J Appl Biomed. 2024 Sep;22(3):123-128. doi: 10.32725/jab.2024.016. Epub 2024 Sep 2.

ABSTRACT

Cancer research is linked to modern life-sciences, encompassing achievements in virology, yeast-biology, molecular-biology, genetics, systems-biology, bioinformatics, and so on. With these fascinating developments, it's easy to overlook that the fundamental theories and treatment strategies were established in the early 20th century and have remained valid ever since. Therefore, tribute must be paid to the founders of the field. The main hypotheses on carcinogenesis, the genetic model and the metabolic model, and the concept of cancer-treatment with cytotoxic, targeted or metabolic drugs were proposed more than 100 years ago by great minds such as T. Boveri, O. Warburg, and P. Ehrlich. Hence nothing about these cancer concepts is really new. Through development of powerful new technologies, we have been able to decipher the mechanisms of malignant transformation, thus significantly advancing the field. Our own studies have been focused on the cross-talk between cell-growth-signaling and lipid-metabolism in ovarian cancer to find crossover-points for co-targeting in order to achieve synergistic treatment effects. Notably, a side-effect of the application of current methods of molecular-cell-biology is a deeper knowledge of the laws of normal cell-biology and cell-life. Thus we anticipate the field will advance rapidly in the near future.

PMID:39434508 | DOI:10.32725/jab.2024.016

Genome Biol. 2024 Oct 21;25(1):277. doi: 10.1186/s13059-024-03422-4.

ABSTRACT

Simultaneous profiling of single-cell gene expression and lineage history holds enormous potential for studying cellular decision-making. Recent computational approaches combine both modalities into cellular trajectories; however, they cannot make use of all available lineage information in destructive time-series experiments. Here, we present moslin, a Gromov-Wasserstein-based model to couple cellular profiles across time points based on lineage and gene expression information. We validate our approach in simulations and demonstrate on Caenorhabditis elegans embryonic development how moslin predicts fate probabilities and putative decision driver genes. Finally, we use moslin to delineate lineage relationships among transiently activated fibroblast states during zebrafish heart regeneration.

PMID:39434128 | DOI:10.1186/s13059-024-03422-4

Nature. 2024 Oct 21. doi: 10.1038/s41586-024-07928-6. Online ahead of print.

NO ABSTRACT

PMID:39433908 | DOI:10.1038/s41586-024-07928-6

Commun Biol. 2024 Oct 21;7(1):1360. doi: 10.1038/s42003-024-06943-7.

ABSTRACT

Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. We present GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retaining genes strongly connected by biological networks when GWAS thresholds are relaxed. GRIN was validated on both simulated interrelated gene sets as well as multiple GWAS traits. From multiple GWAS summary statistics of suicide attempt, a complex phenotype, GRIN identified additional genes that replicated across independent cohorts and retained biologically interrelated genes despite a relaxed significance threshold. We present a conceptual model of how these retained genes interact through neurobiological pathways that may influence suicidal behavior, and identify existing drugs associated with these pathways that would not have been identified under traditional GWAS thresholds. We demonstrate GRIN's utility in boosting GWAS results by increasing the number of true positive genes identified from GWAS results.

PMID:39433874 | DOI:10.1038/s42003-024-06943-7

Sci Rep. 2024 Oct 21;14(1):24674. doi: 10.1038/s41598-024-76522-7.

ABSTRACT

An established hallmark of cancer cells is metabolic reprogramming, largely consisting in the exacerbated glucose uptake. Adipocytes in the tumor microenvironment contribute toward breast cancer (BC) progression and are highly responsive to metabolic fluctuations. Metabolic conditions characterizing obesity and/or diabetes associate with increased BC incidence and mortality. To explore BC-adipocytes interaction and define the impact of glucose in such dialogue, Mammary Adipose-derived Mesenchymal Stem Cells (MAd-MSCs) were differentiated into adipocytes and co-cultured with ER+ BC cells while exposed to glucose concentration resembling hyperglycemia or normoglycemia in humans (25mM or 5.5mM). The transcriptome of both cell types in co-culture as in mono-culture was profiled by RNA-Seq to define the impact of adipocytes on BC cells and viceversa (i), the action of glucose on BC cells, adipocytes (ii) and their crosstalk (iii). Noteworthy, we provided evidence that co-culture with adipocytes in a glucose-rich environment determined a re-program of BC cell transcriptome driving lipid accumulation, a hallmark of BC aggressiveness, promoting stem-like properties and reducing Tamoxifen responsiveness. Moreover, our data point out to a transcriptional effect through which BC cells induce adipocytes de-lipidation, paralleled by pluripotency gain, as source of lipids when glucose lowering occurs. Thus, modulating plasticity of peri-tumoral adipocytes may represent a key point for halting BC progression in metabolically unbalanced patients.

PMID:39433816 | DOI:10.1038/s41598-024-76522-7

NPJ Syst Biol Appl. 2024 Oct 22;10(1):122. doi: 10.1038/s41540-024-00453-2.

ABSTRACT

Tumor hypoxia is a dynamic phenomenon marked by fluctuations in oxygen levels across both rapid (seconds to minutes) and slow (hours to days) time scales. While short hypoxia cycles are relatively well understood, the mechanisms behind longer cycles remain largely unclear. In this paper, we present a novel mechanistic mathematical model that explains slow hypoxia cycles through feedback loops involving vascular expansion and regression, oxygen-regulated tumor growth, and toxic cytokine production. Our study reveals that, for the emergence of slow hypoxia cycles, endothelial cells must adapt by decreasing receptor activation as ligand concentration increases. Additionally, the interaction between tumor cells and toxic cytokines influences frequency and intensity of these cycles. By examining the effects of pharmacological interventions, specifically poly (ADP-ribose) polymerase inhibitors, we also demonstrate how targeting cell proliferation can help regulate oxygen levels. Our findings enhance the understanding of hypoxia regulation and suggest PARP proteins as promising therapeutic targets.

PMID:39433780 | DOI:10.1038/s41540-024-00453-2

Int J Biol Macromol. 2024 Oct 19:136735. doi: 10.1016/j.ijbiomac.2024.136735. Online ahead of print.

ABSTRACT

Extracellular vesicles are secretory vesicles involved in cell-to-cell communication via their encapsulated cargo of proteins, lipids, and nucleic acids. Bovine milk provides a rich source of extracellular vesicles (mEVs) that have been studied as therapeutics and drug delivery systems. Therefore, insight into the mEV cargo, such as its proteome, may help in understanding the molecular mechanism underlying the potential health benefits attributed to the mEVs. Hence, mEVs were isolated from healthy buffalo milk after screening the milk somatic cell count. The total proteins of mEVs were analyzed using LC-MS, and 331 proteins were found commonly present among three buffalo milk samples. These proteins were primarily derived from extracellular regions and lysosomes. The major biological roles associated with the proteins were immune response, metabolism, and cell cycle regulation. The molecular functions of the proteins were transporter activity, catalytic activity, and GTPase activity. Further, comparative analysis with the previously available bovine mEVs proteome data showed 114 proteins to be newly identified in the buffalo mEVs. The biological pathways associated with these proteins may play a major role in muscle development. These findings shed a light on the potential health benefits of buffalo mEVs as therapeutics as well as drug delivery vehicles.

PMID:39433188 | DOI:10.1016/j.ijbiomac.2024.136735

Biosystems. 2024 Oct 19:105352. doi: 10.1016/j.biosystems.2024.105352. Online ahead of print.

ABSTRACT

Understanding the function of common motifs in gene regulatory networks is an important goal of systems biology. Feed forward loops (FFLs) are an example of such a motif. In FFLs, a gene (X) regulates another gene (Z) both directly and via an intermediary gene (Y). Previous theoretical studies have suggested several possible functions for FFLs, based on their transient responses to changes in input signals (using deterministic models) and their fluctuations around steady state (using stochastic models). In this paper we study stochastic models of the two most common FFLs, "coherent type 1" and "incoherent type 1". We incorporate molecular noise by treating DNA binding, transcription, translation, and decay as stochastic processes. By comparing the dynamics of these loops with models of alternative networks (in which X does not regulate Y), we explore how FFLs act to process information in the presence of noise. This work highlights the importance of incorporating realistic molecular noise in studying both the transient and steady-state behavior of gene regulatory networks.

PMID:39433119 | DOI:10.1016/j.biosystems.2024.105352

Neurosci Biobehav Rev. 2024 Oct 19:105930. doi: 10.1016/j.neubiorev.2024.105930. Online ahead of print.

ABSTRACT

Interpersonal trust is essential for societal well-being, underpinning relationships from individuals to institutions. Neuroscience research on trust has advanced swiftly since 2001. While quantitative reviews, meta-analyses, and theoretical frameworks have effectively synthesized trust neuroscience research, bibliometric analysis remains underutilized. Our bibliometric analysis aimed to provide a comprehensive overview of trust neuroscience's current state and future directions by examining its historical development, key contributors, geographic distribution, methodological paradigms, influential works, thematic trends, and overall impact. This field has been characterized by the input of a few key contributors through international collaboration, with significant contributions from the U.S., China, the Netherlands, and Germany. Research predominantly utilizes the trust game and fMRI, with a rising focus on neural networks, general trust, and differentiating behavioral from attitudinal trust. Integrating insights from psychology, economics, and sociology, this interdisciplinary field holds promise for advancing our understanding of trust through a neurobiological lens. In conclusion, our bibliographic literature review provides valuable insights and guidance for scholars, spotlighting potential avenues for further investigation in this fast-growing field.

PMID:39433115 | DOI:10.1016/j.neubiorev.2024.105930

PLoS Genet. 2024 Oct 21;20(10):e1011447. doi: 10.1371/journal.pgen.1011447. Online ahead of print.

ABSTRACT

Plants monitor multiple environmental cues, such as light and temperature, to ensure they germinate at the right time and place. Some specialist plants, like ephemeral fire-following weeds and root parasitic plants, germinate primarily in response to small molecules found in specific environments. Although these species come from distinct clades, they use the same HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE 2 (HTL/KAI2) signalling pathway, to perceive different small molecules suggesting convergent evolution on this pathway. Here, we show that HTL/KAI2 signalling in Arabidopsis thaliana bypasses the light requirement for germination. The HTL/KAI2 downstream component, SUPPRESSOR OF MAX2 1 (SMAX1) accumulates in the dark and is necessary for PHYTOCHROME INTERACTING FACTOR 1/PHYTOCHROME INTERACTING FACTOR 3-LIKE 5 (PIF1/PIL5) to regulate hormone response pathways conducive to germination. The interaction of HTL/KAI2 and light signalling may help to explain how specialist plants like ephemeral and parasitic weeds evolved their germination behaviour in response to specific environments.

PMID:39432524 | DOI:10.1371/journal.pgen.1011447

Elife. 2024 Oct 21;12:RP88981. doi: 10.7554/eLife.88981.

ABSTRACT

Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. Drosophila melanogaster is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. The Drosophila Genetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource. To address this, we created a web tool called DGRPool (dgrpool.epfl.ch), which aggregates phenotyping data of 1034 phenotypes across 135 DGRP studies in a common environment. DGRPool enables users to download data and run various tools such as genome-wide (GWAS) and phenome-wide (PheWAS) association studies. As a proof-of-concept, DGRPool was used to study the longevity phenotype and uncovered both established and unexpected correlations with other phenotypes such as locomotor activity, starvation resistance, desiccation survival, and oxidative stress resistance. DGRPool has the potential to facilitate new genetic and molecular insights of complex traits in Drosophila and serve as a valuable, interactive tool for the scientific community.

PMID:39431984 | DOI:10.7554/eLife.88981

Microbiol Resour Announc. 2024 Oct 21:e0093824. doi: 10.1128/mra.00938-24. Online ahead of print.

ABSTRACT

The genus Paenibacillus comprises facultatively anaerobic, endospore-forming, Gram-positive eubacteria known for efficiently producing a diverse array of exoenzymes. We isolated and sequenced the complete genomes of two Paenibacillus bacteria from the pegmatite surface in the fourth ore body in the mine Wagu Kannon Mine, Fukushima Prefecture.

PMID:39431869 | DOI:10.1128/mra.00938-24

Mol Biol Evol. 2024 Oct 21:msae200. doi: 10.1093/molbev/msae200. Online ahead of print.

ABSTRACT

Understanding the main determinants of protein evolution is a fundamental challenge in biology. Despite many decades of active research, the molecular and cellular mechanisms underlying the substantial variability of evolutionary rates across cellular proteins are not currently well understood. It also remains unclear how protein molecular function is optimized in the context of multicellular species and why many proteins, such as enzymes, are only moderately efficient on average. Our analysis of genomics and functional datasets reveals in multiple organisms a strong inverse relationship between the optimality of protein molecular function and the rate of protein evolution. Furthermore, we find that highly expressed proteins tend to be substantially more functionally optimized. These results suggest that cellular expression costs lead to more pronounced functional optimization of abundant proteins, and that the purifying selection to maintain high levels of functional optimality significantly slows protein evolution. We observe that in multicellular species both the rate of protein evolution and the degree of protein functional efficiency are primarily affected by expression in several distinct cell types and tissues. Specifically, in developed neurons with upregulated synaptic processes in animals and in young and fast-growing tissues in plants. Overall, our analysis reveals how various constraints from the molecular, cellular, and species' levels of biological organization jointly affect the rate of protein evolution and the level of protein functional adaptation.

PMID:39431545 | DOI:10.1093/molbev/msae200

Theranostics. 2024 Sep 16;14(16):6088-6108. doi: 10.7150/thno.96707. eCollection 2024.

ABSTRACT

Rationale: Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by neurotoxicity, excessive inflammation, and cognitive impairment. The peroxisome proliferator-activated receptor (PPAR) δ is a potential target for AD. However, its regulatory mechanisms and therapeutic potential in AD remain unclear. We aimed to investigate if the activation of PPARδ using a highly selective and potent agonist could provide an effective therapeutic strategy against AD. Methods: We synthesized a novel PPARδ agonist, 5a, containing a selenazole group and determined the X-ray crystal structure of its complex with PPARδ. The drug-like properties of 5a were assessed by analyzing cytochrome P450 (CYP) inhibition, microsomal stability, pharmacokinetics, and mutagenicity. We investigated the anti-inflammatory effects of 5a using lipopolysaccharide (LPS)-stimulated BV-2 microglia and neuroinflammatory mouse model. The therapeutic efficacy of 5a was evaluated in AD mice with scopolamine-induced memory impairment and APP/PS1 by analyzing cognitive function, glial reactivity, and amyloid pathology. Results: Compound 5a, the most potent and selective PPARδ agonist, was confirmed to bind hPPARδ in a complex by X-ray crystallographic analysis. PPARδ activation using 5a showed potent anti-inflammatory effects in activated glial cells and mouse model of neuroinflammation. Administration of 5a inhibited amyloid plaque deposition by suppressing the expression of neuronal beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), and reduced abnormal glial hyperactivation and inflammatory responses, resulting in improved learning and memory in the APP/PS1 mouse model of AD. Conclusion: We identified that specific activation of PPARδ provides therapeutic effects on multiple pathogenic phenotypes of AD, including neuroinflammation and amyloid deposition. Our findings suggest the potential of PPARδ as a promising drug target for treating AD.

PMID:39431021 | PMC:PMC11488110 | DOI:10.7150/thno.96707

J Mol Cell Cardiol Plus. 2024 Jun;8:100073. doi: 10.1016/j.jmccpl.2024.100073. Epub 2024 Mar 31.

ABSTRACT

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) results from pathogenic variants in sarcomeric protein genes that increase myocyte energy demand and lead to cardiac hypertrophy. However, it is unknown whether a common metabolic trait underlies cardiac phenotype at the early disease stage. To address this question and define cardiac biochemical pathology in early-stage HCM, we studied two HCM mouse models that express pathogenic variants in cardiac troponin T (Tnt2) or myosin heavy chain (Myh6) genes, and have marked differences in cardiac imaging phenotype, mitochondrial function at early disease stage.

METHODS: We used a combination of echocardiography, transcriptomics, mass spectrometry-based untargeted metabolomics (GC-TOF, HILIC, CSH-QTOF), and computational modeling (CardioNet) to examine cardiac structural and metabolic remodeling at early disease stage (5 weeks of age) in R92W-TnT+/- and R403Q-MyHC+/- mutant mice. Data from mutants was compared with respective littermate controls (WT).

RESULTS: Allele-specific differences in cardiac phenotype, gene expression and metabolites were observed at early disease stage. LV diastolic dysfunction was prominent in TnT mutants. Differentially-expressed genes in TnT mutant hearts were predominantly enriched in the Krebs cycle, respiratory electron transport, and branched-chain amino acid metabolism, whereas MyHC mutants were enriched in mitochondrial biogenesis, calcium homeostasis, and liver-X-receptor signaling. Both mutant hearts demonstrated significant alterations in levels of purine nucleosides, trisaccharides, dicarboxylic acids, acylcarnitines, phosphatidylethanolamines, phosphatidylinositols, ceramides and triglycerides; 40.4 % of lipids and 24.7 % of metabolites were significantly different in TnT mutants, whereas 10.4 % of lipids and 5.8 % of metabolites were significantly different in MyHC mutants. Both mutant hearts had a lower abundance of unsaturated long-chain acyl-carnitines (18:1, 18:2, 20:1), but only TnT mutants showed enrichment of FA18:0 in ceramide and cardiolipin species. CardioNet predicted impaired energy substrate metabolism and greater phospholipid remodeling in TnT mutants than in MyHC mutants.

CONCLUSIONS: Our systems biology approach revealed marked differences in metabolic remodeling in R92W-TnT and R403Q-MyHC mutant hearts, with TnT mutants showing greater derangements than MyHC mutants, at early disease stage. Changes in cardiolipin composition in TnT mutants could contribute to impairment of energy metabolism and diastolic dysfunction observed in this study, and predispose to energetic stress, ventricular arrhythmias under high workloads such as exercise.

PMID:39430912 | PMC:PMC11485168 | DOI:10.1016/j.jmccpl.2024.100073

Brain Behav Immun Health. 2024 Oct 2;42:100879. doi: 10.1016/j.bbih.2024.100879. eCollection 2024 Dec.

ABSTRACT

Childhood overweight/obesity is associated with stress-related psychopathology, yet the pathways connecting childhood obesity to stress susceptibility are poorly understood. We employed a systems biology approach with 62 adolescent Lewis rats fed a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a control diet (CD, 13% kcal from fat). A subset of rats underwent a 31-day model of predator exposures and social instability (PSS). Effects were assessed using behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), 16S rRNA gene sequencing for gut microbiome profiling, hippocampal microglia analysis, and targeted gene methylation. Parallel experiments on human microglia cells (HMC3) examined how palmitic acid influences cortisol-related inflammatory responses. Rats exposed to WD and PSS exhibited deficits in sociability, increased fear/anxiety-like behaviors, food consumption, and body weight. WD/PSS altered hippocampal microstructure (subiculum, CA1, dentate gyrus), and microbiome analysis showed a reduced abundance of members of the phylum Firmicutes. WD/PSS synergistically promoted neuroinflammatory changes in hippocampal microglia, linked with microbiome shifts and altered Fkbp5 expression/methylation. In HMC3, palmitate disrupted cortisol responses, affecting morphology, phagocytic markers, and cytokine release, partially mediated by FKBP5. This study identifies gene-environment interactions that influence microglia biology and may contribute to the connection between childhood obesity and stress-related psychopathology later in life.

PMID:39430879 | PMC:PMC11490928 | DOI:10.1016/j.bbih.2024.100879

JAMIA Open. 2024 Oct 18;7(4):ooae105. doi: 10.1093/jamiaopen/ooae105. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Procedural and reporting guidelines are crucial in framing scientific practices and communications among researchers and the broader community. These guidelines aim to ensure transparency, reproducibility, and reliability in scientific research. Despite several methodological frameworks proposed by various initiatives to foster reproducibility, challenges such as data leakage and reproducibility remain prevalent. Recent studies have highlighted the transformative potential of incorporating the FAIR (Findable, Accessible, Interoperable, and Reusable) principles into workflows, particularly in contexts like software and machine learning model development, to promote open science.

OBJECTIVE: This study aims to introduce a comprehensive framework, designed to calibrate existing reporting guidelines against the FAIR principles. The goal is to enhance reproducibility and promote open science by integrating these principles into the scientific reporting process.

METHODS: We employed the "Best fit" framework synthesis approach which involves systematically reviewing and synthesizing existing frameworks and guidelines to identify best practices and gaps. We then proposed a series of defined workflows to align reporting guidelines with FAIR principles. A use case was developed to demonstrate the practical application of the framework.

RESULTS: The integration of FAIR principles with established reporting guidelines through the framework effectively bridges the gap between FAIR metrics and traditional reporting standards. The framework provides a structured approach to enhance the findability, accessibility, interoperability, and reusability of scientific data and outputs. The use case demonstrated the practical benefits of the framework, showing improved data management and reporting practices.

DISCUSSION: The framework addresses critical challenges in scientific research, such as data leakage and reproducibility issues. By embedding FAIR principles into reporting guidelines, the framework ensures that scientific outputs are more transparent, reliable, and reusable. This integration not only benefits researchers by improving data management practices but also enhances the overall scientific process by promoting open science and collaboration.

CONCLUSION: The proposed framework successfully combines FAIR principles with reporting guidelines, offering a robust solution to enhance reproducibility and open science. This framework can be applied across various contexts, including software and machine learning model development stages, to foster a more transparent and collaborative scientific environment.

PMID:39430802 | PMC:PMC11488973 | DOI:10.1093/jamiaopen/ooae105

MethodsX. 2024 Sep 27;13:102982. doi: 10.1016/j.mex.2024.102982. eCollection 2024 Dec.

ABSTRACT

Aphids, as hemipteran insects, reproduce via parthenogenesis and viviparity, resulting in rapid and exponential offspring production. To investigate the molecular mechanisms underlying parthenogenetic viviparity in asexual aphids, precise protein detection through immunostaining is essential. Our previous research demonstrated the need for proteinase K (PK) treatment to improve tissue permeability, enabling antibodies targeting the germ-cell marker Ap-Vas1 to access gastrulating and later-stage embryos. However, optimal PK digestion protocols have not been thoroughly explored. In this study, we propose strategies to optimize PK digestion conditions for early, middle, and late-stage pea aphid embryos, which have varying tissue thicknesses. Additionally, we extend the application of PK treatment to salivary glands, a representative somatic tissue, by optimizing conditions for antibody penetration against the salivary gland marker C002. To enhance spatial precision in signal detection, we provide a detailed protocol for tissue dissection specific to pea aphids, focusing on the preservation of tissue integrity. These comprehensive guidelines, covering tissue dissection and PK titration, are expected to improve the specificity and intensity of protein signals in pea aphids and other aphid species.•Provide aphid-specific dissection methods to obtain intact embryos and salivary glands.•Present strategies for optimizing PK treatment conditions across different tissue types.

PMID:39430779 | PMC:PMC11489042 | DOI:10.1016/j.mex.2024.102982

Iran J Public Health. 2024 Jun;53(6):1332-1342.

ABSTRACT

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a common cancer with a poor prognosis and high recurrence rate. We aimed to identify potential biomarkers for LIHC by investigating the involvement of hub genes, microRNAs (miRNAs), transcription factors (TFs), and protein kinases (PKs) in its occurrence.

METHODS: we conducted a bioinformatics analysis using microarray datasets, the TCGA-LIHC dataset, and text mining to identify differentially expressed genes (DEGs) associated with LIHC. They then performed functional enrichment analysis and gene-disease association analysis. The protein-protein interaction network of the genes was established, and hub genes were identified. The expression levels and survival analysis of these hub genes were evaluated, and their association with miRNAs, TFs, and PKs was assessed.

RESULTS: The analysis identified 122 common genes involved in LIHC pathogenesis. Ten hub genes were filtered out, including CDK1, CCNB1, CCNB2, CCNA2, ASPM, NCAPG, BIRC5, RRM2, KIF20A, and CENPF. The expression level of all hub genes was confirmed, and high expression levels of all hub genes were correlated with poor overall survival of LIHC patients.

CONCLUSION: Identifying potential biomarkers for LIHC can aid in the design of targeted treatments and improve the survival of LIHC patients. The findings of this study provide a basis for further research in the field of LIHC and contribute to the understanding of its molecular pathogenesis.

PMID:39430152 | PMC:PMC11488550

F1000Res. 2024 Jan 18;13:77. doi: 10.12688/f1000research.146156.1. eCollection 2024.

ABSTRACT

Phosphatidylinositol-specific phospholipase C gamma 2 (PLC-gamma-2) is an enzyme that regulates the function of immune cells. PLC-gamma-2 has been implicated in neurodegenerative and autoimmune disorders, yet investigation of this protein has been limited by a lack of independently characterized antibodies. Here we have characterized eleven PLC-gamma-2 commercial antibodies for use in Western Blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

PMID:39429638 | PMC:PMC11489847 | DOI:10.12688/f1000research.146156.1