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1.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638796

RESUMO

Diosmin, a natural flavone glycoside acquired through dehydrogenation of the analogous flavanone glycoside hesperidin, is plentiful in many citrus fruits. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor; the average survival time of GBM patients is less than 18 months after standard treatment. The present study demonstrated that diosmin, which is able to cross the blood-brain barrier, inhibited GBM cell growth in vitro and in vivo. Diosmin also impeded migration and invasion by GBM8401and LN229 GBM cells by suppressing epithelial-mesenchymal transition, as indicated by increased expression of E-cadherin and decreased expression of Snail and Twist. Diosmin also suppressed autophagic flux, as indicated by increased expression of LC3-II and p62, and induced cell cycle arrest at G1 phase. Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.

2.
Int J Mol Sci ; 22(19)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34639192

RESUMO

As with other environmental stresses, cold stress limits plant growth, geographical distribution, and agricultural productivity. CBF/DREB (CRT-binding factors/DRE-binding proteins) regulate tolerance to cold/freezing stress across plant species. ICE (inducer of CBF expression) is regarded as the upstream inducer of CBF expression and plays a crucial role as a main regulator of cold acclimation. Snow lotus (Saussurea involucrata) is a well-known traditional Chinese herb. This herb is known to have greater tolerance to cold/freezing stress compared to other plants. According to transcriptome datasets, two putative ICE homologous genes, SiICE1 and SiICE2, were identified in snow lotus. The predicted SiICE1 cDNA contains an ORF of 1506 bp, encoding a protein of 501 amino acids, whereas SiICE2 cDNA has an ORF of 1482 bp, coding for a protein of 493 amino acids. Sequence alignment and structure analysis show SiICE1 and SiICE2 possess a S-rich motif at the N-terminal region, while the conserved ZIP-bHLH domain and ACT domain are at the C-terminus. Both SiICE1 and SiICE2 transcripts were cold-inducible. Subcellular localization and yeast one-hybrid assays revealed that SiICE1 and SiICE2 are transcriptional regulators. Overexpression of SiICE1 (35S::SiICE1) and SiICE2 (35S::SiICE2) in transgenic Arabidopsis increased the cold tolerance. In addition, the expression patterns of downstream stress-related genes, CBF1, CBF2, CBF3, COR15A, COR47, and KIN1, were up-regulated when compared to the wild type. These results thus provide evidence that SiICE1 and SiICE2 function in cold acclimation and this cold/freezing tolerance may be regulated through a CBF-controlling pathway.

3.
CNS Neurosci Ther ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34643338

RESUMO

AIMS: The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS. METHODS: Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics. RESULTS: Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores. CONCLUSION: STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations.

4.
World Neurosurg ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634505

RESUMO

PURPOSE: Extensive reports have demonstrated the neuroprotection of sevoflurane postconditioning under the background of focal and global cerebral ischemia/reperfusion, the underlying mechanisms are not completely elucidated. This study was to investigate if this effect is related to eNOS and mediated by phosphoinositide-3-kinase pathway in a rat model of hemorrhagic shock and resuscitation. METHODS: Adult male Sprague-Dawley rats were subjected to hemorrhagic shock for 60min and then resuscitation for 30min in exprimental groups. Sevoflurane postconditioning was performed at the beginning of resuscitation till the completion. At 24 hours after resuscitation, the infarct volume of brain was evaluated by TTC staining. The neuronal morphologic changes and apoptosis were determined by H&E staining and immunohistochemistry analysis, respectively. The activity of p-Akt and eNOS were evaluated by Western Blot analysis. RESULTS: The brain injuries such as the cerebral infarct volume and pathological neuronal changes as well as cell apoptosis were observed in the hippocampus after HSR. Postconditioning with 2.4% sevoflurane significantly attenuated brain injuries. Wortmannin prevented the improvements of neuronal characteristics elicited by sevoflurane postconditioning, as well as the hyperactivity of eNOS and p-Akt. CONCLUSION: Sevoflurane postconditioning could attenuate brain injury induced by hemorrhagic shock and resuscitation, and this neuroprotective effect may be partly by upregulation of eNOS through PI3K/Akt signaling pathway.

5.
Dalton Trans ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623362

RESUMO

A series of new organic hybrid polyoxovanadate clusters [V4O4(µ-OH)2(acac)2(Htri)2] (1, H3tri = tris(hydroxymethyl) aminomethane, acac = acetylacetone), [V4O4(acac)2(Htri)2(L)2] {HL = methanol (2), ethanol (3a and 3b), ethylene glycol (4) and benzyl alcohol (5)}, {V4O4(H2O)2(tri-acetamide)2(CH3COO)2} (6, H3tri-acetamide = N-(2-hydroxy-1,1-bis-hydroxymethyl-ethyl)-acetamide), [V6O8(µ-OH)2(Htri)3]·6H2O (7) and [V14O18(tri)2(Htri)6(HCOO)(CH3COO)]·2H2O (8) were prepared by hydro(solvo)thermal methods and characterized structurally. 1 contains [VO(OH)(acac)] and [VO2(Htri)] units, which are further interconnected via common edges to build a tetravanadyl cluster [V4O4(OH)2(acac)2(Htri)2] with the double-deficient cube [V4O6]. The tetravanadyl cluster frameworks of 2-5 can be derived from the tetravanadyl cluster of 1 by replacing two -OH groups with two deprotonated organic alcohol ligands, namely, CH3O- (2), CH3CH2O- (3a and 3b), HO(CH2)2O- (4) and C6H5CH2O- (5). Interestingly, both 3a and 3b have the same chemical structure, but they exhibit different conformational polymorphisms [denoted as α-type (3a) and ß-type (3b)]. Such conformational polymorphisms within the polyoxovanadate clusters incorporating tris(hydroxymethyl)methane derivatives emerged for the first time. 6 displays another tetravanadyl cluster {V4O4(H2O)2(tri-acetamide)2(CH3COO)2} with a [V4O16] fragment, where the tri-acetamide unit comes from the amidation reaction of H3tri and acetic acid and caps the tetrahedral void of the tetravanadyl cluster. The polyoxovanadate cluster of 7 can originate from the Lindqvist-type hexavanadyl cluster [V6O19] by replacing nine µ-oxides with nine alkoxides of three tri-acetamide3- ligands. 8 exhibits a fully reduced tetradecavanadyl cluster based on the linkage of two heptavanadyl clusters via two O bridges. The magnetic properties of 1-8 show typical antiferromagnetic interactions.

6.
J Formos Med Assoc ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34645591

RESUMO

BACKGROUND/PURPOSE: The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. METHODS: Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. RESULTS: The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the "CTA" (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, "TCG" (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). CONCLUSION: Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

7.
Aging Clin Exp Res ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648176

RESUMO

BACKGROUND: Transitional care (TC) has become increasingly important for elders with chronic diseases (CDs) discharged from hospital as the population ages. This study aims to analyze the health quality of life (HQoL) in elders received TC based on the Short Form-36 (SF-36) indicator. METHODS: PubMed, EMBASE, Web of Science and Science Direct were systematically search for studies. Studies compared HQoL used SF-36 between TC and usual care on elders discharged for CDs were included. Analysis was performed with respect to the 8 dimensions of SF-36. RESULTS: A total of 16 studies were included. Compared with usual care, (1) the scores of SF-36 outcomes increase as follow-up time extending; (2) transitional care significantly improved mental health, physical functioning and vitality at both short and long term after discharge; (3) transitional care only significantly improved general health and social function at long term; and role limitation due to emotional problems and bodily pain at short term; (4) transitional care significantly improved general health, mental health, physical functioning, social function and vitality for patients with hip fracture at long term. CONCLUSION: TC can significantly improve physically and mentally HQoL for elder patients discharge for CDs compared with usual care.

8.
Plant Physiol ; 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618068

RESUMO

Sphingolipids are structural components of the lipid bilayer that acts as signaling molecules in many cellular processes, including cell death. Ceramides, key intermediates in sphingolipid metabolism, are phosphorylated by the ceramide kinase ACCELERATED CELL DEATH5 (ACD5). The loss of ACD5 function leads to ceramide accumulation and spontaneous cell death. Here, we report that the jasmonate (JA) pathway is activated in the Arabidopsis (Arabidopsis thaliana) acd5 mutant and that methyl JA treatment accelerates ceramide accumulation and cell death in acd5. Moreover, the double mutants of acd5 with jasmonate resistant1-1 and coronatine insensitive1-2 exhibited delayed cell death, suggesting that the JA pathway is involved in acd5-mediated cell death. Quantitative sphingolipid profiling of plants treated with methyl JA indicated that JAs influence sphingolipid metabolism by increasing the levels of ceramides and hydroxyceramides, but this pathway is dramatically attenuated by mutations affecting JA pathway proteins. Furthermore, we showed that JAs regulate the expression of genes encoding enzymes in ceramide metabolism. Together, our findings show that JAs accelerate cell death in acd5 mutants, possibly by modulating sphingolipid metabolism and increasing ceramide levels.

9.
Vascul Pharmacol ; : 106923, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34600152

RESUMO

Protein-bound uremic toxins (PBUTs) have adverse effects on vascular function, which is imperative in the progression of cardiovascular and renal diseases. The role of sphingolipids in PBUT-mediated vasculo-endothelial pathophysiology is unclear. This study assessed the therapeutic potential of dihydroceramide desaturase 1 (Des1) inhibition, the last enzyme involved in de novo ceramide synthesis, to mitigate the vascular effects of the PBUT indoxyl sulfate (IS). Rat aortic rings were isolated and vascular reactivity was assessed in organ bath experiments followed by immunohistochemical analyses. Furthermore, cultured human aortic endothelial cells were assessed for phenotypic and mechanistic changes. Inhibition of Des1 by a selective inhibitor CIN038 (0.1 to 0.3 µM) improved IS-induced impairment of vasorelaxation and modulated immunoreactivity of oxidative stress markers. Des1 inhibition also reversed IS-induced reduction in endothelial cell migration (1.0 µM) by promoting the expression of angiogenic cytokines and reducing inflammatory and oxidative stress markers. These effects were associated with a reduction of TIMP1 and the restoration of Akt phosphorylation. In conclusion, Des1 inhibition improved vascular relaxation and endothelial cell migration impaired by IS overload. Therefore, Des1 may be a suitable intracellular target to mitigate PBUT-induced adverse vascular effects.

10.
Bioelectrochemistry ; 143: 107969, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637961

RESUMO

Flavonoids, alkaloids, glucosides and tannins with good corrosion inhibition are the main natural components in plants. In this work, procyanidin B2 (PCB2), a natural flavonoid, was firstly isolated from Uncaria laevigata. Corrosion inhibition, chemical reactivity and adsorption of PCB2 on Q235 carbon steel were described by experimental and theoretical studies. The inhibition performance of PCB2 as a green corrosion inhibitor was evaluated by electrochemical and gravimetric tests. The binding active sites and activities thereof on the steel surface were illustrated by quantum chemistry, and the equilibrium configuration was predicted by molecular dynamics simulation. PCB2 exhibits good corrosion inhibition on Q235 steel over a wide temperature range. The electrochemical results show that PCB2 is a mixed inhibitor, and its inhibition efficiency increases with the addition of PCB2 concentration. Moreover, the protective film is formed on the steel and the active corrosion sites are blocked significantly by surface analysis. Additionally, the theoretical calculation proves a strong interaction between PCB2 molecule and carbon steel. Besides, the antimicrobial activity was also preliminarily studied. This suggests that PCB2 exhibits better antimicrobial activity against many Gram-positive and Gram-negative bacteria. As a novel green corrosion inhibitor and antimicrobial agent, PCB2 is worthy of further exploitation.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1601-1605, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627447

RESUMO

OBJECTIVE: To analyze the clinical efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH), and preliminarily explore the role of an improved post-transplantation cyclophosphamide (PTCy) based conditioning regimen in PNH patients receiving transplantation. METHODS: Clinical related data of PNH sufferers receiving allo-HSCT in Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected, and hematopoietic reconstitution, chimerism, PNH cloning, graft-versus-host disease (GVHD), infection, and survival were analyzed. RESULTS: Totally five PNH patients receiving allo-HSCT were enrolled, including 1 case with classic PNH, 3 cases with aplastic anemia-PNH syndrome, 1 case with myelodysplastic syndrome, three of them (case 1-3) received the improved PTCy based conditioning regimen before HSCT. All sufferers engrafted successfully within 28 days, the median time of neutrophil and platelet engraftment was 11 days and 12 days, respectively, no patient occurred acute or chronic GVHD, after a median follow-up of 16 months, all recipients survived and completely eliminated PNH cloning. CONCLUSION: Allo-HSCT can completely clear PNH cloning and restore hematopoietic function with controllable complications, and the improved PTCy based conditioning regimen is proved to be effective in PNH transplantation.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística , Anemia Aplástica/terapia , Hemoglobinúria Paroxística/terapia , Humanos , Condicionamento Pré-Transplante
12.
Anal Chim Acta ; 1183: 338870, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34627528

RESUMO

Nowadays, brain natriuretic peptide (BNP-32) is fundamental to early cardiovascular clinical diagnosis, whose accurate assay is of significance by photoelectrochemistry (PEC) for the low background and high precision. Herein, a novel enhanced PEC platform was built by successive deposition of N-doped ZnO nanopolyhedra (N-ZnO NP) and protoporphyrin IX (PPIX). Specifically, the N-ZnO NP with a narrow bandgap of 2.60 eV was synthesized by direct calcination of zeolitic imidazole framework-8 (ZIF-8), and performed as the substrate to enhance the photocurrents of PPIX (as photosensitizer) whose photoelectron transfer pathway and enhanced PEC mechanism were studied in detail. Under such foundation, a label-free PEC aptasensor was developed by deposition of DNA aptamer onto the PEC platform and then ultrasensitive assay of BNP-32 based on a "signal off" model. The biosensor showed a wide linear range (1 pg mL-1- 0.1 µg mL-1) with a limit of detection (LOD) as low as 0.14 pg mL-1. This doping technique of ZnO nanomaterials provides some valuable guidelines for synthesis of advanced PEC probes in bioanalysis.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Porfirinas , Óxido de Zinco , Peptídeo Natriurético Encefálico
13.
BMC Infect Dis ; 21(1): 1057, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641796

RESUMO

BACKGROUND: Some children hospitalized for severe pertussis need intensive care; moreover, some children die because of deterioration alone or in combination with other complications. The purpose of this study was to identify the mortality risk factors among hospitalized children with severe pertussis. METHODS: This study evaluated the medical records of 144 hospitalized children with severe pertussis at the Guangzhou Women and Children's Medical Centre between January 2016 and December 2019. RESULTS: The median age of patients was 2 months (IQR 1-4 months), with 90.3% of the patients aged < 6 months and 56.9% of the patients aged < 3 months. A total of 38 patients were admitted to intensive care unit (ICU), 13 patients died, and the mortality of severe pertussis was 34.2%, with patients younger than 6 weeks accounting for 76.9% of the deaths. On the multivariate analysis, the independent risk factors for death were WBC > 70.0 × 109/L (odds ratio [OR], 230.66; 95% confidence interval [CI], 5.16-10,319.09 P = 0.005) and pulmonary hypertension (PH) (OR 323.29; 95% CI 16.01-6529.42; P < 0.001). CONCLUSION: Severe pertussis mainly occurred in children aged < 3 months. The mortality of severe pertussis was 34.2%, with patients younger than 6 weeks accounting for the majority of the deaths. We recommend the first dose of diphtheria-tetanus-pertussis (DTP) should be advanced to the age of 2 months or even 6 weeks. The presence of a WBC > 70.0 × 109/L and PH were the prognostic independent variables associated with death.


Assuntos
Coqueluche , Criança , Criança Hospitalizada , Cuidados Críticos , Feminino , Hospitalização , Humanos , Lactente , Fatores de Risco , Coqueluche/complicações , Coqueluche/epidemiologia
14.
Biopharm Drug Dispos ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34651308

RESUMO

BACKGROUND: To explore the clinical application of a population pharmacokinetics (PPK) model of vancomycin in patients with hematological diseases and neutropenia. METHODS: Patients with hematological diseases and neutropenia were included in the PPK model study. Nonlinear mixed effect modeling approach (NONMEM) was used for model establishment. Monte Carlo simulation was carried out. A total of 74 patients were divided into model group and non-model group for clinical application research. The model group was given the initial dose of 1g q8h, and the non-model group was given 1g q12h as an empiric initial dosage.the follow-up dose adjustments were made according to the concentration results. RESULTS: This two-compartment model showed good stability and accuracy. The first trough concentration(C0 ) and the compliance rate of the first C0 were much higher in the model group than that in the non-model group(14.30 ± 4.73 µg/ml and 59.38% vs. 8.02 ± 2.61 µg/ml, 35.71% ). Less patients needed dose adjustments and fewer adjustment times in the model group than those in the non-model group(12.50% and 0.13 ± 0.34times vs 50.00% and 0.61 ± 0.66times). This suggested that for those patients who had a CLCR≥90 ml/min/1.73m2 , the initial dose of 1g q8h may help to reach the target C0 (10∼20µg/ml) quickly. It also helped to reduce the times and number of patients who need dose adjustments. CONCLUSIONS: Our PPK model of vancomycin in patients with hematologic diseases and neutropenia can be used to shorten the time to reach the target concentration anddn reduce the number of dose adjustments. This article is protected by copyright. All rights reserved.

15.
Genome Med ; 13(1): 146, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493320

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood. METHODS: We applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments. RESULTS: Our analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function. CONCLUSIONS: We portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

16.
Lipids Health Dis ; 20(1): 100, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496884

RESUMO

BACKGROUND: The deleterious effect of maternal high-fat diet (HFD) on the fetal rat liver may cause later development of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effect of maternal HFD-induced maternal hepatic steatosis and dysbiosis on the fetal liver and intestines, and the effect of prenatal metformin in a rat model. METHODS: Sprague-Dawley rats were assigned to three groups (N = 6 in each group). Before mating, the rats were randomly assigned to HFD or normal-chow diet (NCD) group for 7 weeks. After mating, the HFD group rats were continued with high-fat diet during pregnancy and some of the HFD group rats were co-treated with metformin (HFMf) via drinking water during pregnancy. All maternal rats and their fetuses were sacrificed on gestational day 21. The liver and intestinal tissues of both maternal and fetal rats were analyzed. In addition, microbial deoxyribonucleic acid extracted from the maternal fecal samples was analyzed. RESULTS: HFD resulted in maternal weight gain during pregnancy, intrahepatic lipid accumulation, and change in the serum short-chain fatty acid profile, intestinal tight junctions, and dysbiosis in maternal rats. The effect of HFD on maternal rats was alleviated by prenatal metformin, which also ameliorated inflammation and apoptosis in the fetal liver and intestines. CONCLUSIONS: This study demonstrated the beneficial effects of prenatal metformin on maternal liver steatosis, focusing on the gut-liver axis. In addition, the present study indicates that prenatal metformin could ameliorate maternal HFD-induced inflammation and apoptosis in the fetal liver and intestines. This beneficial effect of in-utero exposure of metformin on fetal liver and intestines has not been reported. This study supports the use of prenatal metformin for pregnant obese women.

17.
BMC Endocr Disord ; 21(1): 181, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488728

RESUMO

BACKGROUND: In order to recommend the optimal type of exercise for type 2 diabetes prevention, different exercise interventions were compared with respect to their effects on glycemic control and insulin resistance. METHODS: Studies on the curative effect of aerobic exercise training (AET), resistance training (RT), or control training (CT) on prediabetes were retrieved from the PubMed, Embase, SPORTDiscus, and Cochrane Library databases. Body mass index (BMI); homeostasis model assessment of insulin resistance index (HOMA-IR); and fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and insulin levels were used as outcome indicators. The Q statistic was calculated to evaluate heterogeneity within studies. A fixed- or random-effects model was used for pooling data based on nonsignificant or significant heterogeneities. A consistency test was conducted using a node-splitting analysis. RESULTS: A total of 13 eligible studies were included. The results of the direct meta-analysis indicated that AET or RT could significantly reduce the HbA1c level in prediabetic individuals compared to CT [AET vs. CT: standardized mean difference (SMD) = - 0.6739, 95% confidence interval (CI) = - 0.9424 to - 0.4055 to RT vs. CT: SMD = - 1.0014, 95% CI = - 1.3582 to - 0.6446]. The findings from the network meta-analysis showed that there were no statistical differences among the four comparisons for all the indicators except for lower HbA1c level (SMD = - 0.75, 95% CI = - 1.31 to - 0.19) and HOMA-IR (SMD = - 1.03, 95% CI = - 1.96 to - 0.10) in the AET group than in the CT group. In addition, prediabetic individuals in the AET + RT group showed greater control of BMI and insulin and FBG levels than those in the other groups, whereas AET was the most effective in controlling HbA1c and HOMA-IR levels in prediabetic individuals. CONCLUSION: AET, AET + RT, and RT exerted beneficial effects on insulin resistance and glycemic control in prediabetic patients. From the existing data, AET or AET + RT is preferentially recommended for these patients, although further studies may unveil RT as a promising therapy. Benefits from all types of exercise seem to occur in an intensity-dependent manner.

18.
Gynecol Endocrinol ; : 1-5, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34486905

RESUMO

OBJECTIVE: To determine the effects of changes in serum luteinizing hormone (LH) levels in the early stages of the gonadotropin-releasing hormone antagonist (GnRH-A) protocol on in vitro fertilization and embryo transfer/intracytoplasmic sperm injection clinical outcomes. METHODS: Data from 2116 fresh embryo transfer cycles with the GnRH-A protocol were retrospectively analyzed. Patients were divided into two groups, ΔLH-increased and ΔLH-decreased, according to changes in serum LH levels on the day of GnRH-A addition compared with that on the start day of ovarian stimulation. Patients in whom ΔLH increased were categorized according to early-onset LH increases (serum LH level ≥10 mIU/mL or twice the baseline). RESULTS: ΔLH increased and decreased in 14.9% and 85.1% of patients, respectively. The fertilization rate was lower, and fewer oocytes were retrieved in patients with increased ΔLH compared to those with decreased ΔLH (p < .05). The number of AFC, oocytes retrieved, and AMH in patients with early-onset ΔLH increase was lower between the subgroups (p < .05). There were no significant differences in clinical pregnancy, early abortion, biochemical pregnancy, and live birth rates between the groups and subgroups (p > .05). CONCLUSIONS: Early increases in LH levels during GnRH-A protocol might affect the number of oocytes retrieved, but not the clinical outcomes.

19.
J Orofac Orthop ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533584

RESUMO

PURPOSE: To evaluate the effects of anodization on the friction behavior of beta-titanium (ß-Ti) orthodontic archwires in conventional or self-ligating brackets in vitro. METHODS: ß­Ti archwires (0.018â€¯× 0.025 inch) pre- and postanodization were tested in combination with 0.022-inch stainless steel conventional and self-ligating brackets. The surface composition and oxide thickness of the ß­Ti archwires pre- and postanodization were measured using Auger electron spectroscopy (AES) and transmission electron microscopy (TEM). Detailed surface topography and roughness were assessed using atomic force microscopy (AFM). Surface topographies of the ß­Ti archwires pre- and postanodization were examined using scanning electron microscopy (SEM). Friction was measured using a universal testing machine; the data were statistically analyzed. RESULTS: Postanodization, the identified titanium oxide layer on the surface of the ß­Ti archwires increased in thickness from 10 to 100 nm; at the same time, the values for surface roughness were significantly reduced by half (p < 0.001). The archwire surfaces post anodization were harder and had fewer scratches after the friction test. Anodization significantly reduced 23.77% of the static (p < 0.01) and 25.61% of the kinetic (p < 0.001) friction of the ß­Ti archwires in conventional brackets, while it significantly reduced 85.71% of the static and 84.38% of the kinetic friction (p < 0.01) in self-ligating brackets. CONCLUSION: Anodization reduced the ß­Ti archwire friction, which was particularly more effective in combination with self-ligating brackets. The friction reduction via anodization could be attributed to the increased thickness, surface hardness, and decreased surface roughness of the titanium oxide layer.

20.
J Biol Chem ; : 101195, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520760

RESUMO

DNA methylation shows complex correlations with gene expression, and the role of promoter hypermethylation in repressing gene transcription has been well addressed. Emerging evidence indicates that gene body methylation promotes transcription; however, the underlying mechanisms remain to be further investigated. Here, using methylated DNA immunoprecipitation sequencing (MeDIP-seq), bisulfite genomic sequencing and immunofluorescent labeling, we show that gene body methylation is indeed positively correlated with rRNA gene (rDNA) transcription. Mechanistically, gene body methylation is largely maintained by DNA methyltransferase 1 (DNMT1), deficiency or downregulation of which during myoblast differentiation or nutrient deprivation results in decreased gene body methylation levels, leading to increased gene body occupancy of plant homeodomain (PHD) finger protein 6 (PHF6). PHF6 binds to hypomethylated rDNA gene bodies where it recruits histone methyltransferase SUV4-20H2 to establish the repressive histone modification, H4K20me3, ultimately inhibiting rDNA transcription. These findings demonstrate that DNMT1-mediated gene body methylation safeguards rDNA transcription by preventing enrichment of repressive histone modifications, suggesting that gene body methylation serves to maintain gene expression in response to developmental and/or environmental stresses.

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