Search Results (11,538)

Dickkopf-1 (DKK1) is a secreted glycoprotein that traditionally acts as an antagonist of canonical Wnt/β-catenin signaling. Although it functions as a tumor suppressor in some specific biological background and disease stages, growing evidence links DKK1 to tumor progression, immune evasion, and therapy resistance in a variety of multiple malignancies. This review provides a comprehensive bench-to-bedside overview of DKK1 in cancer. We first delineate how DKK1 regulates both Wnt-dependent and Wnt-independent pathways. From a clinical perspective, we evaluate the application potential of DKK1 as a diagnostic and prognostic biomarker. We further discuss the progress of DKK1-targeted interventions, ranging from monoclonal antibodies in clinical trials to next-generation therapeutic modalities. Finally, we discuss the challenges in clinical translation and suggest future directions for DKK1-based precision medicine. In summary, by integrating preclinical insights with current clinical data, this review provides a strategic roadmap for advancing DKK1-targeted therapies in cancer. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathogenesis involving epidermal barrier dysfunction, microbiome dysbiosis, and immune dysregulation. Despite significant advances in therapy, including biologics and targeted treatments, their use may be limited by adverse effects, highlighting the need for safe adjunctive strategies. Polyphenols are naturally occurring bioactive compounds that are abundant in plant-based foods and are known for their anti-inflammatory, antioxidant, and immunomodulatory properties, making them promising candidates for supportive AD management. This review integrates current evidence on the effects of polyphenols on epidermal barrier lipids, microbiome interactions, and key inflammatory pathways, including NF-κB and JAK/STAT signaling. Additionally, the role of polyphenols in modulating dendritic cell and neutrophil activity, and reducing reactive oxygen species (ROS) production and neutrophil extracellular trap (NET) formation, as well as their potential involvement in mitophagy regulation, is discussed. Polyphenols support epidermal barrier integrity by modulating the expression of key structural proteins, including filaggrin, involucrin, and loricrin, leading to a reduction in transepidermal water loss (TEWL). Furthermore, they interact bidirectionally with the gut microbiome, acting as metabolic substrates for beneficial bacteria and promoting the growth of short-chain fatty acid (SCFA)-producing species such as Lactobacillus, Bifidobacterium, and Akkermansia, while simultaneously inhibiting pathogenic strains. These findings highlight the role of polyphenols in maintaining microbiome homeostasis and supporting epidermal barrier integrity. The review encompasses findings from clinical studies, animal models, and mechanistic investigations, while also addressing limitations related to polyphenol bioavailability. Overall, polyphenols may represent a valuable adjunctive approach in AD management; however, further well-designed clinical and mechanistic studies are required to confirm their therapeutic potential. Full article

Adult neural stem cells (NSCs) maintain lifelong neurogenesis, a fundamental process for neuroplasticity, memory and brain homeostasis. Despite decades of research, translating basic NSC biology into effective clinical therapies remains a central challenge. Here we present a narrative review that provides a comprehensive update on the current landscape of adult NSC research, associating molecular mechanisms with the emerging translational technologies. First, we analyze the biological features and neurogenic sequences within canonical niches such as the subventricular lateral zone and the subgranular zone, emphasizing phylogenetic and migratory differences between rodent models and humans. Second, we integrate these mechanisms with the influence of environmental and pathological modulators, describing how aging, metabolic changes, chronic stress and neuroinflammation disrupt NSC quiescence and lineage progression. Finally, we highlight recent technological advances driving the field toward clinical applications. By examining current NSC isolation strategies, induced pluripotent stem cell modeling, direct somatic reprogramming and the use of CRISPR-Cas9-based gene-editing therapies, this review delineates the pathways to overcome existing methodological limitations. Ultimately, we provide an integrated context that connects the modulation of the neurogenic niches with advanced in vitro technologies, offering new perspectives for regenerative medicine and the treatment of neurological disorders. Full article

Chondrosarcoma (CHS), the second most common primary malignant cartilage tumor, is largely resistant to conventional therapies, making surgical resection the standard treatment. Proton therapy offers a physical advantage through the Bragg peak, enabling targeted irradiation while sparing surrounding tissues. However, differential biological responses between malignant and normal cartilage cells remain poorly understood. In this study, CHS SW1353 cells and normal chondrocytes (MC615) were exposed to proton irradiation. Biological responses were assessed via clonogenic survival, cell viability, apoptosis (caspase 3/7), micronucleus formation, cell cycle profiling, and oxidative stress markers. Proteomic changes were analyzed using mass spectrometry and bioinformatics. CHS cells exhibited higher radioresistance (D₁₀ = 6.45 Gy) than normal chondrocytes (D₁₀ = 5.08 Gy), oxidative stress adaptation, G1 arrest and proteomic plasticity, whereas normal chondrocytes displayed increased oxidative stress, extracellular matrix fragility and impaired integrin signaling. Notably, the tumor-specific increased levels of Tyrosine-protein kinase Fyn and Yes1-associated transcriptional regulator (YAP1) signaling suggest molecular drivers of radioresistance. Overall, proton irradiation elicits distinct biological and proteomic responses in malignant versus normal cartilage cells. These findings highlight potential radiosensitization targets, including Fyn/Src and YAP1/Hippo pathways, while underscoring the need to optimize proton therapy to enhance tumor control while minimizing damage to healthy cartilage. Full article

Acute coronary syndromes (ACS) remain time-critical clinical emergencies in which early diagnosis and accurate risk stratification determine management and outcomes. Although symptoms, electrocardiography, and high-sensitivity cardiac troponin (hs-cTn) provide a reliable framework for detecting myocardial injury, they offer limited insight into plaque instability, thromboinflammatory activity, vascular repair, and post-infarction remodeling. In this narrative review, we examine the biological rationale and current clinical evidence supporting brain-derived neurotrophic factor (BDNF) as a candidate biomarker in ACS, with particular attention to pre-analytical, analytical, and phenotypic sources of heterogeneity. Available studies show that circulating BDNF concentrations vary substantially according to biological matrix, timing of sampling, ACS subtype, and assay methodology, which likely contributes to inconsistent findings across cohorts. Overall, current evidence does not support BDNF as a diagnostic alternative to hs-cTn in rule-in or rule-out pathways. However, BDNF may have value in biological phenotyping and risk stratification by reflecting platelet activation, endothelial dysfunction, inflammatory signaling, and remodeling processes after ACS. Further progress will require standardized pre-analytical procedures, separate assessment of mature BDNF and proBDNF, serial sampling, and validation in large multicenter studies. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent mucosal inflammation and dysregulated immune–metabolic responses. Koumiss, a traditional fermented mare’s milk, has long been used in ethnomedicine for gastrointestinal disorders; however, its molecular mechanisms in UC remain unclear. In this study, an integrated multi-omics approach combining network pharmacology, quantitative proteomics, and molecular docking was employed to elucidate the therapeutic mechanism of koumiss powder (KP) in a dextran sulfate sodium (DSS)-induced murine colitis model. Network pharmacology identified twelve bioactive compounds targeting fourteen UC-associated proteins, predominantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In vivo experiments demonstrated that high-dose KP significantly alleviated disease activity, improved colon shortening and histopathological injury, reduced serum TNF-α and IL-6 levels, and restored anti-inflammatory cytokines IL-4 and IL-10. Proteomic analysis further revealed activation of the PPAR signaling pathway, with significant upregulation of Plin4 and Sorbs1. Immunofluorescence staining further confirmed that KP restored the expression of PPARA and increased the levels of Plin4 and Sorbs1 in colonic tissues. Molecular docking confirmed strong binding affinities between key koumiss-derived lipid metabolites, including 13(S)-HOTrE and stearoyl ethanolamide, and PPAR-related target proteins. Collectively, these findings demonstrate that koumiss exerts protective effects against experimental UC primarily through activation of PPAR-mediated lipid metabolic and anti-inflammatory pathways. This study provides mechanistic insight into the biological activity of koumiss and highlights the value of multi-omics integration in natural product research. Full article

As natural nanoscale intercellular messengers, exosomes exhibit considerable potential in modulating inflammation, angiogenesis, immunoregulation, and tissue remodeling, making them attractive candidates for regenerative medicine. However, their clinical translation remains limited by rapid systemic clearance, nonspecific biodistribution, insufficient lesion retention, and functional attenuation in hostile pathological microenvironments. In this review, we propose that biomaterial engineering should evolve from providing passive exosome carriers to constructing active regulatory platforms capable of precise spatiotemporal control. We summarize engineering strategies along two complementary dimensions. In the temporal dimension, biomaterials can enable sustained, sequential, or microenvironment-responsive release to match the dynamic phases of tissue repair. In the spatial dimension, biomaterials can improve local retention, tissue anchoring, structural guidance, endogenous cell recruitment, and lesion-specific delivery. Using cutaneous wound healing, osteochondral regeneration, myocardial repair, and neural regeneration as representative examples, we further analyze these strategies through a “clinical challenge–engineering strategy–biological mechanism” framework, with particular attention to how engineered systems influence key signaling pathways such as PI3K/Akt, Wnt/β-catenin, NF-κB, and PTEN/PI3K/Akt/mTOR. We also discuss translational barriers, including exosome heterogeneity, safety concerns inherited from parental cells, large-scale GMP-compliant manufacturing, product standardization, storage stability, and regulatory classification of exosome–biomaterial hybrids. Finally, we highlight emerging directions, including multi-mechanism combinational systems, closed-loop responsive platforms, and artificial intelligence-assisted design for personalized exosome therapeutics. This review provides a design-oriented framework to accelerate the bench-to-bedside development of biomaterial-enabled precision exosome therapy. Full article

Chronic pain, a complex multidimensional disorder, remains a major healthcare issue and a therapeutic challenge. Neuropathic pain is a chronic pain condition that results from damage or dysfunction in the nervous system. While mechanisms of neuropathic pain at the peripheral and spinal cord level have been extensively studied, pain mechanisms in the brain remain underexplored. The amygdala, a limbic brain region, has emerged as a critical brain area for the emotional–affective dimension of pain and pain modulation. Amygdala neuroplasticity has been associated with pain states, but the exact molecular and cellular mechanisms underlying these states and the transition from acute to chronic pain are not well understood. Here, we used the spinal nerve ligation (SNL) model of neuropathic pain in male rats to investigate changes in gene expression in the amygdala at the chronic pain stage using RNA sequencing (RNA-Seq). Two amygdala nuclei, the basolateral (BLA) and central (CeA), were investigated in a hemisphere-dependent manner. We used an integrative approach that focuses on functional significance and cell-type specificity of differentially expressed genes (DEGs) to nominate mechanistic targets for central regulation of chronic pain. Our integrative transcriptomic and bioinformatic analyses identified individual genes (e.g., Cxcl10, Cxcl12, Mbp, Plp1, Mag, Mog, Slc17a6, Gad1, and Sst), molecular pathways (e.g., cytokine-mediated signaling pathway), biological processes (e.g., myelination, synaptic transmission), and specific cell types (e.g., oligodendrocytes, glutamatergic, and GABAergic neurons) affected by chronic pain. Our results also provide some evidence for the emerging concept of hemispheric lateralization of pain processing in the amygdala. Overall, our study proposes oligodendrocyte dysfunction in the amygdala, neuroimmune signaling in the CeA, and glutamatergic neurotransmission in the BLA as key processes and potential therapeutic targets for the management of chronic neuropathic pain. Full article

Some actinobacterial species have been reported to improve plant growth due to their roles as biostimulants and biological control agents. In this study, the effect of actinobacterial isolate 27, obtained from the rhizospheric soil of melon plants and identified as Streptomyces calvus, was evaluated on the growth of Arabidopsis thaliana and tomato plants. In Arabidopsis, in vitro assays showed that after seven days of interaction, isolate 27 increased fresh weight by 1.4-, 1.5-, and 2.3-fold and lateral root number by 1.7-, 1.3-, and 2.5-fold under physical contact and split-plate systems (MS and ISP2 media), respectively, compared with non-inoculated plants. An increased β-glucuronidase (GUS, encoded by the uidA gene) signal was observed in primary and lateral roots of the Arabidopsis DR5::uidA reporter line during both interaction types, suggesting the activation of auxin-responsive pathways. In addition, isolate 27 rescued the rhd6 (root hair defective 6) mutant phenotype, restoring root hair formation. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that isolate 27 emitted volatile organic compounds (VOCs), including an alcohol and several sesquiterpenes, and that this profile changed during interaction with Arabidopsis plantlets. In soil-based pot assays, inoculation with isolate 27 significantly enhanced the development of Arabidopsis plants after 23 days, both when applied alone and in co-inoculation with Trichoderma atroviride. Furthermore, isolate 27 stimulated tomato plant growth, leading to significant increases in fresh and dry biomass, as well as shoot and root lengths after 28 days. Overall, these results demonstrate that S. calvus isolate 27 promotes plant growth and development through the production of bioactive compounds that modulate plant growth pathways, including hormonal responses, highlighting its potential as a bioinoculant for sustainable and productive agricultural systems. Full article

Background: Targeted therapies directed against oncogenic drivers have substantially improved outcomes for patients with epidermal growth factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Despite high initial response rates, most patients ultimately develop acquired resistance to tyrosine kinase inhibitors (TKIs), reflecting complex biological adaptations under therapeutic pressure. Methods: This narrative review synthesizes experimental, translational, and clinical studies examining how environmental and occupational respiratory exposures may influence resistance mechanisms in EGFR- and ALK-driven NSCLC. The review emphasizes exposure-associated signaling plasticity, inflammatory microenvironmental modulation, metabolic reprogramming, and pharmacokinetic alterations. Results: Recent evidence suggests that respiratory exposures, including cigarette smoke, air pollution, diesel exhaust, and occupational inhalational toxicants, can modulate oncogenic signaling networks relevant to resistance to targeted therapies. These mechanisms include aberrant EGFR activation, bypass signaling through the mesenchymal–epithelial transition receptor (MET) and SRC pathways, epithelial–mesenchymal transition (EMT), adaptive kinome remodeling, and exposure-associated inflammatory signaling, all of which may influence tumor evolution and therapeutic response. Conclusions: This review introduces a novel exposome-driven conceptual framework integrating environmental exposures with signaling plasticity and resistance evolution in oncogene-driven NSCLC. These findings support the concept that the respiratory exposome may represent an underrecognized modifier of targeted therapy response. Incorporating structured exposure assessment into precision oncology approaches may refine risk stratification and inform exposure-aware therapeutic strategies. Full article

Coronary artery disease (CAD), including acute coronary syndromes, frequently co-occurs with depression and is associated with adverse outcomes. Trace elements may influence shared biological pathways, including oxidative stress, inflammation, and neurovascular signaling. This study evaluated the association between trace element status and depressive symptoms in CAD. A systematic review was conducted in accordance with PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251231129). PubMed, Scopus, and the Cochrane Library were searched from inception to 2 December 2025. Studies assessing trace element concentrations in adults with CAD and depressive symptoms were eligible. Due to limited direct evidence, partially aligned and indirect studies were also included. Data were synthesized narratively. Of 699 records, four studies were included. No studies fulfilled Tier 1 criteria. The available evidence consisted of partially aligned (Tier 2) and indirect (Tier 3) studies. Lower zinc and magnesium levels and higher copper concentrations were suggested to be associated, based exclusively on Tier 2–3, low-certainty, predominantly indirect evidence. Interventional studies reported modest improvements following zinc or combined magnesium and zinc supplementation, although not in CAD-specific populations. Evidence directly addressing trace elements and depression in CAD is extremely limited and largely indirect. Current data do not support causal inference or clinical recommendations. Findings should be considered exploratory and hypothesis-generating. Full article

Delayed cerebral ischemia (DCI) is a major complication of aneurysmal subarachnoid hemorrhage (aSAH), strongly associated with neurological deterioration and poor outcomes. Its pathophysiology remains incompletely understood and involves multiple interacting processes. Increasing evidence highlights the role of redox imbalance triggered by hemoglobin breakdown and the subsequent generation of reactive species, leading to vascular dysfunction, impaired nitric oxide signaling, and inflammatory activation This review aims to summarize current knowledge on redox-related mechanisms involved in DCI and to explore the potential role of the peroxiredoxin (PRDX) family in this setting. A narrative review of experimental and preclinical studies was performed, focusing on molecular pathways associated with vascular regulation, cellular injury, and antioxidant defense. Particular attention was given to the distribution and biological functions of PRDX isoforms within the central nervous system. This work addresses a topic not previously systematically discussed, the potential involvement of PRDX proteins in aSAH-related complications. By integrating available data, it provides a conceptual framework linking PRDX to mechanisms relevant for DCI. The manuscript serves as a starting point for future research, particularly translational and clinical studies in humans, which are necessary to verify the relevance of these findings and to better understand their potential clinical implications. Full article

This study concurrently addressed the separation method for carbon dots derived from Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (GRRPM) and the in vitro evaluation of their anti-allergic biological activity. Glycyrrhizae Radix et Rhizoma Praeparata cum Melle Carbon Dots (GRRPM-CDs) were prepared via decoction followed by dialysis, and their properties were characterized using High-Performance Liquid Chromatography (HPLC) and nanomaterial techniques. Anti-allergic activity was evaluated using a C48/80-induced RBL-2H3 mast cell degranulation model. Safety and efficacy were assessed using the CCK-8 assay, direct intervention, and drug-containing serum methods. The release of β-hexosaminidase (β-hex), histamine (HIS), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) was measured by ELISA, and key proteins in the MAPK signaling pathway were analyzed by Western blot. GRRPM-CDs inhibited mast cell degranulation and the release of allergic and inflammatory mediators in a dose-dependent manner. They also significantly downregulated the phosphorylation levels of the JNK, ERK, and p38 proteins in the MAPK signaling pathway. GRRPM-CDs exhibit significant anti-allergic activity, likely via suppression of the MAPK pathway. These findings provide new insights into the bioactive components of processed Glycyrrhiza and suggest potential avenues for developing novel therapies for allergic diseases. Full article

Obesity is characterized by low-grade systemic inflammation and alterations in gut-related immune pathways that may contribute to metabolic dysfunction. Composite biomarker indices may better capture these complex processes than individual markers, although their performance may differ across biological domains. In this cross-sectional study, 88 adults without diabetes or infection were categorized as BMI < 25 kg/m² (n = 20), BMI 25–29.9 kg/m² (n = 34), or BMI ≥ 30 kg/m² (n = 34). Circulating biomarkers reflecting systemic inflammation (high-sensitivity C-reactive protein, ferritin, interleukin-6, presepsin) and intestinal barrier-related activity (β-defensin-2, regenerating islet-derived protein 3 alpha) were measured and subsequently combined into two composite indices: the Inflammatory Load Index, derived from inflammatory markers, and the Barrier Activation Index, derived from barrier-related markers. Group differences were assessed using analysis of variance with post hoc testing. Additional analyses included effect size estimation, receiver operating characteristic (ROC) analysis, and logistic regression. Individual biomarkers showed limited differences across BMI categories. The Inflammatory Load Index differed significantly across BMI categories (p = 0.040), with higher values observed in individuals with BMI ≥ 30 kg/m² compared with those with BMI 25–29.9 kg/m² (p = 0.032; Cohen’s d = 0.80), while the Barrier Activation Index did not differ (p = 0.257). In ROC analysis, the Inflammatory Load Index discriminated BMI ≥ 30 kg/m² with an area under the curve of 0.720 (95% confidence interval 0.576–0.851), yielding 77.8% sensitivity and 67.7% specificity. Each one standard deviation increase in the index was associated with higher odds of obesity (odds ratio 2.34, 95% confidence interval 1.22–4.49; p = 0.011). In conclusion, a composite inflammatory biomarker index, but not a barrier-related index, differentiates degrees of BMI in individuals without diabetes. These findings support integrated biomarker approaches for reflecting obesity-related biological burden beyond single markers. However, these observations are based on cross-sectional data and do not imply causality. Full article

The skin–brain axis constitutes a complex, bidirectional network integrating cutaneous sensory, immune, and neuroendocrine systems with central neural circuits involved in emotion regulation, stress responsivity, and social cognition. Advances in psychodermatology and cosmetic science have progressively extended this framework to the emerging field of neurocosmetics, which explores how topical formulations, sensorial properties, and cutaneous neuromodulators may influence psychological well-being, affective states, and perceived stress. The aim of this narrative review is to synthesize current evidence on the biological foundations of the skin–brain axis and to critically examine the implications of these mechanisms for neurocosmetic interventions from a psychological and psychiatric perspective. It describes the biological substrates underlying skin–brain communication, including the cutaneous hypothalamic–pituitary–adrenal axis, neuropeptides, neurotrophins, transient receptor potential channels, and endocannabinoid signaling, and examines how these pathways are targeted by neurocosmetic interventions. Particular attention is devoted to neuroactive compounds, such as peptides, cannabinoids, botanicals, and aromatherapeutic molecules, as well as to sensorial strategies involving texture, temperature, and olfactory cues, which may modulate mood, anxiety, and self-perception through peripheral mechanisms. From a psychological and psychiatric perspective, the review discusses the intersection between stress-related skin conditions, body image disturbances, and emotional dysregulation, highlighting how cosmetic practices may influence subjective well-being beyond purely aesthetic outcomes. Methodological limitations of the existing literature, including the heterogeneity of study designs and outcome measures, as well as ethical considerations related to mood- and stress-related claims in cosmetic products, are critically examined. Finally, future research directions are outlined, and a translational framework is proposed to integrate dermatology, neuroscience, and mental health within next-generation cosmetic science. Full article