Nur Arfian

Molecular Subtypes, Apoptosis and Proliferation Status in Indonesian Diffuse Large B-Cell Lymphoma Cases

Objective: The diffuse large B-cell lymphoma (DLBCL) has two major molecular subtypes, germinal center B-cell-like (GCB) and non-GCB. These have differing behavior which affects overall patient survival. However, immunohistochemistry based molecular subtyping of Indonesian DLBCLs has been limited. This was the focus of the present study, with a focus of attention on the apoptotic index (AI) and the proliferation index (PI) of the two molecular subtypes. Materials and Methods: During the study period of 3.5 years, a total of 98 cases of DLBCL were identified. Molecular subtypes and PI were determined by immunohistochemistry and TUNEL method was used to determine the AI. Result: GCB accounted for 31 cases (31.6%) and non-GCB the remainder (68.4%). Gender showed a slight male predominance (54 cases, 55.1%), with a higher incidence in the extra-nodal region (57 cases, 58.2%). The AI and PI were significantly higher in GCB (p<0.001 in the Mann-Whitney test) and a Spearman correlation coefficient test showed that PI was positively correlated with AI (r=0.673, p<0.001). Conclusion: The findings indicate that the non-GCB subtype is more common than GCB in Indonesian DLBCL. GCB features significantly higher PI and AI, which themselves appear linked.

Histochemical and Immunohistochemical Study of α-SMA, Collagen, and PCNA in Epithelial Ovarian Neoplasm

Background: Alpha-smooth muscle actin (α-SMA) is an isoform of actin, positive in myofibroblasts and is an epithelial to mesenchymal transition (EMT) marker. EMT is a process by which tumor cells develop to be more hostile and able to metastasize. Progression of tumor cells is always followed by cell composition and extracellular matrix component alteration. Increased α-SMA expression and collagen alteration may predict the progressivity of ovarian neoplasms. Objective: The aim of this research was to analyse the characteristic of α-SMA and collagen in tumor cells and stroma of ovarian neoplasms. In this study, PCNA (proliferating cell nuclear antigen) expression was also investigated. Methods: Thirty samples were collected including serous, mucinous, endometrioid, and clear cell subtypes. The expression of α-SMA and PCNA were calculated in cells and stroma of ovarian tumors. Collagen was detected using Sirius Red staining and presented as area fraction. Results: The overexpressions of α-SMA in tumor cells were only detected in serous and clear cell ovarian carcinoma. The histoscore of α-SMA was higher in malignant than in benign or borderline ovarian epithelial neoplasms (105.3±129.9 vs. 17.3±17.1, P=0.011; mean±SD). Oppositely, stromal α-SMA and collagen area fractions were higher in benign than in malignant tumors (27.2±6.6 vs 20.5±8.4, P=0.028; 31.0±5.6 vs. 23.7±6.4, P=0.04). The percentages of epithelial and stromal PCNA expressions were not significantly different between benign and malignant tumors. Conclusion: Tumor cells of serous and clear cell ovarian carcinoma exhibit mesenchymal characteristic as shown by α-SMA positive expression. This expression might indicate that these subtypes were more aggressive. This research showed that collagen and α-SMA area fractions in stroma were higher in benign than in malignant neoplasms.

Antimigration Activity of an Ethylacetate Fraction of Zanthoxylum acanthopodium DC. Fruits in 4T1 Breast Cancer Cells

Objective: This study was carried out to investigate the antimigration activity of Zanthoxylum acanthopodium DC. in the 4T1 breast cancer cell line. Methods: Zanthoxylum acanthopodium DC. fruit powder was extracted by maceration method with n-hexane and ethylacetate solvents. Cytotoxicity and proliferation were assessed using the MTT method and the cell cycle by flow cytometry. In addition, wound healing assays were conducted by a microscopic method, and expression of COX-2 and VEGFR-2 were determined using qRT-PCR. Results: The IC50 of the ethylacetate fraction (EAF) was 48.1 ± 1.06 µg/mL. The EAE at a concentration 10 µg/mL with viable cells was 62.3 ± 0.28% after 72 h incubation, with accumulation in the G2-M phase, inhibition of cell migration in the wound healing assay, and decrease in expression of COX-2 (0.62 ± 0.01) and VEGFR-2 (0.39 ± 0.003). Conclusion: The results reveal that an ethylacetate fraction of Zanthoxylum acanthopodium DC. fruits provides effective antimigration effects. Further studies are now planned to assess the potential of the ethylacetate fraction to inhibit angiogenesis in breast cancer and determine underlying mechanisms.

Strain Gauge Sensors Implemented in a New Female Torso Model Have Increased Student's Motivation and Confidence in Gynecologic Bimanual Examination on Clinical Skill Training

A good mannequin is needed to improve the quality of clinical skill learning. A strain sensors gauge can be applied into gynecologic bimanual examination mannequin. This study compared a new strain gauge sensors mannequin and non-sensor mannequin for gynecologic bimanual examination training in undergraduate medical student. We made a new female torso model implemented with strain gauge sensors in the definitive landmark, then used this new mannequin for gynecologic bimanual examination training in undergraduate medical student, and evaluated using questioner. We observed 4 parameters: mannequin appearance, student’s self confidence to palpate uterus and ovary, and student’s learning motivation. The new model improved student’s confident to palpate ovary (p<0.05) and student’s motivation (p<0.001) compared to non-sensor mannequin. In contrast, the gross appearance of the new mannequin was inferior (p<0.05). However, there was no difference in defining the uterus position during examination (p>0.05) in both mannequins. A new female torso model with strain gauge sensors can be applied for gynecologic examination training.

Endothelial cell/INS;-derived endothelin-1 exaggerates kidney fibrosis through ETAR activation in renal interstitial cells

excretion, inner medullary (IM) ET receptor (ETR) expression from mice on a NSD or 7 day high salt diet (7DHS) and the response of ET1 mediated epithelial sodium channel (ENaC) activity in flox and CDNOS1KO mice. ET-1 excretion was similar between NSD flox and CDNOS1KO mice (0.14 ± 0.02 and 0.17 ± 0.06 pg/day, n = 10) and significantly increased similarly after a 7DHS (0.60 ± 0.1 and 0.60 ± 0.08 pg/day). IM ETR expression was similar between the mice on a NSD (~40% ETA, ~60% ETB receptors) and similarly shifted to ~95% ETB expression on a 7DHS. Basal CD ENaC open probability (Po) was similar (flox: 0.3 ± 0.08 CDNOS1KO: 0.3 ± 0.05). Acute ET1 treatment significantly reduced ENaC Po from flox mice but not CDNOS1KO mice compared to basal (flox 0.1 ± 0.03 and CDNOS1KO 0.3 ± 0.05, n = 6 animals P b 0.05). In conclusion, CD NOS1 appears not to regulate renal ET-1 production or ETR expression. However, the mechanism of ET-1 inhibition of CD ENaC is via NOS1. We propose that the salt-dependent increase in BP and Na retention observed in CDNOS1KO mice is mediated by the loss of ET signaling in the CD.

Ethanol Extracts of Centella asiatica Leaf Improves Memory Performance in Rats after Chronic Stress via Reducing Nitric Oxide and Increasing Brain-Derived Neurotrophic Factor (BDNF) Concentration

Background: Centella asiatica is herbaceous plant that has medicinal value to improve learning and memory. Brainderived neurotrophic factor (BDNF) has a significant role in memory formation process, while oxidative stress causes memory impairment. Objective: This study aimed to investigate the effects of ethanol extracts of Centella asiatica leaf on memory performance and serum BDNF (neurotrophins) and Nitric Oxide(NO) concentration of rats following chronic electrical stress. Materials and Methods : Twenty male rats (Sprague Dawley) were divided into four groups: control/aquadest group and groups treated with three different doses (mg/kg) of Centella asiatica :150 (CeA150), 300 (CeA300) and 600 (CeA600). Memory performance was tested using probe test in Morris Water Maze before and after oral administration of ethanol extracts of Centella asiatica leaf followed by electrical stress for 28 days. At the last day of memory exercise following chronic stress, blood sample was taken from periorbital veins of all rats. Concentration of serum BDNF and total NO was assessed using ELISA. Data were analyzed using one way ANOVA. Results: Treatment groups had higher percentage in probe test water maze and serum BDNF concentration after chronic stress. Mean time percentage (%) of probe test in water maze performance for control group, CeA150, CeA300, and CeA600 were 53.33+2.43, 55.78+4.16, 63.33+4.07, and 73.55+3.29 (p<0.05). Mean concentration of serum BDNF (ng/ml) for control group, CeA150, CeA300, and CeA600 were 1.52+0.89, 1.49+0.20, 1.73+0.15, and 2.16+0.20 (p<0.05 vs control group). Control group had higher serum NO concentration compared to all treatments groups. Mean concentration of serum NO (μmol/L) for control group, CeA150, CeA300, and CeA600 were 5.94+0.52, 3.98+0.35, 3.06+0.33, and 2.82+0.21 (p<0.05). Conclusion: Ethanol extracts of Centella asiatica leaf increases memory performance and serum BDNF concentration, and also decreases Nitric Oxide levels in rats after chronic stress. Keywordslearning and memory; brain-derived neurotrophic factor; nitric oxide; Centella asiatica.