ABSTRACT
Although previous studies on the genotypic diversity and antifungal susceptibility of the Cryptococcus neoformans species complex (CNSC) isolates from China revealed ST5 genotype isolates being dominant, the information about the CNSC isolates from Chinese HIV-infected patients is limited. In this study, 171 CNSC isolates from HIV-infected patients in the Chongqing region of Southwest China were genotyped using the International Society for Human and Animal Mycology-multilocus sequence typing consensus scheme, and their antifungal drug susceptibilities were determined following CLSI M27-A3 guidelines. Among 171 isolates, six sequence types (STs) were identified, including the dominant ST5 isolates, the newly reported ST15, and four diploid VNIII isolates (ST632/ST636). Moreover, a total of 1019 CNSC isolates with STs and HIV-status information were collected and analyzed from Mainland China in the present study. A minimum spanning analysis grouped these 1019 isolates into three main subgroups, which were dominated by the ST5 clonal complex (CC5), followed by the ST31 clonal complex (CC31) and ST93 clonal complex (CC93). The trend of resistance or decreasing susceptibility of clinical CNSC isolates to azole agents within HIV-infected patients from the Chongqing region is increasing, especially resistance to fluconazole.
In this paper, novel ST15 and four diploid VNIII isolates (ST632/ST636) were found in 171 CNSC isolates in Southwest China, including evidence for resistance to fluconazole. Moreover, we clustered the 1019 clinical CNSC isolates reported so far from Mainland China into three major subgroups.
Subject(s)
Cryptococcosis , Cryptococcus neoformans , HIV Infections , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Cryptococcosis/microbiology , Cryptococcosis/veterinary , Diploidy , Microbial Sensitivity Tests/veterinary , Genotype , China/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/veterinaryABSTRACT
Current binary defocus technology mainly focuses on fringe generation suitable for specific frequencies without considering fringe adaptability for defocus-degree variation, which decreases the measuring accuracy for this scenario. To achieve a high-quality measurement, we propose a robust binary fringe generation method to minimize the phase error caused by changes in defocus and the random error in measurement. In the method, we establish a complete phase error model and construct a novel objective function, to the best of our knowledge, to optimize the binarization threshold of each pixel. Through derivation of the threshold gradient calculation formula, we quickly obtain optimal binary fringes that can adapt to different fringe pitches and various degrees of defocus. The experimental results verify that the proposed method can generate robust binary fringes adaptive to different fringe pitches and defocus degree variation, and thus achieve high-quality 3D measurements.
ABSTRACT
BACKGROUND: Evaluating the long-term health consequences of migration requires longitudinal data on migrants and non-migrants to facilitate adjustment for time-varying confounder-mediators of the effect of migration on health. METHODS: We merged harmonized data on subjects aged 50+ from the US-based Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Our exposed group includes MHAS-return migrants (n = 1555) and HRS Mexican-born migrants (n = 924). Our unexposed group includes MHAS-never migrants (n = 16,954). We constructed a lifecourse data set from birth (age 0) until either age at migration to the United States or age at study entry. To account for confounding via inverse probability of treatment weights (IPTW), we modeled the probability of migration at each year of life using time-varying pre-migration characteristics. We then evaluated the effect of migration on mortality hazard estimated with and without IPTW. RESULTS: Mexico to the United States migration was predicted by time-varying factors that occurred before migration. Using measured covariates at time of enrollment to account for selective migration, we estimated that, for women, migrating reduces mortality risk by 13%, although this estimate was imprecise and results were compatible with either large protective or deleterious associations (hazard ratio [HR] =0.87, 95% confidence interval [CI]: 0.60, 1.27). When instead using IPTWs, the estimated effect on mortality was similarly imprecise (HR = 0.98, 95% CI: 0.77, 1.25). The relationship among men was similarly uncertain in both models. CONCLUSIONS: Although time-varying social factors predicted migration, IPTW weighting did not affect our estimates. Larger samples are needed to precisely estimate the health effects of migration.
Subject(s)
Emigration and Immigration , Transients and Migrants , Aging , Female , Humans , Infant, Newborn , Male , Mexico/epidemiology , United States/epidemiologyABSTRACT
The measurement accuracy of high-speed binary defocusing fringe projection profilometry depends on the fringe pitch and defocus degree. During the measurement process, the degree of defocus changes with the measurement depth of the scenes. This makes it difficult to obtain a suitable defocus degree and achieve high-precision measurement owing to dynamic changes in the measurement object or environment. To address this problem, we propose a highly dynamic defocus response method to adaptively adjust fringe pitches for binary defocusing fringe projection profilometry. As the defocus degree changes significantly, the proposed method can respond quickly and adjust the fringe pitches adaptively to the scenes. Therefore, a high-precision dynamic measurement can be achieved for the current measuring scene. In this study, considering the effect of random error and nonlinear error, we established a complete phase-error model and used it as an optimization function. Based on this function, we obtained the optimal fringe pitch expression with the defocus degree and harmonic response parameters as variables. With the proposed method, we can obtain the defocus degree and harmonic response parameters during the measurement process and calculate the optimal fringe pitches for the current scenes. Thus, the proposed method can dynamically adapt to the measuring depth change and achieve an accurate measurement without modifying any hardware parameters.
ABSTRACT
Recent technology has made it possible to measure DNA methylation profiles in a cost-effective and comprehensive genome-wide manner using array-based technology for epigenome-wide association studies. However, identifying differentially methylated regions (DMRs) remains a challenging task because of the complexities in DNA methylation data. Supervised methods typically focus on the regions that contain consecutive highly significantly differentially methylated CpGs in the genome, but may lack power for detecting small but consistent changes when few CpGs pass stringent significance threshold after multiple comparison. Unsupervised methods group CpGs based on genomic annotations first and then test them against phenotype, but may lack specificity because the regional boundaries of methylation are often not well defined. We present coMethDMR, a flexible, powerful, and accurate tool for identifying DMRs. Instead of testing all CpGs within a genomic region, coMethDMR carries out an additional step that selects co-methylated sub-regions first. Next, coMethDMR tests association between methylation levels within the sub-region and phenotype via a random coefficient mixed effects model that models both variations between CpG sites within the region and differential methylation simultaneously. coMethDMR offers well-controlled Type I error rate, improved specificity, focused testing of targeted genomic regions, and is available as an open-source R package.
Subject(s)
CpG Islands/genetics , DNA Methylation/genetics , Epigenesis, Genetic , Epigenomics/methods , Software , Humans , Models, Biological , PhenotypeABSTRACT
The association between dietary sodium and potassium intake with the development of kidney disease remains unclear, particularly among younger individuals. Here, we determined whether dietary sodium and potassium intake are associated with incident chronic kidney disease (CKD) using data from 1,030 adults (age 23-35 in 1990-1991) from the Coronary Artery Risk Development In Young Adults study, based on repeated measurements of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (ACR) from 1995 through 2015. Urinary sodium and potassium excretion (mg/day), calculated from three 24-hour urine collections in 1990-1991, were averaged to measure sodium and potassium intake. Serum creatinine was used to calculate eGFR using the CKD EPI equation; spot urine albumin and creatinine were used to calculate ACR, each at five visits from 1995-1996 through 2015-2016. CKD was defined as decreased eGFR (under 60 ml/min/1.73m2) or the development of albuminuria (ACR over 30 mg/g). We used log binomial regression models adjusted for socio-demographic, behavioral, and clinical factors to determine whether sodium and potassium intake were associated with incident CKD (decreased eGFR or developed albuminuria) among those free of CKD in 1995. Dietary sodium intake was not significantly associated with incident CKD. However, every 1,000 mg/day increment of potassium intake in 1990 was significantly associated with a 29% lower risk of incident albuminuria (relative risk 0.71, 95% confidence interval 0.53, 0.95), but not eGFR. Thus, higher dietary potassium intake may protect against the development of kidney damage, particularly albuminuria.
Subject(s)
Potassium, Dietary , Renal Insufficiency, Chronic , Adult , Albuminuria/epidemiology , Creatinine , Glomerular Filtration Rate , Humans , Kidney , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/prevention & control , Young AdultABSTRACT
White-light scanning interferometry (WLSI) is an important measurement technique that has been widely used in three-dimensional profile reconstruction. Because of the effects of environmental noise and phase changes caused by surface reflection, existing WLSI algorithms have problems in measurement accuracy and measurement speed. Addressing these problems, this paper proposes a fast template matching method to determine precisely the zero optical path difference (ZOPD) position in the WLSI. Due to the uniform shape of the interference signals, a template interference signal can be obtained in advance by performing a least-square fitting or Fourier interpolation on an interference signal of one pixel. In the method, the ZOPD position is initially obtained by the centroid method. Then, the ZOPD position is determined by a precise matching process through moving the template interference signal on the measured interference signal. Through the two-step processes, the ZOPD position can be obtained precisely with much less time. The method was simulated and verified through the measurement of a spherical surface, a 1.8-µm-height standard step and a flip-chip substrate. The experimental results show that the proposed algorithm can achieve both high precision and fast measurement.
ABSTRACT
BACKGROUND: This study aimed to devise a Cancer symptoms Discrimination Scale (CSDS) suitable for China based on a cross-sectional survey. METHODS: The CSDS was developed using the classical measurement theory. A total of 3610 students from Yunnan province, China, participated in the cross-sectional survey. The test version of the scale was modified by the item analysis method, and after the official version of CSDS was developed, its reliability and validity were verified. A univariate analysis of variance and a multiple linear regression model were used to analyze the influencing factors of cancer symptoms discrimination among the university/college students. RESULTS: There were 21 items in total for the CSDS, including 3 subscales --- common clinical manifestations (11 items), physical appearance defects (6 items), and drainage tube(s) wearing (4 items). This CSDS had good validity (GFI = 0.930, AGFI = 0.905, RMR = 0.013, I-CVIs> 0.80, and the Pearson correlation coefficient was satisfactory.) and reliability (Cronbach's alpha = 0.862, spearman-brown coefficient = 0.875). The multiple linear regression showed that certain factors may affect the students' discrimination level against cancer symptoms (P < 0.05), including gender, major, current education degree, guardian's highest record of formal schooling, self-rated health status, history of care for cancer patients, family relationship, ways of cancer knowledge acquisition, good/poor understanding of cancer-related information, degree of cancer fear, and their perception of cancer infectiousness. CONCLUSION: This CSDS, with good reliability and validity, can be used for the evaluation of the discrimination risk and levels against cancer symptoms among healthy students.
Subject(s)
Neoplasms/psychology , Prejudice/psychology , Social Discrimination/psychology , Students/psychology , Adolescent , Adult , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Neoplasms/epidemiology , Reproducibility of Results , Students, Health Occupations/psychology , Surveys and Questionnaires , Universities , Young AdultABSTRACT
Background and Purpose- It is unclear whether disparities in mortality among stroke survivors exist long term. Therefore, the purpose of the current study is to describe rates of longer term mortality among stroke survivors (ie, beyond 30 days) and to determine whether socioeconomic disparities exist. Methods- This analysis included 1329 black and white participants, aged ≥45 years, enrolled between 2003 and 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) who suffered a first stroke and survived at least 30 days after the event. Long-term mortality among stroke survivors was defined in person-years as time from 30 days after a first stroke to date of death or censoring. Mortality rate ratios (MRRs) were used to compare rates of poststroke mortality by demographic and socioeconomic characteristics. Results- Among adults who survived ≥30 days poststroke, the age-adjusted rate of mortality was 82.3 per 1000 person-years (95% CI, 75.4-89.2). Long-term mortality among stroke survivors was higher in older individuals (MRR for 75+ versus <65, 3.2; 95% CI, 2.6-4.1) and among men than women (MRR, 1.3; 95% CI, 1.1-1.6). It was also higher among those with less educational attainment (MRR for less than high-school versus college graduate, 1.5; 95% CI, 1.1-1.9), lower income (MRR for <$20k versus >50k, 1.4; 95% CI, 1.1-1.9), and lower neighborhood socioeconomic status (SES; MRR for low versus high neighborhood SES, 1.4; 95% CI, 1.1-1.7). There were no differences in age-adjusted rates of long-term poststroke mortality by race, rurality, or US region. Conclusions- Rates of long-term mortality among stroke survivors were higher among individuals with lower SES and among those residing in neighborhoods of lower SES. These results emphasize the need for improvements in long-term care poststroke, especially among individuals of lower SES.
Subject(s)
Stroke/mortality , Age Factors , Aged , Aged, 80 and over , Educational Status , Female , Humans , Male , Middle Aged , Risk Factors , Sex Factors , Socioeconomic Factors , Survival Rate , Survivors , United States/epidemiologyABSTRACT
Neuroinflammation induced by protruded nucleus pulposus (NP) has been shown to play a significant role in facilitation of radicular pain. Resolvin D2 (RvD2), a novel member of resolvin family, exhibits potent anti-inflammatory, pro-resolving and antinociceptive effects. But the effect of RvD2 in radicular pain remains unknown. The radicular pain rat models were induced by application of NP to L5 dorsal root ganglion. Each animal received intrathecal injections of vehicle or RvD2 (10 ng µl-1 or 100 ng µl-1). Mechanical thresholds were determined by measuring the paw withdrawal threshold for 7 days. The expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-ß1 (TGF-ß1) in ipsilateral lumbar segment of rat spinal dorsal horns were measured by using ELISA and real time-PCR. Western blot was used to measure the expressions of phosphorylated Akt (p-Akt) and phosphorylated glycogen synthase kinase 3 beta (p-GSK-3ß). The expressions and distributions of RvD2 receptor, G-protein-coupled receptor 18 (GPR18), were also explored in the spinal cord of rats by using double-label immunofluorescence. RvD2 treatment caused significant reductions in the intensity of mechanical hypersensitivity and spinal expressions of TNF-α and IL-6. Meanwhile, RvD2 increased the expressions of TGF-ß1 and regulated Akt/GSK-3ß signaling. Furthermore, immunofluorescence showed that GPR18 colocalized with neurons and astrocytes in spinal cord. The results suggested that RvD2 might attenuate mechanical allodynia via regulating the expressions of inflammatory mediators and activation of Akt/GSK-3ß signal pathway. RvD2 might offer a hopeful method for radicular pain therapy.
Subject(s)
Docosahexaenoic Acids/administration & dosage , Glycogen Synthase Kinase 3 beta/metabolism , Inflammation Mediators/metabolism , Pain/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Radiculopathy/metabolism , Receptors, Cannabinoid/metabolism , Animals , Inflammation Mediators/antagonists & inhibitors , Injections, Spinal , Intervertebral Disc Displacement/drug therapy , Intervertebral Disc Displacement/metabolism , Lumbar Vertebrae , Male , Pain/drug therapy , Radiculopathy/drug therapy , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
Small extracellular vesicles (sEVs) have been identified as a noteworthy paracrine mechanism of intercellular communication in diagnosing and managing neurological disorders. Current research suggests that sEVs play a pivotal role in the pathological progression of pain, emphasizing their critical function in the pathological progression of pain in acute and chronic pain models. By facilitating the transfer of diverse molecules, such as proteins, nucleic acids, and metabolites, sEVs can modulate pain signaling transmission in both the central and peripheral nervous systems. Furthermore, the unique molecules conveyed by sEVs in pain disorders indicate their potential as diagnostic biomarkers. The application of sEVs derived from mesenchymal stem cells (MSCs) in regenerative pain medicine has emerged as a promising strategy for pain management. Moreover, modified sEVs have garnered considerable attention in the investigation of pathological processes and therapeutic interventions. This review presents a comprehensive overview of the current knowledge regarding the involvement of sEVs in pain pathogenesis and treatment. Nevertheless, additional research is imperative to facilitate their clinical implementation. Schematic diagram of sEVs in the biogenesis, signal transmission, diagnosis, and treatment of pain disorders. Small extracellular vesicles (sEVs) are secreted by multiple cells, loading with various biomolecules, such as miRNAs, transmembrane proteins, and amino acids. They selectively target other cells and regulating pain signal transmission. The composition of sEVs can serve as valuable biomarkers for pain diagnosis. In particular, mesenchymal stem cell-derived sEVs have shown promise as regenerative medicine for managing multiple pain disorders. Furthermore, by modifying the structure or contents of sEVs, they could potentially be used as a potent analgesic method.
ABSTRACT
Traditional linear active disturbance rejection control (LADRC) may have difficulty to achieve a rapid precise disturbance rejection for a permanent magnet synchronous linear motor (PMSLM). By making use of model information, a model predictive and compensated LADRC (MPLADRC) method is proposed in this paper. In this method, a model compensated extended state observer (MESO) is designed to transform the controlled object into an established mathematical model through total disturbance compensation. Meanwhile, considering the delay problem of MESO, a phase advance module is designed to improve the estimation speed of MESO for system disturbance and state, thus the MESO can rapidly compensate various uncertainty disturbances to the controlled object in real time. The model predictive controller (MPC) is then designed based on the mathematical model, and its optimal control law is then obtained through a quadratic objective function to further suppress the disturbance unobserved by the designed MESO. The proposed method can thus realize a dual-degree-of-freedom disturbance rejection through the MESO and MPC. The simulation and experimental results validate the effectiveness of the proposed MPLADRC in rapid anti-disturbance and fast positioning for the motion control of the PMSLM.
ABSTRACT
In response to the issues of foodborne microbial contamination and carbon neutrality goals, sustainable antimicrobial food packaging (SAFP) composed of renewable or biodegradable biopolymer matrices with ecofriendly antimicrobial agents has emerged. SAFP offers longer effectiveness, wider coverage, more controllability, and better environmental performance. Analyzing SAFP information, including the release profile of each antimicrobial agent for each food, the interaction of each biomass matrix with each food, the material size, form, and preparation methods, and its service quality in real foods, is crucial. While encouraging reports exist, a comprehensive review summarizing these developments is lacking. Therefore, this review critically examines recent release-antimicrobial mechanisms, kinetics models, preparation methods, and key regulatory parameters for SAFPs based on slow- or controlled-release theory. Furthermore, it discusses fundamental physicochemical characteristics, effective concentrations, advantages, release approaches, and antimicrobial and preservative effects of various materials in food simulants or actual food. Lastly, inadequacies and future trends are explored, providing practical references to regulate the movement of active substances in different media, reduce the reliance on petrochemical-based materials, and advance food packaging and preservation technologies.
Subject(s)
Anti-Infective Agents , Food Packaging , Food Packaging/methods , Food Preservation/methods , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , BiopolymersABSTRACT
Emerging evidence has demonstrated that several microvesicles (MVs) are secreted in bronchoalveolar lavage fluid (BALF) during the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the impact of alveolar macrophage (AM)-derived MVs on epithelial cells and their in vivo effects on ALI/ARDS require further exploration. In this study, MVs were isolated from BALF of mice or mouse alveolar macrophage (MHS) cells by sequential centrifugation and then delivered to epithelial cells or mice. Enzyme-linked immunosorbent assay revealed that BALF-derived MVs (BALF-MVs) and MHS-derived MVs (AM-MVs) were rich in tumor necrosis factor-α (TNF-α) at the early stage of lung injury. In vitro, both inflammatory BALF-MVs and AM-MVs decreased the expression of α subunit of epithelial sodium channel (α-ENaC), γ-ENaC, and Na+,K+-ATPase α1 and ß1 in lung epithelial cells. However, antibodies against TNF-α inhibited the effects of inflammatory AM-MVs in epithelial cells. In vivo, the inflammatory AM-MVs, delivered intratracheally to mice, impaired lung tissues and increased the injury score. They also resulted in decreased alveolar fluid clearance and increased lung wet weight/dry weight ratio. Furthermore, inflammatory AM-MVs downregulated the α-ENaC, γ-ENaC, and Na+,K+-ATPase α1 and ß1 levels in lung tissues. According to our results, inflammatory AM-derived MVs may potentially contribute to lung injury and pulmonary edema, thereby indicating a potential novel therapeutic approach against ALI/ARDS based on AM-MVs.
Subject(s)
Cell-Derived Microparticles/metabolism , Epithelial Cells/immunology , Inflammation/immunology , Lung/pathology , Macrophages, Alveolar/immunology , Pulmonary Edema/immunology , Respiratory Distress Syndrome/immunology , Animals , Cells, Cultured , Epithelial Sodium Channels/metabolism , Humans , Mice , Mice, Inbred C57BL , Sodium-Potassium-Exchanging ATPase/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Severe acute pancreatitis (SAP) is a condition characterized by highly fatal acute inflammation and is usually associated with multiple organ dysfunction syndrome. Acute lung injury (ALI) is the most common complications of SAP, which is the accelerator of other organ dysfunction caused by SAP and the primary cause of early death due to SAP. Acadesine, an adenosine analog and an AMPK activator, has been discovered to modulate glucose and lipid metabolism, and inhibit the production of pro-inflammatory cytokines and iNOS. However, its role in SAP-ALI and its mechanism remains unclear and need to be explored. Herein, we discovered that acadesine mitigated the generation of reactive oxygen species (ROS) in human pulmonary microvascular endothelial cells (HPMECs), alleviated apoptosis and recovered barrier integrity, thereby contributing to anti-inflammatory effects in vitro and in vivo. Moreover, Nrf2 deficiency partially eliminated the effects of acadesine-induced antioxidant effects and thus weakened the protective effects on cells and Nrf2-knockout (Nrf2-/-) mice. This study demonstrates that acadesine attenuated SAP-ALI associated inflammation and tissue damage by modulating the Nrf2-dependent antioxidant pathway by triggering AMPK. These findings are of great significance for the treatment of SAP-related lung injury.
Subject(s)
Acute Lung Injury , Pancreatitis , AMP-Activated Protein Kinases/metabolism , Acute Disease , Acute Lung Injury/chemically induced , Aminoimidazole Carboxamide/analogs & derivatives , Animals , Antioxidants/pharmacology , Endothelial Cells/metabolism , Humans , Inflammation/metabolism , Mice , NF-E2-Related Factor 2/metabolism , Pancreatitis/complications , Ribonucleosides , Signal TransductionABSTRACT
To better understand DNA methylation in Alzheimer's disease (AD) from both mechanistic and biomarker perspectives, we performed an epigenome-wide meta-analysis of blood DNA methylation in two large independent blood-based studies in AD, the ADNI and AIBL studies, and identified 5 CpGs, mapped to the SPIDR, CDH6 genes, and intergenic regions, that are significantly associated with AD diagnosis. A cross-tissue analysis that combined these blood DNA methylation datasets with four brain methylation datasets prioritized 97 CpGs and 10 genomic regions that are significantly associated with both AD neuropathology and AD diagnosis. An out-of-sample validation using the AddNeuroMed dataset showed the best performing logistic regression model includes age, sex, immune cell type proportions, and methylation risk score based on prioritized CpGs in cross-tissue analysis (AUC = 0.696, 95% CI: 0.616 - 0.770, P-value = 2.78 × 10-5). Our study offers new insights into epigenetics in AD and provides a valuable resource for future AD biomarker discovery.
Subject(s)
Alzheimer Disease , Epigenome , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Brain/pathology , DNA Methylation/genetics , Epigenesis, Genetic , Genome-Wide Association Study , HumansABSTRACT
To investigate the effects of beraprost sodium on the proliferation and oxidative stress of glomerular mesangial cells under high glucose conditions, a rat mesangial cell line (rat mesangial cells; RMCs) was treated with beraprost sodium in the presence of high glucose concentrations. Proliferation rates of mesangial cells were detected by MTT assays and BrdU incorporation analyses. Levels of reactive oxygen species (ROS) were detected by DCFH-DA probes. The mRNA expression levels of CuZnSOD, MnSOD, catalase (CAT), glutathione peroxidase (Gpx), and collagen IV were detected by RT-PCR, and the protein levels of antioxidants (i.e. CuZnSOD, CAT, and MnSOD) and collagen IV were detected by Western blot. Beraprost sodium treatment significantly decreased the proliferation and ROS levels of RMCs cultured in high glucose conditions in a dose-dependent manner (p < 0.05). Beraprost sodium treatment decreased the mRNA and protein levels of CuZnSOD, CAT, and collagen IV in cells under high glucose conditions, while it increased MnSOD protein levels in cells under normal glucose conditions. Therefore, beraprost sodium inhibits high glucose-induced cellular proliferation and the generation of ROS, and it improves the antioxidant capacities of rat glomerular mesangial cells.
Subject(s)
Epoprostenol/analogs & derivatives , Epoprostenol/pharmacology , Glucose/pharmacology , Mesangial Cells/drug effects , Mesangial Cells/metabolism , Oxidative Stress/drug effects , Animals , Antioxidants/metabolism , Catalase/metabolism , Cell Growth Processes/drug effects , Cell Line , Collagen Type IV/metabolism , Glutathione Peroxidase/metabolism , Rats , Reactive Oxygen Species/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Sex is an important factor that contributes to the clinical and biological heterogeneities in Alzheimer's disease (AD), but the regulatory mechanisms underlying sex disparity in AD are still not well understood. DNA methylation is an important epigenetic modification that regulates gene transcription and is known to be involved in AD. We performed the first large-scale sex-specific meta-analysis of DNA methylation differences in AD neuropathology, by re-analyzing four recent epigenome-wide association studies totaling more than 1000 postmortem prefrontal cortex brain samples using a uniform analytical pipeline. For each cohort, we employed two complementary analytical strategies, a sex-stratified analysis that examined methylation-Braak stage associations in male and female samples separately, and a sex-by-Braak stage interaction analysis that compared the magnitude of these associations between different sexes. Our analysis uncovered 14 novel CpGs, mapped to genes such as TMEM39A and TNXB that are associated with the AD Braak stage in a sex-specific manner. TMEM39A is known to be involved in inflammation, dysregulated type I interferon responses, and other immune processes. TNXB encodes tenascin proteins, which are extracellular matrix glycoproteins demonstrated to modulate synaptic plasticity in the brain. Moreover, for many previously implicated genes in AD neuropathology, such as MBP and AZU1, our analysis provided the new insights that they were predominately driven by effects in only one sex. These sex-specific DNA methylation differences were enriched in divergent biological processes such as integrin activation in females and complement activation in males. Our study implicated multiple new loci and biological processes that affected AD neuropathology in a sex-specific manner.
Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/metabolism , DNA Methylation/physiology , Databases, Genetic , Sex Characteristics , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Cohort Studies , Female , Humans , Male , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathologyABSTRACT
PURPOSE: Migrating from Mexico to the U.S. is a major, stressful life event with potentially profound influences on mental health. However, estimating the health effects of migration is challenging because of differential selection into migration and time-varying confounder mediators of migration effects on health. METHODS: We pooled data from the Mexican Health and Aging Study (N = 17,771) and Mexican-born U.S. Health and Retirement Study (N = 898) participants to evaluate the effects of migration to the U.S. (at any age and in models for migration in childhood or adulthood) on depressive symptom-count, measured with a modified Centers for Epidemiologic Studies-Depression scale. We modeled probability of migrating in each year of life from birth to either age at initial migration to the U.S. or enrollment and used these models to calculate inverse probability of migration weights. We applied the weights to covariate-adjusted negative binomial GEE models, estimating the ratio of average symptom-count associated with migration. RESULTS: Mexico to U.S. migration was unrelated to depressive symptoms among men (ratio of average symptom-count= 0.98 [95% CI: 0.89, 1.08]) and women (ratio of average symptom-count = 1.00 [95% CI: 0.92, 1.09]). Results were similar for migration in childhood, early adulthood, or later adulthood. CONCLUSIONS: In this sample of older Mexican-born adults, migration to the U.S. was unrelated to depressive symptoms.