Результаты поиска

Modulation of inflammasome components in patients with heart failure using oral nutritional supplements: investigating the molecular mechanisms beyond the clinical benefit.

PURPOSE: Inflammation is a key contributor to the pathogenesis and progression of heart failure (HF), correlating with increased morbidity a … gulators also shifted, with decreased CDKN2D expression (p < 0.05), suggesting potential effects on cellular senescence and DNA repair pathways. Notably, these molecular changes were absent in patients adhering solely to the Mediterranean diet. CONCLUSIONS: these findings suggest that supplementing a Mediterranean diet with hypercaloric, high-protein, EPA and DHA-enr …

The role of cuproptosis in osteoporosis: Molecular mechanisms and cell-specific regulation in bone metabolic imbalance.

The pathogenic mechanisms of osteoporosis (OP), a systemic metabolic bone disease marked by an imbalance between bone growth and resorption, … CDKN2A) control metabolic reprogramming, the linkage between oxidative stress and inflammation, and cellular senescence, all of which contribute to the development of OP. An additional factor contributing to bone metabolic imbalance is the cuproptosis-dependent control of T-cell cytokine production and macrophage polarization in the bone immunological milieu. Accordi …

Perspectives on intrinsic articular cartilage interfaces.

INTRODUCTION: According to the current concept the joint is an organ composed of multiple tissues forming manifold communicating interfaces. Moreover, cartilage itself presents typical intrinsic zonal interfaces. Since the healthy joint cartilage is not vascularized, soluble mediators are distributed by the synovia fluid flow in the cartilage extracellular matrix (ECM) of the joint compartments. This distribution is dependent on intermittent mechanical loading and water flow in the joint. Hence, soluble factors play a pivotal role in articular cartilage interfacial communication. These mediato

Beyond antioxidation: Retinal neuroprotection by Lycium barbarum polysaccharides via multiple signaling pathways.

Age-related macular degeneration, glaucoma, retinitis pigmentosa, and diabetic retinopathy are the major retinal degenerative disorders, and … harides engages pathways well beyond redox control to interrupt disease-driving cascades: it limits cellular senescence through the SIRT1/p53 axis, preserves blood-retinal barrier integrity by maintaining aquaporin-4 at astrocytic endfeet, and biases microglia from proinflammatory M1 toward reparative M2 states. Beyond immunomodulation, Lycium barbarum polysaccharide …

Redox signaling in chronic airway diseases: pathogenic mechanisms and therapeutic implications.

Chronic airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis, impose a significant global health burden. A central unifying feature of these diseases is redox imbalance, which is characterized by an excess of reactive oxygen and nitrogen species (ROS/RNS) that overwhelms the body's antioxidant defenses, causing cellular dysfunction, inflammation, and tissue damage. Physiological ROS/RNS are essential for immune regulation and transcriptional control, but chronic oxidative stress disrupts these processes, driving disease progression. In asthma, eos

CD109 Drives Stemness and Chemoresistance in Colorectal Cancer via LRRC8A/AKAP12/PKCα-Mediated STAT3 Activation and WNT Signaling.

Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide, with a poor survival rate at the metastatic stage. Here, we id … ous hallmarks of cancer stemness (i.e. LGR5 expression), together with increased TGFβ signaling and cellular senescence. Mechanistically, CD109 interacts with LRRC8A, a subunit of the volume-regulated anion channel (VRAC), which associates with AKAP12 to activate PKCα and promote STAT3 phosphorylation. This CD109/LRRC8A/AKAP12/PKCα axis sustains Wnt signaling, stemne …

Intra-Islet Duct Formation and Gastric-Type Metaplasia in CRY1 C414A Transgenic Mice: Association with Endocrine Cell Plasticity and α-Cell Localization.

BACKGROUND: Transgenic mice expressing the C414A-mutant cryptochrome 1 (CRY1 C414A) develop diabetes with progressive β-cell senescence and the formation of mucinous intra-islet ductal lesions. These lesions exhibit features resembling metaplasia; however, their molecular basis and the potential involvement of endocrine cells remain unclear. This study aimed to define the metaplasia-like program in intra-islet ducts and to characterize endocrine cell phenotypes in this context. METHODS: Gene expression microarrays were analyzed using islets from aged CRY1 C414A transgenic and wild-type mice.

Gut Microbiota and Brain Aging: Identifying Keystone Biomarkers for Cognitive Health.

The fact that the population is getting older has greatly increased the occurrence of cognitive decline and neurodegenerative diseases, unde … of biological aging-such as telomere shortening, epigenetic clocks, oxidative stress, inflammation, cellular senescence, and metabolic dysfunction-as well as established cognitive biomarkers obtained from neuroimaging, cerebrospinal fluid, blood, genetic evaluations, and neuropsychological tests. We also point out that changes associated with age in the composition o …

Osteocyte and vascular network in hip osteoarthritis: A multimodal imaging and histological analysis.

OBJECTIVE: Hip osteoarthritis (OA) is characterised by increased remodelling of the subchondral bone, for which the underlying cellular and microvascular mechanisms are unclear. This study investigated alterations in the osteocyte lacunocanalicular network and vascular canal architecture in the femoral head in human hip OA, using a multimodal imaging and histological approach. DESIGN: Femoral head samples from OA patients (n = 8; 4 female, 4 male; age 69 ± 14) undergoing hip replacement, and healthy controls (n = 8; 5 female, 3 male; age 64 ± 12), were imaged by MRI to assess cartilage volume

Shikonin inhibits bladder cancer progression by targeting deoxyribonuclease 2 to suppress reticulon 3-dependent endoplasmic reticulum autophagy.

BACKGROUND: Bladder cancer (BCa) is a prevalent urinary malignancy with unmet clinical therapeutic needs. Shikonin, a natural anti-tumor compound, exerts anti-BCa activity, yet its direct molecular target and underlying mechanism remain undefined. PURPOSE: This study aimed to identify the direct target of shikonin in BCa and to elucidate the mechanism by which shikonin suppresses tumor progression. METHODS: The anti-BCa effects of shikonin were assessed in vitro and in vivo. Drug affinity responsive target stability (DARTS) combined with 4D quantitative proteomics identified shikonin's direc

Специфические сети miRNA-mRNA в серой и белой материи из прогрессивных множественных склерозов.

ЦЕЛЬ: Множественный склероз (MS) — нейродегенеративное демиелинирующее заболевание центральной нервной системы. Цель этого исследования заключалась в выявлении сетей регулирования микро-РНК (миРНК)-мРНК, лежащих в основе региональных молекулярных механизмов в белой материи и повреждения серы в прогрессивных MS. МЕТОДЫ: Глобальное miRNA и mRNA профилирование выражений ранее проводилось на белых и серых тканях, поврежденных после смерти прогрессивных умов MS. Эти наборы данных были интегрированы с помощью анализа Ингенитетных путей (ИПА) для выявления обогащенных канонических путей на основе экс

Совпадение в аннотации оригинала
OBJECTIVE: Multiple sclerosis (MS) is a neurodegenerative demyelinating disease of the central nervous system. This study aimed to identify … ns (WMLs) and Gray Matter lesions (GMLs). Pathway analysis identified two major downstream pathways-cellular senescence and EIF2 signaling-with opposing predicted activation states (activated in White Matter lesions and inhibited in Gray Matter lesions). Among the shared miRNAs, miR-30a and miR-100 exhibited opposing expression patterns, with downregulation in GMLs a …

Single-Cell RNA Sequencing Reveals an Atlas of Meihua Pig Testis Cells.

Mammalian spermatogenesis is a complex biological process that is regulated by multiple types of cells. The heterogeneity of these cells pos … phosphorylation, Protein processing in endoplasmic reticulum, Retrograde endocannabinoid signaling, Cellular senescence and Insulin signaling. Meanwhile, in the three different germ cells, except for pathways which were the same as the first three pathways for somatic cells, DEGs were also enriched in the Spliceosome, Cell cycle, Autophagy and Mitophagy pathways. Fur …

Deep neural networks and genome-wide associations reveal the polygenic architecture of local brain aging.

Local brain age (LBA) is a regional metric of brain aging that offers a spatially resolved alternative to global brain age, but whose genetic basis is unexplored. This study reports the first genome-wide association study of cortical LBA, as estimated by a deep neural network from the T1-weighted magnetic resonance images of 41,708 cognitively normal adults in the UK Biobank. We identified 1,212 single-nucleotide polymorphisms (SNPs) significantly associated with LBA in at least one brain region. Genes mapped to these SNPs are involved in developmental, metabolic, immune, and cytoskeletal path

Veterans Training Service Dogs for Other Veterans: An Animal-Assisted Intervention for Post-Traumatic Stress Disorder.

Research on the post-deployment reintegration needs of women veterans is limited. Non-traditional support may enhance mental health. Relatio … F(1,11.65) = 3.543, p = 0.085] by intervention. In the SDTP group, TL increased, indicating reduced cellular senescence (i.e., slower biological aging), whereas TL decreased in the CI group. Combat exposure moderated these changes [F(1,12.36) = 5.41, p = 0.038]. HRV changed by intervention group [F(1,389.08) = 10.623, p = 0.001]. HRV decreased (stress increased) in t …

Identification of telomere-related diagnostic markers in osteoarthritis based on bioinformatics analysis and machine learning.

Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related ge…

Identifying the important involvement of cuproptosis in the pathophysiology of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a neurodegenerative disease associated with severe visual impairment in the elders. De … way enrichment analysis showed that cuproptosis was associated with angiogenesis, inflammation, and cellular senescence in AMD. Furthermore, the copper chelator demonstrated a protective effect on retinal function in the AMD mouse model. CONCLUSIONS: Our findings identified an important role of cuproptosis in the pathophysiology of AMD and suggested the potential of …

Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.

In recent years, the development of chimeric antigen receptor (CAR) technology has greatly promoted the progress of cellular immunotherapy. Among them, CAR-T cell therapy has shown remarkable clinical effects in the treatment of hematological malignancies. However, this therapy still faces a series of challenges, including immunogenicity, toxic side effects, and insufficient maintenance of long-term efficacy. The latest research progress has extended CAR technology to mesenchymal stem cells (MSCs), and the resulting CAR-MSCs combine the precise targeting ability of CAR molecules with the inher

Uremic Toxins, CKD, and Cognitive Dysfunction.

Cognitive impairment involves alterations to one's cognitive status that affects everyday life. Individuals with CKD, and particularly kidne … -associated brain injury. Finally, future research directions are suggested, including targeting of cellular senescence abundance with senotherapeutics and capitalizing on anti-inflammatory effects of regenerative, cell-based therapeutics ( e.g ., mesenchymal stem cells and extracellular vesicles), and use of aged murine models. Collectively, CKD-associated cognitive …

A Novel Primary Cell Line Model of Localized Prostate Cancer and Radioresistance-A Role for Nicotinamide N-Methyltransferase.

Prostate cancer cell lines are particularly clinically homogenous, mostly representing metastatic states rather than localized disease. Whil … ant radiosensitization of CaB34-CF cells, which was largely a result of increased radiation-induced cellular senescence. Growth as 3D organoids was significantly higher in the CaB34-CF line, and demonstrated a less structured pattern of expression of cytokeratin markers. Radiosensitization with NNMT siRNA was recapitulated in a 3D organoid clonogenic assay in CaB34-C …

TERT expression in human prostate tissue reveals a potential molecular switch in benign prostatic hyperplasia progression.

PURPOSE: Benign prostatic hyperplasia (BPH) is a leading cause of voiding symptoms in aging men. Telomerase reverse transcriptase (TERT), a key regulator of cellular senescence and tissue remodeling, has not been systematically examined in human voiding symptoms, though genome-wide association studies suggested a role in genetic and sporadic BPH. METHODS: Prostate tissues from patients undergoing laser enucleation for BPH were analyzed by RT-PCR. Clinical parameters were compared between TERT-positive and -negative patients. TERT expression in laser-enucleated tissues was tested for correlati…