Prediction of the Signaling Pathway in Polycystic Ovary Syndrome Using an Integrated Bioinformatics Approach.

Objectives The purpose of this study was to define the underlying biological mechanisms of PCOS utilizing the protein-protein interaction networks that were constructed based on the putative disease-causing genes for PCOS. Design No animals were used in this research because this study is an In-Silico studies which mainly uses softwares and online analysis tools. Participants/Materials, Settings Genes datasets related with PCOS were obtained from Genecard. Methods The protein-protein interaction networks (PPIN) of PCOS were created using the String Database after genes related with PCOS were obtained from Genecard. After that, we performed an analysis of the hub-gene clusters extracted from the PPIN using the ShinyGO algorithm. In the final step of this research project, functional enrichment analysis was used to investigate the primary biological activities and signaling pathways that were associated with the hub clusters. Results The Genecard database provided the source for the identification of a total of 1072 potential genes related with PCOS. The PPIN that was generated by using the genes that we collected above contained a total of 82 genes and three different types of cluster interaction interactions. In addition, after conducting research on the PPIN with the shinyGO plug-in, 19 of the most important gene clusters were discovered. The primary biological functions that were enriched in the key clusters that were developed were ovarian stereoidogenesis, breast cancer pathway, regulation of lipid and glucose metabolism by AMPK pathway, and ovarian stereoidogenesis. The integrated analysis that was performed in the current study demonstrated that these hub clusters and their connected genes are closely associated to the pathogenesis of PCOS. Limitations Several of the significant genes that were identified in this study, such as ACVR1, SMAD5, BMP6, SMAD3, SMAD4 and AMH. It is necessary to do additional research using large samples, several centers, and multiple ethnicities in order to verify these findings. Conclusions The integrated analysis that was performed in the current study demonstrated that these hub clusters and their connected genes are closely associated to the pathogenesis of PCOS. This information may possibly bring unique insights for the treatment of PCOS as well as the investigation of its underlying pathogenic mechanism.

Prediction of Translational Regulation by Network Interaction in Synaptic Plasticity Induced with Centella asiatica.

Background: Recently, human life expectancy, aging, and age-related health disorders, especially neurodegenerative diseases such as Alzheimer's disease (AD), have increased. The increasing number of AD patients causes a heavy social and economic burden on society. Since there is no treatment for AD, utilization of natural products is currently accepted as an alternative or integrative treatment agent against AD. Methods: Selection of protein databases related to synaptic plasticity was obtained from a gene bank. The protein-protein interaction (PPI) analysis was performed using Cytoscape 3.9.1. Prediction of Centella asiatica target constituents and their relationship with target synaptic plasticity was performed using STITCH, followed by GO and KEGG pathway enrichment analysis and molecular binding of ligands to presynaptic and postsynaptic receptors afterwards. Results: From the protein database, 446 protein coding genes related to synaptic plasticity were found. PPI and KEGG pathway analysis showed potentiality to inhibit AKT and mTORC1 pathways. The targeted proteins were TSC1, Rheb, and FMRP. Conclusion: This study showed potentiality of Centella asiatica in AD through its binding to several proteins such as TSC1, Rheb, and FMRP. This compound in Centella asiatica was able to bind to the AKT1 and mTOR signaling pathways. Centella asiatica may behold greater potency in AD therapy.

A narrative review of genomic characteristics, serotype, immunogenicity, and vaccine development of Streptococcus pneumoniae capsular polysaccharide.

This narrative review describes genomic characteristic, serotyping, immunogenicity, and vaccine development of Streptococcus pneumoniae capsular polysaccharide (CPS). CPS is a primary virulence factor of S. pneumoniae. The genomic characteristics of S. pneumoniae CPS, including the role of biosynthetic gene and genetic variation within cps (capsule polysaccharide) locus which may lead to serotype replacement are still being investigated. One hundred unique serotypes of S. pneumoniae have been identified through various methods of serotyping using phenotypic and genotypic approach. The advantages and limitations of each method are various, emphasizing the need for accurate and comprehensive serotyping for effective disease surveillance and vaccine targeting. In addition, we elaborate the critical role of CPS in vaccine development by providing an overview of immunogenicity, ongoing research of pneumococcal vaccines, and the impact on disease burden.

Identification of Potential Breast Cancer Stem Cell Biomarkers in the Secretome Using a Network Interaction Approach Analysis.

BACKGROUND: Breast cancer stem cells (BCSCs) play a role in the high rates of resistance, recurrence, and metastasis. The precise biomarkers of BCSCs can assist effectively in identifying cancer, assessing prognosis, diagnosing, and monitoring therapy. The aim of this study was to give a complete analysis for predicting specific biomarkers of BCSCs. METHODS: We aggregated profile datasets in this work to shed light on the underlying critical genes and pathways of BCSCs. We obtained two expression profiling by array datasets (GSE7513 and GSE7515) from the Gene Expression Omnibus (GEO) database to identify biomarkers in BCSCs. Enrichr was used to do functional analysis, including gene ontology (GO) and reactome pathway. Furthermore, the protein-protein interaction (PPI) of these differential expression genes (DEGs) was visualized using Cytoscape with the search tool for the retrieval of interacting genes (STRING). The hub genes in the PPI network were chosen for further investigation. RESULTS: We identified 65 up-regulated and 190 down- regulated DEGs and the GO enrichment analysis revealed that these DEGs were enriched in biological process related to tumorigenesis and stemness, including alter the extracellular matrix's physicochemical properties, cytoskeletal reorganisation, adhesion, motility, migration, growth, and survival. The Reactome analysis indicated that these DEGs were also involved in modulating function of ECM, regulation cancer metabolism and angiogenesis, tumor growth, proliferation, and metastasis. CONCLUSION: Our bioinformatic study revealed that FYN, INADL, OCLN, F11R, and TOP2A were potential biomarker panel of BCSCs from secretome.

Profibrotic Inflammatory Cytokines and Growth Factors Are Predicted as the Key Targets of Uncaria gambir (Hunter) Roxb. in Keloids: An Epistatic and Molecular Simulation Approach.

Keloid is characterized as the fibrotic tissue resulting from the increase of fibroblast activity. Uncaria gambir (Hunter) Roxb. possesses bioactive compounds that have potential as antifibrotic agents, while the mechanism of action in keloid has not yet been elucidated. The aim of this study was to investigate the interaction of gambir bioactive compounds with keloid target proteins using an epistatic and molecular simulation approach. The known bioactive compounds of gambir targets and keloid-related protein targets were screened using databases. The network was constructed and analyzed to obtain the core protein targets. The targets were enriched to describe the Gene Ontology (GO) and pathway related to the proteins. Eleven targets were defined as the main targets of gambir bioactive compounds related to keloid disease. Gambiriin C, Isogambirine, and Procyanidin B1 were identified as the most promising compounds with the highest binding energy to transforming growth factor beta 1 (TGFß1), AKT serine/threonine kinase 1 (AKT1), and matrix metallopeptidase 1 (MMP1) as the target proteins. GO enrichment and pathway analysis found that gambir bioactive compounds may act on keloid-related target proteins to regulate cell proliferation, migration, transcription, and signal transduction activity via profibrotic cytokine and growth factor signaling pathways. This study provides a reference for potential targets, compounds, and pathways to explain the mechanism of gambir against keloid.

Exploration of the main active metabolites from Tinospora crispa (L.) Hook. f. & Thomson stem as insulin sensitizer in L6.C11 skeletal muscle cell by integrating in vitro, metabolomics, and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora crispa (L.) Hook. f. & Thomson stem (TCS) has long been used as folk medicine for the treatment of diabetes mellitus. Previous study revealed that TCS possesses multi-ingredients and multi-targets characteristic potential as insulin sensitizer activity. However, its mechanisms of action and molecular targets are still obscure. AIM OF THE STUDY: In the present study, we investigated the effects of TCS against insulin resistance in muscle cells through integrating in vitro experiment and identifying its active biomarker using metabolomics and in molecular docking validation. MATERIALS AND METHODS: We used centrifugal partition chromatography (CPC) to isolate 33 fractions from methanolic extract of TCS, and then used UHPLC-Orbitrap-HRMS to identify the detectable metabolites in each fraction. We assessed the insulin sensitization activity of each fraction using enzyme-linked immunosorbent assay (ELISA), and then used confocal immunocytochemistry microscopy to measure the translocation of glucose transporter 4 (GLUT4) to the cell membrane. The identified active metabolites were further simulated for its molecular docking interaction using Autodock Tools. RESULTS: The polar fractions of TCS significantly increased insulin sensitivity, as measured by the inhibition of phosphorylated insulin receptor substrate-1 (pIRS1) at serine-312 residue (ser312) also the increasing number of translocated GLUT4 and glycogen content. We identified 58 metabolites of TCS, including glycosides, flavonoids, alkaloids, coumarins, and nucleotides groups. The metabolomics and molecular docking simulations showed the presence of minor metabolites consisting of tinoscorside D, higenamine, and tinoscorside A as the active compounds. CONCLUSIONS: Our findings suggest that TCS is a promising new treatment for insulin resistance and the identification of the active metabolites in TCS could lead to the development of new drugs therapies for diabetes that target these pathways.

IDeRare: a lightweight and extensible open-source phenotype and exome analysis pipeline for germline rare disease diagnosis.

Objectives: Diagnosing rare diseases is an arduous and challenging process in clinical settings, resulting in the late discovery of novel variants and referral loops. To help clinicians, we built IDeRare pipelines to accelerate phenotype-genotype analysis for patients with suspected rare diseases. Materials and Methods: IDeRare pipeline is separated into phenotype and genotype parts. The phenotype utilizes our handmade Python library, while the genotype part utilizes command line (bash) and Python script to combine bioinformatics executable and Docker image. Results: We described various implementations of IDeRare phenotype and genotype parts with real-world clinical and exome data using IDeRare, accelerating the terminology conversion process and giving insight on the diagnostic pathway based on disease linkage analysis until exome analysis and HTML-based reporting for clinicians. Conclusion: IDeRare is freely available under the BSD-3 license, obtainable via GitHub. The portability of IDeRare pipeline could be easily implemented for semi-technical users and extensible for advanced users.

Hibiscus sabdariffa Linn. Extract Increases the mRNA Expression of the Arcuate Nucleus Leptin Receptor and is Predicted in silico as an Anti-obesity Agent.

BACKGROUND: Leptin is predominant in regulating body weight by stimulating energy expenditure through its neuronal action in the brain. Moreover, it is projected to adipose tissue and induces adipocyte browning by activating the ß3-adrenergic receptor (ß3AR). However, the expression of leptin receptor (Lep-R) and ß3AR in people with obesity is downregulated. AIM: We hypothesized that Hibiscus sabdariffa Linn. extract (HSE) would increase hypothalamus arcuate nucleus (ARC) Lep-R and white adipose tissue (WAT) ß3AR mRNA expression in DIO rats. This study also analyzed the potency of H. sabdariffa bioactive compounds as activators of Lep-R and ß3AR by an in-silico experiment. METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: Control (standard food), DIO (high-fat diet), DIO-Hib200 (HFD+HSE 200 mg/kg BW), and DIO-Hib400 (HFD+HSE400 mg/kg BW). HSE was administered orally for five weeks, once a day. RESULTS: HSE administration significantly (P<0,05) increased the ARC Lep-R expression. The Lee index significantly decreased to the normal range (≤ 310) with p<0,001 for DIO-Hib200 and p<0,01 for DIO-Hib400. Among 39 bioactive compounds, 5-O-caffeoyl shikimic acid exhibited high free binding scores (-8,63) for Lep-R, and myricetin_3_arabinogalactoside had high free binding scores (-9,39) for ß3AR. These binding predictions could activate Lep-R and ß3AR. CONCLUSION: This study highlights that HSE could be a potential therapeutic target for obesity by increasing LepR mRNA and leptin sensitivity, enhancing energy expenditure, and reducing obesity.

In silico docking analysis of beta-defensin 20 against cation channel sperm-associated protein 1-4 to predict its role in the sperm maturation.

Beta-defensin 20 (DEFB20) is widely expressed in the epididymis with gene features involved in epididymal sperm maturation. However, the action mechanism and function of DEFB20 in sperm maturation are still unclear. One of the important roles of beta-defensin is the ion channel activity. The cation channel sperm-associated protein (CatSper) alpha is an ion channel protein found on the sperm surface. This study aimed to investigate the interaction between DEFB20 and CatSper1-4 protein in relation to the sperm maturation process. Protein sequences were obtained from the National Center for Biotechnology Information (NCBI). Protein modeling and validation were carried out by using the Robetta modeling server and the Ramachandran plot method. Rosetta web server was used for the docking analysis. The results revealed a natural interaction between DEFB20 and CatSper1-4. The interaction occurred at the cation channel (close to the casein kinase II), ion transport protein, and kinase c phosphorylation of the CatSper1-4 active site. The DEFB20 region interacting with CatSper2-4 was the beta-defensin domain, while with CatSper1 was the non-beta-defensin domain. Based on the analysis, DEFB20 may interact with CatSper α subunits, particularly CatsSper1, to affect ion channel activity during sperm maturation.

The Antifungal Activities of Syzygium aromaticum and Alpinia purpurata Extracts Against Candida krusei: Bioactivity Tests, Molecular Modeling, and Toxicity Tests.

BACKGROUND: Candida krusei is the cause of the fungal infection candidiasis, which has a high mortality rate. Intrinsic resistance to fluconazole can cause the failure of Krusei candidiasis treatment. Therefore, it is necessary to find alternative drugs to eliminate the fungus. Extracts of Syzygium aromaticum and Alpinia purpurata have been proven to be alternative solutions for treating Candida krusei resistance. OBJECTIVE: This study aims to explore the active compounds Syzygium aromaticum and Alpinia purpurata as treatments against Candida krusei through bioactivity tests, molecular modeling, and toxicity tests. METHODS: Determination of antifungal activity with the agar well diffusion and microbroth dilution method. Molecular modeling was conducted using the following software: Marvin Sketch, LigandScout  4.4.5, AutoDock ver 4.2.6, PyMOL, LigPlus, MOE ver 2008. RESULT: Bioactivity test results of the two natural extracts against C. krusei ATCC 6258, it was found that the S. aromaticum and A. purpurata extracts have MIC50 values of 0.031 µg/mL and 1.435x105 µg/mL. The molecular modeling found that the compounds Benzotriazole, 1-(4-methyl-3-nitrobenzoyl)-, 1,3,4-Eugenol Acetate, Stigmasta-5,22-dien-3-ol, acetate (3 beta)- and Farnesyl acetate from the two natural extracts, interacts with the active site of the enzyme lanosterol-14-α-demethylase with a binding energy of -8.91, -6.04, -13.53, and -7.15 kcal/mol. The oral acute toxicity test of S. aromaticum and A. purpurata extracts proved that the LD50 was >6000 mg/kg BW and >8000 mg/kg BW. The acute dermal toxicity test of the two extracts showed that the LD50 was >6000 mg/kg BW. CONCLUSION: S. aromaticum and A. purpurata extracts have been proven to be alternative solutions for treating Candida krusei resistance.

Synthesis and in vitro Activity of Eugenyl Benzoate Derivatives as BCL-2 Inhibitor in Colorectal Cancer with QSAR and Molecular Docking Approach.

OBJECTIVE: This study is aimed to acquiring new compounds of Eugenyl benzoate (2-methoxy-4-(prop-2-en-1-yl)phenyl benzoate) derivatives that can inhibit HT29 colorectal cancer cells. METHODS: In this research, we used several chemical reactions to synthesize novel compounds, such as Esterification, Demethylation, Halohydrin, and Sharpless reaction. Cytotoxicity assays were performed to test the inhibitory activity of compounds against HT29 colon cancer cells. QSAR analysis were carried out to analyse the relationship of chemical structure of the novel compounds with their cytotoxic activity. RESULT: Ten novel compounds were successfully synthesized and tested in vitro against the HT29 cell. The IC50 of the novel compounds were between 26.56 µmol/ml - 286.81 µmol/ml which compound 4-[(2S)-2,3-dihydroxypropyl]-2-methoxyphenyl 2-hydroxybenzoate (9) showed as best active compound as BCL-2 inhibitors better than other synthesized compounds and Eugenol as well. QSAR analysis of the in vitro results gave a Log equation: 1/IC50 = -0.865-0.210 (LogP)2 + 1,264 (logP)-0.994 CMR (n = 10; r = 0.706; SE: 0.21; F = 0.497, sig = 7.86). The equation shows the log variable P and CMR affect IC50. The properties of hydrophobicity (log P) are more instrumental than the ones of steric (CMR). CONCLUSION: The active compound (9) given best activities as BCL-2 inhibitors than other eugenol derivatives. QSAR indicates the logP and CMR have effect on its colorectal cytotoxic activity which the hydrophobicity parameter (logP) plays more role than the steric parameter (CMR).

Network pharmacology integrated molecular dynamics reveals the bioactive compounds and potential targets of Tinospora crispa Linn. as insulin sensitizer.

Insulin resistance is a metabolic disorder characterized by the decreased response to insulin in muscle, liver, and adipose cells. This condition remains a complex phenomenon that involves several genetic defects and environmental stresses. In the present study, we investigated the mechanism of known phytochemical constituents of Tinospora crispa and its interaction with insulin-resistant target proteins by using network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Tinoscorside A, Makisterone C, Borapetoside A and B, and ß sitosterol consider the main phytoconstituents of Tinospora crispa by its binding with active sites of main protein targets of insulin resistance potential therapy. Moreover, Tinoscorside A was revealed from the docking analysis as the ligand that binds most strongly to the target protein, PI3K. This finding was strengthened by the results of MD simulation, which stated that the conformational stability of the ligand-protein complex was achieved at 15 ns and the formation of hydrogen bonds at the active site. In conclusion, Tinospora crispa is one of the promising therapeutic agent in type 2 diabetes mellitus management. Regulation in glucose homeostasis, adipolysis, cell proliferation, and antiapoptosis are predicted to be the critical mechanism of Tinospora crispa as an insulin sensitizer.

Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population.

Germline predisposition plays an important role in breast cancer. Different ethnic populations need respective studies on cancer risks pertinent to germline variants. We aimed to discover the pathogenic and likely pathogenic variants (P/LP-Vs) of germline breast cancer susceptibility genes and to evaluate their correlation with the clinical characteristics in Jakarta populations. The pure DNA was extracted from the blood buffy coat, using reagents from the QIAamp DNA Mini Kit® (Qiagen, Hilden, Germany). The DNA libraries were prepared using the TargetRich™ Hereditary Cancer Panel (Kailos Genetics®, Huntsville, AL, USA). The barcoded DNA libraries were sequenced using the Illumina NextSeq 500 platform. In-house bioinformatics pipelines were used to analyze the gene variants. We identified 35 pathogenic and likely pathogenic (P/LP-Vs) variants (28 frameshift, 5 nonsense, and 2 splice-site variants). The P/LP-Vs group was statistically significantly different in luminal B status (p < 0.05) compared with the non-P/LP-Vs group. The P/LP-Vs found both in BRCA1/2 genes and non-BRCA genes may increase the risk of breast cancer and alter drug responses. The screening of multigene variants is suggested, rather than BRCA testing only. Prior knowledge of the germline variants status is important for optimal breast cancer diagnosis and optimal therapy.

Whole genome sequencing data of Candida krusei, the pathogen causing Candidaemia, from Department of Parasitology Culture Collection, Faculty of Medicine Universitas Indonesia.

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.

Case series in Indonesia: B.1.617.2 (delta) variant of SARS-CoV-2 infection after a second dose of vaccine.

BACKGROUND: The B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in Maharashtra in late 2020 and has rapidly expanded across India and worldwide. It took only 2 mo for this variant to spread in Indonesia, making the country the new epicenter of the delta variant as of July 2021. Despite efforts made by accelerating massive rollouts of current vaccines to protect against infection, cases of fully-vaccinated people infected with the delta variant have been reported. AIM: To describe the demographic statistics and clinical presentation of the delta variant infection after the second dose of vaccine in Indonesia. METHODS: A retrospective, single-centre case series of the general consecutive population that worked or studied at Faculty of Medicine, Universitas Indonesia with confirmed Delta Variant Infection after a second dose of vaccine from 24 June and 25 June 2021. Cases were collected retrospectively based on a combination of author recall, reverse transcription-polymerase chain reaction (RT-PCR), and whole genome sequencing results from the Clinical Microbiology Laboratory, Faculty of Medicine, Universitas Indonesia. RESULTS: Between 24 June and 25 June 2021, 15 subjects were confirmed with the B.1.617.2 (delta) variant infection after a second dose of the vaccine. Fourteen subjects were vaccinated with CoronaVac (Sinovac) and one subject with ChAdOx1 nCoV-19 (Oxford-AstraZeneca). All of the subjects remained in home isolation, with fever being the most common symptom at the onset of illness (n = 10, 66.67%). The mean duration of symptoms was 7.73 d (± 5.444). The mean time that elapsed from the first positive swab to a negative RT-PCR test for SARS-CoV-2 was 17.93 d (± 6.3464). The median time that elapsed from the second dose of vaccine to the first positive swab was 87 d (interquartile range: 86-128). CONCLUSION: Although this case shows that after two doses of vaccine, subjects are still susceptible to the delta variant infection, currently available vaccines remain the most effective protection. They reduce clinical manifestations of COVID-19, decrease recovery time from the first positive swab to negative swab, and lower the probability of hospitalization and mortality rate compared to unvaccinated individuals.

Virtual screening of Indonesian herbal compounds as COVID-19 supportive therapy: machine learning and pharmacophore modeling approaches.

BACKGROUND: The number of COVID-19 cases continues to grow in Indonesia. This phenomenon motivates researchers to find alternative drugs that function for prevention or treatment. Due to the rich biodiversity of Indonesian medicinal plants, one alternative is to examine the potential of herbal medicines to support COVID therapy. This study aims to identify potential compound candidates in Indonesian herbal using a machine learning and pharmacophore modeling approaches. METHODS: We used three classification methods that had different decision-making processes: support vector machine (SVM), multilayer perceptron (MLP), and random forest (RF). For the pharmacophore modeling approach, we performed a structure-based analysis on the 3D structure of the main protease SARS-CoV-2 (3CLPro) and repurposed SARS, MERS, and SARS-CoV-2 drugs identified from the literature as datasets in the ligand-based method. Lastly, we used molecular docking to analyze the interactions between the 3CLpro and 14 hit compounds from the Indonesian Herbal Database (HerbalDB), with lopinavir as a positive control. RESULTS: From the molecular docking analysis, we found six potential compounds that may act as the main proteases of the SARS-CoV-2 inhibitor: hesperidin, kaempferol-3,4'-di-O-methyl ether (Ermanin); myricetin-3-glucoside, peonidin 3-(4'-arabinosylglucoside); quercetin 3-(2G-rhamnosylrutinoside); and rhamnetin 3-mannosyl-(1-2)-alloside. CONCLUSIONS: Our layered virtual screening with machine learning and pharmacophore modeling approaches provided a more objective and optimal virtual screening and avoided subjective decision making of the results. Herbal compounds from the screening, i.e. hesperidin, kaempferol-3,4'-di-O-methyl ether (Ermanin); myricetin-3-glucoside, peonidin 3-(4'-arabinosylglucoside); quercetin 3-(2G-rhamnosylrutinoside); and rhamnetin 3-mannosyl-(1-2)-alloside are potential antiviral candidates for SARS-CoV-2. Moringa oleifera and Psidium guajava that consist of those compounds, could be an alternative option as COVID-19 herbal preventions.

Case Report: Delayed treatment of tuberculosis of the elbow joint.

Extrapulmonary tuberculosis (TB) is known to occur in the musculoskeletal system, including the elbow joints. These cases are rarely found because the signs and symptoms are not specific to extrapulmonary TB or other diseases. We report a case of a 24-year-old male, who complained about pain in his left elbow and noticed swelling. Initially, he complained about pain all over his left arm, after several reflexology massages to alleviate his toothache. However, instead of seeking medical treatment, he visited a traditional massage therapist every week without improvement in his left arm pain for almost one year. Examination showed skin perforation with discharge. He also had fever during the first few days when the elbow became swollen. Weight loss and a decreased appetite were also noticed by the patient. The patient went to the orthopedic department and underwent surgery. Radiological examination indicated bone erosion on the left humerus and radius, while posteroanterior chest X-ray did not show any abnormality. Histopathological examinations from biopsy and fluid aspiration showed granulomas and datia Langhans cells. Mycobacterium tuberculosis was found on acid-fast bacteria smear and culture. The patient was administered multidrug tuberculosis therapy, which consisted of two months of an intensive phase and seven months of a continuation phase, in accordance with the World Health Organization's guidelines for extrapulmonary tuberculosis treatment. He has currently undergone the continuation phase of the treatment and his condition has improved. Early detection of tuberculosis of the elbow can prevent damage to joint structure and impairment of joint function.

Rhaponticin contained Rheum officinale root extract improved Postmenopause symptom of Ovariectomized Rat.

Postmenopausal women have decreased levels of the hormone estrogen. Reduced estrogen levels will often involve many symptoms that reduced quality of life. This research aims to analyze the effects of Rheum officinale root extract on postmenopausal model rats. To this end, thirty rats underwent ovariectomy (OVX) surgery and six rats were operated without having their ovaries removed. The OVX was confirmed by body weight-uterus weight ratio and a vaginal swab. Six groups of the rats were performed: SHAM group and negative control groups are given vehicle; the positive control was assigned tamoxifen; and the extract has been given three doses 7, 35, and 175 mg/200 g BW, respectively, for 30 days. The calcium content of bone ash was measured using atomic absorption spectrophotometer. Blood pressure was evaluated using CODA®, and the metabolites in the blood were assessed using gas chromatography-mass spectrometry (MS) and high-performance liquid chromatography. As a result, using ultra-performance liquid chromatography (UPLC)-MS, we found that the extract's major component was rhaponticin and its metabolites. The bone calcium levels increased with increasing doses of the extract. In the OVX group, the bone calcium content was decreased significantly 51.56% ± 8.9% g compared with the SHAM group 62.97% ±5.6% g, and the administration of Rheum extract could restore the calcium content of the bone to become 69.27% ± 3.8% g. From the above data, we concluded that Rheum root extracts contain astrigin, rhaponticin, rhapontigenin, and desoxyrhaponticin. Rheum root extract could improve calcium content and lipid profiles of OVX rats by stimulation osteoblastogenesis. Rheum root extracts could control the blood pressure of OVX rats by reducing lipid profiles.

Xanthine Oxidase-Induced Inflammatory Responses in Respiratory Epithelial Cells: A Review in Immunopathology of COVID-19.

Xanthine oxidase (XO) is an enzyme that catalyzes the production of uric acid and superoxide radicals from purine bases: hypoxanthine and xanthine and is also expressed in respiratory epithelial cells. Uric acid, which is also considered a danger associated molecule pattern (DAMP), could trigger a series of inflammatory responses by activating the inflammasome complex path and NF-κB within the endothelial cells and by inducing proinflammatory cytokine release. Concurrently, XO also converts the superoxide radicals into hydroxyl radicals that further induce inflammatory responses. These conditions will ultimately sum up a hyperinflammation condition commonly dubbed as cytokine storm syndrome (CSS). The expression of proinflammatory cytokines and neutrophil chemokines may be reduced by XO inhibitor, as observed in human respiratory syncytial virus (HRSV)-infected A549 cells. Our review emphasizes that XO may have an essential role as an anti-inflammation therapy for respiratory viral infection, including coronavirus disease 2019 (COVID-19).

Targeted genome sequencing data of young women breast cancer patients in Cipto Mangunkusumo national hospital, Jakarta.

Breast cancer is the most common cancer in women, accounting for approximately 25% of all cancer cases worldwide. Some breast cancer patients are genetically predisposed to genes involved in genomic stability. We report the targeted genome sequencing data of 24 young women (aged below 45 years) breast cancer patients admitted to Cipto Mangunkusumo National Hospital, Jakarta, Indonesia. These data will be useful in detecting the genome markers of breast cancer and in deciding the diagnostics and therapies. DNA sequences were obtained using the Illumina NextSeq 500 platform. FASTQ raw files are available under BioProject accession number PRJNA606794 and Sequence Read Archive accession numbers SRR11774092-SRR11774115.