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1.
Neurogastroenterol Motil ; : e14140, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33939232

RESUMO

BACKGROUND: The type 3 adenylyl cyclase (AC3) enzyme is involved in the synthesis of cyclic adenosine monophosphate (cAMP). It is primarily expressed in the central nervous system (CNS) and plays a crucial role in neurogenesis and neural dendritic arborization. However, the AC3's functional role in the gastrointestinal tract remains ambiguous. METHODS: AC3 expression in enteric tissue of AC3+/+ mice was investigated using immunohistochemistry and RT-PCR. AC3 knock-out mice (AC3-/- ) were used to examine the effect of AC3 on the enteric nervous system (ENS) function and the number of cilia and apoptotic cells. Additionally, total gastrointestinal transit time and colonic motility were compared between the AC3-/- and AC3+/+ groups of mice. KEY RESULTS: AC3 was predominately expressed in the myenteric plexus of the large intestine. Colonic-bead expulsion analysis showed accelerated propulsion in the large intestine of the AC3-/- mice. The AC3-/- mice demonstrated reduced nerve fibers and enteric glial cells count in colonic mucosa compared to the AC3+/+ mice. Furthermore, AC3-/- mice exhibited increased cellular apoptosis and reduced ARL13B+ cilium cells in the colonic lamina propria compared to the AC3+/+ mice. CONCLUSIONS: In AC3-/- mice, innervation of the lamina propria in the colonic mucosa was reduced and colonic propulsion was accelerated. AC3 is crucial for the development and function of the adult neural network of ENS. AC3 deficiency caused atrophy in the colonic mucosal neural network of mice.

2.
Eur J Neurol ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33905575

RESUMO

BACKGROUND: Motoric cognitive risk syndrome (MCR) is characterized by slow walking speed and subjective memory complaints (SMCs). This study investigated the prevalence and potential risk factors of MCR and its association with falls in Chinese community-dwelling older adults. METHODS: The analysis was based on data from the Rugao Longevity and Aging Study (RuLAS). MCR was defined as presence of both SMC and slow walking speed in participants free of major neurocognitive disorders. SMCs were determined according to a positive answer to the question "Do you feel you have more problems with memory than most?" in the 15-item Geriatric Depression Scale. Slow walking speed was defined as ≤1 standard deviation below the mean values for patients' age and sex. Data on falls were derived from a standardized questionnaire. RESULTS: The prevalence of SMC, slow walking speed, and MCR in the RuLAS cohort (N=1592) was 51.9%, 15.6%, and 8.3%, respectively. After adjusting for other covariates, an occupation of farming (OR=2.358; 95% CI: 1.007-5.521, P=0.048), history of cerebrovascular disease (OR=2.215; 95% CI: 1.032-4.752, P=0.041), and hospitalization (OR=2.008; 95% CI: 1.120-3.602, P=0.019) were risk factors for MCR. Binary logistic regression analysis indicated that the risk of falls was increased by MCR (OR=1.547; 95% CI: 1.009-2.371), SMC (OR=1.308; 95% CI: 1.003-1.707), and slow walking speed (OR=1.442; 95% CI: 1.030-2.017). CONCLUSIONS: Early identification of potential risk factors of MCR can prevent the occurrence of adverse health events such as falls in the elderly.

3.
Clin Rheumatol ; 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33813619

RESUMO

OBJECTIVES: To compare cardiac function and systolic dyssynchrony of fetuses not exposed to and those exposed to maternal autoimmune antibodies using two-dimensional speckle tracking echocardiography (2DSTE). METHODS: An observational study of 52 fetuses, 18 from mothers with autoimmune antibodies (anti-SSA/Ro60, anti-Ro52 or/and anti-SSB/La) and 34 from healthy mothers without antibodies, was conducted. Maternal baseline characteristics, fetoplacental Doppler parameters, and conventional echocardiographic data were prospectively collected. Systolic global and regional longitudinal strain of left and right ventricle (LV and RV) and the time to peak strain of regional myocardium were measured using 2DSTE. We also calculated the differences in time to peak strain between the LV free wall and RV free wall (two-chamber dyssynchrony, 2C-DYS) and the LV dyssynchrony between the septum and LV free wall (one-chamber dyssynchrony, 1C-DYS). RESULTS: There were no significant differences in conventional systolic and diastolic functional parameters for the LV and RV. No effect modification was demonstrated in a myocardial deformation analysis. However, 1C-DYS was significantly more prolonged in the maternal autoimmune disease group (19.50 [8.00 to 29.25] vs. 28.50 [13.50 to 39.25], P = 0.042). CONCLUSIONS: LV systolic mechanical dyssynchrony in fetuses of mothers with autoimmune antibodies suggests in-utero subclinical damage of the cardiac conduction system. Key points • The left ventricular systolic dyssynchrony was significantly more prolonged in the maternal autoimmune disease (AD) fetuses. • Subclinical damage to the left ventricular conduction system of the fetal heart in maternal AD was observed. • Systolic and diastolic functional of the left and right ventricle were preserved in fetuses exposed to maternal autoimmune disease.

4.
J Dent ; 109: 103673, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33872753

RESUMO

INTRODUCTION: Vital pulp treatment (VPT) maintains tooth vitality with certain dental materials by protecting pulp from noxious stimulation and promoting repair through enhancing cell proliferation/differentiation, migration, and inducing odontogenesis. As a non-psychotropic cannabis constituent, cannabidiol (CBD) possesses the properties of analgesic, anti-inflammation, and osteogenesis. Therefore, we hypothesize that CBD may induce the odonto/osteogenesis of human dental pulp cells (HDPCs), a critical feature using as effective pulp capping agent for VPT. MATERIALS AND METHODS: In this in vitro study, the cytotoxicity of CBD on HDPCs was determined by MTT assay. Scratch assay was performed to analyze HDPC migration. The biomineralization was examined by collagen synthesis and calcium nodule formation and related odonto/osteogenic and angiogenic genes. Cannabinoid receptor (CB) specificity was evaluated by Western blotting and Von Kossa staining using specific antagonists AM251 for cannabinoid receptor 1 (CB1) and AM 630 targeted at cannabinoid receptor 2 (CB2). In addition, the underlying molecular mechanism of CBD-induced biomineralization were investigated by examining CB-dependent MAPK signaling pathways. RESULTS: CBD demonstrated bi-phasic effects on HDPC viability in tested concentrations. We found CBD significantly promoted cell migration, enhanced collagen synthesis and mineralized deposits in HDPCs when treated by 1 µM CBD supplemented in the differentiation media. RT-PCR revealed CBD increased the expression of angiogenic and odontogenic genes, such as DSPP, DMP-1, OPN, ALP, Runx2, VEGFR1 and ICAM-1. These effects were via MAPK activation in a manner mainly mediated by CB2. CONCLUSION: The results from this study suggested that CBD can induce odonto/osteogenesis from HDPCs and has the potential to develop new therapeutics in VPT in dentistry.

5.
Nutrients ; 13(4)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919830

RESUMO

Infantile anaemia has been a severe public health problem in China for decades. However, it is unclear whether there are regional differences in the prevalence of anaemia. In this study, we used data from the China Nutrition and Health Surveillance (CNHS) to assess the prevalence of anaemia and the risk factors associated with its prevalence in different regions. We included 9596 infants aged 0-23 months from the CNHS 2013 database. An infant was diagnosed with anaemia if he/she had a haemoglobin concentration of <110 g/L. We used multivariate logistic regression to investigate the potential risk factors associated with the development of anaemia. We found that anaemia was present in 2126 (22.15%) of the infants assessed. Approximately 95% of these cases were classified as mild anaemia. Based on the guidelines laid out by the World Health Organization, 5.5% and 43.6% of the surveillance sites were categorized as having severe and moderate epidemic levels of anaemia, respectively. The prevalence of infantile anaemia in Eastern, Central and Western China was 16.67%, 22.25% and 27.44%, respectively. Premature birth, low birth weight, breastfeeding and residence in Western China were significantly associated with higher odds of developing anaemia. Female sex and having mothers with high levels of education and maternal birth age >25 years were associated with lower odds of developing anaemia. In conclusion, we observed significant regional disparities in the prevalence of infantile anaemia in China. Western China had the highest prevalence of infantile anaemia, and rural regions showed a higher prevalence of anaemia than urban regions.

6.
Eur J Clin Nutr ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790398

RESUMO

BACKGROUND/OBJECTIVE: To investigate impacts of early postnatal macronutrient intakes on growth and body composition of preterm infants within the first 6 months. SUBJECTS/METHODS: One hundred and thirty-three very preterm (VPT) and/or very low birth weight (VLBW) infants were consecutively included. Enteral and parenteral macronutrient intakes during the first 28 days were recorded and average daily intakes were calculated. Growth was measured at birth, term age, and 6 months of corrected age (CA). Body composition was examined by air displacement plethysmograph at term age and 6 months of CA. Associations of nutrient intakes with growth and body composition over time were analyzed using generalized estimating equation. RESULTS: After adjusting for covariates, higher daily protein, lipid, and energy intake during the first 28 days was associated with higher weight at term age for every 1 g/kg/day increment of protein and lipid intake, and every 10 kcal/kg/day increment of energy intake was associated with 0.50 (95% CI 0.04, 0.96), 0.29 (95% CI 0.07, 0.51), and 0.27 (95% CI 0.10, 0.44) higher weight z-score, respectively. Higher protein intake was associated with lower z-score of fat mass (FM, ß = -1.88, 95% CI -3.53, -0.23) and percentage of body fat (PBF, ß = -2.18, 95% CI -3.98, -0.39) at 6 months of CA, but higher lipid and carbohydrate intake was associated with higher FM and PBF z-scores at 6 months of CA. CONCLUSIONS: Macronutrient intakes during the first month of life have impacts on growth and body composition before 6 months of age. Higher daily protein intake is associated with a better growth and healthier body composition for VPT/VLBW infants.

7.
Atherosclerosis ; 319: 72-78, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33486353

RESUMO

BACKGROUND AND AIMS: Intracranial atherosclerotic disease (ICAD) is a major etiologic cause for acute ischemic stroke (AIS) and transient ischemic attack (TIA). The study was designed to investigate if differential morphological features exist in symptomatic atherosclerotic lesions between AIS and TIA patients. METHODS: The culprit plaques from 45 AIS patients and 42 TIA patients were analyzed for the degree of stenosis, vessel wall irregularity, normalized wall index (NWI), remodeling index, plaque-wall contrast ratio (CR), high signal intensity on T1-weighted images, plaque enhancement ratio and enhancement grade. These plaque features along with clinical characteristics were compared between AIS and TIA groups as well as between their stenosis degree-matched subgroups. RESULTS: Overall, grade 2 enhancement (OR 3.85, 95%CI 1.42-10.46, p = 0.006) and hyperlipidemia (OR 3.04, 95%CI 1.13-8.22, p = 0.025) were independent indicators for AIS, whereas high NWI (OR 1.47, 95%CI 0.76-2.86, p = 0.004) was associated with TIA. In the comparison between the subgroups with moderate (30%-69%) stenosis, high plaque-wall CR (OR 5.38, 95%CI 1.39-20.75, p = 0.008) was associated with AIS, whereas high NWI (OR 2.50, 95%CI 0.61-10.00, p = 0.006) was associated with TIA. CONCLUSIONS: Our study reveals differential morphological features in symptomatic ICAD lesions between AIS and TIA patients. Probing these features with MR vessel wall imaging may provide insights into the prognosis of patients with ICAD.

8.
Carbohydr Polym ; 256: 117556, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33483059

RESUMO

Acute kidney injury (AKI) is a common and serious clinical syndrome of acute renal dysfunction in a short period. One of therapeutic interventions for AKI is to reduce ROS massively generated in the mitochondria and then ameliorate cell damage and apoptosis induced by oxidative stress. In this study, stepwise-targeting chitosan oligosaccharide, triphenyl phosphine-low molecular weight chitosan-curcumin (TPP-LMWC-CUR, TLC), was constructed for sepsis-induced AKI via removing excessive ROS in renal tubular epithelial cells. Benefiting from good water solubility and low molecular weight, TLC was rapidly and preferentially distributed in the renal tissues and then specifically internalized by tubular epithelium cells via interaction between Megalin receptor and LMWC. The intracellular TLC could further delivery CUR to mitochondria due to high buffering capacity of LMWC and delocalized positive charges of TPP. Both in vitro and in vivo pharmacodynamic results demonstrated the enhanced therapeutic effect of TLC in the treatment of AKI.

9.
J Natl Med Assoc ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33478800

RESUMO

Multiple Myeloma (MM) is a neoplastic disorder derived from the malignant proliferation of monoclonal plasma cells. It is characterized by the overproduction of immunoglobulins (Ig). We report a rare case in which bulbar palsy was the initial manifestation of IgG-MM. A 66-year-old woman initially presented with progressive dysphagia and dysarthria for half a year. Physical examination demonstrated a deviation of the uvula, difficulty in protruding tongue, and bilateral tongue atrophy. Laboratory assessments revealed anemia and prominent monoclonal elevation of IgG levels both in serum and cerebrospinal fluid (CSF). The diagnosis of IgG-MM was confirmed by the identification of plasmacytosis in bone marrow aspiration and biopsy and elevation of γ-M protein in serum protein electrophoresis (SPEP). Therefore, the patient began to receive the chemotherapy with PAD (bortezomib-doxorubicin-dexamethasone) regimen. Her condition had been under control. MM as a hematological malignancy can affect cranial nerves and present as chronic progressive bulbar palsy.

10.
Exp Neurol ; 337: 113574, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33345977

RESUMO

Activin A plays important roles in ischemic injury and white matter remyelination, but its mechanisms are unclear. In this study, the adult male C57BL/6 J mice were used to establish the model of 1 h middle cerebral artery occlusion/reperfusion (MCAO/R) 1 d to 28 d-induced ischemic stroke in vivo. We found that the neurological outcome was positively correlated with the levels of myelin associated proteins (include MAG, CNPase, MOG and MBP, n = 6 per group) both in corpus callosum and internal capsule of mice with ischemic stroke. The dynamic changes of Luxol fast blue (LFB) staining intensity, oligodendrocyte (CC1+) and proliferated oligodendrocyte precursor (Ki67+/PDGFRα+) cell numbers indicated demyelination and spontaneous remyelination occurred in the corpus callosum of mice after 1 h MCAO/R 1 d-28 d (n = 6 per group). Activin receptor type I (ACVR1) inhibitor SB431542 aggregated neurological deficits, and reduced MAG, MOG and MBP protein levels of mice with ischemic stroke (n = 6 per group). Meanwhile, recombinant mouse (rm) Activin A enhanced the neurological function recovery, MAG, MOG and MBP protein levels of mice with 1 h MCAO/R 28 d. In addition, the injection of AAV-based ACVR1B shRNA with Olig2 promoter could reverse rmActivin A-induced the increases of CC1+ cell number, LFB intensity, MAG, MOG and MBP protein levels in the corpus callosum (n = 6 per group), and neurological function recovery (n = 10 per group) of mice with 1 h MCAO/R 28 d. These results suggested that Activin A improves the neurological outcome through promoting oligodendroglial ACVR1B-mediated white matter remyelination of mice with ischemic stroke, which may provide a potential therapeutic strategy for ischemic stroke.

11.
J Int Med Res ; 48(11): 300060520967540, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33251892

RESUMO

OBJECTIVE: Waardenburg syndrome type 2 (WS2) is an autosomal dominant syndrome, characterized by bright blue eyes, hearing loss, and depigmented patches of hair and skin. It exhibits high phenotypic and genetic heterogeneity. We explored the molecular etiology in a Chinese family with WS2. METHODS: We recruited a three-generation family with three affected members. Medical history was obtained from all family members who underwent detailed physical examinations and audiology tests. Genomic DNA was extracted from peripheral blood of each individual, and 139 candidate genes associated with hearing loss were sequenced using Illumina HiSeq 2000 (Illumina Inc., San Diego, CA, USA) and verified by Sanger sequencing. RESULTS: Genetic evaluation revealed a novel nonsense heterozygous variant, NM_006941.4: c.342G>A (p.Trp114Ter) in exon 2 of the SOX10 gene in the three affected patients; no unaffected family member carried the variation. We did not detect the variation in 500 Chinese individuals with normal hearing or in 122 unrelated Chinese families with hearing loss, suggesting that it was specific to our patients. CONCLUSIONS: We identified a novel heterozygous nonsense variation in a family with syndromic hearing loss and WS2. Our findings expand the pathogenic spectrum and strengthen the clinical diagnostic role of SOX10 in patients with WS2.

12.
Front Pediatr ; 8: 497447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194880

RESUMO

Background: Abernethy malformation is a rare vascular anomaly of the portal venous system, which is also known as congenital portosystemic shunts (CPSS). The clinical manifestations of this anomaly can be serious, including hepatopulmonary syndrome(HPS), which can lead to significant hypoxemia and cyanosis. Case Presentation: This study reports two cases of patients with Abernethy Malformation. Case 1 was a 6-year-old boy whose blood oxygen saturation was 78%. Case 2 was a 6-year-old girl who had a history of open heart surgery and residual cardiac left to right shunt, whose blood oxygen saturation was 83%. These two children had unexplained cyanosis and were diagnosed with pulmonary arteriovenous fistula by contrast echocardiography with agitated saline. A selective retrograde catheter angiography confirmed the presence of a portosystemic shunt. Case 1 was a type I Abernethy malformation and did not receive any specific treatment and could only wait for liver transplantation. Case 2 was with type II Abernethy and underwent transcatheter closure of the CPSS. A 20mm-diameter, 14mm-long Vascular Plug (SHSMA Inc, Shanghai, China) was used to occlude the shunt. Results: In case 1, the boy developed deteriorating cyanosis and dyspnea on exertion. In case 2, the exercise tolerance of the patient improved after shunt closure. During a follow-up of 3 years, her blood oxygen saturation increased from 83 to 98%. Conclusion: The results indicate that children with unexplained cyanosis require special attention since these patients may have Abernethy malformation, and part of them could be treated by transcatheter occlusion with a good outcome. The key to treatment is how it is diagnosed and carefully assessed.

13.
Front Aging Neurosci ; 12: 274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101005

RESUMO

We previously reported that the levels of astrocyte-derived interleukin-17A (IL-17A) increased both in the peri-infarct region and cerebrospinal fluid (CSF) of mice with 1-h middle cerebral artery (MCA) occlusion/12-h reperfusion (1-h MCAO/R 12 h)-induced ischemic stroke. However, the effects of IL-17A neutralization on the neurological outcome of mice with ischemic stroke and its underlying molecular mechanism are unclear. In this study, we found that the intracerebroventricular injection of IL-17A-neutralizing monoclonal antibody (mAb; 2.0 µg) could reduce the infarct volume, alleviate neuron loss, and improve the neurological outcomes of mice with 1-h MCAO/R 24-h- or 3-day-induced ischemic-stroke mice. The IL-17A neutralization could also significantly inhibit the increase of pro-caspase-3 cleavage through caspase-12-dependent cell apoptosis, as well as preventing the decrease of antiapoptotic factor B-cell lymphoma 2 (Bcl-2) and the increase of proapoptotic Bcl-2-associated X protein (Bax) in the peri-infarct region of mice following ischemic stroke. In addition, we confirmed that the recombinant mouse (rm) IL-17A could significantly aggravate 1-h oxygen-glucose deprivation/24-h reoxygenation (1-h OGD/R 24 h)-induced ischemic injuries in cortical neurons in a dose-dependent manner, and the rmIL-17A could also exacerbate neuronal apoptosis through caspase-12 (not caspase-8 or caspase-9)-dependent pathway. These results suggest that IL-17A neutralization could improve the neurological outcome of mice with ischemic stroke through inhibiting caspase-12-dependent neuronal apoptosis.

14.
Exp Ther Med ; 20(2): 1105-1114, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32742350

RESUMO

Cardiovascular diseases are among the primary causes of decreased quality of life as well as mortality of hemodialysis patients with end-stage renal disease. The aim of the present study was to evaluate the predictive value of the red blood cell distribution width (RDW)-to-platelet ratio (RPR) and neutrophil-to-lymphocyte ratio (NLR) regarding the occurrence or development of cardiovascular events in hemodialysis patients, as well as the prognostic value of this metric. A total of 219 hemodialysis patients with cardiovascular events (HCE group) and 276 hemodialysis patients with no cardiovascular events (HNCE group) were enrolled in the present study. The clinical characteristics and laboratory parameters on admission, including RDW, as well as neutrophil, lymphocyte and platelet counts, were recorded. The NLR and RPR were increased in the HCE group compared with those in the HNCE group and there was a positive association between the NLR or RPR and the incidence of cardiovascular events in hemodialysis patients. In the receiver operating characteristics curve analysis, the area under the curve of the RPR for predicting cardiovascular events in hemodialysis patients was 0.88, while that for the NLR was 0.84. The sensitivity and specificity of the RPR for predicting cardiovascular events in hemodialysis patients were 0.87 and 0.82 respectively, and for the NLR, they were 0.75 and 0.79, respectively. The RPR was an independent risk factor for the prognosis regarding cardiovascular events in hemodialysis patients. In addition, the NLR and RPR were correlated with brain natriuretic peptide (BNP), cardiac troponin I (cTnI), creatine kinase isoenzyme-MB (CK-MB), and associated with ST segment changes in HCE patients. In conclusion, it was possible to predict the incidence of cardiovascular events in hemodialysis patients using the NLR and RPR, while the RPR had a better sensitivity and specificity than the NLR. The RPR was an independent risk factor for the prognosis regarding cardiovascular events in hemodialysis patients. These routinely available parameters should be considered as novel diagnostic markers for the occurrence and development of cardiovascular events in hemodialysis patients and their prognosis.

15.
Int J Pediatr Otorhinolaryngol ; 136: 110143, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32645618

RESUMO

OBJECTIVE: To expose the spectrum and frequency of GJB2, GJB3, SLC26A4 and MT-RNR1 in northwest China and to investigate the underlying causative genes in patients without common mutations. METHODS: We analyzed the mutation screening results of GJB2, GJB3, SLC26A4 and MT-RNR1 in 398 unrelated severe-to-profound probands with bilateral, symmetrical sensorineural hearing loss. Subsequently, we selected 10 probands with a significant family history of inherited hearing loss (HL) that did not have the above four common gene mutations to perform next-generation sequencing (NGS) of 139 known deafness genes, followed by co-segregation analysis of all available family members. RESULTS: Among the 398 patients, 69 (17.34%) had the biallelic GJB2 gene mutations, and the most common mutations were c.235delC, c.109G>A and c.299_300delAT, with allele frequencies of 12.31%, 3.38% and 3.89%, respectively. A total of 63 (15.83%) cases with biallelic SLC26A4 mutations were detected, and the most common pathogenic alleles were c.919-2A>G, c.2168A>G and c.1174A>T, with allele frequencies of 9.17%, 2.26% and 0.88%, respectively. Mitochondrial gene mutations were detected in 9 (2.26%) patients, with 5 cases of mitochondrial DNA (mtDNA) m.1555A>G mutation and 4 cases of mtDNA m.1095T>C mutation. In 10 probands with a clear family history of HL, NGS showed two novel pathogenic variants in 2 families, including c.4129C>T/c.3268C>T in LOXHD1, c.334G>A/c.2968G>T in CDH23. Sanger sequencing confirmed that these variants segregated with the HL in each family. CONCLUSIONS: Our results showed that GJB2 and SLC26A4 were the two major HL-causing genes in northwest China. The most common mutation alleles in GJB2 were c.235delC, c.109G>A and c.299_300delAT, and those in SLC26A4 were c.919-2A>G, c.2168A>G and c.1174A>T. In addition, both genes and their loci can be used as the first selection of deafness gene screening. Additionally, for patients who did not have mutations of these common genes, NGS provided an efficient diagnosis for increasing known deafness genes.

16.
Oral Dis ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640491

RESUMO

OBJECTIVES: To investigate the effects of environmental tobacco smoke (ETS) on the inflammatory process of periodontitis by evaluating bone loss and the expression of cyclooxygenase-2 (COX-2) and Src homology phosphotyrosine phosphatase 2 (SHP-2). MATERIALS AND METHODS: Eighty 6-month-old male SD rats were randomized into four groups (10 rats/group/per time point): (a) normal group, (b) ETS group, (c) ligature-induced periodontitis group, and (d) ligature-induced periodontitis + ETS group. After treatment with ligature and/or ETS for 8 and 12 weeks, the levels of alveolar bone resorption and the expressions of COX-2 and SHP-2 in periodontal tissue were analyzed using histology and immunohistochemistry. RESULTS: The ligature-induced periodontitis group displayed increased bone resorption and elevated expression of COX-2 and SHP-2 in periodontal tissues compared to the normal and ETS groups at 8 and 12 weeks. Furthermore, bone resorption and COX-2 and SHP-2 levels in the ligature-induced periodontitis + ETS group were significantly increased compared to those in the normal and ligature-induced periodontitis groups at both 8 and 12 weeks. CONCLUSION: Environmental tobacco smoke increased alveolar bone loss in periodontitis with enhanced expression of COX-2 and SHP-2 in periodontal tissues. Further investigation is needed to explore the role of COX-2 and SHP-2 in ETS-associated periodontitis.

17.
Medicine (Baltimore) ; 99(27): e20783, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629660

RESUMO

BACKGROUND: To systematically review the effects of Danhong injection on endothelial function and inflammatory factors after the percutaneous coronary intervention (PCI) for coronary heart disease (CHD) and to provide a basis for further research. METHODS: Through computer retrieval, including PubMed, Embase, the Cochrane Library, CNKI, Wan Fang Data, VIP, SinoMed were retrieved on a computer. Randomized controlled trials (RCTs) on the effects of Danhong injection on endothelial function and inflammatory factors after PCI for CHD were collected in strict accordance with the pre-established inclusion and exclusion criteria. Chinese and English literatures in published from the establishment of each database to December 1, 2019, were retrieved by combining subject headings and free terms. Literatures were screened out by 2 researchers independently, and the risk of bias was assessed by 2 independent researchers by using the assessment tool for risk of bias as described Cochrane systematic reviewer's manual 5.1.0. Statistical analysis was performed by using Stata 14.0 software. RESULTS: By collecting the existing evidence, this study would determine the effects of Danhong injection on endothelial function and inflammatory factors after PCI for CHD by meta-analysis. CONCLUSION: Through this study, we will draw a definite conclusion on whether Danhong injection has significant effects on endothelial function and inflammatory factors after PCI for CHD. This conclusion will provide practical and scientific guidance for the use of Danhong injection after PCI for CHD. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020165568.


Assuntos
Doença das Coronárias/cirurgia , Medicamentos de Ervas Chinesas/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Inflamação/tratamento farmacológico , Intervenção Coronária Percutânea/métodos , Terapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Endotélio Vascular/lesões , Humanos , Inflamação/etiologia , Injeções , Intervenção Coronária Percutânea/efeitos adversos
18.
Nat Metab ; 2(2): 167-178, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32617517

RESUMO

The neonatal mammalian heart is capable of regeneration for a brief window of time after birth. However, this regenerative capacity is lost within the first week of life, which coincides with a postnatal shift from anaerobic glycolysis to mitochondrial oxidative phosphorylation, particularly towards fatty-acid utilization. Despite the energy advantage of fatty-acid beta-oxidation, cardiac mitochondria produce elevated rates of reactive oxygen species when utilizing fatty acids, which is thought to play a role in cardiomyocyte cell-cycle arrest through induction of DNA damage and activation of DNA-damage response (DDR) pathway. Here we show that inhibiting fatty-acid utilization promotes cardiomyocyte proliferation in the postnatatal heart. First, neonatal mice fed fatty-acid deficient milk showed prolongation of the postnatal cardiomyocyte proliferative window, however cell cycle arrest eventually ensued. Next, we generated a tamoxifen-inducible cardiomyocyte-specific, pyruvate dehydrogenase kinase 4 (PDK4) knockout mouse model to selectively enhance oxidation of glycolytically derived pyruvate in cardiomyocytes. Conditional PDK4 deletion resulted in an increase in pyruvate dehydrogenase activity and consequently an increase in glucose relative to fatty-acid oxidation. Loss of PDK4 also resulted in decreased cardiomyocyte size, decreased DNA damage and expression of DDR markers and an increase in cardiomyocyte proliferation. Following myocardial infarction, inducible deletion of PDK4 improved left ventricular function and decreased remodelling. Collectively, inhibition of fatty-acid utilization in cardiomyocytes promotes proliferation, and may be a viable target for cardiac regenerative therapies.

19.
Stroke Vasc Neurol ; 5(2): 159-176, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32561535

RESUMO

AIM: Stroke is the leading cause of disability and death in China. Ischaemic stroke accounts for about 60%-80% of all strokes. It is of considerable significance to carry out multidimensional management of ischaemic cerebrovascular diseases. This evidence-based guideline aims to provide the latest detailed and comprehensive recommendations on the diagnosis, treatment and secondary prevention of ischaemic cerebrovascular diseases. METHODS: We had performed comprehensive searches of MEDLINE (via PubMed) (before 30 June 2019), and integrated the relevant information into charts and distributed to the writing group. Writing group members discussed and determined the recommendations through teleconference. We used the level of evidence grading algorithm of Chinese Stroke Association to grade each recommendation. The draft was reviewed by the Guideline Writing Committee of Chinese Stroke Association Stroke and finalised. This guideline is fully updated every 3 years. RESULTS: This evidence-based guideline is based on the treatment, care and prevention of ischaemic cerebrovascular diseases, which emphasises on pathogenesis evaluation, intravenous thrombolysis, endovascular therapy, antiplatelet therapy, prevention and treatment of complications, and risk factor management. CONCLUSIONS: This updated guideline presents a framework for the management of ischaemic cerebrovascular diseases. Timely first-aid measures, professional care in the acute stage, and proactive secondary prevention will be helpful to patients.


Assuntos
Isquemia Encefálica/terapia , Medicina Baseada em Evidências/normas , Neurologia/normas , Acidente Vascular Cerebral/terapia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , China/epidemiologia , Tomada de Decisão Clínica , Consenso , Técnicas de Apoio para a Decisão , Humanos , Valor Preditivo dos Testes , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Tempo para o Tratamento/normas , Resultado do Tratamento
20.
Nature ; 582(7811): 271-276, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32499640

RESUMO

A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2 and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest3. Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.


Assuntos
Calcineurina/metabolismo , Proliferação de Células , Proteínas de Homeodomínio/metabolismo , Proteína Meis1/metabolismo , Miócitos Cardíacos/citologia , Animais , Animais Recém-Nascidos , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Coração/fisiologia , Proteínas de Homeodomínio/genética , Masculino , Camundongos , Miocárdio/citologia , Ligação Proteica , Regeneração
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