Symptoms trend and challenges in dental practice during delta variance COVID-19 pandemic in Indonesia: Google Trends Analysis [version 2; peer review: 2 approved]

Background: The COVID-19 pandemic has grown to be a serious issue on a global scale. Dental care is one of the industries affected by COVID-19. The surveillance utilizing lifetime data, however, is still not clear. The purpose of this study was to use Google Trends (GT) analysis to examine symptom trends and challenges during the COVID-19 outbreak in Indonesia. Methods: Covid-19 cases retrieve from Our World in Data. The cases were collected between 1 April 2021-30 September 2021. The GT was used to discover Indonesian relative search volume (RSVs) covering the timeframe of the first outbreak covid-19 pandemic in Indonesia on 1 March 2020 until 13 February 2022. The duration of the search was chosen to reflect the relative popularity of the keywords "symptoms and dentistry practice challenge-related terms" and "coronavirus". Results: We observed that there was a significant and positive correlation between the COVID-19 daily case using GT RSV data and the COVID-19 case from Our World in Data. The COVID-19 daily case had a strong correlation with search terms related to symptoms (such as fever, sore throat, flu, toothache, and cough), drugs (such as ibuprofen, paracetamol, demacolin, bodrex, and antibiotic), and health management (such as self-isolation and telemedicine). Conclusion: Using GT may be helpful to observe the current symptoms trends as well as its challenge tendencies as a surveillance tool for a continuing pandemic like COVID-19. GT should be considered and used as it has the potential to be a powerful digital epidemiology tool that can provide more insight into disease dynamics

Mapping rheumatoid arthritis susceptibility through integrative bioinformatics and genomics

Rheumatoid arthritis (RA) is an autoimmune disease that influences several organs and tissues, especially the synovial joints, and is associated with multiple genetic and environmental factors. Numerous databases provide information on the relationship between a specific gene and the disease pathogenesis. However, it is important to further prioritize biological risk genes for downstream development and validation.  This study aims to map RA-association genetic variation using genome-wide association study (GWAS) databases and prioritize influential genes in RA pathogenesis based on functional annotations. These functional annotations include missense/nonsense mutations, cis-expression quantitative trait locus (cis-eQTL), overlap knockout mouse phenotype (KMP), protein-protein interaction (PPI), molecular pathway analysis (MPA), and primary immunodeficiency (PID). 119 genetic variants mapped had a potential high risk for RA based on functional scoring. The top eight risk genes of RA are TYK2 and IFNGR2, followed by TNFRSF1A, IL12RB1 and CD40, C5, NCF2, and IL6R. These candidate genes are potential biomarkers for RA that can aid drug discovery and disease diagnosis

Identifikasi Variasi Gen dan Ekspresi Gen Yang Berhubungan Dengan Anemia Aplastik Menggunakan Pendekatan Genomik dan Bioinformatika

Anemia aplastik merupakan anemia yang disertai oleh pansitopenia pada tepi darah yang disebabkan oleh kelainan primer pada sumsum tulang dalam bentuk aplasia atau hipoplasia tanpa adanya infiltrasi, supresi atau pendesakan sumsum tulang. Pada anemia aplastik terjadi penurunan produksi sel darah dari sumsum tulang sehingga menyebabkan retikulositopenia, anemia, granulositopenia, monositopenia dan trombositopenia. Anemia aplastika termasuk dalam penyakit yang rentan disebabkan oleh faktor genetik. Salah satu faktor genetik yang banyak diidentifikasi adalah variasi gen atau single nucleotide polymorphism ( SNP). Hingga hari inimetodologi untuk bantuan variasi gen tersebut sudah tersedia dengan bentuk berbagai macam database dan bioinformatika. Tujuan penelitian ini untuk mengidentifikasi variasi gen yang berhubungan dengan Anemia aplastik dan memprioritaskan variasi gen tersebut berdasarkan tingkat kerentanannya melalui pemanfaatan katalog GWAS dan integrasi beberapa database bioinformatika. Hasil penelitian ini kami menemukan ada dua SNP rs1042151 dan rs28367832 yang rentan terhadap anemia aplastik berdasarkan ekpresi gen di jaringan darah . Variasi gen tesebut juga mengkode gen  HLA- DPB1 dan HLA-B dan menunjukkan ekspresi yang tinggi pada jaringan darah ( whole blood ) .Penelitian ini menunjukkan bahwa integrasi variasi gen dan bioinformatika potensial untuk memberikan informasi kepada si terkait kerentanan suatu variasi gen pada suatu penyakit termasuk pada anemia aplastik

Mapping Rheumatoid Arthritis Susceptibility through Integrative Bioinformatics and Genomics

Rheumatoid arthritis (RA) is an autoimmune disease that influences several organs and tissues, especially the synovial joints, and is associated with multiple genetic and environmental factors. Numerous databases provide information on the relationship between a specific gene and the disease pathogenesis. However, it is important to further prioritize biological risk genes for downstream development and validation. This study aims to map RA-association genetic variation using genome-wide association study (GWAS) databases and prioritize influential genes in RA pathogenesis based on functional annotations. These functional annotations include missense/nonsense mutations, cis-expression quantitative trait locus (cis-eQTL), overlap knockout mouse phenotype (KMP), protein-protein interaction (PPI), molecular pathway analysis (MPA), and primary immunodeficiency (PID). 119 genetic variants mapped had a potential high risk for RA based on functional scoring. The top eight risk genes of RA are TYK2 and IFNGR2, followed by TNFRSF1A, IL12RB1 and CD40, C5, NCF2, and IL6R. These candidate genes are potential biomarkers for RA that can aid drug discovery and disease diagnosis

Role of Glycogen Synthase Kinase-3 in Interferon-γ-Mediated Immune Hepatitis

Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase, is a vital glycogen synthase regulator controlling glycogen synthesis, glucose metabolism, and insulin signaling. GSK-3 is widely expressed in different types of cells, and its abundant roles in cellular bioregulation have been speculated. Abnormal GSK-3 activation and inactivation may affect its original bioactivity. Moreover, active and inactive GSK-3 can regulate several cytosolic factors and modulate their diverse cellular functional roles. Studies in experimental liver disease models have illustrated the possible pathological role of GSK-3 in facilitating acute hepatic injury. Pharmacologically targeting GSK-3 is therefore suggested as a therapeutic strategy for liver protection. Furthermore, while the signaling transduction of GSK-3 facilitates proinflammatory interferon (IFN)-γ in vitro and in vivo, the blockade of GSK-3 can be protective, as shown by an IFN-γ-induced immune hepatitis model. In this study, we explored the possible regulation of GSK-3 and the potential relevance of GSK-3 blockade in IFN-γ-mediated immune hepatiti

Role of Glycogen Synthase Kinase-3 in Interferon-γ-Mediated Immune Hepatitis

Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase, is a vital glycogen synthase regulator controlling glycogen synthesis, glucose metabolism, and insulin signaling. GSK-3 is widely expressed in different types of cells, and its abundant roles in cellular bioregulation have been speculated. Abnormal GSK-3 activation and inactivation may affect its original bioactivity. Moreover, active and inactive GSK-3 can regulate several cytosolic factors and modulate their diverse cellular functional roles. Studies in experimental liver disease models have illustrated the possible pathological role of GSK-3 in facilitating acute hepatic injury. Pharmacologically targeting GSK-3 is therefore suggested as a therapeutic strategy for liver protection. Furthermore, while the signaling transduction of GSK-3 facilitates proinflammatory interferon (IFN)-γ in vitro and in vivo, the blockade of GSK-3 can be protective, as shown by an IFN-γ-induced immune hepatitis model. In this study, we explored the possible regulation of GSK-3 and the potential relevance of GSK-3 blockade in IFN-γ-mediated immune hepatitis

Epithelial-to-mesenchymal transition hinders interferon-γ-dependent immunosurveillance in lung cancer cells

The epithelial-to-mesenchymal transition (EMT) is involved in cancer metastasis; nevertheless, interferon (IFN)-γ induces anticancer activities by causing cell growth suppression, cytotoxicity, and migration inhibition. Regarding the poor response to exogenously administered IFN-γ as anticancer therapy, it was hypothesized that malignant cells may acquire a means of escaping from IFN-γ immunosurveillance, likely through an EMT-related process. A genomic analysis of human lung cancers revealed a negative link between the EMT and IFN-γ signaling, while compared to human lung adenocarcinoma A549 cells, IFN-γ-hyporesponsive AS2 cells exhibited mesenchymal characteristics. Chemically, physically, and genetically engineered EMT attenuated IFN-γ-induced IFN regulatory factor 1 transactivation. Poststimulation of transforming growth factor-β induced the EMT and also selectively retarded IFN-γ-responsive gene expression as well as IFN-γ-induced signal transducer and activator of transcription 1 activation, major histocompatibility complex I, and CD54 expression, cell migration/invasion inhibition, and direct/indirect cytotoxicity. Without changes in IFN-γ receptors, excessive oxidative activation of Src homology-2 containing phosphatase 2 (SHP2) in cells undergoing the EMT primarily caused cellular hyporesponsiveness to IFN-γ signaling and cytotoxicity, while combining an SHP2 inhibitor or antioxidant sensitized EMT-associated AS2 and mesenchymal A549 cells to IFN-γ-induced priming effects on tumor necrosis factor-related apoptosis-inducing ligand cytotoxicity. In cell line-derived xenograft models, combined treatment with IFN-γ and an SHP2 inhibitor induced enhanced anticancer activities. These results imply that EMT-associated SHP2 activation inhibits IFN-γ signaling, facilitating lung cancer cell escape from IFN-γ immunosurveillance