A Network Pharmacology Approach to Explore the Mechanism of HuangZhi YiShen Capsule for Treatment of Diabetic Kidney Disease.

BACKGROUND AND OBJECTIVE: HuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS. METHODS: Chemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes. RESULTS: 179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20ß, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were IL6, MAPK1, AKT1, RELA, BCL2, JUN, MAPK3, MAP2K1, CASP3, and TNF. Quercetin and Luteolin were verified to have good binding capability with the hub potential targets IL6, MAPK1, AKT1 through molecular docking. CONCLUSION: HZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.

Onychomycosis Associated with Exophiala oligosperma in Taiwan.

A fungus was isolated from a nail of a 54-year-old female patient with onychomycosis in Taiwan. Based on ITS rDNA as well as beta tubulin gene sequences and microscopic analyses, this fungus was identified as Exophiala oligosperma. This is the first record of E. oligosperma in Taiwan. Negative keratin azure test indicates that keratin degradation is not involved in cases of E. oligosperma associated with skin and nail diseases.

Renoprotective effect of berberine on type 2 diabetic nephropathy in rats.

Inflammation, fibrosis, and lipid disorder are essential promoters in the pathogenesis of diabetic kidney injury in diabetes mellitus type 2. Berberine (BBR) has been reported to have beneficial effects on diabetic nephropathy, but its action mechanism is still unclear. The present study was designed to elucidate the therapeutic mechanism of BBR in a type 2 diabetic nephropathy rat model induced by a high-fat diet and low-dose streptozotocin injection. The diabetic rats were treated with or without BBR by gavage for 20 weeks and examined by serology, 24-h albuminuria, histology, immunohistochemistry, and molecular analyses. Results showed that treatment with BBR significantly reduced serum levels of blood glucose and lipids, inhibited urinary excretion of albumin, and attenuated renal histological injuries in diabetic rats. Berberine treatment also inhibited renal inflammation, which was associated with inactivation of nuclear factor kappa-light-chain-enhancer of activated B-cell signalling. As a result, the upregulation of pro-inflammatory cytokines (interleukin-1ß, tumour necrosis factor-α) and chemokine (monocyte chemotactic protein-1) was blocked. In addition, BBR treatment also inactivated transforming growth factor-ß/Smad3 signalling and suppressed renal fibrosis, including expression of fibronectin, collagen I, and collagen IV. The present study reveals that BBR is a therapeutic agent for attenuating type 2 diabetic nephropathy by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell-driven renal inflammation and transforming growth factor-ß/Smad3 signalling pathway.

[Relationship among expression of vascular endothelial growth factor-C(VEGF-C), angiogenesis, lymphangiogenesis, and lymphatic metastasis in oral cancer].

BACKGROUND & OBJECTIVE: There may be a close relationship among the vascular endothelial growth factor-C (VEGF-C) expression, peritumour lymphatic vessels, and lymph node metastasis. The purpose of this study was to compare the relationship among VEGF-C mRNA expression, density of lymphatic and blood vessels, and lymphatic metastasis in oral squamous carcinoma. METHODS: VEGF-C mRNA was determined by RT-PCR. Lymphatic and blood vessel differential stain was determined by enzyme-histochemical technique. Automated image analysis quantification was applied to determine the number of total lymphatic and blood vessels in unit area (TNa). RESULTS: The peri-tumor lymphatic TNa of oral carcinoma was significantly higher in VEGF-C-positive group than those in VEGF-C-negative group(26.42 +/- 5.85: 17.34 +/- 6.48) (P < 0.01), but the blood TNa was a few higher(35.16 +/- 15.55: 33.49 +/- 13.73) (P > 0.05). Lymphatic TNa (30.67 +/- 5.76: 21.94 +/- 5.84) (P < 0.01) and blood TNa (44.19 +/- 14.29: 30.61 +/- 11.82) (P < 0.01) were significantly higher in lymph node metastasis group than those in no-metastasis group. CONCLUSION: VEGF-C mainly promotes peri-tumor lymphangiogenesis and has a little effect on angiogenesis. Simultaneous increase of lymphatic and blood vessels may be related to the synergic expression of VEGF, VEGF-C and their receptors.