Hepatocyte growth factor-induced amelioration in renal interstitial fibrosis is associated with reduced expression of -smooth muscle actin and transforming growth factor-1.

Several studies have shown that hepatocyte growth factor (HGF) ameliorates renal interstitial fibrosis, but the mechanism is not fully clear. This study was designed to examine whether HGF can relieve renal interstitial injury in 5/6 nephrectomized rats, and to confirm whether this function was associated with decrease in -smooth muscle actin (-SMA) and transforming growth factor-beta1 (TGF-1) expression. The animals were randomized into 8 groups comprising 6 animals (n = 6) each: control (group I), PCI-neo (group II, 900 μg), sham-operation (group III，not nephrectomy), model or 5/6 nephrectomy group (group IV), lotensin group (an angiotensin converting enzyme inhibitor, group V, 0.6 mg/100 g/day for 5 weeks), low-dose PCI-neo-HGF group (group VI, 690 μg), high-dose PCI-neo-HGF group (group VII, 1380 μg) and lotensin + high-dose PCI-neo-HGF group (group VIII, 0.6 mg/100 g/day for 5 weeks, 1380 μg). The animals were sacrificed in the 5th week after 5/6 nephrectomy. The specimens of kidneys were used for pathological examination (hematoxylin-eosin staining), detection of -SMA and TGF-1 mRNA (Reverse transcriptase-polymerase chain reaction) and protein (Western blot and immunohistochemistry) expression. The results showed that in 5/6 nephrectomized rats blood urea nitrogen (BUN), serum creatinine (CRE) and 24 h urinary albumin excretion (UAE) were increased, renal interstitium was injured seriously and -SMA, TGF-1 mRNA and protein expression were elevated compared with those of control. The above changes were ameliorated and -SMA and TGF-1 expression was reduced by both PCI-neo-HGF and lotensin. The lotensin + high-dose PCI-neo-HGF group rats exhibited the most significant therapeutic effect both in decreasing the BUN, CRE and 24 h UAE and in relieving renal interstitial injury. In conclusion, the study demonstrated that HGF can relieve renal interstitial injury and this protection was associated with down-regulation of –SMA and TGF-1 expressions.

Antitumor screening of deep ocean water and sediment derived fungi and primary investigation of their secondary metabolites / 中国海洋药物

Objective The cytotoxic microbial strains isolated from the deep ocean water and sediments were screened,and the secondary metabolites of bioactive fungus c2b were investi- gated.Methods Active bioactive microbial strains were screened using brine shrimp and chro- nic medulla leucocythemia leukocythemia(K562)cell line.The cytotoxic components of fun- gus c2b were isolated by bioassay-guided fractionation and solvent extraction,silica gel col- umn chromatography and preparative HPLC.Their structures were established by pbysico- chemical properties and spectral analyses.The cytotoxicities of compounds were evaluated by SRB method.Results and Conclusion Twenty-nine strains of fungi were isolated.Among them,seven strains showed cytotoxic activities.Six compounds(1～6)were isolated and i- dentified as N-acetyl histamine(1),chrysogine(2),ergosterol peroxide(3),5,8-epidioxy- 24-methylcholesta-6,22-dien-3?-ol(4)cerevisterol(5)and(4E,8E)-N-[(2'R,3'E)-2'-hy- droxy-3'-hexadecenoyl]-1-O-?-D-glycopyranosyl-9-methyl-4,8-sphingadiene(6),respective- ly.Compound 3 and 4 showed median cytotoxicity.