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1.
J Agric Food Chem ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226078

RESUMO

The simultaneous enhancement of lipophagy and mitochondrial biogenesis has emerged as a promising strategy for lipid lowering. The transcription factor EB (TFEB) exhibits a dual role, whereby it facilitates the degradation of lipid droplets (LDs) through the process of lipophagy while simultaneously stimulating mitochondrial biogenesis to support the utilization of lipophagy products. The purpose of this study was to explore the effect of astragaloside I (AS I) on hyperlipidemia and elucidate its underlying mechanism. AS I improved serum total cholesterol and triglyceride levels and reduced hepatic steatosis and lipid accumulation in db/db mice. AS I enhanced the fluorescence colocalization of LDs and autophagosomes and promoted the proteins and genes related to the autolysosome. Moreover, AS I increased the expression of mitochondrial biogenesis-related proteins and genes, indicating that AS I promoted lipophagy and mitochondrial biogenesis. Mechanistically, AS I inhibits the protein level of p-TFEB (ser211) expression and promotes TFEB nuclear translocation. The activation of TFEB by AS I was impeded upon the introduction of the mammalian target of rapamycin (mTOR) agonist MHY1485. The inhibition of p-mTOR by AS I and the activation of TFEB were no longer observed after administration of the Akt agonist SC-79, which indicated that AS I activated TFEB to promote lipophagy-dependent on the Akt/mTOR pathway and may be a potentially effective pharmaceutical and food additive for the treatment of hyperlipidemia.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39305227

RESUMO

The porous carbon materials, namely, MC700/800, PC700/800, and SC700/800, have been prepared using several biomasses (mushroom dreg, Chinese parasol leaves, and Siraitia grosvenorii leaves) as individual precursors at 700 and 800 °C activation temperatures. Among these carbon-negative electrodes, SC700 exhibits an impressive specific capacitance, nearly 2-fold that of commercial activated carbon (169.5 F g-1). When assembled with a Ni(OH)2 positive electrode in asymmetric supercapacitors, the SC700//Ni(OH)2 device can achieve a specific capacitance of 80 F g-1 and an energy density of 32.16 Wh kg-1 at 1700 W kg-1. In contrast, the MC700 electrode can display inferior performance potentially attributed to the high ash content in the biomass. To further optimize the activated process of the MC700 product, three deashing carbon negative electrodes (denoted as MC(H2O), MC(HF), and MC(Mix)) were prepared by deashing treatment using H2O, HF, and mixed acid, and then a modified composite positive electrode (MC700@MnO2(MCM)) has been prepared by doping with MnO2. Electrochemical testing demonstrates that the deashing strategy achieves a significant capacitance enhancement compared to the primary carbon material while maintaining excellent cyclic stability. The asymmetric supercapacitors, assembled from these decorated electrode materials, exhibited a maximum energy density of 21.08 Wh kg-1 and a power density of 1150 W kg-1 under a high-voltage window of 2.2 V. Additionally, this type of full device can power 28 LEDs for approximately 5 min.

3.
J Hazard Mater ; 480: 135852, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39298944

RESUMO

Bensulfuron methyl (BSM) residues have caused serious yield reductions of sensitive crops. Chemical oxidation is an effective remediation technology, while it affects soil quality and subsequent agricultural activity, necessitating approriate improvement measures. So Fe2O3-Mn3O4 with excellent bimetallic synergistic effect was synthesized to activate peroxymonosulfate (PMS) for BSM degradation. The catalytic activity and influencing factors were systematically predetermined in water in view of soil remediation. Results showed Fe2O3-Mn3O4/PMS oxidized 99.3 % BSM within 60 min with the help of multi-reactive species and electron transfer. Meanwhile, Fe2O3-Mn3O4/PMS treatment exhibited technical feasibility in soil that 97.6 % BSM was degraded in 5 days under the low usages of Fe2O3-Mn3O4 (0.8 %) and PMS (0.15 %). Although Fe2O3-Mn3O4/PMS decreased BSM phytotoxicity and improved maize growth, a few gaps existed between the remediated group and uncontaminated group, including biomass, length, available potassium, organic matters, pH, redox potential (Eh) and sulfate content. The introductions of biochar and chitosan in remediated soils promoted growth, increased organic matters content, improved soil resistance to acidification and decreased Eh, alleviating the negative effects of Fe2O3-Mn3O4/PMS. Overall, the study provided new insights into the combination of Fe2O3-Mn3O4/PMS and biochar and chitosan in BSM-contaminated soil, achieving BSM degradation and improvements of soil quality and plant growth.

4.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1249-1254, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621971

RESUMO

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.


Assuntos
Arecaceae , Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Flavonoides/análise , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodos
5.
Phytomedicine ; 128: 155313, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38520833

RESUMO

BACKGROUND: The occurrence of hyperlipidemia is significantly influenced by lipid synthesis, which is regulated by sterol regulatory element binding proteins (SREBPs), thus the development of drugs that inhibit lipid synthesis has become a popular treatment strategy for hyperlipidemia. Alisol B (ALB), a triterpenoid compound extracted from Alisma, has been reported to ameliorate no-nalcoholic steatohepatitis (NASH) and slow obesity. However, the effect of ALB on hyperlipidemia and mechanism are unclear. PURPOSE: To examine the therapeutic impact of ALB on hyperlipidemia whether it inhibits SREBPs to reduce lipid synthesis. STUDY DESIGN: HepG2, HL7702 cells, and C57BL/6J mice were used to explore the effect of ALB on hyperlipidemia and the molecular mechanism in vivo and in vitro. METHODS: Hyperlipidemia models were established using western diet (WD)-fed mice in vivo and oleic acid (OA)-induced hepatocytes in vitro. Western blot, real-time PCR and other biological methods verified that ALB regulated AMPK/mTOR/SREBPs to inhibit lipid synthesis. Cellular thermal shift assay (CETSA), molecular dynamics (MD), and ultrafiltration-LC/MS analysis were used to evaluate the binding of ALB to voltage-dependent anion channel protein-1 (VDAC1). RESULTS: ALB decreased TC, TG, LDL-c, and increased HDL-c in blood, thereby ameliorating liver damage. Gene set enrichment analysis (GSEA) indicated that ALB inhibited the biosynthesis of cholesterol and fatty acids. Consistently, ALB inhibited the protein expression of n-SREBPs and downstream genes. Mechanistically, the impact of ALB on SREBPs was dependent on the regulation of AMPK/mTOR, thereby impeding the transportation of SREBPs from endoplasmic reticulum (ER) to golgi apparatus (GA). Further investigations indicated that the activation of AMPK by ALB was independent on classical upstream CAMKK2 and LKB1. Instead, ALB resulted in a decrease in ATP levels and an increase in the ratios of ADP/ATP and AMP/ATP. CETSA, MD, and ultrafiltration-LC/MS analysis indicated that ALB interacted with VDAC1. Molecular docking revealed that ALB directly bound to VDAC1 by forming hydrogen bonds at the amino acid sites S196 and H184 in the ATP-binding region. Importantly, the thermal stabilization of ALB on VDAC1 was compromised when VDAC1 was mutated at S196 and H184, suggesting that these amino acids played a crucial role in the interaction. CONCLUSION: Our findings reveal that VDAC1 serves as the target of ALB, leading to the inhibition of lipid synthesis, presents potential target and candidate drugs for hyperlipidemia.


Assuntos
Proteínas Quinases Ativadas por AMP , Colestenonas , Hiperlipidemias , Serina-Treonina Quinases TOR , Canal de Ânion 1 Dependente de Voltagem , Animais , Humanos , Masculino , Camundongos , Alisma/química , Proteínas Quinases Ativadas por AMP/metabolismo , Colestenonas/farmacologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hiperlipidemias/tratamento farmacológico , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5851-5862, 2023 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-38114181

RESUMO

This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1ß, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.


Assuntos
Tecido Adiposo Marrom , PPAR alfa , Camundongos , Animais , Simulação de Acoplamento Molecular , PPAR alfa/metabolismo , Tecido Adiposo Branco , RNA Mensageiro/metabolismo
8.
Glob Med Genet ; 10(3): 144-158, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37501756

RESUMO

Background Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer worldwide. The histopathological features, risk factors, and prognosis of HCC caused by nonalcoholic fatty liver disease (NAFLD) appear to be significantly different from those of HCC caused by other etiologies of liver disease. Objective This article explores the shared gene and molecular mechanism between NAFLD and HCC through bioinformatics technologies such as weighted gene co-expression network analysis (WGCNA), so as to provide a reference for comprehensive understanding and treatment of HCC caused by NAFLD. Methods NAFLD complementary deoxyribonucleic acid microarrays (GSE185051) from the Gene Expression Omnibus database and HCC ribonucleic acid (RNA)-sequencing data (RNA-seq data) from The Cancer Genome Atlas database were used to analyze the differentially expressed genes (DEGs) between NAFLD and HCC. Then, the clinical traits and DEGs in the two disease data sets were analyzed by WGCNA to obtain W-DEGs, and cross-W-DEGs were obtained by their intersection. We performed subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analyses of the cross-W-DEGs and established protein-protein interaction networks. Then, we identified the hub genes in them by Cytoscape and screened out the final candidate genes. Finally, we validated candidate genes by gene expression, survival, and immunohistochemical analyses. Results The GO analysis of 79 cross-W-DEGs showed they were related mainly to RNA polymerase II (RNAP II) and its upstream transcription factors. KEGG analysis revealed that they were enriched predominantly in inflammation-related pathways (tumor necrosis factor and interleukin-17). Four candidate genes (JUNB, DUSP1, NR4A1, and FOSB) were finally screened out from the cross-W-DEGs. Conclusion JUNB, DUSP1, NR4A1, and FOSB inhibit NAFLD and HCC development and progression. Thus, they can serve as potential useful biomarkers for predicting and treating NAFLD progression to HCC.

9.
Ageing Res Rev ; 87: 101899, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36871781

RESUMO

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, generates a serious threat to the health of the elderly. The AD brain is microscopically characterized by amyloid plaques and neurofibrillary tangles. There are still no effective therapeutic drugs to restrain the progression of AD though much attention has been paid to exploit AD treatments. Ferroptosis, a type of programmed cell death, has been reported to promote the pathological occurrence and development of AD, and inhibition of neuronal ferroptosis can effectively improve the cognitive impairment of AD. Studies have shown that calcium (Ca2+) dyshomeostasis is closely related to the pathology of AD, and can drive the occurrence of ferroptosis through several pathways, such as interacting with iron, and regulating the crosstalk between endoplasmic reticulum (ER) and mitochondria. This paper mainly reviews the roles of ferroptosis and Ca2+ in the pathology of AD, and highlights that restraining ferroptosis through maintaining the homeostasis of Ca2+ may be an innovative target for the treatment of AD.


Assuntos
Doença de Alzheimer , Ferroptose , Doenças Neurodegenerativas , Humanos , Idoso , Doença de Alzheimer/metabolismo , Cálcio/metabolismo , Homeostase
10.
Adv Biol (Weinh) ; 7(10): e2300009, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36988430

RESUMO

This study aims to investigate the relevant mechanism by which hydrazinocurcumin (HC) interferes with A431 cell autophagy by inhibiting the STAT3 signaling pathway. Different concentrations of HC are used to treat A431 cells to study the effects of HC on A431 cell proliferation and apoptosis. Real-time fluorescent quantitative polymerase chain reaction (PCR) is used to further explore the relationship of HC with the JAK signaling pathway and autophagy. Double immunofluorescence staining is used to detect the fluorescence localization of LC3 and STAT3 after HC treatment. With increasing HC concentrations, A431 cell viability decreases in a dose-dependent manner, and the apoptosis rate increases significantly. Laser confocal colocalization reveals that the fluorescence of labeled LC3 protein is significantly increased, and the fluorescence of labeled STAT3 is significantly reduced in this study. HC may induce autophagy in A431 cells and affect cell proliferation by downregulating the JAK/STAT3 signaling pathway.

11.
J Ethnopharmacol ; 307: 116243, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36791927

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Yishen Tongluo formula (YSTLF) is formulated based on traditional Chinese medicine theory for the treatment of Diabetic kidney disease (DKD) and has been shown to be effective in improving the symptoms of DKD according to the clinical observation. AIM OF THE STUDY: To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-ß1/Smad2/3 pathway and promoting degradation of TGF-ß1. MATERIALS AND METHODS: The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J (db/db) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-ß1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-ß1 degradation was investigated in HG-stimulated SV40-MES-13 cells. RESULTS: YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen, alpha smooth muscle actin, type IV collagen, and fibronectin in vitro and in vivo, resulting in ameliorating of renal fibrosis. YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-ß1/Smad2/3 signaling pathway. TGF-ß1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment. CONCLUSIONS: YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-ß1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-ß1.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Sirtuínas , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Rim , Fibrose , Diabetes Mellitus/metabolismo , Sirtuínas/metabolismo
12.
Environ Sci Pollut Res Int ; 30(13): 37646-37658, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36574128

RESUMO

In this study, rice straw biochar modified with Co3O4-Fe3O4 (RSBC@Co3O4-Fe3O4) was successfully prepared via calcinating oxalate coprecipitation precursor and employed as a catalyst to activate peroxymonosulfate (PMS) for the treatment of Rhodamine B (RhB)-simulated wastewater. The results indicated that RSBC@Co3O4-Fe3O4 exhibited high catalytic performance due to the synergy between Co3O4 and Fe3O4 doping into RSBC. Approximately 98% of RhB (180 mg/L) was degraded in the RSBC@Co3O4-Fe3O4/PMS system at initial pH 7 within 15 min. The degradation efficiency of RhB maintained over 90% after the fourth cycle, illustrating that RSBC@Co3O4-Fe3O4 displayed excellent stability and reusability. The primary reactive oxygen species (ROS) answerable for the degradation of RhB were 1O2, •OH, and SO4•-. Moreover, the intermediates involved in the degradation of RhB were identified and the possible degradation pathways were deduced. This work can provide a new approach to explore Co-based and BC-based catalysts for the degradation of organic pollutants.


Assuntos
Oryza , Peróxidos
13.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6183-6190, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471943

RESUMO

Taking lipophagy as the breakthrough point, we explored the mechanism of Zexie Decoction(ZXD) in improving lipid metabolism in the hepatocyte model induced by palmitic acid(PA) and in the animal model induced by high-fat diet(HFD) on the basis of protein kinase B(Akt)/transcription factor EB(TFEB) signaling pathway. Co-localization was carried out for the microtubule-associated protein light chain 3(LC3) plasmid labeled with green fluorescent protein(GFP) and lipid droplets(LDs), and immunofluorescence co-localization for liver LC3 of HFD mice and perilipin 2(PLIN2). The results showed that ZXD up-regulated the expression of LC3, reduced lipid accumulation in hepatocytes, and increased the co-localization of LC3 and LDs, thereby activating lipo-phagy. Western blot results confirmed that ZXD increased autophagy-related protein LC3Ⅱ/LC3Ⅰ transformation ratio and lysosome-associated membrane protein 2(LAMP2) in vivo and in vitro and promoted the degradation of sequestosome-1(SQSTM1/p62)(P<0.05). The results above jointly explained that ZXD regulated lipophagy. Furthermore, ZXD activated TFEB expression(P<0.05) and reversed the PA-and HFD-induced decrease of TFEB nuclear localization in hepatocytes(P<0.05). Meanwhile, ZXD activated liver TFEB to up-regulate the expression of the targets Lamp2, Lc3 B, Bcl2, and Atg5(P<0.05). Additionally, ZXD down-regulated the protein level of p-Akt upstream of TFEB in vivo and in vitro. In conclusion, ZXD may promote lipophagy by regulating the Akt/TFEB pathway.


Assuntos
Autofagia , Medicamentos de Ervas Chinesas , Hepatócitos , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Autofagia/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Medicamentos de Ervas Chinesas/farmacologia
14.
J Hazard Mater ; 440: 129794, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36007370

RESUMO

Anodic oxidation with boron-doped diamond (BDD) has been regarded as outstanding option for wastewater treatment. However, in the presence of halide, the extreme promise of the technology may be hampered by the formation of toxic halogenated by-products. While the behaviors of chloride are relatively understood, little is currently known about the role of bromide and its effect on the generation of brominated transformation by-products (BTPs). Herein, we reported for the first time the bromide-mediated electrochemical mineralization of bisphenol A with BDD anodes. Firstly, we employed statistical methodology to determine the impacts of the main operating variables on the mineralization performance, and the novel and peculiar roles of bromides during the electrolytic oxidations were identified. Next, LC/MS analysis was used to identify the reaction intermediates, and plenty of BTPs (including oligomers of complex structures) were thus detected. Detailed transformation mechanisms responsible for the BTPs were also proposed. Lastly, we used ECOSAR program to determine the ecological toxicity of all detected by-products, and the structure-toxicity relation involved was discussed. Overall, the above results are of particular interest to understand BTPs formation mechanism in electrochemical oxidation processes, which as well provide guidelines to minimize potential risks of BDD technology for phenolic wastewater treatment.


Assuntos
Diamante , Poluentes Químicos da Água , Compostos Benzidrílicos , Boro/química , Brometos , Cloretos , Diamante/química , Eletrodos , Oxirredução , Fenóis , Poluentes Químicos da Água/química
15.
J Org Chem ; 87(15): 9479-9487, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35834799

RESUMO

In this study, an efficient method for the synthesis of sulfur-substituted 4-enyl-2-pyrrolidones was successfully developed through AIBN-promoted highly selective 5-exo-dig radical cascade cyclization of 1,6-enynes with sulfur sources with the aid of theoretical and computational chemistry. This protocol enables the first practical and green synthesis of an array of 4-enyl-2-pyrrolidones in moderate-to-good yields with broad substrate scopes and high regioselectivities (>20:1). Moreover, excellent stereoselectivities have also been achieved (up to >20:1, Z/E). Most interestingly, when the sulfur source is electron-rich thiophenol, reverse stereoselectivities were discovered. In addition, the control experiments indicate that the cascade cyclization is realized by radical reactions, and the detailed reaction mechanism and regioselectivities have also been explained by theoretical studies.

16.
Mol Med Rep ; 26(1)2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35656892

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies and primarily presents with hyperandrogenism. Although environmental factors and genetic factors are thought to be the major reason, there still exists a lot of questions need to be answered. High expression of C­terminal­binding protein 1 antisense (CTBP1­AS) was identified as an independent risk factor for PCOS; however, the molecular mechanism of CTBP1­AS in PCOS regulation is unknown. In the present study, the expression level of CTBP1­AS was found to be significantly upregulated in patients with PCOS compared with healthy control patients. CTBP1­AS knockdown was demonstrated to reduce the proliferation and promote the apoptosis of granulosa tumor cells in vitro. It was also identified that the two core catalytic subunits of Polycomb repressive complex 2 (enhancer of zeste homolog 2 and embryonic and ectoderm development protein) interacted with CTBP1­AS in primary granulosa cells and KGN cells. In addition, cryptotanshinone treatment was demonstrated to effectively downregulate CTBP1­AS expression level. Data from the present study suggested a pathophysiological role of CTBP1­AS in PCOS and may provide a new potential target for PCOS treatment.


Assuntos
Síndrome do Ovário Policístico , RNA Antissenso , Oxirredutases do Álcool , Proteínas de Ligação a DNA , Feminino , Humanos , Fenantrenos , Complexo Repressor Polycomb 2 , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , RNA Antissenso/genética , Ativação Transcricional , Regulação para Cima
17.
Front Nutr ; 9: 865257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571927

RESUMO

Atractylodes macrocephala rhizome (called Bái-zhú in China) has a long history as a functional food and herbal medicine in East Asia, especially China. Sesquiterpenoids are one of the main active compounds of Atractylodes macrocephala rhizome. This study aimed to explore the unknown sesquiterpenoids of A. macrocephala rhizome using a molecular networking strategy. Two new nitrogen-containing sesquiterpenoids, atractylenolactam A (1) and atractylenolactam B (2), and 2 new sesquiterpene lactones, 8-methoxy-atractylenolide V (6) and 15-acetoxyl atractylenolide III (7), along with 12 known analogs (3-5 and 8-16) were discovered and isolated. All the structures were assigned based on detailed spectroscopic analyses. The absolute configurations of 1, 2, 6, and 7 were established by time-dependent density functional theory ECD (TDDFT-ECD) calculations. All these compounds had different degrees of concentration-dependent activating effects on nuclear-factor-E2-related factor-2 (Nrf2).

18.
Front Genet ; 13: 880359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559037

RESUMO

Tumor is one of the important factors affecting human life and health in today's world, and scientists have studied it extensively and deeply, among which autophagy and JAK/STAT3 signaling pathway are two important research directions. The JAK/STAT3 axis is a classical intracellular signaling pathway that assumes a key role in the regulation of cell proliferation, apoptosis, and vascular neogenesis, and its abnormal cell signaling and regulation are closely related to the occurrence and development of tumors. Therefore, the JAK/STAT3 pathway in tumor cells and various stromal cells in their microenvironment is often considered as an effective target for tumor therapy. Autophagy is a process that degrades cytoplasmic proteins and organelles through the lysosomal pathway. It is a fundamental metabolic mechanism for intracellular degradation. The mechanism of action of autophagy is complex and may play different roles at various stages of tumor development. Altered STAT3 expression has been found to be accompanied by the abnormal autophagy activity in many oncological studies, and the two may play a synergistic or antagonistic role in promoting or inhibiting the occurrence and development of tumors. This article reviews the recent advances in autophagy and its interaction with JAK/STAT3 signaling pathway in the pathogenesis, prevention, diagnosis, and treatment of tumors.

19.
Int Urol Nephrol ; 54(10): 2555-2566, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35277831

RESUMO

OBJECTIVE: To explore the efficacy and safety of tacrolimus (TAC) combined with corticosteroids in patients with idiopathic membranous nephropathy (IMN). METHODS: A literature search was performed using Embase, Cochrane Library and PubMed from inception through May 31, 2021. All randomized controlled trials (RCTs) exploring the efficacy and safety of TAC combined with corticosteroids in IMN patients were included based on the inclusion and exclusion criteria. Data analyses were conducted using RevMan software (version 5.4). RESULTS: Seven RCTs involving 520 patients were included in this meta-analysis. Compared with control treatment, TAC combined with corticosteroids could significantly increase the complete remission (CR) rate, total remission (TR) rate, and serum albumin levels, as well as decrease the proteinuria levels within 6-month treatment, but the advantage did not persist to 12-month treatment. After 18-month treatment, the effect of TAC combined with corticosteroids on increasing CR rate, TR rate, and serum albumin levels was significantly worse than control treatment. The mean time to remission in TAC combined corticosteroids group was significantly shorter than that in the control group. The relapse rate, no response rate, change in estimate of the glomerular filtration rate (eGFR), and overall incidence of adverse reactions showed no significant difference between TAC combined with corticosteroids group and control group. However, TAC combined with corticosteroids did have a higher risk of hand tremor, nephrotoxicity, and glucose intolerance than control treatment. CONCLUSION: TAC combined with corticosteroids has a significant therapeutic effect for IMN patients within 1-year treatment, especially in the first 6 months. However, in the longer-term treatment, TAC combined with corticosteroids does not have an advantage. TAC combined with corticosteroids has a higher risk of hand tremor, nephrotoxicity, and glucose intolerance. More high-quality studies are needed to further verify the long-term efficacy and safety of TAC combined with glucocorticoids in IMN patients.


Assuntos
Corticosteroides , Glomerulonefrite Membranosa , Tacrolimo , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Quimioterapia Combinada , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/tratamento farmacológico , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Albumina Sérica/análise , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Resultado do Tratamento , Tremor/induzido quimicamente , Tremor/tratamento farmacológico
20.
J Ethnopharmacol ; 290: 115101, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35151834

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zexie Tang (ZXT), only two consists with Alismatis Rhizoma (AR) and Atractylodes macrocephala Rhizoma (AM), a classical Chinese medicine formula from Synopsis of the Golden Chamber with a history of 2000 years. Clinical observation in recent years has found that ZXT has excellent lipid-lowering effect. AIM OF THE STUDY: To explore the potential mechanism of ZXT ameliorates hyperlipidemia based on FKBP38/mTOR/SREBPs pathway. MATERIALS AND METHODS: WD-induced hyperlipidemia mice and oleic acid induced cell lipid accumulation model were used to investigate pharmacodynamic. The effect of ZXT on the transcriptional activity of SREBPs was detected by reporter gene assay. Proteins and downstream genes of mTOR/SREBPs pathway were detected in vivo and in vitro. Combined with network pharmacology and HPLC-Q-TOF/MS, the active ingredients were screened and identified. The interaction between active compounds of ZXT and FKBP38 protein were analyzed by docking analysis. RESULTS: ZXT decreased TC, TG and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo. ZXT also reduced TC, TG and lipid accumulation in cells line, and inhibited SREBPs luciferase activity, protein and its target genes expression such as FASN, HMGCR, etc. Meanwhile, ZXT inhibited protein expression levels of p-mTOR, p-S6K, etc in vitro and in vivo. Combined with network pharmacology and HPLC-Q-TOF/MS, 16 active ingredients were screened and identified. Docking results showed that active compounds of ZXT binding to FKBP38 and formed hydrogen bond. CONCLUSION: Our findings highlighted that ZXT ameliorates hyperlipidemia, in which FKBP/mTOR/SREBPs pathway might be the potential regulatory mechanism.


Assuntos
Hiperlipidemias/patologia , Lipídeos/sangue , Extratos Vegetais/farmacologia , Proteínas de Ligação a Elemento Regulador de Esterol/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Proteínas de Ligação a Tacrolimo/efeitos dos fármacos , Alismatales , Animais , Atractylodes , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Farmacologia em Rede
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