Escherichia coli are one of the commonest bacteria causing bloodstream infection (BSI). The aim of the research was to identify the serotypes, MLST (Multi Locus Sequence Type), virulence genes, and antimicrobial resistance of E. coli isolated from bloodstream infection hospitalized patients in Cipto Mangunkusumo National Hospital Jakarta. We used whole genome sequencing methods rather than the conventional one, to characterized the serotypes, MLST (Multi Locus Sequence Type), virulence genes, and antimicrobial resistance (AMR) of E. coli. The composition of E. coli sequence types (ST) was as follows: ST131 (n = 5), ST38 (n = 3), ST405 (n = 3), ST69 (n = 3), and other STs (ST1057, ST127, ST167, ST3033, ST349, ST40, ST58, ST6630). Enteroaggregative E. coli (EAEC) and Extra-intestinal pathogenic E. coli (ExPEC) groups were found dominant in our samples. Twenty isolates carried virulence genes for host cells adherence and 15 for genes that encourage E. coli immune evasion by enhancing survival in serum. ESBL-genes were present in 17 E. coli isolates. Other AMR genes also encoded resistance against aminoglycosides, quinolones, chloramphenicol, macrolides and trimethoprim. The phylogeny analysis showed that phylogroup D is dominated and followed by phylogroup B2. The E. coli isolated from 22 patients in Cipto Mangunkusumo National Hospital Jakarta showed high diversity in serotypes, sequence types, virulence genes, and AMR genes. Based on this finding, routinely screening all bacterial isolates in health care facilities can improve clinical significance. By using Whole Genome Sequencing for laboratory-based surveillance can be a valuable early warning system for emerging pathogens and resistance mechanisms.

Colorectal cancer (CRC) needs several mutations to occur in various genes, and can vary widely in different individuals; hence it is essential to be discovered in a specific population. Until recently, there has been no known study describing APC, TP53, PIK3CA, KRAS, and MLH1 of CRC in Indonesian population. This study describes the nature and location of mutation in CRC patients treated at three different hospitals in Jakarta. This descriptive study was conducted on CRC patients who underwent neoadjuvant, surgical, and adjuvant therapy at RSCM, RSKJ, and MRCCC in 2017–2018. DNA analysis was performed using next-generation sequencing and aligned against GRCh38. The pathogenic variant was identified using ACMG classification and FATHMM score. Data related to behavior and survival were collected from medical records. Twenty-two subjects in which APC, TP53, and PIKCA were mutated. KRAS mutation occurred in 64%, while MLH1 in 45%. There were five mutation types: nonsense, missense, frameshift, splice-site, and silent mutation. There are four groups of co-occurring mutations: APC, TP53, PIK3CA (triple mutation/TM) alone; TM+KRAS; TM+MLH1; and TM+KRAS+MLH1, presenting different nature and survival. Indonesia has a distinct profile of pathogenic mutation, mainly presenting with locally-advanced stage with various outcomes and survival rate.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis infection. Indonesia is ranked second in the world for TB cases. New anti‐TB drugs from groups A and B, such as bedaquiline, clofazimine, and linezolid, have been shown to be effective in curing drug resistance in TB patients, and Indonesia is already using these drugs to treat patients. However, studies comparing the TB strain types with anti‐TB resistance profiles are still relevant to understanding the prevalent strains in the country and their phenotypic characteristics. This study aimed to determine the association between the TB lineage distribution using whole‐genome sequencing and bedaquiline, clofazimine, and linezolid phenotypic profile resistance among M. tuberculosisrifampicin‐resistant isolates from West Java. M. tuberculosis isolates stock of the Department of Microbiology, Faculty of Medicine, Universitas Indonesia, was tested against bedaquiline, clofazimine, and linezolid using a mycobacteria growth indicator tube liquid culture. All isolates were tested for M. tuberculosis and rifampicin resistance using Xpert MTB/RIF. The DNA genome of M. tuberculosis was freshly extracted from a Löwenstein–Jensen medium culture and then sequenced. The isolates showed phenotypically resistance to bedaquiline, clofazimine, and linezolid at 5%, 0%, and 0%, respectively. We identified gene mutations on phenotypically bedaquiline‐resistant strains (2/3), and other mutations also found in phenotypically drug‐sensitive strains. Mykrobe analysis showed that most (88.33%) of the isolates could be classified as rifampicin‐resistant TB. Using Mykrobe and TB‐Profiler to determine the lineage distribution, the isolates were found to belong to lineage 4 (Euro‐American; 48.33%), lineage 2 (East Asian/Beijing; 46.67%), and lineage 1 (Indo‐Oceanic; 5%). This work underlines the requirement to increase the representation of genotype‐phenotype TB data while also highlighting the importance and efficacy of WGS in predicting medication resistance and inferring disease transmission.

Objective: Sirtuins are protein deacetylases regulating cellular metabolism, lifespan, stress responses, and linked with diseases pathogenesis such as cancer and neurodegenerative diseases. SIRT1, one of human seven sirtuins, the most widely studied today. Hence, identification of SIRT1 drug compound has attracted in drug discovery community. To find good drug candidates could use in insilico methods as a quick tool for analyzing the biological activity of drugs virtually. Method: In silico methods in this research using molecular dynamics simulations that use Indonesia herbal database to identification hits compounds as the SIRT1 inhibitor. Analysis of molecular dynamics simulations in this study includes RMSD (root mean square deviation), RMSF (root mean square fluctuation), molecular mechanism Poisson-Boltzmann/surface area (MMPBSA) and hydrogen bonding. Results: The results showed that hits compounds, dregamine and 5-oxocoronaridine against two of macromolecules SIRT1 (PDB ID: 4I5I and 4ZZI) obtained free energy MMPBSA calculation about -23 kcal/mol Meanwhile occupancy hydrogen bonding of residues Ile347 and Asp348 about 80%. Conclusion: Hits compounds dregamine and 5-oxocoronaridine against two of macromolecules SIRT1 inhibitor (PDB ID: 4I5I and 4ZZI) obtained free energy MMPBSA calculation about -23 kcal/mol meanwhile occupancy hydrogen bonding of residues Ile347 and Asp348 about 80%. Key Words: Sirtuin, SIRT1, Pharmacophore, Herbaldb, Molecular Dynamics Simulations.

Background In 2020, breast cancer has become the most common cancer in the world and in Indonesia. Searching for anticancer drugs using computational methods is considered more effective and selective than other methods. Gallic acid and its derivatives (esters and amides) are compounds that have biological activities such as anticancer effects. The purpose of this study was to analyse the molecular modelling and ADMET (Adsorption, Distribution, Metabolism, Excretion and Toxicity) profile of gallic acid derivative compounds (N-alkyl gallamides) as anticancer agents. Methods Target proteins were selected by analysis of protein-protein and drug-protein interactions. Molecular modelling was done by molecular docking and molecular dynamic simulation. Predictive analysis of the ADMET profile of gallic acid and its derivatives (N-alkyl gallamide) was conducted using Marvin Sketch, Swissadme, protox II, and pkCSM pharmacokinetics. The selected target proteins were JUN, AKT1, CASP3, and CASP7. Results Compounds N-octyl gallamide, N-ters-butyl gallamide, and N-isoamil gallamide were the three best gallic acid derivatives based on molecular modelling analysis of target proteins associated with breast cancer. The ADMET profile of the N-alkyl gallamide compound is predictable and shows a good profile as a candidate for anticancer drugs. Conclusion N-octyl gallamide, N-ters-butyl gallamide, and N-isoamil gallamide have potential as anti-breast cancer agents.

Background In 2020, breast cancer has become the most common cancer in the world and in Indonesia. Searching for anticancer drugs using computational methods is considered more effective and selective than other methods. Gallic acid and its derivatives (esters and amides) are compounds that have biological activities such as anticancer effects. The aim of this study was to perform in-silico and in-vitro analysis of gallic acid derivatives (N-alkyl gallamide) as apoptosis agents for MCF7 breast cancer cells. Methods Target proteins were selected by analysis of protein-protein and drug-protein interactions. Molecular modelling was done by molecular docking. Predictive analysis of the ADMET profile of gallic acid and its derivatives (N-alkyl gallamide) was conducted using Marvin Sketch, Swissadme, protox II, and pkCSM pharmacokinetics. The selected target proteins were JUN, AKT1, CASP3, and CASP7. The MTT method was used to assess the three best compounds for their cytotoxic activity against MCF7 cells, while annexin V-FITC/PI and flow cytometry were used to analyze apoptosis. These tests were based on in-silico research. Results Compounds N-octyl gallamide, N-ters-butyl gallamide, and N-isoamyl gallamide were the three best gallic acid derivatives based on molecular modelling analysis of target proteins associated with breast cancer. The ADMET profile of the N-alkyl gallamide compound is predictable and shows a good profile as a candidate for anticancer drugs. The cytotoxic activity of the three compounds was expressed by their IC50 values of 205.2 ± 0.44 μM, 372.6 ± 4.09 μM, and 441.7 ± 1.41 μM, respectively. The apoptosis activity reaches 55 to 56% compared to control cells. Conclusion N-octyl gallamide, N-ters-butyl gallamide, and N-isoamyl gallamide have potential as an apoptosis agent of breast cancer MCF-7 Cells