Omics A Journal of Integrative Biology最新文献

Pharmacists play a pivotal role in pharmacogenomic (PGx) implementation in clinical practice, and their university education is considered a strong driver in holding favorable intentions toward PGx adoption. Using a survey developed based on the Theory of Planned Behavior (TPB), this study aimed to evaluate the determinants of senior pharmacy students' intentions to pursue postgraduate training in PGx and personalized medicine (PM), and with an eye to propose interventions to inform pharmacy students' career choices in the field. Students manifested considerably favorable attitudes toward PGx clinical practice and had acquired a relatively satisfactory level of knowledge. However, they conceded of having a hardly moderate level of confidence in PGx clinical application, and claimed to be moderately satisfied with their PGx training. Interestingly, students alleged to have a relatively limited interest to pursue postgraduate training studies in PGx and PM. Gender was a key and significant demographic moderator of the students' intentions to pursue postgraduate training in PGx and PM. We found that the students' attitudes exerted a strong positive impact on intentions for future PGx training, while self-confidence and training satisfaction had a moderate positive effect, respectively. We propose a set of key interventions that include, inter alia, the update of existing pharmacy curricula and the promotion of interdisciplinary collaborations with other health professionals, to reinforce the pharmacists' role in PM and PGx implementation in clinical practice. To the best of our knowledge, this is the first study using the TPB to identify the role of certain factors such as gender, attitudes, self-confidence, and training satisfaction on the final-year pharmacy undergraduate students' intentions to pursue PGx-related postgraduate studies in the future.

Chronic inflammation is an important contributor to tumorigenesis in many tissues. However, the underlying mechanisms of inflammatory signaling in the tumor microenvironment are not yet fully understood in various cancers. Therefore, this study aimed to uncover the gene expression signatures of inflammation-associated proteins that lead to tumorigenesis, and with an eye to discovery of potential system biomarkers and novel drug candidates in oncology. Gene expression profiles associated with 12 common cancers (e.g., breast invasive carcinoma, colon adenocarcinoma, liver hepatocellular carcinoma, and prostate adenocarcinoma) from The Cancer Genome Atlas were retrieved and mapped to inflammation-related gene sets. Subsequently, the inflammation-associated differentially expressed genes (i-DEGs) were determined. The i-DEGs common in all cancers were proposed as tumor inflammation signatures (TIS) after pan-cancer analysis. A TIS, consisting of 45 proteins, was evaluated as a potential system biomarker based on its prognostic forecasting and secretion profiles in multiple tissues. In addition, i-DEGs for each cancer type were used as queries for drug repurposing. Narciclasine, parthenolide, and homoharringtonine were identified as potential candidates for drug repurposing. Biomarker candidates in relation to inflammation were identified such as KNG1, SPP1, and MIF. Collectively, these findings inform precision diagnostics development to distinguish individual cancer types, and can also pave the way for novel prognostic decision tools and repurposed drugs across multiple cancers. These new findings and hypotheses warrant further research toward precision/personalized medicine in oncology. Pan-cancer analysis of inflammatory mediators can open up new avenues for innovation in cancer diagnostics and therapeutics.

Systems biology tools offer new prospects for industrial strain selection. For bacteria that are significant for industrial applications, whole-genome sequencing coupled to flux balance analysis (FBA) can help unpack the complex relationships between genome mutations and carbon trafficking. This work investigates the l-tyrosine (l-Tyr) overproducing model system Corynebacterium glutamicum ATCC 21573 with an eye to more rational and precision strain development. Using genome-wide mutational analysis of C. glutamicum, we identified 27,611 single nucleotide polymorphisms and 479 insertion/deletion mutations. Mutations in the carbon uptake machinery have led to phosphotransferase system-independent routes as corroborated with FBA. Mutations within the central carbon metabolism of C. glutamicum impaired the carbon flux, as evidenced by the lower growth rate. The entry to and flow through the tricarboxylic acid cycle was affected by mutations in pyruvate and α-ketoglutarate dehydrogenase complexes, citrate synthase, and isocitrate dehydrogenase. FBA indicated that the estimated flux through the shikimate pathway became larger as the l-Tyr production rate increased. In addition, protocatechuate export was probabilistically impossible, which could have contributed to the l-Tyr accumulation. Interestingly, aroG and cg0975, which have received previous attention for aromatic amino acid overproduction, were not mutated. From the branch point molecule, prephenate, the change in the promoter region of pheA could be an influential contributor. In summary, we suggest that genome sequencing coupled with FBA is well poised to offer rational guidance for industrial strain development, as evidenced by these findings on carbon trafficking in C. glutamicum ATCC 21573.

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.