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In this study, a previously undescribed cassane diterpenoid, named caesalpinin JF (1), along with two known cassane diterpenoids caesanine C (2) and tomocinol B (3), was isolated from 95% EtOH extract of the seeds of Caesalpinia sappan Linn. Additionally, three known compounds including pulcherrin R (4), syringaresinol-4'-O-ß-D-glucopyranoside (5) and kaempferol (6) were also identified. The structures of the isolated compounds were elucidated by comprehensive 1D and 2D NMR spectroscopic analyses. Additionally, electronic circular dichroism (ECD) calculation was used to identify the absolute structure of compound 1. Among the isolated compounds, compound 1 displayed a potent anti-neuroinflammation with an IC50 value of 9.87 ± 1.71 µM.
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Mecobalamin is commonly used in the adjuvant intervention of various peripheral nerve injuries. Actin cytoskeleton plays a role in the regeneration of myelin and axon. Therefore, the purpose of this study was to explore the possibility of mecobalamin regulating actin cytoskeleton in repairing nerve injury. In this study, a crush injury on the right sciatic nerve of two groups of rats (12 in each group) was established. The control group was only given normal saline (i.g.), and the intervention group was given mecobalamin 1 mg/kg (i.g.). The rats were sacrificed on 28th day and the injured nerves were collected for proteomics. The result shows that regulation of actin cytoskeleton pathway changed significantly. The expression of protein Vav1 was verified by Western blot and immunofluorescence. In the intervention group, the nerve fiber structure was complete, the axons were dense and symmetrical, and the myelin sheath was compact and uniform in thickness. The positive rate of myelin basic protein and ßâ ¢-tubulin was higher than that in the control group. The findings of the study show that mecobalamin regulates the actin cytoskeleton in the repair of nerve damage and upregulates Vav1 in the regulation of actin cytoskeleton pathway.
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Traumatismos de los Nervios Periféricos , Proteómica , Animales , Axones/metabolismo , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-vav/metabolismo , Ratas , Nervio Ciático/metabolismo , Vitamina B 12/análogos & derivadosRESUMEN
Acquired drug-resistant non-small cell lung cancer (NSCLC) has strong proliferation ability and is prone to epithelial-mesenchymal transition (EMT) and subsequent metastasis. Notch pathway mediates cell survival and EMT and is involved in the induction of multidrug resistance (MDR). ZLDI-8 is an inhibitor of Notch activating/cleaving enzyme ADAM-17 we found before. However, the effects of ZLDI-8 on resistant NSCLC was unclear. Here, we demonstrated for the first time that ZLDI-8 could induce apoptosis in lung cancer, especially in chemotherapy-resistant non-small cell lung cancer cells, and also inhibit migration, invasion and EMT phenotype of drug-resistant lung cancer. ZLDI-8 inhibits the Notch signaling pathway, thereby regulating the expression of survival/apoptosis and EMT-related proteins. Moreover, ZLDI-8 suppresses multidrug-resistant lung cancer xenograft growth in vivo and blocks metastasis in a tail vein injection mice model. Therefore, ZLDI-8 is expected to be an effective agent in the treatment of drug-resistant lung cancer.
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Proteína ADAM17/antagonistas & inhibidores , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Metástasis de la Neoplasia/tratamiento farmacológico , Células A549 , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Transducción de Señal/efectos de los fármacosRESUMEN
Oxidative stress has been confirmed as a contribution to the pathogenesis and pathophysiology of many neurological disorders such as Alzheimer's disease and Parkinson's disease. Caffeoylquinic acids (CQAs) are considered to have anti-oxidative stress ability in a previous study, but the structure-activity relationships (SARs) of CQAs in neuroprotective effects are still unclear. In the present study, we primarily expound the SARs of CQAs in counteracting H2O2-induced injury in SH-SY5Y cells. We found that CQAs (1-10) represented the protection of SH-SY5Y cells against H2O2-induced injury in varying degrees and malonyl groups could obviously increase the anti-oxidative stress ability of CQAs. Intensive studies of 4,5-O-dicaffeoyl-1-O-(malic acid methyl ester)-quinic acid (MDCQA) indicated that the mechanisms could potentially involve activation of endogenous antioxidant enzymes and the regulation of the phosphorylation of MAPKs and AKT. In conclusion, MDCQA could serve as a neuroprotective agent with a potential to attenuate oxidative stress.
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Peróxido de Hidrógeno/toxicidad , Neuroblastoma/patología , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Ácido Quínico/análogos & derivados , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glutatión Peroxidasa/metabolismo , Humanos , Malondialdehído/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neuroblastoma/enzimología , Fármacos Neuroprotectores/química , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ácido Quínico/química , Ácido Quínico/farmacología , Superóxido Dismutasa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Previous studies have examined rotenone toxicity on the human central nervous system, especially in the pathogenesis of Parkinson's disease, but few have investigated the effects of rotenone on the kidney. Here, rotenone-induced nephrotoxicity was evaluated by determining morphological, biochemical, oxidative stress-related, and apoptotic factor alterations in rat renal tissue. Morphological and biochemical analyzes showed that rotenone administration to rats damaged renal tissue. Western blot results revealed that rotenone-induced oxidative damage, causing overproduction of glutathione, malonaldehyde, and reactive oxygen species (ROS), and inhibiting superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Rotenone also decreased the mitochondrial membrane potential and increased voltage-dependent anion channel (VDAC), caspase-3, and caspase-9 protein levels, indicating an association of apoptosis with renal damage. Our results suggest that glutathione, malonaldehyde, and ROS may be signals of rotenone-induced oxidative damage, and that the mitochondrial pathway plays a key role in apoptosis of renal cells following rotenone administration.
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Apoptosis/efectos de los fármacos , Insecticidas/toxicidad , Riñón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Insuficiencia Renal/inducido químicamente , Rotenona/toxicidad , Desacopladores/toxicidad , Animales , Biomarcadores/metabolismo , Relación Dosis-Respuesta a Droga , Glutatión/agonistas , Glutatión/metabolismo , Insecticidas/administración & dosificación , Riñón/metabolismo , Riñón/patología , Dosificación Letal Mediana , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/agonistas , Especies Reactivas de Oxígeno/metabolismo , Insuficiencia Renal/metabolismo , Insuficiencia Renal/patología , Rotenona/administración & dosificación , Pruebas de Toxicidad Aguda , Desacopladores/administración & dosificación , Canales Aniónicos Dependientes del Voltaje/agonistas , Canales Aniónicos Dependientes del Voltaje/metabolismoRESUMEN
Rehmannia glutinosa is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within Rehmannia glutinosa, the compound known as catalpol (CAT) holds significant importance as a bioactive constituent. However, the protective effects of CAT on kidneys, including ameliorative effects on chronic kidney disease - most prominently renal anemia and renal fibrosis - have not been clearly defined. In this study, the kidney injury model of NRK-52E cells and C57BL/6N male mice was prepared by exposure to aristolochic acid I (AA-I), and it was discovered that CAT could ameliorate oxidative stress injury, inflammatory injury, apoptosis, renal anemia, renal fibrosis, and other renal injuries both in vivo and in vitro. Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-[Formula: see text]B inhibitors (PDTC), validated CAT's ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-[Formula: see text]B p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-[Formula: see text]B, and then inhibited the expression of IL-6, p-STAS3, TGF-[Formula: see text]1 protein. Therefore, CAT can regulate Nrf2/NF-[Formula: see text]B signaling pathway, significantly correct renal anemia and renal fibrosis, and is conducive to the preservation of renal structure and function, thus achieving a protective effect on the kidneys.
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OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.
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Escisión del Ganglio Linfático , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Escisión del Ganglio Linfático/métodos , Masculino , Neoplasias Nasofaríngeas/cirugía , Neoplasias Nasofaríngeas/patología , Carcinoma Nasofaríngeo/cirugía , Carcinoma Nasofaríngeo/patología , Femenino , Persona de Mediana Edad , Terapia Recuperativa/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Cadáver , Adulto , Faringe/cirugía , Anciano , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patología , Resultado del TratamientoRESUMEN
AIMS: The chemotherapy drugs for NSCLC often face the consequences of treatment failure due to acquired drug resistance. Tumor chemotherapy resistance is often accompanied by angiogenesis. Here, we aimed to investigate the effect and underlying mechanisms of ADAM-17 inhibitor ZLDI-8 we found before on angiogenesis and vasculogenic mimicry(VM) in drug-resistant NSCLC. MAIN METHODS: The tube formation assay was used to evaluate angiogenesis and VM. Migration and invasion were assessed with transwell assays in the co-culture condition. To explore the underlying mechanisms of how ZLDI-8 inhibited tubes formation, ELISA assay and western blot assay were preformed. The effects of ZLDI-8 on angiogenesis in vivo were investigated in Matrigel plug, CAM and Rat aortic ring assays. KEY FINDINGS: In the present study, ZLDI-8 significantly inhibited the tube formation of human umbilical vein endothelial cells (HUVECs) in either normal medium or in tumor supernatants. Furthermore, ZLDI-8 also inhibited VM tubes formation of A549/Taxol cells. In the co-culture assay, the interaction between lung cancer cells and HUVECs promotes increased cell migration and invasion, while ZLDI-8 eliminates this promotion. Moreover, the VEGF secretion were decreased by ZLDI-8 and the expression of Notch1, Dll4, HIF1α and VEGF were inhibited by ZLDI-8. In addition, ZLDI-8 can inhibit blood vessel formation in the Matrigel plug, CAM and Rat aortic ring assays. SIGNIFICANCE: ZLDI-8 inhibits angiogenesis and VM in drug-resistant NSCLC through suppressing Notch1-HIF1α-VEGF signaling pathway. This study lays the foundation for the discovery of drugs that inhibit angiogenesis and VM in drug resistant NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Ratas , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Células Endoteliales/patología , Factor A de Crecimiento Endotelial Vascular , Línea Celular Tumoral , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patologíaRESUMEN
Since Alzheimer's disease (AD) is a complex and multifactorial neuropathology, the discovery of multi-targeted inhibitors has gradually demonstrated greater therapeutic potential. Neurofibrillary tangles (NFTs), the main neuropathologic hallmarks of AD, are mainly associated with hyperphosphorylation of the microtubule-associated protein Tau. The overexpression of GSK3ß and DYRK1A has been recognized as an important contributor to hyperphosphorylation of Tau, leading to the strategy of using dual-targets inhibitors for the treatment of this disorder. ZDWX-12 and ZDWX-25, as harmine derivatives, were found good inhibition on dual targets in our previous study. Here, we firstly evaluated the inhibition effect of Tau hyperphosphorylation using two compounds by HEK293-Tau P301L cell-based model and okadaic acid (OKA)-induced mouse model. We found that ZDWX-25 was more effective than ZDWX-12. Then, based on comprehensively investigations on ZDWX-25 in vitro and in vivo, 1) the capability of ZDWX-25 to show a reduction in phosphorylation of multiple Tau epitopes in OKA-induced neurodegeneration cell models, and 2) the effect of reduction on NFTs by 3xTg-AD mouse model under administration of ZDWX-25, an orally bioavailable, brain-penetrant dual-targets inhibitor with low toxicity. Our data highlight that ZDWX-25 is a promising drug for treating AD.
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Enfermedad de Alzheimer , Ratones , Animales , Humanos , Enfermedad de Alzheimer/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Células HEK293 , Proteínas tau/metabolismo , Fosforilación , Ácido Ocadaico/metabolismo , Ácido Ocadaico/farmacología , Ácido Ocadaico/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Although people all know that nicotine in tobacco smoke is the key to cause health damage, they ignore the synergistic effect of a large number of Volatile Organic Compounds (VOCs) produced by incomplete tobacco combustion on nicotine or cotinine metabolism. Our aim is to investigate the association between serum VOCs and cotinine in smokers infected with HIV, HBV or HCV. National Health and Nutrition Examination Survey (NHANES 2005-2018) database, including 13,652 nationally representative subjects' sociodemographic characteristics and serological indicators, was used in this study. Smokers living with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) were compared to non-infected population. The correlation between VOCs and cotinine as well as the effects of VOCs on cotinine metabolism were analyzed by Spearman correlation analysis and multivariable logistic regression analysis, respectively. Among HIV, HBV, or HCV infected smokers with the largest exposure dose to tobacco, the intensity of the association between VOCs and cotinine was the strongest. The results of multivariable binary logistic regression showed that high concentrations of 1,2-Dichlorobenzene (OR:1.036, CI:1.009-1.124), Benzene (OR:1.478, CI:1.036-2.292), Carbon Tetrachloride (OR:1.576, CI:1.275-2.085) and 2,5-Dimethylfuran (OR:1.091, CI:1.030-1.157) in blood might be independent risk factors leading to the increase of serum metabolite cotinine in smokers.
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Infecciones por VIH , Hepatitis C , Contaminación por Humo de Tabaco , Compuestos Orgánicos Volátiles , Adulto , Humanos , Cotinina/análisis , Virus de la Hepatitis B/metabolismo , Compuestos Orgánicos Volátiles/análisis , Encuestas Nutricionales , Hepacivirus/metabolismo , Nicotina/análisis , Contaminación por Humo de Tabaco/efectos adversos , VIH/metabolismo , Hepatitis C/epidemiología , Infecciones por VIH/epidemiologíaRESUMEN
Although the smoking rate of human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infected people was much higher than that of the general population, smoking cessation interventions have long been ineffective. We aimed to examine the estimates of prevalence, time-trend, and association of smoking among people living with HIV, HBV, or HCV. This cohort was composed of 32,115 individuals from the NHANES database (1999-2018) and they were collected in the US. The time trend analysis of smoking and quitting rates was conducted using different years of survey follow-up and different infected groups. Multivariable logistic regression analysis was used to identify the risk factors related to smoking behavior of these infected people. Compared to non-infected smokers, infected smokers were more likely to be older (aged 30-39, OR = 9.92, CI 6.07-16.21; aged 40-49,OR = 3.51, CI 2.49-4.94), males (1.99, 1.54-2.55), lower education and economic level (1.78, 1.39-2.29; 2.05, 1.59-2.65), unemployed (1.63, 1.21-2.20), suffering depression (1.35, 1.05-1.72), and drug users (7.65, 5.04-11.59). Taken together, our study showed that these complex psychosocial characteristics and unhealthy behavioral factors might be major independent risk factors for increasing smoking rate and decreasing smoking cessation rate among these infected people.
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Infecciones por VIH , Hepatitis C , Humanos , Adulto , Masculino , Hepacivirus , Virus de la Hepatitis B , Prevalencia , Encuestas Nutricionales , Hepatitis C/epidemiología , Hepatitis C/complicaciones , Fumar/epidemiología , Fumar/psicología , Infecciones por VIH/complicacionesRESUMEN
Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical benefits in Alzheimer's disease (AD). We used liquid chromatography coupled with mass spectrometry to identify 27 unique chemical components of YZD. Analyzing these using network pharmacology and molecular docking models identified 34 potential interacting molecular targets involved in 26 biochemical pathways. When tested in an animal model of AD, the APP/PS1 transgenic mice showed measurable improvements in spatial orientation and memory after the administration of YZD. These improvements coincided with significantly reduced deposition of Aß plaques and tau protein in the hippocampi in the treated animals. In addition, a decreased BACE1 and beta-amyloid levels, a downregulation of the p-GSK-3ß/GSK-3ß, and an upregulation of the PI3K and p-AKT/AKT pathway was seen in YZD treated animals. These in vivo changes validated the involvement of molecular targets and pathways predicted in silico analysis of the chemical components of YZD. This study provides scientific support for the clinical use of YZD and justifies further investigations into its effects in AD. Furthermore, it demonstrates the utility of network pharmacology in elucidating the biochemical mechanisms underlying the beneficial effects of traditional Chinese medicines (TCM).
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Previous studies showed that acetyl-11-keto-beta-boswellic acid (AKBA), the active ingredient in the natural Chinese medicine Boswellia, can stimulate sciatic nerve injury repair via promoting Schwann cell proliferation. However, the underlying molecular mechanism remains poorly understood. In this study, we performed genomic sequencing in a rat model of sciatic nerve crush injury after gastric AKBA administration for 30 days. We found that the phagosome pathway was related to AKBA treatment, and brain-derived neurotrophic factor expression in the neurotrophic factor signaling pathway was also highly up-regulated. We further investigated gene and protein expression changes in the phagosome pathway and neurotrophic factor signaling pathway. Myeloperoxidase expression in the phagosome pathway was markedly decreased, and brain-derived neurotrophic factor, nerve growth factor, and nerve growth factor receptor expression levels in the neurotrophic factor signaling pathway were greatly increased. Additionally, expression levels of the inflammatory factors CD68, interleukin-1ß, pro-interleukin-1ß, and tumor necrosis factor-α were also decreased. Myelin basic protein- and ß3-tubulin-positive expression as well as the axon diameter-to-total nerve diameter ratio in the injured sciatic nerve were also increased. These findings suggest that, at the molecular level, AKBA can increase neurotrophic factor expression through inhibiting myeloperoxidase expression and reducing inflammatory reactions, which could promote myelin sheath and axon regeneration in the injured sciatic nerve.
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Nuclear magnetic resonance (NMR) technology has been applied in soil science due to the characte-ristics of high efficiency, rapidity, no damage to soil structure, and harmlessness to the human body. However, the effect of the presence of paramagnetic materials in soils on the characteristics of NMR signals was still unclear. In this study, we investigated the effects of paramagnetic material on the low field nuclear magnetic (LF-NMR) signals and soil water content measurement in soils with different texture. The results showed that the LF-NMR signal of soil water could reach about 150, while that of all the solid materials including soil minerals, organic matter and microbes was less than 0.3, which was relatively negligible. Compared with the NMR signals produced by solid materials in soils, soil texture and paramagnetic material had stronger impact on the measured LF-NMR signals of soil water. LF-NMR equipment had a relaxation time monitoring blind area, and the loss of NMR signal was mainly due to the acceleration of the relaxation process of hydrogen protons in water by magnetic materials, resulting in extremely fast LF-NMR signals feed back by water in small pores that could not be captured by monitoring equipment. For loamy fluvo-aquic soil (1.2%) and clay loamy black soil (1.3%) with low paramagnetic material contents, the loss of LF-NMR signals was not large, which was linearly related to soil water content. For clayey red soil with high content of clay (45.3%) and paramagnetic materials (4.0%), a part of the LF-NMR signals would be lost in the measurement, and the monitored LF-NMR signal was not linearly related to the soil water content. In addition, external addition of paramagnetic materials (3.0 g·L-1 MnCl2 solution) would further reduce the LF-NMR signals that could be monitored in black and red soils. The maximum signal loss rates of black soil and red soil were 41.0% and 46.7%, respectively, which greatly changed the quantitative relationship between it and soil water content. Therefore, the influence of paramagnetic materials on the LF-NMR signals should be reduced first through correction when using LF-NMR to measure the water content of clay soil with rich internal paramagnetic materials (>1.3%) or external addition of paramagnetic materials. Our results would provide valuable insights into the study of soil water content measurement and soil pore structure analysis using low field nuclear magnetic resonance technology.
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Suelo , Agua , Humanos , Agua/análisis , Arcilla , Espectroscopía de Resonancia Magnética/métodos , MagnetismoRESUMEN
To cost-efficiently produce biofuels, new methods are needed to convert lignocellulosic biomass into fermentable sugars. One promising approach is to degrade biomass using cellulosomes, which are surface-displayed multicellulase-containing complexes present in cellulolytic Clostridium and Ruminococcus species. In this study we created cellulolytic strains of Bacillus subtilis that display one or more cellulase enzymes. Proteins containing the appropriate cell wall sorting signal are covalently anchored to the peptidoglycan by coexpressing them with the Bacillus anthracis sortase A (SrtA) transpeptidase. This approach was used to covalently attach the Cel8A endoglucanase from Clostridium thermocellum to the cell wall. In addition, a Cel8A-dockerin fusion protein was anchored on the surface of B. subtilis via noncovalent interactions with a cell wall-attached cohesin module. We also demonstrate that it is possible to assemble multienzyme complexes on the cell surface. A three-enzyme-containing minicellulosome was displayed on the cell surface; it consisted of a cell wall-attached scaffoldin protein noncovalently bound to three cellulase-dockerin fusion proteins that were produced in Escherichia coli. B. subtilis has a robust genetic system and is currently used in a wide range of industrial processes. Thus, grafting larger, more elaborate minicellulosomes onto the surface of B. subtilis may yield cellulolytic bacteria with increased potency that can be used to degrade biomass.
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Bacillus subtilis/metabolismo , Pared Celular/metabolismo , Celulosomas/metabolismo , Lignina/metabolismo , Proteínas de la Membrana/metabolismo , Aminoaciltransferasas/biosíntesis , Aminoaciltransferasas/genética , Bacillus subtilis/genética , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Bioingeniería , Proteínas de Ciclo Celular , Celulasa/metabolismo , Proteínas Cromosómicas no Histona , Clostridium thermocellum/enzimología , Cisteína Endopeptidasas/biosíntesis , Cisteína Endopeptidasas/genética , Escherichia coli/metabolismo , Immunoblotting , Proteínas de la Membrana/genética , Microscopía Fluorescente , Complejos Multienzimáticos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , CohesinasRESUMEN
BACKGROUND: Cinnamomum cassia (L.) J.Presl (Cinnamon) was known as a kind of hot herb, improved circulation and warmed the body. However, the active components and mechanisms of dispelling cold remain unknown. METHODS: The effects of several Chinses herbs on thermogenesis were evaluated on body temperature and activation of brown adipose tissue. After confirming the effect, the components of cinnamon were identified using HPLC-Q-TOF/MS and screened with databases. The targets of components were obtained with TCMSP, SymMap, Swiss and STITCH databases. Thermogenesis genes were predicted with DisGeNET and GeneCards databases. The protein-protein interaction network was constructed with Cytoscape 3.7.1 software. GO enrichment analysis was accomplished with STRING databases. KEGG pathway analysis was established with Omicshare tools. The top 20 targets for four compounds were obtained according to the number of edges of PPI network. In addition, the network results were verified with experimental research for the effects of extracts and major compounds. RESULTS: Cinnamon extract significantly upregulated the body temperature during cold exposure.121 components were identified in HPLC-Q-TOF/MS. Among them, 60 compounds were included in the databases. 116 targets were obtained for the compounds, and 41 genes were related to thermogenesis. The network results revealed that 27 active ingredients and 39 target genes. Through the KEGG analysis, the top 3 pathways were PPAR signaling pathway, AMPK signaling pathway, thermogenesis pathway. The thermogenic protein PPARγ, UCP1 and PGC1-α was included in the critical targets of four major compounds. The three major compounds increased the lipid consumption and activated the brown adipocyte. They also upregulated the expression of UCP1, PGC1-α and pHSL, especially 2-methoxycinnamaldehyde was confirmed the effect for the first time. Furthermore, cinnamaldehyde and cinnamon extract activated the expression of TRPA1 on DRG cells. CONCLUSION: The mechanisms of cinnamon on cold resistance were investigated with network pharmacology and experiment validation. This work provided research direction to support the traditional applications of thermogenesis.
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Tejido Adiposo Pardo/efectos de los fármacos , Cinnamomum aromaticum/química , Medicamentos Herbarios Chinos/farmacología , Extractos Vegetales/farmacología , Termogénesis , Acroleína/análogos & derivados , Acroleína/farmacología , Animales , Células Cultivadas , Frío , Regulación de la Expresión Génica , Ontología de Genes , Masculino , Potencial de la Membrana Mitocondrial , Ratones , Estructura Molecular , Mapas de Interacción de Proteínas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Objective: Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated kukoamine A (KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP+-induced PD models in vivo and in vitro. It is necessary to evaluate the efficacy of the anti-PD effects under various models. Methods: In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex. Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD. Results: Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of α-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxin-induced PD due to the apoptosis inhibition and iron homeostasis maintaining. Conclusion: KuA treatment might represent a neuroprotective treatment for PD.
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BACKGROUND: Oral carcinomas is a concerning condition around the world. Globally, it is the 11th most common form of cancer. Over 90% of oral carcinomas are squamous cell carcinomas. Smoking, tobacco intake, smokeless tobacco (snuff or chewing tobacco), excessive sunlight exposure, alcohol, betel nut consumption, human papillomavirus, and reverse end smoking are the most common causes of oral carcinomas. Oral carcinomas are prone to neck lymph mode metastasis, which has an impact on the prognosis of patients and the five-year survival rate. Thus, precise lymph node metastasis and staging of oral carcinomas are critical. With the development of nuclear medicine and molecular imaging, an increasing number of studies have found that Contrast-Enhanced Computed Tomography (CECT) has high diagnostic value for tumors. METHODS AND ANALYSES: The reviewers will conduct a thorough search for related literature in 6 online databases, including The Cochrane Library, PubMed, WanFang database, Web of Science, Chinese biomedical literature database, and the China National Knowledge Infrastructure. The authors will obtain full text of studies deemed to be eligible to extract and synthesize data. The present systematic review will be reported in accordance with the Preferred Reporting Project (PRISMA-P) of the 2015 System Review and Meta-Analysis Protocol. RESULTS: The present systematic analysis will pool the results of individual studies to assess the value of CECT in cervical lymph node metastasis of oral carcinomas. CONCLUSION: The results in the proposed research will determine whether CECT is an efficient diagnostic method for cervical lymph node metastasis of oral carcinomas. ETHICS AND DISSEMINATION: This study will utilize secondary data from pre-published studies. Therefore, an ethical clearance is not required. The research outcomes shall be disseminated in conference reports and peer-reviewed publications. OSF REGISTRATION NUMBER: Oct 13, 2021.osf.io/k5nr9. (https://osf.io/k5nr9/).