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1.
J Nanobiotechnology ; 19(1): 210, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261493

RESUMO

BACKGROUND: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. METHODS: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. RESULTS: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. CONCLUSION: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.

2.
J Sci Food Agric ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34265089

RESUMO

BACKGROUND: The beneficial function of Phytase and 25-hydroxyvitamin D3 on the feed utilization rate has been widely investigated. However, study about its influence on weaned piglets is largely lag behind. The aim of this study is to investigate the effects of Phytase and 25-hydroxyvitamin D3 supplementation on the growth performance and bone development in weaned piglets, which are under dietary Ca and P deficiency. RESULTS: The results showed that dietary Ca and P deficiency decreased (P<0.05) the content of serum P in 6-10 kg piglets, as well as reduced (P<0.05) the contents of serum Ca and P, average daily gain (ADG), bone mineral density (BMD), breaking force (BF), bone ash and skim femur Ca in 10-20 kg piglets. Compared with the control group, the feed to gain ratio (F/G) of 6-10 kg piglets in the Phy group was decreased (P<0.05), while the ADG, blood Ca and P, BMD, BF, bone ash, P apparent digestibility, Ca, and P retention rate of 10-20 kg piglets were increased (P<0.05). The contents of serum BGP and HyD in 6-10 kg piglets and ADG were higher than control group (P<0.05), as well as the contents of serum Ca and HyD in10-20 kg piglets in HyD treatment group. Supplementation with both Phy and HyD had decreased the F/D (P<0.05) and increased the contents of serum Ca, P and HyD in 6-10 kg piglets as well as enhanced the ADG, BMD, BF, bone ash, skim femur Ca and P, serum Ca and P, HyD and the apparent digestibility and retention of Ca and P (P<0.05) in 10-20 kg piglets. Supplementation with Phy and HyD in Ca and P deficient dietary decreased bone resorption, improved tight arrangement of fibers and oblique fibers in weaned piglets. CONCLUSION: These data indicated that supplementation with both 1500 U/kg Phy and 50 µg/kg HyD could enhance dietary Ca and P utilization and promote bone 'development in low Ca and P dietary, and supplementation with both Phy and HyD had significant synergy effect compare to single supplement. This article is protected by copyright. All rights reserved.

3.
J Pharmacol Exp Ther ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253647

RESUMO

Our previous studies have shown that cathepsin L (CTSL) is involved in the ability of tumors to resist ionizing radiation (IR), but the specific mechanisms responsible for this remain unknown. We report here that mutant p53 (mut-p53) is involved in IR-induced transcription of CTSL. We found that irradiation caused activation of CTSL in mut-p53 cell lines whereas there was almost no activation in p53 wild-type (wt-p53) cell lines. Additionally, luciferase reporter gene assay results demonstrated that IR induced the p53 binding region on the CTSL promoter. We further demonstrated that the expression of p300 and Egr-1 was up-regulated in mut-p53 cell lines after IR treatment. Accordingly, the expression of Ac-H3, Ac-H4, AcH3K9 was up-regulated after IR treatment in mut-p53 cell lines, while HDAC4 and HDAC6 were reciprocally decreased. Moreover, knockdown of either Egr-1 or p300 abolished the binding of mut-p53 to the promoter of CTSL. ChIP assay results showed that the IR-activated transcription of CTSL was dependent on p300. To further delineate the clinical relevance of interactions between Egr-1/p300, mut-p53 and CTSL, we accessed primary tumor samples to evaluate the relationships between mut-p53, CTSL and Egr-1 /p300 ex vivo. The results support the notion that mut-p53 is correlated with CTSL transcription involving the Egr-1/p300 pathway. Taken together, the results of our study revealed that p300 is an important target in the process of IR induced transcription of CTSL, which confirms that CTSL participates in mut-p53 gain of function. Significance Statement Transcriptional activation of cathepsin L by ionizing radiation required the involvement of mutated p53 and Egr-1/p300. Interference with Egr-1 or p300 could inhibit the expression of cathepsin L induced by ionizing radiation. The transcriptional activation of cathepsin L by p300 may be mediated by p53 binding sites on the cathepsin L promoter.

4.
Chem Biol Drug Des ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34288496

RESUMO

Lung cancer is the leading cause of cancer death. Pyronaridine, a synthetic drug of artemisinin has been used in China for over 30 years for the treatment of malaria, but its effect on non-small cell lung cancer (NSCLC) cells is rarely reported. In this study, we determined the efficacy of pyronaridine in four different NSCLC cell lines and explored its mechanism in H1975. The data showed that pyronaridine could upregulate the expression of TRAIL (TNF-related apoptosis-inducing ligand)-mediated DR5 (Death receptor 5) to promote cellular apoptosis. Meanwhile, the JNK (c-Jun N-terminal kinase) level was detected to be significantly increased after treating with pyronaridine. We used JNK inhibitor and found that it could partially inhibit cell apoptosis. The results showed that EGFR (Epidermal growth factor receptor), PI3K and AKT were downregulated after the treatment of pyronaridine. In summary, pyronaridine can selectively kill NSCLC by regulating TRAIL-mediated apoptosis and downregulating the protein level of EGFR. It is a promising anticancer drug for NSCLC.

5.
Biotechnol Adv ; : 107793, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34217814

RESUMO

Enzymes offering chemo-, regio-, and stereoselectivity enable the asymmetric synthesis of high-value chiral molecules. Unfortunately, the drawback that naturally occurring enzymes are often inefficient or have undesired selectivity toward non-native substrates hinders the broadening of biocatalytic applications. To match the demands of specific selectivity in asymmetric synthesis, biochemists have implemented various computer-aided strategies in understanding and engineering enzymatic selectivity, diversifying the available repository of artificial enzymes. Here, given that the entire asymmetric catalytic cycle, involving precise interactions within the active pocket and substrate transport in the enzyme channel, could affect the enzymatic efficiency and selectivity, we presented a comprehensive overview of the computer-aided workflow for enzymatic selectivity. This review includes a mechanistic understanding of enzymatic selectivity based on quantum mechanical calculations, rational design of enzymatic selectivity guided by enzyme-substrate interactions, and enzymatic selectivity regulation via enzyme channel engineering. Finally, we discussed the computational paradigm for designing enzyme selectivity in silico to facilitate the advancement of asymmetric biosynthesis.

6.
Macromol Biosci ; : e2100191, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34263547

RESUMO

Human organoids mimic the physiology and tissue architecture of organs and are of great significance for promoting the study of human diseases. Traditionally, organoid cultures rely predominantly on animal or tumor-derived extracellular matrix (ECM), resulting in poor reproducibility. This limits their utility in for large-scale drug screening and application for regenerative medicine. Recently, synthetic polymeric hydrogels, with high biocompatibility and biodegradability, stability, uniformity of compositions, and high throughput properties, have emerged as potential materials for achieving 3D architectures for organoid cultures. Compared to conventional animal or tumor-derived organoids, these newly engineered hydrogel-based organoids more closely resemble human organs, as they are able to mimic native structural and functional properties observed in-situ. In this review, recent developments in hydrogel-based organoid culture will be summarized, emergent hydrogel technology will be highlighted, and future challenges in applying them to organoid culture will be discussed.

7.
Adv Mater ; : e2100837, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242441

RESUMO

Metal sulfides are attractive anodes for alkali metal ion batteries due to the high theoretical capacity, while their practical implementation is hampered by the inherent poor conductivity and vast volume variation during cycles. Approaching rational designed microstructures with good stability and fast charge transfer is of great importance in response to these issues. Herein, a partial sulfuration strategy for the rational construction of multi-yolk-shell (m-Y-S) structures, from which multiple Fe1- x S nanoparticles are confined within hollow carbon nanosheet with tunable interior void space is reported. As anode materials, the m-Y-S Fe1- x S@C composite can display high capacity and excellent rate capability (134, 365, and 447 mA h g-1 for K+ , Na+ , and Li+ storage at 20 A g-1 ). Remarkably, it exhibits ultra-stable potassium storage up to 1200, 6000, and 20 000 cycles under current densities of 0.1, 0.5, and 1 A g-1 , which is much superior to previous yolk-shell structures and metal-sulfide anodes. Based on comprehensive experimental analysis and theoretical calculations, the exceptional performance of m-Y-S structure can be ascribed to the optimized interior void space for good structure stability, as well as the multiple connection points and conductive carbon layer for superior electron/ion transportation.

8.
J Exp Med ; 218(9)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34254999

RESUMO

Astrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation.

9.
Anesthesiology ; 135(2): 218-232, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34195765

RESUMO

BACKGROUND: Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery. METHODS: Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days. RESULTS: Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 [1.8%] of 857 patients) than in the general anesthesia group (43 [5.0%] of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 [49%] vs. 288 [33%]; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 [58%] vs. 387 [45%]; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001). CONCLUSIONS: Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34284134

RESUMO

The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep understanding of T cells. To date, the complete landscape and systematic characterization of long noncoding RNAs (lncRNAs) in T cells in cancer immunity are lacking. Here, by systematically analyzing full-length single-cell RNA sequencing (scRNA-seq) data of more than 20,000 libraries of T cells across three cancer types, we provide the first comprehensive catalog and the functional repertoires of lncRNAs in human T cells. Specifically, we developed a custom pipeline for de novo transcriptome assembly and obtained a novel lncRNA catalog containing 9433 genes. This increased the number of current human lncRNA catalog by 16% and nearly doubled the number of lncRNAs expressed in T cells. We found that a portion of expressed genes in single T cells were lncRNAs which had been overlooked by the majority of previous studies. Based on metacell maps constructed by the MetaCell algorithm that partitions scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNAs were identified. They associated with effector, exhausted, and regulatory T cell states. 84 of them were functionally annotated based on the co-expression network, indicating that lncRNAs might broadly participate in the regulation of T cell functions. Our findings provide a new point of view and resource for investigating the mechanisms of T cell regulation in cancer immunity as well as for novel cancer-immune biomarker development and cancer immunotherapies.

11.
BMJ Open ; 11(7): e045929, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285006

RESUMO

INTRODUCTION: Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide. Reducing dietary salt consumption is a potentially cost-effective way to reduce blood pressure and the burden of CVD. To date, economic evidence has focused on sodium reduction in food industry or processed food with blood pressure as the primary outcome. This study protocol describes the planned within-trial economic evaluation of a low-sodium salt substitute intervention designed to reduce the risk of stroke in China. METHODS AND ANALYSES: The economic evaluation will be conducted alongside the Salt Substitute and Stroke Study: a 5-year large scale, cluster randomised controlled trial. The outcomes of interest are quality of life measured using the EuroQol-5-Dimensions and major adverse cardiovascular events. Costs will be estimated from a healthcare system perspective and will be sought from the routinely collected data available within the New Rural Cooperative Medical Scheme. Cost-effectiveness and cost-utility analyses will be conducted, resulting in the incremental cost-effectiveness ratio expressed as cost per cardiovascular event averted and cost per quality-adjusted life year gained, respectively. ETHICS AND DISSEMINATION: The trial received ethics approval from the University of Sydney Ethics Committee (2013/888) and Peking University Institutional Review Board (IRB00001052-13069). Informed consent was obtained from each study participant. Findings of the economic evaluation will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02092090).

13.
Chaos ; 31(5): 053112, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34240944

RESUMO

Mathematical epidemiology that describes the complex dynamics on social networks has become increasingly popular. However, a few methods have tackled the problem of coupling network topology with complex incidence mechanisms. Here, we propose a simplicial susceptible-infected-recovered-susceptible (SIRS) model to investigate the epidemic spreading via combining the network higher-order structure with a nonlinear incidence rate. A network-based social system is reshaped to a simplicial complex, in which the spreading or infection occurs with nonlinear reinforcement characterized by the simplex dimensions. Compared with the previous simplicial susceptible-infected-susceptible (SIS) models, the proposed SIRS model can not only capture the discontinuous transition and the bistability of a complex system but also capture the periodic phenomenon of epidemic outbreaks. More significantly, the two thresholds associated with the bistable region and the critical value of the reinforcement factor are derived. We further analyze the stability of equilibrium points of the proposed model and obtain the condition of existence of the bistable states and limit cycles. This work expands the simplicial SIS models to SIRS models and sheds light on a novel perspective of combining the higher-order structure of complex systems with nonlinear incidence rates.

14.
J Immunol Res ; 2021: 5538612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222495

RESUMO

Purpose: Aspergillus fumigatus, as an opportunistic fungus, has developed a series of escape mechanisms under the host's immune response to obtain nutrients and promote fungal growth in the hostile environment. The immune escape of pathogens may be through suppressing the inflammatory response mediated by regulatory T cells (Tregs). The aim of this study was to explore whether A. fumigatus influences Gasdermin-D-dependent pyroptosis of the lung by regulating Toll-like receptor 2-mediated regulatory T cell differentiation. Methods: Collect peripheral blood from patients with A. fumigatus. ELISA kits we used to detect the expression levels of IL-1ß, IL-6, IL-2R, and IL-10 in the serum and flow cytometry to detect the percentage of CD4+CD25+Foxp3+ Tregs in the patients' peripheral blood mononuclear cells (PBMCs). The mouse model of A. fumigatus infection was constructed by tracheal instillation. The pathological changes in the lungs of the mice were observed under a microscope. The fungal load in the lung tissue was determined by the plate colony count. ELISA kit was used to detect the lung tissue homogenate proinflammatory cytokines TNF-α, IL-6, CCL2, and VEGF. Q-PCR was used for the detection of the expression of Foxp3 and TLR2 genes in the lung. Western blot was used for the detection of the expression of TLR2, Gasdermin-D (GSDMD), IL-1α, and IL-1ß in the lung. Flow cytometry was used to detect splenic CD4+CD25+FOXP3+ Tregs. Using magnetic beads to extract CD4+ T cells from mice spleen, the effects of A. fumigatus conidia or TLR2 inhibitor (C29) to differentiate CD4+ T cells in vitro were tested. Results: The expression of Foxp3 and TLR2 in the lung tissue of mice infected with A. fumigatus increased, and we observed that the proportion of Tregs in both A. fumigatus infection patients and mice was upregulated. After using the CD25 neutralizing antibody, the number of Tregs in the mice spleen was significantly reduced. However, lung damage was reduced and the ability to clear lung fungi was enhanced. We found that the Tregs in TLR2-/- mice were significantly reduced and the nonlethal dose of A. fumigatus conidia did not cause severe lung damage in TLR2-/- mice. Compared with that of wild-type mice, the fungal burden in the lung of TLR2-deficient mice was reduced and the knockout of TLR2 changed the expression of GSDMD, IL-1α, and IL-1ß in A. fumigatus. In in vitro experiments, we found that the inhibition of TLR2 can reduce Treg differentiation. Conclusions: A. fumigatus triggers CD4+CD25+FOXP3+ Treg proliferation and differentiation by activating the TLR2 pathway, which may be a potential mechanism for evading host defenses in A. fumigatus. This effect can modulate GSDMD-dependent pyroptosis and may partly involve TRL2 signaling.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34148842

RESUMO

BACKGROUND: The COVID-19 pandemic highlights the critical role of pharmacists in pandemic response. To enhance pharmacist's involvement in future emergency situations, there is a critical need to understand pharmacists' knowledge, willingness and preparedness in response to various emergency situations. OBJECTIVE: This study aimed to describe pharmacists and pharmacist extenders on their participation in emergency response activities and training, preparedness and willingness to respond in emergency situations, and knowledge of the Memorandum of Understanding (MOU) and their pharmacy's emergency preparedness plans. METHODS: A cross-sectional design with an online survey of pharmacist, pharmacy owner, and pharmacy technician members of the National Community Pharmacists Association was employed in the United States in July - August 2020. Descriptive statistics summarized participants' level of actual participation and their willingness to participate in emergency situations and training and their knowledge of MOU and their pharmacy's emergency plans. A non-response bias investigation was conducted by comparing the early and late responders. RESULTS: Of the 6,486 members, 255 completed the questionnaire (RR1 = 4.0%). With the confidence level of 95%, the margin of error was 6%. About 60% were independently owned and in urban areas. More than 80% and 64% of the participants have not volunteered in any emergency or participated in any emergency training program, respectively. Over 60% were very willing to assist with the distribution of medications and vaccine administration. Less than 10% had MOUs with health departments. More than 60% of respondents were not aware of what MOU is. CONCLUSION: Despite limited involvement in actual emergency activities and training, pharmacists and pharmacist extenders exhibited a high level of willingness to participate in emergency training and assist in case of emergencies. This study recommends the development of programs aimed at increasing pharmacists' and pharmacist extenders' participation in emergency training and in future public health emergencies.

16.
BMC Gastroenterol ; 21(1): 264, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118868

RESUMO

BACKGROUND: The aim of this study is to investigate the difference of serum pepsinogen (PG) baseline levels in different regions of China and its influencing factors. METHODS: From October 2016 to October 2018, asymptomatic health checkup people who underwent nasal endoscopy in nine health management centers in different regions of China were collected. Lifestyle questionnaires were conducted, and serum PG and gastroscopy were performed. The differences in PG levels in baseline population (OLGA-0 grade) were studied according to geographical subregions of China. SPSS software was used for statistical analysis. RESULTS: 1922 patients were included in the final analysis. Compared with the non-atrophy (OLGA-0) group, PGR levels in atrophy group (OLGA-I to IV) were significantly decreased with the atrophy degree (p < 0.05). A total of 1590 baseline people (OLGA-0) were included in the study, including 254 from South China, 574 from East China, 210 from Southwest China, 332 from Northeast China, and 220 from Central/Northern China. There were significant differences in baseline PGI levels among the five regions (p < 0.05). The PGII levels were also different among the five regions, except for Central/Northern versus Southern China. PGR (PGI/PGII ratio) levels in Southern China were higher than other four regions. Further studies were conducted on the related factors that might affect the baseline PG level, which was affected by nationality, dietary habits, smoking, Helicobacter pylori infection and other related factors. CONCLUSION: Influenced by many factors, the baseline PG levels are different in different regions of China. In the follow-up studies of PG cut-off value, different PG cut-off value based on region may be more effective in the screening of gastric cancer and precancerous lesions in China.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , China/epidemiologia , Estudos Transversais , Infecções por Helicobacter/epidemiologia , Humanos , Pepsinogênio A , Pepsinogênio C
17.
BMC Med Genomics ; 14(1): 156, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118937

RESUMO

Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P < 0.05). Post 8-week of treatment, newly diagnosed T2DM patients showed a less reduction in fasting plasma glucose levels and less increase in the carriers of genotype CG + GG at rs10830963 when compared with the CC genotype (P < 0.05). MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.Trial registration Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.

18.
Sci Total Environ ; 791: 148152, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34118673

RESUMO

The extensive pollution of antibiotics and antibiotic resistance genes (ARGs) in drinking water has aroused worldwide concern. Successive monitoring of these pollutants has noteworthy significance for drinking water safety. Accordingly, this study conducted successive monitoring of antibiotics and ARGs from 2015 to 2017 in a drinking water source in East China. The total antibiotic concentration ranged from 19.68 ng/L to 497.00 ng/L, and decreased slightly from 2015 to 2017. Eighteen out of forty-one ARG subtypes showing resistance to six antibiotic classes and one class I integrase gene intI1, were detected in the drinking water source at concentrations ranging from 6.5 × 104 copies/mL to 1.6 × 106 copies/mL. Importantly, the total ARG concentration increased on an annual basis from 2015 to 2017 with an average annual increment of 0.25 orders of magnitude, which was mainly attributed to the increase in specific ARG subtypes, such as sul1, sul2, sul3, tetA, qnrB, and ermB. Most ARGs was positively correlated with the intI1 genes (r = 0.47-0.55, P < 0.01). Furthermore, the variation of antibiotics and ARGs appeared to be related to the water indices, particularly of the values of COD, BOD5, NO2-N (P < 0.05). This study provides basic data on antibiotic and ARG pollution in the studied drinking water source. Importantly, the findings expound that although the residual antibiotics in this drinking water source decreased slightly from 2015 to 2017, while its biological effect, the antibiotic resistance, increased annually, which give a warning of the antibiotic resistance pollution in the drinking water source.

19.
Microvasc Res ; 138: 104195, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34116070

RESUMO

BACKGROUND: This study was carried out to investigate the effect of microRNA miR-532-5p on the proliferation of hypertension endothelial cells. METHODS: Angiotensin II (Ang II)-treated human umbilical vein endothelial cells (HUVECs) and primary human aortic endothelial cells (HAECs) were used as cell models to imitate the pathological changes in endothelial cells under hypertensive conditions. The expression levels of miR-532-5p and programmed cell death protein 4 (PDCD4) were detected by Quantitative Real-time PCR (qRT-PCR). The effects of miR-532-5p and PDCD4 on the proliferation of HUVECs and HAECs treated with Ang II were detected by Methyl Thiazolyl Tetrazolium (MTT) assay. The effects of miR-532-5p and PDCD4 on the apoptosis and cell cycle of HUVECs and HAECs treated with Ang II were detected by flow cytometry. Western blot was used to detect the expression levels of PDCD4, apoptosis-related proteins and cycle-related proteins in HUVECs and HAECs treated with Ang II. Bioinformatics analysis and Luciferase gene reporter assay were used to assess the relationship between miR-532-5p and PDCD4. RESULTS: The expression levels of miR-532-5p were reduced, while the expression levels of PDCD4 were raised in Ang II-treated HUVECs and HAECs. MiR-532-5p mimic and si-PDCD4 restrained the apoptosis, promoted the proliferation of Ang II-treated HUVECs and HAECs and caused S-phase arrest of cells. PDCD4 was identified as a potential target for miR-532-5p. Knockdown of PDCD4 significantly affected apoptosis and proliferation of Ang II-treated HUVECs. MiR-532-5p regulates apoptosis and proliferation of Ang II-induced HUVECs and HAECs. In addition, overexpression of PDCD4 attenuated the effect of miR-532-5p on the proliferation of Ang II-treated HUVECs and HAECs. CONCLUSION: MiR-532-5p inhibited the expression of PDCD4, thereby inhibiting apoptosis and promoting proliferation of Ang II-treated HUVECs and HAECs.

20.
Soft Matter ; 17(26): 6298-6304, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34160542

RESUMO

Chiral assemblies by combining natural biomolecules with plasmonic nanostructures hold great promise for plasmonic enhanced sensing, imaging, and catalytic applications. Herein, we demonstrate that human serum albumin (HSA) and porcine serum albumin (PSA) can guide the chiral assembly of gold nanorods (GNRs) with left-handed chiroptical responses opposite to those by a series of other homologous animal serum albumins (SAs) due to the difference of their surface charge distributions. Under physiological pH conditions, the assembly of HSA or PSA with GNRs yielded left-handed twisted aggregates, while bovine serum albumin (BSA), sheep serum albumin, and equine serum albumin behaved on the contrary. The driving force for the chiral assembly is mainly attributed to electrostatic interaction. The opposite chiroptical signals acquired are correlated with the chiral surface charge distributions of the tertiary structures of SAs. Moreover, the chirality of the assembly induced by both HSA and BSA can be enhanced or reversed by adjusting the pH values. This work provides new insights into the modulation of protein-induced chiral assemblies and promotes their applications.


Assuntos
Nanoestruturas , Nanotubos , Animais , Ouro , Cavalos , Albumina Sérica , Soroalbumina Bovina , Ovinos
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