• Title/Summary/Keyword: Cause of Diabetes

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Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions

  • Reddy, Rallabandi Harikrishna;Kim, Hackyoung;Cha, Seungbin;Lee, Bongsoo;Kim, Young Jun
    • Journal of Microbiology and Biotechnology
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    • v.27 no.5
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    • pp.878-895
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    • 2017
  • Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

Diabetic Foot and Soft Tissue Necrosis Caused by Moxibustion Burn Injury (뜸치료에 의한 화상으로 발생한 당뇨족 및 연부조직 괴사)

  • Han, Song Hyun;Jo, Dong In;Kim, Cheol Keun;Kim, Soon Heum
    • Journal of the Korean Burn Society
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    • v.23 no.2
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    • pp.60-63
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    • 2020
  • A 72-year-old man with diabetes, who underwent moxibustion, developed a foot wound but did not receive proper treatment. Examination showed a soft tissue defect (6×6 cm) on the dorsal aspect of the right foot with involvement of the first and second toes along with some phalangeal bone loss. The wound was treated with a skin graft and healed without complications. The right calf showed a raw surface (4×3 cm), which underwent epithelialization after conservative treatment. We observed four focal necrotic lesions (1.5×1.5 cm) on the right lower leg and anterior chest, which served as indicators of moxibustion, and debridement and primary closure were performed. Moxibustion is increasingly used as a therapeutic option; however, statistical data describing its adverse effects are limited. Moxibustion significantly increases skin temperature and can cause burn injuries. It is important to prevent moxibustion-induced adverse effects and avoid severe complications, particularly in patients with diabetes.

Natural History of the Calcaneal Avulsion Fracture in Neuropathic Arthropathy in a Young Diabetic Patient (A Case Report) (젊은 당뇨 환자에서 신경병성 관절병증 종골 견열 골절의 자연 경과(1예보고))

  • Ko, Young-Chul;Eun, Il-Soo;Jung, Chul-Young;Kim, Jin-Wan;Choi, Hyeon-Soo;Kim, Ok-Gul
    • Journal of Korean Foot and Ankle Society
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    • v.12 no.2
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    • pp.230-233
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    • 2008
  • The avulsion fracture of the calcaneal tuberosity is rare injury. Usually, it occurs from indirect trauma in old patients with osteoporosis or in patients with diabetic neuropathy. Especially, the bone and joint damage occurred in active patient with severe sensory loss or arthropathy related to nerve damage regardless of the cause is referred to neuropathic arthropathy. Generally, a patient with nondisplacement or minimally displacement is treated by conservative therapy and a patient with severe displacement is treated by open reduction and internal fixation. We experienced a 33 years-old woman with diabetes mellitus who had the displaced avulsion fracture of the calcaneal tuberosity without significant trauma and did not treat. We report upon this case at the 2 years follow-up.

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ORI2 is a Strong Inhibitor of Coxsackievirus B4 Replication (오리방풀로부터 분리된 ORI2의 췌장염 유발 콕사키바이러스B4 증식억제)

  • Lim, Byung-Kwan;Jo, Soyeon;Kim, Jin Hee
    • Korean Journal of Pharmacognosy
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    • v.45 no.4
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    • pp.282-287
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    • 2014
  • The ORI2 (3-[3,4-dihydroxyphenyl]acrylic acid 1-[3,4-dihydroxyphenyl]-2-methoxycarbonylethyl ester) was purified from the extract of Isodon excisus. We confirmed the antiviral effect of ORI2 in a coxsackievirus-induced pancreatitis model. Coxsackievirus B4 (CVB4) is a common cause of pancreatitis and may be reason of the type-1 diabetes. Anti-enteroviral compounds were screened by HeLa cell survival assay. Purified natural compounds were added to HeLa cells cultured 96-well plates after $10^4PFU/ml$ CVB4 pre-incubation for 30 min. ORI2 significantly improved HeLa cell survival in a dose-dependent manner. In addition, ORI2 (1 mM) treatment was dramatically decreased virus protease 2A induced eIF4G-I cleavage and viral VP1 capsid protein production. HeLa cell virus titers and viral RNA replication were significantly decreased in ORI2-treatment in a dose dependent manner (1 mM~0.001 mM). These results demonstrate that ORI2 has a strong antiviral effect. It was significantly decreased virus replication. ORI2 may be developed as a potential therapeutic agent for CVB4.

In Search for a Common Pathway for Health Issues in Men - the Sign of a Holmesian Deduction

  • Aoun, Fouad;Chemaly, Anthony Kallas;Albisinni, Simone;Zanaty, Marc;Roumeguere, Thierry
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.1-13
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    • 2016
  • The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions.

Relationships between Breast Cancer and Common Non-Communicable Disease Risk Factors: an Ecological Study

  • Abbastabar, Hedayat;Hamidifard, Parvin;Roustazadeh, Abazar;Mousavi, Seyyed Hamid;Mohseni, Shokrallah;Sepandi, Mojtaba;Barouni, Mohsen;Alizadeh, Ali
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5123-5125
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    • 2013
  • Background: Breast cancer is one the most common cause of cancer-related deaths among women worldwide. The aims of this study were to investigate the impact of dietary factors and health status indicators on breast cancer (BC) incidence. Materials and Methods: Risk factor data (RFD) of 89,404 individuals (15-64 years old) were gathered by questionnaire and laboratory examinations through a cross sectional study from the Non-Communicable Disease Surveillance Centre (NCDSC) of Iran. BC incidences of all provinces through 2001-2006 segregated by age and gender were obtained from the Cancer Registry Ministry of Health (CRMH). Results: a significant positive relationship was seen between diabetes mellitus, fish comsupmption, percent of academic education and non-consumption of fruit, and breast cancer in women. However, non fish consumption, percent age illiteracy and taking fruit showed a significant negative relationship with the incidence of breast cancer. In addition, multiple linear regression analysis showed associations among percentage with academic education, fruit consumption and diabetes. Conclusions: We conclude that dietary factors such as fish and furit consumption, dairy products, health status indicators, academic education, and some diseases like diabetes mellitus can affect the BC incidence, although the results of ecologic studies like this must naturally be interpreted with caution.

Subgingival microbiome in periodontitis and type 2 diabetes mellitus: an exploratory study using metagenomic sequencing

  • Lu, Xianjun;Liu, Tingjun;Zhou, Jiani;Liu, Jia;Yuan, Zijian;Guo, Lihong
    • Journal of Periodontal and Implant Science
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    • v.52 no.4
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    • pp.282-297
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    • 2022
  • Purpose: To explore differences in the subgingival microbiome according to the presence of periodontitis and/or type 2 diabetes mellitus (T2D), a metagenomic sequencing analysis of the subgingival microbiome was performed. Methods: Twelve participants were divided into 4 groups based on their health conditions (periodontitis, T2D, T2D complicated with periodontitis, and generally healthy). Subgingival plaque was collected for metagenomic sequencing, and gingival crevicular fluids were collected to analyze the concentrations of short-chain fatty acids. Results: The shifts in the subgingival flora from the healthy to periodontitis states were less prominent in T2D subjects than in subjects without T2D. The pentose and glucuronate interconversion, fructose and mannose metabolism, and galactose metabolism pathways were enriched in the periodontitis state, while the phosphotransferase system, lipopolysaccharide (LPS) and peptidoglycan biosynthesis, bacterial secretion system, sulfur metabolism, and glycolysis pathways were enriched in the T2D state. Multiple genes whose expression was upregulated from the red and orange complex bacterial genomes were associated with bacterial biofilm formation and pathogenicity. The concentrations of propionic acid and butyric acid were significantly higher in subjects with periodontitis, with or without T2D, than in healthy subjects. Conclusions: T2D patients are more susceptible to the presence of periodontal pathogens and have a higher risk of developing periodontitis. The pentose and glucuronate interconversion, fructose and mannose metabolism, galactose metabolism, and glycolysis pathways may represent the potential microbial functional association between periodontitis and T2D, and butyric acid may play an important role in the interaction between these 2 diseases. The enrichment of the LPS and peptidoglycan biosynthesis, bacterial secretion system, and sulfur metabolism pathways may cause T2D patients to be more susceptible to periodontitis.

Association of Type II Diabetes Mellitus with Hepatocellular Carcinoma Occurrence - a Case Control Study from Kathmandu Valley

  • Jha, Dipendra Kumar;Mittal, Ankush;Gupta, Satrudhan Pd.;Pandeya, Dipendra Raj;Sathian, Brijesh
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5097-5099
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    • 2012
  • Objective: To assess associations of Type II DM with hepatocellular carcinoma occurrence in Nepal. Materials and Methods: This case control study was carried out using data retrieved from the register maintained in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between 1st January, 2012, and 31st August, 2012. The variables collected were age, gender, HbA1c. All biochemical parameters were analyzed in the Central Laboratory of our hospital by standard validated methods. One way ANOVA was used to examine the statistical significant difference between groups with the LSD post-hoc test for comparison of means of case groups. Odds ratios (OR) were calculated using simple logistic-regression analysis. Results: Etiological factors for HCC were HBV, HCV, alcohol and cryptogenic cirrhosis. The highest age group belonged to the etiological category of HCV with a mean of $71.9{\pm}3.6$ (CI 69.3, 74.5) years and the lowest age group to the etiological category of HBV with $61.7{\pm}5.3$(CI 57.9, 65.5) years. The main imperative basis of HCC in present study was HCV (39.5%) and second most significant cause of HCC was alcohol (26%). Glycated hemoglobin was found to be more in males with HCC (7.9%) as compared to females (7.3%). The percentage of Type II diabetes mellitus was greater in HCC patients when compared to controls. This difference was statistically significant with an odd ratio of 4.63 (p<0.001). Conclusion: Type II DM influences incidence, risk of recurrence, overall survival, and treatment-related complications in HCC patients.

Comparison of sevoflurane and propofol anesthesia on the incidence of hyperglycemia in patients with type 2 diabetes undergoing lung surgery

  • Kim, Hyuckgoo;Han, Jisoo;Jung, Sung Mee;Park, Sang-Jin;Kwon, Nyeong Keon
    • Journal of Yeungnam Medical Science
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    • v.35 no.1
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    • pp.54-62
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    • 2018
  • Background: The type and regimen of anesthesia may affect perioperative hyperglycemia following major surgical stress. This study compared the effects of sevoflurane and propofol on the incidence of hyperglycemia and clinical outcomes in diabetic patients undergoing lung surgery. Methods: This retrospective study included 176 patients with type 2 diabetes mellitus who had undergone lung surgery. Blood glucose levels and clinical outcomes from the preoperative period to the first 2 postoperative days (PODs) were retrospectively examined in patients who received sevoflurane (group S, n= 87) and propofol (group P, n=89) for maintenance of general anesthesia. The primary endpoint was the incidence of persistent hyperglycemia (2 consecutive blood glucose levels >180 mg/dL [10.0 mmol/L]) during the perioperative period. The secondary composite endpoint was the incidence of major postoperative complications and 30-day mortality rate after surgery. Results: Blood glucose levels similarly increased from the preoperative period to the second POD in both groups (p=0.857). Although blood glucose levels at 2 hours after surgery were significantly lower in group P than in group S (p=0.022; 95% confidence interval for mean difference, -27.154 to -2.090), there was no difference in the incidence of persistent hyperglycemia during the perioperative period (group S, 70%; group P, 69%; p=0.816). The composite of major postoperative complications and all-cause in-hospital and 30-day mortality rates were also comparable between the two groups. Conclusion: Sevoflurane and propofol were associated with a comparable incidence of perioperative hyperglycemia and clinical outcomes in diabetic patients undergoing lung surgery.

Therapeutic Effect of Doinseunggi-tang on Diabetic Vascular Dysfunction (도인승기탕에 의한 당뇨병성 혈관장애 개선효과)

  • Lee, Yun Jung;Kim, Eon Kuk;Kim, Hye Yoom;Yoon, Jung Joo;Lee, So Min;Lee, Yong-Pyo;Lee, Geon Mok;Kang, Dae Gill;Lee, Ho Sub
    • Herbal Formula Science
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    • v.21 no.1
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    • pp.119-130
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    • 2013
  • Objectives : Diabetes mellitus is the leading cause for vascular complications such as atherosclerosis. The present study is to investigate whether Doinseunggi-tang (DST) improves diabetic vascular dysfunction in type II diabetes. Methods : The db/db mice were treated with high fat/high cholesterol diet and DST (200 mg/kg/day) for 8 weeks. Results : DST significantly lowered blood glucose and systolic blood pressure. In addition, DST also markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol, whereas increased the HDL-cholesterol. Vascular relaxation of aortic rings by acetylcholine or SNP was ameliorated by DST in a dose-dependent manner. Damage of vascular intima and hypertrophic of media was improved by DST. Immunohistological study revealed that DST attenuated the increase of ICAM-1, VCAM-1, and ET-1 expression in thoracic aorta. Conclusions : Taken together, DST suppressed hyperglycemia and diabetic vascular dysfunction in type II db/db mice. The present data suggests that Doinseunggi-tang may be prevent a development of diabetic atherosclerosis.