ABSTRACT
·AIM: To investigate the relationship between the severity of diabetic retinopathy (DR) in middle-aged and elderly diabetic patients with serum HbA1c and TNF-α. ·METHODS: Totally 200 patients with diabetes mellitus was selected, 60 patients with diabetes mellitus (DM group), 80 patients with non - proliferative diabetic retinopathy ( NPDR) and 60 patients with diabetic retinopathy (PDR),and 80 healthy subjects were selected as normal control group (NC group). Patient's physical examination index was observed, the levels of fasting plasma glucose (FPG), 2h postprandial blood glucose (2hPG), serum lipids, serum HbA1c, serum tumor necrosis factor-α (TNF-α) and tear TNF-α of patients were measured. ·RESULTS:There were significant differences in body mass index (BMI), FPG, 2hPG, total cholesterol (TC), trilycerides (TG), high density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) among the four groups (F= 37.211, 395.421, 42.515, 7.385, 121.764, 121.568, 34.567,P<0.05). The levels of BMI,FPG,2hPG,TC,TG, HDL-C and LDL-C of DM, NPDR and PDR groups were significantly higher than those in the NC group(P<0.05). The levels of BMI, FPG, 2hPG, TC, TG, HDL-C and LDL-C of PDR group were significantly higher than those in the NPDR group (P<0.05). The differences of serum TNF-α,tear TNF-α and serum HbA1c in four groups were statistically significant (F=337.256, 215.471, 40.522, P<0.05). The levels of serum TNF-α,tear TNF-α and serum HbA1c in the DM, NPDR and PDR groups were significantly higher than those in the NC group;the serum levels of serum TNF-α, tear TNF-α and serum HbA1c of the NPDR and PDR groups were significantly higher than those in the DM group (P<0.05), the serum levels of serum TNF-α, tear TNF-α and serum HbA1c of PDR group were significantly higher than those in the NPDR group (P < 0. 05). There was a positive correlation between tear TNF - α and serum TNF-α (r=0.289, P<0.01), and a positive correlation between serum TNF-α and serum HbA1c (r=0.375,P<0.01). ·CONCLUSION: The tear TNF-α levels in middle-aged patients with diabetic retinopathy is higher than normal, and with the increase of retinopathy severity, tear TNF-α levels increases. There is a positive correlation between TNF-α in tear fluid and serum TNF-α and HbA1c.
ABSTRACT
<p><b>BACKGROUND</b>Cathepsin L (CatL) is a cysteine protease with strong matrix degradation activity that contributes to photoaging. Mannose phosphate-independent sorting pathways mediate ultraviolet A (UVA)-induced alternate trafficking of CatL. Little is known about signaling pathways involved in the regulation of UVA-induced CatL expression and activity. This study aims to investigate whether a single UVA irradiation affects CatL expression and activity and whether mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) pathway is involved in the regulation of UVA-induced CatL expression and activity in human dermal fibroblasts (HDFs).</p><p><b>METHODS</b>Primary HDFs were exposed to UVA. Cell proliferation was determined by a cell counting kit. UVA-induced CatL production and activity were studied with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and fluorimetric assay in cell lysates collected on three consecutive days after irradiation. Time courses of UVA-activated JNK and p38MAPK signaling were examined by Western blotting. Effects of MAPK inhibitors and knockdown of Jun and Fos on UVA-induced CatL expression and activity were investigated by RT-PCR, Western blotting, and fluorimetric assay. Data were analyzed by one-way analysis of variance.</p><p><b>RESULTS</b>UVA significantly increased CatL gene expression, protein abundance, and enzymatic activity for three consecutive days after irradiation (F = 83.11, 56.14, and 71.19, respectively; all P < 0.05). Further investigation demonstrated phosphorylation of JNK and p38MAPK activated by UVA. Importantly, inactivation of JNK pathway significantly decreased UVA-induced CatL expression and activity, which were not affected by p38MAPK inhibition. Moreover, knockdown of Jun and Fos significantly attenuated basal and UVA-induced CatL expression and activity.</p><p><b>CONCLUSIONS</b>UVA enhances CatL production and activity in HDFs, probably by activating JNK and downstreaming AP-1. These findings provide a new possible molecular approach for antiphotoaging therapy.</p>
Subject(s)
Child , Child, Preschool , Humans , Anthracenes , Pharmacology , Cathepsin L , Metabolism , Cells, Cultured , Enzyme Inhibitors , Pharmacology , Extracellular Signal-Regulated MAP Kinases , Fibroblasts , Cell Biology , Metabolism , Radiation Effects , Imidazoles , Pharmacology , MAP Kinase Signaling System , Radiation Effects , Oncogene Proteins v-fos , Genetics , Metabolism , Proto-Oncogene Proteins c-jun , Genetics , Metabolism , Pyridines , Pharmacology , Skin , Cell Biology , Ultraviolet RaysABSTRACT
<p><b>AIM</b>To develop high bioavailability preparations without irritation for Panax notoginsenosides.</p><p><b>METHODS</b>The effects of some additives such as microcrystalline cellulose, beta-cyclodextrin and hydroxypropyl cellulose on drug in the preparations were examined.</p><p><b>RESULTS</b>Saponins of Panax notoginseng (PNS) was absorbed in rabbits more when administered intranasally than through other routines, and the formulations including MCC both gave high bioavailability and low irritation.</p><p><b>CONCLUSION</b>Bioavailability of Panax notoginsenosides can be increased through changing routine of administration and formulations.</p>