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1.
Cancer Med ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034945

RESUMO

OBJECTIVE: This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II-IVa nasopharyngeal carcinoma (NPC) based on Epstein-Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax-N) of [18 F]-fluorodeoxyglucose positron emission tomography. PATIENTS AND MATERIALS: A total of 679 patients diagnosed with stage II-IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. RESULTS: Both high levels of EBV DNA (>1500 copies/mL) and SUVmax-N (>12.3) indicated worse survival conditions. All patients were divided into low- and high-risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) (all p-values<0.05). The addition of IC to CCRT was associated with survival improvement in OS, PFS, and DMFS in high-risk patients, while no survival difference was found between CCRT and IC+CCRT in low-risk patients. CONCLUSIONS: Our study can help clinicians select stage II-IVa NPC patients who benefit from IC, which is important in guiding individual treatment.

2.
Front Immunol ; 11: 2131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013899

RESUMO

Background and methods: Host genomic alterations are closely related to dysfunction of CD4+ T lymphocytes in the HIV-host interplay. However, the roles of aberrant DNA methylation and gene expression in the response to HIV infection are not fully understood. We investigated the genome-wide DNA methylation and transcriptomic profiles in two HIV-infected T lymphocyte cell lines using high-throughput sequencing. Results: Based on DNA methylation data, we identified 3,060 hypomethylated differentially methylated regions (DMRs) and 2,659 hypermethylated DMRs in HIV-infected cells. Transcription-factor-binding motifs were significantly associated with methylation alterations, suggesting that DNA methylation modulates gene expression by affecting the binding to transcription factors during HIV infection. In support of this hypothesis, genes with promoters overlapping with DMRs were enriched in the biological function related to transcription factor activities. Furthermore, the analysis of gene expression data identified 1,633 upregulated genes and 2,142 downregulated genes on average in HIV-infected cells. These differentially expressed genes (DEGs) were significantly enriched in apoptosis-related pathways. Our results suggest alternative splicing as an additional mechanism that may contribute to T-cell apoptosis during HIV infection. We also demonstrated a genome-scale correlation between DNA methylation and gene expression in HIV-infected cells. We identified 831 genes with alterations in both DNA methylation and gene expression, which were enriched in apoptosis. Our results were validated using various experimental methods. In addition, consistent with our in silico results, a luciferase assay showed that the activity of the PDX1 and SMAD3 promoters was significantly decreased in the presence of HIV proteins, indicating the potential of these genes as genetic markers of HIV infection. Conclusions: Our results suggest important roles for DNA methylation and gene expression regulation in T-cell apoptosis during HIV infection. We propose a list of novel genes related to these processes for further investigation. This study also provides a comprehensive characterization of changes occurring at the transcriptional and epigenetic levels in T cells in response to HIV infection.

3.
Int J Immunopathol Pharmacol ; 34: 2058738420963818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33016797

RESUMO

Sepsis, a severe infectious disease in the neonatal period, is considered a risk factor for necrotizing enterocolitis (NEC). To investigate the specific risk factors for NEC in septic infants, septic infants admitted to our center from January 2010 to April 2018 were included. Septic neonates with proven NEC (Bell's stage ⩾II) were enrolled in the NEC group, and those without NEC were enrolled in the control group. Demographics, clinical characteristics, and risk factors were compared between the two groups. Univariate and logistic regression analyses were used to evaluate the potential risk factors for NEC. A total of 610 septic neonates were included, of whom 78 (12.8%) had complicated NEC. The univariate analysis indicated that infants with NEC had a lower birth weight, a lower gestational age, and older age on admission than those without NEC (P < 0.05). Higher rates of anemia, prolonged rupture of membranes (PROM) (⩾18 h), pregnancy-induced hypertension, late-onset sepsis (LOS), red blood cell transfusion and hypoalbuminemia were observed in the NEC group than in the non-NEC group (P<0.05). Logistic regression analysis revealed LOS (P = 0.000), red blood cell transfusion (P = 0.001) and hypoalbuminemia (P = 0.001) were associated with the development of NEC. Among NEC infants, those who needed red blood cell transfusion had a longer hospitalization duration than those who did not need transfusion (P < 0.05). LOS, red blood cell transfusion and hypoalbuminemia were independent risk factors for the development of NEC in infants with sepsis. Taking measures to reduce the occurrence of hypoproteinemia and severe anemia may help to reduce the occurrence of NEC in septic neonates.

4.
Org Biomol Chem ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026017

RESUMO

A novel and efficient one-pot synthesis of symmetrical N-aryl dialkynylimines via palladium-catalyzed and copper-promoted isocyanide insertion, cross-coupling and elimination has been developed. This method features readily available starting materials, mild reaction conditions and high atom efficiency as well as simple one-pot operation, which make this strategy highly attractive. Moreover, 2-iodobenzo[f]quinoline derivatives can be obtained via electrophilic cyclization of N-aryl dialkynylimines.

5.
Nanoscale ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006354

RESUMO

There are only a handful of reports on indium sulfide (In2S3) in the electrochemical energy storage field without a clear electrochemical reaction mechanism. In this work, a simple electrospinning method has been used to synthesize In2S3/C nanofibers for the first time. In lithium-ion batteries (LIBs), the In2S3/C nanofiber electrode can not only deliver a high initial reversible specific capacity of 696.4 mA h g-1 at 50 mA g-1, but also shows ultra-long cycle life with a capacity retention of 80.5% after 600 cycles at 1000 mA g-1. In sodium-ion batteries (SIBs), the In2S3/C nanofibers electrode can exhibit a high initial reversible specific capacity (393.7 mA h g-1 at 50 mA g-1) and excellent cycling performance with a high capacity retention of 97.3% after 300 cycles at 1000 mA g-1. The excellent electrochemical properties mainly benefited from In2S3 being encapsulated by a carbon matrix, which buffers the volume expansion and significantly improves the conductivity of the composite. Furthermore, the structural evolution of In2S3 during the first lithiation/delithiation and sodiation/desodiation processes has been illustrated by ex situ XRD. The results confirm that the reaction mechanism of In2S3 in both LIBs and SIBs can be summarized as conversion reactions and alloying reactions, which provide theoretical support for the development of In2S3 in the field of electrochemistry.

6.
Braz J Med Biol Res ; 53(11): e8930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053113

RESUMO

This study aimed to investigate whether the routine administration of escitalopram for three months would improve the prognosis of patients with ischemic stroke and decrease the plasma copeptin level. A total of 97 patients with acute cerebral infarction were randomly allocated to receive escitalopram (5-10 mg once per day, orally; n=49) or not to receive escitalopram (control group; n=48) for 12 weeks starting at 2-7 days after the onset of stroke. Both groups received conventional treatments, including physiotherapy and secondary prevention of stroke. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the disability of patients at the initial evaluation and at the monthly follow-up visits for three months. Impairment in the daily activities was assessed using the Barthel Index (BI), while cognitive impairment was assessed using Mini-Mental State Examination (MMSE) score. The psychiatric assessment included the administration of the Present State Examination modified to identify Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptoms of depression. The severity of depression was measured using the 17-item Hamilton Rating Scale for Depression (HAMD). During the 3-month follow-up period, 95 patients were included in the analysis (two patients withdrew from the escitalopram group). NIHSS and BI improvement at the 90th day were significantly greater in the escitalopram group (P<0.05), while HAMD and plasma copeptin levels significantly decreased, compared to the control group (P<0.01). In patients with acute ischemic stroke, the earlier administration of escitalopram for three months may improve neurological functional prognosis and decrease copeptin level.

7.
Ann Clin Lab Sci ; 50(5): 578-583, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33067203

RESUMO

Angiotensin II (Ang II) contributes to renal dysfunction, while hepatocyte growth factor (HGF) protects against renal dysfunction. However, the relationship between Ang II and HGF in chronic kidney disease (CKD) remains unknown. This study aimed to investigate the effect of HGF on Ang II expression in CKD. A rat model of CKD was established using female Wistar rats subjected to 5/6 nephrectomy (5/6 Nx). HGF was overexpressed in rat renal tissues using PCI-neo-HGF. Immunohistochemical staining and western blot analysis of renal Ang II expression were performed in 5/6 Nx rats treated with vehicle (negative control), Lotensin (positive control), or HGF for different periods of time (before 5/6 Nx, 5 and 9 weeks after 5/6 Nx). Compared with the 0-week group (before 5/6 Nx group), the protein expression of Ang II was significantly induced in rat renal tissues at 5 and 9 weeks after 5/6 Nx (p<0.05), suggesting the possible involvement of Ang II in 5/6 Nx-induced CKD. Importantly, HGF treatment for 5 or 9 weeks markedly inhibited renal Ang II expression and greatly improved the renal morphology in 5/6 Nx rats, compared with the vehicle-treated group (p<0.05). The effects of HGF on renal Ang II expression and renal morphology were similar to those of Lotensin, suggesting that HGF may protect against 5/6 Nx-induced CKD through downregulating Ang II. HGF is a novel regulator of Ang II expression and plays a protective role in 5/6 Nx-induced CKD.

8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1683-1688, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067974

RESUMO

OBJECTIVE: To compare the clinical efficacy between frontline haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) and salvage haplo-HSCT for patients with severe aplastic anemia (SAA). METHODS: A total of 39 patients with severe aplastic anemia or very severe aplastic anemia from May 1st, 2013 to December 31st, 2018 were analyzed retrospectively. All of them underwent bone marrow + peripheral blood hemopoietic stem cell transplantation. There were 20 cases who accepted frontline haplo-HSCT for a median course of 1 (1-3) month, and 19 cases who accepted salvage haplo-HSCT for a median course of 72 (6-168) months. Conditioning regimen: 22 cases received Flu/Cy+ATG, and 17 cases received Bu/Cy+ATG. RESULTS: The time of hematopoietic reconstitution, infection rate, and grade I-Ⅱ and Ⅲ-Ⅳ acute/chronic graft versus host disease showed no statistically significance between the frontline haplo-HSCT group and the salvage haplo-HSCT group. In the frontline haplo-HSCT group, 1 case (5%) failed in second engraftment, in the salvage haplo-HSCT group 2 cases (10.5%) failed in primary engraftment and 4 cases (21.1%) in second engraftment. The incidence of engraftment failure was higher in the salvage haplo-HSCT group than that in the frontline haplo-HSCT group (P=0.04). The median time of follow-up after allo-HSCT was 45 months (ranging from 3 to 92). The mortality was 10% (2/20) in the frontline haplo-HSCT group, and 42.1% (8/19) in the salvage haplo-HSCT group. The estimated 5-year failure-free survival rate (FFS) of the frontline haplo-HSCT group was higher than that of the salvage haplo-HSCT group (90% vs 57.4%) (P=0.02). CONCLUSION: The frontline haplo-HSCT is an effective and safe approach for the patients with severe aplastic anemia who lack a HLA-matched sibling donor.

9.
Aging (Albany NY) ; 122020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33041262

RESUMO

BACKGROUND: Apathy is common in Alzheimer's disease (AD) patients. However, its relation with other clinical symptoms in AD and brain structural changes in magnetic resonance imaging is unclear. RESULTS: Compared with AD with no apathy group, cognitive function and activities of daily living were significantly impaired and neuropsychiatric symptoms were obviously presented in AD with apathy group (P<0.05). The frequency of Apolipoprotein E genotypes was not significantly different (P>0.05). Correlation analyses and multiple linear analyses revealed that thickness of left temporal pole and volume of posterior corpus callosum were significantly and negatively correlated with Modified Apathy Estimation Scale score in AD patients (P<0.05). CONCLUSIONS: Apathy with AD is positively correlated with cognitive impairment, neuropsychiatric symptoms and poor activities of daily living. Atrophy of left temporal pole and posterior corpus callosum presented by MRI is positively related with apathy of AD. METHODS: In this study, 137 AD patients were recruited and divided into AD with apathy group and AD with no apathy group according to Modified Apathy Estimation Scale score. We evaluated patients' cognitive function, neuropsychiatric symptoms and activities of daily living, detected the frequency of Apolipoprotein E genotypes and measured cortical thickness and volume by magnetic resonance imaging (MRI).

10.
J Diabetes Investig ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33035409

RESUMO

AIM: This study aimed to explore the association between glycemic control prior to admission with severity and mortality of COVID-19, and tried to reveal the mechanism. METHODS: 77 inpatients were grouped into sufficient control group (HbA1c<6.5%, n=49) and insufficient control group (HbA1c ≥ 6.5%, n=28). Regression models were used to analyze the clinical data. RESULTS: Compared with patients with HbA1C < 6.5, patients with HbA1C ≥ 6.5 showed higher heart rate (101 vs. 89 beats per min, P=0.012), lower percutaneous oxygen saturation (93% vs. 97%, P=0.001), higher levels of multiple indicators of inflammation, such as white blood cell count (7.9 vs. 5.9 ×109/L, P=0.019), neutrophil count (6.5 vs. 4.1 ×109/L, P=0.001), high-sensitivity C-reactive protein (52 vs. 30 mg/L, P=0.025), and serum ferritin (1287 vs. 716 µg/L, P=0.023), as well as lower level of lymphocyte count (0.7 vs. 0.8 ×109/L P=0.049) at hospital admission. Thus, patients with HbA1C ≥ 6.5 were more likely to develop secondary respiratory infections (25 [89%] vs. 33 [67%], P=0.032) and acute respiratory distress syndrome (ARDS) (17 [61%] vs. 14 [29%], P=0.006) than patients with HbA1C < 6.5, resulting in a higher proportion of critically ill cases (19 [68%] vs. 18 [37%], P=0.009) and non-survivors (13 [46%] vs. 11 [22%], P=0.029). After adjustment for potential risk factors, HbA1C was independently associated with in-hospital death. CONCLUSION: HbA1c was an independent risk factor for poor outcomes in COVID-19 patients. Severe pulmonary infection and consequent ARDS might be the primary causes of death in insufficient glycemic control patients.

12.
Theranostics ; 10(24): 11080-11091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042271

RESUMO

Microsatellite instability (MSI) has been approved as a pan-cancer biomarker for immune checkpoint blockade (ICB) therapy. However, current MSI identification methods are not available for all patients. We proposed an ensemble multiple instance deep learning model to predict microsatellite status based on histopathology images, and interpreted the pathomics-based model with multi-omics correlation. Methods: Two cohorts of patients were collected, including 429 from The Cancer Genome Atlas (TCGA-COAD) and 785 from an Asian colorectal cancer (CRC) cohort (Asian-CRC). We established the pathomics model, named Ensembled Patch Likelihood Aggregation (EPLA), based on two consecutive stages: patch-level prediction and WSI-level prediction. The initial model was developed and validated in TCGA-COAD, and then generalized in Asian-CRC through transfer learning. The pathological signatures extracted from the model were analyzed with genomic and transcriptomic profiles for model interpretation. Results: The EPLA model achieved an area-under-the-curve (AUC) of 0.8848 (95% CI: 0.8185-0.9512) in the TCGA-COAD test set and an AUC of 0.8504 (95% CI: 0.7591-0.9323) in the external validation set Asian-CRC after transfer learning. Notably, EPLA captured the relationship between pathological phenotype of poor differentiation and MSI (P < 0.001). Furthermore, the five pathological imaging signatures identified from the EPLA model were associated with mutation burden and DNA damage repair related genotype in the genomic profiles, and antitumor immunity activated pathway in the transcriptomic profiles. Conclusions: Our pathomics-based deep learning model can effectively predict MSI from histopathology images and is transferable to a new patient cohort. The interpretability of our model by association with pathological, genomic and transcriptomic phenotypes lays the foundation for prospective clinical trials of the application of this artificial intelligence (AI) platform in ICB therapy.

13.
Med Sci Monit ; 26: e924343, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006960

RESUMO

BACKGROUND Gastric cancer (GC) is the third leading cause of cancer-associated mortality in the world. Expression of circular RNA circ_C16orf62 is reported to be low in GC. The role and mechanism of circ_C16orf62 remain unclear. MATERIAL AND METHODS Expression levels of circ_C16orf62 and tubulin beta-2A chain (TUBB2A) in GC tissues and cells, and microRNA-421 (miR-421) level in GC cells were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The predominant cytoplasmic localization of circ_C16orf62 was identified by subcellular fractionation. The protein level of TUBB2A was detected by western blot assay. Cell proliferative ability, migration, and invasion were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, and several transwell assaysy. The binding relationship between miR-421 and circ_C16orf62 or TUBB2A was predicted by starBase3.0 or Targetscan, and then verified by the dual-luciferase reporter assay. The biological role ofcirc_C16orf62 was examined by xenograft tumor model in vivo. RESULTS Circ_C16orf62 andTUBB2A were downregulated in GC tissues and cells. Circ_C16orf62 was predominantly located in the cytoplasm of GC cells, and repressed proliferation, migration, and invasion of GC cells. Mechanistically, circ_C16orf62 worked as the miR-421 sponge to upregulate TUBB2A in GC, thereby hindering GC growth. Circ_C16orf62 repressed GC tumor growth in vivo. CONCLUSIONS These findings demonstrate that circ_C16orf62 impeded proliferation, migration, and invasion in vitro and retarded tumor growth in vivo by the miR-421/TUBB2A axis in GC, providing a potential therapeutic strategy for patients with GC.

14.
Small ; : e2003096, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33015944

RESUMO

Configuring metal single-atom catalysts (SACs) with high electrocatalytic activity and stability is one efficient strategy in achieving the cost-competitive catalyst for fuel cells' applications. Herein, the atomic layer deposition (ALD) strategy for synthesis of Pt SACs on the metal-organic framework (MOF)-derived N-doped carbon (NC) is proposed. Through adjusting the ALD exposure time of the Pt precursor, the size-controlled Pt catalysts, from Pt single atoms to subclusters and nanoparticles, are prepared on MOF-NC support. X-ray absorption fine structure spectra determine the increased electron vacancy in Pt SACs and indicate the Pt-N coordination in the as-prepared Pt SACs. Benefiting from the low-coordination environment and anchoring interaction between Pt atoms and nitrogen-doping sites from MOF-NC support, the Pt SACs deliver an enhanced activity and stability with 6.5 times higher mass activity than that of Pt nanoparticle catalysts in boosting the oxygen reduction reaction (ORR). Density functional theory calculations indicate that Pt single atoms prefer to be anchored by the pyridinic N-doped carbon sites. Importantly, it is revealed that the electronic structure of Pt SAs can be adjusted by adsorption of hydroxyl and oxygen, which greatly lowers free energy change for the rate-determining step and enhances the activity of Pt SACs toward the ORR.

15.
Sensors (Basel) ; 20(19)2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998290

RESUMO

Total hatching egg set (for both egg production chicks and broilers) in the Agriculture and Agri-Food Canada report 2017 was over 1.0 billion. With the fertility rate for this year observed to be around 82%, there were about 180 million unhatched eggs (worth over 300 million Canadian dollars) incubated in Canada for the year 2017 alone. These non-hatching (non-fertile) eggs can find useful applications as commercial table eggs or low-grade food stock if they can be detected early and isolated accordingly preferably prior to incubation. The conventional method of chicken egg fertility assessment termed candling, is subjective, cumbersome, slow, and eventually inefficient, leading to huge economic losses. Hence, there is a need for a non-destructive, fast and online prediction technology to assist with early chicken egg fertility identification problem. This paper reviewed existing non-destructive approaches including ultrasound and dielectric measurements, thermal imaging, machine vision, spectroscopy, and hyperspectral imaging. Hyperspectral imaging was extensively discussed, being an emerging new technology with great potential. Suggestions were finally proffered towards building futuristic robust model(s) for early detection of chicken egg fertility.

16.
Minerva Ginecol ; 72(3): 138-148, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33000614

RESUMO

BACKGROUND: Poor communication between patients and providers can lead to misunderstanding and misclassification of clinical information, including pregnancy outcomes by women. This qualitative study with maternity care providers explores patient-provider communications regarding stillbirths (SB) and early neonatal deaths (END) and potential SB-END misclassification in Ethiopia. METHODS: Qualitative data were collected through 8 in-depth interviews and 3 focus group discussions with maternity care providers at Tikur Anbessa and Gandhi Memorial hospitals in Addis-Ababa. RESULTS: Twenty-six maternity care providers (10 physicians;16 nurses/midwives) were interviewed. Providers noted that high patient loads negatively influence their provision of quality care to patients. Yet, despite patients generally not asking many questions during their delivery hospitalization, maternity care providers reported offering information about pregnancy outcomes at hospital discharge. The level of education was the most cited factor influencing patients' understanding of the information communicated to them, especially with regard to adverse pregnancy outcomes. Respondents reported that women do not have significant misconceptions about either SB or END. Nevertheless, they also revealed that both purposeful and accidental SB-END misclassification occurs. Reports of the direction of such misclassification differed by type of provider - physicians noted that misclassification of SB as END is most common, while nurses and midwives identified the opposite direction for this type of misclassification. CONCLUSIONS: Maternity care providers' reporting practices and the quality of their communication with patients contribute to the SB-END misclassification in Ethiopia. There is need to increase providers' awareness of the importance of capturing and reporting reliable and valid information on pregnancy outcomes.

17.
Adv Mater ; : e2004835, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000881

RESUMO

Elemental 2D materials with fascinating characteristics are regarded as an influential portion of the 2D family. Iodine is as a typical monoelemental molecular crystal and exhibits great prospects of applications. To realize 2D iodine, not only is it required to separate the weak interlayer van der Waals interactions, but also to reserve the weak intramolecular halogen bonds; thus, 2D iodine is still unexploited until now. Herein, atomically thin iodine nanosheets (termed "iodinene") with the thickness around 1.0 nm and lateral sizes up to hundreds of nanometers are successfully fabricated by a liquid-phase exfoliation strategy. When used for the cathode of rechargeable sodium-ion batteries, the ultrathin iodinene exhibits superb rate properties with a high specific capacity of 109.5 mA h g-1 at the high rate of 10 A g-1 owing to its unique 2D ultrathin architecture with remarkably enhanced pseudocapacitive behavior. First-principles calculations reveal that the diffusion of sodium ions in few-layered iodinene changes from the original horizontal direction in bulk to the vertical with a small energy barrier of 0.07 eV because of the size effect. The successful preparation and intensive structural investigation of iodinene paves the way for the development of novel iodine-based science and technologies.

18.
J Ethnopharmacol ; : 113422, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007391

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Gentiana dahurica Fisch (called Qin-Jiao in China), a traditional Chinese medicine, is used in China to treat alcoholic liver disease (ALD), but there has been no scientific report on the treatment of ALD. AIM OF THE STUDY: To investigate the therapeutic effects of Gentiana dahurica Fisch ethanol extract (GDEE) on ALD and to reveal its possible mechanism of action using RNA sequencing. MATERIALS AND METHODS: The model of ALD was established by continuous gavage with alcohol in mice, and GDEE was used to treat ALD. Pathological observation (HE staining, oil red O staining) and biochemical indicators were performed to evaluate liver tissue lesions and efficacy of GDEE. RNA sequencing analysis of liver tissues was carried out to elucidate the pathogenesis of ALD and the mechanism of hepatoprotective effect by GDEE. The RNA sequencing results were verified by detecting mRNA and protein expressions of acetyl coenzyme A carboxylase α (Acacα), fatty acid synthase (Fasn) and carnitine palmitoyltransferase 1A (Cpt1a) by quantitative real-time polymerase chain reaction (PCR) and Western blot. RESULTS: Measurements of biochemical parameters showed that GDEE could inhibit the increased transaminase activities in the serum and lipid levels in the liver caused by alcohol. It was observed that GDEE could alleviate fatty degeneration, edema and cell necrosis caused by alcohol in the liver tissue. RNA sequencing analysis of liver tissues found that 719 genes and 1137 genes were significantly changed by alcohol and GDEE, respectively. GDEE reversed most of the changes in triglycerides synthesis-related genes up-regulated by alcohol. GDEE up-regulated most of the genes involved in the fatty acid degradation in ALD mice, while alcohol had little effect on them. In addition, GDEE suppressed most of the genes involved in cholesterol synthesis that were up-regulated by alcohol. GDEE up-regulated genes related to bile acid synthesis in ALD mice, and down-regulated genes related to bile acid reabsorption, while alcohol had no significant effect on genes related to bile acid metabolism. In the validation experiments, the Acacα, Fasn and Cpt1a expressions quantified by real-time PCR and Western blot were consistent with the RNA sequencing results. CONCLUSIONS: GDEE can alleviate liver damage and steatosis in ALD mice, and its mechanism of action may be related to the process of regulating triglycerides and cholesterol.

19.
Materials (Basel) ; 13(19)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007907

RESUMO

The fundamental challenge for creating the crystal structure model used in a multi-principle element design is the ideal combination of atom components, structural stability, and deformation behavior. However, most of the multi-principle element alloys contain expensive metallic and rare earth elements, which could limit their applicability. Here, a novel design of low-cost AlCrTiFeNi multi-principle element alloy is presented to study the relationship of structure, deformation behavior, and micro-mechanism. This structured prediction of single-phase AlCrTiFeNi by the atomic-size difference, mixing enthalpy ΔHmix and valence electron concentration (VEC), indicate that we can choose the bcc-structured solid solution to design the AlCrTiFeNi multi-principle element alloy. Structural stability prediction by density functional theory calculations (DFT) of single phases has verified that the most advantageous atom occupancy position is (FeCrNi)(AlFeTi). The experimental results showed that the structure of AlCrTiFeNi multi-principle element alloy is bcc1 + bcc2 + L12 phases, which we propose as the fundamental reason for the high strength. Our findings provide a new route by which to design and obtain multi-principle element alloys with targeted properties based on the theoretical predictions, first-principles calculations, and experimental verification.

20.
BJOG ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010098

RESUMO

OBJECTIVE: Preeclampsia (PE) is a pregnancy-associated condition initiated by placental factors. We have demonstrated that placental extracellular vesicles (pcEVs) cause hypertension and proteinuria in pregnant and non-pregnant mice. STUDY DESIGN: An observational study with both case-control and longitudinal designs. SETTING: A single center at the Department of Obstetrics and Gynecology, Tianjin Medical University. POPULATION: We collected blood samples and clinical information from 54 PE patients, 33 normally pregnant women with at 30-36 gestational weeks and on postpartum days 1 and 4 for the cross-sectional study, and at 22-31, 32-35, and 36-40 weeks for the longitudinal study. Non-pregnant women were also recruited. METHODS: Blood samples were analyzed using flow cytometry, coagulation tests, and ELISA. MAIN OUTCOME MEASURES: The primary outcome was plasma pcEVs and other extracellular vesicles (EVs), and their expressions of anionic phospholipids and von Willebrand factor (VWF). Secondary variables included coagulation, ADAMTS-13, and the anionic phospholipid-binding proteins. RESULTS: Plasma pcEVs progressively increased from NW women to PE patients (IQR for NW: 206/µl [116-255], NP: 1,108 [789-1,969], and PE: 8,487 [4,991-16,752]) and predicted PE. EVs from endothelial cells, platelets, and erythrocytes accounted for <10% of pcEVs. VWF became hyper-adhesive in PE patients and contributed to the pregnancy-associated hypercoagulability. CONCLUSION: Placental, platelet- and endothelial cell-derived EVs were significantly elevated in PE patients, but only pcEVs predicted PE. These EVs played a causal role in the pregnancy-induced hypercoagulability.

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