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1.
Sci Rep ; 14(1): 10076, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698064

RESUMEN

While COVID-19 becomes periodical, old individuals remain vulnerable to severe disease with high mortality. Although there have been some studies on revealing different risk factors affecting the death of COVID-19 patients, researchers rarely provide a comprehensive analysis to reveal the relationships and interactive effects of the risk factors of COVID-19 mortality, especially in the elderly. Through retrospectively including 1917 COVID-19 patients (102 were dead) admitted to Xiangya Hospital from December 2022 to March 2023, we used the association rule mining method to identify the risk factors leading causes of death among the elderly. Firstly, we used the Affinity Propagation clustering to extract key features from the dataset. Then, we applied the Apriori Algorithm to obtain 6 groups of abnormal feature combinations with significant increments in mortality rate. The results showed a relationship between the number of abnormal feature combinations and mortality rates within different groups. Patients with "C-reactive protein > 8 mg/L", "neutrophils percentage > 75.0 %", "lymphocytes percentage < 20%", and "albumin < 40 g/L" have a 2 × mortality rate than the basic one. When the characteristics of "D-dimer > 0.5 mg/L" and "WBC > 9.5 × 10 9 /L" are continuously included in this foundation, the mortality rate can be increased to 3 × or 4 × . In addition, we also found that liver and kidney diseases significantly affect patient mortality, and the mortality rate can be as high as 100%. These findings can support auxiliary diagnosis and treatment to facilitate early intervention in patients, thereby reducing patient mortality.


Asunto(s)
COVID-19 , Minería de Datos , Humanos , COVID-19/mortalidad , Anciano , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , Anciano de 80 o más Años , Algoritmos
2.
Int J Biol Macromol ; 268(Pt 2): 131944, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38692531

RESUMEN

Efficient removal and recycling of phosphorus from complex water matrices using environmentally friendly and sustainable materials is essential yet challenging. To this end, a novel bio-based adsorbent (DX-FcA-CS) was developed by coupling oxidized dextran-crosslinked chitosan with ferrocene carboxylic acid (FcA). Detailed characterization revealed that the incorporation of FcA reduced the total pore area of DX-FcA-CS to 7.21 m2·g-1, one-third of ferrocene-free DX-CS (21.71 m2·g-1), while enhancing thermal stability and PO43- adsorption performance. Adsorption kinetics and isotherm studies demonstrated that the interaction between DX-FcA-CS and PO43- followed a pseudo-second-order kinetic model and Langmuir model, indicating chemical and monolayered adsorption mechanisms, respectively. Moreover, DX-FcA-CS exhibited excellent anti-interference properties against concentrated co-existing inorganic ions and humic acid, along with high recyclability. The maximum adsorption capacity reached 1285.35 mg·g-1 (∼428.45 mg P g-1), three times that of DX-CS and surpassing many other adsorbents. PO43--loaded DX-FcA-CS could be further carbonized into electrode material due to its rich content of phosphorus and nitrogen, transforming waste into a valuable resource. These outstanding characteristics position DX-FcA-CS as a promising alternative for phosphate capture and recycling. Overall, this study presents a viable approach to designing environmentally friendly, recyclable, and cost-effective biomaterial for wastewater phosphate removal and value-added applications.

3.
Eur J Med Chem ; 271: 116398, 2024 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38614061

RESUMEN

In contemporary studies, the predominant utilization of C60 derivatives pertains to their role as photosensitizers or agents that scavenge free radicals. The intriguing coexistence of these divergent functionalities has prompted extensive investigation into water-soluble fullerenes. The photodynamic properties of these compounds find practical applications in DNA cleavage, antitumor interventions, and antibacterial endeavors. Consequently, photodynamic therapy is progressively emerging as a pivotal therapeutic modality within the biomedical domain, owing to its notable levels of safety and efficacy. The essential components of photodynamic therapy encompass light of the suitable wavelength, oxygen, and a photosensitizer, wherein the reactive oxygen species generated by the photosensitizer play a pivotal role in the therapeutic mechanism. The remarkable ability of fullerenes to generate singlet oxygen has garnered significant attention from scholars worldwide. Nevertheless, the limited permeability of fullerenes across cell membranes owing to their low water solubility necessitates their modification to enhance their efficacy and utilization. This paper reviews the applications of fullerene derivatives as photosensitizers in antitumor and antibacterial fields for the recent years.

4.
Eur J Med Chem ; 269: 116294, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38508119

RESUMEN

Lamellarins are polyaromatic alkaloids isolated from marine organisms, including mollusks, tunicates, and sponges. Currently, over 60 structurally distinct natural lamellarins have been reported, and most of them exhibit promising biological activities, such as topoisomerase inhibition, mitochondrial function inhibition, multidrug resistance reversing, and anti-HIV activity. There has also been a significant progress on the synthetic study of lamellarins which has been regularly updated by numerous medicinal chemists as well. This review provides a detailed summary of the synthesis, pharmacology, and structural modification of lamellarins over the past decades.


Asunto(s)
Alcaloides , Productos Biológicos , Urocordados , Animales , Relación Estructura-Actividad , Resistencia a Múltiples Medicamentos , Mitocondrias , Urocordados/química , Alcaloides/química
5.
Biomater Sci ; 12(9): 2302-2311, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38497169

RESUMEN

Tumor penetration is a critical determinant of the therapy efficacy of nanomedicines. However, the dense extracellular matrix (ECM) in tumors significantly hampers the deep penetration of nanomedicines, resulting in large drug-untouchable areas and unsatisfactory therapy efficacy. Herein, we synthesized a third-generation PAMAM-cored multiarm copolymer and modified the polymer with collagenase to enhance its tumor penetration. Each arm of the copolymer was a diblock copolymer of poly(glutamic acid)-b-poly(carboxybetaine), in which the polyglutamic acid block with abundant side groups was used to link the anticancer agent doxorubicin through the pH-sensitive acylhydrazone linkage, and the zwitterionic poly(carboxybetaine) block provided desired water solubility and anti-biofouling capability. The collagenase was conjugated to the ends of the arms via the thiol-maleimide reaction. We demonstrated that the polymer-bound collagenase could effectively catalyze the degradation of the collagen in the tumor ECM, and consequently augmented the tumor penetration and antitumor efficacy of the drug-loaded polymers.


Asunto(s)
Colagenasas , Doxorrubicina , Colagenasas/metabolismo , Animales , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Ratones , Polímeros/química , Polímeros/metabolismo , Humanos , Línea Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Ácido Poliglutámico/química , Portadores de Fármacos/química
6.
Biochem Pharmacol ; 222: 116077, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38395264

RESUMEN

Compound G-4 is a derivate of cyclin-dependent kinase inhibitor Rocovitine and showed strong sensitivity to triple negative breast cancer (TNBC) cells. In this study, the antitumor activity, mechanism and possible targets of G-4 in TNBC were investigated. Flow cytometry and immunoblotting showed that G-4 not only arrested the S phase of the cell cycle, but also induced apoptosis in TNBC cells via the mitochondrial pathway through inhibiting epidermal growth factor receptor (EGFR), AKT and MAPK pathways. In addition, G-4 induced the iron-mutagenesis process in TNBC cells and down-regulated differentially expressed gene lipid carrier protein 2 (LCN2) by RNA-seq. Moreover, G-4 elevated levels of cytosolic reactive oxygen species (ROS), lipid ROS, Fe and malondialdehyde (MDA), but decreased levels of superoxide dismutase (SOD) and glutathione (GSH), consistent with the effects of iron-mutagenic agonists Erastin and RSL3, which were inhibited by the iron inhibitor ferrostatin-1 (Fer-1). Furthermore, a LCN2 knockdown cell model was established by siRNA transfection, the IC50 of G-4 was increased nearly 100-fold, accompanied by a trend of no ferroptosis characteristic index. The results indicated that G-4 suppressed the malignant phenotype of TNBC, induced apoptosis by inhibiting EGFR pathway and promoted LCN2-dependent ferroptosis.


Asunto(s)
Ferroptosis , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/metabolismo , Proteínas Portadoras/farmacología , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Apoptosis , Receptores ErbB/metabolismo , Hierro/metabolismo , Lípidos/farmacología , Lipocalina 2
7.
Biol Direct ; 19(1): 11, 2024 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-38268026

RESUMEN

BACKGROUND: To create a dual-acting vaccine that can fight against tuberculosis, we combined antigenic arabino-mannan analogues with the Ag85B protein. To start the process, we studied the impact of modifying different parts of the Ag85B protein on its ability to be recognized by antibodies. RESULTS: Through our research, we discovered that three modified versions of the protein, rAg85B-K30R, rAg85B-K282R, and rAg85B-K30R/K282R, retained their antibody reactivity in healthy individuals and those with tuberculosis. To further test the specificity of the sugar AraMan for AraMan antibodies, we used Human Serum Albumin glycosylated with AraMan-IME and Ara3Man-IME. Our findings showed that this specific sugar was fully and specifically modified. Bio-panning experiments revealed that patients with active tuberculosis exhibited a higher antibody response to Ara3Man, a sugar found in lipoarabinomannan (LAM), which is a major component of the mycobacterial cell wall. Bio-panning with anti-LAM plates could eliminate this increased response, suggesting that the enhanced Ara3Man response was primarily driven by antibodies targeting LAM. These findings highlight the importance of Ara3Man as an immunodominant epitope in LAM and support its role in eliciting protective immunity against tuberculosis. Further studies evaluated the effects of glycosylation on the antibody affinity of recombinant Ag85B and its variants. The results indicated that rAg85B-K30R/K282R, when conjugated with Ara3Man-IME, demonstrated enhanced antibody recognition compared to unconjugated or non-glycosylated versions. CONCLUSIONS: Coupling Ara3Man to rAg85B-K30R/K282R could lead to the development of effective dual-acting vaccines against tuberculosis, stimulating protective antibodies against both AraMan and Ag85B, two key tuberculosis antigens.


Asunto(s)
Tuberculosis , Vacunas , Humanos , Glicosilación , Tuberculosis/prevención & control , Azúcares
8.
Int J Biol Macromol ; 261(Pt 1): 129699, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38281517

RESUMEN

Dye-containing wastewater treatment has been a major long-term global challenge. For this purpose, a novel bio-based microspheres (CS-FC) with high specific surface area (63.24 m2·g-1) and nano-channels (17.95 nm) was prepared using chitosan as the framework and ferrocene as a crosslinking active group. CS-FC not only has the ability to rapidly enrich methyl orange (MO) through hydrogen-bonding and electrostatic attraction, but also almost completely degrades it in the presence of H2O2/K2S2O8 through a synergistic radical/non-radical mechanism under the activating effect of ferrocene. Without H2O2/K2S2O8, the maximum MO adsorption capacity of CS-FC is in the range 871-1050 mg·g-1, and conforms to a Langmuir isothermal model with pseudo-second-order kinetics. In the presence of H2O2/K2S2O8, the removal of MO dramatically increased from 32 % to nearly 100 % after incubation for 60 min, due to the simultaneous formation of highly reactive 1O2 and ·OH. The significant contribution from 1O2 endowed CS-FC/H2O2/K2S2O8 with high universality for degrading various organic pollutants (including azo dyes and antibiotics), a wide pH window (2-8), and low sensitivity to co-existing ions. Such cost-effective, recyclable porous bio-based microspheres are suitable for heterogeneous Fenton-like catalysis in organic wastewater treatment that rely on synergistic radical/non-radical reaction pathways.


Asunto(s)
Compuestos Azo , Quitosano , Contaminantes Ambientales , Compuestos Ferrosos , Contaminantes Químicos del Agua , Metalocenos , Microesferas , Peróxido de Hidrógeno , Adsorción , Concentración de Iones de Hidrógeno , Cinética
9.
Bioorg Chem ; 143: 107031, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38086242

RESUMEN

Hypobromous acid (HOBr), one of the significant reactive oxygen species (ROS) that acts as an important role in human immune system, however the increasing level of HOBr in human body can cause the disorder of eosinophils (EPO), leading to oxidative stress in organelles, and further causing a series of diseases. In this study, a ratiometric fluorescent probe DMBP based on Nile red skeleton was developed to detect HOBr specifically by the electrophilic substitution with HOBr. DMBP emits near-infrared (NIR) fluorescence at 653 nm, after reacting with HOBr, the emission wavelength of DMBP shifted blue and a new peak appeared at 520 nm, realizing a ratiometric examination of HOBr with a limit of detection of 89.00 nM. Based on its sensitive and specific response to HOBr, DMBP was applied in the visual imaging of HOBr in HepG2 cells and zebrafish. Foremost, probe DMBP has excellent lysosome targeting ability and NIR emission reduced the background interference of biological tissues, providing a potential analytical tool to further investigate the role of HOBr in lysosome.


Asunto(s)
Bromatos , Colorantes Fluorescentes , Oxazinas , Árboles , Animales , Humanos , Pez Cebra , Lisosomas , Esqueleto
10.
Environ Res ; 242: 117766, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38029811

RESUMEN

Theoretically, agricultural insurance influences farmers' use of pesticides by changing the expected income of agricultural production. Full-cost insurance, with high guarantee and high compensation characteristics, may significantly affect farmers' pesticide use. First, this paper constructs a production function to characterize and compare the marginal incomes of insured and uninsured farmers under risk uncertainty and analyses how insured farmers can increase marginal income by increasing or reducing factor inputs. Considering scale differentiation, it discusses pesticide use strategies different types of farmers may adopt to maximize household utility. Second, using survey data of the pilot counties of full-cost insurance for wheat in Henan Province, China, the simultaneous equation model is used for empirical testing. The results reveal the following: (i) Farmers' insurance participation and pesticide application behaviour are not mutually independent. (ii) For the whole sample, full-cost insurance for wheat has a significant pesticide reduction effect. (iii) However, considering scale differentiation, pesticide application decreases significantly among insured ordinary farmers but does not change significantly among insured large-scale farmers. Third, policy measures are proposed to activate the green development function of agricultural insurance.


Asunto(s)
Plaguicidas , Humanos , Agricultores , Triticum , Conocimientos, Actitudes y Práctica en Salud , Agricultura , China
11.
Langmuir ; 40(1): 938-949, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38134444

RESUMEN

The superamphiphiles exhibit broad prospects for fabricating stimuli-responsive emulsions. Because the superamphiphiles are assembled via noncovalent interactions, they have the advantage of fast response and high efficiency. Recently, a series of switchable emulsions using CO2-responsive superamphiphiles have been developed, which extends the applications of CO2-responsive materials in widespread field. However, there is still a lack of fundamental understanding on the switching mechanism related to the assembled structure of superamphiphiles at the oil-water interface. We employed molecular dynamics (MD) simulations to investigate the reversible emulsification/demulsification process of a responsive emulsion system stabilized by a recently developed responsive superamphiphile (BTOA), which consists of oleic acid (OA) and cationic amine (named 1,3-bis(aminopropyl)tetramethyldisiloxane, BT). The simulation results present the morphologies in both the emulsion and demulsification states. It is found that the ionized OA- and the protonated BT+ together form an adsorption layer at the oil-water interface. The hydrophobic parts of BT+ are inserted into the adsorption layer, and the two amine groups contact the water phase. This adsorption layer reduces the interfacial tension and stabilizes the emulsion. After the bubbling of CO2, the surfactants were fully protonated to OA and BT2+. Because of the changes in the molecular polarity, OA and BT2+ entered the oil and water phases, respectively, resulting in demulsification. The structural and dynamical properties were analyzed to reveal the different intermolecular interactions that were responsible for the reversible reversibility of the emulsion. The observations are considered to be complementary to experimental studies and are expected to provide deeper insights into studies on developing responsive materials via supramolecular assemblies.

12.
Curr Med Chem ; 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38013439

RESUMEN

α-Glucosidase inhibitors (AGIs) showcase versatile biochemical activities with respect to antidiabetic, anticancerous, antiobese and antiviral effects. They have drawn a great deal of attention from the scientific community. While α-glucosidase inhibitors are mostly discovered from plants and microorganisms, the recent advance in natural αglucosidase inhibitors over the past five years has been reviewed in this article, and 139 distinct α-glucosidase inhibitors from the plants and microorganisms were classified into ten groups based on their chemical structures, including flavonoids (34), xanthones (6), alkaloids (8), benzopyrones / benzofuranones (8), terpenes (23), saponins (8), phenols / alcohols (25), esters (18), chalcone (5) and other compounds (4). In this review, we mainly focused on the novel chemical structures and the various biological activities of theses natural AGIs. Some of the selected natural compounds exhibit powerful α-glucosidase inhibitory activity and anti-tumor activity, may hold promise to become the candidate drugs for treating type II diabetes and cancer in future.

13.
Eur J Med Chem ; 261: 115797, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37708799

RESUMEN

Triple negative breast cancer (TNBC) is considered to be the most difficult subtype of breast cancer to treat because of its extremely prone to metastasis and the lack of targeted therapy drugs. New purine derivatives were synthesized and evaluated in a series of kinases and cell lines. The most active compounds 3g and 3j were selected based on their antiproliferative activities, then their pharmaceutical activity and mechanism in MDA-MB-231 cells were analyzed. The results in vitro indicated that compounds 3g and 3j can induce MDA-MB-231 cells apoptosis, and inhibit its migration and angiogenesis through influencing protein expression such as Bcl-2, Bax, Bcl-xl, P38, MMP2, MMP9, AKT and EGFR. In vivo results indicate that compounds 3g and 3j can inhibit tumor growth and metastasis and reduce the expression of Ki67 and CD31 protein in TNBC xenograft models. These findings not only broaden our understanding of the anti-TNBC effects and mechanisms of compounds 3g and 3j, but also provide new ideas and reference directions for the treatment of TNBC.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Línea Celular Tumoral , Apoptosis , Purinas/farmacología , Purinas/uso terapéutico , Proliferación Celular
14.
Eur J Med Chem ; 260: 115723, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37595545

RESUMEN

N-acetylneuraminic acid (Neu5Ac) is a glycan receptor of viruses spread in many eukaryotic cells. The present work aimed to design, synthesis and biological evaluation of a panel of Neu5Ac derivatives based on a cyclodextrin (CD) scaffold for targeting influenza and coronavirus membrane proteins. The multivalent Neu5Ac glycoclusters efficiently inhibited chicken erythrocyte agglutination induced by intact influenza virus in a Neu5Ac density-dependent fashion. Compared with inhibition by Neu5Ac, the multivalent inhibitor with 21 Neu5Ac residues on the primary face of the ß-CD scaffold afforded 1788-fold higher binding affinity inhibition for influenza virus hemagglutinin with a dissociation constant (KD) of 3.87 × 10-7 M. It showed moderate binding affinity to influenza virus neuraminidase, but with only about one-thirtieth the potency of that with the HA protein. It also exhibited strong binding affinity to the spike protein of three human coronaviruses (severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome coronavirus 2), with KD values in the low micromolar range, which is about 10-time weaker than that of HA. Therefore, these multivalent sialylated CD derivatives have possible therapeutic application as broad-spectrum antiviral entry inhibitors for many viruses by targeting the Neu5Ac of host cells.


Asunto(s)
COVID-19 , Ciclodextrinas , Inhibidores de Fusión de VIH , Gripe Humana , Humanos , Animales , Ácido N-Acetilneuramínico , Antivirales/farmacología , Pollos
15.
Eur J Med Chem ; 259: 115662, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37482018

RESUMEN

Two series of NSAIDs-EBS derivatives (5a-j and 9a-i) based on the hybridization of nonsteroidal anti-inflammatory drugs (NSAIDs) skeleton and Ebselen moiety were synthesized. Their cytotoxicity was evaluated against five types of human cancer cell lines, BGC-823 (human gastric cancer cell line), SW480 (human colon adenocarcinoma cells), MCF-7 (human breast adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells). Moreover, the most active compound 5j showed IC50 values below 3 µM in all cancer cell lines and with remarkable anticancer activity against MCF-7 (1.5 µM) and HeLa (1.7 µM). The redox properties of the NSAIDs-EBS derivatives prepared herein were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Finally, TrxR1 inhibition activity assay and molecular docking study revealed NSAIDs-EBS derivatives could serve as potential TrxR1 inhibitor.


Asunto(s)
Adenocarcinoma , Antiinflamatorios no Esteroideos , Antineoplásicos , Humanos , Antineoplásicos/química , Antioxidantes/farmacología , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon , Ensayos de Selección de Medicamentos Antitumorales , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología
16.
Eur J Med Chem ; 258: 115536, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37295260

RESUMEN

ONS donor ligands L1-L4 were utilized in the preparation of monofunctional dimetallic Ru(η6-arene) complexes (C1-C4). These ONS donor ligand based novel tricoordinated Ru(II) complexes bearing η6-arene co-ligand were prepared for the first time. The current methodology resulted in excellent isolated yields and these complexes were characterized in detail by different spectroscopic and spectrometric techniques. The structures of C1-C2 and C4 were characterized in solid state by single crystal X-ray analysis. The in vitro anticancer analyses showed these novel complexes suppressed the growth of breast (MCF-7), liver (HepG2) and lung (A549) cancer cells. C2 suppressed the growth of these cells in dose-dependent manner revealed form the MTT and crystal violet cell viability assays. Moreover, C2 was observed the most potent complex that was used further in detailed mechanistic analyses in cancer cells. C2 showed good cytotoxic activity at 10 µM dose level as compared to cisplatin or oxaliplatin in these cancer cells. We observed morphological changes in cancer cells upon treatment with C2. Moreover, C2 suppressed the invasion and migration ability of cancer cells. C2 induced cellular senescence to retard cell growth and suppressed the formation of cancer stem cells. Importantly, C2 showed synergistic anticancer effect in combination with cisplatin and Vitamin C to further inhibit cell growth which suggested the potential role of C2 in cancer therapy. Mechanistically, C2 inhibited NOTCH1 dependent signaling pathway to suppress cancer cell invasion, migration and cancer stem cells formation. Thus, these data suggested potential role of C2 in cancer therapy by targeting NOTCH1-dependent signaling to suppress tumorigenesis. The results obtained in this study for these novel monofunctional dimetallic Ru(η6-arene) complexes showed their high anticancer potency and this study will pave to further cytotoxicity exploration on this class of complexes.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Rutenio , Cisplatino/farmacología , Ácido Ascórbico/farmacología , Ligandos , Antineoplásicos/farmacología , Antineoplásicos/química , Transducción de Señal , Rutenio/farmacología , Rutenio/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales
17.
J Colloid Interface Sci ; 647: 384-394, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37269735

RESUMEN

HYPOTHESIS: Stimulus-responsive microemulsions have aroused significant attention because of their versatile and reversible switchability between stable and unstable states. However, most stimuli-responsive microemulsions are based on stimuli-responsive surfactants. We posit that the change in the hydrophilicity of a selenium-containing alcohol triggered by a mild redox reaction could also influence the stability of microemulsions and provide a new nanoplatform for the delivery of bioactive substances. EXPERIMENTS: A selenium-containing diol (3,3'-selenobis(propan-1-ol), PSeP) was designed and used as a co-surfactant in a microemulsion with ethoxylated hydrogenated castor oil (HCO40), diethylene glycol monohexyl ether (DGME), 2-n-octyl-1-dodecanol (ODD) and water. The redox-induced transition in PSeP was characterized by 1H NMR, 77Se NMR, and MS. The redox-responsiveness of the ODD/HCO40/DGME/PSeP/water microemulsion was investigated through determination of a pseudo-ternary phase diagram, analysis by dynamic light scattering, and electrical conductivity, and its encapsulation performance was evaluated by determination of the solubility, stability, antioxidant activity, and skin penetrability of encapsulated curcumin. FINDINGS: The redox conversion of PSeP enabled efficient switching of ODD/HCO40/DGME/PSeP/water microemulsions. Addition of oxidant (H2O2), oxidized PSeP into more hydrophilic PSeP-Ox (selenoxide), disrupting the emulsifying capacity of the combination of HCO40/DGME/PSeP, markedly reducing the monophasic microemulsion region in the phase diagram, and inducing phase separation in some formulations. Addition of reductant (N2H4·H2O), reduced PSeP-Ox and restored the emulsifying capacity of the combination of HCO40/DGME/PSeP. In addition, PSeP-based microemulsions can significantly enhance the solubility in oil (by 23 times), stability, antioxidant capacity (DPPH∙ radical scavenging by 91.74 %), and skin penetrability of curcumin, showing clear potential for encapsulation and delivery of curcumin and other bioactive substances.

18.
Carbohydr Polym ; 312: 120770, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37059526

RESUMEN

Treating wastewater containing malachite green (MG) using porous materials with both adsorption and degradation functions have become a major challenge in achieving the carbon neutrality goal. Herein by incorporating the ferrocene (Fc) group as a Fenton active center, a novel composite porous material (DFc-CS-PEI) was prepared using chitosan (CS) and polyethyleneimine (PEI) as skeletons and oxidized dextran as a crosslinker. DFc-CS-PEI not only possesses satisfactory adsorption performance to MG but also excellent degradability in the presence of a minor amount of H2O2 (3.5 mmol/L) without any additional assistance, due to high specific surface area and active Fc group. The maximum adsorption capacity is ca. 177.73 ± 3.11 mg/g, outperforming most CS-based adsorbents. The removal efficiency of MG is significantly enhanced from 20 % to 90 % as DFc-CS-PEI and H2O2 coexist, due to ·OH-dominated Fenton reaction, and remained in a wide pH range (2.0-7.0). Cl- exhibits notable suppression on the degradation of MG because of quenching effects. Note that DFc-CS-PEI has a very small iron leaching (0.2 ± 0.015 mg/L), and can be rapidly recycled by simple water-washing, without any harmful chemicals and potential second pollution. Such versatility, high stability, and green recyclability make the as-prepared DFc-CS-PEI a promising porous material for the treatment of organic wastewater.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 296: 122658, 2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-36989690

RESUMEN

Hydrogen polysulfide (H2Sn, n > 1) has a valuable function in various aspects of biological regulation. Therefore, it is of great significance to realize the visual monitoring of H2Sn levels in vivo. Herein, a series of fluorescent probes NR-BS were constructed by changing types and positions of substituents on the benzene ring of benzenesulfonyl. Among them, probe NR-BS4 was optimized due to its wide linear range (0 âˆ¼ 350 µM) and little interference from biothiols. In addition, NR-BS4 has a broad pH tolerance range (pH = 4 âˆ¼ 10) and high sensitivity (0.140 µM). In addition, the PET mechanism of probe NR-BS4 and H2Sn was demonstrated by DFT calculations and LC-MS. The intracellular imaging studies indicate that NR-BS4 can be successfully devoted to monitor the levels of exogenous and endogenous H2Sn in vivo.


Asunto(s)
Colorantes Fluorescentes , Sulfuro de Hidrógeno , Colorantes Fluorescentes/química , Hidrógeno , Esqueleto
20.
Gastric Cancer ; 26(4): 528-541, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36959335

RESUMEN

Gastric cancer (GC) is one of the most common malignancies in China and is associated with high mortality. The occurrence and development of gastric cancer are related to genetic and environmental factors. Focal adhesion kinase (FAK) is a cytoplasmic nonreceptor protein tyrosine kinase that is activated by the extracellular matrix and growth factors. FAK is highly expressed in cancer and promotes its development by regulating cancer cell proliferation, migration, and angiogenesis. The expression of IL-8 is increased in many types of malignant tumor cells and is linked to their proliferation, migration, invasion, angiogenesis, and EMT. In this study, we found FAK to be essential for the proliferation, migration, and peritoneal metastasis of gastric cancer cells. To examine the molecular regulatory mechanisms of FAK in the peritoneal dissemination of gastric cancer, we performed RNA-seq analysis of MKN-45-FAK-/- and MKN45 cells and demonstrated that IL-8 was downregulated in FAK-deficient cells. Conversely, we confirmed that IL-8 activates FAK activity. We established that IL-8 promotes the proliferation, colony formation, and migration of gastric cancer cells that are partially mediated by FAK. Thus, we propose that an IL-8-FAK-IL-8 positive feedback loop effects the proliferation and migration of gastric cancer cells.


Asunto(s)
Neoplasias Gástricas , Humanos , Proteína-Tirosina Quinasas de Adhesión Focal/genética , Neoplasias Gástricas/patología , Interleucina-8/genética , Proliferación Celular , Movimiento Celular/genética , Línea Celular Tumoral
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