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Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are bone marrow disorders characterized by cytopenias and progression to acute myeloid leukemia. Hypomethylating agents (HMAs) are Food and Drug Administration-approved therapies for MDS and MDS/MPN patients. HMAs have improved patients’ survival and quality of life when compared with other therapies. Although HMAs are effective in MDS and MDS/MPN patients, they are associated with significant toxicities that place a large burden on patients. Our goal is to develop a safer and more effective HMA from natural products. We previously reported that black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice. In addition, BRBs exert hypomethylating effects in patients with colorectal cancer and familial adenomatous polyposis. In the current study, we conducted a pilot clinical trial to evaluate the hypomethylating effects of BRBs in patients with low-risk MDS or MDS/MPN. Peripheral blood mononuclear cells (PBMCs) were isolated before and after three months of BRB intervention. CD45 + cells were isolated from PBMCs for methylation analysis using a reduced-representation bisulfite sequencing assay. Each patient served as their own matched control, with their measurements assessed before intervention providing a baseline for post-intervention results. Clinically, our data showed that BRBs were well-tolerated with no side effects. When methylation data was combined, BRBs significantly affected methylation levels of 477 promoter regions. Pathway analysis suggests that BRB-induced intragenic hypomethylation drives leukocyte differentiation. A randomized, placebo-controlled clinical trial of BRB use in low-risk MDS or MDS/ MPN patients is warranted.
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BACKGROUND:Overproduction of thyroid hormones is shown to increase the activities of osteoblasts and osteoclasts, stimulating bone resorption and transformation. Inadequate compensation of increased bone resorption by bone transformation results in an increased loss of bone mass. OBJECTIVE:To investigate the effects of hyperthyroidism on the density of the alveolar bone. METHODS:Twenty-four New Zealand rabbits were equal y randomized into hyperthyroidism group and control group. Rabbits in the hyperthyroidism group or control group were daily injected intraperitoneal y with 50μg/kg levothyrocine diluted in physiological saline solution or equal volume of physiological saline. At 8 weeks after treatment, serum levels of thyroid hormones (FT3 and FT4), alkaline phosphatase, magnesium and calcium, phosphorus were determined;meanwhile, the bone densities of the lumbar vertebra, mandible, bilateral distal femur were determined by dual energy X-ray absorptiometry and the correlation analysis was performed. RESULTS AND CONCLUSION:At 8 weeks after treatment, serum levels of FT3, FT4, alkaline phosphatase calcium, phosphorus, and magnesium in the hyperthyroidism group were significantly increased (P<0.01), while the bone densities of the lumbar vertebra, mandible, bilateral distal femur were significantly decreased (P<0.05), compared with the control group. Bone density of the mandible was positively correlated with the bone density the lumbar vertebra and bilateral distal femur. These findings suggest that the changes in FT3 and FT4 are sufficient for the diagnosis of hyperthyroidism. Hyperthyroidism results in the decreased density of the alveolar bone, indicating the occurrence of osteoporosis.
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<p><b>OBJECTIVE</b>To study the phosphorylation activity of mitochondrial signal transducer and activator of transcription 3 (STAT3) in the myocardium of rats with selenium deficiency and its association with myocardial injury.</p><p><b>METHODS</b>Thirty-six rats were randomized into normal control group (n=18) and selenium deficiency model group (n=18) for feeding with normal and low-selenium chow, respectively, for 20, 30 and 40 weeks. The cardiac function of the rats was evaluated by carotid artery intubation, and the damage of cardiac mitochondria was observed under electron microscopy. The cardiac mitochondria were extracted for assessing succinate dehydrogenase and cytochrome C oxidase activities, and the protein expressions of phosphorylated and total STAT3 were detected.</p><p><b>RESULTS</b>Compared with the corresponding control groups, the rats in the model group showed significantly decreased cardiac function with obvious structural and functional damage of the cardiac mitochondria (P<0.05), which aggravated as the low-selenium feeding time extended (P<0.05). The rats in the model group also showed significantly decreased mitochondrial STAT3 activity (p-STAT3/STAT3) in the myocardium as the low-selenium feeding time prolonged (P<0.05). Pearson linear correlation analysis showed that the activity of cardiac mitochondrial STAT3 had positive correlations with the left ventricular systolic pressure, maximal increased rate of the left ventricular pressure, and the activities of succinate dehydrogenase and cytochrome C oxidase (P<0.01).</p><p><b>CONCLUSION</b>Selenium deficiency down-regulates the activity of mitochondrial STAT3 in rat heart to contribute to cardiac mitochondrial injury and the progression of heart failure.</p>
Subject(s)
Animals , Female , Male , Rats , Diet , Electron Transport Complex IV , Metabolism , Heart Injuries , Metabolism , Mitochondria, Heart , Metabolism , Rats, Sprague-Dawley , STAT3 Transcription Factor , Metabolism , Selenium , Pharmacology , Signal Transduction , Succinate Dehydrogenase , MetabolismABSTRACT
Objective To discuss the emergency management and treatment measures of critically severe craniocerebral trauma.Methods A retrospective study was conducted on the emergency management in 82 patients with critically severe craniocerebral trauma admitted to our hospital from September 2005 to May 2011.Results According to the Glasgow Outcome scale ( GOS),there were 10 patients with good recovery (12％),17 with moderate disability (21％),12 with severe disability (20％),four in vegetable status (2％) and 39 deaths (48％).Conclusion The success rate in the treatment of critically severe craniocerebral injury can be enhanced through rapid and effective pre-hospital care,prompt surgical intervention,standardized subsequent therapy,adherence to damage control surgery concept,and emphasis on prevention and cure of secondary brain injury.
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OBJECTIVE: To observe whether curcumin could inhibit the accumulation of the collagen IV and fibronectin in the glomeruli in nephrotoxi sera nephritis rats. METHODS: Seventy-two healthy male Sprague-Dawley rats were divided into three groups, with 24 animals in each group. For normal control group, normal saline (0.5 ml/d) was injected through intra-caudal-vein for two days, and at the same time normal saline (0.5 ml/kg) was also daily administered intraperitoneally. For nephrotoxic sera nephritis group, nephrotoxic sera (0.5 ml/d) was injected through the tail vein for two days and dimethyl sulfoxide (0.5 ml/kg) was given intraperitoneally daily. For curcumin group, nephrotoxic sera was injected as above and meanwhile curcumin (50 mg.kg(-1).d(-1)) was administered intraperitoneally every day. Six rats in each group were killed on the 3rd, 7th, 14th and 28th day. Their renal tissue was fixed in 10% formalin for examining the expression of collagen IV and fibronectin. RESULTS: Minimal staining of collagen IV and fibronectin was detected in the basement membrane of normal control rats glomeruli. In the nephrotoxic sera nephritis rats and curcumin treated nephrotoxic sera nephritis rats, the accumulation of collagen IV and fibronectin was increased progressively, with significant difference in the accumulation of collagen IV (P<0.01) between these two groups at the same time points, while the significant difference in fibronectin accumulation (P<0.05) appeared only after the 7th days. CONCLUSION: Curcumin can reduce the accumulation of collagen IV and fibronectin in the glomeruli. Hence we postulated that curcumin might have beneficial effect for retarding glomerulosclerosis.
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OBJECTIVE:To study the effects of soluble cluster differentiation 14 (sCD14) on serum pro-and anti-inflammatory cytokines in mice with serious scald endotoxemia. METHODS: A total of 60 healthy Kunming mice were randomly assigned to sCD14 (5 mg?kg-1) group, treatment control group (normal saline) and normal control group (normal saline). The first two groups were established into scald model (scald of 30% body surface area, Ⅲ degree scald) followed by intravenous injection of the corresponding drugs in every 12 h via vena caudalis for 3 consecutive days. On day 4, the model mice were sacrificed to obtain the serum sample for the detection of levels of proinflammatory cytokines (TNF?, IL-6) and anti-inflammatory cytokines (IL-4 and IL-10). RESULTS: In sCD14 treatment group, serum levels of TNF?, IL-6 were significantly lower than in treatment control group (P
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OBJECTIVE:To evaluate the effects of the individualized treatment with GIK(Glucose-insulin-potassium)polarized solution on the discharged surgical patients with hyperglycemia.METHODS:2 287 surgical patients with hyperglycemia(including 125 who had diabetes before hospitalization)receiving individualized treatment with GIK(Glucose-insulin-potassium)polarized solution and who had been discharged from hospital for 1 year were surveyed by questionnaire to collect the data of adverse drug reactions of the polarized solution.RESULTS:None of the patients had secondary diabetes mellitus,hypertension,hypoglycemia or psychological dependence on insulin;0.6% worried about the sequela of GIP;98.5% of the patients who had diabetes prior to hospitalization and have been taking insulin after been discharged from hospital agreed that the symptom of their diabetes was greatly lessened by insulin;100.0% of the patients who had diabetes prior to hospitalization and received no insulin after been discharged from hospital agreed that taking large dose of insulin during hospitalization had no effect on the symptom of their diabetes or hypertension;99.3% of patients received supplemental nutrition of polarized solution;96.9% given hyperglycemia control;38.3% received antiinflammation therapy,5.5% received protective therapy for ? cell function.CONCLUSION:Individual treatment with GIK on the surgical glycemia patients is a safe remedy without sequela.But a few of surgical glycemia patients are afraid of the ADR of the polarized solution,suggesting the importance of publicizing the use of GIK.