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Sofia M. Haryana
Department of Anatomy, Faculty of Medicine, Gadjah Mada University Yogyakarta
Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Public Health

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HUVECs-derived exosomes increase neovascularization and decrease limb necrosis in hindlimb ischemia Ismail, Muhamad T.; Anggrahini, Dyah W.; Haryana, Sofia M.; Setianto, Budi Y.
Narra J Vol. 4 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i3.1358

Abstract

Chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral arterial disease (PAD) and imposes a significantly high burden due to its high risk of mortality and amputation. Revascularization is the first-line treatment for CLTI; however, the amputation rate remains high, and approximately one-third of patients are not eligible for this treatment. Therefore, there is an urgent need for more effective therapeutic strategies. The aim of this study was to investigate the effects and mechanisms of human umbilical vein endothelial cells (HUVECs)-derived exosomes on neovascularization and the degree of necrosis in a hindlimb ischemia model and to study the biological processes underlying their mechanisms. This is an in vivo experimental study with a post-test-only control group design. Forty BALB/c mice were randomized to receive injections of exosomes, conditioned media, and phosphate-buffered saline (PBS) one day after unilateral double ligation. A sham-operated group was also included as a control. Capillary density, arteriole lumen diameter, and histopathological necrosis were measured after seven days, while clinical necrosis was observed daily. MicroRNA profiling, in silico analysis, and transcriptomic analysis of vascular endothelial growth factor (VEGF) mRNA expression were performed to determine the possible biological processes. No amputation was found in the exosome group, as well as in the conditioned media and sham-operated groups, compared to three out of seven mice (43%) in the PBS group. The capillary density was higher in the exosome than in the PBS group (p=0.026). The arteriole lumen diameter in the exosome group was larger than in the PBS (p=0.033) and sham-operated (p=0.034) groups. The scores of clinical necrosis and histopathological necrosis in the exosome group were lower than the PBS group (p=0.005), while the histopathological necrosis scores were also lower but statistically insignificant. In silico analysis showed improvement in neovascularization and necrosis, possibly through energy regulation, PI3K/AKT and TGF-β activation, the ubiquitin-proteasome system, and tyrosine kinases receptors. HUVEC exosomes were associated with lower VEGF mRNA expression, which may indicate a more effective compensatory mechanism under ischemic conditions. The exosome group had the lowest VEGF mRNA expression compared to other groups, although the difference was not statistically significant. This study highlights that HUVECs-derived exosomes improve neovascularization and decrease necrosis in a hindlimb ischemia mice model, potentially by modulating several possible mechanisms.
Research trends in microRNA profiling as a biomarker for lung adenocarcinoma via liquid biopsy: A bibliometric analysis Kartika, Aprilia I.; Dafip, Muchamad; Wijayanti, Nastiti; Heriyanto, Didik S.; Haryana, Sofia M.; Taroeno-Hariadi, Kartika W.
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.1372

Abstract

Research related to the development of diagnostic biomarkers in lung adenocarcinoma in various countries is important. Research on microRNA as a biomarker in lung adenocarcinoma varies depending on the population, specimen, and technology used for profiling and validation. The aim of this study was to map and analyze bibliometric data of publications related to the topic of microRNA as a candidate biomarker in lung adenocarcinoma and to determine any potential research gaps. A total of 8,506 articles were collected from Crossref, Google Scholar, Semantic Scholar, PubMed, and Scopus databases using Harzing's Publish or Perish platform. A systematic search was conducted using four keywords: “profiling,” “validating,” “microRNA,” and “lung adenocarcinoma,” and synonyms of these keywords based on the MeSH on NCBI. The data extraction process followed the chart from PRISMA-P. The article’s elimination was conducted using Mendeley Desktop and then was analyzed based on the authors' keywords using VOSviewer and Biblioshiny. A bibliometric analysis of 692 relevant articles identified four primary research clusters: (1) microRNA (19 keywords), which highlights its potential as a biomarker for early detection and diagnosis; (2) lung adenocarcinoma (18 keywords), reflecting advancements in lung cancer research; (3) liquid biopsy (19 keywords), emphasizing the growing interest in non-invasive diagnostic methods; and (4) bioinformatics (nine keywords), underscoring the role of computational approaches in transcriptomic analysis. As a primary topic, microRNAs have become a focal point of research for diagnosing lung cancer across various stages and as biomarkers for cancer cell proliferation, invasion, migration, and metastasis. Numerous studies have demonstrated the successful application of microRNAs in lung cancer diagnosis in the last decade, although the reported types of microRNAs are inconsistent. Therefore, further research on this topic should be continuously conducted, particularly to validate the types of microRNAs and the types of environments that influence them.
Co-Authors Anggrahini, Dyah W. Dafip, Muchamad Eiji Tatsumi Heriyanto, Didik S. Hiroyuki Sakoda Ibnu Purwanto Ismail, Muhamad T. Johan Kurnianda Kaho Furuta Kartika W. Taroeno-Hariadi Kartika, Aprilia I. Katsuyasu Saigo Kayoko Masuda Ken-Ichi Nagai Meilani Syampurnawati Nastiti Wijayanti Seiji Kawano Setianto, Budi Y. Setsuki Isono Shin-Ichi Kondo Shunichi Kumagai Takayuki Takahashi Yoshitaka Hayashi