Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.318
Filtrar
Más filtros

Medicinas Complementárias
Tipo del documento
Intervalo de año de publicación
1.
BMC Plant Biol ; 24(1): 229, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561653

RESUMEN

BACKGROUND: BAHD acyltransferases are among the largest metabolic protein domain families in the genomes of terrestrial plants and play important roles in plant growth and development, aroma formation, and biotic and abiotic stress responses. Little is known about the BAHDs in the tea plant, a cash crop rich in secondary metabolites. RESULTS: In this study, 112 BAHD genes (CsBAHD01-CsBAHD112) were identified from the tea plant genome, with 85% (98/112) unevenly distributed across the 15 chromosomes. The number of BAHD gene family members has significantly expanded from wild tea plants to the assamica type to the sinensis type. Phylogenetic analysis showed that they could be classified into seven subgroups. Promoter cis-acting element analysis revealed that they contain a large number of light, phytohormones, and stress-responsive elements. Many members displayed tissue-specific expression patterns. CsBAHD05 was expressed at more than 500-fold higher levels in purple tea leaves than in green tea leaves. The genes exhibiting the most significant response to MeJA treatment and feeding by herbivorous pests were primarily concentrated in subgroups 5 and 6. The expression of 23 members of these two subgroups at different time points after feeding by tea green leafhoppers and tea geometrids was examined via qPCR, and the results revealed that the expression of CsBAHD93, CsBAHD94 and CsBAHD95 was significantly induced after the tea plants were subjected to feeding by both pricking and chewing pests. Moreover, based on the transcriptome data for tea plants being fed on by these two pests, a transcriptional regulatory network of different transcription factor genes coexpressed with these 23 members was constructed. CONCLUSIONS: Our study provides new insights into the role of BAHDs in the defense response of tea plants, and will facilitate in-depth studies of the molecular function of BAHDs in resistance to herbivorous pests.


Asunto(s)
Aminas , Camellia sinensis , Disulfuros , Camellia sinensis/metabolismo , Filogenia , Genoma de Planta , Té/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
2.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1076-1088, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38658150

RESUMEN

Flavin-containing monooxygenase (FMO) is the key enzyme in the biosynthesis pathway of CSOs with sulfur oxidation. In order to explore the molecular regulatory mechanism of FMO in the synthesis of onion CSOs, based on transcriptome database and phylogenetic analysis, one AcFMO gene that may be involved in alliin synthesis was obtained, the AcFMO had a cDNA of 1 374 bp and encoded 457 amino acids, which was evolutionarily closest to the AsFMO of garlic. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) indicated that AcFMO was the highest in the flowers and the lowest in the leaf sheaths. The results of subcellular localization showed that the AcFMO gene product was widely distributed throughout the cell A yeast expression vector was constructed, and the AcFMO gene was ecotopically overexpressed in yeast to further study the enzyme function in vitro and could catalyze the synthesis of alliin by S-allyl-l-cysteine. In summary, the cloning and functional identification of AcFMO have important reference value for understanding the biosynthesis of CSOs in onions.


Asunto(s)
Clonación Molecular , Cisteína/análogos & derivados , Cebollas , Cebollas/genética , Cebollas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cisteína/biosíntesis , Cisteína/metabolismo , Oxigenasas/genética , Oxigenasas/metabolismo , Secuencia de Aminoácidos , Filogenia , Disulfuros/metabolismo , Datos de Secuencia Molecular , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
3.
Molecules ; 29(6)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38542956

RESUMEN

Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.


Asunto(s)
Antineoplásicos , Neoplasias del Colon , Ajo , Plantas Medicinales , Masculino , Humanos , Extractos Vegetales/química , Estudios Prospectivos , Ácidos Sulfínicos/química , Disulfuros , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Ajo/química
4.
Int J Biol Macromol ; 266(Pt 1): 130838, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38521322

RESUMEN

Innovative antibacterial therapies using nanomaterials, such as photothermal (PTT) and photodynamic (PDT) treatments, have been developed for treating wound infections. However, creating secure wound dressings with these therapies faces challenges. The primary focus of this study is to prepare an antibacterial nanofiber dressing that effectively incorporates stable loads of functional nanoparticles and demonstrates an efficient synergistic effect between PTT and PDT. Herein, a composite nanofiber mat was fabricated, integrating spherical molybdenum disulfide (MoS2) nanoparticles. MoS2 was deposited onto polylactic acid (PLA) nanofiber mats using vacuum filtration, which was further stabilized by sodium carboxymethyl cellulose (CMC) adhesion and glutaraldehyde (GA) cross-linking. The composite nanofibers demonstrated synergistic antibacterial effects under NIR light irradiation, and the underlying mechanism was explored. They induce bacterial membrane permeability, protein leakage, and intracellular reactive oxygen species (ROS) elevation, ultimately leading to >95 % antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), which is higher than that of single thermotherapy (almost no antibacterial activity) or ROS therapy (about 80 %). In addition, the composite nanofiber mats exhibited promotion effects on infected wound healing in vivo. This study demonstrates the great prospects of composite nanofiber dressings in clinical treatment of bacterial-infected wounds.


Asunto(s)
Antibacterianos , Carboximetilcelulosa de Sodio , Disulfuros , Escherichia coli , Molibdeno , Nanofibras , Fotoquimioterapia , Staphylococcus aureus , Molibdeno/química , Molibdeno/farmacología , Disulfuros/química , Disulfuros/farmacología , Nanofibras/química , Antibacterianos/farmacología , Antibacterianos/química , Fotoquimioterapia/métodos , Carboximetilcelulosa de Sodio/química , Carboximetilcelulosa de Sodio/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Escherichia coli/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Terapia Fototérmica/métodos , Vendajes
5.
Blood Adv ; 8(7): 1747-1759, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38324726

RESUMEN

ABSTRACT: Therapeutic vaccination has long been a promising avenue for cancer immunotherapy but is often limited by tumor heterogeneity. The genetic and molecular diversity between patients often results in variation in the antigens present on cancer cell surfaces. As a result, recent research has focused on personalized cancer vaccines. Although promising, this strategy suffers from time-consuming production, high cost, inaccessibility, and targeting of a limited number of tumor antigens. Instead, we explore an antigen-agnostic polymeric in situ cancer vaccination platform for treating blood malignancies, in our model here with acute myeloid leukemia (AML). Rather than immunizing against specific antigens or targeting adjuvant to specific cell-surface markers, this platform leverages a characteristic metabolic and enzymatic dysregulation in cancer cells that produces an excess of free cysteine thiols on their surfaces. These thiols increase in abundance after treatment with cytotoxic agents such as cytarabine, the current standard of care in AML. The resulting free thiols can undergo efficient disulfide exchange with pyridyl disulfide (PDS) moieties on our construct and allow for in situ covalent attachment to cancer cell surfaces and debris. PDS-functionalized monomers are incorporated into a statistical copolymer with pendant mannose groups and TLR7 agonists to target covalently linked antigen and adjuvant to antigen-presenting cells in the liver and spleen after IV administration. There, the compound initiates an anticancer immune response, including T-cell activation and antibody generation, ultimately prolonging survival in cancer-bearing mice.


Asunto(s)
Cisteína , Leucemia Mieloide Aguda , Humanos , Ratones , Animales , Cisteína/uso terapéutico , Modelos Animales de Enfermedad , Leucemia Mieloide Aguda/tratamiento farmacológico , Adyuvantes Inmunológicos , Antígenos de Neoplasias , Activación de Linfocitos , Disulfuros/uso terapéutico
6.
Molecules ; 29(3)2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38338360

RESUMEN

Currently, the obvious side effects of anti-tumor drugs, premature drug release, and low tumor penetration of nanoparticles have largely reduced the therapeutic effects of chemotherapy. A drug delivery vehicle (MCN-SS-GQDs) was designed innovatively. For this, the mesoporous carbon nanoparticles (MCN) with the capabilities of superior photothermal conversion efficiency and high loading efficiency were used as the skeleton structure, and graphene quantum dots (GQDs) were gated on the mesopores via disulfide bonds. The doxorubicin (DOX) was used to evaluate the pH-, GSH-, and NIR-responsive release performances of DOX/MCN-SS-GQDs. The disulfide bonds of MCN-SS-GQDs can be ruptured under high glutathione concentration in the tumor microenvironment, inducing the responsive release of DOX and the detachment of GQDs. The local temperature of a tumor increases significantly through the photothermal conversion of double carbon materials (MCN and GQDs) under near-infrared light irradiation. Local hyperthermia can promote tumor cell apoptosis, accelerate the release of drugs, and increase the sensitivity of tumor cells to chemotherapy, thus increasing treatment effect. At the same time, the detached GQDs can take advantage of their extremely small size (5-10 nm) to penetrate deeply into tumor tissues, solving the problem of low permeability of traditional nanoparticles. By utilizing the photothermal properties of GQDs, synergistic photothermal conversion between GQDs and MCN was realized for the purpose of synergistic photothermal treatment of superficial and deep tumor tissues.


Asunto(s)
Antineoplásicos , Grafito , Hipertermia Inducida , Nanopartículas , Neoplasias , Puntos Cuánticos , Humanos , Puntos Cuánticos/química , Grafito/química , Antineoplásicos/farmacología , Antineoplásicos/química , Doxorrubicina , Nanopartículas/química , Fototerapia , Carbono/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Disulfuros , Microambiente Tumoral
7.
Anim Sci J ; 95(1): e13917, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38323750

RESUMEN

Allicin is a sulfur-containing compound extracted from raw garlic (Allium sativum L.). We compared the effect of allicin addition on growth performance, serum biochemical parameters, and rumen microbiota of goats compared to monensin. Twenty-four Anhui white goats were assigned randomly to one of three dietary treatments: 1) a basal diet (CON); 2) the basal diet with allicin addition at 750 mg per head per day (AC); 3) the basal diet with monensin addition at 30 mg per kg of diet (MS). Animals were fed for 8 weeks. Results showed the average daily gain, and feed efficiency was increased with allicin and monensin addition. Serum levels of IgG, total superoxide dismutase, and glutathione peroxidase were higher in the AC group than those in the CON and MS groups. The microbiota analysis revealed that monensin addition mainly affected genera related to carbohydrate and protein metabolism, and allicin mainly affected genera related to energy metabolism and intestinal health. In conclusion, allicin could improve growth performance and have advantages over monensin in improving the antioxidant capacity and immune function of goats. Allicin may be a potential alternative to monensin.


Asunto(s)
Disulfuros , Ajo , Microbiota , Ácidos Sulfínicos , Animales , Alimentación Animal/análisis , Antioxidantes/metabolismo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Cabras/metabolismo , Monensina/farmacología , Rumen/metabolismo
8.
ACS Appl Mater Interfaces ; 16(3): 3202-3214, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38207171

RESUMEN

Bacterial biofilm infection threatens public health, and efficient treatment strategies are urgently required. Phototherapy is a potential candidate, but it is limited because of the off-targeting property, vulnerable activity, and normal tissue damage. Herein, cascade-responsive nanoparticles (NPs) with a synergistic effect of phototherapy and chemotherapy are proposed for targeted elimination of biofilms. The NPs are fabricated by encapsulating IR780 in a polycarbonate-based polymer that contains disulfide bonds in the main chain and a Schiff-base bond connecting vancomycin (Van) pendants in the side chain (denoted as SP-Van@IR780 NPs). SP-Van@IR780 NPs specifically target bacterial biofilms in vitro and in vivo by the mediation of Van pendants. Subsequently, SP-Van@IR780 NPs are decomposed into small size and achieve deep biofilm penetration due to the cleavage of disulfide bonds in the presence of GSH. Thereafter, Van is then detached from the NPs because the Schiff base bonds are broken at low pH when SP@IR780 NPs penetrate into the interior of biofilm. The released Van and IR780 exhibit a robust synergistic effect of chemotherapy and phototherapy, strongly eliminate the biofilm both in vitro and in vivo. Therefore, these biocompatible SP-Van@IR780 NPs provide a new outlook for the therapy of bacterial biofilm infection.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Nanopartículas , Vancomicina/farmacología , Nanopartículas/química , Biopelículas , Concentración de Iones de Hidrógeno , Disulfuros/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
9.
Elife ; 122024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38252473

RESUMEN

Fibroblast growth factor 2 (FGF2) exits cells by direct translocation across the plasma membrane, a type I pathway of unconventional protein secretion. This process is initiated by phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent formation of highly dynamic FGF2 oligomers at the inner plasma membrane leaflet, inducing the formation of lipidic membrane pores. Cell surface heparan sulfate chains linked to glypican-1 (GPC1) capture FGF2 at the outer plasma membrane leaflet, completing FGF2 membrane translocation into the extracellular space. While the basic steps of this pathway are well understood, the molecular mechanism by which FGF2 oligomerizes on membrane surfaces remains unclear. In the current study, we demonstrate the initial step of this process to depend on C95-C95 disulfide-bridge-mediated FGF2 dimerization on membrane surfaces, producing the building blocks for higher FGF2 oligomers that drive the formation of membrane pores. We find FGF2 with a C95A substitution to be defective in oligomerization, pore formation, and membrane translocation. Consistently, we demonstrate a C95A variant of FGF2 to be characterized by a severe secretion phenotype. By contrast, while also important for efficient FGF2 secretion from cells, a second cysteine residue on the molecular surface of FGF2 (C77) is not involved in FGF2 oligomerization. Rather, we find C77 to be part of the interaction interface through which FGF2 binds to the α1 subunit of the Na,K-ATPase, the landing platform for FGF2 at the inner plasma membrane leaflet. Using cross-linking mass spectrometry, atomistic molecular dynamics simulations combined with a machine learning analysis and cryo-electron tomography, we propose a mechanism by which disulfide-bridged FGF2 dimers bind with high avidity to PI(4,5)P2 on membrane surfaces. We further propose a tight coupling between FGF2 secretion and the formation of ternary signaling complexes on cell surfaces, hypothesizing that C95-C95-bridged FGF2 dimers are functioning as the molecular units triggering autocrine and paracrine FGF2 signaling.


Asunto(s)
Espacio Extracelular , Factor 2 de Crecimiento de Fibroblastos , Dimerización , ATPasa Intercambiadora de Sodio-Potasio , Disulfuros
10.
J Control Release ; 367: 354-365, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38286337

RESUMEN

Synergistic photothermal immunotherapy has attracted widespread attention due to the mutually reinforcing therapeutic effects on primary and metastatic tumors. However, the lack of clinical approval nanomedicines for spatial, temporal, and dosage control of drug co-administration underscores the challenges facing this field. Here, a photothermal agent (Cy7-TCF) and an immune checkpoint blocker (NLG919) are conjugated via disulfide bond to construct a tumor-specific small molecule prodrug (Cy7-TCF-SS-NLG), which self-assembles into prodrug-like nano-assemblies (PNAs) that are self-delivering and self-formulating. In tumor cells, over-produced GSH cleaves disulfide bonds to release Cy7-TCF-OH, which re-assembles into nanoparticles to enhance photothermal conversion while generate reactive oxygen species (ROSs) upon laser irradiation, and then binds to endogenous albumin to activate near-infrared fluorescence, enabling multimodal imaging-guided phototherapy for primary tumor ablation and subsequent release of tumor-associated antigens (TAAs). These TAAs, in combination with the co-released NLG919, effectively activated effector T cells and suppressed Tregs, thereby boosting antitumor immunity to prevent tumor metastasis. This work provides a simple yet effective strategy that integrates the supramolecular dynamics and reversibility with stimuli-responsive covalent bonding to design a simple small molecule with synergistic multimodal imaging-guided phototherapy and immunotherapy cascades for cancer treatment with high clinical value.


Asunto(s)
Nanopartículas , Neoplasias , Profármacos , Humanos , Profármacos/uso terapéutico , Nanomedicina Teranóstica , Neoplasias/terapia , Fototerapia , Nanopartículas/química , Antígenos de Neoplasias , Inmunoterapia , Disulfuros , Línea Celular Tumoral
11.
J Phys Chem B ; 128(4): 973-984, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38236012

RESUMEN

Metalloproteins make up a class of proteins that incorporate metal ions into their structures, enabling them to perform essential functions in biological systems, such as catalysis and electron transport. Azurin is one such metalloprotein with copper cofactor, having a ß-barrel structure with exceptional thermal stability. The copper metal ion is coordinated at one end of the ß-barrel structure, and there is a disulfide bond at the opposite end. In this study, we explore the effect of this disulfide bond in the high thermal stability of azurin by analyzing both the native S-S bonded and S-S nonbonded (S-S open) forms using temperature replica exchange molecular dynamics (REMD). Similar to experimental observations, we find a 35 K decrease in denaturation temperature for S-S open azurin compared to that of the native holo form (420 K). As observed in the case of native holo azurin, the unfolding process of the S-S open form also started with disruptions of the α-helix. The free energy surfaces of the unfolding process revealed that the denaturation event of the S-S open form progresses through different sets of conformational ensembles. Subsequently, we compared the stabilities of individual ß-sheet strands of both the S-S bonded and the S-S nonbonded forms of azurin. Further, we examined the contacts between individual residues for the central structures from the free energy surfaces of the S-S nonbonded form. The microscopic origin of the lowering in the denaturation temperature is further supplemented by thermodynamic analysis.


Asunto(s)
Azurina , Metaloproteínas , Azurina/química , Cobre/química , Metaloproteínas/metabolismo , Disulfuros/química , Temperatura , Iones , Pliegue de Proteína
12.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 703-724, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37615709

RESUMEN

The main objective of this review is to highlight the therapeutic potential of allicin, a defense molecule in garlic known for its diverse health benefits, and address the key challenges of its bioavailability and stability. The research further aims to evaluate various formulation strategies and nanotechnology-based delivery systems that can resolve these issues and improve allicin's clinical efficacy, especially in cancer therapy. We conducted a comprehensive review of the available literature and previous studies, focusing on the therapeutic properties of allicin, its bioavailability, stability issues, and novel formulation strategies. We assessed the mechanism of action of allicin in cancer, including its effects on signaling pathways, cell cycle, apoptosis, autophagy, and tumor development. We also evaluated the outcomes of both in vitro and in vivo studies on different types of cancers, such as breast, cervical, colon, lung, and gastric cancer. Despite allicin's significant therapeutic benefits, including cardiovascular, antihypertensive, cholesterol-lowering, antimicrobial, antifungal, anticancer, and immune-modulatory activity, its clinical utility is limited due to poor stability and unpredictable bioavailability. Allicin's bioavailability in the gastrointestinal tract is dependent on the activity of the enzyme alliinase, and its stability can be affected by various conditions like gastric acid and intestinal enzyme proteases. Recent advances in formulation strategies and nanotechnology-based drug delivery systems show promise in addressing these challenges, potentially improving allicin's solubility, stability, and bioavailability. Allicin offers substantial potential for cancer therapy, yet its application is hindered by its instability and poor bioavailability. Novel formulation strategies and nanotechnology-based delivery systems can significantly overcome these limitations, enhancing the therapeutic efficacy of allicin. Future research should focus on refining these formulation strategies and delivery systems, ensuring the safety and efficacy of these new allicin formulations. Clinical trials and long-term studies should be carried out to determine the optimal dosage, assess potential side effects, and evaluate their real-world applicability. The comparative analysis of different drug delivery approaches and the development of targeted delivery systems can also provide further insight into enhancing the therapeutic potential of allicin.


Asunto(s)
Disulfuros , Neoplasias , Humanos , Disponibilidad Biológica , Ácidos Sulfínicos/uso terapéutico , Ácidos Sulfínicos/metabolismo , Ácidos Sulfínicos/farmacología , Resultado del Tratamiento , Neoplasias/tratamiento farmacológico
13.
Chem Biol Drug Des ; 103(1): e14385, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37914430

RESUMEN

Kaempferol is the active ingredient of Er-Xian decoction (EXD), a traditional Chinese medicine formula used clinically to treat ovarian dysfunction, but the mechanism of kaempferol relieving age-related diminished ovarian reserve (AR-DOR) is still unclear. In this study, 36 volunteers and 78 DOR patients (37 patients with EXD treatment) were enrolled in the clinical research. Meanwhile, 32-week-old female mice were used to establish the AR-DOR model, and these model mice were intragastrically administered with 100 mg/kg kaempferol in the presence or absence of 200 mg/kg geranylgeranylacetone (GGA) or 1 mg/kg geldanamycin (GDA). The effects of kaempferol on serum hormone levels and oxidative stress-related indexes were detected by enzyme-linked immunosorbent assay. Antral follicle count (AFC) was determined by hematoxylin-eosin staining. The protein levels of HSP90 and nuclear factor erythroid 2-related factor 2 (NRF2) were assayed by Western blot. This study displayed that the serum anti-Mullerian hormone (AMH) level in DOR patients with EXD treatment was higher than that in DOR patients without EXD treatment. Kaempferol treatment reversed the low levels of AMH, estradiol (E2), AFC, superoxide dismutase (SOD), and catalase (CAT), as well as the high levels of follicle-stimulating hormone (FSH), reactive oxygen species (ROS), and malonaldehyde (MDA). The results showed that HSP90 was predicted to have high affinity with kaempferol, and its expression was inhibited by kaempferol, while the expression of NRF2, the target of HSP90, was up-regulated by kaempferol. However, the above effects of kaempferol were reversed by GGA. On the contrary, GDA enhanced the therapeutic effects of kaempferol on AR-DOR mice. Moreover, the treatment of kaempferol resulted in a reduction in the phosphorylation level of heat shock factor 1 (HSF1), the transcription factor associated with HSP90, and an increase in the phosphorylation level of Src, a client protein of HSP90. In summary, kaempferol exerts an antioxidant effect on AR-DOR by inhibiting HSP90 expression to up-regulate NRF2 expression. This study provides a theoretical basis for the clinical application of kaempferol in AR-DOR.


Asunto(s)
Antioxidantes , Disulfuros , Reserva Ovárica , Tionas , Femenino , Humanos , Animales , Ratones , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Factor 2 Relacionado con NF-E2 , Reserva Ovárica/fisiología , Quempferoles/farmacología , Quempferoles/uso terapéutico
14.
Acta Biomater ; 173: 457-469, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37984631

RESUMEN

Magnetic nanoparticles (MNPs) are promising in tumor treatments due to their capacity for magnetic hyperthermia therapy (MHT), chemodynamic therapy (CDT), and immuno-related therapies, but still suffer from unsatisfactory tumor inhibition in the clinic. Insufficient hydrogen peroxide supply, glutathione-induced resistance, and high-density extracellular matrix (ECM) are the barriers. Herein, we hierarchically decorated MNPs with disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx) to form a nanosystem (MNPs-SS-R-GOx). Its outer GOx layer not only enhanced the H2O2 supply to produce .OH by Fenton reaction, but also generated stronger oxidants (ONOO-) together with the interfaced R layer. The inner S-S layer consumed glutathione to interdict its reaction with oxidants, thus enhancing CDT effects. Importantly, the generated ONOO- tripled the MMP-9 expression to induce ECM degradation, enabling much deeper penetration of MNPs and benefiting CDT, MHT, and immunotherapy. Finally, the MNPs-SS-R-GOx demonstrated a remarkable 91.7% tumor inhibition in vivo. STATEMENT OF SIGNIFICANCE: Magnetic nanoparticles (MNPs) are a promising tumor therapeutic agent but with limited effectiveness. Our hierarchical MNP design features disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx), which boosts H2O2 supply for ·OH generation in Fenton reactions, produces potent ONOO-, and enhances chemodynamic therapy via glutathione consumption. Moreover, the ONOO- facilitates the upregulation of matrix metalloprotein expression beneficial for extracellular matrix degradation, which in turn enhances the penetration of MNPs and benefits the antitumor CDT/MHT/immuno-related therapy. In vivo experiments have demonstrated an impressive 91.7% inhibition of tumor growth. This hierarchical design offers groundbreaking insights for further advancements in MNP-based tumor therapy. Its implications extend to a broader audience, encompassing those interested in material science, biology, oncology, and beyond.


Asunto(s)
Hipertermia Inducida , Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Humanos , Glucosa Oxidasa , Peróxido de Hidrógeno , Nanopartículas de Magnetita/uso terapéutico , Estrés Oxidativo , Arginina , Glutatión , Nanopartículas/uso terapéutico , Neoplasias/terapia , Oxidantes , Disulfuros , Fenómenos Magnéticos , Línea Celular Tumoral , Microambiente Tumoral
15.
J Gene Med ; 26(1): e3617, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37935422

RESUMEN

OBJECTIVE: Erxian Decoction (EXD) is traditionally employed in the treatment of menopausal syndromes, although its underlying mechanisms remain largely undefined. Given that the senescence of bone marrow mesenchymal stem cells (BMSCs) is intertwined with organismal aging and associated diseases, this study endeavored to elucidate the influence of EXD on aging BMSCs and uncover the mechanisms through which EXD impedes BMSC senescence. METHODS: Initially, we probed the anti-senescent mechanisms of EXD on BMSCs via network pharmacology. We subsequently isolated and identified exosomes from the serum of EXD-fed rats (EXD-Exos) and administered these to H2 O2 -induced aging BMSC. Assays were conducted to assess BMSC senescence indicators and markers pertinent to mitochondrial autophagy. Treatments with mitophagy inhibitors and activators were then employed to substantiate our findings. RESULTS: Protein-protein interaction (PPI) network analyses spotlighted AKT1, TP53, TNF, JUN, VEGFA, IL6, CASP3 and EGFR as focal targets. Gene Ontology and Kyoto Encylcopedia of Genes and Genomes pathway analyses underscored oxidative stress, mitophagy and cell proliferation as pivotal processes. Our cellular assays ascertained that EXD-Exos mitigated H2 O2 -induced senescence phenotypes in BMSCs. Moreover, EXD-Exos ameliorated disrupted mitophagy in BMSCs, as evidenced by enhanced cellular membrane potential and diminished reactive oxygen species levels. Intriguingly, EXD-Exos also preserved the osteogenic differentiation potential of BMSCs while curtailing their adipogenic propensity. CONCLUSION: Our findings compellingly suggest that EXD counteracts BMSC senescence by fostering mitophagy.


Asunto(s)
Disulfuros , Medicamentos Herbarios Chinos , Exosomas , Células Madre Mesenquimatosas , Tionas , Ratas , Animales , Osteogénesis , Mitofagia , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo
16.
Int J Biol Macromol ; 254(Pt 2): 127822, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37926302

RESUMEN

Our aim was to investigate the preparation of self-assembled garlic essential oil-amylose inclusion complexes (SGAs) using garlic essential oil (GEO) and corn starch (CS), and evaluated their release properties. SGAs were fabricated by pre-gelatinization coupling with high-speed shear at different GEO-CS mass ratios. When the mass ratio of GEO to pre-gelatinized corn starch was set at 15 % (SGA-15 %), with a fixed shear rate of 9000 rpm and a shear time of 30 min, the allicin content was 0.573 ± 0.023 mg/g. X-ray diffraction (XRD) results revealed a starch V-type crystalline structure in SGAs with peaks at 13.0°, 18.0°, and 20.0° (2θ). Fourier Transform Infrared (FTIR) spectra of SGAs displayed a shift in the characteristic peak of diallyl trisulfide from 987.51 cm-1 to 991.45 cm-1. Scanning electron microscope (SEM) images revealed that SGAs exhibited lamellar structures covered with small granules. SGAs exhibited higher residual mass (approximately 12 %) than other samples. The resistant starch content of SGAs increased from 10.1 % to 18.4 % as GEO contents varied from 5 % to 15 %. In vitro digestion tests showed that about 53.21 % of allicin remained in SGA-15 % after 8 h. Therefore, this dual treatment can be a new method for fabricating controlled-release inclusion complexes of guest molecules.


Asunto(s)
Amilosa , Ajo , Amilosa/química , Almidón/química , Disulfuros , Difracción de Rayos X
17.
Int J Biol Macromol ; 257(Pt 2): 128779, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38100959

RESUMEN

The effect of pectin concentration on the structural and emulsifying properties of black soldier fly larvae albumin (BSFLA) modified by pH-shifting (pH12) and ultrasound (US) was studied. The results (intrinsic fluorescence, surface hydrophobicity, Fourier transform infrared spectrum, and disulfide bonds) showed that modified BSFLA samples, especially pH12-US, were more likely to bind to pectin through hydrogen bonding, electrostatic interactions, and hydrophobic interactions due to the unfolding of BSFLA, the collapse of disulfide bonds and exposure of hydrophobic groups. Thus, a BSFLA-pectin complex with smaller particle size, more negative charges, and a relatively loose structure was formed. The emulsifying activity (EAI) and stability index (ESI) of pH12-US modified BSFLA were significantly enhanced by the addition of pectin, reaching the highest values (associated with 174.41 % and 643.22 % increase, respectively) at pectin concentration of 1.0 %. Furthermore, the interface modulus of the emulsion prepared by the modified BSFLA was mainly viscous, and had higher apparent viscosity, smaller particle size and droplet size, contributing to higher EAI and ESI. The study findings suggest the addition of pectin to pH12-US treated BSFLA could be used in industry to prepare BSFLA-pectin emulsion with exceptional/desirable properties.


Asunto(s)
Dípteros , Pectinas , Animales , Larva , Emulsiones/química , Pectinas/química , Albúminas , Concentración de Iones de Hidrógeno , Disulfuros
18.
J Agric Food Chem ; 71(49): 19207-19220, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-37943254

RESUMEN

Garlic has been used worldwide as a spice due to its pungent taste and flavor-enhancing properties. As a main biologically active component of the freshly crushed garlic extracts, allicin (diallyl thiosulfinate) is converted from alliin by alliinase upon damaging the garlic clove, which has been reported to have many potent beneficial biological functions. In this work, allicin formation, stability, bioavailability, and metabolism process are examined and summarized. The biological functions of allicin and potential underlying mechanisms are reviewed and discussed, including antioxidation, anti-inflammation, antidiabetic, cardioprotective, antineurodegenerative, antitumor, and antiobesity effects. Novel delivery systems of allicin with enhanced stability, encapsulation efficiency, and bioavailability are also evaluated, such as nanoparticles, gels, liposomes, and micelles. This study could provide a comprehensive understanding of the physiochemical properties and health benefits of allicin, with great potential for further applications in the food and nutraceutical industries.


Asunto(s)
Disulfuros , Ajo , Disponibilidad Biológica , Suplementos Dietéticos , Ajo/química , Ácidos Sulfínicos/química , Antioxidantes/metabolismo
19.
Eur Rev Med Pharmacol Sci ; 27(18): 8523-8530, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37782168

RESUMEN

OBJECTIVE: We aimed to investigate the relationship between intraoperative body temperature and thiol/disulfide balance in geriatric patients scheduled for elective transurethral prostate resection surgery with spinal anesthesia. PATIENTS AND METHODS: 71 patients classified as categories 1 and 2, according to American Society of Anesthesiologists (ASA) classification, were included in the study. The core temperature of the patients was recorded in the operating room after monitoring, at 5 and 30 minutes after spinal anesthesia. Total thiols, native thiols, disulfide amounts, disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were calculated as percentages after monitorization (Tpreoperative) and at 60 minutes after spinal anesthesia (Tintraoperative). RESULTS: The disulfide levels in the Tintraoperative period (29±8.9 mmol/L) were higher than the disulfide levels measured in the Tpreoperative period (18.2±8.8 mmol/L) (p<0.001). In the Tpreoperative period, the disulfide/native thiol (%) level was 4.6±2, while the disulfide/total thiol (%) level was 4.2±1.6. In the Tintraoperative period, the disulfide/native thiol (%) level was 8±2.3, while the disulfide/total thiol (%) level was 6.8±1.7. Native thiol/total thiol (%) levels for the Tpreoperative and Tintraoperative periods were 91.5±3.3 mmol/L and 86.3±3.4 mmol/L, respectively. A correlation was found between native, total thiol levels and patient age in the Tpreoperative and Tintraoperative periods. CONCLUSIONS: Oxidative stress can be reduced in geriatric patients with the possibility of developing involuntary perioperative hypothermia by regularly monitoring body temperature and applying warming techniques.


Asunto(s)
Anestesia Raquidea , Resección Transuretral de la Próstata , Masculino , Humanos , Anciano , Temperatura Corporal , Disulfuros , Compuestos de Sulfhidrilo , Estrés Oxidativo , Biomarcadores
20.
Molecules ; 28(18)2023 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-37764332

RESUMEN

Coffee processing generates a huge amount of waste that contains many natural products. Here, we report the discovery of a panel of novel cell-penetrating and metal ion-binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and a database search, we show that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif, but without a chitin-binding domain. NMR determination of cC1a reveals a compact structure that confers its resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis reveals that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement, like ginsentide precursors. Molecular modeling, together with experimental validation, revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have the potential to target intracellular proteins.


Asunto(s)
Coffea , Café , Cisteína , Disulfuros , Micropéptidos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA