Cryptanshinone extract of Salvia miltiorrhiza stimulates pediatric acute myeloid leukemia stem cell apoptosis and the anti-inflammatory mechanism via accelerating microRNA-211-5p to supress Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway activation.

This study was designed to explore cryptanshinone (CPT) extract of Salvia miltiorrhiza stimulating pediatric acute myeloid leukemia (AML) stem cell (LSC) apoptosis and anti-inflammatory mechanism via accelerating microRNA (miR)-211-5p to restrain Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway activation. Obtaining blood samples from pediatric acute myeloid leukemia patients and healthy volunteers and detecting miR-211-5p and JAK2 were performed. Purchase of the human AML cell line KG1a was conducted, and sorting of KG1a cells was to gain LSC. Test of miR-211-5p and JAK2, the phosphorylation of JAK2/STAT3 was implemented. Pretreatment of LSCs was with CPT. Variation of miR-211-5p and JAK2 in LSCs was via plasmid transfection to explore their actions in cell advancement with apoptosis and inflammation. Identification of the targeting of miR-211-5p with JAK2 was implemented. In results: MiR-211-5p was declined in endometrial cancer, while JAK2 was elevated; CPT was available to boost LSC apoptosis and restrain the inflammation; elevated miR-211-5p or repressive JAK2 was available to strengthen the acceleration of CPT on LSCs apoptosis and the repression of inflammation; MiR-211-5p targeted JAK2; augmented JAK2 was available to turn around the action of elevated miR-211-5p. We conclude that CPT extract of Salvia miltiorrhiza stimulated pediatric LSC apoptosis and restrained the inflammation via accelerating microRNA (miR)-211-5p to suppress JAK2/STAT3 pathway activation.

Changes of gene expression profiles across different phases of vascular calcification in rats.

This study investigated the alteration of gene expression profiles in order to gain a deeper understanding into the molecular mechanism involved in different processes of vascular calcification (VC). Sprague Dawley (SD) rats were injected with 300,000 µg/kg vitamin D3 and gavaged with 25 mg/kg nicotine for 8 or 16 weeks to create 8- and 16-week VC calcification groups. Histological analysis and quantification of aortic calcium content were used to determine the severity of vascular calcification. The suppression subtractive hybridization (SSH) method was employed to screen for up and downregulated genes in early and later phases of vascular calcification. Changes in calcium and phosphorus levels in tissue were used as markers of vascular calcification. Quantification of aortic calcium content revealed that vascular calcification might regress over time. In the early phase of vascular calcification, many calcification-promoting genes were upregulated, including ossification, oxidation, and inflammatory genes. In contrast, in later phase of vascular calcification, various calcification-inhibitor genes were highly expressed, including pyrophosphoric acid synthesis genes, glutamate signal peptide-related, reduction activity, and apoptosis regulation genes. The relatively higher expression of calcification-inhibitor genes compared to that of calcification-promoting genes might explain the genetic mechanism leading to the regression of vascular calcification. Therefore, this study provides a genomic basis to facilitate understanding of the molecular mechanism underlying vascular calcification regression.

Randomized clinical trial of intravenous soybean oil alone versus soybean oil plus fish oil emulsion after gastrointestinal cancer surgery.

BACKGROUND: Specific immunonutrients may reduce the incidence of postoperative complications and shorten recovery time. This randomized trial evaluated the clinical efficacy of a fish oil emulsion on outcome and immune function after gastrointestinal cancer surgery. METHODS: A total of 206 patients with gastrointestinal or colonic cancer were randomized to receive isocaloric and isonitrogenous intravenous infusions of either soybean oil alone (1.2 g per kg bodyweight per day; control group, 103 analysed) or soybean plus fish oil emulsion (1.0 and 0.2 g per kg per day respectively; treatment group, 100 analysed) over 20-24 h daily for 7 days after surgery. RESULTS: Baseline data were comparable in the two groups. There were fewer infectious complications (four versus 12 on day 8; P = 0.066), systemic inflammatory response syndrome (SIRS) was significantly less common (four versus 13; P = 0.039) and hospital stay was significantly shorter (mean(s.d.) 15(5) versus 17(8) days; P = 0.041) in the treatment group. Total postoperative medical costs were comparable in the two groups (mean(s.d.) US $ 1269(254) and 1302(324) in treatment and control groups respectively; P = 0.424). The median (interquartile range) difference in CD4/CD8 between days 1 and 8 after surgery was + 0.30 (0.06 to 0.79) in patients receiving fish oil and + 0.20 (-0.19 to 0.55) in controls (P = 0.021). No severe adverse events occurred in either group. CONCLUSION: Fish oil emulsion-supplemented parenteral nutrition significantly reduced SIRS and length of hospital stay. These clinical benefits may be related to normalization of cellular immune functions and modulation of the inflammatory response.

Osteoblastic proliferative activity of Epimedium brevicornum Maxim.

The effect of the extracts of Epimedium brevicornum Maxim. was investigated on proliferative activity in vitro. The osteoblast-like UMR106 cells was employed as an osteoblast model. The EtOH extract and the n-butanol fraction from the crude extract were found to show proliferation stimulating activity. Three flavonoid compounds (icariin, epimedin B and epimedin C) were isolated from this fraction by activity-guided assay, and the effects on cell proliferation were studied. Icariin produced the most significant promoting effect on the proliferation in osteoblast-like UMR106 cells. The results suggested that E. brevicornum Maxim. extracts might have potential activity against osteoporosis, and flavonoids such as icariin might be the active constituents stimulating osteoblasts.

[The role of immune enhanced enteral nutrition on plasma amino acid, gut permeability and clinical outcome (a randomized, double blind, controlled, multi-center clinical trail with 120 cases)].

OBJECTIVE: To evaluate the role of arginine, RNA and omega 3 fatty acid enriched enteral nutrition. METHODS: The study was designed as a prospective, randomized, double blind, multi-central trial. It was an isocaloric and isonitrogenous intake in both groups. The protocol was approved by the Ethic Committee and, written informed consents were obtained. RESULTS: There were 120 patients enrolled in this protocol. After data were input to computer, open the code. 118 out of 120 patients completed the study and, 2 of them were dropped out. One is because the nasal jejunum tubes dropped and not willing to be replaced. Second patient had fistula of anastomosis on 4th days after operation. There were finally 60 patients in the study group and 58 in the control group. There were no liver or renal functions damage and, obvious adverse in both groups. Plasma amino acid profile: There was significant difference (delta) of plasma arginine levels pre- and after study [(33.7 +/- 58.5) mumol/L vs (-2.4 +/- 30.7) mumol/L] (P = 0.004). Intestinal Permeability (lactulose/mannitol ratio): The differences (delta) of lactulose/mannitol ratio pre- and after the study were 0.017 +/- 0.012 in study group and, 0.027 +/- 0.016 in control group. (P = 0.047). Immunological markers: Humoral immunity: The differences of IgM levels pre- and after the study were (0.6 +/- 0.4) g/L in study group and, (0.2 +/- 0.4) g/L in control group(P = 0.006). Cellular immunity: The differences (delta) of CD3 levels pre- and after the study were (3.8 +/- 5.2)% in study group and (0.3 +/- 6.5)% in control group (P = 0.01). In CD4, (3.4 +/- 5.3)% in study group and, (-0.3 +/- 5.7)% in control group (P = 0.032). Clinical Outcomes: There was no infection-related in study group and, 2 abdominal infection patients in control group. No significant difference was found between groups (P = 0.46). The hospital stays were (13 +/- 2.5) days in study group and, (14.5 +/- 3.0) days in control group (P = 0.004). The cost for full hospitalization was (15,122 +/- 6,279) Yuan in study group and, (17,403 +/- 7,091) Yuan in control group. There was 2,281 Yuan lower in study group (P = 0.07). The costs for nutritional drugs were (1,383 +/- 242) Yuan in study group and, (707 +/- 111) Yuan in control group. The difference was 676 Yuan higher in study (P = 0.001). CONCLUSION: Immune enhanced enteral nutrition had better plasma arginine level, intestinal permeability marker, IgM, CD3 and CD4. Also had less hospital stay and, less totaled hospital cost in study group.

Effects of alanyl-glutamine on gut barrier function.

Traditional parenteral nutrition (PN) and chemotherapy may lead to changes of mucosal morphology and gut barrier function. This study investigated the effect of alanyl-glutamine (Ala-Gln) on intestinal morphology and gut barrier function in PN-fed rats challenged with 5-fluorouracil (5-FU). Male Wistar rats were centrally catheterized and then randomized to receive PN devoid of glutamine (control group; n = 10) or 3% Ala-Gln-supplemented PN (study group; n = 10) for 7 d. Intestinal permeability to lactulose and mannitol was measured before and 72 h post 5-FU administration on day 4. Serum glutamine concentration and jejunal mucosal structure were maintained in the study group compared with the control group (P < 0.05). The bacterial translocation rates of mesenteric lymph nodes in the study group were significantly lower than the control (30% versus 90%; P < 0.05). No significant differences was found between the control and study groups with respect to ratio of lactulose and mannitol excreted in urine (L/M) (0.026 +/- 0.005575 versus 0.022 +/- 0.03079; P > 0.05) on day 3. On day 7, L/M was unaltered in the study group, whereas it increased in the control (0.042 +/- 0.004634 versus 0.029 +/- 0.002020; P < 0.05). We concluded that glutamine dipeptide maintained intestinal mucosal morphology and barrier function in PN-fed rats challenged with 5-FU.

Alanyl-glutamine preserves hepatic glutathione stores after 5-FU treatment.

Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. 5-fluorouracil (5-FU) considered the most active antineoplastic agent in the treatment of advanced gastrointestinal malignancies, causes hepatic GSH depletion. Glutamine (GLN) augments host defenses and may be important in GSH synthesis. We hypothesized that alanyl-glutamine (ALA-GLN) may protect liver cells from oxidant injury, like GLN, by increasing hepatic GSH stores. Two rat groups received standard parenteral nutrition (STD) supplemented with or without ALA-GLN for 7 days. After the antineoplastic agent 5-FU was injected, the concentration measurements were significantly different in ALA-GLN group compared with STD animals for serum GLN (687.3 +/- 49.8 vs. 504.9 +/- 38.6 uMol/L, P < 0.05), serum GSH (14.37 +/- 5.16 vs. 7.08 +/- 3.16 uMol/L, P < 0.01) and in liver GSH content (6.86 +/-2.46 vs. 4.38 +/-1.63 uMol/g liver tissue, P < 0.05). Rats in ALA-GLN group had lower elevations in hepatic enzymes induced by 5-FU. The experiment demonstrated that the supplemented nutrition ALA-GLN, like glutamine, protected the liver function and improved survival during 5-FU treatment by increasing GSH biosynthesis and by preserving the GSH stores of hepatic tissue.

Comparison of parenteral nutrition supplemented with L-glutamine or glutamine dipeptides.

Although glutamine is an important fuel used by the intestinal mucosa and other visceral organs, it is not present in any commercially available parenteral amino acid solution. To compare the effects of L-glutamine with glutamine dipeptides, we studied the effects of each in 8 dogs and 60 Wistar rats. In the dog study, three amino acid solutions were compared: standard commercial amino acid solution (control), alanine-glutamine dipeptide-enriched solution (glutamine 3.4%), and glycine-glutamine dipeptide-enriched solution (glutamine 3.6%). Arterial and venous samples were collected to compare the effects of the three solutions on skeletal muscle amino acid exchange. In the rat study, two studies were undertaken: group 1 rats underwent only central venous catheterization; group 2 rats underwent central venous catheterization and a 50% intestinal resection. Within each group, three different solutions were infused: standard amino acid solution (control), glutamine-enriched (1.5% glutamine) solution, or glutamine dipeptide-enriched (1% glutamine) solution. After 7 days of parenteral nutrition, samples of gut, blood, and muscle were collected for determination of mucosal thickness, villus area, serum amino acid profile, liver and renal function tests, and muscle composition. When glutamine or glutamine-dipeptide solutions were administered, the dogs showed increasing serum glutamine concentrations and enhanced glutamine uptake across the hind leg muscle. Similarly, both groups of rats demonstrated significant differences in serum glutamine levels, nitrogen balance, intestinal mucosa thickness, and villus area. We conclude that both glutamine and glutamine-dipeptide infusions increase serum glutamine concentrations and result in regional tissue effects. Both exerted similar metabolic effects with no apparent complications.

Postoperative fall in serum zinc concentrations unaffected by intravenous zinc therapy.

The serum zinc levels and urinary zinc outputs before and after a middle severity operative trauma were investigated. The serum zinc concentration dropped markedly 6 hr after operation in both supplemented and nonsupplemented groups. It gradually returned to near normal without exogenous supplies of zinc. Provision of therapeutic doses of zinc could not prevent the abrupt dip of the serum zinc level. The possible mechanism of such changes are discussed briefly.