Protective effects of sinomenine against doxorubicin-induced nephrosis in rats.

Sinomenine (SN, 1) is a pure compound extracted from the Sinomenium acutum plant. We investigated the protective effects and mechanism of action of SN in a rat model of doxorubicin (DOX)-induced nephrosis. Nephrosis was induced by a single dose of 5 mg/kg DOX, and DOX-treated rats received a daily i.p. injection of 10 or 30 mg/kg SN, or saline (n = 6). Urine and serum biochemical parameters, serum TNF-α and IL-1ß levels, nephrin, podocin, α-actinin-4, and peroxisome proliferator-activated receptor-α (PPAR-α) protein expression, and renal ultrastructure were examined at day 28. Compound 1 significantly attenuated the effect of DOX on urine and serum biochemical parameters. Electron microscopy demonstrated that 1 suppressed DOX-induced increases in foot process width. Compared with those in control rats, nephrin, podocin, and PPAR-α protein expressions decreased in the glomeruli of DOX-treated rats, and this effect was significantly attenuated by 1. However, no appreciable alterations were observed in the expression level of α-actinin-4. DOX significantly increased serum TNF-α and IL-1ß compared with those in control rats, and 1 significantly reduced the serum levels of TNF-α and IL-1ß. SN ameliorates DOX-induced nephrotic syndrome in rats, resulting in a modulation of renal nephrin, podocin expression, and thereby protecting podocytes from injury.

Lectin-induced renal local complement activation is involved in tubular interstitial injury in diabetic nephropathy.

BACKGROUND: Complement has been suggested to be involved in diabetic nephropathy (DN), but the exact significance and underlying mechanisms remain unclear. Data about renal local complement activation in DN patients is scarce. The purpose of the study was to clarify the significance and mechanism of renal local complement activation in DN. METHODS: Sixty-two biopsy-proven DN patients were recruited. Renal expression of C1Q, factor B, C5b-9, MBL and MBL-associated serine protease 1 (MASP1) were detected and associated with the kidney damage. RESULTS: C5b-9, MBL and MASP1 was found to increase with the progression of DN. Especially, the level of C5b-9, MBL and MASP1 in tubular interstitium was closely associated with the damage degree of tubular interstitium. In addition, MBL and MASP1 co-localized and their levels in tubular interstitium correlated with the levels of C5b-9 in tubules and tubular interstitium. CONCLUSION: Increased renal local complement activation was present in DN patients and might contribute to the kidney damage, especially tubular interstitial damage. MBL pathway might play an important role in renal tubular interstitial complement activation. Methods against complement activation or MBL pathway might be effective in reducing renal tubular interstitial damage in DN patients.

Longikaurin E induces apoptosis of pancreatic cancer cells via modulation of the p38 and PI3K/AKT pathways by ROS.

Pancreatic cancer is a devastating disease with a poor prognosis. It ranks as the fourth or fifth most common cancer in men and women and has the lowest 5-year survival rate. Therefore, there is an urgent need to develop novel therapeutic agents for pancreatic cancer. Longikaurin E (LE), which is derived from the traditional herbal medicine Rabdosia longituba, had been reported to have anti-proliferative and pro-apoptotic properties in several types of cancers. In this study, we investigated the cytotoxic properties of LE against pancreatic cancer cells and explored the mechanism behind the observed apoptosis. Pancreatic cancer cell lines cultured in the presence of LE exhibited dose- and time-dependent growth suppression by clone formation, methylthiazoltetrazolium assay, lactate dehydrogenase cytotoxicity assay, and fluorescence-activated cell sorting analysis, respectively. In addition, these culture conditions also induced the generation of cellular reactive oxygen species (ROS). In order to determine the mechanisms underlying LE-induced cytotoxicity, we used reverse transcription polymerase chain reaction and Western blot analysis in the pancreatic cancer cell line PANC1. The results showed that the expression of Bax was noticeably upregulated and the expression levels of Bcl-2, Bcl-XL, survivin, and c-Myc were significantly downregulated. We also observed increased p38 phosphorylation and decreased phosphorylation of the PI3K/AKT pathway. Interestingly, we also found that LE activated caspase-3. However, N-acetyl-L-cysteine, a kind of antioxidant, reversed all of these cellular activities. In conclusion, this study suggested that LE induced apoptosis of pancreatic cancer cells via ROS generation to modulate the p38 and PI3K/AKT pathways and could be a promising anti-pancreatic agent.

[Nephrotic syndrome complicated with intracranial venous thrombosis treated with urokinase: report of 5 cases].

OBJECTIVE: To explore the effect of urokinase and low molecular weight heparin in children with nephrotic syndrome complicated with intracranial venous thrombosis. METHODS: Urokinase and low molecular weight heparin were administered to the 5 patients intravenously. The initial dose of urokinase was 2000 - 4000 U/(kg.d), the initial pulse dose was 20 000 - 40 000 U given within 15 - 30 minutes, and the left was infused by using a pump, from the second day 2000 U/(kg.d) urokinase was infused daily for 3 to 7 days. During the treatment thrombin time (TT), activated partial thromboplastin time (APTT) were tested 3 times every week, with particular attention to bleeding. Low molecular weight heparin 100 - 120 AXaIU/kg, 1 or 2 times per day was hypodermally injected for a course of two weeks. Anti-platelet drugs: long-term oral administration of dipyridamole 3 - 5 mg/(kg.d) was applied 2 - 3 times every day for 3 months. RESULTS: The clinical symptoms disappeared after one month of the combined therapy of urokinase, low molecular weight heparin and dipyridamole in 5 cases of nephrotic syndrome complicated with intracranial venous thrombosis in children, the plasma viscosity returned to normal in 1 month, activated partial thromboplastin time, prothrombin time, fibrinogen degradation products returned to normal in 1 to 2 months, venous thrombosis disappeared after 1 to 3 months in head CT or MRI examination, showing the cerebral venous sinus thrombosis complete recanalization without relapse cases in follow-up. CONCLUSION: The early application of urokinase and low molecular heparin and anti-platelet coagulation drugs was effective. The early diagnosis, treatment and prevention of intracranial vein thrombosis in patients with nephrotic syndrome is important.

[Clinical and pathological study of 47 cases with Alport syndrome].

OBJECTIVE: To analyze the clinical and pathological features of children with Alport syndrome (AS). METHODS: A series of 47 patients with AS from unrelated families hospitalized from Jan. 1990 to Jan. 2007 were involved in this study. The clinical and histopathological data were collected and analyzed. RESULTS: Of the 47 cases, 32 were male and 15 female, M/F: 2.1:1. The patient's age ranged from 15 months to 13 years, mean 9 years. Thirty-nine of the 47 cases had positive family history, X-linked dominant inheritance AS was diagnosed in 37 cases, autosomal recessive inheritance AS in 2 cases. Gross hematuria or microscopic hematuria were found in 59.3% of the cases as the first manifestations, while 29.8% showed edema or proteinuria. The major clinical manifestations were isolated hematuria (23.4%), hematuria and proteinuria (36.2%), nephrotic syndrome (29.8%), and renal failure (10.6%). Hematuria and proteinuria existed in all the cases, while only 7 to 13 years children had nephrotic syndrome and renal failure. Of the 47 patients, 33 (70.2%) showed mesangial proliferative glomerulonephritis (MsPGN) under the light microscope, 13 (27.6%) focal segmental glomerulosclerosis (FSGS), 1 (2.1%) membrane proliferative glomerulonephritis (MPGN). For immunofluorescence, there was IgM (40.4%) as the dominant deposition in 19 patients, IgA in 9 (19.1%), IgG in 9 (19.1%), and 10 (21.4%) were negative. Thirty-nine cases showed typical glomerular basement membrane (GBM) pathological changes under electron microscope, while thin basement membrane in 8 cases; 46 showed abnormal skin and/or renal alpha-chain distribution. CONCLUSION: For Alport syndrome, number of male patients was higher than that of female patients. There was a significant difference among different age groups. Hematuria might be present throughout the course, while urine protein increases gradually. MsPGN was the dominant pathological change. The GBM pathological changes in younger children is not typical, so the immunofluorescence test of alpha-chain in collagen IV should be used as an important diagnostic method.