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1.
Neural Regen Res ; 20(3): 740-750, 2025 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38886939

RESUMEN

Lipid droplets serve as primary storage organelles for neutral lipids in neurons, glial cells, and other cells in the nervous system. Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum. Previously, lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis; however, recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system. In addition to their role in regulating cell metabolism, lipid droplets play a protective role in various cellular stress responses. Furthermore, lipid droplets exhibit specific functions in neurons and glial cells. Dysregulation of lipid droplet formation leads to cellular dysfunction, metabolic abnormalities, and nervous system diseases. This review aims to provide an overview of the role of lipid droplets in the nervous system, covering topics such as biogenesis, cellular specificity, and functions. Additionally, it will explore the association between lipid droplets and neurodegenerative disorders. Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

2.
Foods ; 13(17)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39272543

RESUMEN

This study aimed to establish the preparation process of peptide-calcium chelates (TMP-Ca) using skipjack tuna meat and investigate the function and mechanism of TMP-Ca in an osteoporosis model of rats. The results indicated that trypsin is more suitable for preparing the Ca-chelating hydrolysates of tuna meat, and the optimal hydrolysis conditions were derived as follows: digestion time 4 h, material-liquid ratio 1:10, and enzyme dose 3%. The conditions for chelating Ca with tuna meat hydrolysate were optimized to be chelation time 50 min, temperature 50 °C, pH 8.0, and a peptide-Ca ratio 1:10. The prepared hydrolysate was subjected to ultrafiltration, and the fraction (TMP) (MW <1 kDa) showed the highest Ca chelation rate (51.27 ± 1.42%) and was made into the peptide-Ca chelates (TMP-Ca). In osteoporotic rats, TMP-Ca significantly improved the decrease in ovarian indexes caused by retinoic acid. It also elevated serum Ca, phosphorus, and bone turnover indexes, increased the number of bone trabeculae, and improved bone microstructure. In addition, we confirmed that TMP-Ca could regulate the OPG/TRAF6 pathway to reduce osteoclast differentiation, inhibit bone resorption, and promote bone formation. Therefore, TMP-Ca could significantly ameliorate osteoporosis, and this study provides a functional component for the preparation of healthcare products using skipjack tuna meat to treat osteoporosis.

3.
Arch Virol ; 169(9): 192, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225747

RESUMEN

Nanoparticles have gained attention as potential antiviral agents, but the effects of graphene oxide nanoparticles (GONPs) on influenza virus remain unclear. In this study, we evaluated the antiviral activity of GONPs against influenza virus strain A/Hunan-Lengshuitan/11197/2013(H9N2). Our results show that GONPs with a diameter of 4 nm exerted an antiviral effect, whereas those with a diameter of 400 nm had no effect. Treatment with 4-nm GONPs reduced viral titers by more than 99% and inhibited viral nucleoprotein expression in a dose-dependent manner. We also confirmed that 4-nm GONPs inhibited the infectivity of H9N2 in MDCK cells. A transmission electron microscopic analysis revealed morphological abnormalities in the GONP-treated virus, including the destruction of the envelope glycoprotein spikes and an irregular shape, suggesting that GONPs cause the destruction of the viral coat proteins. Our results highlight the potential utility of GONPs in the prevention and treatment of viral infections, especially those of emerging and re-emerging viruses.


Asunto(s)
Antivirales , Grafito , Subtipo H9N2 del Virus de la Influenza A , Nanopartículas , Grafito/farmacología , Grafito/química , Subtipo H9N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H9N2 del Virus de la Influenza A/fisiología , Subtipo H9N2 del Virus de la Influenza A/genética , Animales , Perros , Antivirales/farmacología , Células de Riñón Canino Madin Darby , Nanopartículas/química , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Replicación Viral/efectos de los fármacos
4.
J Clin Transl Endocrinol ; 37: 100369, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39308769

RESUMEN

Background: Vertebral compression fractures (VCFs) are prevalent in patients with osteoporosis and pose significant health risks. Although chronic low-grade inflammation plays a crucial role in the pathogenesis of osteoporosis, the relationship between various inflammatory indices and the occurrence of fractures remains unclear. Objective: This study aims to evaluate the correlation between multiple inflammatory indices, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI), and VCFs, to explore the significance of these indices in clinical application. Methods: Clinical data of 310 patients diagnosed with osteoporosis from November 2020 to June 2023 in the hospital were collected. The general conditions between fracture and non-fracture groups were described. Spearman analysis and binary logistic regression analysis were used to assess the relationship between inflammatory indices and VCFs. Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of these inflammatory indices for VCFs. Results: VCFs were diagnosed in 43.55 % of patients with osteoporosis. NLR(ρ = 0.169, P=0.003), MLR(ρ = 0.293, P<0.001), SII(ρ = 0.126, P=0.027), and SIRI(ρ = 0.273, P<0.001) were positively correlated with the occurrence of VCFs. NLR(OR=1.480, 95 %CI 1.114 âˆ¼ 1.966, P=0.007), MLR(multiplied by 100, OR=1.048, 95 %CI 1.011 âˆ¼ 1.087, P=0.011), and SIRI(OR=3.327, 95 %CI 1.510 âˆ¼ 7.330, P=0.003) were independent risk factors for VCFs, hip bone mineral density (BMD) (OR=0.011, 95 %CI 0.001 âˆ¼ 0.151, P=0.001) was an independent protective factor for VCFs. MLR(AUC 0.671, 95 % CI=0.610 âˆ¼ 0.732, P <0.001) had relatively high clinical diagnostic efficacy. Conclusion: The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic inflammatory response index (SIRI) are independent risk factors for vertebral compression fractures.

5.
Am J Clin Nutr ; 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39218306

RESUMEN

BACKGROUND: A proinflammatory diet has been associated with a risk of individual chronic diseases, however, evidence on the association between inflammatory dietary patterns and the trajectory of chronic disease multimorbidity is sparse. OBJECTIVES: We aimed to investigate the associations of a low-inflammatory diet with the multimorbidity trajectory. METHODS: Within the UK Biobank, 102,424 chronic disease-free participants (mean age 54.7 ± 7.9 y, 54.8% female) were followed up to detect multimorbidity trajectory (annual change in the number of 59 chronic diseases). Baseline inflammatory diet index (IDI) and empirical dietary inflammatory pattern (EDIP) were separately calculated from the weighted sum of 32 posteriori-derived (15 anti-inflammatory) and 18 prior-defined (9 anti-inflammatory) food groups, and tertiled as low-, moderate-, and high-inflammatory diet. Data were analyzed using linear mixed effects model, Cox model, and Laplace regression with adjustment for potential confounders. RESULTS: During the follow-up (median 10.23 y), 15,672 and 35,801 participants developed 1 and 2+ chronic conditions, respectively. Adherence to a low-inflammatory diet was associated with decreased multimorbidity risk (hazard ratio [HRIDI] = 0.84, 95% confidence interval [CI]: 0.81, 0.86; HREDIP = 0.91, 95% CI: 0.89, 0.94) and a slower multimorbidity accumulation (ßIDI = -0.033, 95% CI: -0.036, -0.029; ßEDIP = -0.006, 95% CI: -0.010, -0.003) compared with a high-inflammatory diet, especially in participants aged > 60 y (ßIDI = -0.051, 95% CI: -0.059, -0.042; ßEDIP = -0.020, 95% CI: -0.029, -0.012; both P-interactions < 0.05). The 50th percentile difference (95% CI) of chronic disease-free survival time was prolonged by 0.81 (0.64, 0.97) and 0.49 (0.34, 0.64) y for participants with a low IDI and EDIP, respectively. Higher IDI and EDIP were associated with the development of 4 and 3 multimorbidity clusters (especially for cardiometabolic diseases), respectively. CONCLUSIONS: A low-inflammatory diet is associated with a lower risk and slower accumulation of multimorbidity (especially in participants aged > 60 y). A low-inflammatory diet may prolong chronic disease-free survival time.

6.
J Matern Fetal Neonatal Med ; 37(1): 2397722, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39284761

RESUMEN

OBJECTIVE: The inconsistency in conclusions from early observational studies has sparked our interest in elucidating the relationship between lipid levels and susceptibility to hyperemesis gravidarum (HG). This study wishes to employed Mendelian randomization analysis to investigate the causal relationship between low-density lipoprotein cholesterol (LDL-C) and HG. METHODS: We employed Tow-Sample MR analysis to investigate the causal associations between LDL-C and HG. Specific variables were selected from GWAS database for MR analysis, using single nucleotide polymorphisms (SNPs) as our instruments. The threshold for significant SNPs as genetic instruments has been set at 5 × 10-8. F-statistic was employed to validate the strength of exposure instruments. The causality was mainly evaluated by Inverse Variance Weighted method (IVW). To address potential bias from the selection of genetic variants with pleiotropic effects, sensitivity analysis was performed by Cochrane Q-test, MR Egger, weighted median, MR-PRESSO and Leave-one-out methods. To validate the directionality of causal relationships, we employed Steiger test to filter SNPs. At last, we conducted reverse MR to exclude the causal impact of HG on LDL-C levels. RESULTS: Our MR results identified the effect of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG (OR:1.30; 95%CI:1.03-1.65; p = 0.028). In reverse MR analyses, no evidence was found for causal effect of HG on LDL-C levels (OR:1.00; 95%CI:1.00-1.01; p = 0.163). Sensitivity analyses were used to confirm reliability. CONCLUSION: This study may have provided evidence of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG. Appropriate lowering LDL-C levels may serve as a preventive and treatment measure for HG.


Asunto(s)
LDL-Colesterol , Hiperemesis Gravídica , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Embarazo , LDL-Colesterol/sangre , Hiperemesis Gravídica/genética , Hiperemesis Gravídica/sangre , Hiperemesis Gravídica/epidemiología , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Factores de Riesgo
7.
Mol Med Rep ; 30(5)2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39301631

RESUMEN

Fibrosis is the basis of structural remodeling in atrial fibrillation (AF), during which inflammation is crucial. Programmed cell death factor 4 (PDCD4) is a newly identified inflammatory gene, with unknown mechanisms of action in AF. The present study aimed to elucidate the effects of PDCD4 on the inflammation and structural remodeling of atrial myocytes. For this purpose, a PDCD4 overexpression plasmid (oePDCD4) and PDCD4 small interfering (si)RNA (siPDCD4) were used to modulate PDCD4 expression in mouse atrial myocytes (HL­1 cells). The expression of PDCD4 was detected using reverse transcription­quantitative PCR and western blot analysis. The optimal drug concentrations of peroxisome proliferator­activated receptor γ (PPARγ) agonist (pioglitazone hydrochloride), NF­κB inhibitor (CBL0137), PPARγ inhibitor (GW9962) and NF­κB agonist (betulinic acid) were screened using a Cell Counting Kit­8 assay. The levels of inflammatory factors were detected using enzyme­linked immunosorbent assays, the expression levels of fibrosis­related proteins and NF­κB subunits were detected using western blot analysis, and the expression of phosphorylated (p­)p65/p65 was detected using immunofluorescence staining. The results revealed that PDCD4 overexpression increased the levels of fibrotic factors (collagen I, collagen III, fibronectin, α­smooth muscle actin and matrix metalloproteinase 2), pro­inflammatory cytokines (IFN­Î³, IL­6, IL­17A and TNF­α) and p­p65, whereas it reduced the levels of anti­inflammatory cytokines (IL­4) in HL­1 cells. Additionally, treatment with the PPARγ agonist and NF­κB inhibitor reversed the levels of fibrotic­, pro­inflammatory and anti­inflammatory factors in oePDCD4­HL­1 cells. By contrast, PDCD4 silencing exerted the opposite effects on fibrotic factors, pro­inflammatory cytokines, anti­inflammatory cytokines and p­p65. In addition, treatment with the PPARγ inhibitor and NF­κB agonist reversed the levels of fibrotic­, pro­inflammatory and anti­inflammatory factors in siPDCD4­HL­1 cells. In conclusion, the present study demonstrated that PDCD4 may induce inflammation and fibrosis by activating the PPARγ/NF­κB signaling pathway, thereby promoting the structural remodeling of atrial myocytes in AF.


Asunto(s)
Proteínas Reguladoras de la Apoptosis , Fibrosis , Inflamación , Miocitos Cardíacos , FN-kappa B , PPAR gamma , Proteínas de Unión al ARN , Transducción de Señal , Animales , PPAR gamma/metabolismo , PPAR gamma/agonistas , PPAR gamma/genética , Ratones , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Inflamación/metabolismo , Inflamación/patología , Inflamación/genética , FN-kappa B/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Atrios Cardíacos/metabolismo , Atrios Cardíacos/patología , Línea Celular
8.
Br J Nutr ; : 1-7, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39300827

RESUMEN

Recent studies suggest an association between greater dietary inflammatory index (DII) and higher biological ageing. As α-Klotho has been considered as a longevity protein, we examined whether α-Klotho plays a role in the association between DII and ageing. We included 3054 participants from the National Health and Nutrition Examination Survey. The associations of DII with biological and phenotypic age were assessed by multivariable linear regression, and the mediating role of α-Klotho was evaluated by mediation analyses. Participants' mean age was 58·0 years (sd 11·0), with a median DII score of 1·85 and interquartile range from 0·44 to 2·79. After adjusting for age, sex, race/ethnicity, BMI, education, marital status, poverty income ratio, serum cotinine, alcohol, physical activity, a higher DII was associated with both older biological age and phenotypic age, with per DII score increment being associated with a 1·01-year increase in biological age (1·01 (95 % CI: 1·005, 1·02)) and 1·01-year increase in phenotypic age (1·01 (1·001, 1·02)). Negative associations of DII with α-Klotho (ß = -1·01 pg/ml, 95 % CI: -1·02, -1·006) and α-Klotho with biological age (ß= -1·07 years, 95 % CI: -1·13, -1·02) and phenotypic age (ß= -1·03 years, 95 % CI: -1·05, -1·01) were found. Furthermore, α-Klotho mediated 10·13 % (P < 0·001) and 9·61 % (P < 0·001) of the association of DII with biological and phenotypic age, respectively. Higher DII was associated with older biological and phenotypic age, and the potential detrimental effects could be partly mediated through α-Klotho.

9.
Heliyon ; 10(17): e37367, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296114

RESUMEN

Severe pneumonia (SP) is a prevalent respiratory ailment characterized by high mortality and poor prognosis. Current scoring systems for pneumonia are not only time-consuming but also exhibit limitations in early SP prediction. To address this gap, this study aimed to develop a machine-learning model using inflammatory markers from peripheral blood for early prediction of SP. A total of 204 pneumonia patients from seven medical centers were studied, with 143 (68 SP cases) in the training cohort and 61 (32 SP cases) in the test cohort. Clinical characteristics and laboratory test results were collected at diagnosis. Various models including Logistic Regression, Random Forest, Naïve Bayes, XGBoost, Support Vector Machine, and Decision Tree were built and evaluated. Seven predictors-age, sex, WBC count, T-lymphocyte count, NLR, CRP, TNF-α, IL-4/IFN-γ ratio, IL-6/IL-10 ratio-were selected through LASSO regression and clinical insight. The XGBoost model, exhibiting best performance, achieved an AUC of 0.901 (95 % CI: 0.827 to 0.985) in the test cohort, with an accuracy of 0.803, sensitivity of 0.844, specificity of 0.759, and F1_score of 0.818. Indeed, SHAP analysis emphasized the significance of elevated WBC counts, older age, and elevated CRP as the top predictors. The use of inflammatory biomarkers in this concise predictive model shows significant potential for the rapid assessment of SP risk, thereby facilitating timely preventive interventions.

10.
Int J Clin Health Psychol ; 24(3): 100500, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282223

RESUMEN

Social avoidance refers to the tendency to be alone and non-participating to social interactions, which is considered to hamper health interpersonal relationship. However, the neural underpinnings of social and emotional interactions among social avoidant individuals have not been fully studied. In the present study, we used EEG hyperscanning technology to investigate the brain activity and its synchronization of 25 socially avoidant dyads and 28 comparison dyads during an emotional communication task. The emotional communication task consisted of the emotional processing stage and emotional interaction stage. Event-related potentials (ERPs) of the senders during the emotional processing stage and the interbrain synchrony (IBS) of the dyads during the emotional interaction stage were analyzed. Results showed that (1) socially avoidant group showed higher beta, theta and gamma IBS in the negative condition than in the positive and neutral condition; (2) in positive condition, the N1 and LPP amplitudes during the emotional processing stage of socially avoidant individuals were negatively correlated with the IBS within dyads during the emotional communication stage. The findings suggest that the dysfunctional emotional interaction of social avoidant individuals may be attributed to the negative impact of emotional stimuli processing during emotional communication.

11.
J Hazard Mater ; 480: 135821, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39276731

RESUMEN

Antibiotic resistance can be transferred into the food chain, leading to increased risks to human health from ready-to-eat vegetables. Mitigating the transmission of antibiotic resistance from soil to vegetables by green materials is of great significance. Here, we deciphered the roles of biochar and theaflavins in mitigating antibiotic resistance genes (ARGs) and antibiotic-resistant pathogens (ARPs) in a soil-lettuce continuum. Metagenomic results showed that biochar led to a significant decrease in the abundance of ARGs in lettuce leaves, while theaflavins contributed to a significant reduction in the diversity and abundance of ARGs in soil, particularly targeting dominant ARG types such as sulfonamide and aminoglycoside resistance genes. Meanwhile, biochar and theaflavins alleviated the potential mobility of ARGs, in lettuce leaves and soil, respectively, including the spread of ARGs to human pathogens. In addition, the diversity of ARG hosts was reduced in the soil-lettuce continuum and ARPs were not detected in lettuce leaves after the application of biochar or theaflavins. Overall, this study provides a novel perspective on green materials for mitigating the antibiotic resistome and ARPs in the soil-lettuce continuum, contributing to food security and human health.

12.
Food Funct ; 15(18): 9552-9562, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39225754

RESUMEN

Tea consumption is avoided by some due to concerns about its potential to cause anemia. To clarify this impact, we assessed the association between tea intake and anemia in a Chinese prospective cohort study and by Mendelian randomization (MR). We analyzed associations of tea intake with anemia using data from the baseline (N = 30 085) and three subsequent follow-ups (the first: N = 17 898; the second: N = 10 435; the third: N = 5311) in the Guangzhou Biobank Cohort Study (GBCS). We also assessed the causal effect of tea intake on anemia, hemoglobin (Hgb) and hematocrit (Hct) using two-sample MR with summary statistics from relevant genome-wide association studies and the UK Biobank (N = 447 485). At the baseline, compared with never-drinkers, regular tea drinkers had higher levels of Hgb and Hct and a lower risk of anemia after adjustment for confounders (all P < 0.05; all P for trend ≤0.006). Prospectively, compared with never-drinkers, regular tea drinkers had higher Hgb (g L-1) (ß = 0.69; 95% CI, 0.28 to 1.10; P for trend <0.001) and Hct (%) (ß = 0.30; 95% CI, 0.19 to 0.41; P for trend <0.001), but no significant difference in anemia risk (OR = 0.91; 95% CI, 0.82 to 1.02; P for trend = 0.071). MR analyses showed no association between tea intake and anemia, Hgb and Hct. Through triangulation of evidence using a Chinese cohort and genetics, tea consumption appears unlikely to impact anemia risk.


Asunto(s)
Anemia , Hemoglobinas , Análisis de la Aleatorización Mendeliana , , Humanos , Persona de Mediana Edad , Femenino , Masculino , Estudios Prospectivos , Anemia/epidemiología , Anciano , Hemoglobinas/metabolismo , Hemoglobinas/análisis , China/epidemiología , Adulto , Factores de Riesgo , Estudio de Asociación del Genoma Completo , Estudios de Cohortes
13.
Mar Pollut Bull ; 207: 116904, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39226821

RESUMEN

Biodiversity in the Bohai Sea is threatened by climate change and human activities. An analysis based on decadal macrobenthic community data was conducted to assess the ecological health. These findings revealed the temporal and spatial variations in species composition and biodiversity, which were primarily influenced by depth, temperature and dissolved oxygen content. The community structure in 2014 exhibited a 70 % dissimilarity compared to other years, and biodiversity was lower in 2014. The dominant species showed a trend towards miniaturization. Abundance-biomass comparison curves indicated that community disturbance improved by implementing various policies. Overall, communities in the Bohai Sea remained stable, except in the Bohai Strait (BH), where synchronous fluctuations with an increasing trend were observed. Enhancing biodiversity and addressing the risks associated with losing single species are essential for maintaining community stability. The community also displayed synchronous tendencies in Laizhou Bay, emphasizing the need for continued long-term monitoring.


Asunto(s)
Biodiversidad , Invertebrados , China , Animales , Monitoreo del Ambiente , Cambio Climático , Océanos y Mares , Organismos Acuáticos , Biomasa , Ecosistema
14.
Geroscience ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230773

RESUMEN

BACKGROUND: To examine the associations of physical activity (PA) and sedentary behavior (SB) with longevity and age acceleration (AA) using observational and Mendelian randomization (MR) studies, and quantify the mediating effects of lipids. METHODS: In Guangzhou Biobank Cohort Study (GBCS), PA and SB were assessed by the Chinese Version of the International Physical Activity Questionnaire. Longevity was defined as participants whose age at follow-up or at death was at or above the 90th age percentile. AA was defined as the residual resulting from a linear model that regressed phenotypic age against chronological age. Linear regression and Poisson regression with robust error variance were used to assess the associations of total and specific PA in different intensities, and SB with AA and longevity, yielding ßs or relative risks (RRs) and 95% confidence intervals (CIs). Two-sample MR was conducted to examine the causal effects. Mediation analysis was used to assess the mediating effects of lipids. RESULTS: Of 20,924 participants aged 50 + years in GBCS, during an average follow-up of 15.0 years, compared with low PA, moderate and high PA were associated with higher likelihood of longevity (RR (95% CI): 1.56 (1.16, 2.11), 1.66 (1.24, 2.21), respectively), and also cross-sectionally associated with lower AA (ß (95% CI): -1.43 (-2.41, -0.45), -2.09 (-3.06, -1.11) years, respectively). Higher levels of moderate PA (MPA) were associated with higher likelihood of longevity and lower AA, whereas vigorous PA (VPA) showed opposite effects. The association of PA with longevity observed in GBCS was mediated by low-density lipoprotein cholesterol (LDL-C) by 8.23% (95% CI: 3.58-39.61%), while the association with AA was mediated through LDL-C, triglycerides and total cholesterol by 5.13% (3.94-7.30%), 7.81% (5.98-11.17%), and 3.37% (2.59-4.80%), respectively. Additionally, in two-sample MR, SB was positively associated with AA (ß (95% CI): 1.02 (0.67, 1.36) years). CONCLUSIONS: PA showed protective effects on longevity and AA, with the effects being partly mediated through lipids. Conversely, SB had a detrimental impact on AA. MPA was associated with higher likelihood of longevity and reduced AA, whereas VPA showed adverse effects. Our findings reinforce the recommendation of "sit less and move more" to promote healthy longevity, and highlight the potential risks associated with VPA in the elderly.

15.
Vet Comp Oncol ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221701

RESUMEN

Canine mammary gland tumour (CMT) is the most common spontaneous tumour in intact female dogs and often exhibits metastases. Auranofin (AF) is a gold complex used for treating rheumatism. The excellent anti-tumour ability of AF has been demonstrated in various types of human and canine tumours. In this study, five CMT cell lines (CIPp, CMT-7364, CHMp, CIPm and CTBp) and three CMT primary cells (G7894, L1883 and L6783) were used to explore the anti-tumour effect of AF on CMT. Two CMT cell lines (CIPp and CMT-7364) were used to search the underlying mechanism of the effect of AF on CMT. The results showed that AF inhibited the growth, migration, invasion, and colony formation abilities of CMT cells. Additionally, the growth of CMT in a 3D cell culture model was effectively suppressed by AF. Furthermore, AF induced cell apoptosis of CMT cells via the PI3K/AKT pathway. In conclusion, AF effectively induces CMT apoptosis by regulating the PI3K/AKT pathway, indicating that AF should be explored as a potential CMT treatment in future studies.

16.
BMC Musculoskelet Disord ; 25(1): 630, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39113005

RESUMEN

BACKGROUND: Hemoglobin-to-red blood cell distribution width ratio (HRR) had great predictive value for the prognosis of malignant tumors and cardiovascular disease. However, its predictive value for the occurrence of acute kidney injury (AKI) in elderly intertrochanteric fracture patients remains unclear. This study aims to analyze the correlation between the early postoperative HRR and the risk of postoperative AKI in elderly intertrochanteric fracture patients. METHODS: We reviewed the medical records of 307 elderly intertrochanteric fracture patients in this single-center retrospective cohort study. We performed univariate analysis on the relevant parameters, and parameters with significant differences were included in the following logistic regression model for multivariate analysis. Then, we used a receiver operating characteristic (ROC) curve to evaluate the predictive value of the early postoperative HRR level for AKI in elderly intertrochanteric fracture patients. Patients were divided into a high HRR group and a low HRR group according to the cutoff point determined by ROC curve analysis. Subsequently, the relevance between postoperative HRR and AKI was further determined using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: The area under the curve of the early postoperative HRR for predicting postoperative AKI was 0.714 (95% CI: 0.618-0.809). The cutoff value was 5.44. The sensitivity was 72.7%, and the specificity was 70.8%. Patients were divided into low HRR (⩽ 5.44) and high HRR (> 5.44) groups according to the cutoff value. PSM and IPTW analysis indicated that the risk of AKI in the low HRR group was significantly higher than that in the high HRR group in both the matched cohort (OR = 6.914, 95% CI: 1.714-46.603, p = 0.016) and the weighted group (OR = 2.784, 95% CI: 1.415-5.811, p = 0.040). CONCLUSIONS: Early postoperative HRR is an accurate, accessible, and economical blood test parameter that can predict the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture.


Asunto(s)
Lesión Renal Aguda , Índices de Eritrocitos , Hemoglobinas , Fracturas de Cadera , Complicaciones Posoperatorias , Valor Predictivo de las Pruebas , Humanos , Femenino , Masculino , Fracturas de Cadera/cirugía , Fracturas de Cadera/sangre , Anciano , Estudios Retrospectivos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Anciano de 80 o más Años , Hemoglobinas/análisis , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Curva ROC , Factores de Riesgo , Pronóstico
17.
Carbohydr Res ; 544: 109230, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39137472

RESUMEN

Lycium barbarum L. is of great significance medicinal and edible plant, which is native to N. & Central China. The extensive health benefits of L. barbarum have earned it great respect in traditional medicine for centuries. Lycium barbarum polysaccharides (LBPs) being recognized as one of the most crucial bioactive compounds found within this plant, with it exhibit a diverse range of pharmacological activities and nutritional functions, thereby generating substantial market demand and broad application prospects. To gain a more comprehensive understanding of LBPs, the review discussed the extraction, purification and structural-property relationships of these compounds. In addition, this review provides a comprehensive summary of the potential mechanisms underlying various biological activities attributed to LBPs, including immune modulation, antioxidant effects, neuroprotection, hepatoprotection, and antitumor properties. The application status and the future research directions of LBPs were subsequently presented. This review will establish a robust foundation and serve as an invaluable resource for future research and advancements in the field of LBPs.


Asunto(s)
Medicamentos Herbarios Chinos , Lycium , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Humanos , Lycium/química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Relación Estructura-Actividad , Animales , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología
18.
Exp Neurol ; 380: 114922, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39142371

RESUMEN

OBJECTIVE: Multiple factors contribute to the development of perioperative neurocognitive disorders (PND). This study was designed to investigate whether Histone Deacetylase 6 (HDAC6) was involved in the formation of postoperative cognitive dysfunction in elderly mice by regulating the degree of acetylation of heat shock protein (HSP90) and related protein functions and quantities. METHODS: C57BL/6 J male mice were randomly divided into six groups: control naive (group Control), anesthesia (group Anesthesia), splenectomy surgery (group Surgery), splenectomy surgery plus dissolvent (group Vehicles), splenectomy surgery plus the inhibitor ACY-1215 (group Ricolinostat), and splenectomy surgery plus the inhibitor RU-486(group Mifepristone). After the mice were trained for Morris Water Maze (MWM) test for five days, anesthesia and operational surgery were carried out the following day. Cognitive function was assessed on the 1st, 3rd and 7th days post-surgery. The hippocampi were harvested on days 1, 3, and 7 post-surgeries for Western blots and ELISA assays. RESULTS: Mice with the splenectomy surgery displayed the activation of the hypothalamic-pituitary-adrenal axis (HPA-axis), marked an increase in adrenocorticotropic hormone (ACTH), glucocorticoid, mineralocorticoid at the molecular level and impaired spatial memory in the MWM test. The hippocampus of surgical groups showed a decrease in acetylated HSP90, a rise in glucocorticoid receptor (GR)-HSP90 association, and an increase in GR phosphorylation and translocation. HDAC6 was increased after the surgical treated. Using two specific inhibitors, HDAC6 inhibitor Ricolinostat (ACY-1215) and GR inhibitor Mifepristone (RU-486), can partially mitigate the effects caused by surgical operation. CONCLUSIONS: Abdominal surgery may impair hippocampal spatial memory, possibly through the HDAC6-triggered increase in the function of HSP90, consequently strengthening the negative role of steroids in cognitive function. Targeting HDAC6- HSP90/GR signaling may provide a potential avenue for the treatment of the impairment of cognitive function after surgery.


Asunto(s)
Proteínas HSP90 de Choque Térmico , Ratones Endogámicos C57BL , Receptores de Glucocorticoides , Transducción de Señal , Animales , Masculino , Ratones , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/antagonistas & inhibidores , Histona Desacetilasa 6/metabolismo , Histona Desacetilasa 6/antagonistas & inhibidores , Esplenectomía , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/etiología , Mifepristona/farmacología , Trastornos Neurocognitivos/metabolismo , Trastornos Neurocognitivos/etiología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Envejecimiento/metabolismo , Histona Desacetilasas/metabolismo , Pirimidinas/farmacología , Ácidos Hidroxámicos/farmacología
19.
J Hazard Mater ; 479: 135574, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39197278

RESUMEN

Tire wear particles (TWPs) pollution is widely present in soil, especially in areas severely affected by traffic. Herein, regular variation of fungal biomass with TWPs was found in soils with different distances from the highway. In addition, the concentrations of benzothiazole compounds (BTHs), an important class of rubber vulcanization accelerators, were found to be positively correlated to the TWPs abundance. Sixty days' soil microcosm experiments were conducted to further confirm the adverse effect of TWPs and BTHs on soil fungi. TWPs spiking at 1000 mg/kg, a detectable level in the roadside, resulted in significant reduction of biomass and significant changes of soil fungal community structure, with Eurotium and Polyporales being the sensitive species. BTH+ 2-hydroxybenzothiazole (OHBT) (the dominant BTHs in soil) spiking at 200 ng/kg, the dose equivalent to 1000 mg/kg TWPs pollution, also caused a similar magnitude of soil fungal biomass reduction. Adonis demonstrated no significant difference of fungal community structure between TWPs and BTH+OHBT spiked soil, suggesting the adverse effect of TWPs on soil fungi may be explained by the act of BTHs. Pure culture using the representative soil fungi Eurotium and Polyporales also confirmed that BTHs were the main contributors to the adverse effect of TWPs on soil fungi.


Asunto(s)
Benzotiazoles , Hongos , Goma , Microbiología del Suelo , Contaminantes del Suelo , Hongos/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Biomasa
20.
J Org Chem ; 89(18): 13735-13743, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39213645

RESUMEN

With the assistance of nickel as catalyst, 2,2'-bipyridine (bpy) as ligand, and manganese as reducing metal, the reductive amidation of isocyanates with readily accessible aryl fluorosulfates could be successfully accomplished. The reactions proceeded effectively via C-O bond activation in DMF at room temperature, enabling the facile synthesis of a range of structurally diverse amides in moderate to high yields with broad functionality compatibility. In addition, the synthetic usefulness of the method was further demonstrated by applying the reaction in scale-up synthesis and the late-stage functionalization of complex molecules with biological activities.

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