The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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The Correlation of Gamma-Glutamyl Transferase (γ-GT), Glutathione Peroxidase (GPx) and Total Antioxidant Status (TAS) with Inflammatory Marker in Individuals with Metabolic Syndrome
No full textBACKGROUND: γ-GT is known as a primary enzyme that constituent extracellular glutathione catabolism. Various researches have proven that an increase in γ-GT concentration is related to oxidative stress and to components of metabolic syndrome. With individuals having metabolic syndrome as research subjects, our objective is to find the correlation of γ-GT, GPx and SAT.METHODS: This was a cross sectional study done on 36 subjects with metabolic syndrome who met the IDF 2005 criteria. Statistical analysis was carried out using SPSS for Windows ver.11.5 with a significance level of p<0.05. The correlation among biomarkers were assessed using Spearman’s Rho test.RESULTS: γ-GT concentration was correlated negatively with GPx concentration (r=-0.411, p=0.014), but correlated positively with hs-CRP concentration (r=0.385, p=0.022). The increase of γ-GT concentration had a potential risk 8.5 times higher than the increase of hs-CRP concentration, which proved to be more dominant in comparison to its risk to γ-GT/GPx or γ-GT/SAT ratios (p<0.05).CONCLUSIONS: An increase in γ-GT concentration characterizes signs of oxidative stress syndrome and of inflammation in individuals with metabolic syndrome.KEYWORDS: γ-GT, GPx, SAT, inflammation, metabolic syndrom
Aloe Gel Enhances Angiogenesis in Healing of Diabetic Wound
No full textBACKGROUND: Diabetic micro and macroangiophathy lead to the incident of diabetic foot ulcers characterized by an increased number of circulating endothelial cells (CECs) and decreased function of endothelial progenitor cells (EPCs). This fact is correlated with ischemia and diabetic wound healing failure. Aloe vera gel is known to be able to stimulate vascular endothelial growth factor (VEGF) expression and activity by enhancing nitric oxide (NO) production as a result of nitric oxide synthase (NOS) enzyme activity. Aloe vera is a potential target to enhancing angiogenesis in wound healing.OBJECTIVE: The objective of this study was to explore the major role of Aloe vera gel in wound healing of diabetic ulcers by increasing the level of EPCs, VEGF, and endothelial nitric oxide synthase (eNOS), as well as by reducing the level of CECs involved in angiogenesis process of diabetic ulcers healing.METHODS: The experimental groups was divided into five subgroups consisting of non diabetic wistar rats, diabetic rats without oral administration of aloe gel, and treatment subgroup (diabetic rats) with 30, 60 and 120 mg/day of aloe gel doses for 14 days. All subgroups were wounded and daily observation was done on the wounds areas. Measurement of the number of EPCs (CD34), and CECs (CD45 and CD146) was done by flowcytometry, followed by measurement of VEGF and eNOS expression on dermal tissue by immunohistochemical method on day 0 and day 14 after treatment. The quantitative data were analyzed by One-Way ANOVA and Linear Regression, with a cofidence interval 5% and significance level (p<0.05) using SPSS 16 software to compare the difference and correlation between wound diameters, number of EPCs and CECs as well as the levels of VEGF and eNOS.RESULTS: The results of this study showed that aloe gel oral treatment in diabetic wistar rats was able to accelerate the wound healing process. It was shown by significant reduction of wound diameter (0.27±0.02); the increased number of CECs (0.42±0.57), respectively (p<0.05). On the other hand, the wound diameter and eNOS indicators showed significant differences at the dose of 60 mg, while the number of EPCs and CECs and the level of VEGF showed significantly different results at a dose of 120 mg. Aloe gel oral therapy showed a positive indication of wound healing acceleration at the optimum dose range 60-120 mg a day.CONCLUSIONS: Aloe gel is potential to be a herbal therapy candidate for diabetic wound healing through enhancing EPCs homing, decreasing the CECs number, and stimulating the increase of VEGF and eNOS levels,hence proving to be a dominant factor in the angiogenesis process.KEYWORDS: aloe gel, diabetes, wound healing, angiogenesi
Caffeic Acid Inhibits NFkappaB Activation of Osteoclastogenesis Signaling Pathway
No full textBACKGROUND: Caffeic acid (3,4-dihydroxycinnamic acids) is involved in various green plants. Based on our previous report, a major component of sweet potato extracts, possibly caffeic acid, was shown as a promising inhibitor of osteoclastogenesis. However, the effect of caffeic acid in inhibiting osteoclastogenesis needs to be confirmed. The underlying mechanism needs to be disclosed as well.METHODS: Caffeic acid in various concentrations was added to in vitro osteoclastogenesis of receptor activator nuclear factor kB ligand (RANKL)-tumor necrosis factor alpha (TNF-α)-macrophage colony stimulating factor (M-CSF)-induced bone marrow-derived monocyte/macrophage precursor cells (BMMs) and RANKL-TNF-α-induced RAW264 cells D-Clone (RAW-D cells). Tartrate resistant acid phosphatase (TRAP) staining was performed and TRAP-positive polynucleated cells (PNCs) were counted. For apoptosis analysis, caffeic acid-treated BMMs, RAW-D cells and osteoclast-like PNCs were subjected to Sub-G1 Apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. To measure NFkB activity, RAW-D cells were transfected with pNFkB-TA-Luc and subjected to Dual Luciferase Reporter Assay System.RESULTS: Caffeic acid inhibited osteoclastogenesis of RANKL-TNF-α-M-CSF-induced BMMs as well as RANKL-TNF-α-induced RAW-D cells in a dose dependent manner. Caffeic acid did not induce apoptosis in BMMs, RAW-D cells and osteoclast-like PNCs. RANKL-TNF-α-induced NFkB activity in RAW-D was diminished by caffeic acid in a dose dependent manner. Significant NFkB activity inhibtion was observed starting from 1 µg/mL caffeic acid. CONCLUSIONS: Caffeic acid could be a potent osteoclastogenesis inhibitor through inhibition of NFkB activity. Our present study should be further followed up to disclose caffeic acid's possible overlying signaling pathways in inhibiting osteoclastogenesis.KEYWORDS: caffeic acid, osteoclastogenesis, NFkB, RANKL, TNF-
Epigenetic Reprogramming Induced Pluripotency
Get PDFBACKGROUND: The ability to reprogram mature cells to an embryonic-like state by nuclear transfer or by inducing the expression of key transcription factors has provided us with critical opportunities to linearly map the epigenetic parameters that are essential for attaining pluripotency.CONTENT: Epigenetic reprogramming describes a switch in gene expression of one kind of cell to that of another unrelated cell type. Early studies in frog cloning provided some of the first experimental evidence for reprogramming. Subsequent procedures included mammalian somatic cell nuclear transfer, cell fusion, induction of pluripotency by ectopic gene expression, and direct reprogramming. Through these methods it becomes possible to derive one kind of specialized cell (such as a brain cell) from another, more accessible tissue, such as skin in the same individual. This has potential applications for cell replacement without the immunosuppression treatments commonly required when cells are transferred between genetically different individuals.SUMMARY: Reprogramming with transcription factors offers tremendous promise for the future development of patient-specific pluripotent cells and for studies of human disease. The identification of optimized protocols for the differentiation of iPS cells and ES cells into multiple functional cell types in vitro and their proper engraftment in vivo will be challenged in the coming years. Given that the first small molecule approaches aimed at activating pluripotency genes have already been devised and that murine iPS cells have recently been derived by using non-integrative transient expression strategies of the reprogramming factors, we expect that human iPS cells without permanent genetic alterations will soon be generated.KEYWORDS: epigenetics, reprogramming, pluripotency, stem cells, iPS cells, chromatin, DNA methylatio
Correlation of Ghrelin and Obestatin with Waist Circumference in Central Obese Men
No full textBACKGROUND: Central obesity is known as the cause of many metabolic disorders called Metabolic Syndrome. Accumulation of adipocytes in central obesity increases production of cytokines proinflammation. Free fatty acid increases in obesity that drives atherogenic dyslipidemia and insulin resistance. IDF 2005 states that waist circumference (WC) is regarded as the simple criteria of obesity. Energy imbalance lasting for a long period is a determinant factor for obesity, e.g. when energy intake is greater than energy expenditure. The brain and gastrointestinal tract work together to maintain this system. Ghrelin and Obestatin are two gut hormones that work in different ways to keep the energy balance. Ghrelin increases appetite but Obestatin decreases it. The two hormones play an important role in maintaining the dynamic equilibrium of energy balance. This study was aimed to determine correlation of Ghrelin and Obestatin with WC in central obese men.METHODS: This was a cross sectional study involving 53 central obese men. Based on IDF 2005 central obesity is most easily measured by waist circumference using the guidelines ethnic group (not country of residence) specific. We used South Asia ethnic which including Chinese, Malay and Asian Indian population as criteria for this study, that was WC >90 cm, aged 20-60 years. Subjects who had smoking habit, any infectious disease, and ACS were excluded from the study. No restriction was applied on the kind of meals the subjects were having or activities they were doing. The correlation of waist circumference with ghrelin and obestatin was assessed with a significance level of 95% (α=0,05).RESULTS: Patient's age was 40.9623±7.9080 year, waist circumferences was 102.1981±10.2696 cm, weight was 85.8679±16.5475 kg, height was 168.8066±6.3535 cm, BMI was 29.9723±2.4937 kg/m2. Concentration of Ghrelin were 0.70-13.72 ng/mL, and Obestatin 16.66-148.84 pg/mL. Pearson correlation showed that Ghrelin (r=-0.1114, p=0.4271) and Obestatin (r=-0.1781, p=0.2020) had no significant correlation with WC. But in patients WC ≥120 cm had significant negative correlation with Obestatin (r=-0.375, p=0.049).CONCLUSIONS: There was no significant correlation of Ghrelin and Obestatin with WC in obese men. However, there was a negative correlation tendency found in patients with greater WC (≥102 cm).KEYWORDS: obesity, ghrelin, obestatin, waist circumference (WC
Correlation between Systemic Arterial Hypertension and Bone Morphogenetic Protein-2 in Central Obese Non-Diabetic Men with Evidence of Coronary Artery Calcification
No full textBACKGROUND: Previous studies have confirmed separately the relationship between obesity, insulin-resistance, hypertension and bone morphogenetic protein-2 (BMP-2) with coronary artery calcification, a parameter of subclinical atherosclerosis. It was also reported that BMPs may function as proinflammatory, prohypertensive and proatherogenic mediators. The study aimed to assess the correlation between systemic hypertension and BMP-2 plasma concentration in central-obese non-diabetic men with evidence of coronary artery calcification.METHODS: This was a cross sectional study on 60 central-obese non-diabetic men, of an average age of 55.2 years, with evidence of coronary calcification, who came for health check-up and met the inclusion criteria consecutively as defined by waist circumference >90 cm and fasting blood glucose <126 mg/dL. Coronary calcification was defined by coronary artery calcium (CAC) score ≥10 Agatson-unit Dual Source 64 slice CT scan.RESULTS: There is positive correlation between hypertension and BMP-2 in central-obese non-diabetic men with evidence of coronary artery calcification. BMP-2 plasma concentration was higher in the hypertensive subjects. The correlation was stronger in younger (<55 years old) subjects and subjects with insulin-resitance.KEYWORDS: hypertension, BMP-2, coronary calcification, central obesity, age, insulin resistanc
MicroRNAs in Obesity, Metabolic Syndrome and Diabetes Mellitus
Get PDFBACKGROUND: MicroRNAs (miRNAs) are small regulatory RNAs that play important roles in development of diseases. Several studies have provided evidences showing that miRNAs affect pathways that are fundamental for metabolic control in adipocyte and skeletal muscle differentiations. Some miRNAs have been implicated in lipid, amino acid, and glucose homeostasis. This leads to the possibility that miRNAs may contribute to common metabolic diseases and point to novel therapeutic opportunities based on targeting of miRNAs.CONTENT: miRNAs have been recognized as a class of epigenetic regulators of metabolism and energy homeostasis, primarily because the simultaneous regulation of a large number of target genes can be accomplished by a single miRNA. Emerging evidences suggest that miRNAs play a key role in the pathological development of obesity by affecting adipocyte differentiation. miRNAs have been implicated as novel protagonists in the pathogenesis of Diabetes Mellitus (DM), regulation of insulin production, secretion and action. They also appear to play a role in the development of diabetic complications such as nephropathy and cardiac hypertrophy.SUMMARY: Involvement of miRNAs in glucose and lipid metabolism has provided strong evidences to confirm their roles as key players in regulation of complex metabolic pathways. Additionally, it indicates potential outlook for novel therapeutic strategies in the management of obesity, metabolic syndrome and DM. Further research in this field is needed to ascertain the full potential of miRNAs as novel metabolic biomarkers and potent therapeutic agents against obesity and its metabolic disorders.KEYWORDS: obesity, metabolic syndrome, diabetes, miRNAs, adipogenesis, insulin, pancreatic cell
Metaflammation, NLRP3 Inflammasome Obesity and Metabolic Disease
Get PDFBACKGROUND: Increasing prevalence of obesity gives rise to many problems associated with multiple morbidities, such as diabetes, hypertension, heart disease, sleep apnea and cancer. The mechanism of obesity is very complex, thus its link to various disease is poorly understood. This review highlights important concepts in our understanding of the pathogenesis of obesity and related complications.CONTENT: Many studies have tried to explore the exciting and puzzling links between metabolic homeostasis and inflammatory responses. A form of subclinical, low-grade systemic inflammation is known to be associated with both obesity and chronic disease. This, later called as "metaflammation", refers to metabolically triggered inflammation. The nutrient-sensing pathway and the immune response coordination are facilitated by these molecular sites in order to maintain homeostasis under diverse metabolic and immune conditions. Recent studies have found that the NLRP3 inflammasome during metabolic stress forms a tie linking TXNIP, oxidative stress, and IL-1β production. This provides new opportunities for research and therapy for the disease often described as the next global pandemic: type 2 diabetes mellitus (T2DM).SUMMARY: The crucial role of metaflammation in many complications of obesity shown by the unexpected overlap between inflammatory and metabolic sensors and their downstream tissue responses. Then great interest arose to explore the pathways that integrate nutrient and pathogen sensing, give more understanding in the mechanisms of insulin resistance type 2 diabetes, and other chronic metabolic pathologies. A family of intracellular sensors called NLR family is a critical component of the innate immune system. They can form multiprotein complexes, called inflammasome which is capable of responding to a wide range of stimuli including both microbial and self molecules by activating the cysteine protease caspase-1, leading to processing and secretion of the proinflammatory cytokines IL-1β and IL-18, which play crucial roles in host defense. Inflammasome dysregulation has been linked to some autoinflammatory and metabolic diseases. These provide opportunities to continue to improve our understanding of the nature of metaflammation in the hope of modifying it to prevent and treat diseasese.KEYWORDS: Inflammation, metaflammation, inflammasome, metabolic disease, obesit
The Effects of Administration of Mangosteen Pericap's Ethanolic Extract and Xanthone on Angiogenesis of Gastric Ulcer Healing in Wistar Rats Observed Through the Increase in the level of NO and VEGF and CD-31 Expressions
No full textBACKGROUND: NSAIDs can cause gastric ulcer or may delay the healing of it. Upon exposure to indomethacin, gastric ulcer can occur due to oxidants. Mangosteen rind contains xanthone, which is a natural antioxidant. Administration of this antioxidant may increase angiogenesis that can accelerate healing of gastric ulcer.METHODS: This study used an experimental method with randomized post test control only design using Wistar rats. The rats were put on fasting for 24 hours, then a single dose of 30mg/kg body weight (BW) Indomethacine was given. The rats were divided into control group and treatment group. The treatment group was further divided into two subgroups: one group was given a daily 200 mg/kg BW mangosteen pericap extract, and the other group was given 35 mg/kg BW Xanthone. Both the control group and treatment group were decapitated on the 3rd day, 6th day and 12th day, respectively. After decapitation, the stomach of each rat was taken and divided into two portions, one portion was used for NO examination by ELISA, and the other portion for hispathological examination and immunohistochemical analysis for assessing CD 31 and VEGF expressions.RESULTS: Administration of mangoosteen pericap and xanthone could accelerate healing of gastric ulcers as compared with the control, as shown by the decrease in the severity level of the ulcers. Mangoosteen pericap and xanthone could also increase NO, VEGF expression, and CD-31 as compared with the control, especially on the 3rd day of treatment. Explanation of this finding might be that the antioxidants contained in the mangoosteen pericap or in xanthone could bind with radical superoxide and accelerate release of free NO. The increase of NO caused increase of VEGF and CD-31 that could accelerate angiogenesis, which eventually could accelerate healing of the gastric ulcers.CONCLUSIONS: The effect of mangosteen pericap's extract and xanthone can improve healing of gastric ulcers by increasing nitric oxide and also can increase angiogenesis as shown by the increase of VEGF and CD-31 expressions.KEYWORDS: mangosteen, healing, gastric Ulcer, angiogenesi
Inflammation is Associated with Vascular Remodeling - Repairing Balances in Hypertensive Obese Subjects
No full textBACKGROUND: Hypertension and obesity are proinflammatory conditions. Vascular remodeling is one of the pathomechanisms reflecting increased cardiovascular (CV) risks and represented as ratio of MMP-9 and sVEGFR-2 concentration. There is no association confirmed between inflammation and remodeling yet. This study was conducted to investigate the correlation between inflammation and vascular remodeling-repairing balances in hypertensive obese subjects.METHODS: This was a cross–sectional study recruited 34 hypertensive obese subjects and 10 hypertensive non obese subjects. They had no antihypertensive medications, neither diabetics nor renal disease and nor acute inflammation detected. Inflammation was assessed as increased hsCRP concentration. Vascular remodeling and repairing were consecutively represented by ratio of MMP-9 and sVEGFR-2.RESULTS: Concentration of hsCRP and MMP-9 were significantly higher in hypertensive obese group than non obese group (2.094±1.90 vs. 0.714±0.40 mg/L; p=0.029; 363.43±143.64 vs. 261.15±61.13 ng/mL, p=0.035, respectively), nonetheless no significant differences of sVEGFR-2 concentration (9.77±2.30 vs. 9.76±1.38 pg/mL, p=0.980) found in both groups. Ratio of MMP-9/sVEGFR-2 was significantly higher in hypertensive obese group than those in non-obese group (38.67±16 vs. 27.22±10, p=0.038). Likewise, they had more subjects with ratio of MMP-9/sVEGFR-2 ≥31.53. This figure is considered as cut-off point of vascular remodeling versus repairing.CONCLUSION: In hypertensive obese subjects, inflammation was activated and vascular remodeling more dominant than repairing process. Inflammation was associated with increased remodeling-repairing balances.KEYWORDS: Matrix Metalloproteinase-9 (MMP-9), soluble Vascular Endothelial Growth Factor Receptor-2 (sVEGFR-2), high sensitivity C-Reactive Protein (hsCRP)