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1.
J Cardiovasc Pharmacol ; 82(4): 333-343, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37506377

RESUMEN

ABSTRACT: Many studies have confirmed that macrophage autophagy injury negatively impacts the pathogenesis of atherosclerosis (AS). Meanwhile, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway affects AS progression by regulating macrophage autophagy. We previously reported that the herbal formula San Jie Tong Mai Fang (SJTMF) elicits lipid regulatory and anti-inflammatory properties. Hence, the current study used an ApoE -/- high-fat diet-fed mouse model to determine whether SJTMF elicits protective effects against AS progression by means of the regulation of macrophage autophagy through the PI3K/AKT/mTOR signaling pathway. Our results show that SJTMF reduced the number of atherosclerotic plaques, foam cell formation, and intimal thickness in mouse aorta. In addition, SJTMF improved blood lipid metabolism and inflammatory levels in mice. We also observed that SJTMF caused macrophages to be polarized toward the M2 phenotype through the inhibition of the PI3K/AKT/mTOR signaling pathway. In addition, the abundances of LC3-II/I and beclin1 proteins-key autophagy molecules-were increased, whereas that of p62 was decreased, resulting in the promotion of macrophage autophagy. Taken together, these findings indicate that SJTMF may regulate the polarization of macrophages by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby reducing atherosclerotic plaque damage in ApoE -/- mice, thereby promoting macrophage autophagy and eliciting a significant antiarteriosclerosis effect. Hence, SJTMF may represent a promising new candidate drug for the treatment of AS.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Macroautofagia , Serina-Treonina Quinasas TOR/metabolismo , Ratones Noqueados para ApoE , Transducción de Señal , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Aterosclerosis/genética , Autofagia , Apolipoproteínas E/farmacología , Mamíferos/metabolismo
2.
Angew Chem Int Ed Engl ; 61(30): e202202894, 2022 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-35441399

RESUMEN

Transition metal (e.g. Ni) ions dissolved from layered-structured Ni-rich cathodes can migrate to the anode side and accelerate the failure of lithium-ion batteries. The investigations of the impact and distribution of Ni species on the solid electrolyte interphase (SEI) on the anode are crucial to understand the failure mechanism. Herein, we used time-of-flight secondary ion mass spectroscopy (TOF-SIMS) coupled with multivariate curve resolution (MCR) analysis to intuitively characterize the distribution of Ni species in the SEI. We find that the SEI on the graphite electrode using an EC-based electrolyte exhibits a multi-stratum structure. During accelerated aging of the LiNi0.88 Co0.08 Mn0.04 O2 /graphite full cell, the dissolution of Ni aggravates significantly upon cycling. A strong correlation between the dissolved-Ni and organic species in the SEI on graphite is illustrated. The ion-exchange reaction between Ni2+ and Li+ ions in the SEI is demonstrated to be the main reason for the increase of SEI resistivity.

3.
Biochem Biophys Res Commun ; 495(1): 325-331, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29108993

RESUMEN

Salvianolic acid B (SalB) is one of the most bioactive components extracted from Salvia miltiorrhiza, and its antioxidant capacity corresponds with its protective effects against cell injury from oxidative stress. The aim of the present study was to evaluate the effect of SalB on experimental pulmonary fibrosis and its ability to ameliorate the oxidative/antioxidative imbalance during fibrosis pathogenesis. The anti-fibrotic activity of SalB was first confirmed in Transforming growth factor ß1(TGF-ß1)-stimulated MRC-5 cells. The protection of SalB against oxidative stress during fibrogenesis in vitro was verified by detecting ROS production, the levels of glutathione (GSH) and malondialdehyde (MDA). The Western blot and PCR results indicated that SalB could up-regulate nuclear factor erythroid-derived 2-like 2 (Nrf2) at both the protein and mRNA levels and induce Nrf2 nuclear translocation in vitro, which may be the mechanism underlying the anti-fibrotic capacity of SalB. Furthermore, the anti-fibrotic and antioxidant capacities of SalB in vivo were confirmed in rats with BLM-induced pulmonary fibrosis. The immunohistochemistry results showed that Nrf2 was absent in fibroblastic foci (FF) areas, while the SalB treatment could increase the expression of Nrf2 in lung tissues, especially in FF areas.


Asunto(s)
Benzofuranos/administración & dosificación , Transdiferenciación Celular/efectos de los fármacos , Miofibroblastos/efectos de los fármacos , Miofibroblastos/patología , Factor 2 Relacionado con NF-E2/metabolismo , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Fibrosis Pulmonar/patología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacos
4.
Biochem Biophys Res Commun ; 468(1-2): 214-20, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26523510

RESUMEN

Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-ß1 (TGF-ß1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-ß1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-ß1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-ß1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening.


Asunto(s)
Antioxidantes/uso terapéutico , Benzofuranos/uso terapéutico , Pulmón/efectos de los fármacos , Pulmón/patología , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/patología , Animales , Antioxidantes/farmacología , Benzofuranos/farmacología , Bleomicina , Línea Celular , Evaluación Preclínica de Medicamentos/métodos , Módulo de Elasticidad , Humanos , Pulmón/metabolismo , Masculino , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Ratas , Ratas Wistar , Factor de Crecimiento Transformador beta1/metabolismo
5.
Cardiovasc Diabetol ; 13: 78, 2014 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-24725502

RESUMEN

UNLABELLED: Previous studies showed that the accumulation of advanced glycation end products (AGEs) induce cardiomyocyte apoptoisis, leading to heart dysfunction. However, the effect of AGEs on another cell death pathway, autophagy, in cardiomyocytes remains unknown. METHODS: Rat neonate cardiomyocytes were cultured and treated with AGEs at different concentration. Two classic autophagy markers, microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mTOR pathway were applied to cells, respectively. RESULTS: AGEs administration enhanced the expression of Beclin-1 and LC3 II in cardiomyocytes, increased the number of autophagic vacuoles and impaired the cell viability in dose-dependant manners. Also, AGEs inhibited the PI3K/Akt/mTOR pathway via RAGE. Inhibition of RAGE with RAGE antibody reduced expression of Beclin-1 and LC3 II/I and inhibited the cellular autophagy, accompanied by the reactivation of PI3K/Akt/mTOR pathway in cultured cells. Notably, the presence of inhibition of PI3K/Akt/mTOR pathway abolished the protective effect of RAGE inhibition on cardiomyocytes. CONCLUSION: This study provides evidence that AGEs induces cardiomyocyte autophagy by, at least in part, inhibiting the PI3K/Akt/mTOR pathway via RAGE.


Asunto(s)
Autofagia/efectos de los fármacos , Productos Finales de Glicación Avanzada/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Inmunológicos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Animales Recién Nacidos , Autofagia/fisiología , Células Cultivadas , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Ratas , Ratas Wistar , Receptor para Productos Finales de Glicación Avanzada , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores
6.
Front Neurol ; 15: 1389697, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38784908

RESUMEN

Multiple Sclerosis (MS) is an immune-mediated condition that persistently harms the central nervous system. While existing treatments can slow its course, a cure remains elusive. Stem cell therapy has gained attention as a promising approach, offering new perspectives with its regenerative and immunomodulatory properties. This article reviews the application of stem cells in MS, encompassing various stem cell types, therapeutic potential mechanisms, preclinical explorations, clinical research advancements, safety profiles of clinical applications, as well as limitations and challenges, aiming to provide new insights into the treatment research for MS.

7.
Biomed Pharmacother ; 179: 117382, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39241565

RESUMEN

Stroke has emerged as the primary cause of disability and death globally in recent years. Intracerebral hemorrhage (ICH), a particularly severe kind of stroke, is occurring in an increasing number of people. The two main clinical treatments for ICH now in use are conservative pharmaceutical therapy and surgical intervention, both of which have risks and drawbacks. Consequently, it is crucial to look into the pathophysiology of ICH and consider cutting-edge therapeutic approaches. Recent research has revealed that pyroptosis is a newly identified type of cell death distinguished by the break of the cell membrane and the discharge of pro-inflammatory substances through different routes. Following ICH, glial cells experience pyroptosis, which worsens neuroinflammation. Hence, the onset and progression of ICH are strongly linked to pyroptosis, which is facilitated by different inflammasomes. It is essential to conduct a comprehensive investigation of ICH damage processes and uncover new targets for treatment. The impact and function of pyroptosis in ICH, as well as the activation and regulation of inflammasomes and their mediated pyroptosis pathways will be fully discussed in this review.

8.
J Ethnopharmacol ; 301: 115804, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36228892

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The ancient Chinese medicine book "Huangdi Neijing" reports that "the brain is the sea of marrow" and that the kidney "mainly induces bones to produce marrow". Therefore, Chinese medicine has a "kidney-brain axis" theory, but supporting evidence is lacking. In this study, curculigoside, the main component of the kidney-tonifying drug Rhizoma Curculiginis, was used to explore whether a kidney-tonifying drug could regulate the pathological state of the brain. AIM OF THE STUDY: To explore the efficacy of curculigoside in protecting against ischemic brain injury (IBI) through the regulation of oxidative stress and NF-κB and PI3K/Akt expression. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) was used to induce IBI in rats, and curculigoside was administered. The degree of IBI, morphological changes and severity of nerve injury (using neurological severity scores; NSSs) in the rats were assessed. Enzyme-linked immunosorbent assays (ELISAs), Western blotting, and immunohistochemistry were used to evaluate changes in hydrogen peroxide (H2O2), nitric oxide (NO), malondialdehyde (MDA), TNF-α, IL-1ß, catalase (CAT), superoxide dismutase (SOD), nitric oxide synthase (NOS), NF-κB, PI3K and Akt levels. RESULTS: Curculigoside significantly alleviated behavioral deficits and reduced the degree of cerebral ischemia in the rats. After curculigoside treatment, the levels of H2O2, NO, MDA, NOS, iNOS, TNF-α, IL-1ß, intercellular adhesion molecule-1 (ICAM-1) and NF-κB in the ischemic area of the brain were significantly reduced. The activities of CAT, SOD, PI3K and Akt were significantly increased. CONCLUSION: Curculigoside is a potentially effective drug for the treatment of IBI.


Asunto(s)
Lesiones Encefálicas , FN-kappa B , Ratas , Animales , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Peróxido de Hidrógeno/farmacología , Transducción de Señal , Estrés Oxidativo , Infarto de la Arteria Cerebral Media/patología , Superóxido Dismutasa/metabolismo
9.
J Vis Exp ; (200)2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37902327

RESUMEN

Colorectal cancer (CRC) is a common malignancy of the digestive system and has become the third most common malignancy worldwide and the second leading cause of malignancy-related death. Ulcerative coloproctitis (UC) is a precancerous lesion, and UC-associated CRC (UC-CRC) is the most common subtype of CRC. Therefore, a reasonable UC-CRC model is the cornerstone and guarantee of new drug development. Traditional Chinese medicine (TCM) has been widely used in the treatment of UC-CRC due to its good efficacy. As a classic tonic prescription of TCM, Liujunzi decoction (LJZD) has been widely used in the treatment of UC-CRC. In this study, a UC-CRC model was established by combining azomethane and dextran sulfate sodium, and the LJZD was administered. The data confirmed that LJZD can effectively inhibit cancer transition in UC-CRC by using mouse body weight, colorectal length, pathological and inflammatory factors, colorectal barrier function, and cancer markers. This protocol provides a system for evaluating the efficacy of TCM in the prevention and treatment of UC-CRC.


Asunto(s)
Colitis Ulcerosa , Neoplasias Colorrectales , Ratones , Animales , Colitis Ulcerosa/tratamiento farmacológico , Medicina Tradicional China/efectos adversos , Neoplasias Colorrectales/etiología , Sulfato de Dextran
10.
ACS Appl Mater Interfaces ; 15(22): 26627-26636, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37220156

RESUMEN

Lithium-rich layered oxides (LRLOs), with the chemical formula of xLi2MnO3·(1 - x)LiMO2, delivering higher specific discharge capacity, are potential cathode materials for lithium-ion batteries. However, the dissolution of transition metal ions and the instability of the cathode-electrolyte interphase (CEI) hinder the commercial application of LRLOs. Herein, a simple and affordable method is developed for the construction of a robust CEI layer by quenching a kind of cobalt-free LRLO, Li1.2Ni0.15Fe0.1Mn0.55O2 (denoted as NFM), in 1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl ether solvent. This robust CEI, with well-distributed LiF, TMFx, and partial organic component CFx, performs as a physical barrier to prevent NFM from direct contact with the electrolyte, suppresses the oxygen release, and ensures the CEI layer stability. The customized CEI with LiF and TMFx-rich phase considerably enhances the NFM cycle stability and the initial coulomb efficiency and inhibits voltage fading. This work provides a valuable strategy for designing stable interface chemistry on the cathode of lithium-ion batteries.

11.
ACS Nano ; 17(17): 16827-16839, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37582222

RESUMEN

Severe capacity/voltage fading still poses substantial obstacles in the commercial applications of Li-rich layered oxides, which stems from the aggregation of Li2MnO3-like domains and unstable surface structure. Here, we report highly stabilized Co-free Li1.2Ni0.2Mn0.6O2 with uniformly dispersed Li2MnO3-like domains and a protective rock-salt structure shell by reducing the oxygen partial pressure during high-temperature calcination. Experimental characterizations and DFT calculations reveal that the uniformly dispersed and small-sized Li2MnO3-like domains suppress the peroxidation of lattice oxygen, enabling highly reversible oxygen redox and excellent structural stability. Moreover, the induced rock-salt structure shell significantly restrains lattice oxygen release, TM dissolution, and interfacial side reactions, thereby improving the interfacial stability and facilitating Li+ diffusion. Consequently, the obtained Li1.2Ni0.2Mn0.6O2 which was calcinated under an oxygen partial pressure of 0.1% (LNMO-0.1) delivers a high reversible capacity of 276.5 mAh g-1 at 0.1 C with superior cycling performance (a capacity retention rate of 85.4% after 300 cycles with a small voltage fading rate of 0.76 mV cycle-1) and excellent thermal stability. This work links the synthesis conditions with the domain structure and electrochemical performance of Li-rich cathode materials, providing some insights for designing high-performance Li-rich cathodes.

12.
Metabolites ; 12(10)2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36295806

RESUMEN

Artificial night light (ALAN) could lead to circadian rhythm disorders and disrupt normal lipid metabolism, while time-restricted feeding (TRF) could maintain metabolic homeostasis. In mammals, TRF has been demonstrated to have extraordinary effects on the metabolic regulation caused by circadian rhythm disorders, but studies in lower vertebrates such as fish are still scarce. In this study, the impacts of ALAN on the body composition and lipid metabolism of juvenile rainbow trout were investigated by continuous light (LL) exposure as well as whether TRF could alleviate the negative effects of LL. The results showed that LL upregulated the expression of lipid synthesis (fas and srebp-1c) genes and suppressed the expression of lipid lipolysis (pparß, cpt-1a, and lpl) genes in the liver, finally promoting lipid accumulation in juvenile rainbow trout. However, LL downregulated the expression of genes (Δ6-fad, Δ9-fad, elovl2, and elovl5) related to long-chain polyunsaturated fatty acid (LC-PUFA) synthesis, resulting in a significant decrease in the proportion of LC-PUFA in the dorsal muscle. In serum, LL led to a decrease in glucose (Glu) levels and an increase in triglyceride (TG) and high-density lipoprotein cholesterol (H-DLC) levels. On the other hand, TRF (mid-dark stage feeding (D)) and mid-light stage feeding (L)) upregulated the expression of both the lipid synthesis (srebp-1c and pparγ), lipolysis (pparα, pparß, and cpt-1a), and lipid transport (cd36/fat and fatp-1) genes, finally increasing the whole-body lipid, liver protein, and lipid content. Meanwhile, TRF (D and L groups) increased the proportion of polyunsaturated fatty acid (PUFA) and LC-PUFA in serum. In contrast, random feeding (R group) increased the serum Glu levels and decreased TG, total cholesterol (T-CHO), and H-DLC levels, suggesting stress and poor nutritional status. In conclusion, ALAN led to lipid accumulation and a significant decrease in muscle LC-PUFA proportion, and TRF failed to rescue these negative effects.

13.
Artículo en Inglés | MEDLINE | ID: mdl-36523422

RESUMEN

Constipation commonly occurs during childhood, and more than 95% of cases are classified as functional constipation. If not effectively treated, 20% of patients with childhood constipation can continue to exhibit symptoms into adulthood, which seriously affects their mental health and quality of life. The main feature of acupuncture or acupoint stimulation, a special branch of traditional Chinese medicine, is the selection of different acupoints for different diseases, and many worthy guidelines have been established for matching acupoints. The back-shu and front-mu point combination adheres to an important acupoint compatibility law that has been used since its proposal 2,500 years ago but has not yet been verified by the modern evidence-based experiments. This study focused on the back-shu and front-mu point combination using the Dachangshu (BL25) and Tianshu (ST25) points as examples to explore possible research methods for network acupoint-based stimulation based on existing evidence and to elucidate the mechanisms induced by BL25 and ST25 in the treatment of functional constipation in children (FCC). The study found that BL25 and ST25 have 20 common targets, namely, AQP8, DRD2, VIP, TAC1, IL6R, TNF, FOS, KIT, CHAT, HTR3A, GAS8, SOD3, TRPV1, MPO, CALCA, IL1B, P2RX7, NPY2R, IL10RA, and TPH1, and these targets may provide a strategy for the combined usage of BL25 and ST25. In addition, BL25 and ST25 can affect FCC treatment through inflammation-relatedTh17-cell differentiation, the NF-kappa B signaling pathway, and the Toll-like receptor signaling pathway. Adipocytokines or leptin may also comprise the mechanism through which BL25 and ST25 regulate FCC. In addition, BL25 and ST25 regulate FCC through 13 core targets, namely, NFKBIA, RELA, TNF, IKBKB, IRAK1, TLR4, MYD88, TNFRSF1A, IL1R1, TLR2, IL1B, TRAF6, and TNFRSF1B. In short, this study provides new ideas and methods for studying the mechanism of acupuncture points.

14.
Medicine (Baltimore) ; 101(50): e31454, 2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36550882

RESUMEN

BACKGROUND: Immunosuppressive drugs are routinely used to treat myasthenia gravis (MG). However, current recommendations provide limited evidence to support treatment options, leading to considerable variation in practice among healthcare specialists. Hence, we present a protocol for a systematic review and network meta-analysis (NMA) to update the evidence by comparing the efficacy and acceptability of oral immunosuppressive drugs for the treatment of MG. METHODS: We will conduct a systematic review and NMA of all randomized controlled trials evaluating the following oral immunosuppressive drugs for the treatment of MG. Published studies will be searched using the following databases from inception to November 23, 2021: CENTRAL, the CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, and 3 Chinese databases (Chinese Biomedical Literatures Database, CNKI, and Wan Fang database). Assessment of study eligibility and data extraction will be conducted independently by 2 reviewers. The main outcome will be a quantitative MG scoring system. We will conduct Bayesian NMA to synthesize all evidence for each outcome and obtain a comprehensive ranking of all treatments. The quality of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations framework. RESULTS: The objective of this study was to assess the relative clinical efficacy and acceptability of first-line immunosuppressants for the treatment of MG, using a systematic review and NMA approach. CONCLUSION: In the absence of head-to-head trials comparing therapies, evidence from this NMA of available clinical trials will inform clinicians, patients, and families the risk-benefit profiles of different treatment options.


Asunto(s)
Inmunosupresores , Miastenia Gravis , Humanos , Inmunosupresores/uso terapéutico , Metaanálisis en Red , Teorema de Bayes , Resultado del Tratamiento , Miastenia Gravis/tratamiento farmacológico , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto
15.
Clin Cancer Res ; 28(13): 2830-2843, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35435984

RESUMEN

PURPOSE: Since CD7 may represent a potent target for T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) immunotherapy, this study aimed to investigate safety and efficacy of autologous CD7-chimeric antigen receptor (CAR) T cells in patients with relapsed and refractory (R/R) T-ALL/LBL, as well as its manufacturing feasibility. PATIENTS AND METHODS: Preclinical phase was conducted in NPG mice injected with Luc+ GFP+CCRF-CEM cells. Open-label phase I clinical trial (NCT04004637) enrolled patients with R/R CD7-positive T-ALL/LBL who received autologous CD7-CAR T-cell infusion. Primary endpoint was safety; secondary endpoints included efficacy and pharmacokinetic and pharmacodynamic parameters. RESULTS: CD7 blockade strategy was developed using tandem CD7 nanobody VHH6 coupled with an endoplasmic reticulum/Golgi-retention motif peptide to intracellularly fasten CD7 molecules. In preclinical phase CD7 blockade CAR T cells prevented fratricide and exerted potent cytolytic activity, significantly relieving leukemia progression and prolonged the median survival of mice. In clinical phase, the complete remission (CR) rate was 87.5% (7/8) 3 months after CAR T-cell infusion; 1 patient with leukemia achieved minimal residual disease-negative CR and 1 patient with lymphoma achieved CR for more than 12 months. Majority of patients (87.5%) only had grade 1 or 2 cytokine release syndrome with no T-cell hypoplasia or any neurologic toxicities observed. The median maximum concentration of CAR T cells was 857.2 cells/µL at approximately 12 days and remained detectable up to 270 days. CONCLUSIONS: Autologous nanobody-derived fratricide-resistant CD7-CAR T cells demonstrated a promising and durable antitumor response in R/R T-ALL/LBL with tolerable toxicity, warranting further studies in highly aggressive CD7-positive malignancies.


Asunto(s)
Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptores Quiméricos de Antígenos , Animales , Antígenos CD7 , Humanos , Ratones , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/uso terapéutico , Anticuerpos de Dominio Único/uso terapéutico
16.
Artículo en Inglés | MEDLINE | ID: mdl-34306143

RESUMEN

BACKGROUND: Pneumonia is a serious global health problem. In traditional Chinese medicine, acupuncture or moxibustion is used to directly stimulate select acupoints on the surface of the human body and produce physical stimulation to further stimulate regulatory functions in the body, strengthening bodily resistance, eliminating disease, and adjusting the viscera. However, this Chinese medicine knowledge does not include the specific mechanisms of action or targets of acupoints. Therefore, an in-depth research is needed. METHODS: An acupoint-element database was constructed, and the target elements of the Feishu point were screened. The UniProt-Swiss-Prot sublibrary was used to obtain correct gene name information. The National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database and GEO2R were used to analyze differentially expressed genes in pneumonia. The STRING database was used to analyze interactions, construct a network of the Feishu point efficacy system in pneumonia, and elucidate the mechanisms of action. RESULTS: The Feishu point comprises 34 elements in total. The protein interaction analysis has 38 nodes and 115 edges. The Feishu point efficacy system-pneumonia system network shows that cytokine signaling in the immune system, signaling by interleukins (ILs), IL-4 and IL-13 signaling, and the immune system may be related to immunity and inflammation. The Feishu point efficacy system regulating pneumonia showed that FCER2, IL4R, FASLG, TGFB1, IL6R, STAT6, IL1B, CASP3, IL5RA, IL2RB, MYD88, SQSTM1, IL12RB1, IFNGR1, ADAM17, and CDH1 are the main targets. CONCLUSION: From the perspective of systematic acupuncture and moxibustion, the Feishu point regulates cytokine signaling in the immune system, signaling by ILs, IL-4 and IL-13 signaling, and the immune system by targeting FCER2, IL4R, FASLG, TGFB1, IL6R, STAT6, IL1B, CASP3, IL5RA, IL2RB, MYD88, SQSTM1, IL12RB1, IFNGR1, ADAM17, and CDH1, thereby regulating pneumonia.

17.
Nat Commun ; 11(1): 3629, 2020 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-32686673

RESUMEN

The low Coulombic efficiency during cycling hinders the application of Cobalt-free lithium-rich materials in lithium-ion batteries. Here we demonstrated that the dissolution of iron, rather than traditionally acknowledged manganese, is mainly responsible for the low Coulombic efficiency of the iron-substituted cobalt-free lithium-rich material. Besides, we presented an approach to inhibit the dissolution of transition metal ions by using concentrated electrolytes. We found that the cathode electrolyte interphase (CEI) layer formed in the concentrated electrolyte is a uniform and robust LiF-rich CEI, which is a sharp contrast with the uneven and fragile organic-rich CEI formed in the dilute electrolyte. The LiF-rich CEI not only effectively inhibits the dissolution of TMs but also stabilizes the cathode structure. The Coulombic efficiency, cycling stability, rate performance, and safety of the Fe-substituted cobalt-free lithium-rich cathode material in the concentrated electrolyte have been improved tremendously.

18.
ACS Appl Mater Interfaces ; 12(15): 17538-17546, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32202750

RESUMEN

Sodium-ion batteries have been considered as one of ideal power sources for energy storage system. However, the choice of cathode material with good cycling stability and high capacity is limited. Herein, a nanocomposite of hierarchical mesoporous iron fluoride and reduced graphene oxide is prepared by an in situ approach. The as-prepared nanocomposite exhibits remarkably high discharge specific capacity of 227.5 mAh/g at 0.1C. Specifically, the discharge specific capacity of the sample still remains 87.5 mAh/g at a high rate of 15C after the 100th cycle. The electrochemical impedance spectroscopy (EIS) and galvanostatic intermittent titration technique (GITT) measurements show that the addition of reduced graphene oxide can effectively reduce the charge transfer resistance and enhance the Na+ diffusion rate in the FeF3·0.33H2O nanoparticles. The structural changes of FeF3·0.33H2O is further investigated by ex-situ XRD, XPS, and ex situ high-resolution transmission electron microscopy.

19.
Sensors (Basel) ; 9(7): 5446-59, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-22346707

RESUMEN

Mercury is a very toxic element that is widely spread in the atmosphere, lithosphere, and surface water. Concentrated mercury poses serious problems to human health, as bioaccumulation of mercury within the brain and kidneys ultimately leads to neurological diseases. To control mercury pollution and reduce mercury damage to human health, sensitive determination of mercury is important. This article summarizes some current sensors for the determination of both abiotic and biotic mercury. A wide array of sensors for monitoring mercury is described, including biosensors and chemical sensors, while piezoelectric and microcantilever sensors are also described. Additionally, newly developed nanomaterials offer great potential for fabricating novel mercury sensors. Some of the functional fluorescent nanosensors for the determination of mercury are covered. Afterwards, the in vivo determination of mercury and the characterization of different forms of mercury are discussed. Finally, the future direction for mercury detection is outlined, suggesting that nanomaterials may provide revolutionary tools in biomedical and environmental monitoring of mercury.

20.
ACS Appl Mater Interfaces ; 11(25): 22364-22370, 2019 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-31187615

RESUMEN

Owing to their natural abundance, the low potential, and the low cost of potassium, potassium-ion batteries are regarded as one of the alternatives to lithium-ion batteries. In this work, we successfully fabricated a FeP/C composite, a novel electrode material for PIBs, through a simple and productive high-energy ball-milling method. The electrode delivers a reversible capacity of 288.9 mA·h·g-1 (2nd) at a discharge rate of 50 mA g-1, which can meet the future energy storage requirements. Density functional theory calculations suggest a lower diffusion barrier energy of K+ than Na+, which allows faster K+ diffusion in FeP.

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