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1.
Front Pharmacol ; 15: 1347750, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420197

RESUMO

Once hailed as miraculous solutions, antibiotics no longer hold that status. The excessive use of antibiotics across human healthcare, agriculture, and animal husbandry has given rise to a broad array of multidrug-resistant (MDR) pathogens, posing formidable treatment challenges. Antimicrobial resistance (AMR) has evolved into a pressing global health crisis, linked to elevated mortality rates in the modern medical era. Additionally, the absence of effective antibiotics introduces substantial risks to medical and surgical procedures. The dwindling interest of pharmaceutical industries in developing new antibiotics against MDR pathogens has aggravated the scarcity issue, resulting in an exceedingly limited pipeline of new antibiotics. Given these circumstances, the imperative to devise novel strategies to combat perilous MDR pathogens has become paramount. Contemporary research has unveiled several promising avenues for addressing this challenge. The article provides a comprehensive overview of these innovative therapeutic approaches, highlighting their mechanisms of action, benefits, and drawbacks.

2.
Int J Biol Macromol ; 254(Pt 3): 127892, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37952799

RESUMO

Underwater superoleophobic (UWSO) materials have garnered significant attention in separating oil/water mixtures. But, the majority of these materials are made from non-degradable and non-renewable raw materials, polluting the environment and wasting scarce resources while using them. Against this backdrop, this study aimed to fabricate an environmental-friendly UWSO textile using biobased materials. To achieve this, hydrogel consisting of chitosan (CS) and poly(tannic acid) (PTA) were formed and coated on cotton fabric (CTF) via dip-coating followed by oxidative polymerization. CS&PTA hydrogel endowed the CTF with a rough surface and high surface energy, leading to an UWSO CTF with an underwater oil contact angle as high as 166.84°. The CS&PTA/CTF had excellent separation capability toward various oil/water mixtures, showing separation efficiency above 99.84 % and water flux higher than 23, 999 L m-2 h-1. Moreover, CS&PTA/CTF possessed excellent mechanical and environmental stability with underwater superoleophobicity unchanged after sandpaper friction, ultrasonication, organic solvents, NaCl (m/v, 30 %) solution, and acid/base solution immersion, due to the strong interaction between the hydrogel and cotton fabric generated by the mussel-inspired adhesion owing to the presence of PTA. The fully biobased UWSO CTF exhibits great promising to be an alternative to traditional superwetting materials for separation of oil/water mixtures.


Assuntos
Quitosana , Hidrogéis , Humanos , Caquexia , Têxteis
3.
Int J Biol Macromol ; 244: 125202, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37270117

RESUMO

Cellulose nanocrystal (CNC) shows great potential in reinforced composites but it is difficult to disperse in epoxy thermosets due to its poor dispersity in epoxy monomers. Herein, we reported a novel approach to disperse CNC in epoxidized soybean oil (ESO)-derived epoxy thermosets uniformly by using the reversibility of dynamic imine-containing ESO-derived covalent adaptable network (CAN). The crosslinked CAN was deconstructed by an exchange reaction with ethylenediamine (EDA) in dimethyl formamide (DMF), leading to a solution of deconstructed CAN with plenty of hydroxyl and amino groups, which could form strong hydrogen bonds with hydroxyl groups of CNC and thus facilitated and stabilized dispersion of CNC in the deconstructed CAN solution. Epoxy composite with well-dispersed CNC was finally achieved by a reformation of CAN through the removal of DMF and EDA. In this way, the epoxy composites with CNC content up to 30 wt% were successfully prepared and showed drastically reinforced mechanical properties. The tensile strength and Young's modulus of the CAN were improved by up to ∼70 % and ∼45 times with the incorporation of 20 and 30 wt% CNC, respectively. The composites showed excellent reprocessability without significant loss in mechanical properties after reprocessing.


Assuntos
Celulose , Nanopartículas , Celulose/química , Resistência à Tração , Módulo de Elasticidade , Nanopartículas/química , Resinas Epóxi
4.
Cancer Lett ; 563: 216181, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37086953

RESUMO

P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR) in cancers severely limit chemotherapeutic efficacy. We recently reported that phosphatidylinositol-3-kinase (PI3K) 110α and 110ß subunits can be novel targets for reversal of P-gp mediated MDR in cancers, and BAY-1082439 as an inhibitor specific for PI3K 110α and 110ß subunits could reverse P-gp-mediated MDR by downregulating P-gp expression in cancer cells. However, BAY-1082439 has very low solubility, short half-life and high in-vivo clearance rate. Till now, nano-system with the functions to target PI3K P110α and P110ß and reverse P-gp mediated MDR in cancers has not been reported. In our study, a tumor targeting drug delivery nano-system PBDF was established, which comprised doxorubicin (DOX) and BAY-1082439 respectively encapsulated by biodegradable PLGA-SH nanoparticles (NPs) that were grafted to gold nanorods (Au NRs) modified with FA-PEG-SH, to enhance the efficacy to reverse P-gp mediated MDR and to target tumor cells, further, to enhance the efficiency to inhibit MDR tumors overexpressing P-gp. In-vitro experiments indicated that PBDF NPs greatly enhanced uptake of DOX, improved the activity to reverse MDR, inhibited the cell proliferation, and induced S-phase arrest and apoptosis in KB-C2 cells, as compared with free DOX combining free BAY-1082439. In-vivo experiments further demonstrated that PBDF NPs improved the anti-tumor ability of DOX and inhibited development of KB-C2 tumors. Notably, the metastasis of KB-C2 cells in livers and lungs of nude mice were inhibited by treatment with PBDF NPs, which showed no obvious in-vitro or in-vivo toxicity.


Assuntos
Antineoplásicos , Neoplasias , Animais , Camundongos , Antineoplásicos/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Camundongos Nus , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Humanos
5.
Int J Biol Macromol ; 236: 123960, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36921823

RESUMO

Biobased poly(lactic acid)/lignin (PLA/lignin) composites are limited by poor mechanical properties resulted from poor compatibility and low interfacial adhesion. Herein, we reported a novel approach to improve compatibility and interfacial adhesion of PLA/lignin composites via reactive compatibilization with epoxidized natural rubber (ENR) as a compatibilizer. Interfacial tension calculation indicated that lignin tended to act as interfacial phase between PLA and ENR, but morphology analysis demonstrated lignin was wrapped with a layer of ENR and dispersed in PLA matrix, which was attributed to the interfacial reaction of ENR with both PLA and lignin. The interfacial reaction was confirmed by Fourier transform infrared spectroscopy. The compatibility and interfacial adhesion between PLA and lignin were improved significantly by incorporation and increase in the content of ENR, as evidenced by the reduced interfacial gaps, blurry phase boundaries, and enhanced elastic response. As such, the mechanical properties of PLA/lignin composites were enhanced significantly. The tensile strength and elongation at break of PLA/lignin (W/W, 80/20) were improved by 15 % and 77 %, respectively, with the incorporation of only 1 wt% ENR. We believe this approach to compatibilize PLA/lignin composites is promising because it would not require costly modification of lignin and would not compromise the sustainability of composites.


Assuntos
Lignina , Borracha , Lignina/química , Borracha/química , Poliésteres/química , Resistência à Tração
6.
Drugs Today (Barc) ; 59(2): 91-104, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36811409

RESUMO

Melanoma is a highly lethal type of skin cancer. Although an early diagnosis, in combination with surgery for nonmetastatic melanomas, significantly increases the probability of survival, there are no efficacious treatments for metastatic melanoma. Nivolumab and relatlimab are monoclonal antibodies that selectively interact with and block the proteins programmed cell death protein 1 (PD-1) and lymphocyte activation protein 3 (LAG-3), respectively, and thus, their activation by their cognate ligands. The combination of these immunotherapy drugs was approved in 2022 by the United States Food and Drug Administration (FDA) for the treatment of melanoma. Data from clinical trials indicated that, compared to nivolumab monotherapy, nivolumab and relatlimab produced more than a 2-fold median increase in progression-free survival (PFS) and a higher response rate in melanoma patients. This is an important finding as the response of patients to immunotherapies is limited due to dose-limiting toxicities and secondary drug resistance. This review article will discuss the pathogenesis of melanoma and the pharmacology of nivolumab and relatlimab. In addition, we will provide i) a summary of the anticancer drugs that inhibit LAG-3 and PD-1 in cancer patients and ii) our perspective about the use of nivolumab in combination with relatlimab to treat melanoma.


Assuntos
Melanoma , Nivolumabe , Humanos , Receptor de Morte Celular Programada 1 , Melanoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico
7.
Front Oncol ; 12: 904637, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719983

RESUMO

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm and is characterized as the most common subtype of non-Hodgkin lymphoma (NHL). Despite 60-70% of all patients being cured with R-CHOP therapeutic regimen (Cyclophosphamide, doxorubicin, vincristine, and prednisone, combined with rituximab), remaining patients display aggressive disease. Therefore, there is an urgent need to develop novel diagnostic, prognostic, and predictive biomarkers. Recently, exosomal miRNAs have been approved as novel biomarkers in DLBCL due to their potential involvement in lymphomagenesis. Material and Methods: We conducted an investigation on the potential role of exosomal miRNAs as diagnostic, prognostic, and predictive biomarkers in DLBCL in the PubMed, Scopus, and Web of Science search engines. We searched by using a combination of keywords, such as diffuse large B-cell lymphoma, DLBCL, miRNA, microRNA, miR, exosome, exosomes, exosomal, extracellular vesicles, EVs, and secretome. Then, search results were narrowed based on specific inclusion and exclusion criteria. Results: Twelve articles were eligible for our systematic reviews. Among them, nine discussed diagnostic biomarkers, three considered prognostic significance, four evaluated therapeutic efficacy, two studies were conducted in vitro, and three assessed molecular pathways associated with these exosomal miRNAs in DLBCL. Discussion: According to our systematic review, exosomal miRNAs are not only useful for diagnosis and prognosis in DLBCL but are also promising therapeutic tools and predictors of response to therapy. Although promising results so far, more research is required to develop innovative biomarkers.

8.
Front Pharmacol ; 13: 867128, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450042

RESUMO

The efficacy of cancer chemotherapy can be attenuated or abrogated by multidrug resistance (MDR) in cancer cells. In this study, we determined the effect of the CDK4/6 inhibitor, ribociclib (or LEE011), on P-glycoprotein (P-gp)-mediated MDR in the human epidermoid carcinoma MDR cell line, KB-C2, which is widely used for studying P-gp-mediated MDR in cancers. The incubation of KB-C2 cells with ribociclib (3-9 µM) increased the efficacy of colchicine, a substrate for P-gp. The cell expression of P-gp was down-regulated at both translation and transcription levels. Furthermore, ribociclib produced a 3.5-fold increase in the basal activity of P-gp ATPase, and the concentration required to increase basal activity by 50% (EC50) was 0.04 µM. Docking studies indicated that ribociclib interacted with the drug-substrate binding site of P-gp. The short-term and long-term intracellular accumulation of doxorubicin greatly increased in the KB-C2 cells co-cultured with ribociclib, indicating ribociclib inhibited the drug efflux activity of P-gp. The results of our study indicate that LEE011 may be a potential agent for combined therapy of the cancers with P-gp mediated MDR.

9.
Cell Death Dis ; 13(4): 384, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35444236

RESUMO

Chronic myeloid leukemia (CML) are initiated and sustained by self-renewing malignant CD34+ stem cells. Extensive efforts have been made to reveal the metabolic signature of the leukemia stem/progenitor cells in genomic, transcriptomic, and metabolomic studies. However, very little proteomic investigation has been conducted and the mechanism regarding at what level the metabolic program was rewired remains poorly understood. Here, using label-free quantitative proteomic profiling, we compared the signature of CD34+ stem/progenitor cells collected from CML individuals with that of healthy donors and observed significant changes in the abundance of enzymes associated with aerobic central carbonate metabolic pathways. Specifically, CML stem/progenitor cells expressed increased tricarboxylic acid cycle (TCA) with decreased glycolytic proteins, accompanying by increased oxidative phosphorylation (OXPHOS) and decreased glycolysis activity. Administration of the well-known OXPHOS inhibitor metformin eradicated CML stem/progenitor cells and re-sensitized CD34+ CML cells to imatinib in vitro and in patient-derived tumor xenograft murine model. However, different from normal CD34+ cells, the abundance and activity of OXPHOS protein were both unexpectedly elevated with endoplasmic reticulum stress induced by metformin in CML CD34+ cells. The four major aberrantly expressed protein sets, in contrast, were downregulated by metformin in CML CD34+ cells. These data challenged the dependency of OXPHOS for CML CD34+ cell survival and underlined the novel mechanism of metformin. More importantly, it suggested a strong rationale for the use of tyrosine kinase inhibitors in combination with metformin in treating CML.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Metformina , Animais , Antígenos CD34/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Metformina/farmacologia , Camundongos , Células-Tronco Neoplásicas/metabolismo , Fosforilação Oxidativa , Inibidores de Proteínas Quinases/farmacologia , Proteômica
10.
Int J Biol Macromol ; 209(Pt A): 279-289, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35398058

RESUMO

Superhydrophilic and underwater superoleophobic materials exhibit excellent oil/water separation performance but are usually fabricated from nonrenewable and nondegradable feedstocks and thus would cause secondary pollution after use. Herein, we report a fully biobased and mussel-inspired underwater superoleophobic hydrogel coated cotton fabric (CF) prepared by surface coating and subsequent oxidation polymerization of chitosan & dopamine mixtures. The obtained chitosan & polydopamine hydrogel coated CF (CS&PDA/CF) showed superhydrophilicity and underwater superoleophobicity, due to the formed rough surface structure with hydrophilic complex hydrogel. The CS&PDA/CF exhibited excellent oil/water separation performance with separation efficiency higher than 99.5% for various oil/water mixtures. Moreover, the CS&PDA/CF showed excellent resistance against various harsh conditions such as boiling water, ultrasonication, and concentrated salt solution, due to the mussel-inspired strong adhesion stabilized structure and morphology. We believe that the fully biobased and mussel-inspired underwater superoleophobic cotton fabric shows great potential as an eco-friendly and high-efficient oil/water separation material.


Assuntos
Quitosana , Purificação da Água , Hidrogéis , Interações Hidrofóbicas e Hidrofílicas , Óleos/química
11.
Front Immunol ; 13: 818017, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281012

RESUMO

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis-induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease.


Assuntos
Asma , Eosinofilia , Sinusite , Animais , Aspergillus , Asma/patologia , Eosinofilia/patologia , Inflamação , Pulmão/patologia , Camundongos , Fator de Transcrição STAT6
12.
Drugs Today (Barc) ; 58(2): 85-94, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35188143

RESUMO

Ibrutinib, an oral small-molecule targeted drug, has been the first Bruton tyrosine kinase (BTK) inhibitor in the world to be approved for the market. It works by regulating cell proliferation, apoptosis and migration, and has been proven to exhibit high efficacy and good safety in the treatment of B-cell lymphomas, including chronic lymphocytic leukemia or small lymphocytic lymphoma and mantle cell lymphoma. However, some patients inevitably have drug resistance and disease recurrence, resulting in a poor prognosis. This article serves as a clinical reference by summarizing the related literature on ibrutinib resistance inhibitors.


Assuntos
Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Adulto , Antineoplásicos/uso terapêutico , Resistência a Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos
13.
Front Cell Dev Biol ; 9: 766371, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692712

RESUMO

Despite their small size, the membrane-bound particles named extracellular vesicles (EVs) seem to play an enormous role in the pathogenesis of acute leukemia. From oncogenic hematopoietic stem cells (HSCs) to become leukemic cells to alter the architecture of bone marrow (BM) microenvironment, EVs are critical components of leukemia development. As a carrier of essential molecules, especially a group of small non-coding RNAs known as miRNA, recently, EVs have attracted tremendous attention as a prognostic factor. Given the importance of miRNAs in the early stages of leukemogenesis and also their critical parts in the development of drug-resistant phenotype, it seems that the importance of EVs in the development of leukemia is more than what is expected. To be familiar with the clinical value of leukemia-derived EVs, this review aimed to briefly shed light on the biology of EVs and to discuss the role of EV-derived miRNAs in the development of acute myeloid leukemia and acute lymphoblastic leukemia. By elaborating the advances and challenges concerning the isolation of EVs, we discuss whether EVs could have a prognostic value in the clinical setting for leukemia.

14.
J Evid Based Med ; 14(3): 232-256, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34388310

RESUMO

The ATP-binding cassette (ABC) transporter superfamily is one of the largest membrane protein families existing in wide spectrum of organisms from prokaryotes to human. ABC transporters are also known as efflux pumps because they mediate the cross-membrane transportation of various endo- and xenobiotic molecules energized by ATP hydrolysis. Therefore, ABC transporters have been considered closely to multidrug resistance (MDR) in cancer, where the efflux of structurally distinct chemotherapeutic drugs causes reduced itherapeutic efficacy. Besides, ABC transporters also play other critical biological roles in cancer such as signal transduction. During the past decades, extensive efforts have been made in understanding the structure-function relationship, transportation profile of ABC transporters, as well as the possibility to overcome MDR via targeting these transporters. In this review, we discuss the most recent knowledge regarding ABC transporters and cancer drug resistance in order to provide insights for the development of more effective therapies.


Assuntos
Antineoplásicos , Neoplasias , Transportadores de Cassetes de Ligação de ATP/farmacologia , Transportadores de Cassetes de Ligação de ATP/uso terapêutico , Trifosfato de Adenosina/farmacologia , Trifosfato de Adenosina/uso terapêutico , Antineoplásicos/uso terapêutico , Resistência a Múltiplos Medicamentos , Humanos , Neoplasias/tratamento farmacológico
15.
Biochem Pharmacol ; 190: 114652, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34126072

RESUMO

Multidrug resistance-associated protein 7 (MRP7) is an important member of ABC transporter superfamily and has been revealed to mediate the cross-membrane translocation of a wide range of chemotherapeutic agents including taxanes, epothilones, Vinca alkaloids, Anthracyclines and Epipodophyllotoxins.In our previous study, a 1,2,3-triazole-pyrimidine hybridCMP25was synthesized and found able to efficiently reverse multidrug resistance (MDR) mediated by P-glycoprotein. In this study, we evaluated the efficacy of compound CMP25in reversing MDR mediated by MRP7in vitro. The results showed that CMP25significantly sensitized MRP7-overexpressing cells to anticancer drugs that are MRP7 substrates. Mechanistic study showed that CMP25reversed MRP7-mediated MDR by increasing the intracellular accumulation of anticancer drugs and decreasing drug efflux, without altering protein expression level or subcellular localization. Currently, very few studies on synthetic MRP7 modulators have been published. Our findings provide a valuable prototype for designing drugs to combine with conventional anticancer drugs to overcome MDR-mediated by MRP7.


Assuntos
Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Quimioterapia Combinada , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Estrutura Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Conformação Proteica
16.
Front Cell Dev Biol ; 8: 865, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984343

RESUMO

Overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) remains one of the most vital factors leading to multidrug resistance (MDR). It is important to enhance the effect and bioavailability of chemotherapeutic drugs that are substrates of ABCB1 transporter in ABCB1-overexpression cancer cells and reverse ABCB1-mediated MDR. Previous, we uncovered that the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is a potent reversal agent to overcomes paclitaxel resistance in ABCB1-overexpressing cells and tumors. In this study, we explored whether RN486, another BTK inhibitor, was competent to surmount ABCB1-mediated MDR and promote relevant cancer chemotherapy. We found that RN486 significantly increased the efficacy of paclitaxel and doxorubicin in both drug-selected carcinoma cells and transfected cells overexpressing ABCB1. Mechanistic studies indicated that RN486 dramatically attenuated the drug efflux activity of ABCB1 transporter without altering its expression level or subcellular localization. The ATPase activity of ABCB1 transporter was not affected by low concentrations but stimulated by high concentrations of RN486. Moreover, an interaction between RN486 with ABCB1 substrate-binding and inhibitor binding sites was verified by in silico docking simulation. The results from our study suggest that RN486 could be a reversal agent and could be used in the novel combination therapy with other antineoplastic drugs to conquer MDR-mediated by ABCB1 transporter in clinics.

17.
Front Oncol ; 10: 932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676451

RESUMO

In this study, we investigated the efficacy of methyl-cantharidimide (MCA), a cantharidin (CTD) analog, as an anticancer drug, in cancer cells overexpressing either ABCB1 or ABCG2 transporters and in cisplatin-resistant cancer cells. The results indicated that: (i) MCA was efficacious in the ABCB1-overexpressing cell line, KB-C2, and the ABCB1-gene-transfected cell line, HEK293/ABCB1 (IC50 from 6.37 to 8.44 mM); (ii) MCA was also efficacious in the ABCG2-overexpressing cell line, NCI-H460/MX20, and the ABCG2-gene-transfected cell lines, HEK293/ABCG2-482-R2, HEK293/ABCG2-482-G2, and the HEK293/ABCG2-482-T7 cell lines (IC50 from 6.37 to 9.70 mM); (iii) MCA was efficacious in the cisplatin resistant cancer cell lines, KCP-4 and BEL-7404/CP20 (IC50 values from 7.05 to 8.16 mM); (iv) MCA (up to 16 mM) induced apoptosis in both BEL-7404 and BEL-7404/CP20 cancer cells; (v) MCA arrested both BEL-7404 and BEL-7404/CP20 cancer cells in the G0/G1 phase of the cell cycle; (vi) MCA (8 mM) upregulated the expression level of the protein, unc-5 netrin receptor B (UNC5B) in HepG2 and BEL-7404 cancer cells. Overall, our results indicated that MCA's efficacy in ABCB1- and ABCG2-overexpressing and cisplatin resistant cancer cells is due to the induction of apoptosis and cell cycle arrest in the G0/G1 phase.

18.
Carbohydr Polym ; 244: 116449, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32536394

RESUMO

Superhydrophilic and underwater superoleophobic textiles exhibit excellent oil/water separation performance but are limited by the poor stability and environmental incompatibility. Inspired by strong adhesion of marine mussels, we designed and fabricated a stable and eco-friendly superhydrophilic and underwater superoleophobic cotton fabric (CF) from all renewable resources through in-situ surface deposition of polydopamine (PDA) particles followed by adsorption of hydrophilic chitosan via dip coating at room temperature. The as-prepared superhydrophilic and underwater superoleophobic CF exhibited outstanding oil/water separation performance with separation efficiency and water flux higher than 99 % and 15,000 L m-2 h-1, respectively. Moreover, it not only showed excellent resistance to mechanical abrasion and ultrasound treatment but also had outstanding superwetting stability against acid/alkali/salt erosion. We believed that the eco-friendly superhydrophilic and underwater superoleophobic CF would exhibit great potential in oil/water separation especially under harsh conditions.


Assuntos
Quitosana/química , Fibra de Algodão , Indóis/química , Polímeros/química , Purificação da Água , Emulsões/química , Filtração , Óleos/química
19.
FASEB J ; 34(6): 7540-7560, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32301538

RESUMO

The vascular endothelium has been discovered in the past several years to be important in shaping the cellular immune response. During the immune response the vascular endothelium is constantly perturbed by biologically potent molecules, including the complement activation peptides, C3a and C5a. Despite the importance of C3a and C5a in inflammation and immunity, their role in modulating lymphocyte function via activation of vascular endothelial cells is unknown. Accordingly, we investigated the regulated expression of the C3a and C5a receptors (complement anaphylatoxin C3a receptor [C3aR] and complement anaphylatoxin C5a receptor 1 [C5aR1]) on human umbilical vascular endothelial cells (HUVECs) and examined how C3a or C5a activation of HUVECs affects the activation and polarization of lymphatic cells. Our findings demonstrated that C3a and C5a increase C3aR and C5aR1 expression by HUVECs as well as directing their cellular transmigration and spreading through transwell filters. Moreover, C3a- or C5a-stimulated endothelial cells: (1) caused activation of B-lymphoblasts with significant increase in Fas Ligand (CD95L) (FasL), CD69, and IL-R1 expression, and (2) skewed T-lymphoblast cells toward a Th1 subtype, (CD4+ /CCR5+ ) that correlated with significant increase of IFN-γ. Collectively, these data indicate that C3a and C5a signaling is important in the activation and polarization of lymphocytes as they traffic through the vascular endothelium during the immune response.


Assuntos
Anafilatoxinas/imunologia , Linfócitos B/imunologia , Complemento C3a/imunologia , Complemento C5a/imunologia , Peptídeos/imunologia , Linfócitos T/imunologia , Células Cultivadas , Ativação do Complemento/imunologia , Endotélio Vascular/imunologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/imunologia , Receptor da Anafilatoxina C5a/imunologia , Receptores de Complemento/imunologia , Transdução de Sinais/imunologia
20.
Int J Biol Macromol ; 140: 1175-1182, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465799

RESUMO

Traditional superhydrophobic cotton fabrics (SCFs) for oil/water separation were usually fabricated by surface coating with inorganic nanoparticles combined with nonrenewable and nonbiodegradable or even toxic fossil-based chemicals, which would lead to secondary environmental pollution after their lifetime. In this study, we report robust, nanoparticle-free, fluorine-free SFC, which was prepared by acid etching followed by surface coating with epoxidized soybean oil resin (CESO) and subsequent modification with stearic acid (STA). No toxic compound and no nanoparticle were included within the SCF and all the raw materials including cotton fabric, CESO and STA are biodegradable and derived from biological resources. The SCF showed excellent mechanical stability and chemical/environmental resistances. The superhydrophobicity of the SFC survived from mechanical abrasion, tape peeling, ultrasonication, solvent erosion and low/high temperature exposure. The SCF also exhibited good acid/alkali resistance with contact angle over 150° toward different pH water droplets. Moreover, the SCF could efficiently separate oil/water mixtures with efficiency above 97.9% and the superhydrophobicity remained after reusing for at least 10 times. The fully biological-derived SCF with excellent mechanical and chemical resistances exhibit great potential for separation of oil/water mixtures.


Assuntos
Fibra de Algodão , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Óleo de Soja/química , Água/química , Ácidos Decanoicos/química , Ácidos Dicarboxílicos/química , Temperatura , Molhabilidade
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