Search Results (6,692)

Worldwide, prostate cancer (PC) has a rising incidence and is the sixth leading cause of death globally, especially with increasing cases in developing countries. Risk factors for PC include genetic predisposition, family history, race/ethnicity, and various occupational factors like diet, obesity, smoking, and transmitted diseases. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway can be activated by hormones, cytokines, and growth factors, and it plays a role in many vital biological processes such as cell growth, differentiation, immune regulation, and apoptosis. Dysregulation of JAK/STAT3 can lead to cancer, inflammation, diabetes, and neurodegenerative disorders. In cancers, including PC, STAT3 promotes cell survival, progression, angiogenesis, and metastasis. Inhibitors targeting JAK and STAT3 tested in vivo have shown potential to inhibit malignant cell growth. Additionally, flavonoids are bioactive plant compounds that are important in preventing inflammation, oxidative stress, and cancer. Research indicates that natural flavonoids can be developed into cancer-preventive and therapeutic agents. Experimental studies have demonstrated that some flavonoids can inhibit PC development. The main goal of this review is to present the incidence and risk factors of PC, the JAK/STAT3 pathway and its inhibitors, and how flavonoids may influence this pathology. Full article

The global aging population has led to a rising prevalence of cognitive impairment, posing a significant public health challenge. Resistance training (RT) is a non-pharmacological intervention that has been increasingly investigated for its potential to support cognitive function in older adults. Clinical evidence suggests that RT may be associated with benefits in certain cognitive domains, including memory, executive function, processing speed, and visuospatial ability. However, findings across studies remain heterogeneous, with several trials reporting neutral outcomes. Most intervention studies involve structured RT programs conducted at moderate to high intensity and performed multiple times per week. However, optimal training parameters have not yet been clearly established due to variability in study design and the absence of formal dose–response analyses. Emerging evidence suggests that the cognitive effects of RT may be mediated, at least in part, through muscle–brain axis signaling involving exercise-induced myokines. Factors such as irisin, brain-derived neurotrophic factor, interleukin-6, interleukin-15, and insulin-like growth factor-1 have been implicated in processes related to neuroplasticity, neuroinflammatory regulation, and neurovascular function, primarily based on preclinical and translational research. This review synthesizes current evidence on RT-related molecular mechanisms and clinical findings to provide an integrative perspective on the potential role of resistance training in mitigating age-related cognitive decline. Full article

Metastasis is still the leading cause of cancer-related death. It happens when disseminated tumor cells (DTCs) successfully navigate a series of steps and adapt to the unique conditions of distant organs. In this review, key molecular and immune mechanisms that shape metastatic spread, long-term survival, and eventual outgrowth are examined, with a focus on how tumor-intrinsic programs interact with extracellular matrix (ECM) remodeling, angiogenesis, and immune regulation. Gene networks that sustain tumor-cell plasticity and invasion are described, including EMT-linked transcription factors such as SNAIL and TWIST, as well as broader transcriptional regulators like SP1. Also, how epigenetic mechanisms, such as EZH2 activity, DNA methylation, chromatin remodeling, and noncoding RNAs, lock in pro-metastatic states and support adaptation under therapeutic pressure. Finally, proteases and matrix-modifying enzymes that physically and biochemically reshape tissues, including MMPs, uPA, cathepsins, LOX/LOXL2, and heparinase, are discussed for their roles in releasing stored growth signals and building permissive niches that enable seeding and colonization. In parallel, immune-evasion strategies that protect circulating and newly seeded tumor cells are discussed, including platelet-mediated shielding, suppressive myeloid populations, checkpoint signaling, and stromal barriers that exclude effector lymphocytes. A major focus is metastatic dormancy, cellular, angiogenic, and immune-mediated, framed as a reversible survival state regulated by stress signaling, adhesion cues, metabolic rewiring, and niche constraints, and as a key determinant of late relapse. Tumor-specific metastatic programs across mesenchymal malignancies (osteosarcoma, chondrosarcoma, and liposarcoma) and selected high-burden cancers (melanoma, hepatocellular carcinoma, glioblastoma, and breast cancer) are highlighted, emphasizing shared principles and divergent organotropisms. Emerging therapeutic strategies that target both the “seed” and the “soil” are also discussed, including immunotherapy combinations, stromal/ECM normalization, chemokine-axis inhibition, epigenetic reprogramming, and liquid-biopsy-enabled minimal residual disease monitoring, to prevent reactivation and improve durable control of metastatic disease. Full article

Tibia morphology is a significant factor in poultry germplasm and market traits. Copy number variation (CNV) has been identified as a structural source of genetic variation for complex traits. We profiled genome-wide CNVs in Dong Tao chickens and nine other local breeds and performed a breed-based case–control CNV-GWAS (Dong Tao vs. reference breeds). We sequenced 152 chickens, including 46 Dong Tao, and annotated genes and pathways. A total of 22,972 CNVs were detected, of which 2193 were retained after filtration across 33 chromosomes, with sizes ranging from 2 kilobases to 12.8 megabases. Principal component analysis indicated an overall weakness in the breed structure and a sex-related trend within Dong Tao. A deletion on chromosome 3 at 36,529,501 to 36,539,000 was observed in Dong Tao. The exploratory screen identified 44 CNV regions at nominal significance (p < 0.05), distinguishing Dong Tao from other breeds. Thirty-seven regions contained 99 genes, including CHRM3 within the chromosome 3 deletion and CRADD overlapping two CNVs. Enrichment analysis indicated thiamine metabolism and growth hormone receptor signalling as the primary pathways of interest, with TPK1, SOCS2, and FHIT identified as potential candidates. These results provide a CNV landscape for Dong Tao and prioritize variant regions and pathways potentially relevant to its robust tibia morphology; however, no direct CNV–tibia phenotype regression was performed. Full article

Background: Lung adenocarcinoma in non-smoking women represents a distinct clinical entity that cannot be fully explained by traditional exposure-centered carcinogenic models. Although ambient air pollution is a recognized risk factor, sex-specific vulnerability suggests the involvement of additional biological modulators shaping inflammatory, immune, and proliferative responses. Main body: In this conceptual review, we integrate epidemiological, experimental, and mechanistic evidence to propose a multisystem framework of lung carcinogenesis in non-smoking women. We delineate a central carcinogenic spine encompassing lung epithelial injury, chronic inflammation, growth factor signaling activation—particularly epidermal growth factor receptor (EGFR) pathways—and tumor microenvironment remodeling. Within this framework, three interacting domains function as biological modulators that amplify carcinogenic processes: chemosensory–neural–immune modulation, hormonal–endocrine signaling including estrogen–EGFR crosstalk, and psychosocial stress–hypothalamic–pituitary–adrenal (HPA) axis dysregulation. These domains converge through feedback mechanisms that reinforce systemic dysregulation and tumor-promoting microenvironments. Implications: This integrative model provides a biologically grounded perspective on female-specific vulnerability to lung adenocarcinoma and informs precision prevention, risk stratification, and ESG-informed public health strategies beyond conventional exposure reduction. Full article

Maize (Zea mays L.) is a major economic crop highly susceptible to Colletotrichum graminicola, the causal agent of anthracnose leaf blight, which causes substantial annual yield losses. This fungal pathogen employs numerous effectors to manipulate plant immunity, yet the functions of many secreted proteins during biphasic infection remain poorly characterized. In this study, we identified CgMas2, a candidate secreted protein in C. graminicola and a homolog of Magnaporthe oryzae MoMas2. Deletion of CgMAS2 in the wild-type strain CgM2 did not affect fungal vegetative growth or conidial morphology but significantly impaired virulence on maize leaves. Leaf sheath infection assays revealed that CgMas2 is required for biotrophic invasive hyphal growth, as the mutant showed defective spreading of invasive hyphae to adjacent cells. Subcellular localization analysis indicated that CgMas2 localizes to the cytoplasm of conidia and to the primary infection hyphae. Furthermore, DAB staining demonstrated that disrupt of CgMAS2 leads to host reactive oxygen species (ROS) accumulation. Comparative transcriptome analysis of maize infected with ΔCgmas2 versus CgM2 revealed enrichment of GO terms related to peroxisome and defense response, along with up-regulation of benzoxazinoid biosynthesis genes (benzoxazinone biosynthesis 3, 4 and 5) at 60 h post-inoculation (hpi). Conversely, six ethylene-responsive transcription factors (ERF2, ERF3, ERF56, ERF112, ERF115 and ERF118) involved in ethylene signaling pathways were down-regulated at 96 hpi. These expression patterns were validated by RT-qPCR. Collectively, our results demonstrate that CgMas2 not only promotes invasive hyphal growth during the biotrophic stage but may also modulate phytohormone signaling and defense compound biosynthesis during the necrotrophic phase of infection. Full article

Redox (reduction–oxidation) processes underlie all forms of life and are a universal regulatory mechanism that maintains homeostasis and adapts the organism to changes in the internal and external environments. From capturing solar energy in photosynthesis and oxygen generation to fine-tuning cellular metabolism, redox reactions are key determinants of life activity. Proteins containing sulfur- and selenium-containing amino acid residues play a crucial role in redox regulation. Their reversible oxidation by physiological oxidants, such as hydrogen peroxide (H₂O₂), plays the role of molecular switches that control enzymatic activity, protein structure, and signaling cascades. This enables rapid and flexible cellular responses to a wide range of stimuli—from growth factors and nutrient signals to toxins and stressors. Mitochondria, the main energy organelles and also the major sources of reactive oxygen species (ROS), play a special role in redox balance. On the one hand, mitochondrial ROS function as signaling molecules, regulating cellular processes, including proliferation, apoptosis, and immune response, while, on the other hand, their excessive accumulation leads to oxidative stress, damage to biomolecules, and the development of pathological processes. So, mitochondria act not only as a “generator” of redox signals but also as a central link in maintaining cellular and systemic redox homeostasis. Redox signaling forms a multi-layered cybernetic system, which includes signal perception, activation of signaling pathways, the initiation of physiological responses, and feedback regulatory mechanisms. At the molecular level, this is manifested by changes in the activity of redox-regulated proteins of which the redox proteome consists, thereby affecting the epigenetic landscape and gene expression. Physiological processes at all levels of biological organization—from subcellular to systemic—are controlled by redox mechanisms. Studying these processes opens a way to understanding the universal principles of life activity and identifying the biochemical mechanisms whose disruption causes the occurrence and development of pathological reactions. It is important to emphasize that new approaches to redox balance modulation are now actively developed, ranging from antioxidant therapy and targeted intervention on mitochondria to pharmacological and nutraceutical regulation of signaling pathways. This article analyzes the pivotal role of redox balance and its regulation at various levels of living organisms—from molecular and cellular to tissue, organ, and organismal levels—with a special emphasis on the role of mitochondria and modern strategies for influencing redox homeostasis. Full article

Genome editing of late myogenic regulators provides a way to dissect the mechanisms through which transcriptional programs and growth-related signaling pathways shape muscle-gene-expression programs in farmed fish. This study disrupted myogenic regulatory factor 4 (MRF4) in Nile tilapia using CRISPR/Cas9 to examine downstream transcriptional changes in fast skeletal muscle across the trunk, belly, and head regions. Adult F0 crispants carried a frameshift mutation that truncated the basic helix–loop–helix domain and showed an approximate 80–85% reduction in MRF4 mRNA across the trunk, belly, and head muscles. The expression of 23 genes representing myogenic regulatory factors, MEF2 paralogs, structural and contractile components, nonmyotomal regulators, cell adhesion and fusion-related transcripts, and growth-related genes within the GH–IGF–MSTN axis was quantified and compared between wild-type and MRF4-crispants. Expressions of major structural genes remained unchanged despite MRF4 depletion, whereas MyoG and MyoD were upregulated together with MEF2B and MEF2D, indicating strong transcriptional compensation. Twist1, ID1, PLAU, CDH15, CHRNG, NCAM1, MYMK, GHR, and FGF6 were also significantly elevated, while IGF1 was reduced, and MSTN remained stable. Together, these results show that MRF4 loss is associated with coordinated transcriptional changes in regulatory and growth-related pathways, while major fast-muscle structural and contractile transcript levels remain stable, thereby highlighting candidate transcriptional targets for future studies that will evaluate links to muscle phenotype and growth performance in Nile tilapia. Full article

Hair loss disorders, particularly androgenetic alopecia (AGA), are common conditions that carry significant psychosocial impact. Current standard therapies, including minoxidil, finasteride, and hair transplantation, primarily slow progression or re-distribute existing follicles and do not regenerate lost follicular structures. In recent years, regenerative medicine has been associated with a gradual shift toward approaches that aim to restore follicular function and architecture. Stem cell-derived conditioned media and exosomes have shown the ability to activate Wnt/β-catenin signaling, enhance angiogenesis, modulate inflammation, and promote dermal papilla cell survival, resulting in improved hair density and shaft thickness with favorable safety profiles. Autologous cell-based therapies, including adipose-derived stem cells and dermal sheath cup cells, have demonstrated the potential to rescue miniaturized follicles, although durability and standardization remain challenges. Adjunctive interventions such as microneedling and platelet-rich plasma (PRP) further augment follicular regeneration by inducing controlled micro-injury and releasing growth and neurotrophic factors. In parallel, machine learning-based diagnostic tools and deep hair phenotyping offer improved severity scoring, treatment monitoring, and personalized therapeutic planning, while robotic Follicular Unit Excision (FUE) platforms enhance surgical precision and graft preservation. Advances in tissue engineering and 3D follicle organoid culture suggest progress toward producing transplantable follicle units, though large-scale clinical translation is still in early development. Collectively, these emerging biological and technological strategies indicate movement beyond symptomatic management toward more targeted, multimodal approaches. Future progress will depend on standardized protocols, regulatory clarity, and long-term clinical trials to define which regenerative approaches can reliably achieve sustainable follicle renewal in routine cosmetic dermatology practice. Full article

Nickel allergy remains the most prevalent cause of allergic contact dermatitis worldwide, imposing a substantial socio-epidemiological and economic burden. Beyond its classical cutaneous presentation, systemic nickel allergy syndrome highlights the systemic dimension of Nickel hypersensitivity, wherein dietary nickel intake may provoke both gastrointestinal and cutaneous symptoms through mechanisms involving gut barrier impairment and mucosal immune priming. Recent evidence highlights the contribution of angiogenesis and lymph-angiogenesis to Nickel-induced allergic contact dermatitis, through crosstalk among keratinocytes, mast cells, endothelial cells, and pro-angiogenic mediators such as vascular endothelial growth factor. Against this background, we propose to revisit palmitoylethanolamide, an endogenous ALIAmide with well-documented anti-inflammatory, anti-angiogenic, and anti-allergic properties. Already studied in pain and inflammatory disorders and employed in veterinary dermatology, palmitoylethanolamide down-modulates mast cell degranulation, suppresses VEGF expression via PPAR-α/Akt/mTOR signaling, and enhances intestinal barrier integrity, acting as a promising “gatekeeper” molecule that reduces gut hyperpermeability characterizing systemic nickel allergy as well as other gut disorders with systemic consequences. This paper is presented as a viewpoint intended to highlight the untapped therapeutic potential of palmitoylethanolamide, suitable for both oral and topical administration, as a candidate to address the multifactorial pathophysiology of Nickel allergic contact dermatitis and systemic nickel allergy. Our purpose is not to provide definitive answers, but to stimulate scientific debate on its rational use within emerging gut–skin therapeutic strategies. We thus encourage future experimental and clinical studies to explore its potential integration within emerging gut–skin therapeutic paradigms. Full article

Pulmonary arterial hypertension (PAH) is a severe, progressive vasculopathy characterized by endothelial dysfunction, medial hypertrophy, and maladaptive vascular and cardiac remodelling that ultimately leads to right-heart failure and premature death. Despite advances in vasodilator therapies targeting endothelin, nitric oxide, and prostacyclin pathways, a substantial proportion of patients fail to achieve or maintain a low-risk profile, highlighting the need for disease-modifying strategies. Dysregulation of transforming growth factor-β (TGF-β) superfamily signalling, with excessive activin and growth differentiation factor activity and impaired bone morphogenetic protein signalling, plays a central role in PAH pathobiology. Sotatercept, a first-in-class activin signalling inhibitor, restores this imbalance by selectively trapping pro-proliferative ligands, thereby addressing a key molecular driver of pulmonary vascular remodelling. Evidence from pivotal phase II and III trials—PULSAR, STELLAR, ZENITH, and HYPERION—demonstrates that sotatercept significantly improves exercise capacity, haemodynamics, and risk status when added to background therapy. This review summarises the molecular mechanisms underlying sotatercept’s therapeutic effects, synthesises the current clinical evidence, and discusses its emerging role as a disease-modifying agent capable of promoting reverse pulmonary vascular remodelling within contemporary PAH management. Full article

Invasive alien species pose a major threat to global biodiversity, especially within Europe. Understanding their spatial and temporal dynamics is essential for effective management planning and implementation. The ring-necked parakeet (Psittacula krameri, hereafter RNP) has been established in Greece for over four decades, yet its invasion dynamics remain unstudied despite pilling evidence of ecological impacts. During 2024 and 2025, we conducted repeated transect surveys across 99 1 km² grid squares within the urban complex of Thessaloniki to assess environmental factors influencing occupancy and abundance, and to estimate RNP population trends. Dynamic occupancy and N-mixture models revealed that both the presence and abundance of RNP were positively associated with the proportion of dense urban fabric and urban green areas. The proportion of occupied sites increased by more than 10% between survey years (2024–2025), while the estimated population growth rate for this interval was 1.64, signaling a substantial short-term increase. Our findings provide the first detailed evidence of an established and growing RNP population within the urban complex of Thessaloniki, Greece. Continued monitoring and research on ecological impacts are essential, while any management actions should be developed with public engagement to ensure social acceptance and long-term effectiveness. Full article

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage “vicious cycle” of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of underappreciated cellular players in this metastatic takeover: megakaryocytes, erythroid lineage cells, and perivascular stromal subsets. Far from being passive bystanders, these cells actively shape the metastatic niche. For instance, megakaryocytes and platelets go beyond their role in transport; they orchestrate immune evasion and dormancy through mechanisms such as transforming growth factor-β1 (TGF-β1) signaling and the physical shielding of tumor cells. In parallel, we uncover a distinct “erythroid-immune” axis: here, stress-induced CD71⁺ erythroid progenitors suppress T-cell responses via arginase-mediated nutrient depletion and checkpoint engagement, forming a potent metabolic barrier against immune attack. Furthermore, leptin receptor–positive (LepR⁺) perivascular stromal cells emerge as key structural players. These stromal subsets not only act as anchoring points for DTCs but also maintain them in protective vascular zones via CXCL12 chemokine gradients. Altogether, these findings reveal that the metastatic bone marrow niche is not static; it is a highly dynamic, multi-lineage ecosystem. By mapping these intricate cellular interactions, we argue for a paradigm shift: targeting these early and cooperative crosstalk, whether through glycoprotein-A repetitions predominant (GARP) blockade, metabolic reprogramming, or other niche-disruptive strategies, could unlock new therapeutic avenues and prevent metastatic relapse at its root. Full article

The Transforming Growth Factor-β (TGF-β) superfamily comprises highly conserved cytokines that orchestrate key cellular functions, including proliferation, differentiation, and apoptosis. Within the ovary, TGF-β family members serve as pivotal regulators of folliculogenesis, exerting stage-specific actions from embryonic germ cell development to advanced follicular maturation. During fetal development, activins and SMAD-dependent signaling pathways are essential for primordial germ cell proliferation, survival, and the breakdown of germ cell cysts, enabling the establishment of the primordial follicle pool. Throughout folliculogenesis, TGF-β supports follicle activation, promotes the transition from dormant to growing follicles, stimulates granulosa cell proliferation, sustains follicular viability, and modulates steroidogenesis through theca cell regulation. Notably, anti-müllerian hormone, a TGF-β family member, plays a central role in inhibiting premature follicle recruitment and serves as a key biomarker of ovarian reserve. Dysregulation of TGF-β signaling contributes to various ovarian disorders, including polycystic ovary syndrome and premature ovarian insufficiency. A deeper understanding of these complex signaling networks is critical for identifying novel therapeutic targets and advancing clinical interventions in female reproductive pathologies. This review provides an integrated overview of the roles of the TGF-β superfamily in ovarian physiology and its contributions to disease development. Full article

Background: Diabetic nephropathy (DN) is largely driven by transforming growth factor-β1 (TGF-β1)-mediated fibrosis. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) ribonucleoprotein (RNP) complexes offer precise gene disruption, yet effective non-viral delivery remains a challenge. This study developed cationic lipid-based hybrid nanostructured lipid carriers (NLCs) for intracellular delivery of TGFB1-targeting RNP as an early-stage platform for DN gene modulation. Methods: A single-guide RNA (sgRNA) targeting human TGFB1 was assembled with Cas9 protein (1:1 and 1:2 molar ratios). Hybrid NLCs comprising squalene, glyceryl trimyristate, and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were formulated via optimized emulsification–sonication to achieve sub-100 nm particles. Physicochemical properties, including polydispersity index (PDI), were assessed via dynamic light scattering (DLS), while silencing efficacy in HEK293T cells was quantified using quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: Optimized NLCs achieved hydrodynamic diameters of 65–99 nm (PDI < 0.5) with successful RNP complexation. The 1:2 Cas9:sgRNA formulation produced the strongest gene-editing response, reducing TGFB1 mRNA by 67% (p < 0.01) compared with 39% for the 1:1 ratio. This translated to a significant reduction in TGF-β1 protein (p < 0.05) within 24 h. Conclusions: DOTAP-based hybrid NLCs enable efficient delivery of CRISPR–Cas9 RNP and achieve significant suppression of TGFB1 expression at both transcriptional and protein levels. These findings establish a promising non-viral platform for upstream modulation of profibrotic signaling in DN and support further evaluation in kidney-derived cells and in vivo renal models. Full article