Search Results (17,945)

Background: Head and neck squamous cell carcinoma remains a highly aggressive malignancy with limited predictive biomarkers for prognosis and radiotherapy response. Increasing evidence indicates that pseudogenes are functionally active regulators of cancer biology, yet their clinical relevance in HNSCC is poorly defined. Methods: Using transcriptomic and clinical data from The Cancer Genome Atlas, we analyzed the expression and clinical significance of two pseudogenes, ANXA2P2 and PA2G4P4, in HNSCC. Associations with clinicopathological features, HPV status, tumor subtypes, survival, genomic instability, radiotherapy response, and immune landscape were assessed using bioinformatic tools. Results: Both pseudogenes were significantly upregulated in HNSCC compared to normal tissues. Higher expression levels correlated with adverse clinicopathological features, increased tumor proliferation and wound-healing capacity, and unfavorable TCGA molecular subtypes. High ANXA2P2 and PA2G4P4 expression was associated with reduced overall survival, while their combined low-expression signature identified patients with significantly improved overall and disease-free survival. Notably, lower expression of both pseudogenes was observed in patients responding to radiotherapy, whereas higher expression was linked to genomic instability parameters and enrichment of oncogenic pathways, including MYC, PI3K/AKT/mTOR, cell cycle regulation, and DNA repair. ANXA2P2 expression differed significantly by HPV status, showing reduced levels in HPV-positive tumors. Furthermore, pseudogene expression stratified distinct immune profiles, including immune subtypes, stromal and immune scores, and specific immune cell populations. Conclusions:ANXA2P2 and PA2G4P4 are clinically relevant pseudogenes associated with tumor aggressiveness, immune modulation, and radiotherapy response in HNSCC. These findings support their potential utility as prognostic and predictive biomarkers and provide a rationale for further functional validation in experimental models. Full article

Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather than being a uniform event, mesenchymal condensation rapidly segregates into progenitor pools with distinct fates. Centrally located Sox9⁺/Fgfr3⁺ chondroprogenitors expand into the growth plate and metaphyseal stroma, peripheral Hes1⁺ boundary cells refine condensation via asymmetric division, and outer-layer Dlx5⁺ perichondrial cells generate the bone collar and cortical bone. Concurrently, dorsoventral polarity established by Wnt7a–Lmx1b and En1 ensures that dorsal progenitors retain positional identity throughout development. These lineage divergences integrate with signaling networks, including the Ihh–PTHrP, FGF, BMPs, and WNT/β-catenin networks, which impose temporal control over chondrocyte proliferation, hypertrophy, and vascular invasion. Perturbations in these programs, exemplified by mutations in Fgfr3, Sox9, and Dlx5, underlie region-specific skeletal dysplasias, such as achondroplasia, campomelic dysplasia, and split-hand/foot malformation, demonstrating the lasting impacts of embryonic patterning errors. Based on these insights, regenerative strategies are increasingly drawing upon developmental principles, with organoid cultures recapitulating ossification centers, biomimetic hydrogels engineered for spatiotemporal morphogen delivery, and stem cell- or exosome-based therapies harnessing developmental microRNA networks. By bridging developmental biology with biomaterials science, these approaches provide both a roadmap to unravel skeletal disorders and a blueprint for next-generation therapies to reconstruct functional bones with the precision of the embryonic blueprint. Full article

Early prevention of pathological changes underlying gastric cancer (GC) development is a critical strategy, offering the most effective opportunity to limit malignant progression and improve patient outcomes. We have previously demonstrated that Helicobacter pylori (Hp) (cagA⁺vacA⁺) contributes to GC development by activating gastric fibroblasts toward CAF-like phenotype, eliciting aggressive, cancer stem cells (CSCs)-related malignant transformation of LGR5⁺ normal epithelial cells. A key mediator of these processes appears to be the NF-κB/STAT3 axis. Therefore, our aim was to investigate the protective role of hydrogen sulfide (H₂S) as a potential novel strategy for counteracting Hp-induced fibroblast reprogramming. Human fibroblasts were infected with Hp (cagA+vacA+) for 120 h. The fast-releasing H₂S donor NaHS (50, 100, 200 and 400 µM) was added every 24 h. Activation markers, corresponding signaling pathways, H₂S release and activities of H₂S-metabolizing enzymes were determined. NaHS reduced Hp-induced fibroblast activation and their pro-inflammatory, pro-tumorigenic markers, which was associated with the inhibition of NF-κB/STAT3 axis and Twist expression. Additionally, it modulated sulfur metabolism while preserving sulfur-enzyme homeostasis. NaHS limited Hp adhesion (high doses), reduced reinfection-induced activation and increased sensitivity of Hp to metronidazole. These findings suggest that H₂S signaling may represent a modulatory factor of NF-κB/STAT3-driven inflammatory responses during Hp infection and warrant further investigation. Full article

As we become older, systems throughout the body gradually decline in function. Contributing factors include the accumulation of senescent cells and the dysfunction and exhaustion of stem and progenitor cells. A promising approach to mitigate these changes and enhance cellular function in aged animals is the discovery that differentiated cells retain plasticity, enabling them to revert to pluripotent states when exposed to Yamanaka factors. This method has shown promise in models of rapid aging, and recent studies have demonstrated notable life extension in both flies and mice. These findings, along with the development of senolytics and aging clocks, could revolutionize aging research and interventions. Here, we review recent discoveries in the field and propose new directions for intervention discovery. Full article

Background: Hair loss (alopecia) is primarily driven by the premature transition of hair follicles from the anagen (growth) to the catagen (regression) phase. Intracellular calcium signaling is implicated in hair follicle biology, including the regulation of Wnt/β-catenin activity and the modulation of catagen-associated factors such as TGF-β2. Cyclic ADP-ribose (cADPR), a calcium-mobilizing second messenger synthesized by CD38, has recently emerged as a potential modulator of intracellular calcium dynamics. This study investigated whether cADPR is associated with changes in intracellular calcium retention and anagen-associated signaling pathways in human hair follicle dermal papilla cells (HHDPCs). Methods: HHDPCs were treated with cADPR (0.001–0.5 ppm) and analyzed for cell viability, intracellular calcium retention, β-catenin-dependent transcription, and the gene expression of LEF-1 and TGF-β2. Cell viability was evaluated using the MTT assay, intracellular calcium content was quantified by ICP–OES, β-catenin activation was assessed using a TOPFlash luciferase assay, and gene expression was measured by qRT-PCR. Results: cADPR did not induce marked cytotoxicity, maintaining more than 98% cell viability across all concentrations. The highest response was observed at 0.05 ppm, at which intracellular calcium content remained elevated for up to six hours as assessed by ICP–OES. At this concentration, β-catenin-dependent transcription increased by approximately 2.3-fold relative to control, LEF-1 expression was significantly upregulated (~2.5-fold), and TGF-β2 expression was significantly downregulated (~0.3-fold). These responses showed an overall concentration-dependent trend across assays. Conclusions: These findings indicate an association between cADPR treatment and modulation of intracellular calcium retention and anagen-related signaling readouts in HHDPCs, supporting the need for further studies to establish mechanistic causality and physiological relevance. Full article

The progression of neoplastic diseases is driven by a complex interplay of biological processes, including uncontrolled proliferation, enhanced invasion, metastasis, and profound metabolic reprogramming. Among the hallmarks of cancer, as revised by Hanahan and Weinberg, the reprogramming of energy metabolism has emerged as a critical feature that enables cancer cells to meet their heightened bioenergetic and biosynthetic demands. One significant aspect of this metabolic adaptation is the accumulation of lipid droplets (LDs) dynamic, cytoplasmic organelles primarily involved in lipid storage and metabolic regulation. LDs serve as reservoirs of neutral lipids and play a multifaceted role in cancer cell physiology. Their accumulation is increasingly recognized as a marker of tumor aggressiveness and poor prognosis. By storing lipids, LDs provide a readily accessible source of energy and essential building blocks for membrane synthesis, supporting rapid cell division and growth. Moreover, LDs contribute to cellular homeostasis by modulating oxidative stress, maintaining redox balance, and regulating autophagy, particularly under nutrient-deprived or hypoxic conditions commonly found in the tumor microenvironment. Importantly, LDs have been implicated in the development of resistance to cancer therapies. They protect cancer cells from the cytotoxic effects of chemotherapeutic agents by buffering endoplasmic reticulum (ER) stress, inhibiting apoptosis, and facilitating survival pathways. The presence of LDs has been shown to correlate with increased resistance to a variety of chemotherapeutic drugs, although the precise molecular mechanisms underlying this phenomenon remain incompletely understood. Emerging evidence suggests that chemotherapy itself can induce changes in LD accumulation, further complicating treatment outcomes. Given their central role in cancer metabolism and therapy resistance, LDs represent a promising target for therapeutic intervention. Strategies aimed at disrupting lipid metabolism or inhibiting LD biogenesis have shown potential in sensitizing cancer cells to chemotherapy and overcoming drug resistance. In this review, we comprehensively examine the current understanding of LD biology in cancer, highlight studies that elucidate the link between LDs and drug resistance, and discuss emerging approaches to target lipid metabolic pathways to enhance therapeutic efficacy across diverse cancer types. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring. Full article

Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL⁻¹. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC. Full article

This work was inspired by quercetin, a natural bioflavonoid with well-known neuroprotective properties. We synthesized a new functional monomer, 3-acryloxy-3′,4′,5,7-tetramethylquercetin 1, and used it to prepare, for the first time, a molecularly imprinted polymer (MIP) selective for donepezil, the main drug used in Alzheimer’s disease therapy. The polymer was designed to be fluorescent and responsive to pH changes, aiming for controlled drug release. The optimized MIP-4, produced from a 1:1 mixture of the monomer 1 and acrylic acid, was characterized by FTIR-ATR, fluorescence spectroscopy, SEM, and DLS, confirming its chemical composition, morphology, particle size distribution and zeta potential. Adsorption studies showed higher donepezil binding capacity for MIP than for NIP, highlighting the polymer’s selective recognition. In vitro release experiments at pH 3, 5.5, and 7 revealed a pH-dependent behaviour, with nearly 98% cumulative donepezil release at pH 7. The polymer was non-cytotoxic and successfully released donepezil in in vitro assays, enabling effective inhibition of eeAChE. These results provide a proof of concept supporting the potential of quercetin-derived fluorescent molecularly imprinted polymers as selective and stimuli-responsive platforms for donepezil delivery. Full article

Vitamin A in the form of 11-cis-retinaldehyde is the chromophore essential to vision. Thus, deficiencies in vitamin A necessitate the implementation of vitamin A supplementation. Moreover, some vitamin A is lost from the visual cycle due to random reactions that generate diretinaldehyde (bisretinoid) molecules; the latter are photoreactive and contribute to retinal disease. Here, we measured the systemic and ocular uptake of vitamin A along with bisretinoid as a function of vitamin A availability when supplied in the diet or by weekly i.p. injection in light- and dark-reared mice. Retinyl palmitate delivered as an i.p. bolus served to elevate plasma ROL but an associated increase in ocular 11-cisRAL was not observed in light- or dark-reared mice. In dark-reared mice, 11-cisRAL was more abundant when retinyl palmitate was provided in chow versus weekly i.p. injection; moreover, by the latter route, retinyl acetate was more effective. Conversely in dark-reared mice given retinyl palmitate by weekly i.p. injection versus chow, ocular atRAL was elevated. Liver atRE was elevated by increased retinyl palmitate in chow; the latter also favored elevated 11-cisRAL in dark-reared mice. In cyclic light-reared mice, ocular stores of atRE were increased by i.p. retinyl palmitate. With dark-rearing, there was no difference in bisretinoid (A2E) with retinyl palmitate in chow, nor by weekly i.p. injection; notably, bisretinoid levels were lower in cyclic light-reared mice due to photooxidative loss. In summary, light modulates the ocular retinoid, plasma atROL does not predict ocular levels of retinoid or bisretinoid and atRAL is elevated with sustained darkness. Full article

This study aimed to evaluate the effects of an ethanolic extract from Punica granatum L. (EE-PG) on bovine ovarian tissue vitrification, focusing on follicular morphology, ultrastructure, stromal cell density, collagen distribution, redox status, and mRNA expression of antioxidant-related genes. Bovine ovarian cortex fragments were divided into a fresh control group for in vivo tissue evaluation or vitrified either with the base vitrification solution (αMEM) alone or supplemented with different concentrations of EE-PG (10, 50, and 100 µg/mL), and subsequently stored in liquid nitrogen for 5 days. After warming, fragments were allocated for morphological and oxidative stress analyses or incubated for 24 h to resumption of cellular metabolism. The concentrations of 10 and 100 µg/mL preserved follicular morphology immediately after warming, and were therefore selected for ultrastructural evaluation. Both concentrations mitigated vitrification-induced damage. Gene expression analysis showed decreased levels of catalase (cat), Glutathione Peroxidase 1 (gpx1), and Nuclear Factor Erythroid 2-Related Factor 2 (nrf2) compared with the fresh control, whereas Superoxide Dismutase (SOD) enzymatic activity increased after incubation with 10 µg/mL EE-PG compared with all experimental groups. Moreover, Malondialdehyde (MDA) levels in tissues treated with 10 or 100 µg/mL were comparable to fresh controls after incubation. Overall, EE-PG at 10 or 100 µg/mL in the vitrification solution supported the maintenance of tissue morphology, redox balance—despite the downregulation of essential antioxidant genes, which may be associated with a reduced demand for enzymatic antioxidant defense—and cellular metabolism, indicating potential for improving bovine ovarian tissue vitrification outcomes. Full article

Thymic carcinoma (TC) is a rare and aggressive malignancy with poor prognosis, and its genomic landscape remains incompletely defined. Identifying the somatic alterations that shape TC biology is essential for improving diagnostic precision, developing targeted therapies, and informing early detection strategies. We performed a retrospective genomic analysis of 141 TC tumor specimens from 134 patients using de-identified data from the American Association for Cancer Research (AACR) Project GENIE^® database. Somatic mutations and copy number alterations (CNAs) were characterized, and statistical analyses were conducted to evaluate associations with patient demographics (sex, race) and tumor site (primary vs. metastatic). The cohort was predominantly male (56.7%) and White (56.7%). The most frequently altered genes were TP53 (27.7%), CYLD (17.6%), and CDKN2A (12.1%). Recurrent homozygous deletions at chromosome 9p21.3 involving CDKN2A and CDKN2B were common. Sex-stratified analysis revealed several significant male-specific alterations. Although the Pacific Islander subgroup was small (n = 2), preliminary analysis suggested enrichment of alterations in key cancer-associated genes, including TP53, BRCA1, and STAT5B, underscoring the need for diverse representation in TC genomics. Notably, MTOR mutations were significantly enriched in a subset of local recurrences and lymph node metastases (n = 3; q = 0.013), suggesting a potential role in disease progression. This large-scale genomic analysis reinforces the central involvement of TP53, cell-cycle control, and chromatin-modifying pathways in TC. The identification of sex-associated and race-associated mutational patterns, together with the enrichment of MTOR alterations in recurrent and metastatic disease, highlights biologically plausible mechanisms of progression and potential therapeutic vulnerabilities. These findings support the value of comprehensive genomic profiling in TC and emphasize the need for prospective, multi-omic studies to validate these observations and guide the development of more personalized treatment strategies. Full article

Background: Advanced glycation end-products (AGEs) are formed and deposited in tissues, contributing to various disorders, including diabetes, other metabolic diseases, and aging. A new epitope, AGE10, was identified in human and animal tissues using a monoclonal antibody raised against synthetic melibiose-derived glycation end-products (MAGE), which were synthesized under anhydrous conditions with bovine serum albumin or myoglobin. The biology of the AGE10 epitope, particularly its role in diseases and in cancer tissues, is not well understood. Methods: The study was aimed at investigating the immunohistochemical recognition of AGE10 with the MoAb-anti-MAGE antibody. Results: Data obtained show that AGE10 is recognized in striated muscles but not in tumors of muscular origin. AGE10 is also stained in both normal and cancerous salivary glands and in adenomas of the large intestine. The staining is cytoplasmic. Discussion: Our approach may provide a methodology for cell biology research; AGE10 may be related to an advanced lipoxidation end-product; further investigation of MAGE may clarify disease mechanisms, support the development of novel therapeutic strategies. Conclusions: The key finding is that antibodies recognize mainly the epitope in epithelial and some mesenchymal tissues. Thus, the potential for AGE10 as a diagnostic marker is limited. The implications concern the biology of this epitope, the unique tissue distribution, and a role in cellular metabolism. Full article

Choy sum (Brassica rapa var. parachinensis) is an important vegetable crop in Brassicaceae. However, its mitochondrial genome has not been well studied. In this study, Illumina and Nanopore sequencing technologies were combined to assemble the complete mitochondrial genome of choy sum. The mitochondrial genome is a circular molecule of 219,775 bp, with a GC content of 45.23%. A total of 60 genes were annotated, including 33 protein-coding genes (PCGs), 23 transfer RNA (tRNA) genes, 3 ribosomal RNA (rRNA) genes, and one pseudogene. A total of 466 RNA editing sites were identified in the PCGs. Codon usage analysis revealed that leucine (leu) was the most frequently used amino acid. Twenty-nine codons showed a relative synonymous codon usage (RSCU) value greater than 1. Most of these preferred codons ended with A or U. A total of 308 repetitive sequences were detected, including 136 dispersed repeats, 17 tandem repeats, and 55 simple sequence repeats (SSRs). Evolutionary analysis indicated that most mitochondrial genes are under negative selection. The highest nucleotide diversity detected in the cox2 gene suggests that this gene could serve as a valuable molecular marker for mitochondrial research in the species. Homology analysis found 22 homologous fragments between the mitochondrial and chloroplast genomes of choy sum. These fragments total 13,325 bp, representing 6.06% of the mitochondrial genome. Phylogenetic analysis showed that choy sum is most closely related to B. rapa var. purpuraria. This study offers a genomic resource for genetic improvement and breeding of choy sum. It also provides molecular insights into the evolution of Brassica species. Full article