mimic in SH-SY5Y cells reduced the levels of GSK-3ß, phosphorylated GSK-3ß, and cleaved caspase-7 following exposure to MPP+. The miR-29a mimic also upregulated the expressions of α-synuclein clearance proteins FYCO1 and Rab7 in this cellular PD model, thereby inhibiting the production of α-synuclein. Luciferase activity analysis confirmed the specific binding of miR-29a to the 3' untranslated region (3'UTR) of GSK-3ß, leading to its repression. Our findings demonstrated miR-29a's neuroprotective role in mitochondrial function and highlighted its potential to inhibit ROS and α-synuclein production, offering possible therapeutic avenues for PD treatment.
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Glucógeno Sintasa Quinasa 3 beta , MicroARNs , Enfermedad de Parkinson , Especies Reactivas de Oxígeno , alfa-Sinucleína , Humanos , 1-Metil-4-fenilpiridinio/toxicidad , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Línea Celular Tumoral , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Potencial de la Membrana Mitocondrial/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
INTRODUCTION: Agarwood, a fragrant resinous wood mainly formed by Aquilaria spp., is used worldwide as a natural fragrance and traditional medicine. A large amount of Aquilaria sinensis (Lour.) Gilg leaves are underutilised during the process of the agarwood industry, and the development of A. sinensis leaves as tea has recently attracted more and more attention. However, the small molecule profile of A. sinensis leaves and their bioactivities has been rarely reported. OBJECTIVE: To conduct a rapid untargeted liquid chromatography-mass spectrometry (LC-MS) analysis of A. sinensis leaves with a molecular networking (MN) strategy and evaluate its antioxidant and antidiabetic value. METHOD: A MN-assisted tandem mass spectrometry (MS/MS) analysis strategy was used to investigate the small molecule profile of A. sinensis leaves. Additionally, the integration of antioxidant and α-glucosidase inhibitory assays with MN analysis was executed to expeditiously characterise the bioactive compounds for potential prospective application. RESULTS: Five main chemical groups including phenol C-glycosides, organic acids, 2-(2-phenylethyl) chromones, benzophenone O-glycosides and flavonoids were rapidly revealed from the A. sinensis leaves. Eighty-one compounds were provisionally identified by comparing their MS/MS fragments with canonical pathways. The featured xanthone C-glycosides and benzophenone C-glycosides were recognised as the primary components of A. sinensis leaves. Several dimers and a trimer of mangiferin were reported firstly in A. sinensis leaves. Furthermore, 17 and 14 potential bioactive molecules were rapidly annotated from antioxidant and α-glucosidase inhibitory fraction, respectively. CONCLUSION: Our findings will help expand the utilisation of A. sinensis leaves and thus promote the high-quality development of agarwood industry.
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Espectrometría de Masas en Tándem , Thymelaeaceae , Antioxidantes/farmacología , alfa-Glucosidasas , Flavonoides/química , Glicósidos , Thymelaeaceae/química , BenzofenonasRESUMEN
BACKGROUND: Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men with coronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke and congestive heart failure. METHODS: Six thousand six hundred forty-seven patients with CAD who received successful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), including cardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CV events). RESULTS: During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariate analyses showed that women were independently associated with an increased risk of cardiac death (HR, 1.78; 95% CI, 1.32-2.41), hospitalization for heart failure (HR, 1.53; 95% CI, 1.23-1.89), MACE (HR, 1.34; 95% CI, 1.10-1.63), and total CV events (HR, 1.39; 95% CI, 1.20-1.62). In the subgroup analysis, women aged under 60 years had higher cardiovascular risks than men of the same age category. CONCLUSION: Women with CAD after successful PCI had poorer cardiovascular outcomes than men. Additionally, younger women (aged <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes.
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Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Intervención Coronaria Percutánea/efectos adversos , Enfermedad de la Arteria Coronaria/etiología , Accidente Cerebrovascular/etiología , Muerte , Factores de Riesgo , Resultado del TratamientoRESUMEN
Enhanced Recovery After Surgery (ERAS), an all-encompassing perioperative care approach, has been demonstrated to enhance surgical results, mitigate postoperative issues, and decrease the length of hospital stay (LOS) in diverse surgical specialties. In this retrospective study, our objective was to examine the influence of muscle relaxant selection on LOS and perioperative results in adult patients undergoing open spine surgery. Specifically, we compared 201 patients who received cisatracurium and neostigmine with 201 patients who received rocuronium and sugammadex, after 1:1 propensity score matching. The utilization of the rocuronium and sugammadex combination in anesthesia for open spinal surgery did not lead to a reduction in the LOS but was associated with a decreased incidence of postoperative chest radiographic abnormalities, including infiltration, consolidation, atelectasis, or pneumonia (p = 0.027). In our secondary analysis, multivariate analysis revealed multiple determinants influencing the prolonged LOS (>7 days) during open spine surgery. Bispectral index-guided anesthesia emerged as a protective factor, while variables such as excessive intraoperative blood loss and fluid administration as well as postoperative chest radiographic abnormalities independently contributed to prolonged LOS.
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OBJECTIVES: Febrile disease and age of children were associated with a variation in hemoglobin (Hb) level. Both CRP and Hb serve as laboratory markers that offer valuable insights into a patient's health, particularly in relation to inflammation and specific medical conditions. Although a direct correlation between CRP and Hb levels is not established, the relationship between these markers has garnered academic attention and investigation. This study aimed to determine updated reference ranges for Hb levels for age and investigated its correlation with CRP in febrile children under the age of 18. METHODS: This is a cohort study of in Chang Gung Memorial Hospitals conducted from January 2010 to December 2019. Blood samples were collected from 98,572 febrile children who were or had been admitted in the pediatric emergency department. The parameters of individuals were presented as the mean ± standard deviation or 2.5th and 97.5th percentiles. We also determined the variation of Hb and Z score of Hb between CRP levels in febrile children. RESULT: We observed that the Hb levels were the highest immediately after birth and subsequently underwent a rapid decline, reaching their lowest point at around 1-2 months of age, and followed by a steady increment in Hb levels throughout childhood and adolescence. In addition, there was a significant and wide variation in Hb levels during the infant period. It revealed a significant association between higher CRP levels and lower Hb levels or a more negative Z score of Hb across all age subgroups. Moreover, in patients with bacteremia, CRP levels were higher, Hb concentrations were lower, and Z scores of Hb were also lower compared to the non-bacteremia group. Furthermore, the bacteremia group exhibited a more substantial negative correlation between CRP levels and a Z score of Hb (r = -0.41, p < 0.001) compared to the non-bacteremia group (r = -0.115, p < 0.049). CONCLUSION: The study findings revealed that the Hb references varied depending on the age of the children and their CRP levels. In addition, we established new reference values for Hb and its Z scores and explore their relationship with CRP. It provides valuable insights into the Hb status and its potential association with inflammation in febrile pediatric patients.
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OBJECTIVE: The combined impact of disease status and treatment phase on the quality of life (QoL) of women with ovarian cancer has not been fully considered. Therefore, this clinical, epidemiologic study compared the QoL of patients with ovarian cancer between five different treatment phases and identified the factors predicting their QoL through multivariate modeling. DATA SOURCES: This study had a cross-sectional survey design. The participants total of 183 were recruited from the inpatient and outpatient departments of the medical center in northern Taiwan. QoL was measured using the Quality of Life Scales QLQ-C30 and QLQ-OV28 and the Pittsburgh Sleep Quality Index. The patient's clinical characteristics data were obtained from the databank of the Taiwan Gynecologic Cancer Network, a registry of active patients being treated with gynecologic cancer. CONCLUSION: Chemotherapeutic agents were the major predictors of poor global health status in patients with ovarian cancer. However, good sleep was beneficial to patients' QoL. The study results can be used as a reference to adjust oncological treatment regimens for more effective symptom management and to promote patient education to improve patients' QoL. IMPLICATIONS FOR NURSING PRACTICE: The predicting factors can be considered by physicians and nurses to adjust treatment regimens and enhance patient education.
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Neoplasias de los Genitales Femeninos , Neoplasias Ováricas , Femenino , Humanos , Calidad de Vida , Estudios Transversales , Neoplasias Ováricas/terapia , Estado de SaludRESUMEN
BACKGROUND: Primary cancer of the appendix is rare and often difficult to diagnose preoperatively due to the lack of specific clinical symptoms. Autoimmune encephalitis (AIE) is the most common cause of non-infectious encephalitis. The etiologies of AIE include tumors (paraneoplastic), infections (parainfections), or recessive infections. The tumors that have been reported to cause AIE include thymomas, ovarian teratomas, lung cancers, and breast cancers. However, there are no reports of AIE occurring after surgery for appendiceal cancer. This report describes the diagnosis and treatment of a patient with an appendiceal cancer and postoperative AIE. CASE SUMMARY: We report the case of a 47-year-old man who was transferred to our hospital due to a recurrent low intestinal obstruction. Abdominal enhanced computed tomography was used to consider the possibility of a terminal ileal tumor with serous infiltration and lymph node metastasis. A right hemi-colectomy was performed under general anesthesia with an ileo-transcolon anastomosis and laparoscopic exploration. The postoperative pathologic evaluation revealed a high-grade goblet cell carcinoma of the appendix, accompanied by mesangial and abdominal lymph node metastases, and neural tube and vascular infiltration. The operation was completed without complication. The patient developed restlessness on postoperative day 4, and gradually developed a disturbance of consciousness on postoperative day 6. He was transferred to West China Hospital of Sichuan University and diagnosed with AIE. CONCLUSION: Albeit rare, the occurrence of neurologic and psychiatric symptoms in patients with an appendiceal cancer postoperatively suggests the possibility of AIE.
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Few studies have focused on the consequence of exposure to general anesthesia (GA) in children's early life with the risk of asthma and disease outcomes. The present study examines the correlation between exposure to GA under three years old and the subsequent course of asthma in a nationwide population-based cohort study. Our cases were acquired from Taiwan's National Health Insurance Research Database (NHIRD). Children under three years old with either GA exposure or not during in-patient treatment from 1997 to 2008 were included. The study group was age- and sex-matched with a ratio of 1:2 to create the control group for comparison. The cohort included 2261 cases with GA and 4522 cases without GA as a control group. The incidence of asthma onset was significantly reduced in patients with GA exposure under 3 three years old (hazard ratio 0.64 (95% confidence interval 0.57~0.72), p < 0.001). In addition, regardless of whether the asthmatic clinical visits were before or after GA exposure, asthma onset patients before GA exposure have significantly fewer clinical visits than those without GA exposure (both p < 0.001, respectively). Using the Kaplan-Meier method, we also demonstrated that GA exposure was associated with favorable clinical visits in patients with asthma, whether their asthma was onset before GA (p = 0.0102) or after GA exposure (p = 0.0418) compared to non-GA-exposed controls. In the present study, we demonstrated that children with early GA exposure under three years old were at a reduced risk of developing asthma compared to the general population. Furthermore, we first reported that GA exposure significantly reduced clinical visits in patients with asthma regardless of whether their asthma onset was before or after GA exposure. It is indicated that GA exposure at a younger age could have potential clinical benefits for asthma than non-GA-exposed controls.
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SCOPE: miR-29a expression patterns influence numerous physiological phenomena. Of note, upregulation of miR-29a ameliorates high-fat diet (HFD)-induced liver dysfunctions in mice. However, the miR-29a effect on gut microbiome composition and HFD-induced gut microbiota changes during metabolic disturbances remains unclear. The study provides compelling evidence for the protective role of miR-29a in gut barrier dysfunction and steatohepatitis. METHODS AND RESULTS: miR-29a overexpressed mice (miR-29aTg) are bred to characterize intestinal, serum biochemical, and fecal microbiota profiling features compared to wild-type mice (WT). Mice are fed an HFD for 8 months to induce steatohepatitis, and intestinal dysfunction is determined via histopathological analysis. miR-29aTg has better lipid metabolism capability that decreases total cholesterol and triglyceride levels in serum than WT of the same age. The study further demonstrates that miR-29aTg contributes to intestinal integrity by maintaining periodic acid Schiff positive cell numbers and diversity of fecal microorganisms. HFD-induced bacterial community disturbance and steatohepatitis result in more severe WT than miR-29aTg. Gut microorganism profiling reveals Lactobacillus, Ruminiclostridium_9, and Lachnoclostridium enrichment in miR-29aTg and significantly decreases interleukin-6 expression in the liver and intestinal tract. CONCLUSION: This study provides new evidence that sheds light on the host genetic background of miR-29a, which protects against steatohepatitis and other intestinal disorders.
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Hígado Graso , MicroARNs , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Disbiosis , Inflamación , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hígado Graso/genética , Hígado Graso/metabolismoRESUMEN
Lilii Bulbus is a commonly used Chinese herbal medicine with both medicinal and edible values, while the market products usually has the problem of sulfur fumigation. Therefore, the quality and safety of Lilii Bulbus products deserve attention. In this study, ultra-high performance liquid chromatography-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to analyze the differential components of Lilii Bulbus before and after sulfur fumigation. We identified ten markers generated after sulfur fumigation, summarized their mass fragmentation and transformation patterns, and verified the structures of phenylacrylic acid markers of sulfur fumigation. At the same time, the cytotoxicity of the aqueous extracts of Lilii Bulbus before and after sulfur fumigation was evaluated. The results showed that in the concentration range of 0-800 mg·L~(-1), the aqueous extract of Lilii Bulbus after sulfur fumigation had no significant effect on the viability of human liver LO2 cells, human renal proximal tubular HK-2 cells, and rat adrenal pheochromocytoma PC-12 cells. Moreover, the viability of the cells exposed to the aqueous extract of Lilii Bulbus before and after sulfur fumigation showed no significant difference. This study identified phenylacrylic acid and furostanol saponins as markers of sulfur-fumigated Lilii Bulbus for the first time, and made clear that proper sulfur fumigation of Lilii Bulbus would not produce cytotoxicity, providing a theoretical basis for the rapid identification and quality and safety control of sulfur-fumigated Lilii Bulbus.
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Fumigación , Espectrometría de Masas en Tándem , Humanos , Animales , Ratas , Cromatografía Líquida de Alta Presión , Células Epiteliales , AzufreRESUMEN
BACKGROUND: Antrodin C, a maleimide derivative compound isolated from the ethanol extract of the mycelium of Antrodia cinnamomea, is an endemic fungus of Taiwan and a potential chemoprotective agent. However, the molecular mechanisms underlying the mode of action of antrodin C on cancer cells, especially in human colorectal cancer (CRC), remain unclear. METHODS: The cell death and ROS of the antrodin-C-treated HCT-116 cells were measured by annexin V-FITC/propidium iodide staining, DCFDA, and Fluo-3 fluorescence staining assays. Moreover, signaling molecules regulating TNFα cell death pathways and ROS/AKT/ERK/P38 pathways were also detected in cells treated with antrodin C by Western blotting and chromatin immunoprecipitation. The effects of antrodin C were determined in HCT-116 cell xenograft animal models in terms of tumor volumes and histopathological evaluation. RESULTS: Treatment with antrodin C triggered the activation of extrinsic apoptosis pathways (TNFα, Bax, caspase-3, and -9), and also suppressed the expression of anti-apoptotic molecules Bcl-2 in HCT-116 cells in a time-dependent manner. Antrodin C also decreased cell proliferation and growth through the inactivation of cyclin D1/cyclin for the arrest of the cell cycle at the G1 phase. The activation of the ROS/AKT/ERK/P38 pathways was involved in antrodin-C-induced transcriptional activation, which implicates the role of the histone H3K9K14ac (Acetyl Lys9/Lys14) of the TNFα promoters. Immunohistochemical analyses revealed that antrodin C treatment significantly induced TNFα levels, whereas it decreased the levels of PCNA, cyclin D1, cyclin E, and MMP-9 in an in vivo xenograft mouse model. Thus, antrodin C induces cell apoptosis via the activation of the ROS/AKT/ERK/P38 signaling modules, indicating a new mechanism for antrodin C to treat CRC in vitro and in vivo.
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BACKGROUND AND AIM: The objective was to decrease patient menopausal symptoms, sleep disturbance, and body image using a nonpharmacological therapy for cultivating key healthy lifestyle habits in patients with breast cancer. MATERIALS AND METHODS: The participants were 26 women with breast cancer who had recently received structured mindfulness-based stress reduction (MBSR) training in a clinical trial. Focus groups and interviews were conducted, during which the participants were asked semistructured, open-ended questions regarding the experiences of MBSR. RESULTS: The participants indicated that MBSR helped them to alleviate hot flashes and night sweats, and improve sleep quality and be more at ease with the external aspect of their body. On the other hand, during MBSR intervention in a group manner, the participants felt more psychological support and an outlet for sharing negative emotional experiences. CONCLUSION: This study identified the short-term benefits associated with group-based MBSR for women with breast cancer. In addition, our research identified the difficulties of intervention measures and coping methods. The study described the benefits of MBSR for patients with breast cancer. The findings of this study will help nursing staff identify the main coping menopausal symptoms and control negative mental health.
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Neoplasias de la Mama , Atención Plena , Humanos , Femenino , Neoplasias de la Mama/complicaciones , Estrés Psicológico/terapia , Estrés Psicológico/psicología , Atención Plena/métodos , Imagen Corporal , Calidad de Vida , Menopausia , SueñoRESUMEN
Blood pressure variability (BPV) is independently associated with higher cardiovascular risks. However, whether BPV is associated with poor outcomes for coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remained undetermined. We aimed to investigate the relationship between BPV and the outcomes of CAD patients undergoing PCI. Two thousand seven hundred and sixty-two CAD patients (1938 males, mean age 69.6 ± 12.9) who received PCI at Taipei Veterans General Hospital from 2006 to 2015 with multiple blood pressure measurements before and after the index PCI were enrolled. We calculated the standard deviation of systolic blood pressure, diastolic blood pressure, and pulse pressure as parameters of BPV. The primary endpoint was the composite of major adverse cardiovascular events [MACE comprising of cardiovascular death, nonfatal myocardial infarction (MI), and non-fatal stroke] and heart failure hospitalization (HHF). The key secondary endpoint was MACE. Both pre-PCI and post-PCI BPV were associated with CV events even after adjusting for co-morbidities and mean blood pressure. In Cox analysis, for every 1 mmHg increase in systolic BPV, the hazard ratio for the MACE + HHF, MACE, HHF, and cardiovascular death was 1.04 (95%CI: 1.03-1.05), 1.04 (95%CI: 1.02-1.05), 1.05 (95%CI: 1.04-1.06), and 1.06 (95%CI: 1.03-1.09), respectively. The association between BPV and cardiovascular risk is independent of blood pressure control status. The prognostic value of BPV was superior to mean blood pressure in both pre-PCI and post-PCI period. BPV is independently associated with cardiovascular events after PCI and has a better prognostic value than mean blood pressure suggesting the importance of maintaining stable blood pressure for CAD patients.
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Enfermedad de la Arteria Coronaria , Hipertensión , Intervención Coronaria Percutánea , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/complicaciones , Intervención Coronaria Percutánea/efectos adversos , Hipertensión/complicaciones , Hipertensión/epidemiología , Factores de RiesgoRESUMEN
Parkinson's disease (PD) primarily affects the motor system and is the second most common age-related neurodegenerative disorder after Alzheimer's disease. Mitochondrial complex I deficiency and functional abnormalities are implicated in the development of PD. MicroRNA-29a (miR-29a) has emerged as a critical miRNA in PD. This study aims to investigate the protective role of miR-29a in MPP+ in SH-SY5Y cell lines in vitro PD model by targeting mitochondrial antiviral signaling protein (MAVS). Administration of MPP + inhibited miR-29a expression in SH-SY5Y cell lines. Our findings prove that miR-29a mimic treatment decreased cell death, ROS production, MAVS, p-IRF3, p-NFκBp65, IL-6, cleaved caspase-3, cleaved-PARP, LC3BII, and death while increasing glutathione peroxidase 1 and manganese superoxide dismutase after MPP + treatment in SH-SY5Y cells. Furthermore, MAVS expression was significantly corrected with the above genes in our in vitro model of PD. Luciferase activity analysis also confirmed that miR-29a specific binding 3'UTR of MAVS repressed expression. In conclusion, this research provides novel insight into a neuroprotective pathway of miR-29a and could thus serve as a possible therapeutic target for improving the treatment of PD.
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MicroARNs , Neuroblastoma , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , 1-Metil-4-fenilpiridinio , Caspasa 3/genética , Especies Reactivas de Oxígeno/metabolismo , Regiones no Traducidas 3' , Apoptosis/genética , Interleucina-6/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Línea Celular Tumoral , Neuroblastoma/genética , MicroARNs/genética , MicroARNs/metabolismo , Muerte Celular , Superóxido Dismutasa/metabolismo , Inflamación/genética , Antivirales/farmacologíaRESUMEN
Internet-based applications (apps) are rapidly developing in the e-Health era to assess the dietary intake of essential macro-and micro-nutrients for precision nutrition. We, therefore, validated the accuracy of an internet-based app against the Nutrition Data System for Research (NDSR), assessing these essential nutrients among various social-ethnic diet types. The agreement between the two measures using intraclass correlation coefficients was good (0.85) for total calories, but moderate for caloric ranges outside of <1000 (0.75) and >2000 (0.57); and good (>0.75) for most macro- (average: 0.85) and micro-nutrients (average: 0.83) except cobalamin (0.73) and calcium (0.51). The app underestimated nutrients that are associated with protein and fat (protein: −5.82%, fat: −12.78%, vitamin B12: −13.59%, methionine: −8.76%, zinc: −12.49%), while overestimated nutrients that are associated with carbohydrate (fiber: 6.7%, B9: 9.06%). Using artificial intelligence analytics, we confirmed the factors that could contribute to the differences between the two measures for various essential nutrients, and they included caloric ranges; the differences between the two measures for carbohydrates, protein, and fat; and diet types. For total calories, as an example, the source factors that contributed to the differences between the two measures included caloric range (<1000 versus others), fat, and protein; for cobalamin: protein, American, and Japanese diets; and for folate: caloric range (<1000 versus others), carbohydrate, and Italian diet. In the e-Health era, the internet-based app has the capacity to enhance precision nutrition. By identifying and integrating the effects of potential contributing factors in the algorithm of output readings, the accuracy of new app measures could be improved.
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Inteligencia Artificial , Telemedicina , Carbohidratos , Dieta , Ingestión de Energía , Internet , Nutrientes , Estados Unidos , United States Department of Agriculture , Vitamina B 12RESUMEN
Kawasaki disease (KD) is a febrile coronary vasculitis that affects younger children and includes complications such as coronary artery aneurysm. KD diagnoses are diagnosed based on clinical presentations, a process that still poses a challenge for front-line physicians. In the current study, we developed a novel predictor using the hemoglobin-for-age z-score (HbZ) and plasma hepcidin to differentiate Kawasaki disease (KD) from febrile children (FC). There were 104 FC and 115 KD subjects (89 typical KD; 26 incomplete KD) for this study, and data were collected on the biological parameters of hemoglobin and plasma hepcidin levels. A receiver operating characteristic curve (auROC), multiple logistics regression, and support vector machine analysis were all adopted to develop our prediction condition. We obtained both predictors, HbZ and plasma hepcidin, for distinguishing KD and FC. The auROC of the multivariate logistic regression of both parameters for FC and KD was 0.959 (95% confidence interval = 0.937-0.981), and the sensitivity and specificity were 85.2% and 95.9%, respectively. Furthermore, the auROC for FC and incomplete KD was 0.981, and the sensitivity and specificity were 92.3% and 95.2%, respectively. We further developed a model of support vector machine (SVM) classification with 83.3% sensitivity and 88.0% specificity in the training set, and the blind cohort performed well (78.4% sensitivity and 100% specificity). All data showed that sensitivity and specificity were 81.7% and 91.3%, respectively, by SVM. Overall, our findings demonstrate a novel predictor using a combination of HbZ and plasma hepcidin with a better discriminatory ability for differentiating from WBC and CRP between children with KD and other FC. Using this predictor can assist front-line physicians to recognize and then provide early treatment for KD.
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In preparation for personalized nutrition, an accurate assessment of dietary intakes on key essential nutrients using smartphones can help promote health and reduce health risks across vulnerable populations. We, therefore, validated the accuracy of a mobile application (app) against Food Frequency Questionnaire (FFQ) using artificial intelligence (AI) machine-learning-based analytics, assessing key macro- and micro-nutrients across various modern diets. We first used Bland and Altman analysis to identify and visualize the differences between the two measures. We then applied AI-based analytics to enhance prediction accuracy, including generalized regression to identify factors that contributed to the differences between the two measures. The mobile app underestimated most macro- and micro-nutrients compared to FFQ (ranges: -5% for total calories, -19% for cobalamin, -33% for vitamin E). The average correlations between the two measures were 0.87 for macro-nutrients and 0.84 for micro-nutrients. Factors that contributed to the differences between the two measures using total calories as an example, included caloric range (1000-2000 versus others), carbohydrate, and protein; for cobalamin, included caloric range, protein, and Chinese diet. Future studies are needed to validate actual intakes and reporting of various diets, and to examine the accuracy of mobile App. Thus, a mobile app can be used to support personalized nutrition in the mHealth era, considering adjustments with sources that could contribute to the inaccurate estimates of nutrients.
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Aplicaciones Móviles , Telemedicina , Inteligencia Artificial , Dieta , Promoción de la Salud , Nutrientes , Encuestas y CuestionariosRESUMEN
A high-fat diet is responsible for hepatic fat accumulation that sustains chronic liver damage and increases the risks of steatosis and hepatocellular carcinoma (HCC). MicroRNA-29a (miR-29a), a key regulator of cellular behaviors, is present in anti-fibrosis and modulator tumorigenesis. However, the increased transparency of the correlation between miR-29a and the progression of human HCC is still further investigated. In this study, we predicted HIF-1α and ANGPT2 as regulators of HCC by the OncoMir cancer database and showed a strong positive correlation with HIF-1α and ANGPT2 gene expression in HCC patients. Mice fed the western diet (WD) while administered CCl4 for 25 weeks induced chronic liver damage and higher HCC incidence than without fed WD mice. HCC section staining revealed signaling upregulation in ki67, severe fibrosis, and steatosis in WD and CCl4 mice and detected Col3a1 gene expressions. HCC tissues significantly attenuated miR-29a but increased in HIF-1α, ANGPT2, Lox, Loxl2, and VEGFA expression. Luciferase activity analysis confirms that miR-29a specific binding 3'UTR of HIF-1α and ANGPT2 to repress expression. In summary, miR-29a control HIF-1α and ANGPT2 signaling in HCC formation. This study insight into a novel molecular pathway by which miR-29a targeting HIF-1α and ANGPT2 counteracts the incidence of HCC development.
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Angiopoyetina 2/genética , Carcinoma Hepatocelular/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Regiones no Traducidas 3' , Angiopoyetina 2/metabolismo , Animales , Tetracloruro de Carbono/efectos adversos , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Incidencia , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Transducción de SeñalRESUMEN
Kawasaki disease (KD) is a febrile childhood vasculitis that involves the coronary arteries. Most previous studies have focused on the genes activated in the acute phase of KD. However, in this study, we focused on suppressed genes in the acute stage of KD and identified novel targets with clinical significance and potential prognostic value for KD patients. We enrolled 18 patients with KD, 18 healthy controls (HC), and 18 febrile controls (FC) for human transcriptome array analysis. Another 19 healthy controls, 20 febrile controls, and 31 patients with KD were recruited for RT-PCR validation of target mRNA expressions. The results of Human Transcriptome Array (HTA) 2.0 showed 461 genes that were significantly higher in KD and then normalized after IVIG, as well as 99 suppressed genes in KD. Furthermore, we identified the four genes in KD with the most downregulation, including BCL11B, DUSP2, DDX24, and CDR2, as well as the upregulation of their expression following IVIG administration. The mRNA expression of CDR2 by qRT-PCR was the most compatible with the pattern of the HTA2.0 results. Furthermore, we found higher DDX24 mRNA expression in KD patients with CAL when compared to those without CAL 3 weeks after IVIG administration. In summary, activated gene expression represented a majority in the immune response of KD. In this study, we identified CDR2 as a novel suppressed gene for Kawasaki disease via human transcriptome array analysis and DDX24 associated with CAL formation, which may contribute to further understanding of CAL pathogenesis in KD.