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1.
Support Care Cancer ; 28(1): 373-380, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31049672

RESUMO

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

2.
J Neurochem ; : e14928, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784978

RESUMO

Short-chain fatty acids (SCFAs) are a group of fatty acids predominantly produced during the fermentation of dietary fibers by the gut anaerobic microbiota. SCFAs affect many host processes in health and disease. SCFAs play an important role in the 'gut-brain axis', regulating central nervous system processes e.g. cell-cell interaction, neurotransmitter synthesis and release, microglia activation, mitochondrial function and gene expression. SCFAs also promote the growth of neurospheres from human neural stem cells and the differentiation of embryonic stem cells into neural cells. It is plausible that maternally derived SCFAs may pass the placenta and expose the fetus at key developmental periods. However, it is unclear how SCFA exposure at physiological levels influence the early-stage neural cells. In this study, we explored the effect of SCFAs on the growth rate of human neural progenitor cells (hNPCs), generated from human embryonic stem cell line (HS980), with IncuCyte live-cell analysis system and immunofluorescence. We found that physiologically relevant levels (µM) of SCFAs (acetate, propionate, butyrate) increased the growth rate of hNPCs significantly and induced more cells to undergo mitosis, while high levels (mM) of SCFAs had toxic effects on hNPCs. Moreover, no effect on apoptosis was observed in physiological-dose SCFA treatments. In support, data from q-RT PCR showed that SCFA treatments influenced the expression of the neurogenesis, proliferation and apoptosis related genes ATR, BCL2, BID, CASP8, CDK2, E2F1, FAS, NDN, VEGFA To conclude, our results propose that SCFAs regulates early neural system development. This might be relevant for a putative 'maternal gut-fetal brain-axis'.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31791584

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. MicroRNAs (miRNAs) have been proven to play essential roles in different cancers, including HCC. The current study was mainly focused on the role of miR-1470 in HCC progression. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression levels of miR-1470 and Aristaless-like homeobox-4 (ALX4). The CCK-8 and EdU assays were used to examine cell proliferation. Flow cytometric analysis was used to elucidate the cell cycle and cell apoptosis. A xenograft tumor assay was carried out to verify the effect of miR-1470 on tumor formation in vivo. RESULTS: According to the qRT-PCR assay, miR-1470 was proven to be overexpressed in HCC. As shown by the CCK-8 assay, EdU assay and flow cytometric analysis, miR-1470 overexpression promoted cell proliferation and inhibited cell apoptosis. ALX4 was proven via a dual luciferase reporter assay to be a downstream target gene of miR-1470. ALX4 was downregulated in HCC. The results of a rescue assay revealed that miR-1470 had an oncogenic role in HCC by regulating ALX4. CONCLUSION: miR-1470 exhibits an oncogenic role in HCC by targeting ALX4. The data from our study may provide novel insight for the identification of new biomarkers and treatment strategies for HCC.

4.
J Hypertens ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31790055

RESUMO

OBJECTIVE: The clinical utility of screening for pediatric metabolic syndrome (MetS) in children and adolescents is still controversial. We examined the performance of pediatric MetS vs. clustering of cardiovascular risk factors (which are the components of MetS) for predicting high carotid intima-media thickness (cIMT) in children and adolescents. METHODS: Participants included 2427 children and adolescents aged 6-17 years from population-based studies in three countries (Brazil, China and Italy). Pediatric MetS was defined using either the modified National Cholesterol Education Program Adult Treatment Panel III criteria or the modified International Diabetes Federation criteria. Clustering of cardiovascular risk factors was calculated as the sum of five components of MetS (i.e. central obesity, elevated blood pressure, elevated triglycerides, reduced HDL-cholesterol and elevated fasting blood glucose). High cIMT was defined as cIMT at least 95th percentile values for sex and age developed from European children. RESULTS: Presence of one, two or at least three cardiovascular risk factors (using the National Cholesterol Education Program Adult Treatment Panel III criteria), as compared with none, was associated with gradually increasing odds of high cIMT [odds ratios (95% confidence intervals): 1.60 (1.29-1.99), 2.89 (2.21-3.78) and 4.24 (2.81-6.39), respectively]. High cIMT was also associated with presence (vs. absence) of MetS (odds ratio = 2.88, 95% confidence interval = 1.95-4.26). However, clustering of cardiovascular risk factors predicted high cIMT markedly better than MetS (area under the curve of 0.66 vs. 0.54, respectively). Findings were similar using the International Diabetes Federation criteria for pediatric MetS. CONCLUSION: In children and adolescents, a graded score based on five cardiovascular risk factors (used to define MetS) predicted high cIMT markedly better than MetS. These findings do not support the clinical utility of MetS for screening youth at increased cardiovascular risk, as expressed in this study by high cIMT.

5.
Cell Rep ; 29(10): 2936-2943.e4, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31801061

RESUMO

Adrenergic G-protein-coupled receptors (GPCRs) mediate different cellular signaling pathways in the presence of endogenous catecholamines and play important roles in both physiological and pathological conditions. Extensive studies have been carried out to investigate the structure and function of ß adrenergic receptors (ßARs). However, the structure of α adrenergic receptors (αARs) remains to be determined. Here, we report the structure of the human α2C adrenergic receptor (α2CAR) with the non-selective antagonist, RS79948, at 2.8 Å. Our structure, mutations, modeling, and functional experiments indicate that a α2CAR-specific D206ECL2-R409ECL3-Y4056.58 network plays a role in determining α2 adrenergic subtype selectivity. Furthermore, our results show that a specific loosened helix at the top of TM4 in α2CAR is involved in receptor activation. Together, our structure of human α2CAR-RS79948 provides key insight into the mechanism underlying the α2 adrenergic receptor activation and subtype selectivity.

6.
Cell Death Dis ; 10(12): 930, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804468

RESUMO

Natural antisense lncRNAs can interfere with their corresponding sense transcript to elicit concordant or discordant regulation. LncRNA ZNF667-AS1 and its sense gene ZNF667 were found to be downregulated in esophageal squamous cell carcinoma (ESCC) tissues by RNA sequencing; however, the exact roles of both genes in ESCC occurrence and development have not been clarified. This study was to investigate the expression patterns, epigenetic inactivation mechanisms, function, and prognostic significance of ZNF667-AS1 and ZNF667 in ESCC tumorigenesis. Frequent downregulation of ZNF667-AS1 and ZNF667 was detected in esophageal cancer cells and ESCC tissues. The expression levels of ZNF667-AS1 and ZNF667 were significantly reversed by treatment with 5-Aza-dC and TSA in esophageal cancer cell lines. The CpG sites hypermethylation within proximal promoter influenced the binding ability of transcription factor E2F1 to the binding sites and then affected the transcription and expression of ZNF667-AS1 and ZNF667. Overexpression of ZNF667-AS1 and ZNF667 suppressed the viability, migration, and invasion of esophageal cancer cells in vitro. Overexpression of ZNF667-AS1 increased mRNA and protein expression level of ZNF667. ZNF667-AS1 interacts with and recruits TET1 to its target gene ZNF667 and E-cadherin to hydrolyze 5'-mc to 5'-hmc and further activates their expression, meanwhile, ZNF667-AS1 also interacts with UTX to decrease histone H3K27 tri-methylation to activate ZNF667 and E-cadherin expression. Furthermore, ZNF667-AS1 or ZNF667 expression and promoter methylation status were correlated with ESCC patients' survival. Thus, these findings suggest that ZNF667-AS1 and ZNF667 may act as tumor suppressors and may serve as potential targets for antitumor therapy.

7.
Cell Death Differ ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804607

RESUMO

The major function of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is to regulate cell metabolism. However, emerging evidence indicates that IGF2BP2 plays a role in cancer, but the underlying mechanism is largely unknown. Here we showed that upregulation of IGF2BP2 is associated with poor outcomes of pancreatic cancer patients and suppression of IGF2BP2 inhibits cell proliferation. We further showed that IGF2BP2 regulates lncRNA DANCR. Ectopic expression IGF2BP2 enhances, whereas knockdown (KD) or knockout (KO) of IGF2BP2 suppresses DANCR expression. Moreover, in vivo RNA precipitation and reciprocal RNA immunoprecipitation revealed that IGF2BP2 interacts with DANCR. DANCR promotes cell proliferation and stemness-like properties. Experiments with xenograft models revealed that while ectopic expression of DANCR promotes, DANCR KO suppresses tumor growth. Mechanistically, DANCR is modified at N6-methyladenosine (m6A) and mutagenesis assay identified that adenosine at 664 of DANCR is critical to the interaction between IGF2BP2 and DANCR where IGF2BP2 serves a reader for m6A modified DANCR and stabilizes DANCR RNA. Together, these results suggest that DANCR is a novel target for IGF2BP2 through m6A modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like properties and pancreatic cancer pathogenesis.

8.
Drug Des Devel Ther ; 13: 3683-3692, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695335

RESUMO

Background: Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4ß-triazolyl-podophyllotoxin glycosides show good anticancer activity, the per-acetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied. Methods: A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 (leukemia), SMMC-7721 (hepatoma), A-549 (lung cancer), MCF-7 (breast cancer), and SW480 (colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure-activity relationship and the physicochemical property-anticancer activity relationship of these compounds. Results: Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27±0.21 to 11.37±0.52 µM. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA < 20, ClogP > 2, MW > 700 Da, and RB > 10. Conclusion: We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents.

9.
Blood ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31697823

RESUMO

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, where multiple subclones harbor mutations in the same drug resistance gene, was observed in six relapses and confirmed by single-cell sequencing in one case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently two-step process where a persistent clone survived initial therapy, and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from pre-existing resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2,540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.

10.
Cell Prolif ; : e12725, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746058

RESUMO

OBJECTIVES: Activation of the sympathetic system and adrenergic ß-receptors following traumatic bone defects negatively impairs bone regeneration. Whether preventing ß-receptor activation could potentially improve bone defect repair is unknown. In this study, we investigated the effect of systematic administration and local delivery of propranolol through composite scaffolds on bone healing. MATERIALS AND METHODS: Collagen/PVA/propranolol/hydroxyapatite(CPPH)composite scaffolds were fabricated with 3D printing technique and characterized by scanning electron microscope (SEM). Micro-CT analysis and bone formation histology were performed to detect new bone formation. Osteogenic differentiation of bone marrow stromal cells (BMSCs) and osteoclastogenesis of bone marrow monocytes cultured with scaffolds extract were performed for further verification. RESULTS: Intraperitoneal injection of propranolol did not significantly improve bone repair, as indicated by micro-CT analysis and bone formation histology. However, CPPH scaffolds exhibited sustained release of propranolol in vitro and significantly enhanced bone regeneration compared with vehicle collagen/PVA/hydroxyapatite (CPH) scaffolds in vivo. Moreover, in vitro experiments indicated the scaffolds containing propranolol promoted the osteogenic differentiation and migration of rat BMSCs and inhibited osteoclastogenesis by preventing ß-receptor activation. CONCLUSIONS: This study demonstrates that local adrenergic ß-receptor blockade can effectively enhance the treatment of bone defects by stimulating osteogenic differentiation, inhibiting osteoclastogenesis and enhancing BMSCs migration.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31746066

RESUMO

Wilms tumor is a kidney malignancy that typically occurs in children. Aberrant expression of HMGA2 gene is commonly seen in many malignant tumors. Yet, HMGA2 gene polymorphisms on Wilms tumor risk is not established. We carried out the first four-center case-control study with 355 patients and 1070 controls to assess the association of HMGA2 polymorphisms (rs6581658 A>G, rs8756 A>C, and rs968697 T>C) with Wilms tumor risk. All of these three polymorphisms in single could not impact Wilms tumor risk. Stratified analysis revealed a contributing Wilms tumor risk role of rs968697 TC/CC in subgroup of male [TC/CC vs. TT: adjusted odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.03-2.08, P = 0.035]. However, we found that presence of 1-3 protective genotypes were less likely to develop tumor in subgroup of female (adjusted OR = 0.69, 95% CI = 0.48-0.99, P = 0.045). Our findings suggest that HMGA2 gene polymorphisms might influence Wilms tumor predisposition in a weak manner, under certain circumstances. The current study represents the first one to explore the relationship between HMGA2 gene polymorphisms and Wilms tumor risk. We firstly demonstrated that rs6581658 A>G, rs8756 A>C, and rs968697 T>C could not impact Wilms tumor risk, respectively. We shed light on the participation of HMGA2 gene polymorphisms in the risk of Wilms tumor, under certain circumstances. This article is protected by copyright. All rights reserved.

12.
Oncol Rep ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746396

RESUMO

Maintenance of an appropriate oxygen concentration is essential for the function of the liver. However, in many pathological conditions, and particularly in the tumor microenvironment, cells and tissues are frequently in a hypoxic state. In the presence of hypoxia, the cells adapt to the low oxygen levels through the hypoxia­inducible factor (HIF) pathway. Overgrowth of tumor cells restricts the diffusion of oxygen in tumors, leading to insufficient blood supply and the creation of a hypoxic microenvironment, and, as a consequence, activation of the expression of HIFs. HIFs possess a wide range of target genes, which function to control a variety of signaling pathways; thus, HIFs modulate cellular metabolism, immune escape, angiogenesis, metastasis, extracellular matrix remodeling, cancer stem cells and other properties of the tumor. Given their crucial role in the occurrence and development of tumors, HIFs are expected to become new targets of precise treatment of hepatocellular carcinoma.

13.
J Cell Mol Med ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742861

RESUMO

IL-2R pathway is a key regulator in the development of immune cells and has emerged as a promising drug target in cancer treatment, but there is a scarcity of related inhibitors. TPD7 is a novel biphenyl urea taspine derivate, which has been shown anti-cancer effect. Here, we demonstrated the anti-cancer activity of TPD7 in cutaneous T cell lymphoma and investigated the underlying mechanism of TPD7 through IL-2R signalling. The inhibitory effect of TPD7 on cell viability exhibited a strong correlation with the expression level of IL-2R, and cutaneous T cell lymphoma H9 and HUT78 cells were most sensitive to TPD7. TPD7 was nicely bound to IL-2R and down-regulated the mRNA and protein levels of IL-2R. Furthermore, TPD7 suppressed the downstream cascades of IL-2R including JAK/STAT, PI3K/AKT/mTOR and PLCγ/Raf/MAPK signalling, resulting in Bcl-2 mitochondrial apoptosis pathway and cell cycle proteins CDK/Cyclins regulation. And, these were verified by flow cytometry analysis that TPD7 facilitated cell apoptosis in H9 cells via mitochondrial pathway and impeded cell cycle progression at G2/M phase. TPD7 is a novel anti-cancer agent and may be a potential candidate for cutaneous T cell lymphoma treatment by regulating IL-2R signalling pathway.

14.
Appl Opt ; 58(30): 8282-8289, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674500

RESUMO

The paper introduces a silica-on-silicon monolithic integrated cyclic arrayed waveguide grating (AWG) with Mach-Zehnder interference (MZI) filters and arrayed vertical reflecting mirrors in silicon to realize effective and stable optical transmission between waveguides and photodiodes. The cyclic AWG acts as both multiplexer over the L-band for upstream traffic and demultiplexer over the C-band for downstream traffic. The integrated chip, including AWG, MZI filters, and arrayed reflecting mirrors, has been made successfully with a 6.0 dB insertion loss, which is less than the discrete devices. At the same time, the arrayed reflecting mirrors are more stable than separate reflectors.

15.
Cell Death Dis ; 10(12): 887, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767864

RESUMO

Chordoma is a malignant primary osseous spinal tumor with pronounced chemoresistance. However, the mechanisms of how chordoma cells develop chemoresistance are still not fully understood. Cytokeratin 8 (KRT8) is a molecular marker of notochordal cells, from which chordoma cells were believed to be originated. In this study, we showed that either doxorubicin or irinotecan promoted KRT8 expression in both CM319 and UCH1 cell lines, accompanied by an increased unfolded protein response and autophagy activity. Then, siRNA-mediated knockdown of KRT8 chemosensitized chordoma cells in vitro. Mechanistic studies showed that knockdown of KRT8 followed by chemotherapy aggravated endoplasmic reticulum stress through PERK/eIF2α arm of unfolded protein response and blocked late-stage autophagy. Moreover, suppression of the PERK/eIF2α arm of unfolded protein response using PERK inhibitor GSK2606414 partially rescued the apoptotic chordoma cells but did not reverse the blockage of the autophagy flux. Finally, tumor xenograft model further confirmed the chemosensitizing effects of siKRT8. This study represents the first systematic investigation into the role of KRT8 in chemoresistance of chordoma and our results highlight a possible strategy of targeting KRT8 to overcome chordoma chemoresistance.

16.
Opt Lett ; 44(23): 5848-5851, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774795

RESUMO

We demonstrate an effective method to obtain high-repetition-rate femtosecond mid-infrared (mid-IR) pulses by nonlinear optical modulation of mid-IR continuous-wave (CW) quantum and interband cascade lasers (ICLs and QCLs). In the experiment, a high-repetition-rate femtosecond ytterbium-doped fiber laser with nanojoule-level pulse energy was used as the pump source of optical parametric amplifiers to modulate and amplify the mid-IR CW laser. Near transform-limited 84 fs duration (7.3 cycles) mid-IR pulses were generated with above 200 mW average power and a repetition rate of 160 MHz. Moreover, the spectral tunability was demonstrated using CW QCL at different wavelengths. The scheme offered a simple method to produce high-repetition-rate ultrashort pulses and that can be flexibly adopted in other mid-IR regions.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31773539

RESUMO

As a recently discovered process of nitrogen cycling, anaerobic ammonium oxidation coupled to ferric iron reduction (Feammox) has attracted more attentions. This study investigated the spatial variation of Feammox in the sediment of different zones of a shallow freshwater lake and the effect of organic matter derived from algae and macrophyte on Feammox process. The potential Feammox rates showed significant differences among sediments from algae-dominated area (ADA), transitional area in the center of the lake (TDA), and macrophyte-dominated area (MDA), and in a descending order, ADA, MDA, and TDA. The potential Feammox rate ranged from 0.14 to 0.34 mg N kg-1day-1 in the freshwater lake sediment. The potential Feammox rates of the sediment with algae or macrophyte amendment were 12.29% and 15.31% higher than the control test without algae and macrophyte amendment. The addition of algae or macrophyte to the sediment from TDA could improve the amount of HCl-extractable total Fe, Fe(III) reduction rate, and the abundance of FeRB. These results demonstrated that organic matter is one of the key regulators of Feammox process.

18.
Hepatology ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774566

RESUMO

BACKGROUND: Interleukin-22 (IL-22) has beneficial effects on inflammation and impaired hepatic regeneration, that characterize AH. F-652 is a recombinant fusion protein of human IL-22 and IgG2-Fc. AIMS: To assess safety and efficacy signals of F-652 in patients with moderate and severe AH. METHODS: A phase-2 dose escalating study was carried out. F-652 (10, 30 or 45 µg/kg) administered on day-1 and 7 was tested in 3 patients each with moderate (MELD-scores:11-20) and severe AH (MELD-scores:21-28). Safety was defined by absence of serious adverse events (SAE) and efficacy was assessed by Lille score, changes in MELD score, and serum bilirubin and aminotransferases at days 28 and 42. Three independent propensity matched comparator patient cohorts were used. Plasma extracellular vesicles (EVs) and multiplex serum cytokines were measured to assess inflammation and hepatic regeneration. RESULTS: 18 patients (9 moderate and 9 severe AH) were enrolled, 66% male, mean age 48 years. The half-life of F-652 following the first dose was 61-85 hours. There were no SAE leading to discontinuation. MELD score, and serum aminotransferases decreased significantly at days 28 and 42 from baseline (p<0.05). Day-7 Lille score was ≤0.45 in 83% patients as compared with 6%,12%, and 56% among the comparator cohorts. EV counts decreased significantly at day-28 (p<0.013). Cytokine inflammatory markers were downregulated, and regeneration markers were upregulated at days 28 and 42. CONCLUSIONS: F-652 is safe in doses up to 45 µg/kg and associated with high rate of improvement as determined by Lille and MELD scores, reductions in markers of inflammation and increases in markers of hepatic regeneration. This study supports the need for randomized placebo-controlled trials to test efficacy of F-652 in AH.

19.
Sensors (Basel) ; 19(22)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703279

RESUMO

A medical electronic nose (e-nose) with 31 gas sensors is used for wound infection detection by analyzing the bacterial metabolites. In practical applications, the prediction accuracy drops dramatically when the prediction model established by laboratory data is directly used in human clinical samples. This is a key issue for medical e-nose which should be more worthy of attention. The host (carrier) of bacteria can be the culture solution, the animal wound, or the human wound. As well, the bacterial culture solution or animals (such as: mice, rabbits, etc.) obtained easily are usually used as experimental subjects to collect sufficient sensor array data to establish the robust predictive model, but it brings another serious interference problem at the same time. Different carriers have different background interferences, therefore the distribution of data collected under different carriers is different, which will make a certain impact on the recognition accuracy in the detection of human wound infection. This type of interference problem is called "transfer caused by different sample carriers". In this paper, a novel subspace alignment-based interference suppression (SAIS) method with domain correction capability is proposed to solve this interference problem. The subspace is the part of space whose dimension is smaller than the whole space, and it has some specific properties. In this method, first the subspaces of different data domains are gotten, and then one subspace is aligned to another subspace, thereby the problem of different distributions between two domains is solved. From experimental results, it can be found that the recognition accuracy of the infected rat samples increases from 29.18% (there is no interference suppression) to 82.55% (interference suppress by SAIS).

20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1073-1076, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703128

RESUMO

OBJECTIVE: To assess the association of single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) with refractory epilepsy in children. METHODS: Peripheral blood samples were collected from 200 children with epilepsy and 100 healthy controls. Genomic DNA was extracted and subjected to PCR amplification, agarose gel electrophoresis and target site sequencing. Genotypes of rs1922242, rs2235048, rs10808072, rs868755 and rs1202184 loci of the MDR1 gene were analyzed. RESULTS: No significant difference was found in genotypic distribution and allelic frequencies of the rs1922242, rs2235048, rs10808072 and rs868755 loci between the drug-resistant and drug-sensitive groups. For the rs1202184 locus, a significant difference in genotypic distribution was found (P=0.008). No significant difference was found in the frequencies of various haplotypes between the two groups. CONCLUSION: Genotypes of the rs1202184 locus of the MDR1 gene are associated with refractory epilepsy in children, for which the AA genotype plays a dominant role.


Assuntos
Epilepsia Resistente a Medicamentos/genética , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Estudos de Casos e Controles , Criança , Frequência do Gene , Genótipo , Haplótipos , Humanos
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