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1.
Sci Rep ; 14(1): 17924, 2024 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095651

RESUMO

Children with attention-deficit hyperactivity disorder (ADHD) have difficulties in social interactions. Studying brain activity during social interactions is difficult with conventional artificial stimuli. This pioneering study examined the neural correlates of social perception in children with ADHD and matched controls using naturalistic stimuli. We presented 20 children with ADHD and 20 age-and-sex-matched controls with tailored movies featuring high- or low-level social interactions while recording electroencephalographic signals. Both groups exhibited synchronized gamma-band oscillations, but controls demonstrated greater inter-subject correlations. Additionally, the difference in inter-subject correlations between high- and low-interaction movies was significantly larger in controls compared to ADHD patients. Between 55 and 75 Hz comparing viewing high interaction movies with low interaction moves, controls had a significantly larger weighting in the right parietal lobe, while ADHD patients had a significantly smaller weighting in the left occipital lobe. These findings reveal distinct spatiotemporal neural signatures in social interaction processing among children with ADHD and controls using naturalistic stimuli. These neural markers offer potential for group differentiation and assessing intervention efficacy, advancing our understanding ADHD-related social interaction mechanisms.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Eletroencefalografia , Interação Social , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Masculino , Criança , Feminino , Biomarcadores , Ritmo Gama/fisiologia , Estudos de Casos e Controles , Encéfalo/fisiopatologia , Adolescente
2.
J Clin Med ; 13(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38930008

RESUMO

Background: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). Methods: Data from 15,181 preterm infants (2009-2013) and 151,810 controls were analyzed using Taiwan's National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. Results: This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (<20 and >40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. Conclusions: LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants.

3.
Biomed Pharmacother ; 174: 116431, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522238

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening lung disease with high mortality rates. The limited availability of effective drugs for IPF treatment, coupled with concerns regarding adverse effects and restricted responsiveness, underscores the need for alternative approaches. Kefir peptides (KPs) have demonstrated antioxidative, anti-inflammatory, and antifibrotic properties, along with the capability to modulate gut microbiota. This study aims to investigate the impact of KPs on bleomycin-induced pulmonary fibrosis. METHODS: Mice were treated with KPs for four days, followed by intratracheal injection of bleomycin for 21 days. Comprehensive assessments included pulmonary functional tests, micro-computed tomography (µ-CT), in vivo image analysis using MMPsense750, evaluation of inflammation- and fibrosis-related gene expression in lung tissue, and histopathological examinations. Furthermore, a detailed investigation of the gut microbiota community was performed using full-length 16 S rRNA sequencing in control mice, bleomycin-induced fibrotic mice, and KPs-pretreated fibrotic mice. RESULTS: In KPs-pretreated bleomycin-induced lung fibrotic mice, notable outcomes included the absence of significant bodyweight loss, enhanced pulmonary functions, restored lung tissue architecture, and diminished thickening of inter-alveolar septa, as elucidated by morphological and histopathological analyses. Concurrently, a reduction in the expression levels of oxidative biomarkers, inflammatory factors, and fibrotic indicators was observed. Moreover, 16 S rRNA sequencing demonstrated that KPs pretreatment induced alterations in the relative abundances of gut microbiota, notably affecting Barnesiella_intestinihominis, Kineothrix_alysoides, and Clostridium_viride. CONCLUSIONS: Kefir peptides exerted preventive effects, protecting mice against bleomycin-induced lung oxidative stress, inflammation, and fibrosis. These effects are likely linked to modifications in the gut microbiota community. The findings highlight the therapeutic potential of KPs in mitigating pulmonary fibrosis and advocate for additional exploration in clinical settings.


Assuntos
Bleomicina , Microbioma Gastrointestinal , Kefir , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Fibrose Pulmonar , Animais , Estresse Oxidativo/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Kefir/microbiologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , Fibrose Pulmonar/tratamento farmacológico , Inflamação/patologia , Masculino , Peptídeos/farmacologia , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças
4.
Pediatr Neurol ; 154: 26-35, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38458101

RESUMO

BACKGROUND: Febrile seizures occur commonly in children aged between six months and six years. A previous Danish study found a positive correlation between febrile seizures and the overall incidence of psychiatric disorders. This population-based nationwide observational study was conducted to investigate the association between febrile seizures and different psychiatric disorders in Taiwan and the associated risk factors. METHODS: This cohort study used data from the National Health Insurance Research Database in Taiwan-a nationwide claims database covering >99% of the Taiwanese population. The study period was from January 2000 to December 2015; the overall median follow-up time was 11.04 ± 10.95 years. Overall, 2464 children with febrile seizures diagnosed between 2000 and 2015 met the inclusion criteria, and 7392 children without febrile seizures matched by index year, age, and sex were included in the control cohorts. Febrile seizures and psychiatric disorders were measured as the exposure and main outcomes, respectively. RESULTS: Children with febrile seizures (n = 2463) were at a high risk of psychiatric disorders (adjusted hazard ratio, 4.70; 95% confidence interval [CI], 2.44 to 7.30; P < 0.001). The risk for anxiety was the highest (adjusted hazard ratio, 21.92; 95% CI, 11.40 to 34.05; P < 0.001). CONCLUSIONS: When treating children with febrile seizures, particular attention should be paid to the symptoms of psychiatric disorders, as early referral may be beneficial for these children.


Assuntos
Transtornos Mentais , Convulsões Febris , Criança , Humanos , Lactente , Estudos de Coortes , Convulsões Febris/epidemiologia , Convulsões Febris/complicações , Taiwan/epidemiologia , Transtornos Mentais/etiologia , Fatores de Risco , Incidência
5.
Medicina (Kaunas) ; 60(1)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38256380

RESUMO

Background and Objectives: Type 1 diabetes mellitus (T1DM) is a chronic and serious condition that is characterized by inadequate pancreatic-ß-cells' insulin production. The connection between T1DM and Helicobacter pylori infection remains uncertain. This study aimed to conduct a systematic meta-analysis to examine the association between H. pylori infection, hemoglobin A1c levels, and the development of T1DM. Materials and Methods: The initial search identified 451 articles on the association between H. pylori infection and T1DM. Among them, 12 articles had 2797 participants who met the inclusion criteria for an advanced meta-analysis. Results: A significant association was observed between H. pylori infection and T1DM (OR 1.77, 95% CI 1.47-2.12, p < 0.0001), with heterogeneity: Tau2 = 0.47; Chi2 = 57.07, df = 11 (p < 0.0001); I2 = 81%. Subgroup analysis showed that H. pylori infection was significantly associated with a longer duration of T1DM and higher hemoglobin A1c levels (p < 0.001 for both) but not with age at T1DM diagnosis (p = 0.306). Conclusions: These findings contribute to the understanding of the association between H. pylori infection and T1DM and highlight the potential role of H. pylori in influencing the duration and glycemic control of diabetes. Therefore, pediatric patients who have longstanding T1DM and poor glycemic control should be screened for H. pylori infection.


Assuntos
Diabetes Mellitus Tipo 1 , Infecções por Helicobacter , Helicobacter pylori , Humanos , Criança , Lactente , Diabetes Mellitus Tipo 1/complicações , Infecções por Helicobacter/complicações , Hemoglobinas Glicadas , Controle Glicêmico
6.
Prev Med ; 177: 107753, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37931660

RESUMO

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) ensures favorable outcomes and reduces the risk of cardiac events in patients on dialysis. However, the effect of PPSV23 vaccination on renal function remains unknown, particularly in patients with chronic kidney disease (CKD). Therefore, we investigated the association between PPSV23 efficacy and renal progression in older patients (age ≥ 75 years) with CKD. METHODS: This multicenter, longitudinal cohort study was conducted using data (2008-2016) from the Epidemiology and Risk Factors Surveillance of CKD database. This database was associated with Taiwan's National Health Insurance Research Database (for period: 2008-2019). A total of 1195 older patients with CKD were recruited from 14 hospitals and communities across Taiwan. Renal progression was defined as a > 25% reduction in estimated glomerular filtration rate from the baseline value. RESULTS: A significant reduction in the risk of renal progression was observed in patients who had received PPSV23 (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.35-0.91). However, when stratified by CKD stage, this significant reduction was observed in patients with early-stage CKD but not in those with late-stage CKD. Furthermore, a significant reduction in the risk of renal progression was noted in male patients and those with hypertension. CONCLUSION: Our findings support the protective effect of PPSV23 against renal deterioration in older patients with CKD.


Assuntos
Infecções Pneumocócicas , Pneumonia Pneumocócica , Insuficiência Renal Crônica , Humanos , Masculino , Idoso , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Estudos Longitudinais , Vacinas Pneumocócicas/uso terapêutico , Insuficiência Renal Crônica/epidemiologia , Rim , Infecções Pneumocócicas/prevenção & controle
7.
Int J Mol Sci ; 24(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38003601

RESUMO

Hemophilia is a genetic disorder linked to the sex chromosomes, resulting in impaired blood clotting due to insufficient intrinsic coagulation factors. There are approximately one million individuals worldwide with hemophilia, with hemophilia A being the most prevalent form. The current treatment for hemophilia A involves the administration of clotting factor VIII (FVIII) through regular and costly injections, which only provide temporary relief and pose inconveniences to patients. In utero transplantation (IUT) is an innovative method for addressing genetic disorders, taking advantage of the underdeveloped immune system of the fetus. This allows mesenchymal stromal cells to play a role in fetal development and potentially correct genetic abnormalities. The objective of this study was to assess the potential recovery of coagulation disorders in FVIII knockout hemophilia A mice through the administration of human amniotic fluid mesenchymal stromal cells (hAFMSCs) via IUT at the D14.5 fetal stage. The findings revealed that the transplanted human cells exhibited fusion with the recipient liver, with a ratio of approximately one human cell per 10,000 mouse cells and produced human FVIII protein in the livers of IUT-treated mice. Hemophilia A pups born to IUT recipients demonstrated substantial improvement in their coagulation issues from birth throughout the growth period of up to 12 weeks of age. Moreover, FVIII activity reached its peak at 6 weeks of age, while the levels of FVIII inhibitors remained relatively low during the 12-week testing period in mice with hemophilia. In conclusion, the results indicated that prenatal intrahepatic therapy using hAFMSCs has the potential to improve clotting issues in FVIII knockout mice, suggesting it as a potential clinical treatment for individuals with hemophilia A.


Assuntos
Hemofilia A , Hemostáticos , Células-Tronco Mesenquimais , Gravidez , Feminino , Humanos , Camundongos , Animais , Lactente , Hemofilia A/genética , Hemofilia A/terapia , Líquido Amniótico/metabolismo , Fator VIII/genética , Fator VIII/metabolismo , Hemostáticos/metabolismo , Camundongos Knockout , Células-Tronco Mesenquimais/metabolismo
8.
Cell Transplant ; 32: 9636897231198172, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37698258

RESUMO

Cell expansion of human pluripotent stem cells (hPSCs) commonly depends on Matrigel as a coating matrix on two-dimensional (2D) culture plates and 3D microcarriers. However, the xenogenic Matrigel requires sophisticated quality-assurance processes to meet clinical requirements. In this study, we develop an innovative coating-free medium for expanding hPSCs. The xenofree medium supports the weekend-free culture and competitive growth of hPSCs on several cell culture plastics without an additional pre-coating process. The pluripotent stemness of the expanded cells is stably sustained for more than 10 passages, featured with high pluripotent marker expressions, normal karyotyping, and differentiating capacity for three germ layers. The expression levels of some integrins are reduced, compared with those of the hPSCs on Matrigel. This medium also successfully supports the clonal expansion and induced pluripotent stem cell establishment from mitochondrial-defective MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) patient's peripheral blood mononuclear cells. This innovative hPSC medium provides a straightforward scale-up process for producing clinical-orientated hPSCs by excluding the conventional coating procedure.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Humanos , Leucócitos Mononucleares , Células-Tronco Pluripotentes/metabolismo , Técnicas de Cultura de Células/métodos , Diferenciação Celular
9.
Front Cell Dev Biol ; 11: 1158812, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091976

RESUMO

Aims: Vascular calcification (VC) and osteoporosis were previously considered two distinct diseases. However, current understanding indicates that they share common pathogenetic mechanisms. The available medicines for treating VC and osteoporosis are limited. We previously demonstrated that kefir peptides (KPs) alleviated atherosclerosis in high-fat diet (HFD)-induced apolipoprotein E knockout (ApoE -/- ) mice. The present study further addressed the preventive effects of KPs on VC and osteoporosis in ApoE -/- mice fed a high-cholesterol atherogenic diet (AD). Main methods: Seven-week-old ApoE -/- and wild-type C57BL/6 mice were randomly divided into five groups (n = 6). The development of VC and osteoporosis was evaluated after AD feeding for 13 weeks in KP-treated ApoE -/- mice and compared to C57BL/6 and ApoE -/- mice fed a standard chow diet (CD). Key findings: The results indicated that KP-treated ApoE -/- mice exhibited lower serum total cholesterol, oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) levels, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine kinase (CK) activities, which suggested that KPs prevented hyperlipidemia and possible damages to the liver and muscle in ApoE -/- mice. KPs reduced serum tumor necrosis factor-α (TNF-α) and the local expression of TNF-α, IL-1ß, and macrophage-specific CD68 markers in aortic tissues, which suggested that KPs inhibited inflammatory responses in AD-fed ApoE -/- mice. KPs reduced the deposition of lipid, collagen, and calcium minerals in the aortic roots of AD-fed ApoE -/- mice, which suggested that KPs inhibited the calcific progression of atherosclerotic plaques. KPs exerted osteoprotective effects in AD-fed ApoE -/- mice, which was evidenced by lower levels of the bone resorption marker CTX-1 and higher levels of the bone formation marker P1NP. KPs improved cortical bone mineral density and bone volume and reduced trabecular bone loss in femurs. Significance: The present data suggested that KPs attenuated VC and osteoporosis by reducing oxidative stress and inflammatory responses in AD-fed ApoE -/- mice. Our findings contribute to the application of KPs as preventive medicines for the treatment of hyperlipidemia-induced vascular and bone degeneration.

10.
Int J Mol Sci ; 24(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36982345

RESUMO

Comorbidities are common in children with epilepsy, with nearly half of the patients having at least one comorbidity. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by hyperactivity and inattentiveness level disproportional to the child's developmental stage. The burden of ADHD in children with epilepsy is high and can adversely affect the patients' clinical outcomes, psychosocial aspects, and quality of life. Several hypotheses were proposed to explain the high burden of ADHD in childhood epilepsy; the well-established bidirectional connection and shared genetic/non-genetic factors between epilepsy and comorbid ADHD largely rule out the possibility of a chance in this association. Stimulants are effective in children with comorbid ADHD, and the current body of evidence supports their safety within the approved dose. Nonetheless, safety data should be further studied in randomized, double-blinded, placebo-controlled trials. Comorbid ADHD is still under-recognized in clinical practice. Early identification and management of comorbid ADHD are crucial to optimize the prognosis and reduce the risk of adverse long-term neurodevelopmental outcomes. The identification of the shared genetic background of epilepsy and ADHD can open the gate for tailoring treatment options for these patients through precision medicine.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Epilepsia , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Qualidade de Vida , Estimulantes do Sistema Nervoso Central/efeitos adversos , Epilepsia/complicações , Epilepsia/epidemiologia , Epilepsia/genética , Comorbidade
11.
Artigo em Inglês | MEDLINE | ID: mdl-36674404

RESUMO

Whole-body vibration (WBV) is a novel exercise training measure that promotes the muscle strength, flexibility, and balance abilities of elderly groups. The feasibility and applicability of 20-30 min (lowering a heat pack at 73 °C by wrapping it in multiple layers of towels to 40-43 °C before it touched the skin) thermotherapy are increasingly being demonstrated by applications and clinical trials. Studies show that it increases the flexibility of macules and ligament. However, no studies have examined the interactions between the pre-exercise and post-exercise application of heat therapy (duration a training course). Therefore, this study investigates the effects of WBV and heat therapy on the muscle strength, flexibility, and balance abilities of elderly groups. Eighty middle-age and elderly participants with no regular exercise habits were enrolled in this study. They were randomly assigned to a WBV group, a WBV plus heat therapy group, a heat therapy alone group, and a control group. The WBV groups underwent 5-min, fixed-amplitude (4 mm), thrice-weekly WBV training sessions for 3 consecutive months on a WBV training machine. Participants' balance was measured using the limits of stability (LOS) test on a balance system. The pretest and posttest knee extensor and flexor strength were tested using an isokinetic lower extremity dynamometer. Pretest and posttest flexibility changes were measured using the sit-and-reach test. Significantly larger pretest and posttest differences in flexibility and muscle strength were observed in the WBV and WBV plus heat therapy groups. The addition of heat therapy to WBV resulted in the largest flexibility improvements.


Assuntos
Hipertermia Induzida , Vibração , Idoso , Humanos , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Temperatura Alta , Força Muscular/fisiologia , Vibração/uso terapêutico
12.
Int J Mol Sci ; 25(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38203200

RESUMO

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.


Assuntos
Epilepsias Mioclônicas , Epilepsia Generalizada , Epilepsia , Humanos , Medicina de Precisão , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/terapia , Convulsões
13.
Artigo em Inglês | MEDLINE | ID: mdl-36498210

RESUMO

(1) Background: Recently, a growing number of studies have provided evidence to suggest a strong correlation between air pollution exposure and attention-deficit/hyperactivity disorder (ADHD). In this study, we assessed the relationship between early-life exposure to particulate matter (PM)10, PM2.5, and ADHD; (2) Methods: The National Health Insurance Research Database (NHIRD) contains the medical records, drug information, inspection data, etc., of the people of Taiwan, and, thus, could serve as an important research resource. Air pollution data were based on daily data from the Environmental Protection Administration Executive Yuan, R.O.C. (Taiwan). These included particulate matter (PM2.5 and PM10). The two databases were merged according to the living area of the insured and the location of the air quality monitoring station; (3) Results: The highest levels of air pollutants, including PM2.5 (adjusted hazard ratio (aHR) = 1.79; 95% confidence interval (CI) = 1.58-2.02) and PM10 (aHR = 1.53; 95% CI = 1.37-1.70), had a significantly higher risk of ADHD; (4) Conclusions: As such, measures for air quality control that meet the WHO air quality guidelines should be strictly and uniformly implemented by Taiwanese government authorities.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Transtorno do Deficit de Atenção com Hiperatividade , Pré-Escolar , Humanos , Material Particulado/análise , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Taiwan/epidemiologia , Exposição Ambiental/análise
14.
Biomed Pharmacother ; 156: 113859, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36252352

RESUMO

The AKR1A1 protein is a member of the aldo-keto reductase superfamily that catalyzes the transformation of D-glucuronate to L-gulonate in the synthesis of L-ascorbic acid (vitamin C, Vit C). We previously demonstrated that AKR1A1 knockout mice (AKR1A1eGFP/eGFP) with Vit C deficiency exhibited aberrant bone formation and osteoporosis. In this study, we aimed to evaluate the osteoprotective effects of kefir peptides (KPs) in AKR1A1eGFP/eGFP mice and uncover the underlying mechanism of KPs in the modulation of bone remodeling. Six male CD-1 mice and 24 male AKR1A1eGFP/eGFP mice were used in this study, in which the AKR1A1eGFP/eGFP mice were randomly divided into four groups (n = 6). KPs treatment for 12 weeks exerted several effects in AKR1A1eGFP/eGFP mice including the reduction of serum proinflammatory cytokines (IL-1ß, IL-6, TNF-α), bone resorption markers (CTX-1, RANKL), and the increase of serum bone formation markers (P1NP, OPG, OC). µ-CT analysis indicated that KPs prevented the bone loss in the femurs of AKR1A1eGFP/eGFP mice by significantly increasing the trabecular parameters of bone mineral density, bone volume and bone number. Nanoindentation analysis demonstrated that KPs enhanced the elasticity and hardness of femoral cortical bones in AKR1A1eGFP/eGFP mice. KPs promoted bone marrow mesenchymal stem cells (BMMSCs)-derived osteoblast differentiation and mineralization by upregulating positive regulators of osteoblastogenesis (Runx2, ß-catenin, BMP-2, NFATc1). Conversely, KPs inhibited bone marrow macrophages (BMMs)-derived osteoclast differentiation and bone resorption, which was demonstrated by the facts that KPs suppressed RANKL-induced p38, NF-κB, Akt, PLCγ2 and CREB-1 phosphorylation, decreased the nuclear translocation of NFATc1 and c-Fos. Our findings demonstrate the efficacy of KPs in the prevention of osteoporosis in AKR1A1eGFP/eGFP mice and also unveil the dual effects of KPs in osteogenic promotion and osteoclastic inhibition. This study supports the use of KPs as nutritional supplements for the prevention of osteoporosis.


Assuntos
Deficiência de Ácido Ascórbico , Reabsorção Óssea , Kefir , Osteoporose , Masculino , Camundongos , Animais , Osteogênese , Camundongos Knockout , Ligante RANK/metabolismo , Osteoclastos , Deficiência de Ácido Ascórbico/metabolismo , Diferenciação Celular , Osteoporose/prevenção & controle , Osteoporose/metabolismo , Reabsorção Óssea/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo
15.
PLoS One ; 17(8): e0273646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36026496

RESUMO

Diabetes mellitus (DM) is an important risk factor in patients with end-stage renal disease (ESRD). DM is associated with the development of cardiovascular diseases, such as atrial fibrillation (AF), due to poor glycemic control. However, few studies have focused on the risk of developing ESRD among DM patients with and without AF. This study evaluated ESRD risk among DM patients with and without AF in Taiwan. Data were retrieved from one million patients randomly sampled from Taiwan's National Health Insurance Research Database, including 6,105 DM patients with AF propensity score-matched with 6,105 DM patients without AF. Both groups were followed until death, any dialysis treatment, or December 31, 2013, whichever occurred first. AF was diagnosed by a qualified physician according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), using the diagnostic code 427.31. Patients aged <20 years or diagnosed with ESRD before the index date were excluded. A Cox proportional hazard regression model was used to calculate the relative ESRD risk. Among DM patients, those with AF have more comorbidities than those without AF. We also found a 1.18-fold (95% confidence interval [CI]: 1.01-1.46) increase in ESRD risk among patients with AF compared with those without AF. In addition, DM patients with hypertension, chronic kidney disease (CKD), or higher Charlson Comorbidity Index scores also have significantly increased ESRD risks than those without these complications. A 1.39-fold (95% CI: 1.04-1.86) increase in risk was observed for patients with AF among the non-CKD group. Our findings suggest that patients with DM should be closely monitored for irregular or rapid heart rates.


Assuntos
Fibrilação Atrial , Diabetes Mellitus , Falência Renal Crônica , Insuficiência Renal Crônica , Adulto , Humanos , Incidência , Diálise Renal , Estudos Retrospectivos , Fatores de Risco , Taiwan
16.
Children (Basel) ; 8(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34943278

RESUMO

Whether meconium-stained amniotic fluid (MSAF) serves as an indicator of fetal distress is under debate; however, the presence of MSAF concerns both obstetricians and pediatricians because meconium aspiration is a major contributor to neonatal morbidity and mortality, even with appropriate treatment. The present study suggested that thick meconium in infants might be associated with poor outcomes compared with thin meconium based on chart reviews. In addition, cell survival assays following the incubation of various meconium concentrations with monolayers of human epithelial and embryonic lung fibroblast cell lines were consistent with the results obtained from chart reviews. Exposure to meconium resulted in the significant release of nitrite from A549 and HEL299 cells. Medicinal agents, including dexamethasone, L-Nω-nitro-arginine methylester (L-NAME), and NS-398 significantly reduced the meconium-induced release of nitrite. These results support the hypothesis that thick meconium is a risk factor for neonates who require resuscitation, and inflammation appears to serve as the primary mechanism for meconium-associated lung injury. A better understanding of the relationship between nitrite and inflammation could result in the development of promising treatments for meconium aspiration syndrome (MAS).

17.
Diagnostics (Basel) ; 11(12)2021 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-34943577

RESUMO

The intravoxel incoherent motion (IVIM) model may enhance the clinical value of multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer (PCa). However, while past IVIM modeling studies have shown promise, they have also reported inconsistent results and limitations, underscoring the need to further enhance the accuracy of IVIM modeling for PCa detection. Therefore, this study utilized the control point registration toolbox function in MATLAB to fuse T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) MRI images with whole-mount pathology specimen images in order to eliminate potential bias in IVIM calculations. Sixteen PCa patients underwent prostate MRI scans before undergoing radical prostatectomies. The image fusion method was then applied in calculating the patients' IVIM parameters. Furthermore, MRI scans were also performed on 22 healthy young volunteers in order to evaluate the changes in IVIM parameters with aging. Among the full study cohort, the f parameter was significantly increased with age, while the D* parameter was significantly decreased. Among the PCa patients, the D and ADC parameters could differentiate PCa tissue from contralateral normal tissue, while the f and D* parameters could not. The presented image fusion method also provided improved precision when comparing regions of interest side by side. However, further studies with more standardized methods are needed to further clarify the benefits of the presented approach and the different IVIM parameters in PCa characterization.

18.
Medicine (Baltimore) ; 100(51): e28018, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34941042

RESUMO

ABSTRACT: Microalbuminuria is associated with both with chronic kidney disease and various cardiovascular abnormalities. Given the common use of electrocardiograms (EKGs) in diagnosing cardiovascular dysfunction, this study is analyzing the relationship between EKG abnormalities and diabetic nephropathy in type 2 diabetes mellitus (DM) patients. The enrollments of this study were from the 10-year follow-up data (2003-2012) of the Diabetes Management through an Integrated Delivery System project. All study subjects underwent at least 1 EKG measurement. The urinary microalbuminuria was recorded annually. The logistic regression model was used to evaluate the association between EKG abnormalities and the occurrence of diabetic nephropathy in type 2 DM patients. The total of 1189 patients with type 2 DM are included in this study and a total of 552 patients had microalbuminuria during a 10-year follow-up. A significantly higher odds ratio of microalbuminuria occurrence (4.85) was found in the patients with premature supraventricular contraction or tachycardia compared to those without EKG abnormalities. The odds ratios of microalbuminuria occurrence were 1.00, 2.43, 2.64, and 2.98, respectively, for patients with insulin resistance in the Q (quartile) 1(as the reference), Q2, Q3, and Q4, respectively. Our findings can serve as a reference for the association between EKG abnormalities and the development of microalbuminuria in type 2 diabetes.


Assuntos
Albuminúria/urina , Diabetes Mellitus Tipo 1/urina , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/epidemiologia , Eletrocardiografia , Idoso , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade
19.
Life (Basel) ; 11(12)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34947936

RESUMO

Telomeres cap the ends of eukaryotic chromosomes and are indispensable chromatin structures for genome protection and replication. Telomere length maintenance has been attributed to several functional modulators, including telomerase, the shelterin complex, and the CST complex, synergizing with DNA replication, repair, and the RNA metabolism pathway components. As dysfunctional telomere maintenance and telomerase activation are associated with several human diseases, including cancer, the molecular mechanisms behind telomere length regulation and protection need particular emphasis. Cancer cells exhibit telomerase activation, enabling replicative immortality. Telomerase reverse transcriptase (TERT) activation is involved in cancer development through diverse activities other than mediating telomere elongation. This review describes the telomere functions, the role of functional modulators, the implications in cancer development, and the future therapeutic opportunities.

20.
Life (Basel) ; 11(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34832987

RESUMO

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.

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