Search Results (1,735)

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 and Clinical Significance: Granulomatosis with polyangiitis (GPA), an immune-mediated systemic small-vessel vasculitis affecting the upper/lower respiratory tracts and kidneys, frequently presents with non-specific nasal symptoms that lead to misdiagnosis. Case Presentation: We report a case of a 55-year-old female with GPA complicated by Bartter syndrome. She presented with one month of left nasal congestion, rhinorrhea, epistaxis, and headache. Initial diagnosis was acute sinusitis. Computed tomography (CT) revealed left maxillary and ethmoid sinus inflammation with bone destruction, while metagenomic next-generation sequencing (mNGS) suggested conventional bacterial infection. Postoperative pathology demonstrated chronic mucosal inflammation with lymphoid tissue hyperplasia. GPA was ultimately diagnosed based on PR3-ANCA seropositivity and chest CT findings of cavitary pulmonary nodules. Postoperatively, severe hypokalemia and hypomagnesemia secondary to Bartter syndrome emerged. Following electrolyte correction, induction therapy with glucocorticoids and cyclophosphamide was initiated. Conclusions: This case underscores that GPA’s head and neck manifestations are frequently misdiagnosed as infections or malignancies. Early diagnosis requires vigilance for GPA ‘red flags’, such as refractory nasal symptoms to conventional therapy (e.g., bloody rhinorrhea), characteristic CT findings (e.g., sinus opacification without ostiomeatal complex obstruction), and nasal endoscopy findings (e.g., ulcers/crusting). Otolaryngologists play a pivotal role in recognizing early disease onset and initiating timely treatment. Full article

The corticotropin-releasing factor (CRF) and its type 1 receptor (CRF₁R) play a key role in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Dysregulation of the HPA axis is associated with congenital adrenal hyperplasia (CAH) and depression. Non-peptide CRF₁R-selective antagonists displayed antidepressant effects on animal models and are used for the management of CAH. To develop novel non-peptide CRF₁R antagonists, we have previously designed and synthesized a series of substituted pyrimidines. Among these analogs, molecule 43 (M43) binds to CRF₁R with the highest affinity. Based on this finding, we selected M43 for further pharmacological characterization in the present study. The results suggest that M43 is a potent CRF₁R antagonist, blocking the ability of the CRF-related agonist, Tyr⁰-sauvagine, to stimulate (1) cAMP accumulation in HEK 293 cells expressing CRF₁R and (2) the proliferation rate of RAW 264.7 macrophages. Computational studies suggest that the antagonist properties of M43 are mostly attributed to its ability to interact with residues in the allosteric pocket of CRF₁R, comprised of the third, fifth, and sixth transmembrane domain residues, which block activation-associated structural rearrangements of the receptor. Our data will be used to design novel non-peptide CRF₁R antagonists for clinical use. Full article

Background/Objectives: Prostate artery embolization (PAE) has emerged as a relatively new, minimally invasive alternative for the treatment of benign prostatic hyperplasia. We aimed to compare the perioperative outcomes and trends of PAE versus transurethral resection of the prostate (TURP) and laser enucleation. Materials and Methods: We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics, and performed multiple patient-level analyses. Patients with prostate cancer, acute hematuria, and emergent referral to the hospital were excluded. Results: Between 2017 and 2022, a total of 3665 PAEs were performed in Germany compared to 218,388 TURPs and 50,863 laser enucleations. Patients selected for PAE were slightly younger and presented with fewer comorbidities at baseline. The number of laser enucleations increased exponentially in these years, PAEs remained stable, whereas TURPs slightly decreased. Compared to PAE, laser enucleation was associated with higher odds of in-hospital incontinence (4.2% versus 2.7%, OR: 1.6, 95%CI: 1.3–1.9, p < 0.001). On the contrary, PAE was associated with lower odds of in-hospital urinary retention and shorter length of hospital stay compared to TURP (3.2% versus 7.1%, OR: 2.2, 95%CI: 1.8–2.6, p < 0.001, and a 2.6-day difference, 95%CI: 2.5–2.7, p < 0.001, respectively) and laser enucleation (3.2% versus 5%, OR: 1.5, 95%CI: 1.3–1.8, p < 0.001, and a 1.5-day difference, 95%CI: 1.4–1.6, p < 0.001, respectively). Conclusions: PAE offers more favorable perioperative outcomes compared to TURP and laser enucleation, but the use of this relatively new procedure has remained nearly stable in recent years. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is a prevalent condition in aging men and a major cause of lower urinary tract symptoms (LUTSs). While traditional treatments such as transurethral resection of the prostate (TURP) are effective, they are associated with notable morbidity. Ultrasound-guided transperineal laser ablation (TPLA) has emerged as a minimally invasive alternative. This study aimed to assess the 12-month efficacy, safety, and functional outcomes of TPLA in patients with LUTS secondary to BPH. Methods: This was a single-center, retrospective observational cohort study including 53 patients with moderate-to-severe LUTS due to BPH who underwent TPLA between November 2021 and May 2024. Baseline and follow-up assessments were conducted at 1, 3, 6, and 12 months, including IPSS, Qmax, PVR, prostate volume (MRI), QoL, IIEF-5, and MSHQ-ED/Bother scores. The procedure was performed under local anesthesia using the EchoLaser™ system, and ablation was guided via real-time transrectal ultrasonography. Results: Statistically significant improvements were observed in IPSS (median decrease from 30 to 13), Qmax (5.5 to 13.0 mL/s), and PVR (200 to 85 mL). Prostate and adenoma volumes decreased by 41.2% and 58.3%, respectively. Quality of life scores improved, and erectile function remained stable. Ejaculatory function improved significantly based on MSHQ-ED and MSHQ-Bother scores. No major complications or conversions to surgery occurred. Conclusions: TPLA appears to be a safe, effective, and minimally invasive treatment modality for LUTS caused by BPH. It offers sustained symptomatic relief, prostate volume reduction, and preservation of sexual function, making it a promising alternative for patients unfit or unwilling to undergo invasive surgery. Full article

Background/Objectives: Lower urinary tract symptoms (LUTS), such as frequency, urgency, nocturia, and urge incontinence, are commonly linked to overactive bladder (OAB) and benign prostatic hyperplasia (BPH). Oxytocin receptor (OXTR) upregulation has been proposed to enhance bladder and prostate contractility, while obesity is a recognized risk factor for LUTS, OAB, and BPH. This study aimed to investigate whether the OXTR antagonist atosiban attenuates spontaneous and oxytocin-induced contractions in bladder and prostate tissues from obese and non-obese rats. Methods: Bladder and prostate tissues were obtained from obese and non-obese rats and studied in in vitro organ bath preparations. The effects of atosiban (1 µM and 10 µM) on spontaneous contractility and oxytocin-induced responses were examined. Immunohistochemistry was performed to evaluate OXTR expression in the bladder. Results: Atosiban significantly reduced spontaneous contractions in the bladder (p < 0.0001 in obese; p < 0.01 in non-obese) and prostate (p < 0.01 in obese; p < 0.0001 in non-obese). Oxytocin-induced bladder contractions were significantly increased in obese rats but were attenuated by atosiban at 10 µM (p < 0.05), an effect absent in non-obese rats. Immunohistochemical analysis confirmed elevated OXTR expression in both epithelial and stromal compartments of the bladder in obese rats (p < 0.05). Conclusions: These findings indicate that oxytocin contributes to bladder and prostate hypercontractility, particularly in obesity. Targeting OXTR with atosiban may represent a novel therapeutic strategy for the management of LUTS, OAB, and BPH. Full article

Background/Objectives: Psoriasis is a chronic systemic inflammatory disease. Evidence on the efficacy of different mesenchymal stem cell (MSC) exosomes for psoriasis remains limited. This study aimed to evaluate the therapeutic effects of different MSC exosomes in mitigating psoriasis. Methods: The efficacy of human placenta MSC (hPMSC) and human umbilical cord MSC (hUCMSC) exosomes was compared in an imiquimod (IMQ)-induced psoriasis murine model. A meta-analysis was performed to incorporate the results of studies using IMQ-induced psoriasis murine models to compare MSC exosome treatments (exosome group) with vehicle or no-treatment controls (control group). Results: In this murine study, both the hPMSC and hUCMSC exosomes showed better effectiveness in reducing epidermal thickness and skin tissue cytokines than controls, but no significant difference was observed between the two MSC exosomes. Seven studies were included in the meta-analysis. Clinical severity scores were significantly lower in the exosome group than in the controls (standardized mean difference [SMD]: −1.886; 95% confidence interval [CI]: −3.047 to −0.724). Epidermal thickness was significantly reduced (SMD: −3.258; 95% CI: −4.987 to −1.529). No significant differences were found in most skin cytokines between the groups, although tumor necrosis factor-α mRNA (SMD: −0.880; 95% CI: −1.623 to −0.136) and interleukin-17A protein levels (SMD: −2.390; 95% CI: −4.522 to −0.258) were both lower in the exosome group. Meta-regression revealed a greater improvement in clinical scores in studies using hUCMSC exosomes compared to other MSC sources (p = 0.030). Conclusions: hUCMSC exosomes have been studied more extensively than other MSC exosomes. MSC exosomes reduce clinical severity and epidermal hyperplasia. Full article

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by chronic inflammation of the synovial membrane, leading to synovial hyperplasia, infiltration of immune cells, and subsequent cartilage and bone erosion. This progressive joint pathology results in persistent pain and functional impairment. Currently, convenient oral traditional disease-modifying anti-rheumatic drugs (DMARDs) are available, and increasingly precise biologic agents and targeted synthetic DMARDs (tsDMARDs) have been developed, offering promising therapeutic options. However, systemic administration generally fails to achieve therapeutic drug concentrations in the joints owing to poor biodistribution and dose-limiting systemic toxicity. Intra-articular (IA) administration has demonstrated promising potential in addressing these challenges. Among the various strategies employed for IA administration, hydrogels have gained significant attention due to their tunable mechanical properties, biocompatibility, and controlled release capabilities. These unique properties enable hydrogel-based IA delivery systems to simultaneously modulate the inflammatory microenvironment and protect cartilage tissue. This review comprehensively summarizes the histopathological changes and associated cellular and molecular events in RA, while also highlighting the design principles of hydrogels and advanced strategies for hydrogel-based IA administration. By addressing the limitations of conventional treatments, hydrogel-based IA injection holds significant promise for improving RA treatment. Full article

Background/Objectives: Lichen simplex chronicus (LSC) of the vulva is a chronic dermatologic disorder characterized by persistent pruritus, compulsive scratching, and progressive thickening of the vulvar skin. Currently, LSC diagnosis primarily relies on clinical presentation, with histopathological examination performed when the diagnosis is unclear. However, the precise pathogenic mechanisms driving the disease remain poorly understood. This study aimed to investigate the pathogenesis of LSC and evaluate the feasibility of tape stripping as a non-invasive diagnostic technique. Methods: Skin specimens were obtained using both traditional biopsy and tape stripping methods, and the metabolites and oxidized lipids in these samples were analyzed using advanced mass spectrometry techniques. Results: Our findings suggest that 20-hydroxyeicosatetraenoic acid (20-HETE), an oxidized derivative of arachidonic acid (AA), activates the TRPV1 receptor, thereby exacerbating the itch–scratch cycle. This activation upregulates energy metabolism and promotes epidermal hyperplasia, providing new insights into the disease’s pathophysiology. Conclusions: Our study suggests that tape stripping could serve as a viable non-invasive diagnostic tool for LSC, with linoleic acid (LA) and AA potentially acting as biomarkers for the disease. Full article

Pituitary pars intermedia dysfunction (PPID) is a common, slowly progressive, neurodegenerative disorder of the older horse. Oxidative damage to the hypothalamic periventricular neurons results in loss of dopaminergic inhibition of the pars intermedia region of the pituitary gland. Consequently, there is increased production of the pro-opiomelanocortin (POMC)-derived hormones normally produced by this region, as well as initial melanocyte hypertrophy and hyperplasia, followed by adenomatous change. Clinical signs that are highly suggestive of the disease are generalised and regional hypertrichosis and delayed/abnormal coat shedding. Numerous clinical signs provide a moderate clinical suspicion, including hyperhidrosis, abnormal fat distribution/regional adiposity, epaxial muscle atrophy/loss of topline, laminitis, weight loss, recurrent infections, behavioural changes/lethargy, polyuria and polydipsia, a pot-bellied appearance, bulging supraorbital fat pads, reduced wound healing, lordosis and infertility. In all animals, a diagnosis of PPID is made based on the signalment, clinical signs and results of further diagnostic tests, with age being a crucial factor to consider. Currently recommended further diagnostic tests are measurement of basal adrenocorticotrophic hormone (ACTH) concentrations (all year) and evaluation of the ACTH response to thyrotrophin-releasing hormone (TRH) using seasonally adjusted references intervals (non-autumn). Animals should also be tested for insulin dysregulation, as laminitis risk in PPID is associated with hyperinsulinaemia. PPID can be managed but not cured; it is a lifelong condition. The individual clinical signs can be managed, e.g., clipping the excessive haircoat and providing unrestricted access to water for individuals with polydipsia. Alternatively, pharmacological management can be employed, and the dopamine-2 receptor agonist pergolide is licensed/approved for the treatment of equine PPID. This should be prescribed in combination with dietary recommendations based on the body condition score and insulin sensitivity status of the individual animal. Full article

Objectives: Silodosin, a selective α1A-adrenoceptor antagonist, is used to treat lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Genetic polymorphisms in drug-metabolizing enzymes and transporters may contribute to interindividual variability in its efficacy and safety. This study aimed to investigate the influence of CYP3A4, CYP3A5, UGT2B7, and ABCB1 polymorphisms on silodosin pharmacokinetics, efficacy, and safety in Russian patients with BPH. Methods: A prospective observational study included 103 Russian male patients with moderate-to-severe LUTS (IPSS > 8) due to BPH, treated with silodosin (8 mg daily) for 8 weeks. Genotyping for CYP3A4*1B, CYP3A4*22, CYP3A5*3, UGT2B7 (rs73823859, rs7439366, and rs7668282), and ABCB1 (rs4148738, rs1045642, rs2032582, and rs1128503) was performed using real-time PCR. The silodosin minimum steady-state plasma concentration (Css min) was measured via HPLC-MS. Efficacy was evaluated by the International Prostate Symptom Score (IPSS), quality of life scale, maximum urinary flow rate (Qmax), residual urine volume (RUV), and prostate volume at the baseline and week 8. Adverse drug reactions (ADRs) were recorded. Results: CYP3A4*22 CT carriers (n = 6) exhibited higher Css min (17.59 ± 2.98 vs. 9.0 ± 10.47 ng/mL, p = 0.049) but less absolute IPSS improvement (p < 0.05), likely due to higher baseline symptom severity. However, the change in IPSS (ΔIPSS_1–4) from the baseline to week 8 did not differ significantly (−5.78 ± 5.29 vs. −6.0 ± 4.54, p = 0.939). CYP3A5*3 GG homozygotes (n = 96) showed greater ΔIPSS_1–4 improvement (−6.25 ± 4.60 vs. 0.0 ± 9.53, p = 0.042) and a lower IPSS at day 28 (7.64 ± 4.50 vs. 20.0 ± 6.55, p < 0.001). UGT2B7 rs7439366 TT carriers (n = 34) had an improved Qmax (ΔQmax_1–4 5.4 vs. 3.3 and 2.0 mL/s for CC and CT, p = 0.041). ABCB1 1236C>T TT homozygotes (n = 25) showed a trend toward reduced RUV (p = 0.053). No polymorphisms were associated with adverse drug reactions (15 events in 42 patients, 35.7%). Conclusions: Genetic polymorphisms CYP3A4*22, CYP3A5*3, and UGT2B7 rs7439366 may modulate silodosin pharmacokinetics and efficacy parameters in BPH patients but not safety. Larger-scale studies are warranted to validate these initial findings. Full article

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by synovial hyperplasia and joint destruction. Previous studies have demonstrated that the alkaloids of Rushanhu (ARSHs), the dried root and stem of Zanthoxylum nitidum var. tomentosum, exhibit favorable therapeutic effects on RA, and this study aims to investigate the underlying molecular mechanisms involved. Methods: A complete Freund’s adjuvant (CFA)-induced arthritis model in male SD rats (n = 64) was used to evaluate ARSHs. Groups included control, model, methotrexate (MTX), and ARSH-treated. Therapeutic effects were assessed via arthritis index, paw swelling, and serum cytokines (IL-1β, IL-6, IL-17A). Network pharmacology identified bioactive alkaloids and core targets, validated by molecular docking. In vitro mechanisms (proliferation, apoptosis, signaling pathways) were examined in MH7A synovial cells. Results: ARSHs significantly attenuated joint inflammation and damage in CFA rats (* p < 0.01 vs. model), reducing pro-inflammatory cytokines. Fifteen alkaloids (e.g., dihydrochelerythrine, magnoflorine) and 24 targets (e.g., SRC, STAT3, MAPK3) were prioritized. Molecular docking confirmed strong binding (binding energy < −7.0 kcal/mol). In vitro, ARSHs suppressed MH7A proliferation and induced apoptosis via Bcl-2/Bax dysregulation and the inhibition of SRC/STAT3/MAPK3 phosphorylation. Conclusions: ARSHs mitigate RA pathogenesis by targeting the SRC/STAT3/MAPK3 signaling axis in synovial cells. This study provides mechanistic validation of ARSHs as multi-target phytotherapeutic agents against inflammatory arthritis. Full article

Drug-coated balloons (DCBs) have transformed percutaneous coronary intervention (PCI) by delivering antiproliferative drugs directly to the arterial wall, offering a stent-less approach that mitigates the risks associated with permanent metallic implants. Initially developed for in-stent restenosis (ISR), DCBs have demonstrated robust efficacy in reducing neointimal hyperplasia and target lesion revascularization (TLR) rates across diverse coronary lesions, including small vessel disease (SVD), de novo lesions, and complex anatomies such as bifurcation lesions. Paclitaxel-coated balloons have long been the cornerstone of DCB therapy due to their established clinical outcomes, but sirolimus-coated balloons are emerging as a promising alternative with potentially superior safety profiles and sustained drug release. The pharmacological mechanism of DCBs relies on rapid drug transfer during brief balloon inflation, achieving high local concentrations without residual foreign material. Landmark trials, such as BASKET-SMALL 2, RESTORE SVD, and AGENT IDE, have demonstrated comparable or non-inferior outcomes of DCBs versus drug-eluting stents (DESs) in specific settings, with lower rates of stent thrombosis and shorter dual antiplatelet therapy (DAPT) requirements. Despite these advances, challenges persist, including optimizing drug formulations, ensuring uniform delivery, and addressing calcified lesions. Ongoing research into novel coatings, dual–drug systems, and artificial intelligence (AI)-guided interventions is poised to redefine PCI strategies. This review provides a comprehensive analysis of drug-coated balloon (DCB) angioplasty, not limited to specific clinical scenarios such as in-stent restenosis, small vessel disease, or bifurcation lesions, highlighting their transformative role in coronary artery disease (CAD) management. Instead, it addresses the full spectrum of pharmacological principles, mechanisms of action, clinical indications, comparative efficacy across various coronary artery disease contexts, and future directions of DCBs. Full article

Endotracheal prosthesis placement is employed as a therapeutic intervention for tracheal lesions in cases where conventional surgical approaches are not feasible. The learning curve for endotracheal stent placement can vary depending on the type of stent, the training environment, and the clinician’s prior experience; however, it is generally considered moderately complex. Inadequate practice can have serious consequences, as the procedure involves a critical area such as the airway. The main risks and complications associated with inadequate technique or improper execution can include stent migration, formation of granulation tissue or hyperplasia, tracheal or pulmonary infection, obstruction or fracture of the stent, hemorrhage and tracheal perforation, among others. The purpose of the present study is to summarize important information and evaluate the role of different material features in the 3D printing manufacturing of an appropriate tracheobronchial medical device, which should be as appropriate as possible to facilitate placement during surgical practice. A complex stent design was fabricated using three different biodegradable materials, polycaprolactone (PCL), polydioxanone (PDO), and polymer blend of polylactic acid/polycaprolactone (PLA/PCL), through additive manufacturing, specifically fused filament fabrication (FFF)3D printing. Parameter optimization of the 3D printing process was required for each material to achieve an adequate geometric quality of the stent. Experimental analyses were conducted to characterize the mechanical properties of the printed stents. Flexural strength and radial compression resistance were evaluated, with particular emphasis on radial force due to its clinical relevance in preventing collapse after implantation in the trachea. The results provide valuable insights into how material selection could influence device behavior during placement to support surgical requirements. Full article

Objectives: Atopic dermatitis (AD) is a long-term, recurring inflammatory skin condition characterized by impaired epidermal barrier function and abnormal immune system regulation. Pine pollen has traditionally been used for dermatological treatments, though its active components remain unclear. The primary objective of this study was to pinpoint the active constituents of pine pollen and elucidate its therapeutic effects against AD. Methods: The safety concentration ranges and protective efficacy of nine pine pollen constituents against 2,4-dinitrochlorobenzene (DNCB)-induced HaCaT cell damage were evaluated using the CCK-8 assay. Furthermore, models of DNCB-induced damage were established both in vitro (HaCaT cells) and in vivo (BALB/c mice) to explore the protective effects of the key functional component. Results: Our findings identified pine pollen polysaccharides (PPPS) as the principal bioactive constituent, characterized by a unique infrared absorption spectral profile and a sponge-like architecture with three-dimensional interconnected porous networks. In vitro, PPPS inhibited DNCB-induced decreases in cell viability, morphological abnormalities, oxidative stress, and apoptosis. In vivo, PPPS alleviated DNCB-induced skin lesions by attenuating epidermal hyperplasia, suppressing mast cell infiltration, inhibiting cell apoptosis, and downregulating the expression of IL-4 and IL-17A. Conclusions: This study provides evidence that PPPS from pine pollen can alleviate epidermal damage in AD, offering a novel therapeutic strategy for AD treatment. Full article