Computational identification of novel signature of T2DM-induced nephropathy and therapeutic bioactive compounds from Azanza garckeana.
Bashir LawalYu-Cheng KuoSunday Amos OnikanniYi‐Fong ChenTawakaltu Abdulrasheed-AdelekeAdewale Oluwaseun FadakaJanet Olayemi OlugbodiHalimat Yusuf LukmanFemi OlawaleMohamed H. MahmoudGaber El‐Saber BatihaAlexander T.H. WuHsu‐Shan Huang
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Diabetic nephropathy (DN) is one of the most prevalent secondary complications associated with diabetes mellitus. Decades of research have implicated multiple pathways in the etiology and pathophysiology of diabetic nephropathy. There has been no reliable predictive biomarkers for the onset or progression of DN and no successful treatments are available.In the present study, we explored the datasets of RNA sequencing data from patients with Type II diabetes mellitus (T2DM)-induced nephropathy to identify a novel gene signature. We explored the target bioactive compounds identified from Azanza garckeana, a medicinal plant commonly used by the traditional treatment of diabetes nephropathy.Our analysis identified lymphotoxin beta (LTB), SRY-box transcription factor 4 (SOX4), SOX9, and WAP four-disulfide core domain protein 2 (WFDC2) as novel signatures of T2DM-induced nephropathy. Additional analysis revealed the pathological involvement of the signature in cell-cell adhesion, immune, and inflammatory responses during diabetic nephropathy. Molecular docking and dynamic simulation at 100 ns conducted studies revealed that among the three compounds, Terpinen-4-ol exhibited higher binding efficacies (binding energies (ΔG) = -3.9~5.5 kcal/mol) against the targets. The targets, SOX4, and SOX9 demonstrated higher druggability towards the three compounds. WFDC2 was the least attractive target for the compounds.The present study was relevant in the diagnosis, prognosis, and treatment follow up of patients with diabetes induced nephropathy. The study provided an insight into the therapeutic application of the bioactive principles from Azanza garckeana. Continued follow-up invitro validations study are ongoing in our laboratory.Cite
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Diabetes mellitus is a worldwide major health problem mostly associated with End Stage Renal Disease (ESRD). In most countries diabetic nephropathy has become the single most frequent cause of ESRD which requires Renal Replacement Therapy. The incidence of reported ESRD is 4.3% with type-1 diabetes mellitus and 4.5% with type-2 diabetes mellitus. The Glycosylated haemoglobin (HbA1c) is widely accepted and used as the most reliable test for assessing chronic glycemia. The HbA1c reflects overall blood glucose levels over a period of 2-3 months and further, used to monitor diabetic treatment. Therefore, in the present investigation a biochemical approach of the HbA1c in diabetes associated nephropathy is proposed to explore in Chhattisgarh population. The study was undertaken including both male and female subjects and the fasting blood sugar, post prandial blood sugar, HbA1c, urea and creatinine were analyzed in the blood. The result indicated that the levels of fasting, post-prandial blood sugar and glycosylated haemoglobin were elevated significantly (P<0.05) in diabetes associated nephropathy compared to control and nephropathy, however, there was no change compared to diabetes. Further, urea level increased significantly (P<0.05) in both nephropathy and diabetes associated nephropathy compared to both control and diabetes. Similarly, creatinine level increased significantly (P<0.05) in both nephropathy and diabetes associated nephropathy compared to both control and diabetes. Moreover, the creatinine level decreased significantly (P<0.05) in diabetes associated nephropathy compared to nephropathy only. In conclusion,glycosylated haemoglobin along with creatinine level would be an important tool in the pathobiogenesis and management of diabetes associated nephropathy.
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Glycemic variability in patients with diabetes mellitus and different stages of diabetic nephropathy
The relevance of the study of glycemic variability in patients with diabetes mellitus and diabetic nephropathy is due to disability of the able-bodied population and high mortality against the background of the almost irreversible progression of diabetic nephropathy. The article highlights modern ideas about the influence of various factors on the occurrence of diabetic nephropathy and its course. The article is devoted to a review of current recommendations on diabetes mellitus and diabetic nephropathy; the etiopathogenesis of diabetic nephropathy was described in detail. The role of the kidneys in glucose homeostasis, renal gluconeogenesis, and glucose reabsorption by the kidneys in healthy and in pathology is described. Detailed expositions of glycemic variability parameters, their changes in patients with diabetes mellitus depending on the stage of diabetic kidney damage are presented. The role of the kidneys in maintaining energy homeostasis, impaired glucose homeostasis in conditions of chronic kidney disease is described. We analyzed different options for insulin therapy, their advantages, and disadvantages in patients with diabetes mellitus with diabetic nephropathy. The presented material is extremely relevant for the development and implementation in the clinical practice of glycemic control methods to optimize treatment tactics, prevent the formation of microvascular complications, and early disability of patients with diabetes mellitus.
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Objective:To diagnose and treat diabetes mellitus(DM)in time,and prevent diabetic nephropathy.Methods:Retrospectively analyzing the clinical data of 86 cases DN patients during the last seven years.Results:46 cases got better,32 cases didn't get better even got worse,8 cases died.Conclusion:There is no special treatment for DN,besides to control blood glucose,blood pressure and blood fat strictly.And early diagnosis and treatment can improve patients'living quality and decrease the incidence of diabetic nephropathy and death rate.
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In a busy diabetes clinic, it is always easy for the diabetologist to equate nephropathy and diabetes to “diabetic nephropathy”. Certain clinical clues should arouse suspicion of non-diabetic renal disease as this may have important implications in patient management. We report a case of multiple myeloma in a patient with diabetes presenting as “diabetic nephropathy”.
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Pathogenesis
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About 246 million people worldwide had diabetes in 2007. The global figure of people with diabetes is projected to increase to 370 million in 2030. As the prevalence of diabetes has risen to epidemic proportions worldwide, diabetic nephropathy has become one of the most challenging health problems. Therapeutic options such as strict blood glucose and blood pressure controls are effective for preventing diabetic nephropathy, but are far from satisfactory, and the number of diabetic patients on end‐stage renal disease is still increasing. Therefore, a novel therapeutic strategy that could halt the progression of diabetic nephropathy should be developed. There is accumulating evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate under diabetes, play a role in diabetic nephropathy via oxidative stress generation. In this paper, we review the pathophysiological role of AGEs and their receptor (RAGE)‐oxidative stress system in diabetic nephropathy.
RAGE
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Introduction: Diabetic nephropathy is an important complication of diabetes mellitus leading to significant morbidity and mortality. Objectives: To study the awareness of diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM) and the factors influencing patient awareness of diabetic nephropathy. Patients and Methods: Four hundred subjects, aged above 18 years with T2DM as per American Diabetes Association (ADA) criteria, were selected. Patient awareness regarding diabetic nephropathy was assessed as per a prefixed questionnaire. Results: Awareness of basic information concerning diabetes was present in more than 60% of patients. No significant differences were seen between awareness scores of male and female (P = 0.385), rural and urban (P = 0.120) and literate and illiterate (P = 0.567) diabetic patients. Awareness scores were higher in diabetic patients exceeding 50 years of age (P = 0.004) and patients having diabetes for more than10 years (P < 0.0001), controlled diabetes (P = 0.026) and diabetic nephropathy (P < 0.0001). Awareness of diabetic nephropathy was independently associated with duration of diabetes (P = 0.010) and diabetic nephropathy (P = 0.011) but not with age (P = 0.754) and control of diabetes (P = 0.229). Conclusion: A substantial proportion of diabetic patients are still unaware of the basic facts about diabetes and diabetic nephropathy. Awareness of diabetic nephropathy depended upon duration of diabetes and presence of diabetic nephropathy and requires promotion during early stages of diabetes to improve control of diabetes and prevent diabetic nephropathy.
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Type 2 diabetes mellitus which is an universal public health problem is associated with the development of micro- and macrovascular complications. Complications of diabetes on eyes, kidneys and nerves are well documented but studies on lung involvement in diabetes and its correlation with nephropathy are sparse. This study was taken to assess pulmonary functions in patients with diabetic nephropathy and to find out correlation of pulmonary function with duration of diabetes and assess the prevalence pulmonary hypertension in patients with nephropathy.This was a cross-sectional study which included 50 diabetic subjects, 50 diabetics with overt nephropathy, and 50 healthy subjects without diabetes as the control group. Diabetic subjects were matched to the control group in terms of age, sex, and BMI. Pulmonary function tests were performed and the results were compared between groups. Pulmonary artery pressures were assessed by 2D ECHO and results were interpreted using SPSS 21.0 version for windows.Mean FEV 1% was 98.12 (+/-10.06), 75.88 (+/-14.10) and 57.64 (+/-13.49), Mean FVC% was 86.78 (+/- 8.77), 69.82(+/-13.88) and 53.02(+/-13.41), The mean PEF% was 88.62 (+/-14.47), 59.40 (+/-18.59) and 48.96 (+/-20.94) among healthy subjects with no diabetes, diabetes mellitus group and diabetic nephropathy group respectively and the difference observed was statistically significant (p value <0.001). Restrictive pattern of lung function impairment was observed in diabetic patients which was more pronounced in Diabetic nephropathy group. Mean FEV1% was 71.03 (+/-13.19), 66.74 (+/-18.34) and 60.29 (+/-15.25),Mean FVC% was 65.66 (+/-11.06), 60.79 (+/-18.00) and 56.38 (+/-16.55) was observed among the participants having diabetes less than 10yrs, 10 to 20 years and > 20 years respectively. The difference in mean FEV1%, FVC % with duration of DM was not statistically significant. PAH was present in 3 patients (6%) in diabetes mellitus group and in 20 (40%) in diabetes nephropathy group and the difference observed was statistically significant p < 0.0001. FEV1, FVC and PEF % were significantly reduced in PAH group when compared to the No PAH group with p values <0.0001.This study showed that Pulmonary function tests are impaired in diabetics, showing a restrictive pattern and impairment was pronounced in diabetics with nephropathy. Derangement of pulmonary functions was independent of duration of diabetes. Pulmonary hypertension was more common in diabetic nephropathy group.
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Objective To observe the effect of monitoring diabetes nephropathy be the examination diabetes of patients U-mAlb. Methods The levels of U-mALb by dot immune gode filtration assay(DIFA) in 49 dependent diabetic patients. Results The levels of GHb and U-mALB in diabetes mellitus with nephropathy were significantly higher than those in contrds.The values of GHb were positively associated with the values of U-Alb(p0.05) Conclusions The values of GHb and U-mALb were higher the diabetes mellitus were more dangerous. detection of U-mALb is great importance for early discovery diabetes nephropathy.
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