The latest research progress of torpor occurrence mechanism / 药学学报

Torpor refers to a state in which the metabolic activity in the body of the living animal is greatly reduced during the period of reduced food supply, which is manifested as a substantial decrease in body temperature, metabolic level, and exercise level. Mammals have a strict body temperature regulation system to maintain a constant body temperature. When the energy supply is insufficient for a long time, some mammals will enter a hibernation state. Torpor is very similar to the hibernation state. The research on the mechanism of torpor state is of great significance in aerospace, military medicine and other fields. This review summarizes the specific mechanisms regulating the occurrence of torpor from four aspects: adenylate cyclase activating polypeptide (adcyap) neurons, leptin, pyroglutamylated RFamide peptide (QRFP) neurons, and sympathetic nervous system, aiming to provide ideas for further research on the mechanism of torpor.

The inhibitory effects of nobiletin on P-glycoprotein and the study of molecular mechanism / 药学学报

Nobiletin is a kind of polymethoxyflavonoid with many pharmacological effects, such as antiinflammatory and antioxidation activities. This study was carried out to investigate the inhibitory effects of nobiletin on P-glycoprotein (P-gp) in vitro and in vivo. The molecular mechanism for structure-inhibition relationships of nobiletin with P-gp was investigated. Nobiletin exhibited significant inhibition (IC50=2.21 μmol·L-1) on P-gp in MDR1-MDCKⅡ cells. In the cell toxicity test, the paraquat-treated cell viability was decreased with nobiletin by inhibiting P-gp activity. In the rats PK study, the AUC0-t of digoxin was increased 2.02 folds while the Cmax of digoxin was increased 3.29 folds, when nobiletin was used in the pretreatment of SD rats. Molecular docking analysis elucidated that the formation of Pi-Pi bonds with Phe974 was the key factor for P-gp inhibition. The research findings provide important guideline for prediction of potential interaction between nobiletin and P-gp.

Research advances in study of Sab protein / 药学学报

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.

Role of carboxylesterase in drug metabolism / 药学学报

Carboxylesterases (CESs) belong to the esterase family, which are mainly responsible for catalyzing metabolism of a variety of drug as well as endogenous and exogenous compounds. CESs are widely distributed in the body, mainly expressed in lung, liver, intestine, kidney, skin epithelial cells, etc. There are significant species differences in the expression of CESs, which results in the difference on the drug metabolism with genetic polymorphism. In this paper, an overview of the classification and distribution, physiological function and mechanism, species differences and gene polymorphism of CESs are provided for the research of CESs and drug design.

Neuroprotective effect and mechanisms of Homer1a:research advances / 国际药学研究杂志

Homer1a, encoded by immediate early genes (IEG), is a scaffold protein of post-synaptic density, which is widely expressed in the central nervous system. Homer1a overexpression has been found in many neuropsychiatric disorders, and its regulatory signal transduction plays an important role in synaptic plasticity and neuroprotection, which has gradually become a research focus. The research and development of the neuroprotective drugs targeting Homer1a has also attracted a great attention. In addition, studies in recent years have showed that the development and treatment of neurological diseases are correlated with the Homer1a level.This article reviews the basic structural characteristics of Homer1a, its protective effect on the schizophrenia, depression and epilepsy as well as the neuroprotective mechanism of Homer1a based on the latest research reports.

Knock-down of apollon gene by antisense oligodeoxynucleotide inhibits the proliferation of Lovo cells and enhances chemo-sensitivity / 药学学报

In this study, the effects of apollon antisense oligodeoxynucleotide (ASODN) on the proliferation and apoptosis of human Lovo cells in vitro were investigated. Apollon ASODN was incubated with human colorectal Lovo cells for 48 h, the proliferation inhibition and the clone forming rates were detected by WST method and clone formation assay, respectively. The expression of apollon mRNA was analyzed by real time fluorescent quantitative reverse transcription polymerase chain reaction. The percentage of apoptotic cells and cell cycle distribution were determined by flow cytometry. The morphology of apoptotic cells was examined by fluorescence microscope. Lovo cells incubated with apollon ASODN combined with 5-fluorouracil (5-FU), cisplatin (DDP) or epirubicin (EPI) of different concentrations, cell proliferation inhibition rates were detected with WST method and IC50 was calculated. It was found that ASODN targeting apollon gene could all suppress the growth of Lovo cells and induce apoptosis of these cells significantly (P < 0.05). After Lovo cells treated with apollon ASODN for 48 hours, the expression of the apollon mRNA level was suppressed significantly. And a marked concentration-dependent decline of cell proliferation and clone forming, increasing of cell apoptosis levels were observed. The percentage of G0/G1 phage cells was abated and that of S phage cells was increased and the Lovo cells arrested at S phage of the cell cycle detected with flow cytometry. Many Lovo cells stained with Hoechst 33258 exhibited apoptotic morphology such as cell shrinkage, nuclear condensation and nuclear fragmentation. Cell proliferation inhibition was detected and their chemo-therapeutic effects of 5-FU, DDP and EPI on Lovo cells combined with apollon ASODN (0.08 micromol x L(-1)) were enhanced independently compared with single 5-FU, DDP and EPI groups, and the sensitivity enhanced about 2.58, 4.47, and 5.33 times respectively. It can be concluded that ASODN targeting apollon can suppress the expression of apollon mRNA, and inhibit the proliferation, induce apoptosis, arrest cell cycle at S phase of colorectal cancer Lovo cells in vitro and enhance the chemo-sensitivity to 5-FU, DDP and EPI.

Binding characteristics of interleukin 11 analogue-cyclic nonapeptide c(CGRRAGGSC) to human prostate cancer PC-3 cells: an in vitro study / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the binding characteristics of interleukin 11 (IL-11) analogue-cyclic nonapeptide c(Cys-Gly-Arg-Arg-Ala-Gly-Gly-Ser-Cys) NH2 C30H54N16O10S2, c(CGRRAGGSC), and human prostate cancer PC-3 cells.</p><p><b>METHODS</b>c(CGRRAGGSC) was labeled with fluorescent dye LSS670, and the location of LSS670-cyclic nonapeptide in the PC-3 cells was investigated by fluorescent microscopy. Flow cytometry was used to detect the fluorescence intensity of the in vitro binding of LSS670-c (CGRRAGGSC) to PC-3 cells and calculate its IC50 and Ki in competitive inhibition experiments. 99Tcm-DTPA-c(CGRRAGGSC) was synthesized by the reaction of 99mTcO4- with c(CGRRAGGSC). The binding characteristics of 99mTc-DTPA-c(CGRRAGGSC) and IL11R in the PC-3 cells were analyzed by radioreceptor assay. Bmax and Kd were calculated in saturability and reversibility experiments.</p><p><b>RESULTS</b>The binding of LSS670-c(CGRRAGGSC) to the PC-3 cells showed the characteristics of saturability and concentration-time dependence. Unlabeled c(CGRRAGGSC) and LSS670-c(CGRRAGGSC) exhibited a competitive inhibition on the PC-3 cells (IC50 = [6.31 +/- 0.12] nmol/L, Ki = [2.11 +/- 0.14] nmol/L). Fluorescence was mainly distributed in the cell membrane (Kd = [0.32 +/- 0.02] nmol/L, Bmax = [754 +/- 34] fmol/mg pro).</p><p><b>CONCLUSION</b>c (CGRRAGGSC) could bind PC-3 cells through a receptor-mediated pathway.</p>

Sodium valproate induces mitochondria-dependent apoptosis in human hepatoblastoma cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sodium valproate inhibits proliferation in neuroblastoma and glioma cells, and inhibits proliferation and induces apoptosis in hepatoblastoma cells. Information describing the molecular pathways of the antitumor effects of sodium valproate is limited; therefore, we explored the mechanisms of action of sodium valproate in the human hepatoblastoma cell line, HepG2.</p><p><b>METHODS</b>The effects of sodium valproate on the proliferation of HepG2 cells were evaluated by the Walsh-schema transform and colony formation assays. Sodium valproate-induced apoptosis in HepG2 cells was investigated with fluorescence microscopy to detect morphological changes; by flow cytometry to calculate DNA ploidy and apoptotic cell percentages; with Western blotting analyses to determine c-Jun N-terminal kinases (JNK), p-JNK, Bcl-2, Bax, and caspase-3 and -9 protein expression levels; and using JC-1 fluorescence microscopy to detect the membrane potential of mitochondria. Statistical analyses were performed using one-way analysis of variance by SPSS 13.0 software.</p><p><b>RESULTS</b>Our results indicated that sodium valproate treatment inhibited the proliferation of HepG2 cells in a dose-dependent manner. Sodium valproate induced apoptosis in HepG2 cells as it: caused morphologic changes associated with apoptosis, including condensed and fragmented chromatin; increased the percentage of hypodiploid cells in a dose-dependent manner; increased the percentage of annexin V-positive/propidium iodide-negative cells from 9.52% to 74.87%; decreased JNK and increased phosphate-JNK protein expression levels; reduced the membrane potential of mitochondria; decreased the ratio of Bcl-2/Bax; and activated caspases-3 and -9.</p><p><b>CONCLUSION</b>Sodium valproate inhibited the proliferation of HepG2 cells, triggered mitochondria-dependent HepG2 cell apoptosis and activated JNK.</p>

Survivin antisense oligodeoxynucleotides inhibits the proliferation of hepatocellular carcinoma cells and enhances 5-FU sensitivity / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of survivin antisense oligodeoxynuleotides (ASODN) mediated by polyethylenimine (PEI) on hepatocelluar carcinoma SMMC-7721 cell proliferation and its effect on chemosensitivity to 5-FU in tumor-bearing mice.</p><p><b>METHODS</b>The inhibitory effect of PEI-ASODN on SMMC-7721 cell proliferation was assayed by WST-8 test, Trypan blue exclusion test, and cell clone formation assay. In mouse models of transplanted H22 cell hepatocarcinoma and ascites tumor, the effect of 5-FU combined with PEI-ASODN on the weight and volume of the subcutaneous tumors was examined. The tumor inhibition rate in the tumor-bearing mice was calculated and the average survival time recorded.</p><p><b>RESULTS</b>SMMC-7721 cells incubated with different concentrations of PEI-ASODN for 48 h showed significantly reduced cell proliferation in comparison with the control cells, while PEI or ASODN alone produced no such inhibitory effect. Incubation of SMMC-7721 cells with 0.75 micromol/L PEI-ASODN for 24, 48, 72, and 96 h resulted in significantly suppressed cell proliferation, and a 7-day incubation of the cells with PEI-ASODN at different concentrations (0.25-0.75 micromol/L) significantly inhibited the cell clone formation. In the tumor-bearing mice, the tumor weight and volume were obviously reduced with a tumor inhibition rate of 56.91% and volume inhibition rate of 57.83%, significantly different from those in saline-treated mice (P<0.01). In the mice bearing ascites tumor, the average survival time was 22.0 days in saline group and 42.7 days in 5-FU+PEI-ASODN treatment group, showing a a life-prolonging rate of 94.09% in the latter group. A synergetic effect was noted between 5-FU and PEI-ASODN.</p><p><b>CONCLUSION</b>PEI-ASODN complex can significantly inhibit the proliferation of hepatocarcinoma SMMC-7721 cells and enhance 5-FU chemosensitivity of the tumor cells in vitro and transplanted H22 tumors in mice.</p>

Survivin antisense oligodeoxynucleotides inhibits the proliferation of hepatocellular carcinoma cells and enhances the cell chemosensitivity to 5-Fu / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of survivin antisense oligodeoxynucleotides (ASODN) mediated by polyethylenimine(PEI) on the proliferation of hepatocellular carcinoma SMMC-7721 cells, and assess its detect on the chemosensitivity of the cells to 5-FU.</p><p><b>METHODS</b>The inhibitory effect of PEI-ASODN on SMMC-7721 cell proliferation was assessed using WST-8 test, trypan blue staining, and cell clone formation test. In mice bearing transplanted hepatocarcinoma and ascites tumor derived from H22 cells, 5-FU combined with PEI-ASODN was administered, and the weight and volume of the subcutaneous tumors were measured to calculate the tumor inhibition rate, and the average survival time of the mice was calculated.</p><p><b>RESULTS</b>Incubation of the cells with different concentrations of PEI-ASODN for 48 h significantly inhibited the cell proliferation as compared with the control group, but PEI or ASODN alone produced no significant inhibitory effects. At 24, 48, 72, 96 h of incubation of the SMMC-7721 cells with 0.75 micromol/L PEI-ASODN, the cell proliferation was suppressed significantly, and incubation with PEI-ASODN at 0.25-0.75 micromol/L for 7 days resulted in significantly inhibited cell clone formation. No significant inhibition was detected in ASODN and PEI group. The tumor weight and volume were reduced in all the treated groups. The tumor inhibition rate was 56.91% and volume inhibition rate was 57.83% in 5-FU+PEI-ASODN group, significantly different from those in the normal saline group (P<0.01). In mice bearing ascites tumor, the average survival time was 22.0 days in saline group, and 42.7 days 5-FU+PEI-ASODN group. The life-prolongation rate of 5-FU+PEI-ASODN was 94.09% when compared with the survival time in saline group. A cooperative effect was detected between 5-FU and PEI-ASODN.</p><p><b>CONCLUSION</b>PEI-ASODN complex can significantly inhibit the proliferation of hepatocarcinoma SMMC-7721 cells and enhance the chemosensitivity of the tumor cells to 5-FU.</p>

Antisense oligonucleotides targeting protein kinase C alpha inhibits the proliferation of A549 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of antisense oligonucleotides (ASODN) targeting protein kinase C alpha (PKCalpha) on the proliferation of A549 cells.</p><p><b>METHODS</b>PKCalpha ASODN and random oligonucleotides (RODN) were transfected into A549 cells mediated by polyethyleneimine, and the proliferation and clone formation of A549 cells were detected by CCK-8 and clone formation assay, respectively. The expression of PKCalpha in the transfected cells was analyzed by RT-PCR and Western blotting.</p><p><b>RESULTS</b>Compared with those in the control group, PEI group and PEI-RODN group, the proliferation and clone formation of A549 cells treated with ASODN targeting PKCalpha were significantly inhibited (P<0.05). The expressions of PKCalpha mRNA and protein in PKCalpha ASODN-transfected A549 cells were significantly lower than those in the other 3 groups (P<0.05).</p><p><b>CONCLUSION</b>The PKCalpha ASODN mediated by PEI down-regutates the expression of PKCalpha gene and suppress the proliferation and clone formation of A549 cells.</p>

Immunigical effect of CpG oligodeoxynucleotide as immune adjuvant of hepatitis B vaccine on pregnant mice and neonatal mice / 实用儿科临床杂志

0.05); serum HBsAb levels of pregnant mice and neonatal mice in group with CpG-1826 (20 ?g)+hepatitis B vaccine significantly higher than those in group with CpG-1826 (10 ?g, 40 ?g)+ hepatitis B vaccine,hepatitis B vaccine and control respectively(P0.05).Conclusions Combination injection of CpG-1826 20 ?g and hepatitis B vaccine can markedly increase serum antibody levels of pregnant mice and neonatal mice, but don′t affect the survival quantity, the growth and development of neonatal mice.CpG-1826 is an ideal immune adjuvant for neonates with immature immune system during pregnancy.