Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation / 中国天然药物

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

Research progress on mechanism of phytohormones in regulating flavonoid metabolism / 中国中药杂志

Phytohormones play an important role at all stages of plant growth, influencing plant growth and development and regulating plant secondary metabolism, such as the synthesis of flavone, flavonol, anthocyanin, and other flavonoids. Flavonoids, a group of important secondary metabolites ubiquitous in plants, have antioxidative, anti-microbial, and anti-inflammatory activities and thus have a wide range of potential applications in Chinese medicine and food nutrition. With the development of biotechnology, phytohormones' regulation on flavonoids has become a research focus in recent years. This study reviewed the research progress on the mechanism of common phytohormones, such as abscisic acid, gibberellin, methyl jasmonate, and salicylic acid, in regulating flavonoid metabolism, and discussed the molecular mechanism of the synthesis and accumulation of flavonoids, aiming at clarifying the key role of phytohormones in modulating flavonoid metabolism. The result is of guiding significance for improving the content of flavonoids in plants through rational use of phytohormones and of reference value for exploring the mechanism of hormones in regulating flavonoid metabolism.

Association of the TLR9 gene rs187084 single nucleotide polymorphism with tuberculosis in the Chinese Tibetan population / 医学研究生学报

Objective The purpose of this study was to investigate the correlation between single nucleotide polymorphisms (SNP) of Toll-like receptor 9 (TLR9) and tuberculosis in the Chinese Tibetan population . Methods A total of 613 active tubercu-losis patients and 603 healthy controls were enrolled in this case -control study.Two SNPs in TLR9 (rs187084 and rs5743836) were genotyped using the multiplex ligation detection reaction technique .The association of the SNPs with the susceptibility of TB was inves -tigated using logistic regression analysis . Results There was no statistically significant difference in the allele distribution of rs 187084 G/A between the TB patients and the healthy controls (P=0.668) or correlation between the genotype of rs 187084 and the genetic suscepti-bility of TB ( P >0.05).Dominant, recessive and additive models showed no association of this SNP with TB , either (P >0.05). Conclusion The rs187084 polymorphism of TLR9 is not correlated with the genetic susceptibility of tuberculosis in the Chinese Tibetan population.

Immune regulation effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque / 中国中药杂志

To evaluate the effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque. Eight SIV rhesus macaques of the same age were randomly divided into Chinese medicine of invigorating spleen and kidney detoxification group(hereinafter referred to as Chinese medicine group) and anti-virus drug(HAART) group. The traditional Chinese medicine and antiviral therapy were given for 8 weeks, and peripheral blood was collected for detection in every 4 weeks. The results showed that Chinese medicine of invigorating spleen and kidney detoxification could not obviously decrease plasma viral load as HAART, but it can increase CD4 number in peripheral blood, especially the CD4 naive cells, and increase the number of CD4 and CD8 cells, enhance the immune response to pathogens. Therefore, it delayed the occurrence and development of spleen deficiency to a certain extent, indicating that the medicine had immune regulation effect, with considerable clinical value and application prospects.

Risk and solutions to chimeric antigen receptor-engineered T cell-based cancer immunotherapy / 药学学报

The potential of cancer immunotherapy has been demonstrated recently using the chimeric antigen receptors-engineered (CAR) T cells, in which B cell haematological malignancies was successfully treated in clinical trials. However, challenges remain in the translation of the potential benefits into therapy of other types of cancer with similar efficacy and safety. Excessive activation of genetically-modified T cells may cause severe toxicities, such as cytokine storm, on-target toxicities, and tumor lysis syndrome. Genomic integration of viral vectors may cause genetic toxicities due to insertional mutagenesis of important genes. Strategies to overcome these toxicities are proposed and discussed, including the use of suicide genes, combinatorial antigen recognition, on-switch, non-viral vector and other innovative gene therapy strategies, to enhance safety of this promising immunotherapy.

A rabbit pulmonary vein myocyte isolation method based on simultaneous heart and pulmonary vein perfusion / 生理学报

Myocytes in the pulmonary veins (PV) play a pivotal role in the development of paroxysmal atrial fibrillation (AF). It is therefore important to understand physiological characteristics of these cells. Studies on these cells are, however, markedly impeded by the fact that single PV myocytes are very difficult to obtain due to lack of effective isolation methods. In this study, we described a novel PV myocyte isolation method. The key aspect of this method is to establish a combination of retrograde heart perfusion (via the aorta) and anterograde PV perfusion (via the pulmonary artery). With this simultaneous perfusion method, a better perfusion of the PV myocytes can be obtained. As results, the output and viability of single myocytes isolated by simultaneous heart and PV perfusion method were increased compared with those in conventional retrograde heart perfusion method.

Preliminary study on effect of Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces on intestinal flora of mice / 中国中药杂志

This study aims to analyze and compare the effect of cell wall-broken decoction pieces, conventional decoction pieces and conventional powder of Rhodiolae Crenulatae Radix et Rhizoma on the intestinal flora of normal mice. The conventional bacterial culture and PCR-DGGE (polymerase chain reaction-denaturing gradient gel electrophoresis) were adopted for the mice after the oral administration for 14 days. According to the bacterial culture results, the 1/8 dose cell wall-broken decoction pieces group showed fewer Enterococcus and Escherichia coli bacillus but more Lactobacillus and Bifidobacterium than the conventional decoction pieces group and the traditional powder group (P <0.05). Meanwhile, on the basis of the PCR-DGGE results, the 1/8 dose cell wall-broken decoction pieces group revealed the highest Shannon-Wiener index (H) and species richness (S) among the seven groups, with extremely significant differences compared with the normal group (P <0.01), significant differences compared with the conventional decoction pieces group and the conventional powder group (P <0.05) and a high intra-group similarity. In conclusion, the long-term intake of 1/8 dose Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces showed a certain effect in regulating intestinal tract by promoting the growth of Lactobacillus and Bifidobacterium. Furthermore, the intestinal flora community will become more stable.

Research on the relationship between thick greasy tongue fur formation and vascular endothelial cell permeability with the protein expression of zonula occludens-1 / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the relationship of thick greasy tongue fur formation and permeability of vascular endothelial cells (ECs) with the protein expression of zonula occludens-1 (ZO-1).</p><p><b>METHODS</b>Sprague Dawley rats were randomly divided into a model group of severe acute pancreatitis (SAP) and a sham-operated (SO) group. The SAP rats were further divided into two subgroups on the basis of tongue-coating status: a thick greasy tongue fur group (SAP-TGF) and a normal tongue fur group (SAP-NF). Six rats were chosen randomly from every group mentioned above for an Evans blue assay 5 days after model establishment. For the histomorphology analysis, the expressions of ZO-1 protein and mRNA were studied by hematoxylin-eosin (H&E) staining, transmission electron microscope, Western blot, and Q-PCR using blood and tongue tissues, which were collected from 8 rats randomly chosen from each group.</p><p><b>RESULTS</b>The papillae density of the rat tongue surface and the caryocinesis frequency of the basal layer were significantly increased in the SAP-TGF group compared with the SO group (P<0.05). Evans blue levels in the tongue tissue of the SAP-TGF group were significantly higher than that of the SO and SAP-NF groups (P<0.05). Vascular ECs were wider and obviously fissured in the SAP-TGF group under transmission electron microscope observation. The protein and mRNA expression of ZO-1 in the SAP-TGF group were lower than those in the SAP-NF (P<0.05).</p><p><b>CONCLUSIONS</b>Reproductive activity enhancement of glossal epithelial cells was one of the main characteristics of thick greasy tongue fur formation. An increase in vasopermeability was closely associated with thick greasy tongue fur formation. Tight junction structural variation of vascular ECs might play an important role in the pathological and physiological process of thick greasy tongue fur formation.</p>

The effect of Nifedipine and mechanical strain on matrix metalloproteinase expression in human periodontal ligament fibroblast / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Nifedipine on matrix metalloproteinase (MMP)-10 and MMP-13 expression in human periodontal ligament fibroblast (HPDLF) induced by mechanical strain in vitro.</p><p><b>METHODS</b>HPDLF was divided into four groups at random by mechanical strain of elongation 0%, 8%, 12% and 16%. Each group was divided into four subgroups again by the concentration of Nifedipine 0, 10, 30, 50 microm. The cells were imposed to state mechanical strain 12 h after incubated with Nifedipine 1 h. And then immunohistochemical staining was used to investigate the expressions of MMP-10 and MMP-13 in intracytoplasm.</p><p><b>RESULTS</b>In 0% group, there was no significant difference of MMP-10 and MMP-13 expression in all subgroups (P>0.05). The expressions of MMP-10 and MMP-13 were high in group 8%, 12% and 16% without Nifedipine, and increasing significantly with elongation (P<0.001). The expressions of MMP-10 and MMP-13 decreased with dose increasing (P<0.001) in HPDLF after imposed to Nifidepine.</p><p><b>CONCLUSION</b>The expressions of MMP-10 and MMP-13 induced by mechanical strain were inhibited by Nifedipine, which suggested calcium ions channels participate in expressions of MMP-10 and MMP-13 induced by loading.</p>

Treating high angle bimaxillary protrusion with three kinds of extraction method: a clinical study / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To compare the effect of three kinds of extraction model on high angle bimaxillary protrusion patients.</p><p><b>METHODS</b>A total of 30 patients with Class I malocclusion and bimaxillary protrusion, aged 14-25 years old, were selected and divided into three groups. Four first premolars were extracted in the first group. The two maxillary first premolars and two mandibular first molars were extracted in the second group. The two maxillary first premolars and two mandibular first molars were extracted in the third group, and two additional micro-implants used as orthodontic anchorage in maxilla. Three groups were all treated with MBT appliance. Cephalometric analysis were carried out before and after treatment, and the results were analyzed with statistics.</p><p><b>RESULTS</b>1) About the hard tissues, compared with the first group, there were statistically significant differences of N-Me, SGo/NMe, ANS-Me, FH/MP, SN/MP, and ODI in the second and the third group after treatment (P<0.01). 2) About the soft tissues, the teeth and the alveolar bone, compared with the first group, there were statistically significant differences of Pg-Pos, Li-SnPos, Si-LiPos, LL-E, L1-NB, L1/NB, U1/L1, L7-MP in the second and the third group after treatment (P<0.01). 3) All patients received consummate orthodontic treatment and obtained fine occlusion. Facial profiles were improved significantly after orthodontic treatment.</p><p><b>CONCLUSION</b>1) After orthodontic treatment with mandibular first molars extraction, FH/MP, SN/MP, N-Me, ANS-Me, L1-NB and L1/NB decreased respectively, and soft tissue profiles were improved significantly. 2) Additional micro-implant used as orthodontic anchorage in maxilla significantly contributed to the maxillary incisor retraction and subsequent soft tissue change. 3) The first molars extraction and additional micro-implant used as orthodontic anchorage are efficient in improving the facial profiles for high angle bimaxillary protrusion patients.</p>

Clinical application of modified distal-jet appliance in distalization of maxillary molar / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the clinical effects of the maxillary molar distalization with modified Distal-Jet appliance.</p><p><b>METHODS</b>15 patients (average age 12.3 year-old) with maxillary molars shifting mesially were selected as the subjects. Maxillary molars of all patients were distalized with modified Distal-Jet appliance.</p><p><b>RESULTS</b>All patients achieved good occlusion, normal overjet and overbite with modified Distal-Jet appliance.</p><p><b>CONCLUSION</b>Modified Distal-Jet appliance can distalize maxillary molars effectively.</p>