Search Results (43,001)

Extracellular vesicles (EVs), as key mediators of intercellular communication, play multifaceted roles in the pathogenesis, treatment, drug resistance, and monitoring of B-cell non-Hodgkin lymphomas (B-NHLs), including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). EVs derived from lymphoma cells or tumor microenvironment cells carry diverse cargoes such as proteins, microRNAs (miRNAs), and viral oncoproteins, which regulate tumor progression by modulating signaling pathways related to cell proliferation, invasion, apoptosis, autophagy, and immune suppression. In terms of treatment, accumulating evidence suggests that EVs may be associated with the efficacy of classical regimens such as R-CHOP, and they also hold potential as therapeutic targets and drug delivery vehicles for B-NHL. They contribute to drug resistance by altering the expression of key molecules or reshaping the tumor niche. Additionally, EV-derived biomarkers enable non-invasive diagnosis and monitoring of treatment response and prognosis. This review summarizes the latest research progress on the roles of EVs in major B-NHL subtypes, aiming to provide new insights for the development of innovative diagnostic and therapeutic strategies for B-NHL. Full article

The optimization of membrane permeability is a pivotal approach for mitigating late-stage failures in peptide drug development. By leveraging linker chemical diversity, stapled peptides utilize linker engineering to precisely modulate key physicochemical parameters—such as lipophilicity and conformational constraints—to overcome the desolvation energy penalty. This review systematically evaluates linker-based strategies for enhancing the permeability of stapled peptides, categorized into two primary dimensions: (1) high-throughput screening (HTS) compatibility, focusing on the integration of functionalized linkers into mRNA display, phage display, and DNA-encoded libraries (DELs) to identify lead scaffolds with inherent permeability potential during early discovery; and (2) post-screening structural refinement, covering rational design strategies including intramolecular hydrogen-bond (IMHB) shielding, “chameleonic” adaptations, and stimuli-responsive reversible stapling. Furthermore, we analyze the paradigm shift in assessment methodologies from qualitative imaging to quantitative cytosolic delivery assays, which have deepened our understanding of mechanisms such as the charge/lipophilicity threshold balance and metabolism-driven trapping. Overall, linker engineering provides a robust technical roadmap for developing the next generation of cell-permeable stapled peptide therapeutics. Full article

Background/Objectives: Ginger has a long history as both a culinary and medicinal plant and is widely recognized in traditional medicine for its ability to promote health and well-being. The principal bioactive compounds of ginger are present in fresh and dried forms and have been largely studied for their therapeutic potential. These compounds exhibit a wide range of biological activities mediated through various mechanisms. Advances in nanotechnology have enabled the development of innovative delivery systems, thereby enhancing the bioavailability and therapeutic efficacy of ginger-derived compounds in modern medical applications. Methods: A comprehensive literature review was conducted to evaluate the characteristics of ginger and its potential role in disease prevention. Relevant studies were identified through the main research databases, publication screening, manual reference checks, and author consensus was conducted. Results: This narrative review provides an overview of the therapeutic potential of bioactive compounds in ginger for the management and prevention of cardiovascular, arthritis, neurodegenerative, and gastrointestinal diseases, with particular emphasis on the molecular mechanisms. In addition, their potential anti-aging properties are extensively discussed. The evidence reported is predominantly preclinical (in vitro and in vivo models), with more limited and heterogeneous clinical data. Recent studies have also highlighted the role of artificial intelligence (AI) in accelerating the discovery and evaluation of bioactive agents with therapeutic relevance across diverse biological systems. Conclusions: This review highlights the emerging applications of ginger extracts in human health and suggests their applications in both traditional medicine and contemporary drug discovery. Full article

Background: The phase of electroencephalogram (EEG) signals critically influences cortical reactivity to external inputs. Phase-dependent effects and their sensitivity to stimulation intensity have been observed at suprathreshold levels, while subthreshold transcranial magnetic stimulation (TMS) cannot induce motor evoked potentials (MEPs), resulting in limited research on phase-dependent responses under subthreshold stimulation. In this study, we used a combined transcranial magnetic stimulation and electroencephalography (TMS–EEG) approach to examine how the ongoing EEG phase influences cortical responses at subthreshold intensity and to characterize these responses in terms of temporal, spatial, and spectral features. Methods: Thirty-four healthy adults received subthreshold single-pulse TMS at the motor hotspot during 64-channel EEG recording. The mu-phase at the time of TMS delivery was estimated using autoregression-based forward prediction and categorized into four bins (0°, 90°, 180°, and 270°). The cortical responses were assessed using inter-trial phase coherence (ITPC), TMS-evoked potentials (TEPs), global mean field power (GMFP), and event-related spectral perturbation (ERSP). Results: Phase estimation reliably distinguished four mu-phase bins. Subthreshold TMS–EEG responses showed clear phase dependence: early ITPC and several TEP components (N15, P30, N45, P60, and N100) differed significantly across phases, with 180° and 270° often eliciting stronger responses. GMFP revealed robust phase effects at mid-latency components, and TMS-induced mu-rhythms were the greatest at 180°. Conclusions: Our results showed that the EEG phase significantly modulates cortical reactivity at subthreshold stimulation levels, supporting mu-phase-based closed-loop TMS as a promising strategy for precise neuromodulation. Full article

Olive mill wastewater (OMW) is an agro-industrial byproduct rich in polyphenols and other bioactive compounds with documented antioxidant and antimicrobial properties. In this study, purified OMW fractions (RO1 and MD2), previously characterized by high polyphenol content and strong antioxidant activity, were incorporated (10% w/w) into cellulose-based hydrogels intended for topical application. Hydrogels were prepared using carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), and methylcellulose (MC) at concentrations of 1.5–2.0% (w/w). The formulations were characterized in terms of organoleptic properties, pH, rheological behavior, swelling capacity, weight loss, antioxidant activity (DPPH assay), and microbiological activity against selected skin pathogens, including antibiotic-resistant strains. Rheological analysis confirmed pseudoplastic behavior suitable for topical administration. OMW-loaded hydrogels exhibited significant radical scavenging activity compared to blank formulations and demonstrated antimicrobial efficacy, supporting the preservation of OMW bioactivity within the polymeric network. The results highlight the potential of cellulose-based hydrogels as sustainable and biocompatible carriers for the valorization of OMW in dermatological applications, particularly for the management of oxidative stress and bacterial skin infections. Full article

Introduction: Acute gallstone pancreatitis is a potentially severe disease associated with morbidity and mortality. Cholecystectomy is recommended to prevent recurrence. During pregnancy, surgical management is challenging, and in the post-partum period small gallstones may spontaneously disappear. Ursodeoxycholic acid (UDCA) is safe during the last 6 months of pregnancy and effective in dissolving small gallstones, although recurrence after discontinuation is common in the general population. The optimal strategy to prevent recurrent acute pancreatitis during and after pregnancy remains unclear. Methods: Between 2002 and 2017 we prospectively treated women with acute pancreatitis related to small gallstones (≤1 cm in diameter) during the last six months of pregnancy or within the first post-partum year who declined surgery. Patients received UDCA until stone dissolution. A patent cystic duct was confirmed by ultrasonography; after delivery, a non-contrast CT scan was performed to exclude calcified stones. Patients were followed for at least 6 years or until recurrence, with serial clinical and ultrasonographic examinations. Results: UDCA was associated with complete dissolution in 13/14 women within a mean ± SD of 7.77 + 3.1 months. One patient experienced gallstone recurrence 75 months after treatment discontinuation. Two patients developed recurrent pancreatitis (at 1 and 88 months respectively). Twelve women remained free of recurrence over a mean ± SD follow-up of 79.5 + 9.4 months. Discussion: This is an observational study in which we document that UDCA may facilitate the spontaneous dissolution of small gallstones after delivery and can be considered a bridge strategy during pregnancy when surgery is not feasible. However, this study cannot determine the additional benefit of UDCA over the spontaneous disappearance of stones observed after delivery because we had no control group. Cholecystectomy remains the standard of care post-partum. Medical therapy should be reserved for women who refuse surgery and it requires close ultrasonographic surveillance. The main strength of this study is the prospective long-term follow-up of a consecutive cohort with a rare condition. Limitations include the small sample size, missing control group and single-center design. Full article

HER2-low breast cancer, also known as IHC 1+ or IHC 2+ without ERBB2 amplification, is a new concept in the biology of breast cancer that has removed the binary classification of HER2-positive or HER2-negative breast cancer. The recent introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd), has improved therapeutic outcomes for HER2-low breast cancer by demonstrating high efficacy in HER2-low tumors through efficient payload delivery. However, differences in ADC efficacy exist among HER2-low breast cancer patients, with tumor cells showing resistance to ADCs. Recent research indicates that the tumor microenvironment (TME) plays a critical role in determining the efficacy of ADCs against tumor cells. TME creates a barrier to the delivery of ADCs to tumor cells that show resistance to ADCs. This review article aims to highlight the current understanding of the biology of HER2-low breast cancer and its response to ADCs with reference to the tumor microenvironment. Full article

Groundwater contamination caused by dense non-aqueous phase liquid (DNAPL) has long been recognized as a persistent environmental challenge, particularly in fractured porous media. DNAPL migration is highly uncertain due to the heterogeneity and complexity of fracture networks, which complicates risk assessment and remediation design. This paper begins with an overview of mathematical models for multiphase flow migration in fractured media, followed by a systematic analysis and classification of DNAPL migration mechanisms based on laboratory experiments and numerical simulations. Subsequently, key challenges in current DNAPL remediation practices are discussed, including difficulties in monitoring and characterizing fractured aquifers, limited delivery and utilization efficiency of remedial agents, and the back-diffusion of DNAPL from low-permeability zones. Based on this analysis, three primary DNAPL remediation approaches—physical, chemical, and biological methods—are reviewed and evaluated. Finally, future research directions for understanding DNAPL migration and improving remediation strategies in fractured media are proposed. Overall, this review bridges mechanistic knowledge, simulation research, and remediation practice, providing insights that contribute to future technological progress and management decision-making in DNAPL-contaminated fractured aquifers. Full article

This study examines the role of Paradoxical Leadership (PL) in enhancing sustainable service performance in Egypt’s hotel industry, with Organizational Citizenship Behavior (OCB) serving as a key mediating mechanism. Moving beyond conventional performance frameworks, the research examines how the dual nature of PL behaviors encourages discretionary employee actions that advance social sustainability, employee well-being, responsible service delivery, and long-term organizational resilience. Employing a survey-based quantitative design, data were collected from 397 hotel employees in Egypt using a structured questionnaire assessing overall PL, its five core dimensions, and OCB. A structured questionnaire was used to measure overall PL, its five core dimensions, OCB, and sustainable service performance. The data were analyzed using SPSS Version 24 and WarpPLS 8, confirmatory factor analysis, reliability analysis, and regression-based mediation analysis to examine the relationships among the study variables. The findings reveal that PL positively influences sustainable service performance, while OCB not only enhances service outcomes but also significantly mediates the relationship between PL and performance. In addition, each dimension of PL—balancing self- and other-centeredness (SO), maintaining distance while fostering closeness (CD), treating employees uniformly while recognizing individuality (UI), preserving decision control while encouraging autonomy (CA), and enforcing work requirements while allowing flexibility (RF)—significantly strengthens employees’ citizenship behaviors. Full article

A rare clinical condition associated with numerous diagnostic and treatment challenges, pregnancy-associated melanoma (PAM), is defined as melanoma diagnosed either during pregnancy or within the first year postpartum. The physiological changes in pregnancy (hormonal changes and immune modulation), along with the normal changes in the pregnant woman’s skin (skin color changes, etc.), may all hinder early detection of this disease and create concerns regarding the advancement of melanoma and the well-being of both the mother and her fetus. The purpose of this review article was to summarize the current literature on the incidence, biology, diagnostic methods and treatments of PAM, with an emphasis on comparison between the two forms of melanoma. More recent research indicates that pregnancy itself is not typically associated with decreased melanoma-specific survival rates. However, when worse results are reported, it appears that this may be more due to delays in initial diagnoses (diagnosis of cancer after delivery) or detection of cancer postpartum, as well as the increased number of stages of melanoma at which women were diagnosed at the time of their first evaluation compared to non-pregnant controls, rather than being a result of enhanced biologic aggressiveness in melanoma driven by pregnancy itself. The preclinical and translational models have suggested that pregnancy may influence melanoma biology through the mechanisms of hormonal signaling, immune system modulation and vascular remodeling; however, these mechanisms remain hypothesis-generating, and current clinical evidence does not indicate that changes in hormone levels during pregnancy negatively affect melanoma survival. Surgical excision is the mainstay of treatment and can be performed safely during pregnancy. In select patients, a sentinel lymph node biopsy may also be performed. Due to the risk of fetal harm, systemic therapy (targeted agents and/or immune checkpoint inhibitors) cannot be used for the treatment of PAM during pregnancy. Post-pregnancy treatment of PAM will follow standard melanoma treatment guidelines; however, the treatment options will need to take into consideration whether or not the patient is breastfeeding and if she desires to become pregnant again in the future. In summary, PAM will require a multidisciplinary, individualized approach to maximize oncologic outcomes while protecting the health of both the mother and her fetus. Awareness of this disease and timely diagnosis are critical to maximizing the prognosis. Full article

Background/Objectives: Nerolidol (NER) is a sesquiterpene alcohol with recognized antimicrobial potential, whose applications as a pure substance are limited by hydrophobicity, instability, and cytotoxicity. Invasomes, i.e., liposomes with terpene ingredients, offer a strategy to improve their delivery; however, the NER loading limits compatible with vesicle integrity are still unclear. Here, Nerolidol-loaded invasomes were produced using a controlled simil-microfluidic coaxial injection process. Methods and Results: As a preliminary step, unloaded liposomes were fabricated to consolidate operating conditions and ensure their reproducible colloidal properties. Thereafter, formulations with progressively decreasing nominal NER loads were investigated to evaluate vesicle size, polydispersity, ζ-potential, encapsulation efficiency, effective loading, and stability. High nominal loads promoted turbidity, size increase (by agglomeration coalescence phenomena), and structural instability, whereas formulations containing approximately 1–2% NER achieved nearly complete encapsulation, Z-average ≈ 300 nm, |ζ| > 30 mV, and satisfactory physical stability. Antimicrobial and cytotoxic profiles of representative formulations, previously evaluated in an independent study are here reported only to contextualize the practical relevance of the optimized systems, while the present work primarily focuses on process–formulation aspects and loading/stability limitations. Conclusions: Overall, the present work identifies a realistic loading window for Nerolidol invasomes and highlights the suitability of the simil-microfluidic approach to obtain scalable, well-controlled formulations, providing a rational basis for their future biological assessment. Nerolidol invasome systems indeed can be considered a promising, versatile platform for antimicrobial applications, including prospective use in animal feed. Full article

The green synthesis of nanomaterials has emerged as a sustainable and environmentally friendly approach, gaining significant attention in recent years for its potential in a wide range of multifunctional applications. Among these materials, zinc oxide nanoparticles (ZnO NPs) stand out due to their remarkable versatility and effectiveness in fields such as industry (food, chemistry, and cosmetics), nanomedicine, cancer therapy, drug delivery, optoelectronics, sensors, and environmental remediation. This study focuses on bioinspired strategies for the facile synthesis of ZnO NPs, employing natural polysaccharide gums as mediators. Acting as both reducing and stabilizing agents, natural gums not only facilitate the eco-friendly production of ZnO NPs but also enhance their stability and functionality. Natural gum-mediated green synthesis typically yields stable, spherical ZnO particles, often in the 10–100 nm range. Typical reaction conditions are the use of zinc acetate dihydrate or zinc nitrate (0.01–0.5 M) as precursors, with low gum concentrations of 0.1–1.0% (w/v) in distilled water, alkaline conditions (pH from 8 to 12), often achieved by adding NaOH, which aids in the reduction and capping by the gum, at reaction temperature between 60 °C and 80 °C, under continuous stirring. The dried precipitate is often calcined at 400 °C to 600 °C to remove organic residues and enhance crystallinity. This approach underscores the potential of biopolymer-assisted synthesis in advancing green nanotechnology for sustainable and practical applications. Utilizing environmentally benign materials such as natural gums for the synthesis of ZnO NPs offers significant advantages, including enhanced eco-friendliness and biocompatibility, making them suitable for a wide range of applications without the involvement of toxic reagents. This review provides an in-depth analysis of the synthesis and characterization techniques employed in the eco-friendly production of ZnO NPs using different natural gums from biological sources and its environmental applications (e.g., pollutant removal and increased agriculture sustainability). Full article

This study examines the influence of photobioreactor (PBR) configuration on the cultivation performance of Chlorococcum sp. using aquaculture wastewater as the growth medium. Four systems were compared: horizontal without aeration (H-Plain), horizontal with aeration (H-Aerated), vertical with aeration (V-Aerated), and vertical with aeration and red LED illumination (V-LED). Over 14 days, the V-LED system achieved the highest biomass concentration (0.50 g L⁻¹) and volumetric productivity (0.063 g L⁻¹ day⁻¹), accompanied by nitrate and phosphate removals of 94% and 55.6%, respectively. Statistical analysis (ANOVA, p < 0.05) confirmed significant differences among configurations, demonstrating that light quality and aeration act synergistically to enhance growth and nutrient assimilation. While aeration improved CO₂ transfer and mixing, it was insufficient without adequate photon delivery. Conversely, red LED illumination mitigated photolimitation in vertical systems, promoting efficient photosynthesis and nutrient uptake. Energy assessment revealed that V-LED offered the highest productivity in expense of power input (1.08 kWh day⁻¹). These findings highlight the critical role of integrated PBR design, emphasizing that optimal combinations of geometry, aeration, and spectral lighting as keys to achieving high biomass yields and efficient nutrient removal in sustainable microalgae-based wastewater treatment systems. Full article

Nanomaterials (NMs) are increasingly utilized in drug delivery, diagnostic imaging, and therapeutic applications. However, their widespread use raises concerns regarding potential neurotoxicity, particularly for metal and metal oxide nanoparticles. Accumulating evidence indicates that these nanoparticles induce neurotoxicity through interconnected mechanisms, including excessive reactive oxygen species generation, activation of neuroinflammatory pathways, mitochondrial dysfunction, and disruption of blood–brain barrier integrity. These molecular events collectively lead to synaptic impairment, neuronal apoptosis, and progressive cognitive and behavioral deficits, with toxicity severity influenced by dose, exposure duration, and age. Given that in vitro models often fail to capture complex systemic interactions such as nanoparticle biodistribution, blood–brain barrier dynamics, and neuroimmune responses, this review places particular emphasis on in vivo studies to provide a more physiologically relevant understanding of nanoparticle-induced neurotoxicity. Importantly, a growing body of in vivo evidence demonstrates that natural bioactive compounds can mitigate these effects by targeting key pathogenic pathways, including oxidative stress, inflammation, and mitochondrial dysfunction, while preserving neuronal integrity. These findings highlight the therapeutic potential of natural bioactives as protective agents against nanoparticle-induced neurotoxicity and as candidates for broader neuroprotective strategies. This review summarizes the mechanistic basis of metal and metal oxide nanoparticle neurotoxicity and critically evaluates the protective role of natural bioactive compounds, with a focus on evidence derived from animal models. Full article