The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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The Effect of Nutmeg Seed (M. fragrans) Extracts Induces Apoptosis in Melanoma Maligna Cell’s (B16-F10)
Get PDFBACKGROUND: Nutmeg (Myristica fragrans H.), one of native plants of Maluku Indonesia, has long been used as traditional medicines especially to treat tumors, externally to treat skin infections. M. fragrans also has important biological activities as anticancer. However, antimelanoma activity of M. fragrans remains unknown. The aim of this study is to compare M. fragrans extracts as anticancer on melanoma B16-F10 cells by inducing apoptosis.METHODS: M. fragrans seed was extracted with ethanol then fractionated with n-hexane, ethyl acetate, and n-butanol. B16-F10 melanoma cells were cultured and treated with various doses and tested using resazurin reduction assay. Apoptosis signalling via caspase-3 was measured by using western blot.RESULTS: The extract and fractions of M. fragrans reduced viability of cells with IC50 value for ethanol extract 21.83 µg/mL, ethyl acetate fraction 21.66 µg/mL, n-hexane fraction 47.53 µg/mL, and n-butanol fraction >1,000 µg/mL. The active fraction of ethyl acetate induced apoptosis via caspase-3 proteins similar with cisplatin as positive control in B16-F10 cells at 10 hours treatment.CONCLUSION: Taken together, M. fragrans ethyl acetate fraction has the highest IC50 than n-hexane and n-butanol fractions that significantly inhibited B16-F10 cell proliferation by inducing apoptosis via caspase-3. It provides the insight that it has the most potential activity as a chemopreventive agent for addressing melanoma skin cancer.KEYWORDS: M. fragrans, apoptosis, fraction, melanom
Intratumoral and Peritumoral Apparent Diffusion Coefficient and MGMT mRNA Expression in Different Meningioma Histopathological Grade
Get PDFBACKGROUND: Histopathological examination is the gold standard for diagnosing meningioma and determining the treatments. However, it is invasive in nature. This study was conducted to identify intratumoral and peritumoral apparent diffusion coefficient (ADC) value and mRNA O6-methylguanine-DNA methyltransferase (MGMT) expression in meningioma.METHODS: Data were collected from 39 patients who were clinically diagnosed with meningioma. However, only 37 patients met the inclusion criteria. These subjects then underwent examinations and received treatment from October 2017 to September 2018. Magnetic resonance imaging (MRI) data with diffusion-weighted imaging-apparent diffusion coefficient (DWI-ADC) sequence, histopathological diagnosis of meningioma, and results of MGMT mRNA expression were obtained.RESULTS: The most frequent type of low-grade and overall tumor was meningioma not otherwise specified (56.8%). For high-grade tumor, there were two atypical cases: atypical meningioma (2.7%) and rhabdoid meningioma (2.7%). Meningothelial meningioma had the highest mean value of minimum intratumoral ADC at 864.57±219 x10-3 mm2/s, whereas rhabdoid meningioma had the lowest at 417 x10-3 mm2/s. For minimum peritumoral ADC, rhabdoid meningioma had the highest mean value at 1,651 x10-3 mm2/s, while atypical meningioma has the lowest at 1,281 x10-3 mm2/s. For MGMT mRNA, meningothelial meningioma had the highest mean value at 10±1.2 fold change, whereas rhabdoid meningioma had the lowest mean at 6.18 fold change.CONCLUSION: WHO grade I meningiomas had higher minimum intratumoral ADC values and higher MGMT mRNA expression than the high-grade tumors. Minimum peritumoral ADC values differed across the histopathological grades.KEYWORDS: meningioma, RNA, messenger, MRI, methyltransferases, RT-PCR, ADC, MGMT mRN
Nutritional Biomarkers for Predicting Pancreatic Beta Cell Failure in Central Obesity
Get PDFBACKGROUND: There is a continuous rise in the prevalence of central obesity and become a pressing health problem in the world. Central obesity followed by many metabolic disorders especially Type 2 Diabetes Mellitus (T2DM). The pathogenesis started from overnutrition signal that force pancreatic beta cells to produce a large number of insulin. Low-grade chronic inflammation that occurred also affects the organs sensitivity against insulin and caused beta cells to compensated this situation and at the end become exhausted and loss its function.CONTENT: Along compensation mechanism, certain nutrients were support the beta cells to maintain their mass and function to produce insulin. Short chain fatty acids (SCFAs) are gut microbiota fermentation product that act as nutrient and give an advantage to the proliferation and survivability of the beta cells. Zinc (Zn) also plays an important role in every step of insulin production. Moreover, these nutrients protecting pancreas against inflammation and oxidative stress through certain mechanism. Most of patients with central obesity are unaware of the presence of this disturbance at early stage. Whereas, at molecular level there is a magnitude of SCFAs and Zn level in the blood that would become an early signal and predict the damage of beta cells.SUMMARY: Quantification of these two nutrients in the blood expected to provide an early warning tool to maintain insulin adequacy and predict the possibility of beta cell failure in central obesity with promising performance.KEYWORDS: central obesity, T2DM, SCFAs, Zinc, beta cell failure
Hyaluronic Acid Accelerates VEGF and PDGF Release from Advance Platelet Rich Fibrin in Diabetic Foot Ulcer
Get PDFBACKGROUND: Hyaluronic acid (HA) is an essential component of extracellular matrix and mediates signaling in wound healing. HA could induce growth factor release from Advanced Platelet Rich Fibrin (A-PRF), including Vascular Endothelial Growth Factor (VEGF) and Platelet-derived Growth Factor (PDGF). However, concentrations of the released-VEGF and PDGF have not been clearly disclosed. Therefore, current study was conducted to measure the release of these growth factors in HA + A-PRF gel of diabetic foot ulcer (DFU) subjects.METHODS: Twenty DFU subjects were included in the study and treated with A-PRF or HA+A-PRF. A-PRF was derived from autologous peripheral blood and processed with low-speed centrifugation. HA was added with a ratio of 1:0.6. A-PRF or HA + A-PRF was applied topically on DFU. Upper tips of A-PRF or HA + A-PRF gels were collected on day 0, 3 and 7 for measurements of VEGF and PDGF concentrations with Enzyme-linked Immune-sorbent Assay (ELISA) methods.RESULTS: On day-3, both VEGF and PDGF concentrations of HA + A-PRF group were significantly higher than the VEGF (p=0.000) and PDGF (p=0.019) concentrations of A-PRF group. The VEGF and PDGF concentrations were continuously and significantly increased on day-7 of HA + A-PRF group, compared to the VEGF (p=0.000) and PDGF (p=0.004) concentrations of A-PRF group.CONCLUSION: Combination HA+A-PRF induces VEGF and PDGF release from A-PRF. A mixture of A-PRF and HA could be more effective than A-PRF alone for treatment of DFU.KEYWORDS: hyaluronic acid, advanced platelet rich fibrin, PRF, growth factor, VEGF, PDGF, diabetic foot ulce
Assessment of sdLDL-C by Three Different Formula and Its Correlation with Clinical Variables Among Diabetes Individuals with and without Nephropathy
Get PDFBACKGROUND: Diabetes mellitus is a common disease worldwide which affects renal function. Cardiovascular morbidity and mortality in diabetes patients can be accelerated by dyslipidemia. Small dense lowdensity lipoprotein-cholesterol (sdLDL-C) is atherogenic and its predominance has been known as a cardiovascular risk factor. The study aimed to assess the validity of calculated sdLDL-C using three different formulae and its association with other clinical variables in diabetic patients with and without nephropathy, and also to determine the best suited formula to measure sdLDL-C.METHODS: The study subjects were divided into two groups based on the amount of albumin excreted in the urine. Group I or the control group consisted of diabetic subjects without microalbuminuria, while group II consisted of diabetic subjects with microalbuminuria. Blood glucose, glycated haemoglobin (HbA1c), creatinine, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), LDL-C and apoB were estimated. Three formulae used for the validation of calculated sdLDL-C were TG/HDL, sdLDL (mg/dL) = 0.580 (nonHDL) + 0.407 (direct-LDL-C) – 0.719 (calculated-LDL-C) – 12.05, and LDL-C/LDL apoB.RESULTS: There was no significant difference in sdLDL-C levels of diabetic subjects with and without nephropathy. The sdLDL-C had strong correlation with TC, TG, LDL-C, very-low-density lipoprotein (VLDL), non-HDL and apoB in both study groups. ROC curve showed that LDL-C/LDL apoB derived sdLDL-C had better sensitivity (85%) and specificity (69%) compared to other two measures.CONCLUSION: Though the calculated sdLDL-C do not predict the occurrence of nephropathy in diabetes subjects, it may still be used in conjunction with the traditional markers since it is cost effective. The LDL-C/LDL apoB formula is the best predictor of sdLDL-C among the three equations.KEYWORDS: HDL-C, LDL-C, Microalbuminuria, sdLDL-C, T2D
Mitochondria: Master Regulator of Metabolism, Homeostasis, Stress, Aging and Epigenetics
Get PDFBACKGROUND: Mitochondria became a driving force in evolution due to their ability to manufacture adenosine triphosphate (ATP) through respiration. The functioning of mitochondria within eukaryotic cells has evolved dramatically as a result of evolution. Recent research has revealed mitochondria form plasticity to keep the cell's needs and function.CONTENT: Mitochondria have long been regarded as the cell's "powerhouse," providing energy for cell metabolism through oxidative phosphorylation (OXPHOS). A lot of physiological processes were known to be mediated by mitochondria including immunity and autophagy, cell death mechanism, and stem cell reprogramming. Mitochondria can change their shape to form a tubular network that is controlled by fission and fusion processes. Mitochondrial dynamics is the equilibrium between these two opposing processes that regulates mitochondrial number, size, and positioning within the cytoplasm.SUMMARY: All of these discoveries opened up new research avenues and revealed new targets for targeted medication development. Calorie restriction, and the mimetic agents were developed to increase mitochondria biogenesis to improve human lifespan.KEYWORDS: mitochondria, metabolism, homeostasis, stress response, aging, epigeneti
Association of AID and MUM1 by Immunohistochemistry in Diffuse Large B-Cell Lymphoma
Get PDFBACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with dysregulation of somatic hypermutation (SHM) and class switch recombination (CSR) have been known to contribute for its lymphomagenesis. Activation-induced cytidine deaminase (AID) enzyme plays a vital role for both processes. Multiple myeloma oncogene 1 (MUM1) is known to upregulate the AID expression in normal and pathological conditions. However, both AID and MUM1 expression association in DLBCL is still unexplored using immunohistochemistry method. We examined DLBCL samples and then retrospectively tested its correlation with clinical findings.METHODS: A retrospective cohort study with 20 cases of DLBCL biopsy tissue with AID and MUM1 antibody was conducted. The samples were then classified into concordant (AID+/MUM1+ or AID-/MUM1-) and discordant group (AID-/MUM1+). The clinicopathological comparison was performed to observe any association between immunohistochemistry expression and clinical findings.RESULTS: Among 20 samples of DLBCL, concordant expression rate of AID and MUM1 was 80% with kappa Cohen’s of 0.578 (p=0.004). A significant association was observed between AID and MUM1 expression with a prevalence ratio of 2.25 (95% CI: 1.08-4.67; p=0.008). Clinical characteristics were not significantly different between each group. Restricted mean survival time was shorter in the concordant group compared with the discordant group but statistically insignificant (21.16 vs. 22.5 months; p=0.531).CONCLUSION: The result of this study showed the association between AID and MUM1 expression in DLBCL. However, whether the association may add further molecular heterogeneity of DLBCL is still to be confirmed by expanding the study.KEYWORDS: AID, CSR, DLBCL, MUM1, SH
Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia
Get PDFBACKGROUND: β-thalassemia is an inherited blood disorder that relatively common in Southeast Asian countries. In Indonesia, it is estimated that 200,000 infants with thalassemia carrier born each year. Mutation causing β-thalassemia is highly varied and relatively specific in a population. This study aimed to identify the mutations responsible for β-thalassemia from Thalassemia Carrier Screening conducted in Yogyakarta Special Region. This information is beneficial for developing a strategic prevention program to control thalassemia in the region.METHODS: Twenty-eight blood samples of haematologically suspected β-thalassemia from participant of thalassemia screening program in Yogyakarta Special Region were investigated for β-globin gene mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS) and DNA sequencing.RESULTS: Our samples showed average HbA2 value of 5±0.81% and HbF value of 2±2.29%. It showed eight abnormal erythrocyte morphologies dominated by hypochromia (96.4%), cigar cell (85.7%), and microcytosis (78.6%). Our molecular investigation identified three splice-site mutations namely InterVening Sequence (IVS)-1-5 (G>C) (71.4%), IVS-1-2 (T>C) (7.1%), and IVS-1-1 (G>T) (3.6%), two frameshift mutations that are CD35 (-C) (10.7%) and CD8/9 (+G) (3.6%), and a missense mutation of CD6 (GAG>GTG) (3.6%).CONCLUSION: Our study concluded on a high prevalence of IVS-1-5 (G>C) mutation in Yogyakarta Special Region. This mutation information is significant for developing a strategic prevention program to control thalassemia in the region, for example for developing a rapid molecular test for future screening program.KEYWORDS: β-Globin gene, thalassemia, screening, carrier, mutation, Yogyakart
A Pilot Study on Immunohistochemical Expressions of NF-ĸB, Cyclin-D1, VEGF, and Cox-2 in Advanced Stage Laryngeal Carcinoma
Get PDFBACKGROUND: Progression of laryngeal carcinoma can be classified with the clinical staging, however there are different patterns of progressions observed in the patient with the same clinical stage which also affects their prognoses. Therefore biomarkers should be used. Nuclear factor (NF)-ĸB, Cyclin-D1, vascular endothelial growth factor (VEGF), cyclooxygenase (Cox)-2 have been reported for laryngeal carcinoma. However, it is still unclear how these markers are expressed and correlated in advanced stage laryngeal carcinoma. Therefore current study was conducted to investigate the expressions of NF-ĸB, Cyclin-D1, VEGF and Cox-2 and their correlations in advanced stage laryngeal carcinoma.METHODS: Subjects were recruited and laryngeal biopsies were collected, fixed in formalin and prepared for immunohistochemistry. The immunohistochemistry was performed using mouse monoclonal anti-NF-kB p65, anti-Cyclin-D12 anti-VEGF, and anti-Cox-2 antibodies. The immunohistochemistry results were documented and measured using ImmunoRatio. Pearson or Spearman correlation test was used based on the results of Shapiro-Wilk test of normality. A p-value of less than 0.05 is considered statistically significant.RESULTS: Twelve male subjects were included in this study. Expressions of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 were clearly observed. Mean of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 IHC expression levels measured with ImmunoRatio were 57.50±20.06%, 45.00±24.31%, 43.33±17.23% and 40.42±16.98%, respectively. There was significant correlation between the expressions of VEGF dan Cox-2 (p=0.031, r=0.622).CONCLUSION: Since correlation between the VEGF and Cox-2 expressions was statistically significant, VEGF and Cox-2 might have important roles in the growth, invasion and metastasis of laryngeal carcinoma.KEYWORDS: advanced stage laryngeal carcinoma, immunohistochemistry, NF-ĸB, Cyclin-D1, VEGF, Cox-
Caffeic Acid Inhibits RANKL and TNFa-induced Osteoclastogenesis by Targeting TAK1-p44/42 MAPK
Get PDFBACKGROUND: The potential of the caffeic acid in other important Receptor Activator Nuclear Factor kB Ligand (RANKL)-Tumor Necrosis Factor (TNF)a-induced osteoclastogenic signaling pathways has not been known. Therefore, the current study was conducted to explore as well as to understand the inhibition potential of caffeic acid.METHODS: RAW264.7 cells were cultured, treated with caffeic acid, RANKL and TNFa. Tartrate Resistant Acid Phosphatase (TRAP) staining was performed to detect TRAP+ osteoclast-like polynuclear cells. To detect the activity of p44/42 Mitogen Activated Protein Kinase (MAPK), Akt, and Transforming Growth Factor-β-activated Kinase (TAK)1, the phosphorylated forms of the proteins were investigated with the immunoblotting assay.RESULTS: Pre-treatment of caffeic acid inhibited the RANKL and TNFa-induced differentiation of RAW264.7 cells into TRAP+ osteoclast-like polynuclear cells. RANKL and TNFa induced phosphorylation of p44/42 MAPK at Thr202/Tyr204, phosphorylation of Akt at both Ser473 and Thr308 and phosphorylation of TAK1 at Ser412. Pre-treatment with caffeic acid prior to the RANKL and TNFa induction, inhibited the phosphorylation of MAPK, and TAK1, but not Akt.CONCLUSION: Caffeic acid might regulate the RANKL-TNFa-induced osteoclastogenic pathway in RAW264.7 by targeting TAK1, which later activation of p44/42 MAPK was abolished.KEYWORDS: caffeic acid, osteoclastogenesis, p44/42, Erk1/2, Akt, TAK1, RAW264.7