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1.
Heart Surg Forum ; 24(2): E278-E281, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33798043

RESUMO

Pulmonary artery sling (PAS) is a rare congenital vascular anomaly. Ninety percent of patients with PAS have respiratory distress and need surgical correction. Asymptomatic adult presentation of PAS is rare. We report the case of a 56-year-old female with an asymptomatic left pulmonary artery sling.

2.
Neoplasma ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33780263

RESUMO

The aim of this study was to investigate the roles and potential mechanisms of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in the proliferation, migration, and invasion of Ewing's sarcoma cells. RT-qPCR was used to detect the expression of TUG1, microRNA-199a-3p (miR-199a-3p), and musashi2 (MSI2) in Ewing's sarcoma tissues and cell lines. Kaplan-Meier overall survival curves showed the survival rates of Ewing's sarcoma patients with high and low expression of TUG1. The association between the expressions of TUG1/MSI2 and miR-199a-3p in Ewing's sarcoma tissues was assessed by Pearson's correlation analysis. Cell proliferation, migration, and invasion were detected by CCK8 assay and Transwell assay, respectively. The protein level of MSI2 was determined using western blotting. The interaction between TUG1/MSI2 and miR-199a-3p was validated by the dual-luciferase reporter assay. The levels of TUG1 and MSI2 were increased, while the level of miR-199a-3p was decreased in Ewing's sarcoma tissues and cells. High expression of TUG1 or MSI2 indicated a decreased overall survival rate of Ewing's sarcoma patients. TUG1/MSI2 level was negatively correlated with miR-199a-3p level. While TUG1 level was positively correlated with MSI2 level. In Ewing sarcoma cells, knockdown of TUG1/MSI2 or overexpression of miR-199a-3p inhibited cell proliferation, migration, and invasion, whereas the overexpression of TUG1/MSI2 presented the opposite results. TUG1 functioned as a competing endogenous RNA to regulate MSI2 expression by sponging miR-199a-3p. Finally, miR-199a-3p inhibitor or MSI2 overexpression counteracted the TUG1 knockdown-mediated inhibitory effect on Ewing's sarcoma cell proliferation, migration, and invasion. TUG1 promotes proliferation, migration, and invasion of Ewing's sarcoma cells via sequestering miR-199a-3p to enhance the MSI2 expression, suggesting that TUG1 might be a potential target for treating Ewing's sarcoma.

3.
Comput Biol Med ; 131: 104293, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33662681

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Up to 20%-30% of patients hospitalized with COVID-19 have evidence of cardiac dysfunction. Xuebijing injection is a compound injection containing five traditional Chinese medicine ingredients, which can protect cells from SARS-CoV-2-induced cell death and improve cardiac function. However, the specific protective mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction remains unclear. METHODS: The therapeutic effect of Xuebijing injection on COVID-19 was validated by the TCM Anti COVID-19 (TCMATCOV) platform. RNA-sequencing (RNA-seq) data from GSE150392 was used to find differentially expressed genes (DEGs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. Data from GSE151879 was used to verify the expression of Angiotensin I Converting Enzyme 2 (ACE2) and central hub genes in both human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) and adult human CMs with SARS-CoV-2 infection. RESULTS: A total of 97 proteins were identified as the therapeutic targets of Xuebijing injection for COVID-19. There were 22 DEGs in SARS-CoV-2 infected hiPSC-CMs overlapped with the 97 therapeutic targets, which might be the therapeutic targets of Xuebijing injection on COVID-19-induced cardiac dysfunction. Based on the bioinformatics analysis, 7 genes (CCL2, CXCL8, FOS, IFNB1, IL-1A, IL-1B, SERPINE1) were identified as central hub genes and enriched in pathways including cytokines, inflammation, cell senescence and oxidative stress. ACE2, the receptor of SARS-CoV-2, and the 7 central hub genes were differentially expressed in at least two kinds of SARS-CoV-2 infected CMs. Besides, FOS and quercetin exhibited the tightest binding by molecular docking analysis. CONCLUSION: Our study indicated the underlying protective effect of Xuebijing injection on COVID-19, especially on COVID19-induced cardiac dysfunction, which provided the theoretical basis for exploring the potential protective mechanism of Xuebijing injection on COVID19-induced cardiac dysfunction.


Assuntos
/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , RNA-Seq , /metabolismo , /tratamento farmacológico , Linhagem Celular , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/patologia , Células-Tronco Embrionárias Humanas/virologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/virologia , Miócitos Cardíacos/patologia , Miócitos Cardíacos/virologia
4.
Commun Biol ; 4(1): 314, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750914

RESUMO

Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed "variant" due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.

5.
CNS Neurosci Ther ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724699

RESUMO

AIMS: Inhibition deficits have been suggested to be a core cognitive impairment in attention-deficit/hyperactivity disorder (ADHD). Exploring imaging patterns and the potential genetic components associated with inhibition deficits would definitely promote our understanding of the neuropathological mechanism of ADHD. This study aims to investigate the multimodal imaging fusion features related to inhibition deficits in adults with ADHD (aADHD) and to make an exploratory analysis of the role of inhibition-related gene, NOS1, on those brain alterations. METHODS: Specifically, multisite canonical correlation analysis with reference plus joint independent component analysis (MCCAR + jICA) was conducted to identify the joint co-varying gray matter volume (GMV) and the functional connectivity (FC) features related to inhibition in 69 aADHD and 44 healthy controls. Then, mediation analysis was employed to detect the relationship among inhibition-related imaging features, NOS1 ex1f-VNTR genotypes, and inhibition. RESULTS: Inhibition-directed multimodal imaging fusion patterns of aADHD were reduced GMV and FC in inhibition network and increased GMV and FC in default mode network. The results showed a significant indirect effect of NOS1 ex1f-VNTR on inhibition via FC component [effect size = -0.54 (SE = 0.29), 95% CI = -1.16 to -0.01]. In addition, the results indicated a significant indirect effect of GMV on the inhibition via FC component [effect size = 0.43 (SE = 0.23), 95% CI = 0.12 to 1.00]. CONCLUSION: The findings suggested that reduced GMV and FC in inhibition network and increased GMV and FC in default mode network were jointly responsible for inhibition deficits in aADHD. Both the NOS1 ex1f-VNTR genotypes and GMV might influence the inhibition through the mediation effect of the aforementioned FC (NOS1/GMV→FC→ Inhibition).

6.
Biomed Pharmacother ; 138: 111527, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33773469

RESUMO

The venom of the Deinagkistrodon acutus snake is composed of numerous bioactive proteins and peptides. In this study, we report the antithrombotic and anticoagulant activities of one of such proteins, herein known as SLPC. This novel protein was isolated and purified via multi-gel chromatography. Its amino acid sequence, structure and function were then determined. This protein was found to exhibit defibration, anticoagulation and general antithrombotic effects based on the results of both in vitro and in vivo studies. Based on same studies, it was found to cleave the α, ß, γ chains of fibrinogen and generally improved antiplatelet aggregation and blood rheology. A metabolomic insight of the antithrombotic effects of SLPC was found to be mainly linked to perturbations in the synthesis of unsaturated fatty acids, glycerophospholipid metabolism, arachidonic acid metabolism and other metabolic pathways. In summary, the novel protein SLPC, elicits its antithrombotic effects via degradation of fibrinogen and regulation of various thrombogenic factors in multiple metabolic pathways.

7.
BMC Pediatr ; 21(1): 141, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761932

RESUMO

BACKGROUND: In the current study, we applied a combination of non-invasive neuromodulation modalities concurrently with multiple stimulating electrodes. Specifically, we used transcranial pulsed current stimulation (tPCS) and transcutaneous electrical nerve stimulation (TENS) as a novel strategy for improving lower limb spasticity in children with spastic cerebral palsy (SCP) categorized on levels III-V of the Gross Motor Function Classification System (GMFCS) with minimal side effects. METHODS: Sixty-three SCP children aged 2-12 years, who were classified on levels III-V of the GMFCS were randomly assigned to one of two groups, resulting in 32 children in the experimental group and 31 children in the control group. The experimental group underwent a combination therapy of tPCS (400 Hz, 1 mA cerebello-cerebral stimulation) and TENS (400 Hz, max 10 mA) for 30 min, followed by 30 min of physiotherapy five times per week for 12 weeks. The control group underwent physiotherapy only 30 mins per day five times per week for 12 weeks. In total, all groups underwent 60 treatment sessions. The primary outcome measures were the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS). Evaluations were performed 3 days before and after treatment. RESULTS: We found a significant improvement in MAS and MTS scores of the lower limbs in the experimental group compared to the control group in the hip adductors (Left: p = 0.002; Right: p = 0.002), hamstrings (Left: p = 0.001; Right: p < 0.001, and gastrocnemius (Left: p = 0.001; Right: p = 0.000). Moreover, MTS scores of R1, R2 and R2-R1 in left and right hip adduction, knee joint, and ankle joint all showed significant improvements (p ≤ 0.05). Analysis of MAS and MTS scores compared to baseline scores showed significant improvements in the experimental group but declines in the control group. CONCLUSION: These results are among the first to demonstrate that a combination of tPCS and TENS can significantly improve lower limb spasticity in SCP children classified on GMFCS levels III-V with minimal side effects, presenting a novel strategy for addressing spasticity challenges in children with severe SCP. TRIAL REGISTRATION: ChiCTR.org, ChiCTR1800020283, Registration: 22 December 2018 (URL: http://www.chictr.org.cn/showproj.aspx?proj=33953 ).

8.
World J Urol ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33725149

RESUMO

PURPOSE: To determine the incidence and risk factors of the venous thromboembolism (VTE) in patients undergoing percutaneous nephrolithotomy (PCNL). METHODS: We retrospectively reviewed the records of 896 consecutive cases receiving PCNL between July 2018 and August 2020 in our institution. Univariate analysis was performed to identify the risk factors of VTE, and multivariate logistic regression analysis was further performed to determine the independent risk factors. Furthermore, the corresponding nomogram was conducted to establish a predicted model for VTE. RESULTS: The overall incidence of VTE was 2.8%. The multivariate logistic regression analysis showed that discontinued anticoagulant or antiplatelet therapies (OR 4.505, 95% CI 1.410-14.401), increased postoperative 12-h D-dimer (OR 11.162, 95% CI 2.370-52.574), hydronephrosis (OR 3.303, 95% CI 1.303-8.375), higher Caprini risk assessment model (RAM) score (OR 3.233, 95% CI 1.207-8.659) and postoperative sepsis or septic shock (OR 3.784, 95% CI 1.163-12.306) were independent risk factors of VTE following PCNL. Moreover, the area under the curve of postoperative 12-h D-dimer, hydronephrosis and Caprini RAM score was 0.826, 0.621 and 0.660, respectively. Based on the identified independent risk factors, the well-calibrated nomogram showed a moderate discriminative ability with concordance index 0.731. CONCLUSIONS: 2.8% of patients developed VTE following PCNL. Regarding those patients who have independent risk factors in this study, due attention should be paid to the effective thromboprophylaxis and the early detection of VTE.

9.
Sci Total Environ ; 771: 144812, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33736168

RESUMO

Atmospheric particulate matter (PM) is one of the main environmental air pollutants, but it can be retained and adsorbed by plants. To systematically and comprehensively conduct qualitative and quantitative research on the relationship between the leaf PM retention ability and the microstructure of leaf surfaces, this study evaluated the PM retention abilities of ten common tree species (1860 leaf pieces in total) in the greenbelts around the Lin'an toll station of the Hang-Rui Expressway in Hangzhou, China, in October 2019. The leaf surface roughness and contact angle were measured with confocal laser scanning microscopy and a contact angle measuring instrument. Scanning electron microscopy was applied to collect data on the stomata and groove morphology. The PM retention ability of the leaves was assessed by quantifying the PM mass and number density on the leaves. The results revealed that Platanus acerifolia and Sapindus mukorossi had a strong ability to retain particulates of different sizes. The mass of the retained PM2.5 on their leaves accounted for the lowest proportion (mean: 8.12%) among the total retained particulate mass, but the number density of the retained PM2.5 accounted for the highest proportion (mean: 97.49%) among the total number density. A significant negative correlation between the PM2.5 mass and the groove width on the adaxial surface (R2 = 0.746, P < 0.05) and a significant positive correlation between the roughness and the PM number density on the adaxial surface (R2 = 0.702, P < 0.01) were observed. No obvious correlations were found among the groove width, roughness and number density of the retained PM on the abaxial surface. Leaf surfaces with dense and narrow grooves, strip-like projections, high roughness and high wettability had strong retention abilities. This study can provide a theoretical reference for selecting plants with strong PM retention ability for green urban garden design.


Assuntos
Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Material Particulado/análise , Folhas de Planta/química , Árvores
10.
Chemosphere ; 276: 130212, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33740654

RESUMO

Rice as a paddy field crops, iron-containing materials application could induce its iron plaque formation, thereby affecting cadmium (Cd) transportation in the rhizosphere and its uptake in root. In this study, a hydroponic experiment was conducted to investigate the effects of three exogenous iron materials, namely nano-Fe3O4-modified biochar (BC-Fe), chelated iron (EDTA-Fe), and ferrous sulfate (FeSO4), on the iron plaque formation on the surface of rice root, and to investigate the effects of formed iron plaque on the absorption, migration, and transportation of Cd and Fe in rice plant. The results showed that yellow-brown and brown iron plaque was formed on surface cells of the Fe-treated rice root, and some black particles were embedded in the iron plaque formed by BC-Fe. The proportion of crystallized iron plaque (31.8%-35.9%) formed by BC-Fe was much higher than that formed by EDTA-Fe and FeSO4. The Cd concentrations in the crystallized iron plaque formed by BC-Fe were 7.64-13.0 mg·kg-1, and increased with the increasing of Fe concentrations in the plaque. The Cd translocation factor from root to stem (TFr-s) and the Cd translocation factor from stem to leaf (TFs-l) with BC-Fe treatment decreased by 84.7% and 80.0%, respectively. The results demonstrated that application BC-Fe promoted the formation of iron plaque and enhanced the sequestration of Cd and Fe in roots, thus reduced the transportation and accumulation of Cd in aerial rice tissues.

11.
Sci Rep ; 11(1): 5893, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723338

RESUMO

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0-18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996-December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008-2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996-2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1-RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008-2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008-2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008-2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents' use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33741211

RESUMO

AIMS: The increase of arterial stiffness is an independent risk factor for cardiovascular diseases (CVD). Fish oil supplementation was shown to reduce the risk of CVD outcomes. However, the effects of fish oil on arterial stiffness remains controversial. This meta-analysis summarized existing randomized clinical trials (RCTs) to determine whether fish oil can affect arterial stiffness in adults. DATA SYNTHESIS: Systematic searches were performed using the PubMed/Medline, EMbase, Cochrane database, Clinical trials, and Web of Science. All RCTs assessed the effect of fish oil intervention on carotid to femoral-Pulse Wave Velocity (cf-PWV), brachial to ankle-PWV (ba-PWV), augmentation index (AIx) and AIx75 were considered. A fixed-effect model was used to calculate the pooled effect. A total of 14 RCTs were included. The pooled data analysis showed that fish oil significantly reduced PWV levels (SMD: -0.145, 95%CI: -0.265 to -0.033, P = 0.012) compared to the control group. In subgroup analyses, a significant decrease in PWV was found in trials that fish oil with low dosages (≤1.8 g/d), short time (<24 weeks), low DHA to EPA ratio (DHA/EPA<1) and among young participant (<50 years old). Besides, the effect of fish oil was more obvious in ba-PWV compared to cf-PWV. In contrast, the effect of fish oil supplementation on AIx (WMD: -0.588%, 95% CI: -2.745 to 1.568, P = 0.593) and AIx75 (WMD: 0.542%, 95% CI: -1.490 to 2.574, P = 0.601) was nonsignificant. CONCLUSIONS: The current study showed that fish oil supplementation had a beneficial effect on pulse wave velocity.

13.
Molecules ; 26(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669807

RESUMO

Dental papilla cells (DPCs), precursors of odontoblasts, are considered promising seed cells for tissue engineering. Emerging evidence suggests that melatonin promotes odontoblastic differentiation of DPCs and affects tooth development, although the precise mechanisms remain unknown. Retinoid acid receptor-related orphan receptor α (RORα) is a nuclear receptor for melatonin that plays a critical role in cell differentiation and embryonic development. This study aimed to explore the role of RORα in odontoblastic differentiation and determine whether melatonin exerts its pro-odontogenic effect via RORα. Herein, we observed that RORα was expressed in DPCs and was significantly increased during odontoblastic differentiation in vitro and in vivo. The overexpression of RORα upregulated the expression of odontogenic markers, alkaline phosphatase (ALP) activity and mineralized nodules formation (p < 0.05). In contrast, odontoblastic differentiation of DPCs was suppressed by RORα knockdown. Moreover, we found that melatonin elevated the expression of odontogenic markers, which was accompanied by the upregulation of RORα (p < 0.001). Utilising small interfering RNA, we further demonstrated that RORα inhibition attenuated melatonin-induced odontogenic gene expression, ALP activity and matrix mineralisation (p < 0.01). Collectively, these results provide the first evidence that RORα can promote odontoblastic differentiation of DPCs and mediate the pro-odontogenic effect of melatonin.


Assuntos
Diferenciação Celular , Papila Dentária/citologia , Melatonina/farmacologia , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Odontoblastos/citologia , Odontoblastos/metabolismo , Odontogênese , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Odontoblastos/efeitos dos fármacos , Odontogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
14.
Dalton Trans ; 50(14): 4783-4788, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33725080

RESUMO

[FeFe]-hydrogenase (H2ase) catalyzes hydrogen evolution reactions (HERs), with an excellent performance that rivals that of platinum, the active site of which is built with crucial structural features required for efficient H-H bond formation. Herein, we report a mononuclear manganese complex (1) that contains a square pyramid coordination sphere and an intramolecular aniline as the proton relay, consistent with the crucial features of the active site in H2ase. Benefitting from these features, complex 1 electrocatalyzes the HER with a turnover frequency (TOF) exceeding 10 000 s-1 at -1.45 V (versus the ferrocenium/ferrocene couple) using anilinium tetrafluoroborate as a proton source. This work provides the first Mn-based functional model of H2ase, serving as a new paradigm for a high performance, low cost, environmentally benign hydrogen production electrocatalyst.

15.
Malar J ; 20(1): 73, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549122

RESUMO

BACKGROUND: The emergence and spread of multidrug resistance poses a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported in China since 2017, and China is approaching national malaria elimination. Therefore, anti-malarial drug resistance surveillance and tracking the emergence and spread of imported drug-resistant malaria cases will be necessary in a post-elimination phase in China. METHODS: Dried blood spots were obtained from Plasmodium falciparum-infected cases returned from Africa to China between 2012 and 2015, prior to anti-malarial drug treatment. Whole DNA were extracted and known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of pfk13 were evaluated by nested PCR and sequencing. The haplotypes and prevalence of these three genes were evaluated separately. Chi-squared test and Fisher's exact test were used to evaluate differences among the different sub-regions of Africa. A P value < 0.05 was used to evaluate differences with statistical significance. The maps were created using ArcGIS. RESULTS: A total of 731 P. falciparum isolates were sequenced at the pfcrt locus. The wild type CVMNK was the most prevalent haplotype with prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype CVIET. A total of 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were observed in only codons 86, 184 and 1246. Twelve haplotypes were identified and the prevalence of the wild type pfmdr1 NYD was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but the haplotype NYY with single mutation in codon 1246 was not observed. The double mutant haplotype YFD was common in Africa. About 1,357 isolates were successfully sequenced of pfk13-propeller domain, the wild type was found in 1,308 samples (96.4%) whereby 49 samples (3.6%) had mutation in pfk13. Of 49 samples with pfk13 mutations, 22 non-synonymous and 4 synonymous polymorphic sites were confirmed. The A578S was the most common mutation in pfk13-propeller domain and three mutations associated with artemisinin resistance (M476I, R539T, P553L) were identified in three isolates. CONCLUSION: This study provides evidence that could give insight into potential issues with anti-malarial drug resistance to inform national drug policy in China in order to treat imported cases.

16.
Anticancer Drugs ; 32(5): 575-579, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33595946

RESUMO

Nivolumab has been used in a variety of advanced malignant tumors. Cases of autoimmune diabetes associated with Nivolumab therapy have been reported gradually in recent years. This article reported a case of primary testicular lymphoma in an elderly patient with type 2 diabetes mellitus (T2DM). After treatment with Nivolumab, the primary disease was hyperprogressive disease but the blood glucose was relieved for a long time. Nivolumab may relieve the previous T2DM in diffuse large B-cell lymphoma patients; the potential mechanism needs to be further explored.

17.
Pediatr Blood Cancer ; 68(4): e28899, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33522704

RESUMO

BACKGROUND: IKZF1deletion is an unfavorable factor in Philadelphia negative (Ph -) B-cell acute lymphoblastic leukemia. However, the effects of IKZF1 deletions co-existing genetic alterations in Ph (-) ALL have not been extensively studied. METHODS: Bone marrow samples from 368 children with Ph (-) ALL were analyzed by using multiplex ligation-dependent probe amplification kit for detection of gene deletions and Sanger sequencing for mutational analysis of RAS pathway genes. The outcome was analyzed on 215 patients treated with Taiwan Pediatric Oncology Group-ALL-2002 protocol. RESULTS: IKZF1 deletions were present in 12.8% and IKZF1plus in 6.3% of patients. Mutations of RAS pathway genes were detected in 25.0% of IKZF1-deleted patients. The 10-year event-free survival (EFS) of IKZF1-undeleted patients was significantly better compared with IKZF1-deleted patients (80.0% vs. 47.8%, p = 0.001). Compared with outcome of patients harboring IKZF1 deletion alone, no difference in EFS was observed in patients with IKZF1plus , whereas three patients carried both IKZF1 and ERG deletions had a superior 10-year EFS (100%). The 10-year EFS of patients with any gene mutation of RAS pathway was worse than that of patients with wild-type genes (79.1% vs. 61.6%, p = 0.033). In multivariate analysis, RAS pathway mutations and IKZF1 deletion were independent predictors of inferior EFS. Co-existence of IKZF1 deletion with RAS pathway mutations had a worst 10-year EFS (11.1 ± 10.5%) and 10-year OS (53.3 ± 17.6%). CONCLUSIONS: Our results showed that RAS pathway mutation is an added-value biomarker in pediatric IKZF1-deleted Ph (-) ALL patients.

18.
Int J Biochem Cell Biol ; 134: 105962, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33636397

RESUMO

INTRODUCTION: SIRT4 is a mitochondrial sirtuin. Owing to its dependance on the cofactor nicotinamide adenine dinucleotide (NAD+), SIRT4 can act as a mitochondrial metabolic sensor of cellular energy status. We have previously shown that enhancement of mitochondrial functions is vital for the odontogenic diff ;erentiation of dental papilla cells (DPCs) during dentinogenesis. However, whether SIRT4 serves as an effective regulator of DPC diff ;erentiation by affecting mitochondrial functions remains unexplored. METHODS: Primary DPCs obtained from the first molar dental papilla of neonatal Sprague-Dawley rats were used in this study. The expression pattern of SIRT4 was observed by immunohistochemistry in the first molar of postnatal day 1 (P1) rats. The changes in SIRT4 expression during odontogenic DPC differentiation were evaluated using real-time quantitative polymerase chain reaction (PCR), western blotting, and immunofluorescence. DPCs with loss (small interfering RNA-mediated knockdown) and gain (plasmid transfection-induced overexpression) of SIRT4 function were used to explore the role of SIRT4 in odontogenic differentiation. Mitochondrial function assays were performed using ATP, reactive oxygen species (ROS), and NAD+/NADH kits to investigate the potential mechanisms involved in SIRT4-mediated dentinogenesis. RESULTS: In the present study, we found that SIRT4 expression increased in a time-dependent manner during odontogenic differentiation bothin vivo and in vitro. Sirt4 knockdown resulted in reduced odontogenic differentiation and mineralization, whereas an opposite effect was observed with SIRT4 overexpression. Furthermore, our results verified that in addition to reducing DPC differentiation, Sirt4 knockdown could also significantly reduce ATP levels, elevate the NAD+/NADH ratio, and increase ROS levels. CONCLUSION: SIRT4 regulates mitochondrial functions and the antioxidant capacity of DPCs, thereby influencing dentin formation and tooth development, a phenomenon that may provide a foundation for better understanding the specific molecular mechanisms underlying dentin regeneration.

19.
PLoS One ; 16(2): e0247622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33630929

RESUMO

Studies about medical care needs for home healthcare (HHC) previously focused on disease patterns but not gender and income differences. We used the Taiwan National Health Research Insurance Database from 1997 to 2013 to examine trends in medical care needs for patients who received HHC, and the gender and income gaps in medical care needs, which were represented by resource utilization groups (RUG). We aimed to clarify three questions: 1. Are women at a higher level of medical care needs for HHC than men, 2. Does income relate to medical care needs? 3. Is the interaction term (gender and income) related to the likelihood of medical care needs? Results showed that the highest level of medical care need in HHC was reducing whereas the basic levels of medical care need for HHC are climbing over time in Taiwan during 1998 and 2013. The percentages of women with income-dependent status in RUG1 to RUG4 are 26.43%, 26.24%, 30.68%, and 32.07%, respectively. Women were more likely to have higher medical care needs than men (RUG 3: odds ratio, OR = 1.17, 95% confidence interval, CI = 1.10-1.25; RUG4: OR = 1.13, 95% CI = 1.06-1.22) in multivariates regression test. Compared to the patients with the high-income status, patients with the income-dependent status were more likely to receive RUG3 (OR = 2.34, 95% CI = 1.77-3.09) and RUG4 (OR = 1.98, 95% CI = 1.44-2.71). The results are consistent with the perspectives of fundamental causes of disease and feminization of poverty theory, implying gender and income inequalities in medical care needs. Policymakers should increase public spending for delivering home-based integrated care resources, especially for women with lower income, to reduce the double burden of female poverty at the higher levels of medical care needs for HHC.

20.
Anal Chem ; 93(8): 3968-3975, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33599499

RESUMO

Accurate counting of single molecules at nanoscale resolution is essential for the study of molecular interactions and distribution in subcellular fractions. By using small-sized carbon dots (CDs), we have now developed a quantitative single-molecule localization microscopy technique (qSMLM) based on spontaneous blinking to count single molecules with a localization precision of 10 nm, which can be accomplished on conventional microscopes without sophisticated laser control. We explore and adapt the blinking of CDs with diverse structures and demonstrate a counting accuracy of >97% at a molecular density of 500 per µm2. When applied to G-protein coupled receptors on a cell membrane, we discriminated receptor oligomerization and clustering and revealed ligand-regulated receptor distribution patterns. This is the first example of adapting nanoparticle self-blinking for molecular counting, and this demonstrates the power of CDs as SMLM probes to reliably decipher sub-diffraction structures that mediate crucial biological functions.

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