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1.
Int J Med Inform ; 139: 104156, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32387819

RESUMO

BACKGROUND: Healthcare wearable devices (HWDs) enable continuous monitoring of consumers' health signals and have great potential to improve the efficiency and quality of healthcare. However, factors influencing consumer acceptance of HWDs are not well understood. Moreover, extant studies seem to fail to consider whether an HWD has appropriate functions to fit the requirements of consumers' healthcare activities. OBJECTIVES: The objective of this study was to develop and empirically test a model by integrating the Unified Theory of Acceptance and Usage of Technology (UTAUT) and Task-Technology Fit (TTF) models to understand how consumers accept HWDs. METHODS: A self-administered questionnaire was designed based on validated measurement scales. Data from 406 valid samples were analyzed using partial least squares structural equation modeling. RESULTS: The results indicated that performance expectancy, effort expectancy, facilitating conditions, social influence, and task-technology fit positively affected consumers' behavioral intention to use HWDs, and together accounted for 68.0 % of its variance. Both task and technology characteristics were significant determinants of task-technology fit and exerted impacts on behavioral intention through the mediating roles of task-technology fit and effort expectancy. CONCLUSIONS: The key findings showed that consumer acceptance of HWDs was affected by both users' perceptions (i.e., performance expectancy, effort expectancy, social influence and facilitating conditions) and the task-technology fit. The theoretical and practical implications and contributions were provided for future researchers and practitioners to increase consumers' use of HWDs in their healthcare activities.

2.
Cytokine ; 131: 155116, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32388485

RESUMO

Longifolioside A is an iridoid glucoside compound isolated from Pseudolysimachion rotundum var. subintegrum, which has been used in traditional herbal medicines to treat respiratory inflammatory diseases. Logifolioside A is a potent antioxidant; however, its underlying pharmacological mechanisms of action in inflammatory diseases are unknown. Here, we investigated the inhibitory effects of longifolioside A in lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using human THP-1 macrophages and HEK293 cells stably expressing human TLR4 protein (293/HA-hTLR4). Longifolioside A significantly reduced the release of inflammatory cytokines such as interleukin (IL)-6, -8, and tumor necrosis factor (TNF)-α in LPS-stimulated THP-1 macrophages. Furthermore, longifolioside A inhibited the expression of inflammatory mediator genes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 that produce nitric oxide (NO) and prostaglandin E2 (PGE2), respectively. Longifolioside A suppressed the phosphorylation of PKCδ, IRAK4, IKKα/ß, IκBα, and mitogen-activated protein (MAP) kinases (ERK 1/2 and JNK, but not p38), thereby inactivating the nuclear localization of NF-κB and AP-1, and thus decreasing the expression of inflammatory response genes. Notably, longifolioside A disrupted the interaction between human TLR4 and the TIR domain-containing adaptor protein (TIRAP), an early step during TLR4 activation, thereby reducing IL-8 secretion in 293/HA-hTLR4 cells. This inhibitory effect was comparable to that of TAK-242 (a TLR4 inhibitor, or resatorvid). Our results indicate that longifolioside A prevents inflammatory response by suppressing TLR4 activation required for NF-κB and AP-1 activation.

4.
Sci Adv ; 6(15): eaaz6980, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32285005

RESUMO

As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosomes offer great potential as a natural therapeutic drug delivery vehicle. The inflammatory responses in various disease models can be attenuated through introduction of super-repressor IκB (srIκB), which is the dominant active form of IκBα and can inhibit translocation of nuclear factor κB into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srIκB into exosomes. We showed that intraperitoneal injection of purified srIκB-loaded exosomes (Exo-srIκBs) attenuates mortality and systemic inflammation in septic mouse models. In a biodistribution study, Exo-srIκBs were observed mainly in the neutrophils, and in monocytes to a lesser extent, in the spleens and livers of mice. Moreover, we found that Exo-srIκB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.

5.
J Ethnopharmacol ; 258: 112767, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32199989

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The abnormal increase in vascular smooth muscle cell (VSMC) proliferation is widely accepted as the pivotal process in the vascular remodeling of hypertension. Qingda granule (QDG) is simplified from Qingxuan Jiangya Decoction (QXJYD) which has been in usage for a long time as a traditional Chinese medicine formula to treat hypertension based on the theory of traditional Chinese medicine. However, its underlying molecular mechanisms of action remain largely unknown. AIM OF STUDY: To investigate the therapeutic efficacy of QDG in the attenuation of elevation of blood pressure and proliferation of VSMCs in vivo and in vitro and explore its possible mechanism of action. MATERIALS AND METHODS: In vivo, we established an angiotensin Ⅱ (Ang Ⅱ)-mediated hypertension model in C57BL/6 mice and orally administered 1.145 g/kg/day of QDG. The systolic and diastolic blood pressures of all mice were measured at the end of the treatment by using the tail-cuff plethysmograph method and CODA™ noninvasive blood pressure system. VSMC proliferation within the aorta was determined by immunohistochemistry. In vitro, primary rat VSMCs were cultured to further verify the effects of QDG on Ang Ⅱ induced VSMC proliferation. Cell proliferation was investigated using cell counting and MTT assays. The protein expression was determined by western blotting. RESULTS: We found that oral administration of QDG significantly attenuated the elevation of blood pressure and proliferation of VSMCs in Ang Ⅱ-induced hypertensive mice. Moreover, QDG remarkably inhibited Ang Ⅱ-induced primary rat VSMCs proliferation and decreased mitogen-activated protein kinase (MAPK) and PI3K/AKT activity by attenuating the expression of phospho-extracellular signaling-regulated kinase 1/2, phospho-p38, phospho-c-Jun N-terminal kinase and phospho-protein kinase B. CONCLUSION: Collectively, our findings suggest that QDG attenuates Ang Ⅱ-induced elevation of blood pressure and proliferation of VSMCs through a decrease in the activation of MAPK and PI3K/AKT pathways. Based on this study, we postulate this could be one of the mechanisms whereby QDG effectively controls hypertension.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32157800

RESUMO

BACKGROUND: Fever and respiratory symptoms are the major causes of hospitalisation in infants aged 90 days or less. Respiratory viruses (RVs) are detected by multiplex reverse transcriptase-polymerase chain reaction (mRT-PCR) in up to 70% of infants tested in this population. Aminotransferase elevation is not uncommon in RV infections, and repeat laboratory investigations are frequent due to concerns regarding the occurrence of hepatic disease. METHODS: This retrospective observational cohort study included 271 infants aged 8-90 days, with positive RV mRT-PCR results. Data were obtained on demographics, laboratory results and final diagnoses of hepatobiliary disease. RESULTS: Fever (73.1%) and/or respiratory symptoms (75.6%) were the major presentations among the hospitalised infants. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels were elevated in 62 (22.9%) of the 271 infants. Twenty-four of these 62 infants had their first follow-up, and 19 (79.2%) showed persistent elevation. All 10 (100%) infants who had their second follow-up showed persistently elevated aminotransferase levels. Eventually, none of the 10 infants were diagnosed with hepatic disease during the median follow-up of 10 days (range 3-232 days). Among the RVs of interest, parainfluenza virus type 1 was significantly associated with aminotransferase elevation (odds ratio: 2.95; 95% confidence interval [CI]: 1.11-7.83). CONCLUSIONS: RV-related non-specific hepatitis is occasionally observed in infants aged 8-90 days, and ALT elevation is the most common abnormality. However, a final diagnosis of primary hepatobiliary disease appears to be rare. Therefore, regular follow-ups and targeted testing may be recommended in this specific population.

7.
Cells ; 9(3)2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120837

RESUMO

The SRC kinase family comprises non-receptor tyrosine kinases that are ubiquitously expressed in all cell types. Although Src is reportedly activated in pulmonary and renal fibrosis, little is known regarding its role in liver fibrosis. This study investigated whether the inhibition of Src protects against liver fibrosis. The expression of Src was upregulated in thioacetamide (TAA)-induced fibrotic mouse liver and cirrhosis of patients, and phospho-Src was upregulated during activation of hepatic stellate cells (HSC). In addition, Src inhibition reduced the expression of α-smooth muscle actin (αSMA) in primary HSCs and suppressed transforming growth factor ß (TGF-ß)-induced expression of connective tissue growth factor (CTGF) in hepatocytes. Src inhibitor Saracatinib also attenuated TAA-induced expression of type I collagen, αSMA, and CTGF in mouse liver tissues. The antifibrotic effect of Src inhibitors was associated with the downregulation of smad3, but not of signal transducer and activator of transcription 3 (STAT3). In addition, Src inhibition increased autophagy flux and protected against liver fibrosis. These results suggest that Src plays an important role in liver fibrosis and that Src inhibitors could be treat liver fibrosis.

8.
J Agric Food Chem ; 68(15): 4546-4556, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32208690

RESUMO

Phosphorylation is a widespread posttranslational protein modification and is important in various biological processes. However, milk fat globule membrane (MFGM) phosphoproteins have not been explored systematically in human milk. Here, we used quantitative phosphoproteomics to analyze phosphorylation sites in human MFGM proteins and their differences at different stages of lactation; 305 phosphorylation sites on 170 proteins and 269 phosphorylation sites on 170 proteins were identified in colostrum and mature MFGM, respectively. Among these, 71 phosphorylation sites on 48 proteins were differentially expressed between the different stages of lactation. Osteopontin in human MFGM was the most heavily phosphorylated protein, with a total of 39 identified phosphorylation sites. Our results shed light on phosphorylation sites, composition, and biological functions of MFGM phosphoproteins in human colostrum and mature milk, and provide novel insights into the crucial roles of protein phosphorylation during infant development.

9.
Expert Rev Vaccines ; 19(2): 163-173, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32174221

RESUMO

Introduction: Mutant KRAS is a genetic driver of multiple cancers that has challenged clinical anti-cancer therapeutics in the last 3 decades. Neo-antigens encoded by KRAS mutations have been identified as tumor-specific with high immunogenicity and can be used to deliver precision cancer vaccines to promote anti-tumor immune responses. KRAS mutation-based cancer vaccines have produced encouraging preclinical and clinical results. Cancer vaccines represent a promising approach to treat KRAS-driven cancers.Areas covered: In this review, we summarize the development and progress of vaccines targeting KRAS and evaluate their potential benefits and obstacles in the current landscape of therapy for KRAS-driven cancers.Expert opinion: KRAS mutation-based cancer vaccines can induce immunogenicity in patients with KRAS-driven cancers. However, the mechanisms of tumor suppression including cellular and molecular factors within the tumor microenvironment may limit vaccine efficacy. Combining KRAS-driven therapeutic cancer vaccines with other methods and adjuvants can circumvent immunosuppression and promote therapeutic successes.

10.
Pflugers Arch ; 472(3): 367-374, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32078030

RESUMO

Recent evidence suggests that mitochondrial complex II is an essential mediator of myocardial ischemia-reperfusion injury. The present study aimed to investigate the effects of fatty acid supplementation or high-fat diet (HFD) on cardiac mitochondrial activity. The changes of complex I and complex II activities and mitochondrial oxygen consumption rate (OCR) following hypoxia and re-oxygenation under these conditions were studied. Our results have shown that OCR (mitochondrial activity) was significantly increased with palmitoylcarnitine supplementation in mitochondria-enriched fraction from C57BL/6 mice hearts. Mitochondrial complex I activity was unaffected by palmitoylcarnitine but complex II activity was enhanced. Re-oxygenation following 30-min hypoxia transiently increased OCR but such an effect on OCR was abolished by complex II inhibitor, malonate, but not by complex I inhibitor, rotenone, despite that complex I activity was significantly increased with re-oxygenation following hypoxia in the presence of palmitoylcarnitine. Furthermore, OCR and complex II activity were significantly increased in the mitochondria from high-fat diet mice heart compared with those of normal or low-fat diet mice. Re-oxygenation to mitochondria following 30-min hypoxia increased OCR in all three groups but significantly more in HFD. Malonate abolished re-oxygenation-induced OCR increment in all groups. Our results indicate that complex II activity and OCR are enhanced with palmitoylcarnitine or in HFD mice heart. Although re-oxygenation following hypoxia enhanced complex II and complex I activities, complex II plays an important role in increasing mitochondrial activity, which may be instrumental in myocardial injury following ischemic reperfusion.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32086220

RESUMO

Non-negative matrix factorization (NMF) is a dimensionality reduction technique based on high-dimensional mapping. It can effectively learn part-based representations. In this paper, we propose a method called Dual Hyper-graph Regularized Supervised Non-negative Matrix Factorization (HSNMF). To encode the geometric information of the data, the hyper-graph is introduced into the model as a regularization term. The advantage of hyper-graph learning is to find higher order data relationship to enhance data relevance. This method constructs the data hyper-graph and the feature hyper-graph to find the data manifold and the feature manifold simultaneously. The application of hyper-graph theory in cancer datasets can effectively find pathogenic genes. The discrimination information is further introduced into the objective function to obtain more information about the data. Supervised learning with label information greatly improves the classification effect. Furthermore, the real datasets of cancer usually contain sparse noise, so the -norm is applied to enhance the robustness of HSNMF algorithm. Experiments under The Cancer Genome Atlas (TCGA) datasets verify the feasibility of the HSNMF method.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32086224

RESUMO

Non-negative Matrix Factorization (NMF) is a dimensionality reduction approach for learning a parts-based and linear representation of non-negative data. It has attracted more attention because of that. In practice, NMF not only neglects the manifold structure of data samples, but also overlooks the priori label information of different classes. In this paper, a novel matrix decomposition method called Hyper-graph regularized Constrained Non-negative Matrix Factorization (HCNMF) is proposed for selecting differentially expressed genes and tumor sample classification. The advantage of hyper-graph learning is to capture local spatial information in high dimensional data. This method incorporates a hyper-graph regularization constraint to consider the higher order data sample relationships. The application of hyper-graph theory can effectively find pathogenic genes in cancer datasets. Besides, the label information is further incorporated in the objective function to improve the discriminative ability of the decomposition matrix. Supervised learning with label information greatly improves the classification effect. We also provide the iterative update rules and convergence proofs for the optimization problems of HCNMF. Experiments under The Cancer Genome Atlas (TCGA) datasets confirm the superiority of HCNMF algorithm compared with other representative algorithms through a set of evaluations.

13.
ACS Appl Mater Interfaces ; 12(9): 10096-10106, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32027119

RESUMO

Paclitaxel (Ptx), a type of microtubule depolymerization inhibitor, is one of the main components in gastric cancer chemotherapy. Some studies have demonstrated that tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has potential antitumor effects in several cancers. Aside from the direct anticancer effect, Tet is proved to synergistically enhance the antitumor effect of Ptx in gastric cancer. However, the application of the combinational strategy is limited by the poor solubility of both drugs. Nanodrug delivery systems including polymeric nanoparticles, self-assembled nanofibers, hydrogels, etc., hold the potential to meet the need. Here, a novel supramolecular nanomaterial, based on the concept of "carrier-free nanodrugs", is reported as a feasible platform for synergistic drug delivery. Ptx-SA-RGD is obtained through the conjugation of Ptx and the tumor-specific peptide RGD (arginine-glycine-aspartic acid) with succinic acid (SA) as a linker. Ptx-SA-RGD could self-assemble into Ptx nanofibers (P-NFs) with high drug-loading efficiency. Tet was then encapsulated into P-NFs to acquire novel Ptx and Tet coloaded self-assembled nanofibers (P/T-NFs). The uptake study shows the dynamic internalization of P/T-NFs by the gastric cancer cell line MGC-803. P/T-NFs significantly triggered the accumulation of reactive oxygen species (ROS) in gastric cancer cells MGC803 and further decreased the mitochondrial membrane potential, which led to the induction of mitochondrial apoptosis with superior cytotoxicity against free drugs. Moreover, P/T-NFs suppressed the expressions of p-STAT3 and p-JAK, initiated cytochrome-C release, and promoted caspase protein expression. Furthermore, P/T-NFs demonstrated the strongest tumor-delaying effect as well as the lowest toxicity. Therefore, self-assembled nanofibers of P/T-NFs demonstrated an increase of the mitochondrial apoptosis level and a stronger antitumor effect both in vitro and in vivo, which could be a potential way to enhance the clinical efficacy and reduce the side-effects of Ptx in gastric cancer.

14.
Biochem Biophys Res Commun ; 524(3): 764-771, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037089

RESUMO

ß-Amyloid (Aß) plaque in the brains of patients with Alzheimer's disease (AD) is mainly caused by impaired clearance of Aß by glial cells, including microglia and astrocytes. Because microglia play an important protective role in the central nervous system, many efforts have been made to identify agents that effectively improve microglial Aß phagocytosis. This study found that TLQP-21, which is cleaved from VGF (VGF nerve growth factor inducible) precursor protein, enhanced Aß phagocytosis and degradation by microglial BV2 cells. TLQP-21 also improved microglial phagocytic activity and promoted fibrillar amyloid-ß (fAß) uptake by microglial BV2 cells via a C3AR1-dependent mechanism. Moreover, TLQP-21 stimulated Aß degradation by enhancing lysosome activity, thereby enhancing fAß clearance. These results suggest that treatment with TLQP-21 may be a novel therapeutic strategy to efficiently enhance microglial Aß clearance in AD.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32016903

RESUMO

This study evaluated the performance of an upflow anaerobic filter (UAF) reactor in the thermophilic methane fermentation of hypersaline molasses wastewater. The high salinity (~ 45 mS/cm) of the undiluted wastewater completely inhibited the biogas production. An acclimation strategy involving gradient dilution of the molasses wastewater was implemented to gradually increase the salt stress. Consequently, the biogas production was recovered, inhibited only slightly by the high salinity of the undiluted wastewater. The reactor steadily achieved a high total organic carbon (TOC) loading rate of 5 g/L/day, with approximately 60% TOC removal efficiency. Acclimation to the gradually increased salt stress leads to a relative abundance of some halotolerant microbes, such as bacteria from Arcobacter, Tissierella, and Ruminococcaceae, which increased as their hydrolytic and acidogenic abilities adjusted to the incremental increase in salinity. Additionally, hydrogenotrophic methanogens, especially Methanoculleus, showed greater resistance to hypersalinity than aceticlastic methanogens. These results suggest that acclimation of the fermentation microbial community to hypersalinity is an effective strategy to improve methane production from hypersaline molasses wastewater in thermophilic UAF reactors.

16.
Biomacromolecules ; 21(2): 803-814, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31995366

RESUMO

Nucleoside analogue drugs are widely used in cancer therapy and antiviral therapy, while fast metabolism, drug resistance, and severe side effects significantly limit their clinical applications. To address these issues, a variety of ester- and amide-linked prodrugs and their nanoparticulate formulations have been devised. However, most of these prodrugs suffer from inefficient transformation to native drugs in tumor. Here, we report an approach to conjugate gemcitabine, a kind of anticancer nucleoside drug and widely used to treat cancers, to polyketal backbone via pH-sensitive ketal linkage, and prepared gemcitabine-containing polyketal prodrug nanoparticles with minimal drug release under physiological conditions and acid-triggerable release of native gemcitabine. Intracellular and intratumoral degradation of the pH-sensitive gemcitabine-containing polyketal prodrug and incorporation of gemcitabine into DNA were confirmed by confocal microscopy using EdU, an analogue of gemcitabine. One single intravenous injection of these gemcitabine-containing polyketal prodrug nanoparticles demonstrated notable anticancer efficacy in the A2780 ovarian xenograft tumor model with increased survival rate and good safety. Our approach can be adopted for other diol nucleoside analogues to synthesize pH-sensitive nucleoside-polyketal prodrugs for developing anticancer and antiviral formulations.

17.
Tissue Eng Regen Med ; 17(2): 203-208, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31997256

RESUMO

BACKGROUND: The stromal vascular fraction (SVF) isolated from adipose tissue, which contains stem cells as well as other cell types, has been applied in various research fields. Although different enzymatic concentrations and treatment durations have been applied to isolate the SVF, optimal conditions have not been established. Thus, we aimed to establish the optimal conditions for isolation of the SVF from adipose tissue by automated systems. METHODS: The SVF was collected from removed adipose tissues of five donors during surgery. The SVF was treated with 0.1% or 0.2% collagenase type I for 20, 40, or 60 min. Then, colony forming unit (CFU) assays and flow cytometry were performed to characterize the adipose stem cells (ASCs). A cytokine array was used to investigate the correlation between colony-formation ability and the secretion of isolated ASCs. RESULTS: Treatment with 0.1% collagenase type I for 60 min resulted in a higher SVF yield, whereas treatment with 0.1% collagenase for 40 min resulted in higher CFU values. In addition, expression of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 in the SVF was higher in the high-CFU group than in the low-CFU group. CONCLUSION: The optimal conditions for isolation of the SVF from adipose tissue were treatment with 0.1% collagenase type I for 40 min. We identified the conditions required for efficient SVF isolation based on high CFU values, and our results will facilitate the development of automated systems.

18.
Int J Oncol ; 56(1): 178-192, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789394

RESUMO

Accumulating evidence has demonstrated that microRNAs are associated with malignant biological behaviour, including tumorigenesis, cancer progression and metastasis via the regulation of target gene expression. Our previous study demonstrated that programmed cell death protein 4 (PDCD4), which is a tumour suppressor gene, is a target of microRNA­21 (miR­21), which affects the proliferation and transformation capabilities of renal cell carcinoma (RCC) cells. However, the role of miR­21 in the molecular mechanism underlying the migration, invasion and angiogenesis of RCC remains poorly understood. The effects of miR­21 on the invasion, migration and angiogenesis of RCC cells was determined through meta­analysis and regulation of miR­21 expression in vitro. After searching several databases, 6 articles including a total of 473 patients met the eligibility criteria for this analysis. The combined results of the meta­analysis revealed that increased miR­21 expression was significantly associated with adverse prognosis in patients with RCC, with a pooled hazard ratio estimate of 1.740. In in vitro experiments, we demonstrated that a miR­21 inhibitor decreased the number of migrating and invading A498 and 786­O RCC cells, along with a decrease in PDCD4, c­Jun, matrix metalloproteinase (MMP)2 and MMP9 expression. Additionally, inhibition of miR­21 was revealed to reduce tube formation and tube junctions in the endothelial cell line HMEC­1 by affecting the expression of angiotensin­1 and vascular endothelial growth factor A, whereas PDCD4 small interfering RNA exerted opposite effects on the same cells. Overall, these findings, along with evidence­based molecular biology, demonstrated that miR­21 expression promoted the migration, invasion and angiogenic abilities of RCC cells by directly targeting the PDCD4/c­Jun signalling pathway. The results may help elucidate the molecular mechanism underlying the development and progression of RCC and provide a promising target for microRNA­based therapy.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31655297

RESUMO

p-Nitrophenol (PNP) is one type of environmental pollutant, which is difficult to degrade and soluble in water. To investigate the effects of PNP on economically important marine fish species, we subjected Larimichthys crocea juvenile to five different concentrations of PNP for 96 h, and the semi-lethal concentration (LC50) was 6.218 mg/L. Then we collected the liver, kidney, and gill tissues to determine enzyme activity and gene expression levels, and analyzed histological changes. In histological analysis, the gills showed curling of lamella, epithelial lifting and hyperplasia; the parenchymal structure of hepatocytes was significantly damaged, with severe vacuolation and loss of original structure. The renal cells were damaged too, with congestion and renal tubular necrosis. Catalase and superoxide dismutase both showed an up- and down-tendency with the rise of concentration in the three tissues, and GSH-px had similar trend in the kidney, which decreased at 8 mg/L in the liver but showed no significant differences in the gills. Malondialdehyde of three tissues was increased with an increase in PNP concentration. The expression of four detoxification (cyp450, gst, gpx, hsp70) and one immune-related (mhc II) genes was induced at low PNP concentrations but inhibited at high PNP concentrations in the kidney. In liver, cyp450, hsp70 and mhc II showed similar trend but gst and gpx didn't increase at low PNP concentrations. Our results indicate that the fish possesses the ability to detoxify PNP; however, at high concentrations, PNP still causes serious damage to them. Our data not only help in understanding the ability of L. crocea to detoxify PNP but also should serve as a basis for the study of toxic effects of nitrobenzenes on marine fish.

20.
Infect Genet Evol ; 78: 104056, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31683010

RESUMO

Since 2017, clade 2.3.4.4b H5N6 highly pathogenic avian influenza viruses (HPAIVs) have been detected over a broad geographic region, including Eurasia. These viruses have evolved through reassortment with Eurasian low pathogenic avian influenza viruses (LPAIVs), resulting in multiple genotypes. Here, we sequenced the full-length genome of 15 H5N6 HPAIVs collected from wild birds and poultry farms in South Korea from January to March 2018. A comparative phylogenetic analysis was then conducted. Three distinct genotypes were identified in South Korea during 2017/2018, including a novel reassortant genotype, H214. The novel reassortant H5N6 viruses isolated in this study possessed PB2, PA, and NP gene segments of Eurasian LPAIV on a genetic backbone of the H35-like genotype, which was identified in Korea and the Netherlands during 2017. Bayesian molecular clock analysis suggested that the novel reassortant viruses were generated most likely during the fall migration/wintering season of migratory waterfowl in 2017. Considering the continued emergence and spread of clade 2.3.4.4 HPAIV, enhanced surveillance of wild waterfowl is needed for early detection of HPAIV incursions.

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