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The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I2 = 98.7%, p = 0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species.
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Animales Salvajes , COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/virología , Animales , Animales Salvajes/virología , Prevalencia , Humanos , Factores de RiesgoRESUMEN
Nucleoprotein (NP) is a key structural protein of influenza ribonucleoprotein complexes and is central to viral RNA packing and trafficking. NP also determines the sensitivity of influenza to myxovirus resistance protein 1 (MxA), an innate immunity factor that restricts influenza replication. A few critical MxA-resistant mutations have been identified in NP, including the highly conserved proline-283 substitution. This essential proline-283 substitution impairs influenza growth, a fitness defect that becomes particularly prominent at febrile temperature (39°C) when host chaperones are depleted. Here, we biophysically characterize proline-283 NP and serine-283 NP to test whether the fitness defect is caused by the proline-283 substitution introducing folding defects. We show that the proline-283 substitution changes the folding pathway of NP, making NP more aggregation prone during folding, but does not alter the native structure of the protein. These findings suggest that influenza has evolved to hijack host chaperones to promote the folding of otherwise biophysically incompetent viral proteins that enable innate immune system escape.
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Gripe Humana , Humanos , Proteínas del Núcleo Viral/genética , Proteínas del Núcleo Viral/química , Proteínas del Núcleo Viral/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de la Nucleocápside/metabolismo , Proteínas de Resistencia a MixovirusRESUMEN
BACKGROUND: As an oncovirus, EBV is associated with multiple cancers, including solid tumors and hematological malignancies. EBV methylation plays an important role in regulating tumor occurrence. However, the EBV methylation profiles in EBV-associated tumor tissues are poorly understood. RESULTS: In this study, EBV methylation capture sequencing was conducted in several different tumor tissue samples, including NPC, EBVaGC, lung LELC and parotid LELC. Besides, EBV capture sequencing and following qMSP were performed on nasopharyngeal brushing samples from NPC and nasal NKTCL patients. Our results showed that the EBV genome among different types of tumors displayed specific methylation patterns. Among the four types of tumors from epithelial origin (NPC, EBVaGC, lung LELC and parotid LELC), the most significant differences were found between EBVaGC and the others. For example, in EBVaGC, all CpG sites within 1,44,189-1,45,136 bp of the EBV genome sequence on gene RPMS1 were hyper-methylated compared to the others. Differently, significant differences of EBV CpG sites, particularly those located on gene BILF2, were observed between NPC and nasal NKTCL patients in nasopharyngeal brushing samples. Further, the methylated level of BILF2 was further detected using qMSP, and a diagnostic model distinguishing NPC and nasal NKTCL was established. The AUC of the model was 0.9801 (95% CI 0.9524-1.0000), with the sensitivity and specificity of 98.81% (95% CI 93.63-99.94%) and 76.92% (95% CI 49.74-91.82%), respectively. CONCLUSIONS: Our study reveals more clues for further understanding the pathogenesis of EBV, and provides a possibility for distinguishing EBV-related tumor by detecting specific EBV CpG sites.
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Carcinoma , Linfoma de Células T , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Herpesvirus Humano 4/genética , Metilación de ADN , Carcinoma/genética , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , Linfoma de Células T/genéticaRESUMEN
Nucleoprotein (NP) is a key structural protein of influenza ribonucleoprotein complexes and is central to viral RNA packing and trafficking. In human cells, the interferon induced Myxovirus resistance protein 1 (MxA) binds to NP and restricts influenza replication. This selection pressure has caused NP to evolve a few critical MxA-resistant mutations, particularly the highly conserved Pro283 substitution. Previous work showed that this essential Pro283 substitution impairs influenza growth, and the fitness defect becomes particularly prominent at febrile temperature (39 °C) when host chaperones are depleted. Here, we biophysically characterize Pro283 NP and Ser283 NP to test if the fitness defect is owing to Pro283 substitution introducing folding defects. We show that the Pro283 substitution changes the folding pathway of NP without altering the native structure, making NP more aggregation prone during folding. These findings suggest that influenza has evolved to hijack host chaperones to promote the folding of otherwise biophysically incompetent viral proteins that enable innate immune system escape. Teaser: Pro283 substitution in flu nucleoprotein introduces folding defects, and makes influenza uniquely dependent on host chaperones.
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PURPOSE: To investigate the predictors of early diagnosis of thrombus of autogenous arteriovenous fistula (aAVF). METHODS: The included patients were divided into the thrombus group with aAVF failure or thrombosis and the control group with good internal fistula function. The general data of the patients, including age, sex, diabetes mellitus, were collected. Platelets (PLT), platelet crit (P-LCR), platelet distribution width (PDW), mean platelet volume (MPV), homocysteine (HCY), and other biochemical data were collected. The predictors of thrombus of aAVF were obtained by the t test and logistic regression analysis, and receiver operating characteristic (ROC) curve analysis was used to compare the area under the ROC curve (AUC) between the combined predictors and the original indicators. The optimal critical value was determined when the Youden index reached its maximum value, and the sensitivity, specificity, accuracy, diagnostic index, and so on were calculated. Finally, prediction was performed by substituting each value in individually. RESULTS: PLT, PDW, P-LCR, MPV, and HCY showed significant differences between two groups (p < 0.05). Logistic regression analysis showed that, for PLT (OR = 1.014, 95% CI 1.006-1.022, p = 0.01), PDW (OR = 1.295, 95% CI 1.009-1.661, p = 0.042), P-LCR (OR = 1.230, 95% CI 1.089-1.389, p = 0.001), MPV (OR = 1.696, 95% CI 1.101-2.613, p = 0.017), and HCY (OR = 1.332, 95% CI 1.182-1.502, p = 0.01), the difference was significant; PLT, PDW, P-LCR, MPV, and HCY were positively correlated with thrombogenesis (p < 0.05). By logistic regression, a group of the five predictors of PLT, PDW, P-LCR, MPV, and HCY was obtained, and the combined predictors were 0.014*PLT + 0.258*PDW + 0.207*P-LCR + 0.528*MPV + 0.287*HCY. The area under the curve of the combined predictor was 0.933, the sensitivity was 92.4%, the specificity was 81.2%, the maximum diagnostic index was 0.736, the diagnostic cutoff point was 21.790, and the accuracy rate was 87%. CONCLUSION: PLT, PDW, P-LCR, MPV, and HCY are predictors of thrombus of aAVF. They can better predict thrombus of aAVF, and the combination of these five indicators is better than a single indicator.
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Danyikangtai powder has a definite therapeutic effect on pancreatitis. However, the internal mechanism is unclear. The purpose of this experiment is to quickly identify the blood components of danyikangtai powder and evaluate its efficacy. 25 blood components were identified by comparing the components with the same mass spectrometry information from in vivo and in vitro samples. The AR42J cells of the pancreatitis model were treated with drug-containing plasma, and the drug efficacy was evaluated by investigating the amylase release rate. This study provides a scientific reference for its pharmacological research and rational clinical application.
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Medicamentos Herbarios Chinos , Pancreatitis , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Polvos , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodosRESUMEN
The sequence space accessible to evolving proteins can be enhanced by cellular chaperones that assist biophysically defective clients in navigating complex folding landscapes. It is also possible, at least in theory, for proteostasis mechanisms that promote strict quality control to greatly constrain accessible protein sequence space. Unfortunately, most efforts to understand how proteostasis mechanisms influence evolution rely on artificial inhibition or genetic knockdown of specific chaperones. The few experiments that perturb quality control pathways also generally modulate the levels of only individual quality control factors. Here, we use chemical genetic strategies to tune proteostasis networks via natural stress response pathways that regulate the levels of entire suites of chaperones and quality control mechanisms. Specifically, we upregulate the unfolded protein response (UPR) to test the hypothesis that the host endoplasmic reticulum (ER) proteostasis network shapes the sequence space accessible to human immunodeficiency virus-1 (HIV-1) envelope (Env) protein. Elucidating factors that enhance or constrain Env sequence space is critical because Env evolves extremely rapidly, yielding HIV strains with antibody- and drug-escape mutations. We find that UPR-mediated upregulation of ER proteostasis factors, particularly those controlled by the IRE1-XBP1s UPR arm, globally reduces Env mutational tolerance. Conserved, functionally important Env regions exhibit the largest decreases in mutational tolerance upon XBP1s induction. Our data indicate that this phenomenon likely reflects strict quality control endowed by XBP1s-mediated remodeling of the ER proteostasis environment. Intriguingly, and in contrast, specific regions of Env, including regions targeted by broadly neutralizing antibodies, display enhanced mutational tolerance when XBP1s is induced, hinting at a role for host proteostasis network hijacking in potentiating antibody escape. These observations reveal a key function for proteostasis networks in decreasing instead of expanding the sequence space accessible to client proteins, while also demonstrating that the host ER proteostasis network profoundly shapes the mutational tolerance of Env in ways that could have important consequences for HIV adaptation.
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Infecciones por VIH , Proteostasis , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico/genética , Infecciones por VIH/metabolismo , Humanos , Chaperonas Moleculares/metabolismo , Respuesta de Proteína DesplegadaRESUMEN
BACKGROUND: A crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. PURPOSE: This study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. METHODS: Streptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aß production pathway and tau phosphorylation kinase cascade were examined in these two models. RESULTS: Sar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aß overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3ß cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aß overproduction was prior to tau hyperphosphorylation in neurons. CONCLUSION: Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aß overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.
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Enfermedad de Alzheimer , Encefalopatías/tratamiento farmacológico , Diabetes Mellitus Experimental , Espirostanos/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Secretasas de la Proteína Precursora del Amiloide , Péptidos beta-Amiloides/metabolismo , Animales , Ácido Aspártico Endopeptidasas , Línea Celular , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucógeno Sintasa Quinasa 3 beta , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , PPAR gamma , Fosforilación , Ratas , Proteínas tau/metabolismoRESUMEN
Diabetes-associated affective disorders are of wide concern, and oxidative stress plays a vital role in the pathological process. This study was to investigate the cerebroprotective effects of hesperetin against anxious and depressive disorders caused by diabetes, exploring the potential mechanisms related to activation of Nrf2/ARE pathway. Streptozotocin-induced diabetic rats were intragastrically administrated with hesperetin (0, 50, and 150 mg/kg) for 10 weeks. Forced swimming test, open field test, and elevated plus maze were used to evaluate the anxiety and depression-like behaviors of rats. The brain was collected for assays of Nrf2/ARE pathway. Moreover, high glucose-cultured SH-SY5Y cells were used to further examine the neuroprotective effects of hesperetin and underlying mechanisms. Hesperetin showed anxiolytic and antidepressant effects in diabetic rats according to the behavior tests, and increased p-Nrf2 in cytoplasm and Nrf2 in nucleus followed by elevations in mRNA levels and protein expression of glyoxalase 1 (Glo-1) and γ-glutamylcysteine synthetase (γ-GCS) in brain, known target genes of Nrf2/ARE signaling. Moreover, hesperetin attenuated high glucose-induced neuronal damages through activation of the classical Nrf2/ARE pathway in SH-SY5Y cells. Further study indicated that PKC inhibition or GSK-3ß activation pretreatment attenuated even abolished the effect of hesperetin on the protein expression of Glo-1 and γ-GCS in high glucose-cultured SH-SY5Y cells. In summary, hesperetin ameliorated diabetes-associated anxiety and depression-like behaviors in rats, which was achieved through activation of the Nrf2/ARE pathway. Furthermore, an increase in nuclear Nrf2 phosphorylation from PKC activation and GSK-3ß inhibition contributed to the activation of Nrf2/ARE pathway by hesperetin.
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Diabetes Mellitus Experimental , Factor 2 Relacionado con NF-E2 , Animales , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Depresión/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hesperidina , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , RatasRESUMEN
Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Espirostanos/farmacología , Animales , Línea Celular , Regulación hacia Abajo , Hipocampo/efectos de los fármacos , Humanos , Inflamasomas/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor PAR-1/genética , Receptor PAR-1/metabolismo , Transducción de Señal/efectos de los fármacos , EstreptozocinaRESUMEN
Ginger, as a food spice, is widely applied due to its extensive effects. Cedrol (CE) found in ginger is a sesquiterpene with anti-inflammatory activity. The objective of this research is to discuss the efficacy of CE on ameliorating rheumatoid arthritis (RA). CE inhibited chronic inflammation and pain in a dose-dependent manner accompanied by rapid onset and long duration. Besides, CE treatment effectively ameliorated the paw edema volume and arthritis score with no significant effect on body weight. Organ index, T-cell and B-cell proliferation, histopathology, and immunohistochemistry demonstrated that CE had immunological enhancement and attenuated RA effects. Remarkably, inhibition of phosphorylated-JAK3 protein, thereby abating the secretion of pro-inflammatory cytokines and inflammation-related mediators, was involved in the potential mechanism of CE efficiency through forming a hydrogen bond with ARG953 and ILE955 in the JAK3 active pocket. At the same time, the pharmacokinetic results showed that the absolute bioavailability of CE at 20, 40, and 80 mg/kg was 30.30, 23.68, and 16.11%, respectively. The current results offered clues for mastering the ameliorated RA of CE and further perfected the effective substance basis on the anti-inflammatory effect of ginger, which was beneficial for further applications.
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Artritis Experimental , Artritis Reumatoide , Zingiber officinale , Animales , Artritis Reumatoide/tratamiento farmacológico , Citocinas , Zingiber officinale/metabolismo , Inflamación/tratamiento farmacológico , Mediadores de Inflamación/metabolismo , Fosforilación , Sesquiterpenos PolicíclicosRESUMEN
BACKGROUND: Sarsasapogenin (Sar) shows good effects on diabetic nephropathy (DN) through inhibition of the NLRP3 inflammasome, yet the potential mechanism is not well known. PURPOSE: This study was designed to explore the regulation of thrombin and/or its receptor protease-activated receptor 1 (PAR-1) on the NLRP3 inflammasome and NF-κB signaling in DN condition, and further expounded the molecular mechanism of Sar on DN. METHODS: Streptozotocin-induced diabetic rats were treated by gavage with Sar (0, 20 and 60 mg/kg) for consecutive 10 weeks. Then urine and serum were collected for protein excretion, creatinine, urea nitrogen, and uric acid assay reflecting renal functions, renal tissue sections for periodic acid-Schiff staining and ki67 expression reflecting cell proliferation, and renal cortex for the NLRP3 inflammasome and NF-κB signaling as well as thrombin/PAR-1 signaling. High glucose-cultured human mesangial cells (HMCs) were used to further investigate the effects and mechanisms of Sar. RESULTS: Sar markedly ameliorated the renal functions and mesangial cell proliferation in diabetic rats, and suppressed activation of the NLRP3 inflammasome and NF-κB in renal cortex. Moreover, Sar remarkably down-regulated PAR-1 in protein and mRNA levels but didn't affect thrombin activity in kidney, although thrombin activity was significantly decreased in the renal cortex of diabetic rats. Meanwhile, high glucose induced activation of the NLRP3 inflammasome and NF-κB, and increased PAR-1 expression while didn't change thrombin activity in HMCs; however, Sar co-treatment ameliorated all the above indices. Further studies demonstrated that PAR-1 knockdown attenuated activation of the NLRP3 inflammasome and NF-κB, and Sar addition strengthened these effects in high glucose-cultured HMCs. CONCLUSION: Sar relieved DN in rat through inhibition of the NLRP3 inflammasome and NF-κB by down-regulating PAR-1 in kidney.
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Nefropatías Diabéticas/tratamiento farmacológico , Células Mesangiales/efectos de los fármacos , Receptor PAR-1/metabolismo , Espirostanos/farmacología , Animales , Glucemia/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Humanos , Inflamasomas/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Células Mesangiales/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Nefritis/tratamiento farmacológico , Nefritis/metabolismo , Ratas Sprague-Dawley , Receptor PAR-1/genética , Trombina/metabolismoRESUMEN
OBJECTIVES: Eurycoma longifolia Jack (Simaroubaceae) is commonly distributed in the Southeast Asia and Indo China, which has been shown to possess antianxiety, antibacterial, anticancer, antifungal, anti-inflammatory, antimalarial and antioxidant biological activities. 14,15ß-dihydroxyklaineanone is a diterpene isolated from E. longifolia Jack, which is cytotoxic against human lung cancer and human breast cancer cell lines. However, the effects and underlying mechanisms of 14,15ß-dihydroxyklaineanone on hepatocellular carcinoma remain unknown. METHODS: Cell viability assay and colony formation assay were used to measure HepG2 cell proliferation. Flow cytometry was used to analyse cell cycle and apoptosis. Wound-healing assay and transwell assay were used to observe cells migration. RNA sequencing and the enrichment of differentially expressed genes (DEGs) in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to find and determine underlying pathways. KEY FINDINGS: We found that 14,15ß-dihydroxyklaineanone inhibited the growth and migration of HepG2 cells but did not induce cell apoptosis. 14,15ß-dihydroxyklaineanone induced S cell cycle arrest by downregulating the expression levels of cyclin A, p-CDK2, cyclin B1, p21, E2F-1 and PCNA. In addition, RNA sequencing showed that 14,15ß-dihydroxyklaineanone regulated MAPK pathway by increasing the expression levels of phosphor-p38. Downregulating of p38 via both p38 inhibitor (SB203580) and p38-siRNA could antagonize the inhibition of cell proliferation and migration and reverse the changes in p-p38, E-cadherin, N-cadherin and PCNA expression induced by 14,15ß-dihydroxyklaineanone treatment. CONCLUSIONS: 14,15ß-dihydroxyklaineanone inhibited cell proliferation and migration through regulating p38 MAPK pathway in HCC cells.
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Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Eurycoma/química , Neoplasias Hepáticas/tratamiento farmacológico , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Regulación hacia Abajo/efectos de los fármacos , Células Hep G2 , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Puntos de Control de la Fase S del Ciclo Celular/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Gestational diabetes mellitus (GDM) is associated with an increased risk of progressing to type 2 DM and cardiovascular disease; however, the pathogenesis is still poorly understood. This study was to investigate roles of thrombin and its receptor protease-activated receptor 1 (PAR-1) and NLRP1 inflammasome in endothelial injury in GDM condition. Umbilical cord and plasma of GDM patients and high glucose (HG) cultured human umbilical vein endothelial cells (HUVECs) were used to examine the pathological changes of these pathways. Meanwhile, ameliorative effects and potential mechanisms of a natural product sarsasapogenin (Sar) were investigated in HUVECs. Thrombin/PAR-1 pathway, advanced glycation endproducts (AGEs) and their receptor (RAGE) axis, and the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome were activated in GDM condition and HG-cultured HUVECs, accompanied by endothelial injury (decreased cell viability and increased lactate dehydrogenase release). Nevertheless, thrombin inhibition or PAR-1 antagonism caused decreases in AGEs formation and RAGE expression in HG-cultured HUVECs, while AGEs inhibition or RAGE antagonism declined PAR-1 expression not thrombin activity. Furthermore, thrombin inhibition or PAR-1 antagonism restrained NLRP1 inflammasome activation in HG-cultured HUVECs; meanwhile, NLRP1 expression and interleukin 18 levels were remarkably reduced in HG-cultured HUVECs after PAR-1 knockdown. Interestingly, Sar co-treatment could suppress thrombin/PAR-1 pathway, NLRP1 inflammasome, and AGEs/RAGE axis. Together, endothelial damages in GDM were likely due to enhanced interaction between AGEs/RAGE axis and thrombin/PAR-1 pathway, followed by NLRP1 inflammasome activation. Moreover, Sar may act as a protective agent against endothelial injury in chronic HG condition.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Diabetes Gestacional/patología , Endotelio Vascular/patología , Inflamasomas/metabolismo , Receptor PAR-1/metabolismo , Trombina/metabolismo , Glucemia/análisis , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Medios de Cultivo/química , Diabetes Gestacional/sangre , Diabetes Gestacional/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Glucosa/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Proteínas NLR , Embarazo , Receptor PAR-1/genética , Transducción de Señal , Espirostanos/farmacología , Cordón Umbilical/efectos de los fármacos , Cordón Umbilical/metabolismoRESUMEN
NAC (NAM, ATAF1/2 and CUC2) proteins are plant-specific transcription factors (TFs) that are important in plant abiotic stress responses. In this study we isolated a NAC gene from Capsicum annuum leaves, designated as CaNAC064. We characterized the amino acid sequence of CaNAC064 and found that it contain conserved domains of the NAC family, including a highly conserved N-terminus domain and a highly variable C-terminus domain. Expression analysis showed that the 40C, 400C, salicylic acid (SA) and abscisic acid (ABA) treatments strongly induced the expression of CaNAC064 through silencing of CaNAC064 in pepper and overexpressing in Arabidopsis. CaNAC064-silenced pepper plants exhibited more serious wilting, higher MDA contents and chilling injury index, lower proline content, and more accumulation of ROS in the leaves after cold stress. The CaNAC064-overexpressing Arabidopsis plants exhibited lower MDA content, chilling injury index and relative electrolyte leakage content as compared to WT plants under cold stress. Transcriptional activation activity analysis indicated that CaNAC064 has transcriptional activation activity in the 691-1071 bp key region. We identified 45 proteins that putatively interact with CaNAC064 using the Yeast Two-Hybrid method. According to the Yeast Two-Hybrid and BIFC results, CaNAC064 interacted with low temperature-induced haplo-proteinase proteins in plant cell. These results suggested that CaNAC064 positively modulates plant cold-tolerance, laying the foundation for future investigations into the role of NACs as regulatory proteins of cold tolerance in plants.
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Capsicum/fisiología , Respuesta al Choque por Frío/genética , Proteínas de Plantas/genética , Factores de Transcripción/genética , Secuencia de Aminoácidos , Capsicum/genética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/fisiología , Alineación de Secuencia , Factores de Transcripción/química , Factores de Transcripción/metabolismoRESUMEN
Due to their unique properties, nanofibers have been widely used in various areas, for example, information industry, pharmaceutical application, environmental industry, textile and clothing, etc. Bubble electrospinning is one of the most important non-needle electrospinning methods for nanofiber fabrication. It usually uses polymer bubbles for the production of nanomaterials by using electrostatic force, flowing air or mechanical force to overcome the surface tension of bubbles. Bubble electrospinning mainly includes bubble electrospinning and blown bubble electrospinning. History of the development of bubble electrospinning is briefly introduced in this article, and the most promising patents on the technology are elucidated. The methods of bubble electrospinning are single bubble electrospinning, porous bubble electrospinning, blown bubble electrospinning, electrostatic-fieldassisted blown bubble spinning and others. These different bubble electrospinning methods are also discussed in this paper.
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Dehydrins play an important role in improving plant resistance to abiotic stresses. In this study, we isolated a dehydrin gene from pepper (Capsicum annuum L.) leaves, designated as CaDHN4. Sub-cellular localization of CaDHN4 was to be found in the nucleus and membrane. To authenticate the function of CaDHN4 in cold- and salt-stress responses and abscisic acid (ABA) sensitivity, we reduced the CaDHN4 expression using virus-induced gene silencing (VIGS), and overexpressed the CaDHN4 in Arabidopsis. We found that silencing of CaDHN4 reduced the growth of pepper seedlings and CaDHN4-silenced plants exhibited more serious wilting, higher electrolyte leakage, and more accumulation of ROS in the leaves compared to pTRV2:00 plants after cold stress, and lower chlorophyll contents and higher electrolyte leakage compared to pTRV2:00 plants under salt stress. However, CaDHN4-overexpressing Arabidopsis plants had higher seed germination rates and post-germination primary root growth, compared to WT plants under salt stress. In response to cold and salt stresses, the CaDHN4-overexpressed Arabidopsis exhibited lower MDA content, and lower relative electrolyte leakage compared to the WT plants. Under ABA treatments, the fresh weight and germination rates of transgenic plants were higher than WT plants. The transgenic Arabidopsis expressing a CaDHN4 promoter displayed a more intense GUS staining than the normal growth conditions under treatment with hormones including ABA, methyl jasmonate (MeJA), and salicylic acid (SA). Our results suggest that CaDHN4 can protect against cold and salt stresses and decrease ABA sensitivity in Arabidopsis.
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Ácido Abscísico/farmacología , Arabidopsis/crecimiento & desarrollo , Capsicum/metabolismo , Proteínas de Plantas/metabolismo , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Capsicum/genética , Núcleo Celular/metabolismo , Respuesta al Choque por Frío , Citoplasma/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Germinación/efectos de los fármacos , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Especies Reactivas de Oxígeno/metabolismo , Estrés SalinoRESUMEN
A series of MgAl hydrotalcite-derived composite oxides were prepared by co-precipitation methods. The effects of calcination temperature, reaction temperature, water vapor volume fraction, and alkali metal addition on the hydrolysis activity of the samples were investigated. The crystal structure, specific surface area, pore structure, and basic position distribution of the composite oxides were characterized using XRD, BET, TPD, and XPS. The results shown that the catalytic activity firstly increased and then decreased with the rise of calcination temperature. Furthermore, the sample that calcined at 650â can achieve the best catalytic activity (complete removal of COS lasted for 180 min). Increasing the reaction temperature improved the catalytic activity, which can present excellent catalytic activity and stability at temperatures above 70â. In addition, the doping of the alkali metal Cs improved the catalytic activity, the complete removal time for COS can be maintained for 480 min.
RESUMEN
Diabetic nephropathy (DN) is one of the most common diabetic complications, and alpha-carbonyl aldehydes and their detoxicating enzyme glyoxalase 1 (Glo-1) play vital roles in pathogenesis of diabetic complications. The aim of this study was to evaluate the renoprotective effects of hesperetin against DN in rats, and to investigate mechanisms from the aspect of Nrf2/ARE/Glo-1 pathway. Streptozotocin-induced diabetic rats were treated orally with hesperetin (50 and 150 mg/kg), or nuclear factor erythroid-derived-2-like 2 (Nrf2) inducer tert-butylhydroquinone (tBHQ, 25 mg/kg) for 10 weeks. Then proteinuria, creatinine, urea nitrogen, and uric acid were assayed for renal functions, fibronectin and collagen IV levels by immunohistochemistry, as well as periodic acid-Schiff staining and electron microscope observation, were used to assess renal morphology. Glo-1 activity, protein, and mRNA levels and the classic Nrf2/ARE pathway were investigated. Moreover, advanced glycation endproducts (AGEs) and its receptor RAGE, interleukin-1ß and tumor necrosis factor-α levels were also examined in the kidney. Hesperetin markedly ameliorated the renal functions and structural changes of diabetic rats, accompanied by up-regulation of Glo-1 as well as inhibition of AGEs/RAGE axis and inflammation. Meanwhile, hesperetin caused significant increases in Nrf2 and p-Nrf2 levels, as well as up-regulation of γ-glutamylcysteine synthetase, a well-known target gene of Nrf2/ARE signaling. Our results demonstrated that hesperetin could slow down the pathological process of DN, and Glo-1 enhancement contributed to the beneficial effects, which was obtained by the activation of Nrf2/ARE pathway.
Asunto(s)
Hidrolasas de Éster Carboxílico/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Hesperidina/farmacología , Lactoilglutatión Liasa/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/metabolismo , Glutamato-Cisteína Ligasa/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Sustancias Protectoras/farmacología , Ratas , Ratas Sprague-Dawley , Estreptozocina/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Alternate forms of drug crystals display different physicochemical properties. These include stability, dissolution rate, bioavailability and solubility, which can affect pharmacokinetics and pharmacodynamics. It is therefore important to compare the crystal forms of cedrol to obtain optimal anti-inflammatory and analgesic effects. This study, for the first time, obtained and reports three novel forms (I-III) of cedrol polymorphs. The three forms of cedrol were recrystallized from seven organic solvents by slow cooling or volatilization and identified by thermal analysis, fourier transform infrared spectroscopy, scanning electron microscopy and powder X-ray diffraction analysis. Form I originated from acetone and cyclohexane. Form II was obtained from ethanol, ethyl acetate, acetonitrile and n-hexane. Form III was recrystallized from methanol. The anti-inflammatory and analgesic activities of the three crystalline forms were evaluated by acetic acid induced writhing in mice, the hot plate method, carrageenan induced mouse paw edema models, Xylene-induced mouse ear edema models and cotton pellet-induced mouse granuloma models. Experimental results revealed that the highest performance was achieved from Form I. These findings are of great significance during the early research study of cedrol polymorphs.