Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro.

Overexpression of hypoxia-inducible factor-1 (HIF-1) α, a transcription factor which immortalizes tumors by inducing expression of the genes involved in cell survival, migration and angiogenesis, is closely associated with poor prognosis, increased risk of metastasis and increased mortality. Oligomer procyanidins (F2), a natural fraction from grape seeds, has been demonstrated to have antioxidant and antitumor activities, however the antitumor effect of F2 targeting HIF-1α remains unknown. The present study showed that F2 markedly decreased HIF-1α and the expression of its target genes in cancer cells through inactivating the EGFR-PI3K-AKT-mTOR and MAPK-ERK1/2 pathways. Moreover, F2 suppressed vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 expressions, followed by the inhibition of tumor angiogenesis and cell invasion in a HIF-1α-dependent manner. Collectively, these findings indicate that the antitumor effect of F2 is, at least in part, mediated by suppressing HIF-1α-dependent pathway, and suggest that F2 may be a potentially useful agent for treatment of human cancer.

Clinical characteristics and long-term follow-up analysis of three cases with newborn aristolochic acid nephropathy / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics and prognosis of newborn aristolochic acid nephropathy induced by akebia.</p><p><b>METHOD</b>Retrospective analysis of clinical manifestations, therapy and prognosis was made upon data of 3 newborn infants with renal function lesion induced by akebia.</p><p><b>RESULT</b>Three infants who were fed with Chinese herbal medicines containing akebia trifoliate suffered from acute renal failure, renal glomerular and tubular injury, with symptoms of vomiting, diarrhea, and oliguria. Laboratory tests manifested hyperpotassemia, hyponatremia, elevation of serum creatinine and urea nitrogen, and metabolic acidosis. Renal glomerular lesion was mild, presented with proteinuria and increased serum β(2) microglobin. Renal dysfunction was manifested with alkaline urine, glucosuria, positiveness of urine glucose, ketone and aminoaciduria, and increased urine β(2) microglobin excretion. After symptomatic treatment for 3 to 4 weeks, the renal function of these infants recovered. Proteinuria, aminoaciduria and glucosuria turned negative within 5 to 8 months, 3 months to 1 year, and 9 months to 3 years, respectively. Urine pH decreased to 7.0 after 5.0 - 5.5 years. All cases took citric acid mixtures for 5.5 to 6 years. A 12-years follow-up demonstrated that serum creatinine of 3 cases were within normal range during the first 11 years of life, however recent follow-up showed increased serum creatinine of case 1 and case 2, except for serum creatinine of case 3 remained normal. The estimated glomerular filtration rate (eGFR) of all the 3 cases decreased. Among which, eGFR of case 1 and case 2 were lower than 90 [ml/(min·1.73 m(2))], and decreased 1.1 [ml/(min·1.73 m(2))] and 0.6 [ml/(min·1.73 m(2))] per year during recent six years, respectively. No obvious decrease of eGFR was observed in case 3. Blood gas analysis and urine routine were normal, yet blood and urine β(2) microglobin excretion were still high. Urinary N-acetyl-β-D-glucosaminidase increased again after having returned to normal.</p><p><b>CONCLUSION</b>Newborn aristolochic acid nephropathy induced by akebia might induce acute renal failure and renal tubules injury. Renal function could recover after symptomatic treatment in short-term. Nevertheless, glomerular filtration rate presents a slow descending tendency and renal tubules lesion lasted for many years, which requires a long-term follow-up.</p>

Effect of parenteral glutamine supplementation in premature infants / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glutamine, proposed to be conditionally essential for critically ill patients, is not added routinely to parenteral amino acid formulations for premature infants and is provided in only small quantities by the enteral route when enteral feeding is low. Parenteral feeding is the basic way of nutrition in the first days of life of premature infants. In this study, we evaluated the effects of glutamine supplemented parenteral nutrition for premature infants on growth and development, feeding toleration, and infective episodes.</p><p><b>METHODS</b>From December 2002 to July 2006, 53 premature infants were given either standard or glutamine supplemented parenteral nutrition for more than 2 weeks. Twenty-eight infants were in glutamine supplemented group, whose gestational age (31.4 +/- 2.0) weeks, birth weight range (1386 +/- 251) g; twenty-five infants were in control group, gestational age (31.1 +/- 1.7) weeks, with birth weight range (1346 +/- 199) g. There were no differences between the two groups. Various growth and biochemical indices were monitored throughout the duration of hospital stay. Data between groups were analyzed with Student's t test. Nonparametric data were analyzed using a Chi-square test. A two-tailed P value < 0.05 was considered statistically significant.</p><p><b>RESULTS</b>The level of serum albumin was lower in the glutamine groups on the second week (3.0 vs 3.2 g/dl, P = 0.028), and blood urea nitrogen was higher in glutamine groups on the fourth week (8.1 vs 4.9 mg/dl, P = 0.014), but normal. Glutamine group infants took fewer days to regain birth weight (8.1 vs 10.4 days, P = 0.017), required fewer days on parenteral nutrition (24.8 vs 30.8 days, P = 0.035), with shorter stays in hospital (32.1 vs 38.6 days, P = 0.047). Episodes of hospital acquired infection in glutamine supplemented infants were lower than that in control group (0.96 vs 1.84 times, P = 0.000).</p><p><b>CONCLUSION</b>Parenteral glutamine supplementation in premature infants can shorten days on parenteral nutrition and length of stay in hospital, and decrease hospital acquired infection episodes.</p>