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1.
World J Gastroenterol ; 26(7): 740-748, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32116421

RESUMO

BACKGROUND: The incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis (PEC) in patients who underwent mechanical lithotripsy (ML) for large stone removal is high (up to 13.3%). One of the main causes is remaining small fragments or sludge that can impair normal biliary drainage. Endoscopic placement of a nasobiliary tube or a conventional plastic biliary stent has been commonly used under such conditions, but the patient may suffer from significant discomfort after the placement of a nasobiliary tube, while additional endoscopy is required for stent removal. We developed a biliary spontaneous dislodgement spiral stent (BSDSS) to overcome those shortcomings. AIM: To evaluate the feasibility, safety, and effectiveness of inserting a BSDSS for patients who underwent ML for large stone removal. METHODS: We conducted a single-center, retrospective, cohort study at West China Hospital, Sichuan University. A total of 91 consecutive patients with large biliary stones (≥ 10 mm) in the common bile duct who underwent ML between November 2017 and July 2018 were included. The 49 eligible patients were divided into the BSDSS group and the nasobiliary tube group. Technical success, post-ERCP adverse events (including PEC, post-ERCP pancreatitis, stone recurrence, BSDSS retention, self-extraction and dislocation of the nasobiliary tube), drainage time, and postoperative stay were measured and compared. RESULTS: Twenty-one patients in the BSDSS group and 28 patients in the nasobiliary tube group were included in the analyses. The baseline characteristics and clinical information were similar in the two groups. Insertions of BSDSS and nasobiliary tube were technically successful in all 49 patients. There was no significant difference in the incidence of overall post-ERCP adverse events between the two groups (4.8% in the BSDSS group vs 17.9% in the nasobiliary tube group, P = 0.219). The median duration of drainage time (3 d in the BSDSS group vs 4 d in the nasobiliary tube group) and length of postoperative stay (4 d in the BSDSS group vs 5 d in the nasobiliary tube group) also did not differ (P = 0.934, and P = 0.223, respectively). CONCLUSION: Endoscopic placement of a BSDSS appears to be feasible, safe and effective for patients who underwent ML for large stone removal.

2.
Dig Dis Sci ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193860

RESUMO

BACKGROUND: Liver metastasis is an indicator of unfavorable responses to immunotherapy in colorectal cancer patients. However, the difference of immune microenvironment between primary tumors and liver metastases has not been well understood. PATIENTS AND METHODS: Fifty-four colon cancer with liver metastasis patients who received resection of both primary and metastasis lesions have been analyzed. The immune score is based on the density of infiltrating immune cells (CD3+ cell, CD8+ cell, CD11b+ cell, CD11c+ cell, and CD33+ cell) in the center and margin of the tumor. The expression of immune markers between the primary tumor and hepatic metastases was analyzed using Wilcoxon's signed rank test. RESULTS: All the five markers had higher expression in tumor margins than center tumor in both primary tumor and hepatic metastases lesions. The expression of CD11c and CD11b had no difference between metastatic lesions and primary tumor. In tumor margins, except CD11b, all the other 4 markers expressed significantly higher in hepatic metastases than in primary tumor. Intra-tumor, CD3 had higher expression in primary tumor than in hepatic metastases, while CD33 had higher expression in hepatic metastases than in primary tumor. CD8+ CD3+ cells of the total CD8+ cell population in primary tumor was significantly higher than in hepatic metastases (36.42% vs. 24.88%, p = 0.0069). CONCLUSIONS: The immune microenvironment between primary tumor and hepatic metastasis is different. More immunosuppressing cells in liver may partially explain why immunotherapy in colon cancer is less effective with liver metastatic disease.

3.
Ecotoxicol Environ Saf ; 195: 110485, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32203776

RESUMO

Soil co-contaminated with cadmium (Cd) and decabromodiphenyl ether (BDE-209) is a widespread environmental problem, especially in electronic waste contaminated surroundings. Accumulation of Cd and BDE-209 in crops has possibly harmful effects on local human health. In order to assess the potential of arbuscular mycorrhizal (AM) fungi and amaranth (Amaranthus hypochondriacus L.) in remediation of soil co-contaminated with Cd and BDE-209, pot trials were performed to investigate interactive effects of AM fungi, Cd and BDE-209 on growth of amaranth, uptake of Cd and BDE-209, distribution of chemical forms of Cd and activities of antioxidant enzymes in shoots and dissipation of BDE-209 in soil. The present results showed that shoot biomass of non-mycorrhizal plants was significantly inhibited by increasing of Cd addition (5-15 mg kg-1), but were only slightly declined with BDE-209 addition (5 mg kg-1). The interaction of Cd and BDE-209 reduced the proportions of ethanol- and d-H2O-extractable Cd in shoots, consequently alleviated Cd toxicity to plants and enhanced root uptake of Cd and BDE-209. Inoculation of AM fungi resulted in significantly greater shoot biomass as well as higher concentrations of Cd and BDE-209 compared with non-mycorrhizal treatment. Moreover, AM fungi played a beneficial role in relieving oxidative stress on amaranth by increasing the activities of dismutase (SOD) and catalase (CAT) in shoots and significantly improved the dissipation of BDE-209 in soil. The present study suggested that combination of AM fungi and amaranth may be a potential option for remediation of Cd and BDE-209 co-contaminated soils.

4.
Environ Int ; 137: 105263, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32087481

RESUMO

Microplastics are emerging contaminants and their presence in water and soil ecosystems has recently drawn considerable attention because they pose a great threat to entire ecosystems. Recent researches have focused on the detection, occurrence, characterization, and toxicology of microplastics in marine and freshwater ecosystems; however, our understanding of the ecological effects of microplastics in soil ecosystems is still limited compared with that in aquatic ecosystems. Here, we have compiled literature, studying the sources, migration of microplastics in soil, negative impacts on soil health and function, trophic transfer in food chains, and the corresponding adverse effects on soil organisms in order to address the potential ecological and human health risks caused by microplastics in soil. This review aims to address gaps in knowledge, shed light on the ecological effects of microplastics in soil, and propose future studies on microplastic pollution and the resultant soil ecotoxicity. Furthermore, this review is focused on limiting microplastics in soil and establishing management and remediation measures to mitigate the risks posed by microplastic pollution.

5.
Adv Mater ; : e1908470, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32108386

RESUMO

Dual-ion batteries (DIBs) have attracted increasing attention due to their high working voltage, low cost, and environmental friendliness, yet their development is hindered by their limited energy density. Pairing silicon-a most promising anode due to its highest theoretical capacity (4200 mAh g-1 )-with a graphite cathode is a feasible strategy to address the challenge. Nevertheless, the cycling stability of silicon is unsatisfactory due to the loss of electrical contact resulting from the high interface stress when using rigid current collectors. In this work, a flexible interface design to regulate the stress distribution is proposed, via the construction of a silicon anode on a soft nylon fabric modified with a conductive Cu-Ni transition layer, which endows the silicon electrode with remarkable flexibility and stability over 50 000 bends. Assembly of the flexible silicon anode with an expanded graphite cathode yields a silicon-graphite DIB (SGDIB), which possesses record-breaking rate performance (up to 150 C) and cycling stability over 2000 cycles at 10 C with a capacity retention of 97%. Moreover, the SGDIB shows a high capacity retention of ≈84% after 1500 bends and a low self-discharging voltage loss of 0.0015% per bend after 10 000 bends, suggesting high potential for high-performance flexible energy-storage applications.

6.
Mol Med Rep ; 21(3): 1658-1666, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016471

RESUMO

Resveratrol (RSV), a natural polyphenol found in grapes and other herbal plants, has been reported to possess anti­inflammatory, anti­oxidative and anti­proliferative activities. The aim of the present study was to investigate the effect of RSV on interleukin (IL)­33­induced inflammatory responses in mast cells and identify the underlying molecular mechanisms. Rat basophilic leukemia (RBL­2H3) cells were stimulated with IL­33 in the presence or absence of RSV. MTT, ELISA, reverse transcription­quantitative PCR and western blot analyses were then performed in order to assess cytotoxicity, inflammatory cytokine production, suppression of tumorigenicity 2 receptor expression, protein expression involved in mitogen­activated protein kinase (MAPK) and nuclear factor (NF)­κB signaling, respectively. Finally, rats were used to determine the biological effect of RSV in vivo. The results revealed that RSV inhibited cell viability and increased cytotoxicity in a dose­dependent manner. Medium concentration of RSV (10 µM) treatment attenuated inflammatory cytokine production, such as IL­6, IL­13, tumor necrosis factor­α and monocyte chemotactic protein­1, and curbed IL­33­induced enhancement of immunoglobulin E­mediated responses in RBL­2H3 cells, which were associated with the suppression of NF­κB­mediated transcription and inhibition of P38 phosphorylation in response to IL­33 stimulation, but not extracellular signal regulated kinase or JNK. Notably, RSV application also decreased the levels of inflammatory cytokines in rats induced by IL­33 injection, which was similar to the anti­inflammatory effect in vitro. The data from the present study demonstrated that RSV played a regulatory role in antagonizing the effects of IL­33 on mast cells both in vitro and in vivo, suggesting that it has therapeutic potential in IL­33­mediated inflammatory diseases that are associated with mast cells.

7.
J Hazard Mater ; 391: 122211, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32036315

RESUMO

This study aims to clarify the interaction mechanism of substrate with catechol 2,3-dioxygenase (C23O) through multi-technique combination. A novel C23O (named C23O-2G) was cloned, heterogeneously expressed, and identified as a new member in subfamily I.2 of extradiol dioxygenases. Based on the simulations of molecular docking and dynamics, the exact binding sites of catechol on C23O-2G were identified, and the catalytic mechanism mediated by key residues was proposed. The roles of the predicted residues during catalysis were confirmed by site-directed mutagenesis, and the mutation of Thr254 could significantly increase catalytic efficiency and substrate specificity of C23O-2G. The binding and thermodynamic parameters obtained from fluorescence spectra suggested that catechol could effectively quench the intrinsic fluorescence of C23O-2G via static and dynamic quenching mechanisms and spontaneously formed C23O-2G/catechol complex by the binding forces of hydrogen bond and van der Waals force. The results of UV-vis spectra, synchronous fluorescence, and CD spectra revealed obvious changes in the microenvironment and conformation of C23O-2G, especially for the secondary structure. The atomic force microscope images further demonstrated the changes from an appearance point of view. This study could improve our mechanistic understanding of representative dioxygenases involved in aromatic compound degradation.

8.
Sci Total Environ ; 707: 135609, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31771853

RESUMO

Phthalate acid esters (PAEs) are of serious concern as a human health risk due to their ubiquitous presence in indoor air. In the present study, fifteen PAEs in the indoor air samples from physical, chemical, and biological laboratories in Guangzhou, southern China were analysed using gas chromatography mass spectrometry. Extremely high levels of PAEs of up to 6.39 × 104 ng/m3 were detected in some laboratories. Diisobutyl phthalate (DiBP), di(methoxyethyl) phthalate (DMEP), and di-n-butyl phthalate (DBP) were the dominant PAEs with median levels of 0.48 × 103, 0.44 × 103, and 0.39 × 103 ng/m3, respectively, followed by di-(2-propylheptyl) phthalate (DPHP) and di(2-ethylhexyl) phthlate (DEHP) (median levels: 0.16 × 103 and 0.13 × 103 ng/m3, respectively). DMEP and DPHP were found for the first time in indoor air. Principal component analysis indicated that profiles of PAEs varied greatly among laboratory types, suggesting notable variations in sources. The results of independent samples t-tests showed that levels of PAEs were significantly influenced by various environmental conditions. Both the non-carcinogenic and carcinogenic health risks from human exposure to PAEs based on the daily exposure dose in laboratory air were acceptable. Further research should be conducted to investigate the long-term health effects of exposure to PAEs in laboratories.

9.
J Agric Food Chem ; 68(1): 48-58, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31829629

RESUMO

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are perfluorinated alkyl substances widely used in industrial and domestic products. The European Food Safety Authority and United States Environmental Protection Agency have recently lowered the reference doses (RfDs) for PFOA and PFOS 4-1800-fold. The recently lowered RfDs call for re-evaluation of potential human health risks from PFOA and PFOS via food consumption. Serious concerns arise because some intakes of PFOA and PFOS exceeded the RfDs. Innovative cultivation of low-accumulating crop varieties becomes an option to decrease human exposure. We present an up-to-date review on low-accumulating crop varieties for PFOA and PFOS in reference to toxic metals and other organic pollutants, including the variety identification, physiological-biochemical mechanisms, molecular uptake mechanisms, and molecular docking, to call for attention and research efforts to decrease human intakes of PFOA and PFOS via crop consumption.


Assuntos
Ácidos Alcanossulfônicos/análise , Caprilatos/análise , Produtos Agrícolas/química , Fluorcarbonetos/análise , Contaminação de Alimentos/prevenção & controle , Ácidos Alcanossulfônicos/metabolismo , Caprilatos/metabolismo , Qualidade de Produtos para o Consumidor , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Fluorcarbonetos/metabolismo , Contaminação de Alimentos/análise , Inocuidade dos Alimentos , Humanos , Melhoramento Vegetal
10.
Sci Total Environ ; 702: 134878, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31726350

RESUMO

Sorption of organic contaminants by biochar greatly affects their bioavailability and fate in soils. Nevertheless, very little information is available regarding the effects of biochar on sorption and desorption of organic contaminants in different soil particle-size fractions. In this study, di-n-butyl phthalate (DBP), a prevalent organic contaminant in agricultural soils, was taken as a model contaminant. The effects of biochar on DBP sorption and desorption in six particle-size fractions (i.e., coarse sand, fine sand, coarse silt, fine silt, clay, and humic acid fractions) of paddy soil were investigated using batch sorption-desorption experiments. A straw-derived biochar with high specific surface area (116 m2/g) and high content of organic matter (OM) rich in aromatic carbon (67%) was prepared. Addition of this biochar (1% and 5%) significantly promoted the sorption and retention of DBP in all the paddy soil particle-size fractions at environmentally relevant DBP concentrations (2-12 mg/L) with 1.2-132-fold increase of the Kd values. With increasing addition rates of biochar, DBP retention by the biochar enhanced. The biochar's effectiveness was remarkably influenced by the physicochemical properties of the soil particle-size fractions, especially, the OM contents and pore size showed the most striking effects. A parameter (rkd) reflecting the biochar's effectiveness showed negative and positive correlations with OM contents and pore size of the soil particle-size fractions, respectively. Accordingly, strong effect of the biochar was found in the soil fractions with low OM contents and high pore size. The findings of this study gave insight into the effects and influencing factors of biochar on sorption and desorption of organic contaminants in soils at scale of various particle-size factions.


Assuntos
Carvão Vegetal/química , Dibutilftalato/química , Poluentes do Solo/química , Adsorção , Agricultura , Carbono/química , Substâncias Húmicas , Tamanho da Partícula , Solo/química
11.
Bioresour Technol ; 296: 122319, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31689612

RESUMO

A kind of reduced graphene oxide decorated with titanium-based (RGO/TiO2) composites are successfully synthesized and employed in this current study as a novel nonprecious metal catalyst for enhancing bioelectricity generation and cathodic oxygen reduction reaction (ORR) in single chamber microbial fuel cells (MFCs). Compared with commercial Pt/C, RGO/TiO2 shows obviously enhanced oxygen reduction reaction activity due to the appropriately-permeated, large electrochemical active area, enough exposure of electrocatalytic active sites of RGO/TiO2. The air-cathode MFC with RGO/TiO2-1 cathode achieves 1786.7 mW m-3 of power density, 86.7% ±â€¯1.2% of COD removal and 31.6% ±â€¯1.1% of CE, which are higher than commercial Pt/C. Moreover, RGO/TiO2-1 cathode exhibits high-effective electrocatalytic activity, and the power density of RGO/TiO2-1 can keep a stable level and only has a minor decline (5.35%) during 30-cycles operation. These results indicate that RGO/TiO2-1 is a potential cathode catalyst, markedly enhancing cathode ORR, wastewater treatment efficiency, and bioelectricity generation of MFC.


Assuntos
Oxigênio , Titânio , Eletrodos , Características da Família , Grafite
12.
Cell Mol Immunol ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797905

RESUMO

His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4+ and CD8+ T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome.

13.
Cancer Cell Int ; 19: 316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798345

RESUMO

Background: Glioma is a lethal malignant brain tumor, which affects the brain functions and is life-threatening. LncRNA UCA1 was identified as a pivotal regulator for tumorigenesis of glioma. MiR-206 was discovered to promote tumorigenesis and is critical in the regulation of cell proliferation in glioma. This study will discuss the expression of UCA1 regarding miR-206 and CLOCK, and their integrative effects in the proliferation and cell cycle of glioma cells. Methods: qRT-PCR was conducted to measure the mRNA expressions of IgG and Ago2 in cells co-transfected with UCA1, and miR-216 in U251. Bioinformation was analyzed for the prediction of association between UCA1 and miR-206. Transwell migrations assays and invasion assays were utilized to observe the cell invasive ability. Western blot and immunofluorescence imaging were used to examine the protein expressions. In vivo comparisons and observations were also performed to investigate the role of UCA1 in glioma growth. Results: LncRNA UCA1 was up-regulated in glioma cell lines and tissues. It elevated cell invasion via the inducing of epithelial-mesenchymal transition. We found that UCA1 can modulate miR-206 expression and serve as an endogenous sponge of miR-206. The EMT-inducer CLOCK was validated as a messenger RNA target of miR-206. At last, we demonstrated that UCA1 exerted the biology function through regulating miR-206 and CLOCK in vivo. Conclusions: Overall, the results demonstrated that UCA1/miR-206/CLOCK axis participated in the progressing of glioma and could act as a promising therapeutic target.

15.
Nat Commun ; 10(1): 5045, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695036

RESUMO

Charcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT.

16.
Exp Ther Med ; 18(6): 4303-4312, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31772629

RESUMO

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia. The liver has a critical role in regulating glucose homeostasis. The present study aimed to analyze hepatic gene expression profiles and to identify the key genes and pathways involved in T2DM. Gene expression profiles of 10 patients with T2DM and 7 subjects with normal glucose tolerance were downloaded from the Gene Expression Omnibus database. Subsequently, differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed. In addition, a protein-protein interaction network was built and hub genes were identified. In total, 1,320 DEGs were identified, including 698 up- and 622 downregulated genes, and these were mainly enriched in positive regulation of transcription from RNA polymerase II promoter, cell adhesion, inflammatory response, positive regulation of apoptotic process, signal transduction and the Tolllike receptor signaling pathway. A total of 8 hub genes (G-protein subunit gamma transducin 2, ubiquitinconjugating enzyme E2 D1, glutamate metabotropic receptor 1, G-protein signaling modulator 1, C-X-C motif chemokine ligand 9, neurotensin, purinergic receptor P2Y1 and ring finger protein 41) were screened from the network. The present study may contribute to the elucidation of the hepatic pathology of T2DM.

17.
Med Sci Monit ; 25: 7694-7701, 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31606729

RESUMO

BACKGROUND Alprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of alprostadil in decreasing acute pancreatitis (AP) injury remains unknow. This study aimed to investigate the possible protective effects and mechanism of alprostadil against AP in rats. MATERIAL AND METHODS Forty healthy Sprague­Dawley rats were randomly divided into a control group, an AP group, an AP-alprostadil group, an AP-AG490 group, and an AP-(alprostadil+AG490) group. An animal model of acute pancreatitis was established. The pathological changes of the pancreases in each group were observed. We assessed levels of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO), as well as serum IL-1ß, IL-6, IL-10, and TNF-alpha. TUNEL assay was used to detect apoptosis of pancreatic cells. The proteins p-Jak2 and p-Stat3 were investigated by Western blot. RESULTS Compared with the control group, pancreatic pathological score, pancreatic apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha levels were significantly higher in the AP group, and SOD levels were significantly decreased. Compared with the AP group, after treatment with alprostadil, AG490, and alprostadil+AG490, respectively, the pancreatic pathological score, apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha were significantly decreased in AP rats, while SOD levels were significantly increased. The protein levels of p-JAK2 and p-STAT3 were significantly upregulated in the AP group compared with the control group, and the protein levels of p-JAK2 and p-STAT3 after treatment with alprostadil, AG490, and alprostadil+AG490 were significantly decreased, and the effect of alprostadil+AG490 was the strongest. CONCLUSIONS Alprostadil can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas.


Assuntos
Alprostadil/uso terapêutico , Janus Quinase 2/metabolismo , Pancreatite/tratamento farmacológico , Pancreatite/metabolismo , Substâncias Protetoras/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Células Acinares/efeitos dos fármacos , Células Acinares/metabolismo , Células Acinares/patologia , Doença Aguda , Alprostadil/farmacologia , Amilases/sangue , Animais , Apoptose/efeitos dos fármacos , Arginina , Citocinas/sangue , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/sangue , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
18.
Proc Natl Acad Sci U S A ; 116(39): 19440-19448, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31501329

RESUMO

Aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) are the largest protein family causatively linked to neurodegenerative Charcot-Marie-Tooth (CMT) disease. Dominant mutations cause the disease, and studies of CMT disease-causing mutant glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase (TyrRS) showed their mutations create neomorphic structures consistent with a gain-of-function mechanism. In contrast, based on a haploid yeast model, loss of aminoacylation function was reported for CMT disease mutants in histidyl-tRNA synthetase (HisRS). However, neither that nor prior work of any CMT disease-causing aaRS investigated the aminoacylation status of tRNAs in the cellular milieu of actual patients. Using an assay that interrogated aminoacylation levels in patient cells, we investigated a HisRS-linked CMT disease family with the most severe disease phenotype. Strikingly, no difference in charged tRNA levels between normal and diseased family members was found. In confirmation, recombinant versions of 4 other HisRS CMT disease-causing mutants showed no correlation between activity loss in vitro and severity of phenotype in vivo. Indeed, a mutation having the most detrimental impact on activity was associated with a mild disease phenotype. In further work, using 3 independent biophysical analyses, structural opening (relaxation) of mutant HisRSs at the dimer interface best correlated with disease severity. In fact, the HisRS mutation in the severely afflicted patient family caused the largest degree of structural relaxation. These data suggest that HisRS-linked CMT disease arises from open conformation-induced mechanisms distinct from loss of aminoacylation.

19.
Environ Int ; 133(Pt A): 105142, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513927

RESUMO

Frequent cyanobacterial blooms in the eutrophic waters produce a variety of toxins such as the monocyclic heptapeptide microcystins, greatly harming aquatic ecosystems and human health. However, little information of microcystins in agricultural fields is known. This field study of three common microcystin variants (MC-LR, MC-RR, and MC-YR) in vegetables (n = 161), soils (n = 161) and irrigation water samples (n = 23) collected from southern China regions affected by cyanobacteria blooms, shows their prevalence with total concentrations up to 514 µg/L water, 187 µg/kg soil (dry weight) and 382 µg/kg vegetable (fresh weight). MC-RR was the primary variant in all types of samples, accounting for 51.3-100% of total microcystin concentrations. Significant concentration-dependent correlations (p < 0.05) demonstrated that microcystin-contained irrigation waters were the major source of microcystin accumulation in both vegetables and soils. Meanwhile, intracellular-microcystins in irrigation water was found to play an important role in microcystins bioaccumulation in vegetables for the first time. Most vegetable samples (≥60%), particularly celery posed moderate or high human health risk via diet based on toxicity equivalents of the microcystins and reference dose for MC-LR (0.04 µg/kg/d), showing high food safety hidden dangers. Soil microcystins, especially MC-RR in 46.4-88.3% of soils could pose high ecological risks. This study highlights the potential high ecological and human health risks of microcystins in the real soil-vegetable systems of areas affected by cyanobacteria blooms, implying the profound significance and urgent need of investigation on microcystins in terrestrial ecosystems.

20.
Biomed Pharmacother ; 120: 109385, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542613

RESUMO

Long non-coding RNA (lncRNA) linc00152 has been recognized as an oncogenic lncRNA in various cancers. This study attempts to investigate the roles of linc00152 in the metastasis-related traits of infantile hemangioma (IH). Linc00152 was overexpressed in the proliferating-phase hemangioma tissues when compared with that in involuting-phase. Downregulation of linc00152 strikingly suppressed the cell viability, migration and invasion of hemangioma cells. Furthermore, silence of linc00152 repressed the growth and lung metastasis of hemangioma cell in vivo. Subsequent analysis revealed that linc00152 bound with miR-139-5p and linc00152 expression was inversely correlated with the level of miR-139-5p in IH. Same effects of miR-139-5p transfection on HemECs cells were observed as downregulation of linc00152. Moreover, tumor protein D52 (TPD52) was confirmed to be the target of miR-139-5p. Besides, the anti-tumor effect of linc00152 silence on hemangioma cell was reversed by rexpression of TPD52. This study demonstrates that downregulatuon of linc00152 restrains the aggressiveness of hemangioma cell in vitro and in vivo via interacting with miR-139-5p and further modulates the level of TPD52.

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