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1.
Medicine (Baltimore) ; 102(43): e35726, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37904430

RESUMEN

BACKGROUND: It was hypothesized that governor vessel moxibustion (GVM) therapy may improve the course of mild to moderate psoriasis (PS) in patients. METHODS: A randomized, controlled clinical trial lasting 40 days was conducted at the Shaanxi Provincial Hospital of Chinese Medicine. Investigators were blinded to patient groupings. Individuals with mild to moderate PS ranging in age from 18 to 70 years were enrolled. GVM therapy was administered one every 10 days for 40 days with 1.5 hours on the governor meridian in the GVM therapy group. The PS area and severity index (PASI) and dermatological life quality index (DLQI) scores were monitored before and after treatment. RESULTS: There was a significant reduction in the mean PASI score in the GVM therapy group of 0.76 points (2.37 [2.61]; SE, 0.39) after 40 days of treatment compared with the control group (3.12 [2.12], SE, 0.32) (P < .01). There were also significantly greater changes in the DLQI scores of the GVM therapy group (4.23 [2.25]; SE, 0.34) compared with those in the control group (8.91 [3.85]; SE, 0.59) (P < .001). CONCLUSION: GVM therapy effectively reduced both PASI and DLQI scores in patients with mild to moderate PS.


Asunto(s)
Medicina Tradicional de Asia Oriental , Moxibustión , Psoriasis , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Calidad de Vida , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
2.
Adv Sci (Weinh) ; 9(29): e2202679, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36031399

RESUMEN

Excess iron accumulation occurs in organs of patients with certain genetic disorders or after repeated transfusions. No physiological mechanism is available to excrete excess iron and iron overload to promote lipid peroxidation to induce ferroptosis, thus iron chelation becomes critical for preventing ion toxicity in these patients. To date, several iron chelators have been approved for iron chelation therapy, such as deferiprone and deferoxamine, but the current iron chelators suffer from significant limitations. In this context, new agents are continuously sought. Here, a library of new deferric amine compounds (DFAs) with adjustable skeleton and flexibility is synthesized by adopting the beneficial properties of conventional chelators. After careful evaluations, compound DFA1 is found to have greater efficacy in binding iron through two molecular oxygens in the phenolic hydroxyl group and the nitrogen atom in the amine with a 2:1 stoichiometry. This compound remarkably ameliorates iron overload in diverse murine models through both oral and intravenous administration, including hemochromatosis, high iron diet-induced, and iron dextran-stimulated iron accumulation. Strikingly, this compound is found to suppress iron-induced ferroptosis by modulating the intracellular signaling that drives lipid peroxidation. This study opens a new approach for the development of iron chelators to treat iron overload.


Asunto(s)
Ferroptosis , Hemocromatosis , Sobrecarga de Hierro , Aminas , Animales , Deferiprona , Deferoxamina/farmacología , Deferoxamina/uso terapéutico , Dextranos , Humanos , Hierro/metabolismo , Quelantes del Hierro/farmacología , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Ratones , Nitrógeno , Piridonas/farmacología , Piridonas/uso terapéutico
3.
Theranostics ; 10(14): 6384-6398, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32483459

RESUMEN

To circumvent the huge cost, long R&D time and the difficulty to identify the targets of new drugs, repurposing the ones that have been clinically approved has been considered as a viable strategy to treat different diseases. In the current study, we outlined the rationale for repurposing disulfiram (DSF, an old alcohol-aversion drug) to treat primary breast cancer and its metastases. Methods: To overcome a few shortcomings of the individual administration of DSF, such as the dependence on copper ions (Cu2+) and limited capability in selective targeting, we here artificially synthesized the active form of DSF, diethyldithiocarbamate (DTC)-Cu complex (CuET) for cancer therapeutics. To achieve a greater efficacy in vivo, smart nanomedicines were devised through a one-step self-assembly of three functional components including a chemically stable and biocompatible phase-change material (PCM), the robust anticancer drug (CuET) and a near-infrared (NIR) dye (DIR), namely CuET/DIR NPs. A number of in vitro assays were performed including the photothermal efficacy, light-triggered drug release behavior, nuclear localization, DNA damage and induction of apoptosis of CuET/DIR NPs and molecular mechanisms underlying CuET-induced repression on cancer metastatic behaviors. Meanwhile, the mice bearing 4T1-LG12-drived orthotopic tumors were employed to evaluate in vivo biodistribution and anti-tumor effect of CuET/DIR NPs. The intravenous injection model was employed to reflect the changes of the intrinsic metastatic propensity of 4T1-LG12 cells responding to CuET/DIR NPs. Results: The rationally designed nanomedicines have self-traceability for bioimaging, long blood circulation time for enhanced drug accumulation in the tumor site and photo-responsive release of the anticancer drugs. Moreover, our data unearthed that CuET/DIR nanomedicines behave like "Trojan horse" to transport CuET into the cytoplasm, realizing substantial intracellular accumulation. Upon NIR laser irradiation, massive CuET would be triggered to release from the nanomedicines and reach a high local concentration towards the nucleus, where the pro-apoptotic effects were conducted. Importantly, our CuET/DIR nanomedicines revealed a pronounced capability to leash breast cancer metastases through inhibition on EMT. Additionally, these nanomedicines showed great biocompatibility in animals. Conclusion: These combined data unearthed a remarkably enhanced tumor-killing efficacy of our CuET nanomedicines through nuclear targeting. This work may open a new research area of repurposing DSF as innovative therapeutic agents to treat breast cancer and its metastases.


Asunto(s)
Antineoplásicos/farmacología , Cobre , Disulfiram , Ditiocarba , Nanopartículas , Animales , Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral/efectos de los fármacos , Núcleo Celular , Cobre/química , Cobre/farmacología , Disulfiram/química , Disulfiram/farmacología , Ditiocarba/química , Ditiocarba/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Reposicionamiento de Medicamentos , Femenino , Humanos , Terapia por Luz de Baja Intensidad , Ratones , Nanomedicina , Nanopartículas/química , Nanopartículas/uso terapéutico , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Nanomedicina Teranóstica/métodos
4.
J Ethnopharmacol ; 230: 9-19, 2019 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-30359762

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Involucrum castaneae(IC)is used in Chinese folk medicine to treat various lung diseases, as well as for its reducing phlegm and anti-inflammatory properties. AIM OF THE STUDY: The purpose of this experiment is to verify the effect of IC on airway inflammation, responsiveness in ovalbumin (OVA)-induced asthmatic guinea pigs. The main chemical components of IC were also analyzed. MATERIALS AND METHODS: The potential of the ethanol extract of Involucrum castaneae (EEIC) to protect against OVA-induced allergic airway response in guinea pigs was investigated. The latency of asthma in guinea pigs were recorded after the allergic asthma induced. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of immunoglobulin E (IgE), interleukin-5 (IL-5), nerve growth factor (NGF) and interferon-γ (IFN-γ) in asthma allergy. Reverse transcription-PCR (RT-PCR) was used to detect the expression of IL-5 mRNA in asthmatic guinea pig lungs. Paraffin sections of lung tissue were used to analyze pathological changes. The total flavonoid content was determined and the chemical components were analyzed by LC-MS/MS. RESULTS: It was found that EEIC was able to reduce the number of eosinophil (EOS) in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) in the guinea pig model of OVA -induced asthma. Meanwhile, it also significantly reduced the levels of inflammation-related factors IgE and IL-5, decreased the expression of IL-5 mRNA in lung tissue, and increased the level of IFN-γ. Pathological examination of paraffin section of lung tissue showed that EEIC can reduce the thickening of bronchial smooth muscle and reduce the infiltration damage of tissues by various inflammatory cells. The presence of flavonoids, terpenoids and phenolic compounds in EEIC might be responsible for these activities. CONCLUSION: IC alleviated airway inflammation and smooth muscle thickening in guinea pigs with OVA-sensitized allergic asthma. The paper explains the traditional efficacy and material basis of IC and lays a foundation for further development.


Asunto(s)
Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Fagaceae , Extractos Vegetales/uso terapéutico , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Alérgenos , Animales , Antiasmáticos/farmacología , Asma/inducido químicamente , Asma/inmunología , Asma/patología , Etanol/química , Cobayas , Inmunoglobulina E/inmunología , Interferón gamma/inmunología , Interleucina-5/genética , Interleucina-5/inmunología , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Músculo Liso/efectos de los fármacos , Músculo Liso/patología , Ovalbúmina , Extractos Vegetales/farmacología , Solventes/química
5.
Chem Biodivers ; 15(12): e1800395, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30294975

RESUMEN

Eight secondary metabolites, including a new polyketide, named asperetide (1) and a new prenylxanthone derivative, called asperanthone (4), and six known compounds, (S)-3-butyl-7-methoxyphthalide (2), ruguloxanthone C (3), tajixanthone hydrate (5), tajixanthone methanoate (6), salimyxin B (7), and ergosterol (8), were isolated and identified from the medicinal plant-derived fungus, Aspergillus sp. TJ23. The new structures and their absolute configurations were elucidated via multiple methods, including 1D- and 2D-NMR, HR-ESI-MS, UV, IR, and the electronic circular dichroism (ECD) calculations. All of the isolates were characterized from the strain for the first time. The in vitro bioassay showed that compounds 3-5 and 8 exerted inhibitory activities against five cancer cell lines (B16, MDA-MB-231, 4T1, HepG2, and LLC) with IC50 values ranging from 5.13 to 36.8 µm.


Asunto(s)
Aspergillus/química , Policétidos/química , Xantonas/química , Aspergillus/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Dicroismo Circular , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Policétidos/aislamiento & purificación , Policétidos/farmacología , Espectrometría de Masa por Ionización de Electrospray , Xantonas/aislamiento & purificación , Xantonas/farmacología
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