ABSTRACT
ObjectiveTo establish a traditional Chinese medicine （TCM） syndrome model with yin deficiency and internal heat， discuss the rationality of model evaluation， and analyze differentially expressed genes in multiple dimensions to explore the molecular mechanism-signaling pathways as well as key targets of Baihe Dihuangtang （BHDH） in treating depression with Yin deficiency and internal heat. MethodForty male SD rats were randomly divided into a blank control group，a model group，a fluoxetine group （positive drug），a BHDH group， and a Zhibai Dihuangtang group （positive drug for Yin deficiency and internal heat）. The depression model with Yin deficiency and internal heat was induced by chronic unpredictable mild stress （CUMS）combined with Chinese herbal drugs with warm and heat nature. The model established was comprehensively evaluated by the detection of the basic condition， behavioral performance， and biochemical indicators of rats in each group. The differentially expressed genes were screened out by mRNA sequencing and underwent Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The protein-protein interaction （PPI） network was plotted and key genes were analyzed to explore the underlying mechanism of BHDH in treating depression with Yin deficiency and internal heat. ResultThe comparison of basic conditions， behavioral assays， energy metabolism， endocrine hormones， cytokines， and neurotransmitters showed that the model was properly induced. BHDH could significantly improve depression with Yin deficiency and internal heat by regulating the pathways related to the nervous system， endocrine system， and inflammatory and immune system. The key genes of the PPI network were Fos， Epha8， Npy2r， Htr2c， and Nr4a1. ConclusionUnder the guidance of TCM theories of treatment based on syndrome differentiation and etiology and pathogenesis，this study established a depression model with yin deficiency and internal heat in animals and evaluation system in accordance with the symptoms and signs of emotional diseases， and further confirmed the scientificity of the modeling method and the underlying mechanism of BHDH in interfering with depression with Yin deficiency and internal heat based on the results of mRNA sequencing.
ABSTRACT
Diabetes and depression are both incurable chronic diseases， which are complementary and integrated. They are clinically called diabetic depression. A large number of epidemiological and clinical studies have confirmed that diabetes interacts with depression， leading to complex conditions of diabetic depression， difficult treatment， and poor prognosis. Diabetes and depression are considered two independent diseases in the majority of the existing clinical methods for the treatment of diabetic depression， with many defects such as low efficiency and severe side effects. Traditional Chinese medicine （TCM） treatment of diabetic depression， characterized by multiple targets， multiple pathways， and overall coordination， can adjust the synergy between multiple systems of the body and is advantageous in the treatment of diabetic depression. However， the evaluation of the efficacy of TCM in the treatment of diabetic depression is mostly limited to the improvement of clinical symptoms， the control of blood sugar level， and the score of depression scale， and there is a lack of in-depth research on the mechanism of action. Therefore， many researchers are devoted to exploring the underlying mechanism of TCM in the treatment of diabetes combined with depression. Clarifying the comorbidity mechanism is the key in treating diabetic depression. In this study， we made an introduction according to the mechanism based on the relevant research reports on the treatment of diabetic depression with TCM and summarized its specific mechanisms， including insulin resistance， oxidative stress and inflammation， and nervous system disorder. The interaction between the various mechanisms has further aggravated the complexity of diabetic depression. We have drawn a diagram of the mechanism pathways of diabetic depression in order to provide new ideas for clinical diagnosis and treatment.
ABSTRACT
Aim To investigate the effects of mono-clonal antibody NCX-2D2 on isoproterenol-induced ar-rhythmias in rat hearts, and to explore the electrophys-iological mechanism. Methods Using isoproterenol to establish in vitro and in vivo arrhythmic rat models to observe the effect of NCX-2D2 antibody on ventricular arrhythmias in rats. The whole-cell patch clamp tech-nique was used to investigate the effects of NCX-2D2 antibody on INa/Ca, ICa-Lat voltage-clamp mode and on DADs at current-clamp mode in single rat ventricular myocytes. Results 10 mg·L-1NCX-2D2 antibody significantly inhibited cardiac arrhythmias induced by ISO in vitro ( P<0.01) . 80 μg·kg-1NCX-2D2 anti-body markedly inhibit the occurrence of arrhythmias in ISO-induced anesthetized rats in vivo ( P <0.01 ) . 5 mg·L-1NCX-2D2 antibody partially inhibited the in-crease of INa/Ca(P<0.01) and the increase of ICa-L(P<0.01 ) , and could effectively inhibit ISO-induced DADs in rat ventricular myocytes ( P <0.05 ) . Con-clusions The sodium-calcium exchanger monoclonal antibody NCX-2D2 significantly inhibits isoproterenol-induced ventricular arrhythmias in rats. The mecha-nism against ventricular arrhythmias is mainly due to its inhibition of cardiomyocyte sodium-calcium exchanger and L-type calcium channel and marked suppression of DADs in rat ventricular myocytes.
ABSTRACT
How to deliver small interfering RNA(siRNA)molecules into target cells efficiently and safely to silence target genes is a bottleneck in the clinical application of RNA interference. In recent years,siRNA delivery technology based on cell pene-trating peptides has developed rapidly. Among them,the secondary amphipathic peptide,called CADY,has little cytotoxicity and no immunogenicity,forms stable siRNA complexes and improves their delivery into a wide variety of cell lines. Therefore,it has become a very promising delivery carrier for siRNA applications. This review summarizes the design idea,structural characteristic,spatial con-figuration,internalization mechanism,modification and application of CADY.