Search Results (2,832)

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

Background: Exposure-based cognitive behavioral therapy (Ex-CBT) is widely seen as the gold-standard treatment for anxiety and obsessive-compulsive disorder (OCD). Yet, minoritized youth are underrepresented in efficacy studies, raising questions about the applicability of Ex-CBT to minoritized youth. Effectiveness data suggest systematic adaptation of Ex-CBT to address youth culture and context is likely needed, and many clinicians make adaptations and augmentations in practice. However, research on the specific strategies clinicians use to address their youth clients’ culture and context within anxiety and OCD treatment is lacking. In the current study, we assess practice-based adaptations, augmentations, and process-based approaches utilized when delivering treatment to youth for OCD and anxiety in public mental health clinics. Methods: We conducted qualitative interviews with 16 clinicians from both specialty anxiety and general mental health clinics serving youth with anxiety or OCD in the public mental health system. Participating clinicians had a mean age of 32.19 (SD = 5.87) and 69% of therapists identified as female; 69% identified as White, 25% identified as Asian, and 6% as Black or African American. In qualitative interviews, clinicians shared how they addressed clients’ culture and context (e.g., social identities, stressors and strengths related to social identities and lived environment). Thematic analysis identified the strategies clinicians employed to address culture and context. Results: Clinicians reported incorporating culture and context through process-based approaches (e.g., building trust gradually, considering clients’ social identity stressors, engaging in self-awareness to facilitate cultural responsiveness) and through culturally adapting and augmenting treatment to promote person-centered care. Core strategies included proactive and ongoing assessment of clients’ cultural and contextual factors, adapting exposures and augmenting Ex-CBT with strategies such as case management and discussion of cultural context, and taking a systems-informed approach to care. Conclusions: Examining practice-based adaptations, augmentations, and process-based approaches to treatment for minoritized youth with OCD or anxiety can inform efforts to understand what comprises person-centered culturally responsive Ex-CBT. Empirical testing of identified strategies is a needed area of future research. Full article

Background: Neuropathic pain (NP), resulting from damage to the somatosensory nervous system, affects 7–10% of the global population and remains poorly managed despite available therapies. Smoking has been associated with increased pain severity and disease burden, yet its role in neuropathy/NP has not been systematically reviewed. This systematic review synthesizes the existing literature on smoking status and its relationship with neuropathy/NP incidence, prevalence, and severity. Methods: The review was conducted in accordance with PRISMA guidelines and included studies that assessed smoking consumption, dependency, quantity, and cessation in individuals with neuropathy/NP. Summary estimates were stratified by exposure type, and pooled odds ratios and relative risks were calculated. Results: Across 62 studies comprising cohort, case–control, and cross-sectional designs, smoking was consistently associated with greater NP prevalence and pain severity. Smoking dependency was linked to increased incidence, while cessation was associated with reduced risk of NP. Despite considerable heterogeneity and risk of bias, particularly from subjective exposure measurement and inconsistent classification, this relationship remained statistically significant. Conclusions: Findings support the role of smoking as a modifiable risk factor in various etiologies of neuropathy/NP. Cessation may represent a low-cost, low-risk, low-tech adjunctive therapy; however, further robust cessation interventional trials are needed, particularly for less common infectious causes of chronic NP such as leprosy. Full article

Background: Androgenetic alopecia (AGA) and alopecia areata (AA) impose significant psychosocial burdens. While pharmacological and surgical treatments exist, the role of dietary factors remains underexplored due to methodological limitations in observational studies. This Mendelian randomization (MR) study investigates causal relationships between 187 dietary exposures and hair loss, leveraging genetic variants to address confounding biases. Methods: Genome-wide association study (GWAS) data from 161,625 UK Biobank participants were analyzed, focusing on food preferences and intake patterns. Genetic instruments for each of the 187 dietary exposures were selected at a genome-wide significance threshold (p < 5 × 10⁻⁸), with rigorous sensitivity analyses (MR-Egger, MR-PRESSO) to validate causality. Outcomes included AA and AGA datasets from the FinnGen consortium. Results: MR analysis identified 18 specific dietary exposures significantly associated with non-scarring hair loss (FDR < 0.05). Protective effects emerged for antioxidant-rich dietary exposures, represented by higher preferences for melon, onions, and tea. Elevated risks were observed for certain exposures, including croissants, goat cheese, and whole milk. Alcohol consumption exhibited the strongest risk associations. Our extensive analysis of alcohol intake, combining data from multiple studies, consistently identified it as a significant risk factor for both alopecia areata and androgenetic alopecia. Conclusions: These findings imply modifiable dietary patterns in hair loss pathophysiology. A dual strategy is proposed: prioritizing polyphenol-rich plant foods while minimizing pro-inflammatory triggers like processed carbohydrates and alcohol. Clinically, tailored dietary adjustments—reducing ultra-processed foods and alcohol—may complement existing therapies for hair loss management. Full article

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Reactive oxygen species (ROS) are often seen solely as harmful byproducts of oxidative metabolism, yet evidence reveals their paradoxical roles in both promoting and inhibiting cancer progression. Despite advances, precise context-dependent mechanisms by which ROS modulate oncogenic signaling, therapeutic response, and tumor microenvironment dynamics remain unclear. Specifically, the spatial and temporal aspects of ROS regulation (i.e., the distinct effects of mitochondrial versus cytosolic ROS on the PI3K/Akt and NF-κB pathways, and the differential cellular outcomes driven by acute versus chronic ROS exposure) have been underexplored. Additionally, the specific contributions of ROS-generating enzymes, like NOX isoforms and xanthine oxidase, to tumor microenvironment remodeling and immune modulation remain poorly understood. This review synthesizes current findings with a focus on these critical gaps, offering novel mechanistic insights into the dualistic nature of ROS in cancer biology. By systematically integrating data on ROS source-specific functions and redox-sensitive signaling pathways, the complex interplay between ROS concentration, localization, and persistence is elucidated, revealing how these factors dictate the paradoxical support of tumor progression or induction of cancer cell death. Particular attention is given to antioxidant mechanisms, including NRF2-mediated responses, that may undermine the efficacy of ROS-targeted therapies. Recent breakthroughs in redox biosensors (i.e., redox-sensitive fluorescent proteins, HyPer variants, and peroxiredoxin–FRET constructs) enable precise, real-time ROS imaging across subcellular compartments. Translational advances, including redox-modulating drugs and synthetic lethality strategies targeting glutathione or NADPH dependencies, further highlight actionable vulnerabilities. This refined understanding advances the field by highlighting context-specific vulnerabilities in tumor redox biology and guiding more precise therapeutic strategies. Continued research on redox-regulated signaling and its interplay with inflammation and therapy resistance is essential to unravel ROS dynamics in tumors and develop targeted, context-specific interventions harnessing their dual roles. Full article

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article

Background/Objectives: The rapid emergence of multidrug-resistant bacterial infections demands innovative non-antibiotic therapeutic strategies. Dual-modal photoresponse therapy integrating photodynamic (PDT) and photothermal (PTT) effects offers a promising rapid antibacterial approach, yet designing single-material systems with synergistic enhancement remains challenging. This study aims to develop uniform Cu-based metal–organic framework micrometer cubes (Cu-BN) for efficient PDT/PTT synergy. Methods: Cu-BN cubes were synthesized via a one-step hydrothermal method using Cu(NO₃)₂ and 2-amino-p-benzoic acid. The material’s dual-mode responsiveness to visible light (420 nm) and near-infrared light (808 nm) was characterized through UV–Vis spectroscopy, photothermal profiling, and reactive oxygen species (ROS) generation assays. Antibacterial efficacy against multidrug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was quantified via colony counting under dual-light irradiation. Results: Under synergistic 420 + 808 nm irradiation for 15 min, Cu-BN (200 μg/mL) achieved rapid eradication of multidrug-resistant E. coli (99.94%) and S. aureus (99.83%). The material reached 58.6 °C under dual-light exposure, significantly exceeding single-light performance. Photodynamic analysis confirmed a 78.7% singlet oxygen (¹O₂) conversion rate. This enhancement stems from PTT-induced membrane permeabilization accelerating ROS diffusion, while PDT-generated ROS sensitized bacteria to thermal damage. Conclusions: This integrated design enables spatiotemporal PDT/PTT synergy within a single Cu-BN system, establishing a new paradigm for rapid-acting, broad-spectrum non-antibiotic antimicrobials. The work provides critical insights for developing light-responsive biomaterials against drug-resistant infections. Full article

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

Introduction: Actinic cheilitis (AC) is a common precancerous condition affecting the lips, primarily caused by prolonged ultraviolet radiation exposure. Various treatment options are available. However, the optimal treatment approach remains a subject of debate. Objective: To summarize and compare practice-relevant interventions for AC. Materials and Methods: A pre-defined protocol was registered in PROSPERO (CRD42021225182). Systematic searches in Medline, Embase, and Central, along with manual trial register searches, identified studies reporting participant clearance rates (PCR) or recurrence rates (PRR). Quality assessment for randomized controlled trials (RCTs) was conducted using the Cochrane Risk of Bias tool 2. Uncontrolled studies were evaluated using the tool developed by the National Heart, Lung, and Blood Institute. The generalized linear mixed model was used to pool proportions for uncontrolled studies. A pairwise meta-analysis for RCTs was applied, using the odds ratio (OR) as the effect estimate and the GRADE approach to evaluate the quality of the evidence. Adverse events were analyzed qualitatively. Results: A comprehensive inclusion of 36 studies facilitated an evaluation of 614 participants for PCR, and 430 patients for PRR. Diclofenac showed the lowest PCR (0.53, 95% confidence interval (CI) [0.41; 0.66]), while CO₂ laser showed the highest PCR (0.97, 95% CI [0.90; 0.99]). For PRR, Er:YAG laser showed the highest rates (0.14, 95% CI [0.08; 0.21]), and imiquimod the lowest (0.00, 95% CI [0.00; 0.06]). In a pairwise meta-analysis, the OR indicated a lower recurrence rate for Er:YAG ablative fractional laser (AFL)-primed methyl-aminolevulinate photodynamic therapy (MAL-PDT) (Er:YAG AFL-PDT) compared to methyl-aminolevulinate photodynamic therapy (MAL-PDT) alone (OR = 0.22, 95% CI [0.06; 0.82]). The CO₂ laser showed fewer local side effects than the Er:YAG laser, while PDTs caused more skin reactions. Due to qualitative data, comparability was limited, highlighting the need for individualized treatment. Conclusions: This study provides a complete and up-to-date evidence synthesis of practice-relevant interventions for AC, identifying the CO₂ laser as the most effective treatment and regarding PCR and imiquimod as most effective concerning PRR. Full article

Background: Various predisposing factors contribute to the emergence and dissemination of the multidrug-resistant (MDR) phenotype in Escherichia coli and Klebsiella pneumoniae. Understanding these factors is crucial for guiding appropriate antimicrobial therapy and infection control strategies. This study investigated the predisposing factors contributing to the MDR characteristics of E. coli and K. pneumoniae isolated in a community hospital in northeastern Thailand. Methods: This case–control study utilized retrospective data from bacterial culture, as well as demographic, clinical, and antibiotic susceptibility records collected during 5 years (January 2016–December 2020). E. coli and K. pneumoniae isolates were analyzed from various clinical samples, including blood, urine, pus, sputum, and other body fluids. Data were analyzed using descriptive statistics and univariate logistic regression. Results: In total, 660 clinical isolates were analyzed (421 E. coli and 239 K. pneumoniae). Blood was the most common source of the detection of E. coli (63.0%) and sputum was the most common source of K. pneumoniae (51.0%). The median ages of patients were 67 and 63 years for E. coli and K. pneumoniae, respectively. E. coli cases were significantly associated with prior antibiotic use (OR = 1.79, 95% CI: 1.17–2.74 p = 0.008). MDR was observed in 50.1% of E. coli and 29.7% of K. pneumoniae (p < 0.001). E. coli compared to K. pneumoniae had lower resistance to third-gen cephalosporins (64.9% versus 95.8%) and carbapenems (8.0% versus 6.9%). ICU admission was the only factor significantly associated with MDR E. coli (OR = 2.40, 95% CI: 1.11–5.20 p = 0.026). No significant differences were observed in gender, age, or comorbidities between MDR cases. Antibiotic usage patterns also differed, with E. coli more likely to receive third-gen cephalosporins compared to carbapenems (OR = 3.02, 95% CI:1.18–7.74 p = 0.021). Conclusions: The use of third-generation cephalosporin may drive MDR E. coli more than K. pneumoniae. Prior antibiotic exposure was linked to E. coli bloodstream infections, while MDR E. coli showed greater clinical severity. These findings highlighted the need for improved antibiotic stewardship in rural hospitals. Full article

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Background and Clinical Significance: Traumatic dental injuries, particularly complicated crown fractures of permanent incisors, are common in adolescents, with maxillary central incisors most frequently affected due to their prominent position. These injuries, often resulting from sports or accidents, require prompt management to prevent complications such as pulp necrosis or infection, which can compromise long-term prognosis. Fragment reattachment offers a conservative, esthetically favorable approach when the fractured segment is intact, with outcomes comparable to composite restorations. This case report underscores the importance of timely intervention and advanced restorative techniques in pediatric dentistry. Case Presentation: A 16-year-old male presented with a complicated crown fracture of the upper left central incisor sustained during a soccer game. The fracture extended subgingivally with pulp exposure. The patient preserved the fragment in saline. Treatment involved fragment reattachment using a dentin bonding agent and flowable composite resin, followed by single-visit root canal therapy due to delayed presentation (48 h). A glass fiber post was placed to reinforce the restoration due to significant coronal loss. Three years of follow-up visits (1, 3, 6, 12, 24, and 36 months) revealed no clinical or radiographic complications, with the tooth remaining asymptomatic and functional. Conclusions: This case underscores the effectiveness of fragment reattachment when combined with meticulous technique and long-term monitoring. Full article

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

Phosphatidylinositol-3-kinase (PI3K) inhibition has emerged as a therapeutic option against indolent lymphoma, including relapsed follicular lymphoma (FL). While inhibition of active signaling in the lymphoma cell represents the primary mode of action, PI3K inhibition also exerts immunomodulatory effects. Here we have analyzed 17 consecutive advanced treatment line FL patients treated with the delta-selective PI3K inhibitor idelalisib in a retrospective single-center observational study, with a specific focus on response and immune effects. Eleven patients achieved complete remission (CR) or partial remission (PR) with median response duration of 22 (11–88) months following a median idelalisib exposure of 15 (4–88) months. Disease response persisted in three patients for a median of 37 (21–63) months following cessation of idelalisib without another therapy being initiated. Autoimmune side effects occurred in eight of the eleven patients who responded, compared to none in six patients whose disease did not respond. In conclusion, a time-limited exposure to idelalisib may induce sustained remissions in a portion of patients with recurrent and/or refractory (r/r) FL, suggesting immunomodulatory effects of PI3K inhibition to be involved in the control of the disease. Full article