Search Results (43,373)

Background: The role of vascular endothelial growth factor (VEGF) in intimal hyperplasia has been investigated and discussed numerous times in the literature, producing contrary results and controversial outcomes. In particular, research concerned with the effects of VEGF after catheter-mediated injuries regarding the development of neointimal hyperplasia resulted in diverging conclusions. Methods: A systematic review based on PRISMA principles using MEDLINE was conducted. In summary, 66 publications met the qualifying criteria to be included in this review. Results: VEGF can both cause and attenuate neointimal hyperplasia depending on its site of application and production. Endogenous VEGF produced in the media and adventitia promotes intimal hyperplasia after vascular injury, while exogenous VEGF delivered through drug eluting-stents or by gene therapy can ameliorate re-endothelialization and thereby inhibit intima hyperplasia. Conclusions: The understanding of post-injury released cytokines such as VEGF holds great promise for currently used therapeutic applications and potential for applications to be investigated in the future. Full article

Background/Objectives: Ascorbic acid (AA)is a micronutrient with concentration-dependent anticancer properties, acting either as a reactive oxygen species (ROS) scavenger or inducer. Methods: Conventional redox-based assays such as MTS/MTT often overestimate cell proliferation due to AA’s interaction with tetrazolium salts, leading to increased formazan production. To overcome this limitation, we employed the Propidium Iodide Triton X-100 (PI/TX-100) assay to evaluate AA’s cytotoxic effects across a diverse panel of cancer and normal cell lines, including prostate (22Rv1, C4-2B, DU-145, LNCaP), breast (MCF-7, MDA-MB-231, MDA-MB-453), lung (A549), liver (HepG2, SK-HEP-1, Huh7), and kidney (Vero) cells. Results: AA significantly suppressed cancer cell viability compared to normal cells (RWPE1 and Vero), with the strongest effects observed in hormone receptor-positive lines. The relative sensitivity to AA followed distinct patterns within each cancer type. Mechanistically, AA-induced cell death involved ROS generation, lipid peroxidation, cell cycle arrest, ferroptosis, apoptosis, and downregulation of pyruvate dehydrogenase kinase 1 (PDHK1). Conclusions: These findings further support the potential of AA as a selective anticancer agent and highlight the importance of assay choice in evaluating its therapeutic efficacy. Full article

Breast cancer is a common and chronic condition, and despite improvements in diagnosis, treatment, and prevention, the number of cases of breast cancer is rising annually. New therapeutic drugs that target specific checkpoints should be created to fight breast cancer. Mandragora autumnalis possesses substantial cultural value as a herb and is regarded as one of the most significant medicinal plants; however, little is known about its anticancerous biological activity and chemopreventive molecular pathways against the triple-negative breast cancer (MDA-MB-231) cell line. In this study, the antioxidant, anticancer, and underlying molecular mechanisms of the Mandragora autumnalis ethanolic leaves extract (MAE) were evaluated, and its phytochemical composition was determined. Results indicated that MAE diminished the viability of MDA-MB-231 cells in a concentration- and time-dependent manner. Although MAE exhibited 55% radical scavenging activity at higher concentrations in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the attenuation of its cytotoxic effects in MDA-MB-231 cells with N-acetylcysteine (NAC) co-treatment suggests a potential role of oxidative stress. Additionally, MAE caused an increase in the tumor suppressor p53. Moreover, this extract caused a significant decrease in the expression of Ki-67 (a cellular proliferation marker), MMP-9 (matrix metalloproteinase-9, an enzyme involved in extracellular matrix degradation and metastasis), and STAT-3 (a transcription factor regulating cell growth and survival). Also, MAE altered cell cycle, cell migration, angiogenesis, invasion, aggregation, and adhesion to suppress cellular processes linked to metastasis. All of our research points to MAE’s potential to function as an anticancer agent and opens up new possibilities for the development of innovative triple-negative breast cancer treatments. Full article

Background: Diabetic foot ulcers (DFUs) in patients with peripheral artery disease (PAD) are difficult to treat and associated with poor healing outcomes. Photobiomodulation therapy (PBMT) and exercise have shown individual benefits, but evidence on their combined effects is limited. Objective: To evaluate whether PBMT combined with resistance exercise improves wound healing and walking ability in patients with DFU and PAD. Methods: In this pilot randomized trial, 11 patients with DFU and PAD were allocated to either PBMT plus supervised exercise or exercise alone for 4 weeks. Outcome measures included wound size, skin temperature, and 6-min walking distance. Results: PBMT combined with exercise improved wound healing and walking capacity compared with baseline; however, no significant between-group differences were observed. A positive correlation was observed between post-PBMT plantar skin temperature and percentage of wound reduction. Conclusions: PBMT combined with resistance exercise may enhance wound healing and functional mobility in patients with DFU and PAD. Full article

Feline infectious peritonitis (FIP) is a progressive and often fatal disease caused by a virulent biotype of feline coronavirus (FCoV). Although antiviral treatments are now available, relapse and resistance remain ongoing concerns. This study investigates the therapeutic potential of P. indusiatus, a medicinal mushroom, for its antiviral and anti-inflammatory activities against FIP. The main protease (FIPV M^pro) of feline infectious peritonitis virus (FIPV) was recombinantly expressed and purified to facilitate enzyme inhibition screening. P. indusiatus exhibited the strongest FIPV M^pro inhibitory activity among the 17 mushroom extracts tested (69.2%), showing a notable level of inhibition relative to standard antiviral agents such as lopinavir and ritonavir. To assess its anti-inflammatory potential, PBMCs derived from healthy cats and FIP-associated effusions (FIP fluid) were cultured and stimulated with LPS to induce inflammation. In healthy PBMCs, P. indusiatus significantly reduced nitrite levels, with effects similar to dexamethasone. However, PBMCs from FIP fluid, already in an activated state, showed no additional response. Notably, this study is the first to successfully isolate and culture PBMCs from FIP fluid, providing a new platform for future immunological research. These findings suggest that P. indusiatus possesses both antiviral and anti-inflammatory properties, positioning it as a potential dual-action therapeutic candidate for FIP. Further investigation into cytokine signaling pathways is warranted to clarify its mechanisms of action and advance future therapeutic development. Full article

Background/Objectives: The intranasal (IN) route of administration is a promising non-invasive approach for brain targeting, bypassing the blood–brain barrier and enhancing bioavailability. Citalopram hydrobromide (CT), a widely prescribed sparingly water-soluble selective serotonin reuptake inhibitor (SSRI), faces challenges with oral and intravenous administration, including delayed onset, adverse effects, and patient compliance issues. Methods: This study aimed to develop a novel thermoresponsive polymeric micelle (PM) system based on Pluronic^® copolymers (Pluronic F127 and Poloxamer 188) improving CT’s solubility, stability, and nasal permeability for enhanced antidepressant efficacy. A preliminary study was conducted to select the optimized formulation. The preparation process involved using the thin-film hydration method, followed by freeze-drying. Comprehensive evaluations of optimized formulation characteristics included Z-average, polydispersity index (PdI), thermal behavior (lower critical solution temperature, LCST), encapsulation efficiency, X-ray powder diffraction (XRPD), thermodynamic solubility, and biological stability. Additionally, in vitro CT release and CT permeability in nasal conditions were studied. Stability under storage was also evaluated. Results: The optimized CT-PM formulation showed nanoscale micelle size (Z-average of 31.41 ± 0.99 nm), narrow size distribution (polydispersity index = 0.241), and a suitable thermal behavior for intranasal delivery (lower critical solution temperature (LCST) ~31 °C). Encapsulation efficiency reached approximately 90%, with an amorphous structure confirmed via XRPD, leading to a 95-fold increase in CT solubility. The formulation demonstrated appropriate biological and physical stability. In vitro studies showed a 25-fold faster CT release from optimized formulation compared to the initial CT, while CT-PM permeability in nasal conditions increased four-fold. Conclusions: This novel nanoscale thermosensitive formulation is a value-added strategy for nasal drug delivery systems, offering enhanced drug solubility, rapid drug release, stability, and improved permeability. This smart nanosystem represents a promising platform to overcome the limitations of conventional CT administration, improving therapeutic outcomes and patient compliance in depression management. Full article

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality worldwide, with a high proportion of cases diagnosed at advanced stages. Accurate mediastinal staging is essential to guide optimal therapeutic decisions. This study aimed to evaluate the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to develop a composite clinical–molecular score (EXPoSURE) for risk stratification. Methods: A retrospective study was performed that included 131 patients diagnosed with lung cancer between December 2023 and December 2024 at a regional oncology center in Oltenia, Romania. All patients underwent bronchoscopy and EBUS-TBNA using a standardized protocol. Clinical, pathological, and molecular data were collected to assess diagnostic yield, staging performance, and the association with molecular markers. The EXPoSURE score integrated PD-L1, p63, EGFR status, comorbidities, histological type, and TNM stage. Results: EBUS-TBNA provided a conclusive diagnosis in 91.6% of cases, with a low rebiopsy rate of 8.4% and no requirement for mediastinoscopy. Most patients (68%) were diagnosed at stage IV. PD-L1, p63, and EGFR expression showed no significant correlation with TNM stage, while the EXPoSURE score demonstrated promising stratification capability. Occupational exposure appeared to influence disease severity in some subgroups, although further validation is needed. Conclusions: EBUS-TBNA is a valuable, safe, and effective approach for minimally invasive diagnosis and mediastinal staging of lung cancer. The proposed EXPoSURE composite score may contribute to a multidimensional risk assessment, supporting more tailored management strategies and warranting prospective validation. Full article

Neuroblastoma (NB) is an aggressive pediatric cancer, with high-risk patients facing a five-year survival rate of ~50%. Standard therapies, including surgery, chemotherapy, radiation, and immunotherapy, are associated with significant long-term toxicities and frequent relapse. Histone deacetylase (HDAC) inhibitors have emerged as promising agents for cancer therapy, given their role in modulating gene expression and tumor phenotypes. This study evaluated M344 [4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide], an HDAC inhibitor, for its efficacy and mechanisms of action against NB. Analysis of clinical NB Gene Expression Omnibus data revealed advanced-stage tumors exhibit higher HDAC expression relative to early-stage samples. M344 treatment effectively increased histone acetylation, induced G0/G1 cell cycle arrest, and activated caspase-mediated cell death. Relative to vorinostat, an HDAC inhibitor in clinical use for lymphoma and clinical trials for NB, M344 displayed superior cytostatic, cytotoxic, and migration-inhibitory effects. In vivo, metronomic M344 dosing suppressed tumor growth and extended survival. Combination therapy with M344 and topotecan improved topotecan tolerability, while M344 co-administration with cyclophosphamide reduced tumor rebound post-therapy. In total, M344 demonstrated strong therapeutic potential for NB, offering improved tumor suppression, reduced off-target toxicities, and enhanced control of tumor growth post-therapy. These findings support further investigation of HDAC inhibitors, such as M344, for clinical application in NB treatment. Full article

The efficient and targeted delivery of pharmaceutical substances remains a major challenge in modern therapeutics. Traditional drug delivery systems often suffer from limited bioavailability, rapid clearance, and off-target effects. Red blood cells (erythrocytes), due to their long circulation time, biocompatibility, and immune-evasive properties, have emerged as promising carriers in the development of novel nanotechnology-based drug delivery platforms.A comprehensive literature review was conducted, analyzing recent studies on erythrocyte membrane-coated nanoparticles, their interactions with loaded therapeutic agents, and their performance in vitro and in vivo. Special focus was given to applications in chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and immunotherapy. Erythrocyte-based nanocarriers demonstrated improved circulation times, reduced immune clearance, and enhanced targeting capabilities compared to traditional nanoparticles. Encapsulation of nanoparticles within erythrocyte membranes preserved the functional integrity of the carrier while minimizing systemic toxicity. However, challenges such as membrane stability, hemocompatibility, and the potential for nanoparticle-induced hemoglobin dysfunction were identified as areas requiring further research. In conclusion, erythrocyte membrane-coated nanoparticles represent a unique and promising strategy for drug delivery, combining the natural advantages of red blood cells with the versatility of nanotechnology. Full article

N-acetylcysteine (NAC) has garnered increasing interest for its neurotherapeutic capabilities beyond its recognized functions as a mucolytic agent and an antidote for acetaminophen toxicity. This review consolidates findings from both preclinical and clinical studies to investigate NAC’s diverse modulatory effects on the central nervous system (CNS). NAC primarily functions as an antioxidant by replenishing glutathione and mitigating oxidative stress; however, it produces glutathione-independent effects through the modulation of mitochondrial redox systems, ferroptosis, and the Nrf2-ARE signaling pathway. It plays a significant role in neuroinflammatory processes by inhibiting the production of cytokines, the expression of iNOS, and the activation of microglia. Furthermore, NAC affects various neurotransmitter systems—including glutamatergic, dopaminergic, GABAergic, serotonergic, cholinergic, and adrenergic pathways—by modulating synaptic transmission, receptor activity, and transporter functionality. It promotes neuroprotection through the enhancement of neurotrophic factors, the preservation of mitochondrial integrity, and the upregulation of survival signaling pathways. Recent evidence also emphasizes NAC’s role in gene expression and the regulation of cortisol levels. The extensive range of NAC’s neurobiological effects highlights its therapeutic potential in treating neurodegenerative and neuropsychiatric disorders. Nevertheless, the variability in clinical outcomes indicates a pressing need for more focused, mechanism-based research. Full article

Background/Objectives: The clinical impact of antipsychotics on the human body remains inadequately investigated, hence we aimed to compere the effects olanzapine (OLZ) and Clozapine (CLZ) on different body systems. Methods: 48 patients and 24 healthy individuals were involved, and followed over six months. PANSS, metabolic, cardiovascular, inflammatory, and neuronal transmitter parameters were determined. Results: No significant difference was found between the effects of the two drugs on blood mineral and cardiovascular parameters, except for CK-MB, which showed a greater increase in the OLZ group than in the CLZ group. Both drugs increased the lipid profile and HbA1C levels, with the effect of CLZ being more prominent. Both drugs increased the patients’ body weights, with no significant difference between their effects. Regarding renal and hepatic functions, OLZ had a more notable effect on creatinine and albumin levels than CLZ, while AST and ALT showed markedly greater increases in the CLZ-treated group than in the OLZ-treated group. Regarding the effects on neurotransmitters and inflammatory mediators, both drugs increased serotonin and ghrelin levels, in addition to decreasing leptin concentrations, and decreased the inflammatory mediators IL-1β, IL-6, and –TNF-α, with the effect of OLZ being more prominent. Regarding therapeutic efficacy, CLZ was more effective at reducing general and negative symptoms than OLZ. Conclusions: The present study revealed that CLZ had a greater impact on metabolic parameters and better therapeutic efficacy in attenuating both general and negative symptoms, whereas OLZ had more detectable anti-inflammatory effects, aid determining the appropriate treatment for schizophrenic patients. Full article

In the context of expanding research on the development of compounds with multiple therapeutic actions, this study aims to consolidate findings from the last decade on new synthetic sulfonamide therapies for managing type 2 diabetes mellitus (T2DM) associated with oxidative stress (OS). The novelty of this synthesis study lies in the synergistic approach of antidiabetic molecular targets with those against oxidative stress, having the sulfonylurea class as a common point. By utilizing international databases, we identified and selected conclusive studies for this review. Promising results have been achieved through dual therapies that combine antioxidants (such as sesame oil, naringin, alpha-lipoic acid, resveratrol, and quercetin) with sulfonylureas (including glipizide, glibenclamide, gliclazide, and glimepiride). Additionally, triple therapies that associated sulfonylureas with other classes of antidiabetic medications have also shown encouraging outcomes. These findings are supported by in vivo tests conducted on experimental laboratory models as well as on human subjects. These recent advancements in synthetic sulfonamide research point to a promising future in diabetes management, especially considering the dual functionalities demonstrated by in vivo studies—specifically, their antidiabetic and antioxidant effects. Moreover, the synergy between sulfonamides and other antioxidant agents represents a beneficial strategy for optimizing future chemical structures, potentially allowing for their integration into personalized treatments aimed at combating T2DM. Full article

Background. Orthodontic extrusion (OE), or forced eruption, is a conservative technique used to recover teeth affected by coronal fractures, traumatic intrusions, or severe caries. It involves applying light, continuous forces to induce vertical tooth movement, promoting tissue remodeling through periodontal ligament stimulation. Materials and Methods. This narrative review included studies investigating OE as a therapeutic approach for the management of deep or subgingival carious lesions, traumatic dental injuries (such as intrusion or fracture), or for alveolar ridge augmentation in implant site development. OE is typically performed using fixed appliances such as the straight-wire system or, in selected cases, clear aligners. Forces between 30 and 100 g per tooth are applied, depending on the clinical situation. In some protocols, OE is combined with fiberotomy to minimize gingival and bone migration. Results. Studies show that OE leads to significant vertical movement and increases in buccal bone height and interproximal septa. It enhances bone volume in targeted sites, making it valuable in implant site development. Compared to surgical crown lengthening, OE better preserves periodontal tissues and improves esthetics. Conclusions. In this narrative review is analized how OE is effective for managing traumatic intrusions and compromised periodontal sites, particularly when paired with early endodontic treatment. It reduces the risks of ankylosis and root resorption while avoiding invasive procedures like grafting. Although clear aligners may limit axial tooth movement, OE remains a minimally invasive, cost-effective alternative in both restorative and implant dentistry. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by lung scarring, impaired function, and high mortality. Effective therapies to reverse fibrosis are lacking. This study aims to uncover the molecular mechanisms of IPF, explore diagnostic biomarkers, and identify therapeutic targets. Methods: Multi-omics data were integrated to identify biomarkers with causal associations to IPF using Mendelian randomization and transcriptomic analysis. Machine learning was employed to construct a diagnostic model, and single-cell transcriptomic analysis determined gene expression patterns in fibrotic lung tissue. Results: Seven core genes (GREM1, UGT1A6, CDH2, TDO2, HS3ST1, ADGRF5, and MPO) were identified, showing strong diagnostic potential (AUC = 0.987, 95% CI: 0.972–0.987). These genes exhibited distinct distribution patterns in fibroblasts, endothelial cells, epithelial cells, macrophages, and dendritic cells. Conclusions: This study highlights key genes driving IPF, involved in pathways related to metabolism, immunity, and inflammation. However, their utility as fluid-based biomarkers remains unproven and requires protein-level validation in prospective cohorts. By integrating genomic, immunological, and cellular insights, it provides a framework for targeted therapies and advances mechanism-based precision medicine for IPF. Full article

Alcohol use disorder (AUD) is a widespread, multifaceted disorder involving overproduction of pro-inflammatory cytokines, oxidative liver injury, and dysfunction of the brain’s dopaminergic reward circuits. Korean red ginseng (KRG), an herbal supplement derived from Panax ginseng, has demonstrated qualities potentially useful to the treatment of AUD, including antioxidative, anti-inflammatory, neuroprotective, and anxiolytic effects. This review examines active constituents of KRG, their pharmacological actions, and evidence supporting KRG’s therapeutic potential in the context of AUD, while also assessing its safety profile, adverse effects, and potential drug interactions. KRG’s main bioactive constituents, ginsenosides, appear to have roles in modulating alcohol-metabolizing enzymes, ethanol-activated inflammatory cytokine cascades, and neurological systems disrupted by AUD, including GABAergic and dopaminergic pathways. Evidence from animal models and limited small-scale human trials suggests KRG may alleviate symptoms of alcohol withdrawal, enhance cognitive performance, and attenuate anxiety through these pathways. While generally safe for consumption, several case reports and animal studies have indicated KRG’s potential to pose a variety of risks in vulnerable populations at high, prolonged doses, including hepatotoxicity, cardiovascular changes, mood disturbances, and hormonal effects. Furthermore, KRG’s neuromodulating role and influence on cytochrome P450 enzymes make it liable to interact with several medications, including warfarin, midazolam, selegiline, and serotonergic agents. Overall, KRG shows promise as a complementary supplement in managing aspects of AUD, though current evidence is limited by low sample sizes, inconsistent reports regarding nuances of ginsenosides’ mechanisms, and a low number of human trials. Further human-focused research is needed to elucidate its safety, efficacy, and mechanism. Full article