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Previous studies have demonstrated the regulatory roles of Transmembrane protein 147 (TMEM147) in various diseases, including cancer. However, systematic pan-cancer analyses investigating the role of TMEM147 in diagnosis, prognosis, and immunological prediction are lacking. An analysis of data from The Cancer Genome Atlas (TCGA) revealed differential TMEM147 expression across various types of cancer as well as within immune and molecular cancer subtypes. Moreover, high TMEM147 expression was associated with poor disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) across cancers, suggesting its potential as a prognostic biomarker. Our study further revealed a significant correlation between TMEM147 expression and T helper cell and Tcm cell infiltration in most cancer types. In the case of liver hepatocellular carcinoma (LIHC), the effect of TMEM147 on prognosis varied among different clinical subtypes. Additionally, functional enrichment analysis revealed an association between TMEM147 and metabolic pathways. Finally, experiments on the MIHA cell line and four LIHC cell lines confirmed the role of TMEM147 in promoting liver cancer cell proliferation, further confirming the clinical value of TMEM147 in liver cancer diagnosis. Our findings suggest that TMEM147 may serve as a diagnostic and prognostic biomarker across cancers while also playing a significant role in LIHC.
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PURPOSE: The role of adherence to the recommendations for 24-hour movement behaviors (24-HMB), including physical activity (PA), screen time (ST), and sleep duration (SLP), in relation to emotional and behavioral problems in Chinese adolescents remains uncertain. This study aimed to investigate these associations and explore potential sex differences. METHODS: This school-based cross-sectional study included 15,071 Chinese adolescents with a mean age of 14.53 (SD: 1.65) years. Data on emotional and behavioral problems and 24-HMB (including PA, ST, and SLP) were collected. Analysis was performed using general linear mixed models, with additional sex-stratified analyses conducted. RESULTS: The number of 24-HMB recommendations met was negatively associated with total difficulties (ß estimate=-0.96, 95% CI: -1.07 to -0.85) and positively related to prosocial behavior (ß estimate = 0.41, 95% CI: 0.37 to 0.46) among adolescents. Compared with none of the recommendations met, meeting all recommendations (total difficulties: ß estimate=-2.98, 95% CI: -3.41 to -2.55; prosocial behaviors: ß estimate = 1.05, 95%CI: 0.87 to 1.24) demonstrated the strongest association with both difficulties and prosocial behaviors, followed by meeting recommendations for PA + ST (total difficulties: ß estimate=-2.15, 95% CI: -2.41 to -1.90; prosocial behaviors: ß estimate = 0.98, 95% CI: 0.87 to 1.09). These associations were consistently significant in both boys and girls. CONCLUSION: Adherence to more 24-HMB recommendations, particularly meeting all recommendations or combined PA + ST recommendations, could improve emotional and behavioral well-being among adolescent girls and boys. The significance of balanced movement behaviors for promoting adolescent mental health merits increased attention.
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Lilium brownii (L. brownii) is a plant that can be used for both medicine and food. Its bulbs are commonly used to treat neurological disorders like depression, insomnia, and Parkinson's disease (PD). However, the mechanism by which it treats PD is not yet fully understood. This study aims to investigate the possible mechanism of L. brownii extract in treating PD and to compare the efficacy of ethanol and aqueous extracts of L. brownii. In this study, mice with PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) were given L. brownii extracts for 30 days, and the effects of both extracts were then evaluated. Our study demonstrated that both extracts of L. brownii effectively improved motor dysfunction in PD mice induced by MPTP. Additionally, they increased the number of neurons in the substantia nigra region of the mice. Moreover, both extracts reduced levels of malondialdehyde (MDA) and ferrous ion (Fe2+), while increasing levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum. They also influenced the expression of proteins associated with the p62-Keap1-Nrf2 pathway. Interestingly, while both extracts had similar behavioral effects, the ethanol extract appeared to have a more significant impact on individual proteins in the p62-Keap1-Nrf2 pathway compared to the aqueous extract, possibly due to its higher phenolic acid glyceride content. In conclusion, L. brownii shows promise as an effective and safe treatment for PD.
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The precise determination of polypeptide antibiotics (PPTs) in foods has been always challenging because of the interference of various endogenous peptides in complex matrix. Herin, a novel large-pore covalent organic framework (TABPT-SPDA-COF) with accessible pore size of 7.9 nm was synthesized as a solid phase extraction (SPE) absorbent for efficiently enriching four PPTs existed in foods originating from animals. The parameters of SPE process were systematically optimized. Subsequently, four PPTs were determined by UHPLC-MS/MS. Under the optimal conditions, TABPT-SPDA-COF shows outstanding enrichment capacity for PPTs in contrast to commercial absorbents ascribed to size selectivity and multiple interaction effects. The method exhibits excellent linear range (0.005-100 ng mL-1), satisfactory limits of detection (0.1 pg mL-1) as well as relative recoveries (86.2-116 %). This work offers a practicable platform to monitor trace PPTs from complex animal-derived foodstuffs.
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Antibacterianos , Límite de Detección , Estructuras Metalorgánicas , Péptidos , Extracción en Fase Sólida , Espectrometría de Masas en Tándem , Extracción en Fase Sólida/métodos , Antibacterianos/análisis , Antibacterianos/aislamiento & purificación , Antibacterianos/química , Animales , Estructuras Metalorgánicas/química , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Péptidos/análisis , Péptidos/aislamiento & purificación , Péptidos/química , Contaminación de Alimentos/análisisRESUMEN
Background: Limited and conflicting evidence exists for the associations between tea, coffee, and caffeine intake and risk of dementia and Alzheimer's disease (AD). This meta-analysis aimed to elucidate these associations and quantify potential dose-response relationships. Methods: PubMed, EMBASE, and Web of Science were searched up to 11 June 2024 for cohort studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs), with the dose-response relationship assessed using restricted cubic splines. The Grading of Recommendations Assessment Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: Our analysis encompassed 38 cohorts, totalling 751 824 participants and 13 017 dementia and 17 341 AD cases. For dementia, compared with the lowest category, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine were 0.84 (0.74-0.96, n = 6), 0.95 (0.87-1.02, n = 9), and 0.94 (0.70-1.25, n = 5), with all rated as low certainty in GRADE. For AD, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine compared to the lowest category were 0.93 (0.87-1.00, n = 6), 1.01 (0.90-1.12, n = 10), and 1.34 (1.04-1.74, n = 2), with certainty ratings of low, low, and very low, respectively. Dose-response analysis indicated a non-linear relationship between coffee intake (Poverall = 0.04 and Pnonlinear = 0.01) and dementia risk, showing the protective association of risk of dementia with 1 to 3 cups per day of coffee intake. There is a linear association between tea intake and risk of dementia, with a significantly decreased risk of dementia for each 1 cup per day increase in tea consumption (0.96, 95% CI 0.94-0.99, Poverall = 0.01 and Pnonlinear = 0.68). Conclusion: Increased tea consumption was associated with a decreased risk of dementia and AD, and a non-linear relationship was found between coffee and dementia, supporting public health recommendations for dementia prevention.
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Enfermedad de Alzheimer , Cafeína , Café , Demencia , Té , Té/química , Café/química , Humanos , Enfermedad de Alzheimer/prevención & control , Cafeína/administración & dosificación , Demencia/epidemiología , Demencia/prevención & control , Estudios de Cohortes , Femenino , Anciano , Masculino , Factores de RiesgoRESUMEN
The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.
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Aminofenoles , Ferroptosis , Peroxidación de Lípido , Animales , Aminofenoles/farmacología , Aminofenoles/química , Ferroptosis/efectos de los fármacos , Ratones , Peroxidación de Lípido/efectos de los fármacos , Humanos , Relación Estructura-Actividad , Acetaminofén/farmacología , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Masculino , Descubrimiento de Drogas , Ratones Endogámicos C57BLRESUMEN
A new phenanthroline derivative bearing imidazole group, (2-(3,5-di(pyridin-4-yl)phenyl)-1-p-tolyl-1H-imidazo[4,5-f][1,10]phenanthroline) (1), has been devised. 1 can be used as a multifunctional probe exhibiting a highly sensitive colorimetric response to Fe2+ and a selectively ratiometric ï¬uorescent response to Zn2+ in a buffer-ethanol solution. The absorption enhancement accompanied by a visual color change from colorless to red upon addition of Fe2+, makes 1 a suitable naked-eye sensor for Fe2+. Moreover, 1 displayed a Zn2+-induced red-shift of emission (44 nm) showing a color change from blue to light cyan under a 365-nm UV lamp. Its practical imaging applicability for intracellular Zn2+ was confirmed in HeLa cells using a confocal microscope. The improved emission properties and cell imaging capability would provide a new approach for fluorescence sensation for Zn2+.
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Background: Numerous studies reported inconsistent association between breakfast skipping and all-cause, cardiovascular disease (CVD) and cancer mortality. Therefore, we conducted a systematic review and meta-analysis to elucidate these associations. Methods: PubMed, Embase, and Web of Science databases were searched up to July 2023 for prospective cohort studies that assessed the association between breakfast skipping and all-cause, CVD and cancer mortality in general adults. A random effect model was used to estimate the pooled hazard ratio (HR) and 95% confidence intervals (CIs), with subgroup analysis and sensitivity analysis performed. The Newcastle-Ottawa Scale (NOS) was used to assess the study and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: The final analysis included 9 cohort studies including 242 095 participants, with 6 studies for all-cause mortality, 4 studies for CVD mortality, and 2 studies for cancer mortality. Compared to regular breakfast consumption, skipping breakfast was associated with a higher risk of all-cause (HR: 1.27, 95% CI, 1.07-1.51, I2 = 77%), CVD (HR 1.28, 95% CI 1.10-1.50, I2 = 0), and cancer (HR: 1.34, 95% CI: 1.11-1.61, I2 = 0%) mortality. Sensitivity analysis revealed inconsistent results in all-cause and CVD mortality. Subgroup analysis showed significant association in studies with larger participants, longer follow-up, adjustments for energy intake, and high-quality articles. GRADE showed very low evidence for all-cause mortality and low evidence for CVD and cancer mortality. Conclusion: The findings underscore the importance of regular breakfast habits for health and longevity. However, these results require careful interpretation due to geographic limitations, potential heterogeneity, and instability.
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Desayuno , Enfermedades Cardiovasculares , Neoplasias , Humanos , Neoplasias/mortalidad , Enfermedades Cardiovasculares/mortalidad , Estudios Prospectivos , Adulto , Conducta Alimentaria , Masculino , Factores de Riesgo , Femenino , Persona de Mediana Edad , Ayuno IntermitenteRESUMEN
Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive form of osteopetrosis. Here, the peripheral blood mononuclear cells (PBMCs) extracted from a patient with IMO carrying a compound heterozygous mutation in T cell immune regulator 1, ATPase H + transporting V0 subunit a3 (TCIRG1) gene (c.242delC; c.1114C > T) were successfully reprogrammed using Sendai virus encoding the four Yamanaka factors. The generated hiPSCs, IMO-hiPSCs, displayed typical embryonic stem cell-like morphology and were verified by expression of pluripotency markers such as OCT4, SOX2, NANOG, TRA-1-60 and SSEA4, as well as in vivo and in vitro differentiation into derivatives of three germ layers.
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Células Madre Pluripotentes Inducidas , Osteopetrosis , ATPasas de Translocación de Protón Vacuolares , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Osteopetrosis/metabolismo , Leucocitos Mononucleares/metabolismo , Mutación , Genes Homeobox , Diferenciación Celular , ATPasas de Translocación de Protón Vacuolares/genéticaRESUMEN
Bulbs of Lilium brownii, commonly known as "Bai-he" in China, serve both edible and medicinal purposes in clinical practice. In this study, two new isospirostanol-type saponins were isolated from L. brownii, and their structures were identified by spectroscopic method, and absolute configurations were elucidated by comprehensive analysis of spectral data obtained from combined acid hydrolysis. Two compounds were finally identified as 3-O-[α-L-rhamnopyranosyl-(1â2)-ß-D-glucopyranoside]-(22R,25R)-5α-spirosolane-3ß-ol (1) and 3-O-{α-L-rhamnopyranosyl-(1â2)-[ß-D-glucopyranosyl-(1â4)]-ß-D-glucopyranoside}-(22R,25R)-5α-spirosolane-3ß-ol (2), respectively. Further, we found that compound 2 significantly suppressed the proliferation of SMMC-7721 and HepG2 cells with IC50 values of 26.3±1.08â µM and 30.9±1.59â µM, whereas compound 1 didn't inhibit both of the two hepatocellular carcinoma. Subsequently, compound 2 effectively decreased the levels of interleukin-1ß and tumor necrosis factor-α and the expression of Bcl-2, and increased the expression of Bax and Caspase-3 proteins. Which indicated that the anti-hepatocellular carcinoma effect of compound 2 involves reducing the level of inflammation and inducing apoptosis.
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Apoptosis , Proliferación Celular , Lilium , Neoplasias Hepáticas , Raíces de Plantas , Saponinas , Humanos , Saponinas/farmacología , Saponinas/química , Saponinas/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Lilium/química , Raíces de Plantas/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Apoptosis/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , Espirostanos/farmacología , Espirostanos/química , Espirostanos/aislamiento & purificación , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Interleucina-1beta/metabolismo , Interleucina-1beta/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Células Hep G2 , Estructura Molecular , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Conformación MolecularRESUMEN
BACKGROUND: This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). METHODS: Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. RESULTS: Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (ß= - 0.060, 95% CI - 0.044 to - 0.076; P = 2.416e-14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (ß= - 0.021, 95% CI - 0.003 to - 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. CONCLUSIONS: Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Dislipidemias , Insuficiencia Cardíaca , Hipertensión , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , ADN Mitocondrial/genética , Variaciones en el Número de Copia de ADN , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/genética , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/genética , Obesidad/diagnóstico , Obesidad/epidemiología , Obesidad/genética , Dislipidemias/diagnóstico , Dislipidemias/epidemiología , Dislipidemias/genéticaRESUMEN
BACKGROUND AND PURPOSE: Stroke is a leading cause of global morbidity and mortality, indicating the necessity and urgency of effective prevention and treatment. Remote ischemic conditioning (RIC) is a convenient, simple, non-intrusive, and effective method that can be easily added to the treatment regime of stroke patients. Animal experiments and clinical trials have proved the neuroprotective effects of RIC on brain injury including (examples of neuroprotective effects). This neuroprotection is achieved by raising brain tolerance to ischemia, increasing local cerebral blood perfusion, promoting collateral circulations, neural regeneration, and reducing the incidence of hematomas in brain tissue. This current paper will summarize the studies within the last 2 years for the comprehensive understanding of the use of RIC in the treatment of stroke. METHODS: This paper summarizes the clinical research progress of RIC on stroke (ischemic stroke and hemorrhagic stroke (HS)). This paper is a systematic review of research published on registered clinical trials using RIC in stroke from inception through November 2022. Four major databases (PUBMED, WEB OF SCIENCE, EMBASE, and ClinicalTrials.gov) were searched. RESULTS: Forty-eight studies were identified meeting our criteria. Of these studies, 14 were in patients with acute ischemic stroke with onset times ranging from 6 h to 14 days, seven were in patients with intravenous thrombolysis or endovascular thrombectomy, 10 were in patients with intracranial atherosclerotic stenosis, six on patients with vascular cognitive impairment, three on patients with moyamoya disease, and eight on patients with HS. Of the 48 studies, 42 were completed and six are ongoing. CONCLUSIONS: RIC is safe, feasible, and effective in the treatment of stroke. Large-scale research is still required to explore the optimal treatment options and mechanisms of RIC in the future to develop a breakthrough in stroke prevention and treatment.
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Isquemia Encefálica , Precondicionamiento Isquémico , Accidente Cerebrovascular Isquémico , Fármacos Neuroprotectores , Accidente Cerebrovascular , Animales , Humanos , Isquemia Encefálica/prevención & control , Precondicionamiento Isquémico/métodos , Accidente Cerebrovascular/prevención & control , IsquemiaRESUMEN
The suppression of ferroptosis is emerging as a promising therapeutic strategy for effectively treating a wide range of diseases, including neurodegenerative disorders, organ ischemia-reperfusion injury, and inflammatory conditions. However, the clinical utility of ferroptosis inhibitors is significantly impeded by the limited availability of rational drug designs. In our previous study, we successfully unraveled the efficacy of ferrostatin-1 (Fer-1) attributed to the synergistic effect of its ortho-diamine (-NH) moiety. In this study, we present the discovery of the ortho-hydroxyl-amino moiety as a novel scaffold for ferroptosis inhibitors, employing quantum chemistry as well as in vitro and in vivo assays. 2-amino-6-methylphenol derivatives demonstrated remarkable inhibition of RSL3-induced ferroptosis, exhibiting EC50 values ranging from 25 nM to 207 nM. These compounds do not appear to modulate iron homeostasis or lipid reactive oxygen species (ROS) generation pathways. Nevertheless, they effectively prevent the accumulation of lipid peroxides in living cells. Furthermore, compound 13 exhibits good in vivo activities as it effectively protect mice from kidney ischemia-reperfusion injury. In summary, compound 13 has been identified as a potent ferroptosis inhibitor, warranting further investigation as a promising lead compound.
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Peróxidos Lipídicos , Daño por Reperfusión , Animales , Ratones , Peroxidación de Lípido , Peróxidos Lipídicos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Fenoles/farmacologíaRESUMEN
The contact state of a seamless internal threaded copper tube and an aluminium foil fin not only affects the heat transfer efficiency of a tube-fin heat exchanger but also seriously affects its service life. In this study, hydraulic expansion technology was used to connect the copper tube with an internal thread with a 7 mm diameter to the fin of the heat exchanger. The influence of the expansion pressure and pressure holding time on the contact state was analysed through experiments and finite element simulation, and the variation law of the two on the contact state was obtained. The contact state was characterised by the contact gap and contact area. In order to obtain the specific contact area value, a new method of measuring the contact area was developed to reveal the variation in contact area between the copper tube and the fin after expansion. The results show that the contact gap decreases with an increase in expansion pressure, while the pressure holding time remains the same. The contact area increases with an increase in expansion pressure, and the rate of increase slows. When the expansion pressure is 18 MPa, the average contact gap is approximately 0.018 mm. When the expansion pressure reaches 16 MPa, the contact area ratio is 91.0%. When the expansion pressure increases to 18 MPa, the contact area ratio only increases by approximately 0.6%. Compared with the influence of the expansion pressure on the increase in contact area, the influence of the pressure holding time on the contact area is lower.
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BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative and remains incurable. Aluminum is a potent neurotoxin associated with AD. The main pathological features of AD are extracellular amyloid-ß protein deposition and intracellular hyperphosphorylated Tau protein. A body of evidence suggest that oxidative stress and autophagy are involved in the pathogenesis of AD. Andrographis paniculata (AP) is a native plant with anti-inflammatory, anti-oxidative stress, and regulation of autophagy properties. AP significantly alleviated cognitive impairments, reduced Aß deposition and has neuroprotective effect. However, its effects on aluminum-induced AD model have not been studied much. In this study, we investigated whether AP protect against aluminum-induced neurotoxicity through regulation of p62-Kelch-like ECH-associated protein 1(Keap1)-Nuclear factor E2 related factor 2 (Nrf2) pathway and activation autophagy in vivo and in vitro. METHODS: UPLC-ESI-qTOF-MS/MS was used to identify the chemical constituents of AP ethanol extract. The mice with cognitive deficit were established by injecting aluminum chloride and D-galactose, and treated with either AP extract (200, 400, or 600 mg/kg/d) or andrographolide (2 mg/kg/2d).The spatial memory ability was detected by Morris water maze, HE staining were used to detect in brain tissue,Oxidative stress indexs and SOD activity in both serum and brain tissue were detected by kit.The expression of p62-Nrf2 pathway proteins were measured via western blotting. Furthermore, the neurotoxicity model was induced by aluminum maltolate (700 µM) in PC12 cells. Following AP and andrographolide treatment, the cell viability was detected. The relevant mRNA and protein expressions were detected in cells transfected with the p62 siRNA. RESULTS: The main active components of AP included andrographolide, neoandrographolide and deoxyandrographolide as identified. AP and andrographolide significantly improved the spatial memory ability of mice, attenuated pathological changes of hippocampal cells, reduced the level of malondialdehyde, and increased superoxide dismutase activity in serum or brain tissue as compared to model control. In addition, the Nrf2, p62 and LC3B-II proteins expression were increased, and p-Tau and Keap1 proteins were decreased in the hippocampus after AP and andrographolide treatment.Furthermore, AP increased aluminum maltolate-induced cell viability in PC12 cells. Silencing p62 could reverse the upregulation expression of Nrf2 and downregulation of Keap1 and Tau proteins induced by AP in aluminum maltolate-treated cells. CONCLUSIONS: AP had neuroprotective effects against aluminum -induced cognitive dysfunction or cytotoxicity, which was involved in the activation of the p62-keap1-Nrf2 pathway and may develop as therapeutic drugs for the treatment of AD. However, this study has certain limitations, further optimize the protocol or model and study the molecular mechanism of AP improving AD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Fármacos Neuroprotectores , Transducción de Señal , Animales , Ratones , Ratas , Aluminio/toxicidad , Andrographis paniculata/química , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Etanol , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Fármacos Neuroprotectores/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Espectrometría de Masas en Tándem , Transducción de Señal/efectos de los fármacos , Extractos Vegetales/químicaRESUMEN
The assembled camshaft is a novel manufacturing product which connects the cam and the mandrel by tube hydroforming (THF) technology after they are processed separately. However, in the process of THF, the structure of the cam-bores has a crucial influence on the connection strength of the assembled camshafts. Therefore, three kinds of cam-bores with circular structure, isometric-trilateral profile and logarithmic spiral profile are selected for hydroforming with a hollow mandrel (tube) in this study. The finite-element-analysis is carried out by ABAQUS software, the variations of (residual) contact pressure and contact area under different structures are obtained, and the torsional angle variations after assembly are measured. Further, the connection strength of the assembled camshaft under three structures is discussed. The results show that the evaluation of connection strength of the assembled camshaft is affected by many factors, including contact pressure, maximum residual contact pressure, axial and circular residual contact pressure, contact area and its rate, residual contact area percentage and torsional angle. Through the comprehensive analysis of various factors, the torsional angle of the camshaft with circular structure is the largest, i.e. poor connection strength. By contrast, the torsional strength of the camshaft with isometric-trilateral profile is the largest, namely, the best connection strength.
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Objective: The objective of this study is to investigate the effects of emergency nursing interventions, specifically those based on the Pediatric Early Warning Score (PEWS), on children diagnosed with acute asthma, to promote the recovery of children with asthma and improve the quality of care for children with asthma. Methods: A total of 80 children, Acute asthma attacks under the age of 12, diagnosed with acute asthma and admitted to the Emergency Department of Hebei Children's Hospital between June 2018 and June 2019 were selected as participants for this study. They were randomly assigned to either the control group or the PEWS group. There was no significant statistical difference in age, gender, course of disease, and disease severity between the two groups of children. In the control group, children received standard emergency nursing interventions, while in the PEWS group, children received emergency nursing interventions based on the Pediatric Early Warning Score (PEWS). To evaluate the effectiveness of these interventions, several outcome measures were compared between the two groups. This included assessing the duration for symptoms to disappear, analyzing pulmonary function indicators and respiratory dynamics indicators, measuring scores from the Pediatric Asthma Quality of Life Questionnaire (PAQLQ), and evaluating nursing satisfaction. Results: Following the implementation of the nursing interventions, 1. The average cough disappearance time of children in the PEWS group was 1.97 days shorter than that in the control group, the average wheezing disappearance time was 0.97 days shorter, the average dyspnea disappearance time was 0.64 days shorter, and the average lung wheezing disappearance time was 1.19 days shorter, which indicated that emergency care based on PEWS shortened the duration of symptoms in children with asthma. 2. The average FEV1 of children in the PEWS group was 9.87% higher than the control group, the average FVC was 0.62L higher, the average PEF was 9.84% higher, the average V70 was 0.91% higher, the average V50 was 0.43% higher , and the average V25 was 0.37% higher, when compared with control group. These results indicates that emergency care based on PEWS enhances the lung function of children with asthma. 3. The average respiratory rate of children in the PEWS group was 8.05 times/min lower, and the average dynamic respiratory system compliance was 6.91 mL/cmH2O higher, than that in the control group, which indicated that emergency care based on PEWS improved respiratory dynamics indicators in children with asthma. 4. The average PAQLQ symptom dimension score of children in the PEWS group was 0.84 points higher, the average activity dimension score was 0.34 points higher, and the average emotional dimension score was 0.47 points higher when compared with the control group. This indicated that emergency care based on PEWS improves the quality of life of children with asthma. 5. The nursing satisfaction of children in the PEWS group was 95%, higher than 72.5% in the control group, indicating that emergency care based on PEWS improved the satisfaction of asthma children with the nursing process. Conclusion: The implementation of PEWS based emergency care in pediatric asthma patients has important clinical significance in promoting recovery and improving the quality of care for asthma patients. The implementation of emergency nursing interventions based on the Pediatric Early Warning Score (PEWS) for children with acute asthma has been found to be effective in promoting the recovery of their condition, enhancing their quality of life, and improving nursing satisfaction.
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Objectives: To conduct a systematic review and meta-analysis of prospective cohort studies to investigate the association between total, vegetable, fruit, cereal, soluble and insoluble fiber intake and risk of all causes, cardiovascular disease (CVD), and cancer mortality and quantitatively assess the dose-response relation. Methods: Eligible studies were identified by searching PubMed, Embase and Web of science before August 2023. Random effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CI) and restricted cubic splines to model the linear/non-linear association. Results: The summary RR for all-cause, CVD and cancer mortality of dietary fiber was 0.90 (95% CI: 0.86,0.93), 0.87 (0.84,0.91), 0.91 (0.88,0.93), respectively. Significant association was observed for all-cause and CVD mortality with fruit, vegetable cereal and soluble fiber intake and cancer mortality with cereal fiber intake. No significant association was found for insoluble fiber, vegetable or fruit fiber intake and cancer mortality. Dose-response analysis showed a significant non-linear relation of dietary fiber intake with all-cause mortality, and linear relation for others. Conclusions: Higher dietary fiber including different type and food sources of fiber intake were associated with lower risk of mortality. Our findings provide more comprehensive evidence on dietary fiber intake with mortality. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier: CRD42022338837.
RESUMEN
OBJECTIVES: To better demonstrate the relationship between common eye diseases and the risk of dementia, we conducted a systematic review and meta-analysis of cohort studies to investigate the relationship between common eye diseases and dementia. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Patients with common eye diseases. METHODS: We conducted a systematic search of articles published up to August 25, 2022, of online databases including PubMed, EMBASE, and Web of Science. We included cohort studies that evaluated the association of glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and cataracts with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Relative risks (RRs) and 95% CIs were pooled using random effects model, and heterogeneity was assessed by the I2 statistic. Subgroup analysis and sensitivity analysis were also performed. RESULTS: In total, 25 studies were included in the meta-analysis, with a total of 11,410,709 participants. Pooled estimates suggested an increased risk of all-cause dementia associated with AMD (RR, 1.29; 95% CI, 1.13-1.48), glaucoma (RR, 1.16; 95% CI, 1.03-1.32), DR (RR, 1.40; 95% CI, 1.21-1.63), and cataract (RR,1.23; 95% CI, 1.09-1.40); an increased risk of AD associated with AMD (RR, 1.27; 95% CI, 1.06-1.52), glaucoma (RR, 1.18; 95% CI, 1.02-1.38), DR (RR, 1.21; 95% CI, 1.04-1.41), and cataracts (RR,1.22; 95% CI, 1.07-1.38). No association was observed between incident VaD and any eye diseases. The results of subgroup analyses were consistent with those in meta-analysis of DR and risk of all-cause dementia. Meta-regressions suggested geographic regions as potential sources of heterogeneity for the association between AMD and all-cause dementia, AMD and AD, glaucoma and dementia, glaucoma, and AD, respectively. CONCLUSIONS AND IMPLICATIONS: AMD, glaucoma, DR, and cataract may be associated with an increased risk of all-cause dementia and AD, but not VaD. However, the results should be interpreted cautiously because of the high heterogeneity and unstable findings in some subgroup analyses.
Asunto(s)
Enfermedad de Alzheimer , Demencia Vascular , Oftalmopatías , Humanos , Oftalmopatías/epidemiología , Incidencia , Demencia Vascular/epidemiología , Enfermedad de Alzheimer/epidemiologíaRESUMEN
OBJECTIVES: We performed a systematic review and dose-response meta-analysis to assess the association of total sugars, added sugars, fructose, and sucrose with all-cause, cardiovascular disease (CVD), and cancer mortality. METHODS: We searched PubMed, Embase, and Web of Science for prospective cohort studies up to May 10, 2022. Pooled relative risks and 95% CIs were calculated by random effect models, and the linear and non-linear dose-response associations were explored by restricted cubic splines. RESULTS: Comparing the highest with the lowest categories of total sugars, the summary RR was 1.09 (95% CI, 1.02-1.15; I2 = 71.9%) for all-cause mortality, 1.10 (1.02-1.18; I2 = 12.7%) for CVD mortality, and 1.00 (0.94-1.05; I2 = 0) for cancer mortality. For fructose, the summary relative risk was 1.09 (1.03-1.16; I2 = 58.4%) for all-cause mortality, 1.11 (1.03-1.20; I2 = 37.4%) for CVD mortality, and 1.00 (0.95-1.06; I2 = 0) for cancer mortality. Restricted cubic splines found non-linear associations of total sugars and fructose with all-cause and CVD mortality (P for non-linearity < 0.001). A significant increment in risk of all-cause and CVD mortality was observed with >10% energy intake to 20% energy intake for total sugars and fructose. No association was found for the added sugars and sucrose with all-cause, CVD, and cancer mortality. CONCLUSIONS: Increased intake of total sugars and fructose is associated with all-cause and CVD mortality but not associated with cancer mortality, which could have implications for guideline recommendations regarding the risk of mortality related to sugar intake.