The Role of Differentially Expressed miRNAs and Potential miRNA-mRNA Regulatory Network in Prostate Cancer Progression and Metastasis

Purpose: Aberrant expression of microRNAs (miRNAs) has been discovered in prostate cancer progression however their function is not well understood, thereby further investigation is required to understand the importance of underlying mechanisms and their involvement in multiple signaling pathways, as well as their potential as therapeutic targets. In this study the role and expression levels of three miRNAs were evaluated: miR-21, miR-221 and miR-200c in different prostate cancer cell lines. In addition, based on the latest studies on miRNAs function, their association with other target genes and molecules were analyzed using bioinformatic tools. Methods: Three PCa cell lines PC3, LNCaP and VCaP and normal prostate epithelial cell line PNT1A were screened for miRNA expression levels using qPCR. miRNA target genes and their association with signaling pathways were analyzed through several Network and pathway analysis online tools. Findings: Upregulation of miR-21 and miR-221 was observed in PC3 and VCaP prostate cancer cells, respectively. According to KEGG analysis, we found that Hippo signaling pathway and cytokine-cytokine receptor interactions were affected by miR-21 while miR-221 would interfere with ECM-receptor interaction, Fatty acid elongation and Huntington disease molecular networks. Exposure of PC3 cells to TGF-β (10 µM) caused upregulation of miR-21 with the evidence with increased invasion potential. Discussion and Conclusion: miRNAs could regulate several genes in multiple signaling pathways. Here, we demonstrated that in a panel of PCa cell lines, both mir-21 and miR-221 expressions were upregulated. miR-21 may be a dignostic and prognosticbiomarker for PCa

PENGEMBANGAN MEDIA PEMBELAJARAN MATEMATIKA BERBASIS YOUTUBE BERBANTUAN APLIKASI KINE MASTER

ABSTRAKTujuan penelitian ini adalah untuk mengembangkan channel Youtube yaitu Pelita Ilmu sebagaiChannel pembelajaran matematika yang diterima sebagai partner youtube. Conten video yangdikembangkan adalah pembelajaran matematika berbasis aplikasi android dan berbasis aplikasiSquid. Hasil penelitian dan pembahasan disimpulkan sebagai berikut:(a) Channel Pelita Ilmudengan jumlah conten video sebanyak 150 dan Jumlah view sebanyak 67.981 sudah diterimasebagai partner youtube, atau dengan kata lain sudah berhasil dimonitisasi pihak youtube.(b)Jumlah conten video pada channel Pelita Ilmu berdasarkan kategori tingkatan kelas secaraberurutan adalah sebagai berikut: SMA/SMK (45), PT (42), SMP (40) dan SD (23). (c) Jumlahconten video pada channel Pelita Ilmu berdasarkan kategori basis video secara berurutan adalahsebagai berikut: Aplikasi Squid (80), dan Aplikasi Android (70). (d) Jumlah view conten videopada channel Pelita Ilmu berdasarkan kategori tingkatan kelas secara berurutan adalah sebagaiberikut: SMA/SMK (20.340), PT (19.145), SMP (18.080) dan SD (10.396).Kata Kunci: Media Pembelajaran Matematika, Pengembangan youtube, Aplikasi KineMaste

Pengaruh Model Pembelajaran Blended Learning Terhadap Pemahaman Konsep Dan Kemandirian Belajar Pada Mata Kuliah Matematika Kelas Awal

Penelitian ini bertujuan untuk mendeskripsikan pengaruh penerapan model blended learning terhadap pemahaman konsep dan kemandirian belajar matematis mahasiswa. Penelitian ini merupakan eksperimen semu dengan rancangan posttest only control group design. Populasi penelitian mencakup seluruh mahasiswa semester dua PGSD Universitas Katolik Santho Thomas tahun Pelajaran 2021/2022. Sampel penelitian sebanyak 2 kelas dipilih menggunakan Teknik simple random sampling. Model pembelajaran blended learning yang digunakan dalam penelitian ini adalah flipped classrrom model dengan Youtube, Whatsapp dan Zoom yang digunakan sebagai media pendukung dalam pembelajaran online. Pemahaman konsep dan kemandirian belajar diukur menggunakan tes berbentuk soal uraian yang valid dan reliabel. Selanjutnya data yang diperoleh dianalisis menggunakan uji MANOVA dengan taraf signifikan 5% (α = 0,05). Hasil pengujian hipotesis menunjukkan bahwa pembelajaran blended learning berpengaruh positif terhadap pemahaman konsep dan kemandirian belajar matematis mahasiswa. Kata Kunci : pemahaman konsep; kemandirian belajar ; blended learning ABSTRACT This study aims to describe the effect of the application of the blended learning model on the understanding of students' mathematical concepts and learning independence. This research is a quasi-experiment with a posttest only control group design. The research population includes all second semester students of PGSD at the Catholic University of Santho Thomas in the 2021/2022 academic year. The research sample was 2 classes selected using simple random sampling technique. The blended learning model used in this study is the flipped class-rom model with Youtube, Whatsapp and Zoom which are used as supporting media in online learning. Concept understanding and learning independence were measured using a test in the form of a valid and reliable description of the question. Furthermore, the data obtained were analyzed using the MANOVA test with a significant level of 5% (α = 0.05). The results of hypothesis testing indicate that blended learning has a positive effect on understanding concepts and students' mathematical learning independence. Keywords: understanding the concept; independent learning; blended learnin

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the betacoronavirus family, which causes COVID-19 disease. SARS-CoV-2 pathogenicity in humans leads to increased mortality rates due to alterations of significant pathways, including some resulting in exacerbated inflammatory responses linked to the "cytokine storm" and extensive lung pathology, as well as being linked to a number of comorbidities. Our current study compared five SARS-CoV-2 sequences from different geographical regions to those from SARS, MERS and two cold viruses, OC43 and 229E, to identify the presence of miR-like sequences. We identified seven key miRs, which highlight considerable differences between the SARS-CoV-2 sequences, compared with the other viruses. The level of conservation between the five SARS-CoV-2 sequences was identical but poor compared with the other sequences, with SARS showing the highest degree of conservation. This decrease in similarity could result in reduced levels of transcriptional control, as well as a change in the physiological effect of the virus and associated host-pathogen responses. MERS and the milder symptom viruses showed greater differences and even significant sequence gaps. This divergence away from the SARS-CoV-2 sequences broadly mirrors the phylogenetic relationships obtained from the whole-genome alignments. Therefore, patterns of mutation, occurring during sequence divergence from the longer established human viruses to the more recent ones, may have led to the emergence of sequence motifs that can be related directly to the pathogenicity of SARS-CoV-2. Importantly, we identified 7 key-microRNAs (miRs 8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) with significant links to KEGG pathways linked to viral pathogenicity and host responses. According to Bioproject data (PRJNA615032), SARS-CoV-2 mediated transcriptomic alterations were similar to the target pathways of the selected 7 miRs identified in our study. This mechanism could have considerable significance in determining the symptom spectrum of future potential pandemics. KEGG pathway analysis revealed a number of critical pathways linked to the seven identified miRs that may provide insight into the interplay between the virus and comorbidities. Based on our reported findings, miRNAs may constitute potential and effective therapeutic approaches in COVID-19 and its pathological consequences

INOVASI PEMBELAJARAN BERBASIS DIGITAL DALAM MENYONGSONG ERA REVOLUSI INDUSTRY 4.0 BAGI CALON GURU DENGAN MODEL ADDIE BERBANTUAN EDMODO

Inovasi Pembelajaran Berbasis Digital Dalam Menyongsong Era Revolusi Industry 4.0Bagi Calon Guru Dengan Model Addie Berbantuan Edmodo. Tujuan penelitian ini adalahterbentuknya calon guru yang terampil dalam menggunakan pembelajaran aktif berbasisdigital (video pembelajaran, pembelajaran berbasis aplikasi android dan pemanfatan media elearningberbasis Edmodo). Tahapan metode penelitian yang digunakan adalah metodepenelitian dan pengembangan (Research and Development). Model yang digunakan adalahmodel pengembangan ADDIE (Analysis, Design, Development, Implementation, Evaluation).Rincian data yang diperoleh dari hasil pengujian antara lain: pengujian ahli materi diperolehskor 4,83 dengan kategori sangat baik, pengujian ahli media diperoleh skor 4,3 dengankategori sangat baik, dan pengujian user diperoleh skor 4,7 (Dosen) dengan kategorisangat baik dan skor 4,03 (mahasiswa) dengan kategori baik, sehingga Media Pembelajaranberbasis digital layak digunakan untuk kegiatan belajar mengajar.Kata Kunci: Pembelajaran Berbasis Digital, Media Pembelajaran Matematika BerbasisAplikasi Androi

Putative Roles for Peptidylarginine Deiminases in COVID-19

Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. In addition, BioProject Data PRJNA631753, analysing patients tissue biopsy data (n = 5), was utilised. We report a high individual variation observed for all PADI isozymes in the patients’ tissue biopsies, including lung, in response to SARS-CoV-2 infection, while PADI2 and PADI4 mRNA showed most variability in lung tissue specifically. The other tissues assessed were heart, kidney, marrow, bowel, jejunum, skin and fat, which all varied with respect to mRNA levels for the different PADI isozymes. In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells. In A549 cells, PADI2 mRNA was elevated, PADI3 and PADI6 mRNA was downregulated, and no effect was observed on the PADI4 or PADI6 mRNA levels in infected cells, compared with control mock cells. Our findings indicate a link between PADI expression changes, including modulation of PADI2 and PADI4, particularly in lung tissue, in response to SARS-CoV-2 infection. PADI isozyme 1–6 expression in other organ biopsies also reveals putative links to COVID-19 symptoms, including vascular, cardiac and cutaneous responses, kidney injury and stroke. KEGG and GO pathway analysis furthermore identified links between PADs and inflammatory pathways, in particular between PAD4 and viral infections, as well as identifying links for PADs with a range of comorbidities. The analysis presented here highlights roles for PADs in-host responses to SARS-CoV-2, and their potential as therapeutic targets in COVID-19

PENERAPAN IDEOLOGI DAN TUJUAN PENDIDIKAN MATEMATIKA SECARA EPISTEMOLOGI DALAM KURIKULUM MERDEKA BELAJAR

ABSTRAK Tujuan artikel ini adalah mengetahui penerapan ideolgi dan tujuan pendidikan matematika secara epistemology dalam kurikulum merdeka belajar. Metode yang digunakan pada artikel ini adalah study kepustakaan. Study kepustakaan, yaitu menelaah sumber-sumber, baik itu buku, artikel, referensi-referensi yang berkaitan dengan landasan ideologi dan tujuan pendidikan secara epistomologi serta kurikulum merdeka belajar yang bisa dijadikan acuan dalam melaksanakan program pendidikan. Kurikulum merdeka belajar jika kita kaji dari dimensi atau elemen, prinsip pembelajaran dan pelaksanaan kurikulum  sangat baik dalam penerpan ideology dan tujuan pendidikan matematika secara epistemology.Kata Kunci: Ideologi Pendididkan Matematika, Tujuan Pendidikan Matematika, Merdeka BelajarABSTRACT The purpose of this article is to find out the epistemological application of ideology and goals of mathematics education in the independent learning curriculum. The method used in this article is library research. Literature study, namely examining sources, be it books, articles, references related to the ideological basis and epistemological goals of education as well as the independent learning curriculum which can be used as a reference in implementing educational programs. The independent learning curriculum, if we examine it from the dimensions or elements, the principles of learning and implementation of the curriculum are very good in implementing ideology and epistemological goals of mathematics education. Keywords: Ideology of Mathematics Education, Objectives of Mathematics Education, Independent Learning

Upregulated wnt-11 and mir-21 expression trigger epithelial mesenchymal transition in aggressive prostate cancer cells

Prostate cancer (PCa) is the second-leading cause of cancer-related death among men. microRNAs have been identified as having potential roles in tumorigenesis. An oncomir, miR-21, is commonly highly upregulated in many cancers, including PCa, and showed correlation with the Wnt-signaling axis to increase invasion. Wnt-11 is a developmentally regulated gene and has been found to be upregulated in PCa, but its mechanism is unknown. The present study aimed to investigate the roles of miR-21 and Wnt-11 in PCa in vivo and in vitro. First, different Gleason score PCa tissue samples were used; both miR-21 and Wnt-11 expressions correlate with high Gleason scores in PCa patient tissues. This data then was confirmed with formalin-fixed paraffin cell blocks using PCa cell lines LNCaP and PC3. Cell survival and colony formation studies proved that miR-21 involves in cells’ behaviors, as well as the epithelial-mesenchymal transition. Consistent with the previous data, silencing miR-21 led to significant inhibition of cellular invasiveness. Overall, these results suggest that miR-21 plays a significant role related to Wnt-11 in the pathophysiology of PCa

MicroRNAs for Virus Pathogenicity and Host Responses, Identified in SARS-CoV-2 Genomes, May Play Roles in Viral-Host Co-Evolution in Putative Zoonotic Host Species

Our recent study identified seven key microRNAs (miR-8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) similar between SARS-CoV-2 and the human genome, pointing at miR-related mechanisms in viral entry and the regulatory effects on host immunity. To identify the putative roles of these miRs in zoonosis, we assessed their conservation, compared with humans, in some key wild and domestic animal carriers of zoonotic viruses, including bat, pangolin, pig, cow, rat, and chicken. Out of the seven miRs under study, miR-3611 was the most strongly conserved across all species; miR-5197 was the most conserved in pangolin, pig, cow, bat, and rat; miR-1307 was most strongly conserved in pangolin, pig, cow, bat, and human; miR-3691-3p in pangolin, cow, and human; miR-3934-3p in pig and cow, followed by pangolin and bat; miR-1468 was most conserved in pangolin, pig, and bat; while miR-8066 was most conserved in pangolin and pig. In humans, miR-3611 and miR-1307 were most conserved, while miR-8066, miR-5197, miR-3334-3p and miR-1468 were least conserved, compared with pangolin, pig, cow, and bat. Furthermore, we identified that changes in the miR-5197 nucleotides between pangolin and human can generate three new miRs, with differing tissue distribution in the brain, lung, intestines, lymph nodes, and muscle, and with different downstream regulatory effects on KEGG pathways. This may be of considerable importance as miR-5197 is localized in the spike protein transcript area of the SARS-CoV-2 genome. Our findings may indicate roles for these miRs in viral–host co-evolution in zoonotic hosts, particularly highlighting pangolin, bat, cow, and pig as putative zoonotic carriers, while highlighting the miRs’ roles in KEGG pathways linked to viral pathogenicity and host responses in humans. This in silico study paves the way for investigations into the roles of miRs in zoonotic disease