Omics A Journal of Integrative Biology最新文献

International cooperation beyond borders, institutions, and intergenerationally is an important aspect of science and research-based learning. Timing of learning also matters. Early exposure to group research-based learning can potentially have lasting positive impacts on youth and their careers in life sciences. Here, we report our work on the International Group Project (IGP), which builds on the International Biology Olympiad (IBO) organized in Yerevan, Armenia, in 2022. The IBO is an annual international competition for high school students held since 1990 around the world. We envisioned the IGP as a novel opportunity for life sciences research-based education among youth. We formed diverse IGP research teams 2 months before the IBO, and comprised high school students from 32 countries, communicating in a digital environment via videoconferencing. Each team formulated a research question in an IGP theme from five domains of life sciences: "Biomedicine," "Molecular and cell biology," "Bioinformatics and Artificial Intelligence," "Bionics and Biomimicry," "Across Species." Subsequently, team members collectively solved their research question by applying life sciences methodologies under supervision from a facilitator scientist. Each team created a poster based on their research and presented in-person to the public at a satellite activity at the IBO. A special subcommittee of the IBO International Jury graded posters and allocated prizes based on scientific ingenuity and presentation quality. This experience from the IGP lends evidence to the feasibility of research-based learning in life sciences for high school youth beyond borders. Moving research-based learning upstream and internationally is well poised to advance 21st century life sciences from both interdisciplinary and intergenerational standpoints. The historic impact of the COVID-19 pandemic suggests that youth engagement in research-based learning and innovation in life sciences is timely.

MicroRNA aberrations including that of miR-24-2 have been reported in various cancers. However, the target genes for miR-24-2 are yet to be identified and validated in invasive breast cancer and the triple-negative breast cancer (TNBC). Using in silico approaches and gene expression analyses, we identified and validated the target genes of miR-24-2 in invasive breast cancer, majority of which were TNBC. We studied the translational potential of these target genes using berberine in a TNBC cell line. Differentially expressed genes targeted by miR-24-2 were identified and analyzed for their survival effects using the The Cancer Genome Atlas-Breast Invasive Carcinoma (-BRCA) samples. Furthermore, we carried out protein-protein interaction, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene expression, and Kaplan-Meier survival analyses using common targets of miR-24-2 in invasive breast cancer/TNBC. We identified 11 biomarker candidate genes as crucial targets of miR-24-2. The survival of breast cancer patients was significantly associated with the low expressions of nine genes, including RACGAP1, KIAA1199, TIMM17A, LYRM7, IL1R1, SLC1A3, DTX4, L1CAM, and SAP30-like (SAP30L), and high expressions of two genes, SOD2 and HLA-DQB2. These in silico findings were validated by overexpressing miR-24-2 and assessing the expression pattern of these target genes in the TNBC MDA-MB-231 cells. miR-24-2 overexpression inhibited (by 20%; p < 0.001) cell proliferation and sensitized the anticancer effect of berberine. In all, this study reports on the novel target genes of miR-24-2 in invasive breast cancer/TNBC, and that miR-24-2 sensitizes MDA-MB-231 cells to berberine. These data lend evidence for the translational potentials of miR-24-2 for invasive breast cancer diagnostic and therapeutic innovation.

Precision/personalized medicine in oncology has two key pillars: molecular profiling of the tumors and personalized reporting of the results in ways that are clinically contextualized and triangulated. Moreover, neurosurgery as a field stands to benefit from precision/personalized medicine and new tools for reporting of the molecular findings. In this context, glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Precision/personalized medicine has emerged as a promising approach for personalized therapy in GBM. In this study, we performed whole exome sequencing of tumor tissue samples from six newly diagnosed GBM patients and matched nontumor control samples. We report here the genetic alterations identified in the tumors, including single nucleotide variations, insertions or deletions (indels), and copy number variations, and attendant mutational signatures. Additionally, using a personalized cancer genome-reporting tool, we linked genomic information to potential therapeutic targets and treatment options for each patient. Our findings revealed heterogeneity in genetic alterations and identified targetable pathways, such as the PI3K/AKT/mTOR pathway. This study demonstrates the prospects of precision/personalized medicine in GBM specifically, and neurosurgical oncology more generally, including the potential for genomic profiling coupled with personalized cancer genome reporting. Further research and larger studies are warranted to validate these findings and advance the treatment options and outcomes for patients with GBM.

For precision in clinical oncology practice, detection of tumor-derived peptides and proteins in urine offers an attractive and noninvasive alternative for diagnostic or screening purposes. In this study, we report comparative quantitative proteomic profiling of urine samples from patients with gastric cancer and healthy controls using tandem mass tags-based multiplexed mass spectrometry approach. We identified 1504 proteins, of which 246 were differentially expressed in gastric cancer cases. Notably, ephrin A1 (EFNA1), pepsinogen A3 (PGA3), sortilin 1 (SORT1), and vitronectin (VTN) were among the upregulated proteins, which are known to play crucial roles in the progression of gastric cancer. We also found other overexpressed proteins, including shisa family member 5 (SHISA5), mucin like 1 (MUCL1), and leukocyte cell derived chemotaxin 2 (LECT2), which had not previously been linked to gastric cancer. Using a novel approach for targeted proteomics, SureQuant, we validated changes in abundance of a subset of proteins discovered in this study. We confirmed the overexpression of vitronectin and sortilin 1 in an independent set of urine samples. Altogether, this study provides molecular candidates for biomarker development in gastric cancer, and the findings also support the promise of urinary proteomics for noninvasive diagnostics and personalized/precision medicine in the oncology clinic.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disease of the lung with poor prognosis. Fibrosis results from remodeling of the interstitial tissue. A wide range of gene expression changes are observed, but the role of micro RNAs (miRNAs) and circular RNAs (circRNA) is still unclear. Therefore, this study aimed to establish an messenger RNA (mRNA)-miRNA-circRNA competing endogenous RNA (ceRNA) regulatory network to uncover novel molecular signatures using systems biology tools. Six datasets were used to determine differentially expressed genes (DEGs) and miRNAs (DEmiRNA). Accordingly, protein-protein, mRNA-miRNA, and miRNA-circRNA interactions were constructed. Modules were determined and further analyzed in the Drug Gene Budger platform to identify potential therapeutic compounds. We uncovered common 724 DEGs and 278 DEmiRNAs. In the protein-protein interaction network, TMPRSS4, ESR2, TP73, CLEC4E, and TP63 were identified as hub protein coding genes. The mRNA-miRNA interaction network revealed two modules composed of ADRA1A, ADRA1B, hsa-miR-484 and CDH2, TMPRSS4, and hsa-miR-543. The DEmiRNAs in the modules further analyzed to propose potential circRNA regulators in the ceRNA network. These results help deepen the understanding of the mechanisms of IPF. In addition, the molecular leads reported herein might inform future innovations in diagnostics and therapeutics research and development for IPF.

Prostate cancer (PCa) represents a huge public health burden among men. Many susceptibility genetic factors for PCa still remain unknown. In this study, we performed a large splicing transcriptome-wide association study (spTWAS) using three modeling strategies to develop alternative splicing genetic prediction models for identifying novel susceptibility loci and splicing introns for PCa risk by assessing 79,194 cases and 61,112 controls of European ancestry in the PRACTICAL, CRUK, CAPS, BPC3, and PEGASUS consortia. We identified 120 splicing introns of 97 genes showing an association with PCa risk at false discovery rate (FDR)-corrected threshold (FDR <0.05). Of them, 33 genes were enriched in PCa-related diseases and function categories. Fine-mapping analysis suggested that 21 splicing introns of 19 genes were likely causally associated with PCa risk. Thirty-five splicing introns of 34 novel genes were identified to be related to PCa susceptibility for the first time, and 11 of the genes were enriched in a cancer-related network. Our study identified novel loci and splicing introns associated with PCa risk, which can improve our understanding of the etiology of this common malignancy.

Cigarette smoking is the major cause of chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD). It is paramount to develop pharmacological interventions and delivery strategies against the cigarette smoke (CS) associated oxidative stress in COPD. This study in Wistar rats examined cysteamine in nanoemulsions to counteract the CS distressed microenvironment. In vivo, 28 days of CS and 15 days of cysteamine nanoemulsions treatment starting on 29th day consisting of oral and inhalation routes were established in Wistar rats. In addition, we conducted inflammatory and epithelial-to-mesenchymal transition (EMT) studies in vitro in human bronchial epithelial cell lines (BEAS2B) using 5% CS extract. Inflammatory and anti-inflammatory markers, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-8, IL-10, and IL-13, have been quantified in bronchoalveolar lavage fluid (BALF) to evaluate the effects of the cysteamine nanoemulsions in normalizing the diseased condition. Histopathological analysis of the alveoli and the trachea showed the distorted, lung parenchyma and ciliated epithelial barrier, respectively. To obtain mechanistic insights into the CS COPD rat model, "shotgun" proteomics of the lung tissues have been carried out using high-resolution mass spectrometry wherein genes such as ABI1, PPP3CA, PSMA2, FBLN5, ACTG1, CSNK2A1, and ECM1 exhibited significant differences across all the groups. Pathway analysis showed autophagy, signaling by receptor tyrosine kinase, cytokine signaling in immune system, extracellular matrix organization, and hemostasis, as the major contributing pathways across all the studied groups. This work offers new preclinical findings on how cysteamine taken orally or inhaled can combat CS-induced oxidative stress.