Stages Of Remodeling Research Articles

Porphyromonas gingivalis-mediated disruption in spiral artery remodeling is associated with altered uterine NK cell populations and dysregulated IL-18 and Htra1

Impaired spiral artery remodeling (IRSA) underpins the great obstetrical syndromes. We previously demonstrated that intrauterine infection with the periodontal pathogen, Porphyromonas gingivalis, induces IRSA in rats. Since our previous studies only examined the end stage of arterial remodeling, the aim of this study was to identify the impact of P. gingivalis infection on the earlier stages of remodeling. Gestation day (GD) 11 specimens, a transition point between trophoblast-independent remodeling and the start of extravillous trophoblast invasion, were compared to late stage GD18 tissues. P. gingivalis was found in decidual stroma of GD11 specimens that already had reduced spiral artery remodeling defined as smaller arterial lumen size, increased retention of vascular smooth muscle, and decreased invasion by extravillous trophoblasts. At GD11, P. gingivalis-induced IRSA coincided with altered uterine natural killer (uNK) cell populations, decreased placental bed expression of interleukin-18 (IL-18) with increased production of temperature requirement A1 (Htra1), a marker of oxidative stress. By GD18, placental bed IL-18 and Htra1 levels, and uNK cell numbers were equivalent in control and infected groups. However, infected GD18 placental bed specimens had decreased TNF + T cells. These results suggest disturbances in placental bed decidual stroma and uNK cells are involved in P. gingivalis-mediated IRSA.

Pooled human bone marrow-derived mesenchymal stromal cells with defined trophic factors cargo promote dermal wound healing in diabetic rats by improved vascularization and dynamic recruitment of M2-like macrophages.

Human Mesenchymal Stromal Cells (hMSCs) are a promising source for cell-based therapies. Yet, transition to phase III and IV clinical trials is remarkably slow. To mitigate donor variabilities and to obtain robust and valid clinical data, we aimed first to develop a manufacturing concept balancing large-scale production of pooled hMSCs in a minimal expansion period, and second to test them for key manufacture and efficacy indicators in the clinically highly relevant indication wound healing. Our novel clinical-scale manufacturing concept is comprised of six single donor hMSCs master cell banks that are pooled to a working cell bank from which an extrapolated number of 70,000 clinical doses of 1x106 hMSCs/cm2 wound size can be manufactured within only three passages. The pooled hMSC batches showed high stability of key manufacture indicators such as morphology, immune phenotype, proliferation, scratch wound healing, chemotactic migration and angiogenic support. Repeated topical hMSCs administration significantly accelerated the wound healing in a diabetic rat model by delivering a defined growth factor cargo (specifically BDNF, EGF, G-CSF, HGF, IL-1α, IL-6, LIF, osteopontin, VEGF-A, FGF-2, TGF-β, PGE-2 and IDO after priming) at the specific stages of wound repair, namely inflammation, proliferation and remodeling. Specifically, the hMSCs mediated epidermal and dermal maturation and collagen formation, improved vascularization, and promoted cell infiltration. Kinetic analyses revealed transient presence of hMSCs until day (d)4, and the dynamic recruitment of macrophages infiltrating from the wound edges (d3) and basis (d9), eventually progressing to the apical wound on d11. In the wounds, the hMSCs mediated M2-like macrophage polarization starting at d4, peaking at d9 and then decreasing to d11. Our study establishes a standardized, scalable and pooled hMSC therapeutic, delivering a defined cargo of trophic factors, which is efficacious in diabetic wound healing by improving vascularization and dynamic recruitment of M2-like macrophages. This decision-making study now enables the validation of pooled hMSCs as treatment for impaired wound healing in large randomized clinical trials.

Review on Collagen as a wound healer.

In reaction to the tissue injury, normal wound healing process goes through inflammatory, proliferative, and remodeling stages. Impairments any one of these stages cause the wound to become chronic and non-healing, necessitating intervention to bring returning the process to its original state. Collagen, a fundamental has a role in the matrix extracellular an important function in wound healing regulation, whether in its native fibrillar form or in the wound as soluble components environment. Collagen has been used as an additional wound treatment to aid healing since it is involved in the control a combination of a few of these processes. The importance of collagen in various biological processes related to wound healing is discussed in this paper, additionally to a survey of the existing research in regards to the utilization of collagen-based wound care. There are several techniques to developing recommendations, but no gold standard has emerged so till now.
 
 
 

Recent Progress in Electrospun Polyacrylonitrile Nanofiber-Based Wound Dressing.

Bleeding control plays a very important role in worldwide healthcare, which also promotes research and development of wound dressings. The wound healing process involves four stages of hemostasis, inflammation, proliferation and remodeling, which is a complex process, and wound dressings play a huge role in it. Electrospinning technology is simple to operate. Electrospun nanofibers have a high specific surface area, high porosity, high oxygen permeability, and excellent mechanical properties, which show great utilization value in the manufacture of wound dressings. As one of the most popular reactive and functional synthetic polymers, polyacrylonitrile (PAN) is frequently explored to create nanofibers for a wide variety of applications. In recent years, researchers have invested in the application of PAN nanofibers in wound dressings. Research on spun nanofibers is reviewed, and future development directions and prospects of electrospun PAN nanofibers for wound dressings are proposed.

Estimating a Building’s Energy Performance using a Composite Indicator: A Case Study

Several studies have analyzed the integration of energy-saving strategies in buildings to mitigate their environmental impact. These studies focused mainly on a disaggregated analysis of such strategies and their effects on the building's energy consumption and thermal behavior, using energy engine simulation software (EnergyPlus, TRNSYS, and DOE2) or graphical interface software (DesignBuilder, eQuest, and ESP-r). However, buildings are complex systems whose energy behavior depends on the interaction of passive (e.g., location and construction materials) and dynamic (e.g., occupation) components. Therefore, this study proposes a composite indicator Building’s Energy Performance (BEP) as an alternative to deal with this complex and multidimensional phenomenon in a simplified way. This indicator considers energy efficiency and thermal comfort. The Electrical Engineering Building (EEB) of the Universidad Industrial de Santander was selected to verify the performance of the BEP indicator. In addition, a sensitivity analysis was performed for different mathematical aggregation methods and weighting values to test their suitability to reproduce the building behavior. Different simulation scenarios modeled with DesignBuilder software were proposed, in which the energy-saving strategies integrated with the building was individually analyzed. The results confirmed that the integration of the building's energy-saving strategies improved the BEP indicator by approximately 16%. It has also been possible to verify that the BEP indicator adequately reproduces the building’s energy behavior while guaranteeing comfort conditions. Finally, the Building Energy Performance indicator is expected to contribute to the integration of sustainability criteria in the design and remodeling stages of buildings.

Surgical considerations in skin of colour: minimizing pathological scars.

In most surgeries, the primary aim, for both surgeons and patients, is the success of the operation being undertaken. A secondary aim is for optimal wound healing with minimal scar formation. The normal wound-healing process involves four distinct but overlapping stages: haemostasis, inflammation, proliferation and remodelling. In some patients, the cellular process involved in the proliferation and remodelling stages can be deranged, resulting in the formation of hypertrophic or keloid scars, a phenomenon more frequently seen in skin of colour. The first report of excessive scarring is thought to be the Smith papyrus about 1700 BC. In the 20th century, both Mancini and Quaife (in 1962) and Peacock etal. (in 1970) classified excessive scarring into hypertrophic and keloid scar formation. Clinicians can minimize the risk of these pathological scars developing by using good preoperative, perioperative/intraoperative and postoperative surgical practices. This paper reviews the wound-healing processes in association with good surgical principles and practice, discusses how implementing these principles in practice helps in this prevention and management of pathological surgical scars such as hypertrophic scars and keloid scars. and offers a practical step-by-step clinical guide that can be used by any clinician.

Arterial stiffness and atherosclerosis in systemic lupus erythematosus patients

IntroductionSystemic lupus erythematosus (SLE) is characterized by early atherothrombosis. Pulse wave velocity (PWV) is a promising tool for the diagnosis of early vascular remodelling and initial atherosclerotic plaque formation. Our objective was to evaluate PWV and its relationship with coronary atherosclerosis and thrombotic biomarkers in patients with SLE.Material and methodsIn 26 patients with SLE with stable clinical conditions, mean age of 39.1 ±11.7 years and without a history of coronary artery disease, multidetector computed tomography (MDCT)-based coronary calcium scoring (CACS) was performed and PWV measured.Laboratory evaluation included serum levels of anticardiolipin and anti-β2-glycoprotein antibodies (anti-β2-GPI), lupus anticoagulant (LA), D-dimers, thrombin–antithrombin complexes (TAT), and von Willebrand factor (vWF).ResultsMultidetector computed tomography revealed coronary calcifications in 8 (30.8%) patients and the median CACS was 52.4 HU (range 2–843.2). The mean PWV was 9.0 ±3.2 m/s and was higher in patients aged > 50 years (+33.7% vs. < 50 years), those with positive LA (+28.2% vs. LA negative), TAT ≥ 10 μg/l (+18.1% vs. < 10 μg/l), vWF ≥ 200 IU/dl (+51.8% vs. < 200 IU/dl) and with coronary atherosclerosis (CACS > 0; +21.4% vs. CACS = 0).In contrast, the duration of the disease, D-dimers, anticardiolipin, and anti-β2-GPI antibodies did not influence PWV. In the group without atherosclerosis (CACS = 0, n =18), patients with vWF ≥ 200 IU/dl had a 19.3% higher PWV compared to the rest.ConclusionsIn patients with SLE, PWV was associated with the presence of coronary atherosclerotic lesions in MDCT. Furthermore, arterial stiffness was higher in patients with markers of endothelial dysfunction and a prothrombotic state, suggesting their contribution to the early stages of arterial remodelling in SLE.

Beyond the Scar: A Basic Science Review of Wound Remodeling.

Significance: Increasing development of experimental animal models has allowed for the study of scar formation. However, many pathophysiological unknowns remain in the longest stage of healing, the remodeling stage, which may continue for a year or more. The wound healing process results in different types of scarring classified as normal or pathological depending on failures at each stage. Failures can also occur during wound remodeling, but the molecular mechanisms driving the wound remodeling process have yet to be investigated. Recent Advances: While the current understanding of wound repair is based on investigations of acute healing, these experimental models have informed knowledge of key components of remodeling. This review examines the components that contribute to collagen organization and the final scar, including cell types, their regulation, and signaling pathways. Dysregulation in any one of these components causes pathologic healing. Critical Issues and Future Directions: As wounds continue to remodel months to years after reepithelialization, new models to better understand long-term remodeling will be critical for improving healing outcomes. Further investigation of the contributions of fibroblasts and cell signaling pathways involved during remodeling as well as their potential failures may inform new approaches in promoting regenerative healing beyond reepithelialization.

The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing.

Poor wound healing in individuals with diabetes has long plagued clinicians, and immune cells play key roles in the inflammation, proliferation and remodeling that occur in wound healing. When skin integrity is damaged, immune cells migrate to the wound bed through the actions of chemokines and jointly restore tissue homeostasis and barrier function by exerting their respective biological functions. An imbalance of immune cells often leads to ineffective and disordered inflammatory responses. Due to the maladjusted microenvironment, the wound is unable to smoothly transition to the proliferation and remodeling stage, causing it to develop into a chronic refractory wound. However, chronic refractory wounds consistently lead to negative outcomes, such as long treatment cycles, high hospitalization rates, high medical costs, high disability rates, high mortality rates, and many adverse consequences. Therefore, strategies that promote the rational distribution and coordinated development of immune cells during wound healing are very important for the treatment of diabetic wounds (DW). Here, we explored the following aspects by performing a literature review: 1) the current situation of DW and an introduction to the biological functions of immune cells; 2) the role of immune cells in DW; and 3) existing (or undeveloped) therapies targeting immune cells to promote wound healing to provide new ideas for basic research, clinical treatment and nursing of DW.

Evaluation of echocardiography indicators of cows and calves with myocardial dystrophy

Echocardiography is the most informative non‐invasive method of heart disease diagnosis, which makes it possible to determine the structural and functional state of the heart through visualization using reflected ultrasound wave. The purpose of this study is to analyze echocardiograms of the cows and calves with myocardial dystrophy. The studies were carried out in of the Agricultural production cooperative “Gridino” (Russia, Kostroma region) on highly productive cows of the Kostroma breed 20 days after calving (3‐4 lactation) and 2‐month‐old calves obtained from these cows. Four experimental groups of animals were formed: group 1 ‐ clinically healthy cows (n=15), group 2 ‐ cows with symptoms of myocardial dystrophy (n=15), group 3 ‐ calves obtained from clinically healthy cows (n=15), group 4 ‐ calves obtained from cows with symptoms of myocardial dystrophy (n=15). An ultrasonic veterinary machine AcuVista VT98C with a convex scanning transducer with a frequency of 3.5 MHz was used to get the echocardiograms. Access points for the study were prepared according to the heart anatomy; echocardiography was performed in B‐ and M‐modes. The following indices were determined: left ventricular end‐diastolic size (LVd), right ventricular end‐diastolic size (RVd), left ventricular end‐systolic size (LVs), right ventricular end‐systolic size (RVs), thickness of the interventricular septum in diastole (VSd), thickness of left ventricular posterior wall in diastole (LVWd), left ventricular posterior wall thickness in systole (LVWs), left atrial diameter (LA), and aortic root diameter (AO).According to the results of echocardiography, cows with symptoms of myocardial dystrophy had RVs 16.0±1.15 mm, which was 16.79% higher than in clinically healthy cows. At the same time, calves obtained from sick mothers, had a higher value of RVs (11.3±0.65 mm) by 4.63% in comparison with calves from clinically healthy mothers. A lower LA was determined among sick cows and their calves by 13.29% (P&lt;0.001) and 5.29%, respectively, compared with the indices of clinically healthy animals. Cows of both groups did not have significant differences in LVs: for clinically healthy animals, this indicator was 38.1±1.51 mm, for unhealthy ‐ 39.88±0.96 mm. Calves obtained from cows with signs of myocardial dystrophy showed LVs within 23.6±0.72 mm, which was 10.94% less (P&lt;0.05) compared with calves from clinically healthy cows. The VSd index did not have significant differences in comparison for the corresponding groups. The indices of LVWd and LVWs did not differ significantly in the groups of cows. Calves obtained from unhealthy mothers had a tendency to lower values of LVWd and LVWs respectively, by 7.5% and 2.13% in comparison with young calves from clinically healthy cows. Among the cows with symptoms of myocardial dystrophy, the AO index was lower by 14.77% (P&lt;0.001) compared with healthy animals and amounted to 50.2±1.23 mm. Among the calves of both groups, there was no significant difference in AO data.The revealed changes characterized the development of dystrophic processes in the myocardium and the initial stage of heart remodeling in high‐yielding cows in presence of high physiological stress. A similar tendency of the structural and functional myocardium disturbance was observed in calves obtained from cows with symptoms of myocardial dystrophy.

A staging classification of right heart remodelling for patients undergoing transcatheter edge-to-edge mitral valve repair.

In patients with severe mitral regurgitation (MR) who are scheduled for transcatheter mitral valve repair (TMVR), risk stratification is predominantly based on surgical risk scores. We sought to characterise and define stages of right heart remodelling in patients undergoing TMVR and evaluate the impact of this staging classification on survival. According to echocardiographic parameters, 929 patients undergoing MitraClip treatment were classified into three stages: severe MR without right heart damage (stage 0), with moderate-to-severe tricuspid regurgitation (TR) (stage 1), with right ventricular dysfunction defined as a reduced fractional area change <35% and a tricuspid annular plane systolic excursion <17 mm, or with increased right atrial area >25 cm2 and/or indexed right ventricular volume >30 ml/m2 (stage 2). We compared clinical outcomes and performed a multivariate analysis to evaluate the predictive value of the extent of cardiac damage. Rates of one-year all-cause mortality increased with more advanced stages of right heart remodelling (stage 0: 8% vs stage 1: 9.7% vs stage 2: 18.1%; p<0.001). In the multivariate analysis, advanced cardiac damage was an independent predictor of one-year all-cause mortality (stage 2: p=0.007). A simple staging classification objectively characterises the extent of right heart remodelling caused by MR and allows risk prediction in patients undergoing a MitraClip procedure.

Asthma and Post-Asthmatic Fibrosis: A Search for New Promising Molecular Markers of Transition from Acute Inflammation to Pulmonary Fibrosis.

Asthma is a heterogeneous pulmonary disorder, the progression and chronization of which leads to airway remodeling and fibrogenesis. To understand the molecular mechanisms of pulmonary fibrosis development, key genes forming the asthma-specific regulome and involved in lung fibrosis formation were revealed using a comprehensive bioinformatics analysis. The bioinformatics data were validated using a murine model of ovalbumin (OVA)-induced asthma and post-asthmatic fibrosis. The performed analysis revealed a range of well-known pro-fibrotic markers (Cat, Ccl2, Ccl4, Ccr2, Col1a1, Cxcl12, Igf1, Muc5ac/Muc5b, Spp1, Timp1) and a set of novel genes (C3, C3ar1, Col4a1, Col4a2, Cyp2e1, Fn1, Thbs1, Tyrobp) mediating fibrotic changes in lungs already at the stage of acute/subacute asthma-driven inflammation. The validation of genes related to non-allergic bleomycin-induced pulmonary fibrosis on asthmatic/fibrotic lungs allowed us to identify new universal genes (Col4a1 and Col4a2) associated with the development of lung fibrosis regardless of its etiology. The similarities revealed in the expression profiles of nodal fibrotic genes between asthma-driven fibrosis in mice and nascent idiopathic pulmonary fibrosis in humans suggest a tight association of identified genes with the early stages of airway remodeling and can be considered as promising predictors and early markers of pulmonary fibrosis.

Molecular mediators involved in skin healing: a narrative review

Background: The expression of biological mediators, such as growth factors and cytokines, after skin damage, and their balance, is important to guarantee proliferation, differentiation and migration of cells and extracellular matrix, as well as to the homeostasis during tissue remodeling. The present review means to clarify their functions over inflammation, proliferation and remodeling stages of skin regeneration. Methods: Reviews, experimental studies and clinical trials included in this paper were search on PubMed database using the following terms: platelet-derived growth factor, interleukin 1, tumor necrosis factor alpha, keratinocyte growth factor, transforming growth factor beta, endothelial vascular growth factor, matrix metalloproteinase 9, tissue metalloproteinase inhibitor 1, interferon gamma, transcription nuclear factor kappa B, skin inflammation, skin cell proliferation, skin extracellular matrix and skin regeneration. Results and Discussion: Several studies on the signaling mechanism of these mediators in normal and impaired healing have already been developed and have shown promising results. Currently, some of these mediators are already direct focuses of potential clinical therapies that address the treatment of acute and chronic skin wounds. These mediators, basically synthetized by platelets, macrophages, vascular endothelial cells, fibroblasts and keratinocytes, act on epidermis and dermis proliferation, hypertrophy and cell migration, resulting in formation of granulation tissue, reepithelization and extracellular matrix remodeling and angiogenesis. A better understanding of the action of these mediators can provide greater knowledge not only of their roles in the natural healing process but also in the presence of disorders that affect skin repair. Conclusion: Future studies aimed to understand the mechanism of action of these mediators in the different types of cells involved in wound healing may lead to the discovery of new therapeutics to optimize the treatment of skin pathologies.

Assessment of Wound Healing Potential of Cleome viscosa Seeds Extracts

In a natural way, wound healing is slow phenomenon and sometimes may become long lasting with a long clinical course there by causing constant liberation of inflammatory modulators that cause pain and redness. Wound healing begins at the time of injury and can vary in length depending on the severity of the wound. The wound healing process can be divided into three stages: the inflammatory stage, the growth stage, and finally the remodeling stage, which determines the strength and appearance of the healed tissue. In the present work an attempt had been made to evaluate wound healing potential of Simple ointment base B.P was applied on control group rats. Cipladine (Povidone-Iodine IP 5% w/w, Batch no. UZ300) ointment was applied on standard group rats. Ointments with different extracts concentrations i.e. 0.5% (w/w), 1% (w/w) and 2% (w/w) assimilated in simple ointment base were applied on test group rats, in each model.

Differential Nanoscale Topography Dedicates Osteocyte-Manipulated Osteogenesis via Regulation of the TGF-β Signaling Pathway.

Osteocytes function as the master orchestrator of bone remodeling activity in the telophase of osseointegration. However, most contemporary studies focus on the manipulation of osteoblast and/or osteoclast functionality via implant surface engineering, which neglects the pivotal role of osteocytes in de novo bone formation. It is confirmative that osteocyte processes extend directly to the implant surface, but whether the surface physicochemical properties can affect the functionality of osteocytes and determine the fate of the osseointegration in the final remodeling stage remains to be determined. Titania nanotube arrays (NTAs) with distinct diameters were fabricated to investigate the relationship between the nanoscale topography and the functionality of osteocytes. In vitro results pinpointed that NTA with a diameter of 15 nm (NTA-15) significantly promote osteogenesis of osteocytes via the enhancement of spreading, proliferation, and mineralization. The osteocyte transcriptome of each group further revealed that the TGF-β signaling pathway plays a pivotal role in osteocyte-mediated osteogenesis. The in vivo study definitely mirrored the aforementioned results, that NTA-15 significantly promotes bone formation around the implant. Consequently, nanoscaled topography-induced osteocyte functionality is important in late osseointegration. This suggests that surface designs targeting osteocytes may, therefore, be a potential approach to solving the aseptic loosening of the implant, and thus strengthen osseointegration.

Epicardial fat and atrial fibrillation: the perils of atrial failure.

Obesity is a heterogeneous condition, characterized by different phenotypes and for which the classical assessment with body mass index may underestimate the real impact on cardiovascular (CV) disease burden. An epidemiological link between obesity and atrial fibrillation (AF) has been clearly demonstrated and becomes even more tight when ectopic (i.e. epicardial) fat deposition is considered. Due to anatomical and functional features, a tight paracrine cross-talk exists between epicardial adipose tissue (EAT) and myocardium, including the left atrium (LA). Alongside-and even without-mechanical atrial stretch, the dysfunctional EAT may determine a pro-inflammatory environment in the surrounding myocardial tissue. This evidence has provided a new intriguing pathophysiological link with AF, which in turn is no longer considered a single entity but rather the final stage of atrial remodelling. This maladaptive process would indeed include structural, electric, and autonomic derangement that ultimately leads to overt disease. Here, we update how dysfunctional EAT would orchestrate LA remodelling. Maladaptive changes sustained by dysfunctional EAT are driven by a pro-inflammatory and pro-fibrotic secretome that alters the sinoatrial microenvironment. Structural (e.g. fibro-fatty infiltration) and cellular (e.g. mitochondrial uncoupling, sarcoplasmic reticulum fragmentation, and cellular protein quantity/localization) changes then determine an electrophysiological remodelling that also involves the autonomic nervous system. Finally, we summarize how EAT dysfunction may fit with the standard guidelines for AF. Lastly, we focus on the potential benefit of weight loss and different classes of CV drugs on EAT dysfunction, LA remodelling, and ultimately AF onset and recurrence.

Morphological features of heart remodeling in the postcompression period of crush syndrome

Summary. In the postcompression period of crush syndrome regenerative processes develop restorative processes in target organs, in particular in the heart. However, the dynamics of myocardial regenerative changes in the postcompression period in crush syndrome is insufficiently covered in professional literature and requires comprehension study and clarified. The aim of the study – to find out features of regenerative changes in heart of laboratory rats in the dynamics in the postcompression period of crush syndrome. Materials and Methods. Light-optical and polarization were performed examination of the myocardium of 48 laboratory rats after 1, 3, 7 and 14 days (12 animals in each period) after cessation of 6 hour compression of the thigh right pelvic limb. Crush syndrome was modeled under anesthesia by intraperitoneal input of ketamine hydrochloride (100 mg/kg body weight) in a specially designed device, the compression force was 7 kg/cm2, the compressive surface area – 5 cm2. The control group consisted of 12 animals. Results. The stages of myocardial remodeling in the postcompression period are noted, reflecting its structural recovery. In the early postcompression period light-optical disorders predominated microcirculation and alternate changes in acquired cardiomyocytes maximum development after 3 days. After 7 days in myocardial stroma registered cellular infiltrates in which predominate lymphocytes and fybroblasts. Cardiomyocytes lose a compact, gait cells became fortuous, microfoci of contractures were detected and fragmentation, there was a weak proliferation of collagen fibers. After 14 days in the late postcompression period the manifestation do not fade microcirculation disorders. Processes were registered in some areas collagen formation. Conclusions. In the first three days after the cessation of compression of compression of the lower extremity dystrophic–necrotic changes of the myocardium persist in combination with microcirculatory disorders. After 7 days the development of interstitial lympho–histiocytic infiltration is observed against the background of a gradual decrease alternative and hemodynamic processes. After 14 days registration a restoration of myocardial histostructure with residual processes of microfocal contracture of cardiomyocyte degeneration and increased collagen formation are registere

Contribution of vascular smooth muscle cell apoptosis to spiral artery remodeling in early human pregnancy.

Uterine spiral artery remodeling is one of the key maternal adaptations of pregnancy, allowing delivery of the large volumes of maternal blood required for both placental and fetal growth. Failure of this process is associated with obstetric complications including preeclampsia, fetal growth restriction and miscarriage. Spiral artery remodeling is characterized by loss of the musculoelastic wall which is replaced by fibrinoid and intramural extravillous trophoblast cells (EVT). In recent years attention has focused on the initial stages of spiral artery remodeling which include separation of the vascular smooth muscle cells (VSMCs) and their phenotypic switch to a more synthetic phenotype, facilitating their migration away from the vessel wall. However, less is known about the final fate of the VSMCs. In vitro studies suggested that EVT could induce VSMC apoptosis, though VSMC apoptosis is not seen within the wall of the spiral arteries undergoing remodeling. However, apoptotic VSMCs have been observed amongst those cells which had migrated away from the vessel wall. This review article gives a brief overview of the current state of knowledge of the processes involved in spiral artery remodeling, and then concentrates on the mechanisms involved in VSMC apoptosis, drawing on knowledge from other vascular beds.

Ceramide kinase regulates acute wound healing by suppressing 5-oxo-ETE biosynthesis and signaling via its receptor OXER1

The sphingolipid, ceramide-1-phosphate (C1P), has been shown to promote the inflammatory phase and inhibit the proliferation and remodeling stages of wound repair via direct interaction with group IVA cytosolic phospholipase A2, a regulator of eicosanoid biosynthesis that fine-tunes the behaviors of various cell types during wound healing. However, the anabolic enzyme responsible for the production of C1P that suppresses wound healing as well as bioactive eicosanoids and target receptors that drive enhanced wound remodeling have not been characterized. Herein, we determined that decreasing C1P activity via inhibitors or genetic ablation of the anabolic enzyme ceramide kinase (CERK) significantly enhanced wound healing phenotypes. Importantly, postwounding inhibition of CERK enhanced the closure rate of acute wounds, improved the quality of healing, and increased fibroblast migration via a “class switch” in the eicosanoid profile. This switch reduced pro-inflammatory prostaglandins (e.g., prostaglandin E2) and increased levels of 5-hydroxyeicosatetraenoic acid and the downstream metabolite 5-oxo-eicosatetraenoic acid (5-oxo-ETE). Moreover, dermal fibroblasts from mice with genetically ablated CERK showed enhanced wound healing markers, while blockage of the murine 5-oxo-ETE receptor (oxoeicosanoid receptor 1) inhibited the enhanced migration phenotype of these cell models. Together, these studies reinforce the vital roles eicosanoids play in the wound healing process and demonstrate a novel role for CERK-derived C1P as a negative regulator of 5-oxo-ETE biosynthesis and the activation of oxoeicosanoid receptor 1 in wound healing. These findings provide foundational preclinical results for the use of CERK inhibitors to shift the balance from inflammation to resolution and increase the wound healing rate.

Novel multifunctional dual-dynamic-bonds crosslinked hydrogels for multi-strategy therapy of MRSA-infected wounds

Wound healing is a complex dynamic process involving hemostasis, inflammation, proliferation and remodeling stages. It is urgent need to develop multifunctional hydrogels to treat multiple links of wound healing. In this work, we designed novel multifunctional dual-dynamic-bonds crosslinked hydrogels through the electrostatic interaction between phenylboric acid and the amino group of chitosan, and the dynamic borate ester bond between phenylboric acid and the catechol structure of PDA-modified CNTs. This dual dynamic cross-linking mechanism endowed hydrogels with very fast self-healing properties, which could quickly form a whole dressing after being injected into the wound site. The phenylboric acid and catechol structures endowed hydrogels with excellent adhesion properties, the adhesion strength to pig skin was up to 27.6 kPa, could be used for hemostasis in vivo. Moreover, hydrogels displayed the advantages of injectable, rapid shape adaptation, antioxidant, biocompatibility, blood compatibility, electrical conductivity and photothermal antibacterial properties. In the MRSA-infected wound model, hydrogels could effectively reduce the expression level of wound inflammatory factors, accelerate collagen deposition, epithelial tissue and vascular regeneration, and thus promote wound healing. This work provides a new idea for the design of multi-strategy therapy for wound healing and has broad clinical application prospects.