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All Journal Universa Medicina Molecular and Cellular Biomedical Sciences (MCBS) Jurnal Profesi Medika: Jurnal Kedokteran dan Kesehatan Majalah Patologi Indonesia JOURNAL LA MEDIHEALTICO Indonesian Journal of Medical Chemistry and Bioinformatics
Arleni Bustami
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Biochemistry, Genetics & Molecular Biology Chemistry Computer Science & IT Dentistry Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Nursing Public Health Veterinary

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A Review of Endometriosis: Focus on its Pathophysiology, Quality of Oocyte and Embryo, and the Management of Infertility Yuningsih, Tita; Bustami, Arleni
Jurnal Profesi Medika : Jurnal Kedokteran dan Kesehatan Vol 17 No 2 (2023): Jurnal Profesi Medika : Jurnal Kedokteran dan Kesehatan
Publisher : Fakultas Kedokteran UPN Veteran Jakarta Kerja Sama KNPT

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33533/jpm.v17i2.6789

Abstract

Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial tissue/lesion outside of the uterus. Unveiling pathogenesis and pathophysiology of the disease remains an elusive target to be discovered. Among many other mechanistic theories, menstrual retrograde theory is favorable in explaining endometriosis which corroborated with certain survival factors that allow endometrial cells to grow and persist. This review set out to provide an update on oocyte and embryo quality derived from women with endometriosis who undergo IVF cycles. Database searching was conducted using PUBMED and the keyword used for literature searching was endometriosis, oocyte quality, and embryo quality. As a chronic inflammation occurs in reproductive tract, endometriosis has been demonstrated to negatively impact the oocyte quality and endometrial receptivity that leads to infertility. Account for about 10-40% of women with endometriosis administered in-vitro fertilization (IVF) programs to achieve pregnancy and healthy live-birth babies. Through IVF, oocytes can be fertilized and cultured in-vitro; thus, avoiding pra-implantation embryos to grow under unfavorable in-vivo tubal and endometrium environments due to endometriosis. IVF could be a method of choice for infertility treatment owing to endometriosis. Improved quality of oocyte, embryo as well as clinical pregnancy could be attained depending on endometriosis severity.
Hypertrophy Determination of H9c2 Cardiomyoblast Cell Line Using Wright-Giemsa Staining: An Experience in Developing an Acceptable and Easy-to-handle In-vitro Protocol Fadhillah, Muhamad Rizqy; Arozal, Wawaimuli; Wibowo, Heri; Bustami, Arleni; Sukmawati, Dewi; Kusmardi, Kusmardi; Triana, Novi; Khatimah, Nurul Gusti
Majalah Patologi Indonesia Vol. 33 No. 2 (2024): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v33i2.682

Abstract

Introduction Cell-size area (CSA) becomes the standard parameter routinely tested in vitro for cardiac hypertrophy studies. Thus, staining is an essential tool for this purpose. As reported in a previous study, immunofluorescence staining is an established method for CSA. However, because it is expensive and requires a specialized microscope, e.g., immunofluorescence or confocal microscope, it is not applicable in a laboratory with limited equipment. Wright-Giemsa staining is a standard procedure in hematology laboratories and is inexpensive and convenient. Here, we shared our experience developing a CSA determination protocol using Wright-Giemsa in H9c2 cardiomyoblast. Methods The viability tests were performed on H9c2 to determine the effective dosage of angiotensin II and Irbesartan (standard drug). The H9c2 were divided into three groups: the control group (without either angiotensin II or irbesartan), the negative control (with angiotensin II), and the positive control (with angiotensin II and Irbesartan), triplicate for each group. The cells then are acclimatized overnight, serum-starved for one day, and incubated with angiotensin and irbesartan for 48 hours. Lastly, Wright-Giemsa was observed using a light microscope in three fields. The CSA was determined by three independent observers blindly, statistically different if the p<0.05 using ANOVA ways or Kruskal-Wallis. Results After the H9c2 induced by angiotensin-II 1 μM and Irbesartan 1μM, we found the CSA significantly differed among each group (p<0,0001). The negative control has a higher median and interquartile range (IQR) CSA (10.78 (6.79) um2) compared to the control group (median (IQR) 7.27 (4.91) um2) and positive control (median (IQR) 7.849(5.31) um2). Conclusion It can be concluded that the Wright-Giemsa might help determine the CSA for in-vitro hypertrophic studies.
In Vitro Anti-inflammatory Effect of Secretome from Umbilical Cord-derived Mesenchymal Stem Cells in COVID-19 Patient Blood: A Study on sIL-6R, sgp130, IL-1RA and Anti/pro Inflammatory Cytokines Asysyifa, Nisrina; Wibowo, Heri; Abdullah, Murdani; Liem, Isabella Kurna; Bustami, Arleni
Journal La Medihealtico Vol. 5 No. 5 (2024): Journal La Medihealtico
Publisher : Newinera Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37899/journallamedihealtico.v5i5.1522

Abstract

COVID-19 exhibits a wide range of clinical manifestations which severity of the disease is linked to uncontrolled escalation of inflammatory mediators. Ongoing research has identified the immunomodulatory effects of the MSC-derived secretome as a potential therapy for COVID-19. However, the precise mechanism by which the secretome exerts its therapeutic effect on COVID-19 remains unclear. This study aims to investigate whether the components of the UC-MSC-derived secretome can alter the inflammatory characteristics of immune cells. To achieve this, an in vitro study will be conducted involving co-incubation of whole blood with secretomes, followed by LPS stimulation. A total of 12 blood samples from severe COVID-19 and healthy subjects were cultured into three groups (RPMI control, 3μl and 9μl secretome group) incubated for 24 hours. Then, the cultures were exposed to LPS for 48 hours. The levels of sIL-6R, sgp130, IL-1RA, IL-6, TNF-α, IFN-γ, and IL-10 were measured. Results showed that LPS increased IL-6, TNF-α, and IL-10 production, while reducing sIL-6R, and sgp130, but no changes seen in IFN-γ in secretome-incubated blood cultures. The post-LPS/pre-LPS ratio analysis was conducted to investigate the anti-inflammatory potential of secretome. It was found that the secretome provides its anti-inflammatory effects through the role of IL-1RA.
In Silico Analysis of CD40 Mutations and Their Implications for Quinoline-benzoic acid derivatives Based Therapy in Graves' Disease Yunaini, Luluk; Kristanty, Diyah; Sari, Puji; Dwira, Surya; Suryandari, Dwi Anita; Bustami, Arleni
Indonesian Journal of Medical Chemistry and Bioinformatics Vol. 3, No. 2
Publisher : UI Scholars Hub

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Abstract

Graves' disease is an autoimmune disorder in which the CD40-CD154 interaction plays a critical role in T-cell activation. In this study, in silico methods were employed to analyze the binding interactions of quinoline-benzoic acid derivatives (NSB, FSB, and NQB) with the CD40 receptor and to investigate the implications of specific CD40 mutations for drug efficacy. In this reseach conducted by molecular simulation approach with molecular docking Results Mutation analysis of CD40 identified alterations in key residues, such as R203C, which may impact ligand-independent activation and downstream TRAF binding, crucial for signal transduction. These findings highlight the therapeutic potential of quinoline-benzoic acid derivatives for targeting CD40 in Graves' disease, particularly in the context of receptor mutations. The integration of molecular docking, mutation analysis, and pharmacokinetic profiling provides a comprehensive framework for designing effective CD40-targeted therapies.
UC-MSCs Secretome Induces Proliferation of CD4+ T Cells, CD8+ T Cells, NK Cells, and Increases sPD-1 Levels in Severe COVID-19’s Whole Blood Soleha, Winna; Wibowo, Heri; Abdullah, Murdani; Pradipta, Saraswati; Syari, Lucky Novita; Liem, Isabella Kurnia; Bustami, Arleni; Rozaliyan, Anna
Molecular and Cellular Biomedical Sciences Vol 9, No 1 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i1.538

Abstract

Background: Clinical features of severe coronavirus disease 2019 (COVID-19) predominantly include respiratory symptoms and exacerbated multi-organ complications, especially in patients with comorbidities. Cellular immunity, including lymphocytes, is a critical factor in combating SARS-CoV-2 infection. However, immune dysregulation occurs in severe COVID-19 patients, characterized by cytokine storm and lymphopenia. The effectiveness of mesenchymal stem cell (MSC) therapies for COVID-19 is being assessed. The secretome released by MSC functions similarly to the cells themselves as an immunomodulator, offering potential advantages in terms of safety and cost-effectiveness. This study was conducted to assess the effect of umbilical cord MSC-derived (UC-MSC) secretome treatment on lymphocyte count and soluble programmed cell death-1 (sPD-1) levels in severe COVID-19 patient's whole blood.Materials and methods: Twelve whole blood samples from healthy individuals and severe COVID-19 patients were analyzed for lymphocyte count and functional activation using flow cytometry, along with sPD-1 level measurement in pre-treatment and post-secretome conditions.Results: The lymphocyte count in severe COVID-19 patients was significantly decreased, particularly for T cells and NK cells, indicating lymphopenia. Following secretome treatment, CD4+ T cell counts significantly increased compared to pre-treatment, although this change was not significant in the negative control group. Additionally, there was a minimal reduction in B cell count and an increase in sPD-1 levels. Elevated sPD-1 may alleviate T cell exhaustion by interfering with PD-1 binding to programmed death-ligand 1 (PD-L1).Conclusion: Administration of UC-MSC secretome to the whole blood of severe COVID-19 patients suggested immune improvement, with significant increases in CD4+ T cell counts, enhanced B cell survival, and elevated sPD-1 levels. Keywords: COVID-19, cellular immunity, lymphocytes, secretome, MSC
The Role of Centella asiatica and Its Main Bioactive Compound, Asiatic Acid in Cardiac Remodeling: A Systematic Review of Animal Studies Fadhillah, Muhamad Rizqy; Arozal, Wawaimuli; Wibowo, Heri; Bustami, Arleni; Primadhani, Suci Widya; Gusti Khatimah, Nurul; Putri, Rizky Clarinta; Riski Amanda, Clara; Azizah, Nur
Molecular and Cellular Biomedical Sciences Vol 9, No 1 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i1.482

Abstract

Cardiac remodeling is a phenotype of heart failure characterized by a molecular, cellular, and interstitial change in the heart, which manifests in the change of size and function of the heart after specific insults with multiple mechanisms. Centella asiatica (CA) and its main bioactive triterpenoid, asiatic acid (AA), pose antioxidant and anti-inflammatory effects. Still, no adequate clinical trials support the potency of CA and AA as anti-cardiac remodeling. Hence, this systematic review aims to provide an in-depth analysis of CA extract and AA in animal studies' prevention or therapy of cardiac remodeling. The search strategies were conducted based on preferred reporting Items for systematic reviews and meta-analysis (PRISMA) protocol through Pubmed, EMBASE, Scopus, and Web of Science using keywords as follows: “Centella asiatica” OR “Asiatic Acid” AND “Cardiac Remodeling” OR “Cardiac Hypertrophy” OR “Cardiac Fibrosis” along with their synonym. The data collected included hemodynamic parameters based on echocardiography, biomolecular tests such as quantitative polymerase chain reaction (qPCR), Western blotting, or biochemistry procedures. The paper quality was assessed using Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias (RoB). The previous selected study has shown that CA and AA might prevent and cure cardiac remodeling by inhibiting various pathways and protein expressions through AMPKα, NOX2/4, PI3K/Akt/mTOR, p70S6K, YAP/TAZ, and IL-1β, IL-6, and IL-18 cytokines. CA and AA, thus, exhibit cardioprotective effects in the animal model, which need to be confirmed in the clinical trials on humans. Keywords: cardiac remodeling, cardiac hypertrophy, cardiac fibrosis, Centella asiatica, asiatic acid
Macrophage modulation in activation process induced immune thrombocytopenia Mahdaleny, Mahdaleny; Bustami, Arleni; Iswanti, Febriana Catur
Universa Medicina Vol. 43 No. 1 (2024)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2024.v43.76-87

Abstract

The immune system operates like an orchestra that harmoniously maintains the homeostasis balance while protecting from external or internal pathogens attack. Inflammation is one of the key critical immune defenses to eradicate pathogens and encourage tissue repair and recovery by activating the host’s immune and non-immune cells. As a part of the immune response during inflammation, blood platelets serve various functions; however, their activation and involvement in inflammation can also contribute to pathological conditions, such as thrombosis, which results in myocardial infarction, stroke, and venous thromboembolism. Activated platelets can mobilize and release intracellular granules (alpha and dense granules), which include secondary mediators like chemokine PF4/CXCL4. In contrast to most other chemokines, PF4 participates in several long-term regulatory processes, such as cell differentiation, survival, and proliferation. However, recent findings suggest that PF4 is also responsible for modulating macrophage polarization, which can substantially impact the development of induced immune thrombotic thrombocytopenia. This review aims to explain how PF4 induced vascular problems by modulation of macrophage development during immunological thrombocytopenia. A literature search using the keywords PF4, CXCL4, macrophage M4, platelet macrophage M4, and induced immune thrombocytopenia was done using the following databases: Google Scholar, ProQuest, ScienceDirect, and Scopus for articles published from 2000 to 2023. The literature study was done to find the connection between platelet activation, macrophage modulation, and vascular problems such as atherosclerosis and thromboembolism in induced immune thrombotic thrombocytopenia. Several recent studies on PF4, macrophage modulation, and vaccine-induced thrombotic thrombocytopenia were carefully reviewed. This review concludes that macrophage polarization modulation is promising in managing vascular problems in patients with induced immune thrombotic thrombocytopenia.
Therapeutic Options for COVID-19: Drug Repurposing of Serine Protease Inhibitor Against TMPRSS2 Abiyyi, Mohammad Wildan; Dwira, Surya; Bustami, Arleni; Erlina, Linda
Indonesian Journal of Medical Chemistry and Bioinformatics Vol. 1, No. 2
Publisher : UI Scholars Hub

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Abstract

The SARS-Coronavirus 2 (SARS-CoV-2) outbreak is a serious global public health threat. Researchers around the world are conducting mass research to control this epidemic, starting from the discovery of vaccines, to new drugs that have specific activities as antivirals. Drug repurposing is a potential method of using drugs with known activity for reuse as COVID-19 therapy. This method has the advantage that it can reduce costs and also the duration in the development of potential drugs. The initial step in drug repurposing can be done computationally to determine the effectiveness and specificity of the drug on the target protein. Molecular docking analysis can see the specific interactions of potential compounds with target proteins by analyzing the energy of the bonds formed. The spike protein of SARS-CoV-2 is a major target in the design and discovery of new drugs for the treatment of Covid-19 disease. In addition, transmembrane protein serine protease (TMPRSS2) from host cells has been shown to have an important role in the proteolytic cleavage of viral spike protein to the ACE2 receptor present in human cells. Based on screening studies, it is known that there are several drugs that have been established that have the potential to inhibit the SARS-CoV-2 transfection mechanism into host cells. 10 potential drug candidates used in this study namely Arbecacin, Bromhexine hydrochloride, Hydroxychloroquine, Camostat mesylate, Darunavir, Dequalinium, Fleroxacin, Lopinavir, Remdesivir, and Octopamine were used in molecular docking. Docking analysis revealed that there were three potential compounds, namely Bromhexine hydrochloride, Camostat mesylate and Octopamine with low binding affinity and inhibition constants. Based on the docking result, Camostat mesylate as the best candidate has a high specific binding affinity for the Ser441 and Asp435 residues present in the TMPRSS2 catalytic triad. Thus, these results reveal the mechanism of inhibition of TMPRSS2 by the known inhibitor Camostat mesylate in detail at the molecular level. Where, Camostat mesylate has a strong bond. This structural information could also be useful for designing and discovering new inhibitors of TMPRSS2, which may be useful for preventing the entry of SARS-CoV 2 into human cells.
Serum Metabolomic Profiling for Colorectal Cancer using Machine Learning Sari, Ria Nur Puspa; Hidayati, Diah Balqis Ikfi; Bustami, Arleni
Indonesian Journal of Medical Chemistry and Bioinformatics Vol. 2, No. 1
Publisher : UI Scholars Hub

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Abstract

Background: Colorectal cancer is one of the deadliest diseases with a high prevalence worldwide and is characterized by the appearance of adenomatous polyps in the colon mucosa which are at high risk of developing into colorectal cancer. This study aims to use serum metabolites as promising non-invasive biomarkers for colorectal cancer detection and prognostication. Differences in serum metabolites in patients with adenomatous polyps, colorectal cancer, and healthy controls are considered to be able to support the prognosis of colorectal cancer. Methods: Metabolite dataset is taken from the Metabolomic Workbench. Analysis and validation are carried out in silico using machine learning methods. Results: From a total of 234 samples, 113 metabolites were found and 5 metabolites; histidine, lysine, glyceraldehyde, linolenic acid, and aspartic acid were identified as the most significant in differentiating the sample groups. CTD analysis showed that aspartic acid and histidine are associated with the biological pathways of colorectal cancer progression and significant metabolites are associated with cancer-related phenotypes. Conclusion: The serum metabolites differ in colorectal cancer and healthy control. The significant metabolites can be used as a consideration in selecting colorectal cancer biomarkers, but improvisation is needed to obtain more accurate biomarkers.
Co-Authors Abiyyi, Mohammad Wildan Asysyifa, Nisrina Dewi Sukmawati Dwi Anita Suryandari Dwira, Surya Erlina, Linda Fadhillah, Muhamad Rizqy Febriana Catur Iswanti Gusti Khatimah, Nurul Heri Wibowo Hidayati, Diah Balqis Ikfi Jeanne A. Pawitan Khatimah, Nurul Gusti Kristanty, Diyah Kusmardi Kusmardi Lia Damayanti Liem, Isabella Kurna Liem, Isabella Kurnia Luluk Yunaini Mahdaleny, Mahdaleny Murdani Abdullah Ni M. Swantari Nur Azizah Pradipta, Saraswati Primadhani, Suci Widya Puji Sari Putri, Rizky Clarinta Radiana D. Antarianto Riski Amanda, Clara Rozaliyan, Anna Sari, Ria Nur Puspa Soleha, Winna Syari, Lucky Novita Triana, Novi Wawaimuli Arozal Yuningsih, Tita