Sacral Nerve Stimulation in Patients With Refractory Pudendal Neuralgia.

BACKGROUND: Pudendal neuralgia (PN) is one of the most common forms of genital pain. Only 42.2% of PN patients respond to the first-line treatment. Novel neuromodulation techniques in the treatment of refractory PN patients are urgently required. OBJECTIVES: The aim of this study was to evaluate the treatment effects and adverse events of sacral nerve stimulation (SNS) for patients with refractory PN. STUDY DESIGN: A prospective nonrandomized study. SETTING: This prospective analysis included 33 patients who received the phase II surgical implantation. METHODS: A total of 55 eligible PN patients were recruited for SNS treatment after informed consent, and 33 of 55 patients with a minimum 50% improvement were candidates for surgical implantation. Visual Analog Scale (VAS) scores, Self-rating Anxiety and Depression Scale, Quality of life score (SF-36), and sleep monitoring indicators before and after surgery were used to assess the effects of SNS on patients with refractory PN. RESULTS: Thirty-three patients were included in the final analysis, involving 24 women and 9 men with a mean age of 49.5 years (26-70 years). There was a favorable decrease in pain severity (VAS scores) from 7.1 ± 1.1 at baseline to 6.1 ± 1.0 on postoperative day 1, and 2.8 ± 0.7 at 1 week, 1.7 ± 0.5 at 1 month, 1.1 ± 0.7 at 6 months, and 1.0 ± 0.6 at 12 months after surgery, respectively (P < 0.05). The mean score of each section of SF-36 after SNS was significantly higher than that at baseline (P < 0.05). Total sleep time and sleep time in each period were significantly prolonged after SNS implantation compared with that before surgery (6 months vs Pre, total: 5.32 ± 1.49 hours vs 3.66 ± 1.19 hours, deep: 2.52 ± 0.63 hours vs 1.36 ± 0.43 hours, light: 1.78 ± 0.42 hours vs 0.99 ± 0.30 hours, rapid eye movement: 1.41 ± 0.29 hours vs 0.89 ± 0.27 hours, P < 0.05). No serious device complications were reported during the follow-up period. LIMITATIONS: Large-scale randomized clinical trials are warranted to evaluate the risk factors for prediction of refractory PN. CONCLUSIONS: These data imply that SNS can have beneficial effects on patients with refractory PN.

Pharmacodynamic Evaluation of the Gexia Zhuyu Decoction in the Treatment of NAFLD and the Molecular Mechanism Underlying the TRPM4 Pathway Regulation.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome of abnormal lipid deposition in the liver mediated by nonalcohol intake. The Gexia Zhuyu decoction, a classic traditional Chinese medicine compound, is widely used in the clinical treatment of NAFLD. However, its specific efficacy and underlying mechanisms have not been elucidated yet. This study aimed to quantitatively evaluate the efficacy of the Gexia Zhuyu decoction using pharmacodynamics and to explore its molecular mechanisms in conjunction with proteomics. High-fat diets and methionine choline-deficient diets were used to induce various NAFLD progression stages in mouse models. The effects of oral Gexia Zhuyu decoction administration on NAFLD were evaluated by measuring the serum and liver indicators of the treated mice before and after drug intervention and by comparing the changes in liver tissue. Liver TRPM4 mRNA and protein levels were measured using reverse transcription-polymerase chain reaction and Western blotting, respectively. Experimental data showed that serum ALT, AST, and liver triglyceride (TG) levels in each disease stage group of drug intervention mice decreased, and high-density lipoprotein (HDL) and superoxide dismutase (SOD) levels increased. Liver TG levels decreased after drug intervention in the liver fibrosis mice, but serum TG levels increased. Furthermore, cellular fatty changes, inflammatory changes, and fibrous tissue proliferation were all relieved. The TRPM4 protein and mRNA levels in the liver tissue were decreased, and the microRNA (miRNA)-24 expression was increased. The Gexia Zhuyu decoction has a clear therapeutic effect at each stage of NAFLD. It likely acts by altering miRNA-24 expression and regulating the target TRPM4 protein pathway to achieve NAFLD treatment.

Feibi Recipe Reduced Pulmonary Fibrosis Induced by Bleomycin in Mice by Regulating BRP39/IL-17 and TGFß1/Smad3 Signal Pathways.

Fibrotic remodeling has become the result of many lung diseases, and these disorders can be categorized with known as well as unknown etiologies. Idiopathic pulmonary fibrosis is the most fatal disease among the unknown etiology. TGFß1/Smad3 signal pathway plays an important role in lung fibrosis and epithelial regeneration. This study investigated the effects and mechanism of Feibi Recipe (FBR) on pulmonary fibrosis. In this experiment, C57BL/6 mice were used and bleomycin was used to induce the lung injury. Meanwhile, the study showed a significant reduction in pathological response and mediators of inflammation and fibrosis such as IL-6, ICAM-1, IL-13, IL-17, BRP-39, TGFß1, Smad3, and Smad7 were identified. Collectively, the FBR appears to attenuate the lung injury and the modeling of fibrosis in mice.

Antidepressant pathways of the Chinese herb jiaweisinisan through genetic ontology analysis.

Active compounds and corresponding targets of the traditional Chinese herb, jiaweisinisan, were obtained from systems pharmacological database and placed into ClueGO for gene ontology analysis. The targets of depression were obtained from the Online Mendelian Inheritance in Man, the Therapeutic Target Database, and the Pharmacogenomics Knowledge Base. Compound-target and target-pathway networks were constructed using Cytoscape, and then their topological parameters were analyzed. The targets of jiaweisinisan and depression were mapped to pathways, thereby constructing antidepressant pathways of jiaweisinisan. It was found that jiaweisinisan has 82 different active compounds and 306 relevant potential targets. Also, 107 unrepeatable targets related to depression were found. In all, 26 common targets were found to be the direct anti-depression targets of jiaweisinisan and 9 pathways of jiaweisinisan related to depression were divided into three modules (synaptic transmission, cell apoptosis, and immune-inflammatory). The jiaweisinisan formula was found to have synergistic antidepressant effects due to aspects of its herb composition and the active compounds therein, giving rise to potential targets and signaling pathways related to depression. Its antidepressant mechanisms were found to mainly involve the regulation of synaptic transmission, cell apoptosis, and immune-mediated inflammation.

[7-hydroxy sulfonation of liquiritigenin by recombinant SULT1A3 enzyme and HEK-SULT1A3 cells].

In this study,liquiritigenin sulfonation was characterized using recombinant human sulfotransferases( SULTs). The chemical structure of liquiritigenin sulfate was determined by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). Then model fitting and parameter estimation were performed using the Graphpad Prism V5 software. Various SULT enzymes( SULT1 A1,1 A2,1 A3,1 B1,1 C2,1 C4,1 E1 and 2 A1) were able to catalyze the formation of liquiritigenin-7-O-sulfate. Sulfonation of liquiritigenin-7-hydroxy( 7-OH) by these eight SULT enzymes consistently displayed the classical Michaelis-Menten profile. According to the intrinsic clearance( CLint) value,the sulfonation rates of liquiritigenin-7-OH by expressed SULT enzymes followed the following rank order: SULT1 C4 > SULT1 A3 > SULT1 E1 > SULT1 A1 > SULT1 A2 > SULT1 B1 >SULT1 C2>SULT2 A1. Further,liquiritigenin-7-O-sulfonation was significantly correlated with the SULT1 A3 protein levels( P<0. 05).Then,human embryonic kidney( HEK) 293 cells over expressing SULT1 A3( named as HEK-SULT1 A3 cells) were conducted. As a result,liquiritigenin-7-O-sulfate( L-7-S) was rapidly generated upon incubation of the cells with liquiritigenin. Consistent with SULT1 A3,sulfonation of liquiritigenin-7-OH in HEK-SULT1 A3 cells also followed the Michaelis-Menten kinetics. The derived Vmaxvalues was( 0. 315±0. 009) µmol·min-1·g-1,Kmwas( 7. 04±0. 680) µmol·L-1,and CLintwas( 0. 045±0. 005) L·min-1·g-1. Moreover,the sulfonation characters of liquiritigenin( 7-OH) in SULT1 A3 were strongly correlated with that in HEK-SULT1 A3 cells( P<0. 001).The results indicated that HEK-SULT1 A3 cells have shown the catalytic function of SULT1 A3 enzymes. In conclusion,liquiritigenin was subjected to efficient sulfonation,and SULT1 A3 enzyme plays an important role in the sulfonation of liquiritigenin-7-OH. Significant sulfonation should be the main reason for the low bioavailability of liquiritigenin. In addition,HEK-SULT1 A3 cells were conducted and successfully used to evaluate liquiritigenin sulfonation,which will provide an appropriate tool to accurately depict the sulfonation disposition of liquiritigenin in vivo.

Synthesis, characterization and inhibitory effects of crocetin derivative compounds in cancer and inflammation.

Crocetin is a natural product possessing extraordinary therapeutic effects for various diseases. However, its extremely low solubility limits its application greatly. Conjugation of organic compounds containing heteroatoms such as N to poor soluble molecules can help the synthesized derivative to form stable hydrogen bonds by lowering the salvation energy, which will improve the solubility of the synthesized compounds. Herein, crocetin was modified by conjugating with piperidyl, diethylin and benzylamine to improve their solubility and bioactivities. In the present study, the conjugation of crocetin with piperidyl, diethylin and benzylamine and their influence on the solubility and the pharmacological effects of crocetin were investigated. With the described strategy, crocetin derivatives were synthesized and their structures were elucidated by 1H NMR, 13C NMR and UPLC-MS spectroscopic analysis. The solubility of crocetin and its derivatives were identified. Upon that, the pharmacological effects of the crocetin derivatives on the tumor and inflammation treatment were investigated. It was shown that, in contrast to crocetin, of which, the solubility and pharmacological effects were low and limited, the synthesized compounds have significantly higher solubility and possess broad spectrum of anticancer effects in multiple tumor cell lines, including B16F10, MCF-7, A549 and SKOV3, as well as enhanced anti-inflammation efficacy in macrophage (RAW264.7) without causing cells damage. Conjugation of piperidyl, diethylin and benzylamine with the crocetin was demonstrated to be a highly efficient strategy to improve the solubility of crocetin. The synthesized crocetin derivatives were shown the promising therapeutics for the tumor and inflammation treatment with high safety.

Evidence based anti-osteoporosis effects of Periplaneta americana L on osteoblasts, osteoclasts, vascular endothelial cells and bone marrow derived mesenchymal stem cells.

BACKGROUND: Kangfuxin (KFX) is the ethanol extract of Periplaneta americana L, which has been widely used in the Traditional Chinese Medicine for the repair and regeneration of injured organ and tissues with long history. This study is to investigate the influence of KFX in the various cellular activities and evaluate the anti-osteoporosis potential of KFX. METHODS: The influence of the KFX in the cellular activities, including: 1) migration, osteocalcin secretion of osteoblasts; 2) apoptosis of osteoclasts; 3) migration and tube formation of human umbilical vein endothelial cell (HUVEC); and 4) proliferation, cell cycle regulation and migration of bone marrow mesenchymal stem cells (BMSCs), were investigated systematically. RESULTS: KFX was shown to significantly 1) Promote of the migration of osteoblasts, HUVEC, and BMSCs; 2) Increase the secretion of osteocalcin and mineralization of osteoblasts; 3) Accelerate the apoptosis of osteoclasts; 4) Stimulate the proliferation and regulate the cell cycle of BMSCs. CONCLUSION: Taken together, these results provide the evidence for the osteogenesis, anti-osteoporosis and angiogenesis effects of KFX, with the mechanism of activating the bone formation through stimulating the osteoblasts and HUVECs, as well as inhibiting the bone absorption by inhibiting the osteoclasts activities. The KFX was definitely shown a promising bone turnover agent with great potential for anti-osteoporosis treatment.