Genome-Wide Association Study in Pigmentation as One of Skin Aging Characteristics

Skin aging is a physiological process marked by changes in the skin's structure, giving rise to the characteristics of skin aging, such as pigmentation. Genome-Wide Association Studies (GWAS) identify genetic profiles that play a role in skin aging characteristics such as pigmentation. This study aimed to gather information about candidate SNPs and genes related to pigmentation characteristics of skin aging across different populations. We systematically searched relevant articles published in PubMed and ProQuest in the last ten years. Out of 212 articles screened, seven studies pertinent to our research are included in the analysis. Results indicated that in European and East Asian populations, several gene candidates such as IRF4, MC1R, ASIP, BNC2, PPARGC1B, RAB11FIP2, and CYP1A associated with SNPs that are known to have functions related to skin aging. However, further comprehensive analysis is needed to understand the functional correlation between SNP or gene candidates and pigmentation. In addition, the diversity of the subjects in the GWAS is still concerning. The future comprehensive analysis of GWAS, which involves underrepresented ones, is needed to broaden the knowledge of skin aging mechanisms across different populations

COMBINATION OF SAMBILOTO (ANDROGRAPHIS PANICULATA (BURM.F.) NEES) EXTRACT AND SPIRULINA (ARTHROSPIRA PLATENSIS GOMONT) TO PREVENT ANEMIA IN MICE INFECTED WITH PLASMODIUM BERGHEI ANKA

Objective: Anemia in acute malaria occurs because there is massive lysis of erythrocytes as a result of an increase in parasitemia or use of drugs that may induce hemolysis. In this research, it was tested the effect of administration of a combination of sambiloto (Andrographis paniculata Nees) extract and spirulina (Arthrospira platensis Gomont). This combination is aimed to obtain antiparasite activity of sambiloto and increasing of hemoglobin (Hb) from spirulina.Methods: This research was conducted with a completely randomized design using 75 mice of Swiss Webster strain. Test groups were consisted of AP, AP+ES, AP+PS, carboxymethyl cellulose, and dihydroartemisinin-piperaquine. All mice were infected with Plasmodium berghei on the day 0. The test material extracts were given 3 days before infection (H-3) and every day for 28 days after infection. Parasitemia data were taken on day 3, 7, 10, 15, 21, and 28, while the data for erythrocyte count and Hb level were taken on day 3, 10, and 21. Data processing was conducted using one-way ANOVA, followed by post hoc test.Results: This study showed that combination of sambiloto extract and spirulina powder (AP+PS) gave a significant difference result in suppressing the percentage of parasitemia (p=0.02), increasing the erythrocyte count (p=0.03), and Hb level (p=0.01) at the 15th day, compared to the group given only sambiloto (AP).Conclusion: Combination of spirulina powder and sambiloto extract will decrease parasitemia and increase the number of erythrocyte and Hb in mice that infected by P. berghei. Â

MOLECULAR DOCKING OF ANTIMYCIN A3 ANALOGS AND ITS AROMATIC SEGMENTS AS INHIBITORS OF APOPTOSIS PROTEIN MARKER BCL-XL AND MCL-1

  Objective: Apoptosis is an important cellular process that causes the death of damaged cells. Its malfunction can lead to cancer development and poor response to conventional chemotherapy. Cellular proteins from the B-cell lymphoma 2 (BCL-2) family are crucial for apoptosis. Breast cancer is the most commonly diagnosed cancer among women worldwide. The aim of this work was to design using in silico docking antimycin A3, antimycin analogs, and its aromatic segments as inhibitors of Bcl-xl and Mcl-1.Methods: In silico molecular docking approach has been utilized to find the potential anticancer from antimycin A3 analogs and its aromatic segments. Antimycin A3 analogs and its aromatic segments were modeled into three-dimensional (3D) structures using Marvin Sketch. Based on Protein Data Bank, 3ZLN for Bcl-xl, and 5IEZ for Mcl-1 were selected as apoptosis protein marker from BCL-2 family. Geometry optimization and minimization of energy 3D structure of antimycin A3 analogs and segments (ligands) using the AutoDock software. Docking process and amino acid residue analysis were executed using AutoDock software. The best docking score was shown by the lowest binding energy and also checked with Lipinski rule of five.Results: In silico molecular docking showed antimycin A3 analogs, amide 5 and aromatic segment 14 have the best interaction and activity for Bcl-xl receptor inhibition. Moreover, amide 5 and segment 15 showed the best interaction and activity for Mcl-1 receptor inhibition.Conclusion: Our results clearly demonstrate that amide 5, segment 14, and segment 15 of antimycin A3 analog have a strong inhibitory activity against Bcl-xl and Mcl-1, and should be further developed as a promising candidate for the new anti-apoptosis agents.Â

Identification of Antiviral Compounds against Hepatitis C Virus (HCV) targeting NS3 protein by Pharmacophore Modeling, Molecular Docking, and ADMET Approach

The NS3 protein plays an important role in HCV replication, where its N-terminal domain acts as a protease to process most of the viral polypeptides. In addition, this protein also functions as an RNA helicase and NTPase and triggers liver fibrosis which accelerates the development of liver disease. Resistance-associated substitution (RAS) is commonly detected in failed DAA regimens. RAS has been identified in proteins involved in HCV infection, one of which is NS3. Thus, this study has a design to identify natural compounds that are able to target the HCV NS3 protein. To identify natural compounds, a ligand-based and structure-based pharmacophore model to the cavity of the active protein site was generated after virtual screening and molecular docking. Three compounds namely stigmasterol, gamma mangostin, and erycristagallin have been found as HCV antiviral candidates that target the NS3 protein with a lower binding affinity than the original ligand. Based on ADMET analysis, the three compounds have high absorption in the small intestine. Analysis of the cytotoxicity of stigmasterol compounds did not have the potential to be mutagenic. The LD50 value of stigmasterol is also lower than other compounds. However, the stigmasterol compound has a lower MRTD

Ligand Based Pharmacophore Modelling, Virtual Screening, Molecular Docking, and ADMETOX of Natural Compounds as Antibiotic Candidates against Urinary Tract Infections (UTI)

The use of antibiotic drugs requires close supervision that patients take antibiotics according to the rules. Irregular antibiotic use led to increased ADR cases (Antibiotic Drug-resistant). ADR is when an individual becomes resistant to an antibiotic drug that cannot kill bacteria. The high number of ADR cases prompted drug discovery to be implemented in analysis for Antibiotic candidates with good effectiveness through the Molecular Docking approach. The search for candidate test compounds as antibiotics were performed using the pharmacophore modelling method and molecular docking. And piperine, withaferin, has some of the same amino acids Ala101, Val103, Glu166, Trp165, and Leu102. Based on the prediction of the promising potential test ligand compound is Corosolic acid. In addition to assessing drug-likeness, pharmacokinetic and toxicity parameters, corosolic acid also has the lowest binding energy among other compounds. Through a textual bioinformatics approach, molecular docking simulations can be used as a first step in the search for new drug candidates in silico by considering various aspects, starting from the physicochemical properties of protein-ligand compounds and the environment. Analysis during the docking process to ADMETOX is an analysis to see the effectiveness and in silico compound safety. 

Pharmacophore Modeling, Molecular Docking, and ADMET Approach for Identification of Anti-Cancer Agents Targeting the C-Jun N-Terminal Kinase (JNK) Protein

One of the most prevalent cancers in Indonesia is breast cancer, based on Indonesia's pathological-based registration.    Breast cancer is a complex, heterogeneous disease classified into hormone-receptor-positive, human epidermal growth factor receptor-2 overexpressing (HER2+) and triple-negative breast cancer (TNBC) based on histological features. Patients with HR+, HER2- Early Breast Cancer (EBC) do not experience recurrence or recurrence for a long time with currently available standard therapy [11]. However, up to 30% of patients with high-risk clinical and/or pathological features may experience a relapse in the first few years. This results in the need for research and development regarding updates in medicine both in terms of treatment and targets and drug compounds used. The c-Jun N-terminal kinase (JNK) protein functions in signaling and influences the apoptotic pathway as well as cancer cell survival. In this study, an insilico screening experiment of inhibitory compounds was carried out on the JNK protein receptor target by screening compounds and molecular docking of compounds for breast cancer therapy.Two novel herbal compounds, Mangostin and ent-Copalyl Dyphospate, have the potential to be turned into medicines that may cause apoptosis through JNK protein targets according to an in-silico-based molecular simulation techniqu

Structure-Based Virtual Screening and Molecular Docking on the Indonesian Herbal Compound as a Promising Insulin Receptor (INSR) Inhibitor to Suppress Tumor Growth

A healthy cell maintains a homeostasis condition of glucose level, whereas cancer cells do not. Increased glucose uptake is a hallmark of cancer cells that helps them survive, proliferate, and spread. INSR is one of key feature that take part in glucose metabolism through insulin signaling. To block the entry of glucose into cells, researchers were aiming to disrupt the insulin signaling pathway as the upstream activation in glucose metabolism by inhibiting insulin receptor (INSR) using Indonesian herbal compounds. The approach during the screening was structure-based drug discovery (SBDD) method where INSR was determined as the macromolecules. Some parameters such as binding affinity, constant inhibition, drug-likeness, pharmacokinetics, and toxicity were applied to help the search of potential inhibitor. According to the test results, Heterophylin, Sanggenofuran A, and Epigallocatechin-3-O-caffeate had the strongest molecular binding activity against the INSR protein. Heterophylin is discovered in jackfruit fruit trees and Sanggenofuran A is present in mulberry trees. While Epigallocatechin-3-O-caffeate, is abundantly found in green tea plan

Whole genome sequencing data of Candida krusei, the pathogen causing Candidaemia, from Department of Parasitology Culture Collection, Faculty of Medicine Universitas Indonesia [version 2; peer review: 2 approved]

Candida krusei is a Candida non-albicans species with a high prevalence, which causes candidaemia. Current treatment guidelines include fluconazole as a primary therapeutic option for the treatment of these infections; however, it is only a fungistatic against Candida spp., and both inherent and acquired resistance to fluconazole have been reported. C. krusei species is also reported as the only Candida sp. which has an intrinsic resistance factor to fluconazole. Therefore, in dealing with antifungal resistance, it is necessary to develop new antifungal agents that are efficient in the treatment of fungal infections, especially those caused by C. krusei. The purpose of this study was to investigate the genome of clinical C. krusei isolates and correlate the resistant phenotypes with mutations in resistance genes. A total of 16 samples of C. krusei from clinical samples from hospitals in Jakarta were used in the experiment. All colonies were extracted using the QIAamp DNA Mini Kit. The library was prepared using the Illumina DNA Prep Kit. The sequencing process was carried out on the Illumina MiSeq Platform using a 2x301 paired-end configuration. FASTQ raw files are available under the BioProject Accession Number PRJNA819536 and Sequence Read Archive Accession Numbers SRR18739949 and SRR18739964

Immunoinformatics Approach for Epitope-Based Vaccine Design: Key Steps for Breast Cancer Vaccine

Vaccines are an upcoming medical intervention for breast cancer. By targeting the tumor antigen, cancer vaccines can be designed to train the immune system to recognize tumor cells. Therefore, along with technological advances, the vaccine design process is now starting to be carried out with more rational methods such as designing epitope-based peptide vaccines using immunoinformatics methods. Immunoinformatics methods can assist vaccine design in terms of antigenicity and safety. Common protocols used to design epitope-based peptide vaccines include tumor antigen identification, protein structure analysis, T cell epitope prediction, epitope characterization, and evaluation of protein–epitope interactions. Tumor antigen can be divided into two types: tumor associated antigen and tumor specific antigen. We will discuss the identification of tumor antigens using high-throughput technologies. Protein structure analysis comprises the physiochemical, hydrochemical, and antigenicity of the protein. T cell epitope prediction models are widely available with various prediction parameters as well as filtering tools for the prediction results. Epitope characterization such as allergenicity and toxicity can be done in silico as well using allergenicity and toxicity predictors. Evaluation of protein–epitope interactions can also be carried out in silico with molecular simulation. We will also discuss current and future developments of breast cancer vaccines using an immunoinformatics approach. Finally, although prediction models have high accuracy, the opposite can happen after being tested in vitro and in vivo. Therefore, further studies are needed to ensure the effectiveness of the vaccine to be developed. Although epitope-based peptide vaccines have the disadvantage of low immunogenicity, the addition of adjuvants can be a solution

Amino Acid Profile of Luminal A and B Subtypes Breast Cancer

BACKGROUND: Amino acids are important for proliferation and maintenance of tumor cells. Breast cancer patients were found to have significant changes in the number of amino acids, which are assumed to be correlated with the molecular subtypes of breast cancer. Therefore, current study was conducted to analyze plasma amino acids in breast cancer patients with luminal A and B subtypes.METHODS: Breast cancer and control subjects were recruited, and venous blood was collected for the measurement of plasma amino acids. Total 19 plasma amino acids were measured using reverse-phase high-performance liquid chromatography with C18 column. Mean comparison for normally distributed and homogeneous data was further analzyed using independent sample T-test, with p<0.05 was considered as significant.RESULTS: From total 19 amino acids, only 7 amino acids; cysteine, glutamic acid, histidine, ornithine, threonine, tyrosine, valine, were statistically different between the healthy control and breast cancer subjects. Eventhough no amino acids was found to be statistically different between breast cancer subjects with luminal A and B subtypes, but some amino acids were found to be significantly different when correlated to various breast cancer risk factors.CONCLUSION: Amino acid profile of patients with Luminal A and B subtypes of breast cancer differs compared to healthy controls and is also correlated with breast cancer risk factors. Increase in cysteine level in Luminal A subtype patients and decrease of alanine and leucine in Luminal B subtype patients can be used as a biomarker.KEYWORDS: amino acid, plasma, breast cancer, risk factor, biomarke