Search Results (2,945)

Cellular senescence is a stress-induced type of irreversible cell cycle arrest, driven by telomere attrition, oxidative stress, DNA damage, mitochondrial dysfunction, oncogene activation, and chronic inflammation. Senescent cells remain metabolically active, secreting cytokines, chemokines, growth factors, matrix metalloproteinases, extracellular vesicles and oxidative mediators, comprising a senescence-associated secretory phenotype (SASP) that affects the tissue microenvironment. With aging, impaired immune clearance results in senescent cell accumulation, promoting inflammation, immunosuppression and fibrosis. Emerging evidence implicates cellular senescence in obstructive airway diseases, reflecting the lung’s continuous exposure to environmental and oxidative insults, and several pathways, including DNA damage response and p53/p21 and p16^INK4a signaling, telomere dysfunction, reactive oxygen species production, and mitochondrial defects, integrate stress signals to enforce senescence. In chronic obstructive pulmonary disease, a SASP-associated inflammatory milieu supports stress-induced tissue injury, while uncertainty still exists about the effects of chronic SASP on tumor suppression versus tumor promotion. In asthma, senescence processes have been associated with both Type(T)2-high and T2-low endotypes, underlying the interplay between environmental exposures, airway epithelial dysfunction and induced senescence mechanisms. Finally, in bronchiectasis, the neutrophilic, dysbiotic airway environment links dysregulated senescence with disease persistence and progression. Conventional therapies, antioxidants, serine protease inhibitors and novel senotherapeutic strategies represent promising approaches for therapeutic interventions. Full article

Background: Matrix metalloproteinases (MMPs) have been found to be associated with reproductive complications, including female infertility. This study was conducted to explore the link between MMPs in non-obese women with unexplained infertility (UI) in comparison to women with male factor infertility (MFI) as controls. Methods: This pilot exploratory study was carried out on 25 women, 11 with UI and 14 with MFI, undergoing IVF. Blood was drawn on day 21 of the luteal phase. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for 12 matrix metalloproteinase proteins. Welch’s t-test and a permutation test were used to compare group means, and Pearson’s correlations to examine relationships with matrix metalloproteinases. Results: No significant differences were seen for baseline demographics and hormonal parameters between the groups, and parameters of the response following IVF did not differ. In the UI group, MMP-3 levels were lower (p = 0.045), while MMP-1 and MMP-17 levels were higher (p = 0.007 and p = 0.010, respectively) compared to the MFI group. In MFI alone, MMP-1 positively correlated with vitamin D₃ (p < 0.05). Conclusions: This exploratory study suggests altered circulating MMP-1, MMP-3, and MMP-17 profiles in women with unexplained infertility. These findings require confirmation in larger cohorts and in studies examining endometrial tissue expression and MMP functional activity. Full article

Ultraviolet (UV) irradiation induces complex skin damage, including hyperpigmentation, oxidative stress, and alterations in proteins related to keratinocyte differentiation and epidermal barrier-associated status. This study investigated the multifunctional protective effects of Padina arborescens ethanolic extract (PAEE) against skin damage in melanocytes, keratinocytes, and zebrafish. In alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells, PAEE effectively suppressed the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling pathway, which was associated with reduced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, leading to decreased melanin synthesis. PAEE also exhibited photoprotective properties by reducing reactive oxygen species (ROS), inhibiting interleukin-1 beta (IL-1β), and attenuating matrix metalloproteinase-1 (MMP-1) upregulation associated with UVB (ultraviolet B)-induced photodamage in HaCaT keratinocytes. Notably, PAEE restored the UVB-reduced expression of filaggrin and involucrin, representative markers of keratinocyte differentiation and epidermal barrier-associated status, in HaCaT keratinocytes. In zebrafish embryos, PAEE suppressed α-MSH-induced melanin accumulation and UVB-induced ROS generation at non-toxic concentrations. Taken together, these results suggest that PAEE exerts anti-melanogenic and photoprotective effects in cellular and zebrasfish models and may serve as a promising marine-derived ingredient for cosmeceutical applications targeting UVB-related skin damage. Full article

Porphyra suborbiculata exhibits strong heat tolerance and has considerable commercial potential under rising sea temperatures; however, its bioactive components remain insufficiently explored. In this study, a heat-tolerant new strain of P. suborbiculata (PS-M4), cultivated by the College of Fisheries, was used as the experimental material. Polysaccharides were extracted using an ultrasound-assisted composite enzymatic method, and extraction conditions were optimized through single-factor experiments and response surface methodology, yielding a maximum extraction yield of 12.45 ± 0.09%. Crude polysaccharides were further purified using a purification apparatus, yielding two fractions, designated PSP-I and PSP-II. Preliminary structural characterization showed that PSP-I possessed a weight-average molecular weight (Mw) of 26.149 kDa, a number-average molecular weight (Mn) of 11.267 kDa, and a polydispersity index of 2.321. Monosaccharide composition analysis indicated that PSP-I was predominantly composed of galactose. Fourier transform infrared spectroscopy (FT-IR) revealed typical polysaccharide functional groups, and scanning electron microscopy (SEM) analysis revealed a porous lamellar morphology. In vitro cell-based assays demonstrated that PSP-I significantly alleviated ultraviolet B (UVB)-induced damage in HaCaT cells by reducing intracellular reactive oxygen species (ROS) levels, enhancing antioxidant enzyme activities, inhibiting apoptosis, and downregulating the expression of matrix metalloproteinases (MMPs). These results suggest that PSP-I has potential as a functional ingredient for mitigating UVB-induced skin damage. Full article

Exosomes (EXs) mediate intercellular communication in the tissue microenvironment. We previously demonstrated that endothelial progenitor cell-derived exosomes (EPC-EXs) from exercised mice protect neurons and cerebral endothelial cells from hypoxia- and hypertension- induced injury ex vivo, suggesting their therapeutic potential in hypertensive ischemic injury. Here, we investigated whether exercise-conditioned EPC-EXs (ET-EPC-EXs) confer protection against acute ischemic injury. Hypertensive transgenic mice were divided into donor and recipient groups. Donor mice underwent treadmill exercise to generate ET-EPC-EXs. Recipient mice was subjected to middle cerebral artery occlusion and received ET-EPC-EXs via tail vein injection (2 × 10⁸/100 μL saline) two hours after stroke onset. Cerebral blood flow (CBF) was assessed, and brains were collected on day two for histological and molecular analyses. Our data showed that ET-EPC-EXs were robustly taken up by cerebral cells, predominantly in the penumbra in the ipsilateral hemisphere. ET-EPC-EXs reduced cell death and microglia activation and restored tight-junction proteins. Moreover, ET-EPC-EX treatment preserved CBF and improved sensorimotor function on day two post-stroke. Mechanistically, ET-EPC-EXs suppressed p38 activation, accompanied by reduced matrix metalloproteinase-3 and cytochrome c levels in the ipsilateral brain. Collectively, these findings demonstrate that EPC-EXs from exercise mice improve sensorimotor functions and confer protection in hypertensive ischemic brain injury, likely through attenuation of neuroinflammation and preservation of vascular integrity via modulation of the p38 signaling. Full article

Recent studies support the concept of a bidirectional lung–brain axis. While neural, immune, and microbial pathways are increasingly recognized in lung-to-brain communication, the role of matrikines—bioactive peptides generated by extracellular matrix (ECM) proteolysis during remodeling—in this inter-organ communication remains underexplored. This review highlights matrikines originating from the lung, particularly the collagen-derived tripeptide Pro-Gly-Pro (PGP) and the elastin-derived hexapeptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG), as potential mediators linking pulmonary pathology with neurological outcomes. The lung is rich in ECM proteins, and inflammatory conditions such as chronic obstructive pulmonary disease (COPD) and emphysema trigger proteolytic activity by matrix metalloproteinases (MMPs) and neutrophil elastase, releasing matrikines into circulation. Under conditions of blood–brain barrier (BBB) dysfunction, they may access the central nervous system (CNS), where they influence neurons, microglia, and astrocytes, modulating neuroinflammation, autophagy, and synaptic integrity. While PGP can exhibit context-dependent neuroprotective effects, its acetylated form and VGVAPG are associated with neurotoxicity, Tau hyperphosphorylation, and microglial activation. Additional matrikines, including Gly-His-Lys (GHK) and endorepellin, may further modulate CNS homeostasis. Collectively, these findings support lung-derived matrikines as circulating mediators of lung-to-brain signaling, providing a novel mechanistic framework linking chronic pulmonary inflammation to neuropathologies, such as stroke and neurodegenerative disorders, and highlighting potential targets for therapeutic intervention. Full article

A new series of eight novel etodolac-based 1,3,4-oxadiazoles was synthesized, characterized, and tested in silico in multidimensional routes, starting with etodolac, a well-known nonsteroidal anti-inflammatory medication (NSAID). In silico studies were performed prior to synthesis using the molecular docking technique in CCDC GOLD suite software (2025.3) to assess the interactions with two key targets involved in cancer pathogenesis: the crystal structure of the epidermal growth factor receptor EGFR tyrosine kinase domain (PDB ID: 4HJO) and the matrix metalloproteinase (MMP-9) complex (PDB ID: 5CUH). ADME studies were performed to assess the physicochemical properties of the synthesized molecules. Importantly, biotransformation prediction also indicated that the derivatives possess high metabolic stability, with hydroxylation of the thio-ether group as the primary predicted biotransformation route. All compounds were characterized using melting point, FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopy. In vitro and/or in vivo experiments are needed to confirm this preliminary anticancer study. Full article

Open-heart surgery with cardiopulmonary bypass (CPB) is a high-risk procedure with significant morbidity and mortality. CPB, tissue injury, blood loss, endotoxemia and ischemia–reperfusion injury induce a pronounced systemic inflammatory response, leading to endothelial glycocalyx (EG) damage and vascular endothelial dysfunction. Consequently, immune cells, reactive oxygen species, and enzymes gain free access to vascular endothelial cells, resulting in their dysfunction and enhancing inflammation, vascular permeability, and microvascular impairment. EG degradation is most commonly assessed by measuring the circulating levels of its degradation products. Additionally, CPB triggers an early inflammatory response that is characterized by the secretion of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, and IL-18, which play roles in initiating the process of EG injury. EG damage is further propagated by the sustained release of cytokines, inhibiting the regeneration of the glycocalyx layer. Heparanase and matrix metalloproteinases are enzymatic pathways involved in cytokine-mediated EG degradation after cardiac surgery, and the balance between the pro- and anti-inflammatory cytokines determines the magnitude and duration of the inflammatory response and EG impairment, which correlates with adverse clinical outcomes, including myocardial dysfunction, acute lung and kidney injury, neurological complications, and prolonged need for intensive care. Thus, identifying patients with an exaggerated cytokine response could potentially provide more personalized therapy based on the circulating biomarkers of EG shedding, and cytokine-directed preservation of EG represents a promising therapeutic strategy in vascular dysfunction prevention during and after open-heart surgery. In this review, we summarize the current knowledge on cytokine-mediated EG impairment following open-heart surgery with CPB. Full article

Background/Objectives: To evaluate the relationships between meibomian gland dysfunction (MGD), ocular surface parameters, and matrix metalloproteinase-9 (MMP-9)-mediated inflammation in glaucoma patients, we specifically assessed the impact of prostaglandin analogue use, preservative exposure, and number of medications. Methods: This retrospective cross-sectional study included patients treated with topical antiglaucoma medications for at least six months. Meibomian gland expressibility, meibum quality, and MGD grade were assessed along with tear film break-up time (TBUT), Schirmer I test, and Oxford staining score. Tear MMP-9 levels were measured using a Point-of-Care immunoassay (InflammaDry^®) and graded on a 0 to 4 scale. Results: Elevated MMP-9 grades were significantly correlated with worsening meibum expressibility, meibum quality, and MGD grade (all p < 0.001), whereas no significant associations were found with traditional parameters such as TBUT and Schirmer I test. Prostaglandin analogue use was associated with worse meibomian gland parameters and higher MMP-9 levels compared to non-use. Patients receiving preservative-containing medications exhibited poorer meibomian gland parameters and MMP-9 levels, as well as worse corneal staining scores. An increased number of medications was associated with a stepwise deterioration in meibomian gland function and elevated MMP-9 levels. Conclusions: Prostaglandin analogue use, preservative exposure, and increased number of medications are significant factors associated with the exacerbation of MGD and ocular surface inflammation. Semi-quantitative grading of tear MMP-9 revealed a stepwise association with meibomian gland dysfunction severity that was not detected by conventional dry eye metrics, indicating that MMP-9 may be considered a potential indicator of subclinical ocular surface inflammation in glaucoma patients. Full article

Bladder cancer (BC) is one of the most commonly diagnosed cancers of the genitourinary system and ranks ninth in terms of incidence worldwide. Due to the varied clinical course of the disease and the frequent tendency for tumor recurrence, diagnostic studies are being conducted to find non-invasive and prognostic markers that could be helpful in diagnosing BC. The aim of this review was to present the current state of knowledge on the role of extracellular matrix metalloproteinases (MMPs) and pro-inflammatory cytokines in the pathogenesis of bladder cancer, as well as to assess their potential as biomarkers measured in body fluids. The study reviewed the literature published in English between 2012 and 2025. The studies included clinical and experimental research analysing the expression and activity of selected metalloproteinases, including MMP-2, MMP-9, MMP-7 and MMP-1, and pro-inflammatory cytokines such as interleukins (ILs): IL-6, IL-8, IL-17, and IFN-γ in serum, urine, and tumor tissues of patients with BC, using immunochemical methods and genetic analyses. The collected data indicate that MMPs play a key role in the degradation of the extracellular matrix, facilitating invasion, angiogenesis, and metastasis. Elevated concentrations of MMP-2 and MMP-9, especially in urine, correlate with the clinical stage and histopathological malignancy of the tumor. MMP-7 may be important in the early stages of carcinogenesis, while MMP-1 shows promising potential in multi-marker panels. At the same time, chronic inflammation and increased pro-inflammatory cytokine activity play a key role in modulating the tumor microenvironment. IL-6 and IL-8 have high diagnostic value in urine tests, with IL-6 also serving as a prognostic marker. IL-17 is associated with more aggressive forms of the disease, while IFN-γ may reflect the immune response to BC treatment. There is also evidence of positive feedback between cytokines and MMPs, which intensifies the process of tumor invasion and progression. Therefore, both extracellular matrix metalloproteinases and pro-inflammatory cytokines may be promising non-invasive biomarkers of bladder cancer. Their combined assessment can increase the diagnostic and prognostic value compared to the analysis of individual parameters. However, further multicentre prospective studies are needed for clinical validation and standardisation of the methods of determination. Full article

Background: Intracranial fusiform aneurysms represent a rare but clinically aggressive subtype of cerebrovascular disease, characterized by circumferential arterial dilation and a high risk of growth, ischemic complications, and rupture. Unlike saccular aneurysms, fusiform lesions lack well-established medical therapies to prevent progression or stabilize the aneurysm wall. Tumor necrosis factor-alpha (TNF-α) has emerged as a central mediator of aneurysm-associated inflammation and vascular remodeling, raising interest in TNF-α modulation as a potential therapeutic strategy. This study aimed to systematically review and synthesize the available clinical and translational evidence evaluating TNF-α signaling and anti-TNF-α therapies in the context of intracranial fusiform aneurysms. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, and Google Scholar from database inception through February 2026 in accordance with PRISMA guidelines. Eligible studies included human, animal, and translational investigations examining TNF-α biology or anti-TNF-α interventions in relation to intracranial fusiform aneurysms, intracranial dolichoectasia, or vertebrobasilar dolichoectatic aneurysms. Study selection, deduplication, and screening were performed using Covidence systematic review software. Extracted outcomes included aneurysm growth, rupture, ischemic events, imaging characteristics, inflammatory signaling, and vascular remodeling. Given substantial heterogeneity in study design and outcome reporting, findings were synthesized narratively using structured evidence mapping. Results: From the 368 records identified, 14 studies met inclusion criteria following full-text review. Included studies encompassed preclinical models, translational mechanistic investigations, and limited clinical observational data. Across experimental models, TNF-α signaling was consistently associated with macrophage infiltration, matrix metalloproteinase activation, vascular smooth muscle cell phenotypic modulation, and aneurysm wall degeneration. TNF-α inhibition was associated with reduced aneurysm progression and rupture in preclinical settings, including when initiated after aneurysm formation. Clinical evidence remains limited but suggests a potential association between TNF-α modulation and aneurysm stability, although direct therapeutic data in intracranial fusiform aneurysm populations are sparse. Conclusions: The existing translational and preclinical evidence supports a contributory role for TNF-α-mediated inflammation in the progression of intracranial fusiform aneurysms and suggests that TNF-α inhibition may represent a promising disease-modifying strategy. However, clinical data remain insufficient to support routine therapeutic use. Prospective observational studies and early-phase clinical trials are needed to define the safety, timing, and efficacy of anti-TNF-α therapies in patients with intracranial fusiform aneurysms. Full article

Background/Objectives: Osteoarthritis is a chronic joint disorder involving the progressive breakdown of articular cartilage, which leads to joint pain and impaired mobility. The present study investigated the effects of curcuminoids phospholipid (CP) on osteoarthritis progression, assessed its cartilage-protective effects, and elucidated the underlying mechanisms. Methods: Male Sprague–Dawley rats were randomly allocated to six experimental groups. One group received an intra-articular saline injection as the normal control (NC), while the remaining five groups were injected with monosodium iodoacetate (MIA) and consisted of an MIA control group (MC), a positive control group treated with celecoxib (PC, 3 mg/kg), and three groups treated with CP (31.25, 62.5, or 125 mg/kg). Results: Compared with the MC group, CP administration significantly improved pain-related behavior, as assessed by weight-bearing measurements. Micro-computed tomography and histological analyses demonstrated that CP administration mitigated subchondral bone erosion and preserved cartilage integrity. Additionally, the CP treatment significantly reduced markers associated with cartilage degradation, including matrix metalloproteinases and cartilage oligomeric matrix proteins; downregulated the expression of matrix-degrading enzymes; and restored aggrecan expression. Serum levels of inflammatory mediators, including nitric oxide; prostaglandin E₂; C-reactive protein; and pro-inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, were reduced following CP administration. Furthermore, CP decreased the activation of nuclear factor kappa B (NF-κB) signaling. Conclusions: These findings suggest that CP may be a promising functional agent for osteoarthritis, demonstrating beneficial effects on pain-related outcomes and cartilage integrity, potentially mediated by its anti-inflammatory activity. Full article

Herein, we have identified the polyfunctionalized 1-(phenylsulfonyl)-1H-indole-2-carboxylic acid derivative MTP150 for the treatment of neurodegenerative diseases owing to its efficacy in reducing protein aggregation, modulating matrix metalloproteinase activity, mitigating neuroinflammation, and enhancing DNA damage repair pathways across in vivo Caenorhabditis elegans models of Alzheimer’s disease, Parkinson’s disease (PD), and Huntington’s disease. Further experiments in an in vivo Drosophila model of PD showed that MTP150 increased motor performance, reduced oxidative stress levels, and restored mitochondrial function in model flies. In addition, MTP150 exhibited neuroprotective effects in PD model cells, thereby supporting its therapeutic potential for this disease. Full article

Corneal fibrosis, clinically referred to as corneal scarring, disrupts the normal architecture and transparency of the cornea and remains a major cause of visual impairment worldwide. Although corneal transplantation can restore vision, its effectiveness is constrained by limited accessibility, donor tissue shortages, and the risk of allograft rejection. Treatments with human corneal stromal stem cells (hCSSCs) have demonstrated scarless healing in preclinical models of acute corneal injury. Here, we report that hCSSCs also modulated pre-existing corneal opacities. We established a reproducible in vivo model of chronic corneal opacity. Given that scar severity varies among corneas even after identical injuries, we developed a non-invasive, image-based method to quantify opacity volume longitudinally in individual corneas. Using this approach, we evaluated the scar-reducing potential of three hCSSC batches previously shown to inhibit acute scarring. Following cell treatment, the pre-existing opacity volumes gradually decreased. In vitro, hCSSCs exposed to pro-inflammatory stimulus exhibited increased metalloproteinase (MMP) activity relative to tissue inhibitor of metalloproteinase (TIMP), as indicated by an elevated MMP2/TIMP2 ratio. This shift may promote matrix remodeling and scar resolution. Overall, our findings provide proof-of-concept for hCSSC-based therapy as a strategy to reduce established corneal scarring and restore corneal transparency. 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