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1.
Hepatology ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377452

RESUMO

BACKGROUND AND AIMS: Protein tyrosine sulfation (PTS) is a common posttranslational modification that regulates a variety of physiological and pathological processes. However, the role of PTS in cancer remains poorly understood. The goal of this study was to determine whether and how PTS plays a role in HCC progression. APPROACH AND RESULTS: By mass spectrometry and bioinformatics analysis, we identified SAV1 as a novel substrate of PTS in HCC. Oxidative stress upregulates the transcription of SLC35B2, a Golgi-resident transporter of sulfate donor 3'-phosphoadenosine 5'-phosphosulfate, leading to increased sulfation of SAV1. Sulfation of SAV1 disrupts the formation of the SAV1-MST1 complex, resulting in a decrease of MST1 phosphorylation and subsequent inactivation of Hippo signaling. These molecular events ultimately foster the growth of HCC cells both in vivo and in vitro. Moreover, SLC35B2 is a novel transcription target gene of the Hippo pathway, constituting a positive feedback loop that facilitates HCC progression under oxidative stress. CONCLUSIONS: Our findings reveal a regulatory mechanism of the SLC35B2/SAV1 sulfation axis in response to oxidative stress, highlighting its potential as a promising therapeutic target for HCC.

2.
Drug Resist Updat ; 66: 100906, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36565657

RESUMO

It was well known that P-glycoprotein (P-gp/ABCB1) is a master regulator of multidrug resistance (MDR) in cancers. However, the clinical benefit from blocking this pathway remains inconclusive, which motivates a paradigm shift towards alternative strategies for enhancing drug influx. Using a patient-derived organoid (PDO)-based drug screening platform, we report that the combined use of chemotherapy and CCT251545 (CCT) displays robust synergistic effect against PDOs and reduces proliferation of MDR cancer cells in vitro, and results in regression of xenograft tumors, reductions in metastatic dissemination and recurrence rate in vivo. The synergistic activity mediated by CCT can be mainly attributed to the intense uptake of chemotherapeutic agents into the cells, accompanied by alterations in cell phenotypes defined as a mesenchymal epithelial transformation (MET). Mechanistically, analysis of the transcriptome coupled with validation in cellular and animal models demonstrate that the chemosensitizing effect of CCT is profoundly affected by Rac1-dependent macropinocytosis. Furthermore, CCT binds to NAMPT directly, resulting in elevated NAD levels within MDR cancer cells. This effect promotes the assembly of adherents junction (AJ) components with cytoskeleton, which is required for continuous induction of macropinocytosis and consequent drug internalization. Overall, our results illustrate the potential use of CCT as a combination partner for the commonly used chemotherapeutic drugs in the management of MDR cancers.


Assuntos
Antineoplásicos , Neoplasias , Animais , Humanos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Neoplasias/patologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/farmacologia
3.
Emerg Infect Dis ; 29(6): 1244-1249, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37209677

RESUMO

Two novel reassortant highly pathogenic avian influenza viruses (H5N1) clade 2.3.4.4b.2 were identified in dead migratory birds in China in November 2021. The viruses probably evolved among wild birds through different flyways connecting Europe and Asia. Their low antigenic reaction to vaccine antiserum indicates high risks to poultry and to public health.


Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Aviária , Animais , Influenza Aviária/epidemiologia , Filogenia , Aves , Animais Selvagens , Aves Domésticas , China/epidemiologia , Vírus da Influenza A/genética
4.
Anal Chem ; 95(26): 10034-10043, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37350701

RESUMO

Subcellular compartmentalization ensures orderly and efficient intracellular metabolic activities in eukaryotic life. Investigation of the subcellular metabolome could provide in-depth insight into cellular biological activities. However, the sensitive measurement of multi-subcellular metabolic profiles is still a significant challenge. Herein, we present a comprehensive subcellular fractionation, characterization, and metabolome analysis strategy. First, six subcellular fractions including nuclei, mitochondria, lysosomes, peroxisomes, microsomes, and cytoplasm were generated from a single aliquot of liver homogenate. Then, a dansyl-labeling-assisted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring 151 amino/phenol- or carboxyl-containing metabolites in the subcellular fractions was established and validated. Last, the strategy was applied to a rat model of carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The metabolic profile of individual organelles was compared with that of the liver. Interestingly, many unique changes were observed specifically in organelles, while the liver failed to capture these changes. This result indicates that metabolic investigation at the tissue level might lead to erroneous results due to the leveling effect. Our study demonstrates a feasible approach for the broad-spectrum-targeted metabolic profiling of multi-subcellular fractions, which can be of great use in driving our further understanding of intracellular metabolic activities in various physical and pathological conditions.


Assuntos
Metaboloma , Espectrometria de Massas em Tandem , Animais , Ratos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Metabolômica/métodos , Núcleo Celular , Marcação por Isótopo
5.
Small ; 19(23): e2207201, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36899444

RESUMO

Insufficienct T lymphocyte infiltration and unresponsiveness to immune checkpoint blockade therapy are still major difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). Although econazole has shown promise in inhibiting PDAC growth, its poor bioavailability and water solubility limit its potential as a clinical therapy for PDAC. Furthermore, the synergistic role of econazole and biliverdin in immune checkpoint blockade therapy in PDAC remains elusive and challenging. Herein, a chemo-phototherapy nanoplatform is designed by which econazole and biliverdin can be co-assembled (defined as FBE NPs), which significantly improve the poor water solubility of econazole and enhance the efficacy of PD-L1 checkpoint blockade therapy against PDAC. Mechanistically, econazole and biliverdin are directly released into the acidic cancer microenvironment, to activate immunogenic cell death via biliverdin-induced PTT/PDT and boost the immunotherapeutic response of PD-L1 blockade. In addition, econazole simultaneously enhances PD-L1 expression to sensitize anti-PD-L1 therapy, leading to suppression of distant tumors, long-term immune memory effects, improved dendritic cell maturation, and tumor infiltration of CD8+ T lymphocytes. The combined FBE NPs and α-PDL1 show synergistic antitumor efficacy. Collectively, FBE NPs show excellent biosafety and antitumor efficacy by combining chemo-phototherapy with PD-L1 blockade, which has promising potential in a precision medicine approach as a PDAC treatment strategy.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Econazol/uso terapêutico , Biliverdina/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Imunoterapia , Água , Microambiente Tumoral , Linhagem Celular Tumoral , Neoplasias Pancreáticas
6.
J Virol ; 96(3): e0171721, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-34787451

RESUMO

A 2-year surveillance study of influenza A viruses in migratory birds was conducted to understand the subsequent risk during the migratory seasons in Dandong Yalu River Estuary Coastal Wetland National Nature Reserve, Liaoning Province, China, a major stopover site on the East Asian-Australasian flyway. Overall, we isolated 27 influenza A viruses with multiple subtypes, including H3N8 (n = 2), H4N6 (n = 2), H4N7 (n = 2), H7N4 (n = 9), H7N7 (n = 1), H10N7 (n = 7), and H13N6 (n = 4). Particularly, a novel reassortant influenza A(H7N4) virus was first identified in a woman and her backyard poultry flock in Jiangsu Province, China, posing a serious threat to public health. Here, we describe the genetic characterization and pathogenicity of the nine influenza A(H7N4) isolates. Phylogenetic analysis indicated that complex viral gene flow occurred among Asian countries. We also demonstrated a similar evolutionary trajectory of the surface genes of the A(H7N4) isolates and Jiangsu human-related A(H7N4) viruses. Our A(H7N4) isolates exhibited differing degrees of virulence in mice, suggesting a potential risk to other mammalian species, including humans. We revealed multiple mutations that might affect viral virulence in mice. Our report highlights the importance and need for the long-term surveillance of avian influenza virus in migratory birds combined with domestic poultry surveillance along migratory routes and flyways and, thereby, the development of measures to manage potential health threats. IMPORTANCE The H7 subtype avian influenza viruses, such as H7N2, H7N3, H7N4, H7N7, and H7N9, were documented as being capable of infecting humans, and the H7 subtype low pathogenicity avian influenza viruses are capable of mutating into highly pathogenic avian influenza; therefore, they pose a serious threat to public health. Here, we investigated the evolutionary history, molecular characteristics, and pathogenicity of shorebird-origin influenza A(H7N4) viruses, showing a similar evolutionary trajectory with Jiangsu human A(H7N4) viruses in HA and NA genes. Moreover, our isolates exhibited variable virulence (including moderate virulence) in mice, suggesting a potential risk to other mammalian species, including humans.


Assuntos
Doenças Transmissíveis Emergentes/veterinária , Vírus da Influenza A Subtipo H7N7/classificação , Vírus da Influenza A Subtipo H7N7/genética , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Animais , Evolução Biológica , Aves , China/epidemiologia , Sequência Conservada , Modelos Animais de Doenças , Suscetibilidade a Doenças , Evolução Molecular , Feminino , Camundongos , Mutação , Filogenia , Filogeografia , Matrizes de Pontuação de Posição Específica , RNA Viral , Virulência
7.
J Magn Reson Imaging ; 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37578031

RESUMO

BACKGROUND: Patients undergoing surgery for spinal metastasis are predisposed to hidden blood loss (HBL), which is associated with poor surgical outcomes but unpredictable. PURPOSE: To evaluate the role of MRI-based radiomics models for assess the risk of HBL in patients undergoing spinal metastasis surgery. STUDY TYPE: Retrospective. SUBJECTS: 202 patients (42.6% female) operated on for spinal metastasis with a mean age of 58 ± 11 years were divided into a training (n = 162) and a validation cohort (n = 40). FIELD STRENGTH/SEQUENCE: 1.5T or 3.0T scanners. Sagittal T1-weighted and fat-suppressed T2-weighted imaging sequences. ASSESSMENT: HBL was calculated using the Gross formula. Patients were classified as low and high HBL group, with 1000 mL as the threshold. Radiomics models were constructed with radiomics features. The radiomics score (Radscore) was obtained from the optimal radiomics model. Clinical variables were accessed using univariate and multivariate logistic regression analyses. Independent risk variables were used to build a clinical model. Clinical variables combined with Radscore were used to establish a combined model. STATISTICAL TESTS: Predictive performance was evaluated using area under the curve (AUC), accuracy, sensitivity, specificity, and F1 score. Calibration curves and decision curves analyses were produced to evaluate the accuracy and clinical utility. RESULTS: Among the radiomics models, the fusion (T1WI + FS-T2WI) model demonstrated the highest predictive efficacy (AUC: 0.744, 95% confidence interval [CI]: 0.576-0.914). The Radscore model (AUC: 0.809, 95% CI: 0.664-0.954) performs slightly better than the clinical model (AUC: 0.721, 95% CI: 0.524-0.918; P = 0.418) and the combined model (AUC: 0.752, 95% CI: 0.593-0.911; P = 0.178). DATA CONCLUSION: A radiomics model may serve as a promising assessment tool for the risk of HBL in patients undergoing spinal metastasis surgery, and guide perioperative planning to improve surgical outcomes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

8.
Liver Int ; 43(4): 928-944, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36776105

RESUMO

BACKGROUND AND AIMS: Human hepatocellular carcinoma (HCC) is an aggressive malignancy with poor clinical outcomes. There are limited therapeutic options for those diagnosed with terminal HCC and therefore incorporating novel agents into standard-of-care regimens is urgently needed. In contrast to de novo drug discovery, the strategy of repurposing compounds initially designed to treat animals might yield substantial advantages in terms of efficacy and safety. Given the evidence for the clinical efficacy of toceranib phosphate (TOC) against canine carcinomas, we aimed to investigate its therapeutic effect on human HCC. METHODS: The antitumor effects of TOC were evaluated using human HCC cell lines and cell-line-derived xenograft models. Changes in autophagic response upon TOC exposure were quantified through immunoblotting and immunofluorescence analysis. The role of TOC-triggered autophagy was addressed via pharmacological and genetic inhibition. RESULTS: We demonstrated TOC exhibited potent antitumor activity against human HCC cells by stimulating apoptosis in vitro and in vivo by a concomitant increase in autophagic flux. Blocking the TOC-triggered autophagy inhibited cellular proliferation and decreased tumour burden, indicating a protective role of autophagy against TOC-mediated HCC cell death. This role played by TOC-induced autophagy was further linked to the inactivation of the Akt/mTOR pathway that could be attributed to the upregulation of Cyr61. Moreover, treatment with sorafenib plus TOC resulted in pronounced synergistic effects on HCC cells. CONCLUSION: Our results elucidate a newly identified therapeutic potential of TOC in treating HCC, sparking a growing interest in repurposing such canine drugs for human use.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Cães , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Autofagia/genética
9.
Eur Radiol ; 33(7): 4812-4821, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36735042

RESUMO

OBJECTIVE: To investigate the correlation of conventional MRI, DCE-MRI and clinical features with pain response after stereotactic body radiotherapy (SBRT) in patients with spinal metastases and establish a pain response prediction model. METHODS: Patients with spinal metastases who received SBRT in our hospital from July 2018 to April 2022 consecutively were enrolled. All patients underwent conventional MRI and DCE-MRI before treatment. Pain was assessed before treatment and in the third month after treatment, and the patients were divided into pain-response and no-pain-response groups. A multivariate logistic regression model was constructed to obtain the odds ratio and 95% confidence interval (CI) for each variable. C-index was used to evaluate the model's discrimination performance. RESULTS: Overall, 112 independent spinal lesions in 89 patients were included. There were 73 (65.2%) and 39 (34.8%) lesions in the pain-response and no-pain-response groups, respectively. Multivariate analysis showed that the number of treated lesions, pretreatment pain score, Karnofsky performance status score, Bilsky grade, and the DCE-MRI quantitative parameter Ktrans were independent predictors of post-SBRT pain response in patients with spinal metastases. The discrimination performance of the prediction model was good; the C index was 0.806 (95% CI: 0.721-0.891), and the corrected C-index was 0.754. CONCLUSION: Some imaging and clinical features correlated with post-SBRT pain response in patients with spinal metastases. The model based on these characteristics has a good predictive value and can provide valuable information for clinical decision-making. KEY POINTS: • SBRT can accurately irradiate spinal metastases with ablative doses. • Predicting the post-SBRT pain response has important clinical implications. • The prediction models established based on clinical and MRI features have good performance.


Assuntos
Radiocirurgia , Neoplasias da Coluna Vertebral , Humanos , Resultado do Tratamento , Radiocirurgia/efeitos adversos , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/radioterapia , Coluna Vertebral , Imageamento por Ressonância Magnética
10.
Emerg Infect Dis ; 28(5): 1039-1042, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35447054

RESUMO

During October 2020, we identified 13 highly pathogenic avian influenza A(H5N8) clade 2.3.4.4b viruses from wild ducks in Ningxia, China. These viruses were genetically related to H5N8 viruses circulating mainly in poultry in Europe during early 2020. We also determined movements of H5N8 virus‒infected wild ducks and evidence for spreading of viruses.


Assuntos
Vírus da Influenza A Subtipo H5N8 , Influenza Aviária , Influenza Humana , Doenças das Aves Domésticas , Animais , Animais Selvagens , Aves , Patos , Humanos , Vírus da Influenza A Subtipo H5N8/genética , Influenza Aviária/epidemiologia , Filogenia
11.
Emerg Infect Dis ; 27(6): 1732-1734, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33834988

RESUMO

In October 2020, highly pathogenic avian influenza A(H5N8) viruses were detected in 2 dead swans in Inner Mongolia, China. Genetic analysis showed that the H5N8 isolates belong to clade 2.3.4.4b and that the isolates cluster with the H5N8 viruses isolated in Eurasia in the fall of 2020.


Assuntos
Vírus da Influenza A Subtipo H5N8 , Influenza Aviária , Animais , Animais Selvagens , Aves , China , Filogenia
12.
Hepatology ; 71(5): 1643-1659, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31509262

RESUMO

BACKGROUND AND AIMS: Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down-regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis. APPROACH AND RESULTS: Functional studies indicate that PDLIM1 knockdown induces epithelial-to-mesenchymal transition (EMT) of HCC cells, elevates their invasive capacity, and promotes metastasis in vitro and in vivo, whereas overexpression of PDLIM1 exhibits opposite phenotypes. Mechanistically, PDLIM1 competitively binds to the cytoskeleton cross-linking protein alpha-actinin 4 (ACTN4), leading to the disassociation of ACTN4 from F-actin, thus preventing F-actin overgrowth. In contrast, loss of PDLIM1 induces excessive F-actin formation, resulting in dephosphorylation of large tumor suppressor kinase 1 and activation of Yes-associated protein, thereby promoting HCC metastasis. Moreover, Asn145 (N145) of PDLIM1 is critical for its interaction with ACTN4, and N145A mutation abolishes its regulatory function in Hippo signaling and HCC metastasis. CONCLUSIONS: Our findings indicate that PDLIM1 suppresses HCC metastasis by modulating Hippo signaling, suggesting that PDLIM1 may be a potential prognostic marker for metastatic HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundário , Proteínas com Domínio LIM/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fatores de Transcrição/metabolismo , Actinina/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Via de Sinalização Hippo , Humanos , Proteínas com Domínio LIM/genética , Neoplasias Hepáticas/genética , Metástase Neoplásica , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Proteínas de Sinalização YAP
13.
Chem Res Toxicol ; 34(7): 1759-1768, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34110802

RESUMO

Cisplatin is a chemotherapeutic agent widely employed in the treatment of various solid tumors. However, its use is often restricted by acute kidney injury (AKI) which is the dose-limiting adverse effect of cisplatin. While numerous studies aiming to alleviate the AKI have been conducted, there are no effective remedies in clinical practice. In this paper, a targeted metabolomics study was performed to reveal the potential relationship between tryptophan metabolism and cisplatin-induced AKI. A chemical derivatization integrated liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) approach was utilized to quantify 29 metabolites in the tryptophan pathway in rat kidney medulla and cortex after cisplatin administration. Results showed that tryptophan metabolism was remarkably disturbed both in the medulla and cortex after cisplatin administration. We also found that the tryptophan pathway in the medulla was more sensitive to cisplatin exposure compared with the cortex. Among these metabolites, indoxyl sulfate was focused for further study because it accumulated most significantly in the kidney cortex and medulla in a dose-dependent manner. A function verification study proved that chlormethiazole, a widely used CYP2E1 inhibitor, could reduce the production of indoxyl sulfate in the liver and attenuate cisplatin-induced AKI in rats. In conclusion, our study depicted the tryptophan pathway in cisplatin-induced AKI for the first time and demonstrated tryptophan metabolism is closely associated with the renal toxicity caused by cisplatin, which can be of great use for the discovery of renal toxicity attenuating remedies.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Triptofano/metabolismo , Injúria Renal Aguda/metabolismo , Animais , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
14.
Prostate ; 80(4): 352-364, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31905248

RESUMO

BACKGROUND: Signal regulatory protein ß1 (SIRPB1) is a signal regulatory protein member of the immunoglobulin superfamily and is capable of modulating receptor tyrosine kinase-coupled signaling. Copy number variations at the SIRPB1 locus were previously reported to associate with prostate cancer aggressiveness in patients, however, the role of SIRPB1 in prostate carcinogenesis is unknown. METHODS: Fluorescence in situ hybridization and laser-capture microdissection coupled with quantitative polymerase chain reaction was utilized to determine SIRPB1 gene amplification and messenger RNA expression in prostate cancer specimens. The effect of knockdown of SIRPB1 by RNA interference in PC3 prostate cancer cells on cell growth in colony formation assays and cell mobility in wound-healing, transwell assays, and cell cycle analysis was determined. Overexpression of SIPRB1 in C4-2 prostate cancer cells on cell migration, invasion, colony formation and cell cycle progression and tumor take rate in xenografts was also determined. Western blot assay of potential downstream SIRPB1 pathways was also performed. RESULTS: SIRPB1 gene amplification was detected in up to 37.5% of prostate cancer specimens based on in silico analysis of several publicly available datasets. SIRPB1 gene amplification and overexpression were detected in prostate cancer specimens. The knockdown of SIRPB1 significantly suppressed cell growth in colony formation assays and cell mobility. SIRPB1 knockdown also induced cell cycle arrest during the G0 /G1 phase and enhancement of apoptosis. Conversely, overexpression of SIPRB1 in C4-2 prostate cancer cells significantly enhanced cell migration, invasion, colony formation, and cell cycle progression and increased C4-2 xenograft tumor take rate in nude mice. Finally, this study presented evidence for SIRPB1 regulation of Akt phosphorylation and showed that Akt inhibition could abolish SIRPB1 stimulation of prostate cancer cell proliferation. CONCLUSIONS: These results suggest that SIRPB1 is a potential oncogene capable of activating Akt signaling to stimulate prostate cancer proliferation and could be a biomarker for patients at risk of developing aggressive prostate cancer.


Assuntos
Moléculas de Adesão de Célula Nervosa/genética , Moléculas de Adesão de Célula Nervosa/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Ativação Enzimática , Amplificação de Genes , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Moléculas de Adesão de Célula Nervosa/biossíntese , Células PC-3 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais
15.
Microb Pathog ; 135: 103613, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254602

RESUMO

Avian influenza viruses (AIVs) in wild birds pose a pandemic threat to humans and to the poultry industry. To assess AIV and AIV antibody prevalence in wild birds in China, a systematic review and meta-analysis were conducted. We searched PubMed, Google Scholar, Cochrane Library, Clinical Trial, VIP, CNKI, and WANFANG for published papers related to the prevalence of AIVs and their associated antibodies in wild birds in China from Mar. 10, 2005 to Sept. 20, 2018. Repeat studies, reviews, and other host studies were excluded, as well as those with inconsistent data, incomplete information, or only prevalence data or data from outside of mainland China. In total, data from 28 publications were compiled and analyzed. Based on out meta-analysis, the pooled prevalence of AIVs in wild birds in China was found to be 2.5% (571/23,024), and the pooled prevalence of AIV antibodies was 26.5% (1,210/4,566). The pooled prevalence of AIVs was significantly higher in wild birds from Central China (5.5%, 271/4, 955) compared to all other regions and the pooled prevalence of AIV antibodies was significantly in wild birds from South China (56.8%, 92/162) in comparison to all other regions. The prevalence of both AIVs and AIV antibodies in Anseriformes were higher compared to non-Anseriformes. In addition, the largest number of studies found in this review were on the HA subtypes of AIVs (H5, H7, and H9) and their associated antibodies. In summary, our findings suggest that the prevalence of AIVs and their antibodies in wild birds vary among regions and species of wild bird. Thus, further monitoring of the prevalence of AIVs and their antibodies in wild birds in China is necessary and should be used for guiding powerful and effective regulatory measures that will prevent the spread of AIVs across species.


Assuntos
Animais Selvagens/virologia , Anticorpos/sangue , Aves/virologia , Vírus da Influenza A , Influenza Aviária/epidemiologia , Influenza Aviária/imunologia , Animais , China/epidemiologia , Bases de Dados Factuais , Pandemias , Prevalência
16.
Microb Pathog ; 128: 136-138, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30602126

RESUMO

Toxoplasma gondii is an obligate intracellular apicomplexan parasite that can infect almost all homoiothermal animals, including domestic raccoon dogs (Nyctereutes procyonoides). However, related reports on T. gondii infection in domestic raccoon dogs were limited in China. Therefore, a serological investigation was undertaken to investigate the seroprevalence and risk factors for T. gondii infection in domestic raccoon dogs. A total of 962 serum samples were collected from Jilin, Liaoning, Heilongjiang and Hebei provinces, northern China between April 2016 and November 2017, and were detected by the indirect hemagglutination test (IHA). The seroprevalence of T. gondii infection was 7.28% in the overall surveyed raccoon dogs by IHA, which was different among the four provinces ranging from 6.54% to 7.57%. The seroprevalence of T. gondii infection in male and female raccoon dogs was 6.62% and 7.79%, respectively. Based on statistical analysis, age was regarded as an important risk factor for T. gondii infection in raccoon dogs in this study (P < 0.05). This study reported the seroprevalence and risk factors of T. gondii infection in domestic raccoon dogs in northern China, which provided essential data for prevention and control of T. gondii infection in raccoon dogs in Jilin province, Liaoning province, Heilongjiang province and Hebei province.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/epidemiologia , Cães Guaxinins/parasitologia , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/imunologia , Fatores Etários , Animais , Animais Domésticos/parasitologia , China/epidemiologia , Doenças do Cão/sangue , Doenças do Cão/parasitologia , Cães , Feminino , Testes de Hemaglutinação , Masculino , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Sexuais , Toxoplasmose Animal/sangue , Toxoplasmose Animal/parasitologia
17.
Chem Res Toxicol ; 32(12): 2411-2421, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31682104

RESUMO

Renal injury is the main adverse reaction of cisplatin, and many traditional Chinese medicines (TCMs) were proven active against renal toxicity. Here, an integrated metabolomics and network pharmacology strategy was proposed to discover active TCM ingredients for the alleviation of cisplatin nephrotoxicity. First, by interrogating the Human Metabolome Database (HMDB) we collected targets connected to 149 cisplatin nephrotoxicity-related metabolites. Second, targets of kidney damage were obtained from the Therapeutic Target Database (TTD), PharmGKB, Online Mendelian Inheritance in Man (OMIM), and Genetic Association Database (GAD). Common targets of both dysregulated metabolites and kidney damage were then used for TCM active ingredient screening by applying the network pharmacology approach. Eventually, 22 ingredients passed screening criteria, and their antinephrotoxicity activity was assessed in human kidney tubular epithelial (HK2) cells. As a result, 14 ingredients were found to be effective, in which kaempferol showed relatively better activity. Further metabolomics analysis revealed that kaempferol exerted an antinephrotoxicity effect in rats by regulating amino acid, pyrimidine, and purine metabolism as well as lipid metabolism. Collectively, this proposed integrated strategy would promote the transformation of metabolomics research in the field of drug pair discovery for the purpose of reduced toxicity and increased efficiency.


Assuntos
Cisplatino/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Transformada , Medicamentos de Ervas Chinesas/análise , Humanos , Quempferóis/análise , Quempferóis/farmacologia , Rim/patologia , Metabolômica/métodos , Farmacologia/métodos , Substâncias Protetoras/análise , Ratos
18.
BMC Vet Res ; 15(1): 410, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730490

RESUMO

BACKGROUND: Little information about the prevalence of gastrointestinal parasites in yaks (Bos grunniens) in northwest China is available. Therefore, the objective of the study was to quantify faecal egg counts of gastrointestinal parasites (helminths and coccidia) in free-range yaks from Gannan Tibetan Autonomous Prefecture, Gansu Province, Northwest China. RESULTS: Parasites were detected in 290 of 733 (39.56%) faecal samples. The results showed that Strongylidae, Trichuris spp. and Eimeria spp. were detected all year round, Strongyloides papillosus was detected in autumn and summer, and Nematodirus spp. was detected in both autumn and spring. In contrast, Fasciola spp. was only detected in spring. The prevalence rates of parasitic infections in different seasons were significantly different. CONCLUSIONS: To our knowledge, this is the first investigation of gastrointestinal parasites in yaks (Bos grunniens) in Gansu, China. The results demonstrated a high prevalence of gastrointestinal parasitic infections, specifically GN infections, in yaks in GTAP and these infections can cause economic losses to the local cattle industry.


Assuntos
Doenças dos Bovinos/parasitologia , Helmintíase Animal/parasitologia , Enteropatias Parasitárias/veterinária , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , China/epidemiologia , Fezes/parasitologia , Helmintíase Animal/epidemiologia , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Contagem de Ovos de Parasitas/veterinária , Prevalência
19.
BMC Infect Dis ; 18(1): 430, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157863

RESUMO

BACKGROUND: Pet ownership in China has been steadily increasing over recent years. However, the risk of pet-associated zoonotic infection with the protozoan parasite Toxoplasma gondii remains poorly defined. METHODS: In a cross-sectional survey, we have determined the seroprevalence of T. gondii infection in pet dogs and cats, and pet owners. Serum samples were collected from 360 pets and 460 corresponding pet owners between March 2016 to June 2017, from Shandong province, eastern China. Sera from the animals were tested for anti-T. gondii antibodies using an indirect haemagglutination assay (IHA) and from the pet owners using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Antibodies against T. gondii were detected in 67 of 360 (18.61%) pets. Seroprevalence of T. gondii in pet cats and dogs was 21.67% and 15.56%, respectively. IgG and IgM antibodies were detected in 79 (17.17%) and 4 (0.87%) of pet owners, respectively; with a total of 83 of 460 (18.04%) pet owners testing seropositive for T. gondii. Our seroprevalence data also suggest that cat owners in general and female pet owners in particular could face a higher risk of acquiring T. gondii infection. CONCLUSIONS: Significant levels of anti-T. gondii antibodies were detected in the pets and their owners in Shandong province, eastern China, indicating a potential zoonotic risk. Prophylactic measures should be implemented to reduce the risk of pet owner's exposure to T. gondii infection.


Assuntos
Anticorpos Antiprotozoários/sangue , Animais de Estimação/sangue , Toxoplasma/imunologia , Toxoplasmose Animal/sangue , Toxoplasmose Animal/epidemiologia , Toxoplasmose/sangue , Toxoplasmose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Gatos/sangue , Gatos/imunologia , China/epidemiologia , Estudos Transversais , Cães/sangue , Cães/imunologia , Cães/parasitologia , Ensaio de Imunoadsorção Enzimática , Feminino , Vínculo Humano-Animal , Humanos , Masculino , Pessoa de Meia-Idade , Animais de Estimação/imunologia , Animais de Estimação/parasitologia , Prevalência , Estudos Soroepidemiológicos , Toxoplasmose/imunologia , Toxoplasmose Animal/imunologia , Adulto Jovem , Zoonoses/sangue , Zoonoses/epidemiologia , Zoonoses/imunologia
20.
J Med Virol ; 89(11): 1988-1994, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28577316

RESUMO

Hepatitis E virus (HEV) infection is a serious public health concern in developing countries. China is regarded as an HEV-endemic area, but epidemiological data for HEV among different nationalities is limited. This study was conducted to estimate the seroprevalence and risk factors of HEV infection in Koreans (n = 520), Manchus (n = 303), Mongols (n = 217), and Hans (n = 802) in Eastern and Northeastern China between 2013 and 2015. A total of 366 (19.87%) out of 1842 samples were seropositive for IgG or IgM HEV-antibodies detected by enzyme-linked immunoassays. Among these groups, the Mongols had the highest seroprevalence of HEV infection (25.35%, 55/217), followed by the Koreans (23.65%, 123/520), the Manchus (19.80%, 60/303), and the Hans (15.96%, 128/802). Multiple analysis showed that the gender, consumption of raw/undercooked meat, source of drinking water, residence area, and age were significantly associated with HEV infection in four ethnic groups. The present results indicated that HEV infection was prevalent in Mongols, Koreans, Manchus, and Hans in the surveyed regions, which demonstrated the higher risk of transmitting HEV in multiple nationalities in Eastern and Northeastern China.


Assuntos
Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Hepatite E/etnologia , Estudos Soroepidemiológicos , Adolescente , Adulto , Idoso , Povo Asiático , Criança , Pré-Escolar , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Etnicidade , Feminino , Hepatite E/imunologia , Hepatite E/virologia , Vírus da Hepatite E/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
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