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Hao K, Kong FP, Gao YQ, Tang JW, Chen J, Evans AM, Lightman SL, Chen XQ, Du JZ. Inactivation of corticotropin-releasing hormone-induced insulinotropic role by high-altitude hypoxia. Diabetes. 2015;64(3):785–95. In the present study, we explored the role of GAS5 in the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells by regulating the expression of miR-452-5p. The results of this experiment showed that GAS5 was downregulated and miR-452-5p was up-regulated obviously in the HG-induced HK-2 cells. miR-452-5p was demonstrated to be a potential target of GAS5. GAS5 overexpression inhibited the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells by downregulating the expression of miR-452-5p. Celastrol, mainly derived from the root of Tripterygium wilfordii, is a quinone methyl triterpene compound, which is one part of Tripterygium wilfordii [ 1]. In recent years, researchers have carried out many studies on celastrol at the animal level and cellular level, respectively. It has been reported that celastrol plays an anti-inflammatory role in numerous animal pathological models, such as rheumatoid arthritis, collagen-induced arthritis, Alzheimer’s disease, asthma and systemic lupus erythematosus [ 2, 3, 4, 5, 6]. Especially, a recent discovery that celastrol can prevent and treat insulin resistance and obesity has aroused intense attention. The multi-target action of traditional Chinese medicine has the characteristics of multi-effect and multi-use of one drug, which helps to reduce the risk of multi-drug interaction and adverse drug effects. Celastrol not only reduced blood creatinine and urea nitrogen levels in diabetic rats, but also reduced urinary protein excretion, improved renal pathological damage, and down-regulated p38MAPK and NF-κBp65 expression in diabetic rats [ 7]. Celastrol could prevent high glucose (HG)-induced podiatric cell damage, inflammation and insulin resistance by restoring HO-1-mediated autophagy, suggesting a therapeutic strategy for diabetic nephropathy (DN) [ 8]. Celastrol delayed the progression of diabetic liver disease in type 2 diabetic rats by inhibiting the TLR4/MyD88/NF-κB signaling cascade pathway and its downstream inflammatory factors [ 9]. The expressions of AMPK, PGC1α, Sirt3 and MnSOD in skeletal muscle of diabetic patients were decreased, and celastrol partially regulated the AMPK-PGC1α-Sirt3 signaling pathway to exert antioxidant effect on skeletal muscle [ 10]. Celastrol plays a certain role in the improvement of various diabetic complications, but its function in diabetic retinopathy (DR) has not been explored. Taken together, CTPI2- or octyl-D-2-HG-treatment lowered mitochondrial function and shifted the balance of the co-enzymes and energy carrier-molecules NAD and NADP to an oxidative state compared to untreated controls. This pronounced metabolic reprograming may contribute to the effects on cell proliferation and short-term survival of NCI-H460 cells described above. Pharmacologic inhibition of SLC25A1 by CTPI2 sensitizes cancer cells to treatment with inhibitors of end joining pathways alone or in combination with IR in vitro and in vivo
Kim JE, Lee MH, Nam DH, Song HK, Kang YS, Lee JE, Kim HW, Cha JJ, Hyun YY, Han SY, et al. Celastrol, an NF-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice. PLoS ONE. 2013;8(4): e62068. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides in length. Citation7 Recently, various lncRNAs have been studied in the treatment of DN. Citation8 – Citation10 lncRNA MEG3 promoted fibrosis and inflammatory response by targeting the miR-181a in vitro and in vivo experiments of DN. Citation11 Ma et al Citation12 found that lncRNA NEAT1 was increased in the DN cellular model, and silencing of lncRNA NEAT1 suppressed cell proliferation, fibrosis and inflammation but increased cell apoptosis in the DN cellular model. Li et al Citation13 indicated that lncRNA GAS5 was obviously downregulated in ovarian cancer tissues, and GAS5 overexpression inhibited proliferation, colony formation and apoptosis of ovarian cancer cells. Moreover, GAS5 was related to inflammasome formation and pyroptosis in ovarian cancer cells. A previous study has shown that the expression of GAS5 in the serum of diabetic patients is reduced, Citation14 while the effect of GAS5 on DN is unknown. miR-452-5p expression was increased in the umbilical vein endothelial cells of patients with gestational diabetes. Citation15 Therefore, it can be speculated that miR-452-5p is involved in metabolic diseases.
ORIGINAL RESEARCH article
et al. Microarray analysis reveals long non-coding RNA SOX2OT as a novel candidate regulator in diabetic nephropathy. Mol Med Rep. 2018; 18( 6):5058–5068. doi:10.3892/mmr.2018.9534 30320339 If you need additional help with lowering blood sugar levels and do not feel Metformin is suitable for you, then please be aware that in the majority of cases, insulin will be offered as an alternative. Zhang RP, Liu HL. Protective effect of small interfering RNA targeting HIF-1α in retina of diabetic retinopathy mice and its mechanism. Int Eye Ence. 2019;19(12):2017–21.
There are no reported side effects reported from the use of insulin for HG sufferers. The biggest problem with insulin for anyone who is regularly vomiting is that rapid release insulin works with the food eaten at the time injected and if you vomit following eating, there could be concern of having a hypo. Hypos can be managed and controlled, but you should discuss any concerns with your health care professionals. Your diabetes team will best to advise and support you with which course of treatment suits you best. Next, we compared the ability of cells to repair radiation-indued DSBs upon CTPI2 or octyl-D-2-HG treatment by quantifying radiation-induced γ-H2AX foci using flow cytometry [ 28]. Again, treatment with CTPI2 or octyl-D-2-HG in combination with irradiation with a single dose of 5 Gy led to an increase in the number of γ-H2AX compared to irradiation alone. However, in line with the data obtained by the alkaline Comet assay (Fig. 3b), the effects of octyl-D-2-HG treatment on the number of γH2AX foci determined 6 h after irradiation with a single dose of 5 Gy, which was lower compared to CTPI2-treatment (Figs. 3d, S2m). Nevertheless, CTPI2- and octyl-D-2-HG-treatment maintained irradiation-induced DNA damage state at a higher level, supporting an inhibitory effect of both treatments on DNA repair. Diabetes is a kind of metabolic and noncommunicable disease, characterized by a continuous increase of blood glucose, and often involves multiple organs. About 30% of diabetic patients will eventually develop into diabetic nephropathy (DN). Citation1 – Citation3 DN not only has a high incidence rate, but also a high mortality rate, which brings great physical and mental pressure and economic burden to individual family and society. Therefore, how to effectively treat DN has become a focusing problem.
Allison AC, Cacabelos R, Lombardi VR, Alvarez XA, Vigo C. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2001;25(7):1341–57. It has also been reported that GAS5 can regulate the inflammation, oxidative stress and apoptosis in some diseases. For instance, Wang et al Citation16 indicated that GAS5 interference weakened the apoptosis and inflammatory injury in the mouse model of middle cerebral artery occlusion (MCAO). Chen et al Citation17 found that silencing of GAS5 promoted cell viability, cell cycle and oxidative stress in malignant melanoma (MM) cells. In addition, GAS5 interference increased inflammation and reduced pyroptosis, thereby promoting the proliferation of ovarian cancer cells and reducing apoptosis. Citation13 Therefore, the expression of GAS5 was various in different diseases, and changing the expression of GAS5 could alleviate or deteriorate the progression of diseases. The present study indicated that GAS5 overexpression could alleviate the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells.
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