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1.
Sci Rep ; 11(1): 22875, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819569

RESUMO

Previous studies exploring the influence of glycemic variability (GV) on the pathogenesis of distal symmetrical polyneuropathy (DSPN) in type 1 diabetes (T1DM) produced conflicting results. The aim of this study was to assess the relationship between GV and DSPN in T1DM. Adults with T1DM were included in this cross-sectional study and asked to undergo 3-day CGM. GV quantified by coefficient of variation (CV) and mean amplitude of glucose excursions (MAGE) were obtained from CGM. Clinical characteristics and biochemical assessments were collected for analysis. The study comprised 152 T1DM patients (53.9% males) with mean age of 44.2 year. Higher levels of age and duration of diabetes and lower levels of total cholesterol, LDL, fasting C-peptide and postprandial C-peptide were observed in DSPN subjects. DSPN groups displayed a higher blood glucose between 00:00 and 12:59 according to the CGM profile. Higher MAGE and CV were associated with increased risk of DSPN in the fully adjusted model. Meanwhile, a significant association between measurements of hypoglycemia, especially nocturnal hypoglycemia, and DSPN was found after multiple tests. CGM parameters describing the glycemic variability and hypoglycemia were potential risk factors for DSPN in adults with T1DM.

2.
Environ Toxicol ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34612572

RESUMO

The aim of this study was to investigate the protective effects of Nano-Se against nickel (Ni)-induced hepatotoxicity and the potential mechanism. Hence, we constructed in vivo and in vitro models of Ni-induced hepatotoxicity. Sprague-Dawley (SD) rats were exposed to nickel sulfate (NiSO4 , 5.0 mg/kg, i.p.) with or without Nano-Se (0.5, 1, and 2 mg/kg, oral gavage) co-administration for 14 days, and HepG2 cells were exposed to NiSO4 (1500 µM) with or without Nano-Se (20 µM) for 24 h. Nano-Se obviously prevented Ni-induced hepatotoxicity indicated by ameliorating pathological change and decreasing Ni accumulation in rat livers. Ni induced a significant increase in hepatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH-Px), and malondialdehyde (MDA) level, decreased the glutathione (GSH) content while compared to those in the control group. Nano-Se administration improved the hepatic antioxidant capacity through increase hepatic GSH contents and GSH-Px activity, decrease the activities of SOD, CAT, and MDA level. Nano-Se improved the cell viability, decreased active oxygen (ROS) generation and ameliorated morphological changes of nuclear structures in Ni-treated HepG2 cells. In addition, Nano-Se inhibited the Ni-induced increases of cytochrome c, caspase-9, cleaved caspase-3, increased PI3K and AKT phosphorylation both in vivo and in vitro. Besides, the PI3K inhibitor Y294002 could inhibit the protective effects of Nano-Se on apoptosis. Thus, Nano-Se significantly activates PI3K/AKT signaling to ameliorate apoptosis in Ni-induced hepatotoxicity.

3.
Biomed Res Int ; 2021: 3482879, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712730

RESUMO

Background: The relationship between uncoupling protein (UCP) 1-3 polymorphisms and susceptibility to type 2 diabetes mellitus (T2DM) has been extensively studied, while conclusions remain contradictory. Thus, we performed this meta-analysis to elucidate whether the UCP1-3826A/G, UCP2-866G/A, Ala55Val, and UCP3-55C/T polymorphisms are associated with T2DM. Methods: Eligible studies were searched from PubMed, Cochrane Library, and Web of Science database before 12 July 2020. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Heterogeneity analysis, subgroup analysis, sensitivity analysis, and publication bias were also performed. Results: A total of 38 case-control studies were included in this meta-analysis. The overall results revealed significant association between T2DM and the UCP2 Ala55Val polymorphism (recessive model: OR = 1.25, 95% CI 1.12-1.40, P < 0.01; homozygous model: OR = 1.33, 95% CI 1.03-1.72, P = 0.029, respectively). In subgroup analysis stratified by ethnicity, T2DM risk was increased with the UCP2 Ala55Val polymorphism (allele model: OR = 1.17, 95% CI 1.02-1.34, P = 0.023; recessive model: OR = 1.28, 95% CI 1.13-1.45, P < 0.01; homozygous model: OR = 1.39, 95% CI 1.05-1.86, P = 0.023, respectively), while decreased with the UCP2-866G/A polymorphism in Asians (dominant model: OR = 0.86, 95% CI 0.74-1.00, P = 0.045). Conclusions: Our results demonstrate that the UCP2-866G/A polymorphism is protective against T2DM, while the UCP2 Ala55Val polymorphism is susceptible to T2DM in Asians.

4.
Biomed Res Int ; 2021: 3361309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34580638

RESUMO

Introduction: Hypoglycemic drugs affect the bone quality and the risk of fractures in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and insulin on bone mineral density (BMD) in T2DM. Methods: In this single-blinded study, a total of 65 patients with T2DM were randomly assigned into four groups for 52 weeks: the exenatide group (n = 19), dulaglutide group (n = 19), insulin glargine group (n = 10), and placebo (n = 17). General clinical data were collected, and BMD was measured by dual-energy X-ray absorptiometry. Results: Compared with baseline, the glycosylated hemoglobin (HbA1c) decreased significantly in the exenatide (8.11 ± 0.24% vs. 7.40 ± 0.16%, P = 0.007), dulaglutide (8.77 ± 0.37% vs. 7.06 ± 0.28%, P < 0.001), and insulin glargine (8.57 ± 0.24% vs. 7.23 ± 0.25%, P < 0.001) groups after treatment. In the exenatide group, the BMD of the total hip increased. In the dulaglutide group, only the BMD of the femoral neck decreased (P = 0.027), but the magnitude of decrease was less than that in the placebo group; the BMD of L1-L4, femoral neck, and total hip decreased significantly (P < 0.05) in the placebo group, while in the insulin glargine group, the BMD of L2, L4, and L1-4 increased (P < 0.05). Compared with the placebo group, the BMD of the femoral neck and total hip in the exenatide group and the insulin glargine group were increased significantly (P < 0.05); compared with the exenatide group, the BMD of L4 in the insulin glargine group was also increased (P = 0.001). Conclusions: Compared with the placebo, GLP-1RAs demonstrated an increase of BMD at multiple sites of the body after treatment, which may not exacerbate the consequences of bone fragility. Therefore, GLP-1RAs might be considered for patients with T2DM. This trial is registered with ClinicalTrials.gov NCT01648582.

5.
Diabetes Ther ; 12(11): 2955-2969, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34542866

RESUMO

INTRODUCTION: Prevalence of sarcopenia has increased in patients with type 2 diabetes. The influence of glucose-lowering drugs on muscles in these patients remains unclear. We aimed to investigate the association between muscle mass/function and glucose-lowering drugs. METHODS: Data of 1042 hospitalized patients with type 2 diabetes were included in this retrospective, cross-sectional study. All the patients had stable hypoglycemic therapy in the last 3 months, and performed bioelectrical impedance analysis, grip strength, and gait speed tests on admission. RESULTS: Skeletal muscle index [6.81 (95% CI 6.67, 6.94) vs. 7.17 (7.09, 7.24) kg/m2], handgrip strength [23.41 (22.24, 24.58) vs. 26.93 (26.33, 27.54) kg], and gait speed [1.19 (1.15, 1.22) vs. 1.27 (1.25, 1.28) m/s] decreased in patients using acarbose compared with the others (all p < 0.001). Gait speed and skeletal muscle index remained lower in patients using acarbose compared to their matched patients in propensity score matching (p = 0.036 and 0.010, respectively). Among drug-naïve patients and patients using insulin, metformin, sulfonylureas, or acarbose monotherapy, the acarbose group had lowest skeletal muscle index and handgrip strength [6.81 (6.52, 7.11) kg/m2 and 22.54 (19.28, 25.79) kg, p = 0.028 and 0.001, respectively]. CONCLUSION: Acarbose treatment was associated with decreased muscle mass and strength. Assessment and exercise of muscles in patients with long-term acarbose treatment should be considered.

6.
Biomed Res Int ; 2021: 6618257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497852

RESUMO

Background: This study is aimed at investigating whether dapagliflozin adjunct to insulin therapy further improves glycemic control compared to insulin therapy alone in patients with newly diagnosed type 2 diabetes (T2D). Methods: This single-centre, randomized, controlled, open-labeled trial recruited newly diagnosed T2D patients. Subjects were randomized 1 : 1 to the dapagliflozin add-on to continuous subcutaneous insulin infusion (CSII) group (DAPA) or the CSII therapy group for 5 weeks. Standard meal tests were performed 3 times at days -3, 7, and 35 for glucose, C-peptide, and insulin level determination. Two-time continuous glucose monitoring (CGM) was performed at baseline and at the end of the study. The primary endpoint was the difference in the mean amplitude of glycemic excursions (MAGEs) between the groups. Results: A total of 66 subjects completed the study, with 34 and 32 patients in the DAPA and CSII groups, respectively. Patients in the DAPA group exhibited significant decreases in MAGE levels at the endpoint. We also observed that patients in the DAPA group had a lower homoeostasis model assessment insulin resistance (HOMA-IR) and a higher homoeostasis model assessment B (HOMA-B) value at 1 week and 5 weeks compared to those with insulin therapy, respectively. In addition, our data showed that patients in the DAPA group showed a significantly lower insulin dose (0.07 U/kg) and weighed less than those in the CSII group. Conclusion: Our data indicate that dapagliflozin adjunct to insulin is a safe and effective therapy for improving glycemic variations, insulin sensitivity, and weight loss in newly diagnosed T2D patients.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Insulina/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Glicemia/metabolismo , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Combinação de Medicamentos , Feminino , Glucosídeos/efeitos adversos , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Infusões Subcutâneas/métodos , Masculino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
7.
Metab Brain Dis ; 36(8): 2589-2595, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34468915

RESUMO

Studies have already illustrated the role of long non-coding RNAs (lncRNAs) in the progression of atherosclerosis, while the potential role of lncRNA gene variation in susceptibility to large artery atherosclerotic stroke (LAAS) remains controversial. We therefore conducted this study to explore and verify the gene expression modules of LAAS. Differentially expressed genes (DEGs) in atherosclerosis were screened in 3 patients with LAAS, and 3 healthy control patients. A further 31 individuals were used to screen DEGs, and MALAT1, MEG3, or SENCR were identified. Real-time PCR and western blotting were used to assess the difference in DEGs between the atherosclerotic and the non-atherosclerotic artery models. A total of 454 DEGs were detected from the initial screening step, and MALAT1, MEG3, or SENCR were applied to predict the risk of LAAS. The AUC of MALAT1, MEG3, and SENCR in predicting the risk of LAAS was 0.746 (95% CI: 0.398-0.753; P = 0.005), 0.575 (95% CI: 0.398-0.753; P = 0.389), and 0.629 (95% CI: 0.449- .808; P = 0.141), respectively. Moreover, there were significant differences between the atherosclerotic and non-atherosclerotic artery models for the expression of MALAT1, GCNT1, VEGFA, and VCAM-1. This study found that the MALAT1 contributes to LAAS susceptibility, and might play an important role in the progression of LAAS.

8.
J Diabetes Res ; 2021: 5524313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337072

RESUMO

To observe whether different insulin glargine titration algorithms based on fasting blood glucose (FBG) levels lead to different glycaemic variations (GVs) in type 2 diabetes (T2D) patients, a prospective, randomized, single-centre, comparative, three-arm parallel-group, open-label, treat-to-target, 24-week study was performed. A total of 71 uncontrolled T2D patients were recruited and randomized 1 : 3 : 3 into Groups 1, 2, and 3 (insulin titration goals of FBG ≤ 5.6, ≤6.1, and ≤7.0) for this study. The initiated insulin glargine dose was recommended at 0.2 U/kg/day and was then titrated following the FBG target. Patients were subjected to two 3-day continuous glucose monitoring (CGM) at baseline and the endpoint, wherein the CGM data were analysed, and the study's primary endpoint was the difference in 24 hrs mean amplitude of glycaemic excursion (MAGE) among the three groups. We observed that patients in the three groups had similar MAGE levels at the endpoint; however, Group 2 achieved a significant decrease in the MAGE level from baseline to the endpoint as compared to Groups 1 and 3 (all p < 0.05). We also observed that these patients had significant glycated haemoglobin A1c (HbA1c) value improvements as compared to the other two groups (all p < 0.05). Therefore, choosing an FBG level of 6.1 mmol/L as an insulin titration target provided significant GVs and HbA1c value improvements in T2D patients. Moreover, our data indicated that an FBG of 6.1 mmol/L could possibly be an insulin glargine titration target in T2D patients.

9.
Pain Ther ; 10(2): 1355-1373, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34363598

RESUMO

INTRODUCTION: This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices. METHODS: A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded. RESULTS: The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350). CONCLUSION: Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.

10.
PeerJ ; 9: e11735, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268015

RESUMO

Background: Diabetes-related kidney disease is associated with end-stage renal disease and a high mortality rate. However, data on risk factors associated with kidney disease in patients with newly diagnosed type 2 diabetes mellitus (DM) remains insufficient. The aim of the present study was to identify the risk factors significantly associated with chronic kidney disease progression in patients with newly diagnosed type 2 DM. Methods: We reviewed a total of 254 consecutive patients who were newly diagnosed with type 2 diabetes at Nanjing First Hospital from January to December 2014. They were observed for two years, and baseline and biochemical variables were used to identify significant predictors of kidney failure progression. Kidney failure progression was defined as a ≥ 30% increase in serum creatine level. Results: The mean age of patients was 58.96 years, 37.4% were women, and 57.1% had hypertension. Kidney function progressed in 40 patients (15.75%). Multivariable logistic regression analyses showed that serum albumin (p = 0.015) and microalbuminuria (p < 0.001) were associated with kidney failure progression in patients with newly diagnosed type 2 DM. Those with lower estimated glomerular filtration rate (eGFR; 30-60 ml/min/1.73 m2) at baseline had lower serum albumin levels compared to those of patients with higher eGFR. The albuminuria levels were higher in patients with lower eGFR than in those with eGFR ≥ 90 ml/min/1.73 m2. Receiver operating characteristic curve analysis showed that the area under the curve was 0.754 (95% CI [0.670-0. 0.837]). Conclusions: The overall rate of chronic kidney disease progression is relatively high, and low serum albumin and high albuminuria levels are associated with kidney failure progression in newly diagnosed diabetic patients.

11.
Front Oncol ; 11: 657002, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221975

RESUMO

Head and neck cancer (HNC) is the fifth most common cancer worldwide. In this study, we performed an integrative analysis of the discovery set and established an eight-gene signature for the prediction of prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Univariate Cox analysis was used to identify prognosis-related genes (with P < 0.05) in the GSE41613, GSE65858, and TCGA-HNSC RNA-Seq datasets after data collection. We performed LASSO Cox regression analysis and identified eight genes (CBX3, GNA12, P4HA1, PLAU, PPL, RAB25, EPHX3, and HLF) with non-zero regression coefficients in TCGA-HNSC datasets. Survival analysis revealed that the overall survival (OS) of GSE41613 and GSE65858 datasets and the progression-free survival(DFS)of GSE27020 and GSE42743 datasets in the low-risk group exhibited better survival outcomes compared with the high-risk group. To verify that the eight-mRNA prognostic model was independent of other clinical features, KM survival analysis of the specific subtypes with different clinical characteristics was performed. Univariate and multivariate Cox regression analyses were used to identify three independent prognostic factors to construct a prognostic nomogram. Finally, the GSVA algorithm identified six pathways that were activated in the intersection of the TCGA-HNSC, GSE65858, and GSE41613 datasets, including early estrogen response, cholesterol homeostasis, oxidative phosphorylation, fatty acid metabolism, bile acid metabolism, and Kras signaling. However, the epithelial-mesenchymal transition pathway was inhibited at the intersection of the three datasets. In conclusion, the eight-gene prognostic signature proved to be a useful tool in the prognostic evaluation and facilitate personalized treatment of HNSCC patients.

12.
Angiology ; : 33197211028022, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212759

RESUMO

Ventricular arrest is a rare arrhythmic disease in the clinic; 35% to 55% of cases are associated with atrial fibrillation (AF). It is well known that ventricular arrest for ≥3 seconds can lead to brain symptoms such as dizziness and even syncope, but it is not clear whether ventricular pauses (≥3 seconds) with AF will lead to sudden cardiac death. If the implantation of a pacemaker can improve the quality of life of patients with permanent AF with ventricular arrest and whether it has a long-term protective effect on sudden cardiac death. To this end, we conducted a prospective follow-up observation study, which was conducted through telephone interviews and clinical hospital observation to obtain information on the quality of life, survival rate, and other details. The results show that for patients with permanent AF with ventricular arrest, pacemaker implantation cannot reduce sudden cardiac death, cardiovascular events, and stroke nor can it improve the cumulative survival rate. Fortunately, the implantation of pacemakers can improve the quality of life of patients.

13.
Infect Dis Ther ; 10(3): 1451-1463, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34120314

RESUMO

INTRODUCTION: A trade-off between successful surgery and minimizing the operation delay for patients with spinal tuberculosis (TB) is a major consideration to determine the duration of preoperational anti-TB treatment (AAT). In this study, 2 and 4 weeks preoperative AAT durations were compared for their influence on the operation outcomes. METHOD: A multicenter, prospective, randomized trial was conducted in four hospitals in China. New patients with spinal TB were recruited and randomly allocated to two groups (2 or 4 weeks' preoperative treatment) and administered the standardized first-line anti-TB drugs. The symptom changing and indicators reflecting recovery and side effects of the treatment were monitored. Patient was followed up for another 18 months after completion of treatment. RESULTS: In total, 150 eligible patients were enrolled between June 2014 and December 2016, and 13 patients were excluded after the enrollment. The remaining 137 participants were randomly allocated to the 2-week group (n = 68) or the 4-week group (n = 69). These two groups acquired similar surgical outcomes, considering wound healing rate within 3 months after the operation (94.20%, 65/69 vs 89.71%, 61/68; P = 0.333) and bony fusion rate within 6 months (98.46%, 64/65 vs 95.45%, 63/66; P = 0.317). However, the culture positive rate of pus collected during operation in the 4-week group (41.94%) was significantly lower than that of the 2-week group (60.94%, P = 0.033). No reoccurrence of disease was observed in either group during the 18-month follow-up period. CONCLUSION: Patients with spinal TB administered 2 or 4 weeks of preoperative anti-TB treatment acquired similar surgical outcomes. However, patients who underwent the operation sooner suffered 2 weeks less agony from the disease.

14.
Med Phys ; 48(9): 5165-5178, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34085282

RESUMO

PURPOSE: To evaluate the impact of respiratory motion on radiomics features in 18 F-fluoro-2-deoxy-D-glucose three dimensional positron emission tomography (18 F-FDG 3D PET) imaging and optimize feature stability by combining preprocessing configurations and aggregation strategies. METHODS: An in-house developed respiratory motion phantom was imaged in 3D PET scanner under nine respiratory patterns including one reference pattern. In total, 487 radiomics features were extracted for each respiratory pattern. Feature stability to respiratory motion was first evaluated by metrics of coefficient of variation (COV) and relative difference (RD) in a fixed preprocessing configuration. Further, one-way ANOVA and trend analysis were performed to evaluate the impact of preprocessing configuration (voxel size, discretization scheme) and aggregation strategy on feature stability. Finally, an optimization framework was proposed by selected feature-specific configurations with minimum COV value, and the diagnostic performance was validated in stable versus unstable features and fixed versus optimal features by a set of 46 patients with lung disease. RESULTS: PET radiomics features were sensitive to respiratory motion, only 79/487 (16%) features were identified to be very stable in the fixed configuration. Preprocessing configuration and aggregation strategy had an impact on feature stability. For different voxel size, bin number, bin size and aggregation strategy, 188/487 (39%), 70/487 (15%), 148/487 (30%), and 38/95 (29%) features appeared significant changes in feature stability. The optimized configuration had the potential to improve feature stability compared to fixed configuration, with the COV decreased from 22% ±24% to 16% ±20%. Regarding the diagnostic performance, the stable and optimal configuration features outperformed the unstable and fixed configuration features, respectively (AUC 0.88, 0.87 vs. 0.83, 0.85). CONCLUSIONS: Respiratory motion shows considerable impact on feature stability in 3D PET imaging, while optimizing preprocessing configuration may improve feature stability and diagnostic performance.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Humanos , Imageamento Tridimensional , Movimento (Física) , Imagens de Fantasmas
15.
Front Cell Dev Biol ; 9: 667252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136485

RESUMO

Induced pluripotent stem cells derived cells (iPSCs) not only can be used for personalized cell transfer therapy, but also can be used for modeling diseases for drug screening and discovery in vitro. Although prior studies have characterized the function of rodent iPSCs derived endothelial cells (ECs) in diabetes or metabolic syndrome, feature phenotypes are largely unknown in hiPSC-ECs from patients with diabetes. Here, we used hiPSC lines from patients with type 2 diabetes mellitus (T2DM) and differentiated them into ECs (dia-hiPSC-ECs). We found that dia-hiPSC-ECs had disrupted glycine homeostasis, increased senescence, and impaired mitochondrial function and angiogenic potential as compared with healthy hiPSC-ECs. These signature phenotypes will be helpful to establish dia-hiPSC-ECs as models of endothelial dysfunction for understanding molecular mechanisms of disease and for identifying and testing new targets for the treatment of endothelial dysfunction in diabetes.

16.
Sci Total Environ ; 788: 147889, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34134394

RESUMO

Excess sludge contains large amounts of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), posing a risk for human health. However, most current studies usually ignored their abundance and removal in excess sludge. Therefore, this study aimed to reduce ARGs/MGEs in sludge by Fenton process, and applied single-factor experiment (SFE) and response surface methodology (RSM) to optimize the Fenton reaction condition for higher removal rates of ARGs/MGEs. The results demonstrated that the removal rates of target genes by SFE optimized condition ranged from 10.91% to 66.86%, while the removal rates caused by RSM optimized condition were 48.02% - 76.36%, indicating RSM was a useful tool to improve the removal rates of ARGs in excess sludge. Additionally, the scanning electron microscope and cell apoptosis results suggested that the Fenton treatment altered the structure of sludge and reduced the numbers of normal cells, thus causing the reductions of target genes.


Assuntos
Antibacterianos , Esgotos , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Humanos
17.
Libyan J Med ; 16(1): 1943924, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34151749

RESUMO

Quercetin (QN) is a naturally occurring phenolic compound found largely in vegetables and fruits. Lycopene (LY) is yet another natural phytocompound, found abundantly in red-colored fruits and vegetables. Both have been reported to have beneficial activities in humans. In this study, we document in vivo experimental model for isoproterenol (ISO) cardiac injury toxicity in Sprague-Dawley (SD) rats and treatment with a combined optimized concentration of quercetin and lycopene (QL). Male SD rats of different groups were treated with QL (80 mg/kg QN and 3 mg/kg LY together p.o.) for 10 days with ISO administration (100 mg/kg i.p.) on days 7 and 8. After experimental period, CK-MB, TROP, AST, ALT, LDH, GST, GPx, CAT, SOD, Vit.E, Vit. C, GSH, GSSG and MDA were estimated. SD rats administered with ISO showed an obvious rise in the serum marker enzyme levels and tissue oxidative stress markers (MDA and GSSG). Furthermore, marked reductions in the body weight and increases enzymic and non-enzymic antioxidant levels were noticed. Histological features of the heart also indicated a disruption in the cardiac myofibrils structure of ISO-intoxicated rats. Also, quantitative PCR analysis revealed an involvement of antioxidant and related pathway genes such as Nrf2, HO-1, NQO1, GSTµ, SOD1, SOD2, CAT and BCl-2 genes. QL pretreatment prevented all these adverse effects of ISO cardiotoxicity and significantly reduced the myocardial damage. Decrease in oxidative stress was observed, possibly through alterations in the expression levels of enzymic antioxidant genes (GSTµ, SOD1, SOD2 and CAT). In general, QL exert a strong protective effect through the modulations in enzymic antioxidant activity and associated molecular pathways-regulating effect in cardiovascular disease.


Assuntos
Antioxidantes , Infarto do Miocárdio , Animais , Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Isoproterenol/toxicidade , Licopeno/farmacologia , Masculino , Infarto do Miocárdio/tratamento farmacológico , Estresse Oxidativo , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley
18.
IEEE Trans Med Imaging ; 40(11): 3030-3041, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34138703

RESUMO

Deep learning (DL) is bringing a big movement in the field of computed tomography (CT) imaging. In general, DL for CT imaging can be applied by processing the projection or the image data with trained deep neural networks (DNNs), unrolling the iterative reconstruction as a DNN for training, or training a well-designed DNN to directly reconstruct the image from the projection. In all of these applications, the whole or part of the DNNs work in the projection or image domain alone or in combination. In this study, instead of focusing on the projection or image, we train DNNs to reconstruct CT images from the view-by-view backprojection tensor (VVBP-Tensor). The VVBP-Tensor is the 3D data before summation in backprojection. It contains structures of the scanned object after applying a sorting operation. Unlike the image or projection that provides compressed information due to the integration/summation step in forward or back projection, the VVBP-Tensor provides lossless information for processing, allowing the trained DNNs to preserve fine details of the image. We develop a learning strategy by inputting slices of the VVBP-Tensor as feature maps and outputting the image. Such strategy can be viewed as a generalization of the summation step in conventional filtered backprojection reconstruction. Numerous experiments reveal that the proposed VVBP-Tensor domain learning framework obtains significant improvement over the image, projection, and hybrid projection-image domain learning frameworks. We hope the VVBP-Tensor domain learning framework could inspire algorithm development for DL-based CT imaging.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Algoritmos , Redes Neurais de Computação , Imagens de Fantasmas
19.
Phys Med Biol ; 66(11)2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34081027

RESUMO

Cerebral perfusion computed tomography (CPCT) can depict the functional status of cerebral circulation at the tissue level; hence, it has been increasingly used to diagnose patients with cerebrovascular disease. However, there is a significant concern that CPCT scanning protocol could expose patients to excessive radiation doses. Although reducing the x-ray tube current when acquiring CPCT projection data is an effective method for reducing radiation dose, this technique usually results in degraded image quality. To enhance the image quality of low-dose CPCT, we present a prior image induced diffusion tensor (PIDT) for statistical iterative reconstruction, based on the penalized weighted least-squares (PWLS) criterion, which we referred to as PWLS-PIDT, for simplicity. Specifically, PIDT utilizes the geometric features of pre-contrast scanned high-quality CT image as a structure prior for PWLS reconstruction; therefore, the low-dose CPCT images are enhanced while preserving important features in the target image. An effective alternating minimization algorithm is developed to solve the associated objective function in the PWLS-PIDT reconstruction. We conduct qualitative and quantitative studies to evaluate the PWLS-PIDT reconstruction with a digital brain perfusion phantom and patient data. With this method, the noise in the reconstructed CPCT images is more substantially reduced than that of other competing methods, without sacrificing structural details significantly. Furthermore, the CPCT sequential images reconstructed via the PWLS-PIDT method can derive more accurate hemodynamic parameter maps than those of other competing methods.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Algoritmos , Circulação Cerebrovascular , Humanos , Imagens de Fantasmas , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador
20.
Medicine (Baltimore) ; 100(21): e26086, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032745

RESUMO

RATIONALE: Dumping syndrome is a frequent and potentially severe complication after gastric surgery. Beinaglutide, a recombinant human glucagon-like peptide-1 (GLP-1) which shares 100% homology with human GLP-1(7-36), has never been reported in the treatment of dumping syndrome before. PATIENT CONCERNS: The patient had undergone distal gastrectomy for gastric signet ring cell carcinoma 16 months ago. He presented with symptoms of paroxysmal palpitation, sweating, and dizziness for 4 months. DIAGNOSIS: He was diagnosed with late dumping syndrome. INTERVENTIONS AND OUTCOMES: The patient was treated with dietary changes and acarbose for 4 months before admitted to our hospital. The treatment with dietary changes and acarbose did not prevent postprandial hyperinsulinemia and hypoglycemia according to the 75 g oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) on admission.Therefore, the patient was treated with beinaglutide 0.1 mg before breakfast and lunch instead of acarbose. After the treatment of beinaglutide for 1 month, OGTT showed a reduction in postprandial hyperinsulinemia compared with before starting treatment, and the time in the range of 3.9 to 10 mmol/L became 100% in CGM. No side effect was observed in this patient during beinaglutide treatment. LESSONS: These findings suggest that beinaglutide may be effective for treating post-gastrectomy late dumping syndrome.


Assuntos
Síndrome de Esvaziamento Rápido/tratamento farmacológico , Gastrectomia/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Hiperinsulinismo/tratamento farmacológico , Hipoglicemia/tratamento farmacológico , Fragmentos de Peptídeos/administração & dosagem , Glicemia/análise , Carcinoma de Células em Anel de Sinete/cirurgia , Síndrome de Esvaziamento Rápido/sangue , Síndrome de Esvaziamento Rápido/diagnóstico , Síndrome de Esvaziamento Rápido/etiologia , Teste de Tolerância a Glucose , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/etiologia , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Proteínas Recombinantes/administração & dosagem , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
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