Bioorg Chem. 2025 Apr 9;160:108454. doi: 10.1016/j.bioorg.2025.108454. Online ahead of print.

ABSTRACT

Altered histone deacetylase 6 (HDAC6) expression and function have been linked to cancer progression, positioning it as a promising therapeutic target for cancer treatment. Herein, we introduce HDAC6 inhibitors based on the tetrahydro-β-carboline scaffold, with compound 18d exhibiting the strongest HDAC6 inhibitory potency, achieving an IC50 of 1.3 nM. Compound 18d exhibited significant growth inhibitory activity against an NCI panel of 60 human cancer cell lines with a minimal cytotoxic effect on non-tumor cells. In vitro mechanistic investigations were conducted in HCT-116 colorectal cancer cells where the capability of 18d to enhance the acetylation of α-tubulin (HDAC6 substrate) rather than nuclear H3 histone (HDAC1 substrate) confirmed selective inhibition of HDAC6 subtype. Additionally, compound 18d was observed to suppress the S phase and promote accumulation in the apoptotic sub-G1 phase, potentially through increasing cleaved caspase 3 and reducing Bcl-2 levels in HCT-116 cells. A wound healing assay also elicited the ability of 18d to hinder cell migration. Notably, 18d could suppress the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, a crucial signaling pathway implicated in cancer cell proliferation, migration and apoptosis. Moreover, downregulation of the critical immune checkpoint protein programmed death-ligand 1 (PD-L1) revealed a potential role of 18d in augmenting immune response towards tumor cells. In summary, these findings highlight 18d's dual role in direct tumor growth suppression and immune system sensitization, highlighting a broader cancer therapeutic potential beyond conventional HDAC inhibition.

PMID:40252366 | DOI:10.1016/j.bioorg.2025.108454

Plant Cell. 2025 Apr 19:koaf086. doi: 10.1093/plcell/koaf086. Online ahead of print.

ABSTRACT

Photosynthetic organisms coordinate their metabolism and growth with diurnal light, which can range in intensity from limiting to excessive. Little is known about how light intensity impacts the diurnal program in Chlamydomonas reinhardtii, nor how diurnal rhythms in gene expression and metabolism shape photoprotective responses at different times of day. To address these questions, we performed a systems analysis of synchronized Chlamydomonas populations acclimated to low, moderate, and high diurnal light. Transcriptomic and proteomic data revealed that the Chlamydomonas rhythmic gene expression program is resilient to limiting and excess light: genome-wide, waves of transcripts and proteins peak at the same times in populations acclimated to stressful light intensities as in populations acclimated to moderate light. Yet, diurnal photoacclimation gives rise to hundreds of gene expression changes, even at night. Time-course measurements of photosynthetic efficiency and pigments responsive to excess light showed that high-light-acclimated cells partially overcome photodamage in the latter half of the day prior to cell division. Although gene expression and photodamage are dynamic over the diurnal cycle, Chlamydomonas populations acclimated to low and high diurnal light maintain altered photosystem abundance, thylakoid architecture, and non-photochemical quenching capacity through the night phase. This suggests that cells remember or anticipate the light intensities that they have typically encountered during the day. The integrated data constitute an excellent resource for understanding photoacclimation in eukaryotes under environmentally relevant conditions.

PMID:40251989 | DOI:10.1093/plcell/koaf086

New Phytol. 2025 Apr 18. doi: 10.1111/nph.70154. Online ahead of print.

NO ABSTRACT

PMID:40251862 | DOI:10.1111/nph.70154

Sci Rep. 2025 Apr 18;15(1):13448. doi: 10.1038/s41598-025-96687-z.

ABSTRACT

JQ1, a small cell-permeable molecule is known for its potent inhibitory action on bromodomain and extraterminal (BET) proteins. Although earlier studies have shown its inhibitory effect on male gametogenesis, limited information is available about its influence on oocyte development. Since BET genes are known to exhibit regulatory functions on oocyte development and maturation, the present study aimed to investigate the effect of JQ1 on oocyte developmental competence under in vitro conditions. Germinal vesicle (GV) stage oocytes were collected from adult Swiss albino mice and subjected to in vitro maturation (IVM) in the presence of various concentrations of JQ1 (25, 50, and 100 μM). The metaphase II (MII) stage oocytes were assessed for cytoplasmic organization and functional competence at 24 h after IVM. A significant decrease in nuclear maturation (at 50 and 100 μM), symmetric cytokinesis, altered distribution of mitochondria and cortical granules, poorly organized actin and meiotic spindle, misaligned chromosomes, and elevated endoplasmic reticulum (ER) stress and oxidative stress was observed in JQ1-exposed oocytes. Presence of N-acetyl cysteine (NAC), in IVM medium resulted in significant reduction in JQ1-induced oxidative stress and symmetric cytokinesis. Administration of JQ1 (50 mg/kg, intra peritoneal) to adult Swiss albino mice primed with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) did not affect the ovulation. However, a high degree of oocyte degeneration, elevated intracellular reactive oxygen species (ROS), and GRP78 expression was observed in JQ1-administered mice. In conclusion, our study reveals that BET inhibitor JQ1 has detrimental effects on oocyte function and development.

PMID:40251236 | DOI:10.1038/s41598-025-96687-z

Nat Commun. 2025 Apr 18;16(1):3700. doi: 10.1038/s41467-025-58878-0.

ABSTRACT

How cells change shape is crucial for the development of tissues, organs and embryos. However, studying these shape changes in detail is challenging. Here we present a comprehensive real-time cellular map that covers over 95% of the cells formed during Caenorhabditis elegans embryogenesis, featuring nearly 400,000 3D cell regions. This map includes information on each cell's identity, lineage, fate, shape, volume, surface area, contact area, and gene expression profiles, all accessible through our user-friendly software and website. Our map allows for detailed analysis of key developmental processes, including dorsal intercalation, intestinal formation, and muscle assembly. We show how Notch and Wnt signaling pathways, along with mechanical forces from cell interactions, regulate cell fate decisions and size asymmetries. Our findings suggest that repeated Notch signaling drives size disparities in the large excretory cell, which functions like a kidney. This work sets the stage for in-depth studies of the mechanisms controlling cell fate differentiation and morphogenesis.

PMID:40251161 | DOI:10.1038/s41467-025-58878-0

Trends Biochem Sci. 2025 Apr 17:S0968-0004(25)00052-0. doi: 10.1016/j.tibs.2025.03.003. Online ahead of print.

ABSTRACT

Brassinosteroids (BRs) are essential plant steroidal hormones that regulate growth and development. The recent discoveries of ATP-binding cassette subfamily B (ABCB) members, ABCB19 and ABCB1, as BR transporters highlight the significance of active export to the apoplast in maintaining BR homeostasis and enabling effective signaling. This review focuses on the latest progress in understanding ABCB-mediated BR transport, with particular attention to the structural and functional characterization of arabidopsis ABCB19 and ABCB1. These findings reveal both conserved and distinct features in substrate recognition and transport mechanisms, providing valuable insights into their roles in hormonal regulation. Additionally, the evolutionary conservation of ABC transporters in mediating steroid-based signaling across biological kingdoms underscores their fundamental biological significance.

PMID:40251078 | DOI:10.1016/j.tibs.2025.03.003

Food Chem Toxicol. 2025 Apr 16:115457. doi: 10.1016/j.fct.2025.115457. Online ahead of print.

ABSTRACT

The liver is considered a target organ for the accumulation and toxic effects of nanomaterials exposed to the body, especially after oral exposure, but the key toxic pathways have not been fully defined. This study focused on the hepatotoxicity of titanium dioxide nanoparticles (TiO2 NPs) in vivo and in vitro, and tried to identify key toxic pathways using the concept of systems biology and multi-omics methods. In vivo, protein and metabolomic sequencing were performed on the liver of SD rats (0, 50 mg/kg, 90 days), and 386 differential proteins and 29 differential metabolites were screened out, respectively, and the joint analysis found that they were significantly enriched in alanine, aspartate and glutamate metabolism, and butanoate metabolism. In vitro, exposure to TiO2 NPs could induce cytotoxicity and omics changes at different molecular levels in human hepatocellular carcinoma cells. Single omic analysis showed that differentially expressed proteins and metabolites were 80 and 222, respectively. The enriched pathways related to steroid biosynthesis, cholesterol metabolism at the combine levels of proteome and metabolome. KEGG enrichment analysis showed that PI3K-Akt signaling pathway and PPAR signaling pathway were both significantly affected in vitro and in vivo. Through multi-omics analysis, this work offered fresh perspectives and avenues for research on the toxicity mechanism of TiO2 NPs.

PMID:40250523 | DOI:10.1016/j.fct.2025.115457

Mol Cell. 2025 Apr 17;85(8):1477-1479. doi: 10.1016/j.molcel.2025.03.022.

ABSTRACT

In this issue of Molecular Cell, Schärfen et al.1 describe an advanced RNA structure-probing technology called CoSTseq that enables transcriptome-wide detection of nascent RNA base pairing during transcription in living yeast cells.

PMID:40250407 | DOI:10.1016/j.molcel.2025.03.022

Sci Immunol. 2025 Apr 18;10(106):eadr4977. doi: 10.1126/sciimmunol.adr4977. Epub 2025 Apr 18.

ABSTRACT

Lung interstitial macrophages (IMs) are monocyte-derived parenchymal macrophages whose tissue-supportive functions remain unclear. Despite progress in understanding lung IM diversity and transcriptional regulation, the signals driving their development from monocytes and their functional specification remain unknown. Here, we found that lung endothelial cell-derived Tgfβ1 triggered a core Tgfβ receptor-dependent IM signature in mouse bone marrow-derived monocytes. Myeloid-specific impairment of Tgfβ receptor signaling severely disrupted monocyte-to-IM development, leading to the accumulation of perivascular immature monocytes, reduced IM numbers, and a loss of IM-intrinsic identity, a phenomenon similarly observed in the absence of endothelial-specific Tgfβ1. Mice lacking the Tgfβ receptor in monocytes and IMs exhibited altered monocyte and IM niche occupancy and hallmarks of aging including impaired immunoregulation, hyperinflation, and fibrosis. Our work identifies a Tgfβ signaling-dependent endothelial-IM axis that shapes IM development and sustains lung integrity, providing foundations for IM-targeted interventions in aging and chronic inflammation.

PMID:40249827 | DOI:10.1126/sciimmunol.adr4977

Sci Adv. 2025 Apr 18;11(16):eads4609. doi: 10.1126/sciadv.ads4609. Epub 2025 Apr 18.

ABSTRACT

Molecular movement and interactions at the single-molecule level, particularly in live cells, are often studied using fluorescence correlation spectroscopy (FCS). While powerful, FCS has notable drawbacks: It requires high laser intensities and long acquisition times, increasing phototoxicity, and often relies on problematic statistical assumptions in data fitting. We introduce fluorescence intensity trace statistical analysis (FITSA), a Bayesian method that directly analyzes fluorescence intensity traces. FITSA offers faster, more stable convergence than previous approaches and provides robust parameter estimation from far shorter measurements than conventional FCS. Our results demonstrate that FITSA achieves comparable precision to FCS while requiring substantially fewer photons. This advantage becomes even more pronounced when accounting for statistical dependencies in FCS analysis, which are often overlooked but necessary for accurate error estimation. By reducing laser exposure, FITSA minimizes phototoxicity effects, representing a major advancement in the quantitative analysis of molecular processes across fields.

PMID:40249821 | DOI:10.1126/sciadv.ads4609

Proc Natl Acad Sci U S A. 2025 Apr 22;122(16):e2424474122. doi: 10.1073/pnas.2424474122. Epub 2025 Apr 18.

ABSTRACT

Bestrophin-1 (BEST1) is a chloride channel expressed in the eye and other tissues of the body. A link between BEST1 and the principal inhibitory neurotransmitter γ-aminobutyric acid (GABA) has been proposed. The most appreciated receptors for extracellular GABA are the GABAB G-protein-coupled receptors and the pentameric GABAA chloride channels, both of which have fundamental roles in the central nervous system. Here, we demonstrate that BEST1 is directly activated by GABA. Through functional studies and atomic-resolution structures of human and chicken BEST1, we identify a GABA binding site on the channel's extracellular side and determine the mechanism by which GABA binding stabilizes opening of the channel's central gate. This same gate, "the neck," is activated by intracellular [Ca2+], indicating that BEST1 is controlled by ligands from both sides of the membrane. The studies demonstrate that BEST1, which shares no structural homology with GABAA receptors, is a GABA-activated chloride channel. The physiological implications of this finding remain to be studied.

PMID:40249777 | DOI:10.1073/pnas.2424474122

Plant J. 2025 Apr;122(1):e70160. doi: 10.1111/tpj.70160.

ABSTRACT

Willows can alleviate soil salinisation while generating sustainable feedstock for biorefinery, yet the metabolomic adaptations underlying their tolerance remain poorly understood. Salix miyabeana was treated with two environmentally abundant salts, NaCl and Na2SO4, in a 12-week pot trial. Willows tolerated salts across all treatments (up to 9.1 dS m-1 soil ECe), maintaining biomass while selectively partitioning ions, confining Na+ to roots and accumulating Cl- and SO 4 2 - $$ {\mathrm{SO}}_4^{2-} $$ in the canopy and adapting to osmotic stress via reduced stomatal conductance. Untargeted metabolomics captured >5000 putative compounds, including 278 core willow metabolome compounds constitutively produced across organs. Across all treatments, salinity drove widespread metabolic reprogramming, altering 28% of the overall metabolome, with organ-tailored strategies. Comparing salt forms at equimolar sodium, shared differentially abundant metabolites were limited to 3% of the metabolome, representing the generalised salinity response, predominantly in roots. Anion-specific metabolomic responses were extensive. NaCl reduced carbohydrates and tricarboxylic acid cycle intermediates, suggesting potential carbon and energy resource pressure, and accumulated root structuring compounds, antioxidant flavonoids, and fatty acids. Na2SO4 salinity triggered accumulation of sulphur-containing larger peptides, suggesting excess sulphate incorporation leverages ion toxicity to produce specialised salt-tolerance-associated metabolites. This high-depth picture of the willow metabolome underscores the importance of capturing plant adaptations to salt stress at organ scale and considering ion-specific contributions to soil salinity.

PMID:40249060 | DOI:10.1111/tpj.70160

J Chem Inf Model. 2025 Apr 18. doi: 10.1021/acs.jcim.5c00165. Online ahead of print.

ABSTRACT

Here, we introduce the Structural Systems Biology (SSB) toolkit, a Python library that integrates structural macromolecular data with systems biology simulations to model signal-transduction pathways of G-protein-coupled receptors (GPCRs). Our framework streamlines simulation and analysis of the mathematical models of GPCRs cellular pathways, facilitating the exploration of the signal-transduction kinetics induced by ligand-GPCR interactions: the dose-response of the ligand can be modeled, along with the corresponding change in the concentration of other signaling molecular species over time, like for instance [Ca2+] or [cAMP]. SSB toolkit brings to light the possibility of easily investigating the subcellular effects of ligand binding on receptor activation, even in the presence of genetic mutations, thereby enhancing our understanding of the intricate relationship between ligand-target interactions at the molecular level and the higher-level cellular and (patho)physiological response mechanisms.

PMID:40248991 | DOI:10.1021/acs.jcim.5c00165

Nucleic Acids Res. 2025 Apr 10;53(7):gkaf320. doi: 10.1093/nar/gkaf320.

ABSTRACT

With the explosive growth of whole-genome datasets, accurate detection of orthologous synteny has become crucial for reconstructing evolutionary history. However, current methods for identifying orthologous synteny face great limitations, particularly in scaling with varied polyploidy histories and accurately removing out-paralogous synteny. In this study, we developed a scalable and robust approach, based on the Orthology Index (OI), to effectively identify orthologous synteny. Our evaluation across a large-scale empirical dataset with diverse polyploidization events demonstrated the high reliability and robustness of the OI method. Simulation-based benchmarks further validated the accuracy of our method, showing its superior performance against existing methods across a wide range of scenarios. Additionally, we explored its broad applications in reconstructing the evolutionary histories of plant genomes, including the inference of polyploidy, identification of reticulation, and phylogenomics. In conclusion, OI offers a robust, interpretable, and scalable approach for identifying orthologous synteny, facilitating more accurate and efficient analyses in plant evolutionary genomics.

PMID:40248914 | DOI:10.1093/nar/gkaf320

Metab Eng Commun. 2025 Apr 2;20:e00261. doi: 10.1016/j.mec.2025.e00261. eCollection 2025 Jun.

ABSTRACT

Engineered type I polyketide synthases (T1PKSs) are a potentially transformative platform for the biosynthesis of small molecules. Due to their modular nature, T1PKSs can be rationally designed to produce a wide range of bulk or specialty chemicals. While heterologous PKS expression is best studied in microbes of the genus Streptomyces, recent studies have focused on the exploration of non-native PKS hosts. The biotechnological production of chemicals in fast growing and industrial relevant hosts has numerous economic and logistic advantages. With its native ability to utilize alternative feedstocks, Pseudomonas putida has emerged as a promising workhorse for the sustainable production of small molecules. Here, we outline the assessment of P. putida as a host for the expression of engineered T1PKSs and production of 3-hydroxyacids. After establishing the functional expression of an engineered T1PKS, we successfully expanded and increased the pool of available acyl-CoAs needed for the synthesis of polyketides using transposon sequencing and protein degradation tagging. This work demonstrates the potential of T1PKSs in P. putida as a production platform for the sustainable biosynthesis of unnatural polyketides.

PMID:40248344 | PMC:PMC12005932 | DOI:10.1016/j.mec.2025.e00261

Ecancermedicalscience. 2025 Feb 6;19:1839. doi: 10.3332/ecancer.2025.1839. eCollection 2025.

ABSTRACT

BACKGROUND: As one of the non-communicable diseases, cancer will overtake communicable, maternal, neonatal and nutritional diseases combined as the leading cause of mortality by 2040. Gastrointestinal (GI) cancers are predicted to increase by over 50% in the next 20 years, with a higher incidence in developing countries. In this study, we describe the national GI cancer trends in Zimbabwe using the annual reports from the Zimbabwe National Cancer Registry (ZNCR) from 2009 to 2018.

METHODS: Demographic data and incidence of GI cancer subtypes were collected and analysed from the ZNCR annual reports from 2009 to 2018. Age standardised rates (ASRs) for each GI cancer subtype were calculated and simple trend analysis was performed over the 10-year study period.

RESULTS: In total, 10,859 new GI cancer cases were reported during the study period, accounting for 17.2% of all cancers in Zimbabwe and 55% of these were males. The most prevalent GI cancers were oesophageal, liver, gastric, colon and rectal malignancies. In males, on average the incidence of ASR of oesophageal, liver and gastric cancer increased annually by 14.7%, 17% and 16%, respectively. In females, on average the ASR of oesophageal, liver and gastric cancer increased annually by 27.2%; 18% and 13%, respectively. Overall, one in ten new cases of oesophageal cancer were diagnosed in patients under 45 years of age and for liver cancer, one in four new male cases were diagnosed below the age of 45 years.

CONCLUSION: Zimbabwe faces an increasing trend in all GI cancer subtype incidence over the decade reviewed. The rate of increase in oesophageal and gastric cancers in females was particularly high and the male-to-female ratio observed requires further etiological studies. The increasing rate of young GI cancer patients requires both education regarding risk factors and national screening policies that are tailored to the Zimbabwean population's characteristics and context.

PMID:40248268 | PMC:PMC12003983 | DOI:10.3332/ecancer.2025.1839

Front Genet. 2025 Apr 3;16:1520325. doi: 10.3389/fgene.2025.1520325. eCollection 2025.

ABSTRACT

INTRODUCTION: The existing evidence indicates that atherosclerosis (AS) plays a pivotal role in the progression and exacerbation of cardiovascular diseases and their associated complications. Current diagnostic and therapeutic strategies for atherosclerosis are limited in their ability to facilitate early detection and personalized treatment. This study employs a systems biology approach to investigate the role of lactylation-related genes (LRGs) in the pathogenesis of atherosclerosis, while considering the well-established correlation between inflammatory responses and atherosclerosis development.

METHODS: In this study, we utilized datasets obtained from the Gene Expression Omnibus (GEO) as well as data from previous studies on lactylation-related genes (LRGs). Following this, we identified 17 lactylation related genes associate with atherosclerosis (AS-LRGs) from the GSE100927 dataset. Subsequently, we employed the validation dataset (GSE43292) to assess these 17 AS-LRGs, resulting in the identification of 12 more reliable candidate genes. These genes were further analyzed for functional enrichment through Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). To elucidate the potential utility of AS-LRGs in diagnosing high-risk plaques, we assessed their expression in both early and late stages of atherosclerosis, as well as in high- and low-risk plaques. We then constructed interaction networks to elucidate the potential regulatory relationships among LRGs, miRNAs, transcription factors, and drugs. Finally, we utilized the single sample Gene Set Enrichment Analysis (ssGSEA) method to investigate immune infiltration in AS and evaluate the levels of immune cell infiltration.

RESULTS: We identified 12 lactylation-related genes that are more reliably associated with atherosclerosis: five upregulated genes (LSP1, IKZF1, MNDA, RCC2, and WAS) and seven downregulated genes (CSRP2, PPP1CB, CSRP1, HEXIM1, CALD1, PDLIM1, and RANBP2).

DISCUSSION: This study elucidates the pivotal role of lactylation in atherosclerosis (AS) and establishes a robust foundation for future research into targeted therapies and clinical applications of the identified biomarkers.

PMID:40248193 | PMC:PMC12003320 | DOI:10.3389/fgene.2025.1520325

Front Plant Sci. 2025 Apr 1;16:1538669. doi: 10.3389/fpls.2025.1538669. eCollection 2025.

ABSTRACT

The HKT protein family plays a vital role in plant responses to salt stress by mediating sodium (Na+) and potassium (K+) transport and maintaining Na+-K+ balance. Ipomoea pes-caprae (IPC), a pantropical creeping plant distributed along coastal regions in tropical and subtropical zones, exhibits exceptional salt tolerance. Understanding its salt tolerance mechanisms provides valuable insights for developing salt-tolerant crops and identifying candidate genes for genetic engineering. In this study, we identified two HKT genes, IpcHKT1;1 and IpcHKT1;2, in IPC. Phylogenetic analysis with HKT genes from other Ipomoea species revealed that all analyzed species contain two HKT genes located adjacently on the same chromosome. Comparative analysis of conserved motifs and intron-exon structures indicated that, despite their close evolutionary relationship, the HKT genes in IPC may exhibit functional divergence. Promoter analysis showed that their regulatory regions are enriched with cis-elements associated with responses to biotic and abiotic stresses, hormonal signaling, and growth, highlighting functional diversity within the HKT family. Subcellular localization experiments demonstrated that IpcHKT1;1 and IpcHKT1;2 are ion transporters localized to the plasma membrane. Heterologous expression in yeast confirmed their role in Na+/K+ symporter. Furthermore, RT-qPCR analysis revealed distinct expression patterns under salt stress: IpcHKT1;2 was significantly upregulated in roots, while IpcHKT1;1 expression was transitionally downregulated at 400 mM NaCl treatment. Prolonged high expression of IpcHKT1;2 in roots suggests its critical role in sustained salt stress tolerance. These findings provide new insights into the molecular mechanisms of salt tolerance in IPC. The identification of IpcHKT1;1 and IpcHKT1;2 as key players in salt stress responses offers promising genetic resources for enhancing crop resilience to soil salinity, addressing challenges associated with global salinization.

PMID:40247947 | PMC:PMC12005088 | DOI:10.3389/fpls.2025.1538669

J Neurosci Res. 2025 Apr;103(4):e70039. doi: 10.1002/jnr.70039.

ABSTRACT

Sex and gender differences in the analgesic efficacy and side effects of opioids have been widely reported, but their underlying neurobiological mechanisms remain poorly understood. Preclinical animal models are essential tools for investigating these differences and providing insights into the neurobiology of opioid effects. Although studies in rats have revealed sex-specific effects of opioids, the sex-dependent behavioral profiles of opioids in mice, particularly across strains, remain largely unexplored. In this study, we characterized sex and strain differences in the antinociceptive and hyperlocomotor effects of morphine in the two most widely used mouse strains-CD1 and C57BL/6-and quantified regional expression of the μ-opioid receptor (MOR) in key brain and spinal cord regions. Both strains exhibited clear, dose-dependent antinociceptive and hyperlocomotor responses to morphine. While no significant sex or strain differences were observed in antinociceptive effects, C57BL/6 mice displayed significantly greater hyperlocomotor activity than CD1 mice. Western blot analyses revealed strain-specific MOR expression, with CD1 mice showing higher spinal cord and periaqueductal gray MOR levels, particularly in females, while C57BL/6 mice exhibited elevated MOR expression in the caudoputamen. Morphine treatment increased spinal MOR expression in CD1 mice but not C57BL/6, suggesting strain-dependent regulation of MOR. These findings highlight strain-specific behavioral and molecular responses to morphine, emphasizing the importance of strain and sex considerations in preclinical opioid research.

PMID:40247818 | DOI:10.1002/jnr.70039

Anal Chem. 2025 Apr 18. doi: 10.1021/acs.analchem.4c05407. Online ahead of print.

ABSTRACT

Liquid biopsy is an appealing approach for early diagnosis and assessment of treatment efficacy in cancer. Typically, liquid biopsy involves the detection of endogenous biomarkers, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), and proteins. The levels of these endogenous biomarkers are higher in cancer patients compared to those in healthy individuals. However, the clinical application of liquid biopsy using endogenous biomarker analysis faces challenges due to its low abundance and poor stability in circulation. Recently, a promising strategy involving the engineering of exogenous probes has been developed to overcome these limitations. These exogenous probes are activated within the tumor microenvironment, generating distinct exogenous markers that can be easily distinguished from background biological signals. Alternatively, these exogenous probes can be labeled with intrinsic endogenous biomarkers in vivo and detected in vitro after metabolic processes. In this review, we primarily focus on microfluidic-based liquid biopsy techniques that allow for the transition from analyzing existing endogenous biomarkers to emerging exogenous ones. First, we introduce common endogenous biomarkers, as well as synthetic exogenous ones. Next, we discuss recent advancements in microfluidic-based liquid biopsy techniques for analyzing both existing endogenous and emerging exogenous biomarkers. Lastly, we provide insights into future directions for liquid biopsy on microfluidic systems.

PMID:40247704 | DOI:10.1021/acs.analchem.4c05407