Search Results (2,717)

Diabetic wounds are a major clinical challenge, driven by hyperglycemia, oxidative stress, persistent inflammation, and bacterial infection. Conventional dressings offer limited benefit, creating demand for advanced therapeutic strategies. This review analyzes hydrogel-based wound dressings and flexible electronic devices. Hydrogels are categorized by angiogenesis promotion, antioxidant activity, anti-inflammatory regulation, antibacterial action, and electrical conductivity. Flexible electronics are examined for adaptability, sensitivity, and real-time monitoring potential. Hydrogels maintain moist environments, support tissue regeneration, and deliver multifunctional bioactivity. Growth factor-loaded and electroactive hydrogels promote angiogenesis. Reactive oxygen species (ROS)-responsive systems restore redox balance. Anti-inflammatory and antibacterial hydrogels regulate macrophages and reduce infection risk. Conductive hydrogels accelerate healing through electrical stimulation. Flexible electronics provide continuous monitoring, intelligent feedback, and remote management, enhancing treatment precision. Their integration with hydrogels represents a paradigm shift from passive dressings to active diagnostic and therapeutic systems. Challenges remain in material design, interfacial stability, and long-term biocompatibility. These issues guide future innovation and clinical translation, offering a foundation for smart diabetic wound management. Full article

Background and Objectives: This study aimed to describe the clinical characteristics and survival outcomes of three representative complex karyotype soft tissue sarcoma (STS) subtypes—undifferentiated sarcoma (US, primarily undifferentiated pleomorphic sarcoma (UPS)), myxofibrosarcoma (MFS), and leiomyosarcoma of soft tissue (LMS-ST)—using data from a single-institution cohort. Materials and Methods: A retrospective review of 124 patients treated at a single tertiary referral center between 2002 and 2024 was conducted. Clinicopathologic characteristics and survival outcomes were analyzed. Kaplan–Meier methods were used to estimate overall survival (OS). Cox proportional hazards regression models were applied to identify independent prognostic factors for survival, incorporating variables such as age, sex, tumor stage, and treatment modality. Results: The cohort comprised 36 cases of US, 64 of MFS, and 24 of LMS-ST. OS and survival after cohort enrollment (S-NCC) were evaluated both by subtype and across the entire cohort to assess potential differences across tumor subgroups. In both univariable and multivariable analyses, US subtypes showed poorer survival than MFS and LMS-ST. FNCLCC grade 3 emerged as a significant adverse prognostic factor for survival across all three subtypes. For FNCLCC grade 3 patients, the presence of benign prostatic hyperplasia (BPH) was significantly associated with an increased risk of death. Conclusions: Among the three subtypes, US demonstrated the most aggressive clinical course, MFS was notable for frequent local recurrence but relatively favorable survival, and LMS-ST showed intermediate outcomes. These findings highlight the clinical heterogeneity of complex karyotype STS and provide a foundation for future studies integrating molecular and multi-omics data to refine risk stratification and therapeutic strategies. Full article

Background/Objectives: Fertility-sparing treatment is an accepted option for selected women with early-stage endometrial carcinoma, yet comparative evidence on oncologic durability and reproductive success remains limited. This systematic review and meta-analysis aimed to evaluate oncologic and reproductive outcomes across available fertility-preserving strategies in early-stage endometrial carcinoma. Methods: A systematic search of MEDLINE, Embase, Web of Science, CENTRAL, and Scopus was conducted from inception to 13 April 2025. Eligible studies included women of reproductive age with FIGO stage IA endometrial carcinoma undergoing fertility-sparing treatment. Studies enrolling mixed populations were included only if carcinoma-specific outcomes could be clearly identified; cases of atypical endometrial hyperplasia or endometrial intraepithelial neoplasia were not included in the quantitative synthesis. Outcomes included the rates of complete response, recurrence, partial response, no response, pregnancy, and live birth. Meta-analyses with random-effect models were performed, with subgroup analyses by treatment strategy. Risk of bias was assessed using ROBINS-I and RoB 2 tools. The review was preregistered in PROSPERO. Meta-analyses were conducted using R software, v4.4.2 (R Foundation for Statistical Computing, Vienna, Austria). Results: Seventy-six studies involving 2507 women were included. The pooled complete response rate was 74% (95% CI: 69–79%), while recurrence occurred in 35% (95% CI: 28–42%) of complete responders. Strategies incorporating hysteroscopic resection, alongside other combination regimens, consistently demonstrated higher complete response rates (85%) and lower recurrence (14–16%) compared with oral progestin or LNG-IUD monotherapy. Early treatment failure, with pooled partial and no response rates of 6% and 16%, respectively, particularly affecting monotherapy regimens. The pooled pregnancy and live birth rates were 48% (95% CI: 41–54%) and 36% (95% CI: 29–43%), with more consistent reproductive outcomes observed with combination strategies. Conclusions: Fertility-sparing treatment in early-stage endometrial carcinoma is associated with high initial remission rates; however, the durability of response remains limited, while overall reproductive success is moderate. Accumulating evidence suggests that combination strategies, particularly those incorporating hysteroscopic resection, are associated with more favorable oncologic control and reproductive outcomes compared with hormonal monotherapy. Accordingly, fertility preservation should be regarded as a carefully selected, time-limited approach that requires close surveillance and individualized patient counseling. Full article

Background/Objectives: The development of small-molecule agents that selectively target DNA replication remains a central strategy in anticancer drug discovery. In this study, we report the biological characterization of a novel 6-nitro-benzodioxin-naphthalimide (NI) derivative (compound 5a), evaluated as a potential DNA-targeted anticancer lead. Methods/Results: The antiproliferative activity of 5a was assessed in a small panel of human lung carcinoma cell models (A549, H1299) and a non-malignant control (MRC-5), revealing pronounced cytotoxic effects in tumor cells, accompanied by favorable selectivity indices. Mechanistic investigations demonstrated that treatment with 5a results in strong inhibition of DNA synthesis, as evidenced by a marked reduction in EdU incorporation and a robust induction of the DNA damage marker γH2AX. These effects were associated with cell-cycle perturbations characterized by accumulation in G₁ and G₂/M phases, followed by activation of apoptotic pathways. Importantly, clonogenic survival assays confirmed that even transient exposure to 5a leads to a sustained loss of proliferative capacity, indicating irreversible long-term cellular damage. These results support a replication stress-driven mechanism of action for compound 5a, consistent with interference in DNA-associated processes during S phase. Conclusions: While the precise molecular initiating event remains to be elucidated, the observed biological profile positions 5a as a promising DNA-targeted lead structure with potential for further pharmaceutical optimization. These findings provide a solid foundation for the continued development of naphthalimide-based compounds as anticancer agents within a pharmaceutically relevant framework. Full article

Background/Objectives: Lactic acid bacteria have long been recognized as pivotal microorganisms in food fermentation and health promotion. However, their significance has recently grown due to innovative applications in various fields, particularly at the intersection of biotechnology and nanotechnology. This study aimed to provide a comprehensive overview of these emerging applications. Methods: The latest scientific literature was drawn from online databases and thoroughly reviewed. The new nomenclature system based on the post-2020 reclassification was used for reports. Results: The current study highlighted the evolving role of lactic acid bacteria, beyond their traditional use as starter cultures for food fermentation, in newer challenges, including the production of high-value bioactive compounds through bioprocessing under optimal conditions to enhance the yield, underlining the involved genes and pathways. Furthermore, this review addressed the beneficial effects of lactic acid bacteria as probiotics, postbiotics, and paraprobiotics in the treatment of various diseases and disorders, their application in the production of functional foods, and the encapsulation of their bioproducts to produce advanced health-promoting functional ingredients. The potential use of lactic acid bacteria to synthesize metallic nanoparticles, minicells, and carbon dots was also explored, promising significant advancements in nanomedicine. Conclusions: This review could open a new horizon for leveraging the potential of lactic acid bacteria in biotechnology, food science, and nanomedicine. The multilateral perspective offered here would provide a foundation for future research and development to exploit the capabilities of lactic acid bacteria across these innovative fields. Full article

Vascular diseases remain a major global health burden despite remarkable technological advances in vascular surgery and endovascular therapies. Conditions such as peripheral arterial disease, abdominal aortic aneurysm, carotid stenosis, chronic venous disease, diabetic vasculopathies, and vascular chronic ulcers are not only biological entities but are deeply shaped by social structures, cultural norms, and economic inequalities. This article introduces Vascular Sociology as an interdisciplinary field that integrates vascular surgery with medical sociology to provide a more comprehensive understanding of vascular health and disease. Drawing on classical and contemporary sociological theory, including concepts such as social determinants of health, embodiment, illness narratives, and the disease–illness–sickness triad, the article argues that vascular pathology reflects cumulative social exposures across the life course. Socially patterned behaviors, work conditions, food environments, healthcare access, gender norms, and geographic inequalities profoundly influence disease onset, progression, treatment decisions, and outcomes. The paper highlights how surgical success is contingent not only on technical excellence but also on patients’ social contexts, including health literacy, trust in institutions, caregiving resources, and the capacity to adhere to long-term follow-up and rehabilitation. By outlining conceptual foundations, epidemiological evidence, and mixed-methods research strategies, the article positions Vascular Sociology as a framework capable of bridging biomedical knowledge with lived experience. This approach expands the definition of vascular outcomes to include social reintegration, identity transformation, and equity of care, ultimately aiming to improve patient-centered practice, reduce disparities, and inform more socially responsive vascular health policies. Full article

Background: Spondylolysis is a stress fracture of the pars interarticularis, most common in adolescents and athletes involved in sports requiring repetitive spinal loading, extension, and rotation. The condition is often underdiagnosed due to delays in presentation and diagnosis, particularly among non-orthopedic providers. Aims: This review aims to summarize the current understanding of spondylolysis, focusing on its etiology, diagnosis, management strategies, and identify gaps in research for future exploration. Methods: A structured literature search was conducted in PubMed to identify studies relevant to pediatric and adolescent spondylolysis, spondylosis, and spondylolisthesis, particularly in the context of athletic injuries. The initial search yielded 143 citations. Applying filters for English language publications within the past five years reduced this to 125 citations. Limiting to populations that were aged 18 years and under returned 50 studies. After screening the titles and abstracts, 12 non-specific or irrelevant articles (including letters to the editor) were excluded, leaving a final dataset of 38 articles for detailed review. In addition, foundational and landmark studies outside this window were included to provide historical and conceptual context, bringing the total evidence base to 50 papers. Findings: Spondylolysis most commonly affects the L5 vertebra, with a higher incidence in male athletes. Conservative treatments like physical therapy and bracing are effective, especially when initiated early. However, the efficacy of bracing remains debated, with limited evidence on long-term clinical benefits. Surgical intervention is considered for severe or non-responsive cases. Diagnostic methods, including CT and MRI, are preferred, with emerging techniques like ultrasound showing potential for non-ionizing, cost-effective, early detection. Implications: Early diagnosis and treatment are crucial for preventing progression to spondylolisthesis. While conservative treatments often yield favorable outcomes, more research is needed to compare the effectiveness of bracing and pharmacological interventions. Future studies should focus on long-term outcomes, cost-effective, non-ionizing diagnostic methods, and the role of emerging therapies like regenerative medicine. A multi-disciplinary approach is vital for optimal patient care, particularly in young athletes. Full article

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (tPA) remains a keystone of acute ischemic stroke treatment but in a subset of patients is complicated by angioedema, a potentially life-threatening adverse event largely mediated by bradykinin signaling. The unpredictable and idiosyncratic nature of this reaction has long suggested an underlying genetic contribution, yet its molecular architecture has remained poorly characterized. We hypothesized that alteplase-associated angioedema represents a multigenic susceptibility phenotype, arising from the convergence of rare genetic variants across multiple interacting physiological systems rather than from a single causal variant. To explore this hypothesis, we performed clinical exome sequencing in a cohort of 11 patients who developed angioedema following alteplase administration. Rather than identifying a shared pathogenic variant, we observed distinct yet convergent patterns of genetic vulnerability, allowing patients to be grouped according to dominant, but overlapping, biological axes. These included alterations affecting bradykinin regulation (e.g., ACE, SERPING1, XPNPEP2), endothelial structure and hemostasis (e.g., VWF, COL4A1), neurovascular and calcium signaling (e.g., SCN10A, RYR1), and vascular repair or remodeling pathways (e.g., PSEN2, BRCA2). Notably, many of the identified variants were classified as Variant of Uncertain Significance (VUS) or likely benign significance in isolation. However, when considered within an integrated, pathway-based framework, these variants can be interpreted as capable of contributing cumulatively to system level fragility, a phenomenon best described as “contextual pathogenicity”. Under the acute biochemical and proteolytic stress imposed by thrombolysis, this reduced physiological reserve may allow otherwise compensated vulnerabilities to become clinically manifest. Together, these findings support a model in which severe alteplase-associated angioedema appears as an emergent property of interacting genetic networks, rather than a monogenic disorder. This systems level perspective underscores the limitations of gene centric interpretation for adverse drug reactions and highlights the potential value of pathway informed, multi-genic approaches to risk stratification. Such frameworks may ultimately contribute to safer, more personalized thrombolytic decision, while providing a conceptual foundation for future functional and translational studies. Full article

Drought stress severely limits wheat growth, development and yield. Endophytic fungi play a crucial role in plant growth and drought resistance. In agricultural production, they hold significant application potential as biocontrol agents capable of mitigating drought-induced damage. However, the mechanisms underlying changes in endophytic fungal community structure under drought stress remain unclear. Our study employed amplicon sequencing to investigate the structure of endophytic fungal communities in wheat roots under different water treatments, comparing structural and functional changes between different treatments. Results revealed that drought stress led to the greatest accumulation of relative abundance in the phylum Ascomycota (86.4%). At the genus level, Stachybotrys (increase 994.2%), Fusarium (increase 94.6%) and Aspergillus (increase 295.6%) showed the most significant increases in relative abundance. Co-occurrence network and Sankey diagram analysis revealed that wheat roots formed a drought-specific endophytic fungal community centered around Stachybotrys, Fusarium and Aspergillus, which indirectly enhanced crop drought tolerance. Our findings provide a theoretical foundation for future agricultural strategies to improve crop drought resistance through precise regulation of microbial communities. Full article

This study investigates the synergistic effects of Cr–Zr and Mn–Zr additions on the microstructural evolution and mechanical properties of Al–6 wt.%Cu alloys. Alloys were designed with solute concentrations positioned below, near, and above their maximum solubility limits, and were evaluated under as-cast, T4, and T6 heat treatment conditions. Mechanical testing revealed distinct behavioral trends depending on the heat treatment: the T4 heat treatment condition generally exhibited superior hardness and yield strength, whereas the T6 heat treatment condition resulted in a slight reduction in hardness but facilitated a significant recovery in tensile strength and structural stability, particularly in alloys designed near the solubility limit. To elucidate the crystallographic origins of these mechanical variations, X-ray diffraction analysis was conducted to monitor changes in lattice parameters, dislocation density, and micro-strain. The results showed that T4 heat treatment induced lattice contraction and a decrease in dislocation density, suggesting that the high strength under T4 heat treatment conditions arises from lattice distortion caused by supersaturated solute atoms. Conversely, T6 aging led to lattice relaxation approaching that of pure aluminum, yet simultaneously triggered a re-accumulation of dislocation density and micro-strain due to the coherency strain fields surrounding precipitates, which effectively impede dislocation motion. Therefore, rather than proposing a single, definitive optimization condition, this study aims to secure foundational data regarding the correlation between these microstructural descriptors and mechanical behavior, providing a guideline for balancing the strengthening contributions in transition metal-modified Al–Cu alloys. Full article

Background: Cellulite is a highly prevalent condition with dermal and subcutaneous alterations poorly captured by visual grading systems. Ultrasound has emerged as a non-invasive imaging modality capable of objectively quantifying morphological features relevant to cellulite. This systematic review evaluated the evidence on ultrasound for the diagnosis, structural characterization, and treatment monitoring of cellulite, identifying methodological limitations and research gaps. Methods: This systematic review (PROSPERO:CRD420251185486) followed the PRISMA statement. Searches were conducted in PubMed, Scopus, and CENTRAL up to November 2025. Risk of bias was evaluated using ROBINS-I and the Newcastle–Ottawa Scale. Results: Nine studies involving 785 participants were included. Ultrasound frequencies ranged from 12 to 35 MHz, with some scanners operating across broader bandwidths. Despite variability in devices, acquisition protocols, and clinical comparators, all studies consistently demonstrated that ultrasound quantifies key structural characteristics of cellulite. Diagnostic investigations reported moderate-to-strong correlations (r ≈ 0.31–0.64) between ultrasound-derived measures and clinical severity scores. Interventional studies showed measurable reductions in dermal and subcutaneous thickness, decreased adipose protrusion height, and improved dermal echogenicity across multiple treatment modalities. Ultrasound frequently detected microstructural remodeling not readily visible on clinical examination. Conclusions: Ultrasound is a valuable imaging modality for objectively characterizing cellulite and monitoring treatment-induced tissue remodeling. Standardized acquisition protocols, validated analytic criteria, and larger controlled studies are needed to support integration into routine dermatologic and esthetic practice. The quantitative and reproducible nature of ultrasound-derived parameters also provides a suitable foundation for future integration with data-driven and artificial intelligence–based image analysis frameworks. Full article

UDP-N-acetylglucosamine pyrophosphorylase (UAP) is an essential enzyme in the insect chitin biosynthesis pathway; however, little is known regarding its molecular functions in Oedaleus asiaticus Bey-Bienko (Orthoptera: Acrididae). Here, two UAP genes, OaUAP1 and OaUAP2, were identified and characterized in O. asiaticus. The effects of exogenous treatments, including the molting hormone 20-hydroxyecdysone (20E) and the chitin biosynthesis inhibitor validamycin (VA), were assessed on chitin synthesis. Sequence analyses have shown that the cDNA and deduced amino acid sequences of O. asiaticus share over 90% identity with UAPs in Locusta migratoria. OaUAP1 and OaUAP2 are widely expressed in many tissues and developmental stages but exhibit different expression patterns: OaUAP1 shows higher expression in the epidermis and fifth-instar nymphs, while OaUAP2 is primarily expressed in the fat body and in the fifth-instar nymphs and adults. The functional analysis of two OaUAPs revealed that OaUAP2 was crucial in molting; moreover, its implication also exists in other biosynthetic processes since nymphs maintained normal growth and development. Both OaUAP expressions were upregulated by 20E and downregulated by VA in the chitin biosynthesis pathway. Our findings provide a vital molecular insight into the chitin biosynthesis pathway of O. asiaticus and lay a solid foundation for developing environmentally safe biological insecticides. Full article

Bovine mastitis remains a globally prevalent disease, with the limitations of antibiotic-based treatments—such as the rise in antimicrobial resistance and the presence of drug residues—highlighting the urgent need for alternative therapeutic approaches. Inflammation is intricately linked to various cytokines and immunomodulatory proteins, among which cyclophilin A (CypA) serves as a pivotal inflammatory mediator, significantly contributing to the initiation and amplification of inflammatory responses under such conditions. The acquisition of high-purity recombinant protein is a fundamental prerequisite for in vitro functional studies of bovine CypA. This study aimed to construct a eukaryotic expression vector for bovine CypA and verify its expression in CHO-K1 cells. Utilizing the bovine CypA gene sequence available in GenBank, the coding region was artificially synthesized and optimized for codon usage, subsequently being inserted into the pPB[Exp] backbone vector via BsrGI and BstEII double digestion. The resulting polycistronic expression vector contained a CAG promoter driving the CypA transcription, an EF1α promoter driving the EGFP reporter gene, a PGK promoter controlling the puromycin resistance gene, and a C-terminal His-tag. Restriction enzyme digestion and bidirectional Sanger sequencing confirmed that the inserted fragment sequence was completely consistent with the optimized design. Robust EGFP fluorescence was observed 24 h post-transfection and remained stable after puromycin selection. qPCR analysis showed that the Ct value of CypA in the experimental group was 16.20 ± 0.04, while no amplification signal was detected in the control group. Additionally, Western blot analysis identified a CypA-specific band at approximately 18 kDa, confirming the correct expression of the exogenous CypA protein in CHO-K1 cells. Collectively, these results demonstrate the successful construction and validation of a bovine CypA eukaryotic expression vector. The established CHO-K1 expression system exhibited stable and efficient expression, thereby providing a robust foundation for future research on the production and application of recombinant CypA protein. Full article

Background: Comprehensive genomic profiling (CGP) is a tool used in precision oncology to identify genomic alterations and match them with targeted therapies across several tumor types. However, real-world data on its clinical utility and impact remains limited. The FRONTAL study (Foundation Medicine Real wOrld evideNce in porTugAL) is a multicenter academic initiative that established a national registry of Portuguese patients with solid tumors who underwent CGP with FoundationOne CDx, Liquid CDx or FoundationOne Heme assays. Methods: Eligible patients had advanced solid tumors not suitable for curative treatment at the time of recruitment. Prior CGP testing was permitted if taken within 12 months before study initiation. Genomic profiling data were extracted from FoundationOne Medicine reports, and clinical information was extracted from medical records. Actionable alterations were defined as those associated with approved treatments or with clinical evidence of benefit in other cancers, per NCCN guidelines. Variant interpretation was also reviewed according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines. The primary outcome was disease control at 16 weeks, defined by the absence of progression. Results: The study included 205 patients between 2020 and 2025 across 10 sites, with colorectal (40, 19.5%), sarcomas (28, 13.7%), and other gastrointestinal tumors (22, 10.7%) being the most common pathologies. Actionable alterations were identified in 104 cases (50.7%). Genomic findings guided therapy decisions in 50 patients (24.4%), of whom 30 achieved disease control at 16 weeks (14.6%). Conclusions: The FRONTAL study highlighted the clinical relevance of CGP in advanced solid tumors. Over half of the patients had actionable alterations, a quarter had therapy changes based on CGP results, and improved disease outcome was observed in approximately 15% of the cohort. Full article

The 25 kDa glycoprotein lipocalin-2 (LCN2) is widely expressed and has diverse functions, ranging from physiological to pathophysiological processes. In the liver, LCN2 is primarily associated with inflammatory processes and is considered a potential biomarker in metabolic disorders. However, a significant challenge is the absence of a suitable human in vitro model for studying LCN2 and its associated signaling pathways. Therefore, we have successfully generated patient-derived liver organoids of both male and female origin, providing a novel in vitro model for LCN2 research. Our data show that the self-renewing organoids mimic essential architectural features of hepatocytes, as demonstrated by electron microscopy and F-actin staining. Consistent with the expression profile observed in liver tissue, the isolated 3D organoids exhibit minimal endogenous LCN2 levels. Next, the LCN2 expression was studied at the protein and mRNA levels under inflammatory conditions by treating the organoids with various cytokines and lipopolysaccharides (LPS). Our results show that LCN2 expression is significantly upregulated by IL-1β and TNF-α in an NF-κB-dependent manner, but remains unchanged with IL-6 or LPS. In conclusion, we have established human patient-derived liver organoids as a valuable model for investigating LCN2 signaling mechanisms. This study lays the foundation for future research on the role of LCN2 in liver pathologies, aiding in disease progression understanding and facilitating patient-specific treatment predictions. Full article