Changes In Gene Expression Research Articles

Transcriptomic insights into the anti-inflammatory mechanisms of Protaetia brevitarsis seulensis larvae in IL-1β-driven chondrosarcoma cells.

Osteoarthritis (OA) is a complex, degenerative, multi-factorial joint disease. Because of the difficulty in treating OA, developing new targeting strategies that can be used to understand its molecular mechanisms is critical. Protaetia brevitarsis seulensis larvae offer much therapeutic value; however, the presence of various active compounds and the multi-factorial risk factors for OA render the precise mechanisms of action unclear. A systematic transcriptome analysis was used to investigate the key mechanisms of action of P. brevitarsis seulensis larvae aqueous extract (PBSL) and its compounds on OA. Major mechanisms and transcription factors of PBSL were analyzed by profiling gene expression changes in interleukin (IL)-1β-induced human chondrosarcoma cell (SW1353) treated with PBSL. An in vitro assay was performed to validate the efficacy of the novel mechanism and targets of PBSL. PBSL exerted anti-inflammatory effects on SW1353 cells by regulating many molecular pathways. The IL-6/JAK/STAT3 pathway was significantly downregulated by PBSL, and STAT3 was identified as a major transcription factor regulating PBSL-induced target gene expression. Of the six PBSL compounds, the major compound was regulated by the IL-6/JAK/STAT3 pathway. This study provided potential novel mechanisms and transcription factors for PBSL and its active compounds against OA and indicated that inhibiting the IL-6/JAK/STAT3 pathway is a therapeutic target for treating OA.

Lateral olivocochlear neurons modulate cochlear responses to noise exposure

The sense of hearing originates in the cochlea, which detects sounds across dynamic sensory environments. Like other peripheral organs, the cochlea is subjected to environmental insults, including loud, damage-inducing sounds. In response to internal and external stimuli, the central nervous system directly modulates cochlear function through olivocochlear neurons (OCNs), which are located in the brainstem and innervate the cochlear sensory epithelium. One population of OCNs, the lateral olivocochlear (LOC) neurons, target spiral ganglion neurons (SGNs), the primary sensory neurons of the ear. LOCs alter their transmitter expression for days to weeks in response to noise exposure (NE), suggesting that they could tune SGN excitability over long time periods in response to auditory experience. To examine how LOCs affect auditory function after NE, we characterized OCN transcriptional profiles and found transient LOC-specific gene expression changes after NE, including upregulation of multiple neuropeptide-encoding genes. Next, by generating intersectional mouse lines that selectively target LOCs, we chemogenetically ablated LOCs and assayed auditory responses at baseline and after NE. Compared to controls, mice with reduced LOC innervation showed greater NE-induced functional deficits 1 d later and had worse auditory function after a 2-wk recovery period. The number of remaining presynaptic puncta at the SGN synapse with inner hair cells did not differ between control and LOC-ablated animals, suggesting that the primary role of LOCs after NE is likely not to protect but instead to compensate, ensuring that SGN function is enhanced during periods of need.

Human health risk assessment by exposure to contaminants from an urban reservoir: a pilot study in the Madin Dam (México).

Water contamination greatly impacts human health. The Metropolitan Area of the Valley of Mexico (MAVM) is one of the most densely inhabited and polluted places globally, with a significant problem being the rising water demand. The research aims to assess the impact of metals such as iron, aluminum, lead, cadmium, and total chromium, among others, in the water of the Madin Dam, a key reservoir in the area's water supply. The assessment concentrated on individuals who were in good health and had been exposed to these pollutants. It analyzed factors such as levels of oxidized proteins; changes in the function of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase); and their genetic expression, the occurrence of micronuclei, and the amount of DNA methylation. The findings were linked to the metals present in the MAVM drinking water, and the risk was evaluated. The research included four groups: two associated with the Madin Dam, consisting of persons living nearby or using water from the reservoir, and two acting as a control. The study highlighted a significant link between long-term exposure to pollutants in drinking water and elevated levels of oxidized proteins, increased micronuclei frequency, changes in antioxidant enzyme activity and gene expression, and a higher percentage of 5-methylcytosine. The risk assessment showed that people who use drinking water and/or consume fish from Madin Dam have a potential higher risk associated with metal contamination.

Chromatin Regulation of Acetic Acid Stress Tolerance by Ino80 in Budding Yeast Saccharomyces cerevisiae.

Enhanced environmental stress tolerance is important for microbial production of biofuels and biobased chemicals. However, the roles of chromatin regulation in stress tolerance and bioproduction remain unclear. Here, we explore the effects of Ino80, the core subunit of the INO80 chromatin remodeling complex, on yeast stress adaptation. We found that deletion of INO80 led to increased sensitivity of budding yeast Saccharomyces cerevisiae to acetic acid, which is a common inhibitor in lignocellulosic biomass and also serves as a food preservative. Integrated ATAC-seq and RNA-seq analyses further showed that deleting INO80 resulted in extensive changes in chromatin accessibility and gene expression in cell wall-related genes. Genetic interaction between INO80 and AHC2, which is a subunit of the ADA acetyltransferase complex was proved, and the direct role of INO80 in the expression of AHC2 transcription was also confirmed. These findings benefit the development of robust yeast strains and food preservatives by targeting chromatin regulation.

Exploring Epigenetic Complexity in Regulation of Hematopoietic Stem Cells Niche: A Mechanistic Journey from Normal to Malignant Hematopoiesis.

Epigenetic regulation in hematopoietic stem cells (HSCs) research has emerged as a transformative molecular approach that enhances understanding of hematopoiesis and hematological disorders. This chapter investigates the intricate epigenetic mechanisms that control HSCs function, including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. It also explores the role of non-coding ribonucleic acid (RNAs) as epigenetic regulators, highlighting how changes in gene expression can occur without alterations to the DNA sequence. Epigenetic mechanisms play a pivotal in regulating HSC self-renewal and differentiation, processes essential for maintaining a balanced hematopoietic system in which lineage-specific hematopoietic stem and progenitor cells (HSPCs) pool is sustained. Recent advancements in epigenetic mapping and sequencing technologies have illuminated the dynamic epigenetic landscapes that characterize HSCs and their progeny. Numerous studies have revealed that dysregulation of epigenetic pathways is a hallmark of various hematological malignancies, including leukemias, lymphomas, and myelodysplastic syndromes. This review highlights key findings that demonstrate the impact of epigenetic abnormalities on the disruption of HSPC niches and the progression of oncogenesis in hematological malignancies. Furthermore, this chapter explores the therapeutic potential of targeting epigenetic modifications that are critical in formation and progression of hematologic malignancies. It also discusses the latest developments in epigenetic therapies, including the use of DNA methyltransferase inhibitors, histone deacetylase inhibitors, and emerging drugs targeting other epigenetic regulators. These therapies represent a promising strategy for resetting aberrant epigenetic states, potentially restoring normal hematopoiesis. Conclusively, this chapter offers a thorough overview of the current landscape and future directions of epigenetic research related to the maintenance of the HSPC niches. The insights presented here aim to contribute significantly to the field, offering a reference point for molecular approaches that enhance our understanding of hematopoiesis and its associated hematological malignancies.

Eco-friendly decolorization of synthetic dyes using radiation-induced whole cell biocatalyst with enhanced copper resistance.

Toxic and carcinogenic compounds, such as synthetic dyes and polyphenols, were widely employed and released as pollutants in a variety of industries, including textiles, food, and cosmetics. Biological oxidation process that used oxidizing enzymes to breakdown pollutant compounds were environmentally favorable. However, due to the cell toxicity of metal ions supplements used for the biosynthesis of oxidizing enzymes like laccase, their efficient application for biological degradation is limited. In this study, we aimed to boost laccase activity by introducing high copper resistance into whole-cell biocatalysts through irradiation-based accelerated evolution. Bacillus velezensis MBLB 0692, a laccase producing bacterium, was employed as model strain that exhibited severe sensitivity under 10 mM copper. The selected Cu-resistant mutants not only overcame growth inhibition, but also increased laccase activity by 2.6-fold. The qRT-PCR analysis confirmed that mutants showed significant change in gene expressions related to laccase generation and copper-related functions. Furthermore, dye decolorization assays showed that mutants degrade synthetic dyes more efficiently under high copper conditions. The varying decolorization efficiencies across dyes were attributed to differences in dye structure and the potential influence of copper on enzyme activity. Collectively, these findings emphasize the interaction between copper concentration and laccase activity, and present implications for environmental bioremediation.

Multilevel gene expression changes in lineages containing adaptive copy number variants.

Copy-number variants (CNVs) are an important class of genetic variation that can mediate rapid adaptive evolution. Whereas CNVs can increase the relative fitness of the organism, they can also incur a cost due to the associated increased gene expression and repetitive DNA. We previously evolved populations of Saccharomyces cerevisiae over hundreds of generations in glutamine-limited (Gln-) chemostats and observed the recurrent evolution of CNVs at the GAP1 locus. To understand the role that gene expression plays in adaptation, both in relation to the adaptation of the organism to the selective condition and as a consequence of the CNV, we measured the transcriptome, translatome, and proteome of 4 strains of evolved yeast, each with a unique CNV, and their ancestor in Gln- conditions. We find CNV-amplified genes correlate with higher mRNA abundance; however, this effect is reduced at the level of the proteome, consistent with post-transcriptional dosage compensation. By normalizing each level of gene expression by the abundance of the preceding step we were able to identify widespread differences in the efficiency of each level of gene expression. Genes with significantly different translational efficiency were enriched for potential regulatory mechanisms including either upstream open reading frames (uORFs), RNA binding sites for Ssd1, or both. Genes with lower protein expression efficiency were enriched for genes encoding proteins in protein complexes. Taken together, our study reveals widespread changes in gene expression at multiple regulatory levels in lineages containing adaptive CNVs highlighting the diverse ways in which genome evolution shapes gene expression.

The blood transcriptional response in patients developing intensive care unit-acquired pneumonia.

Immune response dysregulation has been implicated in the development of intensive care unit (ICU)-acquired pneumonia. We aimed to determine differences in the longitudinal blood transcriptional response between patients who develop ICU-acquired pneumonia (cases) and those who do not (controls). We performed a case-cohort study in mechanically ventilated trauma and surgery patients with ICU stays >2 days, enrolled in 30 hospitals across Europe. We collected blood for RNA sequencing at baseline, day 7 and (in cases) the day of pneumonia diagnosis. We performed gene set enrichment analysis and analysed longitudinal gene expression changes using linear mixed models. External validation was performed using an independent trauma cohort. We enrolled 113 cases and 115 controls, with similar baseline characteristics. At baseline (median 2 days after ICU admission), cases showed upregulated gene pathways relating to innate immunity, hemostasis and metabolism, and downregulated adaptive immune pathways. These changes persisted at the day of pneumonia diagnosis (median 6 days, compared to day 7 in controls). In the longitudinal comparison, cases exhibited enhanced upregulation of innate immunity, adaptive immunity and hemostasis pathways, along with enhanced downregulation of metabolism pathways relative to controls (all p<0.00001, except hemostasis p<0.05). These findings were largely externally validated. Cases had higher quantitative sepsis response signature scores (p<0.001), reflective of immune dysregulation. Patients developing ICU-acquired pneumonia exhibit distinct blood transcriptional responses shortly after ICU admission and in the subsequent path to pneumonia, suggestive of broad immune dysfunction with both immunosuppressive and inflammatory features.

Twelve-hour ultradian rhythmic reprogramming of gene expression in the human ovary during aging.

The 12-h ultradian rhythm plays a crucial role in metabolic homeostasis, but its role in ovarian aging has not been explored. This study investigates age-related changes in 12-h rhythmic gene expression across various human tissues, with a particular focus on the ovary. We analyzed transcriptomic data from the GTEx project to examine 12-h ultradian rhythmic gene expression across multiple peripheral human tissues, exploring sex-specific patterns and age-related reprogramming of both 12-h and 24-h rhythmic gene expression. Our findings revealed sex-dimorphic patterns in 12-h rhythmic gene expression, with females exhibiting stronger 12-h rhythms than males. Midlife (ages 40-49) was identified as a critical period for the reprogramming of both 12-h and 24-h rhythmic gene expression. The ovary was notable among other organs due to its high number of genes exhibiting 12-h rhythmic expression and a distinct pattern of rhythmic gene expression reprogramming during aging. This reprogramming involved two gene subsets: one subset adopted de novo 12-h rhythms, while another subset shifted from 24-h rhythms in younger individuals to dual 12-h and 24-h rhythms in middle-aged individuals. Both subsets were primarily associated with angiogenesis. This study is the first to report age-related reprogramming of 12-h rhythms in human tissues, with a particular focus on the amplification of 12-h rhythms in angiogenesis-related genes in the aging ovary. These findings provide novel insights into the mechanisms structured format of the abstract text underlying ovarian aging and suggest potential therapeutic strategies targeting rhythmic gene expression in the ovary.

Time-series analysis reveals metabolic and transcriptional dynamics during mulberry fruit development and ripening.

Understanding the global transcriptomic and metabolic changes during mulberry growth and development is essential for the enhancing fruit quality and optimizing breeding strategies. By integrating phenotypic, metabolomic, and transcriptomic data across 18 developmental and ripening stages of Da10 mulberry fruit, a global map of gene expression and metabolic changes was generated. Analysis revealed a gradual progression of morphological, metabolic, and transcriptional changes throughout the development and ripening phases. In this study, a new transcriptome transition, which was highly related to stress resistance, was observed after the full ripening stage. Moreover, a novel method was devised by integrating metabolome and phenotypic data to assess fruit quality and determine optimal harvest times early in the supply chain. Phase-specific co-expression networks involved in photosynthesis, quality regulation, and plant immunity were also constructed. Notably, eight flavonoids and six hub genes emerged as potential natural edible coatings or gene-editing targets for mulberry fruit to enhance resistance against biotic and abiotic stress. These findings should facilitate further research on stress resistance, post-harvest management, and sustainable agricultural development.

Multi-stressor dynamics: Effects of marine heatwave stress and harmful algal blooms on juvenile mussel (Perna canaliculus) survival and physiology.

In New Zealand, the frequency and intensity of marine heatwaves (MHWs) and blooms of the harmful algal species, Alexandrium pacificum, are increasing in areas where there are natural reefs and commercial farms of the mussel, Perna canaliculus. In this study, we assessed the whole organism, tissue and molecular-level response of juvenile (spat) P. canaliculus exposed to these abiotic and biotic stressors, alone and together. Spat of P. canaliculus were held at a control temperature of 17°C or a MHW temperature of 22°C for the duration of the experiment and exposed to two environmentally relevant concentrations of the dinoflagellate A. pacificum for 4days, followed by a recovery period of 4days. The MHW temperature alone had no detrimental effect on mussel survival; however, exposure to A. pacificum at both temperatures led to reduced spat survival, especially at higher microalgal concentrations (< 90% survival vs 100% at the control temperature, no A. pacificum). The combination of both MHW temperature and A. pacificum exposure resulted in higher mortality than either stressor alone (as low as 59% survival compared to 99% at the MHW temperature alone). Spat exposed to A. pacificum alone showed up to a 4-fold reduction in byssal plaque production, crucial for spat attachment and therefore survival. Growth rate was >7.5 times slower, and there were increased histological alterations as compared to mussels in the control treatment. Similarly, spat exposed to A. pacificum showed significant changes in gene expression, particularly in pathways related to lipid metabolism and detoxification. Spat exposed to MHW temperatures alone had fewer differentially expressed genes, most being heat shock proteins. These findings emphasise the importance of understanding multi-stressor impacts in marine environments, particularly in the context of climate change and harmful algal blooms (HABs).

Cold climate-driven convergent evolution among angiosperms.

Convergent and parallel evolution occur more frequently than previously thought. Here, we focus on the evolutionary adaptations of angiosperms to sub-zero temperatures. We begin by introducing the research history of convergent and parallel evolution, defining all independent similarities as convergent evolution. Our analysis reveals that frost zones (periodic or constant), covering 49.1% of Earth's land surface, host 137 angiosperm families with over 90% of their species thriving in these regions. On this context, we revisit the global biogeography and evolutionary trajectories of plant traits, such as herbaceous form and leaf deciduousness, which are likely evasion strategies for frost adaptation. At the physiological and molecular levels, many angiosperms have independently evolved cold-acclimation mechanisms through multiple pathways beyond the well-characterized CBF/DREB1 regulatory pathway. The convergent adaptations occur across various molecular levels, including amino acid substitutions and changes in gene duplication and expression within the same or similar functional pathways; however, identical amino acid changes are rare. Moreover, we highlight the prevalence of polyploidy in frost zones and occurrence of paleopolyploidization events during global cooling. These patterns suggest repeated evolution in cold climates. Finally, we discuss plant domestication, predict climate zone shifts due to global warming, and their effects on plant migration and in-situ adaptation. Overall, integrating ecological and molecular perspectives is essential for understanding and forecasting plant responses to climate change.

Identification of robust RT-qPCR reference genes for studying changes in gene expression in response to hypoxia in breast cancer cell lines

Hypoxia is common in breast tumours and is linked to therapy resistance and advanced disease. To understand hypoxia-driven breast cancer progression, RT-qPCR is a widely used technique to quantify transcriptional changes that occur during malignant transformation. Reference genes (RGs) are endogenous RT-qPCR controls used to normalise mRNA levels, allowing accurate assessment of transcriptional changes. However, hypoxia reprograms transcription and post-transcriptional processing of RNA such that favoured RGs including GAPDH or PGK1 are unsuitable for this purpose. To address the need for robust RGs to study hypoxic breast cancer cell lines, we identified 10 RG candidates by analysing public RNA-seq data of MCF-7 and T-47D (Luminal A), and, MDA-MB-231 and MDA-MB-468 (triple negative breast cancer (TNBC)) cells cultured in normoxia or hypoxia. We used RT-qPCR to determine RG candidate levels in normoxic breast cancer cells, removing TBP and EPAS1 from downstream analysis due to insufficient transcript abundance. Assessing primer efficiency further removed ACTB, CCSER2 and GUSB from consideration. Following culture in normoxia, acute, or chronic hypoxia, we ascertained robust non-variable RGs using RefFinder. Here we present RPLP1 and RPL27 as optimal RGs for our panel of two Luminal A and two TNBC cell lines cultured in normoxia or hypoxia. Our result enables accurate evaluation of gene expression in selected hypoxic breast cancer cell lines and provides an essential resource for assessing the impact of hypoxia on breast cancer progression.

Characterizing the regulatory effects of H2A.Z and SWR1-C on gene expression during hydroxyurea exposure in Saccharomyces cerevisiae.

Chromatin structure and DNA accessibility are partly modulated by the incorporation of histone variants. H2A.Z, encoded by the non-essential HTZ1 gene in S. cerevisiae, is an evolutionarily conserved H2A histone variant that is predominantly incorporated at transcription start sites by the SWR1-complex (SWR1-C). While H2A.Z has often been implicated in transcription regulation, htz1Δ mutants exhibit minimal changes in gene expression compared to wild-type. However, given that growth defects of htz1Δ mutants are alleviated by simultaneous deletion of SWR1-C subunits, previous work examining the role of H2A.Z in gene expression regulation may be confounded by deleterious activity caused by SWR1-C when missing its H2A.Z substrate (apo-SWR1-C). Furthermore, as H2A.Z mutants only display significant growth defects in genotoxic stress conditions, a more substantive role for H2A.Z in gene expression may only be uncovered after exposure to cellular stress. To explore this possibility, we generated mRNA transcript profiles for wild-type, htz1Δ, swr1Δ, and htz1Δswr1Δ mutants before and after exposure to hydroxyurea (HU), which induces DNA replication stress. Our data showed that H2A.Z played a more prominent role in gene activation than repression during HU exposure, and its incorporation was important for proper upregulation of several HU-induced genes. We also observed that apo-SWR1-C contributed to gene expression defects in the htz1Δ mutant, particularly for genes involved in phosphate homeostasis regulation. Furthermore, mapping H2A.Z incorporation before and after treatment with HU revealed that decreases in H2A.Z enrichment at transcription start sites was correlated with, but generally not required for, the upregulation of genes during HU exposure. Together this study characterized the regulatory effects of H2A.Z incorporation during the transcriptional response to HU.

Exposure to lower temperature during early development decreases hypoxia tolerance in juvenile Fundulus heteroclitus.

Cross-protection occurs when exposure to one stressor confers heightened tolerance against a different stressor. Alternatively, exposure to one stressor could result in reduced tolerance against other stressors. Although cross-protection has been documented in a wide range of taxa at juvenile and adult life stages, whether early developmental exposure to a stressor confers cross-protection or reduced tolerance to other stressors later in life through developmental plasticity remains largely unexplored. In this study, we examined whether altered temperature during embryonic development results in developmental plasticity in upper thermal tolerance or hypoxia tolerance using a small topminnow, Fundulus heteroclitus, and examined potential underlying molecular mechanisms. We incubated embryos at one of two ecologically relevant temperatures (20 °C or 26 °C) until hatch. Once hatched, fish were raised at a common temperature of 20 °C for one year, and tolerance was assessed in both juveniles (6 months) and early adults (1 year). Developmental temperature had no significant effect on thermal tolerance (CTmax) in juvenile fish, or on the transcript abundance of thermal-tolerance related genes (constitutive heat shock proteins, hsc70, hsp90b). In contrast, reduced developmental temperature decreased hypoxia tolerance but increased transcript levels of the hypoxia inducible factor hif1α in juvenile fish but the effects were less evident in older fish. Overall, we found no indication of developmental plasticity for thermal tolerance, but there was evidence of negative impacts of lower developmental temperature on hypoxia tolerance in juveniles associated with changes in gene expression, providing evidence of developmental plasticity across stressors and levels of organization.

Transcriptomic and enzymatic analysis of peroxidase families at the early growth stage of halophyte ice plant (Mesembryanthemum crystallinum L.) under salt stress

Ice plant (Mesembryanthemum crystallinum L.) is a halophyte and an inducible CAM plant. Ice plant seedlings display moderate salt tolerance, with root growth unaffected by 200 mM NaCl treatments, though hypocotyl elongation is hindered in salt-stressed etiolated seedlings. Superoxide anion accumulation was prominent in cotyledons and primary leaves but decreased in root tissues over time, with no significant effect from salt treatment. Hydrogen peroxide levels initially surged in both control and salt-treated seedlings, with higher and more persistent accumulation in the salt-treated seedlings. The activities of H2O2-scavenging ascorbate-glutathione cycle enzymes ascorbate peroxidase (APX), monodehydroascorbate reductase, and dehydroascorbate reductase increased, while guaiacol-dependent peroxidase activity decreased and catalase activity showed no change, indicating APX activity as the primary response to salt stress. Salt-induced APX activities were detected mainly in the microsomal fraction for light-grown seedlings and the cytosolic fraction for etiolated seedlings, highlighting plastids as the primary site of ROS accumulation under salt stress. An RNA-seq analysis of etiolated seedlings revealed about 8% unigenes showing more than a four-fold change in expression after a 6-h 200 mM NaCl treatment. GO enrichment analysis indicated that differentially expressed genes (DEGs) with increased transcript abundance were associated with ion transport, antioxidant activity, and stress responses, while DEGs with decreased transcript abundance were linked to metabolic and biosynthesis processes such as ribosomal protein synthesis and cell wall formation. This indicates that salt stress hinders growth but enhances ion homeostasis and stress response mechanisms. The expression of all eight APX genes were induced by a 48-hour salt treatment, with varying expression patterns. For class III peroxidase family, 14 out of 53 identified unigenes qualified as DEGs. The time-course expression patterns revealed that the transcript levels of McPrx4.1, McPrx12.1, and McPrx12.3 increased, while McPrx60.3 decreased. These findings highlight the distinct roles of class III peroxidases in balancing plant growth and stress responses, advancing our understanding of the mechanisms behind salt tolerance in halophytes. This study comprehensively analyzed changes in gene expression, antioxidant enzyme activity, and ROS accumulation in ice plant seedlings. Unveiling these responses will advance our understanding of the growth–stress balance in the intrinsic salt tolerance in halophytes.

Genetically Engineered Brain Organoids Recapitulate Spatial and Developmental States of Glioblastoma Progression.

Glioblastoma (GBM) is an aggressive form of brain cancer that is highly resistant to therapy due to significant intra-tumoral heterogeneity. The lack of robust in vitro models to study early tumor progression has hindered the development of effective therapies. Here, this study develops engineered GBM organoids (eGBOs) harboring GBM subtype-specific oncogenic mutations to investigate the underlying transcriptional regulation of tumor progression. Single-cell and spatial transcriptomic analyses revealed that these mutations disrupt normal neurodevelopment gene regulatory networks resulting in changes in cellular composition and spatial organization. Upon xenotransplantation into immunodeficient mice, eGBOs form tumors that recapitulate the transcriptional and spatial landscape of human GBM samples. Integrative single-cell trajectory analysis of both eGBO-derived tumor cells and patient GBM samples reveal the dynamic gene expression changes in developmental cell states underlying tumor progression. This analysis of eGBOs provides an important validation of engineered cancer organoid models and demonstrates their utility as a model of GBM tumorigenesis for future preclinical development of therapeutics.

Study on the effects of Mogroside V in inhibiting NLRP3-mediated granulosa cell pyroptosis and insulin resistance to improve PCOS

ObjectivePolycystic Ovary Syndrome (PCOS) is a prevalent endocrinopathy in reproductive-aged women, contributing to 75% of infertility cases due to ovulatory dysfunction. The condition poses significant health and psychological challenges, making the study of its pathogenesis and treatment a research priority. This study investigates the effects of Mogroside V (MV) on PCOS, focusing on its anti-inflammatory and anti-insulin resistance properties.MethodsForty-five female Sprague–Dawley rats were divided into three groups: control, PCOS model, and MV treatment. The PCOS model was induced using a high-fat diet and letrozole. The MV treatment group was subsequently administered MV after the establishment of the PCOS model. The study monitored body mass, assessed estrous cycle changes, and measured serum hormone levels. Transcriptome sequencing and bioinformatics were used to identify differentially expressed genes related to inflammation and insulin resistance. Expression of pyroptosis and insulin resistance markers was analyzed using qRT-PCR, Western blot, and IHC. Additionally, an in vitro model assessed MV's impact on inflammation and insulin resistance.ResultsThe PCOS group exhibited elevated serum testosterone (T), luteinizing hormone (LH), insulin, and fasting glucose levels, along with increased insulin resistance (HOMA-IR) and decreased estradiol (E2), which were reversed by MV treatment. Transcriptome analysis identified significant gene expression changes between groups, particularly in pathways related to NLRP3 inflammation and insulin metabolism. MV treatment normalized the expression of ovarian pyroptosis factors (NLRP3, Caspase-1, GSDMD) and inflammatory cytokines (IL-1β, IL-18). In cellular models, MV increased E2 levels, reduced LDH release, and decreased the expression of insulin resistance and pyroptosis markers. Correlation analysis showed pyroptosis factors were positively correlated with HOMA-IR and IGF1, and negatively with IGF1R and E2 levels.ConclusionMV improves PCOS by reducing pyroptosis and insulin resistance, enhancing insulin sensitivity, and promoting estrogen synthesis, thereby restoring granulosa cell function and follicular development.

Toxicity mechanism of metal-organic framework HKUST-1 and its carbonized product to Tetradesmus obliquus: Physiological and transcriptomic analysis.

Metal-organic frameworks (MOFs) are emerging materials with unique structures and properties, which have been widely used in many fields due to their various advantages. However, compared with its popular application research, the ecological safety of MOFs has rarely been reported. In this paper, a biological model, the common freshwater green algae Tetradesmus obliquus (T. obliquus) was used to study the effects of the copper-based MOF HKUST-1 and its carbonation product DHKUST-1 on the physiology and transcription level of the algae. A suite of advanced material characterization techniques has been utilized to multidimensionally reveal the physicochemical properties of HKUST-1 and its carbonation product. Notably, DHKUST-1 exhibit higher stability than HKUST-1 in aqueous environments, with lower ion release. During a 96-h exposure experiment, relevant indicators such as algae density, chlorophyll-a content and antioxidant enzyme activities were measured. Additionally, an intriguing IBR model was employed to comprehensively assess the toxicity of HKUST-1 and DHKUST-1 on the antioxidant system of T. obliquus. Furthermore, an in-depth analysis was conducted on the differential gene expression changes in T. obliquus under 10 mg/L HKUST-1 stress, exploring the impact on various pathways within algal cells. Briefly, the toxicity mechanism of HKUST-1 on T. obliquus is multi-involved. The findings of this study are expected to provide important basic data and references for the evaluation of the ecological safety of MOFs.

Constructing mechanosensitive signalling pathways de novo in synthetic cells.

Biological mechanotransduction enables cells to sense and respond to mechanical forces in their local environment through changes in cell structure and gene expression, resulting in downstream changes in cell function. However, the complexity of living systems obfuscates the mechanisms of mechanotransduction, and hence the study of these processes in vitro has been critical in characterising the function of existing mechanosensitive membrane proteins. Synthetic cells are biomolecular compartments that aim to mimic the organisation, functionality and behaviours of biological systems, and represent the next step in the development of in vitro cell models. In recent years, mechanosensitive channels have been incorporated into synthetic cells to create de novo mechanosensitive signalling pathways. Here, I will discuss these developments, from the molecular parts used to construct existing pathways, the functionality of such systems, and potential future directions in engineering synthetic mechanotransduction. The recapitulation of mechanotransduction in synthetic biology will facilitate an improved understanding of biological signalling through the study of molecular interactions across length scales, whilst simultaneously generating new biotechnologies that can be applied as diagnostics, microreactors and therapeutics.