Publications by authors named "Xu Zhu"

287 Publications

Self-Powered Photoelectrochemical Aptasensor for Oxytetracycline Cathodic Detection Based on a Dual Z-Scheme WO/g-CN/MnO Photoanode.

Anal Chem 2021 07 21;93(26):9129-9138. Epub 2021 Jun 21.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, China.

With the high sensitivity and anti-interference provided by a dual Z-scheme structure photoanode and a two-electrode system, a high-performance self-powered photoelectrochemical (PEC) aptasensor for oxytetracycline (OTC) detection was established in this work. Graphitic carbon nitride (g-CN) with excellent photoelectric properties was used to be combined with WO and MnO to form a kind of dual Z-scheme heterojunction. The designed unique structure and the complementary performances of the three materials collectively guaranteed the highly stable photocurrent output of the photoanode due to the wide range of light absorption and the high separation rate of electron-hole pairs. The aptamer-based cathode modified with reduced graphene oxide (rGO) and Au nanoparticles (Au NPs) provided high conductivity and aptamer-binding sites, which brought excellent selective recognition of OTC as well as the self-powered capacity by receiving electrons from the photoanode. In the PEC sensing of OTC, the device presented a wide detection range from 1 pM to 150 nM and a low detection limit of 0.1 pM. Besides, the developed PEC aptasenor showed good selectivity, reproducibility, and stability, so as to be applied to real samples. The proposed PEC sensing method can be considered an effective and promising direction for the detection of antibiotics in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.1c00929DOI Listing
July 2021

Sociodemographic predictors and transportation patterns of COVID-19 infection and mortality.

J Public Health (Oxf) 2021 Jun 17. Epub 2021 Jun 17.

Corporate Finance, Northwell Health, Westbury NY 11590, USA.

Background: The United States Centers for Disease Control and Prevention (CDC)-sanctioned prevention strategies have included frequent handwashing with soap and water, covering the mouth and nose with a mask when around others, cleaning and disinfecting maintaining a distance of at least 6 feet from others, etc. Although many of these recommendations are based upon observation and past infection control practices, it is important to combine and explore public data sets to identify predictors of infection, morbidity and mortality to develop more finely honed interventions, based on sociodemographic factors.

Method: Cross-sectional study of both states in the US and counties in NY state.

Results: Population density was found to be significantly associated with state-level coronavirus infection and mortality rate (b = 0.49, 95% confidence interval (CI): 0.34, 0.64, P < .0001). States that have lower socioeconomic status, lower mean age and denser populations are associated with higher incidence rates. In regard to NY state, counties with a higher percentage of minority residents had higher COVID-19 mortality rates (b = 2.61, 95% CI: 0.36, 4.87, P = 0.023). Larger population cohorts were associated with lower COVID-19 mortality rates after adjusting for other variables in the model (b = -1.39, 95% CI: -2.07, -0.71, P < 0.001). Population density was not significantly associated with COVID-19 mortality rates after adjustment across counties in the NY state. Public ridership was not indicative of cases or mortality across states in the USA; however, it is a significant factor associated with incidence (but not mortality) in NY counties.

Conclusion: Population density was the only significant predictor of mortality across states in the USA. Lower mean age, lower median household incomes and more densely populated states were at higher risk of COVID-19 infection. Population density was not found to be a significant independent variable compared to minority status and socioeconomic factors in the New York epicenter. Meanwhile, public ridership was found to be a significant factor associated with incidence in New York counties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pubmed/fdab191DOI Listing
June 2021

Cartilage tissue miR-214-3p regulates the TrkB/ShcB pathway paracrine VEGF to promote endothelial cell migration and angiogenesis.

Bone 2021 10 6;151:116034. Epub 2021 Jun 6.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, China. Electronic address:

Background: This study was designed to explore the mechanisms through which chondrocytes regulated endothelial cell migration and angiogenesis in osteoarthritis (OA).

Methods: The expressions of related genes of OA were detected by Western blot and real-time quantitative PCR. Chondrocytes were co-cultured with endothelial cells, and migration as well as angiogenesis rates, and vascular endothelial growth factor (VEGF) secretion of the cells were detected. The relationship between miRNA and TrkB were analyzed by bioinformatics analysis, RNA immunoprecipitation and dual-luciferase assays. The effects of miRNA on the histopathology of the OA mice were determined.

Results: The expressions of NGF, TrkA, TrkB, and ShcB were increased significantly in OA patients. IL-1β promoted the expressions of TrkA, TrkB, and ShcB in chondrocytes and inhibited the expressions of chondrogenic differentiation markers, but shTrkB partially reversed IL-1β-mediated chondrogenic differentiation. Overexpression of TrkB promoted cell migration, angiogenesis, and VEGF levels, while silencing ShcB reversed the regulation of TrkB. Moreover, chondrocytes miR-214-3p regulated endothelial cell migration and angiogenesis by targeting TrkB paracrine VEGF to activate PI3K/Akt pathway proteins. In addition, overexpressed miR-214-3p improved collagenase-induced cartilage and synovial damage in OA mice.

Conclusion: The activation of TrkB/ShcB signaling pathway paracrine VEGF is mediated by miR-214-3p in chondrocytes and it regulates endothelial cell migration and angiogenesis in the development of OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2021.116034DOI Listing
October 2021

Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway.

J Nanobiotechnology 2021 Jun 6;19(1):170. Epub 2021 Jun 6.

Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.

Background: Inflammatory osteolysis after total joint replacement (TJR) may cause implant failure, periprosthetic fractures, and be a severe threat to global public health. Our previous studies demonstrated that melatonin had a therapeutic effect on wear-particles induced osteolysis. Gut microbiota is closely related to bone homeostasis, and has been proven to be affected by melatonin. However, whether melatonin could play its anti-osteolysis effects through reprogramming gut microbiota remains elusive.

Results: Here, we demonstrated that melatonin could alleviate Ti-particles induced osteolysis, while this therapeutic effect was blocked by antibiotic cocktail treatment. Interestingly, transplantation of fecal microbiota from mice treated with melatonin reappeared the same beneficial effect. Analysis of the 16S rRNA revealed that melatonin could reverse dysbacteriosis triggered by osteolysis, and elevate the relative abundance of some short chain fatty acid (SCFA) producing bacteria. Moreover, butyrate was enriched by exogenous melatonin administration, while acetate and propionate did not show an evident difference. This was consistent with the results of the metagenomic approach (PICRUSt2) analysis, which revealed a general increase in the synthetic enzymes of butyrate. More importantly, direct supplementation of butyrate could also recapitulate the anti-osteolysis effect of melatonin. Further analysis identified that butyrate alleviated osteolysis via activating its receptor GPR109A, and thus to suppress the activation of NLRP3 inflammasome triggered by Ti-particles.

Conclusions: Taken together, our results suggested that the benefits of melatonin mainly depend on the ability of modulating gut microbiota and regulating butyrate production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12951-021-00915-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182936PMC
June 2021

Reusable membrane with multifunctional skin layer for effective removal of insoluble emulsified oils and soluble dyes.

J Hazard Mater 2021 08 17;415:125677. Epub 2021 Mar 17.

State Key Laboratory of Heavy Oil Processing, School of Materials Science and Engineering, China University of Petroleum, Qingdao 266580, Shandong, PR China. Electronic address:

The organic pollutants, typical of emulsified oils and soluble organic dyes, is commonly found in wastewater, however simultaneous removal of them remains challenging because of their difference in surface charge, molecule size, and solubility in water. Inspired by the water purification of the earth's multilayer strata, a fibrous membrane with multifunctional skin is fabricated by coupling sub-micrometer pores layer of polyaniline (PANI) and nano molecular brush of polyacrylic acid (PAA)/polyethyleneimine (PEI) on polyacrylonitrile membrane, for cross-scale organic pollution/water separation. This ultrathin skin of PANI/PAA/PEI is endowed with sub-micrometer pores and strong hydration, which can effectively prevent tiny oil droplets from entering or adhering the membrane pores. Furthermore, this skin with double electric layer can selectively adsorb and even filtrate anionic/cationic dyes by protonation and deprotonation effect in different pH solutions. The synergy of these features enables this membrane with ultra-high water flux (>3000 L m h bar), oil rejection rates (>99.6%), and anionic/cationic dyes adsorbability (>49.1 mg/g). Besides, the membrane also exhibits desirable reusability, excellent mechanical durability and outstanding acid/alkali resistance, promising for removal of insoluble emulsified oils and soluble organic dyes in wastewater.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.125677DOI Listing
August 2021

PKD2 deficiency suppresses amino acid biosynthesis in ADPKD by impairing the PERK-TBL2-eIF2ɑ-ATF4 pathway.

Biochem Biophys Res Commun 2021 Jul 18;561:73-79. Epub 2021 May 18.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China. Electronic address:

Metabolic reprogramming is emerging as a key pathological contributor to the progression of autosomal dominant polycystic kidney disease (ADPKD), but the molecular mechanisms underlying dysregulated cellular metabolism remain elusive. Here we report that amino acid biosynthesis is reprogrammed in Pkd2-knockout mouse kidneys via a defective PERK-eIF2ɑ-ATF4 pathway. Transcriptomic analysis revealed that the amino acid biosynthesis pathways such as serine, arginine and cysteine were impaired, and associated critical enzymes were downregulated in Pkd2-knockout mouse kidneys. ATF4 and CHOP, transcription factors downstream of the endoplasmic reticulum (ER) stress sensor PERK, were identified as master regulators of these enzymes' expression. PKD2 deficiency impaired the expression of ATF4 and amino acid synthesis enzymes in RCTEC cells under ER stress. Mechanistically, as an ER-resident protein, PKD2 interacts with TBL2, which functions as an adaptor bridging eIF2ɑ to PERK. PKD2 depletion impaired the recruitment of eIF2ɑ to TBL2, thus impeding activation of the PERK-eIF2ɑ-ATF4 pathway and downstream amino acid biosynthesis. These findings illuminate a molecular mechanism linking the PKD2-mediated PERK-eIF2ɑ-ATF4 pathway and amino acid metabolic reprogramming in ADPKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.05.012DOI Listing
July 2021

Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

Lancet Gastroenterol Hepatol 2021 Jul 8;6(7):559-568. Epub 2021 May 8.

Department of Intervention, Fujian Cancer Hospital, Fuzhou, China.

Background: Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma.

Methods: AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov, NCT02329860.

Findings: Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand-foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators.

Interpretation: Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile.

Funding: Jiangsu Hengrui Medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2468-1253(21)00109-6DOI Listing
July 2021

Electrochemical aptasensor for 17β-estradiol using disposable laser scribed graphene electrodes.

Biosens Bioelectron 2021 Aug 28;185:113247. Epub 2021 Apr 28.

Polymer Biointerface Centre, School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand; MacDiarmid Institute for Advanced Materials and Nanotechnology, Victoria University of Wellington, PO Box 600, Wellington, New Zealand. Electronic address:

17β-Estradiol (E2), the strongest of the three major physiological estrogens in females, is an important factor in the female reproductive system. The abnormal level of E2 causes health issues, such as weak bones, urinary tract infections and even depression. Here, we present a novel, sensitive and selective, electrochemical aptasensor for detection of 17β-estradiol (E2). The E2 recognition aptamer was split into two fragments: the first fragment, functionalised with adamantane, is attached to poly(β-cyclodextrin) (poly(β-CD))-modified electrode surface through host-guest interactions between the adamantane and poly(β-CD). The second fragment, labelled with gold nanoparticles, forms the stem-loop structure with the first fragment only in the presence of E2. That specific recognition process triggers the change in the electrochemical signal (a change in the peak current from reduction of AuNPs), recorded by means of differential pulse voltammetry (DPV). The feasibility of the sensing design was firstly investigated on the commercially available glass carbon electrodes (GCE), with achieved a linear detection range of 1.0 × 10 to 1.0 × 10 M and a limit of detection (LoD) 0.7 fM. The sensing methodology was then translated onto single-use, disposable, laser-scribed graphene electrodes (LSGE) on a plastic substrate. The dynamic sensing range of E2 on LSGE was found to be 1.0 × 10 to 1.0 × 10 M, with a LoD of 63.1 fM, comparable to these of GCE. The successful translation of the developed E2 aptasensor from GCE to low-cost, disposable LSGE highlights a potential of this sensing platform in commercial, portable sensing detection systems for E2 and similar targets of biological interest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2021.113247DOI Listing
August 2021

Biochar-mediated reduction of m-nitrotoluene: Interaction between reduction of m-nitrotoluene and sequestration of contaminants.

Sci Total Environ 2021 Jun 8;773:145662. Epub 2021 Feb 8.

College of geographical Science, Ministry of Education Key Laboratory of Humid Subtropical Eco-geographical Process, Fujian Provincial Key Laboratory for Plant Eco-Physiology, Fujian Normal University, Fuzhou, Fujian 350007, China.

Biochar is a highly effective adsorbent for nitroaromatic compounds (NACs), and acts as an electron shuttle that mediates the reduction of NACs. Hence, when biochar is used to mediate NAC reduction, adsorption and reduction will occur simultaneously and affect each other. However, the effect of biochar-mediated NAC reduction on sorption remains unknown. Eight biochars with different physicochemical properties were used to adsorb m-nitrotoluene and mediate its reduction. The results showed that the adsorption of m-nitrotoluene onto the various biochars facilitated its reduction, whereas biochar-mediated reduction retarded and weakened contaminant adsorption, which increased the environmental risk posed by m-nitrotoluene. Nevertheless, biochars with a high graphitization degree and developed porosity not only had a great catalytic ability, but also significantly alleviated the negative effect of reduction on adsorption. This was ascribed to the π-π interaction and pore-filling effect, which played more important roles than the hydrophobic effect in adsorbing the reduction product (m-toluidine) onto the studied biochars during reduction. Furthermore, the methanol extraction results indicated that the eight biochars presented significantly stronger sequestration abilities for adsorbed m-toluidine than for adsorbed m-nitrotoluene. This resulted from the hydrogen bonding and the Lewis acid-base effect between m-toluidine and each biochar, which were absent for m-nitrotoluene. These results suggest that biochars with a high graphitization degree and developed porosity are applicable for mediating reduction-enhancing sequestration of NACs, which could be a novel strategy for NAC remediation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.145662DOI Listing
June 2021

Small molecule natural compound targets the NF-κB signaling and ameliorates the development of osteoarthritis.

J Cell Physiol 2021 Apr 19. Epub 2021 Apr 19.

Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.

Osteoarthritis (OA) is a multifactorial and chronic disease describing the destruction of cartilage that can lead to defects in the elderly. There is currently no practical strategy that can reverse the OA process. Here, we describe nepetin, a small natural compound with extracellular matrix (ECM) and inflammation regulating functions. In this study, we investigated the therapeutic effects of nepetin on interleukin-1β (IL-1β)-induced inflammation in mice chondrocyte and OA model. In chondrocytes, treatment with nepetin inhibited the overexpression of pro-inflammatory cytokines and mediators induced by IL-1β. Moreover, pretreatment or posttreatment with nepetin also reduced the ECM catabolism and enhanced the ECM anabolism. Mechanistically, nepetin suppressed NF-κB signaling pathway in IL-1β stimulated chondrocyte. Meanwhile, our molecular docking studies indicated nepetin had a powerful binding capacity to p65. Furthermore, nepetin showed a protective and therapeutic effect on the mouse OA model. To sum up, this study indicated nepetin had a new potential therapeutic option in OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.30392DOI Listing
April 2021

Eradication of specific donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance therapeutic values.

Cell Death Dis 2021 04 6;12(4):357. Epub 2021 Apr 6.

Stem Cell Translational Research Center, Tongji Hospital, Tongji University, School of Medicine, Shanghai, 200065, China.

Mesenchymal stem cells (MSCs) are one of the most widely clinically trialed stem cells, due to their abilities to differentiate into multiple cell lineages, to secrete regenerative/rejuvenative factors, and to modulate immune functions, among others. In this study, we analyzed human umbilical-cord-derived MSCs from 32 donors and revealed donor-dependent variations in two non-correlated properties, (1) cell proliferation, and (2) immune modulatory functions in vitro and in vivo, which might explain inconsistent clinical efficacies of MSCs. Through unbiased transcriptomic analyses, we discovered that IFN-γ and NF-κB signaling were positively associated with immune modulatory function of MSCs. Activation of these two pathways via IFN-γ and TNF-α treatment eradicated donor-dependent variations. Additional transcriptomic analyses revealed that treatment with these two factors, while having abolished donor-dependent variations in immune modulatory function, did not overall make different donor-derived MSCs the same at whole transcriptomic levels, demonstrating that the cells were still different in many other biological perspectives, and may not perform equally for therapeutic purposes other than immune modulation. Pre-selection or pre-treatment to eradicate MSC variations in a disease-treatment-specific manner would therefore be necessary to ensure clinical efficacies. Together this study provided novel insights into the quality control perspective of using different-donor-derived MSCs to treat inflammation-related clinical conditions and/or autoimmune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03644-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024246PMC
April 2021

Cobalt exposure in relation to cardiovascular disease in the United States general population.

Environ Sci Pollut Res Int 2021 Mar 31. Epub 2021 Mar 31.

Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, 210029, China.

Cobalt exposure has adverse health effects on the cardiovascular system in occupational and laboratory studies, but these effects have not been assessed in the general population. We aimed to determine whether serum cobalt levels had relationship with the prevalence of cardiovascular disease (CVD) in the general population. Using data from the National Health and Nutrition Examination Survey (NHANES) (2015-2016), we performed the cross-sectional study. We analyzed the baseline characteristics of 3389 participants (1623 men and 1766 women). Generalized linear models and restricted cubic spline plots curve were undertaken to elucidate the relationship. Stratified subgroup analysis was tested to exclude interaction between different variates and cobalt. Our results showed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the quartiles of cobalt were 0.94 (0.67, 1.30), 1.55 (1.15, 2.10), and 1.74 (1.28, 2.35) compared with lowest quartile. The restricted cubic spline curve also suggested nonlinear and positive association between cobalt and CVD (P for nonlinearity = 0.007). In summary, our cross-sectional results verify that higher cobalt levels are associated with a higher prevalence of cardiovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-13620-3DOI Listing
March 2021

Prognostic value of the modified model for end-stage liver disease (MELD) score including albumin in acute heart failure.

BMC Cardiovasc Disord 2021 Mar 9;21(1):128. Epub 2021 Mar 9.

Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Guangzhou Road 300, Nanjing, 210029, China.

Background: Liver and renal function evaluated by the model for end-stage liver disease (MELD) score, the MELD excluding the international normalized ratio (MELD_XI) score and the MELD including sodium (MELD_sodium) score have been considered predictors of adverse events for patients with acute heart failure (AHF). However, the prognostic value of the MELD including albumin (MELD_albumin) score in patients with AHF has not been assessed.

Methods: A total of 466 patients with AHF were prospectively evaluated. We compared the accuracy of the 4 MELD score formulas using the time-dependent receiver operating characteristic (ROC) curve and corresponding areas under the curve (AUC).

Results: During a median follow-up period of 34 months, 196 deaths occurred. In the fully adjusted Cox regression model, standardized hazard ratios with 95% confidence interval expressing the risk of all-cause mortality were 1.22 (1.06-1.40), 1.20 (1.04-1.39), 1.23 (1.06-1.42) and 1.21 (1.05-1.41) for MELD, MELD_XI, MELD_sodium and MELD_albumin scores, respectively. The MELD_albumin score showed the best prognostic accuracy (AUC = 0.658) for the prediction of long-term all-cause mortality, followed by the MELD_sodium score (AUC = 0.590), the MELD score (AUC = 0.580), and the MELD_XI score (AUC = 0.544); the MELD_albumin score performs significantly more accurate than MELD and MELD_XI score for predicting the risk of all-cause mortality. Considering reclassification, MELD_albumin score increased the net reclassification improvement over and beyond MELD (13.1%, P = 0.003), MELD_XI (14.8%, P = 0.002), and MELD_sodium (11.9%, P = 0.006) scores for all-cause mortality.

Conclusions: The MELD_albumin score increases risk stratification of all-cause mortality over and beyond the MELD score and the other modified MELD scores in patients with acute heart failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-021-01941-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941696PMC
March 2021

Association of acrylamide hemoglobin biomarkers with serum lipid levels in general US population: NHANES 2013-2016.

Ecotoxicol Environ Saf 2021 May 6;214:112111. Epub 2021 Mar 6.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing 210029, China. Electronic address:

The aim of present study was to investigate the association of acrylamide (AA) hemoglobin biomarkers and serum lipids level in a general population. Data set of our study were extracted from an open database - National Health and Nutrition Examination Surveys (NHANES) 2013-2016. In total 2899 participants were enrolled. The associations between AA hemoglobin parameters [hemoglobin adducts of AA (HbAA) and glycidamide (HbGA), total of HbAA and HbGA (HbAA+HbGA), and ratio of HbGA to HbAA (HbGA/HbAA)] and lipid levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C)] were analyzed. Generalized linear models and restricted cubic spline plots were conducted to address the relationship between lipid levels and acrylamide markers. Comparing the lowest quantiles, HbGA and HbGA/HbAA both remained a significant trend regardless of lipid types. Analyses using a generalized linear model with restricted cubic spline and validated with regression models, all 4 AA parameters demonstrated a linear association and positive correlation with TG. Furthermore, there were also opposite nonlinear association between HbGA/HbAA and LDL-C (positive correlation), and HbGA/HbAA and HDL-C (negative correlation). Further analysis with threshold effect analysis or regression analysis showed HbGA and HbGA/HbAA remained significant association with all TC, TG, LDL-C, and HDL-C. The hemoglobin adducts AA parameters as long-term exposure biomarkers are associated with the atherosclerotic lipid changes in a population of US adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.112111DOI Listing
May 2021

Removal of roosters alters the domestic phenotype and microbial and genetic profile of hens.

Sci China Life Sci 2021 Feb 4. Epub 2021 Feb 4.

Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding; School of Life Science and Engineering, Foshan University, Foshan, 528225, China.

Hens are raised apart from roosters in modern poultry production, a substantial change from their natural social structure. We compared productivity, injuries, behavior, physiology, microbiome and transcriptome of hens housed with (R+) or without (R-) roosters to quantify the effects of this change in social structure. Hens were raised free-range from 70 to 280 days when 30 birds per treatment were assigned to battery cages until Day 315 (R+C vs. R-C), while 30 birds per treatment remained in free-range pens (R+F vs. R-F). Response to a novel environment and object, behavioral time budgets, cecum microbiome, blood composition and transcriptomic sequencing of thigh muscle and spleen were analyzed. Hens housed without roosters showed better survival, consumed less food, produced more eggs and had better feed conversion. R+F hens clustered around the rooster and were less mobile in the novel environment and object tests. R+F hens displayed the richest microbiome, and the presence of roosters resulted in differentially expressed genes related to muscle development, cellular processes, environmental information processing and immune function. Removing roosters from housed hens intensified desirable characteristics favored by domestication probably operating by deprivation of mating behavior and reduced fear, along with altered microbial and genetic function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-020-1770-1DOI Listing
February 2021

Mental Health Literacy from the Perspective of Multi-Field Experts in the Context of Chinese Culture.

Int J Environ Res Public Health 2021 02 3;18(4). Epub 2021 Feb 3.

School of Psychology, Central China Normal University, Wuhan 430079, China.

The study aimed to explore the opinions of multi-field Chinese experts on mental health literacy and further build a comprehensive picture of mental health literacy based on these opinions. Semi-structured interviews were conducted with ten Chinese experts from the fields of psychiatry, clinical psychology, mental health education, and social work. A mixed deductive-inductive thematic analysis was used in the analysis of the qualitative data. The experts noted that mental health literacy applies both to persons with mental illness and the people who help them. The comprehensive view of mental health literacy that emerged from the interviews included knowledge about mental illness, an attitude of acceptance, respectful behavior, and recognition of the importance of getting help. Characteristically, Chinese components of mental health literacy included living in harmony with others and achieving balance in all aspects of life. To the best of our knowledge, this is the first qualitative study of experts' views of the concept of mental health literacy in the context of Chinese culture. The experts' responses to the interviews generated a comprehensive view of mental health literacy, including several elements that may be especially salient in Chinese culture. The results have implications for researchers and clinicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18041387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913242PMC
February 2021

Predictors of mortality in a multiracial urban cohort of persons with type 2 diabetes and novel coronavirus 19.

J Diabetes 2021 Jan 23. Epub 2021 Jan 23.

Center for Health Innovations and Outcomes Research, Northwell Health, Manhasset, New York, USA.

Background: Diabetes has been identified as a risk factor for intubation and mortality in patients with coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We seek to examine the impact of clinical variables such as glycosylated hemoglobin (HbA1c) on mortality and need for intubation, as well as demographic variables such as age, sex, and race on persons with type 2 diabetes and COVID-19.

Methods: Analyses were conducted on 4413 patients with an International Classification of Diseases and Related Health Problems (ICD-10) diagnosis of type 2 diabetes and COVID-19. Survival analysis was conducted using Kaplan-Meier curves and the log-rank test to compare subgroup analyses.

Results: In this multivariate analysis, male gender, older age, and hyperglycemia at admission were associated with increased mortality and intubation, but this was not seen for race, ethnicity, insurance type, or HbA1c. Based on Kaplan-Meier analysis, having comorbid conditions such as hypertension, chronic kidney disease, and coronary artery disease was associated with a statistically significant increased risk of mortality.

Conclusions: Glycemic levels at admission have a greater impact on health outcomes than HbA1c. Older men and those with comorbid disease are also at greater risk for mortality. Further longitudinal studies need to be done to evaluate the impact of COVID-19 on type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1753-0407.13158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013168PMC
January 2021

Optimization of Micafungin Dosage for Chinese Patients with Sepsis in the Intensive Care Unit Based on a Population Pharmacokinetic-Pharmacodynamic Analysis.

Pharm Res 2021 Jan 6;38(1):67-77. Epub 2021 Jan 6.

Department of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Purpose: This study aimed to identify parameters that influence micafungin pharmacokinetics in Chinese patients with sepsis in the intensive care unit and optimize micafungin dosage by determining the probability of reaching pharmacodynamic targets.

Methods: Blood samples were collected from 32 Chinese patients with sepsis who were treated with micafungin. The samples were analyzed and used to build a population pharmacokinetic model. Monte Carlo simulations were performed to estimate the probability of achieving adequate plasma levels of micafungin against Candida species.

Results: Alanine aminotransferase and sequential organ failure assessment score were found to significantly influence the clearance and peripheral distribution volume of micafungin, respectively. Monte Carlo simulations based on area under the plasma concentration-time curve over 24 h showed that patients must be administered at least 200 and 250 mg micafungin daily to reach minimum inhibitory concentration breakpoints of 0.032 and 0.064 mg/L for Candida glabrata and Candida tropicalis, respectively. Additionally, a probability of target attainment of ≥ 90% could not be achieved for Candida krusei or Candida parapsilosis with a 300 mg daily dose.

Conclusions: The recommended daily dose of micafungin (100 mg) may produce low clinical success ratios in non-Candida albicans infections; therefore, higher doses should be administered to improve clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-020-02980-zDOI Listing
January 2021

Synthesis and characterization of CD133 targeted aptamer-drug conjugates for precision therapy of anaplastic thyroid cancer.

Biomater Sci 2021 Feb;9(4):1313-1324

Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China. and Department of Public Health, and Department of Hematology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China and Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 311121, China.

Anaplastic thyroid cancer (ATC) is an undifferentiated and highly aggressive type of thyroid cancer and is extremely resistant to standard therapies such as surgical resection and radioactive iodine therapy. Although targeted therapeutic agents including small molecule drugs and monoclonal antibodies are rapidly developed in recent years, no ATC targeted drugs are available to date; thereby, novel targeted therapies are needed to improve the outcomes of ATC patients. Aptamers are single-stranded DNA (or RNA) molecules that can selectively bind to cancer specific antigens, and aptamer-based targeted therapy has certain advantages over that based on antibodies due to its high binding affinity and low immunogenicity. Here, we identified that CD133, a cancer stem cell marker, was specifically expressed in ATC tumor tissues and cells, implying that CD133 is a potential drug target for ATC therapy. Additionally, we successfully obtained a CD133 targeted aptamer AP-1 by paired cell-based SELEX, which can precisely recognize CD133 antigen in vitro. Furthermore, the truncated AP-1-M aptamer from its precursor AP-1 has shown higher binding affinity for CD133, and specifically accumulated in anaplastic thyroid cancer FRO cell derived tumor in vivo. Conjugation of truncated AP-1-M with doxorubicin could dramatically inhibit CD133 positive FRO cell proliferation, induce cell apoptosis in vitro, and also suppress tumor growth in FRO cell xenograft mice in vivo. Our results clearly demonstrated that the CD133 targeted aptamer AP-1-M conjugated with anticancer drugs has potential to become a promising therapeutic approach against ATC in the near future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0bm01832eDOI Listing
February 2021

COPII genes SEC31A/B are essential for gametogenesis and interchangeable in pollen development in Arabidopsis.

Plant J 2021 03 1;105(6):1600-1614. Epub 2021 Feb 1.

Hebei Key Laboratory of Molecular and Cellular Biology, College of Life Science, Hebei Normal University, Shijia Zhuang, Hebei, 050024, P.R. China.

In eukaryotes, coat protein complex II (COPII) vesicles mediate anterograde traffic from the endoplasmic reticulum to the Golgi apparatus. Compared to yeasts, plants have multiple COPII coat proteins; however, the functional diversity among them is less well understood. SEC31A and SEC31B are outer coat proteins found in COPII vesicles in Arabidopsis. In this study, we explored the function of SEC31A and compared it with that of SEC31B from various perspectives. SEC31A was widely expressed, but at a significantly lower level than SEC31B. SEC31A-mCherry and SEC31B-GFP exhibited a high co-localization rate in pollen, but a lower rate in growing pollen tubes. The sec31a single mutant exhibited normal growth. SEC31A expression driven by the SEC31B promoter rescued the pollen abortion and infertility observed in sec31b. A sec31asec31b double mutant was unavailable due to lethality of the sec31asec31b gametophyte. Transmission electron microscopy revealed that one quarter of male gametogenesis was arrested at the uninuclear microspore stage, while confocal laser scanning microscopy showed that 1/4 female gametophyte development was suspended at the functional megaspore stage in sec31a-1/+sec31b-3/+ plants. Our study highlights the essential role of SEC31A/B in gametogenesis and their interchangeable functions in pollen development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tpj.15136DOI Listing
March 2021

Chimeric Antigen Receptor T Cell Therapies: A Review of Cellular Kinetic-Pharmacodynamic Modeling Approaches.

J Clin Pharmacol 2020 10;60 Suppl 1:S147-S159

Pharmacometrics, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA.

Chimeric antigen receptor T cell (CAR-T cell) therapies have shown significant efficacy in CD19+ leukemias and lymphomas. There remain many challenges and questions for improving next-generation CAR-T cell therapies, and mathematical modeling of CAR-T cells may play a role in supporting further development. In this review, we introduce a mathematical modeling taxonomy for a set of relatively simple cellular kinetic-pharmacodynamic models that describe the in vivo dynamics of CAR-T cell and their interactions with cancer cells. We then discuss potential extensions of this model to include target binding, tumor distribution, cytokine-release syndrome, immunophenotype differentiation, and genotypic heterogeneity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcph.1691DOI Listing
October 2020

Dual-functional membrane decorated with flower-like metal-organic frameworks for highly efficient removal of insoluble emulsified oils and soluble dyes.

J Hazard Mater 2021 Apr 2;408:124444. Epub 2020 Nov 2.

State Key Laboratory of Heavy Oil Processing, School of Materials Science and Engineering, China University of Petroleum, Qingdao 266580, Shandong, PR China. Electronic address:

High-performance membranes for simultaneously removing insoluble emulsified oils and soluble organic dyes are in urgently demand for industrial wastewater treatment, but are strictly limited by the single-function and serious fouling problem. Herein, a dual-functional membrane with excellent antifouling ability for efficiently dye/oil/water emulsion separation has been fabricated by growing flower-like metal-organic frameworks (MIL-53-OH) on polyacrylonitrile/polyethyleneimine membrane for the first time. The synergistic effect of the hierarchical flower-like structure and superhydrophilic compositions with high hydration ability endows the obtained membrane with a stable and ultra-strong oil-repelling hydration layer, thus imparting the membrane formidable oil resistance and exceptional oil/water emulsion separation performance (permeate flux>4000 L m h). What's more, the superhydrophilic compositions render the membrane an excellent dye remove capacity by electrostatic forces and hydrogen bonding. The membrane rejections for dyes and emulsified oils are above 99%, and the dyes and oils on the used membrane can be easily washed away with methanol and water, respectively, confirming that the membrane has desirable recyclability. Besides, the membrane possesses excellent mechanical performance and outstanding acid and alkali resistance, indicating that the membrane is a promising candidate for removing insoluble emulsified oils and soluble dyes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2020.124444DOI Listing
April 2021

Prognostic value of integrative analysis of electrical and mechanical dyssynchrony in patients with acute heart failure.

J Nucl Cardiol 2021 02 4;28(1):140-149. Epub 2020 Nov 4.

College of Computing, Michigan Technological University, Houghton, MI, USA.

Background: Left ventricular mechanical dyssynchrony has been shown to provide significant clinical values for chronic heart failure (HF) and cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate whether electrical dyssynchrony combined with mechanical dyssynchrony has an incremental benefit over electrical dyssynchrony or mechanical dyssynchrony alone to predict clinical events in patients with acute heart failure (AHF).

Methods: Ninety-six AHF patients who received standard 12-lead ECG, gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and echocardiography were enrolled. Thirty-two normal subjects were collected as the control group to get the normal database of mechanical dyssynchrony. The end point is the composite of all-cause death and heart transplantation. Electrical dyssynchrony was defined as QRS duration > 120 ms. Mechanical dyssynchrony was defined as > mean + 2 × SD phase standard deviation (PSD) or phase bandwidth (PBW) based on our normal database.

Results: During the follow-up of 28 ± 10 months, complete data were obtained in 92 patients. 26 (28.3%) Patients who reached the end point were classified into the event group. There were no significant differences in PSD or PBW between the event and non-event groups. However, PBW > 77.76° was independently associated with the end point in the univariate and multivariate analysis (hazard ratio 2.92, 95% confidence interval 1.00-8.47, P = .049; hazard ratio 3.89, 95% confidence interval 1.01-14.97, P = .048). The Kaplan-Meier curve with a log-rank test showed that the end point rate was significantly higher in the patients with PBW > 77.76° (log-rank P = .039). Moreover, the ROC curve analysis showed that the area under the curve (AUC) for predicting end point events by the integrative analysis of QRS > 120 ms and PBW > 77.76° was significantly improved compared to QRS duration > 120 ms (AUC: 0.75 vs 0.68, P = .001) or PBW > 77.76° (AUC: 0.75 vs 0.62, P = .049), respectively. The model of combined electrical and mechanical dyssynchrony yielded a further significantly improved risk prediction for adverse events in the global χ.

Conclusions: The combination of QRS duration > 120 ms and PBW > 77.76° was an independent predictor of all-cause death and heart transplantation in AHF patients. The integrative analysis of electrical and mechanical dyssynchrony provides incremental prognostic value for clinical use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12350-020-02429-1DOI Listing
February 2021

Electrochemical oxidation of aniline using Ti/RuO-SnO and Ti/RuO-IrO as anode.

Chemosphere 2021 Apr 25;269:128734. Epub 2020 Oct 25.

School of Water Resources and Environment, China University of Geosciences (Beijing), No.29 Xueyuan Road, Haidian District, Beijing, 100083, China.

Electrocatalytic properties of anode and the electrolyte composition are important parameters influence the degradation efficiency for aniline wastewater. Ti/RuO-SnO and Ti/RuO-IrO have been fabricated using thermal decomposition method and experiments in electrolyte containing 0.05 M NaSO, 0.05 M NaCl and 0.05 M NaSO+0.005 M FeSO at different current density were conducted to study the influence on aniline degradation. Linear sweep voltammetry (LSV) showed that Ti/RuO-SnO had higher oxygen evolution potential and degrade aniline through electrochemical transformation and electrochemical combustion while Ti/RuO-IrO degrade aniline mainly through electrochemical transformation. The study showed that Ti/RuO-SnO had higher electrocatalytic activity towards the degradation of aniline than Ti/RuO-IrO anode in 0.05 M NaSO and in 0.05 M NaCl electrolyte. The maximum TOC removal efficiency for Ti/RuO-SnO was 64.2% at 40 mA cm in NaSO electrolyte while the average MCE was 1.6% and the average EC was 1.51 kWh (g TOC). On the contrary, the maximum TOC removal efficiency for Ti/RuO-IrO was 63.1% at 40 mA cm in NaCl electrolyte while the average MCE was 1.6% and the average EC was 1.95 kWh (g TOC). The presence of Fe in NaSO electrolyte would decrease the TOC removal efficiency except at low current density (20 mA cm) for Ti/RuO-SnO. These results indicated that Ti/RuO-SnO and Ti/RuO-IrO anode were suitable in NaSO and NaCl electrolyte, respectively, while the presence of Fe would inhibit aniline degradation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.128734DOI Listing
April 2021

Blood Urea Nitrogen to Creatinine Ratio and Long-Term Mortality in Patients with Acute Heart Failure: A Prospective Cohort Study and Meta-Analysis.

Cardiorenal Med 2020 28;10(6):415-428. Epub 2020 Oct 28.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China,

Objective: To further explore the relationship between the blood urea nitrogen to creatinine (BUN/Cr) ratio and the prognosis of patients with acute heart failure (AHF), a two-part study consisting of a prospective cohort study and meta-analysis were conducted.

Methods: A total of 509 hospitalized patients with AHF were enrolled and followed up. Cox proportional hazards regression was used to analyze the relationship between the BUN/Cr ratio and the long-term prognosis of patients with AHF. Meta-analysis was also conducted regarding the topic by searching PubMed and Embase for relevant studies published up to October 2019.

Results: During a median follow-up of 2.8 years, 197 (42.6%) deaths occurred. The cumulative survival rate of patients with a BUN/Cr ratio in the bottom quartile was significantly lower than in the other 3 groups (log-rank test: p = 0.003). In multivariate Cox regression models, the mortality rate of AHF patients with a BUN/Cr ratio in the bottom quartile was significantly higher than in the top quartile (adjusted HR 1.52; 95% CI 1.03-2.24). For the meta-analysis, we included 8 studies with 4,700 patients, consisting of 7 studies from the database and our cohort study. The pooled analysis showed that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (pooled HR 1.77; 95% CI 1.52-2.07).

Conclusions: Elevated BUN/Cr ratio is associated with poor prognosis in patients with AFH and is an independent predictor of all-cause mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509834DOI Listing
October 2020

Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Gallbladder Cancer.

Cardiovasc Intervent Radiol 2021 Feb 19;44(2):271-280. Epub 2020 Oct 19.

Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China.

Purpose: The aim of this study was to assess the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil for patients with advanced gallbladder cancer (GBC).

Materials And Methods: Twenty-six patients with advanced GBC, who underwent HAIC with oxaliplatin and 5-fluorouracil from January 2012 to July 2019, were enrolled in this retrospective study. The HAIC regimen consisted of infusions of oxaliplatin at 40 mg/m for 2 h, followed by 5-fluorouracil at 800 mg/m for 22 h on days 1-3 every 3-4 weeks. A maximum of six cycles of HAIC were applied for tumor control patients followed by maintenance with oral capecitabine or S-1. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were investigated.

Results: Six of the 26 patients (23.1%) had failed systemic chemotherapy, 8/26 (30.8%) patients had failed various local therapies, and 9/26 (34.6%) patients had contraindications to systemic chemotherapy. The median OS was 13.5 months, and the median PFS was 10.0 months. The overall response rate was 69.2% (18/26), and disease control rate was 92.3% (24/26). Carcinoembryonic antigen (CEA) ≥ 10 U/ml (p = 0.003) and carbohydrate antigen 19-9 (CA19-9) ≥ 200 U/ml (p = 0.000) were independent risk factors for decreased survival. The most frequent Grade 3 or 4 treatment-related adverse event was liver dysfunction (4, 15.4%).

Conclusion: HAIC with oxaliplatin and 5-fluorouracil is an acceptable and well-tolerated treatment for advanced gallbladder cancer even for patients in whom systemic chemotherapy had failed or is contraindicated.

Level Of Evidence: Level 2, Observation Study with Dramatic Effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00270-020-02661-9DOI Listing
February 2021

γ-Glutamyltranspeptidase as a Prognostic Biomarker in Advanced Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

J Vasc Interv Radiol 2021 03 14;32(3):419-428.e2. Epub 2020 Oct 14.

Department of Interventional therapy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, China. Electronic address:

Purpose: To evaluate the prognostic value of pretreatment serum γ-glutamyltransferase (GGT) level in patients with advanced hepatocellular carcinoma (HCC) receiving transarterial chemoembolization.

Materials And Methods: This retrospective study included 140 patients (123 male, 17 female; mean age, 56.9 y ± 12.0; range, 22.0-82.0 y) with Barcelona Clinic Liver Cancer class C HCC who received first-line conventional chemoembolization between December 2013 and March 2018. Patients were divided into low and high GGT groups based on a cutoff value calculated with a receiver operating characteristic curve. Overall survival (OS) was compared between groups by log-rank test. Univariate and multivariate survival analyses were performed.

Results: The optimal cutoff values of GGT were 119.5 U/L in men and 175.0 U/L in women. The 6-, 9-, and 12-mo OS rates were 81.7%, 72.4%, and 62.9%, respectively, for patients in the low GGT group (n = 44) and 58.8%, 35.7%, and 28.8%, respectively, for patients in the high GGT group (n = 96; P < .001). Multivariable Cox regression analysis identified high pretreatment serum GGT level (hazard ratio [HR], 2.71; 95% confidence interval [CI], 1.67-4.40; P < .001), multiple tumors (HR, 3.05; 95% CI, 1.23-7.53; P = .02), and performance of target treatment (ie, sorafenib; HR, 0.41; 95% CI, 0.24-0.72; P = .002) or ablation (HR, 0.35; 95% CI, 0.18-0.66; P = .001) as independent prognostic factors for OS.

Conclusions: Pretreatment serum GGT level was an independent prognostic factor for OS in patients with advanced HCC treated with chemoembolization, suggesting that GGT is a useful prognostic biomarker for advanced HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvir.2020.07.020DOI Listing
March 2021

MicroRNA-613 alleviates IL-1β-induced injury in chondrogenic CHON-001 cells by targeting fibronectin 1.

Am J Transl Res 2020 15;12(9):5308-5319. Epub 2020 Sep 15.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan, P. R. China.

Background: Osteoarthritis (OA) is an aging-related chronic degenerative joint disease. A number of miRNAs have been found to be involved in the development of OA, but the role of miR-613 in OA remains unclear. Thus, this study aimed to investigate the role of miR-613 during the progression of OA.

Methods: CHON-001 cells were transfected with miR-613 agonist for 48 h, and then exposed to 10 ng/mL IL-1β for 24 h. Cell viability, cell proliferation and cell apoptosis in CHON-001 cells were assessed by CCK-8, immunofluorescence, and flow cytometry assays, respectively. In addition, the dual luciferase reporter system assay was used to determine the interaction of miR-613 and fibronectin 1 in CHON-001 cells.

Results: The level of miR-613 was significantly decreased in IL-1β-treated CHON-001 cells. Overexpression of miR-613 markedly inhibited IL-1β-induced apoptosis in CHON-001 cells. In addition, upregulation of miR-613 obviously alleviated IL-1β-induced inflammatory response and cartilage matrix degradation in CHON-001 cells. Meanwhile, fibronectin 1 was identified as a direct binding target of miR-613 in CHON-001 cells. Overexpression of miR-613 alleviated IL-1β-induced injury in CHON-001 cells via downregulating the expression of fibronectin 1. Furthermore, overexpression of miR-613 alleviated cartilage degradation, and reduced OARSI scores and subchondral bone thickness in a mouse model of OA.

Conclusion: Our data indicated that overexpression of miR-613 could inhibit IL-1β-induced injury in CHON-001 cells via decreasing the level fibronectin 1 , and alleviate the symptoms of OA . Therefore, miR-613 might be a potential therapeutic option for the treatment of OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540165PMC
September 2020

LncRNA NEAT1 regulates chondrocyte proliferation and apoptosis via targeting miR-543/PLA2G4A axis.

Hum Cell 2021 Jan 10;34(1):60-75. Epub 2020 Oct 10.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No.1, East Jianshe Road, Zhengzhou, 450000, Henan Province, China.

Osteoarthritis (OA), which is characterized by articular cartilage degeneration, shows a gradually increasing incidence with age. This study explored the molecular mechanism underlying the proliferation and apoptosis of chondrocytes during OA progression. In this study, chondrocytes were isolated from human knee cartilages. The targeted relationship among nuclear enriched abundant transcript 1 (NEAT1), microRNA-543 (miR-543) and PLA2G4A was predicted on TargetScan V7.2 and starBase and validated by performing dual-luciferase reporter assay. High-expressed NEAT1 was detected in OA cartilage and chondrocytes. NEAT1 was negatively correlated with miR-543 and was low-expressed in OA cartilage and PLA2G4A was negatively correlated with miR-543 and was high-expressed in OA cartilage. In OA chondrocytes, the overexpressed NEAT1 inhibited the expressions of p-Akt1 and Bcl-2 and upregulated that of matrix metalloprotease (MMP)-3, MMP-9, MMP-13, interleukin (IL)-6 and IL-8, but such effects of overexpressed NEAT1 were reversed by miR-543 mimic. SiRNA-NEAT1 exerted an opposite effect to NEAT1 overexpression on OA chondrocytes, but this could be reversed by miR-543 inhibitor. The effect of PLA2G4A overexpression was the opposite to miR-543 mimic on OA chondrocytes. In conclusion, NEAT1 could sponge miR-543 to induce PLA2G4A expression, inhibit chondrocyte proliferation and promote apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13577-020-00433-8DOI Listing
January 2021

DLX6-AS1 accelerates cell proliferation through regulating miR-497-5p/SNCG pathway in prostate cancer.

Environ Toxicol 2021 Mar 9;36(3):308-319. Epub 2020 Oct 9.

Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Prostate cancer (PCa) has become the second leading cause of cancer-related mortality in males worldwide. Although the long noncoding RNA DLX6-AS1 has been recognized to be an oncogene in multiple cancers, the biological function and regulatory mechanism of DLX6-AS1 in prostate cancer are still obscure. In the present study, we observed that DLX6-AS1 was significantly upregulated in PCa tissues and cells. Knockdown of DLX6-AS1 inhibited PCa progression by suppressing cell proliferation and accelerating cell apoptosis. Molecular mechanism exploration indicated that DLX6-AS1 acted as a sponge for miR-497-5p and synuclein gamma (SNCG) was a downstream target gene of miR-497-5p. In addition, there was a negative correlation between DLX6-AS1 and miR-497-5p in PCa tissues. Rescue assays showed that SNCG overexpression could partially recover DLX6-AS1 knockdown-mediated inhibition of progression in PCa. Furthermore, xenograft tumor model was established to determine the role of DLX6-AS1 in PCa tumor growth and the results suggested that DLX6-AS1 could facilitate tumor growth by regulating SNCG in vivo. In conclusion, our study investigated the biological function and underlying mechanism of DLX6-AS1 in PCa and validated that DLX6-AS1 functioned as an oncogene through miR-497-5p/SNCG axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/tox.23036DOI Listing
March 2021
-->