Effects of interleukin-4-modified gold nanozymes on the full-thickness skin defects in diabetic mice / 中华烧伤杂志

Objective: To investigate the effects and mechanism of interleukin-4-modified gold nanoparticle (IL-4-AuNP) on the wound healing of full-thickness skin defects in diabetic mice. Methods: Experimental research methods were adopted. Gold nanoparticle (AuNP) and IL-4-AuNP were synthesized by improving the methods described in published literature. The morphology of those two particles were photographed by transmission electron microscopy, and their particle sizes were calculated. The surface potential and hydration particle size of the two particles were detected by nanoparticle potentiometer and particle size analyzer, respectively. The clearance rate of IL-4-AuNP to hydrogen peroxide and superoxide anion was measured by hydrogen peroxide and superoxide anion kits, respectively. Mouse fibroblast line 3T3 cells were used and divided into the following groups by the random number table (the same below): blank control group, hydrogen peroxide alone group treated with hydrogen peroxide only, hydrogen peroxide+IL-4-AuNP group treated with IL-4-AuNP for 0.5 h and then treated with hydrogen peroxide. After 24 h of culture, the reactive oxygen species (ROS) levels of cells were detected by immunofluorescence method; cell count kit 8 was used to detect relative cell survival rate. The macrophage Raw264.7 mouse cells were then used and divided into blank control group and IL-4-AuNP group that treated with IL-4-AuNP. After 24 h of culture, the expression of arginase 1 (Arg-1) in cells was observed by immunofluorescence method. Twelve male BALB/c mice (mouse age, sex, and strain, the same below) aged 8 to 10 weeks were divided into IL-4-AuNP group and blank control group, treated accordingly. On the 16th day of treatment, whole blood samples were collected from mice for analysis of white blood cell count (WBC), red blood cell count (RBC), hemoglobin level, or platelet count and the level of aspartate aminotransferase (AST), alanine transaminase (ALT), urea, or creatinine. The inflammation, bleeding, or necrosis in the heart, liver, spleen, lung, and kidney tissue of mice were detected by hematoxylin-eosin (HE). Another 36 mice were selected to make diabetic model, and the full-thickness skin defect wounds were made on the back of these mice. The wounds were divided into blank control group, AuNP alone group, and IL-4-AuNP group, with 12 mice in each group, and treated accordingly. On the 0 (immediately), 4th, 9th, and 15th day of treatment, the wound condition was observed and the wound area was calculated. On the 9th day of treatment, HE staining was used to detect the length of neonatal epithelium and the thickness of granulation tissue in the wound. On the 15th day of treatment, immunofluorescence method was used to detect ROS level and the number of Arg-1 positive cells in the wound tissue. The number of samples was 6 in all cases. Data were statistically analyzed with independent sample t test, corrected t test, Tukey test, or Dunnett T3 test. Results: The size of prepared AuNP and IL-4-AuNP were uniform. The particle size, surface potential, and hydration particle size of AuNP and IL-4-AuNP were (13.0±2.1) and (13.9±2.5) nm, (-45.8±3.2) and (-20.3±2.2) mV, (14±3) and (16±4) nm, respectively. For IL-4-AuNP, the clearance rate to hydrogen peroxide and superoxide anion were (69±4)% and (52±5)%, respectively. After 24 h of culture, the ROS level of 3T3 in hydrogen peroxide alone group was significantly higher than that in blank control group (q=26.12, P<0.05); the ROS level of hydrogen peroxide+IL-4-AuNP group was significantly lower than that in hydrogen peroxide alone group (q=25.12, P<0.05) and close to that in blank control group (P>0.05). After 24 h of culture, the relative survival rate of 3T3 cells in hydrogen peroxide+IL-4-AuNP group was significantly higher than that in hydrogen peroxide alone group (t=51.44, P<0.05). After 24 h of culture, Arg-1 expression of Raw264.7 cells in IL-4-AuNP group was significantly higher than that in blank control group (t'=8.83, P<0.05).On the 16th day of treatment, there were no significant statistically differences in WBC, RBC, hemoglobin level, or platelet count and the level of AST, ALT, urea, or creatinine of mice between blank control group and IL-4-AuNP group (P>0.05). No obvious inflammation, bleeding or necrosis was observed in the heart, liver, spleen, lung, and kidney of important organs in IL-4-AuNP group, and no significant changes were observed compared with blank control group. On the 0 and 4th day of treatment, the wound area of diabetic mice in blank control group, AuNP alone group, and IL-4-AuNP group had no significant difference (P>0.05). On the 9th day of treatment, the wound areas both in AuNP alone group and IL-4-AuNP group were significantly smaller than that in blank control group (with q values of 9.45 and 14.87, respectively, P<0.05), the wound area in IL-4-AuNP group was significantly smaller than that in AuNP alone group (q=5.42, P<0.05). On the 15th day of treatment, the wound areas both in AuNP alone group and IL-4-AuNP group were significantly smaller than that in blank control group (with q values of 4.84 and 20.64, respectively, P<0.05), the wound area in IL-4-AuNP group was significantly smaller than that in AuNP alone group (q=15.80, P<0.05); moreover, inflammations such as redness and swelling were significantly reduced in IL-4-AuNP group compared with the other two groups. On the 9th day of treatment, compared with blank control group and AuNP alone group, the length of neonatal epithelium in the wound of diabetic mice in IL-4-AuNP group was significantly longer (all P<0.05), and the thickness of the granulation tissue in the wound was significantly increased (with q values of 11.33 and 9.65, respectively, all P<0.05). On the 15th day of treatment, compared with blank control group, ROS levels in wound tissue of diabetic mice in AuNP alone group and IL-4-AuNP group were significantly decreased (P<0.05). On the 15th day of treatment, the number of Arg-1 positive cells in the wounds of diabetic mice in IL-4-AuNP group was significantly more than that in blank control group and AuNP alone group, respectively (all P<0.05). Conclusions: IL-4-AuNP is safe in vivo, and can improve the oxidative microenvironment by removing ROS and induce macrophage polarization towards M2 phenotype, thus promote efficient diabetic wound healing and regeneration of full-thickness skin defects in diabetic mice.

Mechanism of Fuzi Lizhongwan Improving Injury in Cisplatin-induced CIPN Mice by Regulating MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Fuzi Lizhongwan alleviating the damage of chemotherapy-induced peripheral neuropathy （CIPN） mice caused by cisplatin based on mitogen-activated protein kinase （MAPK） signaling pathway. MethodA total of 40 female KM mice were randomized into blank group （distilled water， ig）， model group （distilled water， ig）， Fuzi Lizhongwan group （3.5 g·kg-1， ig）， and aspirin group （0.026 g·kg-1， ig）. Cisplatin （3 mg·kg-1， ip， 5 days） was used to induce CIPN in mice. Administration began while modeling and lasted 12 days. The general conditions and behaviors of mice were observed. After the last administration， samples were collected. Pathological changes of the soles were observed based on hematoxylin-eosin （HE） staining. Biochemical assay was employed to determine the levels of serum superoxide dismutase （SOD）， hydrogen peroxide （H2O2）， malondialdehyde （MDA）， and nitric oxide （NO）， enzyme-linked immunosorbent assay （ELISA） the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and glutathione peroxidase-3 （GPX-3） in kidney tissue， and Western blotting the expression of extracellular signal-regulated kinase1/2 （ERK1/2）， phosphorylated-ERK1/2 （p-ERK1/2）， p38 MAPK， and phosphorylated-p38 MAPK （p-p38 MAPK） in kidney tissue. ResultCompared with the blank group， model group demonstrated obvious pathological damage on the soles， hyperkeratosis of the epidermis with a basketweave pattern， atrophy of stratum spinosum， reduction of cells， and intracellular edema. Compared with the model group， Fuzi Lizhongwan significantly alleviated the pathological damage of the skin tissue of the soles. The model group showed lower body weight， mechanical pain threshold， thermal pain threshold （P<0.01）， and SOD activity （P<0.05）， higher content of H2O2， MDA， and NO （P<0.01）， and higher expression of IL-6， IL-1β， and TNF-α （P<0.01） than the blank group. Fuzi Lizhongwan group demonstrated higher body weight， mechanical pain threshold， thermal pain threshold （P<0.01）， and SOD activity （P<0.05）， lower content of H2O2， MDA， and NO （P<0.05）， and lower expression of IL-6， IL-1β， and TNF-α （P<0.01） than the model group. The expression of ERK1/2， p-ERK1/2， p38 MAPK， and p-p38 MAPK increased significantly （P<0.01） in the model group compared with that in the blank group， while the expression decreased significantly （P<0.01） in the Fuzi Lizhongwan group compared with that in the model group. ConclusionFuzi Lizhongwan can relieve the neurological injury of cisplatin-induced CIPN mice and increase the pain threshold of mice， possibly by regulating the MAPK signaling pathway and inhibiting inflammatory response and oxidative stress.

Curcumin alleviates the manganese-induced neurotoxicity by promoting autophagy in rat models of manganism / 北京大学学报(医学版)

OBJECTIVE@#To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl2), which mimics mangnism.@*METHODS@#Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H2O intragastrically (ig), MnCl2 group received 15 mg/kg MnCl2(Mn2+ 6.48 mg/kg) intraperitoneally plus dd H2O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl2+ CUR1 group received 15 mg/kg MnCl2 intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl2+ CUR2 group received 15 mg/kg MnCl2 intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum.@*RESULTS@#After exposure to MnCl2 for four weeks, MnCl2-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH+ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl2 group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl2 group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl2 group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl2+ CUR2 group were significantly improved compared with MnCl2 group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl2+ CUR2 group compared with MnCl2 group. Further, compared with MnCl2 group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl2+ CUR2 group (P < 0.05).@*CONCLUSION@#Curcumin alleviated the MnCl2-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.

Clinical Observation of Modified Buzhong Yiqitang Combined with Erxian Decoction in Treatment of Stress Urinary Incontinence in Perimenopausal Women / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of the modified Buzhong Yiqitang combined with Erxian decoction in treating stress urinary incontinence （SUI） of perimenopausal women due to spleen and kidney Qi deficiency. Method:One hundred and six patients were randomly divided into a control group （52 cases） and an observation group（54 cases）. Patients in both groups received lifestyle intervention and pelvic floor muscle training （PFMT）. On this basis， patients in the observation group were further treated with the modified Buzhong Yiqitang combined with Erxian decoction， 1 bag/day， while those in the control group were provided with Suoquan pills， 6 g/time， 2 times/day， for eight weeks. Following the international consultation on incontinence questionnaire-short form （ICIQ-SF） scoring before and after treatment， the urodynamic parameters such as maximum urinary flow rate （Q_max）， maximum urethral closure pressure （MUCP）， residual urine volume （RUV）， abdominal pressure leakage point pressure （ALPP）， and bladder capacity （BC） were measured. The number of incontinence episodes per 24 h， the degree of urinary incontinence， the amount of 1 h urine leakage， and the spleen and kidney Qi deficiency syndrome score were recorded before and after treatment. The levels of estradiol （E₂）， follicle stimulating hormone （FSH）， pituitary adenylate cyclase activating peptide （PACAP）， and vasoactive intestinal peptide （VIP） were measured before and after treatment. Result:The ICIQ-SF sub-scores of the urinary incontinence frequency， severity， and impact on quality of life as well as the total score in the observation group were all lower than those in the control group （<italic>P</italic><0.01）. Q_max， MUCP， ALPP and BC in the observation group were elevated in contrast to those in control group （<italic>P</italic><0.01）， while the RUV declined （<italic>P</italic><0.01）. Compared with the control group， the observation group exhibited a decreased number of incontinence episodes per 24 h， milder degree of urinary incontinence， reduced amount of 1 h urine leakage， and lower spleen and kidney Qi deficiency syndrome score （<italic>P</italic><0.01）. The E₂， PACAP， and VIP in the observation group were up-regulated as compared with those in the control group （<italic>P</italic><0.01）， whereas the FSH was down-regulated （<italic>P</italic><0.01）. The cure and effective rates of the observation group were （29/50） 58.00% and （47/50）94.00%， respectively， significantly better than （18/48）37.50% and （38/48）79.17% of the control group （<italic>χ</italic>²=4.124， <italic>χ</italic>²=4.683， <italic>P</italic><0.05）. Conclusion:On the basis of the lifestyle intervention and PFMT， the modified Buzhong Yiqitang combined with Erxian decoction obviously alleviates urinary incontinence， adjusts sex hormones， PACAP and VIP， ameliorates urodynamic parameters， and enhances the quality of life of patients with SUI due to spleen and kidney Qi deficiency. The resulting cure and effective rates are superior to those of the positive control.

Primary exploration of integrating the humanistic quality education into histology and embryology teaching / 中华医学教育探索杂志

In order to enable the teachers of professional basic courses to play a role adequately in teaching and educating students, the elements of humanistic quality education are excavated from Histology and Embryology chapters and integrated with professional basic knowledges. The effects of teaching are tested through students' writing experience, teachers' interview and national peer review. The results show that students have received the education of gratitude, dedication and responsibility, meanwhile their enthusiasm for learning has been significantly improved. Teachers believe that teaching and learning has achieved self-education at the same time. The national colleagues agree that it's feasible to integrate humanistic quality education into the teaching process of professional basic courses, and the better teaching effect is also be achieved.

Prospects for histone deacetylase inhibitors as antidepressants / 药学学报

Depression is a serious mental illness with a high incidence. At present, we do not fully understand the specific pathological mechanisms of depression, and the efficacy of drug treatments is very limited. Recent studies have shown that epigenetic changes that occur in specific brain regions may be a key mechanism by which environmental factors to interact with individuals to influence the risk of depression. Therefore, drugs that target epigenetic regulation may become a new direction for the development of antidepressants. Histone deacetylase inhibitors (HDACi) are a class of compounds that inhibit histone deacetylase activity, which has been reported to be associated with depression; this article addresses the use of HDACi in preclinical studies, and their potential therapeutic role and limitations of use in depression.

Projections from D2 Neurons in Different Subregions of Nucleus Accumbens Shell to Ventral Pallidum Play Distinct Roles in Reward and Aversion / 神经科学通报·英文版

The nucleus accumbens shell (NAcSh) plays an important role in reward and aversion. Traditionally, NAc dopamine receptor 2-expressing (D2) neurons are assumed to function in aversion. However, this has been challenged by recent reports which attribute positive motivational roles to D2 neurons. Using optogenetics and multiple behavioral tasks, we found that activation of D2 neurons in the dorsomedial NAcSh drives preference and increases the motivation for rewards, whereas activation of ventral NAcSh D2 neurons induces aversion. Stimulation of D2 neurons in the ventromedial NAcSh increases movement speed and stimulation of D2 neurons in the ventrolateral NAcSh decreases movement speed. Combining retrograde tracing and in situ hybridization, we demonstrated that glutamatergic and GABAergic neurons in the ventral pallidum receive inputs differentially from the dorsomedial and ventral NAcSh. All together, these findings shed light on the controversy regarding the function of NAcSh D2 neurons, and provide new insights into understanding the heterogeneity of the NAcSh.

Exploratory screening of potential pan-cancer biomarkers based on The Cancer Genome Atlas database / 北京大学学报(医学版)

OBJECTIVE@#To screen potential pan-cancer biomarkers based on The Cancer Genome Atlas (TCGA) database, and to provide help for the diagnosis and prognosis assessment of a variety of cancers.@*METHODS@#"GDC Data Transfer Tool" and "GDCRNATools" packages were used to obtain TCGA database. After data sorting, a total of 13 cancers were selected for further analysis. False disco-very rate (FDR) < 0.05 and fold change (FC) >1.5 were used as the differential expression criteria to screen genes and miRNAs that were up- or down-regulated in all the 13 cancers. In the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), the best cut-off value and the corresponding sensitivity and specificity were used to reflect diagnostic significance. The Kaplan-Meier method was used to calculate the survival probability and then the log-rank test was performed. Hazard ratio (HR) was calculated to reflect prognostic evaluation significance. DAVID tool were used to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for differentially expressed genes. STRING and TargetScan tools were used to analyze the regulatory network of differentially expressed genes and miRNAs.@*RESULTS@#A total of 48 genes and 2 miRNAs were differentially expressed in all the 13 cancers. Among them, 25 genes were up-regulated, 23 genes and 2 miRNAs were down-regulated. Most differentially expressed genes and miRNAs had good ability to distinguish between the cases and controls, with AUC, sensitivity and specificity up to 0.8-0.9. Survival analysis results show that differentially expressed genes and miRNAs were significantly associated with patient survival in a variety of cancers. Most up-regulated genes were risk factors for patient survival (HR>1), while most down-regulated genes were protective factors for patient survival (0 < HR < 1). The enrichment analysis of GO and KEGG showed that the differentially expressed genes were mostly enriched in biological events related to cell proliferation. In the regulatory network analysis, a total of 13 differentially expressed genes and 2 differentially expressed miRNAs had regulatory and interaction relationships.@*CONCLUSION@#The 48 genes and 2 miRNAs that were differentially expressed in 13 cancers may serve as potential pan-cancer biomarkers, providing help for the diagnosis and prognosis evaluation of a variety of cancers, and providing clues for the development of broad-spectrum tumor therapeutic targets.

Study of anti-atherosclerosis effect and potential mechanisms of piperine in ApoE / 中国药理学通报

Aim To investigate the therapeutic effects of piperine (PIP) on atherosclerosis in ApoE mice fed with high fat diet and the potential mechanisms. Methods After PIP was administered for 20 weeks, aorta was stained by oil red O with the area of aortic plaque analyzed. The levels of blood lipids and serum inflammatory factors were detected. Hepatic expressions of oxidative stress related factors were determined. Human umbilical vein endothelial cells (HUVECs) were cultured and treated with a series of concentrations of PIP after LPS induction. The levels of NO and oxidative lipids were detected and factors of PI3K/Akt/eNOS pathway were analyzed. Results Serum levels of TG, LDL-C, TNF-α and CRP were significantly reduced by PIP in ApoE

Effect of Modified Wendantang on LEP, ACC and MCA in Female Nutritional Obese Rats / 中国实验方剂学杂志

<b>Objective::To detect the expression levels of leptin (LEP), acety-coenzyme A carboxylase(ACC) and malonyl-CoA (MCA)-related proteins and their genes in rat tissues, in order to explore the mechanism and dose-effect relationship of modified Wendantang in alleviating lipid metabolism disorder in female nutritional obese rats. <b>Method::Totally 50 SD female rats were randomly divided into 5 groups according to body weight, namely the normal control group, the model control group, and high, medium and low-dose modified Wendantang groups (18.2, 9.1, 4.55 g·kg^-1). Except the normal control group, the remaining rats were fed with " common feed + high fat emulsion + carbonated beverage" to establish the model of nutritional obesity, and then continuously given drugs by gavage for 5 weeks. After the last drug administration to animals in each group, the rats were anaesthetized to collect materials. The serum LEP, and liver and gastrocnemius ACC levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) was used to detect the expressions of LEP, MCA and ACC2 mRNA in the hypothalamus and liver tissues of each group. <b>Result::Compared with the normal control group, the body weight and fat index of the model control group increased significantly (<italic>P</italic><0.05). Compared with the model control group, the medium-dose modified Wendantang group could significantly down-regulate the expressions of LEP, MCA mRNA in rat hypothalamus (<italic>P</italic><0.01). The low-dose group can significantly down-regulate the expression levels of serum LEP, hypothalamus tissue LEP, MCA mRNA and liver tissue ACC2 mRNA (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the high-dose modified Wendantang group and the middle-dose modified Wendantang group had the best effect in down-regulating the expressions of LEP and MCA mRNA in the hypothalamus of rats, which were followed by the low-dose group (<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion::The mechanism of modified Wendantang against nutritional obesity in female rats is related to the intervention of LEP resistance and the decrease of the expression level of ACC2 mRNA in liver tissue and MCA mRNA in hypothalamus tissue. The middle and low-dose groups have a better effect.

Case report of X-linked intellectual disability caused by DDX3X gene mutation and literature review / 中华实用儿科临床杂志

Retrospective analysis of the clinical data of a child with type 102 mental retardation caused by DDX3X gene mutation in the pediatric diagnosis of the First Affiliated Hospital of Zhengzhou University in April 2019.A 2 years and 3 months old girl with " delay for more than 1 year" , using second-generation sequencing technology for full exon detection, and the result is DDX3X gene 13 th exon c. 1463G>A hybridization mutation, this is a new mutation.There are no Chinese cases reported with DDX3X gene mutations, and there are 8 related cases were reported in foreign literature, all children have different degrees of intellectual disability.So patients with unexplained intellectual disability(especially female patients) need to be wary of the possibility of DDX3X gene mutation.

Progress in research of N-acetylaspartate in central nervous system / 药学学报

italic>N-Acetylaspartate (NAA) is a highly abundant brain metabolite. Nowadays, as an important marker reflecting the function of nervous system, NAA is widely used in the results analysis of nuclear magnetic resonance spectroscopy (1H MRS). NAA is synthesized in mitochondria of neurons and metabolized in oligodendrocytes. Additionally, NAA may be converted to the dipeptide N-acetylaspartylglutamate (NAAG), and catabolized into NAA and glutamate in astrocytes. NAA is related to a variety of central nervous system diseases, including Canavan disease, multiple sclerosis, depression, schizophrenia and other mental diseases. Therefore, NAA may be a biomarker of these diseases, and its related enzymes may be used as therapeutic targets for drug screening. Here, we combined the current research on the molecular mechanisms of NAA to reveal the process of NAA generation, metabolism and transport in the brain, explain the possible physiological effects of NAA and discuss its relationship with central nervous system diseases, explore the prospect of NAA in disease prediction and diagnosis, as well as the targeted treatment that may become the breakthrough of refractory diseases.

Current quality standards of Andrographis Herba of different countries and regions / 中国中药杂志

Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.

Research status of correlation between type IX collagen gene and musculoskeletal diseases / 中国骨伤

As an important component of articular cartilage, type IX collagen plays an important role in regulating homeostasis of bone and cartilage. The mutation or deletion of gene could disequilibrate homeostasis leads to deformity of corresponding bone and joint, and finally causes multiple epiphyseal dysplasia. Moreover, anatomic variation also leads to biomechanics change of corresponding functional unit, combine with micro-environment change caused by change of genes, osteoarthritis and disc degeneration were occurred under the function of stress over and over again. In addition, lack of type IX collagen could effect repair of articular cartilage, intervertebral disc tissue injury. However, musculoskeletal diseases related with type IX collagen has so much not limited this, the reports about it is less for lack of evidence, and need further work to study. Clear relationship of type IX collagen and its disease could provide an effective diagnostic method, and develop a new pathway for follow-up treatment.

Effect of inhibitor of differentiation 1 deficiency on ocular neovascularization / 上海交通大学学报（医学版）

Objective • To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods • The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results • Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models(P<0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion • ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.

Role of endocytosis in cell surface CXC chemokine receptor 4 expression of stem cells from apical papilla / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the change of cell surface CXC chemokine receptor 4 (CXCR4) expression of stem cells from apical papilla (SCAP) after the inhibition of endocytotic pathway, thus to provide experimental basis for the mechanism of SCAP migration.@*METHODS@#The immunofluorescence analysis was conducted to examine the co-expression of CXCR4 and endocytotic compartments, including early endosomes, recycling endosomes and lysosomes in SCAP. Several Rab proteins were applied as markers of organelles in the endocytotic pathway, including Rab5 for early endosomes, Rab11A for recycling endosomes, and Lamp1 for lysosomes. The co-localization of CXCR4 with these endodontic compartments was further observed by proximity ligation assay (PLA). SCAP was treated with two kinds of endocytotic inhibitors, Blebbistatin and Dynasore, at a concentration of 80 μmol/L, respectively. The conditioning time was 1 hour. Flow cytometry was carried out to evaluate the proportion of SCAP that expressed CXCR4 on cell surface. The data were analysed by analysis of variance (ANOVA).@*RESULTS@#The red staining of CXCR4 on immunofluorescence confocal microscopy predominantly overlapped with the green staining of Rab5 and Rab11A, and partly overlapped with Lamp1. It indicated that most CXCR4 molecules were located in early endosomes and recycling endosomes, and some were located in lysosomes. The PLA results revealed that the co-localizaiton of CXCR4 with endocytotic compartments could be observed in early endosomes, recycling endosomes and lysosomes. According to the results of flow cytometry, the proportion of SCAP that expressed CXCR4 on cell surface was as low as 0.13%±0.10%. After the inhibition of endocytosis by pretreating the cells with the following two inhibitors, Blebbistatin and Dynasore, the percentage of SCAP that positively expressed CXCR4 on cell surface was significantly increased to 13.34%±1.31% in Blebbistatin group and 4.03%±0.92% in Dynasore group (F=16.721, P<0.001). Moreover, the number of SCAP that expressed CXCR4 on cell surface in Blebbistatin group was significantly higher than that in Dynasore group (P<0.001).@*CONCLUSION@#The inhibition of endocytotic pathway could increase the number of SCAP that expressed CXCR4 on cell surface, and provide potency for the migration of SCAP.

Effect of Shaoyao Gancaotang and Its Disassembled Prescriptions on Expressions of TRPV3, TRPV4 in Myocardium and Hypothalamus of Rats with Ultra-high Temperature / 中国实验方剂学杂志

Objective:To observe the effect of Shaoyao Gancaotang and its disassembled prescriptions on the expressions of transient receptor potential vanilloid 3 (TRPV3) and transient receptor potential vanilloid 4 (TRPV4) in myocardium and hypothalamus of rats in the ultra-high temperature environment, in order to explore the mechanism of Shaoyao Gancaotang and its disassembled prescriptions against the high temperature. Method:Seventy five male SPF-grade SD rats were randomly divided into 5 groups according to their body weight, namely normal control group, high temperature normal control group, Shaoyao Gancaotang group (2.16 g·kg-1), single Paeoniae Radix Alba(PRA) group (1.08 g·kg-1) and single Glycyrrhizae Radix et Rhizoma(GRR) group (1.08 g·kg-1). Except normal control group, the remaining groups were fed in artificial climate boxes for 13 days. The normal control group and the high temperature normal control group were given the same volume of pure water. Western blot and quantitative real-time fluorescence polymerase chain reaction(Real-time PCR) were used to determine expressions of TRPV3, TRPV4 protein and mRNA in myocardium and hypothalamus of each group. Result:Compared with the normothermic control group, the expressions of TRPV3 protein, TRPV4 mRNA, TRPV3 protein and TRPV3 mRNA in the myocardium of the hyperthermic control group were significantly higher than those of the normal control group (PPPConclusion:TRPV3, TRPV4 channels in rat myocardium and hypothalamus were activated in the high temperature environment. The anti-hyperthermic mechanism of Shaoyao Gancaotang and its disassembled prescriptions was related to the regulation of TRPV3, TRPV4 channel protein and mRNA expressions in rat myocardium and hypothalamus.

Effect of inhibitor of differentiation 1 deficiency on ocular neovascularization / 上海交通大学学报（医学版）

Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models (P＜0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.

A network pharmacology approach to explore mechanisms of Buyang Huanwu decoction for treatment of cerebral infarction / 中国中药杂志

The point of this study is to explore and investigate mechanisms of Buyang Huanwu decoction for treatment of cerebral infarction (CI) using a network pharmacology approach. First, TCMSP database, DrugBank database and PharmMapper server were used and combined with oral bioavailability and drug analysis to screen the components of Buyang Hanwu decoction and predict the potential targets. Then, Cytoscape 3.5.1 software was used to construct compounds-targets network and the protein-protein interaction (PPI) networks for targets of compounds and CI-related targets and merge the two PPI networks to acquire active targets. Finally, gene ontology (GO) and KEGG pathway analysis of active targets were carried out by DAVID online analysis tool and KOBAS 3.0 software. In total of 150 screened compounds and 232 potential targets were obtained. And in total of 208 active targets were finally determined by merging networks. Results indicated that Buyang Huanwu decoction might have a role in treating CI by regulating some biological processes including response to drug, aging, response to hypoxia, and blood coagulation, and some molecular function, such as protein binding, enzyme binding and serine-type endopeptidase activity. The mechanisms might be concerned with PI3K-Akt signaling pathway, TNF signaling pathway, HIF-1 signaling pathway and cAMP signaling pathway. Among them, the regulation of PI3K-Akt signaling pathway might be one of the most crucial mechanisms.

Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCalpha Signaling Pathway

Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-alpha, IL-1beta, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKCalpha). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-alpha, IL-1beta, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKCalpha signaling pathway.