Search Results (6,944)

Introduction/Objective: Common hop (Humulus lupulus L.) is a multi-component plant material that has been extensively studied for its antioxidant, anti-inflammatory, cardioprotective, metabolic, neuroprotective, immunomodulatory and anti-cancer properties. This review summarises current data on the molecular mechanisms of action of hop compounds, their therapeutic potential, metabolic interactions and biological significance, with particular emphasis on bioavailability, signalling pathways and organ-specific effects. Methods: A comprehensive literature review was conducted, covering in vitro and in vivo studies and available clinical trials analysing the biochemical activity, molecular targets and physiological effects of bioactive compounds in hops. Particular attention was paid to the regulation of oxidative stress, inflammatory signalling, mitochondrial function, metabolic pathways, interactions with the gut microbiota and their impact on the development of chronic diseases. Results: Bioactive compounds in hops modulate numerous key signalling pathways, including NF-κB, Nrf2, AMPK, MAPK, PPAR and PI3K/AKT/mTOR. They have been shown to reduce oxidative stress, inhibit the production of pro-inflammatory cytokines, regulate apoptosis, improve mitochondrial function, and activate endogenous antioxidant systems. Hops have a protective effect in cardiovascular diseases, metabolic disorders, neurodegenerative diseases and selected cancers through anti-inflammatory, anti-proliferative and metabolic mechanisms. In addition, hop compounds modulate the composition and activity of the gut microbiota, which promotes improved metabolic homeostasis. Despite relatively good intestinal absorption, systemic bioavailability remains limited; however, modern delivery systems significantly increase the stability and plasma concentrations of these compounds. Conclusions: Common hops have broad therapeutic potential due to their ability to regulate oxidative, inflammatory, metabolic and apoptotic processes at multiple levels. Their pleiotropic activity makes them a promising candidate for the prevention and treatment of chronic diseases. The development of delivery systems and consideration of the role of the gut microbiota may further increase its clinical application. Full article

Background: Urticaria, particularly chronic urticaria (CU), is a highly prevalent inflammatory skin disorder characterized by recurrent wheals and/or angioedema with a fluctuating and unpredictable course that significantly impairs quality of life and requires long-term monitoring. Despite established therapeutic guidelines, disease control remains suboptimal in a considerable proportion of patients. Telemedicine has emerged as a promising adjunctive strategy for chronic disease management. This review aims to critically evaluate the role, applications, benefits, and limitations of telemedicine and digital health interventions in urticaria management. Methods: A scoping review of the literature was conducted focusing on studies addressing telemedicine, digital patient-reported outcomes, mobile health applications, and remote monitoring strategies in urticaria. Evidence from pandemic and post-pandemic telemedicine models was also analyzed to identify transferable approaches. Results: Telemedicine demonstrates significant potential in urticaria management by enabling structured symptom monitoring, facilitating remote follow-up during therapeutic escalation (including biologic therapies), improving patient empowerment and adherence, and reducing healthcare utilization and indirect costs. Digital tools such as electronic diaries and validated PRO-based applications support continuous disease assessment. However, telemedicine cannot replace direct clinical examination, and limitations include diagnostic uncertainty, digital inequalities, data privacy concerns, and lack of large disease specific trials. Conclusions: Telemedicine represents a valuable complementary and integrative model for urticaria care, particularly suited for chronic disease monitoring. Hybrid care pathways combining remote and in-person management appear to be the most effective and sustainable strategy. Further high-quality urticaria-specific studies and standardized digital frameworks are required to optimize its clinical implementation. Full article

We investigated the synthesis and characterization of biodegradable films composed of poly (lactic acid) (PLA) and poly(butylene adipate-co-terephthalate) (PBAT), with lignin as a natural additive and dicumyl peroxide (DCP) as a compatibilizer. The PLA/PBAT ratio of 70:30 was optimized and the DCP was incorporated at different concentrations to enhance interfacial adhesion. The effects of lignin addition (0.005–0.02%) on the mechanical, thermal, and biodegradation properties were evaluated using SEM, FTIR, XRD, and TGA analyses. The optimal formulation had improved tensile strength, elongation at break, and thermal stability, with the highest degradation rate of 44.22% after 90 days of soil burial. Life cycle assessment using SimaPro software (SimaPro 9.1.1.1) and ReCiPe 2016 Midpoint indicated that the film containing 0.005% lignin had the lowest environmental impact. The primary environmental concerns were marine and freshwater ecotoxicity, associated with solvent use. Based on the results, incorporating small amounts of lignin enhanced the biodegradability and reduced the environmental footprint of the PLA/PBAT films, highlighting their potential for sustainable packaging applications. Full article

Background/Objectives: Pancreatic cancer-associated cachexia (CAC) is a complex, multifactorial and multi-organ metabolic syndrome affecting approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC). Recent epidemiological data show that cachexia is a primary cause of mortality in PDAC, directly accounting for approximately 30% of cancer-related deaths and significantly limiting the tolerability of cancer therapy and is associated with adverse effects of treatment. It is defined by systemic weight loss, skeletal muscle atrophy (sarcopenia), and adipose tissue depletion, often driven by systemic inflammation and metabolic dysregulation. Methods: The literature was searched in PubMed and Scopus using combinations of keywords. The search covers the literature between 2016 and 2026, but papers before this period were also included because of their historical importance. Studies with higher evidential value, such as prospective studies, randomized controlled trials, and meta-analyses, were prioritized and emphasized in our analysis. Results: CAC in PC arises from a systemic inflammatory response driven by tumor–host interactions and the release of pro-inflammatory mediators, such as growth differentiation factor 15 (GDF-15) and parathyroid hormone-related protein (PTHrP), which promotes anorexia and weight loss. The most commonly used diagnostic criteria include unintentional weight loss of more than 5% of body mass within 6 months, a body mass index (BMI) below 20 kg/m², or weight loss greater than 2% in the presence of sarcopenia. Emerging evidence supports the use of AI-based body composition analysis and novel biomarkers, including GDF-15 levels, to improve the detection and monitoring of cachexia. This review highlights that, despite the absence of pharmacological agents specifically approved for CAC in the United States and Europe, current guidelines recommend multimodal supportive care, including low-dose olanzapine, nutritional support, and exercise-based interventions. Furthermore, we identify recent phase 2 trials targeting the GDF-15 pathway, such as the GDF-15 inhibitor ponsegromab, which have demonstrated significant improvements in body weight and physical activity, suggesting a potential breakthrough in targeted therapies for CAC. Conclusions: CAC in PDAC represents a critical unmet medical need in oncology. It manifests as a lethal systemic pathology that demands early identification and targeted personalized pharmacological and nutritional interventions. Early diagnosis and targeted intervention represent promising strategies for improving survival and quality of life in this high-risk patient population. Full article

Loss of epithelial polarity is a critical driver of tumor progression; however, how core polarity regulators interface with oncogenic signaling pathways in hepatocellular carcinoma (HCC) remains incompletely defined. LLGL scribble cell polarity complex component 1 (LLGL1) is an evolutionarily conserved polarity protein with well-established tumor-suppressive roles in multiple epithelial malignancies. Nevertheless, how LLGL1 loss shapes oncogenic signaling outputs and cellular phenotypes in HCC remains unclear. In this study, we investigated the consequences of LLGL1 knockout (KO) in epithelial-like Huh-7 HCC cells. LLGL1 loss resulted in enhanced proliferative capacity and increased clonogenic potential, accompanied by altered cell-cycle distribution characterized by reduced G1-phase and increased S-phase fractions (p < 0.001). At the signaling level, LLGL1 KO cells displayed potentiated EGFR-driven RAS/MAPK pathway activation, with increased EGFR phosphorylation, enhanced downstream RAF1–MEK–ERK–RSK signaling, elevated EGFR abundance, and selective modulation of RAF1 protein levels. Functionally, LLGL1 loss markedly enhanced migratory and invasive behavior (p < 0.0001). Despite increased motility, LLGL1 KO cells exhibited remodeling of epithelial–mesenchymal transition (EMT)-associated markers without evidence of a classical EMT program. Collectively, these findings position LLGL1 loss as a central factor associated with altered MAPK signaling, EMT marker remodeling, and tumor-promoting cellular phenotypes in HCC. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide and is characterized by high aggressiveness and therapeutic resistance, partly driven by mitotic dysregulation. Key mitotic regulators, including kinases such as PLK1, AURKA, AURKB, and MPS1 and kinesins such as CENPE and Eg5, are frequently overexpressed in NSCLC and SCLC, contributing to chromosomal instability, aneuploidy, and highly proliferative tumor phenotypes. Although multiple inhibitors targeting these proteins have been developed, their clinical efficacy as monotherapies has been limited. This is largely due to insufficient target dependency, adaptive resistance mechanisms, mitotic slippage, activation of compensatory pathways, and dose-limiting toxicity. This review integrates current knowledge on the physiological roles of major mitotic regulators, their dysregulation in lung tumorigenesis, and the biological and pharmacological barriers that underlie the limited success of antimitotic drugs. We further highlight preclinical and clinical evidence supporting rational combination strategies designed to enhance the antitumor activity of mitotic inhibitors while minimizing toxicity. Together, these insights underscore the need for refined therapeutic approaches that better exploit vulnerabilities in mitotic control to improve outcomes for patients with lung cancer. Full article

Background/Objectives: Wound healing is a complex biological process involving inflammatory, proliferative, and remodeling phases. Plant-derived essential oils are increasingly investigated as topical therapeutic agents, although their biological effects are strongly influenced by composition and formulation. The present study evaluated the effects of topical Mentha spicata essential oil on cutaneous wound healing in a rat excisional wound model and explored potential molecular mechanisms using a network-based bioinformatic approach. Methods: Twenty-one male Wistar rats were randomly assigned to three groups and treated twice daily for 14 days with a formulation containing 5% Mentha spicata essential oil diluted in olive oil, olive oil alone, or no treatment. Wound healing was assessed through macroscopic monitoring and histological scoring. The chemical composition of the essential oil was characterized using gas chromatography–mass spectrometry analysis. Predicted molecular targets of the major monoterpenes were analyzed through protein interaction networks and pathway enrichment analysis. Results: Macroscopic wound closure progressed in all groups by day 14. Histological analysis revealed that the olive oil group showed more advanced collagen deposition, re-epithelialization, and granulation tissue maturation, whereas the Mentha spicata group displayed a more pronounced inflammatory and proliferative histological pattern. Network-based analysis highlighted signaling pathways related to receptor-mediated cellular responses as potential molecular mechanisms associated with early inflammatory and proliferative processes. Conclusions: These findings suggest that the biological effects of Mentha spicata essential oil in wound repair may be phase-dependent and influenced by concentration and formulation. The results support further studies aimed at optimizing dose and delivery strategies for essential oil–based wound therapies. Full article

Eriodictyol, a naturally occurring flavanone, has appeared as a biologically versatile compound with increasing relevance in biomedical research, especially in cancers. Evidence over the past few decades indicates that eriodictyol influences cancer cell fate through coordinated modulation of cell-cycle control, survival, and regulated cell death pathways. Eriodictyol appears to reshape oncogenic signaling networks, including PI3K/Akt/mTOR and associated kinase cascades, thereby restricting proliferative capacity and lowering resistance thresholds. Studies consistently report cell-cycle arrest at critical checkpoints, accompanied by activation of both mitochondrial- and death-receptor-mediated apoptotic pathways through disruption of BCL-2 family balance, caspase engagement, and mitochondrial destabilization. Furthermore, eriodictyol alters intracellular redox dynamics in a dose-dependent manner, selectively sensitizing cancer cells to oxidative and metabolic stress. More recent findings extend its significance to inflammation-driven tumor progression and to the regulation of ferroptosis. Beyond intrinsic pharmacological activity, advances in nanocarrier-based delivery and balanced combination strategies have started to address critical challenges and limitations regarding solubility and bioavailability, while allowing precise therapeutic applications. In this review, we have discussed the plausible mechanisms, experimental evidence, and translational insights of eriodictyol as a systems-level modulator of cancer biology. We also outlined research priorities essential for progressing its clinical relevance as future perspectives. Full article

This review synthesises the existing literature on meaningful experiences in nature and their potential to shape conservation behaviour in urban protected areas. Empirical evidence suggests that individuals are more likely to engage in environmental stewardship when they have meaningful encounters with nature. Such experiences, characterised by strong emotional connection and lasting cognitive impact, can transform perceptions, emotions, and behaviours, as a result motivating pro-conservation actions. To achieve this, a thematic synthesis approach was adopted, guided by inclusion criteria that consider empirical studies, theoretical frameworks, and cultural and spiritual narratives. Drawing on theories such as biophilia and constructivism, the review explores how emotional responses (e.g., awe, wonder, transcendence and life-changing moments) nurture a deeper connection to nature and inspire conservation-oriented behaviours. The findings highlight the importance of designing nature-based activities that evoke meaningful experiences, bridging the gap between emotional connection and practical conservation action. Full article

Background/Objectives: Head and neck cancer survivors experience many late toxicities following radiation therapy. This study aims to identify symptom clusters of late toxicities and their related factors in head and neck cancer survivors. Methods: A cross-sectional study was conducted with 83 survivors (pharyngeal or laryngeal cancer) who had received radiation therapy at least one year earlier. Nine late toxicities were assessed using the Japanese version of the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and a custom questionnaire. Quality of life (QoL) and related factors were evaluated with the European Organization for Research and Treatment of Cancer (EORTC QLQ-C 30), Hospital Anxiety and Depression Scale (HADS), UCLA Loneliness Scale, and Liebowitz Social Anxiety Scale (LSAS). Exploratory factor analyses and multiple regression analyses were performed. Results: All participants reported at least one symptom. Dry mouth (90.4%) and difficulty swallowing (72.3%) were particularly prevalent. Exploratory factor analysis (EFA) identified two symptom clusters (SCs): an oropharyngeal dysfunction cluster (pain, trismus, taste changes, difficulty swallowing, hoarseness) and a dry mouth cluster (dry mouth, sticky saliva). Regression analysis indicated that higher scores in both clusters were significantly associated with lower global QoL (oropharyngeal dysfunction SC: β = −0.427, p < 0.001; dry mouth SC: β = −0.268, p = 0.009). Chemoradiotherapy (CRT) was also significantly associated with higher cluster scores (oropharyngeal dysfunction SC: β = 0.233, p = 0.020; dry mouth SC: β = 0.343, p = 0.001). Conclusions: Late toxicities following radiation therapy include two clusters: oropharyngeal dysfunction cluster and dry mouth cluster. Head and neck cancer survivors with higher SC scores had lower global QoL scores and had undergone CRT. These findings may aid in the assessment and self-management support of head and neck cancer survivors after radiation therapy. Full article

Background/Objectives: Psoriasis and periodontitis share inflammatory pathways. Current evidence suggests a bidirectional non-causal relation. However, the evidence on the effects of periodontal treatment on psoriasis outcomes (severity, inflammatory markers, quality of life) is limited. This study aims to synthetize the available clinical and preclinical evidence of periodontal treatment effects on psoriasis outcomes, in patients with comorbid psoriasis and periodontitis (CRD420261298145). Methods: Several databases (PubMed, WebOfScience, ScienceDirect, ProQuest and GoogleScholar) were searched for relevant articles, without language or time restrictions. We included randomised and non-randomised clinical studies on humans, and controlled animal experiments. Interventions included periodontal treatment (surgical and non-surgical). Outcomes were the Psoriasis Area and Severity Index and dermatology-specific quality of life scores; secondary outcomes included inflammatory biomarkers and periodontal parameters. Studies were screened in duplicate, data extracted independently and risk of bias was assessed using Cochrane RoB 2, ROBINS I, NOS and SYRCLE. Results: A total of five studies were included in this systematic review (four clinical studies and one preclinical studies). Three studies directly assessed post-treatment psoriasis outcomes, with two studies investigating inflammation mediators as secondary outcomes. Two studies directly assessed PASI (Psoriasis Area and Severity Index) modifications, both studies confirming PASI scores decreasing post-periodontal treatment; one study also reported DLQI (Dermatology Life Quality Index). Typical follow-up durations ranged from 8 to 10 weeks for interventional studies, to 5 years for one cohort study. Conclusions: Although momentarily limited by the small number of available studies, the results of this review suggest that periodontal treatment may be associated with improvements in psoriasis outcomes. Further studies on larger samples, with longer follow-up periods would be necessary to confirm and possibly strengthen the existing results. Full article

The endothelial protein C receptor (EPCR) is an important component of the protein C (PC) system, recognised for its diverse roles in blood coagulation, inflammation, and stem cell regulation. Wound healing is a complex physiological process that can be divided into four distinct but overlapping phases: haemostasis, inflammation, proliferation and remodelling. Recently, EPCR has emerged as a key regulator in wound repair and regeneration. During haemostasis, EPCR enhances the conversion of PC to its activated form (APC) to optimise local and systemic anticoagulation. In the inflammatory phase, EPCR modulates immune cell activity, inhibits inflammatory factors, and maintains tissue barrier integrity. As the process transitions to the proliferative phase, EPCR promotes endothelial and epithelial cell proliferation, migration, neovascularisation and re-epithelization, and mediates the expression of matrix metalloproteinases to facilitate tissue reconstruction. Finally, during the remodelling phase, EPCR exerts a potential antifibrotic effect by regulating fibroblast activation and collagen deposition via the Transforming growth factor (TGF)-β1/Smad3 pathway, ensuring functional repair. While therapeutic potential has been shown in animal models, translating EPCR-mediated therapies to clinical application faces many challenges, including wound heterogeneity, dosage control, targeted delivery, and potential bleeding risks. Studies have shown that local drug delivery strategies, non-anticoagulant APC variants, and individualised treatment based on EPCR expression will be the key directions for future development. Additionally, EPCR may serve as a potential biomarker for assessing wound severity and guiding personalised interventions. Full article

Background: This study aims to evaluate the real-world efficacy and safety of dalpiciclib in patients with hormone receptor-positive (HR+) advanced breast cancer and explore the impact of different clinical characteristics on treatment outcomes. Methods: This was a two-center, retrospective cohort study involving 76 patients treated with dalpiciclib between January 2022 and June 2024 at two affiliated hospitals of Anhui Medical University in China. Data on progression-free survival (PFS), adverse events, and key clinical factors were collected and analyzed. Kaplan–Meier estimates were used for statistical analysis. Results: The median PFS (mPFS) for the entire cohort was 12.00 months (95% CI: 10.09–13.91 months). Patients receiving dalpiciclib as first-line therapy had significantly better outcomes (mPFS: 17.00 months, 95% CI: 9.19–24.81 months) than those receiving later-line therapy (p < 0.001). Patients with prior exposure to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and those with endocrine resistance had poorer outcomes. Multivariate Cox proportional hazards regression analysis confirmed that earlier treatment line (HR for second-line vs. first-line: 3.89, p = 0.015; HR for third-line or later vs. first-line: 5.56, p = 0.006) and prior CDK4/6i treatment (HR = 3.42, p = 0.040) were independent predictors of PFS. The most common adverse events were hematologic toxicities, including leukopenia (76.6%) and neutropenia (72.4%), mostly grade 1–2. No febrile neutropenia cases were reported, indicating a manageable safety profile. Conclusions: Dalpiciclib combined with endocrine therapy is associated with favorable efficacy and safety in real-world settings, with early-line treatment and lower tumor proliferative activity associated with better outcomes. While findings suggest potential for clinical application, further large-scale prospective studies are needed to validate its effectiveness in different patient subgroups and optimize treatment strategies. Full article

Background/Objectives: Optical coherence tomography angiography (OCTA) enables noninvasive quantitative assessment of the retinal microvasculature and is widely used in diabetic retinopathy (DR). However, OCTA-derived metrics are highly dependent on post-processing techniques, particularly vessel binarization. This study aimed to compare local and global binarization methods applied after Frangi filtering for vessel enhancement in parafoveal vessel density analysis. Methods: This cross-sectional study included 69 participants: 17 healthy controls and 52 diabetic patients, classified as the following: no DR (n = 14), non-proliferative DR (NPDR, n = 18), or proliferative DR (PDR, n = 20). All subjects underwent comprehensive ophthalmological examination and OCTA imaging of the superficial capillary plexus using a Topcon OCTA system. Images were processed using a custom MATLAB protocol. Following Frangi filtering, five binarization methods were applied: three local (Phansalkar, local Otsu, adaptive mean) and two global (global mean and global Otsu). Parafoveal vessel density was quantified within the four inner quadrants of the ETDRS grid. Results: Statistically significant differences in vessel density were consistently observed between PDR group and both the control and no DR groups across all local binarization methods. Among global methods, only global Otsu thresholding detected a significant difference between PDR and control. The most robust differences were predominantly identified in the nasal and inferior quadrants. Conclusions: Local adaptive binarization methods demonstrated superior sensitivity and structural preservation for parafoveal vessel density analysis in DR. Global methods showed limited discriminative capability. These findings support the preferential use of local adaptive techniques for reliable OCTA-based vascular assessment in diabetic retinopathy. Full article

Background: Ovarian cancer (OC) is characterized by aggressive progression, high metastatic potential, and frequent resistance to conventional chemotherapy, highlighting the need for novel combination-based therapeutic strategies. Metformin has emerged as a promising antineoplastic agent; however, its efficacy may be enhanced through combination with bioactive compounds. This study aimed to investigate the antineoplastic effects of metformin in SKOV3 human OC cells and to evaluate whether these effects could be potentiated by boric acid (BA) and resveratrol, with particular emphasis on their modulatory impact on key inflammatory and tumor-associated biomarkers, including interleukin-17 (IL-17), nuclear factor kappa-B (NF-κB), and midkine (MDK). Methods: SKOV3 cells were treated with metformin, BA, and resveratrol as monotherapies or in combination. Cell viability was assessed using a colorimetric assay, while migratory capacity was evaluated by wound healing analysis. The expression levels of IL-17, NF-κB, and MDK were quantified in cell lysates, and p21 protein expression was analyzed by immunocytochemistry. Results: All treatments induced concentration- and time-dependent reductions in cell viability. Combination treatments, particularly metformin with boric acid or resveratrol, produced more pronounced inhibitory effects on cell survival and migration compared with single-agent treatments. Inflammatory and tumor-associated biomarkers, including IL-17, NF-κB, and MDK, were significantly modulated following treatment. Additionally, increased p21 expression was observed in treated cells, indicating enhanced cell cycle regulatory activity. Conclusions: These findings indicate that BA and resveratrol enhance the antineoplastic activity of metformin in SKOV3 OC cells by suppressing proliferative and migratory capacities and modulating inflammatory mediators such as IL-17, NF-κB, and MDK. However, since toxicity assessments in non-cancerous cells were not performed, the safety profile of this combination remains unclear and requires further investigation in non-cancerous models. Full article