MR may interact with NFAT1 and activator protein-1 to control IFN-γ in T cells and to regulate target organ damage and ultimately BP. Targeting MR in T cells specifically may be an effective novel approach for hypertension treatment.
Mineralocorticoid receptor (MR) blockade has been shown to suppress cardiac hypertrophy and remodeling in animal models of pressure overload (POL). This study aims to determine whether MR deficiency in myeloid cells modulates aortic constriction-induced cardiovascular injuries. Myeloid MR knockout (MMRKO) mice and littermate control mice were subjected to abdominal aortic constriction (AAC) or sham operation. We found that AAC-induced cardiac hypertrophy and fibrosis were significantly attenuated in MMRKO mice. Expression of genes important in generating reactive oxygen species was decreased in MMRKO mice, while that of manganese superoxide dismutase increased. Furthermore, expression of genes important in cardiac metabolism was increased in MMRKO hearts. Macrophage infiltration in the heart was inhibited and expression of inflammatory genes was decreased in MMRKO mice. In addition, aortic fibrosis and inflammation were attenuated in MMRKO mice. Taken together, our data indicated that MR deficiency in myeloid cells effectively attenuated aortic constriction-induced cardiac hypertrophy and fibrosis, as well as aortic fibrosis and inflammation.
The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte‐specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at baseline and had more severe cardiac hypertrophy and dysfunction after pressure overload. Knockdown of NCoR1 exacerbated whereas overexpression mitigated phenylephrine‐induced cardiomyocyte hypertrophy. Mechanistic studies revealed that myocyte enhancer factor 2a (MEF2a) and MEF2d mediated the effects of NCoR1 on cardiomyocyte hypertrophy. The receptor interaction domains (RIDs) of NCoR1 interacted with MEF2a to repress its transcriptional activity. Furthermore, NCoR1 formed a complex with MEF2a and class IIa histone deacetylases (HDACs) to suppress hypertrophy‐related genes. Finally, overexpression of RIDs of NCoR1 in the heart attenuated cardiac hypertrophy and dysfunction induced by pressure overload. In conclusion, NCoR1 cooperates with MEF2 and HDACs to repress cardiac hypertrophy. Targeting NCoR1 and the MEF2/HDACs complex may be an attractive therapeutic strategy to tackle pathological cardiac hypertrophy.
Hydroxy-α-sanshool (HAS) improves cognitive dysfunction, but its structural instability has limited its clinical application. The present study was conducted to investigate the optimal formulation of hydroxy-α-sanshool liposomes (HAS-LPs) and its effect on ameliorating learning and memory disorders in an Alzheimer's disease (AD) model. Methods: In this study, HAS was prepared as HAS-LP using a thin film dispersion method. After selecting the optimal preparation conditions, HAS-LP was characterized using transmission electron microscopy (TEM) and by measuring the zeta potential, particle size, and in vitro drug release. Next, evaluated the effect of HAS-LP on the rat nasal mucosa and then applied it to AD mice. By performing behaviour experiments, pathological test and related pharmacokinetic parameters, we explored its effect on attenuating learning and memory impairment in mice. Results: When the mass ratio of HAS:cholesterol:soybean lecithin was 1:4:16 and 15 mL of ultrapure water were added, the highest encapsulation efficiency and drug loading were obtained. HAS-LP had a particle size of 181.77 nm, a polydispersity index of 0.207 and a zeta potential of −53.8 mV, and it remained stable at 25 °C for 1 week and 4 °C for 8 weeks. Moreover, HAS-LP exhibited slow drug release and was highly consistent with the Higuchi release model. HAS-LP was not significantly toxic to the nasal mucosa and effectively alleviated D-galactose-induced learning memory deficits and protected mouse hippocampal neuronal cells. HAS-LP was highly enriched in plasma and brain tissue after administration via the nasal route and obtained some ability to target the brain. Conclusion: HAS encapsulated in soybean lecithin and cholesterol was successfully developed, suggesting that treatment with the nanoparticles might reverse some AD symptoms. Therefore, these nanoparticles might be used as promising new candidates for the delivery of HAS to treat AD.
Objectives Nowadays, one of the most common gastrointestinal cancers is colorectal cancer (CRC). Chemotherapy is still one of the main methods to treat cancer. However, the currently available synthetic chemotherapy drugs often cause serious adverse reactions. Apoptosis is generally considered as an ideal way for induction the death of tumour cells without the body’s inflammatory response, and it is reported that lots of natural agents could trigger various cancer cells to apoptosis. The overarching aim of this project was to elucidate the specific mechanisms by which natural substances induce apoptosis in CRC cells and to be used as an alternative therapeutic option in the future. Key findings The mechanisms for the pro-apoptotic effects of natural substances derived from herbs or plants include death receptor pathway, mitochondrial pathway, endoplasmic reticulum stress pathway, related signal transduction pathways (PI3K/Akt, MAPK, p53 signalling), and so on. Summary This paper updated this information regarding the anti-tumour effects of natural agents via induction of apoptosis against CRC, which would be beneficial for future new drug research regarding natural products from herbs or plants.
Objectives Gout is a common disease caused by hyperglycemia. Traditional drugs for gout have both good therapeutic effects and serious side effects. Traditional Chinese medicine (TCM) is one of the potential sources of modern medicine, and is the development of new drugs for many diseases, including gout. TCM is an indispensable part of gout treatment. Compared with anti-gout medication commonly used in clinic (e.g. the xanthine oxidase inhibitors allopurinol and febuxostat), traditional Chinese medicine has fewer side effects in the treatment of gout and can safely control serum uric acid and the level of inflammation. However, there have been few studies on how traditional Chinese medicine controls uric acid and inflammation levels in patients with gout. Key findings Herbs are a valuable resource in the search for new drugs to treat many diseases, including gout. Phytochemicals in TCM treatment of gout mainly includes two aspects, anti-inflammatory and reducing uric acid content. The anti-inflammatory mechanism is mainly through the inactivation of NF-κB and NLRP3 inflammasome to reduce the inflammatory response induced by uric acid crystals. The mechanism of lowering uric acid is mainly through inhibiting the activity of xanthine oxidase and up-regulating the expression of URAT1 and GLUT9.In recent years, the intestinal flora has become a new field of understanding diseases. It has been observed that the occurrence of gout is closely related to changes in the intestinal flora. Herbaceous plants contain fiber, polyphenols, polysaccharides and other active components. When taken orally, Chinese herbs act like prebiotics. After traditional Chinese medicine treatment, the abundance levels of Bifidobacterium, Lactobacillus, Bacteroidetes and Prevotella were increased, while the abundance of Proteus and the Firmicutes/Bacteroidetes ratio were decreased. Changes in the intestinal flora led to further changes in its metabolites, including short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS), which ultimately down-regulate the TLR4/NF-κB inflammatory signaling pathway, up-regulate GLUT9 and URAT1 gene expression and inhibition of xanthine oxidase activity. Destruction of the intestinal barrier is also an important factor in the occurrence of gout. Disruption of the intestinal barrier allows LPS to enter the bloodstream and activates the expression of various inflammatory factors, which causes gout.
Benzaldehyde 1, 2-propanediol acetal was synthesized from benzaldehyde and 1, 2-propanediol in the presence of ionic liquid [HMIM]HSO4. The effect of the amount of catalyst, reaction time, reaction temperature, and the molar ratio of raw materials agent on the product yield was investigated respectively. Experimental results demonstrate that ionic liquid [HMIM]HSO4is a good catalyst for preparation of benzaldehyde 1, 2-propanediol acetal. Results showed the optimal reaction conditions are as follows: the mole ratio of benzaldehyde to 1, 2-propanediol is 1:1.3, the amount of catalyst is 3.0g, the reaction temperature is 343K, and the reaction time is 4h. The achieved yield of acetal is 78. 7%.
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