Search Results (5,227)

Airway remodeling is a process that occurs in chronic obstructive diseases, such as asthma and COPD. It is associated with adverse changes in the structure and function of the airways. An increasing amount of literature points to the potential protective effects of vitamin D and caffeine against inflammation and fibrosis. The aim of the study is to evaluate the effect of calcitriol and caffeine on the expression of genes and proteins associated with airway remodeling. The Calu-3 cell line was treated with TGF-β, calcitriol, and caffeine in different combinations. Subsequently, the expression of VDR, CDH1, VIM, MMP-2, and MMP-9 were examined at the mRNA and protein levels using real-time PCR and Western blot, respectively. One-way analysis of variance was used to determine differences in several groups. Both calcitriol and caffeine were associated with a decrease in the expression of MMP-2 and VIM in TGF-β-treated cells (p = 0.01 and p = 0.006, respectively). Both compounds also reduced the expression of MMP-9 in comparison to TGF-β alone (p = 0.03), though the changes in MMP-9 protein levels did not reach statistical significance. Calcitriol was associated with a decrease in CDH1 expression at both levels in comparison to TGF-β (p < 0.0001 and p = 0.02, respectively). A potential synergistic effect was demonstrated for CDH1 at the mRNA level and for the vitamin D receptor at the protein level. Both vitamin D and caffeine may influence the pathways involved in airway remodeling. Preliminary in vitro findings suggest a potential role of these substances for future therapeutic strategies targeting obstructive diseases; however, the observations require confirmation in further in vivo studies. Full article

Melatonin, a well-known antioxidant, has been widely used in sperm cryopreservation of various animals, but its regulatory mechanism in fish remains unclear. This first study on teleosts suggests a potential molecular mechanism by which melatonin may improve post-thaw sperm quality of Epinephelus fuscoguttatus via targeting mitochondrial function. Compared with the melatonin group, the MT1 receptor-inhibited group showed slightly higher sperm motility (77.09 ± 3.41% vs. 76.50 ± 1.10%), significantly inhibited mitochondrial permeability transition pore (mPTP) opening (12.64 ± 1.05% vs. 18.29 ± 1.38%), and maintained higher mitochondrial membrane potential (MMP; 85.86 ± 0.18% vs. 81.81 ± 0.69%), with both groups performing better than the control. In contrast, the MT2-inhibited and MT1/2 dual-inhibited groups exhibited reduced sperm quality compared with the MT group, suggesting that MT2 may serve as the core receptor for melatonin to regulate mitochondrial homeostasis in teleosts. Mechanistically, melatonin-activated MT2 potentially inhibits mPTP opening via the PI3K/Akt/GSK-3β pathway, and this protective effect was abrogated by the PI3K and GSK-3β inhibitors. This receptor-mediated process synergized with melatonin’s direct antioxidant effect, as ROS levels in all melatonin-treated groups were significantly lower than the control. This study is the first to find pharmacological evidence for the melatonin–MT2/PI3K/GSK-3β axis in maintaining teleost sperm mitochondrial function; it also reveals potential mechanistic differences between teleosts and mammals and fills a critical knowledge gap regarding this signaling cascade in teleost reproductive biology. Full article

Background: Oral Lichen Planus (OLP) is a chronic inflammatory, autoimmune disorder affecting the skin and mucosa classified within the broad group of Oral Potentially Malignant Disorders (OPMDs). Topical treatment is usually effective in resolving the oral inflammation associated with the process, and the possible relationship to a systemic immunological reaction has not been widely discussed. The aim of this study was to explore the relationship between local and systemic inflammatory signatures in OLP by identifying potential markers in salivary and serum samples, as well as the topical treatment used to relieve inflammation. Methods: The study design was a cross-sectional case–control hospital-based study. A total of 50 blood samples, comprising 31 patients with OLP (study group) and 19 individuals without OLP status (control group), were tested for HLA-B27 in this study. Salivary and serum levels of Prostaglandin E2 (PGE2), matrix metalloprotease 8 (MMP-8), and human IL-1 beta (IL-1β) were measured within and between the control and OLP groups. Results: Salivary IL-1β levels were significantly higher in the OLP group than in controls (p = 0.001; W = 101.5). Serum MMP-8 concentrations were significantly lower in patients with OLP. Serum PGE2 levels were elevated in the OLP group; however, the difference was only borderline statistically significant after correction. HLA-B27 allele frequency in the study and control groups was compared with that in the Polish population. Using Fisher’s Exact Test for Count Data, p-value = 0.1404, no statistically significant differences were found between the control and study groups. Conclusions: These findings could suggest that inflammatory activity in OLP might be predominantly localized to the oral cavity rather than systemic. Elevated salivary IL-1β and reduced systemic MMP-8 levels could support the concept of local immune dysregulation; moreover, salivary IL-1β may serve as a potential non-invasive biomarker for the diagnosis and monitoring of OLP. Studies involving a larger number of subjects should be conducted to strengthen the provided conclusion. Full article

Lumbar spinal stenosis (LSS) is caused by multiple degenerative changes including the hypertrophy of the ligamentum flavum (LFH). Inflammation and fibrosis contribute to LFH and glucocorticoid drugs (GCDs) are generally used to manage LSS symptoms. However, a thorough understanding of the molecular mechanisms exerted by GCD in ligamentum flavum (LF) cells remains incomplete. Primary human LF cells were isolated from surgical specimens and stimulated with pro-inflammatory agents (IL-1α, IL-1β, LPS) or the profibrotic cytokine TGFβ1, in the presence or absence of dexamethasone. Gene and protein expression levels of inflammatory, fibrotic, and ossification-related markers were analysed using RT-qPCR and Western blotting. Dexamethasone significantly suppressed the expression of key pro-inflammatory, fibrotic, and ossification markers (IL-6, COX2, COL3A1, MMPs, TNFRSF11b) in both acute and prolonged models of LF inflammation. However, under TGFβ1 stimulation, dexamethasone attenuated inflammatory gene expression but failed to reduce the expression of major fibrosis-associated genes, such as COL3A1, bFGF, and POSTN. Dexamethasone effectively suppresses inflammation-mediated fibrosis in LF-derived cells, indicating its potential to both prevent and reverse LFH progression in the context of LSS. However, its limited efficacy against TGFβ1-driven fibrotic pathways highlights the need for combination therapies targeting both inflammation and fibrosis for more comprehensive management of LFH. These findings support further exploration of corticosteroids as therapeutic agents for hypertrophic ligament disorders. Full article

Cutaneous fibrosis is characterized by aberrant wound healing with excessive extracellular matrix deposition, sustained inflammation, and oxidative stress, while currently available therapies show limited efficacy and safety. A Dual Hyaluronic Acid Compound (DHC), consisting of high-molecular-weight, low-molecular-weight, and minimally cross-linked hyaluronic acid, has demonstrated regenerative and antioxidant properties, but its anti-fibrotic effects have not been fully explored. This study investigated the anti-fibrotic potential of DHC using a bleomycin-induced murine dermal fibrosis model and a UVB-irradiated ex vivo human skin model. In C57BL/6 mice, dermal fibrosis was induced by daily bleomycin injections for three weeks, followed by intradermal DHC administration. Histological and biomechanical analyses showed that DHC significantly reduced dermal thickness, collagen deposition, and skin hardness compared with untreated fibrotic controls. DHC decreased α-SMA expression and increased MMP1 levels, indicating attenuation of myofibroblast activation and enhanced matrix remodeling. It also reduced macrophage markers (CD68, CD163) and pro-inflammatory cytokines (IL-1β, TNF-α). Furthermore, DHC restored superoxide dismutase (SOD) and catalase (CAT) activity and upregulated NRF2, HO-1, and NQO1 expression in the in vivo model. Similarly, DHC upregulated SOD and CAT activity and reduced pro-inflammatory cytokines (IL-6, TNF-α) in the ex vivo human skin model. These findings suggest that DHC exerts multimodal anti-fibrotic effects through coordinated regulation of fibroblast activation, inflammation, and oxidative stress, supporting its potential as a therapeutic approach for cutaneous fibrosis. Full article

Background: The power profile is a reliable tool for monitoring performance in the cycling segment of triathlon. This study aimed to analyze the evolution of Mean Maximal Power (MMP) in international triathletes and to examine its relationship with external load-based training characteristics. Methods: Cycling training and competition data from 14 junior and U23 international triathletes (seven males: 21 ± 1 years, 69 ± 3 kg, and 181 ± 7 cm; seven females: 22 ± 3 years, 54 ± 5 kg, and 166 ± 3 cm) were analyzed longitudinally for three consecutive seasons. The MMP from the power profile was recorded, along with the training volume accumulated in each 2.0 W·kg⁻¹ power band. Results: All the MMP values, except values of 10 s, 30 s and 5 min, increased (p < 0.05) over the three seasons (Δ = 0.9% to 4.8%; ES = 0.30–0.47), as did the total time (Δ = 22.1%; ES = 0.42) and total distance (Δ = 32.8%; ES = 0.61). Specifically, the percentage of time spent in the 4–6 W·kg⁻¹ power band (ES = 0.42) and MMP values for1- 20 min durations (ES = 0.25–0.47) increased (p < 0.05) from the second to the third season. MMP values ≤ 30 s showed a very large correlation (above r = 0.74) with the percentage of time spent in power bands of 12–14 W·kg⁻¹. All the MMP values showed a negative correlation with the percentage of time spent in the 0–2 W·kg⁻¹ power band. Conclusions: Improvements in MMP ≥ 1 min values over consecutive seasons were associated with greater total training volume and time spent in moderate-intensity power bands, whereas MMP ≤ 30 s were linked to very high-intensity power outputs. Full article

Thoracoabdominal aortic aneurysms (TAAAs) are uncommon and usually silent until rupture, causing a substantial burden to the health care system. Aneurysm growth and rupture prediction is mainly based on aneurysm diameter measurement by imaging modalities, meaning that the biology of aneurysm growth is not part of a potentially more adequate surveillance of aortic aneurysm patients. Alternatives or complementary options for aortic aneurysm surveillance are an ongoing, non-addressed open issue of vascular medicine. The application of different biomarkers has been discussed, yet so far, an adequate candidate for aortic aneurysm surveillance, if it comes to the thoracic or thoracoabdominal aorta, preferably without radiation exposure, has not been named. Elastin breakdown, as a component of aortic wall degeneration primarily driven by matrix metalloproteinases (MMPs), is a core element of aneurysm development. Desmosine is an elastin-specific cross-link increasingly studied as a circulating or urinary biomarker of compromised aortic wall integrity and disease activity. Accordingly, this review investigated whether plasma desmosine (pDES), a highly specific marker of elastin degradation, could be used as a non-invasive biomarker for detecting aortic aneurysms and assessing their risk profile. The existing literature of desmosine in fields of aortic pathologies in the acute and chronic setting will be assessed based on the current literature; furthermore, future perspectives of desmosine as a biomarker of aortic pathologies, such as aortic aneurysm dynamics, will be discussed. Full article

Norfloxacin has been widely found in water bodies and exhibits a strong toxic effect on aquatic organisms. To uncover its toxic mechanism on algae, the cell growth, reactive oxygen species (ROS) levels, physiological activities, mitochondrial membrane potential (MMP), caspase-3-like activity, cell morphology, TUNEL-positive nuclei and DNA ladders were determined in Chlamydomonas reinhardtii in exposure to norfloxacin. With raising norfloxacin concentration, the inhibitory and lethal effects on C. reinhardtii cells gradually enhanced, and the whole of the cells were dead under 50 μM for 24 h. During the cell death, respiratory and photosynthetic rate gradually reduced and disappeared after 24 h, while ROS quickly burst and maintained high levels during the 24 h. The MMP was markedly broken after 0.5 h, while caspase-3-like was activated, with the highest activity at the 2nd h. With prolonging the treatment time, the algal cells showed a gradual shrinking and wrinkling trend, while the numbers and fluorescence intensity of TUNEL-positive nuclei gradually increased. Meanwhile, the DNA was degraded by Ca²⁺-dependent endonucleases to show ladders after 6 h, and the degradation gradually enhanced during the death process. These characteristics demonstrate that norfloxacin can poison algae by triggering programmed cell death induced by the elevated ROS. Full article

This study estimates the association between respiratory outcomes among employees of a secondary aluminum plant and airborne pollutants. Additionally, it looks into the relationship between pulmonary dysfunction in workers and X-Ray repair cross-complementing one (XRCC1) gene polymorphisms. 110 exposed workers and 58 non-exposed workers were enrolled in the study. Measurements were conducted on sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and particulate particles. Pulmonary function was tested. Eosinophil cationic protein (ECP), C-reactive protein (CRP), matrix metalloproteinase-1 (MMP-1), interleukin 6 (IL6), granulocyte-macrophage colony-stimulating factor (GM-CSF), XRCC1 protein, and genotyping of XRCC1 gene polymorphisms were examined. The annual average concentrations of particulate matter (PM_2.5, PM₁₀), total suspended particulates (TSP), SO₂, and NO₂ were lower than the permissible limit. The areas around ovens, evaporators, and cold rolling mills exhibited the highest amounts. The majority of employees in these departments had impaired lung function. Prolonged exposure was associated with a significant decrease in forced expiratory volume in 1 s (FEV1%) and forced vital capacity (FVC%) among the exposed group (p = 0.001 & 0.04, respectively). Serum XRCC1 levels were significantly higher among exposed workers (p = 0.02). Inflammatory biomarkers showed no statistically significant differences between groups. Aluminum workers are at risk of developing respiratory disorders. The level of serum XRCC1 may serve as a potential biomarker for detecting susceptible workers. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a five-year survival rate of approximately 13%. Patients with PDAC also have an elevated incidence of venous thromboembolism (VTE), despite prophylactic anticoagulation. Thus, there is an urgent need for therapeutic strategies that target tumor progression and hypercoagulability. Protein S (PS), a physiological anticoagulant encoded by the PROS1 gene, has recently been shown to inhibit PDAC growth in preclinical models. To further examine the physiological relevance of intratumoral PS in PDAC, we performed a meta-analysis of four independent PDAC patient cohorts obtained from cBioPortal. Patients were stratified based on low versus high intratumoral PROS1 expression based on below- and above-average mean expression, overall survival, and gene expression of select pro-growth genes, implementing a fixed-effects model. High intratumoral PROS1 expression was associated with a 41.8% reduction in the risk of death compared with low PROS1 expression (pooled hazard ratio = 0.581) within 30 months of diagnosis from survival data in three cohorts. Elevated PROS1 expression correlated with marked downregulation of key genes implicated in PDAC invasion and metastasis, including MMP2 and SNAI2, in all four cohorts. Collectively, these findings suggest that PROS1 is a potential prognostic biomarker and molecular regulator in PDAC and thus support further investigation into the dual role of PS in tumor progression. Full article

Dental implants are a popular clinical procedure for the rehabilitation of fully and partially ede ntulous patients. There is long-term evidence that implant-supported dental prostheses represent a predictable treatment for replacing missing teeth. However, several types of complications may arise, which can compromise implant treatment outcome. Peri-implant disease is a growing biological complication, consisting of a progressive loss of supporting bone, associated with microbial biofilm and clinical inflammation. It represents a concern for clinicians and patients, having a negative impact on quality of life. This narrative review aimed at summarize the current knowledge on etiology, epidemiology, risk factors, and pathogenesis of peri-implant disease. It also focused on the diagnostic potential of active matrix metalloproteinase-8 (aMMP-8) in peri-implant sulcular fluid for assessing the status of peri-implant tissues and the risk of developing peri-implantitis. A literature search was conducted in PubMed and Scopus databases using search terms like: peri-implantitis, peri-implant biomarkers, aMMP-8, implant maintenance, risk assessment. Clinical studies, systematic reviews, meta-analysis and consensus papers published up to June 2025 were considered. Finally, based on the main factors involved in the onset and progression of peri-implant disease, a new protocol was conceived for determining the optimal implant maintenance scheduling for individual patients. The Biomarker-Guided Implant Maintenance (BGIM) protocol considers a few key parameters, among which aMMP-8 level, and proposes three categories associated with different levels of risk for peri-implantitis. The higher the risk, the more frequently a patient should undergo professional maintenance, to prevent peri-implant disease, with potential favorable effects on implant longevity. The proposed BGIM protocol, that requires prospective validation, represents a structured and clinically applicable biomarker-driven framework for individualizing implant maintenance scheduling by integrating real-time chairside quantification of aMMP-8 with established patient-related risk factors. Full article

Background/Objectives: Thoracic aortic aneurysms have long been associated with germline mutations such as FBN1, TGFBR2, and COL3A1, which predispose to Marfan, Loeys–Dietz, and Ehlers–Danlos syndromes, respectively. However, recent research has identified a correlation between the JAK2 V617F somatic mutation and thoracic aortic aneurysm formation. This review aims to synthesize the current evidence on the relationship between JAK2 V617F and TAA development. Methods: A literature review was conducted using PubMed reviewed articles up to June 2025. Search terms included “thoracic aortic aneurysm”, “somatic mutations” and “JAK2 V617F”. Relevant clinical datasets and population-based cohort studies were identified and evaluated. Results: The available studies demonstrated a consistent association between JAK2 V617F and thoracic aortic aneurysm formation, with JAK2 V617F variant allele frequency (VAF) being a valuable biomarker of aneurysm risk. The mutation is accompanied by the onset of increased cytokine production, pro-inflammatory leukocytes, and elevated expression levels of MMPs—all of which drive elastin degradation and are classically associated with thoracic aortic aneurysm development. Conclusions: Compelling emerging evidence supports an association between the JAK2 V617F somatic mutation and the formation of thoracic aortic aneurysms, with VAF acting as a valuable biomarker for aneurysm risk. However, no studies have evaluated whether increasing VAF influences aneurysm growth rate, highlighting the need for future clinical research. Full article

Background: Obesity is associated with alterations in the immune response through increased systemic inflammation. This systemic inflammatory state may increase the risk of peri-implantitis, a condition characterized by infection and tissue destruction around dental implants. Therefore, this cross-sectional clinical study aimed to investigate the association between obesity and peri-implant health. Methods: In this observational clinical study, a total of 80 patients were evaluated, including a peri-implant healthy non-obese control group (CG) (n = 20), peri-implantitis non-obese group (PG) (n = 20), peri-implant healthy obese group (OG) (n = 20), and peri-implantitis obese group (POG) (n = 20). Peri-implant clinical measurements (plaque index [PI], gingival index [GI], bleeding on probing [BOP], and probing depth [PD]) were obtained from the participants. In addition, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and matrix metalloproteinase-8 (MMP-8) levels were measured in peri-implant crevicular fluid (PICF) samples. Results: PI, GI, BOP, and PD levels were significantly higher in the POG and PG than in the other groups (p < 0.05). PICF volume was found to be higher in the POG and PG than in the control group (p < 0.05). TNF-α levels increased significantly in all groups compared with the control group, and IL-1β levels were highest in the POG (p < 0.05). Conclusions: The findings of this cross-sectional study suggest a potential association between increased proinflammatory cytokine levels and altered peri-implant inflammatory responses in patients with obesity. Trial registration: This study was registered on ClinicalTrials.gov (Identifier: NCT07183163) on 18 September 2025 (retrospectively). Full article

Bladder cancer (BCa) is the second most common cancer of the genitourinary tract globally. It has limited treatment options, high recurrence rate, and acquires resistance to platinum-based therapy. Therefore, identifying novel therapeutic targets is urgently needed. Analysis of the TCGA data revealed that the enzyme galactokinase-1 (GALK1) is overexpressed (p < 0.0001) in bladder tumors compared to normal tissue. Our data also confirmed GALK1 protein upregulation in multiple human BCa cell lines and rodent bladder tumors. However, the precise role of GALK1 in BCa progression and effects of its specific inhibitor remain unexamined. In this study, we demonstrate that GALK1 gene silencing using shRNA resulted in a significant reduction in BCa cell proliferation, migration, and invasion. Pharmacological inhibition of GALK1 using small molecule Cpd36 resulted in anticancer efficacy against BCa. Cpd36 inhibited proliferation, migration, and invasion of BCa cells. Further, Cpd36 induced G1 phase cell cycle arrest, apoptosis, mitochondrial membrane depolarization, and ROS production in the BCa cells. Mechanistically, Cpd36-induced reduction in cell proliferation was associated with a decrease in expression of GALK1, PCNA proteins. Inhibition of metastatic potential was accompanied by decreased migration, invasion, and MMP-9 expression. Cell cycle arrest was associated with decrease in Cyclin D1 and increased expression of p21 and p27. Induction of apoptosis was linked with increased expression of cleaved caspase-3 and cleaved PARP, while downregulating p-AKT. Additionally, Cpd36 in combination with cisplatin or gemcitabine showed a strong synergistic effect on BCa cells. Taken together, our findings suggest that GALK1 plays a significant role in BCa cell survival and validates its inhibitors as promising therapeutic options for managing this disease. Full article

Background/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by genetic and epigenetic alterations. This study aimed to assess the methylation status of E-Cadherin and MMP-9 gene promoters and to explore their relationships with disease pathogenesis and hematological parameters in CLL patients. Methods: A case–control study was conducted with 70 newly diagnosed CLL patients and 70 age- and sex-matched healthy controls. Promoter methylation of E-Cadherin and MMP-9 genes was evaluated using methylation-specific PCR (MSP) and methylation-sensitive restriction enzyme PCR (MSRE-PCR), respectively. Results: The median patient age was 62 years, and 68.5% were males. Binet stage A was the most common stage (57.3%). E-Cadherin promoter methylation was detected in 75.7% of CLL patients and 77.1% of controls (p = 0.91), showing no significant association with disease occurrence; however, it showed a significant correlation with higher lymphocyte counts (p = 0.01). In contrast, MMP-9 promoter methylation was significantly less frequent in CLL cases (70.0%) than in controls (100%, p = 0.001). Unmethylated MMP-9 correlated significantly with female gender (p = 0.02), lower hemoglobin (p = 0.031), reduced platelet counts (p = 0.001), and higher lymphocyte counts (p = 0.035). Conclusions: MMP-9 promoter hypomethylation may play a pathogenic role in CLL and is associated with female gender and cytopenia, whereas E-Cadherin methylation appears to be non-specific. MMP-9 methylation status could therefore serve as a potential biomarker for CLL biology and prognosis. Full article