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1.
Nihon Yakurigaku Zasshi ; 156(2): 71-75, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-33642533

RESUMEN

The basal levels of intracellular Zn2+ and extracellular Zn2+ are in the range of ~100 pM and ~10 nM, respectively, in the hippocampus. Extracellular Zn2+ dynamics, which serves bidirectionally and involved in cognitive activity and cognitive decline, is modified by extracellular glutamate signaling and the presence of amyloid-ß1-42 (Aß1-42), a causative peptide in Alzheimer's disease (AD) pathogenesis. When human Aß1-42 reaches 100-500 pM in the extracellular compartment of the rat hippocampus, Zn-Aß1-42 complexes are produced and readily taken up into dentate granule cells in a synaptic activity-independent manner. Furthermore, intracellular Zn-Aß1-42 complexes release Zn2+ followed by intracellular Zn2+ dysregulation. Aß1-42-mediated intracellular Zn2+ toxicity is accelerated with aging, because extracellular Zn2+ is age-relatedly increased. We have reported that Aß1-42 released physiologically from neuron terminals disrupts intracellular Zn2+ homeostasis, resulting in age-related cognitive decline and neurodegeneration. Metallothioneins (MTs), zinc-binding proteins can capture Zn2+ released from intracellular Zn-Aß1-42 complexes and serve for intracellular Zn2+-buffering under acute intracellular Zn2+ dysregulation. Aß1-42-induced pathogenesis leads the AD development and its defense strategy may prevent the development. This review summarizes extracellular Zn2+-dependent Aß1-42 neurotoxicity, which is accelerated with aging, and the potential defense strategy against AD.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Animales , Hipocampo/metabolismo , Fragmentos de Péptidos , Ratas , Zinc
2.
Zhongguo Zhong Yao Za Zhi ; 46(3): 526-531, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33645016

RESUMEN

Mechanism study was performed to explore how Shouhui Tongbian Capsules promotes energy metabolism of gastrointestinal stromal cells. In this study, gastrointestinal stromal cells line GIST-882 was used as the model to explore energy metabolism regulation effects of Shouhui Tongbian Capsules extract(10, 20, 50 and 100 µg·mL~(-1)) by measuring the cell proliferation, ATP level, mitochondrial membrane potential, and mitochondrial isocitrate dehydrogenase activity. Meanwhile, Western blot was used to detect the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Our results showed that Shouhui Tongbian Capsules promoted cell proliferation and increased ATP level of gastrointestinal stromal cells. In addition, Shouhui Tongbian Capsules obviously improved mitochondrial structural integrity, and increased mitochondrial membrane potential in GIST-882 cells. Mechanism study revealed that Shouhui Tongbian Capsules increased mitochondrial isocitrate dehydrogenase activity and up-regulated the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Collectively, our study indicated that Shouhui Tongbian Capsules promoted the energy metabolism for gastrointestinal stromal cells proliferation by activating mitochondrial isocitrate dehydrogenase to induce ATP production, as well as activating SCF/c-Kit and CDK2/cyclin A signaling pathways.


Asunto(s)
Tumores del Estroma Gastrointestinal , Cápsulas , Línea Celular Tumoral , Metabolismo Energético , Humanos , Proteínas Proto-Oncogénicas c-kit/metabolismo , Células del Estroma/metabolismo
3.
Zhongguo Zhong Yao Za Zhi ; 46(3): 591-598, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33645024

RESUMEN

Nano-LC MS/MS was used to analyze trypsin digested deer-hide gelatin(DHG) samples, hydroxylation and O-glycosylation on lysine sites of DHG were comprehensive identified by using PEAKS Studio software. The sites, sorts and amounts of hydroxylation and O-glycosylation on Type Ⅰ collagen α1 chain(COL1 A1) and α2 chain(COL1 A2) of DHG were revealed. As a result, 5 284 peptides were identified from DHG samples, which were mainly from COL1 A1 and COL1 A2. Among these peptides, there were 449 peptides with hydroxylysine, 442 with galactosyl-hydroxylysine, 449 with glucosyl-galactosyl-hydroxylysine. The major modified sites of hydroxylation and O-glycosylation in DHG were shown as follow: α1-9 N and α2-5 N in N-telopeptides, α1-87, α1-174, α1-930, α2-87, α2-174, α2-933 in triple helix domain, and α1-16 C in C-telopeptides. These hydroxylation and O-glycosylation were correlated with the formation and stability of collagen molecules and collagen fibrils. It is feasible for the collagens and peptides dissolving from deer skin collagen fibrils under high temperature and pressure decocting, high temperature and pressure also might destroy inter-molecular covalent cross-linking and help those glycol-peptides formations. The present study provided ideas and strategies for the in-depth investigation on DHG chemical constituents, and showed good theoretical significance and application value.


Asunto(s)
Ciervos , Lisina , Animales , Ciervos/metabolismo , Gelatina , Glicosilación , Hidroxilación , Lisina/metabolismo , Procesamiento Proteico-Postraduccional , Espectrometría de Masas en Tándem
4.
Zhongguo Zhong Yao Za Zhi ; 46(3): 670-677, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33645034

RESUMEN

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1ß and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.


Asunto(s)
Neoplasias del Colon , Curcumina , Animales , Neoplasias del Colon/tratamiento farmacológico , Fluorouracilo/toxicidad , Interleucina-6/genética , Mucosa Intestinal/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal
5.
Zhongguo Zhong Yao Za Zhi ; 46(1): 6-14, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645045

RESUMEN

Hypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure, which may be accompanied by functional or organic damage of heart, brain, kidney and other organs. The pathogenesis and development of hypertension are affected by genetic, environmental, epigenetic, intestinal microbiota and other factors. They are the result of multiple factors that promote the change of blood pressure level and vascular resistance. G protein coupled receptors(GPCRs) are the largest and most diverse superfamily of transmembrane receptors that transmit signals across cell membranes and mediate a large number of cellular responses required by human physiology. A variety of GPCRs are involved in the control of blood pressure and the maintenance of normal function of cardiovascular system. Hypertension contributes to the damages of heart, brain, kidney, intestine and other organs. Many GPCRs are expressed in various organs to regulate blood pressure. Although many GPCRs have been used as therapeutic targets for hypertension, their efficacy has not been fully studied. The purpose of this paper is to elucidate the role of GPCRs in blood pressure regulation and its distribution in target organs. The relationship between GPCRs related to intestinal microorganisms and blood pressure is emphasized. It is proposed that traditional Chinese medicine may be a new way to treat hypertension by regulating the related GPCRs via intestinal microbial metabolites.


Asunto(s)
Microbioma Gastrointestinal , Hipertensión , Presión Sanguínea , Proteínas de Unión al GTP , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 46(1): 24-32, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645047

RESUMEN

Nrf2 is the key transcription factor mainly for regulating oxidative homeostasis and cytoprotective responses against oxidative stress. Nrf2/Keap1 pathway is one of the most important cellular defense mechanisms against endogenous or exogenous oxidative stress. With its activation, a wide range of stress-related genes is transactivated to restore the cellular homeostasis. Recent studies revealed that the aberrant activation of Nrf2 is related to the malignant progression, chemotherapeutic drug resistance and poor prognosis. Nrf2 plays a crucial role in cancer malignancy and chemotherapeutic resistance by controlling the intracellular redox homeostasis through the activation of cytoprotective antioxidant genes. Nrf2 inhibitor containing many natural products has been deemed as a novel therapeutic strategy for human malignancies. This article reviews the progress of studies of the Nrf2/Keap1 pathway, and its biological impact in solid malignancies and molecular mechanisms for causing Nrf2 hyperactivation in cancer cells. In conclusion, we summarized the deve-lopment of Nrf2 inhibitors in recent years, in the expectation of providing reference for further drug development and clinical studies.


Asunto(s)
Factor 2 Relacionado con NF-E2 , Neoplasias , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Oxidación-Reducción , Estrés Oxidativo
7.
Zhongguo Zhong Yao Za Zhi ; 46(1): 52-56, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645051

RESUMEN

ATP-binding cassette(ABC) transporters are one of the largest protein families in organisms, with important effects in regulating plant growth and development, root morphology, transportation of secondary metabolites and resistance of stress. Environmental stress promotes the biosynthesis and accumulation of secondary metabolites, which determines the quality of medicinal plants. Therefore, how to improve the accumulation of secondary metabolites has been a hotspot in studying medicinal plants. Many studies have showed that ABC transporters are extremely related to the transportation and accumulation of secondary metabolites in plants. Recently, with the great development of genomics and transcriptomic sequencing technology, the regulatory mechanisms of ABC transporters on secondary metabolites have attached great attentions in medicinal plants. This paper reviewed the mechanisms of different groups of ABC transporters in transporting secondary metabolites through cell membranes. This paper provided key theoretical basis and technical supports in studying the mechanisms of ABC transporters in medicinal plant, and promoting the accumulation of secondary metabolites, in order to improve the quality of medicinal plants.


Asunto(s)
Transportadoras de Casetes de Unión a ATP , Plantas Medicinales , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Transporte Biológico , Desarrollo de la Planta , Plantas Medicinales/genética , Plantas Medicinales/metabolismo , Estrés Fisiológico
8.
Zhongguo Zhong Yao Za Zhi ; 46(1): 146-154, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645064

RESUMEN

This study aimed to assess whether chrysin(ChR) can inhibit epithelial-mesenchymal transition(EMT) of type Ⅱ alveolar epithelial cell and produce anti-pulmonary fibrosis effect by regulating the NF-κB/Twist 1 signaling pathway. Sixty rats were randomly divided into the control group, the bleomycin(BLC) group, BLC+ChR(50 mg·kg~(-1)) group and BLC+ChR(100 mg·kg~(-1)) group, with 15 rats in each group. The pulmonary fibrosis model was induced by intratracheal injection of BLC(7 500 U·kg~(-1)). Rats were orally administered with different doses of ChR after BLC injection for 28 days. The cells were divided into control group, TGF-ß1 group(5 ng·mL~(-1)), and TGF-ß1+ChR(1, 10, 100 µmol·L~(-1)) groups. The type Ⅱ alveolar epithelial cells were treated with TGF-ß1 for 24 h, and then treated with TGF-ß1 for 48 h in the presence or absence of different doses of ChR(1, 10 and 100 µmol·L~(-1)). The morphological changes and collagen deposition in lung tissues were analyzed by HE staining, Masson staining and immunohistochemistry. The mRNA and protein expression levels of collagen Ⅰ, E-cadherin, zonula occludens-1(ZO-1), vimentin, alpha smooth muscle actin(α-SMA), inhibitor of nuclear factor kappa B alpha(IκBα), nuclear factor-kappa B p65(NF-κB p65), phospho-NF-κB p65(p-p65) and Twist 1 in lung tissues and cells were detected by qPCR and Western blot, respectively. The animal experiment results showed that as compared with the BLC group, after administration of ChR for 28 days, bleomycin-induced pulmonary fibrosis in rats was significantly relieved, collagen Ⅰ expression in lung tissues was significantly reduced(P<0.05 or P<0.01), and EMT of alveolar epithelial cells was obviously inhibited [the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], concomitantly with significantly reduced IκBα and p65 phosphorylation level in cytoplasm and decreased NF-κB p65 and Twist 1 expression in nucleus(P<0.05 or P<0.01). The cell experiment results showed that different doses of ChR(1, 10 and 100 µmol·L~(-1)) significantly reduced TGF-ß1-induced collagen Ⅰ expression(P<0.05 or P<0.01), significantly inhibited EMT of type Ⅱ alveolar epithelial cells[the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], and inhibited IκBα and p65 phosphorylation in cytoplasm and down-regulated NF-κB p65 and Twist 1 expression in nucleus induced by TGF-ß1(P<0.05 or P<0.01). The results suggest that ChR can reverse EMT of type Ⅱ alveolar epithelial cell and alleviate pulmonary fibrosis in rats, and its mechanism may be associated with reducing IκBα phosphorylation and inhibiting NF-κB p65 phosphorylation and nuclear transfer, thus down-regulating Twist 1 expression.


Asunto(s)
Transición Epitelial-Mesenquimal , FN-kappa B , Células Epiteliales Alveolares/metabolismo , Animales , Flavonoides , FN-kappa B/genética , FN-kappa B/metabolismo , Ratas , Transducción de Señal , Factor de Crecimiento Transformador beta1/genética
9.
Zhongguo Zhong Yao Za Zhi ; 46(4): 845-854, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33645089

RESUMEN

Network pharmacology and liver fibrosis(LF) model in vitro were used to analyze the underly mechanism of anti-liver fibrosis effect that induced by Piperis Longi Fructus and its major active compounds. TCMSP and TCMIP were used to search for the chemical constituents of Piperis Longi Fructus, as well as the oral bioavailability(OB), drug-likeness(DL), intercellular permeability of intestinal epithelial cells(Caco-2) and Drug-likeness grading were set as limiting conditions. The related target genes of Piperis Longi Fructus were queried by TCMSP database, while related targets of LF were screened by GeneCards databases. Interaction network was constructed using Cytoscape 3.7.1. These above data were imported into STRING database for PPI network analysis. Enrichment of gene ontology(GO) and pathway analysis(KEGG) within Bioconductor database were utilized to note functions of related targets of Piperis Longi Fructus. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The effects of piperlongumine(PL), the major active component of Piperis Longi Fructus, on proliferation of rat liver stellate cells(HSC-T6) and expression of α smooth muscle actin(α-SMA) and collagen Ⅰ were investigated. The major factors TNF-α of tumor necrosis factor(TNF) pathway and NF-κB p65, IL-6 protein expressions of LF process were examined. A total of 12 active compounds such as PL were obtained by analyzing the bioavailability and drug-like properties, which inferred to 48 targets. The functional enrichment analysis of GO obtained 1 240 GO items, mainly involving in process of biology and molecular function. A total of 99 signaling pathways were enriched in the KEGG pathway enrichment analysis, including TNF signaling pathway, cGMP-PKG signaling pathway, calcium signaling pathways. CCK-8 assay showed that PL inhibited proliferation of HSC-T6 induced by transforming growth factor-ß1(TGF-ß1). Western blot analysis found that treated with PL suppressed the protein expressions of α-SMA, collagen Ⅰ, TNF-α and p65 in HSC-T6. Enzyme linked immunosorbent assay(ELISA) showed that PL inhibited the expressions of TNF-α and IL-6 in the cluture supertant of HSC-T6 cells. In conclusion, PL could play an anti-liver fibrosis role by regulating TNF/NF-κB signaling pathway. This study provided the mechanism basis of anti-LF effects induced by Piperis Longi Fructus and its major active compounds, which might help for the further study of the mechanism and key targets of Piperis Longi Fructus.


Asunto(s)
Células Estrelladas Hepáticas , Cirrosis Hepática , Animales , Células CACO-2 , Células Estrelladas Hepáticas/metabolismo , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , FN-kappa B/metabolismo , Ratas , Transducción de Señal
10.
Zhongguo Zhong Yao Za Zhi ; 46(2): 359-365, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645122

RESUMEN

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.


Asunto(s)
Aceites Volátiles , Sesquiterpenos , Humanos , Monoterpenos/metabolismo , Aceites Volátiles/metabolismo , Aceites Volátiles/toxicidad , Sesquiterpenos/metabolismo , Piel/metabolismo , Absorción Cutánea
11.
Sheng Wu Gong Cheng Xue Bao ; 37(2): 429-447, 2021 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-33645146

RESUMEN

Higher alcohols are one of the main by-products of Saccharomyces cerevisiae in brewing. High concentration of higher alcohols in alcoholic beverages easily causes headache, thirst and other symptoms after drinking. It is also the main reason for chronic drunkenness and difficulty in sobering up after intoxication. The main objective of this review is to present an overview of the flavor characteristics and metabolic pathways of higher alcohols as well as the application of mutagenesis breeding techniques in the regulation of higher alcohol metabolism in S. cerevisiae. In particular, we review the application of metabolic engineering technology in genetic modification of amino transferase, α-keto acid metabolism, acetate metabolism and carbon-nitrogen metabolism. Moreover, key challenges and future perspectives of realizing optimization of higher alcohols metabolism are discussed. This review is intended to provide a comprehensive understanding of metabolic regulation system of higher alcohols in S. cerevisiae and to provide insights into the rational development of the excellent industrial S. cerevisiae strains producing higher alcohols.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Bebidas Alcohólicas , Alcoholes/análisis , Fermentación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
12.
Sheng Wu Gong Cheng Xue Bao ; 37(2): 473-485, 2021 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-33645149

RESUMEN

Lignocellulose is the most abundant renewable organic carbon resource on earth. However, due to its complex structure, it must undergo a series of pretreatment processes before it can be efficiently utilized by microorganisms. The pretreatment process inevitably generates typical inhibitors such as furan aldehydes that seriously hinder the growth of microorganisms and the subsequent fermentation process. It is an important research field for bio-refining to recognize and clarify the furan aldehydes metabolic pathway of microorganisms and further develop microbial strains with strong tolerance and transformation ability towards these inhibitors. This article reviews the sources of furan aldehyde inhibitors, the inhibition mechanism of furan aldehydes on microorganisms, the furan aldehydes degradation pathways in microorganisms, and particularly focuses on the research progress of using biotechnological strategies to degrade furan aldehyde inhibitors. The main technical methods include traditional adaptive evolution engineering and metabolic engineering, and the emerging microbial co-cultivation systems as well as functional materials assisted microorganisms to remove furan aldehydes.


Asunto(s)
Aldehídos , Lignina , Fermentación , Furanos , Lignina/metabolismo
13.
Sheng Wu Gong Cheng Xue Bao ; 37(2): 500-512, 2021 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-33645151

RESUMEN

Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.


Asunto(s)
Metabolismo de los Lípidos , Factores de Transcripción , Animales , Metabolismo Energético/genética , Homeostasis , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
14.
Sheng Wu Gong Cheng Xue Bao ; 37(2): 604-614, 2021 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-33645158

RESUMEN

Proton-pumping rhodopsin (PPR) is a simple photosystem widely distributed in nature. By binding to retinal, PPR can transfer protons from the cytoplasmic to the extracellular side of the membrane under illumination, creating a proton motive force (PMF) to synthesize ATP. The conversion of light into chemical energy by introducing rhodopsin into nonphotosynthetic engineered strains could contribute to promoting growth, increasing production and improving cell tolerance of microbial hosts. Gloeorhodopsin (GR) is a PPR from Gloeobacter violaceus PCC 7421. We expressed GR heterologously in Escherichia coli and verified its functional activity. GR could properly function as a light-driven proton pump and its absorption maximum was at 539 nm. We observed that GR was mainly located on the cell membrane and no inclusion body could be found. After increasing expression level by ribosome binding site optimization, intracellular ATP increased, suggesting that GR could supply additional energy to heterologous hosts under given conditions.


Asunto(s)
Cianobacterias , Rodopsina , Cianobacterias/genética , Cianobacterias/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Bombas de Protones , Rodopsina/genética , Rodopsina/metabolismo , Rodopsinas Microbianas/genética , Rodopsinas Microbianas/metabolismo
15.
Biomed Khim ; 67(1): 5-16, 2021 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-33645518

RESUMEN

This review discusses our current knowledge on the nociceptin/orphanin (N/OFQ) system regarding its role in regulation of brain functions. Nociceptin receptor (NOPr) was identified in 1994 [Bunzow et al., 1994; Mollereau et al., 1994]. In 1995 a 17 amino acid endogenous peptide was found to be the high-affinity ligand for the NOPr [Reinscheid et al., 1995]. N/OFQ has a broad spectrum of activity and can act as on opioid-like as well as an anti-opioid peptide. Considering high level of N/OFQ and NOPr mRNA expression in the limbic brain regions, the N/OFQ/NOP system is suggested to be involved in regulation of emotions, resward, pain sensitivity, stress responsibility, sexual behavior, aggression, drug abuse and addiction. However it is still not well understood whether an increased vulnerability to drugs of abuse may be associated with dysregulation of N/OFQ/NOP system. Current review further highlights a need for further research on N/OFQ/NOP system as it could have clinical utility for substance abuse, depression, and anxiety pharmacotherapy.


Asunto(s)
Analgésicos Opioides , Péptidos Opioides , Ansiedad , Encéfalo/metabolismo , Péptidos Opioides/metabolismo
16.
Biomed Khim ; 67(1): 17-33, 2021 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-33645519

RESUMEN

Ca2+-activated chloride channels (CaCC) are a class of intracellular calcium activated chloride channels that mediate numerous physiological functions. In 2008, the molecular structure of CaCC was determined. CaCC are formed by the protein known as anoctamine 1 (ANO1 or TMEM16A). CaCC mediates the secretion of Cl- in secretory epithelia, such as the airways, salivary glands, intestines, renal tubules, and sweat glands. The presence of CaCC has also been recognized in the vascular muscles, smooth muscles of the respiratory tract, which control vascular tone and hypersensitivity of the respiratory tract. TMEM16A is activated in many cancers; it is believed that TMEM16A is involved in carcinogenesis. TMEM16A is also involved in cancer cells proliferation. The role of TMEM16A in the mechanisms of hypertension, asthma, cystic fibrosis, nociception, and dysfunction of the gastrointestinal tract has been determined. In addition to TMEM16A, its isoforms are involved in other physiological and pathophysiological processes. TMEM16B (or ANO2) is involved in the sense of smell, while ANO6 works like scramblase, and its mutation causes a rare bleeding disorder, known as Scott syndrome. ANO5 is associated with muscle and bone diseases. TMEM16A interacts with various cellular signaling pathways including: epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPK), calmodulin (CaM) kinases, transforming growth factor TGF-ß. The review summarizes existing information on known natural and synthetic compounds that can block/modulate CaCC currents and their effect on some pathologies in which CaCC is involved.


Asunto(s)
Carcinogénesis , Canales de Cloruro , Anoctamina-1 , Anoctaminas , Calcio/metabolismo , Canales de Cloruro/genética , Humanos
17.
Biomed Khim ; 67(1): 51-65, 2021 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-33645522

RESUMEN

Mitochondrial dysfunction and ubiquitin-proteasome system (UPS) failure contribute significantly to the development of Parkinson's disease (PD). The proteasome subunit Rpn13 located on the regulatory (19S) subparticle play an important role in the delivery of proteins, subjected to degradation, to the proteolytic (20S) part of proteasome. We have previously found several brain mitochondrial proteins specifically bound to Rpn13 (Buneeva et al. (2020) Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 14, 297-305). In this study we have investigated the effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the neuroprotector isatin on the mitochondrial subproteome of Rpn13-binding proteins of the mouse brain. Administration of MPTP (30 mg/kg) to animals caused movement disorders typical of PD, while pretreatment with isatin (100 mg/kg, 30 min before MPTP) reduced their severity. At the same time, the injection of MPTP, isatin, or their combination (isatin + MPTP) had a significant impact on the total number and the composition of Rpn13-binding proteins. The injection of MPTP decreased the total number of Rpn13-binding proteins in comparison with control, and the injection of isatin prior to MPTP or without MPTP caused an essential increase in the number of Rpn13-binding proteins, mainly of the functional group of proteins participating in the protein metabolism regulation, gene expression, and differentiation. Selected biosensor validation confirmed the interaction of Rpn13 subunit of proteasome with some proteins (glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, histones H2A and H2B) revealed while proteomic profiling. The results obtained testify that under the conditions of experimental MPTP-induced parkinsonism the neuroprotective effect of isatin may be aimed at the interaction of mitochondria with the components of UPS.


Asunto(s)
Isatina , Neurotoxinas , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Encéfalo/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Isatina/metabolismo , Isatina/farmacología , Ratones , Mitocondrias/metabolismo , Neurotoxinas/metabolismo , Neurotoxinas/farmacología , Proteómica
18.
Biomed Khim ; 67(1): 88-94, 2021 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-33645526

RESUMEN

Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene - p=0.009 (AUC (95%CI) = 0.76 (0.59-0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6-0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.


Asunto(s)
Neoplasias de la Mama , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Metilación de ADN , Femenino , Humanos , Metástasis Linfática , Fenobarbital , Receptores Estrogénicos/metabolismo
19.
Biomed Khim ; 67(1): 95-99, 2021 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-33645527

RESUMEN

Intracellular signaling mediated by the HMGB1 protein, an agonist of TLRs, is considered as a possible target for the correction of pathologies of the neuroimmune system, however, the expression level of the Hmgb1 gene has not been previously studied in various brain structures of rats exposed to prolonged alcoholization followed by ethanol withdrawal. The study showed that long-term use of ethanol caused to an increase in the level of Hmgb1 mRNA in the striatum of rat brain. Alcohol withdrawal changed the level Hmgb1 mRNA in the striatum and amygdala on the 1st and 14th day. The data obtained may indicate that in different structures of the brain there are multidirectional changes in the molecular mechanisms of the neuroimmune response with prolonged use of ethanol and its withdrawal.


Asunto(s)
Alcoholismo , Proteína HMGB1 , Síndrome de Abstinencia a Sustancias , Alcoholismo/genética , Animales , Encéfalo/metabolismo , Etanol/toxicidad , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Ratas , Síndrome de Abstinencia a Sustancias/genética
20.
Nat Commun ; 12(1): 1260, 2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33627662

RESUMEN

A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.


Asunto(s)
/inmunología , Pulmón/patología , Pulmón/virología , Animales , Modelos Animales de Enfermedad , Femenino , Inmunidad Celular/fisiología , Interferón gamma/metabolismo , Macaca fascicularis , Macaca mulatta , Masculino , Pandemias , /patogenicidad
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