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1.
Article in English | MEDLINE | ID: mdl-38551432

ABSTRACT

Objective: This study aims to comprehensively evaluate the diagnostic implications of white blood cell (WBC) count, serum C-reactive protein (CRP), and procalcitonin (PCT) in neonatal pneumonia. Methods: A cross-sectional study design was employed, and a total of 30 neonates diagnosed with pneumonia were recruited from Shenzhen Longgang Central Hospital between March 2020 and March 2021. Patients were categorized into three groups: bacterial infection, viral infection, and mycoplasma infection, with 30 cases in each group. Additionally, 30 healthy neonates with normal physical indicators were included as controls. The study assessed WBC counts, serum CRP, and PCT levels. Diagnostic efficiency was investigated, including concentration alterations, sensitivity, and specificity. Results: Infections resulted in a substantial increase in WBC counts and serum concentrations of CRP and PCT. Bacterial infections displayed the most notable alterations, followed by viral and mycoplasma infections (P < .05). Stand-alone PCT testing exhibited superior diagnostic efficiency, followed by WBC and CRP, as evidenced by heightened sensitivity and specificity (P < .05). However, the disparity in diagnostic efficiency between WBC and CRP alone did not attain statistical significance (P > .05). The WBC, CRP, and PCT hybrid assay demonstrated markedly superior sensitivity and specificity compared to stand-alone tests (P < .05). Conclusions: The combined detection of WBC, CRP, and PCT yields a superior diagnostic outcome for neonatal pneumonia compared to individual tests. This approach enhances the potential for early interventions and contributes significantly to improving patient prognosis. The findings underscore the importance of adopting a multi-marker approach in diagnosing neonatal pneumonia.

2.
J Environ Manage ; 344: 118659, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37478721

ABSTRACT

The aims of this study were to use metagenomics to reveal the fates of antibiotic resistance genes (ARGs) during composting under the regulation of peroxydisulfate and clarify the relationship between ARGs and cell membrane permeability. Results showed that peroxydisulfate increased cell membrane permeability by effectively regulating the expression of outer membrane protein and lipopolysaccharide related genes. Besides, it reduced polysaccharides and proteins in extracellular polymer substances by 36% and 58%, respectively, making it easier for intracellular ARGs (i-ARGs) to reach the extracellular environment, among which the absolute intracellular abundance of mphK, Erm(31), and tet(44) decreased to 1.2, 1.0, and 0.89 fold of the control, respectively. Finally, variation partitioning analysis showed that i-ARGs dominated the removal of ARGs. These results revealed that the removal of i-ARGs by activated peroxydisulfate was the key to the removal of ARGs and increased cell membrane permeability played a key role for peroxydisulfate to remove i-ARGs during composting.


Subject(s)
Anti-Bacterial Agents , Composting , Anti-Bacterial Agents/pharmacology , Genes, Bacterial , Cell Membrane Permeability , Manure , Drug Resistance, Microbial/genetics
3.
J Environ Manage ; 334: 117509, 2023 May 15.
Article in English | MEDLINE | ID: mdl-36801799

ABSTRACT

In this study, the amendment of biochar-activated peroxydisulfate during composting to remove antibiotic resistance genes (ARGs) by direct (microbial community succession) and indirect methods (physicochemical factors) was analyzed. When implementing indirect methods, the synergistic effect of peroxydisulfate with biochar optimized the physicochemical habitat of compost, maintaining its moisture within a range of 62.95%-65.71%, and a pH of 6.87-7.73, and causing the compost to mature 18 days earlier than the control groups. The direct methods caused the optimized physicochemical habitat to adjust the microbial communities and reduce the abundance of most of the ARG host bacteria (Thermopolyspora, Thermobifida, and Saccharomonospora), thus inhibiting this substance's amplification. Heatmap analysis confirmed the necessary connection between physicochemical factors, microbial communities, and ARGs. Moreover, a mantel test confirmed the direct significant effect of the microbial communities on ARGs and the indirect significant effect of physicochemical factors on ARGs. The results showed that the abundance of more ARGs was down-regulated at the end of composting and regulated by biochar-activated peroxydisulfate, especially for the abundance of AbaF, tet(44), golS, and mryA, which was significantly decreased by 0.87-1.07 fold. These results provide new insights into the removal of ARGs during composting.


Subject(s)
Composting , Genes, Bacterial , Composting/methods , Anti-Bacterial Agents/pharmacology , Manure/microbiology , Drug Resistance, Microbial/genetics
4.
J Environ Manage ; 308: 114682, 2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35144065

ABSTRACT

This study investigated the effects of biochar-based solid acids (SAs) on carbon conversion, alpha diversity and bacterial community succession during cow manure composting with the goal of providing a new strategy for rapid carbon conversion during composting. The addition of SA prolonged the thermophilic phase and accelerated the degradation of lignocellulose; in particular, the degradation time of cellulose was shortened by 50% and the humus content was increased by 22.56% compared with the control group (CK). In addition, high-throughput sequencing results showed that SA improved the alpha diversity and the relative abundance of thermophilic bacteria, mainly Actinobacteria, increased by 12.955% compared with CK. A redundancy analysis (RDA) showed that Actinobacteria was positively correlated with the transformation of carbon.


Subject(s)
Composting , Animals , Bacteria/genetics , Carbon , Cattle , Charcoal , Female , Manure/microbiology , Soil
5.
Biomed Chromatogr ; 32(11): e4345, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30030850

ABSTRACT

A rapid, sensitive and enantioselective method was developed and fully validated for the separation and determination of lansoprazole enantiomers in rat plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analytes and the internal standard (esomeprazole) were both extracted from plasma samples by liquid-liquid extraction with diethyl ether-dichloromethane (70:30; v/v). Satisfactory resolution (Rs = 2.0) was achieved within 7.3 min on a Chiralpak ID column (250 × 4.6 mm, 5 µm) employing acetonitrile-water (60:40, v/v) as the mobile phase at a flow rate of 0.6 mL/min. The acquisition of mass spectrometric data was performed in the multiple reaction monitoring mode coupled with a positive electrospray ionization source. A comprehensive validation of this method was rigorously conducted over the concentration range of 1.00-500.0 ng/mL for both enantiomers. All of the validation data demonstrated that the desirable linearity, sensitivity, accuracy, precision, recovery and stability were attained from the proposed approach. The established method was successfully applied to a stereoselective pharmacokinetic study of lansoprazole enantiomers in rat plasma after oral administration of 3 mg/kg racemic lansoprazole or dexlansoprazole. No chiral inversion was observed during the experimental procedure.


Subject(s)
Chromatography, Liquid/methods , Lansoprazole/blood , Lansoprazole/pharmacokinetics , Tandem Mass Spectrometry/methods , Animals , Linear Models , Male , Rats , Rats, Wistar , Reproducibility of Results , Sensitivity and Specificity , Stereoisomerism
6.
J Sep Sci ; 40(14): 2999-3007, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28544353

ABSTRACT

Chiral separation of 12 pairs of basic analyte enantiomers including oxybutynin, bambuterol, tradinterol, clenbuterol, clorprenaline, terbutaline, tulobuterol, citalopram, phencynonate, fexofenadine, salbutamol, and penehyclidine was conducted by capillary electrophoresis using a single-isomer anionic ß-cyclodextrin derivative, heptakis-(2,3-diacetyl-6-sulfato)-ß-cyclodextrin as the chiral selector. Parameters influencing separation were studied, including background electrolyte pH, heptakis-(2,3-diacetyl-6-sulfato)-ß-cyclodextrin concentration, buffer concentration, and separation voltage. A background electrolyte consisting of 50 mM Tris-H3 PO4 and 6 mM heptakis-(2,3-diacetyl-6-sulfato)-ß-cyclodextrin at pH 2.5 was found to be highly efficient for the separation of most enantiomers, with other conditions of normal polarity mode at 10 kV, detection wavelength of 210 nm using hydrodynamic injection for 3 s. Under the optimal conditions, baseline resolution (>1.50) for 11 pairs of enantiomers and somewhat lower resolution for penehyclidine enantiomers (1.17) were generated. Moreover, the possible mechanism of separation of clenbuterol, oxybutynin, salbutamol, and penehyclidine was investigated using a computational modeling method.


Subject(s)
Cyclodextrins , Pharmaceutical Preparations/isolation & purification , Buffers , Diacetyl , Electrophoresis, Capillary , Hydrogen-Ion Concentration , Stereoisomerism , beta-Cyclodextrins
7.
Onco Targets Ther ; 17: 545-556, 2024.
Article in English | MEDLINE | ID: mdl-39006885

ABSTRACT

Recently, bispecific antibodies (BsAbs) are evolving the landscape of cancer treatment and have significantly improved the outcomes of relapsed or refractory cancer patients. As increasing BsAbs entered clinical practice, specific toxicities have emerged, and renal side-effects have been described. However, there are a lack of studies analyzing the nephrotoxicity in the anti-cancer BsAbs recipients systematically. In this review, we demonstrate the etiologies, mechanisms, other risk factors and treatment options of kidney injury in the BsAbs recipients to provide a more comprehensive insight into the nephrotoxicity post-BsAbs therapy. Significantly, due to the limited clinical trial data on each subject, we mainly conclude the related etiologies, mechanisms, and risk factors of nephrotoxicity that occur in T-cell-engaging BsAbs recipients. Nephrotoxicity associated with non-T-cell BsAbs may be associated with adverse nephrotoxicity of related monoclonal antibodies to two specific antigens. The aim of this paper is to provide nephrologists and oncologists with theoretical knowledge to provide better medical management for recipients who receive BsAbs, especially T-cell-engaging BsAbs treatment.

8.
Int Urol Nephrol ; 56(6): 2021-2030, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38180581

ABSTRACT

PURPOSE: Gut microbiota transplantation has been reported to improve the renal function of membranous nephropathy (MN). However, whether there is a causal effect of gut microbiota on MN remained unclear. METHODS: We performed two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used as the main approach to evaluate the causal relationship between gut microbiota and MN. Additional methods including MR-Egger regression, weighted median, and MR-weighted mode were also conducted. Cochrane's Q test, MR-Egger regression, and MR-PRESSO were employed to detect heterogeneity and pleiotropy, respectively. RESULTS: A total of 196 gut microbiota were examined. After IVW and sensitivity analysis, eight gut bacteria taxa were observed causal effects on the risk of MN. Specifically, Genus. Oscillibacter was a protective factor (OR: 0.57; 95% CI 0.328-0.979; P = 0.042), while Class. Melainabacteria (OR: 1.51; 95% CI 1.004-2.277; P = 0.048), Genus. Butyricicoccus (OR: 2.16; 95% CI 1.005-4.621; P = 0.048), Genus. Catenibacterium (OR: 1.49; 95% CI 1.043-2.134; P = 0.028), Genus.Ruminiclostridium5 (OR: 1.74; 95% CI 1.053-2.862; P = 0.030), Genus. Ruminococcaceae UCG-003 (OR: 1.73; 95% CI 1.110-2.692; P = 0.015), Order. Bacillales (OR: 1.52; 95% CI 1.135-2.025; P = 0.0048) and Order. Gastranaerophilales (OR: 1.45; 95% CI 1.010-2.085; P = 0.044) were risk factors. Heterogeneity was not significant for most single-nucleotide polymorphisms, and no statistical difference in pleiotropy. CONCLUSIONS: This study first indicated the causal association between specific gut microbiota and MN, which would be of great significance to guide clinical prevention and treatment in MN.


Subject(s)
Gastrointestinal Microbiome , Glomerulonephritis, Membranous , Mendelian Randomization Analysis , Humans , Glomerulonephritis, Membranous/microbiology , Glomerulonephritis, Membranous/genetics , Gastrointestinal Microbiome/genetics
9.
Article in English | MEDLINE | ID: mdl-39017863

ABSTRACT

Humus (HS) reservoirs can embed microbial necromass (including cell wall components that are intact or with varying degrees of fragmentation) in small pores, raising widespread concerns about the potential for C/N interception and stability in composting systems. In this study, fresh cow manure and sawdust were used for microbial solid fermentation, and the significance of microbial residues in promoting humification was elucidated by measuring their physicochemical properties and analyzing their microbial informatics. These results showed that the stimulation of external carbon sources (NaHCO3) led to an increase in the accumulation of bacterial necromass C/N from 6.19 and 0.91 µg/mg to 21.57 and 3.20 µg/mg, respectively. Additionally, fungal necromass C/N values were about 3 times higher than the initial values. This contributed to the increase in HS content and the increased condensation of polysaccharides and nitrogen-containing compounds during maturation. The formation of cellular debris mainly depends on the enrichment of Actinobacteria, Proteobacteria, Ascomycota, and Chytridiomycota. Furthermore, Euryarchaeota was the core functional microorganism secreting cell wall lytic enzymes (including AA3, AA7, GH23, and GH15). In conclusion, this study comprehensively analyzed the transformation mechanisms of cellular residuals at different profile scales, providing new insights into C/N cycles and sequestration.

10.
Sci Total Environ ; 915: 170000, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38242453

ABSTRACT

To address the challenge of increasing nitrogen retention in compost, this study investigated the effects of microbial communities on denitrification and ammonia assimilation during sludge composting by inoculating microbial inoculants. The results showed that the retention rates of total Kjeldahl nitrogen (TKN) and humic acid (HA) in MIs group (with microbial inoculants) were 4.94 % and 18.52 % higher than those in the control group (CK), respectively. Metagenomic analysis showed that Actinobacteria and Proteobacteria were identified as main microorganisms contributing to denitrification and ammonia assimilation. The addition of microbial agents altered the structure of the microbial community, which in turn stimulated the expression of functional genes. During cooling period, the ammonia assimilation genes glnA, gltB and gltD in MIs were 15.98 %, 24.84 % and 32.88 % higher than those in CK, respectively. Canonical correspondence analysis revealed a positive correlation between the dominant bacterial genera from the cooling stage to the maturity stage and the levels of NO3--N, NH4+-N, HA, and TKN contents. NH4+-N was positively correlated with HA, indicating NH4+-N might be incorporated into HA. Heat map and network analyses revealed NH4+-N as a key factor affecting functional genes of denitrification and ammonia assimilation, with Nitrospira identified as the core bacteria in the microbial network. Therefore, the addition of microbial agents could increase nitrogen retention and improve compost product quality.


Subject(s)
Agricultural Inoculants , Composting , Sewage/microbiology , Agricultural Inoculants/metabolism , Denitrification , Ammonia/metabolism , Nitrogen/metabolism , Bacteria/metabolism , Soil
11.
Sci Total Environ ; 902: 166487, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37611721

ABSTRACT

In this study, nano zero-valent iron loaded on biochar (BC-nZVI) was analyzed for its effects on antibiotic resistance genes (ARGs) in composting. The results showed that BC-nZVI increased reactive oxygen species (ROS) production, and the peak values of H2O2 and OH were 22.95 % and 55.30 % higher than those of the control group, respectively. After 65 days, the relative abundances of representative ARGs decreased by 56.12 % in the nZVI group (with BC-nZVI added). An analysis of bacterial communities and networks revealed that Actinobacteria, Proteobacteria, and Firmicutes were the main hosts for ARGs, and BC-nZVI weakened the link between ARGs and host bacteria. Distance-based redundancy analysis showed that BC-nZVI altered the microbial community structure through environmental factors and that most ARGs were negatively correlated with ROS, suggesting that ROS significantly affected the relative abundance of ARGs. According to these results, BC-nZVI showed potential for decreasing the relative abundance of ARGs in composting.


Subject(s)
Composting , Reactive Oxygen Species , Hydrogen Peroxide/pharmacology , Anti-Bacterial Agents/pharmacology , Bacteria/genetics , Genes, Bacterial , Drug Resistance, Microbial/genetics , Manure
12.
Environ Pollut ; 317: 120795, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36462475

ABSTRACT

In this study, the amendment of red mud (RM) in dairy manure composting on the fate of antibiotic resistance genes (ARGs) by both direct (bacteria community, mobile genetic elements and quorum sensing) and indirect ways (environmental factors and antibiotics) was analyzed. The results showed that RM reduced the total relative abundances of 10 ARGs and 4 mobile genetic elements (MGEs). And the relative abundances of total ARGs and MGEs decreased by 53.48% and 22.30% in T (with RM added) on day 47 compared with day 0. Meanwhile, the modification of RM significantly increased the abundance of lsrK, pvdQ and ahlD in quorum quenching (QQ) and decreased the abundance of luxS in quorum sensing (QS) (P < 0.05), thereby attenuating the intercellular genes frequency of communication. The microbial community and network analysis showed that 25 potential hosts of ARGs were mainly related to Firmicutes, Proteobacteria and Actinobacteria. Redundancy analysis (RDA) and structural equation model (SEM) further indicated that RM altered microbial community structure by regulating antibiotic content and environmental factors (temperature, pH, moisture content and organic matter content), which then affected horizontal gene transfer (HGT) in ARGs mediated by QS and MGEs. These results provide new insights into the dissemination mechanism and removal of ARGs in composting process.


Subject(s)
Composting , Genes, Bacterial , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Bacteria/genetics , Manure/microbiology
13.
Bioresour Technol ; 381: 129134, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37164230

ABSTRACT

This study revealed a novel carbon-nitrogen coupled metabolic pathway. Results showed that the addition of inorganic carbon sources slowed down the decomposition of urea and conserved more nutrients in composting. Metagenomic analysis showed that the main bacteria involved in this new pathway were Actinobacteria, Proteobacteria and Firmicutes. During the late composting period, the dominant genus Microbacteium involved in denitrification accounted for 22.18% in control (CP) and only 0.12% in treatment group (T). Moreover, ureC, rocF, argF, argI, argG were key genes involved in urea cycle. The abundance of functional gene ureC and denitrification genes decreased in thermophilic and cooling phases, respectively. The genes hao, nosZ, ureA and nifH were more closely associated with Chloroflexi_bacterium and Bacillus_paralichenformis. In conclusion, composting habitats with additional inorganic carbon sources could not only weaken denitrification but also allow more nitrogen to be conserved through slow-release urea to improve resource utilization and decrease the environmental risk.


Subject(s)
Carbon , Composting , Carbon/metabolism , Nitrogen/metabolism , Bacteria/genetics , Bacteria/metabolism , Ecosystem , Metabolic Networks and Pathways , Soil , Manure
14.
Bioresour Technol ; 380: 129125, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37127171

ABSTRACT

The purpose of this paper was to explore the promotion of maleic anhydride on the polymerization of precursors into humus in composting, and analyze the changes of key functional enzymes. The results showed that the content of humus in the treatment group added maleic anhydride (MAH) was higher than that in the control check (CK). The decrease rate of humus precursor concentration of MAH was also higher than that of CK. In MAH, the activities of laccase and tyrosinase were improved, thus enhanced the catalytic conversion of humus precursors. The analysis of bacterial community showed that maleic anhydride optimized the community structure of humification functional enzymes producing bacteria, with the most obvious increase of Firmicutes. In conclusion, this study provided theoretical supports for the introduction of maleic anhydride into the compost system to promote the polymerization of precursors to form humus.


Subject(s)
Composting , Soil , Maleic Anhydrides/chemistry , Bacteria , Polymerization , Manure
15.
J Hazard Mater ; 457: 131819, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37307729

ABSTRACT

This study aimed to explore the effect of peroxydisulfate on the removal of heavy metals, antibiotics, heavy metal resistance genes (HMRGs), and antibiotic resistance genes (ARGs) during composting. The results showed that peroxydisulfate achieved the passivation of Fe, Mn, Zn, and Cu by promoting their speciation variations, thus reducing their bioavailability. And the residual antibiotics were better degraded by peroxydisulfate. In addition, metagenomics analysis indicated that the relative abundance of most HMRGs, ARGs, and MGEs was more effectively down-regulated by peroxydisulfate. Network analysis confirmed Thermobifida and Streptomyces were dominant potential host bacteria of HMRGs and ARGs, whose relative abundance was also effectively down-regulated by peroxydisulfate. Finally, mantel test showed the significant effect of the evolution of microbial communities and strong oxidation of peroxydisulfate on the removal of pollutants. These results suggested that heavy metals, antibiotics, HMRGs, and ARGs shared a joint fate of being removed driven by peroxydisulfate during composting.


Subject(s)
Composting , Metals, Heavy , Anti-Bacterial Agents , Genes, Bacterial , Manure/microbiology
16.
Sci Total Environ ; 856(Pt 1): 159009, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36162579

ABSTRACT

In this study, the effect of Fe3+ on the quinone redox cycling driving lignocellulosic degradation in composting systems was investigated. The results showed that the degradation rates of cellulose, hemicellulose, and lignin were higher in the experimental group (CT) with Fe2(SO4)3 addition than in the blank group (CK) (CT, 52.55 %, 45.14 %, 56.98 %; CK, 49.63 %, 37.34 %, 52.3 %). Changes in the abundance of key enzymes for quinone reduction (AA3_1, AA3_2, AA6) and the structural succession of microbial communities were analyzed by metagenomic analysis. Among them, Fe2(SO4)3 had the most significant effect on AA3_2, with an approximately 8-fold increase in abundance compared to the beginning of composting. The dominant phylum in the composting process was Actinobacteria. In conclusion, the addition of Fe2(SO4)3 contributed to the quinone redox cycling and effectively improved the degradation rate of lignocellulose in composting.


Subject(s)
Composting , Lignin/metabolism , Metagenomics , Soil , Quinones , Oxidation-Reduction , Manure/microbiology
17.
Bioresour Technol ; 363: 127949, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36108576

ABSTRACT

This study was the first to explore the effect of shell powder (SP) on lignin degradation and humus (HS) formation during composting. The results showed that the treatment group (T) with SP consumed more polyphenols, reducing sugar and amino acids than the control group (CK), especially the rate of reducing sugar consumption in T (50.61 %) was significantly higher than CK (28.40 %). SP greatly enhanced the efficiency of lignin degradation (T:45.47 %; CK:24.63 %) and HS formation (T:34.93 %; CK:20.16 %). The content of HA in T was 12.94 mg/g while CK was 12.06 mg/g. SP maintained a continuous increase in the relative abundance of AA1, AA3 after cooling phase. Meanwhile, T (48.98 %) significantly increased the abundance of Actinobacteria compared with CK (37.19 %). Actinobacteria, AA1 and AA3 were identified as the main factors promoting lignin degradation and HS formation by correlation analysis. Therefore, adding SP could be a novel strategy to improve compost quality.


Subject(s)
Actinobacteria , Composting , Actinobacteria/metabolism , Amino Acids , Bacteria/metabolism , Dietary Sugars , Lignin/metabolism , Manure , Powders , Soil , Sugars
18.
Bioresour Technol ; 361: 127708, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35907603

ABSTRACT

In this study, HCO3- was used as a co-substrate for cyanate metabolism to investigate its effect on nitrogen cycle in composting. The results showed that the carbamate content in experimental group (T) with HCO3- added was higher than that in control group (CP) during cooling period. Actinobacteria and Proteobacteria were the dominant phyla for cyanate metabolism, and the process was mediated by cyanase gene (cynS). The cynS abundance was 16.6% higher in T than CP. In cooling period, the nitrification gene hao in T was 8.125% higher than CP. Denitrification genes narG, narH, nirK, norB, and nosZ were 25.64%, 35.33%, 45.93%, 36.62%, and 36.12% less than CP, respectively. The nitrogen fixation gene nifH in T was consistently higher than CP in the late composting period. Conclusively, cyanate metabolism drove the nitrogen cycle by promoting nitrification, nitrogen fixation, and inhibiting denitrification, which improved nitrogen retention and compost quality.


Subject(s)
Composting , Carbon , Cyanates/metabolism , Denitrification , Nitrogen/metabolism , Nitrogen Cycle , Soil
19.
Exp Ther Med ; 21(6): 661, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33968191

ABSTRACT

Atherosclerosis causes stroke and coronary heart disease and is associated with a high mortality rate worldwide. However, the pathogenesis of atherosclerosis remains unclear. Endothelial cell apoptosis is one of the early changes observed in atherosclerosis. Previous studies have found that microRNA (miR)-616-3p may be involved in the development of atherosclerosis, but the specific mechanism is not clear. The present study aimed to investigate whether miR-616-3p is involved in endothelial cell apoptosis and its underlying mechanism. The present study demonstrated that compared with normal HUVECs, HUVECs treated with oxidized low-density lipoprotein expressed higher miR-616-3p and lower X-linked inhibitor of apoptosis protein (XIAP) levels. In the present study, HUVECs were transfected with miR-616-3p mimic and Cell Counting Kit-8 (CCK-8), flow cytometry and TUNEL staining assays demonstrated that compared with miR-616-3p mimic control, the miR-616-3p mimic promoted HUVEC apoptosis. In addition, using StarBase 3.0 for bioinformatics analysis it was predicted that miR-616-3p may bind to the 3'untranslated region (UTR) of XIAP mRNA. The present study performed the CCK-8, flow cytometry, TUNEL staining and dual-luciferase reporter assays and demonstrated that miR-616-3p binds to the 3'UTR of the XIAP mRNA and inhibits its expression and that this further promotes apoptosis in HUVECs. In addition, western blotting demonstrated that compared with miR-616-3p mimic control, the miR-616-3p mimic increases the level of cleaved caspase-3 in HUVECs. In summary, the present study demonstrated that miR-616-3p can directly inhibit the expression of XIAP mRNA by targeting its 3'UTR which promoted apoptosis in HUVECs. miR-616-3p and XIAP may be used as therapeutic targets of atherosclerosis in the future.

20.
Onco Targets Ther ; 13: 7305-7316, 2020.
Article in English | MEDLINE | ID: mdl-32801757

ABSTRACT

OBJECTIVE: To study the characteristics of polymerase epsilon (POLE) exonuclease domain mutations in Chinese patients with endometrial carcinoma (EC). METHODS: This study analyzed data from 529 patients with EC in The Cancer Genome Atlas (TCGA) and 467 EC patients evaluated at the Shanghai First Maternity and Infant Hospital (SFMIH). POLE mutation heterogeneity was analyzed in paired curettage and hysterectomy samples from 120 SFMIH patients. Sanger sequencing identified mutations in the POLE exonuclease domain, and correlations between POLE mutation status and various clinicopathological features were determined by chi-squared testing and Cohen's kappa analysis, with Kaplan-Meier survival curves generated to assess correlations between POLE mutation status and overall survival (OS). RESULTS: Thirty-five mutations were identified in 467 samples (7.5%), and novel mutations were detected in the SFMIH cohort. Compared to the TCGA cohort, the SFMIH cohort had fewer POLE mutations when matched by age (<60) and histology (endometrioid) (p < 0.001 and p = 0.010, respectively). In our study cohort, POLE mutations were significantly associated with adjuvant treatment (p = 0.029), and patients with POLE mutations who underwent chemoradiotherapy had a poor OS (p < 0.0001). Notably, shorter OS was significantly associated with POLE mutations in hysterectomy samples from patients aged >60 years or with stage I disease in the paired curettage-hysterectomy group. CONCLUSION: The significant difference in POLE mutation profiles between the TCGA and SFMIH cohorts, as well as the poor consistency between the curettage and hysterectomy samples, suggests that different parameters need to be applied to determine the prognosis of patients with EC in China.

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