GeneHub software developed by us can be applied to evaluate the significance of expression similarity of genes in each functional unit of different gene function classification systems, and thus to select experiment condition related gene functional units. With different expression similarity measurement and different experiment data, we have applied GeneHub to analyze the expression correlation of functional related genes classified respectively with gene chromosome location, celluar location and interaction, metabolic pathway and signal transduction pathway relationship of protein products of genes. Genes classified according to these multiple ways all showed significant experimental condition related co-expression in our analysis. Our results provide further evidence for the assumption that functional related genes express similarly, which is widely adopted in gene expression profile analysis.
Chromosome Mapping ; methods ; Expressed Sequence Tags ; Gene Expression Profiling ; methods ; Gene Expression Regulation ; physiology ; Humans ; Oligonucleotide Array Sequence Analysis ; methods ; Software ; User-Computer Interface

OBJECTIVETo observe the effect of Huzhang on the progress of pulmonary fibrosis in rats, evaluate the role of Huzhang in this process and explore its mechanism.

METHODWistar male rats were randomized into 7 groups (normal control group, model group, positive control group, prophylactic group, 3rd day treatment group, 7th day treatment group and 14th day treatment group). Bleomycin was administered by intratracheal injection to produce pulmonary fibrosis groups except the normal control group. The positive control group began to be given DXM (4 mL x kg(-1) x d(-1)) on the day of the model-making. The normal control group and model group were given NS (4 mL x kg(-1) x d(-1)) on the day of the model-making. The prophylactic group was given reagent (4 mL x kg(-1) x d(-1)) 2 days ahead of the model-making, whereas the 3rd day treatment group, the 7th day treatment group and the 14th day treatment group given the same dose respectively on the third day, the seventh day and the fourth day behind of the model-making. Lung tissue was stained with hematoxylin-eosin (HE) and Masson's trichrome to determine the pathological grading. The lung fibroblast (LF) was cultured in vitro by way of pancreatic enzyme digestion, which was used to detect the contents of the expression of MMP-2 and TIMP-1mRNA with RT-PCR method.

RESULTCompared with those in the model group, the alveolitis, pulmonary fibrosis and collagen accumulation were significantly alleviated in the positive control group, Huzhang prophylactic group and each treatment groups. In the positive control group, Huzhang prophylactic group, the 3rd day treatment group, the 7th day treatment group and the 14th day treatment group, the expression of MMP-2 mRNA was weaker significantly than that in the BLM model group (P < 0.05 or P < 0.01) except that on the 42nd day. The expression of TIMP-1mRNA was also weaker significantly than that in the BLM model group at all set times in all treatment groups (P < 0.05 or P < 0.01). The inhibition of TIMP-1 lasted until the 42nd day.

CONCLUSIONHuzhang inhibited the expression of MMP-2mRNA and TIMP-1mRNA of lung fibroblast in different periods to reduce the alveolitis and pulmonary fibrosis, which was probably one of the anti-fulmonary fiborsis mechanisms of Huzhang.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Fibroblasts ; drug effects ; metabolism ; Humans ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Pulmonary Fibrosis ; drug therapy ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.