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Electrochemical reduction of CO2 to multicarbon (C2+) products with added value represents a promising strategy for achieving a carbon-neutral economy. Precise manipulation of the catalytic interface is imperative to control the catalytic selectivity, particularly toward C2+ products. In this study, a unique Cu/UIO-Br interface is designed, wherein the Cu(111) plane is co-modified simultaneously by Br and O from UIO-66-Br support. Such Cu/UIO-Br catalytic interface demonstrates a superior Faradaic efficiency of ≈53% for C2+ products (ethanol/ethylene) and the C2+ partial current density reached 24.3 mA cm-2 in an H-cell electrolyzer. The kinetic isotopic effect test, in situ attenuated total reflection Fourier transform infrared spectroscopy and density functional theory calculations have been conducted to elucidate the catalytic mechanism. The Br, O co-modification on the Cu(111) interface enhanced the adsorption of CO2 species. The hydrogen-bond effect from the doped Br atom regulated the kinetic processes of *H species in CO2RR and promoted the formation of *COH intermediate. The formed *COH facilitates the *CO-*COH coupling and promotes the C2+ selectivity finally. This comprehensive investigation not only provides an in-depth study and understanding of the catalytic process but also offers a promising strategy for designing efficient Cu-based catalysts with exceptional C2+ products.
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BACKGROUND: Cellular senescence is an emerging hallmark of cancers, primarily fuels cancer progression by expressing senescence-associated secretory phenotype (SASP). Caveolin-1 (CAV1) is a key mediator of cell senescence. Previous studies from our group have evidenced that the expression of CAV1 is downregulated by Celastrol (CeT). PURPOSE: To investigate the impact of CeT on cellular senescence and its subsequent influence on post-senescence-driven invasion, migration, and stemness of clear cell renal cell carcinoma (ccRCC). STUDY DESIGN AND METHODS: The expression levels of CAV1, canonical senescence markers, and markers associated with epithelial-mesenchymal transition (EMT) and stemness in clinical samples were assessed through Pearson correlation analysis. Senescent cell models were induced using DOX, and their impact on migration, invasion, and stemness was evaluated. The effects of CeT treatment on senescent cells and their pro-tumorigenic effects were examined. Subsequently, the underlying mechanism of CeT were explored using lentivirus transfection and CRISPR/Cas9 technology to silence CAV1. RESULTS: In human ccRCC clinical samples, the expression of the canonical senescence markers p53, p21, and p16 are associated with ccRCC progression. Senescent cells facilitated migration, invasion, and enhanced stemness in both ccRCC cells and ccRCC tumor-bearing mice. As expected, CeT treatment reduced senescence markers (p16, p53, p21, SA-ß-gal) and SASP factors (IL6, IL8, CXCL12), alleviating cell cycle arrest. However, it did not restore the proliferation of senescent cells. Additionally, CeT suppressed senescence-driven migration, invasion, and stemness. Further investigations into the underlying mechanism demonstrated that CAV1 is a critical mediator of cell senescence and represents a potential target for CeT to attenuate cellular senescence. CONCLUSIONS: This study presents a pioneering investigation into the intricate interplay between cellular senescence and ccRCC progression. We unveil a novel mechanism of CeT to mitigate cellular senescence by downregulating CAV1, thereby inhibiting the migration, invasion and stemness of ccRCC driven by senescent cells. These findings provide valuable insights into the underlying mechanisms of CeT and its potential as a targeted therapeutic approach for alleviating the aggressive phenotypes associated with senescent cells in ccRCC.
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Carcinoma de Células Renais , Caveolina 1 , Senescência Celular , Transição Epitelial-Mesenquimal , Triterpenos Pentacíclicos , Caveolina 1/metabolismo , Senescência Celular/efeitos dos fármacos , Humanos , Triterpenos Pentacíclicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular Tumoral , Animais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Triterpenos/farmacologia , Movimento Celular/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , CamundongosRESUMO
BACKGROUND: Targeting immunogenic cell death (ICD) is considered a promising therapeutic strategy for cancer. However, the commonly identified ICD inducers promote the expression of programmed cell death ligand 1 (PD-L1) in tumor cells, thus aiding them to evade the recognition and killing by the immune system. Therefore, the finding of novel ICD inducers to avoid enhanced PD-L1 expression is of vital significance for cancer therapy. Celastrol (CeT), a triterpene isolated from Tripterygium wilfordii Hook. F induces various forms of cell death to exert anti-cancer effects, which may make celastrol an attractive candidate as an inducer of ICD. METHODS: In the present study, bioinformatics analysis was combined with experimental validation to explore the underlying mechanism by which CeT induces ICD and regulates PD-L1 expression in clear cell renal cell carcinoma (ccRCC). RESULTS: The results showed that EGFR, IKBKB, PRKCQ and MAPK1 were the crucial targets for CeT-induced ICD, and only MAPK1 was an independent prognostic factor for the overall survival (OS) of ccRCC patients. In addition, CeT triggered autophagy and up-regulated the expressions of HMGB1 and CRT to induce ICD in 786-O cells in vitro. Importantly, CeT can down-regulate PD-L1 expression through activating autophagy. At the molecular level, CeT suppressed PD-L1 via the inhibition of MAPK1 expression. Immunologically, the core target of celastrol, MAPK1, was tightly correlated with CD8+ T cells and CD4+ T cells in ccRCC. CONCLUSION: These findings indicate that CeT not only induces ICD but also suppresses PD-L1 by down-regulating MAPK1 expression, which will provide an attractive strategy for ccRCC immunotherapy.
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Antígeno B7-H1 , Carcinoma de Células Renais , Regulação para Baixo , Neoplasias Renais , Triterpenos Pentacíclicos , Triterpenos Pentacíclicos/farmacologia , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Regulação para Baixo/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Antineoplásicos/farmacologia , Triterpenos/farmacologia , Morte Celular Imunogênica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Copper (Cu), with the advantage of producing a deep reduction product, is a unique catalyst for the electrochemical reduction of CO2 (CO2RR). Designing a Cu-based catalyst to trigger CO2RR to a multicarbon product and understanding the accurate structure-activity relationship for elucidating reaction mechanisms still remain a challenge. Herein, we demonstrate a rational design of a core-shell structured silica-copper catalyst (p-Cu@m-SiO2) through Cu-Si direct bonding for efficient and selective CO2RR. The Cu-Si interface fulfills the inversion in CO2RR product selectivity. The product ratio of C2H4/CH4 changes from 0.6 to 14.4 after silica modification, and the current density reaches a high of up to 450 mA cm-2. The kinetic isotopic effect, in situ attenuated total reflection Fourier-transform infrared spectra, and density functional theory were applied to elucidate the reaction mechanism. The SiO2 shell stabilizes the *H intermediate by forming Si-O-H and inhibits the hydrogen evolution reaction effectively. Moreover, the direct-bonded Cu-Si interface makes bare Cu sites with larger charge density. Such bare Cu sites and Si-O-H sites stabilized the *CHO and activated the *CO, promoting the coupling of *CHO and *CO intermediates to form C2H4. This work provides a promising strategy for designing Cu-based catalysts with high C2H4 catalytic activity.
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Lipid metabolism disorders are pivotal in the development of various lipid-related diseases, such as obesity, atherosclerosis, non-alcoholic fatty liver disease, type 2 diabetes, and cancer. Celastrol, a bioactive compound extracted from the Chinese herb Tripterygium wilfordii Hook F, has recently demonstrated potent lipid-regulating abilities and promising therapeutic effects for lipid-related diseases. There is substantial evidence indicating that celastrol can ameliorate lipid metabolism disorders by regulating lipid profiles and related metabolic processes, including lipid synthesis, catabolism, absorption, transport, and peroxidation. Even wild-type mice show augmented lipid metabolism after treatment with celastrol. This review aims to provide an overview of recent advancements in the lipid-regulating properties of celastrol, as well as to elucidate its underlying molecular mechanisms. Besides, potential strategies for targeted drug delivery and combination therapy are proposed to enhance the lipid-regulating effects of celastrol and avoid the limitations of its clinical application.
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Diabetes Mellitus Tipo 2 , Triterpenos Pentacíclicos , Triterpenos , Animais , Camundongos , Metabolismo dos Lipídeos , Lipídeos , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Triterpenos/metabolismoRESUMO
Objective@#To explore the association between dietary inflammatory index (DII) and metabolic syndrome (MetS) and its components among children aged 6-14 years in Beijing, so as to provide a reference for preventing MetS.@*Methods@#A cross sectional study was carried out in 2 086 records of 1 832 children from the 2017 and 2019 Nutrition and Health Surveillance in Primary and Secondary school students of Beijing (NHSPSB). Three day consecutive 24 hour dietary recalls combined with weighing household cooking oils and condiments were used to collect dietary intake and calculate DII. MetS was diagnosed according to "Definition and Suggestion on the Metabolic Syndrome of Chinese Children and Adolescent". The Generalized estimating equations (GEEs) models were used to analyze the association between DII and the presence of MetS and its components (abdominal obesity, high triglyceride, low high density lipoprotein cholesterol, hypertension, and hyperglycemia).@*Results@#The mean DII score was (1.64±1.07) for the included children. No significant association was found between DII scores and the likelihood of MetS (per 1 point increment: OR =1.16, 95% CI =0.92-1.48, P >0.05). In terms of the components of MetS, DII scores were positively associated with the odds of high triglyceride (per 1 point increment: OR =1.17, 95% CI =1.01-1.36, P <0.05). There was no statistically significant difference in the association among different age groups ( P >0.05). No significant associations were observed between DII and other MetS components( P >0.05).@*Conclusion@#DII scores may not be correlated with the risk of MetS, but proinflammatory diet might increase the risk of high triglyceride. DII score in childhood should be emphasized to identify and prevent MetS as soon as possible.
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The high level of serum cholesterol caused by the excessive absorption of cholesterol can lead to hypercholesteremia, thus promoting the occurrence and development of cancer. Ezetimibe is a drug that reduces cholesterol absorption and has been widely used for the treatment of patients with high circulating cholesterol levels for many years. Mechanistically, ezetimibe works by binding to NPC1L1, which is a key mediator of cholesterol absorption. Accumulating data from preclinical models have shown that ezetimibe alone could inhibit the development and progression of cancer through a variety of mechanisms, including anti-angiogenesis, stem cell suppression, anti-inflammation, immune enhancement and anti-proliferation. In the past decade, there has been heated discussion on whether ezetimibe combined with statins will increase the risk of cancer. At present, more and more evidence shows that ezetimibe does not increase the risk of cancers, which supports the role of ezetimibe in anti-cancer. In this review, we discussed the latest progress in the anti-cancer properties of ezetimibe and elucidated its underlying molecular mechanisms. Finally, we highlighted the potential of ezetimibe as a therapeutic agent in future cancer treatment and prevention.
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Cancer stem cells (CSCs) are a subpopulation of cancer cells with stem cell properties that sustain cancers, which may be responsible for cancer metastasis or recurrence. Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in the plasma membrane that mediate various intracellular signaling. The occurrence and progression of cancer are closely related to lipid rafts. Emerging evidence indicates that lipid raft levels are significantly enriched in CSCs compared to cancer cells and that most CSC markers such as CD24, CD44, and CD133 are located in lipid rafts. Furthermore, lipid rafts play an essential role in CSCs, specifically in CSC self-renewal, epithelial-mesenchymal transition, drug resistance, and CSC niche. Therefore, lipid rafts are critical regulatory platforms for CSCs and promising therapeutic targets for cancer therapy.
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Neoplasias , Células-Tronco Neoplásicas , Transição Epitelial-Mesenquimal , Humanos , Microdomínios da Membrana/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Células-Tronco Neoplásicas/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Disturbance of cholesterol homeostasis is considered as one of the manifestations of cancer. Cholesterol plays an essential role in the pleiotropic functions of cancer cells, including mediating membrane trafficking, intracellular signal transduction, and production of hormones and steroids. As a single transmembrane receptor, the low-density lipoprotein receptor (LDLR) can participate in intracellular cholesterol uptake and regulate cholesterol homeostasis. It has recently been found that LDLR is aberrantly expressed in a broad range of cancers, including colon cancer, prostate cancer, lung cancer, breast cancer and liver cancer. LDLR has also been found to be involved in various signaling pathways, such as the MAPK, NF-κB and PI3K/Akt signaling pathways, which affect cancer cells and their surrounding microenvironment. Moreover, LDLR may serve as an independent prognostic factor for lung cancer, breast cancer and pancreatic cancer, and is closely related to the survival of cancer patients. However, the role of LDLR in some cancers, such as prostate cancer, remains controversial. This may be due to the lack of normal feedback regulation of LDLR expression in cancer cells and the severe imbalance between LDLR-mediated cholesterol uptake and de novo biosynthesis of cholesterol. CONCLUSIONS: The imbalance of cholesterol homeostasis caused by abnormal LDLR expression provides new therapeutic opportunities for cancer. LDLR interferes with the occurrence and development of cancer by modulating cholesterol homeostasis and may become a novel target for the development of anti-cancer drugs. Herein, we systematically review the contribution of LDLR to cancer progression, especially its dysregulation and underlying mechanism in various malignancies. Besides, potential targeting and immunotherapeutic options are proposed.
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Colesterol , Neoplasias , Humanos , Colesterol/metabolismo , Homeostase , Hormônios , Lipoproteínas LDL/metabolismo , NF-kappa B , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Microambiente Tumoral , Neoplasias/metabolismoRESUMO
With the rapid aging in the global population, delay of aging has become a hot research topic. Lipid rafts (LRs) are microdomains in the plasma membrane that contain sphingolipids and cholesterol. Emerging evidence indicates an interesting interplay between LRs and aging. LRs and their components are altered with aging. Further, the aging process is strongly influenced by LRs. In recent years, LRs and their component signaling molecules have been recognized to affect aging by interfering with its hallmarks. Therefore, targeting LRs is a promising strategy to delay aging.
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Lipid metabolism disorder is related to an increased risk of tumorigenesis and is involved in the rapid growth of cancer cells as well as the formation of metastatic lesions. Epidemiological studies have demonstrated that low-density lipoprotein (LDL) and oxidized low-density lipoprotein (ox-LDL) are closely associated with breast cancer, colorectal cancer, pancreatic cancer, and other malignancies, suggesting that LDL and ox-LDL play important roles during the occurrence and development of cancers. LDL can deliver cholesterol into cancer cells after binding to LDL receptor (LDLR). Activation of PI3K/Akt/mTOR signaling pathway induces transcription of the sterol regulatory element-binding proteins (SREBPs), which subsequently promotes cholesterol uptake and synthesis to meet the demand of cancer cells. Ox-LDL binds to the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cluster of differentiation 36 (CD36) to induce mutations, resulting in inflammation, cell proliferation, and metastasis of cancer. Classic lipid-lowering drugs, statins, have been shown to reduce LDL levels in certain types of cancer. As LDL and ox-LDL play complicated roles in cancers, the potential therapeutic effect of targeting lipid metabolism in cancer therapy warrants more investigation.
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Sophorolipids (SLs) are homologous microbial secondary metabolites produced by Starmerella bombicola and have been widely applied in many industrial fields. The biosynthesis of SLs is a highly aerobic process and is often limited by low dissolved oxygen (DO) levels. In this study, the Vitreoscilla hemoglobin (VHb) gene was transformed into S. bombicola O-13-1 by homologous recombination to alleviate oxygen limitation. VHb expression improved the intracellular oxygen utilization efficiency under either oxygen-rich or oxygen-limited conditions. In shake flask culture, the production of SLs was higher in the recombinant (VHb+) strain than in the wild-type (VHb-) strain, while the oxygen uptake rate of the recombinant (VHb+) strain was significantly lower than that of the wild-type (VHb-) strain. In a 5 L bioreactor, the production of SLs did not increase significantly, but the DO level in the fermentation broth of the VHb+ strain was 21.8% higher than that of VHb- strain under oxygen-rich conditions. Compared to wide-type strains (VHb-), VHb expression enhanced SLs production by 25.1% in the recombinants (VHb+) under oxygen-limited conditions. In addition, VHb expression raised the transcription levels of key genes involved in the electron transfer chain (NDH, SDH, COX), TCA cycle (CS, ICD, KDG1) and SL synthesis (CYP52M1 and UGTA1) in the recombinant (VHb+) strains. VHb expression in S. bombicola could enhance SLs biosynthesis and intracellular oxygen utilization efficiency by increasing ATP production and cellular respiration. Our findings highlight the potential use of VHb to improve the oxygen utilization efficiency of S. bombicola in the industrial-scale production of SLs using industrial and agricultural by-products like molasses and waste oil as fermentation feedstock.
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Based on the discharge characteristics of agricultural non-point source pollution in the headstream region of the Kaihui River-a typical small agricultural watershed, an integrated ecological engineering treatment system (IEETS) was constructed with ecological wetland as the core unit to control the pollution. The nitrogen (N) and phosphorus (P) removal performances of the IEETS were discussed in this study. The results showed that the dominant source of N and P in the study area was livestock and poultry breeding, which was urgent to control. The monitoring results indicated that the ecological wetland treatment project resulted in average total nitrogen (TN) and total phosphorus (TP) removal rates of 87.1% and 90.9%, respectively, when treating mixed decentralized domestic and swine wastewater treatment. The multi-stage constructed wetlands had an average of 85.7% of TN and 84.9% of TP removal for mixed farmland drainage and decentralized swine wastewater. The removal rates for landscape-based ecological wetland were within the range of 27.1%-67.4% for TN and 13.3%-81.5% for TP in the catchment terminal water. The total interception amount of TN and TP by the IEETS was 5292 kg·a-1 and 1054 kg·a-1, accounting for 35.3% and 43.6% of total pollution loads in the headstream region, respectively. These findings illustrated that the IEETS presents promising treatment results on non-point source pollution, and is suitable for widespread applications to wastewater treatment in small watersheds of southern China.
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Objective:To provide evidence and lay a foundation for quality control and resources utilization of Kochiae Fructus. Method:A total of 23 samples of Kochiae Fructus were collected from the main distribution areas in China. Momordin Ⅰc content was determined via HPLC-ELSD method, and its correlation with growth traits and habitat factors was analyzed using SPSS 23.0 software,as well as the principle component and clustering analysis. Result:Momordin Ⅰc content had a benign linear relationship with HPLC-ELSD peak area within the range between 29.8 mg·L-1 and 178.8 mg·L-1 (R2=0.999 8),with the quantitation limit at 5.79 mg·L-1 and the detection limit at 2.36 mg·L-1. Significant differences (PChinese Pharmacopeia published in 2015.Origin,growth traits,and habitat factors could impact momordin Ⅰc content accumulation in Kochiae Fructus. Moreover,the content had a negative correlation with plant height,stem diameter,leaf length,leaf width,fruit diameter and longitude,and a positive correlation with ratio of length to width of leaves,altitude and latitude. Those from Shanxi,Jilin,and Shandong provinces had a higher momordin Ⅰc content. The characters tested could be simplified to four principle components, and their cumulative contribution rate was 95.831%. Kochiae Fructus samples tested could be divided into four groups,and those from group Ⅰ had superior growth traits, and those from group Ⅲ had higher momordin Ⅰc content. Conclusion:The optimized HPLC-ELSD method for determining momordin Ⅰc content of Kochiae Fructus is convenient,accurate and reproducible,and could be used to control the herbs quality. Those cultivated in a lower longitude,higher altitude,and higher latitude region could accumulate more momordin Ⅰc content. More attention shall be paid to germplasm in Shanxi and Zhejiang with superior resources screening of Kochiae Fructus.
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The aim of this study was to investigate whether uric acid (UA) might exert neuroprotection via activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and regulating neurotrophic factors in the cerebral cortices after transient focal cerebral ischemia/reperfusion (FCI/R) in rats. UA was intravenously injected through the tail vein (16 mg/kg) 30 min after the onset of reperfusion in rats subjected to middle cerebral artery occlusion for 2 h. Neurological deficit score was performed to analyze neurological function at 24 h after reperfusion. Terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling (TUNEL) staining and hematoxylin and eosin (HE) staining were used to detect histological injury of the cerebral cortex. Malondialdehyde (MDA), the carbonyl groups, and 8-hydroxyl-2'-deoxyguanosine (8-OHdG) levels were employed to evaluate oxidative stress. Nrf2 and its downstream antioxidant protein, heme oxygenase- (HO-) 1,were detected by western blot. Nrf2 DNA-binding activity was observed using an ELISA-based measurement. Expressions of BDNF and NGF were analyzed by immunohistochemistry. Our results showed that UA treatment significantly suppressed FCI/R-induced oxidative stress, accompanied by attenuating neuronal damage, which subsequently decreased the infarct volume and neurological deficit. Further, the treatment of UA activated Nrf2 signaling pathway and upregulated BDNF and NGF expression levels. Interestingly, the aforementioned effects of UA were markedly inhibited by administration of brusatol, an inhibitor of Nrf2. Taken together, the antioxidant and neuroprotective effects afforded by UA treatment involved the modulation of Nrf2-mediated oxidative stress and regulation of BDNF and NGF expression levels. Thus, UA treatment could be of interest to prevent FCI/R injury.
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Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ácido Úrico/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Animais , Western Blotting , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Ensaio de Imunoadsorção Enzimática , Heme Oxigenase-1/metabolismo , Imunoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Carpesium humile Winkl is an endemic Chinese species and no previous phytochemical studies have been reported for this species. Two new germacranolides (1 and 2) and a new phytane diterpene (5), together with five known compounds (two sesquiterpenoids and three diterpenoids), were isolated from the aerial parts of C. humile. Their structures were elucidated on the basis of extensive spectroscopic analysis. The conformations and absolute configurations of 1 and 2 were established by combinative analysis of NMR, CD exciton chirality, and X-ray crystallography data. Four germacranolides (1-4) showed strong cytotoxic activities, with broad spectrum activities against six human cancer (HepG2, HeLa, HL60, SGC7901, Lewis, and MDA231) cell lines in vitro using MTT assay, with IC50 values from 3.09 to 7.71⯵g/mL. Diterpenes (5, 6, and 8) also displayed good cytotoxic activities for selected cancer cell lines, with IC50 values in the range 5.46-8.08⯵g/mL.
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Antineoplásicos Fitogênicos/isolamento & purificação , Asteraceae/química , Diterpenos/isolamento & purificação , Sesquiterpenos de Germacrano/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Componentes Aéreos da Planta/química , Sesquiterpenos de Germacrano/farmacologiaRESUMO
The design and synthesis of metal-organic frameworks (MOFs) enclosed with multiple catalytic active sites is favorable for cooperative catalysis, but is is still challenging. Herein, we developed a sequential postsynthetic ionization and metalation strategy to prepare bifunctional multivariate Zr-MOFs incorporating zinc porphyrin and imidazolium functionalities. Using this facile strategy, tetratopic [5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato]zinc(II) (ZnTCPP) ligands were successfully installed into the cationic Zr-MOF to obtain ZnTCPPâ(Br-)Etim-UiO-66. These MTV-MOFs, including TCPPâIm-UiO-66, TCPPâ(Br-)Etim-UiO-66, and ZnTCPPâ(Br-)Etim-UiO-66, were well characterized and used in CO2 capture and conversion into cyclic carbonate from allyl glycidyl ether and CO2 under cocatalyst-free and 1 bar CO2 pressure conditions. It was found that the structural features and CO2 affinity properties of these MTV-MOFs can be tuned by introducing imidazolium groups or doping zinc sites. Additionally, ZnTCPPâ(Br-)Etim-UiO-66 exhibited enhanced catalytic activities compared to other MTV-MOFs herein for obtaining the 3-allyloxy-1,2-proplyene carbonate product, which was attributed to the cooperative effect of Zn2+ sites and Br- ions in this microporous ionic MTV-MOF. ZnTCPPâ(Br-)Etim-UiO-66 can be recycled easily and used at least three times.
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Extracts of the aerial parts of Scorzonera divaricata afforded sulfoscorzonin D (1) and sulfoscorzonin E (2), two novel pyrrolidine inner salt alkaloids with a sulfated guaiane sesquiterpene lactone nucleus, along with 22 known compounds. Especially, sulfoscorzonin D containing a unusual monoterpene moiety is very rare. The structures of new compounds were established using spectroscopic analysis including one- and two-dimensional NMR and HRESIMS. The cytotoxicities of compounds 1-4 and 10 against three tumor cell lines (K562, Hela, and HepG2) were evaluated using the MTT assay. Compounds 2 and 10 exhibited moderate cytotoxic activity. The biological properties of 1-3, 5-8, 10-14, and 16-24, were screened against nine different gram-positive and gram-negative bacteria. Compounds 1, 5-8, 10, and 18, showed potent antibacterial activities. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Glucozaluzanin C (PubChem CID: 442320); 1ß,4α-dihydroxy-5α,6ß,7α,11ßH-eudermn-12; 6-olide (CID: 11119093); oleanolic acid (CID: 10494); lup-20(29)-ene-3ß,28-diol (CID: 72326); (22E)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol (CID: 5469431); ergosta-3ß,5α, 6ß-trialcohol (CID: 44558918); stigma-5-en-3-O-ß-glucoside (CID: 5742590); vomifoliol (CID: 12444927); trans-caffeic acid (CID: 689043); trans-p-hydroxy coumaric acid (CID: 637542); 4-hydroxy-3-methoxyphenyl ferulate (CID: 11500646); 7,3',4'-trihydroxyflavonol (CID: 5281614); tricin (ID: 5281702); luteolin (CID: 5280445); diosmetin (CID: 5281612); 5,7-dihydroxy-8-methoxyflavone (CID: 5281703); 5,7-dihydroxy-6-methoxyflavone (CID: 5320315); methyl-3,4-dihydroxy benzoate (CID: 287064); m-hydroxy benzoic acid (CID: 7420); 7-hydroxy-coumarin (CID: 5281426); and scopoletin (CID: 5280460).
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Alcaloides/isolamento & purificação , Componentes Aéreos da Planta/química , Scorzonera/química , Sesquiterpenos de Guaiano/isolamento & purificação , Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Estrutura MolecularRESUMO
Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia. C57BL/6 mice were subjected to bilateral common carotid artery occlusion for 20 min and sacrificed 24 h after reperfusion. 5-HMF (12 mg/kg) or an equal volume of vehicle was intraperitoneally injected 30 min before ischemia and 5 min after the onset of reperfusion. At 24 h after reperfusion, neurological function was evaluated by neurological disability status scale, locomotor activity test and inclined beam walking test. Histological injury of the striatum was observed by cresyl violet staining and terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) staining. Oxidative stress was evaluated by the carbonyl groups introduced into proteins, and malondialdehyde (MDA) levels. An enzyme-linked immunosorbent assay (ELISA)-based measurement was used to detect Nrf2 DNA binding activity. Nrf2 and its downstream ARE pathway protein expression such as heme oxygenase-1, NAD (P)H:quinone oxidoreductase 1, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modulatory subunit were detected by western blot. Our results showed that 5-HMF treatment significantly ameliorated neurological deficits, reduced brain water content, attenuated striatum neuronal damage, decreased the carbonyl groups and MDA levels, and activated Nrf2/ARE signaling pathway. Taken together, these results demonstrated that 5-HMF exerted significant antioxidant and neuroprotective effects following transient cerebral ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.
Assuntos
Furaldeído/análogos & derivados , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Elementos de Resposta Antioxidante/fisiologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Furaldeído/farmacologia , Glutamato-Cisteína Ligase/metabolismo , Heme Oxigenase-1/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Six eremophilane-type (parasenolide A-F) and an eudesmane-type (parasenin) sesquiterpenoids, along with eight known sesquiterpenes, were isolated from the whole plants of Parasenecio roborowskii. The structures and absolute configurations of new compounds were elucidated using extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR experiments, the CD exciton chirality methods, and single-crystal X-ray crystallography. All isolated compounds were evaluated for cytotoxicity against five human cancer (HeLa, HepG2, K562, MDA231, and NCI-H460) cell lines and a murine melanoma B16 F10 cell line by MTT assay. Compounds 1-15 showed cytotoxic activities, especially compounds 3, 4, 8, 10, and 12. These five compounds showed broad spectrum activities against all the tested cancer cell lines with IC50 ranging from 9.2 to 35.5µM. The study supports that eremophilenolides and eudesmane-type sesquiterpenes occur mainly in the genus Parasenecio and can be used as a chemosystematic marker of the genus.