Search Results (3,016)

Meningiomas are the most common primary intracranial tumors, showing highly heterogeneous behavior and clinical outcomes. While the majority are benign, about one in five meningiomas are classified as higher grade (WHO Grade II–III), characterized by a more aggressive, treatment-resistant pathology. Although surgical resection remains the first-line therapy, peptide receptor radionuclide therapy is emerging as a novel and promising option for advanced, multifocal, or recurrent disease. The theranostic paradigm allows simultaneous detection and treatment of somatostatin receptor-expressing lesions using a single radiopharmaceutical. In this review, we explore the evolving role of PRRT in the management of meningiomas. We provide an integrated overview of preclinical findings—including radiosensitization mechanisms—and summarize the rapidly expanding clinical literature, which in recent years has grown both in patient numbers and in methodological sophistication. Particular emphasis is placed on advances in dosimetry, quantitative imaging, and radiomics, which are beginning to refine patient selection and improve response prediction. Together, current evidence highlights the therapeutic potential of radionuclide therapy in aggressive or refractory meningiomas and underscores the need for further prospective trials to define its optimal clinical application. Full article

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition that progressively impairs cognitive processes, particularly learning and memory. A key pathological feature of AD involves senile plaques mainly composed of β-amyloid (Aβ) peptides, generated via the amyloidogenic pathway from amyloid precursor protein (APP) through sequential β-secretase (BACE1) and γ-secretase cleavage, positioning BACE1 inhibition as a prime therapeutic target. In this study, we applied bioassay-guided fractionation of the butanol-soluble fraction from Dryopteris crassirhizoma rhizomes, previously reported to inhibit Aβ production, to isolate and characterize Aβ-lowering constituents. Through successive chromatographic steps, nine compounds were isolated and structurally classified into flavonoids, chromones, and phloroglucinols, including epicatechin (1), β-carboxymethyl-(-)-epicatechin (2), 7-methoxy-isobiflorin (3), biflorin (4), eriodictyol (5), noreugenin (6), phloroglucinols (butyrylphloroglucinol (7), 2-propionyl-4-methylphloroglucinol (8), and 2-butyryl-4-methylphloroglucinol (9) by comprehensive spectroscopic analysis (NMR, MS, UV, IR). These compounds were assessed for effects on sAPPβ and BACE1 (β-secretase) levels by Western blot, with Aβ production quantified via ELISA in a cellular AD model (APP-CHO cells). Compounds 5–9 significantly reduced sAPPβ and BACE1 expression while potently suppressing Aβ generation. These results demonstrate that diverse constituents from D. crassirhizoma rhizomes inhibited Aβ production through BACE1 suppression, highlighting their potential as natural lead compounds for AD prevention or therapy. Full article

Background and Clinical Significance: Overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in children is a rare but life-threatening metabolic emergency. The coexistence of hyperosmolality and ketoacidosis increases neurologic vulnerability and complicates fluid and insulin management. Early identification and osmolality-guided therapy are essential to prevent cerebral edema and other complications. This case describes a 5-year-old boy with new-onset type 1 diabetes mellitus (T1D) presenting with DKA/HHS overlap two weeks after influenza vaccination—an unusual temporal association without proven causality. Case Presentation: A previously healthy 5-year-old presented with progressive polyuria, polydipsia, nocturnal enuresis, fatigue, and drowsiness. Two weeks earlier, he had received the influenza vaccine. Examination revealed moderate dehydration without Kussmaul respiration or altered consciousness. Laboratory evaluation showed glucose 45.9 mmol/L (826 mg/dL; reference 3.9–7.8 mmol/L), venous pH 7.29 (reference 7.35–7.45), bicarbonate 12 mmol/L (reference 22–26 mmol/L), moderate ketonuria, and measured serum osmolality 344 mOsm/kg (reference 275–295 mOsm/kg), fulfilling diagnostic criteria for DKA/HHS overlap. After an initial 20 mL/kg 0.9% NaCl bolus, fluids were adjusted to maintenance plus approximately 10% deficit using 0.45–0.75% NaCl according to sodium/osmolality trajectory. Intravenous insulin (approximately 0.03–0.05 IU/kg/h) was initiated once blood glucose no longer decreased adequately with fluids alone and had stabilized near 22.4 mmol/L (≈400 mg/dL). Dextrose was added when glucose reached 13.9 mmol/L (250 mg/dL) to avoid rapid osmolar shifts. Hourly neurological and biochemical monitoring ensured a glucose decline of 2.8–4.2 mmol/L/h (50–75 mg/dL/h) and osmolality decrease ≤3 mOsm/kg/h. The patient recovered fully without cerebral edema or neurologic sequelae. IA-2 antibody positivity with low C-peptide and markedly elevated HbA1c confirmed new-onset T1D. Conclusions: This case highlights the diagnostic and therapeutic challenges of pediatric DKA/HHS overlap. Osmolality-based management, conservative insulin initiation, and vigilant monitoring are crucial for preventing complications. The temporal proximity to influenza vaccination remains incidental. Full article

Glucagon-like peptide-1 (GLP-1) is an incretin hormone and therapeutic agent for Type II diabetes mellitus. However, recombinant production in E. coli yields insufficient quantities, increasing manufacturing costs and limiting patient access. Improving yield and productivity is crucial to make GLP-1 treatments more affordable. An optimized bioprocess was developed to enhance the yield of recombinant GLP-1 (rGLP-1) analogues. Expression constructs encoding monomeric and concatemeric GLP-1 fused to GST were designed. Batch fermentations of these clones at varying pre-induction specific growth rates guided the fed-batch strategy for yield enhancement. The specific yield of monomer construct exhibited higher yields than the concatemer. Process optimization achieved a specific yield (Yp/x) of 116.7 mg/g, a dry cell weight of 88.9 g/L, and a volumetric yield of 10.3 g/L. The specific productivity of soluble rGLP-1 reached 0.4 g/L/h. Purification via affinity chromatography and enterokinase cleavage yielded authentic GLP-1 peptide confirmed by Western blot and mass spectrometry. The developed high-yield fermentation process significantly enhances rGLP-1 productivity in E. coli, potentially reducing upstream production costs by 20–30% and enabling wider accessibility to affordable GLP-1 therapies. Full article

Epigenetics involves heritable changes in gene expression—such as DNA methylation (5-methylcytosine; 5mC), histone modifications, and regulation by non-coding RNAs at the mRNA translation level—without altering the underlying DNA sequence. As targeting these mechanisms enables intervention at the root cause of disease rather than the symptoms alone, epigenetics has become a rapidly advancing field in pharmaceutical sciences. Various epigenetic modulators, including histone deacetylase (HDAC) inhibitors, histone acetyltransferase (HAT) inhibitors, DNA methyltransferase (DNMT) inhibitors, and microRNAs (miRNAs), have been developed, and some have already been approved for cancer therapy. However, these agents often face significant challenges such as poor membrane permeability, enzymatic instability, and suboptimal biodistribution. Incorporating functionalized accessory units—serving as vectors (e.g., transporter recognition units, cell-penetrating peptides, tumor-homing peptides, monoclonal antibodies) or as carriers (e.g., monoclonal antibodies, nanoparticles)—into epigenetic modulators may help overcome these delivery barriers. In this narrative review, I discuss the potential and advantages of effective non-invasive delivery of epigenetic drugs using such functionalized accessory unit conjugates. Full article

Peptide arrays represent a powerful tool for investigating a wide application field for biomedical questions. This review summarizes recent applications of peptide chips in oncology, with a focus on tumor microenvironment, metastasis, and drug mechanism of action for various cancer types. These high-throughput platforms enable the simultaneous screening of thousands of peptides. We report on recent achievements in peptide array technology for tumor microenvironments, an enhanced ability to decipher complex cancer-related signaling pathways, and characterization of cell-adhesion-mediating peptides. Furthermore, we highlight the applications in high-throughput drug screenings for development of immune therapies, e.g., the development of novel neoantigen therapies of glioblastoma. Moreover, epigenetic profiling using peptide arrays has uncovered new therapeutic targets across various cancer types with clinical impact. In conclusion, we discuss artificial intelligence-driven peptide array analysis as a tool to determine tumor origin and metastatic state, potentially transforming diagnostic approaches. These innovations promise to accelerate the development of precision cancer approaches. Full article

Pseudomonas aeruginosa is a resilient Gram-negative pathogen frequently implicated in healthcare associated infections, particularly among immunocompromised individuals and those with chronic conditions such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), or cancer. It is well known for its high resistance to antibiotic treatment. This review briefly mentions P. aeruginosa’s resistance mechanisms, biofilm formation, and virulence factors, while primarily focusing on treatment challenges and recent advancements in therapeutic strategies aimed at overcoming resistance. Covered are novel non-antibiotic interventions such as quorum sensing inhibitors, quorum quenching agents, iron chelators, lectin and efflux pump inhibitors, as well as antimicrobial peptides and nanoparticles. Traditional medicine, phytochemicals, and probiotics are also evaluated. Additionally, this review explores the development of a viable vaccine, bacteriophage therapy, lactoferrin-hypothiocyanite combination, and topical use of electrochemical scaffolds. This review emphasizes the need for extensive safety studies and in vivo validation of these emerging non-antibiotic therapeutic strategies to determine their efficacy, pharmacological behavior, and clinical feasibility before they can be translated into practice. Many of these emerging treatments could play a vital role in future combination therapies by enhancing the efficacy of existing antibiotics and countering resistance and virulence mechanisms. Advancing these approaches from laboratory to clinical application remains a major challenge, making the development of approved therapies or vaccines a critical scientific and public health priority. Full article

The increasing problem of antibiotic resistance is a critical global health issue, necessitating the development of alternative therapeutic strategies to manage infections effectively. Among the promising solutions are human antimicrobial peptides (AMPs), naturally occurring molecules known for their broad spectrum of antimicrobial activity. Background/Objectives: This study investigates the potential of some AMPs, selected through a bioinformatic approach, as alternatives to conventional antibiotics, particularly focusing on their efficacy against species within the Bacteroidota phylum. These species, including pathogens such as Porphyromonas gingivalis, Capnocytophaga ochracea, and Capnocytophaga canimorsus, are well known for their roles in various human infections and related diseases. Non-pathogenic environmental species, such as Flavobacterium johnsoniae, are also included in this group, frequently used as a model organism. Methods: By analyzing the antimicrobial efficacy, mechanisms of action, and potential therapeutic applications of human AMPs, this research underscores their significance in addressing the challenge of antibiotic resistance. Results: This study identified three peptides, KTL24, LIR23, and MFP22, as particularly interesting. These peptides are derived from specific human proteins, namely SPI1, NAPSA and SCUB1. Conclusions: Their notable antimicrobial potential suggests that AMPs could serve either as a complementary treatment alongside traditional antibiotics or as a standalone therapy, mitigating the ongoing spread of antibiotic resistance and offering an alternative in global health strategies. Full article

Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe form of pulmonary hypertension with poor prognosis. It most commonly arises in systemic sclerosis (SSc), followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Its pathogenesis involves a complex interplay of immune dysregulation, chronic inflammation, endothelial injury, vascular remodeling, and fibrosis. Although vasodilators targeting the endothelin, nitric oxide, and prostacyclin pathways remain the therapeutic backbone, newer agents—including the activin signal inhibitor sotatercept and inhaled treprostinil—have expanded treatment options. Immune-targeted therapies such as glucocorticoids, cyclophosphamide, mycophenolate mofetil, rituximab, and IL-6 receptor inhibitors may benefit inflammation-dominant PAH phenotypes, while fibrotic phenotypes continue to demonstrate limited responsiveness. In addition to brain natriuretic peptide (BNP), N-terminal (NT)-proBNP and disease-specific autoantibodies, emerging biomarkers show promise for early detection, risk stratification, and personalized treatment, though validation in CTD-PAH is lacking. Advances in animal models replicating immune-mediated vascular injury and fibrosis have further improved mechanistic understanding. Despite these developments, substantial unmet needs remain, including the absence of disease-specific therapeutic strategies, limited biomarker integration into clinical practice, and a scarcity of large, well-designed trials targeting individual CTD subtypes. Addressing these gaps will be essential for improving prognosis in patients with CTD-PAH. Full article

Heart failure (HF) remains a major cause of morbidity and mortality worldwide, with its prevalence continuing to rise due to an aging population and the increasing burden of cardiometabolic diseases. Advances in understanding HF pathophysiology—neurohormonal, inflammatory, and metabolic mechanisms—have led to significant improvements in diagnosis and management, emphasizing earlier detection and patient-centered approaches. Novel biomarkers have the potential to enhance risk assessment beyond traditional natriuretic peptides. Imaging advances can enhance structural and functional assessment, enabling more accurate phenotyping, disease characterization, and risk stratification. Recent advances and real-world data have been used to implement and optimize guideline-directed medical therapy (GDMT) for HF to reduce HF hospitalizations and cardiovascular mortality across the spectrum of HF etiologies. Adjunctive therapies are reserved for select patients with persistent symptoms or high-risk features despite optimal GDMT. Device- and transcatheter-based interventions include established and emerging technologies that address persistent symptoms, structural abnormalities, and hemodynamic abnormalities despite optimal GDMT, thereby expanding treatment options for high-risk patients. Collectively, these advancements highlight a paradigm shift toward precise, personalized approaches to HF management, thereby improving long-term outcomes across the spectrum of HF etiologies. Full article

Women of reproductive age, especially those with polycystic ovarian syndrome (PCOS), often use glucagon-like peptide-1 receptor agonists (GLP-1RAs) to improve their metabolic functions. A growing body of evidence suggests that GLP-1R signaling may directly affect ovarian physiology, influencing granulosa cell proliferation, survival pathways, and steroidogenic production, in addition to its systemic metabolic effects. Nonetheless, there is a limited comprehension of the molecular mechanisms that regulate these activities and their correlation with menstrual function, reproductive potential, and assisted reproduction. This comprehensive review focuses on ovarian biology, granulosa cell signaling networks, steroidogenesis, and translational fertility outcomes, integrating clinical, in vivo, and in vitro information to elucidate the effects of GLP-1 receptor agonists on reproductive health. We conducted a thorough search of PubMed, Scopus, and Web of Science for randomized trials, prospective studies, animal models, and cellular experiments evaluating the effects of GLP-1RA on reproductive or ovarian outcomes, in accordance with PRISMA criteria. The retrieved data included metabolic changes, androgen levels, monthly regularity, ovarian structure, granulosa cell growth and death, FOXO1 signaling, FSH-cAMP-BMP pathway activity, and fertility or IVF results. Clinical trials shown that GLP-1 receptor agonists improve menstrual regularity, decrease body weight and central adiposity, increase sex hormone-binding globulin levels, and lower free testosterone in overweight and obese women with PCOS. Liraglutide, when combined with metformin, significantly improved IVF pregnancy rates, whereas exenatide increased natural conception rates. Mechanistic studies demonstrate that GLP-1R activation affects FOXO1 phosphorylation, hence promoting granulosa cell proliferation and anti-apoptotic processes. Incretin signaling altered steroidogenesis by reducing the levels of StAR, P450scc, and 3β-HSD, so inhibiting FSH-induced progesterone synthesis, while simultaneously enhancing BMP-Smad signaling. Animal studies demonstrated both beneficial (enhanced follicular growth, anti-apoptotic effects) and detrimental results (oxidative stress, granulosa cell death, uterine inflammation), indicating a context- and dose-dependent response. GLP-1 receptor agonists influence female reproductive biology by altering overall physiological processes and specifically impacting the ovaries via FOXO1 regulation, steroidogenic enzyme expression, and BMP-mediated FSH signaling. Preliminary clinical data indicate improved reproductive function in PCOS, as seen by increased pregnancy rates in both natural and IVF cycles; nevertheless, animal studies reveal a potential risk of ovarian and endometrial damage. These results highlight the need for controlled human research to clarify reproductive safety, molecular pathways, and optimum therapy timing, particularly in non-PCOS patients and IVF settings. Full article

Background/Objective: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have received widespread attention as effective obesity treatments. However, limited research has examined the perspectives of patients contemplating GLP-1RAs. This study explored perceptions, motivations, and barriers among individuals considering GLP-1RA therapy for obesity treatment, with the goal of informing patient-centered care and enhancing clinician engagement. Methods: Adults completed surveys and interviews between June and November 2025. In this pragmatic mixed-methods study, both survey and interview questions explored perceived benefits, barriers, and decision-making processes. Qualitative data, describing themes based on the Health Belief Model, were analyzed using Dedoose (version 9.0.107), and quantitative data were analyzed using SAS (version 9.4). Participant characteristics included marital status, income, educational attainment, employment status, insurance status, age, race/ethnicity, and sex. Anticipated length on GLP-1RA medication and selected self-reported health conditions (depression, anxiety, hypertension, heart disease, back pain, joint pain), reported physical activity level, and perceived weight loss competency were also recorded. Results: Among the 31 non-diabetic participants who were considering GLP-1RA medication for weight loss, cost emerged as the most significant barrier. Life course events, particularly (peri)menopause among women over 44, were commonly cited as contributors to weight gain. Participants expressed uncertainty about eligibility, long-term safety, and treatment expectations. Communication gaps were evident, as few participants initiated discussions and clinician outreach was rare, reflecting limited awareness and discomfort around the topic. Conclusions: Findings highlight that individuals considering GLP-1RA therapy face multifaceted emotional, financial, and informational barriers. Proactive, empathetic clinician engagement, through validation of prior efforts, clear communication of risks and benefits, and correction of misconceptions, can support informed decision-making and align treatment with patient goals. Full article

Obesity has reached epidemic proportions, driven by energy imbalance and limited capacity for adaptive thermogenesis. Brown (BAT) and beige adipose tissues dissipate energy through non-shivering thermogenesis (NST), primarily via uncoupling protein-1 (UCP1), making them attractive targets for increasing energy expenditure (EE). The canonical β-adrenergic pathway robustly activates NST in rodents through β3 adrenoceptors; however, translational success in humans has been limited by low β3 expression, off-target cardiovascular effects, and the emerging dominance of β2-mediated signaling in human BAT. Consequently, attention has shifted to non-adrenergic and UCP1-independent mechanisms that offer greater tissue distribution and improved safety profiles. This review examines a broad spectrum of alternative receptors and pathways—including GPRs, TRP channels, TGR5, GLP-1R, thyroid hormone receptors, estrogen receptors, growth hormone, BMPs, sirtuins, PPARs, and interleukin signaling—as well as futile substrate cycles (Ca²⁺, creatine, and glycerol-3-phosphate) that sustain thermogenesis in beige adipocytes and skeletal muscle. Pharmacological agents (natural compounds, peptides, and small molecules) and non-pharmacological interventions (cold exposure, exercise, diet, and time shift) targeting these pathways are critically evaluated. We highlight the translational gaps between rodent and human studies, the promise of multimodal therapies combining low-dose adrenergic agents with non-adrenergic activators, and emerging strategies such as sarco/endoplasmic reticulum calcium ATPase protein (SERCA) modulators and tissue-specific delivery. Ultimately, integrating adrenergic and non-adrenergic approaches holds the greatest potential for safe, effective, and sustainable obesity management. Full article

The growing global threat of antimicrobial resistance (AMR), particularly in cutaneous wound infections, represents a significant clinical and economic challenge. Biofilm formation by multidrug-resistant pathogens, such as Acinetobacter baumannii, often complicates healing and leads to therapeutic failure. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics due to their potent membrane-disrupting mechanism of action and lower propensity to induce resistance. Background/Objectives: This study aimed to evaluate the antibacterial, antibiofilm, and in vivo efficacy of four snake venom-derived cathelicidin-like peptides—Btn (15-34) and BotrAMP14 from Bothrops atrox, and Ctn (15-34) and CrotAMP14 from Crotalus durissus—against multidrug-resistant A. baumannii, Escherichia coli, and Pseudomonas aeruginosa clinical isolates from skin infections, with emphasis on A. baumannii, a WHO priority pathogen. Methods: Minimal Inhibitory Concentration (MIC), Minimal Bactericidal Concentration (MBC), and Minimal Biofilm Inhibitory Concentration (MBIC) were determined against A. baumannii, Escherichia coli, and Pseudomonas aeruginosa. Time-kill kinetics, hemolytic activity, and cytotoxicity assays were performed. A murine skin wound infection model was established to evaluate in vivo antibacterial efficacy and safety. Results: MIC/MBC values ranged from 0.78 to 25 µM against planktonic cells. In comparison, MBIC ranged from 1.56 to 12.5 µM against biofilms. BotrAMP14 eradicated A. baumannii within 4 min, while CrotAMP14 achieved bactericidal action in 20 min at 1.56 µM. Both peptides exhibited no hemolytic activity up to 128 µM and low cytotoxicity (IC₅₀ > 128 µM). In vivo, BotrAMP14 and CrotAMP14 demonstrated significant antibacterial activity at 24 h and 48 h post-infection, respectively, surpassing that of meropenem. Conclusions: These findings suggest that BotrAMP14 and CrotAMP14 are promising topical antimicrobial agents for managing multidrug-resistant skin infections and may help address the urgent need for alternative therapies against antibiotic-resistant pathogens. Full article

Artificial intelligence (AI) and machine learning (ML) are reshaping cancer research and care. In pediatric oncology, early evidence—most robust in imaging—suggests value for diagnosis, risk stratification, and assessment of treatment response. Pediatric endocrine tumors are rare and heterogeneous, including intra- and extra-adrenal paraganglioma (PGL), adrenocortical tumors (ACT), differentiated and medullary thyroid carcinoma (DTC/MTC), and gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). Here, we provide a pediatric-first, entity-structured synthesis of AI/ML applications in endocrine tumors, paired with a methods-for-clinicians primer and a pediatric endocrine tumor guardrails checklist mapped to contemporary reporting/evaluation standards. We also outline a realistic EU-anchored roadmap for translation that leverages existing infrastructures (EXPeRT, ERN PaedCan). We find promising—yet preliminary—signals for early non-remission/recurrence modeling in pediatric DTC and interpretable survival prediction in pediatric ACT. For PGL and GEP-NEN, evidence remains adult-led (biochemical ML screening scores; CT/PET radiomics for metastatic risk or peptide receptor radionuclide therapy response) and serves primarily as methodological scaffolding for pediatrics. Cross-cutting insights include the centrality of calibration and validation hierarchy and the current limits of explainability (radiomics texture semantics; saliency ≠ mechanism). Translation is constrained by small datasets, domain shift across age groups and sites, limited external validation, and evolving regulatory expectations. We close with pragmatic, clinically anchored steps—benchmarks, multi-site pediatric validation, genotype-aware evaluation, and equity monitoring—to accelerate safe, equitable adoption in pediatric endocrine oncology. Full article