Search Results (18,250)

Cyclodextrins and chitosan are biomaterials largely used as pharmaceutical excipients due to their biocompatibility, biodegradability, and low/absent toxicity, associated with a number of favorable properties. In particular, cyclodextrins complexation is mainly utilized to improve the physicochemical and biological properties of drugs, including solubility, stability, and bioavailability, and to reduce their irritating effect. Nevertheless, some disadvantages related to the fast removal of the complex from blood circulation after in vivo administration, and possible competition effects for interaction with cyclodextrin between the complexed drug and other molecules present in the biological environment, can reduce their efficacy as drug carriers. On the other hand, chitosan is widely employed to take advantage of its mucoadhesive, controlled/targeted release, and permeation-enhancing properties. However, its almost complete insolubility in water and poor affinity towards hydrophobic molecules (as most drugs are) are considered its main drawbacks, which could strongly limit its applicability. Due to the several beneficial properties of both cyclodextrins and chitosan, their joint use could provide additional favorable effects in drug delivery and help overcome their disadvantages, in particular by combining the complexing/solubilizing ability of the former towards hydrophobic molecules with the mucoadhesive and controlled/targeted release properties of the latter. The present review is intended to provide a critical and comprehensive summary of the main relevant investigations performed in the last twenty-five years regarding the applications and possible advantages that can be obtained by the combined use of cyclodextrins and chitosan in the development of more effective drug delivery systems. Full article

The traditional Chinese medicinal herb Gynura segetum is increasingly recognized for its hepatotoxic potential, primarily attributed to its pyrrolizidine alkaloid (PA) content. PAs are a leading cause of herb-induced liver injury (HILI) in China and are strongly linked to hepatic sinusoidal obstruction syndrome (HSOS). This review systematically summarizes the pathogenesis, diagnostic advancements, and therapeutic strategies for PA-induced HSOS. Molecular mechanisms of PA metabolism are detailed, encompassing cytochrome P450-mediated bioactivation and the subsequent formation of pyrrole–protein adducts, which trigger sinusoidal endothelial cell injury and hepatocyte apoptosis. Advances in diagnostic criteria, including the Nanjing Criteria and the Roussel Uclaf Causality Assessment Method (RUCAM)-integrated Drum Tower Severity Scoring System, are discussed. Furthermore, emerging biomarkers, such as circulating microRNAs and pyrrole–protein adducts, are examined. Imaging modalities, such as contrast-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI), have evolved from descriptive tools into quantitative and prognostic instruments. Therapeutic approaches have evolved from supportive care to precision interventions, including anticoagulation, transjugular intrahepatic portosystemic shunt (TIPS), and autophagy-modulating agents. A comprehensive literature review, utilizing databases such as PubMed and Web of Science, was conducted to summarize progress since the introduction of the “Nanjing Guidelines”. Ultimately, this review underscores the critical need for integrated diagnostic and therapeutic frameworks, alongside enhanced public awareness and regulatory oversight, to effectively mitigate PA-related liver injury. Full article

Objective: Glaucoma is a complex optic neuropathy characterized by the progressive loss of retinal ganglion cells (RGCs). Animal models are crucial tools for deciphering its multidimensional pathogenesis and evaluating novel therapeutic strategies. This review aims to systematically summarize the establishment methods, application advances, and future development trends of various glanimal models. Methods: The literature for this review was identified through systematic searches of electronic databases, including PubMed, Web of Science Core Collection, and Google Scholar. The search strategy utilized a combination of keywords and their variants: “glaucoma”, “animal models”, “retinal ganglion cells”, “intraocular pressure”, “neuroprotection”, “immune inflammation”, “fibrosis”, and “filtration surgery”. The search focused on articles published between 2015 and 2025 to cover the major advances of the last decade. The scope encompassed original research articles, reviews, and meta-analyses. Results: Diverse glanimal models successfully replicate different facets of glaucoma, elucidating multidimensional pathogenesis involving mechanical stress, immune inflammation, excitotoxicity, oxidative stress, and fibrosis. These models have played an indispensable role in screening neuroprotective agents, evaluating anti-fibrotic strategies, and validating the application of advanced imaging and functional assessment technologies. Current research is evolving towards model standardization, multi-factor simulation, and the integration of novel drug delivery systems and immunomodulatory strategies. Conclusions: The diversification of glanimal models provides a powerful platform for in-depth investigation of disease mechanisms and the development of innovative therapies. Future research should focus on establishing standardized models that better mimic the clinical pathological state and deeply integrating multimodal assessment technologies with targeted therapies. This will facilitate the translation of basic research into clinical applications, ultimately achieving personalized precision medicine for glaucoma. Full article

Ketamine (KET) administration protocols vary widely in their design, with acute, sub-chronic, and chronic dosing regimens used to induce psychotic-like behavior in rodent models. This review compares representative classic and contemporary studies employing differing KET administration protocols to model psychosis in laboratory rodents. Specifically, we have focused on the behavioral tasks and analytical methods used to validate KET-induced symptoms of psychosis-like and schizophrenia-like behaviors. While variability in behavioral tasks complicates direct comparisons across studies, these findings provide a framework for selecting dosing strategies aligned with specific research objectives. Acute KET protocols are particularly suited for addiction research or as a preliminary approach preceding longer-term studies. In contrast, protocols utilizing repeated or sub-chronic, or chronic administration of KET tend to yield more comprehensive models of psychosis-like behavior and are better suited for examining the associated enduring cognitive and neurobiological impairments. Administering KET intravenously or intraperitoneally at frequent intervals or with a bolus dose, may sustain higher levels of bioavailable KET, thereby producing a more robust and reliable psychosis-like phenotype, especially relevant for investigations of long-term cognitive and neurological dysfunction. Full article

Microbial fuel cells (MFCs) have attracted increasing attention due to their potential applications in renewable energy generation, waste utilization, and biomass upgrading, offering a promising alternative to traditional fossil fuels. By directly converting carbon-rich wastes into electricity, MFCs provide a unique approach to simultaneously address energy demand and waste management challenges. This review systematically examines the effects of various carbon-rich substrates on MFC performance, including lignocellulosic biomasses, molasses, lipid waste, crude glycerol, and C1 compounds. These substrates, characterized by wide availability, low cost, and high carbon content, have demonstrated considerable potential for efficient bioelectricity generation and resource recovery. Particular emphasis is placed on the roles of microbial community regulation and genetic engineering strategies in enhancing substrate utilization efficiency and power output. Additionally, the application of carbon-rich wastes in electrode fabrication is discussed, highlighting their contributions to improved electrical conductivity, sustainability, and overall system performance. The integration of carbon-rich substrates into MFCs offers promising prospects for alleviating energy shortages, improving wastewater treatment efficiency, and reducing environmental pollution, thereby supporting the development of a circular bioeconomy. Despite existing challenges related to scalability, operational stability, and system cost, MFCs exhibit strong potential for large-scale implementation across diverse industrial sectors. Full article

The escalating incidence of colorectal cancer (CRC), particularly the alarming rise in early-onset cases, necessitates a paradigm shift from a purely genetic perspective to a broader investigation of promising pathways. This review explores the “nutri-epigenetic” interface, positioning liquid biopsy as a critical technology for translating dietary impacts into actionable clinical biomarkers. We contrast the molecular consequences of the Western dietary pattern, characterized by methyl-donor deficiency and pro-inflammatory metabolites, with the protective mechanisms of the Mediterranean diet. Mechanistically, we detail how Western-style diets drive a specific “epigenetic double-hit”: promoting global DNA hypomethylation (destabilizing LINE-1) while paradoxically inducing promoter hypermethylation of critical tumour suppressors (MLH1, APC, MGMT) and silencing tumour-suppressive microRNAs (miR-34b/c, miR-137) via methylation of their encoding genes. Conversely, we highlight the capacity of Mediterranean bioactive compounds (e.g., resveratrol, curcumin, butyrate) to inhibit DNA methyltransferases and restore epigenetic homeostasis. Bridging molecular biology and clinical utility, we demonstrate how these diet-sensitive signatures, specifically circulating methylated DNA and dysregulated microRNAs, can be captured via liquid biopsy. We propose that these circulating analytes serve as dynamic, accessible biomarkers for monitoring the molecular progression toward a carcinogenic state, thereby establishing a novel framework for personalized risk stratification and validating the efficacy of preventive nutritional strategies. Full article

Background/Objectives: Drug-induced sleep endoscopy (DISE) is used in obstructive sleep apnea (OSA) to visualize dynamic upper airway collapse, but sedation protocols vary widely with no consensus on the optimal agent or technique. This narrative review aims to clarify current sedation strategies for DISE in OSA and their clinical implications. Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Library for English-language publications on DISE sedation (2000–2025). Relevant clinical studies, guidelines, and reviews were included. Data were qualitatively synthesized due to heterogeneity among studies. Results: Sedation approaches in DISE varied considerably. Propofol, dexmedetomidine, and midazolam were the primary agents identified. Propofol provided rapid, titratable sedation but increased airway collapsibility at higher doses; dexmedetomidine produced a more natural sleep-like state with minimal respiratory depression; midazolam was less favored due to prolonged effects. Use of target-controlled infusion (TCI) and pharmacokinetic–pharmacodynamic (PK–PD) models improved control of propofol sedation. Co-sedative adjuncts (e.g., opioids) reduced the required sedative dose but added risk of respiratory depression. Careful titration to the lowest effective dose-often guided by bispectral index (BIS) monitoring—was emphasized to achieve adequate sedation without artifactual airway collapse. No universal DISE sedation protocol was identified. Conclusions: Optimal DISE sedation balances adequate depth with patient safety to ensure reliable findings. Using the minimum effective dose, guided by objective monitoring (e.g., BIS), is recommended. There is a need for standardized sedation protocols and further research (e.g., in obese patients) to resolve current controversies and improve DISE’s utility in OSA management. Full article

Neuroblastoma is a highly aggressive pediatric malignancy originating from neural crest progenitor cells, predominantly in the adrenal medulla. Amplification of the MYCN oncogene occurs in 20–30% of all neuroblastoma cases and approximately 50% of high-risk tumors, strongly correlating with poor prognosis, relapse, and multidrug resistance. MYCN-driven oncogenesis promotes tumor progression by suppressing apoptotic signaling and enhancing survival pathways, including autophagy—a key mechanism underlying resistance to chemotherapy and immunotherapy. This review examines current therapeutic strategies and resistance mechanisms in MYCN-amplified neuroblastoma, while introducing emerging approaches utilizing exosomes as precision drug delivery systems. Exosomes, nanoscale extracellular vesicles secreted by the tumor cells, exhibit natural tropism and can be engineered to selectively target neuroblastoma-specific biomarkers such as glypican-2 (GPC2), which is highly expressed in MYCN-amplified tumors. Leveraging this property, neuroblastoma-derived exosomes can be purified, modified, and loaded with small interfering RNA (siRNA) to silence MYCN expression, combined with chloroquine—an FDA-approved autophagy inhibitor—to simultaneously inhibit autophagy and induce apoptotic signaling. This dual-targeted approach aims to overcome drug resistance, reduce off-target toxicity, and enhance therapeutic efficacy through exosome-mediated specificity. Furthermore, gut dysbiosis has emerged as a critical factor influencing tumor progression and diminishing treatment efficacy in MYCN-amplified neuroblastoma. We propose integrating microbiota-derived exosomes engineered to deliver anti-inflammatory microRNAs (miRNAs) to the gut mucosa, restoring eubiosis and potentiating systemic anti-tumor responses. Collectively, exosome-based strategies represent a paradigm shift in formulating combination therapies, offering a multifaceted approach to target MYCN amplification, inhibit autophagy, induce apoptosis, and modulate the tumor-microbiome axis. These innovations hold significant promise for improving clinical outcomes in high-risk MYCN-amplified neuroblastoma patients. Full article

Food security and income generation remain a critical issue for small-scale farming households in Sub-Saharan Africa (SSA) due to population growth, climate change, and market instability. Indigenous leafy vegetables (ILVs) offer high nutritional value and have the capability to mitigate food insecurity but are underutilized due to social stigma. This review aims to systematically analyze the food and income contribution of cultivation and utilization of ILVs by small-scale farming households in Sub-Saharan Africa. This review analyses the literature on the role of ILV cultivation in enhancing food security and household income over the past two decades. A systematic search across five databases was conducted and identified 53 relevant studies. Findings indicate that ILVs contribute significantly to household nutrition and income through consumption and surplus sales. However, ILV cultivation faces barriers such as climate change, pest infestations, land degradation, water scarcity, insecure land tenure, limited agricultural training, poor communication networks, and restricted market access. Policy interventions are necessary to support small-scale farmers in ILV cultivation by providing agricultural extension services, promoting sustainable farming practices, and integrating ILVs into food security strategies. Further research should examine policy frameworks and supply chain mechanisms to enhance farmer participation and economic benefits from ILV production. Full article

Background and Objectives: Celiac disease (CD) is a major global public health problem that can occur at any age. Pediatric CD can be typical, atypical, or even asymptomatic. Early diagnosis and early initiation of treatment are essential for improving patients’ quality of life and preventing serious complications later in life. However, it is impossible to identify asymptomatic children and adolescents without screening. In this systematic review, we attempted to identify different mass screening programs that have been reported for CD in apparently healthy children and adolescents across the world, to highlight the advantages and disadvantages of such strategies, and to collect and synthesize data from these studies reporting the prevalence of CD. In addition, where data were available, we also attempted to evaluate the diagnostic accuracy of the tests used, their cost-effectiveness, the reported clinical benefits, and follow-up data from individuals identified through screening. Materials and Methods: Electronic databases, including PubMed and Scopus, were systematically searched. Initially, a total of 316 studies were retrieved. Finally, 55 studies met all inclusion criteria and were included in this review. The included studies were published between 1996 and 2023. Results: The reported age of participants ranged from 6 months to 23 years. Confirmation of CD by biopsy was reported in all but six studies. According to the studies that provided data, the (tTG IgA) seroprevalence of CD in apparently healthy children and adolescents, detected through different mass screening methods around the world, ranged from 0.20% (Turkey) to 3.11% (Italy). In addition, the prevalence of biopsy-confirmed CD ranged from 0.036% (Vietnam) to 3% (Sweden and Spain). Studies from 17 countries reported mass screening strategies based on finger-prick rapid tests. All rapid tests detected CD antibodies, except two, which detected HLA DQ2/DQ8 haplotypes. Rapid tests appeared to be no less sensitive and specific than other screening tests for CD and were probably less expensive, but further studies are needed for more reliable conclusions. Of the 55 studies in the review, only 10 reported follow-up data. After 3 months of a gluten-free diet, the general condition of the patients improved; after 6 months, tTG IgA and EMA IgA levels decreased and hemoglobin values increased; while after 1 year, tTG IgG levels also decreased, symptoms subsided, the children’s weight and height increased, school performance improved, episodes of upper respiratory tract infections decreased, and thyreoperoxidase antibodies that were positive at screening became negative. Conclusions: Mass screening for CD in asymptomatic children and adolescents is a challenge. Future research should provide more answers regarding the most appropriate target age, the frequency of screening, the optimal screening method, the cost-effectiveness, the clinical utility, and the long-term impact of mass screening on patients’ quality of life. Full article

Asparagine synthetase (AS) is a key enzyme in plant nitrogen metabolic network. Beyond its canonical role as a major nitrogen transport and storage molecule, asparagine also serves critical functions in plant immunity and tolerance to environmental stresses. This review systematically summarizes the characteristics of the core AS-mediated asparagine biosynthesis pathway and two other minor pathways in plants. It details the distribution of the AS gene family, protein structure, and evolutionary classification. The mechanisms governing AS expression are analyzed, revealing tissue-specific patterns and precise regulation by nitrogen availability, abiotic stresses, and exogenous hormones, mediated through an interactive network of cis-acting elements and transcription factors. Furthermore, the biological functions of AS are multifaceted: it influences plant biomass and nitrogen use efficiency by regulating nitrogen uptake, transport, and recycling during growth and development; it contributes to abiotic stress tolerance by synthesizing asparagine to maintain cellular osmotic balance and scavenge reactive oxygen species; and it indirectly enhances antibacterial and antiviral capacity by activating the SA signaling pathway and modulating programmed cell death. Current knowledge gaps remain regarding the crosstalk between AS-mediated signaling pathways, the upstream transcriptional regulatory network, and the balance between nitrogen utilization and disease resistance in crop breeding. Future research aimed at addressing these questions will provide a theoretical foundation and molecular targets for improving crop nitrogen use efficiency and breeding resistant cultivars. Full article

Globally, grasslands, savannas, and wetlands are degrading rapidly and increasingly being replaced by woody vegetation. Woody Plant Encroachment (WPE) disrupts natural landscapes and has significant consequences for biodiversity, ecosystem functioning, and key ecosystem services. This review synthesizes findings from 159 peer-reviewed studies identified through a PRISMA-guided systematic literature review to evaluate the drivers of WPE, its ecological impacts, and the remote sensing (RS) approaches used to monitor it. The drivers of WPE are multifaceted, involving interactions among climate variability, topographic and edaphic conditions, hydrological change, land use transitions, and altered fire and grazing regimes, while its impacts are similarly diverse, influencing land cover structure, water and nutrient cycles, carbon and nitrogen dynamics, and broader implications for ecosystem resilience. Over the past two decades, RS has become central to WPE monitoring, with studies employing classification techniques, spectral mixture analysis, object-based image analysis, change detection, thresholding, landscape pattern and fragmentation metrics, and increasingly, machine learning and deep learning methods. Looking forward, emerging advances such as multi-sensor fusion (optical– synthetic aperture radar (SAR), Light Detection and Ranging (LiDAR)–hyperspectral), cloud-based platforms including Google Earth Engine, Microsoft Planetary Computer, and Digital Earth, and geospatial foundation models offer new opportunities for scalable, automated, and long-term monitoring. Despite these innovations, challenges remain in detecting early-stage encroachment, subcanopy woody growth, and species-specific patterns across heterogeneous landscapes. Key knowledge gaps highlighted in this review include the need for long-term monitoring frameworks, improved socio-ecological integration, species- and ecosystem-specific RS approaches, better utilization of SAR, and broader adoption of analysis-ready data and open-source platforms. Addressing these gaps will enable more effective, context-specific strategies to monitor, manage, and mitigate WPE in rapidly changing environments. 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

Accurately assessing the glomerular filtration rate (GFR) is critical in patients with cancer for acute kidney injury diagnosis, chemotherapy selection, drug dosing, and clinical trial eligibility. Yet, traditional equations such as Cockcroft–Gault and MDRD fail due to multiple physiological changes specific to this vulnerable population. Cancer-related sarcopenia, creatinine secretion blockade, and total body volume fluctuations may lead to inaccurate GFR estimations. This ultimately leads to undertreatment of underlying malignancy, overdosing of nephrotoxic therapies with adverse effects, and excluding patients from clinical trials unnecessarily. The 2024 KDIGO guidelines as well as the American Society of Onconephrology position statement recommend the use of combined GFR equation such as CKD-EPI 2021 that utilizes both cystatin C and creatinine to improve GFR estimation accuracy. Direct GFR measurement via exogenous filtration markers should be pursued in high-risk patients when precise values are warranted. This review highlights current challenges associated with GFR evaluation in patients with cancer and outlines clinical implications as well as recent recommendations for optimal clinical practice. Full article

Growth charts are widely used as a clinical and research tool to assess physical growth performance of infants, children, and adolescents. They have been widely accepted as indicators of health and wellness. CDC and WHO growth charts are well known and used for tracking childhood growth. The differences between WHO and CDC growth curves are largely attributable to distinct reference population and curve construction methodologies. The aim of this review is to focus on the construction, utilization, as well as clinical significance of the CDC and WHO growth charts. Full article