Recent advances in deorphanization of GPR35 and its functions in related diseases / 药学学报

G protein-coupled receptors (GPCRs) represent the largest family of membrane proteins and are the target of approximately half of all therapeutic drugs. There are ～300 orphan GPCRs, which have great potential in drug development. G protein-coupled receptor 35 (GPR35), a rhodopsin-like orphan GPCR, is widely involved in immune regulation, gastrointestinal disorders, cardiovascular diseases, cancer, as well as other diseases, suggesting its great potential as a therapeutic target in a variety of diseases. However, the current research on GPR35 is insufficient, including the true endogenous ligand has not been confirmed, the molecular mechanism of its role in disease is not fully understood, and there is a lack of effective intervention strategies targeting GPR35. This article summarizes the deorphatization of GPR35, GPR35-related signaling pathways and their association with various diseases, in order to provide a reference for in-depth study of GPR35 in diseases and development of drugs targeting GPR35.

Efficacy of intraperitoneally injected epirubicin-loaded poly (d, l)-lactic acid microspheres alone or combined with free epirubicin in treating hepatocellular carcinoma in mice / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the efficacy of intraperitoneally injected epirubicin (EPI)-loaded poly (d, l)-lactic acid (PLA) microspheres (MS) alone or combined with free epirubicin (FEPI) in treating hepatocellular carcinoma (HCC) in mice.</p><p><b>METHODS</b>Mice that were transplanted with H22 ascites HCC were randomized into seven groups, which were intraperitoneally injected with blank microspheres, normal saline, three different doses of microspheres (9, 18, and 36 mg/kg EPI) , FEPI (9 mg/kg) , and the combination (microspheres with EPI 4.5 mg/kg + FEPI 4.5 mg/kg). The survival time of all animals was recorded. The rates of increase in life span of all the treatment groups were calculated.</p><p><b>RESULTS</b>EPI-PLA-MS significantly prolonged the survival time of HCC mice in a dose-dependent manner, with a maximal tolerated dose (MTD) of 18 - 36 mg/kg. The combination group had the highest average survival time, median survival time, and rate of increase in life span, which were (40.0 +/- 16.9) days, 33.5 days, and 222.58%, respectively.</p><p><b>CONCLUSION</b>EPI-PLA-MS combined with FEPI is highly effective in treating HCC in mice when intraperitoneally injected.</p>

Preparation and characterization of vincristine sulfate-loaded PLGA microspheres / 中国医学科学院学报

<p><b>OBJECTIVE</b>To prepare the vincristine sulfate (VCR) microspheres by W/O/O solvent evaparation method and evaluate the effect of zinc carbonate (ZnCO3) on the morphology and release kinetics of the microspheres.</p><p><b>METHODS</b>Degradation kinetic of VCR was tested in PBS of four different pH values at 37TC to select the optimal incubation medium for in vitro release. Microspheres were made with or without Zn-CO3 (w/w 5% and 10%) in the polymeric phase. The properties and in vitro release profiles of the microspheres were examed.</p><p><b>RESULTS</b>ZnCO3 increased the stability of VCR in the PLGA microspheres. During the 36 days of in vitro release, the accumulative release of VCR from the microspheres reached > 70% when added with ZnCO3, and was (54.2 +/- 1.1)% when no ZnCO3 was added. 10% ZnCO3 showed superior effect than 5% ZnCO3 in the stabilization of microspheres.</p><p><b>CONCLUSIONS</b>Adding ZnCO3 is essential during the preparation of PLGA microspheres. It can remarkably improve the stability of drugs in the acid microenvironment inside PL-GA microspheres and decrease the VCR degradation during incubation.</p>

Effect of curcumin on the induction of glutathione S-transferases and NADP(H):quinone oxidoreductase and its possible mechanism of action / 药学学报

This study is to investigate the effect of curcumin on the induction of glutathione S-transferases (GST) and NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. The activity of GST, NQO and cellular reduced glutathione (GSH) content were measured by spectrophotometrical methods. Cellular changes in the distribution of NF-E2 related factor 2 (Nrf2) were detected by Western blotting analysis. Nrf2-AREs (antioxidant-responsive elements) binding activity was examined by electrophoretic mobility shift assay (EMSA). Treatment of HT-29 human colon adenocarcinoma cells with curcumin dramatically induced the activity of GST and NQO at the range of 10-30 micromol x L(-1). Curcumin exposure caused a significant increase in cellular GSH content rapidly as early as 3 h. Moreover, curcumin triggered the accumulation of Nrf2 in nucleus, and increased Nrf2 content in ARE complexes. These results demonstrated that induction of GST and NQO activity by curcumin may be mediated by translocation of transcription factor Nrf2 from cytoplasm to nuclear and increased binding activity of Nrf2-ARE complexes.

Treatment of hepatocellular carcinoma in mice with locally administered epirubicin-loaded poly(D, L)-lactic acid microspheres / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effectiveness of treating hepatocellular carcinoma (HCC) in mice with locally administered epirubicin-loaded poly( D, L) - lactic acid microspheres (EPI-PLA-MS ).</p><p><b>METHODS</b>EPI-PLA-MS was prepared with double emulsion solvent evaporation technique. Five groups of mice (n = 8 in each group) were intraperitoneally injected with five different doses of free epirubicin (FEPI), and the maximum tolerated dose (MTD) was calculated. Then 15 mice with transplanted subcutaneous H22 HCC were divided into three groups (n = 5), which were respectively intratumorally injected with normal saline (NS), blank microspheres, and EPI-PLA-MS (with 9 mg/kg of EPI). After two weeks the tumors were excised and weighed. Another 15 mice with transplanted H22 ascites HCC were divided into three groups (n = 5), which were intraperitonealy injected with the same drugs, and the increased life span were registered exactly.</p><p><b>RESULTS</b>The MTD of intraperitoneally injected FEPI was 9 mg/kg. The tumour-inhibiting rates was 40.35% and 36.09% when EPI-PLA-MS were administered by intratumoral injection to the mice with subcutaneous H22 HCC. It significantly prolonged the survival time of mice with H22 ascites HCC and the increased life span by 153.49% and 142.22% when EPI-PLA-MS were intraperitoneally administered.</p><p><b>CONCLUSION</b>EPI-PLA-MS is a new sustained-release preparation with high-efficacy and low-toxicity in treating HCC and has shown promising prospects when administered locally.</p>

Structure and degradation property of the PVA-collagen complex drug membrane / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the structure and degradation property of the polyvinyl alcohol (PVA)-collagen complex drug membrane.</p><p><b>METHODS</b>Drug collagen membrane was complexed with PVA. The physical and chemical properties of the membrane were characterized by transmission electron microscopy, scanning electron microscope, forier transform-infrared spectroscopy and differential scanning calorimetry. Degradation experiment was performed to determine the degradation property of membrane and a degradation curve was therefor drawn.</p><p><b>RESULTS</b>The thermodynamic stability of collagen membrane was not destroyed by adding PVA. Collagen had good compatibility with PVA. Compared with collagen membrane, collagen-PVA complex membrane had smaller and evener pores. Adding PVA decreased the degradation rate of membrane.</p><p><b>CONCLUSIONS</b>PVA-collagen membrane has better microstructure and antidegradation property than collagen membrane.</p>

The construction of two kinds of artificial bone and the comparison of their osteogenesis capability in vivo / 中国医学科学院学报

<p><b>OBJECTIVE</b>To construct artificial bone with collagen-hydroxyapatite (HA) or collagen-HA-chondroitin sulfate (CS) as the scaffolds, and observe their biological properties.</p><p><b>METHODS</b>The artificial bones were constructed by attaching recombinant human bone morphogenetic protein 2 (rhBMP-2) on those scaffolds. And then they were embedded into muscles of rats. Every weekend those newly formed bones were taken from muscles for comparing the difference in osteogenetic capability of two kinds of artificial bone in vivo.</p><p><b>RESULTS</b>Both kinds of artificial bones could induce bone regeneration in muscle. The collagen-HA-CS artificial bone was superior to the collagen-HA artificial in bone-guided degree.</p><p><b>CONCLUSIONS</b>The CS could promote the form action of new bone and accelerate the bone healing.</p>

The application of nanotechnology in biomedicine / 中国医学科学院学报

Nanotechnology is a new comprehensive system, which prepares substances or/material at molecular or nuclear level in nanometer scale, and nano materials can be explored to apply on broad aspects of industrial engineering sciences. This paper reviews the following contents: developing molecular engineering, biological molecular robot and nanometer information processing system, the application of nanobiomaterials in the field of tissue engineering, constructing drug carriers with nanobiomaterials, developing nanotechnology relating to diagnosis and monitoring. Developmental trend of nanotechnology in biomedical science is discussed prospectively.

Construction of a collagen gel dermis with improved biological property / 中国医学科学院学报

<p><b>OBJECTIVE</b>To improve the biological property of artificial skin.</p><p><b>METHODS</b>We have ameliorated Hansburgh and Middelkoop's method of manufacturing artificial dermis. The type I collagenase and Dispase were used to isolated neonate prepuce' dermis fibroblast. The gel dermis was constructed by compounding the fibroblast and collagen swelling solution. The property of the collagen gel dermis was measured.</p><p><b>RESULTS</b>The neonate prepuce's dermis fibroblast had property of high proliferation, high activation of the dermis, and it could secrete abundant extracellular matrix (ECM).</p><p><b>CONCLUSION</b>The collagen gel dermis is an useful dermis substitute.</p>