Search Results (93,536)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritic eczematous lesions that significantly alter quality of life of patients. Dupilumab, a new biologic agent, has demonstrated efficacy and safety in the general adult population with AD. However, evidence on its use in elderly patients is limited. Objectives: The objective of this work was to systematically assess the effectiveness and safety of dupilumab in patients aged ≥60 years with AD, based on published data. Methods: A systematic review and meta-analysis were conducted following the PICO(S) framework. Articles written in English and published before 31 December 2024 that investigated patients ≥ 60 years with AD treated with dupilumab were included. Meta-analysis of the observational studies was performed using a random-effects model with subgroup and meta-regression analyses. Results: Twenty-one articles met the inclusion criteria. After 16 weeks of treatment, dupilumab significantly reduced disease severity (EASI: 21.8; 95% CI: 18.3–25.2), intensity of pruritus (P-NRS: 5.8; 95% CI: 4.2–7.3), and quality of life impairment (DLQI: 11.3; 95% CI: 6.1–16.5); all p < 0.001. Meta-regression revealed previous treatment with cyclosporin A as a predictor of a poorer response to treatment. The generalized-prurigo phenotype was associated with worse control of pruritus. The most common adverse events were conjunctivitis, injection site reactions, and facial flushing. Conclusions: Dupilumab appears to be an effective and well-tolerated treatment for AD in elderly patients. More research is warranted to evaluate its long-term effectiveness and safety in this age group. Full article

Due to their therapeutic potential and effects on cells, exosomes derived from bovine colostrum (BCE) and milk (BME) are molecules that have been at the center of recent studies. Their properties include the ability to cross biological barriers, their natural biocompatibility, and their structure, which enable them to act as stable nanocarriers. Exosomes derived from milk and colostrum stand out in cancer prevention and treatment due to these properties. BMEs can be enriched with bioactive peptides, lipids, and nucleic acids. The targeted drug delivery capacity of BMEs can be made more efficient through these enrichment processes. For example, BME enriched with an iRGD peptide and developed using hypoxia-sensitive lipids selectively transported drugs and reduced the survival rate of triple-negative breast cancer (TNBC) cells. ARV-825-CME formulations increased antitumor activity in some cancer types. The anticancer effects of exosomes are supported by these examples. In addition to their anticancer activities, exosomes also exhibit effects that maintain immune balance. BME and BCE can regulate inflammatory responses with their miRNA and protein loads. These effects of BMEs have been demonstrated in studies on colon, breast, liver, and lung cancers. The findings support the safety and scalability of these effects. However, significant challenges remain in terms of their large-scale isolation, load heterogeneity, and regulatory standardization. Consequently, BMEs represent a new generation of biogenic nanoplatforms at the intersection of nutrition, immunology, and oncology, paving the way for innovative therapeutic approaches. Full article

Background/Objectives: Digestive problems are common in the general population and may be influenced by lifestyle, emotional status and diet. This study aimed to estimate the prevalence of digestive problems in Spanish adults and examined associated factors. Methods: Descriptive cross-sectional analysis of anonymized adult microdata from the 2023 Spanish Health Survey was performed. Data were collected using a mixed-mode design (self-administered web questionnaire with interviewer-administered follow-up). Digestive problems were recoded by combining gastric ulcer, constipation, and prescribed use of laxatives, astringent drugs, and stomach medication. Therefore, digestive problems are primarily defined as the presence of gastric ulcers, diarrhea, and/or constipation. Variables included sociodemographic, Body Mass Index (BMI), smoking, alcohol intake, physical activity, Personal Health Questionnaire Depression Scale (PHQ-8), World Health Organization Well Being Index (WHO-5), and macronutrient intake estimated from a Food-Frequency Questionnaire using the Spanish Food Composition Database (BEDCA). Group comparisons and multivariable logistic regression were conducted (95% CI; significance level set at p < 0.05). Results: Of 34,148 participants, 13,518 provided information on digestive problems; among these respondents, 3860 (28.6%) reported having digestive issues. Prevalence ranged from 5.2% to 36.5% among national territories. Higher odds (OR) of digestive problems were associated with age (OR 1.026, 95% CI 1.023–1.029), female sex (OR 1.168, 1.070–1.276), non-smoking (OR 1.240, 1.005–1.531) and ex-smoking (OR 1.447, 1.272–1.647) compared to current smokers, higher PHQ-8 scores (OR 1.040, 1.029–1.051), greater protein intake (OR 1.016, 1.009–1.023), consumption of sweet pastries (OR 1.058, 1.039–1.077), and dairy products (OR 1.027, 1.002–1.053); in contrast, lower odds were associated with higher WHO-5 scores (OR 0.985, 0.982–0.987), total fiber intake (OR 0.968, 0.949–0.987), and legume consumption (OR 0.894, 0.856–0.933). Conclusions: Digestive problems show considerable variability in prevalence among survey-based Spanish sample. Digestive problems were associated with older age, female sex, depressive symptoms, high-protein intake, and higher consumption of sweet pastries and dairy products, whereas higher well-being scores, higher fiber intake and legume consumption were associated with lower odds of digestive problems. Full article

The naturally occurring, biocompatible and biodegradable biopolymer dextran is a versatile material for the formulation of hydrogels with desirable properties for use in medicine, drug delivery, and tissue engineering applications. The distinctive structural and physicochemical characteristics, such as polymeric nature, gelling ability and excellent swelling properties, present it as an excellent biomaterial for drug delivery. This study explores the synthesis and characterization of dextran hydrogel for the encapsulation of clindamycin as an innovative approach for controlled drug delivery. The dextran hydrogel was synthesized through a simple and cost-effective method, and its swelling behavior, temperature and pH dependence, and surface morphology were investigated. The maximum equilibrium swelling ratio (73 ± 1%) of the hydrogel was observed in water at 25 °C within 120 min, and the hydrogel was found to be pH- and temperature-dependent for more precise and targeted drug delivery. Moreover, the dextran hydrogel was found to retain water for up to 18 h and remain stable for 8 days. The presence of a roughened surface with large openings/pores on the surface illustrated the high swelling capability of the synthesized hydrogel. In addition, the dextran hydrogel loaded with clindamycin demonstrated high drug loading capacity (70 ± 2%), rapid (65 ± 2%) in vitro drug release potential and pathogen-inhibitory activity against Staphylococcus gallinarium and Bacillus subtilis. Full article

Introduction: Magnetic nanoparticles are widely investigated as multifunctional platforms for drug delivery and theranostic applications, yet their biomedical implementation is hindered by aggregation, limited colloidal stability, and insufficient biocompatibility. Hybrid biopolymer coatings can mitigate these issues while supporting drug incorporation. Aim: This study aimed to develop casein–pullulan-coated Fe₃O₄ nanocomposites loaded with xanthohumol, enhancing stability and enabling controlled release for potential theranostic use. Methods: Fe₃O₄ nanoparticles were synthesized through co-precipitation and incorporated into a casein–pullulan matrix formed via polymer complexation and glutaraldehyde crosslinking. A 3² full factorial design evaluated the influence of casein:pullulan ratio and crosslinker concentration on physicochemical performance. Nanocomposites were characterized for size, zeta potential, morphology, composition, and stability, while drug loading, encapsulation efficiency, and release profiles were determined spectrophotometrically. Molecular docking was performed to examine casein–pullulan interactions. Results: Uncoated Fe₃O₄ nanoparticles aggregated extensively, displaying mean sizes of ~292 nm, zeta potential of +80.95 mV and high polydispersity (PDI above 0.2). Incorporation into the biopolymer matrix improved colloidal stability, yielding particles of ~185 nm with zeta potentials near –35 mV. TEM and SEM confirmed spherical morphology and uniform magnetic core incorporation. The optimal formulation, consisting of a 1:1 casein:pullulan ratio with 1% glutaraldehyde, achieved 5.7% drug loading, 68% encapsulation efficiency, and sustained release of xanthohumol up to 84% over 120 h, fitting Fickian diffusion (Korsmeyer–Peppas R² = 0.9877, n = 0.43). Conclusions: Casein–pullulan hybrid coatings significantly enhance Fe₃O₄ nanoparticle stability and enable controlled release of xanthohumol, presenting a promising platform for future targeted drug delivery and theranostic applications. Full article

Cisplatin (CDDP) is a cornerstone chemotherapeutic drug, yet its efficacy is frequently compromised by renal toxicity, primarily manifesting as acute kidney injury (AKI). Magnolol (MG) is a polyphenol from Magnolia officinalis and has been widely documented for its pronounced antioxidant and anti-inflammatory properties. This study evaluated the renoprotective effects of MG in a murine model of CDDP-induced AKI. Male C57BL/6 mice received MG (20 mg/kg) via daily intraperitoneal injection for four consecutive days, starting one day before a single CDDP injection. MG significantly reduced the serum concentrations of blood urea nitrogen and creatinine. Histopathological assessment revealed attenuated tubular damage and reduced expression of tubular injury markers. MG inhibited pro-inflammatory cytokines at both systemic and renal levels, alleviated endoplasmic reticulum stress, and suppressed activation of mitogen-activated protein kinase signaling pathways. Apoptotic damage was mitigated, as shown by the fewer TUNEL-positive cells and lowered expression of pro-apoptotic markers. In parallel, ferroptotic processes were alleviated through downregulation of pro-ferroptotic proteins and preservation of key antioxidant regulators. Importantly, MG restored nuclear factor erythroid 2-related factor 2 activity and upregulated downstream antioxidant effectors. These findings highlight the multi-targeted renoprotective actions of MG and support its possible utility as a therapeutic agent to prevent CDDP-induced renal injury. Full article

Background/Objectives: Mechanisms underlying treatment resistance in hematopoietic malignancies such as acute lymphoblastic leukemia (ALL) include (1) enhanced activity of anticancer drug efflux mechanisms (MRP1); (2) suppressed activity of anticancer drug influx mechanisms (ENT-1); (3) enhanced drug detoxification activity (AKR1B10, AKR1C3, CYP3A4); (4) influence of the tumor microenvironment (GRP94), etc. We conducted this study to comprehensively and clinically examine treatment resistance due primarily to a decrease in the tumor intracellular anticancer drug concentrations. Methods: The subjects were 19 ALL patients who underwent initial induction therapy with alternating Hyper CVAD/MA therapy. Antibodies against 23 types of treatment resistance-associated proteins were used for immunohistochemical analysis of tumor specimens obtained from the patients, and correlations between the results of immunohistochemistry and the overall survival (OS) were retrospectively analyzed using the Kaplan–Meier method. Results: Based on the patterns of expression of the enzymes involved in treatment resistance, we classified the patients (Urayasu classification for ALL, which we believe would be very useful for accurately stratifying patients with ALL according to the predicted prognosis), as follows: Good prognosis group, n = 1, 5%: AKR1B1(+)/AKR1B10(−), 5-year overall survival (OS), 100%; Intermediate prognosis-1 group, n = 9, 5%: AKR1B1(−)/AKR1B10(−) plus MRP1(−), 5-year OS, 68%; Intermediate-2 prognosis group, n = 6.3%: AKR1B1(−)/AKR1B10(−) plus MRP1(+), median survival, 17 months, 5-year OS, 20%; and Poor prognosis group, n = 3, 16%: AKR1B1(−)/AKR1B10(+), median survival, 18 months, 5-year OS, 0%. n = 2. Conclusions: The Urayasu classification for ALL is considered reliable for predicting the prognosis of patients with ALL after the initial Hyper CVAD/MA remission induction therapy. Full article

The continuous emergence of SARS-CoV-2 variants, especially the Omicron strain with its heightened transmissibility, has posed ongoing challenges to the efficacy of existing vaccine and drug regimens. This situation highlights the pressing demand for antiviral drugs employing novel mechanisms of action. Pentacyclic triterpenoids (PTs), a structurally varied group of compounds derived from plants, exhibit both antiviral and anti-inflammatory activities, making them attractive candidates for further therapeutic development. These natural products, along with their saponin derivatives, show broad-spectrum inhibitory effects against multiple SARS-CoV-2 variants (from Alpha to Omicron) via interactions with multiple targets, such as the spike protein, main protease (Mpro), RNA-dependent RNA polymerase (RdRp), and inflammatory signaling pathways. This review consolidates recent findings on PTs and their saponins, emphasizing their influence on the key structural features required for inhibiting viral attachment, membrane fusion, reverse transcription, and protease function. We systematically summarized the structure–activity relationships and their antiviral results of PTs based on different target proteins in existing studies. Furthermore, this work points toward new strategies for designing multi-target PT-based inhibitors with improved efficacy against Omicron and future variants. Full article

Background/Objectives: Malaria remains a major global health burden, increasingly complicated by resistance to artemisinin-based therapies. Because artemisinin activation depends on heme and porphyrin chemistry, we sought to exploit host red blood cell (RBC) heme metabolism as a therapeutic vulnerability. This study aims to develop and evaluate a host-directed “bait-and-kill” strategy that selectively sensitizes malaria-infected RBCs to artemisinin. Methods: We integrated quantitative proteomics, erythropoiesis transcriptomic analyses, flow cytometry, and in vitro malaria culture assays to characterize heme metabolism in mature RBCs and Plasmodium falciparum-infected RBCs (iRBCs). The heme precursor 5-aminolevulinic acid (ALA) was used to induce porphyrin accumulation, and dihydroartemisinin (DHA) was applied as the killing agent. Drug synergy, porphyrin accumulation, reactive oxygen species (ROS) induction, and parasite survival were assessed, including ring-stage survival assays using artemisinin-resistant clinical isolates. Results: Mature RBCs retain a truncated heme biosynthesis pathway capable of accumulating porphyrin intermediates, while uninfected RBCs are impermeable to ALA. In contrast, iRBCs exhibit increased membrane permeability, allowing selective ALA uptake and porphyrin accumulation. ALA alone did not induce cytotoxicity or ROS, whereas DHA induced ROS and parasite killing. The ALA + DHA combination resulted in synergistic parasite elimination, including complete clearance of artemisinin-resistant P. falciparum isolates from the Greater Mekong Subregion, with no recrudescence observed over three weeks of culture. Evidence supports a predominant role for host-derived heme metabolites in mediating this synergy. Conclusions: The bait-and-kill strategy selectively exploits host RBC heme metabolism to restore and enhance artemisinin efficacy while sparing uninfected cells. Using clinically safe compounds, this host-directed approach provides a promising, resistance-bypassing framework for malaria treatment and combination drug development. Full article

Forkhead box class O1 (FOXO1) and fas-associated death domain (FADD) regulate cell death pathways and homeostatic processes such as cell cycle progression and apoptosis. FADD phosphorylation promotes nuclear localization of FOXO1, and FOXO1 regulates FADD expression. Therefore, it is plausible that FOXO1 and FADD have synergistic or antagonistic effects on cell cycle regulation and the response to anticancer drug treatment in cancer cells. In the present study, we report that AS1842856-mediated inhibition of FOXO1 reverses anticancer drug-induced cytotoxicity, while FADD knockdown increases anticancer drug-induced cytotoxicity in osteosarcoma (OS). Reversed anticancer drug-induced cytotoxicity was accompanied by G2/M cell cycle arrest and increased expression of p21. The anticancer function of FOXO1 was further supported by the observation that OS cells that express higher basal levels of FOXO1 had increased sensitivity to camptothecin-induced cytotoxicity. FADD knockdown reversed the FOXO1 inhibition-induced increase in p21 expression. The results presented in this study indicate that FOXO1 has a tumor suppressor function, while FADD has a tumor-promoting function in OS following anticancer drug treatment. The experimental approach used in this investigation also indicates that FADD antagonizes the effect of FOXO1 on p21 expression in OS. Full article

Parkinson’s disease is the second leading neurodegenerative disease of aging. For over five decades, oral levodopa has been used to manage the progressive motor deficits that are the hallmark of the disease. However, individual dose requirements are highly variable, and patients typically require increased levodopa dosage as the disease progresses, which can cause undesirable side effects. It has become increasingly apparent that the gut microbiome can have a major impact on the metabolism and efficacy of therapeutic drugs. In this Perspective, we examine recent studies highlighting the impact of metabolism by Enterococcus faecalis, a common commensal gut bacterium, on levodopa bioavailability. E. faecalis expresses a highly conserved tyrosine decarboxylase that promiscuously converts levodopa to dopamine in the gut, resulting in decreased neuronal uptake of levodopa and reduced dopamine formation in the brain. Mitochondria-targeted antioxidants conjugated to a triphenylphosphonium moiety have shown promise in transiently suppressing the growth of E. faecalis and decreasing microbial levodopa metabolism, providing an approach to modulating the microbiome that is less perturbing than conventional antibiotics. Thus, mitigating metabolism by the gut microbiota is an attractive therapeutic target to preserve and potentiate the efficacy of oral levodopa therapy in Parkinson’s disease. Full article

Objective: To better define potential executive function difficulties in individuals living with HIV but not clinically identified as having HAND, with and without mild to moderate cocaine dependence (CD), our cross-sectional study examined executive function performance on the Stroop Color-Word Test (Stroop) and the Trail Making Test (TMT) in four groups stratified by HIV and CD status. Method: We recruited 101 participants (26 HIV+/CD+; 18 HIV+/CD−; 30 HIV−/CD+; 27 HIV−/CD−). We utilized a 2 (HIV: yes/no) × 2 (Cocaine: yes/no) MANCOVA while controlling for age and premorbid intelligence on the Stroop trials (i.e., color-naming, word-reading, interference), and TMT-A and TMT-B z-scores, number of errors, and the B/A ratio. Results: HIV was associated with significantly slower performance on the Stroop Interference (p = 0.012, η² = 0.064). CD showed a trend towards slower performance on interference trials (p = 0.061, η² = 0.037) and was associated with significantly more errors on the Stroop Word-Reading (p = 0.028, η² = 0.050) and Interference trials (p = 0.046, η² = 0.041), suggestive of difficulties with inhibitory control and written language processing. There were no significant HIV × Cocaine interactions. Conclusions: Our results suggest HIV without clinically identified cognitive impairment and CD are associated with distinct and potentially overlapping executive functioning deficits, particularly for measures of inhibitory control. Notably, CD showed trend-level slowing on Stroop Interference performance, suggesting partial overlap with HIV effects. Clarifying the specific cognitive processes impacted by HIV and CD can help guide tailored interventions to improve functional outcomes in these populations. Full article

Glioblastoma (GBM) remains one of the most treatment-resistant human malignancies, largely due to the interplay between disrupted fluid dynamics, immune evasion, and the structural complexity of the tumor microenvironment; in addition to these, treatment resistance is also driven by intratumoral heterogeneity, glioma stem cell persistence, hypoxia-induced metabolic and epigenetic plasticity, adaptive oncogenic signaling, and profound immunosuppression within the tumor microenvironment. Emerging evidence shows that dysfunction of the glymphatic system, mislocalization of aquaporin-4, and increased intracranial pressure compromise cerebrospinal fluid–interstitial fluid exchange and impair antigen drainage to meningeal lymphatics, thereby weakening immunosurveillance. GBM simultaneously remodels the blood–brain barrier into a heterogeneous and permeable blood–tumor barrier that restricts uniform drug penetration yet enables tumor progression. These alterations intersect with profound immunosuppression mediated by pericytes, tumor-associated macrophages, and hypoxic niches. Advances in imaging, including DCE-MRI, DTI-ALPS, CSF-tracing PET, and elastography, now allow in vivo characterization of glymphatic function and interstitial flow. Therapeutic strategies targeting the fluid-immune interface are rapidly expanding, including convection-enhanced delivery, intrathecal and intranasal approaches, focused ultrasound, nanoparticle systems, and lymphatic-modulating immunotherapies such as VEGF-C and STING agonists. Integrating barrier modulation with immunotherapy and nanomedicine holds promise for overcoming treatment resistance. Our review synthesizes the mechanistic, microenvironmental, and translational advances that position the glymphatic–immune axis as a new frontier in glioblastoma research. Full article

Background: According to the literature, adverse drug reactions (ADRs) account for 5–10% of hospital admissions and affect 25–30% of hospitalized patients, but no data are available for Gabon. Objectives: To estimate the incidence of ADRs among hospitalized patients at the Libreville University Hospital Center (CHUL) and to classify them according to their frequency, severity, mechanism and preventability, while proposing appropriate risk minimization strategies. Patients and Methods: A 14-month, single-center, prospective study included all patients experiencing ADRs, excluding those without ADRs or with intentional overdoses. ADRs were analyzed using the World Health Organization (WHO) causality assessment, the ATC classification, and Rawlins and Thompson criteria. Data were actively collected from patients and hospital records. Results: Among 4999 patients, 105 experienced 177 adverse events (incidence: 3.5%, 95% CI: 1.7–2.5%). Among the identified ADRs, 42% were serious. Nausea and vomiting were the most frequent ADRs, mainly caused by analgesics (nefopam, tramadol) and antibiotics (amoxicillin–clavulanic acid). The gastrointestinal and nervous systems were the most affected. According to the Rawlins and Thompson classification, 90% of ADRs were type A, 8% type B, and 2% type E (withdrawal syndrome). Overall, 90% of ADRs were preventable. Conclusions: This study highlights the importance of pharmacovigilance at CHUL, Gabon, and emphasizes the role of healthcare professionals in ADR reporting and risk minimization. Full article

Atherosclerosis remains a leading cause of cardiovascular mortality despite advances in pharmacological and interventional therapies. Current treatment approaches face limitations including systemic side effects, inadequate local drug delivery, and restenosis following vascular interventions. Gel-based technologies offer unique advantages through tunable mechanical properties, controlled degradation kinetics, high drug-loading capacity, and potential for stimuli-responsive therapeutic release. This review examines gel platforms across multiple scales and applications in atherosclerosis research and intervention. First, gel-based in vitro models are discussed. These include hydrogel matrices simulating plaque microenvironments, three-dimensional cellular culture platforms, and microfluidic organ-on-chip devices. These devices incorporate physiological flow to investigate disease mechanisms under controlled conditions. Second, therapeutic strategies are addressed through macroscopic gels for localized treatment. These encompass natural polymer-based, synthetic polymer-based, and composite formulations. Applications include stent coatings, adventitial injections, and catheter-delivered depots. Natural polymers often possess intrinsic biological activities including anti-inflammatory and immunomodulatory properties that may contribute to therapeutic effects. Third, nano- and microgels for systemic delivery are examined. These include polymer-based nanogels with stimuli-responsive drug release responding to oxidative stress, pH changes, and enzymatic activity characteristic of atherosclerotic lesions. Inorganic–organic composite nanogels incorporating paramagnetic contrast agents enable theranostic applications by combining therapy with imaging-guided treatment monitoring. Current challenges include manufacturing consistency, mechanical stability under physiological flow, long-term safety assessment, and regulatory pathway definition. Future opportunities are discussed in multi-functional integration, artificial intelligence-guided design, personalized formulations, and biomimetic approaches. Gel technologies demonstrate substantial potential to advance atherosclerosis management through improved spatial and temporal control over therapeutic interventions. Full article