Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 415
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Differentiation ; 135: 100742, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38104501

RESUMEN

Hepatic organoids might provide a golden opportunity for realizing precision medicine in various hepatic diseases. Previously described hepatic organoid protocols from pluripotent stem cells rely on complicated multiple differentiation steps consisting of both 2D and 3D differentiation procedures. Therefore, the spontaneous formation of hepatic organoids from 2D monolayer culture is associated with a low-throughput production, which might hinder the standardization of hepatic organoid production and hamper the translation of this technology to the clinical or industrial setting. Here we describe the stepwise and fully 3D production of hepatic organoids from human pluripotent stem cells. We optimized every differentiation step by screening for optimal concentrations and timing of differentiation signals in each differentiation step. Hepatic organoids are stably expandable without losing their hepatic functionality. Moreover, upon treatment of drugs with known hepatotoxicity, we found hepatic organoids are more sensitive to drug-induced hepatotoxicity compared with 2D hepatocytes differentiated from PSCs, making them highly suitable for in vitro toxicity screening of drug candidates. The standardized fully 3D protocol described in the current study for producing functional hepatic organoids might serve as a novel platform for the industrial and clinical translation of hepatic organoid technology.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes , Humanos , Diferenciación Celular/genética , Organoides
2.
J Cell Biochem ; 125(1): 100-114, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38031891

RESUMEN

Osteoporosis (OP) is a bone remodeling disease characterized by an imbalance between bone resorption and formation. Osteoclasts are the primary therapeutic targets for treating bone destruction. Koumine (KM), the most bioactive component in Gelsemium alkaloids, exhibits antitumor, immunosuppressive, anti-inflammatory, and analgesic properties. However, the effects of bone loss have not been well studied. This study conducted in vitro and in vivo verification experiments on KM. The results showed that KM inhibited bone resorption and tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts development by mature osteoclasts in a dose-dependent manner. Moreover, KM prevented OVX-induced OP in vivo and potentially inhibited ubiquitination, a process closely related to various biological activities, including protein interaction, transcription, and transmembrane signal transduction regulation, especially within the nuclear factor-κB (NF-κB) pathway. Previous studies have demonstrated that several proteins ubiquitination promotes osteoclastogenesis, our study indicated that KM inhibits early NF-κB activation and receptor activator of NF-κB ligand induced ubiquitination, a critical factor in osteoclast differentiation. In conclusion, our research suggests that KM holds potential as an effective therapeutic agent for OP.


Asunto(s)
Resorción Ósea , Alcaloides Indólicos , Osteoporosis , Femenino , Humanos , FN-kappa B/metabolismo , Osteoclastos/metabolismo , Osteogénesis , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/prevención & control , Resorción Ósea/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Osteoporosis/prevención & control , Ovariectomía/efectos adversos , Ligando RANK/metabolismo , Diferenciación Celular
3.
J Org Chem ; 89(1): 676-680, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38113931

RESUMEN

An iodine-mediated method for the synthesis of 6-alkylthio-1,3,5-triazine-2,4-diamines by the reaction of N-alkylpyridinium salts and NH4SCN in air is reported. Twenty-seven compounds were obtained under the standard conditions. Pyridinium salts work as benzyl-group transfer reagents to promote the formation of the CBn-SSCN bond and thereby the construction of the triazine skeleton. A plausible mechanism is proposed based on the experimental results and literature survey.

4.
Ecotoxicol Environ Saf ; 269: 115735, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38039852

RESUMEN

In recent years, with the increasing global focus on environmental protection, the issue of microfiber release from denim during the washing process has gained attention. In this study, a programmable washing device simulating household drum washing was designed and developed, microfibers and indigo dyes released from denim washing were quantitatively detected, and we have also developed a novel method for estimating the release of microfibers during washing. The effects of washing time, washing temperature, and washing load on microfiber and indigo dye release from denim were explored. The results showed that the effect of washing load on microfiber and indigo dye release was greater than washing temperature and washing time. The research findings indicate that with an increase in washing time (35-95 min) and washing load (100-250 g), the shedding of microfibers and indigo dye significantly increases, reaching peak release levels of 343.6 µg/g fabric and 0.027 mg/L, respectively. However, there is a decreasing trend in the release of microfibers and indigo dye when the washing temperature exceeds 50 °C. Furthermore, our data suggests that an increase in washing load leads to a significant change in the number of microfibers (from 978 items/g fabric to 1997 items/g fabric) and their mass (from 156.87 µg/g fabric to 343.56 µg/g fabric). The influence of washing time, washing temperature, and washing load on microfiber length shows relatively small fluctuations within the range of 600-900 µm. This study provides new ideas and methods for estimating the release of microfiber and indigo dye in denim washing around the world.


Asunto(s)
Carmin de Índigo , Textiles
5.
J Neuroeng Rehabil ; 21(1): 77, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745227

RESUMEN

BACKGROUND: Over 80% of patients with stroke experience finger grasping dysfunction, affecting independence in activities of daily living and quality of life. In routine training, task-oriented training is usually used for functional hand training, which may improve finger grasping performance after stroke, while augmented therapy may lead to a better treatment outcome. As a new technology-supported training, the hand rehabilitation robot provides opportunities to improve the therapeutic effect by increasing the training intensity. However, most hand rehabilitation robots commonly applied in clinics are based on a passive training mode and lack the sensory feedback function of fingers, which is not conducive to patients completing more accurate grasping movements. A force feedback hand rehabilitation robot can compensate for these defects. However, its clinical efficacy in patients with stroke remains unknown. This study aimed to investigate the effectiveness and added value of a force feedback hand rehabilitation robot combined with task-oriented training in stroke patients with hemiplegia. METHODS: In this single-blinded randomised controlled trial, 44 stroke patients with hemiplegia were randomly divided into experimental (n = 22) and control (n = 22) groups. Both groups received 40 min/day of conventional upper limb rehabilitation training. The experimental group received 20 min/day of task-oriented training assisted by a force feedback rehabilitation robot, and the control group received 20 min/day of task-oriented training assisted by therapists. Training was provided for 4 weeks, 5 times/week. The Fugl-Meyer motor function assessment of the hand part (FMA-Hand), Action Research Arm Test (ARAT), grip strength, Modified Ashworth scale (MAS), range of motion (ROM), Brunnstrom recovery stages of the hand (BRS-H), and Barthel index (BI) were used to evaluate the effect of two groups before and after treatment. RESULTS: Intra-group comparison: In both groups, the FMA-Hand, ARAT, grip strength, AROM, BRS-H, and BI scores after 4 weeks of treatment were significantly higher than those before treatment (p < 0.05), whereas there was no significant difference in finger flexor MAS scores before and after treatment (p > 0.05). Inter-group comparison: After 4 weeks of treatment, the experimental group's FMA-Hand total score, ARAT, grip strength, and AROM were significantly better than those of the control group (p < 0.05). However, there were no statistically significant differences in the scores of each sub-item of the FMA-Hand after Bonferroni correction (p > 0.007). In addition, there were no statistically significant differences in MAS, BRS-H, and BI scores (p > 0.05). CONCLUSION: Hand performance improved in patients with stroke after 4 weeks of task-oriented training. The use of a force feedback hand rehabilitation robot to support task-oriented training showed additional value over conventional task-oriented training in stroke patients with hand dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION: NCT05841108.


Asunto(s)
Fuerza de la Mano , Hemiplejía , Robótica , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Rehabilitación de Accidente Cerebrovascular/instrumentación , Masculino , Femenino , Persona de Mediana Edad , Robótica/instrumentación , Fuerza de la Mano/fisiología , Hemiplejía/rehabilitación , Hemiplejía/fisiopatología , Hemiplejía/etiología , Anciano , Método Simple Ciego , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Dedos/fisiología , Dedos/fisiopatología , Mano/fisiopatología , Adulto , Retroalimentación Sensorial/fisiología , Resultado del Tratamiento , Recuperación de la Función
6.
Reprod Domest Anim ; 59(4): e14565, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38646981

RESUMEN

Mangiferin (MGN) is primarily found in the fruits, leaves, and bark of plants of the Anacardiaceae family, including mangoes. MGN exhibits various pharmacological effects, such as protection of the liver and gallbladder, anti-lipid peroxidation, and cancer prevention. This study aimed to investigate the effects of MGN supplementation during in vitro culture (IVC) on the antioxidant capacity of early porcine embryos and the underlying mechanisms involved. Porcine parthenotes in the IVC medium were exposed to different concentrations of MGN (0, 0.01, 0.1, and 1 µM). The addition of 0.1 µM MGN significantly increased the blastocyst formation rate of porcine embryos while reducing the apoptotic index and autophagy. Furthermore, the expression of antioxidation-related (SOD2, GPX1, NRF2, UCHL1), cell pluripotency (SOX2, NANOG), and mitochondria-related (TFAM, PGC1α) genes was upregulated. In contrast, the expression of apoptosis-related (CAS3, BAX) and autophagy-related (LC3B, ATG5) genes decreased after MGN supplementation. These findings suggest that MGN improves early porcine embryonic development by reducing oxidative stress-related genes.


Asunto(s)
Técnicas de Cultivo de Embriones , Desarrollo Embrionario , Estrés Oxidativo , Xantonas , Animales , Estrés Oxidativo/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Xantonas/farmacología , Técnicas de Cultivo de Embriones/veterinaria , Apoptosis/efectos de los fármacos , Antioxidantes/farmacología , Autofagia/efectos de los fármacos , Porcinos , Blastocisto/efectos de los fármacos , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Partenogénesis
7.
Reprod Domest Anim ; 59(6): e14631, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38828566

RESUMEN

This study examines the impact of Notoginsenoside R1 (NGR1), a compound from Panax notoginseng, on the maturation of porcine oocytes and their embryonic development, focusing on its effects on antioxidant levels and mitochondrial function. This study demonstrates that supplementing in vitro maturation (IVM) medium with NGR1 significantly enhances several biochemical parameters. These include elevated levels of glutathione (GSH), nuclear factor erythrocyte 2-related factor 2 (NRF2) and mRNA expression of catalase (CAT) and GPX. Concurrently, we observed a decrease in reactive oxygen species (ROS) levels and an increase in JC-1 immunofluorescence, mitochondrial distribution, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear NRF2 mRNA levels. Additionally, there was an increase in ATP production and lipid droplets (LDs) immunofluorescence. These biochemical improvements correlate with enhanced embryonic outcomes, including a higher blastocyst rate, increased total cell count, enhanced proliferative capacity and elevated octamer-binding transcription factor 4 (Oct4) and superoxide dismutase 2 (Sod2) gene expression. Furthermore, NGR1 supplementation resulted in decreased apoptosis, reduced caspase 3 (Cas3) and BCL2-Associated X (Bax) mRNA levels and decreased glucose-regulated protein 78 kD (GRP78) immunofluorescence in porcine oocytes undergoing in vitro maturation. These findings suggest that NGR1 plays a crucial role in promoting porcine oocyte maturation and subsequent embryonic development by providing antioxidant levels and mitochondrial protection.


Asunto(s)
Antioxidantes , Desarrollo Embrionario , Ginsenósidos , Técnicas de Maduración In Vitro de los Oocitos , Mitocondrias , Oocitos , Animales , Antioxidantes/farmacología , Ginsenósidos/farmacología , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Mitocondrias/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Oocitos/efectos de los fármacos , Femenino , Porcinos , Especies Reactivas de Oxígeno/metabolismo , Técnicas de Cultivo de Embriones/veterinaria
8.
J Med Virol ; 95(7): e28920, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37386905

RESUMEN

Currently, various problems are being faced in the treatment of influenza, so the development of new safe and effective drugs is crucial. Selenadiazole, an important component of selenium heterocyclic compounds, has received wide attention for its biological activity. This study aimed to verify the antiviral activity of 5-nitrobenzo[c][1,2,5]selenadiazole (SeD-3) in vivo and in vitro. The cell counting kit-8 assay and observation of cytopathic effect verified that SeD-3 could improve the survival of influenza A(H1N1)pdm09-infected Madin-Darby canine kidney cells. Polymerase chain reaction quantification and neuraminidase assay showed that SeD-3 could inhibit the proliferation of H1N1 virus. The time of addition assay demonstrated that SeD-3 may have a direct effect on virus particles and block some stages of H1N1 life cycle after virus adsorption. Cell cycle, JC-1, Annexin V, and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling-4',6-diamidino-2-phenylindole (TUNEL-DAPI) assays showed that SeD-3 inhibited H1N1 infection-induced apoptosis. Cytokine detection demonstrated SeD-3 inhibited the production of proinflammatory factors after infection, including tumor necrosis factor-α (TNF-α), TNF-ß, interferon-γ, interleukin 12 (IL-12), and IL-17F. In vivo experiments suggested that the pathological damage in the lungs was significantly alleviated after treatment with SeD-3 by hematoxylin and eosin staining. The TUNEL assay of lung tissues indicated that SeD-3 inhibited DNA damage during H1N1 infection. Immunohistochemical assays were performed to further explore the mechanism that SeD-3 inhibited H1N1-induced apoptosis via reactive oxygen species-mediated MAPK, AKT, and P53 signaling pathways. In conclusion, SeD-3 may become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.


Asunto(s)
Gripe Humana , Animales , Perros , Humanos , Inflamación/tratamiento farmacológico , Estrés Oxidativo , Especies Reactivas de Oxígeno , Antivirales/farmacología , Antivirales/uso terapéutico
9.
Reprod Biomed Online ; 47(2): 103211, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37246104

RESUMEN

RESEARCH QUESTION: Does the addition of an antioxidant agent, xanthoangelol (XAG), to the culture medium improve in-vitro development of porcine embryos? DESIGN: Early porcine embryos were incubated in the presence of 0.5 µmol/l XAG in in-vitro culture (IVC) media and analysed using various techniques, including immunofluorescence staining, reactive oxygen species (ROS) detection, TdT-mediated dUTP nick-end labelling (TUNEL), and reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR). RESULTS: The addition of 0.5 µmol/l XAG to IVC media increased the rate of blastocyst formation, total cell number, glutathione concentrations and proliferative capacity, while reducing reactive oxygen species concentrations, apoptosis and autophagy. In addition, upon XAG treatment, the abundance of mitochondria and mitochondrial membrane potential significantly increased (both P < 0.001), and the genes related to mitochondrial biogenesis (TFAM, NRF1 and NRF2) were significantly up-regulated (all P < 0.001). XAG treatment also significantly increased the endoplasmic reticulum abundance (P < 0.001) and reduced the concentrations of endoplasmic reticulum stress (ERS) marker GRP78 (P = 0.003) and expression of the ERS-related genes EIF2α, GRP78, CHOP, ATF6, ATF4, uXBP1 and sXBP 1 (all P < 0.001). CONCLUSION: XAG promotes early embryonic development in porcine embryos in vitro by reducing oxidative stress, enhancing mitochondrial function and relieving ERS.


Asunto(s)
Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Embarazo , Animales , Femenino , Porcinos , Especies Reactivas de Oxígeno/metabolismo , Desarrollo Embrionario , Apoptosis , Mitocondrias/metabolismo , Estrés Oxidativo
10.
Biomacromolecules ; 24(9): 3929-3953, 2023 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-37579246

RESUMEN

Hybrid polymer vesicles contain functional nanoparticles (NPs) in their walls, interfaces, coronae, or cavities. NPs render the hybrid vesicles with specific physical properties, while polymers endow them with structural stability and may significantly reduce the high toxicity of NPs. Therefore, hybrid vesicles integrate fascinating multifunctions from both NPs and polymeric vesicles, which have gained tremendous attention because of their diverse promising applications. Various types of delicate hybrid polymeric vesicles with size control and tunable localization of NPs in different parts of vesicles have been constructed via in situ and ex situ strategies, respectively. Their potential applications have been widely explored, as well. This review presents the progress of block copolymer (BCP) vesicle systems containing different types of NPs including metal NPs, magnetic NPs, and semiconducting quantum dots (QDs), etc. The strategies for controlling the location of NPs within hybrid vesicles are discussed. Typical potential applications of the elegant hybrid vesicles are also highlighted.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Puntos Cuánticos , Polímeros/química , Nanopartículas/química
11.
EMBO Rep ; 22(7): e52481, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-34121311

RESUMEN

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter-driven Cre expression (AdipoqCre ) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre ; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)-induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.


Asunto(s)
Resorción Ósea , Osteoclastos , Tejido Adiposo , Animales , Médula Ósea , Células de la Médula Ósea , Resorción Ósea/genética , Diferenciación Celular , Ratones
12.
J Org Chem ; 88(17): 12244-12250, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37606631

RESUMEN

A copper-catalyzed reaction of pyridinium salts and trimethylsilyl cyanide (TMSCN) in the presence of diethyl phosphite is developed. This reaction, which allows the single-step construction of biologically important 2-cyanoimidazo[1,2-a]pyridine from readily available starting materials, is realized for the first time and is feasible at the gram scale. The scope of the protocol is demonstrated with 27 examples. A consecutive double cyanation and cyclization can be achieved in this one-pot process. TMSCN plays a dual role not only as the "CN" source but also as the coupling partner for the cyclization of imidazo[1,2-a]pyridines.

13.
Nanotechnology ; 34(33)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37196644

RESUMEN

Two-dimensional black phosphorus (2D BP), a novel 2D photoelectric material with excellent near-infrared optical absorption, biocompatibility, and degradability, has shown enormous potential in biomedical field. However, under the action of light, oxygen and water, 2D BP is easily degraded to phosphate and phosphonate. In this work, trastuzumab (Tmab) as a positively charged protein was used to modify 2D BP through electrostatic interaction to form BP-Tmab. The Tmab layer on the surface of 2D BP can effectively protect BP from water, which significantly enhanced the water stability of BP. PEGylated 2D BP (BP-PEG) as a control was also prepared. After 7 days in air-exposed water, the attenuation value of BP-Tmab was only 6.62 ± 2.72% at room temperature, which was much lower than that of naked 2D BP (52.47 ± 2.26%) and BP-PEG (25.84 ± 2.80%) under the same conditions. The result was further confirmed by the temperature changes at different time points under laser irradiation, suggesting that the degradation of BP was effectively reduced by Tmab modification. In addition, BP-Tmab displayed satisfactory biocompatibility and can effectively destroy cancer cells under laser irradiation, showing an excellent photothermal therapy effect.


Asunto(s)
Antineoplásicos , Fósforo , Proteínas , Fósforo/química , Proteínas/química , Antineoplásicos/química , Humanos , Línea Celular Tumoral , Fotoquimioterapia
14.
Mol Biol Rep ; 50(10): 8445-8457, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37632633

RESUMEN

BACKGROUND: The overall survival (OS) rate of adult patients suffering from acute myeloid leukaemia (AML) remains unsatisfactory at less than 40%. Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML. METHODS: qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases. RESULTS: PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens. CONCLUSIONS: The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potential biomarker. PLXNB2 might exert an oncogenic role by modulating immune functions, endothelial cell functions and cell interactions. AML patients with high PLXNB2 expression could benefit more from HSCT.


Asunto(s)
Relevancia Clínica , Leucemia Mieloide Aguda , Adulto , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Médula Ósea/patología , Perfilación de la Expresión Génica , ARN Mensajero
15.
Mol Biol Rep ; 50(4): 2991-3000, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36653729

RESUMEN

BACKGROUND: Enterovirus A71 (EV-A71)is a prevalent infection in severe hand, foot and mouth disease HFMD and can induce acute central nervous system seizures. The three EV-A71 vaccines now circulating in the market are produced for a single subtype. While EV-A71 is constantly evolving and the vaccine's efficacy is gradually reducing, no specialized anti-EV-A71 medication has yet been developed. Therefore, it is crucial to consistently develop new anti-EV-A71 medications. METHOD: Ebselen, an organoselenium molecule with glutathione oxidase-like activity, is resistant to a range of viruses. In this investigation, we used the Cell counting kit-8 (CCK-8 kit) assay in a Vero cell model to confirm the effectiveness of ebselen against EV-A71 infection. Later, to examine ebselen's anti-EV-A71 mechanism, we measured the apoptosis level of cells in different treatment groups through Annexin V, JC-1, and cell cycle assays, as well as the intracellular reactive oxygen species (ROS) concentration. Ebselen may have an impact on the apoptotic signaling pathway caused by EV-A71 infection, according to the results of a caspase-3 activity experiment. RESULT: The results showed that Ebselen protected cell damage from ROS generation, decreased the frequency of EV-A71-induced apoptosis, and inhibited caspase-3-mediated apoptosis by lowering caspase-3 activity. CONCLUSION: To summarize, ebselen is a promising anti-EV-A71 medication.


Asunto(s)
Enterovirus Humano A , Infecciones por Enterovirus , Enterovirus , Humanos , Especies Reactivas de Oxígeno , Caspasa 3 , Infecciones por Enterovirus/tratamiento farmacológico , Transducción de Señal , Apoptosis
16.
Bioorg Chem ; 140: 106770, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37604094

RESUMEN

The identification of novel candidate molecules with the potential to revolutionize the treatment of breast cancer holds profound clinical significance. Macropin (Mac)-1, derived from the venom of wild bees, emerges as an auspicious therapeutic agent for combating breast cancers. Nevertheless, linear peptides have long grappled with the challenges of traversing cell membranes and succumbing to protease hydrolysis. To address this challenge, the present study employed hydrocarbon stapling modification to synthesize a range of stapled Mac-1 peptides, which were comprehensively evaluated for their chemical and biological properties. Significantly, Mac-1-sp4 exhibited a remarkable set of improvements, including enhanced helicity, proteolytic stability, cell membrane permeability, induction of cell apoptosis, in vivo antitumor activity, and inhibition of tubulin polymerization. This study explores the significant impact of the hydrocarbon stapling technique on the secondary structure, hydrolase stability, and biological activity of Mac-1, shedding light on its potential as a revolutionary and potent anti-breast cancer therapy. The findings establish a strong basis for the development of innovative and highly effective anti-tumor treatments.


Asunto(s)
Neoplasias , Péptidos , Animales , Abejas , Péptidos/farmacología , Péptidos/uso terapéutico , Péptido Hidrolasas , Apoptosis , Membrana Celular , Hidrocarburos
17.
J Reprod Dev ; 69(1): 10-17, 2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36403957

RESUMEN

Dihydromyricetin (DHM), a dihydroflavonoid compound, exhibits a variety of biological activities, including antitumor activity. However, the effects of DHM on mammalian reproductive processes, especially during early embryonic development, remain unclear. In this study, we added DHM to porcine zygotic medium to explore the influence and underlying mechanisms of DHM on the developmental competence of parthenogenetically activated porcine embryos. Supplementation with 5 µM DHM during in vitro culture (IVC) significantly improved blastocyst formation rate and increased the total number of cells in porcine embryos. Further, DHM supplementation also improved glutathione levels and mitochondrial membrane potential; reduced natural reactive oxygen species levels in blastomeres and apoptosis rate; upregulated Nanog, Oct4, SOD1, SOD2, Sirt1, and Bcl2 expression; and downregulated Beclin1, ATG12, and Bax expression. Collectively, DHM supplementation regulated oxidative stress during IVC and could act as a potential antioxidant during in vitro porcine oocytes maturation.


Asunto(s)
Blastocisto , Oocitos , Femenino , Embarazo , Porcinos , Animales , Oocitos/metabolismo , Blastocisto/metabolismo , Estrés Oxidativo , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Especies Reactivas de Oxígeno/metabolismo , Desarrollo Embrionario , Suplementos Dietéticos , Mamíferos/metabolismo
18.
Zygote ; 31(5): 451-456, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37337719

RESUMEN

Mammalian oocytes not fertilized immediately after ovulation can undergo ageing and a rapid decline in quality. The addition of antioxidants can be an efficient approach to delaying the oocyte ageing process. Onion peel extract (OPE) contains quercetin and other flavonoids with natural antioxidant activities. In this study, we investigated the effect of OPE on mouse oocyte ageing and its mechanism of action. The oocytes were aged in vitro in M16 medium for 16 h after adding OPE at different concentrations (0, 50, 100, 200, and 500 µg/ml). The addition of 100 µg/ml OPE reduced the oocyte fragmentation rate, decreased the reactive oxygen species (ROS) level, increased the glutathione (GSH) level, and improved the mitochondrial membrane potential compared with the control group. The addition of OPE also increased the expression of SOD1, CAT, and GPX3 genes, and the caspase-3 activity in OPE-treated aged oocytes was significantly lower than that in untreated aged oocytes and similar to that in fresh oocytes. These results indicated that OPE delayed mouse oocyte ageing by reducing oxidative stress and apoptosis and enhancing mitochondrial function.


Asunto(s)
Antioxidantes , Cebollas , Femenino , Ratones , Animales , Cebollas/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Oocitos , Quercetina/farmacología , Estrés Oxidativo , Glutatión/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Mamíferos
19.
Lasers Med Sci ; 38(1): 71, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36790539

RESUMEN

Photobiomodulation (PBM) is the use of low irradiance light of specific wavelengths to generate physiological changes and therapeutic effects. However, there are few studies on the effects of PBM of different LED light modes on cells. Here, we investigated the difference of influence between continuous wave (CW) and pulse-PBM on B16F10 melanoma cells. Our results suggested that the pulse mode had a more significant PBM than the CW mode on B16F10 melanoma cells. Our study confirmed that ROS and Ca2+ levels in B16F10 melanoma cells treated with pulse-PBM were significantly higher than those in the control and CW-PBM groups. One mechanism that causes the difference in CW and pulse-PBM action is that pulse-PBM activates autophagy of melanoma cells through the ROS/OPN3/Ca2+ signaling pathway, and excessive autophagy activation inhibits proliferation and apoptosis of melanoma cells. Autophagy may be one of the reasons for the difference between pulse- and CW-PBM on melanoma cells. More importantly, melanoma cells responded to brief PBM pulses by increasing intracellular Ca2+ levels.


Asunto(s)
Terapia por Luz de Baja Intensidad , Melanoma , Humanos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Autofagia , Melanoma/radioterapia , Terapia por Luz de Baja Intensidad/métodos , Opsinas de Bastones
20.
Health Promot Int ; 38(5)2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37748868

RESUMEN

Health literacy may constitute a modifiable determinant of smoking behavior and intention to quit. Little is known about the extent to which health literacy affects smoking or quitting smoking. We assessed the nationally representative cross-sectional datasets from the China Health Literacy Surveillance (CHLS) initiated in 2018. Using polytomous logistic regression models, the study investigated the association of health literacy with smoking behavior and the intention to quit smoking among men aged 15-69 in China. After confounding factors were controlled, compared with having below basic health literacy, having adequate health literacy appeared to be an independent protective factor from current smoking [current smoking vs never smoking: adjusted odds ratio [OR], 0.88; 95% confidence interval (CI), 0.81-0.96; p = 0.003; current smoking vs former smoking: adjusted OR, 0.77; 95% CI, 0.64-0.92; p = 0.003], while having intermediate health literacy was associated with current smoking vs never smoking (adjusted OR, 1.09; 95% CI, 1.02-1.17; p = 0.011) or former smoking vs never smoking (adjusted OR, 1.22; 95% CI, 1.06-1.40; p = 0.005). And having adequate health literacy was associated with intending to quit among current smokers (adjusted OR, 1.25; 95% CI, 1.10-1.42; p < 0.001). Findings provide evidence that health literacy may serve as a critical and independent protective factor for reducing poor smoking behavior or enhancing cessation intention among men. Efforts should focus on developing and evaluating intervention to control tobacco use among men with low health literacy level.


Asunto(s)
Alfabetización en Salud , Fumar Tabaco , Humanos , Masculino , Estudios Transversales , Pueblos del Este de Asia , Alfabetización en Salud/estadística & datos numéricos , Fumar/epidemiología , Fumar Tabaco/epidemiología , Conductas de Riesgo para la Salud , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Cese del Uso de Tabaco/estadística & datos numéricos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA