Uncovering the Mechanisms and Molecular Targets of Weibing Formula 1 against Gastritis: Coupling Network Pharmacology with GEO Database.

Weibing Formula 1, a classic traditional formula, has been widely used clinically to treat gastritis in recent years. However, the potential pharmacological mechanism of Weibing Formula 1 is still unclear to date. A network pharmacology-based strategy was performed to uncover the underlying mechanisms of Weibing Formula 1 against gastritis. Furthermore, we structured the drug-active ingredients-genes-disease network and PPI network of shared targets, and function enrichment analysis of these targets was carried out. Ultimately, Gene Expression Omnibus (GEO) datasets and real-time quantitative PCR were used to verify the related genes. We found 251 potential targets corresponding to 135 bioactive components of Weibing Formula 1. Then, 327 gastritis-related targets were known gastritis-related targets. Among which, 60 common targets were shared between potential targets of Weibing Formula 1 and known gastritis-related targets. The results of pathway enrichment analysis displayed that 60 common targets mostly participated in various pathways related to Toll-like receptor signaling pathway, MAPK signaling pathway, cytokine-cytokine receptor interaction pathway, chemokine signaling pathway, and apoptosis. Based on the GSE60427 dataset, 15 common genes were shared between differentially expressed genes and 60 candidate targets. The verification results of the GSE5081 dataset showed that except for DUOX2 and VCAM1, the other 13 genes were significantly upregulated in gastritis, which was consistent with the results in the GSE60427 dataset. More importantly, real-time quantitative PCR results showed that the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly upregulated and NOS2, EGFR, and IL-10 were downregulated in gastritis patients, while the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly downregulated and NOS2, EGFR, and IL-10 were upregulated after the treatment of Weibing Formula 1. PTGS2, NOS2, EGFR, MMP9, CXCL2, CXCL8, and IL-10 may be the important direct targets of Weibing Formula 1 in gastritis treatment. Our study revealed the mechanism of Weibing Formula 1 in gastritis from an overall and systematic perspective, providing a theoretical basis for further knowing and application of this formula in the future.

Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial-Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis.

BACKGROUND: Tumor cells initiate hypoxia-induced mechanisms to fuel cell proliferation, invasion, and metastasis, largely mediated by low O2-responsive Hypoxia-Inducible Factor 1 Alpha (HIF-1α). Therefore, hyperbaric oxygen therapy (HBO) is now being studied in cancer patients, but its impact upon non-small-cell lung cancer (NSCLC) cell metabolism remains uncharacterized. METHODS: We employed the NSCLC cell lines A549 and H1299 for in vitro studies. Glucose uptake, pyruvate, lactate, and adenosine triphosphate (ATP) assays were used to assess aerobic glycolysis (Warburg effect). A quantitative glycolytic flux model was used to analyze the flux contributions of HIF-1α-induced glucose metabolism genes. We used a Lewis lung carcinoma (LLC) murine model to measure lung tumorigenesis in C57BL/6J mice. RESULTS: HBO suppressed hypoxia-induced HIF-1α expression and downstream HIF-1α signaling in NSCLC cells. One HIF-1α-induced glucose metabolism gene-Phosphofructokinase, Platelet (PFKP)-most profoundly enhanced glycolytic flux under both low- and high-glucose conditions. HBO suppressed hypoxia-induced PFKP transactivation and gene expression via HIF-1α downregulation. HBO's suppression of the Warburg effect, suppression of hyperproliferation, and suppression of epithelial-to-mesenchymal transition (EMT) in hypoxic NSCLC cell lines is mediated by the HIF-1α/PFKP axis. In vivo, HBO therapy inhibited murine LLC lung tumor growth in a Pfkp-dependent manner. CONCLUSIONS: HBO's repression of the Warburg effect, repression of hyperproliferation, and repression of EMT in hypoxic NSCLC cells is dependent upon HIF-1α downregulation. HIF-1α's target gene PFKP functions as a central mediator of HBO's effects in hypoxic NSCLC cells and may represent a metabolic vulnerability in NSCLC tumors.

Discovery and anti-diabetic effects of novel isoxazole based flavonoid derivatives.

3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl] kaempferol is a novel lead compound to discover anti-diabetic and anti-obesity drugs. The present study reported the scaffold hopping of the lead compound to obtain a new isoxazole derivative, C45, which has improved glucose consumption at the nanomolar level (EC50 = 0.8 nM) in insulin resistant (IR) HepG2 cells. Western blotting showed that C45 markedly enhanced the phosphorylation of AMPK (AMP-activated protein kinase) and reduced the levels of the gluconeogenesis key enzymes PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose 6-phosphatase) in HepG2 cells. The potential molecular mechanism of C45 may be activation of the AMPK/PEPCK/G6Pase pathways. We concluded that C45 might be a valuable candidate to discover anti-diabetic drugs.

Effects of Acupoint Application Therapy with TianGui Powder on Osteoporosis in Ovariectomized Rats through TGF-ß1 and Smad2/3 Signaling Pathway.

OBJECTIVES: To explore the effects of acupoint application therapy (AAT) with TianGui Powder (TGP) on the expressions of the transforming growth factor ß1 (TGF-ß1) and Smad-2/3 signaling pathway in ovariectomized osteoporosis rats. METHODS: Sixty rats were randomly divided into four groups: normal group (group A), model group (group B), TGP group (group C), and Western medicine group (group D). Group A had only the corresponding amount of adipose tissue around the ovary removed; rats in the other groups had bilateral ovariectomies. After 1 week, groups A and B were given 1 mL/100 mg normal saline solution by gavage, group C was treated with AAT with TGP on ShenQue acupoint (0.2 piece/rat, 6 h/time, 1 time/d) and group D was given calcium carbonate vitamin D3 (36 mg/kg/d) and alfacalcidol (0.05 µg/kg/d) tablet suspension. In this study, the bone mineral density (BMD) , the levels of BALP, TRAP-5b, and BGP in serum and the changes in bone histomorphology was detected. For acquiring lumbar experimental data, the expression of TGF-ß1, Smad-2/3 proteins and mRNA of TGF-ß1and Smad-2/3 were assessed. After 12 weeks, the data were collected for analysis. RESULTS: Compared with group A, the bone trabecula was thinner and significantly reduced in other groups. The result of BMD improved significantly in both groups C and D compared to group B after intervention (P < 0.05). In contrast, compared to group B, the levels of BALP, TRAP-5b, and BGP significantly declined in both groups C and D. In group C, the results of protein expressions in TGF-ß1, Smad-2/3 were 2.870 ± 0.270, 1.552 ± 0.111, and 1.420 ± 0.079, respectively. In groups C and D, those indications significantly declined compared to group B (P < 0.01). In group C, the level of mRNA expressions of TGF-ß1, Smad-2/3 were 1.872 ± 0.177, 1.672 ± 0.086, and 1.790 ± 0.136, respectively. Compared with group B, those indications had significant difference in groups C and D (P < 0.05). CONCLUSION: Acupoint application therapy with TGP could significantly improve the BMD. The TGF-ß1 and Smad-2/3 signaling pathway could be a therapeutic target of TGP in postmenopausal osteoporosis rats.

[Further promotion effect of variable temperature drying on effective components in roots of Salvia miltiorrhiza f. alba].

To study the effects of different variable temperature drying modes on active components of roots of Salvia miltiorrhiza f. alba, and provide basis for its industrialized drying process. In order to ensure the content of active components, variable temperature drying modes were designed: low temperature at 30 ℃ and high temperature at 60 ℃, low temperature at 30 ℃ and high temperature at 70 ℃, low temperature at 30 ℃ and high temperature at 80 ℃, low temperature at 40 ℃ and high temperature at 60 ℃, low temperature at 40 ℃ and high temperature at 70 ℃, low temperature at 40 ℃ and high temperature at 80 ℃ and air dry oven was used for variable temperature drying process. Then HPLC method was used to determine the changes of active components in roots of S. miltiorrhiza f. alba under different temperature modes; and SPSS 17.0 was used to analyze the data. The results showed that the samples, which were first dried at 40 ℃ for six hours and then dried at 80 ℃ for three hours, had the highest contents in dihydrotanshinone, cryptotanshinone, tanshinone Ⅰ and tanshinone ⅡA as compared with other kinds of drying methods, and the contents were 0.35, 2.76, 0.78, 4.47 mg•g⁻¹, respectively. Additionally, as compared with samples dried in the shade, the contents of dihydrotanshinone, cryptotanshinone and tanshinone Ⅰ were increased 2.9% (P>0.05), 45.3% (P<0.05) and 34.5% (P<0.05), respectively; however, the content of tanshinone ⅡA was decreased by 44.1% (P<0.05). The water-soluble active components (rosmarinic acid and salvianolic acid B) of roots of S. miltiorrhiza f. alba, had the highest contents when the samples were first dried at 30 ℃ for six hours and then 70 ℃ for three hours, and the contents were 3.83,55.44 mg•g⁻¹, increased by 62.3% (P<0.05) and 109.1% (P<0.05) respectively as compared with the samples dried in the shade. Variable temperature drying can significantly affect the contents of active components in roots of S. miltiorrhiza f. alba. As compared with the traditional process of shade-drying process, low temperature drying can significantly increase the content of water-soluble active components and also with significant promotion effect on the liposoluble components such as tanshinone ⅡA, cryptotanshinone and tanshinone Ⅰ. The variable temperature drying mode, can effectively shorten the process of drying and provide theoretical basis for industrial processing of roots of S. miltiorrhiza f. alba.

Intraperitoneal Vancomycin Plus Either Oral Moxifloxacin or Intraperitoneal Ceftazidime for the Treatment of Peritoneal Dialysis-Related Peritonitis: A Randomized Controlled Pilot Study.

BACKGROUND: Intraperitoneal administration of antibiotics is recommended as a first treatment for managing peritoneal dialysis (PD)-related peritonitis. However, the efficacy of oral administration of quinolones has not been well studied. STUDY DESIGN: Randomized controlled pilot study. SETTING & PARTICIPANTS: 80 eligible patients with PD-related peritonitis from Peking University First Hospital (40 in each arm). INTERVENTION: Intraperitoneal vancomycin, 1g, every 5 days plus oral moxifloxacin, 400mg, every day (treatment group) versus intraperitoneal vancomycin, 1g, every 5 days plus intraperitoneal ceftazidime, 1g, every day (control group). OUTCOMES: The primary end point was complete resolution of peritonitis, and secondary end points were primary or secondary treatment failure. MEASUREMENTS: PD effluent white blood cell count. RESULTS: Baseline demographic and clinical characteristics of the 2 groups were comparable. There were 24 and 22 Gram-positive organisms, 6 and 7 Gram-negative organisms, 9 and 10 culture-negative samples, and 1 and 1 fungal sample in the treatment and control groups, respectively. Complete resolution of peritonitis was achieved in 78% and 80% of cases in the treatment and control groups, respectively (OR, 0.86; 95% CI, 0.30-2.52; P=0.8). There were 3 and 1 cases of relapse in the treatment and control groups, respectively. Primary and secondary treatment failure rates were not significantly different (33% vs 20% and 10% vs 13%, respectively). In each group, there was 1 peritonitis-related death and 6 transfers to hemodialysis therapy. During the 3-month follow-up period, 7 and 3 successive episodes of peritonitis occurred in the treatment and control groups, respectively. Only 2 adverse drug reactions (mild nausea and mild rash, respectively) were observed in the 2 groups. LIMITATIONS: Sample size was relatively small and the eligibility ratio was low. Also, the number of peritonitis episodes was low, limiting the power to detect a difference between groups. CONCLUSIONS: This pilot study suggests that intraperitoneal vancomycin with oral moxifloxacin is a safe, well-tolerated, practical, and effective first-line treatment for PD-related peritonitis. Larger adequately powered clinical trials are warranted.

Chemical composition and antioxidant activity of the essential oil of endemic Viola tianshanica.

The composition and in vitro antioxidant activities of the essential oil and methanol extract of the aerial parts of Viola tianshanica were evaluated in this research. GC-MS analysis of the essential oil resulted in the identification of 15 constituents, representing 89.67% of the oil. The major compounds detected in the essential oil were dibutyl phthalate (15.19%), hexadecanoate methyl (8.65%), n-hexadecanoic acid (3.07%) and 2,3-pentanedione (2.62%). Essential oil and methanol extract were tested for their antioxidant activities using 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging and ß-carotene linoleic acid assay. In addition, the total phenol of essential oil, polar subfraction and non-polar subfraction were determined.

Inhibitory effects of Lang-du extract on the in vitro and in vivo growth of melanoma cells and its molecular mechanisms of action.

The purpose of this study is to investigate the effects of Lang-du extract (LDE) from Traditional Chinese Medicine (TCM) Euphorbia fischeriana Steud on the in vitro and in vivo growth of melanoma cells and its molecular mechanisms of action. Our present results have shown that LDE significantly suppressed the in vitro melanoma cell growth in dose- and time-dependent manners. LDE also displayed the synergistic effect with γ-radiation on the reduction of the cell viability in melanoma cells. The animal experimental results further confirmed that compared with the control group without drug treatment, the tumor volume in mice was significantly and time-dependently less in LDE group. The absolute weight of solid tumor in the LDE group was 7-fold lower than that in the control group. Western blot analysis indicated that LDE markedly down-regulated the expression of anti-apoptotic protein Bcl-2 and up-regulated the level of pro-apoptotic protein Bax, eventually leading the reduction of Bcl-2/Bax protein ratios both in the cultured melanoma cells and in the tumors from melanoma-bearing mice. In addition, LDE significantly reduced the tumor progression-associated protein levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor/scatter factor (HGF/SF), and osteopontin (OPN) in tumors from the LDE-treated mice. Our findings suggest that LDE may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of melanoma and other cancer.