Search PubMedSearch

SEARCH · Search PubMed

Results for “Cellular Senescence”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

122 records · Page 6Linked to original sources

Diversification of yeast proteins as an approach for the development of sustainable food systems.

Despite growing trend in sustainable protein sources, yeast proteins have mainly been explored as a source of bioactive peptides using a monospecies and general protein approach. The contribution of highly abundant protein fractions in the yeast proteome to peptide formation remains insufficiently investigated, limiting a comprehensive understanding of yeast proteins as optimized peptide sources. The current review presents a systematic analysis of yeast proteins as emerging protein sources and evaluates the suitability of high-abundance proteins as bioactive peptide precursors by in silico techniques. Moreover, brewery by-product and single-cell yeast protein approaches are compared in terms of composition and techno-functionality whereas peptide formation mechanisms (in situ and ex situ) and regulatory aspects for food applications are also addressed. Cytoplasmic metabolic proteins, particularly glycolytic enzymes (GAPDH), are identified as highly abundant fractions of the yeast proteome. Proteins associated with cell and organelle membranes also contribute substantially based on cellular localization. These findings imply that such proteins may act as key precursors of yeast-derived bioactive peptides. In silico hydrolysis with Alcalase suggests a tendency toward the generation of short-chain peptides (3-11/14 aa), which may support biological activity. Moreover, peptide profiles appear to vary across yeast species, highlighting the role of species diversity in peptide generation. While single-cell yeast protein allows more controlled production than brewery by-products, nucleic acid content in both may limit applications. Overall, yeast proteins appear to be metabolically adaptable and species-diverse sources for various biological peptides.

Saccharomyces cerevisiae

UV-based homogeneous disinfection process for removal of antibiotic resistance genes: Efficiency, mechanisms and influencing factors.

The proliferation and dissemination of antibiotic resistance genes (ARGs) in aquatic environments pose a serious threat to global public health. Ultraviolet-driven homogeneous advanced oxidation processes (UV-AOPs) represent a prospective suite of technologies for the efficient removal of ARGs. This review critically assesses recent advances in the application of UV-AOPs, specifically UV/hydrogen peroxide (UV/H2O2), UV/peracetic acid (UV/PAA), UV/persulfate (UV/PS), and UV/chlorine (UV/Cl), for the elimination of extracellular ARGs and intracellular ARGs. The underlying mechanisms involve direct ultraviolet-induced DNA damage, including pyrimidine dimer formation and strand breakage, as well as oxidation mediated by radicals such as hydroxyl radicals, sulfate radicals, carbon-centered radicals, and reactive chlorine species. The relative contribution of radical and non-radical pathways is strongly influenced by water chemistry and process conditions. We further expound on the critical operational and environmental factors governing ARG removal kinetics, including UV wavelength and fluence, oxidant type and dosage, ARG sequence characteristics, pH, ubiquitous anions, and dissolved organic matter, which collectively affect radical generation, quenching, and reaction microenvironments. Notably, for i-ARGs, UV-AOPs facilitate degradation not only through direct radical attack but also by disrupting cellular integrity and permeabilizing membranes, thereby enhancing the exposure of genetic materials to oxidative and photolytic damage. This review synthesizes current understanding to provide a mechanistic basis for the design and optimization of UV-AOP systems, highlighting their potential as effective barriers against the dissemination of antibiotic resistance in water reuse and purification scenarios.

Disinfection

Genome-wide identification of the HSP70 superfamily in tropical sea cucumber Stichopus monotuberculatus and their expression analysis under low-salinity stress.

Heat shock proteins (HSPs) are a group of evolutionarily conserved molecular chaperones that serve as indispensable core regulators in preserving cellular homeostasis and orchestrating organismal stress responses. The tropical sea cucumber Stichopus monotuberculatus, a high-value aquaculture species, is sensitive to fluctuations in environmental salinity-a challenge that has emerged as a critical bottleneck limiting its large-scale commercial cultivation. However, no systematic investigation has been conducted to characterize the HSP70 superfamily in S. monotuberculatus and elucidate its functional roles in salinity adaptation. In the present study, we performed a comprehensive genome-wide scan and identified 19 HSP70 superfamily genes in the S. monotuberculatus genome, with the HSP70IV subfamily showing remarkable gene expansion, containing 8 distinct copies. Phylogenetic analysis, conserved motif identification, and gene structure characterization demonstrated high evolutionary conservation within each HSP subfamily. These genes were unevenly distributed across the chromosomes of S. monotuberculatus, and prediction of cis-acting elements revealed that their upstream regulatory regions were enriched with numerous functional elements associated with stress response and immune regulation. Salinity stress experiments revealed that under severe low-salinity conditions (18‰), the expression levels of SmHSPA14L and multiple HSP70IV subfamily members were significantly elevated, while SmHYOU1D was significantly downregulated; in contrast, only subtle changes were detected in the expression of most HSP70 genes under moderate low-salinity stress (24‰). These findings strongly suggest that HSP70 genes, particularly the expanded HSP70IV subfamily, may act as key modulators in the low-salinity stress response. This work provides valuable insight into the molecular mechanisms underlying salinity adaptation in tropical sea cucumbers.

Animals

Mechanisms of high-humidity hot air impingement blanching (HHAIB) on microbial counts, functional properties, phenolic profile transformation, and volatile compounds in celery stalks (Apium graveolens L.).

In this study, celery stalks were pretreated with different durations (0-150 s) of high-humidity hot air impingement blanching (HHAIB), followed by far-infrared radiation assisted pulsed vacuum freeze-drying (FIR-PVFD) at 60, 65, and 70 °C. The effects of HHAIB on the physicochemical properties, composition and transformation of phenolic compounds, volatile components, and antioxidant capacity of FIR-PVFD-dried celery stalks were systematically investigated. The results showed that HHAIB not only effectively reduced the counts of total mesophilic aerobic bacteria (TMAB) and total yeast and mold (TYM), but also decreased the relative activities of polyphenol oxidase (PPO) and lipoxygenase (LOX) by more than 91% after 90 s of treatment. HHAIB altered the cellular structure of celery stalks, shortened the drying time by 29.33-41.43%, and improved their hydration properties. HHAIB pretreatment promoted the conversion of bound phenolics to free phenolics in celery stalks, with significant increases in the contents of p-coumaric acid, apigenin, graveobioside A, and other components. The total free phenolic content increased by 56.99%, thus HHAIB enhanced the antioxidant activity. An electronic nose and sensory evaluation revealed that HHAIB-pretreated celery stalks better retained the characteristic herbal and pungent notes. GC-MS results indicated that HHAIB treatment optimized the aroma profile by regulating the contents and composition of terpenes, aldehydes, ketones, alcohols, and aromatic compounds.

Apium

Transforming Curcuma longa leaf waste into cellulose scaffolds.

The constant dearth of transplantable tissues and organs in India required the development of substitute biomaterials for tissue engineering. Plant-based decellularized scaffolds have become attractive options because of their abundance, ethical acceptability, architectural diversity, and lower risks of zoonotic transmission. Curcuma longa leaves were investigated in this study as a possible source of cellulose-based scaffolding for use in biomedical applications. After cuticle removal, an immersion decellularization technique utilizing sodium dodecyl sulphate (SDS) and triton-X-100 was developed to successfully remove cellular and nuclear material while maintaining leaf parenchyma architecture. Histology, DAPI staining, scanning electron microscopy, and a notable decrease in leftover DNA content all demonstrated efficient decellularization. When contrasted with native leaves, the resultant decellularized C. longa leaf scaffolds showed significant increase in porosity, water vapor transmission rate and swelling percent, and significantly lower contact angle with an optimum surface roughness promoting cell adhesion. Mechanical test manifest higher tensile strength with decreased stiffness. Fourier transform infrared spectra of leaf scaffold reveals persistence of different components except cuticle but the intensity of different peaks was decreased. The leaf scaffolds showed superior hemocompatibility and excellent compatibility with Madin-Darby canine kidney cells (MDCK) which is demonstrated by cell attachment and proliferation. MTT assay of seeded scaffold showed significantly higher metabolically active cell. In vivo subcutaneous implantation of decellularized scaffolds showed host tissue incorporation, accumulation of collagen, and neovascularization. C. longa leaf scaffolds can be utilized as cost effective and sustainable biomaterials for soft tissue engineering and regenerative medicine.

Curcuma

Integrin-Linked Kinases 1, 4, and 5 participate in cell wall-mediated innate immunity to leaf and root pathogens.

The cell wall integrity (CWI) pathway is triggered by plasma membrane-localized receptors in plant cells and serves to orchestrate responses to cell wall damage by initiating compensatory changes under stressful environments. The essential role of CWI maintenance as part of plants' interactions with pests or pathogens and during growth is well known. Nevertheless, CWI pathways remain to be fully characterized. Here, we show that altered Integrin-Linked Kinase 1 (ILK1) expression causes widespread defects in the transcriptional program activated by the bacterial elicitor flg22, primarily in genes associated with cell wall integrity and immunity. These transcriptional deficiencies are recapitulated in mutant lines with altered ILK4 or ILK5 expression. Analysis of molecular and cellular defenses in ilk mutants revealed reduced callose accumulation in leaves treated with bacterial (elf18) and plant (pep1) elicitors and increased pathogen susceptibility. Histochemical analysis of cell-wall-associated staining across diverse cells and organs of ilk mutants revealed modified lignin-associated patterns in the root xylem and altered calcofluor staining patterns in the seed coat. All ilk mutants exhibited altered root morphology due to mechano-touch and high-NaCl stress. Based on these results, we propose that ILKs contribute to pathways connecting elicitor-triggered immune signaling with cell-wall-associated stress responses and that ILK-related defense functions may extend to the cotton root-nematode interaction, while the mechanism remains to be elucidated.

Cell Wall

Comprehensive multi-post-translational modifications profiling reveals age-associated remodeling in skeletal muscle.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a major hallmark of aging. Post-translational modifications (PTMs) play essential roles in regulating protein activity and cellular homeostasis; however, how multiple PTMs are remodeled during skeletal muscle aging remains incompletely characterized. Here, we performed comprehensive multi-layered proteomic profiling of skeletal muscle from young (3-month-old) and aged (24-month-old) mice, systematically quantifying the global proteome together with five major PTMs: acetylation, phosphorylation, N-glycosylation, O-glycosylation, and ubiquitination. In total, we identified 5 337 proteins and mapped thousands of PTM sites, generating an integrated atlas of age-associated proteomic and PTM remodeling in skeletal muscle. Pathway enrichment analyses revealed distinct modification-specific patterns: acetylation and phosphorylation were predominantly associated with metabolic and mitochondrial-related pathways; N-glycosylation was enriched in immune- and secretory pathway-related processes; O-glycosylation was associated with muscle contraction-related pathways; and ubiquitination was preferentially linked to cytoskeletal organization in muscle cells. Correlation analyses further uncovered diverse association patterns among different PTMs across protein- and modification-level datasets. Phosphorylation and ubiquitination exhibited consistent positive associations, whereas acetylation and ubiquitination showed both inverse and concordant co-variation patterns across subsets of proteins. Phosphorylation and O-glycosylation displayed heterogeneous association patterns across different proteins, and acetylation and phosphorylation demonstrated positive correlations with distinct age-associated directional changes across protein subsets. Together, these results provide a comprehensive, multi-dimensional view of age-associated remodeling of the skeletal muscle proteome and multiple PTM layers, offering a valuable resource for understanding molecular alterations accompanying muscle aging and sarcopenia.

Animals

Dynamic lysine acetylation and succinylation of platelet proteins regulates platelet storage lesion: mechanistic insights from multi-omics.

OBJECTIVES: Platelet storage lesion (PSL) severely impairs platelet function during storage, presenting a major hurdle in transfusion medicine; however, the dynamic interplay between global proteomic changes and post-translational modifications (PTMs) underlying these functional deteriorations remains insufficiently characterized. Here, we report the first comprehensive multi-omics analysis integrating global proteomics, acetylomics, and succinylomics to dissect the molecular dynamics during platelet storage. METHODS: We performed quantification of global proteomics, acetylome and succinylome based on TMT-labeled LC-MS/MS analysis, combined with antibody-affinity enrichment and purification. Dynamic molecular changes and functional transformation of platelet were also characterized under proper conditions stored for 1, 3, 5, 7 days, respectively. RESULTS: We systematically characterized 3,609 proteins, 1,308 acetylation sites, and 1,947 succinylation sites across multiple storage time points (D1, D3, D5, D7). We distinct temporal patterns of post-translational modifications, with succinylation showing more extensive coverage than acetylation in platelets. Pathway enrichment analysis revealed extensive metabolic reprogramming involving complement activation, energy metabolism, and cellular detoxification processes. The identification of specific motif patterns provided mechanistic insights into the functional specificity of these modifications. Random forest machine learning identified 20 core regulatory proteins representing critical nodes in PSL development. Furthermore, we employed real - time quantitative polymerase chain reaction (RT - QPCR) to measure the expression levels of key genes related to platelet function and PTM - associated pathways. CONCLUSION: By mapping the interplay between proteomic abundance shifts and PTM dynamics, this study provides a multidimensional understanding of PSL, establishing a foundational framework for optimizing storage protocols and enhancing transfusion safety.

Blood Platelets

An Overview of Red Breast Syndrome: A Qualitative Systematic Review of the Literature and a Single-Center Case Series.

Red breast syndrome (RBS) is an uncommon inflammatory complication that may occur following implant-based breast reconstruction and can clinically mimic surgical-site infection. This qualitative systematic review, based on comprehensive PubMed and Scopus searches, summarizes the existing literature on RBS, focusing on its etiology, clinical presentation, diagnostic characteristics, and therapeutic approaches following breast reconstruction using acellular dermal matrices (ADMs). A management protocol is proposed based on available data, and a single-center case series is presented from our Hospital, including patients who developed RBS after direct-to-implant reconstruction with ADM between January 2022 and December 2024. Twenty-nine studies met the inclusion criteria, comprising case reports, case series, and retrospective or prospective cohort studies. The reported incidence of RBS ranged from 0% to 29.6%. Proposed etiologies include endotoxin contamination, residual cellular debris, delayed hypersensitivity reactions, and lymphatic or vascular impairment of mastectomy flaps. Most reports described localized erythema confined to the area of the ADM, with normal inflammatory markers and negative imaging findings, whereas antibiotic therapy frequently failed to achieve improvement. Corticosteroids represented the most consistently effective treatment, although some cases required ADM removal or replacement. In our institutional case series (n = 8), symptom onset occurred between 4 weeks and 7 months postsurgery. Inflammatory markers remained within normal limits, imaging rarely demonstrated fluid collections, and symptoms resolved within days to weeks with corticosteroid therapy or conservative management. This review consolidates current evidence, proposes a diagnostic-therapeutic algorithm and highlights the need for prospective investigations and manufacturer-level endotoxin testing to elucidate pathogenesis and optimize clinical management. Level of Evidence: 2 (Risk) For image description, please refer to the figure legend and surrounding text.

Humans

Transcriptomic insights into the coordinated regulation of signaling, apoptosis, immunity, and metabolism during Sinonovacula constricta larval metamorphosis.

Metamorphosis is a critical ontogenetic transition for marine bivalves, marking the shift from planktonic to benthic lifestyles, where successful transformation dictates survival. The razor clam Sinonovacula constricta is economically important; however, low larval metamorphosis rates remain a major bottleneck in seedling production. To elucidate the mechanisms governing this process, we performed a comparative transcriptome analysis of S. constricta larvae at pre- and post-metamorphosis stages using Illumina sequencing. A total of 3701 differentially expressed genes (DEGs) were identified, including 3254 up-regulated and 447 down-regulated genes. Functional annotation of the respective top 20 significantly up-regulated and down-regulated DEGs indicated their potential pivotal roles in signal transduction (e.g., up-regulated: CAV1, CHRNA2; down-regulated: APP, NOTCH1), cellular proliferation and differentiation (e.g., up-regulated: TUBA, EGF1; down-regulated: KIF23, TTC25), transcriptional and epigenetic regulation (e.g., up-regulated: NFIL3; down-regulated: OVO, HMX1), substance transport (e.g., up-regulated: LRP2, LRP1B; down-regulated: SLC51A, Slc33a1), substance metabolism (e.g., up-regulated: CPK3, CYP26A1; down-regulated: RDMT1, ADAC), immunomodulation (e.g., up-regulated: CPN2, CRISP2), and protein homeostasis (e.g., up-regulated: HSP27, NAS-27). Functional enrichment analysis further revealed that DEGs were significantly enriched in pathways related to signal transduction and developmental regulation (e.g., Ras, TNF), cell death and homeostasis (e.g., apoptosis), immune responses (e.g., Toll-like receptor), energy metabolism (e.g., lipid), cardiovascular related (e.g., Fluid shear stress), cell junction and architecture (e.g., Tight junction), and infectious disease (e.g., measles). These results suggest a synergistic interplay between signaling, apoptosis, immunity, and metabolism during S. constricta metamorphosis. This study advances our understanding of marine bivalve metamorphosis and offers candidate genes for further mechanistic studies.

Animals

An overview of the use of proteomics and peptidomics to characterize alternative protein foods.

The global protein transition is accelerating the development of alternative protein foods, mainly derived from plants, insects, algae, fungi, and cellular agriculture. Ensuring the authenticity, safety, and nutritional adequacy of these emerging protein matrices requires molecular-level characterization beyond traditional compositional analyses. Proteomics and peptidomics have emerged as transformative analytical platforms capable of decoding the molecular signatures that define protein origin, structural integrity, digestibility, functionality, and health potential. The review comprehensively examines the application of proteomics, and peptidomics for profiling alternative protein foods. Further, the source authentication strategies based on species-specific protein and peptide biomarkers, detection of adulteration in complex matrices, and allergenicity assessment is discussed. Special attention is also given to nutritional proteomics with protein digestibility, gastrointestinal peptide release, and identification of bioactive sequences. SIGNIFICANCE: The importance of this review is that proteomics and peptidomics are becoming central in the management of the fast-growing environment of alternative protein foods, such as plant-based, insect, algal, fungal, and cultured meat products. It provides an explanation of the application of mass spectrometry-based processes to decode molecular signatures defining the origin of proteins, their structural integrity, digestibility, allergenicity, and bioactive properties, and thus directly contribute to safety, nutritional analysis, and authenticity of the product. Presentation of the article includes the integration of the knowledge of traditional muscle foods with alternative systems of proteins, where validated protein and peptide biomarkers are used in authentication, fraud detection, and allergy risk assessment in a wide variety of matrices. It also indicates the role of nutritional proteomics and peptidomics in informing the formulation strategy to promote digestibility and release of health-promoting peptides. In general, this review will guide scientists, the food industry, and regulatory bodies to use modern proteomic technologies in quality assurance, and decision-making, for the advancementof sustainable protein-based foods.

Proteomics

Transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora.

Myogenesis involves sequential stages of muscle satellite cell activation, myoblast proliferation, differentiation, and fusion into multinucleated myotubes. Teleost muscle exhibits indeterminate growth and is highly sensitive to environmental temperature, yet the underlying mechanisms by which temperature regulate proliferation and differentiation remain poorly understood. In this study, we established a primary skeletal muscle cell culture from the yellow drum (Nibea albiflora), an economically important marine fish, and integrated morphological observations with comparative transcriptomics analysis to characterize cellular and molecular responses at 28 °C and 20 °C during both proliferation and differentiation stages. Phenotypic analysis revealed that 28 °C significantly enhanced both myoblast proliferation and myogenic differentiation ability compared with 20 °C. Transcriptomic profiling revealed that at 28 °C, differentiation upregulated extracellular matrix(ECM) organization, calcium signaling, and sarcomere assembly, while proliferation enhanced focal adhesion, growth factor signaling, and lipid metabolism. At 20 °C, differentiation was characterized by glutathione metabolism, and ferroptosis, while proliferation involved cytokine-cytokine receptor interaction and negative regulation of signal transduction. Core myogenic regulatory factors (MRFs), particularly myogenin, were strongly upregulated at 28 °C during the differentiation stage, serving as an internal control. Based on these findings, we propose a testable model that elevated temperature coordinates Ca2+-dependent MRF activation with ECM-integrin signaling to drive sarcomere assembly and muscle growth. Key differentially expressed genes (DEGs) regulating myogenesis in N. albiflora were also identified. This study provides a mechanistic framework for temperature adaptation in teleost skeletal muscle and identifies candidate genes for functional validation and marker-assisted selection, as well as a rationale for temperature management strategies to improve aquaculture yield of N. albiflora.

Animals

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals

Transcriptomics reveals species-specific adaptive strategies to calorie restriction in two Argopecten scallops with distinct lifespans.

Calorie restriction (CR) is a well-established non-genetic intervention for lifespan extension in multiple model organisms. Seasonal food shortage in cold and temperate seas may mimic CR, inducing in bivalves a response similar to that in vertebrates and thereby prolonging life expectancy. However, the relationship and the mechanism underlying the food availability and lifespan in bivalves remain largely unexplored. Two closely related scallop species the short-lived warm-water Argopecten irradians (lifespan <2&#xa0;years) and the longer-lived cold-water Argopecten purpuratus (7-10&#xa0;years) provide an ideal comparative system to investigate species-specific adaptive strategies. In this study, we subjected both species to CR for 30 and 56&#xa0;days and performed comparative transcriptomic profiling, weighted gene co-expression network analysis (WGCNA), and physiological assays to elucidate their distinct molecular responses. Transcriptomic analysis revealed that A. purpuratus exhibited substantially more DEGs than A. irradians at both time points under CR, with both species showing downregulation of metabolic pathways but to different extents. A. irradians mounted an early nutrient-sensing response at 30&#xa0;days (IGF1R, PIK3R3, INSR suppression), indicating acute sensitivity to limitation; by contrast, A. purpuratus displayed delayed FoxO activation at 56&#xa0;days, along with its downstream effectors NFKBIA, CREB3L4, and SMAD4, suggesting a gradual adaptive program may link to its extended lifespan. WGCNA identified three negatively correlated modules in each species, with coral2 being the most prominent in A. irradians and darkolivegreen in A. purpuratus. The former was dominated by ciliary motility genes, whereas the latter featured coordinated repression of oxidative phosphorylation. Additionally, both species exhibited conserved suppression of mTOR/S6K growth signaling and activation of cellular maintenance programs. Collectively, these findings expand the understanding of CR-mediated longevity regulation in bivalves and provide candidate gene resources for future functional studies and breeding programs.

Pectinidae

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-&#x3ba;B, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans

Transcriptomic and RNAi analyses reveal chloride channel 3-associated osmoregulation in Litopenaeus vannamei under low-salinity stress.

Chloride channels and transporters are important for cellular volume regulation and salinity adaptation in euryhaline crustaceans, yet the intestinal transcriptional relationship between plasma-membrane and intracellular chloride pathways remains unclear in Litopenaeus vannamei. In this study, RNA interference of anoctamin 1 (ANO1) was combined with intestinal transcriptome sequencing under the production-relevant low-salinity condition of salinity 3. ANO1 silencing produced a focused transcriptional response, with 16 differentially expressed genes (DEGs) identified (11 upregulated and 5 downregulated). Functional enrichment indicated that these genes were associated with transporter activity, cytoskeletal organization, extracellular matrix-receptor interaction, membrane lipid metabolism, and vesicular processes. Notably, a transcript encoding chloride channel protein 3 (CLC-3) was significantly upregulated following ANO1 knockdown, suggesting a potential transcriptional relationship between ANO1 and CLC-3 in chloride homeostasis. Based on this finding, CLC-3 was selected for full-length cDNA cloning, sequence characterization, salinity-gradient expression analysis, and RNAi-based functional assessment. The cloned CLC-3 cDNA was 2883&#xa0;bp in length and encoded an 850 amino acid protein containing a conserved voltage-gated chloride channel (Voltage-CLC) domain and two cystathionine &#x3b2;-synthase domains. Phylogenetic analysis placed LvCLC-3 within the intracellular CLC-c clade, and tissue distribution analysis showed the highest CLC-3 expression in the intestine. Intestinal CLC-3 expression responded nonlinearly to salinity variation, peaking at salinity 20. Under salinity 3, CLC-3 knockdown reduced ANO1, Na+/K+-ATPase alpha subunit, and Na+-K+-2Cl- cotransporter transcript levels, whereas glutamate-gated chloride channel expression increased. Mild hepatopancreatic structural alterations were also observed after CLC-3 knockdown. These findings suggest that CLC-3 is a salinity-responsive intracellular chloride-transporter candidate associated with intestinal ion-transport-related transcriptional responses after ANO1 suppression in L. vannamei, although the underlying physiological mechanism requires further validation.

Animals

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs)-arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin)-led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Actin dysfunction also displayed a more "aged" transcriptome using previously validated transcriptomics clocks, and broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting some links between aging and actin across organisms. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how changes in actin integrity correlate with diverse aging phenotypes across tissues. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics can potentially influence aging.

actin

Feasibility of routine clinical liquid-based cytology for lung cancer compact panel testing.

BACKGROUND: The Lung Cancer Compact Panel (cPANEL) is a recently approved highly sensitive multiplex gene panel in Japan that supports both DNA- and RNA-based next-generation sequencing. Although cytological specimens are acceptable for cPANEL, unfixed cell pellets or dedicated preservation tubes are typically recommended. However, evidence remains limited regarding whether residual liquid-based cytology (LBC) cell suspensions prepared for routine cytological diagnosis can be used directly for cPANEL testing without dedicated molecular preservation or additional preanalytical processing. In this study, we evaluated the feasibility of applying LBC specimens that are widely used in contemporary clinical practice to cPANEL. METHODS: We analyzed DNA and RNA quality in 69 clinical LBC specimens. Among these, 51 specimens containing non-small cell lung cancer cells with previously determined driver alteration status were subjected to cPANEL testing to evaluate assay concordance with clinical companion diagnostic results. RESULTS: DNA integrity was generally well preserved (DNA Integrity Number [DIN]: 6.2&#xa0;&#xb1;&#xa0;1.5). In contrast, RNA integrity showed greater variability (DV200: 16.4&#xa0;&#xb1;&#xa0;12.1%). ThinPrep-fixed specimens demonstrated lower DIN and DV200 values compared with CytoRich Red-fixed specimens. Although all samples successfully passed the DNA-based cPANEL assay, six cases (11.8%) failed the RNA-based assay, with RNA yield being a major contributing factor. Among the 46 evaluable specimens, concordance was 95.7% and sensitivity was 92.3%, or 88.9% including RNA module failures as cPANEL-negative. CONCLUSIONS: With appropriate fixative selection and adequate cellularity, cPANEL using clinical LBC specimens may serve as a practical diagnostic platform. We demonstrated that routine LBC specimens can be directly applied to cPANEL without special preanalytical processing.

Humans