Latest ArticlesThis study was designed to explore the intervention of muscle fatigue in rats with Astragali Radix using 1H NMR metabolomics methods. The fatigue model was induced in rats by forced swimming plus food restriction, and the effects of Astragali Radix (3, 6 and 12 g·kg-1) were investigated using the exhaustive time of rat swimming. After 3 weeks, the gastrocnemius was collected for 1H NMR detection, and the anti-fatigue effects of Astragali Radix were explored using multivariate statistical analysis. Astragali Radix significantly improved the exhaustive swimming time of rats. Compared with control group, the levels of isoleucine, leucine, creatine, phosphatidylcholine, trimethylamine oxide, taurine, guanidinoacetate, AMP, inosine, histidine, hypoxanthine, anserine in rat gastrocnemius of model group were increased. While the levels of lactate, acetone, choline, glycerophosphocholine, glycine were decreased. These 6, 11, 5 potential biomarkers could be reversely regulated by treatment with Astragali Radix (high dose, middle dose, low dose), respectively. Metabolomics analysis revealed that Astragali Radix has a certain anti-fatigue effects and the mechanism may be related to regulation of amino metabolism.
The study was designed to explore the influence of high-fat diet on the metabolism profile of feces and intestinal contents of golden hamster to provide new information for the mechanism of drug action. Twelve golden hamsters fed with high-fat diet and twelve golden hamsters fed with normal diet were used as model group and control group, respectively. Serum samples were collected from the normal group and the model group at 2 weeks, 4 weeks and 8 weeks after the induction of high-fat diet. Serum biochemical parameters were measured in the control and model groups. The levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels in model group were higher than the control group. After 8 weeks, the feces and intestine contents were taken. The intestine was divided into four sections:jejunum, ileum, cecum and colon. The changes of endogenous metabolites in intestinal contents were analyzed by 1H NMR based metabolomics combined with multivariate statistical analysis to find the significant differences in metabolites. The metabolic profiles of hyperlipidemia model group and control group were significantly distinguished by the othorgonal partial least squares-discriminate analysis, (OPLS-DA). Compared with the control group, the endogenous metabolites in feces such as amino acids, fatty acids, tricarboxylic acid cycle intermediates and nucleotides related to intestinal microflora were changed significantly (P < 0.05), and the amino acid metabolites, protein spoilage products and choline metabolites in intestinal contents had significant changes (P < 0.05). The data suggest that the intestinal microflora plays an important role in the development of hyperlipidemia in golden hamsters from the molecular level of metabolites. This result provides useful information for the clinical treatment of hyperlipidemia and development of hyperlipidemia drug.
This study was designed to investigate the impacts of particle shape of micelles on cell uptake and tumor imaging applications. We designed and synthesized an ultra-pH sensitive PEG-iPDPA diblock polymer, and prepared it into wormlike micelles and spherical micelles by thin-film dispersion method and modified solvent evaporation method, respectively. Firstly, the pH responsiveness of two kinds of micelles was investigated in vitro. Both forms of micelles responded to pH sensitively, and each of them could reach 100 times of ON/OFF fold after conjugated with BDP fluorescent probe. Moreover, the cellular uptake of two forms of micelles depended on the concentration and incubation time. However, the amount of cellular uptake of spherical micelles was much higher than that of the wormlike micelles, which proved that the shape of nanoparticles had a great influence on the cellular uptake. The results of in vivo imaging revealed that the spherical micelles had a better tumor accumulation as well as tumor imaging outcomes. Finally, the biosafety of micelles was tested by MTT assay and H & E staining, which indicated that none of the two kinds of micelles had obvious toxicity. Collectively, these results suggest that the spherical micelles could be a better carrier compared with wormlike micelles in terms of cellular uptake, tumor accumulation and tumor detection.
In this study, multivariate statistical analysis was applied to characterize the flowability of different types of microcrystalline cellulose (MCC), and the visualization of R language was used to explore the intrinsic correlation on its performances. To verify the operability of multivariate statistical analysis, we compared the results of the conventional methods such as repose angle method, Hausner ratio method, Carr's index method and the parameter a of Kawakita equation to determine whether there are significant differences between the conventional ones and multivariate statistical analysis. Moreover, the fillibility and compressibility were characterized by parameters 1/b of Kawakita equation and the means of pressure-tensile strength and compressibility curve method, respectively. The data was analyzed through R language for visualizing the correlation among the performance parameters of MCC. The flowability of the series of microcrystalline cellulose PH (MCCPH) were superior to the series of microcrystalline cellulose WJ (MCCWJ), the compressibility of MCCPH-302 was optimum, and the flowability and fallibility of MCCPH-102 were better than others. The results of conventional methods were consistent with multivariate statistical analysis. The fillibility was positively correlated with flowability, both negatively correlated with compressibility by analyzing correlation coefficient diagram, which was statistically significant (P < 0.01). It is reasonable that adopting multivariate statistical analysis to character the flowability of powders, which is more objective than the traditional approach. The correlation visualization of performance parameters of powders provides convenience for screening preparation material via the visualization of R language.
Jasmonic acid (JA) can promote the biosynthesis of artemisinin.To have an insight into the JA signaling in Artemisia annua, two new genes belonging to JAZ family, namely AaJAZ5 and AaJAZ6, were cloned from Artemisia annua, which might be the negative regulators involved in the JA signaling pathway.Bioinformatic analysis showed that AaJAZ5 and AaJAZ6 contained the conserved domains of ZIM and Jas specific to JAZ family.According to tissue profile analysis, AaJAZ5 had the highest expression level in leaf and AaJAZ6 had the highest expression level in root.The expression levels of both AaJAZ5 and AaJAZ6 were markedly elevated by methyl jasmonate and mechanical wounding.The BiFC results indicated that AaJAZ5, as well as AaJAZ6, physically interacted with AaMYC2.Importantly, only AaJAZ5 could interact with AaCOI1.The interaction assays given by BiFC suggested that AaJAZ5 might play a crucial role in JA signaling.This study facilitated the further analysis of the functional divergence of JAZ-family members and the understanding of molecular mechanism on JA signaling to regulate the artemisinin biosynthesis.
A change in vascular smooth muscle cell (VSMC) phenotype, known as converting from a contractile state into a synthetic phenotype, is a crucial event in vascular remodeling, which determines the occurrence, development and prognosis of cardiovascular diseases such as pulmonary hypertension and atherosclerosis. Research shows that the expression level of key signaling molecules, which controls the phenotype change of VSMC, is regulated by microRNA (miRNA), a type of non-encoding RNA. In this article, we provide a review of miRNA in the regulation of VSMC phenotype changes with a focus on the key molecules in MAPK, TGFβ/Smad and PI3K/Akt signaling pathways.
Sab (SH3 domain-binding protein that preferentially associates with Btk) that is also called SH3BP5 (SH3 domain-binding protein 5), is a scaffold protein on mitochondrial outer membrane in the modulation of mitochondrial function. Sab not only combines with the tyrosine kinase Btk (Bruton's tyrosine kinase), but also binds to the serine threonine kinase JNKs (c-Jun amino-terminal kinases) and p38γ. Thus Sab can regulate B cell antigen receptor, mitochondrial JNK and p38γ signaling pathway, which is associated with the critical physiological function, such as B-cell development and differentiation and regulation of mitochondrial signaling transcription. Inhibition or induction on the expression of Sab can ameliorate the diseases arising from the abnormal level of Btk, JNKs and p38γ, such as nervous system diseases and liver injury. Therefore, Sab could be expected as a new target for drug development. In this article, we provide an overview of the structure and functions of Sab and its relationship to diseases of diffuse large B-cell lymphoma, nervous system diseases and liver injury, aiming to provide new ideas and theoretical basis for the development of new drugs.
Histone H3 lysine 79 (H3K79) methyltransferase DOT1L plays an important role in the activation and maintenance of gene transcription; it is also essential for maintenance of embryonic development, as well as the normal function of hematopoietic system, heart and kidney. However, the over expression of DOT1L is associated with the occurring and progress of numerous malignant tumors, so more and more attention has been paid to DOT1L. Therefore, it is of great significance to study and develop inhibitors of DOT1L. The inhibitors could serve as a tool in the investigation of the biological function, and have the potential to be developed into novel anti-cancer agents in the anticancer therapy. This paper mainly describes the structure and function of DOT1L, the relationship between DOT1L and tumors as well as the latest research progress of DOT1L inhibitors; with expect to provide some useful references for the subsequent research.
Apoptosis is an important self-stabilizing mechanism of multicellular organisms, which plays a vital role in the development of normal living organisms and the maintenance of tissue homeostasis. The abnormalities in apoptosis often lead to body lesions including tumors. Studies have shown that Bcl-2 protein with anti-apoptosis activity is an important target in the treatment of cancer. After nearly two decades of efforts, many small molecule Bcl-2 inhibitors have been discovered to induce cell apoptosis. The small-molecule Bcl-2 inhibitor, venetoclax, was developed based on fragment-based drug design strategy and approved by the FDA in 2016 for clinical application. This agent is the first approved small-molecule drug inhibiting Bcl-2 through protein-protein interaction to induce cell apoptosis. The achievement of venetoclax benefits from a combination of drug discovery technologies and represents a milestone in the history of drug discovery. In this review we will introduce the current progress in Bcl-2 inhibitors.
Gene therapy has obvious advantages in the treatment of ocular diseases due to the unique structure of the eye. In recent years, there are more and more therapeutic gene-based drugs for ophthalmic application in clinical trials. Most of the delivery vectors are adeno-associated virus and administered via intraocular injection, which has potential risks. Traditional remedies, such as topical instillationor systemic administration, have limited therapeutic effects on the diseases in the posterior segment of the eye, where the chemical drugs are hard to reach. This makes the research of new strategies for gene drug delivery extremely urgent. For better understanding of the latest hot topics of ocular gene therapy, this article is prepared to introduce application of gene therapy to the typical ocular diseases and the corresponding gene-based medicines. The absorption routes for gene delivery into eyes and existing barriers are summarized. Finally, the gene delivery strategies are highlighted. The clinical application of ocular gene therapy will be boosted by overcoming the absorbing barriers and reducing the potential pitfalls.
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