Research progress of neuronal injury mediated by microglial activation and depression / 中国药理学通报

Depression is a common neurological disorder with high incidence, high recurrence and high disability, but its pathogenesis is unclear. In recent years, the protective and attacking effects of glial cells on neurons have become the frontier of neurological disease research. Neuronal injury caused by abnormal activation of microglia (MG) plays an important role in the pathogenesis of depression. In this paper, through literature retrieval by GeenMedical and CNKI, the relevant pathways and key targets of MG activation in depression are summarized so as to provide a theoretical basis for further clinical research.

Therapeutic effect and mechanism of Xiaoyao Kangai Jieyu Recipe on mice with breast cancer related depression through regulating COX pathway / 中国中药杂志

This study aimed to investigate the intervention effect and mechanism of Xiaoyao Kangai Jieyu Recipe(XKJR) on hip-pocampal microglia and neuronal damage in mice with breast cancer related depression. The mouse model of breast cancer related depression was established by inoculation of 4T1 breast cancer cells in axilla and subcutaneous injection of corticosterone(30 mg·kg~(-1)). The successfully modeled mice were randomly divided into a model group, a positive drug group(capecitabine 60 mg·kg~(-1)+fluoxetine 19.5 mg·kg~(-1)), and XKJR group(19.5 mg·kg~(-1) crude drug), with 6 in each group. Another 6 normal mice were taken as a normal group. The administration groups were given corresponding drugs by gavage, while the normal and model groups were given an equal volume of distilled water, once a day for 21 consecutive days. The depressive behavior of mice was assessed by glucose consumption test, open field test and novelty-suppressed feeding test. Hematoxylin and eosin(HE) staining and tumor suppression rate were used to evaluate the changes of axillary tumors. The mRNA expressions and the relative protein expressions of interleukin-1β(IL-1β), interleukin-18(IL-18), cyclooxyganese-2(COX-2) and glutamyl-prolyl-tRNA synthetase(EPRs) in the hippocampus of mice were determined by quantitative real-time polymerase chain reaction(qRT-PCR) and immunohistochemistry, respectively. Immunofluorescence was performed to detect the mean fluorescence intensity of CD11b, a marker of hippocampal microglia activation. Nissler staining and transmission electron microscopy were employed to observe the morphological changes and the ultramorphological changes of hippocampal neurons, respectively. The experimental results indicated that compared with the normal group, the model group had reduced glucose consumption and lowered number of total activities in open field test(P<0.05, P<0.01), prolonged first feeding latency in no-velty-suppressed feeding test(P<0.01), and significant depression-like behavior; the contents of IL-1β, IL-18, COX-2, and EPRs in hippocampus were increased(P<0.05, P<0.01), with hippocampal microglia activation and obvious neuronal damage. Compared with the model group, the positive drug group and the XKJR group presented an improvement in depressive behaviors, a decrease in the contents of IL-1β, IL-18, COX-2 and EPRs in hippocampus, and an alleviation in the activation of hippocampal microglia and neuronal damage; the tumor suppression rates of positive drug and XKJR were 40.32% and 48.83%, respectively, suggesting a lower tumor growth rate than that of the model group. In summary, XKJR may improve hippocampal microglia activation and neuronal damage in mice with breast cancer related depression through activating COX signaling pathway.

Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Effects of compound Chaijin Jieyu tablets on expression of GABA receptor in brain regions of depressive insomnia rats / 中国药理学通报

Aim To explore compound Chaijin Jieyu tablets on expression of GABA receptor in brain regions of depressive insomnia rats. Methods Seventy-two male SD rats were randomly divided into control, model, positive drug (venlafaxine hydrochloridel3. 5 mg · kg

Current Research Status of Aptamer-mediated Liposome Targeted Delivery of Antitumor Drugs / 中国实验方剂学杂志

Tumor has become the second most serious disease that threatens human health and life. Treating with chemical drugs (referred to as chemotherapy) is the most basic treatment, but most chemotherapeutic drugs cause damage to normal tissues. It is a difficult problem in the field of biomedical research that how to deliver anti-tumor drugs more efficiently, increase the concentration of drugs in tumor tissues, enhance the anti-tumor effect, and decrease the drug distribution in normal tissues to weaken the damage to normal tissues. In order to achieve the goals of accurate delivery of anti-tumor drugs and synergism and attenuation, the researchers used systematic evolution of ligands by exponential enrichment technology (SELEX technology) to screen aptamers that can specifically target tumor markers or tumor cells, and designed the novel liposome targeting drug delivery system with aptamers as targeting molecules (ligands). This paper briefly introduced nucleic acid aptamer technology and common tumor markers, and reviewed the research advances on the antitumor effect of aptamer-liposome drug delivery system. It will provide references for the selection of appropriate tumor markers as targets and the application of aptamer technology in the research and development of high-efficiency and low-toxicity liposome targeting agents of anti-tumor traditional Chinese medicine. Meanwhile, it is of great significance for promoting the application of aptamer technology in targeted drug delivery systems.

Research Progress in Co-Delivery of Anti-multidrug Resistant Small RNA and Anti-tumor Drugs with Nanocarriers / 中国药学杂志

The efficacy of antineoplastic drugs in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. The formation mechanism of multidrug resistance is very complex. Conventional drugs or gene therapy usually only aim at a specific drug target, so it is difficult to effectively control the complex signaling pathways of drug-resistant cells. The co-delivery of small RNA (siRNA ormiRNA) and anti-tumor drugs with nanocarriers can maximize the synergistic effect, and reverse the multidrug resistance of tumor cells by silencing some related proteins. This review summarizes the mechanisms and advantages of the combination therapies involving RNA and antineoplastic drugs, in vitro and in vivo evaluation, as well as the recent advances in the co-delivery nanocarriers for these agents.

Preparation process of galactosylated liposome of modified cantharidin / 中草药

Objective To optimize the formulation ratio and preparation process of galactosylated cantharidin liposome (Lac-CTD- lips) and establish its methodology for content determination. Methods The method of determination of GC-MS cantharidin content was established by film dispersion method. The entrapment efficiency of cantharidin was evaluated as an index. The preparation process of Lac-CTD-lips was optimized by single factor and orthogonal experiments. Its surface characteristics, encapsulation efficiency, particle size, and Zeta potential were also investigated. Results The best prescription was as follow: cantharidin: hydrogenated soya lecithin:cholesterol at 1:20:5, 10% galactoside, film-forming at 50 ℃, film cleaning with 30 mL of PBS solution of pH 6.0, and hydartion at 40 ℃ for 1.5 h. The resulting liposomes exhibited a pale blue opalescent appearance, a spherical particle morphology, and a more rounded surface with no adhesion. The average particle size was (123.9 ± 4.8) nm (n = 3), the particle size distribution was single-peak, the zeta potential was (-0.36 ± 0.81) mV (n = 3), and the encapsulation efficiency was over 75%. Conclusion GC-MS is suitable for the determination and analysis of cantharidin content. The optimal preparation technology from orthogonal experiment is stable and reliable. The obtained liposomes have higher encapsulation efficiency, small particle size, and good appearance.

PCR Identification and Phylogenetic Analysis of Trichomonas gallinae from Domestic Pigeons in Guangzhou, China

Avian trichomoniasis caused by Trichomonas gallinae is a serious protozoan disease worldwide. The domestic pigeon (Columba livia domestica) is the main host for T. gallinae and plays an important role in the spread of the disease. Based on the internal transcribed spacers of nuclear ribosomal DNA of this parasite, a pair of primers (TgF2/TgR2) was designed and used to develop a PCR assay for the diagnosis of T. gallinae infection in domestic pigeons. This approach allowed the identification of T. gallinae, and no amplicons were produced when using DNA from other common avian pathogens. The minimum amount of DNA detectable by the specific PCR assay developed in this study was 15 pg. Clinical samples from Guangzhou, China, were examined using this PCR assay and a standard microscopy method, and their molecular characteristics were determined by phylogenetic analysis. All of the T. gallinae-positive samples detected by microscopic examination were also detected as positive by the PCR assay. Most of the samples identified as negative by microscopic examination were detected as T. gallinae positive by the PCR assay and were confirmed by sequencing. The positive samples of T. gallinae collected from Guangzhou, China, were identified as T. gallinae genotype B by sequencing and phylogenetic analyses, providing relevant data for studying the ecology and population genetic structures of trichomonads and for the prevention and control of the diseases they cause.

Sulfur-fumigation, maintenance method of Chinese herbal medicine-discard or inheritance / 中国中药杂志

Sulfur-fumigation processing technology is an ancient maintenance method, which plays a certain role in storage and preservation for Chinese herbal medicine. But in recent years, with the further explanation of sulfur-fumigation processing mechanism and more attention to the safety of drugs, such traditional maintenance method of Chinese herbal medicine is now being questioned by more and more people. The authors think we should have selective inheritance rather than abslute discard to this ancient processing technology after reviewing the literatures published in recent 20 years, and some suggestions are also put forward, which can supply some references for related drug supervision departments.

Hepatocellular glycogen alleviates hepatic ischemia reperfusion injury and its relationship to ICAM-1 gene expression / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate if higher hepatocellular glycogen contents can alleviate hepatic ischemia reperfusion injury and its relationship to ICAM-1 gene expression in hepatic sinusoidal cells (HSCs).</p><p><b>METHODS</b>Twenty-one rabbits fed with a standard diet were randomly divided into three groups (n=7 in each). All the animals were subjected to hepatic ischemia reperfusion injury then sacrificed. Before the injury, group A rabbits fasted for 24 hours; group C rabbits had 6 intravenous glucose solution (25%, 20 ml) injections, 4 hours between two injections. Hepatic enzymological changes, hepatic ICAM-1 mRNA expressions and leukocytic counts in the sinusoids were observed.</p><p><b>RESULTS</b>The liver glycogen contents of the three groups were significantly different. Livers of group A had higher contents of glycogen (9.85+/-0.91 mg/g. wet tissue); in group B they were 38.93+/-5.72; and in group C they were 48.31+/-6.58. Group C animals had the slightest liver function damage. There were no differences in the pre- and post-ischemic ICAM-1 mRNA contents in the three groups. However, livers with a higher content of glycogen showed less expression of ICAM-1 mRNA (group A: 1.398+/-0.365 ng/mg wet tissue; group B: 0.852+/-0.297; group C: 0.366+/-0.183) and lower leukocytic counts. The relationship analysis showed a negative relationship between hepatocellular glycogen and hepatic ICAM-1 mRNA contents (r= -0.965, P less than 0.01).</p><p><b>CONCLUSIONS</b>Hepatocellular glycogen is important in protecting liver ischemic reperfusion injury. Also hepatocellular glycogen decreases the expression of ICAM-1 mRNA of HSCs.</p>

Rapid and sensitive analysis of mucin-type glycans using an in-line flow glycan-releasing apparatus.

Rapid and sensitive analysis of glycans is essential for glycomics. We previously reported an apparatus, the AutoGlycoCutter (AGC), for rapid release of O-linked glycans under alkaline conditions and its application to rapid analysis of glycans in proteoglycans. We now report an application of the AGC to obtain mucin-type glycans with reducing end (i.e., hemiacetal group) within only 3 min. The released oligosaccharides could be labeled with fluorescent 2-aminobenzoic acid for analysis by normal-phase high-performance liquid chromatography (NP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We could detect O-glycans from as low as 5 pmol of bovine caseino glycomacropeptide (CGMP) by the proposed procedures. The validity of the current method was shown by the analyses of the released O-glycans from some standard glycoproteins: bovine submaxillary mucin, bovine fetuin, porcine stomach mucin, and human colostrum immunoglobulin A. The advantage of the current method was also demonstrated in comparative analysis of mucin-type glycans in CGMP derived from three different animal species.

Development of an apparatus for rapid release of oligosaccharides at the glycosaminoglycan-protein linkage region in chondroitin sulfate-type proteoglycans.

An apparatus, AutoGlycoCutter (AGC), was developed as a tool for rapid release of O-linked-type glycans under alkaline conditions. This system allowed rapid release of oligosaccharides at the glycosaminoglycan-protein linkage region in proteoglycans (PGs). After digestion of PGs with chondroitinase ABC, the oligosaccharides at the linkage region were successfully released from the protein core by AGC within 3 min. The reducing ends of the released oligosaccharides were labeled with 2-aminobenzoic acid and analyzed by a combination of capillary electrophoresis (CE) and matrix-assisted laser desorption time-of-flight mass spectrometry. In addition, the unsaturated disaccharides produced by chondroitinase ABC derived from the outer parts of the glycans were labeled with 2-aminoacridone and analyzed by CE to determine the disaccharide compositions. We evaluated AGC as a method for structural analysis of glycosaminoglycans in some chondroitin-sulfate-type PGs (urinary trypsin inhibitor, bovine nasal cartilage PG, bovine aggrecan, bovine decorin, and bovine biglycan). Recoveries of the released oligosaccharides were 57-73% for all PGs tested in the present study. In particular, we emphasize that the use of AGC achieved ca. 1000-fold rapid release of O-glycans compared with the conventional method.

Effect of Oral Glucose on Heart Rate of Healthy Newborns / 实用儿科临床杂志

0.05).The change of heart rate in 2 groups was greater than that of distilled water respectively(P

Influence of Losartan on Transforming Growth Factor-?1 and Connective Tissue Growth Factor in Rats with Diabetic Nephropathy / 实用儿科临床杂志

Objective To investigate expression of transforming growth factor-?1(TGF-?1)and connective tissue growth factor(CTGF) protein in renal tissues,and detect the levels of urinary TGF-?1 and CTGF in rats with diabetic nephropathy(DN).To observe the influence of losartan on expression of the two protein in renal tissue and excretion in urine.Methods Wistar rats were treated by intravenous injection of streptozotocin after right nephrectomy to induce DN rat model.The DN rats were randomly divided into two groups:DN experimental group and losartan treated group.The expression of TGF-?1 and CTGF in renal tissue were determined with immunohistochemical staining,urinary TGF-?1 and CTGF were assayed by enzyme-linked immunosorbent assay(ELISA) at 6,12 weeks respectively.Results Compared with losartan treated group,urinary protein excretion and the protein expression of TGF-?1 and CTGF significantly increased(P

Changes of Serum Vascular Endothelial Growth Factor and Neopterin Levels in Children with Primary Nephritic Syndrome / 实用儿科临床杂志

0.05).There was a significant positive correlation between serum VEGF,NP and the degree of proteinuria in group A patients,respectively(r=0.47,0.43 Pa

Effect of 1,25-(OH)_2D_3 on the Expression of Nephrin in Diabetic Rat / 实用儿科临床杂志

Objective To explore the effect of 1,25-(OH)2D3 on Nephrin protein expression in renal of diabetic rats.Methods Diabetic rats were induced by streptozotocin(STZ).Groups were divided as follows:diabetic group(DM group),1,25-(OH)2D3 treated group[1,25-(OH)2D3 group] and control group.At the 12th week,haematuria and proteinuria were determined and the kidneys were removed by histopathology,immunostaining,and the expression of Nephrin mRNA and protein in renal cortex were detected by reversed transcription-polymerase chain reaction(RT-PCR).Results Compared with control and 1,25-(OH)2D3 groups,urine erythrocyte and protein excretion and glomerlar cellularity in DM group statistically increased(P0.05).Conclusion The effect of 1,25-(OH)2D3 is in relieving haematuria and proteinuria and up-regulate the expression of nephrin mRNA and protein to protein kidney.

Relationship between Serum Neopterin and D-Dimer Levels and Coronary Artery Dilatation in Kawasaki Disease / 实用儿科临床杂志

Objective To detect the levels of serum neopterin(NP) and D-dimer,and explore whether NP and D-dimer levels respond to coronary artery dilatation(CAD) of Kawasaki disease(KD),and evaluate the risk factors of CAD.Methods This study were conducted on 45 children with KD.Twenty-one children were CAD and 24 cases were not CAD.Active phase serum NP,D-dimer levels were measured by sensitive enzyme-linked immunosorbent assay(ELISA).Multiple regression analysis including platelet(PLT),monocyte(M),creatine kinase-MB(CK-MB),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),cardiac troponin I(cTnI) were studied with CAD.Results Compared with recovery phase,active phase the levels of PLT,M,CK-MB,CRP,ESR,cTnI were significantly higher(Pa

Perspective of pre-operational jaundice-reducing indication in carcinoma of head of pancreas / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the necessity, advantages and disadvantages of reducing the Icterus Index before operation in carcinoma of the head of pancreas.</p><p><b>METHODS</b>A total of 183 patients with serum total bilirubin (TB) level higher than 220 micromol/L were randomized into 2 groups: jaundice-reducing group (92 patients) and non-reducing group (91 patients). In jaundice-reducing group, all the patients were performed ultrasound-guided percutaneous transhepatic bile duct drainage (UPTBD) and endoscopic nasobiliary drainage (ENBD). The jaundice-reducing group was operated on 3 weeks after tube placement. In non-reducing group, all the patients underwent operations only after general pre-operation routine preparation within 5 days after admission. The operation and post-operation recovery in the two groups was investigated and compared.</p><p><b>RESULTS</b>In jaundice-reducing group, the level of TB decreased to 120 micromol/L from 279 micromol/L in 89 patients after biliary drainage. Of the 89 patients, pancreatoduodenectomy was successfully performed in 39 (43.8%), 47 (52.8%) underwent simple internal drainage and the other 3 were just explored. The average blood loss was 250 ml (110 - 980 ml), complications were found in 8 patients (9.0%) and one died. In non-reducing group, pancreatoduodenectomy was successfully performed in 24 (26.4%), simple internal drainage in 58 patients (63.7%) and exploration in 9 (9.9%). The average blood loss was 480 ml (320 - 1750 ml), complications were found in 19 patients (20.9%) and 4 died. In the non-reducing group, the patients with complications were older than those without complications, and the TB level was higher. The excision rate of carcinoma, incidence rate of complications and hospital time in patients whose TB decreased over 30% weekly after reducing the Icterus Index were all better than those of the rest.</p><p><b>CONCLUSIONS</b>It is necessary to reduce the Icterus Index before operation in the patients with carcinoma of head of pancreas complicated with serious jaundice, especially for the elder, which can not only reduce the blood loss but also make operations safer and increase cure rate, in addition. And whether the Icterus Index decreases smoothly with biliary drainage can be used to predict the operational risk, effect and prognosis.</p>

Changes of Transforming Growth Factor-?_1 Levels in Children with Immunoglobulin A Glomerulonephritis and Mesangial Proliferate Glomerulonephrit is / 实用儿科临床杂志

Objective To detect the levels of transforming growth factor-?_1(TGF-?_1) in plasma,serum and urinary of children with Immunoglobulin A glomerulonephritis(IgAGN) and mesangial proliferate glomerulonephritis(MsPGN) and explore the different effects of TGF-?_1 in the two diseases.Methods The plasma,serum and urinary TGF-?_1 levels were measured in 24 children with IgAGN,and 30 children with MsPGN and 30 healthy controls by enzyme-linked immunosorbent assay(ELISA).Results The TGF-?_1 levels in plasma,serum and urinary samples of IgAGN group were increased.The TGF-?_1 levels of IgAGN were significantly higher than those of MsPGN and heathy controls(P(0.05)).Conclusion It is showed that TGF-?_1 plays a diffenent role in IgAGN and MsPGN.

Effect of Protein Kinase C ? Inhibitor LY333531 on Expressions of Vascular Endothelial Growth Factor and Macrophage Migration Inhibitory Factor in Kidney of Diabetic Rats / 实用儿科临床杂志

Objective To explore the expression of vascular endothelial growth factor(VEGF) and macrophage migration inhibitory factor(MIF) in kidney of diabetic rats,the influence of protein kinase C ? inhibitor LY333531 on the expression of VEGF and MIF.Methods Thirty wistar rats were divided at random into three groups:normal control group(NC group);diabetic model group(DM group),the rats models of diabetic mellitus were induced by streptozotocin(SIZ);LY333531 treated group(LT group),which were given LY333531 [10 mg/(kg?d)] by gastric perfusion after DM model inducing success.At the 10th week,the levels of blood glucose(BG),24 hours urine albumin excretion rate(AER),urine VEGF,and MIF were detected using enzyme-linked immunosorbent assay(ELISA).Glomerular cellularity and extracellular matrix(ECM) were observed by light microscope.The expression levels of VEGF and MIF in the kidney tissues in three groups of rats were detected using immunohistochemistry.Results BG,AER,VEGF,MIF in DM group were significantly higher than those in control group(Pa0.05).There was strongly stained of VEGF,MIF in glomerular mesangium in DM group,weakly positive in LT group by immunohistochemistry.The expression of VEGF and MIF in DM gorup significantly increased than those in NC group(P0.05).Conclusions The expression levels of VEGF and MIF in kidney tisues of diabetic rats significantly increase and correlation with the degree of renal tissue injury.LY333531 can contribute to cut down BG,decrease AER,VEGF,MIF excrection in urine,inhibit glomerular cellularity and ECM proliferation,inhibit expressions of VEGF and MIF to protect kidney.