Bisphenol A regulates bladder cells responses via control of G2/M-phase cell cycle, apoptotic signaling, MAPK pathway, and transcription factor-associated MMP modulation.

Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, is widely used to produce polycarbonate plastics. The widely used BPA has been detected in human urine samples, raising public anxiety about the detrimental effects of BPA on the bladder. In this study, we explored regulatory mechanisms for the adverse effects of BPA in human bladder BdFC and T24 cells. BPA induced extrinsic and intrinsic apoptosis and G2/M cell cycle arrest caused by the ATM-CHK1/CHK2-CDC25c-CDC2 signaling, which ultimately inhibited the growth of human bladder cells. We also found that BPA decreased the binding activity of AP-1 and NF-κB transcription factors in human bladder cells, which inhibited migration and invasion through matrix metallopeptidase-2 and -9 inactivation. Phosphorylation of MAPKs was implicated with BPA-mediated detrimental effects in human bladder cells. Collectively, our results provide a novel explanation for the underlying molecular mechanisms that BPA induces cytotoxicity in human bladder cells.

Effects of immediate loading directionality on the mechanical sensing protein PIEZO1 expression and early-stage healing process of peri-implant bone.

BACKGROUND: The reduced treatment time of dental implants with immediate loading protocol is an appealing solution for dentists and patients. However, there remains a significant risk of early peri-implant bone response following the placement of immediately loaded implants, and limited information is available regarding loading directions and the associated in vivo characteristics of peri-implant bone during the early stages. This study aimed to investigate the effects of immediate loading directionality on the expression of mechanical sensing protein PIEZO1 and the healing process of peri-implant bone in the early stage. METHODS: Thirty-two implants were inserted into the goat iliac crest models with 10 N static lateral immediate loading applied, followed by histological, histomorphological, immunohistochemical, X-ray microscopy and energy dispersive X-ray spectroscopy evaluations conducted after 10 days. RESULTS: From evaluations at the cellular, tissue, and organ levels, it was observed that the expression of mechanical sensing protein PIEZO1 in peri-implant bone was significantly higher in the compressive side compared to the tensile side. This finding coincided with trends observed in interfacial bone extracellular matrix (ECM) contact percentage, bone mass, and new bone formation. CONCLUSIONS: This study provides a novel insight into the immediate loading directionality as a potential influence factor for dental implant treatments by demonstrating differential effects on the mechanical sensing protein PIEZO1 expression and related early-stage healing processes of peri-implant bone. Immediate loading directions serve as potential therapeutic influence factors for peri-implant bone during its early healing stage.

Advancements in Regenerative Hydrogels in Skin Wound Treatment: A Comprehensive Review.

This state-of-the-art review explores the emerging field of regenerative hydrogels and their profound impact on the treatment of skin wounds. Regenerative hydrogels, composed mainly of water-absorbing polymers, have garnered attention in wound healing, particularly for skin wounds. Their unique properties make them well suited for tissue regeneration. Notable benefits include excellent water retention, creating a crucially moist wound environment for optimal healing, and facilitating cell migration, and proliferation. Biocompatibility is a key feature, minimizing adverse reactions and promoting the natural healing process. Acting as a supportive scaffold for cell growth, hydrogels mimic the extracellular matrix, aiding the attachment and proliferation of cells like fibroblasts and keratinocytes. Engineered for controlled drug release, hydrogels enhance wound healing by promoting angiogenesis, reducing inflammation, and preventing infection. The demonstrated acceleration of the wound healing process, particularly beneficial for chronic or impaired healing wounds, adds to their appeal. Easy application and conformity to various wound shapes make hydrogels practical, including in irregular or challenging areas. Scar minimization through tissue regeneration is crucial, especially in cosmetic and functional regions. Hydrogels contribute to pain management by creating a protective barrier, reducing friction, and fostering a soothing environment. Some hydrogels, with inherent antimicrobial properties, aid in infection prevention, which is a crucial aspect of successful wound healing. Their flexibility and ability to conform to wound contours ensure optimal tissue contact, enhancing overall treatment effectiveness. In summary, regenerative hydrogels present a promising approach for improving skin wound healing outcomes across diverse clinical scenarios. This review provides a comprehensive analysis of the benefits, mechanisms, and challenges associated with the use of regenerative hydrogels in the treatment of skin wounds. In this review, the authors likely delve into the application of rational design principles to enhance the efficacy and performance of hydrogels in promoting wound healing. Through an exploration of various methodologies and approaches, this paper is poised to highlight how these principles have been instrumental in refining the design of hydrogels, potentially revolutionizing their therapeutic potential in addressing skin wounds. By synthesizing current knowledge and highlighting potential avenues for future research, this review aims to contribute to the advancement of regenerative medicine and ultimately improve clinical outcomes for patients with skin wounds.

Best practices in wound care for gastrointestinal stoma and colorectal cancer patients from a nursing perspective: A meta-analysis.

Colorectal cancer, a type of colon or bowel cancer, poses a major challenge in the treatment of colorectal lesions. Colorectal endoscopic mucosal resection (EMR) is a minimally invasive technique, but the risk of wound infections remains a significant concern. These infections can impede the healing process, affecting daily activities and patient satisfaction. To mitigate the risk of wound infections, various prophylactic measures have been explored, including medication, vaccines, lifestyle adjustments and hygiene practices. This study aims to investigate the prevention of wound infections through prophylactic measures in colorectal EMR. A comprehensive literature review was conducted to identify prophylactic measures that can prevent wound infections. A systematic literature search was conducted using both free words and search terms. The data extraction was performed after a comprehensive literature screening. The meta-analysis was performed using the metabin function of the meta library in R to evaluate the infection incidences in intervention and control groups. A total of 599 infection incidences were considered, with 267 in intervention and 332 in the control group. The results of meta analysis demonstrated significant reduction of wound incidences following the prophylactic measures (risk ratio [RR] = 0.77, 95% confidence interval [CI]: 0.6747; 0.9016, I2 = 78.5%, p < 0.01). The wound infection ratio analysis also exhibited an approximate 6.6% less infection rate in the intervention group, demonstrating significantly less wound infection following the implementation of prophylactic measures. This study highlights the crucial significance of prevention of wound infections by prophylactic measures in colorectal EMR.

Comparison effect of collagen/P3HB composite scaffold and human amniotic membrane loaded with mesenchymal stem cells on colon anastomosis healing in male rats.

Covering surgical wounds with biomaterials, biologic scaffolds, and mesenchymal stem cells (MSCs) improves the healing process and reduces postoperative complications. This study was designed to evaluate and compare the effect of MSC-free/MSC-seeded new collagen/poly(3-hydroxybutyrate) (COL/P3HB) composite scaffold and human amniotic membrane (HAM) on the colon anastomosis healing process. COL/P3HB scaffold was prepared using freeze-drying method. MSCs were isolated and characterized from rat adipose tissue. After biocompatibility evaluation by MTT assay, MSCs were seeded on the scaffold and HAM by micro-mass seeding technique. In total, 35 male rats were randomly divided into five groups. After the surgical procedure, cecum incisions were covered by the MSC-free/MSC-seeded scaffold or HAM. Incisions in the control group were only sutured. One month later, the healing process was determined by stereological analysis. The Kruskal-Wallis followed by Dunn's tests were utilized for statistical outcome analysis (SPSS software version 21). COL/10% P3HB scaffold showed the best mechanical and structural properties (7.86 MPa strength, porosity more than 75%). MTT assay indicated that scaffold and especially HAM have suitable biocompatibility. Collagenization and neovascularization were significantly higher, and necrosis was considerably lower in all treated groups in comparison with the controls. MSC-seeded scaffold and HAM significantly decrease inflammation and increase gland volume compared with other groups. The MSC-seeded HAM was significantly successful in decreasing edema compared with other groups. Newly synthesized COL/P3HB scaffold improves the colon anastomosis healing; however, the major positive effect belonged to HAM. MSCs remarkably increase their healing process. Further investigations may contribute to confirming these results in other wound healing.

Chronological Changes in Mucosal Deformity by Endoscopic Suturing after Gastric Endoscopic Submucosal Dissection: A Multicenter Retrospective Analysis.

INTRODUCTION: Endoscopic suturing of a mucosal defect is expected to prevent postoperative bleeding after endoscopic submucosal dissection (ESD). Endoscopic suturing causes mucosal deformity, which may interfere with endoscopic surveillance thereafter. We retrospectively investigated long-term chronological changes in mucosal suturing by endoscopic suturing. METHODS: Forty-three patients who underwent endoscopic hand suturing (EHS) after gastric ESD at three institutions were enrolled. First, our hypothesis that the suturing sites healed via inflammation, disappearance of mucosal inversion, and flattening was validated. Subsequently, the duration required to reach each healing step was evaluated. RESULTS: A total of 137 follow-up endoscopies were assessed, in which all cases showed the hypothesized chronological course on the suturing sites. The 95th percentiles of the duration when showing the disappearance of the inflammatory change and the inverted change were 63 days and 15.5 months after the procedure, respectively. DISCUSSION/CONCLUSION: The data show that the mucosal deformity induced by EHS disappeared within 16 months. Endoscopic suturing is thus considered to have a negligible effect on endoscopic surveillance following the procedure.

Bisphenol A modulates proliferation, apoptosis, and wound healing process of normal prostate cells: Involvement of G2/M-phase cell cycle arrest, MAPK signaling, and transcription factor-mediated MMP regulation.

Bisphenol A (BPA) is commonly used to produce epoxy resins and polycarbonate plastics. BPA is an endocrine-disrupting chemical that is leaked from the polymer and absorbed into the body to disrupt the endocrine system. Although BPA may cause cytotoxicity in the prostate, a hormone-dependent reproductive organ, its underlying mechanism has not yet been elucidated. Here, we investigated the effects of BPA on cell proliferation, apoptosis, and the wound healing process using prostate epithelial cells (RWPE-1) and stromal cells (WPMY-1). Observations revealed that BPA induced G2/M cell cycle arrest in both cell types through the ATM-CHK1/CHK2-CDC25c-CDC2 signaling pathway, and the IC50 values were estimated to be 150 µM. Furthermore, BPA was found to induce caspase-dependent apoptosis through initiator (caspase-8 and -9) and executioner (caspase-3 and -7) caspase cascades. In addition, BPA interfered with the wound healing process through inhibition of MMP-2 and - 9 expression, accompanied by reductions in the binding activities of AP-1 as well as NF-κB motifs. Phosphorylation of MAPKs was associated with the BPA-mediated toxicity of prostate cells. These results suggest that BPA exhibits prostate toxicity by inhibiting cell proliferation, inducing apoptosis, and interfering with the wound healing process. Our study provided new insights into the precise molecular mechanisms of BPA-induced toxicity in human prostate cells.

The Use of Proteins, Lipids, and Carbohydrates in the Management of Wounds.

Despite the fact that skin has a stronger potential to regenerate than other tissues, wounds have become a serious healthcare issue. Much effort has been focused on developing efficient therapeutical approaches, especially biological ones. This paper presents a comprehensive review on the wound healing process, the classification of wounds, and the particular characteristics of each phase of the repair process. We also highlight characteristics of the normal process and those involved in impaired wound healing, specifically in the case of infected wounds. The treatments discussed here include proteins, lipids, and carbohydrates. Proteins are important actors mediating interactions between cells and between them and the extracellular matrix, which are essential interactions for the healing process. Different strategies involving biopolymers, blends, nanotools, and immobilizing systems have been studied against infected wounds. Lipids of animal, mineral, and mainly vegetable origin have been used in the development of topical biocompatible formulations, since their healing, antimicrobial, and anti-inflammatory properties are interesting for wound healing. Vegetable oils, polymeric films, lipid nanoparticles, and lipid-based drug delivery systems have been reported as promising approaches in managing skin wounds. Carbohydrate-based formulations as blends, hydrogels, and nanocomposites, have also been reported as promising healing, antimicrobial, and modulatory agents for wound management.

Photobiomodulation isolated or associated with adipose-derived stem cells allograft improves inflammatory and oxidative parameters in the delayed-healing wound in streptozotocin-induced diabetic rats.

The single and associated impressions of photobiomodulation (PBM) and adipose-derived stem cells (ADS) on stereological parameters (SP), and gene expression (GE) of some antioxidant and oxidative stressors of repairing injured skin at inflammation and proliferation steps (days 4 and 8) of a delayed healing, ischemic, and infected wound model (DHIIWM) were examined in type one diabetic (DM1) rats. DM1 was induced by administration of streptozotocin (40 mg/kg) in 48 rats. The DHIIWM was infected by methicillin-resistant Staphylococcus aureus (MRSA). The study comprised 4 groups (each, n = 6): Group 1 was the control group (CG). Group 2 received allograft human (h) ADSs transplanted into the wound. In group 3, PBM (890 nm, 80 Hz, 0.2 J/cm2) was emitted, and in group 4, a combination of PBM+ADS was used. At both studied time points, PBM+ADS, PBM, and ADS significantly decreased inflammatory cell count (p < 0.05) and increased granulation tissue formation compared to CG (p < 0.05). Similarly, there were lower inflammatory cells, as well as higher granulation tissue in the PBM+ADS compared to those of alone PBM and ADS (all, p < 0.001). At both studied time points, the GE of catalase (CAT) and superoxide dismutase (SOD) was remarkably higher in all treatment groups than in CG (p < 0.05). Concomitantly, the outcomes of the PBM+ADS group were higher than the single effects of PBM and ADS (p < 0.05). On day 8, the GE of NADPH oxidase (NOX) 1 and NOX4 was substantially less in the PBM+ADS than in the other groups (p < 0.05). PBM+ADS, PBM, and ADS treatments significantly accelerated the inflammatory and proliferative stages of wound healing in a DIIWHM with MRSA in DM1 rats by decreasing the inflammatory response, and NOX1 and 4 as well; and also increasing granulation tissue formation and SOD and CAT. The associated treatment of PBM+ADS was more effective than the individual impacts of alone PBM and ADS because of the additive anti-inflammatory and proliferative effects of PBM plus ADS treatments.

Clinical application of both amniotic membranes and adipose derived mesenchymal stem cells in a cat with a large skin defect.

Surgical procedures on large skin defects can be challenging in the short term due to the size of the lesion, infection, and tissue defect. A regenerative therapy for skin wounds has been applied to promote the healing process. An 8-month-old, Korean domestic short-haired female cat, weighing 3 kg, was rescued with extensive defects on the right flank to right inguinal region caused by bite wounds. In this case, amniotic membranes and adipose-derived mesenchymal stem cells were used as the regenerative therapy to treat the large skin defect rather than a surgical intervention alone. To the best of our knowledge, this is the first report of a case with of a large skin defect treated by applying allogeneic amniotic membranes and allogeneic mesenchymal stem cells to a cat.

Nit-Occlud atrial septal defect occluder device: Histological characterisation of the healing process.

We describe the healing process following transcatheter implantation of the Nit-Occlud ASD-R occluder (PFM medical, Cologne, Germany) for atrial septal defect closure in a sheep model with histological confirmation of neotissue formation covering the device.

Promoting effect of acylated homoserine lactone on the healing of tissue damage in model rats with incontinence-associated dermatitis.

OBJECTIVE: One of the most common complications in patients with incontinence is incontinence-associated dermatitis (IAD). This study was conducted to determine the pathophysiology of the healing process of IAD and to develop an effective therapeutic approach according to its pathophysiology. METHOD: IAD was reproduced on a dorsal rat skin by applying agarose gel containing water and enzymes, and inoculating it with bacteria. Examination of the IAD healing process suggested that the promotion of keratinocyte migration and improvement of basement membrane enhance keratinocyte layer elongations, which contribute to IAD healing. A therapeutic approach using N-(3-oxotetradecanoyl)-L-homoserine lactone, which is one of the acylated homoserine lactones (AHLs) and can promote keratinocyte migration in vitro, was applied on the IAD area in rats. RESULTS: AHL treatment after IAD development resulted in an earlier tipping point for recovery than the vehicle treatment. Histological and immunohistological analyses revealed that the tissue surface was already covered by the epidermis, indicating the results of elongation of the keratinocyte layer from hair follicles. The characteristics of the alignment of basal keratinocytes, the existence of stratum corneum, and the membrane-like distribution of the components of basement membrane were similar to those of a normal epidermis. CONCLUSION: These results suggested that AHL application possibly contributed to earlier IAD healing before progressing to a severe state. Although elongation of the keratinocyte layer was observed in both the AHL and vehicle groups, the possibility that AHL application promotes IAD healing was suggested. The new concept of the enhancement of keratinocyte migration as a therapeutic approach for IAD would change the skin care strategy for IAD in the healthcare setting.

Hard-to-heal wound treated with Integra Flowable Wound Matrix: analysis and clinical observations.

Skin healing defects severely impair the quality of life of millions of people and burden healthcare systems globally. The therapeutic approach to these pathologies still represents a challenge. Novel scaffolds, used as dermal substitutes, possibly represent a promising strategy in complex wound management. Integra Flowable Wound Matrix (IFWM) is composed of a lyophilised, micronised form of collagen/chondroitin sulphate matrix, already used in regenerative medicine and endorsed in the therapy of diabetic foot lesions. In this paper, IFWM was applied to a tunnelling hard-to-heal skin lesion in order to restore tissue integrity. Although the different phases of skin wound healing are well established, the molecular mechanism underpinning IFWM-induced tissue repair are almost unknown. Here, we report, for the first time, the comparative analysis of molecular, histological and clinical observations of the healing process of a hard-to-heal tunnelling skin wound. The therapeutic success of this clinical case allowed us to recommend the use of IFWM as a tissue substitute in this rare type of hard-to-heal wound in which the high inflammatory status hampered the natural healing process.

The impact of incisional negative pressure wound therapy on the wound healing process after midline sternotomy.

Previous studies have reported that the use of incisional negative pressure wound therapy (INPWT) might reduce the incidence of wound infections, although its mechanism remains unknown. We designed a prospective study to explore the effects of INPWT on different stages of the wound healing process. After meeting the inclusion criteria, 108 patients were enrolled. Based on exclusion criteria four patients were excluded and 104 patients were randomised into two groups. INPWT was applied after primary closure of the midline sternotomy in the study group (n = 52), while conventional wound dressing was applied in the control group (n = 52). We documented the incidence of deep sternal wound infections and analysed the pre- and postoperative inflammatory biomarkers and scar size in both groups. No wound infections were observed in the study group compared with six cases (11.1%) in the control group, (P = .026). No significant differences were observed in the inflammatory biomarkers between the groups. Scar size was significantly smaller in the study group. We concluded that INPWT has less effect on the inflammatory phase and appears to have more effect on the proliferation phase through pronounced scar formation.

Activation of TLR4 of Mesenchymal Stem Cells Enhances the Regenerative Properties of Their Secretomes.

Mesenchymal stem cells (MSC), like macrophages, can be polarized in vitro. In particular, activation of type 4 Toll-like receptor in MSC leads to the appearance of the so-called "proinflammatory" MSC phenotype (MSC1). We showed that secretome (conditioned media) of MSC1 can affect the wound healing processes: promote healing and modulate exudative inflammation and subsequent fibroplastic processes in the damaged area. These effects of secretomes of polarized MSC were superior to those of intact MSC.

The influence of «Saprogel¼ in the wound healing process on rats with a full-thickness wound model.

The article presents the study results of the effectiveness and the mechanism of the «Saprogel¼ action on the wound healing process and pro-/antioxidant equilibrium in serum of rats with a full-thickness wound model. The wound healing effect of tested gel samples was evaluated by the dynamics of area change (S) and the percentage reduction of the area (PRA) of wounds on the 3rd, 7th, and 14th days of the treatment. The content of lipid peroxide oxidation (LPO) products and the activity of antioxidant protection enzymes in the serum of rats were determined in the dynamics in different phases of the wound healing process in rats. «Saprogel¼ treatment of full-thickness wounds in rats reduced their healing time by 24.5% (p < 0.05), but there was no statistically significant difference between the effect of «Saprogel¼ and the comparator product on the duration of wound healing. The content of LPO products in the rat serum when using «Saprogel¼ was reduced and the enzymes activity of the antioxidant protection SOD and CAT was normalized, indicating that one of the mechanisms of wound healing action of «Saprogel¼ is its antioxidant properties.

The healing effect of the collagen-glycosaminoglycan copolymer on corneal thinning.

BACKGROUND: To study the healing processes of partial thickness wounds in the adult rabbit cornea after grafting a porous collagen-glycosaminoglycan copolymer matrix (CG). METHODS: In this study, the regeneration of surgically-induced rabbit corneal defect implanted with CG was investigated. The corneal partial thickness wound was created by 7.5 mm trephine. The wound was implanted with CG. Effects on wound healing was analyzed using clinical data on epithelial migration and corneal thickness, and histological data on collagen and alpha smooth muscle actin distribution. RESULTS: Compared with control group, CG induced a relatively severe inflammatory reaction in grafted cornea until the CG matrix was completely degraded. The new vessel ingrowth and stromal regeneration maintained the corneal thickness. The grafted cornea was significantly thicker (P < 0.001) than the control group. On day 90, the corneal opacity score of the control group was one and the grafted cornea was two. CONCLUSION: CG copolymer matrix can successfully repair the damaged corneal stroma by injury, and regain its thickness. However, CG matrix induced inflammatory healing process thus causing mild corneal haziness and neovascularization.

Intermittent Hypoxia and Unsaturated Aldehydes: Effects on Oral Epithelial Wound Healing.

Obstructive sleep apnea (OSA) is a highly prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), leading to blood hypoxemia, hypercapnia, and sleep fragmentation. Studies on the effects of OSA on oral epithelial tissue healing are limited. Smoking is considered a risk factor for OSA through the exposure to chemically active toxins, present in the smoke. Acrolein is the most chemically active unsaturated aldehyde, impairing a variety of biological processes. The aim of this study was to determine the effect of IH on oral epithelial tissue healing, with and without acrolein. HaCaT cells were wounded by a cross-scratch made in the cell cultures, considered as time zero. Then, cells were exposed to 28 IH cycles (5-20% oxygen) during 12 h using the BioSpherix OxyCycler-C42 system. Control cells were maintained in normoxic conditions or in sustained hypoxia (SH) (5% oxygen) for the same durations, after which all cells were maintained for additional 12 h in normoxia. The migrating abilities of cells were measured after 24 h by calculating the percent of the residual cross-scratch area. In parallel experiments, 25 µM acrolein were added to each treatment. We found that the scratch closure was the slowest under IH. After 24 h, the residual scratch area in the IH treated cells was 29.5 ± 13.4% of the initial area, while in normoxia and SH it was 9.2 ± 5.8% and 10.3 ± 11.3%, respectively (p < 0.01 for both vs. IH). Adding acrolein further attenuated the migratory ability in IH as compared to normoxia and SH. We conclude that IH delays the healing process of oral epithelial tissue by slowing the cells' migratory abilities. The healing might be further attenuated by chemically active unsaturated aldehydes such as acrolein.

Lomatuell Pro contact layer and its role in the wound-healing process.

There is a plethora of wound contact layer dressings on the market each with its own properties to promote healing, which makes dressing selection complicated. An effective and efficient choice of dressing depends on holistic patient assessment, along with an understanding of the wound-healing process, moist wound healing and wound bed preparation. This paper, supported by clinical case studies, demonstrates the effectiveness of the Lomatuell® Pro dressing (Lohmann & Rauscher) in the management of graft wounds, although it is known to be effective in the management of dermal and deep dermal wounds as well. Lomatuell Pro offers benefits of conformability, open mesh gel-forming wound contact properties and a low risk of adhering to the wound bed. It enables moist wound healing by allowing exudate to be absorbed by a secondary dressing. Lomatuell® Pro demonstrates excellence in maintaining a moist wound environment, allows atraumatic dressing removal and encourages a healthy periwound area.

Comparison between smaller ruptured intracranial aneurysm and larger un-ruptured intracranial aneurysm: gene expression profile analysis.

As it grows in size, an intracranial aneurysm (IA) is prone to rupture. In this study, we compared two extreme groups of IAs, ruptured IAs (RIAs) smaller than 10 mm and un-ruptured IAs (UIAs) larger than 10 mm, to investigate the genes involved in the facilitation and prevention of IA rupture. The aneurismal walls of 6 smaller saccular RIAs (size smaller than 10 mm), 6 larger saccular UIAs (size larger than 10 mm) and 12 paired control arteries were obtained during surgery. The transcription profiles of these samples were studied by microarray analysis. RT-qPCR was used to confirm the expression of the genes of interest. In addition, functional group analysis of the differentially expressed genes was performed. Between smaller RIAs and larger UIAs, 101 genes and 179 genes were significantly over-expressed, respectively. In addition, functional group analysis demonstrated that the up-regulated genes in smaller RIAs mainly participated in the cellular response to metal ions and inorganic substances, while most of the up-regulated genes in larger UIAs were involved in inflammation and extracellular matrix (ECM) organization. Moreover, compared with control arteries, inflammation was up-regulated and muscle-related biological processes were down-regulated in both smaller RIAs and larger UIAs. The genes involved in the cellular response to metal ions and inorganic substances may facilitate the rupture of IAs. In addition, the healing process, involving inflammation and ECM organization, may protect IAs from rupture.