Aim: To explore the circulating plasma miRNA-21 potential as an early detection biomarker by comparing early-stage breast cancer (BG) and healthy control (HG) in Indonesian population. Materials and methods: The enlisted patients were twenty-six adult female early-stage breast cancer patients (stage 1A, 1B, 2A, and 2B) of Airlangga University Hospital from August until October 2019. Sixteen volunteers were recruited as matched healthy subjects. MiRNA-21 expression was quantified by plasma qRT-PCR. Data analysis performed using IBM SPSS Statistics v.24. MiRNA-21 cutoff , sensitivity, and specificity were analyzed using receiver operating characteristic (ROC) curve. Results: The subject includes 26 BG and 16 HG subjects. The miRNA-21 expression in BG group was 3.933 (1.181-11.794) and 0.905 (0.164-4.532) in HG group (4.34 folds; p=0.001), with 1.66 cutoff (92.3% sensitivity; 81.2% specificity). MiRNA-21 expression separated analysis in HG showed a 0.578 times lower expression in menopause subjects [0.651 (0.164-0.414)] compared to pre-menopause [(1.123 (0.758-4.532); p=0.031]. Yet, in BG group 1.729 times higher miRNA-21 expression was observed in menopause subjects (6.021±3.583) compared to pre-menopause subjects (3.500±1.517;p=0.022). Conclusion: Circulating miRNA-21 expression is a potential biomarker for early detection of breast cancer and might act as a breast cancer risk predictor.
BACKGROUND: Carbohydrate antigens 15-3 (CA 15-3) is a conventional tumor marker in breast cancer, with low sensitivity and specificity. MicroRNA (miRNA)-21 showed its stability in circulation and could serve as powerful biomarker. The aim of this study was to evaluate miRNA-21 as breast cancer biomarker compared to CA 15-3 in Indonesian population.METHODS: Circulating plasma miRNA-21 expression was measured using qRT-PCR in 49 patients at various stages of breast cancer and 16 healthy controls. The relative expression value of miRNA-21 was calculated using 2-ΔΔCt. Meanwhile, CA 15-3 was quantified using electrochemiluminescence immunoassay (ECLIA) methods. The results of miRNA-21 and CA 15-3 plasma circulating expression were compared with controls at each stage and between stages of breast cancer.RESULTS: CA 15-3 median level in breast cancer group was 1.60 times higher compared to control group (p=0.019), 21.00 m/mL and 13.05 m/mL, respectively. Median miRNA-21 expression in breast cancer group was elevated 4.92 folds compared to control group (p=0.001), 4.43 and 0.90, respectively. There was no significant difference of CA 15-3 level between controls and all stages of breast cancer group. CA 15-3 cut-off value was 15.05 m/mL (p=0.016) with 59.2% sensitivity and 62.5% specificity. Meanwhile, there was a significant difference of miRNA-21 expression between controls and most stages of breast cancer group. Circulating miRNA-21 expression cut-off value was 2.07 (p=0.000) with 91.8% sensitivity and 87.5% specificity.CONCLUSION: Circulating miRNA-21 expression and CA 15-3 levels were significantly increased in breast cancer group compared to control group. The miRNA-21 expression increased consistently with breast cancer stage progression. miRNA-21 could serve as superior biomarker compared to CA 15-3.KEYWORDS: biomarker, breast cancer, circulating plasma, liquid biopsy, miRNA-21
Background: An immunoinformatic approach may be useful to investigate the conserved region in the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Indonesia isolates. The aim of this study was to investigate Indonesian SARS-CoV-2 isolates based on B cell epitopes by targeting the conserved regions in the spike glycoprotein to trigger increased multi-variant virus neutralization and memory response for the development of vaccine seed candidates. Methods: SARS-CoV-2 spike glycoprotein gene sequences originating from Indonesia were compared with Wuhan (China), the United Kingdom, South Africa, India, the United States, and Brazil isolates obtained from the NCBI and GISAID databases. The recognition of antigens was carried out directly using B cells through the B cell receptor (BCR). An indirect B cell activation by Cluster of Differentiation (CD)4+ T cells and major histocompatibility complex (MHC)-II was predicted through the binding with human leukocyte antigen (HLA) based on IC50 value. In addition, vaccine allergenicity and toxicity were investigated. During the molecular complex examination, the 3D peptide structure was investigated and the lowest amount of energy formed when the vaccine candidate peptide bound to BCR and MHC-II was calculated. Results: As a result, the spike glycoprotein sequences of Indonesian SARS-CoV-2 isolates had conserved regions which were very similar to reference countries such as China, the United Kingdom, South Africa, India, the United States, and Brazil. Conclusion: It was predicted that the conserved regions could be identified as the epitope of B and T CD4+ cells that produced the peptides for vaccine candidate with antigenic, non-allergen, and non-toxic properties.
Background: Incidents of SARS-CoV-2 in East Java increased steadily, and it became the second epicenter in Indonesia. The COVID-19 pandemic caused a dire multisectoral crisis all around the world. This study investigates and characterizes local isolates from East Java, Indonesia. Methods: There were 54 patients suspected with SARS-COV-2 infection and 27 patients were COVID-19 positive. Virus isolates were obtained from COVID-19 inpatients’ nasopharyngeal swabs at the Dr Soetomo Teaching Hospital, Surabaya. There were only three isolates (#6, #11, #35) with good growth characteristics. Serial blind passage and cytopathic effect observation in the Vero E6 cell line were performed for virus isolation. Confirmation of the SARS-CoV-2 infection was proven by means of reverse transcriptase-polymerase chain reactions using SARS-CoV-2 specific primers, scanning electron microscopy, and scanning transmission electron microscopy examination. Whole genome sequencing was performed using ARTIC protocol. Furthermore, SARS-CoV-2 characterization was identified through a western blot using rabbit serum immunized with inactive SARS-CoV-2 vaccine and human natural COVID-19 infection serum. Results: Spike gene analysis of three samples (#6, #11, #35) found that the D614G mutation was detected in all isolates, although one isolate exhibited the D215Y and E484D mutation. Based on whole genome analysis, those three isolates were included in clade 20A, and two isolates were included in lineage B.1.6 with one isolate belongs to lineage B.1.4.7. Conclusion: Based on molecular characterization and immunogenicity of SARS-CoV-2 East Java, Indonesia showed high titer and it has mutation in some regions.
Purpose: This study aims to evaluate the role of high-sensitivity troponin T (hsTnT) as a complementary tool for determining cardiotoxicity in non-Hodgkin lymphoma (NHL) patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen chemotherapy. Methods: We included 35 patients diagnosed with NHL who received CHOP chemotherapy. Left ventricular ejection fraction (LVEF) and hsTnT were measured at two time points: before the first cycle (pre-test) and after the fourth cycle (post-test). The LVEF and hsTnT were analysed using IBM SPSS version 24 through the paired-sample T-test, Wilcoxon signed-rank test, Pearson’s correlation and Spearman’s correlation. Results: There was a significant difference in both LVEF and hsTnT between pre-chemotherapy and post-4th chemotherapy cycles (p = 0.001). However, more contrast difference from the baseline value of hsTnT compared to LVEF could be observed. LVEF did not detect any deterioration in myocardial function. However, 10 out of 35 subjects exhibit hsTnT higher than the 99th percentile of the population (>14 pg/ml), suggesting that myocardial injury (MI) could be detected. There was no correlation between LVEF and hsTnT (p > 0.05). Conclusion: HsTnT, together with LVEF, could complement each other and offer better coverage for detecting cardiotoxicity during the administration of CHOP in NHL patients. An insignificant correlation between hsTnT and LVEF showed that cardiotoxicity existed in a broad spectrum including cellular damage and functional impairment, as hsTnT represents cellular damage, and LVEF reflects heart functional capacity.
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