Search Results (285)

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article

Background and Objectives: Paediatric palliative care in Romania is underdeveloped and unevenly distributed, which creates major difficulties in accessing services for children with life-limiting illnesses and their families. The lack of a dedicated national strategy, the shortage of specialised staff, and socio-economic barriers exacerbate the vulnerability of these groups. This study aimed to explore parents’ and caregivers’ experiences, to analyse the perspectives of public institutions and NGOs involved in supporting these children, and to identify the main barriers and facilitators in accessing paediatric palliative care. Materials and Methods: Given that all data were collected exclusively through focus group discussions, this study employed a qualitative design based on three focus groups guided by a semi-structured interview guide. The analysis was conducted using MAXQDA software, which enabled the coding and synthesis of emerging themes. Participants were parents/caregivers of children with life-limiting illnesses, representatives of public institutions, and members of relevant NGOs in Bacău County, Romania. Purposive sampling was used to capture diverse and experience-based perspectives, resulting in a total of 24 participants across three focus groups—parents and caregivers (n = 11), public institution representatives (n = 7), and NGO representatives (n = 6). No individual semi-structured interviews were conducted. Results: The analysis highlighted a complex typology of medical, emotional, social, educational, and spiritual needs of children and their families. Parents reported experiences of abandonment in the curative system, emphasising the importance of pain control, safety, and community support. Public institutions acknowledged the lack of skills and inter-sectoral coordination, while NGOs pointed to structural barriers and the low visibility of these children. Major needs include access to specialised care, psychological support, respite services for carers, financial and administrative assistance, education, and spiritual counselling. A significant obstacle is the lack of up-to-date statistical data needed to inform public policy. Conclusions: Paediatric palliative care should be considered a national priority through the development of a dedicated strategy, the expansion of specialised services, and the strengthening of partnerships between the public and non-governmental sectors. An integrated, child- and family-centred approach addressing the medical, social, emotional, and spiritual dimensions of care is essential. The results highlight the need for continuous staff training, information campaigns, and community support mechanisms to reduce inequalities and improve the quality of life of children with life-limiting illnesses. Full article

Sucrose is a key quality trait in peanuts, yet high-sucrose varieties are scarce. Although sucrose transporters (SUT/SUC) play crucial roles in sucrose transport and accumulation during seed development, systematic analyses in peanuts are limited. This study conducted a genome-wide analysis of the SUC gene family in cultivated peanut (Arachis hypogaea L.). Sixteen AhSUC genes were identified and characterized for genomic distribution, phylogeny, and expression across tissues and developmental stages. The genes are unevenly distributed across the genome with clustered chromosomal localization. All AhSUC proteins contain the conserved sucrose/proton co-transporter domain (IPR005989), exhibit the typical 12 transmembrane α-helical structure of the major facilitator superfamily, are hydrophobic, and predicted to localize to the membrane. Promoter analysis revealed cis-regulatory elements associated with growth, development, light, hormone, and stress responses. Expression profiling showed tissue-specific patterns, with eight AhSUC genes being highly expressed in cotyledons and embryos. Comparative analysis between high-sugar and conventional varieties showed higher expression of AhSUC2, AhSUC9, and AhSUC11 in the high-sugar variety, correlating with increased sucrose accumulation. Functional validation using a sucrose transport-deficient yeast mutant confirmed the sucrose transport activity of these genes. These findings provide insight into sucrose accumulation mechanisms and offer genetic targets for breeding high-sugar peanut varieties. Full article

Background/Objectives: A gluten-free diet (GFD) remains the only effective therapy for celiac disease (CD) and non-celiac gluten sensitivity (NCGS). Strict adherence is essential, yet it can impose considerable psychological, social, and financial burdens. This study investigated factors influencing GFD adherence, explored the perceived burden of this therapy, and examined differences between individuals with CD and NCGS. Methods: A cross-sectional anonymous questionnaire was completed by 681 Romanian citizens living in Romania with either a medically confirmed or a self-reported diagnosis of CD or NCGS. The survey assessed GFD adherence and its potential predictors, including gender, family history, comorbidities, diagnostic confirmation, and food security and perceived availability, as well as various psychological, social, and financial factors. Results: Participants with CD showed significantly higher GFD adherence than those with NCGS. Self-diagnosis was more common among NCGS respondents and was associated with poorer adherence, whereas a medically confirmed diagnosis predicted stricter adherence. Longer time since diagnosis, a greater perceived importance of a GFD, consistent label reading, as well as weight gain after starting a GFD were also positively associated with adherence. Although gluten-free (GF) food security has improved over time, cost remains a major barrier. Social activities negatively influenced adherence, reflecting the isolating effects of dietary restrictions. Nearly 25% of respondents reported a family history of gluten-related disorders (GRDs). Women—although more frequently affected by GRDs—exhibited levels of adherence similar to men. Comorbidities were common (33.9%), predominantly autoimmune diseases (56.3%), with autoimmune thyroiditis (32%) and lactose intolerance (19.2%) being the most frequent comorbidities. Conclusions: Diagnostic certainty, motivation, and practical barriers influence GFD adherence. Enhanced public awareness, clear labeling, improved GF food security, and financial support could facilitate sustained adherence and reduce psychosocial burden. To the author’s knowledge, this is the first national study of its kind in Romania. Full article

Marine ecosystems represent an exceptional reservoir of structurally diverse metabolites with remarkable pharmacological potential. Over the past decades, the exploration of marine organisms has led to the discovery of an ever-expanding number of bioactive compounds. Many of these metabolites display highly original chemical scaffolds that are not typically found in terrestrial organisms, offering new opportunities for drug discovery. Among the most promising applications is their development as anticancer agents, given their ability to interfere with key cellular processes. This review highlights marine natural products currently under investigation in preclinical studies as potential anticancer lead compounds. The molecules are classified into major structural families: aromatic and heterocyclic alkaloids, terpenes and their derivatives, macrolide frameworks, and diverse peptide-based scaffolds, alongside other complex classes (polyketides, thiazole lipids, alkylamino alcohols, and pyrrolocarbazole derivatives). A particular emphasis has been placed on the role of total synthesis over the last decade. Advances in synthetic methodology have not only enabled the production of these complex metabolites in sufficient quantities but have also facilitated the development of novel chemotherapeutic agents. To overcome the challenges of limited natural availability, the advanced synthetic approaches are crucial for harnessing the full therapeutic potential of marine-derived compounds. Full article

The transformation of Local Ecological Knowledge (LEK) among minority populations undergoing cultural and linguistic assimilation over time is poorly understood. Arbëreshë communities in Greece, who have preserved Albanian-derived traditions for centuries, offer a unique opportunity to examine how folk plant knowledge adapts over time. This study examines the linguistic labels and culinary uses of wild greens among Arbëreshë (or Arvanites), an ethno-linguistic minority traditionally speaking Arbërisht or Arvanitika, the Tosk dialect of Albanian, who have resided in the Argolis and Corinthia regions of the Peloponnese for several centuries. In 2025, fieldwork was conducted in four rural Arbëreshë villages in the Argolis and Corinthia regions of Greece, combining semi-structured interviews with 24 elderly participants, participant observation, and the collection and identification of botanical specimens. The contemporary dataset was compared with historical ethnobotanical records from the 1970s to assess temporal changes in the use of wild vegetables and folk plant nomenclature. Our results reveal that current Arbëreshë ethnobotanical heritage has undergone profound Hellenisation, with 62% of folk plant names of Greek origin, 14% Albanian, and 24% hybrid, reflecting strong linguistic and cultural assimilation over the past half-century. The traditional boiled green mix (lakra in Arbëreshë, chorta in Greek) remains central to the local cuisine, which is rooted in foraged plants, although its culinary applications have diversified. In total, 37 taxa of wild vegetables across 37 genera and 14 families were documented in 2025, compared with 21 taxa across 21 genera in the filtered 1970 dataset. Core families, such as Asteraceae and Brassicaceae, remained dominant, while new families, like Malvaceae and Portulacaceae, appeared, possibly indicating both ecological and culinary changes. These findings raise questions about whether the Arbëreshë wild vegetable heritage was strongly influenced by the surrounding Greek majority or primarily acquired after migration, potentially facilitated by intermarriages and shared Orthodox Christian affiliation. Overall, our study highlights a largely Hellenised Arbëreshë biocultural heritage and underscores the urgent need for national and regional stakeholders to recognise and celebrate the remaining minority’s linguistic and ethnobotanical diversity. The transformation of local ethnobotanical knowledge over the past fifty years appears influenced by ecological availability, socio-cultural dynamics, and changing taste preferences. Full article

White Spot Syndrome Virus (WSSV) is one of the most devastating viral pathogens affecting shrimp, causing severe economic losses to the global farmed shrimp trade. The globalization of live shrimp trade and waterborne transmission have facilitated the rapid spread of WSSV across major shrimp-producing countries since its initial emergence. The present review gives an updated account of WSSV biology, pathology, transmission dynamics, and recent developments in control measures. The virus, a double-stranded DNA virus of the Nimaviridae family, utilizes advanced immune evasion strategies, resulting in severe mortality. Shrimp lack adaptive immunity and hence rely predominantly on innate immunity, which is insufficient to mount an effective response against severe infections. Traditional disease control measures such as augmented biosecurity, selective breeding, and immunostimulants have, despite extensive research, achieved only limited success. New biotechnological tools such as RNA interference, CRISPR-Cas gene editing, and nanotechnology offer tremendous potential for disease mitigation. In parallel, the development of DNA and RNA vaccines targeting WSSV structural proteins, such as VP28, holds significant promise for stimulating the shrimp immune system. This review highlights the urgent need for a convergent approach to sustainable disease management in global shrimp aquaculture, with interdisciplinarity playing a pivotal role in shaping the future of WSSV control. Full article

Post-translational modifications (PTMs) expand the structural diversity of proteins beyond the standard amino acids, influencing protein-protein interactions. Protein methylation, a prevalent PTM, involves the transfer of methyl groups from S-adenosylmethionine (SAM) to lysine and arginine residues. Arginine methylation is catalyzed by the Protein Arginine Methyltransferase (PRMT) family to yield mono- and dimethylarginine forms. PRMT1, the isozyme responsible for the majority of asymmetric dimethylation (ADMA) is implicated in various diseases, including cancer. Here, we report the synthesis and screening of a second-generation peptide library to identify novel PRMT1 substrates. The library, based on histone peptides, incorporated varying sequences of amino acids, facilitating substrate specificity studies. Screening identified 7 peptide sequences as exceptional PRMT1 substrates, which were confirmed by kinetic analysis. Consensus sequences revealed key recognition elements for PRMT1 catalysis, suggesting roles for small non-polar side chains and specific residues near the substrate arginine. Furthermore, we developed a peptide-based PRMT1 inhibitor by substituting the substrate arginine with a chloroacetamidine warhead. The inhibitor exhibited sub-micromolar inhibitory potency against PRMT1, surpassing previous peptide-based inhibitors. Our findings contribute to understanding PRMT1 substrate specificity and provide a scaffold for developing potent inhibitors targeting PRMT1 in diseases, including cancer. Full article

Background/Objectives: Pediatric mental health is a major public health concern worldwide and primary care providers struggle to meet the growing demand for mental healthcare. Child Psychiatry Access Programs have emerged to fill gaps in primary care provider (PCP) training, confidence, and workflow support. This study aimed to describe the iterative development of a Child Psychiatry Access Program and present initial findings on its reach and feasibility in supporting PCPs. Methods: The Practical, Robust Implementation and Sustainability Model (PRISM) implementation framework guided the development and evaluation of the program. Pre-implementation surveys and invested partner interviews informed the creation of a multidisciplinary program comprising three components: (1) consultation services and resource navigation, (2) education and training, and (3) provider care guides. The program was then implemented, and reach was assessed via consultation calls, attendance at education and training series, resource navigation encounters, and care guide usage. Feasibility was evaluated through pre- and post-series self-reported ratings across six learning objectives. Results: Pre-implementation evaluation indicated high provider interest across all educational modalities. The resulting program included consultation services, education and training, resource navigation, and provider care guides. Educational trainings led to significant improvements in self-reported knowledge and confidence across six learning objectives, including assessment, treatment planning, family engagement, and navigating local resources. Resource navigation primarily facilitated ongoing management within the primary care setting, with PCPs retaining care in the majority of cases. Engagement with the Colorado Care Guide demonstrated sustained reach, with over 4600 page views from 1300 active users, reflecting broad and ongoing utilization of program resources. Consultation call data mirrored these trends, highlighting both frequently addressed diagnoses and expanding program reach over time. Conclusions: Child psychiatry access programs help support access to youth mental health care in the primary care space and offer potential solutions to workforce limitations during an era of increasing mental health concerns in youth and teens. Findings from this implementation may inform adaptation of child psychiatry access programs in other regions seeking to expand mental health support for children and adolescents in primary care settings. Full article

Skin tumors are among the most common neoplasms in dogs and cats, sharing biological and environmental risk factors with human cancers. Owners play a critical role in early detection, yet little is known about their knowledge and attitudes. This study aimed to assess the knowledge, perceptions, attitudes, and practices of Portuguese pet owners regarding skin tumors in companion animals. An online cross-sectional survey was completed by 420 respondents. Overall, awareness of risk factors such as sun exposure and age was relatively high, but most owners were unable to identify specific tumor types or locations. Only one-quarter believed skin tumors are curable, while the majority expressed uncertainty. Women, those with multiple or long-term pet ownership, and individuals with family or personal experience of cancer showed greater knowledge and more proactive behaviors. However, a gap between knowledge and practice still remains. These findings underscore the need for targeted educational strategies to enhance owners’ health literacy, facilitate early detection, and promote timely veterinary care. Full article

Purpose: Genetic polymorphisms within specific genes play a role in both the genetic predisposition to Major Depressive Disorder (MDD) and the variation observed in responses to antidepressant treatments. Pharmacogenetics examines how these polymorphisms affect medication response. This review highlights significant disparities in the pharmacogenetic influences on antidepressant response, with a focus on ethnic and sex-based differences. Methods: This review synthesizes findings from a comprehensive literature search conducted between 2000 and 2025. It utilized databases such as PubMed, Scopus, and Web of Science, using search terms including “pharmacogenetics”, “antidepressants”, “Major Depressive Disorder”, “CYP450”, “neuroplasticity”, and “genetic variations”. This review integrates pharmacogenetics with neurotransmitters and their transporters, neuroplasticity, growth factors, and the cytochrome P450 family, providing promising insights for personalized MDD treatment strategies. We analyzed and synthesized findings from over 50 relevant studies, focusing on those with a clear emphasis on genetic associations with antidepressant efficacy and adverse effects. Results: Pharmacogenetic analysis facilitates personalized antidepressant prescriptions by identifying key genetic variants that influence treatment outcomes. Specifically, variations in CYP2D6 and CYP2C19 can significantly impact drug metabolism and tolerability. A high percentage of patients with non-normal metabolizer phenotypes are predisposed to adverse drug reactions or ineffective responses. Furthermore, this review identifies significant ethnic and sex-based disparities in treatment response. For example, the L allele of the 5-HTTLPR polymorphism confers a higher likelihood of response and remission following SSRI treatment in white people compared to Asians. Additionally, in women, specific 5-HTTLPR polymorphisms have a more pronounced influence on mood and MDD pathophysiology, with a significant reduction in mood in response to tryptophan depletion. Conclusions: Integrating pharmacogenetic insights, encompassing genetic factors, neurotransmitter pathways, neuroplasticity, and the influence of ethnicity and sex, is crucial for developing personalized antidepressant treatment strategies. This will ultimately optimize patient recovery and minimize adverse effects. Full article

Conidiobolus coronatus (Entomophthorales), a fungal pathogen with a broad insect host range, is a promising candidate for biocontrol applications. We sequenced a C. coronatus strain isolated from a Rhopalomyia sp. cadaver using PacBio long-read sequencing to elucidate the molecular basis of its wide host adaptability. The newly assembled 44.21 Mb genome exhibits high completeness (BUSCO score: 93.45%) and encodes 11,128 protein-coding genes, with 23.1% predicted to mediate pathogen–host interactions. Comparative genomics with the aphid-obligate pathogen C. obscurus revealed significant expansions in gene families associated with host adaptation mechanisms, including host recognition, transcriptional regulation, degradation of host components, detoxification, and immune evasion. Functional annotation highlighted enrichment in cellular component organization and energy metabolism. Pfam annotation identified one hundred twenty-five seven-transmembrane receptors (putative GPCRs), sixty-seven fungus-specific transcription factors, three hundred sixty-one peptidases (one hundred ninety-eight serine proteases and one hundred three metalloproteases), one hundred twenty-seven cytochrome P450 monooxygenases (P450s), thirty-five cysteine-rich secretory proteins, and fifty-five tyrosinases. Additionally, four hundred thirty carbohydrate-active enzymes (CAZymes) across six major modules were characterized. Untargeted metabolomics detected 22 highly expressed terpenoids, consistent with terpenoid biosynthesis gene clusters in the genome. Collectively, these expansions underpin the broad host range of C. coronatus by enabling cross-host signal decoding and gene expression reprogramming, breaching diverse host physicochemical barriers, and expanding its chemical ecological niche. This study provides genomic insights into broad host adaptability in entomopathogenic fungi, facilitating further understanding of pathogen–host interactions. Full article

The GLABROUS1 Enhancer Binding Protein (GeBP) gene family plays a crucial role in plant growth, development, and stress responses. In this study, 28 GeBP genes were identified in Brassica oleracea using HMMER and validated through multiple conserved domain databases. A phylogenetic tree was constructed based on the GeBP protein sequences from B. oleracea, Arabidopsis thaliana, Brassica rapa, and Brassica napus, dividing them into four evolutionary clades (A–D), which revealed a close evolutionary relationship within the genus Brassica. Conserved motif and gene structure analyses showed clade-specific features, while physicochemical property analysis indicated that most BoGeBP proteins are hydrophilic, nuclear-localized, and structurally diverse. Gene duplication and chromosomal localization analyses suggested that both segmental and tandem duplication events have contributed to the expansion of this gene family. Promoter cis-element analysis revealed a dominance of light-responsive and hormone-responsive elements, implying potential roles in photomorphogenesis and stress signaling pathways. Notably, the protein encoded by BolC01g019630.2J possesses both a transmembrane domain and characteristics of the Major Facilitator Superfamily (MFS) transporter family, and it is predicted to localize to the plasma membrane. This suggests that it may act as a molecular bridge between environmental signal perception and transcriptional regulation, potentially representing a novel signaling mechanism within the GeBP family. This unique feature implies its involvement in transmembrane signal perception and downstream transcriptional regulation under environmental stimuli, providing valuable insights for further investigation of its role in stress responses and metabolic regulation. Overall, this study provides a theoretical foundation for understanding the evolutionary patterns and functional diversity of the GeBP gene family in B. oleracea and lays a basis for future functional validation and breeding applications. Full article

Background and Objectives: Hypocitraturia is a major risk factor for calcium-containing kidney stone disease. Citrate inhibits stone formation by binding calcium in the urine. The SLC13A2 gene encodes the sodium-dependent dicarboxylate cotransporter 1 (NaDC1), a membrane transport protein that facilitates citrate reabsorption in the proximal renal tubules. Variants in this gene, such as rs11568476 (V477M), have been shown to significantly impair transporter activity. This study aimed to investigate the presence of the rs11568476 polymorphism in SLC13A2 and its association with hypocitraturia in Turkish patients with calcium-containing kidney stones. To our knowledge, this is the first genetic study evaluating this polymorphism in a Turkish cohort. Materials and Methods: This prospective cross-sectional study included 90 patients diagnosed with calcium-containing kidney stones at Düzce University Faculty of Medicine, Department of Urology. Based on 24 h urinary citrate levels, patients were divided into two groups: normocitraturic (n = 38) and hypocitraturic (n = 52). Blood and 24 h urine samples were analyzed for biochemical parameters. The rs11568476 polymorphism in SLC13A2 was analyzed using Real-Time PCR. Results: There were no significant differences between the two groups in terms of age, gender, and most biochemical parameters. Serum uric acid levels were significantly higher in the hypocitraturic group (p = 0.002), whereas family history of stone disease was more prevalent in the normocitraturic group (p = 0.024). Genetic analysis revealed no polymorphism in the rs11568476 region; all patients exhibited the homozygous wild-type genotype (GG). Conclusions: No association was observed between the rs11568476 polymorphism and hypocitraturia in this cohort. The absence of the polymorphism suggests that this variant may be rare or absent in the Turkish population. These findings highlight the importance of investigating additional genetic and environmental contributors to hypocitraturia and nephrolithiasis through larger, multicenter studies. Full article

Background/Objectives: Sudden cardiac arrest (SCA) is a major global health concern with high mortality despite advances in resuscitation techniques. Achieving return of spontaneous circulation (ROSC) represents merely the initial step in the extensive rehabilitation journey. This review highlights the critical role of structured, multidisciplinary rehabilitation following ROSC, emphasizing the necessity of integrated physiotherapy, neurocognitive therapy, and psychosocial support to enhance quality of life and societal reintegration in survivors. Methods: This narrative review analyzed peer-reviewed literature from 2020–2025, sourced from databases such as PubMed, Scopus, Web of Science, and Google Scholar. Emphasis was on clinical trials, expert guidelines (e.g., European Resuscitation Council 2021, American Heart Association 2020), and high-impact journals, with systematic thematic analysis across rehabilitation phases. Results: The review confirms rehabilitation as essential in addressing Intensive Care Unit–acquired weakness, cognitive impairment, and post-intensive care syndrome. Early rehabilitation (0–7 days post-ROSC), focusing on parameter-guided mobilization and cognitive stimulation, significantly improves functional outcomes. Structured interdisciplinary interventions encompassing cardiopulmonary, neuromuscular, and cognitive domains effectively mitigate long-term disability, facilitating return to daily activities and employment. However, access disparities and insufficient randomized controlled trials limit evidence-based standardization. Discussion: Optimal recovery after SCA necessitates early and continuous interdisciplinary engagement, tailored to individual physiological and cognitive profiles. Persistent cognitive fatigue, executive dysfunction, and emotional instability remain significant barriers, underscoring the need for holistic and sustained rehabilitative approaches. Conclusions: Comprehensive, individualized rehabilitation following cardiac arrest is not supplementary but fundamental to meaningful recovery. Emphasizing early mobilization, neurocognitive therapy, family involvement, and structured social reintegration pathways is crucial. Addressing healthcare disparities and investing in rigorous randomized trials are imperative to achieving standardized, equitable, and outcome-oriented rehabilitation services globally. Full article