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The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure (BP). We administered hydroxylamine hydrochloride (HA), a cystathionine-ß-synthase (CBS) inhibitor, into the PVN to suppress endogenous hydrogen sulfide (H2S) and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the NS+PVN vehicle group, the NS+PVN HA group, the HS+PVN vehicle group, and the HS+PVN HA group, with 10 rats in each group. The rats in the NS (normal salt) groups were fed a normal-salt diet containing 0.3% NaCl, while the HS (high salt) groups were fed a high-salt diet containing 8% NaCl. The mean arterial pressure (MAP) was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini-pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H2S in the PVN and plasma norepinephrine (NE) using ELISA. Additionally, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time PCR. In the current study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of high salt-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.
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PURPOSE: The purpose of this study was to evaluate the correlations and consistency among the central corneal thickness (CCT) of healthy myopic patients measured with three different anterior segment analysis systems. DESIGN: This was a retrospective study. The study included myopia patients who had undergone preoperative examinations in the refractive surgery department of our hospital between January 2021 and December 2023. The CCT was measured separately using Pentacam, Sirius, and IOLMaster 700. METHODS: Statistical analysis was conducted using SPSS software. Correlations among the three groups of measured values were assessed using the Pearson method, and a simple scatter plot and fitting line were drawn. BlandâAltman scatter plots and 95% limits of agreement (LoAs) were used to evaluate consistency in the data among the systems. RESULTS: A total of 269 patients participated in the study, including 134 males (49.8%) and 135 females (50.2%). The CCT measurements by Pentacam, Sirius, and IOLMaster 700 instruments were found to be 541.63±31.67µm, 541.74±33.36µm, and 548.90±34.19µm respectively; significant differences were observed among these measurements (p<0.05). Significant differences were also observed in CCT between Pentacam and IOLMaster 700 as well as between Sirius and IOLMaster 700 (p<0.05). The CCT measurements by all three devices showed high positive correlation with all p values less than 0.001: Pentacam and Sirius, r=0.972; Pentacam and IOLMaster 700, r=0.966; and Sirius and IOLMaster 700, r=0.962. The respective 95% LoAs were -0.18â¼0.18; -1.51â¼-1.11; and -1.52â¼-1. CONCLUSION: The results indicate that there is a high correlation in measuring CCT for healthy myopic eyes using three different anterior segment analysis systems. However, the differences in the values measured by the three devices were statistically significant. Therefore, in actual clinical practice, it is suggested that the same device should be used to measureand evaluate the CCT across visits.
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This study aimed to evaluate the effects of dietary supplementation with different types of Saccharomyces cerevisiae fermentation products (SCFP) on lactational performance, metabolism, acute phase protein response, and antioxidant capacities in dairy cows from -21 to 56 d in milk (DIM). One hundred and 80 multiparous Holstein dairy cows were blocked by parity, expected calving date, pre-trial body condition score, and previous 305-d ME yield, and then randomly assigned to 1 of 3 dietary treatments: basal diet (CON; n = 60), basal diet supplemented with 40 g/d of SCFP1 (XPC; n = 60; XPC, Diamond V, Cedar Rapids, IA), and basal diet supplemented with 19 g/d of SCFP2 (NTK; n = 60, NutriTek®, Diamond V, Cedar Rapids, IA). Blood (n = 15, 13 and 12 in the CON, XPC and NTK groups, respectively) was sampled at -7 ± 3, + 3, + 7, + 21, and + 28 d, and milk samples (n = 19, 18 and 15 in the CON, XPC and NTK groups, respectively) was sampled during 1-8 wk from a subset of cows from -21 to 56 d relative to calving. Data were analyzed using the MIXED procedure in SAS (SAS Institute Inc.). All data were subjected to repeated measures ANOVA. Dietary treatment (TRT), time, and their interaction (TRT × time) were considered as fixed effects and cow as the random effect. Cows fed XPC and NTK had greater energy-corrected milk (ECM). Supplementing NTK increased milk fat content and yield, and 3.5% fat-corrected milk (FCM) yield compared with CON. Milk urea nitrogen (MUN) was lower in XPC cows than CON. SCFP supplementation decreased plasma ß-hydroxybutyrate (BHB), ceruloplasmin (CER), haptoglobin (HPT), and interleukin-1ß (IL-1ß) concentrations, whereas increased plasma phosphorus (P) concentrations. In addition, cows fed NTK showed lower creatinine (CR) and cortisol (COR) concentrations but increased plasma calcium (Ca) and myeloperoxidase (MPO) concentrations than those in the CON cows. In addition, cows fed NTK and XPC both had reduced plasma concentrations of serum amyloid-A (SAA) at 3 DIM of lactation compared with CON fed cows. Furthermore, SCFP cows had greater concentrations of plasma glucose (GLU) and calcium (Ca) than CON cows at 7 DIM, and greater concentrations of plasma phosphorus (P) at 21 DIM. Between different SCFP type fed groups, plasma concentrations of nonesterified fatty acids (NEFA), MDA, creatinine (CR), SAA, and HPT were lower in cows fed NTK compared with cows fed XPC at 7 DIM. Overall, our results indicate the potential benefits of supplementing SCFP in transition dairy cows by modulating immunity, liver metabolic function and supporting ECM yield. The results also suggest that NutriTek at 19 g/d appears to support the performance and health of dairy cows better compared with XPC at 40 g/d, based on improved metabolic and inflammatory status during the transition period.
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This study investigated the characteristics of dissolved organic matter (DOM) in two distinct water bodies, through the utilization of three-dimensional fluorescence spectroscopy coupled with self-organizing map (SOM) methodology. Specifically, this analysis concentrated on neurons 3, 14, and 17 within the SOM model, identifying notable differences in the DOM compositions of a coal subsidence water body (TX) and the MaChang Reservoir (MC). The humic substance content of DOM TX exceeded that of MC. The origin of DOM in TX was primarily linked to agricultural inputs and rainfall runoff, whereas the DOM in MC was associated with human activities, displaying distinctive autochthonous features and heightened biological activity. Principal component analysis revealed that humic substances dominated the DOM in TX, while the natural DOM in MC was primarily autochthonous. Furthermore, a multiple linear regression model (MLR) determined that external pollution was responsible for 99.11% of variation in the humification index (HIX) of water bodies.
Subject(s)
Humic Substances , Humic Substances/analysis , Organic Chemicals/analysis , Organic Chemicals/chemistry , Environmental Monitoring/methods , Spectrometry, Fluorescence/methods , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Principal Component AnalysisABSTRACT
PURPOSE: Bilayered restorations have both the strength of the substructure material and the esthetics of the veneer material; however, they should have appropriate bonding between the two materials. This study aimed to evaluate the shear bond strength (SBS) according to the substructure material and veneering technique used in bilayered restorations. MATERIALS AND METHODS: The experimental group was divided into four groups (n = 15 per group) based on the substructure materials (cobalt-chromium [Co-Cr] alloy and 3 mol% yttrium-stabilized tetragonal zirconia polycrystal [3Y-TZP]) and veneering techniques (pressing and layering). Veneering was performed with disk shape (diameter: 5 mm, height: 2 mm) on a substructure using each veneering technique. Shear stress was applied to the interface of the substructure and the veneering ceramic using a universal testing machine. The shear bond strength, according to the substructure and veneering technique, was analyzed using a two-way analysis of variance with a post-hoc Tukey's honestly significant difference test. The failure mode was observed, and the surface was analyzed using a scanning electron microscope and energy-dispersive spectroscopy. RESULTS: The shSBS of the Co-Cr alloy and 3Y-TZP substructure was not different (p > 0.05); however, the pressing technique showed a higher SBS than the layering technique (p < 0.05). The SBS did not differ depending on the veneering technique in the Co-Cr alloys (p > 0.05), whereas the SBS in the pressing technique was higher than that in the layering technique for 3Y-TZP (p < 0.05). In the layering technique, the Co-Cr alloy showed a higher SBS than 3Y-TZP (p < 0.05). In the failure mode, mixed failure occurred most frequently in all groups. Extensive elemental interdiffusion was observed through the opaque layer in the Co-Cr alloy, regardless of the veneering technique. In 3Y-TZP, a wider range of elemental interdiffusion was observed in the pressing technique than in the layering technique. CONCLUSIONS: In bilayered restorations with a 3Y-TZP substructure, the pressing technique yielded higher bonding strength than layering. Using the layering technique, 3Y-TZP showed a lower SBS than the Co-Cr alloy. In bilayered restorations using 3Y-TZP as a substructure, the veneering technique and thermal compatibility of the materials must be considered.
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Touch serves as an important medium for human-environment interaction. The piezoresistive tactile sensor has attracted much attention due to its convenient technology, simple principle, and convenient signal acquisition and analysis. In this paper, conductive beads-on-string polyvinyl alcohol (PVA)/polyaniline doped with dodecyl benzene sulfonic acid (PANI-DBSA) nanofibers were fabricated via the electrospinning technique. Due to the special nanostructure of PVA-coated PANI-DBSA, the tactile sensor presented a wide measuring range of 12 Pa-121 kPa and appreciable sensitivity of 8.576 kPa-1 at 12 Pa~484 Pa. In addition, the response time and recovery time of the sensor were approximately 500 ms, demonstrating promising prospects in the field of tactile sensing for active upper limb prostheses.
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Sodium para-aminosalicylic acid (PAS-Na) treatment for manganese (Mn) intoxication has shown efficacy in experimental and clinical studies, giving rise to additional studies on its efficacy for lead (Pb) neurotoxicity and its associated mechanisms of neuroprotection. The difference between PAS-Na and other metal complexing agents, such as edetate calcium sodium (CaNa2-EDTA), is firstly that PAS-Na can readily pass through the blood-brain barrier (BBB), and complex and facilitate the excretion of manganese and lead. Secondly, PAS-Na has anti-inflammatory effects. Recent studies have broadened the understanding on the mechanisms associated with efficacy of PAS-Na. The latter has been shown to modulate multifarious manganese- and lead- induced neurotoxicity, via its anti-apoptotic and anti-inflammatory effects, as well as its ability to inhibit pyroptosis, and regulate abnormal autophagic processes. These observations provide novel scientific bases and new concepts for the treatment of lead, mercury, copper, thallium, as well as other toxic encephalopathies, and implicate PAS-Na as a compound with greater prospects for clinical medical application.
Subject(s)
Aminosalicylic Acid , Lead Poisoning , Manganese Poisoning , Humans , Animals , Aminosalicylic Acid/therapeutic use , Manganese Poisoning/drug therapy , Lead Poisoning/drug therapy , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Manganese/toxicityABSTRACT
We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment.
Subject(s)
Aminosalicylic Acid , Manganese , Synapses , Animals , Rats , PC12 Cells , Synapses/drug effects , Male , Aminosalicylic Acid/pharmacology , Manganese/toxicity , Cerebral Cortex/drug effects , Cerebral Cortex/pathology , Cerebral Cortex/metabolism , Rats, Sprague-Dawley , Iron/metabolism , Neuroprotective Agents/pharmacology , Maze Learning/drug effects , Neurotoxicity Syndromes/prevention & control , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/pathology , Disease Models, AnimalABSTRACT
PURPOSE: The study object was to determine the relationship between leptin and diabetes. METHODS: We searched for the literature on the relationship between leptin and diabetes from PubMed, EMBASE, Cochrane Library, and CNKI databases. We carried out the meta-analysis by calculating the Std. Mean Difference (SMD) and 95% confidence intervals (CIs) to study the relationship between leptin and diabetes. We performed the Chi-square-based Q test and I2 statistics to evaluate the potential heterogeneity, and the sensitivity analysis was performed to evaluate the stability of our results. Moreover, Begg's test was performed to evaluate the publication bias. RESULTS: There are 10 studies in this study for meta-analysis, which include 1879 patients (diabetic (n = 1024); and nondiabetic patients (n = 855)). The results indicated that the levels of serum leptin were significantly increased in patients with diabetes (SMD = 1.78, 95% CI [0.81, 2.76]), especially those with gestational diabetes mellitus compared with controls (SMD = 3.03, 95% CI [1.21, 4.86]). However, the results showed that there was no difference in serum leptin levels between type 2 diabetes and controls (SMD = 0.34, 95% CI [-1.06, 1.74]). CONCLUSIONS: Our analysis indicated that the levels of serum leptin were significantly elevated in patients with diabetes especially those with gestational diabetes mellitus compared with controls.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Leptin , Humans , Leptin/blood , Diabetes Mellitus, Type 2/blood , Diabetes, Gestational/blood , Female , PregnancyABSTRACT
BACKGROUND: The geriatric nutritional risk index (GNRI) is a prognostic indicator for several diseases, meanwhile, nutrition and inflammation play important roles in the disease progression of amyotrophic lateral sclerosis (ALS). However, the association between the GNRI and ALS remains unknown. METHODS: 443 patients diagnosed with ALS were divided into two groups based on the GNRI levels. Associations between GNRI and survival time were analyzed using Kaplan-Meier curves and compared by the log-rank test. Univariate and multivariate analyses were used to assess their prognostic values for survival time. Spearman correlation analysis was used to evaluate the correlation coefficients between GNRI and other clinical variables. RESULTS: No significant differences were found in diagnostic delay between the two groups. The onset age and disease progression rate (DPR) were significantly lower in high GNRI group while forced vital capacity (FVC), revised version of the ALS functional rating scale (ALSFRS-R), serum albumin and body mass index (BMI) were significantly lower in low GNRI group. Lower GNRI levels were linked with shorter ALS patients' survival time by Kaplan-Meier curves. The univariate and multivariate analysis identified the onset age, gender, onset site, diagnostic delay, DRP and GNRI as predictors of survival time in patients with ALS. CONCLUSION: Nutritional status was closely corelated with ALS progression. The GNRI may be used as a potential prognostic indictor for ALS patients.
Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Aged , Prognosis , Amyotrophic Lateral Sclerosis/complications , Amyotrophic Lateral Sclerosis/diagnosis , Delayed Diagnosis , Nutritional Status , Disease Progression , Risk Factors , Retrospective StudiesABSTRACT
Glucose plays a vital part in milk protein synthesis through the mTOR signaling pathway in bovine mammary epithelial cells (BMEC). The objectives of this study were to determine how glucose affects hexokinase (HK) activity in BMEC and investigate the regulatory effect of HK in kappa casein (CSN3) synthesis via the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway in BMEC. For this, HK1 and HK2 were knocked out in BMEC using the CRISPR/Cas9 system. The gene and protein expression, glucose uptake, and cell proliferation were measured. We found that glucose uptake, cell proliferation, CSN3 gene expression levels, and expression of HK1 and HK2 increased with increasing glucose concentrations. Notably, glucose uptake was significantly reduced in HK2 knockout (HK2KO) BMEC treated with 17.5 mM glucose. Moreover, under the same glucose treatment conditions, the proliferative ability and abundance of CSN3 were significantly diminished in both HK1 knockout (HK1KO) and HK2KO BMEC compared with that in wild-type BEMC. We further observed that the phosphorylation levels of ribosome protein subunit 6 kinase 1 (S6K1) were reduced in HK1KO and HK2KO BMEC following treatment with 17.5 mM glucose. As expected, the levels of glucose-6-phosphate and the mRNA expression levels of glycolysis-related genes were decreased in both HK1KO and HK2KO BMEC following glucose treatment. These results indicated that the knockout of HK1 and HK2 inhibited cell proliferation and CSN3 expression in BMEC under glucose treatment, which may be associated with the inactivation of the S6K1 and inhibition of glycolysis.
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AIMS: Clonal haematopoiesis of indeterminate potential (CHIP), defined as a clonal expansion of age-related recurrent somatic mutations, has recently emerged as a novel cardiovascular risk factor. However, the precise role of CHIP in the development of atherosclerotic cardiovascular disease (ASCVD) remains unclear. METHODS AND RESULTS: Among 4300 asymptomatic Korean participants aged 40-79 years, we investigated the risk of ASCVD by CHIP and the interplay between CHIP and conventional risk factors in ASCVD development. Additionally, we assessed changes in coronary arteries based on the presence of CHIP using coronary computed tomography angiography (CCTA). CHIP was present in 363 participants (8.4%), and its prevalence increased with age. Commonly mutated genes were DNMT3A, TET2, and ASXL1, in order. During the follow-up (median 4.7 years), 18 ASCVD cases (5.0%) were observed in CHIP carriers vs. 62 (1.6%) in non-carriers (P < 0.001), indicating an elevated risk of ASCVD associated with CHIP [adjusted hazard ratio (HR) 2.49; 95% confidence interval (CI) 1.45-4.29; P < 0.001]. Notably, with high levels of LDL cholesterol, CHIP enhanced the risk of ASCVD (adjusted HR 6.20; 95% CI 3.14-12.23; P < 0.001), demonstrating synergism between CHIP and LDL cholesterol levels (S-index 4.94; 95% CI 1.08-22.53; P = 0.039). Serial CCTAs confirmed that CHIP, in conjunction with high LDL cholesterol levels, had a significant early impact on coronary arteries, revealing new measurable coronary atherosclerosis, mainly with unstable plaque, in proximal lesions. CONCLUSION: The presence of CHIP was significantly associated with the risk of ASCVD, promoting the early stage of atherosclerosis through synergy with high LDL cholesterol in the general population.
In this cohort study of 4300 asymptomatic community-dwelling Korean adults, we demonstrated a detailed interplay between clonal haematopoiesis of indeterminate potential (CHIP) and conventional risk factors in the development of atherosclerotic cardiovascular disease (ASCVD).The presence of CHIP significantly increased the risk of ASCVD in the general population, displaying a notable synergistic effect with high levels of LDL cholesterol.Analyses of serial coronary computed tomography angiography scans revealed that CHIP, in conjunction with high LDL cholesterol levels, may contribute to the promotion of 'early' stage in coronary atherosclerosis, providing new insights into CHIP-associated atherosclerosis in the primary prevention.
Subject(s)
Biomarkers , Cholesterol, LDL , Clonal Hematopoiesis , Humans , Middle Aged , Male , Female , Adult , Aged , Republic of Korea/epidemiology , Cholesterol, LDL/blood , Risk Assessment , Biomarkers/blood , Coronary Artery Disease/epidemiology , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/blood , Risk Factors , Computed Tomography Angiography , Prevalence , Coronary Angiography , Mutation , Atherosclerosis/epidemiology , Atherosclerosis/blood , Atherosclerosis/geneticsABSTRACT
BACKGROUND AND AIMS: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. METHODS: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. RESULTS: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). CONCLUSIONS: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.
Subject(s)
Atrial Fibrillation , Brain Ischemia , Diabetes Mellitus , Heart Failure , Ischemic Stroke , Stroke , Aged , Humans , Middle Aged , Atrial Fibrillation/epidemiology , Atrial Fibrillation/genetics , Atrial Fibrillation/complications , Brain Ischemia/complications , Clonal Hematopoiesis/genetics , Cohort Studies , East Asian People , Heart Failure/complications , Ischemic Stroke/complications , Stroke/epidemiologyABSTRACT
BACKGROUND: Environmental lead (Pb) exposure have been suggested as a causative factor for amyotrophic lateral sclerosis (ALS). However, the role of Pb content of human body in ALS outcomes has not been quantified clearly. The purpose of this study was to apply Bayesian networks to forecast the risk of Pb exposure on the disease occurrence. METHODS: We retrospectively collected medical records of ALS inpatients who underwent blood Pb testing, while matched controlled inpatients on age, gender, hospital ward and admission time according to the radio of 1:9. Tree Augmented Naïve Bayes (TAN), a semi-naïve Bayes classifier, was established to predict probability of ALS or controls with risk factors. RESULTS: A total of 140 inpatients were included in this study. The whole blood Pb levels of ALS patients (57.00 µg/L) were more than twice as high as the controls (27.71 µg/L). Using the blood Pb concentrations to calculate probability of ALS, TAN produced the total coincidence rate of 90.00%. The specificity, sensitivity of Pb for ALS prediction was 0.79, or 0.74, respectively. CONCLUSION: Therefore, these results provided quantitative evidence that Pb exposure may contribute to the development of ALS. Bayesian networks may be used to predict the ALS early onset with blood Pb levels.
Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Amyotrophic Lateral Sclerosis/epidemiology , Bayes Theorem , Lead , Retrospective Studies , Risk FactorsABSTRACT
This experiment investigated the effects of different levels of bile acid (BA) additives in diets on the lactation performance, serum antioxidant metabolites, and serum biochemical indices of 60 multiparous mid-lactation dairy cows. The cows were randomized to receive one of the four homogeneous treatments, with the BA preparation supplemented at 0, 6, 12, and 18 g/head/d. The experiment lasted for 14 weeks. The first 2 weeks were the pre-feeding period. The milk yield and composition data were recorded weekly, and the dry matter intake and antioxidative blood index were analyzed on the 6th, 10th, and 14th weeks of the study. On the 84th day of the experiment, the experimental group exhibited significantly higher levels of total protein and albumin, by 57.5% and 55.6%, respectively, compared to the control group (p < 0.05). On both the 28th and 84th days of the trial, the experimental group showed a markedly higher lipase content compared to the control group, by 26.5% and 25.2%, respectively (p < 0.05). Furthermore, the experimental group displayed notably elevated levels of superoxide dismutase, glutathione peroxidase, and total antioxidant capacity, surpassing the control group by 17.4%, 21.6%, and 8.7%, respectively. In conclusion, BA additives improve the serum antioxidant indices of dairy cows, thereby enhancing the performance of these cows.
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In recent years, the ubiquitin-proteasome system (UPS) has become a hot spot in medical research in cervical cancer (CC) and has received extensive attention. Among them, ubiquitin-specific protease 14 (USP14) is involved in a wide variety of typical cell signaling pathways and is recognized to be involved in the progression of most known tumors. However, the expression and significance of USP14 in CC have not been directly studied. Through database analysis, we found that USP14 was overexpressed in CC, which influenced the FIGO stage and prognosis of CC patients, and it was positively correlated with the expression level of ß-catenin. In this study, USP14 promoted the G1-S phase transition of Hela and Siha cells and inhibited cell apoptosis, thereby promoting the proliferation, migration, and invasion of CC cells. In addition, USP14 also significantly promoted the growth of subcutaneous tumor in nude mice. We also found that overexpression of USP14 significantly upregulated ß-catenin expression and increased the activity of Wnt/ß-catenin signaling pathway. While knockdown of USP14 resulted in the opposite. These results suggest that USP14 may promote the proliferation of CC by up-regulating the expression of ß-catenin, contributing to a deeper understanding of the mechanisms of CC and providing a potential therapeutic target.
Subject(s)
Uterine Cervical Neoplasms , beta Catenin , Animals , Female , Humans , Mice , beta Catenin/genetics , beta Catenin/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Mice, Nude , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/metabolism , Uterine Cervical Neoplasms/metabolism , Wnt Signaling PathwayABSTRACT
The aim of study was to address the effects of manganese and iron, alone and in combination, on apoptosis of BV2 microglia cells, and to determine if combined exposure to these metals augments their individual toxicity. We used a murine microglial BV2 cell line. Cell cytotoxicity was analyzed by propidium iodide (PI) exclusion assay. Cell ROS production was analyzed by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) probe staining. Pro-inflammatory cytokine production was monitored by ELISA. Cell apoptosis was analyzed by PE Annexin V/7-AAD staining. Mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting to analyze the effect of manganese, iron alone, or their combined exposure on the activation of caspase9, P53, Bax, and Bcl2 apoptosis signaling pathways. Caspase3 activity was determined using a Colorimetric. Manganese, iron, and their combined exposure for 24 h induced the activation of BV2 microglia cells and increased ROS production and the expression of the inflammatory cytokines, IL-1ß and TNF-α. And we also found that the apoptosis rate increased, mitochondrial membrane potential decreased, apoptosis-related proteins caspase9, P53, Bax, and Bcl2 expression increased, and caspase3 activity increased. Furthermore, we found that combined manganese-iron cytotoxicity was lower than that induced by manganese exposure alone. Manganese, iron alone, or their combination exposure can induce apoptosis in glial cells. Iron can reduce the toxicity of manganese, and there is an antagonistic effect between manganese and iron.
Subject(s)
Iron , Manganese , Mice , Animals , Manganese/toxicity , Manganese/metabolism , Reactive Oxygen Species/metabolism , Iron/metabolism , bcl-2-Associated X Protein/metabolism , Tumor Suppressor Protein p53/metabolism , Apoptosis , Apoptosis Regulatory Proteins/metabolismABSTRACT
BACKGROUND: In the past 20 years, anesthesiology has become one of the most advanced specialties and has undergone rapid development. However, public awareness regarding anesthesiology and anesthesiologists is limited, especially in developing countries. It is important for anesthesiologists to make the public aware of their role during surgery. Therefore, a nationwide survey was set up to investigate public awareness of anesthesiology and anesthesiologists in China. METHOD: A cross-sectional nationwide survey was performed from June 2018 to June 2019 in 34 provinces, municipalities, and autonomous regions across China and an overseas region. The questionnaires of the survey were divided into 2 main parts: general items and research items. General items included the demographic characteristics of the participants; research items consisted of 10 questions about the public's awareness of anesthesiologists and anesthesiology. Data quality control was undertaken by the investigation committee throughout the survey process. RESULTS: The nationwide survey enrolled 1,001,279 participants (male, 40.7%). We found that most of the participants regarded anesthesiologists as doctors. However, public knowledge of anesthesiologists' work and duties during surgery was quite low, with correct response rate ranging from 16.5% to 52.9%, and anesthesiologist responsibilities were often mistakenly attributed to surgeons or nurses. It is disappointing that more than half of participants still thought that, once the patient fell asleep after receiving anesthetics, the anesthesiologist could leave the operating room. Finally, the correct response rate was positively correlated with the economic levels of the regions. CONCLUSIONS: Public awareness regarding anesthesiology and anesthesiologists in China remains inadequate. Due to the biases and characteristics of the participants, the actual situation of the general Chinese public is likely even worse than reflected here. Therefore, extensive measures should be undertaken to improve public knowledge of anesthesiology and anesthesiologists.
Subject(s)
Anesthesiology , Surgeons , Humans , Male , Anesthesiologists , Cross-Sectional Studies , Surveys and Questionnaires , ChinaABSTRACT
Objective: To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD. Methods: Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice. Results: DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA). Conclusion: DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.