The appropriate regulation of intracellular bioenergy and nutrient metabolism is a basic requirement for proper function and survival of pancreatic beta cells, where mitochondria-endoplasmic reticulum (ER)-associations play crucial roles. Mitochondria are changed dynamically according to intracellular energy and nutrients, which provides material foundation for energy homeostasis; while ER regulates metabolic enzymes and protein synthesis in different pathways. This review sheds light upon the development of mitochondria-ER associations and its role in the regulation of insulin secretion in pancreatic beta cell. The impact on beta cell viability is discussed. Interruption of calcium and redox oxidative species results in reduction of glucose-stimulated insulin secretion, while intracellular calcium levels could be partial altered by depleting calcium from the ER. Given the tight link between ER and mitochondria, the association are crucial to the homeostasis and are an indicator of overall beta cell status, with a potential as a novel drug target for treatment of type 2 diabetes mellitus.

Lymphoid-specific tyrosine phosphatase (LYP) is a phosphatase that is encoded by protein tyrosine phosphatase non-receptor type 22 and is mainly distributed in lymphoid. In psychological condition, LYP inhibits T-cell receptor (TCR) signaling in association with C-terminal kinase (CSK). While in pathological condition, mutant LYP dissociates with CSK, which augments the inhibition of TCR signaling and leads to autoimmune diseases. Consequently, LYP is now considered as a new target of type Ⅰ diabetes, rheumatic arthritis and Graves disease and some other autoimmune disorders. This review mainly focuses on the development of LYP inhibitors in their structures and activities.

The paper was aimed to investigate the association of VDR polymorphisms with tacrolimus (FK506) concentration in Chinese renal transplant recipients. A total of 114 renal transplant recipients receiving tacrolimus were genotyped for VDR rs1540339 and rs2853559 by Agena Bioscience MassARRAY^® system and CYP3A5*3 by PCR-RFLP method. Trough concentrations of tacrolimus on day 7 after renal transplantation were collected from clinical data. Statistical analysis was performed with Spearman's correlation, Mann-Whitney U test and Kruskal-Wallis H test. The dose-adjusted concentration of tacrolimus in VDR rs2853559 GA and GG carriers were considerably higher than that of AA carriers. After stratification by CYP3A5*3 genotypes, VDR rs2853559 GA and GG carriers had a higher dose-adjusted tacrolimus concentration than that in AA carriers in CYP3A5 nonexpresser. CYP3A5*3 and VDR rs2853559 explained 45.6% variability of tacrolimus C₀/D. In CYP3A5 non-expressers, VDR rs2853559 explained 14.4% variability of tacrolimus C₀/D. The results illustrated that VDR rs2853559 polymorphisms was associated with tacrolimus concentrations, and the determination of this SNP may be useful for individualized medicine of tacrolimus.

In our study of the chemical constituents of the dried mature fruits of Arctium lappa L., ten compounds were isolated by various chromatography methods and preparative HPLC. Their structures were elucidated as (7R, 8R)-4, 7, 9, 9'-tetrahydroxy-3, 3'-dimethoxy-8-4'-oxyneolign-7'-ene-9'-O-β-D-glucopyranoside (1), (7R, 8R)-4, 7, 9, 9'-tetrahydroxy-3, 3'-dimethoxy-8-O-4'-neolignan-9'-O-β-D-glucopyranoside (2), (7R, 8R)-4, 7, 9, 9'-tertahydroxy-3, 3'-dimethoxy-8-4'-oxyneolignan (3), (7S, 8R)-dihydrodehydrodiconiferylalcohol-4-O-β-D-glucopyranoside (4), (7S, 8R, 7'R, 8'R)-pinoresinol-4, 4'-di-O-β-D-glucopyranoside (5), (8S, 7'S, 8'R)-4, 4', 9'-trihydroxy-3, 3'-dimethoxy-7', 9-epoxylignan-7-oxo-4'-O-β-D-glucopyranoside (6), 2-methoxy-4-hydroxyphenol-1-O-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside (7), 3-methoxy-4-hydroxyphenol-1-O-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside (8), 4-hydroxy-3-methoxybenzylalcohol-4-O-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside (9) and 2-phenethyl β-primeveroside (10) by their spectroscopic data (IR, UV, CD, MS, HR-ESI-MS, and 1D and 2D NMR) and comparison to literature data. Compound 1 is a new 8-O-4'-neolignan. Compounds 2-10 were isolated from the dried mature fruits of Arctium lappa L. for the first time.

To develop a cell-penetrating peptide with high membrane penetrating ability and effective antitumor activity, we designed and synthesized an analogue of penetratin, [Cys-CPT^{2, 9}] penetratin, by substitution of Gln² and Asn⁹ with Cys-CPT. We investigated the transmembrane activity and antitumor activity of [Cys-CPT^{2, 9}] penetratin. The fluorescence intensity of [Cys-CPT^{2, 9}] penetratin in HeLa cells was observed by laser confocal microscopy and flow cytometry, and the cell uptake mechanism of [Cys-CPT^{2, 9}] penetratin was evaluated by using different endocytic inhibitors, finally the anti-tumor activity of [Cys-CPT^{2, 9}] penetratin was tested by MTT assay. The results showed that the membrane activity of [Cys-CPT^{2, 9}] penetratin was significantly enhanced in laser confocal microscopy and flow cytometry assay, and the intracellular fluorescence intensity was 5 times higher than penetratin. The cell uptake mechanism study of [Cys-CPT^{2, 9}] penetratin indicated that it mainly entered the cell through the clathrin and endocytosis. Moreover, [Cys-CPT^{2, 9}] penetratin exhibited anti-tumor activity against HeLa cells, and its inhibitory effect on cancer cells was stronger than CPT. [Cys-CPT^{2, 9}] penetratin is a new cell-penetrating peptide with high translocation ability, and has anti-tumor activity against HeLa cells.

To develop a taste-masking oral preparation of azithromycin for pediatrics, the reversed lipid nano-micelle techniques were used to mask the bitterness of azithromycin. Dry emulsion (DE) for taste-masking was prepared by solidifying the reversed-micelle oil solution containing azithromycin. Colloidal silicon dioxide was used as absorbent and solid carrier. Solidification was confirmed through dying test and observed by scanning electron microscope (SEM). The DE formulation was characterized by X-ray powder diffraction and SEM in order to investigate the crystal state of drug. Reconstitution emulsion droplet size and morphology were also determined using Nano ZS90 Zetasizer and transmission electron microscopy (TEM). The taste testing was performed in two different ways, namely, human taste panel test and the measurement of the amount of drug released in simulated oral cavity condition. The intestinal mucosal irritation test of DE formulation was also investigated in rats in comparison with commercial product (Zithromax). The optimal taste-masking formulation of azithromycin can be re-dispersed immediately with mean diameter of 530.1 nm after agitation in water. The results of taste testing showed that the bitterness of azithromycin was successfully masked by DE formulation similar with Zithromax at the same dose, moreover reduced intestinal irritation compared to Zithromax. These results indicate that the DE formulation for taste-masking of azithromycin is promising and valuable in the future development of azithromycin for pediatrics.

Compound Yizhihao, consists of Radix isatidis, Folium isatidis, Artemisia rupestris, has a significant therapeutic effect on the treatment of influenza and fever. However, the mechanism of its action is still unclear. In this investigation, we collected the key target molecule of influenza disease and the chemical constituents of Compound Yizhihao, and developed Naïve Bayesian classification models based on the input molecular fingerprints and molecule descriptors. The built models were further applied to construct classifiers for predicting the effective constituents. We used the professional network-building software to build the constituent-target network and target-pathway network, which revealed the network pharmacology of the effective constituents in Compound Yizhihao. It will contribute to the further research of mechanism of Compound Yizhihao.

A series of novel benzimidazole and benzothiazole derivatives were designed and synthesized as inhibitors of SIRT1-SIRT3. The target compounds were synthesized from potassium O-ethyldithiocarbonate through a three-step route. The structures of the obtained compounds were elucidated by ¹H NMR and HR-MS. Of all compounds, six showed potent SIRT2-inhibitory activities with IC₅₀ values ranging from 2.8 to 21.2 μmol·L^-1. Among them, compound 10c displayed the most potent SIRT2-inhibitory activities (IC₅₀ = 2.8 μmol·L^-1), with more than 35-fold selectivity over SIRT1 and SIRT3 (IC₅₀ > 100 μmol·L^-1).

Lepidium apetalum was used as an experimental material in this study. By analyzing the tran-scriptome data of L. apetalum and application of the specific primers, cDNA of cinnamate-4-hydroxylase (C4H) gene was isolated from L. apetalum and named as LaC4H (GenBank accession No. KX064050). Meanwhile, the bioinformatic analysis, prokaryotic expression, purification, tissue-specific expression analysis and expres-sion analysis after methyl jasmonate (MeJA) treatment were carried out. The results indicated that: ① The open reading frame (ORF) of LaC4H was 1 518 bp, which encoded a protein of 505 amino acid residues, with a predicted molecular mass of 57.73 kD. ② Bioinformatic analysis showed that LaC4H protein contained the conserved sequences of cytochrome P450 (CYP450) and 5 substrate recognition sites (SRSs) of CYP73A1, therefore LaC4H protein was a member of CYP450 superfamily. The phylogenetic analysis indicated that LaC4H protein showed the highest homology with C4H protein from cruciferous plants (such as AtC4H from Arabidopsis thaliana). ③ Through the construction of the prokaryotic expression vector pET-32a-LaC4H, the recombinant LaC4H protein was successfully expressed in E. coli BL21 (DE3) cells and the recombinant LaC4H protein was purified by Ni²⁺ affinity chromatography. ④ Real-time PCR analysis indicated that LaC4H was expressed in a high transcript level in stems, lower levels in leaves and flowers, the lowest level in roots. After MeJA treatment, the expression level of LaC4H in leaves was increased significantly to reach the highest level at 48 h. Furthermore, the expression levels of LaC4H were positively correlated with the flavonoids contents in leaves. The results of this study provide the fundamental information on LaC4H gene in the flavonoids biosyn-thesis pathway of L. apetalum.

The study was aimed to investigate the correlation between the immunocompetence and the fingerprints of supernatant extracts from Radix Astragali by multi-index integrated evaluation, and reveal the material basis of Radix Astragali improving the immunological function. After oral administration 10 batch of supernatant extracts from Radix Astragali on immunosuppressed mice, phagocytic index, delayed type hypersensitivity (DTH) degree, organs index and the level of cytokines IFN-γ, IL-4 (ELISAs) were measured, and each common peak from HPLC-DAD/HPLC-ELSD fingerprints were correlated with the above data. A number of components in supernatant extracts of Radix Astragali display a substantial correlation with the immunocompetence. Supernatant extracts of Radix Astragali can significantly enhance immunological function on mice, which is related to various components in Radix Astragali.