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1.
Front Vet Sci ; 11: 1395327, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887536

RESUMO

Equine influenza (EI) is a severe infectious disease that causes huge economic losses to the horse industry. Spatial epidemiology technology can explore the spatiotemporal distribution characteristics and occurrence risks of infectious diseases, it has played an important role in the prevention and control of major infectious diseases in humans and animals. For the first time, this study conducted a systematic analysis of the spatiotemporal distribution of EI using SaTScan software and investigated the important environmental variables and suitable areas for EI occurrence using the Maxent model. A total of 517 occurrences of EI from 2005 to 2022 were evaluated, and 14 significant spatiotemporal clusters were identified. Furthermore, a Maxent model was successfully established with high prediction accuracy (AUC = 0.920 ± 0.008). The results indicated that annual average ultraviolet radiation, horse density, and precipitation of the coldest quarter were the three most important environmental variables affecting EI occurrence. The suitable areas for EI occurrence are widely distributed across all continents, especially in Asia (India, Mongolia, and China) and the Americas (Brazil, Uruguay, USA, and Mexico). In the future, these suitable areas will expand and move eastward. The largest expansion is predicted under SSP126 scenarios, while the opposite trend will be observed under SSP585 scenarios. This study presents the spatial epidemiological characteristics of EI for the first time. The results could provide valuable scientific insights that can effectively inform prevention and control strategies in regions at risk of EI worldwide.

2.
ACS Appl Mater Interfaces ; 16(12): 14467-14473, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38491944

RESUMO

Surface-enhanced Raman scattering (SERS) has great potential in biological analysis due to its specificity, sensitivity, and non-invasive nature. However, effectively extracting Raman information and avoiding spectral overlapping from biological background interference remain major challenges. In this study, we developed a background-free SERS nanosensor consisting of gold nanobipyramids (Au NBPs) core-Prussian blue (PB) shell (Au NBPs@PB), for endogenous H2S detection. The PB shell degraded quickly upon contact with endogenous H2S, generating a unique Raman signal response in the Raman silent region (1800-2800 cm-1). By taking advantage of the high SERS-activity of Au NBPs and H2S-triggered spectral changes of PB, these SERS nanosensors effectively minimize potential biological interferences. The nanosensor exhibits a detection range of 2.0 µM to 250 µM and a limit of detection (LOD) of 0.34 µM, with good reproducibility and minimal interference. We successfully applied this background-free SERS platform to monitor endogenous H2S concentrations in human serum samples with satisfied results.


Assuntos
Ferrocianetos , Sulfeto de Hidrogênio , Nanopartículas Metálicas , Humanos , Sulfeto de Hidrogênio/análise , Ouro , Reprodutibilidade dos Testes , Análise Espectral Raman/métodos
3.
Biomed Pharmacother ; 174: 116491, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537582

RESUMO

Non-alcoholic fatty liver disease (NAFLD) represents a complex complication of type 2 diabetes mellitus (T2DM). Oxymatrine (OMT) is an alkaloid extracted from Sophora flavescens with broad pharmacological effects. However, there is currently a lack of research on OMT in the field of NAFLD. The present study aimed to explore the effects and underlying mechanisms of oxymatrine in treating T2DM with NAFLD. The T2DM mice model was induced by high-fat diet (HFD) combined with streptozotocin (STZ) injection in male C57BL/6 J mice. Animals were randomly divided into four groups (n = 8): Control group, DC group, OMT-L group (45 mg/kg i.g.), and OMT-H group (90 mg/kg, i.g.). The drug was administered once a day for 8 weeks. In addition, HepG2 hepatocytes were incubated with palmitic acid (PA) to establish a fatty liver cell model. Treated with OMT, the body weight and fasting blood glucose (FBG) of DC mice were reduced and the liver organ coefficient was significantly optimized. Meanwhile, OMT markedly enhanced the activities of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and also reduced malondialdehyde (MDA) levels. These biochemical alterations were accompanied by noticeable improvements in liver histopathology. Furthermore, OMT down-regulated the expression of NOD-like receptor protein 3 (NLRP3), interleukin-1ß (IL-1ß), transforming growth factor-ß1 (TGF-ß1) and collagen I significantly, highlighting its potential in modulating inflammatory and fibrotic pathways. In conclusion, OMT improved liver impairment effectively in diabetic mice by suppressing oxidative stress, inflammation and fibrosis. These results suggest that OMT may represent a novel therapy for NAFLD with diabetes.


Assuntos
Alcaloides , Dieta Hiperlipídica , Matrinas , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Quinolizinas , Estreptozocina , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Quinolizinas/farmacologia , Alcaloides/farmacologia , Dieta Hiperlipídica/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Humanos , Camundongos , Células Hep G2 , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Inflamação/tratamento farmacológico , Inflamação/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Glicemia/efeitos dos fármacos , Glicemia/metabolismo
4.
Biosens Bioelectron ; 241: 115706, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37757512

RESUMO

The detection of specific DNA sequences and the identification of single nucleotide polymorphisms are important for disease diagnosis. Herein, by combining the high specificity of the base-stacking effect with the high reproducibility of bovine serum albumin (BSA) modified electrodes and the high loading performance of DNA nanoclews (DNA NCs), a novel sandwich-type electrochemiluminescence (ECL) biosensor is reported for the highly specific detection of HPV16 (chosen as the model target). The capture probes are loaded by BSA carrier platforms modified on the gold electrode surface to improve reproducibility. DNA NCs loaded with a large amount of Ru(phen)32+ worked as signal probes. The template probe is composed of the complementary strand of the target and two free nucleic acid anchors at the head and tail. In the presence of the target DNA, the template probes can form stacked base pairs with target, generating high base-stacking energy. This results in the shorter free anchors of template probes being able to bind to the capture and signal probes. This eventually forms a sandwich structure that allows Ru(phen)32+ to be near the electrode surface, producing an ECL signal. There is a linear relationship between the signal and the target concentration range from 10 fM to 100 pM, with a detection limit of 5.03 fM (S/N=3). Moreover, the base-stacking effect has single base recognition ability for base pairs, effectively avoiding false positive signals. The results of this strategy for clinical samples are consistent with classical methods.


Assuntos
Técnicas Biossensoriais , Técnicas Biossensoriais/métodos , Papillomavirus Humano 16/genética , Soroalbumina Bovina , Reprodutibilidade dos Testes , Medições Luminescentes/métodos , DNA/química , Técnicas Eletroquímicas/métodos , Limite de Detecção , Ouro/química
5.
Eur J Pharmacol ; 939: 175423, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36509132

RESUMO

Salvianolic acid B (Sal B) is a component obtained from Salvia miltiorrhiza and is empirically used for liver diseases. The TGF-ß/Smad and Hippo/YAP pathways may interact with each other in hepatocellular carcinoma (HCC). Previously, we found that Sal B mediates the TGF-ß/Smad pathway in mice and delays liver fibrosis-carcinoma progression by promoting the conversion of pSmad3L to pSmad3C, but the effect of Sal B on the Hippo/YAP pathway has not been determined. Therefore, we used a DEN/CCl4/C2H5OH-induced liver cancer model in mice to analyze liver index and tumor incidence, detect AST and ALT serological markers, observe liver pathology and the number of Ki67-positive cells to evaluate the anti-HCC effect of Sal B in vivo. We used a TGF-ß1-induced HepG2 cell model, and applied an MST1/2 inhibitor, XMU-MP-1, to detect the changes in pSmad3C/pSmad3L signaling induced by MST1/2 inhibition. Sal B significantly inhibited tumorigenesis in DEN/CCl4/C2H5OH-induced mice in vivo, and suppressed the growth of HepG2 cells by inhibiting cell proliferation and migration in vitro. Here, our study also validated the role of Sal B in reversing XMU-MP-1-induced proliferation and migration of HepG2 cells in vitro. Most importantly, we elucidated for the first time the potential mechanism of Sal B against HCC via the Hippo/YAP pathway, which may be specifically related to upregulation of MST1 and inhibition of its downstream effector protein YAP. In conclusion, these findings indicate that Sal B possesses anti- HCC effects both in vivo and in vitro by regulating the Hippo/YAP pathway and promoting pSmad3L to pSmad3C synchronously.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Hippo
6.
Biomed Pharmacother ; 153: 113424, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076545

RESUMO

Diabetic nephropathy (DN) is one of the most serious microvascular complications following diabetes mellitus (DM). Ferulic acid (FA), a phenolic acid widely found in plants, has multiple pharmacological effects such as anti-oxidation, anti-inflammation and anti-tumor. However, the current research on FA in the field of DN is insufficient. The present study aimed to explore the nephroprotective effect of FA on DN in mice and reveal its underlying mechanism. DN was induced by high-fat diet (HFD) combined with streptozotocin (STZ) injection in male C57BL/6J mice. Animals were randomly divided into four groups (n = 8): Control group, DN group, FA group (200 mg/kg FA, i.g.) and valsartan (VAL) group (12 mg/kg VAL, i.g.). The drug was administered once a day for 8 weeks. Treated with FA, the body weight and fasting blood glucose (FBG) of DN mice were reduced and the renal organ coefficient was significantly optimized. Meanwhile, FA decreased levels of 24-h urine protein excretion (24-h UP) in urine and blood urea nitrogen (BUN), creatinine (Cr) in serum, reduced levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in serum. In addition, FA promoted light chain 3 (LC3) expression markedly, and inhibited the expressions of p62, NOD-like receptor family pyrin domain containing 3 (NLRP3) and interleukin-1ß (IL-1ß) in renal tissues. In conclusion, FA played a positive role in alleviating renal injury in HFD/STZ-induced DN mice by enhancing autophagy and suppressing excessive inflammation.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Animais , Autofagia , Colesterol/metabolismo , Ácidos Cumáricos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Inflamação/metabolismo , Rim , Camundongos , Camundongos Endogâmicos C57BL , Estreptozocina/farmacologia
7.
J Econ Entomol ; 115(4): 1240-1250, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35583241

RESUMO

Cycloxaprid, 9-((6-chloropyrid-3-yl)methyl)-4-nitro-8-oxa-10,11-dihydroimidazo-[2,3-a]-bicyclo-[3,2,1]-oct-3-ene, is a cis-configuration neonicotinoid insecticide. In the present study, the lethal and sublethal effect of cycloxaprid against Formosan subterranean termites, Coptotermes formosanus Shiraki (Blattodea: Rhinotermitidae), was evaluated and compared with fipronil. Toxicity bioassays showed that cycloxaprid had slightly lower toxicity than fipronil. The minimum cycloxaprid concentration in sand and soil that causes 100% termite mortality was 100 ppm. Similar to fipronil, cycloxaprid significantly reduced wood consumption and tunneling activities of termites. In the tunneling-choice tests, termite tunneling activity measured in both length and area was significantly lower in sand treated with cycloxaprid (10 or 100 ppm) than that in untreated sand. In the aggregation-choice tests, cycloxaprid exhibited inhibition to termite aggregation starting from 100 ppm. In addition, cycloxaprid exhibited significant horizontal transfer effect at 10 ppm. In conclusion, our study showed that cycloxaprid is slightly less toxic than fipronil and more repellent to C. formosanus than fipronil. Future studies are needed to evaluate the effectiveness of cycloxaprid against subterranean termites in the field.


Assuntos
Baratas , Inseticidas , Isópteros , Animais , Compostos Heterocíclicos com 3 Anéis , Inseticidas/farmacologia , Isópteros/fisiologia , Piridinas/farmacologia , Areia
8.
Pest Manag Sci ; 78(6): 2228-2239, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35192738

RESUMO

BACKGROUND: The red imported fire ant, Solenopsis invicta Buren, is a significant urban, agricultural, and medical pest with a wide distribution in the world. Surface or mound treatment using contact insecticide is one of the main methods to control S. invicta. In the present study, cycloxaprid, a newly discovered neonicotinoid insecticide, was evaluated for S. invicta control and compared with two referent insecticides, imidacloprid and bifenthrin. RESULTS: Surfaces or sand treated with cycloxaprid, imidacloprid, or bifenthrin caused high mortality of S. invicta workers, and the action of cycloxaprid or imidacloprid was slower than bifenthrin. Like imidacloprid and bifenthrin, cycloxaprid can be horizontally transferred from corpses or live donor ants to recipient ants. In addition, cycloxaprid- or imidacloprid-treated surfaces significantly induced the activities of acetylcholinesterase (AChE) and detoxification enzymes; nevertheless, they had no significant effect on the foraging behaviors of S. invicta workers. Also, sand treated with cycloxaprid or imidacloprid did not negatively affect the digging activities of ants. Interestingly, S. invicta workers excavated significantly more sand containing 0.01 mg/kg cycloxaprid than untreated sand in the no-choice digging bioassays. In addition, extensive nesting activities (sand excavation and stacking) were observed in the flowerpots containing untreated sand or sand treated with cycloxaprid or imidacloprid. On the contrary, bifenthrin significantly reduced the foraging, digging, and nesting activities of S. invicta workers. CONCLUSION: Cycloxaprid is a slow-acting and nonrepellent insecticide against S. invicta workers, and its contact and horizontal toxicities are slightly higher than imidacloprid. © 2022 Society of Chemical Industry.


Assuntos
Formigas , Inseticidas , Acetilcolinesterase , Animais , Compostos Heterocíclicos com 3 Anéis , Humanos , Inseticidas/farmacologia , Piridinas , Areia
9.
Anal Chim Acta ; 1197: 339496, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35168728

RESUMO

16S ribosomal-RNA (16S rRNA) is often used as an ultrasensitive marker for Chlamydia trachomatis (CT) detection because of its species specificity and high copy number in CT. Robust methods for 16S rRNA detection must be developed to realize the early diagnosis of CT infections. In this work, a highly reproducible and sensitive electrochemical biosensor based on duplex-specific nuclease (DSN)-assisted target-responsive DNA hydrogels and bovine serum albumin (BSA) carrier platform for CT detection was developed. Target rRNA can trigger the DNA hydrogel response, which causes it to be repeatedly cleaved by DSN, ultimately leading to the release of a large amount of horseradish peroxidase-labelled streptavidin (SA-HRP) embedded in the hydrogel beforehand. The released SA-HRP was stably captured by the capture probes that were orderly loaded at the gold electrode with the help of a BSA layer. Then, SA-HRP catalyzed the redox reaction of 3,3',5,5'-tetramethylbenzidine and H2O2, producing a current signal that can be detected. The current signal was proportional to the concentration of CT 16S rRNA from 10 fM to 25 pM with a detection limit of 5.8 fM (S/N = 3). The signal conversion function of the DNA hydrogel avoids the instability of nonhomogeneous nucleic acid hybridization on the gold electrode surface, and combined with optimization by BSA for capture probe modification, this electrochemical biosensor is highly reproducible with a relative standard deviation of 4.3% for the detection of 10 samples of the same concentration. The proposed strategy provides a highly reproducible and sensitive detection method for the extensive screening of CT.


Assuntos
Técnicas Biossensoriais , Soroalbumina Bovina , Chlamydia trachomatis/genética , DNA , Técnicas Eletroquímicas , Ouro , Hidrogéis , Peróxido de Hidrogênio , Limite de Detecção , RNA Ribossômico 16S
10.
Naunyn Schmiedebergs Arch Pharmacol ; 395(4): 397-405, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35092472

RESUMO

Astragaloside IV (AS-IV), one of the major compounds extract from Astragalus membranaceus, has shown attractive anti-cancer effects in certain malignancies. Oxidative stress (OS) is considered as a crucial factor in promoting the progression of hepatocellular carcinoma (HCC). In response to OS, nuclear factor erythroid 2-related factor 2 (Nrf2) upregulates and induces heme oxygenase 1 (HO-1) to combat oxidative damages. The phosphorylation of the COOH-terminal of Smad3 (pSmad3C) activates p21 to resist HCC progression, while the phosphorylation of the linker region of Smad3 (pSmad3L) up-regulates c-Myc transcription to exert promoting effect towards HCC. This study aimed to explore whether AS-IV suppresses migration and invasion of human hepatoma HuH-7 cells by regulating Nrf2/HO-1 and TGF-ß1/Smad3 pathways. HuH-7 cells were induced with TGF-ß1 (9 or 40 pM) to establish HCC model in vitro and pretreated with AS-IV at different concentration (5, 10, and 20 µM) for 24 h. Cell proliferation, migration, invasion, and intracellular reactive oxygen species (ROS) of HuH-7 cells were measured. The expression of Nrf2, pSmad3C, Nrf2/pNrf2, HO-1, pSmad3C/3L, c-Myc, and p21 were detected. Exposure of HuH-7 cells to TGF-ß1 enhanced the cell proliferation, migration, invasion, and ROS production. Pretreatment with AS-IV (5, 10, and 20 µM) significantly reduced the cell proliferation, migration, invasion, and ROS production in HuH-7 cells. Furthermore, AS-IV increased the expressions of Nrf2/pNrf2, HO-1, pSmad3C, and p21, meanwhile reduced the expressions of pSmad3L and c-Myc. In conclusion, our study suggested that AS-IV inhibit HuH-7 cells migration and invasion, which related to activate Nrf2/HO-1 pathway, up-regulation pSmad3C/p21 pathway, and down-regulation pSmad3L/c-Myc pathway. The present research supports the notion that AS-IV may be a latent agent for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Saponinas , Transdução de Sinais , Proteína Smad3/metabolismo , Triterpenos
11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(5): 453-457, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37088751

RESUMO

OBJECTIVE: To investigate the protective effects and possible mechanisms of ferulic acid on diabetic nephropathy by observing the effects of ferulic acid on the level of inflammation and autophagy in glomerular mesangial cells induced by high glucose. METHODS: SV40 MES 13 cells were cultured and randomly divided into the following groups: normal group (Control, 5.6 mmol/L glucose), mannitol group (Man, 30 mmol/L mannitol), high glucose group (HG, 30 mmol/L glucose), ferulic acid group (FA, 30 mmol/L glucose + 12.5, 25, 50, 100, 200 µmol/L ferulic acid), and the proliferation of SV40 MES 13 cells in each group was observed by MTT method. The levels of tumour necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and interleukin 1ß(IL-1ß)in cell supernatant were determined by enzyme-linked immunosorbent assay (ELISA). The expressions of NLRP3, IL-1ß, LC3-II/I and p62 proteins in SV40 MES 13 cells were detected by Western blot. RESULTS: ①The proliferative activity of SV40 MES 13 cells was significantly higher in the HG group compared to the control group (P<0.01), while the proliferative activity of SV40 MES 13 cells was decreased to different degrees in the FA group compared to the HG group (P<0.05~0.01). ②Compared to the control group, the levels of TNF-α, MCP-1 and IL-1ß were increased significantly in the cell supernatant of HG group (P<0.01). Compared with the HG group, the levels of TNF-α, MCP-1 and IL-1ß were decreased significantly in the FA group (P<0.01). ③Compared with the control group, LC3-II/Ⅰ protein expression was decreased in the HG group, while the levels of p62, NLRP3 and IL-1ß protein were increased significantly (P<0.01). Compared with the HG group, the expression of LC3-II/Ⅰ protein was elevated significantly (P<0.05) in the FA group, while the levels of p62, NLRP3 and IL-1ß protein in the FA group were decreased significantly (P< 0.01). CONCLUSION: FA can inhibit the abnormal proliferation of SV40 MES 13 cells induced by high glucose. FA can protect glomerular mesangial cells by inhibiting inflammation and increasing the level of autophagy.


Assuntos
Células Mesangiais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Masculino , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Inflamação , Glucose/metabolismo , Manitol/metabolismo , Manitol/farmacologia
12.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 475-479, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34816655

RESUMO

Objective: To investigate the effects of different doses of ketoconazole (KCZ) on the physiological functions of the liver and testis in Kunming mice. Methods: Forty male Kunming mice were randomly divided into four groups (n=10): normal group, KCZ low-dose group (30 mg/kg), medium-dose group (50 mg/kg), and high-dose group (70 mg/kg). The mice in the drug groups were injected subcutaneously (0.1 ml/10 g) with the corresponding dose of KCZ once a day, and the concentrations of KCZ in the KCZ low, middle, and high dose groups were 3 mg/ml, 5 mg/ml and 7 mg/ml respectively, and the normal group was injected with the same amount of normal saline for 3 weeks. The activities of aspartate transaminase (AST) and alanine aminotransferase (ALT) in serum, and γ-glutamyl transpeptidase (γ-GT), lactate dehydrogenase (LDH) and acid phosphatase (ACP) in testicular tissue were measured. HE staining was used to observe the pathological changes of the liver and testis. Results: Compared with the normal group, the activities of AST and ALT were increased significantly (P<0.01), and the activities of γ-GT, ACP and LDH were decreased markedly in KCZ groups (P<0.01). KCZ could affect the above indexes in a dose-dependent manner. HE staining showed that the hepatocytes were denatured, arranged loosely, and the cytoplasm was light in color. The lumen of the seminiferous tubules of the testis were enlarged, and the number of spermatogenic cells and sperm at all levels were decreased. Conclusion: KCZ could cause physiological function damage and pathological histological changes of the liver and testis, increase the levels of liver transaminase, reduce the activities of testicular specific enzymes of mice. Besides, the degree of damage was increased with the increase of dose.


Assuntos
Cetoconazol , Fígado/efeitos dos fármacos , Testículo , Animais , Hepatócitos , Cetoconazol/farmacologia , Fígado/patologia , Masculino , Camundongos , Testículo/efeitos dos fármacos , Testículo/patologia
13.
J Ethnopharmacol ; 279: 114350, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34157326

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus is a medicinal herb used in China for the prevention and treatment of diseases such as diabetes and cancer. As one of the main active ingredients of astragalus, Astragaloside IV (AS-IV) has a wide range of pharmacological effects, including anti-inflammation and anti-cancer effects. AIM OF THE STUDY: Different phosphorylated forms of Smad3 differentially regulate the progression of hepatic carcinoma. The phosphorylation of the COOH-terminal of Smad3 (pSmad3C) and activation of the Nrf2/HO-1 pathway inhibits hepatic carcinoma, while phosphorylation of the linker region of Smad3 (pSmad3L) promotes progression. Thus, pSmad3C/3L and Nrf2/HO-1 pathways are potential targets for drug of anti-cancer development. AS-IV is anti-apoptotic and can inhibit hepatocellular carcinoma cell (HCC) proliferation, invasion, and tumor growth in nude mice. However, it is not clear whether AS-IV has a therapeutic effect on inhibiting the progression of primary liver cancer by regulating the pSmad3C/3L and Nrf2/HO-1 pathway. The purpose of this study is to investigate whether AS-IV inhibits hepatocellular carcinoma by regulating pSmad3C/3L and Nrf2/HO-1 pathway. MATERIALS AND METHODS: primary liver cancer in mice induced by DEN/CCl4/C2H5OH (DCC) and HSC-T6/HepG2 cell models activated by TGF-ß1 was investigated for the mechanisms of AS-IV. In vivo assays included liver biopsy, histopathology and post-mortem analysis included immunohistochemistry, immunofluorescent, and Western blotting analysis, and in vitro assays included immunofluorescent, and Western blotting analysis. RESULTS: AS-IV significantly inhibited the development of primary liver cancer, reflecting improved liver biopsy, histopathology. The incidence and multiplicity of primary liver cancer were markedly decreased by AS-IV treatment at the 20th week. AS-IV had observable effects on the TGF-ß1/Smad and Nrf2/HO-1 expression in vivo, especially up-regulated pSmad3C, pNrf2, HO-1, and NQO1, while it down-regulated pSmad2C, pSmad2L, pSmad3L, PAI-1, and α-SMA at the 12th week and the 20th week. Furthermore, in vitro analysis further confirmed that AS-IV regulated the expression of pSmad3C/3L and Nrf2/HO-1 pathway in HSC-T6 and HepG2 cells activated by TGF-ß1. CONCLUSION: AS-IV administration delays the occurrence of primary liver cancer by continually suppressing the development of fibrosis, the mechanism of the therapeutic effect involving the regulation of the pSmad3C/3L and Nrf2/HO-1 pathways, especially in regulation reversibility and antagonism of pSmad3C and pSmad3L and promoting the phosphorylation of Nrf2.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Astrágalo/química , Linhagem Celular , Heme Oxigenase-1/metabolismo , Células Hep G2 , Humanos , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Fator 2 Relacionado a NF-E2/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Saponinas/isolamento & purificação , Proteína Smad3/metabolismo , Triterpenos/isolamento & purificação
14.
Naunyn Schmiedebergs Arch Pharmacol ; 394(8): 1779-1786, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34191114

RESUMO

Current researches have confirmed that Smads, mediators of TGF-ß signaling, are strictly controlled by domain-specific site phosphorylation in the process of hepatic disease. Usually, Smad3 phospho-isoform pSmad3L and pSmad3C are reversible and antagonistic; pSmad2L/C could act together with pSmad3L by stimulating PAI-1 expression and ECM synthesis to transmit fibrogenic signals. Our recent study found that pSmad3C mutation is supposed to perform a vigorous role on the early phase of liver injury and abates salvianolic acid B's anti-hepatic fibrotic-carcinogenesis. However, whether pSmad3C mutation expedites pSmad2L/C-mediated signaling transduction during hepatic fibrogenesis remains vague. Presently, Smad3 gene C-terminal phosphorylation site mutation heterozygote (pSmad3C+/-) mice were constructed to probe if and how pSmad3C retards CCl4-induced hepatic fibrogenesis by inhibiting pSmad2L/C-mediated signaling transduction. Twelve 6-week-old pSmad3C+/- C57BL/6J mice were intraperitoneally injection with CCl4 for 6 weeks to induce liver fibrogenesis. Results showed that pSmad3C mutation aggravates the relative liver weight, biochemical parameters, collagenous fibers and fibrotic septa formation, contributes to fibrogenesis in HT-CCl4 mice. Furthermore, fibrotic-related proteins TGF-ß1, pSmad2C, pSmad2L, and PAI-1 were also increased in CCl4-induced pSmad3C+/- mice. These results suggest that pSmad3C mutation exacerbates hepatic fibrogenesis which relates to intensifying pSmad2L/C-mediated signaling transduction.


Assuntos
Cirrose Hepática/fisiopatologia , Fosforilação/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Animais , Tetracloreto de Carbono , Modelos Animais de Doenças , Cirrose Hepática/genética , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Serpina E2/metabolismo , Transdução de Sinais/genética , Fator de Crescimento Transformador beta1/metabolismo
15.
ISME J ; 15(9): 2723-2737, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33772107

RESUMO

Beneficial rhizobacteria promote plant growth and protect plants against phytopathogens. Effective colonization on plant roots is critical for the rhizobacteria to exert beneficial activities. How bacteria migrate swiftly in the soil of semisolid or solid nature remains unclear. Here we report that sucrose, a disaccharide ubiquitously deployed by photosynthetic plants for fixed carbon transport and storage, and abundantly secreted from plant roots, promotes solid surface motility (SSM) and root colonization by Bacillus subtilis through a previously uncharacterized mechanism. Sucrose induces robust SSM by triggering a signaling cascade, first through extracellular synthesis of polymeric levan, which in turn stimulates strong production of surfactin and hyper-flagellation of the cells. B. subtilis poorly colonizes the roots of Arabidopsis thaliana mutants deficient in root-exudation of sucrose, while exogenously added sucrose selectively shapes the rhizomicrobiome associated with the tomato plant roots, promoting specifically bacilli and pseudomonad. We propose that sucrose activates a signaling cascade to trigger SSM and promote rhizosphere colonization by B. subtilis. Our findings also suggest a practicable approach to boost prevalence of beneficial Bacillus species in plant protection.


Assuntos
Arabidopsis , Bacillus subtilis , Bacillus subtilis/genética , Raízes de Plantas , Rizosfera , Sacarose
16.
Food Funct ; 12(3): 1241-1251, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33433547

RESUMO

Diabetic nephropathy (DN) is one of the complex and severe complications of diabetes mellitus (DM). Icariin (ICA) is a flavonoid extracted from the leaves and stems of Herba epimedii with a wide range of pharmacological effects, such as anti-osteoporosis, anti-fibrosis, anti-aging, anti-inflammation and antioxidation. The purpose of our study was to explore the renal protective effect of ICA on DN in mice and its possible mechanisms. ICR mice were exposed to STZ-induced DN. The kidney organ coefficient of mice was computed. 24 h UP in urine was measured. Serum FBG, Cr and BUN were detected. The content of MDA and the activities of SOD, CAT and GSH-Px in renal tissues were tested. HE staining, PAS staining, PASM staining and transmission electron microscopy were used to observe renal pathological changes. Furthermore, TLR4, p-NF-κB p65, TNF-α and IL-6 of renal tissues were assayed by immunohistochemistry and western blotting. Our results indicated that ICA observably optimized the renal organ coefficient, reduced the level of 24 h UP in urine, decreased the content of Cr, BUN in serum and MDA in renal tissues, promoted the activities of SOD, CAT and GSH-Px in renal tissues, and ameliorated pathological lesions of kidneys noticeably. Besides, ICA inhibited the expressions of TLR4, p-NF-κB p65, TNF-α and IL-6 remarkably in renal tissues. ICA, which might lighten the renal inflammatory response by suppressing the TLR4/NF-κB signal pathway, played a protective role in kidneys of STZ-induced DN mice.


Assuntos
Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Flavonoides/farmacologia , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Flavonoides/química , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética
17.
Pest Manag Sci ; 77(4): 1971-1980, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33314506

RESUMO

BACKGROUND: An over-the-counter medicine product of China known as essential balm effectively repelled red imported fire ants, Solenopsis invicta Buren. However, it was not clear which chemical component(s) accounted for the repellency, and whether they would effectively repel S. invicta in the field. RESULTS: Five components, eucalyptol, camphor, menthol, methyl salicylate, and eugenol, were identified in essential balm using gas chromatography-mass spectrometry (GC-MS). Each component elicited concentration-dependent electroantennography (EAG) response. Under field conditions, all components showed repellency against foraging ants. Interestingly, foraging ants managed to access the food items placed on a surface smeared with eucalyptol, camphor, menthol, or methyl salicylate by depositing soil particles on the surface and then walking on soil particles. However, they failed to do so when the surface was smeared with eugenol. Repellency of eugenol lasted for > 24 h, which was much longer than that of the other four components of essential balm and is comparable to that of N,N-diethyl-m-toluamide (DEET), the standard for insect repellants. CONCLUSION: Olfactory response of S. invicta to all five components of the essential balm was confirmed. Each component showed repellency against S. invicta workers in the field. However, only eugenol significantly suppressed both foraging and particle-covering behavior within 24 h. The repellent effect of eugenol lasted much longer than the other four components. Particle-covering behavior has been largely ignored in studying fire ant repellants. Our study demonstrated that it is necessary to consider such behaviors in ant repellent bioassays in the future. © 2020 Society of Chemical Industry.


Assuntos
Formigas , Repelentes de Insetos , Animais , Cânfora , China , Eucaliptol , Humanos , Repelentes de Insetos/farmacologia
18.
ACS Appl Mater Interfaces ; 13(1): 298-305, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33382593

RESUMO

Most DNA-based electrochemiluminescence (ECL) biosensors are established through the self-assembly of thiolated single-stranded DNA (ssDNA) probes on the Au electrode surface. Because of this random assembly process, a significant discrepancy exists in the distribution of a modified DNA film on different electrodes, which greatly affects the reproducibility of a biosensor. In this study, a porous bovine serum albumin (BSA) layer was first modified on the electrode surface, which can improve the position distribution and spatial orientation of the self-assembly ssDNA probe. It was then coupled with hyperbranched rolling circle amplification to develop the high-reproducibility-and-sensitivity ECL biosensor for human papillomavirus 16 E6 and E7 oncogene detection. In the presence of the target DNA, the surface of the electrode accumulates abundant amplified products through reaction, which contain double-stranded DNA (dsDNA) fragments of different lengths, followed by plentiful dichlorotris (1,10-phenanthroline) ruthenium(II) hydrate (Ru(phen)32+, acting as an ECL indicator) insertion into grooves of dsDNA fragments, and a strong signal can be detected. There is a linear relationship between the signal and the target concentration range from 10 fM to 15 pM, and the detection limit is 7.6 fM (S/N = 3). After the BSA modification step, the relative standard deviation was reduced from 9.20 to 3.96%, thereby achieving good reproducibility. The proposed ECL strategy provides a new method for constructing high-reproducibility-and-sensitivity ECL biosensors.


Assuntos
Técnicas Biossensoriais/métodos , Papillomavirus Humano 16/isolamento & purificação , Proteínas Oncogênicas Virais/análise , Proteínas E7 de Papillomavirus/análise , Proteínas Repressoras/análise , Soroalbumina Bovina/química , Animais , Bovinos , Colo do Útero/virologia , Sondas de DNA/química , Sondas de DNA/genética , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Técnicas Eletroquímicas/métodos , Feminino , Papillomavirus Humano 16/química , Humanos , Limite de Detecção , Substâncias Luminescentes , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico , Proteínas Oncogênicas Virais/genética , Compostos Organometálicos/química , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/diagnóstico , Fenantrolinas/química , Proteínas Repressoras/genética , Reprodutibilidade dos Testes , Rutênio/química
19.
Environ Toxicol ; 35(2): 268-276, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31696645

RESUMO

Testicular damage is the anomaly that will often accompany diabetes mellitus. Thus, this study aimed to investigate the role that total flavonoids of Epimedium (TFE) played against streptozotocin (STZ)-induced diabetic testicular dysfunction and to elucidate the mechanism of action. The diabetic rat model was induced by vein injection of STZ in healthy rats. Thirty male healthy Spraque-Dawley rats were randomly divided into following groups: the control group, the diabetic group, and the diabetic + TFE group. Gastrointestinal administration begins at fifth week of TFE for 6 weeks. After TFE administration, all animals were euthanized. Testicular tissue samples and blood samples of rats were collected for histopathological examination and for determination of levels of various biomarkers including blood glucose, testosterone, testicular enzymes, and oxidative stress indicators. All testes were weighted to calculate the testicular organ index. Hematoxylin-eosin staining was used for observing the testis and epididymis pathological changes. Protein expression (monocyte chemoattractant protein-1, transforming growth factor-beta-1, interleukin-6, and 3-beta-hydroxysteroid dehydrogenase) was detected by immunohistochemistry and western blot techniques. There was a significant difference in the changes between the diabetes group and the control group. As a result of treat with TFE, the blood glucose decreased but there was no significant difference, and other indicators showed significant improvement. TFE may protect against STZ-induced testicular injury by suppressing inflammation and oxidative stress.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Epimedium/química , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Biomarcadores/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/imunologia , Epididimo/efeitos dos fármacos , Epididimo/imunologia , Epididimo/patologia , Flavonoides/isolamento & purificação , Inflamação , Masculino , Estresse Oxidativo/imunologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estreptozocina , Testículo/imunologia , Testículo/patologia
20.
Anal Bioanal Chem ; 411(26): 6837-6845, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471682

RESUMO

A new near-infrared-based photothermal immunosensing strategy was developed for the sensitive and feasible detection of human chorionic gonadotropin (HCG) by use of a Prussian blue nanoparticle-based photothermal conversion system. Prussian blue nanospheres synthesized by the one-pot method were used for the labeling of anti-HCG detection antibody. A sandwich-type immunoreaction was initially conducted on a monoclonal anti-HCG antibody-coated microplate with a nanoparticle-labeled signal antibody. Accompanying formation of the sandwiched immunocomplex, Prussian blue nanospheres caused photothermal conversion under 980-nm laser irradiation, thereby resulting in an increase of the temperature of the detection system measured by a portable digital thermometer. The properties and factors influencing the analytical performance of the photothermal immunoassay were studied in detail. Under the optimal conditions, the Prussian blue nanoparticle-based photothermal immunoassay exhibited good temperature responses relative to target HCG concentrations within the dynamic range of 0.01-100 ng mL-1 at a low detection limit of 5.8 pg mL-1. This system also displayed good anti-interference behavior with regard to other cancer biomarkers, good reproducibility, and relatively long storage stability. The method accuracy was evaluated for analysis of human serum specimens, giving results that matched well with those obtained with a commercial HCG enzyme-linked immunosorbent assay kit. Importantly, this protocol is promising for advanced development of photothermal immunoassays. Graphical abstract.


Assuntos
Anticorpos Imobilizados/química , Gonadotropina Coriônica/sangue , Ferrocianetos/química , Imunoensaio/métodos , Nanopartículas/química , Técnicas Biossensoriais/métodos , Temperatura Alta , Humanos , Limite de Detecção , Processos Fotoquímicos
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