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CONTEXT: Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear. OBJECTIVE: This study elucidates the possible mechanisms of QGSTW in treating AAMI. MATERIALS AND METHODS: Network pharmacology and molecular docking approaches were utilized to identify the potential pathway by which QGSTW alleviates AAMI. C57BL/6J mice were divided randomly into control, model, and QGSTW groups. A mouse model of AAMI was established by d-galactose, and the pathways that QGSTW acts on to ameliorate AAMI were determined by ELISA, immunofluorescence staining and Western blotting after treatment with d-gal (100 mg/kg) and QGSTW (20 mL/kg) for 12 weeks. RESULTS: Network pharmacology demonstrated that the targets of the active components were significantly enriched in the cAMP signaling pathway. AKT1, FOS, GRIN2B, and GRIN1 were the core target proteins. QGSTW treatment increased the discrimination index from -16.92 ± 7.06 to 23.88 ± 15.94% in the novel location test and from -19.54 ± 5.71 to 17.55 ± 6.73% in the novel object recognition test. ELISA showed that QGSTW could increase the levels of cAMP. Western blot analysis revealed that QGSTW could upregulate the expression of PKA, CREB, c-Fos, GluN1, GluA1, CaMKII-α, and SYN. Immunostaining revealed that the expression of SYN was decreased in the CA1 and DG. DISCUSSION AND CONCLUSIONS: This study not only provides new insights into the mechanism of QGSTW in the treatment of AAMI but also provides important information and new research ideas for the discovery of traditional Chinese medicine compounds that can treat AAMI.
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Medicamentos Herbarios Chinos , Trastornos de la Memoria , Ratones , Animales , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Western Blotting , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
Purpose: Tangzhiqing formula (TZQ) is a traditional Chinese medicine prescribed to treat lipid metabolism disorders, atherosclerosis, diabetes and diabetic cardiomyopathy. However, some challenges and hurdles remain. TZQ showed promising results in treating diabetes and hyperlipidaemia. However, its effect on and mechanism of action in hyperlipidaemia complicated with myocardial ischaemia (HL-MI) remain unknown. Methods: In this study, a network pharmacology-based strategy integrating target prediction was adopted to predict the targets of TZQ relevant to the treatment of HL-MI and to further explore the involved pharmacological mechanisms. Results: A total of 104 potential therapeutic targets were obtained, including MMP9, Bcl-2, and Bax, which may be related to the apoptosis and PI3K/AKT signalling pathways. Then, we confirmed these potential targets and pathways with animal experimentation. TZQ reduced lipid levels, increased the expression levels of Bcl-2, decreased Bax, caspase-3 and caspase-9 expression levels, and activated the PI3K/AKT signalling pathway. Conclusion: In conclusion, this study provides new insights into the protective mechanisms of TZQ against HL-MI through network pharmacology and pharmacological approaches.
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Sporothrix schenckii (S. schenckii), a ubiquitous thermally dimorphic fungus, is the etiological agent of sporotrichosis, affecting immunocompromised and immunocompetent individuals. Despite current antifungal regimens, sporotrichosis results in prolonged treatment and significant mortality rates in the immunosuppressed population. The innate immune system forms the host's first and primary line of defense against S. schenckii, which has a bi-layered cell wall structure. Many components act as pathogen-associated molecular patterns (PAMPs) in pathogen-host interactions. PAMPs are recognized by pattern recognition receptors (PRRs) such as toll-like receptors, C-type lectin receptors, and complement receptors, triggering innate immune cells such as neutrophils, macrophages, and dendritic cells to phagocytize or produce mediators, contributing to S. schenckii elimination. The ultrastructure of S. schenckii and pathogen-host interactions, including PRRs and innate immune cells, are summarized in this review, promoting a better understanding of the innate immune response to S. schenckii and aiding in the development of protective and therapeutic strategies to combat sporotrichosis.
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Sporothrix , Esporotricosis , Humanos , Esporotricosis/microbiología , Moléculas de Patrón Molecular Asociado a Patógenos , Inmunidad Innata , MacrófagosRESUMEN
Metabolic diseases are often associated with lipid and glucose metabolism abnormalities, which increase the risk of cardiovascular disease. Diabetic cardiomyopathy (DCM) is an important development of metabolic diseases and a major cause of death. Lipids are the main fuel for energy metabolism in the heart. The increase of circulating lipids affects the uptake and utilization of fatty acids and glucose in the heart, and also affects mitochondrial function. In this paper, the mechanism of lipid overload in metabolic diseases leading to cardiac energy metabolism disorder is discussed.
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Cardiomiopatías Diabéticas/metabolismo , Metabolismo de los Lípidos , Enfermedades Metabólicas/metabolismo , Miocardio/metabolismo , Animales , Cardiomiopatías Diabéticas/etiología , Metabolismo Energético , Glucosa/metabolismo , Humanos , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/genéticaRESUMEN
As a potential causative factor in various cardiovascular diseases, the gut microbe-generated metabolite trimethylamine N-oxide (TMAO) has courted considerable research interest as a potential biomarker. TMAO is a small molecule considered to be beneficial for the health of deep-water animals due to its ability to protect proteins against hydrostatic pressure stress. However, it may cause deleterious effects in humans as mounting evidence suggests that TMAO may enhance atherosclerosis, independent of traditional risk factors. This may be mediated by its capacity to enhance inflammation, platelet activation and thrombosis, and inhibit reverse cholesterol transport. In humans, circulating levels of TMAO have been found to be associated with increased risk of developing atherosclerotic diseases such as carotid atherosclerosis, coronary atherosclerotic heart disease, stroke, and peripheral arteriosclerosis. This review aims to discuss the current role of TMAO in the atherosclerosis process, using animal models and clinical studies, with special attention to determining whether TMAO could be used as a marker for monitoring severity and prognosis in atherosclerosis and to evaluate evidence for its role as a mediator in the pathogenesis of atherosclerotic vascular disease.