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1.
Environ Res ; : 119530, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39004391

ABSTRACT

With stringent regulations of internal combustion engine on reducing CO2 emission, ammonia has been used as an alternative fuel. Investigating how engine-related performance is affected by partial ammonia replacement of diesel fuel is essential for understanding the combustion. Therefore, in this study, a three-dimensional numerical simulation model is developed for the burning of two fuels of diesel and ammonia based on relevant parameters (i.e., compression ratio, load, ammonia energy fraction, etc.) in a lab-made diesel engine. The consequences of load and compression proportion on combustion and pollutant emissions are investigated for ammonia energy fractions between 50% and 90%. When the ammonia portion rises, the increased ammonia equivalent ratio causes ammonia to move away from the dilute combustion boundary and accelerates the combustion rate of ammonia. An increase in compression ratio significantly increases the specified thermal performance and combustion efficacy. When the compression ratio is 16, as the ammonia energy fractions increases, due to the increase in the proportion of ammonia, that is, the proportion of nitrogen atoms increases, more NOx is generated during the combustion process. When the ammonia substitution rate is 90%, as the compression ratio increases, the cylinder pressure and temperature increase. The combustion efficiency of ammonia increases, generating more NOx and NOx emissions can reach 0.66 mg/m3. At a compression ratio of 18, the NOx emissions can reach 1.59 mg/m3. However, under medium and low load conditions, as the ammonia fraction increases, the total energy of fuel decreases, and the combustion efficiency of ammonia decreases, resulting in a decrease in the heat released during combustion and a decrease in NOx emissions. When the ammonia substitution rate is 90% and the load is 25%, NOx emissions reach 0.1 mg/m3. This research provides theoretical suggestions for the profitable and use ammonia fuel in internal combustion engines in a clean manner.

2.
Phytomedicine ; 129: 155614, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38692078

ABSTRACT

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.


Subject(s)
Carcinoma, Renal Cell , Caveolin 1 , Cellular Senescence , Epithelial-Mesenchymal Transition , Pentacyclic Triterpenes , Caveolin 1/metabolism , Cellular Senescence/drug effects , Humans , Pentacyclic Triterpenes/pharmacology , Carcinoma, Renal Cell/drug therapy , Cell Line, Tumor , Animals , Epithelial-Mesenchymal Transition/drug effects , Triterpenes/pharmacology , Cell Movement/drug effects , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Mice
3.
J Am Chem Soc ; 146(21): 14835-14843, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38728105

ABSTRACT

The transformation of carbon dioxide (CO2) into functional materials has garnered considerable worldwide interest. Metal-organic frameworks (MOFs), as a distinctive class of materials, have made great contributions to CO2 capture and conversion. However, facile conversion of CO2 to stable porous MOFs for CO2 utilization remains unexplored. Herein, we present a facile methodology of using CO2 to synthesize stable zirconium-based MOFs. Two zirconium-based MOFs CO2-Zr-DEP and CO2-Zr-DEDP with face-centered cubic topology were obtained via a sequential desilylation-carboxylation-coordination reaction. The MOFs exhibit excellent crystallinity, as verified through powder X-ray diffraction and high-resolution transmission electron microscopy analyses. They also have notable porosity with high surface area (SBET up to 3688 m2 g-1) and good CO2 adsorption capacity (up to 12.5 wt %). The resulting MOFs have abundant alkyne functional moieties, confirmed through 13C cross-polarization/magic angle spinning nuclear magnetic resonance and Fourier transform infrared spectra. Leveraging the catalytic prowess of Ag(I) in diverse CO2-involved reactions, we incorporated Ag(I) into zirconium-based MOFs, capitalizing on their interactions with carbon-carbon π-bonds of alkynes, thereby forming a heterogeneous catalyst. This catalyst demonstrates outstanding efficiency in catalyzing the conversion of CO2 and propargylic alcohols into cyclic carbonates, achieving >99% yield at room temperature and atmospheric pressure conditions. Thus, this work provides a dual CO2 utilization strategy, encompassing the synthesis of CO2-based MOFs (20-24 wt % from CO2) and their subsequent application in CO2 capture and conversion processes. This approach significantly enhances overall CO2 utilization.

4.
Ageing Res Rev ; 97: 102294, 2024 06.
Article in English | MEDLINE | ID: mdl-38583577

ABSTRACT

Cellular senescence is a kind of cellular state triggered by endogenous or exogenous stimuli, which is mainly characterized by stable cell cycle arrest and complex senescence-associated secretory phenotype (SASP). Once senescent cells accumulate in tissues, they may eventually accelerate the progression of age-related diseases, such as atherosclerosis, osteoarthritis, chronic lung diseases, cancers, etc. Recent studies have shown that the disorders of lipid metabolism are not only related to age-related diseases, but also regulate the cellular senescence process. Based on existing research evidences, the changes in lipid metabolism in senescent cells are mainly concentrated in the metabolic processes of phospholipids, fatty acids and cholesterol. Obviously, the changes in lipid-metabolizing enzymes and proteins involved in these pathways play a critical role in senescence. However, the link between cellular senescence, changes in lipid metabolism and age-related disease remains to be elucidated. Herein, we summarize the lipid metabolism changes in senescent cells, especially the senescent cells that promote age-related diseases, as well as focusing on the role of lipid-related enzymes or proteins in senescence. Finally, we explore the prospect of lipids in cellular senescence and their potential as drug targets for preventing and delaying age-related diseases.


Subject(s)
Aging , Cellular Senescence , Lipid Metabolism , Humans , Cellular Senescence/physiology , Lipid Metabolism/physiology , Aging/metabolism , Animals , Lipids/physiology
5.
Curr Pharm Des ; 30(16): 1265-1278, 2024.
Article in English | MEDLINE | ID: mdl-38584553

ABSTRACT

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.


Subject(s)
B7-H1 Antigen , Carcinoma, Renal Cell , Down-Regulation , Kidney Neoplasms , Pentacyclic Triterpenes , Pentacyclic Triterpenes/pharmacology , Humans , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Down-Regulation/drug effects , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/immunology , Antineoplastic Agents/pharmacology , Triterpenes/pharmacology , Immunogenic Cell Death/drug effects , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor
6.
Sci Total Environ ; 903: 166477, 2023 Dec 10.
Article in English | MEDLINE | ID: mdl-37625715

ABSTRACT

The continued accumulation of halogenated organic pollutants in soil posed a potential threat to ecosystems and human health. In this study, tetrabromobisphenol A (TBBPA) was used as a typical representative of halogenated organic pollutants in soil, for alkali-thermal activated persulfate (PS) treatment. The results of response surface methodology (RSM) showed a optimal debromination efficiency of TBBPA was 88.99 % under the optimum reaction conditions. Quenching experiments and electron paramagnetic resonance (EPR) confirmed that SO4-•, HO•, O2-• and 1O2 existed simultaneously in the oxidation process. SO4-• played a major role in the initial stage of the reaction, and O2-• played a major role in the the last stage. Based on density functional theory (DFT) and intermediate products, two degradation pathways were proposed, including debromination reaction and ß bond scission. Moreover, the basic physical and chemical properties of the soil were affected to a certain extent, while the soil surface structure, elements and functional group composition rarely changed. In addition, the T.E.S.T. analysis and biotoxicity tests proved that alkali-thermal activated PS can effectively reduce the toxicity of TBBPA-contaminated soil, which is conducive to the subsequent safe secondary utilization of soil.

7.
Materials (Basel) ; 16(14)2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37512244

ABSTRACT

Compared to diesel, liquefied natural gas (LNG), often used as an alternative fuel for marine engines, comes with significant advantages in reducing emissions of particulate matter (PM), SOx, CO2, and other pollutants. Promoting the use of LNG is of great significance for achieving carbon peaking and neutrality worldwide, as well as improving the energy structure. However, compared to diesel engines, medium- and high-speed marine LNG engines may produce higher methane (CH4) emissions and also have nitrogen oxide (NOx) emission issues. For the removal of CH4 and NOx from the exhaust of marine LNG engines, the traditional technical route of combining a methane oxidation catalyst (MOC) and an HN3 selective catalytic reduction system (NH3-SCR) will face problems, such as low conversion efficiency and high operation cost. In view of this, the technology of non-thermal plasma (NTP) combined with CH4-SCR is proposed. However, the synergistic mechanism between NTP and catalysts is still unclear, which limits the optimization of an NTP-CH4-SCR system. This article summarizes the synergistic mechanism of NTP and catalysts in the integrated treatment process of CH4 and NOx, including experimental analysis and numerical simulation. And the relevant impact parameters (such as electrode diameter, electrode shape, electrode material, and barrier material, etc.) of NTP reactor energy optimization are discussed. The work of this paper is of great significance for guiding the high-efficiency removal of CH4 and NOx for an NTP-CH4-SCR system.

8.
Biomed Pharmacother ; 164: 114981, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37285754

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 2 , Pentacyclic Triterpenes , Triterpenes , Animals , Mice , Lipid Metabolism , Lipids , Triterpenes/pharmacology , Triterpenes/therapeutic use , Triterpenes/metabolism
9.
Int J Biol Sci ; 19(8): 2333-2348, 2023.
Article in English | MEDLINE | ID: mdl-37215994

ABSTRACT

Pyroptosis is a novel pro-inflammatory cell programmed death dependent on Gasdermin (GSMD) family-mediated membrane pore formation and subsequent cell lysis, accompanied by the release of inflammatory factors and expanding inflammation in multiple tissues. All of these processes have impacts on a variety of metabolic disorders. Dysregulation of lipid metabolism is one of the most prominent metabolic alterations in many diseases, including the liver, cardiovascular system, and autoimmune diseases. Lipid metabolism produces many bioactive lipid molecules, which are important triggers and endogenous regulators of pyroptosis. Bioactive lipid molecules promote pyroptosis through intrinsic pathways involving reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, lysosomal disruption, and the expression of related molecules. Pyroptosis can also be regulated during the processes of lipid metabolism, including lipid uptake and transport, de novo synthesis, lipid storage, and lipid peroxidation. Taken together, understanding the correlation between lipid molecules such as cholesterol and fatty acids and pyroptosis during metabolic processes can help to gain insight into the pathogenesis of many diseases and develop effective strategies from the perspective of pyroptosis.


Subject(s)
Inflammasomes , Pyroptosis , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Reactive Oxygen Species/metabolism , Lipids
10.
Bioorg Chem ; 134: 106454, 2023 05.
Article in English | MEDLINE | ID: mdl-36889199

ABSTRACT

Glutathione (GSH) is closely related to the occurrence and development of tumors. The intracellular GSH levels are abnormally altered when tumor cells undergo programmed cell death. Therefore, real-time monitoring of the dynamic changes of intracellular GSH levels can better enable the early diagnosis of diseases and evaluate the effects of cell death-inducing drugs. In this study, a stable and highly selective fluorescent probe AR has been designed and synthesized for the fluorescence imaging and rapid detection of GSH in vitro and in vivo, as well as patient-derived tumor tissue. More importantly, the AR probe can be used to track changes in GSH levels and fluorescence imaging during the treatment of clear cell renal cell carcinoma (ccRCC) with celastrol (CeT) via inducing ferroptosis. These findings demonstrate that the developed fluorescent probe AR exhibits high selectivity and sensitivity, as well as good biocompatibility and long-term stability, which can be used to image endogenous GSH in living tumors and cells. Also, a significant decrease in GSH levels was observed by the fluorescent probe AR during the treatment of ccRCC with CeT-induced ferroptosis in vitro and in vivo. Overall, these findings will provide a novel strategy for celastrol targeting ferroptosis in the treatment of ccRCC and the application of fluorescent probes to help reveal the underlying mechanism of CeT in the treatment of ccRCC.


Subject(s)
Carcinoma, Renal Cell , Carcinoma , Ferroptosis , Kidney Neoplasms , Humans , Fluorescent Dyes/pharmacology , Glutathione/metabolism
11.
Molecules ; 28(5)2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36903585

ABSTRACT

The thermal analysis kinetic method was employed to solve the activation energies of the thermal decomposition reactions of urea and cyanuric acid, with the purpose of understanding the formation of deposits in the diesel engine SCR system. The deposit reaction kinetic model was established by optimizing the reaction paths and reaction kinetic parameters based on the thermal analysis test data of the key components in the deposit. The result shows that the established deposit reaction kinetic model can accurately describe the decomposition process of the key components in the deposit. Compared to the Ebrahimian model, the simulation precision of the established deposit reaction kinetic model is significantly improved above 600 K. The activation energies of the urea and cyanuric acid decomposition reactions are 84 kJ/mol and 152 kJ/mol, respectively, after model parameters identification. The identified activation energies were closest to those of the Friedman one-interval method indicating that the Friedman one-interval method is reasonable to solve the activation energies of deposit reactions.

12.
Anal Chim Acta ; 1248: 340933, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-36813462

ABSTRACT

High level of intracellular glutathione (GSH) has been identified as a major barrier for cancer therapy. Therefore, effective regulation of GSH can be regarded as a novel approach for cancer therapy. In this study, an off-on fluorescent probe (NBD-P) is developed for selective and sensitive sensing GSH. NBD-P has a good cell membrane permeability that can be applied in bioimaging endogenous GSH in living cells. Moreover, the NBD-P probe is used to visualize GSH in animal models. In addition, a rapid drug screening method is successfully established using the fluorescent probe NBD-P. A potent natural inhibitor of GSH is identified as Celastrol from Tripterygium wilfordii Hook F, which effectively triggers mitochondrial apoptosis in clear cell renal cell carcinoma (ccRCC). More importantly, NBD-P can selectively respond to GSH fluctuations to distinguish cancer tissues from normal tissues. Thus, the present study provides insights into fluorescence probes for the screening GSH inhibitors and cancer diagnosis, as well as in-depth exploration of the anti-cancer effects of Traditional Chinese Medicine (TCM).


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Animals , Fluorescent Dyes , Precision Medicine , Glutathione/metabolism
13.
Cell Commun Signal ; 21(1): 18, 2023 01 23.
Article in English | MEDLINE | ID: mdl-36691020

ABSTRACT

Resistin-like molecules (RELMs) are highly cysteine-rich proteins, including RELMα, RELMß, Resistin, and RELMγ. However, RELMs exhibit significant differences in structure, distribution, and function. The expression of RELMs is regulated by various signaling molecules, such as IL-4, IL-13, and their receptors. In addition, RELMs can mediate numerous signaling pathways, including HMGB1/RAGE, IL-4/IL-4Rα, PI3K/Akt/mTOR signaling pathways, and so on. RELMs proteins are involved in wide range of physiological and pathological processes, including inflammatory response, cell proliferation, glucose metabolism, barrier defense, etc., and participate in the progression of numerous diseases such as lung diseases, intestinal diseases, cardiovascular diseases, and cancers. Meanwhile, RELMs can serve as biomarkers, risk predictors, and therapeutic targets for these diseases. An in-depth understanding of the role of RELMs may provide novel targets or strategies for the treatment and prevention of related diseases. Video abstract.


Subject(s)
Intercellular Signaling Peptides and Proteins , Lung Diseases , Humans , Resistin/physiology , Interleukin-4 , Phosphatidylinositol 3-Kinases
14.
Environ Res ; 216(Pt 4): 114777, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36370818

ABSTRACT

Facile fabrication of porous carbon materials from waste halogenated plastic is highly attractive but frequently hampered due to potential release of halogenated organic pollutants. In this study, a novel type of carbon hybrid was tentatively synthesized from a real-world halogenated plastic as an inexpensive carbon source by sub/supercritical carbon dioxide carbonization technique. It was found that halogen-free carbon carrier was advantageously synthesized through carbonization of halogenated plastic without using catalysts due to zip depolymerization, random chain cracking and free radical reactions induced by sub/supercritical carbon dioxide technique. Exhibiting with more abundant functional groups including C-O, CO groups than pyrolytic carbon carrier, the derived carbon carrier demonstrated excellent performance in selective recovery of lithium from cathode powder with highest recovery efficiency of 93.6%. Mechanism study indicated that cathode powder was transformed into low-valence states of transition metals/metal oxides and released lithium as lithium carbonate due to collapse of oxygen framework via carbothermic reduction. This work provides an applicable and green process for synthesis of alternative carbon carrier from waste halogenated plastic and its application as carbothermic reductant in lithium recovery.


Subject(s)
Carbon Dioxide , Lithium , Electric Power Supplies , Recycling , Plastics , Powders
15.
Sci Total Environ ; 856(Pt 2): 159187, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36202363

ABSTRACT

The continuous accumulation of chlorinated organic pollutants in soil poses a potential threat to ecosystems and human health alike. Alkali-catalyzed hydrothermal oxidation (HTO) can successfully remove chlorinated organic pollutants from water, but it is rarely applied to soil remediation. In this work, we assessed this technique to degrade and detoxify triclosan (TCS) in soil and we determined the underlying mechanisms. The results showed a dechlorination efficiency of TCS (100 mg per kg soil) of 49.03 % after 120 min reaction (H2O2/soil ratio 25 mL·g-1, reaction temperature 180 °C in presence of 1 g·L-1 NaOH). It was found that soil organic constituents (humic acid, HA) and inorganic minerals (SiO2, Al2O3, and CaCO3) suppressed the dechlorination degradation of TCS, with HA having the strongest inhibitory effect. During alkali-catalyzed HTO, the TCS molecules were effectively destroyed and humic acid-like or fulvic acid-like organics with oxygen functional groups were generated. Fluorescence spectroscopy analysis showed that hydroxyl radicals (OH) were the dominant reactive species of TCS degradation in soil. On the basis of the Fukui function and the degradation intermediates, two degradation pathways were proposed. One started with cleavage of the ether bond between the benzene rings of TCS, followed by dechlorination and the opening of benzene via oxidation. The other pathway started with direct hydroxylation of the benzene rings of TCS, after which they were opened and dechlorinated through oxidation. Analysis of the soil structure before and after treatment revealed that the soil surface changed from rough to smooth without affecting soil surface elements. Finally, biotoxicity tests proved that alkali-catalyzed HTO effectively reduced the toxicity of TCS-contaminated soil. This study suggests that alkali-catalyzed hydrothermal oxidation provides an environmentally friendly approach for the treatment of soil contaminated with chlorinated organics such as TCS.


Subject(s)
Environmental Pollutants , Triclosan , Water Pollutants, Chemical , Humans , Triclosan/metabolism , Humic Substances , Soil , Hydrogen Peroxide , Alkalies , Benzene , Ecosystem , Silicon Dioxide , Catalysis , Water Pollutants, Chemical/analysis
16.
Stem Cell Res Ther ; 13(1): 432, 2022 08 30.
Article in English | MEDLINE | ID: mdl-36042526

ABSTRACT

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.


Subject(s)
Neoplasms , Neoplastic Stem Cells , Epithelial-Mesenchymal Transition , Humans , Membrane Microdomains/metabolism , Neoplasms/metabolism , Neoplasms/therapy , Neoplastic Stem Cells/metabolism , Signal Transduction
17.
Front Pharmacol ; 13: 831657, 2022.
Article in English | MEDLINE | ID: mdl-35924044

ABSTRACT

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.

18.
Cancers (Basel) ; 14(14)2022 Jul 18.
Article in English | MEDLINE | ID: mdl-35884547

ABSTRACT

Dihydromyricetin (DHM) is a natural flavonoid compound extracted from Ampelopsis grossedentata that has been used for centuries in traditional Chinese medicine. DHM has attracted intensive attention due to its numerous beneficial activities, such as hepatoprotection, cardioprotection, antioxidant, and anti-inflammation. In addition, DHM inhibits the progression of cancers such as lung cancer, hepatocellular cancer, breast cancer, melanoma, and malignant reproductive systems through multiple mechanisms, including antiangiogenesis, antiproliferation, apoptosis, and inhibition of invasion and migration. Notably, DHM also activates autophagy at different levels, exerting a dual-regulatory effect on cancers. Mechanistically, DHM can effectively regulate mammalian target of rapamycin (mTOR), noncoding RNA-mediated signaling, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, nuclear factor-κB (NF-κB), p53, and endoplasmic reticulum stress (ER stress)-driven signaling in different types of cancers. DHM has also been shown to have inhibitory effects on various regulators that trigger epithelial-mesenchymal transition (EMT). Furthermore, DHM exhibits a remarkable anticancer reversal ability when used in combination with drugs such as adriamycin, nedaplatin, and other drugs. However, the low bioavailability of DHM limits its potential applications, which are improved through structural modification and the exploration of novel dosage forms. Therefore, DHM may become a promising candidate for treating malignancies alone or combined with conventional anticancer strategies used in clinical practice.

19.
ACS Appl Mater Interfaces ; 14(28): 32105-32111, 2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35791739

ABSTRACT

A nitro-decorated microporous covalent organic framework, TpPa-NO2, has been synthesized in a gram scale with a one-pot reaction. It can effectively selectively separate C2H4 from a C2H2/C2H4/CO2 mixture and capture CO2 from CO2/N2 based on ideal adsorption solution theory calculations and transient breakthrough experiments. Theoretical calculations illustrated that the hydrogen atoms of imine bonds, carbonyl oxygen, and nitro group show high affinity toward C2H2 and CO2, playing vital roles in efficient separation.

20.
Aging Dis ; 13(4): 1042-1055, 2022 Jul 11.
Article in English | MEDLINE | ID: mdl-35855333

ABSTRACT

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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