Search Results (14,863)

Central nervous system (CNS) disorders represent a growing healthcare burden, and various drugs are developed for their treatment. However, the blood–brain barrier (BBB) prevents over 98% of therapeutics from reaching brain tissue. Intranasal delivery provides a promising alternative by exploiting olfactory and trigeminal nerve pathways to circumvent the BBB. This review surveys recent advances in nose-to-brain delivery technologies, from carrier design to evaluation methods. Polymeric and lipid-based nanocarriers show enhanced mucosal penetration and prolonged residence time, and microneedle platforms further enable controlled drug release with minimal discomfort. To evaluate these delivery strategies, sensor-integrated organ-on-chip models provide more physiologically relevant testing than static cultures. Although persistent challenges such as rapid mucociliary clearance and formulation stability remain, combining nanotechnology with microfluidic devices and computational modeling shows potential for developing patient-specific therapeutics. Full article

CRISPR technologies are transforming cardiovascular therapy development by creating an increasingly seamless pipeline from potential target discovery to clinical translation. What began as a genome-editing tool has evolved into a versatile platform that enables researchers to precisely interrogate and modulate cardiac biology with tools such as base- and prime-editors, and CRISPR inhibition and activation. In this review, we follow the use of CRISPR across the stages of biomedical research through to bench-to-bedside application. This review begins by addressing how genome-wide and focused CRISPR screens discover developmental regulators, disease drivers, and drug-response pathways, making the first steps in identifying therapeutic targets. We then explore how CRISPR engineering creates progressively more relevant disease model systems to validate mechanisms of disease and test interventions, helping bridge the translational gaps between the lab and the clinic. Finally, we consider how CRISPR technologies are beginning to enter cardiovascular clinical trials, while highlighting the key challenges that still limit this translation. By linking the latest advances of modern CRISPR platforms to the stages of therapeutic development, this review highlights how CRISPR technology is reshaping the pipeline from molecular insight to clinical innovation in cardiac disease. Full article

Skin wound management in veterinary medicine requires therapies able to control inflammation, limit microbial burden, and support tissue repair. This study evaluated the anti-inflammatory, wound-healing, and immunomodulatory effects of four novel topical formulations combining synthetic anti-inflammatory drugs, antibiotics, and plant extracts in rat experimental models. Burn injury was induced in male Wistar rats for wound-healing assessment, while kaolin- and dextran-induced paw edema models were used to assess anti-inflammatory activity. The tested formulations were meloxicam, dexamethasone, and levofloxacin; thyme extract with meloxicam and dexamethasone; burdock extract with dexamethasone and levofloxacin; and thyme extract combined with burdock extract. Wound evolution was monitored macroscopically, edema was quantified by plethysmometry, and selected inflammatory mediators were measured by immunoassay. In the burn model, the thyme-containing formulation with meloxicam and dexamethasone, and the thyme–burdock formulation, achieved complete wound closure by the end of follow-up, whereas the reference product did not. In the acute inflammation models, all innovative formulations significantly reduced edema at the main early time points compared with the negative control and outperformed the reference product. The thyme–burdock formulation also showed the most favorable immunomodulatory profile, including normalization of interleukin-10 and marked reduction in interleukin-1 beta in both models. These results support the potential of multi-component topical formulations, particularly plant extract-based combinations, as promising candidates for veterinary wound care. Full article

Diabetes mellitus is primarily caused by the loss or malfunction of insulin-producing β-cells, and although current therapies improve glycemic control, they do not restore physiologic insulin secretion. Advances in stem cell biology and organoid engineering have led to the development of pancreatic organoids and induced pluripotent stem cell (iPSC)-derived β-cells as promising platforms for disease modeling, drug testing, and regenerative medicine. Pancreatic organoids generated from ductal, acinar, or progenitor populations can recapitulate key anatomical and functional features of native pancreatic tissue, enabling studies of development, injury, and regeneration. In parallel, improvements in iPSC differentiation protocols have produced β-like cells capable of insulin secretion in response to glucose, although achieving full functional maturity remains a challenge. Bioengineering strategies, including biomaterial scaffolds, microfluidic platforms, endothelial co-culture systems, three-dimensional bioprinting, and CRISPR-based genome editing, have enhanced the stability, vascular compatibility, and functional performance of both organoid and iPSC-derived systems. Despite these advances, variability in differentiation efficiency, limited β-cell maturity, and poor long-term survival continue to hinder clinical translation. Together, pancreatic organoids and iPSC-derived β-cells represent complementary platforms that advance fundamental research and support the development of β-cell replacement therapies, with ongoing integration of bioengineering approaches expected to accelerate progress toward reproducible, scalable, and clinically relevant β-cell regeneration. Full article

Mushroom use dates back to ancient times, and it currently remains significant among indigenous and urban populations as a medicinal option. Psilocybe species are suggested to modify emotions when administered in macro- or microdose form for the treatment of anxiety and depression, both often affected by a delayed onset and adverse effects of current pharmacological therapy. The objective of this study was to evaluate the anxiolytic and/or antidepressant-like effects of P. cubensis mushroom aqueous extract (PcAE) microdosing in mice using open-field and rota-rod tests, followed by plus-maze or forced swimming tests. We also evaluated changes in neuronal activity and dendritic maturation using electrocorticography (ECoG) and immunohistochemical techniques. The outcomes were compared with an effective macrodose of PcAE and antidepressant fluoxetine (FLX). For this study, mice were grouped as follows: (1) vehicle, (2) acute, and (3) repeated (10 days) PcAE microdosing (1 µg/kg); (4) single PcAE macrodose (1 g/kg); and (5) acute and (6) repeated reference drug fluoxetine (FLX, 10 mg/kg).The anxiolytic and antidepressant-like effects using microdosing were similar to those observed with macrodoses of PcAE and FLX; significant dose- and/or time-dependent changes in the ECoG and dendritic maturation of hippocampus neurons were also observed, in addition to altered corticosterone levels. To conclude, P. cubensis mushroom promotes brain effects in mice after micro- and macrodosing, supporting its potential as a therapeutic alternative for mental health. Full article

Introduction: Tuberculous aneurysm of the thoracic aorta (TBAA) is an extremely rare but potentially fatal manifestation of tuberculosis (TB). Clinical presentation may include hemoptysis in the absence of parenchymal lung abnormalities. Case report: We presented a 62-year-old male with cough, chest pain, and minimal hemoptysis. Diagnostic evaluation confirmed an aneurysm of the descending thoracic aorta at a site previously treated with endovascular repair, with no imaging findings suggestive of pulmonary TB. Bronchoscopy revealed blood in the main bronchi without an identifiable endobronchial source. The diagnosis of TB was established by polymerase chain reaction (PCR) testing of bronchial aspirate obtained during bronchoscopy. Emergency surgical intervention was recommended because of an impending aortic rupture, but the patient declined surgery. Standard antituberculous therapy was initiated, and the patient subsequently developed drug-induced liver injury, prompting temporary cessation of treatment. The clinical course was later complicated by the development of an aortoesophageal fistula (AEF), with significant implications for prognosis. Conclusions: Early recognition of TBAA, along with a multidisciplinary approach that integrates advanced diagnostic modalities, timely vascular intervention, and carefully managed antituberculous therapy, is essential to reduce mortality and optimize treatment outcomes. Full article

Background/Objective: This study evaluated the analgesic and anti-inflammatory effects of ambroxol in an experimental model of endometriosis. Methods: Ambroxol was administered at doses of 10, 50, and 100 mg/kg (Abx 10, Abx 50, and Abx 100) by daily gavage for 21 days. A medroxyprogesterone-treated group (Progesterone) was included as a positive control. Pain was assessed using validated behavioral tests, including the Rat Grimace Scale (RGS), the von Frey test, and the rotarod test. Additionally, interleukin-1β (IL-1β) levels and total leukocyte counts were measured in peritoneal lavage fluid. The volumetric reduction in endometriotic implants was evaluated by ultrasonography, while histopathological analysis characterized inflammatory infiltrate and epithelial layer integrity using a standardized scoring system. Results: All ambroxol doses reduced spontaneous pain manifestations throughout the treatment. The mechanical withdrawal threshold significantly increased from the second week onward, and motor quality improved over the course of the study. A significant reduction in IL-1β levels compared with the negative control (Control(−)) was observed on day 21. Abx 50 and Abx 100 significantly reduced implant volumes (48.2% and 56.2%, respectively) and promoted marked disruption of the endometriotic epithelial layer. When compared with Progesterone, higher doses—particularly 100 mg/kg—demonstrated comparable efficacy. Conclusions: Taken together, these pleiotropic effects support the potential for drug repurposing in endometriosis. Full article

This study focuses on the production and characterization of polyvinyl alcohol (PVA)-chitosan (CS)-based nanoparticles loaded with vitamin E (VitE) and ephedrine (Ep) via electrospraying for intranasal drug delivery in narcolepsy treatment. The nanoparticles were successfully synthesized using optimized parameters (15.5 kV voltage, 0.3 mL/h flow rate, 25 G needle size, and 14 cm distance). Scanning electron microscopy (SEM) analysis confirmed the formation of spherical particles with an average size of 350–500 nm, while energy-dispersive X-ray spectroscopy (EDS) mapping revealed a homogeneous elemental distribution with oxygen (51.74%), silicon (24.48%), carbon (6.47%), zinc (6.08%), and aluminum (3.82%). Fourier-transform infrared (FTIR) spectra demonstrated the successful encapsulation of VitE and Ep through characteristic peaks at 3285 cm⁻¹ (OH stretching), 1731 cm⁻¹ (C=O stretching), and 1086 cm⁻¹ (C-O-C stretching). In vitro drug release analysis indicated a controlled and sustained release profile, with cumulative VitE and Ep release reaching 78.6% and 84.3%, respectively, over 48 h in phosphate-buffered saline (PBS, pH 7.4). Antioxidant activity assessment using the DPPH assay confirmed an R² value of 18.84 µg/mL, demonstrating significant free radical scavenging potential. The antibacterial activity, tested via the disk diffusion method, exhibited inhibition zones of 18.31 ± 5.8 mm (E. coli) and 21.51 ± 1.57 mm (S. aureus), confirming strong antimicrobial properties. These findings suggest that the developed electrosprayed PVA/CS nanoparticles loaded with VitE and Ep offer a promising intranasal delivery system with enhanced bioavailability, controlled release, antioxidant capacity, and antibacterial properties, making them a viable candidate for narcolepsy treatment. Full article

Background/Objectives: Research has shown a high prevalence of co-occurring trauma-related disorders and cocaine use disorder (CUD). However, there remains a need for preclinical studies to determine how traumatic event exposure influences vulnerability to CUD development and relapse. In this study, we assessed the impact of traumatic event exposure using a threat conditioning (TC) paradigm, which models traumatic event exposure through associative threat learning on cocaine-seeking behavior in adult male and female rats. Methods: Adult male and female rats were exposed to a single TC session. After TC, the rats underwent cocaine self-administration (SA), extinction training, cue-primed reinstatement, and cocaine-primed reinstatement testing. A parallel cohort was subjected to a sucrose SA cohort to assess whether TC altered non-drug reward seeking in the form of sucrose SA. Results: In the cocaine cohort, stressed male rats exhibited greater cue- and cocaine-primed reinstatement relative to non-stressed males, whereas no reinstatement differences emerged in female rats. In the sucrose cohort, stressed females displayed increased sucrose pellet delivery during self-administration compared to non-stressed females, but no differences were observed during sucrose reinstatement in either male or female rats. Conclusions: These findings indicate that trauma exposure prior to cocaine use influences cocaine relapse-related behavior, as well as non-drug reward reinforcement earning, in a sex-specific manner. Overall, these results highlight the value of associative stress models such as TC for studying trauma–addiction comorbidity and the need to investigate the neurobiological mechanisms driving these sex-specific outcomes. Full article

Background/Objectives: Cancer remains one of the leading global health burdens, mainly because of the lack of specificity and off-target toxicity associated with conventional therapeutic approaches. To move toward more efficient anticancer drug discovery, we have developed an advanced machine-learning-based architecture that allows for predictive modeling of anticancer small molecules. Methods: A total of 3600 compounds with experimentally validated IC₅₀ values were systematically processed to derive a comprehensive suite of molecular representations comprising 2D physicochemical descriptors, structural fingerprints, and hybrid descriptor sets generated via the Mordred and PaDEL frameworks. A total of six machine learning algorithms—Random Forest (RF), Extreme Gradient Boosting (XGB), Gradient Boosting (GB), Extra-Trees classifier (ET), Adaptive Boosting (AdaBoost), and Light Gradient Boosting Machine (LightGBM)—were trained and benchmarked via a rigorous model evaluation protocol incorporating 10-fold cross-validation along with multiple performance metrics. Ensemble voting strategies were also examined to assess potential performance. Result: Of all configurations, the XGB-Hybrid architecture emerged as the most robust and generalizable classifier with an AUC of 0.88 and accuracy of 79.11% on the independent test set. To ensure interpretability and mechanistic insight, SHAP-based feature analysis was conducted, by which feature contributions could be quantified and the molecular determinants most influential for anticancer activity discrimination were revealed. Altogether, the current study establishes an XGB-Hybrid framework as technically rigorous, interpretable, and high-performance predictive modeling with the ability to accelerate early-stage anticancer small molecule identification. Conclusions: The study has brought into focus the transformational effect of machine learning in modern computational oncology and rational drug design pipelines. Full article

Background: The increasing prevalence of multidrug-resistant bacterial infections highlights the need for drug-delivery strategies that improve antimicrobial exposure and sustain therapeutic activity. In this study, ciprofloxacin-loaded nanostructured lipid carriers (NLC-CIP) were developed and evaluated to better understand how formulation-dependent release behavior influences antibacterial performance against Escherichia coli. Methods: NLC-CIP were prepared and characterized in terms of size, polydispersity, encapsulation efficiency, and colloidal stability. In vitro release profiles were evaluated across different pH conditions, followed by kinetic modeling. Stability under refrigerated storage was assessed. Antibacterial performance was determined through IC₅₀ measurements and dynamic growth-kinetic analyses, while cytotoxicity was evaluated in HepG2 cells. Results: Ciprofloxacin incorporation increased hydrodynamic diameter (~116 to 194 nm) while preserving low polydispersity (PdI~0.04), high colloidal stability, and encapsulation efficiency (96%). Release studies showed medium-dependent behavior, with rapid release at pH 1.2, 4.5, and 7.4, and more sustained profile at pH 6.8, consistent with diffusion-controlled kinetics (Weibull model). Refrigerated storage preserved release profiles while slowing early-stage kinetics. NLC-CIP showed improved apparent antibacterial activity, reducing the IC₅₀ from 4.9 to 1.2 ng/mL, and sustained bacterial suppression by decreasing growth rates and prolonging doubling times. Unloaded NLCs showed no antibacterial activity, and cytotoxicity assays confirmed favorable biocompatibility. Conclusion: Overall, these results show that NLC-based encapsulation can modulate ciprofloxacin release and reshape drug exposure over time, thereby improving antibacterial performance under the tested conditions. This study supports integrated release and growth-kinetic analyses as a more informative framework for evaluating lipid-based antibiotic delivery systems. Full article

Microphysiological systems (MPSs) have emerged as promising platforms for drug discovery and in vitro pharmacological testing. MPSs aid to reproduce physiologically relevant microenvironments, in which controlled perfusion can play important role. In this study, an on-chip AC electrothermal (ACET) pump was developed for pulsatile perfusion in microfluidic cell culture systems. The proposed pump generates fluid motion through the interaction between an applied electric field and temperature-dependent gradients in the electrical properties of the fluid. Pulsatile perfusion was produced by periodic application of an AC voltage to the electrode array, and the pulsation cycle could be controlled electrically. The maximum flow velocity increased with the applied AC voltage, demonstrating tunable flow generation by the ACET pump. To evaluate the applicability of the developed system to cell culture, human mesenchymal stem cells (hMSCs) were cultured under pulsatile perfusion conditions for five days. The results showed that osteogenic differentiation under pulsatile perfusion was higher than that under static culture conditions. These findings demonstrate the potential of the proposed on-chip ACET pump as a simple and effective platform for generating physiologically relevant pulsatile perfusion in microphysiological systems. Full article

Background/Objectives: Febrile illness in returning travelers presents a diagnostic and operational challenge for emergency medicine clinicians as early symptoms of high-consequence tropical infections often overlap with common viral syndromes. This review synthesizes current evidence to guide frontline clinicians in the systematic evaluation, diagnosis, and management of internally acquired febrile illnesses with a focus on pathogen of greatest relevance to United States (US) emergency departments (ED). Methods: We conducted a narrative review of the literature addressing epidemiology, clinical presentation, diagnostic testing, and management strategies for key travel-associated infections. Special consideration was given to rapid diagnostic modalities, pediatric risk factors, and infections most frequently implicated in returning travelers, including chikungunya (CHIK), dengue virus (DENV) disease, Ebola virus (EBV) disease, malaria, Mpox, typhoid fever (TF), yellow fever (YF), and Zika virus (ZIKV) disease. Results: Effective evaluation begins with a detailed travel and exposure history, recognition of epidemiologic and clinical red flags, and targeted use of rapid diagnostic tests. Malaria remains the most common life-threatening cause of post-travel fever and the only pathogen with reliable Food and Drug Administration (FDA)-cleared rapid testing available in the ED. Arboviral infections such as DENV, CHIK, ZIKV, and YFrequire region-specific consideration and phase-appropriate molecular or serologic evaluation. Emerging and high-consequence pathogens, including Mpox and EBV, necessitate strict infection control measures and coordination with public health authorities. Pediatric travelers, particularly those visiting friends and relatives, face disproportionate risk for severe systemic infections and often require broader diagnostic testing. Conclusions: A structured approach integrating travel history, focused examination, rapid diagnostics, and early recognition of high-risk features is essential to improving outcomes for febrile returning travelers. Strengthened vector control, enhanced vaccination uptake, and global surveillance are critical to reducing future disease burden. Full article

Carbon quantum dots (CQDs) and stimuli-responsive hydrogels are advanced functional materials whose hybridization yields CQD-enhanced stimuli-sensitive hydrogels, opening new interdisciplinary avenues for smart material applications. This review systematically summarizes the latest advances in these composites, focusing on synthetic strategies, structure–property modulation mechanisms, and practical applications. Distinct from existing reviews that either investigate CQDs or hydrogels independently or discuss their composites in a single research field, this work features core novelties in integration strategy, application scope and critical analysis: it systematically compares the advantages, limitations and applicable scenarios of three typical CQD–hydrogel integration approaches (physical entrapment, in situ synthesis, covalent conjugation), comprehensively covers the multi-field application progress of the composites and conducts in-depth cross-field analysis of their common scientific issues and technical bottlenecks. By incorporating CQDs, the composites achieve remarkable performance optimizations: 40% improved mechanical toughness, sub-ppm-level heavy metal-sensing sensitivity, and over 80% organic dye photocatalytic degradation efficiency, addressing pure hydrogels’ inherent limitations of insufficient strength and single functionality. These enhancements enable sophisticated applications in biomedical field (real-time biosensing, controlled drug delivery), environmental remediation (pollutant detection/degradation), energy storage, and flexible electronics. The synergistic interplay between CQDs and hydrogels facilitates precise single/multi-stimulus responsiveness (pH, temperature, light), a pivotal advance for precision medicine and intelligent environmental monitoring. Despite promising progress, the large-scale practical application of CQD–hydrogel composites still faces prominent challenges: the difficulty in scalable fabrication with the uniform dispersion of CQDs in hydrogel matrices, poor long-term stability of most composites under physiological cyclic stress (service life < 6 months in practical tests), and low accuracy in discriminating multi-stimuli in complex real-world matrices. Future research should prioritize biomass-based eco-friendly CQD synthesis, machine learning-aided multimodal responsive systems, and 3D bioprinting for scalable manufacturing. Full article

Background: In 2018, malaria remained a leading cause of morbidity and mortality in the Democratic Republic of the Congo, accounting for 44% of all outpatient visits and 22% of deaths. This led to the development of the strategic plan for 2020–2023. To meet the objectives of this renewed plan, a monitoring and evaluation program focusing on performance indicators was established. This study aimed to assess the malaria control performance indicators in Kinshasa. Methods: A descriptive cross-sectional study used the National Malaria Control Program dataset of the period 2020–2023 to analyze malaria data from 23 HZ (Health Zone) in Kinshasa. Diagnostic, therapeutic, and preventive use of LLINs (long-lasting insecticidal nets) and sulfadoxine–pyrimethamin-based IPT (intermittent preventive treatment among pregnant women) indicators were evaluated following the targeted thresholds established in the strategic plan for 2020–2023. Results: Malaria was present in all studied HZ from 2020 to 2023, with a heterogeneous distribution. The malaria incidence during the study period was 30%, with an upward trend in both suspected and confirmed cases, peaking in 2022 and showing no further fluctuations thereafter. The proportion of LLINs distributed to pregnant women during antenatal care visits was 62%, 61%, 45%, and 88% in 2020, 2021, 2022, and 2023, respectively. A total of 83.1% of suspected malaria cases were diagnosed using RDT (Rapid Diagnosis Test), and confirmed malaria cases received antimalarial treatment. Conclusions: The objectives of the 2020–2023 strategic plan were only partially achieved, and no HZ reached 100% diagnosis by RDT, with only four HZs reaching at least 95% of the target. Thirty-four HZs were able to benefit from 95% treatment with antimalarial drugs. Full article