The protective role of IMM-H004 on hepatic ischemia-reperfusion injury in mice / 药学学报

This study investigates the protective role of IMM-H004, a novel coumarin derivative, on hepatic ischemia-reperfusion injury (HIRI) in mice. All animal experiments in this paper have been approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The experimental animals were divided into three groups, including sham group, model group, and IMM-H004 treatment group. Serum biochemical indicators were detected and H&E staining was used to assess liver damage. Real-time quantitative PCR (qPCR) was performed to analysis the mRNA content of inflammatory factors. Immunohistochemistry and immunofluorescence were used to observe neutrophil infiltration. Western blot was used to examine the protein levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and interleukin-1β (IL-1β). The results showed that IMM-H004 could significantly reduce the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH). H&E results showed IMM-H004 could alleviate liver damage caused by HIRI. The mRNA expression of tumor necrosis factor-α (TNF-α), IL-1β, and interleukin-6 (IL-6) were decreased by IMM-H004 administration. Meanwhile, IMM-H004 could markedly inhibit neutrophil infiltration. Furthermore, IMM-H004 could significantly down-regulate the protein expression of NLRP3, ASC, caspase-1, and IL-1β, inhibiting the activation of NLRP3 inflammasome pathway. Our results confirmed that IMM-H004 could protect mice from HIRI and provide a theoretical foundation for IMM-H004 application for treating HIRI.

Role of dihydroceramides in the progression of acute-on-chronic liver failure in rats / 中华医学杂志(英文版)

BACKGROUND@#Previously, dihydroceramide (d18:0/24:0) (dhCer (d18:0/24:0)) was reported to be a potential biomarker for acute-on-chronic liver failure (ACLF) prognosis. In this study, we further explored the role of dhCer (d18:0/24:0) in the progression of ACLF to validate the biomarker using ACLF rat model.@*METHODS@#ACLF rats were sacrificed at 4 and 8 h post-D-galactosamine (D-gal)/lipopolysaccharide (LPS) administration to investigate the liver biochemical markers, prothrombin time and liver histopathology. Change in dhCer and other sphingolipids levels were investigated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Rats were treated with N-(4-hydroxyphenyl) retinamide (4-HPR) to examine the mortality rate and its role in improving ACLF.@*RESULTS@#LPS/D-gal administration resulted in significant elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Prothrombin time was prolonged and histopathological examination showed abnormality. HPLC-MS/MS results showed total dhCer levels in ACLF group (64.10 ± 8.90 pmol/100 μL, 64.22 ± 6.78 pmol/100 μL for 4 and 8 h, respectively) were decreased significantly compared with control group (121.61 ± 23.09 pmol/100 μL) (P < 0.05). In particular, dhCer (d18:0/24:0), dhCer (d18:0/20:0), and dhCer (d18:0/22:0) levels were decreased. Treatment with 4-HPR significantly increased the levels of dhCers, including dhCer (d18:0/24:0) compared with ACLF group, for the level of dhCer (d18:0/24:0) in 4-HPR group was 20.10 ± 8.60 pmol/100 μL and the level of dhCer (d18:0/24:0) in ACLF group was 9.74 ± 2.99 pmol/100 μL (P < 0.05). This was associated with reduced mortality rate and prolonged survival time. The ALT and AST in 4-HPR group were significantly decreased compared with ACLF group. The prothrombin time of 4-HPR group (41.49 s) was significantly lower than the prothrombin time of ACLF group (57.96 s) (P < 0.05). 4-HPR also decreased plasma ammonia levels slightly, as the plasma ammonia levels in 4-HPR group and ACLF group were 207.37 ± 60.43, 209.15 ± 60.43 μmol/L, respectively. Further, 4-HPR treatment improved histopathological parameters.@*CONCLUSIONS@#DhCer, especially dhCer (d18:0/24:0), is involved in the progression of ACLF. Increasing the levels of dhCer can reduce the mortality rate of ACLF rats and alleviate liver injury.

Clinical Observation of Jiawei Xiaoyaosan in Treating Liver Depression and Spleen Deficiency Type 2 Diabetes with Emotional Disorder / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Jiawei Xiaoyaosan for patients with anxiety and depression in type 2 diabetes with liver depression and spleen deficiency. Method:The 76 eligible patients with anxiety and depression in type 2 diabetes with liver depression and spleen deficiency were randomly divided into two groups:control group (38 cases) and treatment group (38 cases). In control group, the basic medicines metformin sustained-release tablets combined with deanxit were given; based on the treatment in control group, the patients in treatment additionally received Jiawei Xiaoyaosan. The changes of fasting plasma glucose (FPG), 2 hours postprandial blood glucose (2 hPG), haemoglobin A1c (HbA1c), fasting insulin (FINS) and serum insulin levels 30 minutes after glucose intake (30 min INS), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and so on were observed and compared. Result:As compared with those before treatment, the levels of FPG, 2 hPG and HbA1c were decreased significantly (PPPPPPPPConclusion:Jiawei Xiaoyaosan combined with basic medication can significantly reduce depression and anxiety in patients with type 2 diabetes mellitus of liver depression and spleen deficiency, reduce blood glucose, glycosylated hemoglobin, decrease fasting insulin and increase 30 min INS level. The effect may be related to the improvement of anxiety, depression and other adverse emotions in these patients.

Advances in secondary metabolites produced by actinobacteria derived from animal-microbe mutualism and their biological activities / 药学学报

Actinobacteria remain to be one of the major sources for new antibiotics, which historically play an essential role in human's fight against infectious diseases. Due to the emergence of resistant pathogenic microorganisms such as bacteria, fungi and viruses, it is imperative to develop new and effective drugs against these pathogens. The symbiotic actinobacteria residing inside the animals are becoming more and more important as a new source for drug discovery, as well as a "hotspot" in the field of microbial medicine. During the long period of evolution, a specific host-microbe mutualism is formed between the symbiotic bacteria and their hosts of animals. In this unique ecosystem, the secondary metabolites produced by bacteria are well tolerated by the hosts, meanwhile, are able to selectively suppress pathogenic microorganisms, thus providing a specific protection to their hosts. These secondary metabolites encompass a large variety of structural diversities of natural products, and so far, the reported biological activities are including antibacterial, antifungal, antiviral, antitumor, and immunomodulatory effects, which give them a great potential in the field of drug discovery. Herein, we review the secondary metabolites of animal symbiotic actinobacteria and their biological activities within the recent decade, by which to provide a viewpoint for future research of drug discovery from actinobacteria.

Marsdenia tenacissima extract suppresses A549 cell migration through regulation of CCR5-CCL5 axis, Rho C, and phosphorylated FAK / 中国天然药物

Marsdenia tenacissima, a traditional Chinese medicine, is long been used to treat various diseases including asthma, cancer, trachitis, tonsillitis, pharyngitis, cystitis, and pneumonia. Although Marsdenia tenacissima has been demonstrated to have strong anti-tumor effects against primary tumors, its effect on cancer metastasis remains to be defined, and the molecular mechanism underlying the anti-metastatic effect is unknown. In the present study, we investigated the effects of XAP (an extract of Marsdenia tenacissima) on A549 lung cancer cell migration and explored the role of CCR5-CCL5 axis in the anti-metastatic effects of XAP. Our resutls showed that XAP inhibited A549 lung cancer cell migration and invasion in a dose-dependent manner. The protein levels of CCR5, but not CCR9 and CXCR4, were decreased by XAP. The secretion of CCL5, the ligand of CCR5, was reduced by XAP. XAP down-regulated Rho C expression and FAK phosphorylation. In conclusion, XAP inhibited A549 cell migration and invasion through down-regulation of CCR5-CCL5 axis, Rho C, and FAK.

Recent advances in study of dihydroceramide / 药学学报

Sphingolipids are a class of lipids that have important signaling functions. The most widely studied bioactive shingolipids include ceramides, sphingosine-1-phosphate and so on. In contrast, dihydroce­ramides have received poor attention. However, recent reports indicate that dihydroceramides are in fact bioactive lipids. The biological activity of dihydroceramide derivatives have been proven in the biophysical, genetic and pharmacological models by decreasing dihydroceramide desaturase activity. Current research shows that dihydroceramides are involved in a variety of important physiological and pathological processes, including the response of autophagy, apoptosis and cell cycle arrest. In this review article, we summarizes the recent advances in study of dihydroceramide in the metabolism pathway, the key metabolic enzymes and biological funcitons.

The saponin DT-13 inhibits gastric cancer cell migration through down-regulation of CCR5-CCL5 axis / 中国天然药物

AIM@#To investigate the effect of DT-13 on gastric cancer cell migration, and to explore the possible mechanisms underlying the anti-metastasis activity of DT-13.@*METHODS@#Growth inhibition of DT-13 was analyzed by the MTT assay. Cell migration was measured by the scratch-wound assay and transwell double chamber assay. To investigate the possible mechanisms underlying the anti-metastasis activity of DT-13, chemokine receptors that are involved in cancer metastasis (CCR2, CCR5, CCR7, CXCR4, and CXCR6) were detected by conventional PCR. The effect of DT-13 on CCR5 and CXCR4 expression was further evaluated by quantitative PCR and Western blot, respectively. The secretion of CCL5 (ligand of CCR5) and SDF-1 (ligand of CXCR4) were detected by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#DT-13 inhibited BGC-823 and HGC-27 cell growth in a dose dependent manner, and the estimated IC50 value for 24 h treatment was 23.5 ± 5.1 μmol·L(-1) for BGC-823 cells and 35.6 ± 7.6 μmol·L(-1) for HGC-27 cells. DT-13 also significantly decreased gastric cancer cell migration. DT-13 significantly decreased the gene expression of CCR5 in both BGC-823 and HGC-27 gastric cancer cells, and moderately reduced the expression of CXCR4. Similar to the results of gene expression, significant down-regulation of CCR5 protein was observed, but CXCR4 protein levels were much less affected. CCL5 secretion, but not SDF-1 production, was inhibited by DT-13.@*CONCLUSION@#DT-13 inhibited gastric cancer cell migration by down-regulation of the CCR5-CCL5 axis.

Effect of jujube on the expression of CYP2E1 and TNF-alpha in the hepatic tissue of mice with alcoholic liver disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of jujube pretreatment on serum levels of AST and ALT, liver pathology, and the expression of cytochrome P4502e1 (CYP2E1) and tumor necrosis factor-alpha (TNF-alpha) in the liver tissue of alcoholic liver disease (ALD) mice.</p><p><b>METHODS</b>Totally 88 Kunming mice were randomly divided into the control group (n = 28), the model group (n = 32), and the jujube treatment group (n = 28). The animal model was prepared using intragastric alcoholism for mice in the model group and the jujube treatment group, while distilled water was intragastrically given to those in the control group. Extraction of jujube was intragastrically given to mice in the jujube treatment group at week 4, while equal volume of distilled water was intragastrically given to mice in the rest two groups. The therapeutic course lasted for 12 weeks. Serum levels of AST and ALT, liver pathology, and the expression of CYP2E1 and TNF-alpha in the liver tissue of ALD mice were observed after administration of jujube.</p><p><b>RESULTS</b>Compared with the model group, serum levels of AST and ALT decreased, the liver pathology was improved, and the expression of CYP2E1 and TNF-alpha in the liver tissue decreased, showing statistical difference (P < 0.05).</p><p><b>CONCLUSION</b>Jujube had certain effect in treating ALD.</p>

Application of microfluidics in sperm isolation and in vitro fertilization / 中华男科学杂志

Due to the low effectiveness of traditional assisted reproductive technology (ART), new technological possibilities are constantly explored. Lots of studies have demonstrated the potential of microfluidics to revolutionize the fundamental processes of in vitro fertilization (IVF). With the advantages of high efficiency, short time, harmless collection, real-time observation of separation, similar microenvironment, and automation, the application of microfluidics in sperm isolation and IVF has shown an evident superiority over the conventional approaches and provided a new platform for ART. This review highlights the application of various microfluidic techniques in sperm motility assessment and isolation, sperm chemotaxis assay, IVF, sperm concentration, and sperm separation and enrichment in recent years. It also briefly introduces the basic principles, structural design, and operation processes of the microfluidic platform, focusing on the advantages and disadvantages of each method and the potential of their clinical application. Obviously, there are still some challenges to the application of microfluidics in ART. However, it is believed that the development of this new technology would be toward a highly integrated application of several steps in one single device, known as IVF-lab-on-a-chip.

Preparation technology and dissolution research of Blumea volatile oil suppository / 中国中药杂志

<p><b>OBJECTIVE</b>To research the preparation technology and dissolution of Blumea volatile oil suppository.</p><p><b>METHOD</b>In order to establish the content determination and methodology inspection method of Blumea volatile oil plug, the extraction process of Blumea volatile oil was optimized by using orthogonal test. Optimization on the investigation to the suppository matrix by melting time, appearance and dissolution was carried on. The best prescription craft was determined by determining the best molding temperature, dosage of the matrix and complementary makings. The determination method of dissolution was established by investigating different dissolution method and its impact on the preparation of dissolution.</p><p><b>RESULT</b>The best conditions of steam distillation extracted Blumea volatile oil was as followed, the ratio of gardenia to liquor 1:6, 2.5% drug amount of sodium, 8 hours of extracting time. The optimum temperature for mold was 60-65 degrees C. Preparation technique of Blumea volatile oil suppository was stable, which after 45 minutes and 3 h in pH 4.5 PBS released at least 70% and 90%.</p><p><b>CONCLUSION</b>Blumea volatile oil suppository with rational prescription, simple preparation and good stability.</p>

Effects of postnatal lambda-cyhalothrin exposure on synaptic proteins in ICR mouse brain / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the influence on the synaptic protein expression in different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure during postnatal period.</p><p><b>METHODS</b>Two male and 4 female healthy ICR mice were put in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from postnatal days (PND) 5 to PND13, control animals were treated with normal saline or DMSO by the same route. The brains were removed from pups on PND 14, the synaptic protein expression levels in cortex, hippocampus and striatum were measured by western blot.</p><p><b>RESULTS</b>GFAP levels of cortex and hippocampus in the LCT exposure group increased with doses, as compared with control group (P < 0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed mouse hippocampus and in female ICR mouse cortex increased with doses, as compared with control group (P < 0.05). Presynaptic protein (Synapsin I) expression levels did not change obviously in various brain regions. However, postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT groups, and of female offspring in all exposure groups, of striatum, in 1.0 or 10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05).</p><p><b>CONCLUSIONS</b>Early postnatal exposure to LCT affects synaptic protein expression. These effects may ultimately affect the construction of synaptic connections.</p>

Expression of fascin in human esophageal squamous cell carcinoma and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of fascin, an actin bundling protein, in the development and progression of human esophageal squamous cell carcinoma (ESCC), and explore its association with the clinicopathologic characteristics and 5-year survival of the patients.</p><p><b>METHODS</b>Using tissue array and immunohistochemistry, the expression of fascin was determined in 241 ESCC tissues and the corresponding normal esophageal mucosal tissues.</p><p><b>RESULTS</b>ESCC tissues showed a significantly higher overexpression rate of fascin than the corresponding normal esophageal mucosal tissues (68.9% vs 15.5%, P<0.05). The overexpression of fascin was correlated to lymph node metastasis and TMN stage, but not to the patients' age, gender, tumor differentiation and general classification. Survival analysis showed that abnormal expression of fascin was associated with the 5-year survival rate of patients with ESCC.</p><p><b>CONCLUSIONS</b>The abnormal expression of fascin may play an important role in the progression of ESCC, and detection of fascin expression may have important prognostic values.</p>

Effect of chronic intermittent hypobaric hypoxia on contractile activity of arteries in rats / 生理学报

The present study is aimed to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on contractile activities in isolated thoracic aorta and pulmonary artery rings and the underlying mechanism in rats. Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group (CON), 14 days CIHH treatment group (CIHH14), 28 days CIHH treatment group (CIHH28) and 42 days CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 5 000 m altitude, 6 h daily for 14, 28 and 42 d, respectively. After artery rings were prepared from pulmonary artery and thoracic aorta, the contractile activity of the artery rings was recorded using organ bath technique. Results are shown as follows. (1) There were no significant differences of noradrenaline (NA)- and KCl-induced contractions in thoracic aorta and pulmonary artery rings among CIHH and CON rats. (2) Angiotensin Ⅱ (ANGⅡ)-induced contraction in thoracic aorta rings, not in pulmonary artery rings, of CIHH rats was decreased compared with that in CON rats. There was no significant difference of ANGⅡ-induced contraction in thoracic aorta rings among CIHH rats. (3) Inhibitory effect of CIHH on ANGⅡ-induced contraction in thoracic aorta rings was endothelium-independent, and was reversed by glibenclamide (Gli), an ATP-sensitive potassium channels (K(ATP)) blocker, and L-NAME, a NO synthase inhibitor, but not by indomethacin (Indo), a cyclooxygenase inhibitor. These results suggest that CIHH attenuates the contraction induced by ANGⅡ in thoracic aorta rings of rat, which is related to the opening of K(ATP) channel and the increased production of NO.

Effect of siRNA targeting VEGF on cell apoptosis and the expression of survivin in K562 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the effect of adenovirus vector-mediated siRNA targeting vascular endothelial growth factor(VEGF) on apoptosis and the expression of survivin in K562 cells.</p><p><b>METHODS</b>K562 cells were infected with recombinant adenovirus Ad5-VEGFsi for 72 hours as experimental group (K562/Ad5-VEGFsi), and empty vector group (K562/Ad5) and blank control group (K562) as controls. VEGF mRNA and survivin mRNA expression were determined by RT-PCR. The protein levels of VEGF and survivin were measured by ELISA and Western blot, respectively. The apoptosis of K562 cells was detected by flow cytometry.</p><p><b>RESULTS</b>The levels of VEGF and survivin mRNA expression in experimental group cells were significantly decreased (P < 0.01). The protein concentration of VEGF in experimental group supernatant was (1121 +/- 15) pg/ml, being lower than that in empty vector group \[(1290 +/- 28) pg/ml\] and black control group \[(1303 +/- 28) pg/ml\] (P < 0.01), and the level of survivin protein in experimental group (0.26 +/- 0.11) was significantly reduced compared with that in blank control group (0.74 +/- 0.10) (P < 0.01). The apoptosis rate of K562/Ad5-VEGFsi cells (16.45 +/- 0.14)% was higher than those of K562/Ad5 cells (3.54 +/- 0.17)% and K562 cells (2.56 +/- 0.20)% (P < 0.01).</p><p><b>CONCLUSIONS</b>VEGF can up-regulate the expression of survivin. After inhibition of VEGF by RNAi, the expression of survivin is decreased subsequently and the rates of cell apoptosis are increased.</p>

Effects of Honeysuckle flower and Scutellaria Baicalensis Georgi on constraction and electric activity of rabbit small intestine smooth muscle / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of Honeysuckle flower (HF) and Scutellaria Baicalensis Georgi (SBG) on contraction and electric activity of small intestine smooth muscle in rabbit and the underlying mechanisms.</p><p><b>METHODS</b>Using organ bath technique to observe the effect of HF and SBG on contractive and electric activity of small intestine smooth muscle in rabbit.</p><p><b>RESULTS</b>HF and SBG significantly decreased the amplitude, frequency and area under the curve of contractive, as well as electric activity in a dose-depended manner. IC50 of the contractive amplitude was 6.30 g/L and 1.56 g/L by Logit Loglinear analysis. The inhibitive effect of HF and SBG on contractive activity could be partly decreased by beta-receptor blocker Propranolol, NO synthase inhibitor L-NAME, and K+ channel blocker Glibenclamide. Also HF and SBG inhibited acetylcholine-induced both intracellular and extracellular calcium-depended contraction significantly.</p><p><b>CONCLUSION</b>HF and SBG obviously inhibit the contractive and electric activity of small intestine smooth muscle of rabbit. The mechanisms are related to several pathways.</p>

Decreased basic activity and induced activity of ERK1/2 pathway in hippocampal CA1/CA2 region of ovariectomized rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the relationship between the spatial learning and memory and hippocampal ERK1/2 pathway activity in ovariectomized rats.</p><p><b>METHODS</b>Female SD rats were randomly divided into sham operated group (Sham group) and ovariectomized group (OVX group), and fed 4 months. Then spatial learning and memory of rats were evaluated by the Morris water maze task. Rats in each group were randomly divided into training group and untraining group before the test. Induced activity of ERK 1/2 stimulated by learning and memory was detected in the training group, and basic activity of ERK 1/2 was detected in the untraining group. The protein expression of p-ERK 1/2 and Raf kinase inhibitor protein (RKIP) were assayed by Western blotting respectively.</p><p><b>RESULTS</b>(1) During the training session the OVX rats held longer escape latenci than the sham rats did (P < 0.05). (2) The relative level of pERK1/2 protein in training rats of the both groups was higher than that in untraining rats (P < 0.05). (3) The relative level of p-ERK1/2 protein both training and untraining rats in OVX group was lower than that in sham group correspondingly (P < 0.05). (4) Compared with sham group, the relative expression of RKIP in OVX group was significantly higher (P < 0.05).</p><p><b>CONCLUSION</b>Spatial learning and memory deficits in ovariectomized rats might be correlated with the decreased basic and induced activity of ERK1/2 pathway and increased expression of RKIP in the CA1/CA2 region of hippocampus.</p>

Bio-safety Problem of Cultivating Innovative Talents in Pathogenic Biology / 微生物学通报

We studied on the bio-safety problem of cultivating innovative talents in medical microbiology. The bio-safety of laboratory was controlled by educating bio-safety before the experiments, regulating basic operations during the experiments and constructing management system out of the experiments. Then we got some experience to ensure students’ bio-safety during the research.

Exploring Experiment Teaching and Innovative Ability Cultivating of Students in Medical Microbiology / 微生物学通报

Diathesis education and innovative ability cultivating of students are a new position in higher education.Exploring experiment was applied in medical undergraduates of grade 2004 for enhancing integrative diathesis and cultivating innovative spirit and ability of students.It was proved that application of exploring experiment could increase adequately learning fervor and interest of students.Teaching quality of microbiological experiment was enhanced accordingly.Application of exploring experiment was useful supplement and attempt of traditional teaching mode.