Healing Mechanisms Research Articles

Recombinant bone matrix maintains the graft space, induces vascularized bone regeneration and preserves canine tooth extraction socket structure.

Recombinant bone matrix (RBM) is a newly conceived and engineered porous bone graft granule of average size 600 μm composed of purified recombinant collagen peptide. We sought to examine the behaviour with time of RBM that was grafted in the canine tooth extraction socket. The canine tooth extraction socket of the hemisectioned mandibular third premolar distal root was grafted with RBM granules, whereas the opposite side extraction socket served as non-grafted control. The mandibular samples were harvested at 1, 3 and 6 months of healing and subjected to micro-CT imaging and decalcified paraffin-embedded histology. Separately, the effect of RBM was compared with that of deproteinized cancellous bovine bone (DCBB) and bovine atelocollagen plug (BACP) in the canine tooth extraction model at 3 months of healing. RBM maintained the grafted space in the socket and the gingival connective tissue until new bone was formed within its porous space. The regenerated bone was highly vascularized and continued to mature, while RBM was completely bioresorbed by 6 months. The buccal and lingual alveolar ridge heights of the RBM-grafted extraction socket was better preserved than those of non-grafted control sockets. The degree of socket preservation by RBM was equivalent to that by DCBB, although their healing mechanisms were different. This study demonstrated that RBM induced controlled active bone regeneration and preserved the extraction socket structure in a canine model. Bioresorbable RBM engineered without animal or human source materials presents a novel bone graft category with robust bone regenerative property.

Features of the reparative process after antiglaucoma surgery

Excessive fibrosis and scarring of newly created aqueous humor outflow pathways, mainly at the level of the intrascleral canal and filtering bleb, is a significant disadvantage of the so-called bleb-dependent antiglaucoma surgery. Taking into account the fact that aqueous humor, which flows evenly through the non-healing fistula under the hermetically sutured conjunctiva, is the forming substrate for the newly created outflow pathways, its composition also plays an important role in the body's response to surgical trauma. A large number of publications reliably demonstrate an increase in the concentration of various biologically active molecules in the aqueous humor of the anterior chamber of glaucoma patients. These are transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukins IL-6 and IL-8, etc., which concentration in cases of unsuccessful outcome of trabeculectomy was significantly increased compared to patients who underwent successful surgeries. In addition, it has been established that an imbalance of various matrix metalloproteinase pools, fibroblast activation, wound infiltration by neutrophils and macrophages, which in turn express a significant amount of pro-inflammatory cytokines and growth factors, contribute to the prolongation of inflammation and fibrosis. An important condition for the removal of aqueous humor from the filtering bleb area is the postoperative activation of conjunctival lymphatic angiogenesis, which suppression may be associated with prolonged inflammation or the active use of cytostatics. This literature review presents the complexities of the pathophysiological mechanisms of postoperative healing and the formation of newly created aqueous humor outflow pathways after antiglaucoma operations. At the same time, the question remains open about the effect of initial changes not only on the tissues of the ocular surface, but also in the aqueous humor of the anterior chamber, as well as the general condition of patients on the outcome of the operation.The purpose of this review is to present modern literature data on the pathophysiological mechanisms of the wound healing process and the features of postoperative healing regulation after antiglaucoma surgery.

Wound healing and Cadmium detoxification in the earthworm Lumbricus terrestris - a potential case for coelomocytes?

Earthworms are affected by physical stress, like injury, and by exposure to xenobiotics, such as the toxic metal cadmium (Cd), which enters the environment mainly through industry and agriculture. The stress response to the single and the combination of both stressors was examined in regenerative and unharmed tissue of Lumbricus terrestris to reveal if the stress response to a natural insult like injury (amputation) interferes with Cd detoxification mechanisms. We characterized the roles of metallothionein 1 (MT1) and MT2 isoforms, heat shock protein 70 as well as immune biomarkers such as the toll-like receptors (TLR) single cysteine cluster TLR and multiple cysteine cluster TLR. The role of the activated transcription factors (ATFs) ATF2, ATF7, and the cAMP responsive element binding protein as putative regulatory intersection as well as a stress-dependent change of the essential trace elements zinc and calcium was analyzed. Phosphorylated AMP activated protein kinase, the cellular energy sensor, was measured to explore the energy demand, while the energy status was determined by detecting carbohydrate and protein levels. Taken together, we were able to show that injury rather than Cd is the driving force that separates the four treatment groups - Control, Cd exposure, Injury, Cd exposure and injury. Interestingly, we found that gene expression differed regarding the tissue section that was analyzed and we hypothesize that this is due to the migration of coelomocytes, earthworm immune cells, that take over a key role in protecting the organism from a variety of environmental challenges. Surprisingly, we discovered a role for MT1 in the response to multiple stressors and an isoform-specific function for the two newly characterized TLRs. In conclusion, we gathered novel information on the relation of innate immunity, wound healing, and Cd detoxification mechanisms in earthworms.

Modified Hongyu Decoction promotes wound healing by activating the VEGF/PI3K/Akt signaling pathway.

Wound healing is a considerable problem for clinicians. Ever greater attention has been paid to the role of Chinese herbal monomers and compounds on wound healing. This study aims to elucidate the wound healing mechanism of Modified Hongyu Decoction (MHD) in vivo and in vitro. MHD wound healing activity in vivo was evaluated using an excision rat model. H and E staining, Masson's staining and immunofluorescence of wound tissue on days 7 and 14 were performed to evaluate the efficacy of MHD on wound healing. Subsequently, human umbilical vein endothelial cells (HUVECs) were used to evaluate wound healing characteristics in vitro. Cell Counting Kit-8 (CCK-8) and scratch assays were conducted to assess the effects of MHD on the proliferation and migration of HUVECs. The involvement of the VEGF/PI3K/Akt signaling pathway was assessed by western blotting. The rats in the MHD group displayed more neovascularization and collagen fibers. Western blotting of wound tissue showed that VEGF, PI3K, p-Akt and p-eNOS expression were significantly increased (p<0.05) in the MHD group. Cell Counting Kit-8 and scratch assays demonstrated that MHD promoted HUVECs proliferation and migration. MHD treatment significantly increased VEGF, PI3K, p-Akt and p-eNOS expression in HUVECs (p<0.05), which was inhibited by LY294002. Both in vivo and in vitro data indicated that MHD promotes wound healing by regulating the VEGF/PI3K/Akt signaling pathway.

The regeneration conferring transcription factor complex ERF115-PAT1 coordinates a wound-induced response in root-knot nematode induced galls.

The establishment of root-knot nematode (RKN; Meloidogyne spp.) induced galls in the plant host roots likely involves a wound-induced regeneration response. Confocal imaging demonstrates physical stress or injury caused by RKN infection during parasitism in the model host Arabidopsis thaliana. The ERF115-PAT1 heterodimeric transcription factor complex plays a recognized role in wound-induced regeneration. ERF115 and PAT1 expression flanks injured gall cells likely driving mechanisms of wound healing, implying a local reactivation of cell division which is also hypothetically involved in gall genesis. Herein, functional investigation revealed that ectopic ERF115 expression resulted in premature induction of galls, and callus formation adjacent to the expanding female RKN was seen upon PAT1 upregulation. Smaller galls and less reproduction were observed in ERF115 and PAT1 knockouts. Investigation of components in the ERF115 network upon overexpression and knockdown by qRT-PCR suggests it contributes to steer gall wound-sensing and subsequent competence for tissue regeneration. High expression of CYCD6;1 was detected in galls, and WIND1 overexpression resulted in similar ERF115OE gall phenotypes, also showing faster gall induction. Along these lines, we show that the ERF115-PAT1 complex likely coordinates stress signalling with tissue healing, keeping the gall functional until maturation and nematode reproduction.

Review of Breathing Aesthetics by Jean-Thomas Tremblay (Duke University Press)

Jean-Thomas Tremblay's Breathing Aesthetics draws our attention to how respiration as a cultural analytic maps the uneven distribution of risk in our contemporary moment. Intervening at the intersection of queer theory and the environmental humanities, Tremblay deciphers an archive of cultural texts that range from CAConrad's ritualized poetry to Ana Mendieta's elemental performance art and Toni Cade Bambara's novel The Salt Eaters. In so doing, they reveal an understanding of how breath registers precarity across race, gender, and disability, while also serving as a mechanism for healing and care. This discerning analysis, combined with a focus on the exchange between body and milieu, makes a case for respiration as a distinctly ecological and embodied relation. Ultimately, Breathing Aesthetics provides crucial insight into how aesthetic expressions of respiratory variations evidence a tension between morbidity and vitality within bodies whose ability to breathe is most endangered.

A viscosity-soluble type biomimetic self-healing cement slurry system

With the development of cementing slurry technology, cementing self-healing has become one of the most effective technologies to prevent and treat oil and gas channeling and improve long-term sealing capacity of cement sheath. To solve the technical problem of annulus oil and gas channeling caused by the long-term sealing failure of cement sheath, this paper researches and develops a kind of viscosity-soluble type biomimetic self-healing cement slurry system from the perspective of chemical biomimetics, based on the technical idea of “prevention before blocking”. Then, the engineering performance of this biomimetic self-healing cement slurry system and the mechanical property of self-healing set cement are evaluated respectively. In addition, the mechanical recovery capacity and permeability reducing rate of the self-healing set cement conserved with methane are evaluated by creating fractures through splitting. Finally, the healing mechanisms of the self-healing cement are analyzed by means of SEM microscopic test and infrared spectrography. And the following research results are obtained. First, the set cement has excellent mechanical property. When the compressive strength decreases by 15 %, the elastic modulus of set cement decreases by 41 %, showing good toughness to play the role of “first prevention”. Second, when meeting hydrocarbon, the damaged set cement is excited to generate a kind of viscosity-soluble type gelatinous ester substance, which re-bonds the skeleton of the set cement. When the self-healing set cement is conserved with methane, its compressive strength recovery rate is up to 94.5 %, bending strength recovery rate is 58.6 %, gas log permeability drops by 99 %, and liquid log permeability drops by 100 %, so as to realize “blocking later”. In conclusion, the viscosity-soluble type biomimetic self-healing cement slurry system can effectively achieve cementing integrity and long-term sealing integrity through self-healing after the damage of cement sheath, which provides a strong technical support for preventing the production safety hazard of sustained casing pressure in oil and gas wells and is beneficial to solve the technical problem of annulus oil and gas channeling caused by long-term sealing failure of cement sheath.

THE RELATIONSHIP BETWEEN RESILIENCE AND BREAST CANCER

Resilience can be changed and modified over time, it is affected by many different situations and difficulties that a person overcomes during life. Resilience is a newer concept, which should be applied to the patient from the beginning of life with cancer. Clinicians should invest more time and effort in creating interventions that enable patients to foster their resilience. The term resilience or the ability to recover refers to the process of overcoming adverse events, including stress, trauma and illness. Considering the ability to recover as a personality trait imposes the assumption that the ability to recover represents a constellation of personal characteristics that enable individuals to adapt to different circumstances they encounter. Resilience as a complex phenomenon changes over time and circumstances. Understanding resilience as a complex, multidimensional and dynamic process is very important for understanding therapeutic mechanisms and healing mechanisms. Psychological factors are the most important factors that contribute to the development of resilience. It is necessary to work on the development of psychosocial interventions that will target the psychological resilience of cancer patients. Breast cancer is the most common malignant disease in women. In women with breast cancer who manage to develop the ability to resist and accept life's crisis, greater resilience and personal growth is created, thereby reducing the negative impact associated with the disease. The aim of this work is to explain the relationship between resilience and breast cancer. Key words: connection, resilience, cancer, breast

New developments in erectile dysfunction treatments: A role for regenerative medicine

Erectile dysfunction is a highly prevalent issue related to the sexual wellness of millions of men worldwide. While conventional therapies have been successful for many, there remains a significant subset of individuals who do not respond adequately or experience undesirable side effects. This article reviews the emerging field of regenerative medicine as a potential breakthrough in the management of ED. Regenerative therapies, especially platelet-rich plasma (PRP) therapy along with stem cell therapy, provide novel approaches to tackling the fundamental causes of ED. By harnessing the body's natural healing mechanisms, these treatments hold promise for restoring erectile function and improving patients' quality of life. This review explores the mechanisms of action, benefits, and current research findings related to regenerative therapies for ED, emphasizing their potential to revolutionize the treatment landscape for this prevalent condition. As ongoing research continues to shed light on their safety and efficacy, regenerative therapies may pave the way for a brighter future in the management of erectile dysfunction.

In Vitro and In Vivo Evaluation of Metformin Hydrochloride Hydrogels Developed with Experimental Design in the Treatment of Burns.

Burns alter the normal skin barrier and affect various host defense processes that help prevent infections. An ineffective repair process can lead to serious damage, such as the onset of an infection or skin loss, which can then harm the surrounding tissues and ultimately the entire organism. This study aims to prepare in situ gels containing metformin hydrochloride, a compound known for its wound healing properties. To achieve this, in situ gels were prepared using three different gelling agents (Poloxamer 407®, Carbopol 934®, and sodium carboxymethyl cellulose (Na-CMC)) and three different concentrations of metformin hydrochloride (4 mg/g, 6 mg/g, and 8 mg/g), which were optimized through experimental design. Metformin concentration and gelling agent type were independent variables, and the loaded amount and the percentage of metformin released after 150 min were chosen as dependent variables in the optimization process. After determining the optimum values of the dependent variables according to the ANOVA analysis results, in vivo studies were conducted with optimized hydrogel formulations. Two groups, each consisting of seven Wistar rats with a burn model, were treated with metformin-poloxamer 407® gels at doses of 4 mg/g and 8 mg/g for 29 days. The results were then compared to untreated and placebo gel groups. Rats treated with in situ Poloxamer 407® hydrogels containing metformin hydrochloride showed a significant reduction in the size of the burned area after 29 days of treatment. However, for a comprehensive understanding of the wound healing mechanism, further studies such as immuno-histochemical and cell culture studies are needed.

Cold atmospheric plasma induces the curing mechanism of diabetic wounds by regulating the oxidative stress mediators iNOS and NO, the pyroptotic mediators NLRP-3, Caspase-1 and IL-1β and the angiogenesis mediators VEGF and Ang-1

It has been demonstrated that cold atmospheric plasma (CAP) accelerates the wound healing process, however the underlying molecular pathways behind this effect remain unclear. Thus, the goal of the proposed investigation is to elucidate the therapeutic advantages of CAP on angiogenesis, pyroptotic, oxidative stress, and inflammatory mediators during the wound-healing mechanisms associated with diabetes. Intraperitoneal administration of streptozotocin (STZ, 60 mg/Kg) of body weight was used to induce type-1 diabetes. Seventy-five male mice were randomized into 3 groups: the control non-diabetic group, the diabetic group that was not treated, and the diabetic group that was treated with CAP. The key mediators of pyroptosis and its impact on the slow healing process of diabetic wounds were examined using histological investigations employing H&E staining, immunohistochemistry, ELISA, and Western blotting analysis. Angiogenesis proteins (VEGF, Ang-1, and HO-1) showed a significant decline in expression concentrations in the diabetic wounds, indicating that diabetic animals' wounds were less likely to heal. Furthermore, compared to the controls, the major mediators of pyroptosis (NLRP-3, IL-1β, and caspase-1), oxidative stress (iNOS and NO), and inflammation (TNF-α and IL-6) have higher expression levels in the diabetic wounds. These factors substantially impede the healing mechanism of diabetic wounds. Interestingly, our results disclosed the therapeutic impacts of CAP treatment in the healing process of diabetic wounds via significantly regulating the expression levels of angiogenesis, pyroptosis, oxidative stress and pro-inflammatory mediators. Our findings demonstrated the curative likelihood of CAP and the underlying mechanisms for enhancing the healing process of diabetic wounds.

Cold Atmospheric Pressure Plasma: A Growing Paradigm in Diabetic Wound Healing—Mechanism and Clinical Significance

Diabetes is one of the most significant causes of death all over the world. This illness, due to abnormal blood glucose levels, leads to impaired wound healing and, as a result, foot ulcers. These ulcers cannot heal quickly in diabetic patients and may finally result in amputation. In recent years, different research has been conducted to heal diabetic foot ulcers: one of them is using cold atmospheric pressure plasma. Nowadays, cold atmospheric pressure plasma is highly regarded in medicine because of its positive effects and lack of side effects. These conditions have caused plasma to be considered a promising technology in medicine and especially diabetic wound healing because studies show that it can heal chronic wounds that are resistant to standard treatments. The positive effects of plasma are due to different reactive species, UV radiation, and electromagnetic fields. This work reviews ongoing cold atmospheric pressure plasma improvements in diabetic wound healing. It shows that plasma can be a promising tool in treating chronic wounds, including ones resulting from diabetes.

Stem cell therapy with CRISPR/Cas9-mediated MALAT1 delivery modulates miR-142 and rescues wound healing in rats with age-associated diabetic foot ulcers

BackgroundDiabetic foot ulcer (DFU) is a serious diabetes complication, significantly impacting the quality of life, particularly in the elderly. Age-associated DFUs pose additional challenges due to impaired healing mechanisms. Our study aims to explore the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a miR-142 sponge in repairing diabetic rat foot ulcer tissue under age-associated diabetes, offering a new theoretical basis and therapeutic target for preventing and treating diabetic vascular disease in the elderly. MethodsUsing qPCR, we analyzed MALAT1 and miR-142 expression in EPCs and hUC-MSCs. Targetscan predicted potential interaction targets for MALAT1 and miR-142, confirmed by dual luciferase reporter gene assay. An age-associated diabetic rat model was established using Streptozotocin (STZ) injection. Hypoxia, apoptosis, and angiogenesis-related proteins were assessed through Western Blot. In vitro, miR-142 inhibition and MALAT1 overexpression promoted foot ulcer healing in diabetic rats. ResultsMALAT1 acted as a miR-142 sponge, downregulated in hUC-MSCs under high glucose, relevant to age-associated diabetic foot ulcers. MiR-142 negatively regulated SIRT1 and Nrf2. In vitro experiments demonstrated potential significance for age-related DFU treatment. ConclusionsMALAT1 in human umbilical cord mesenchymal stem cells expedited foot ulcer healing in diabetic rats, particularly in age-associated diabetes, through miR-142 sponge activity. These findings offer insights for novel therapeutic strategies targeting elderly diabetic foot ulcers, emphasizing exogenous stem cell transplantation's potential in effective DFU treatment for the elderly.

Differential vascular endothelial cell toxicity of established and novel BCR-ABL tyrosine kinase inhibitors.

BCR-ABL tyrosine kinase inhibitors (TKIs) have dramatically improved survival in Philadelphia chromosome-positive leukemias. Newer BCR-ABL TKIs provide superior cancer outcomes but with increased risk of acute arterial thrombosis, which further increases in patients with cardiovascular comorbidities and mitigates survival benefits compared to imatinib. Recent studies implicate endothelial cell (EC) damage in this toxicity by unknown mechanisms with few side-by-side comparisons of multiple TKIs and with no available data on endothelial impact of recently approved TKIs or novels TKIs being tested in clinical trials. To characterize BCR-ABL TKI induced EC dysfunction we exposed primary human umbilical vein ECs in 2D and 3D culture to clinically relevant concentrations of seven BCR-ABL TKIs and quantified their impact on EC scratch-wound healing, viability, inflammation, and permeability mechanisms. Dasatinib, ponatinib, and nilotinib, the TKIs associated with thrombosis in patients, all significantly impaired EC wound healing, survival, and proliferation compared to imatinib, but only dasatinib and ponatinib impaired cell migration and only nilotinib enhanced EC necrosis. Dasatinib and ponatinib increased leukocyte adhesion to ECs with upregulation of adhesion molecule expression in ECs (ICAM1, VCAM1, and P-selectin) and leukocytes (PSGL1). Dasatinib increased permeability and impaired cell junctional integrity in human engineered microvessels, consistent with its unique association with pleural effusions. Of the new agents, bafetinib decreased EC viability and increased microvessel permeability while asciminib and radotinib did not impact any EC function tested. In summary, the vasculotoxic TKIs (dasatinib, ponatinib, nilotinib) cause EC toxicity but with mechanistic differences, supporting the potential need for drug-specific vasculoprotective strategies. Asciminib and radotinib do not induce EC toxicity at clinically relevant concentrations suggesting a better safety profile.

Choroidal Vessel and Stromal Volumetric Analysis After Photodynamic Therapy or Focal Laser for Central Serous Chorioretinopathy.

To utilize volumetric analysis to quantify volumetric changes in choroidal vessels and stroma after photodynamic therapy (PDT) and focal laser photocoagulation (PC) for central serous chorioretinopathy (CSCR). This retrospective, comparative study included 58 eyes (58 patients) with CSCR (PC, 33 eyes; PDT, 25 eyes) followed up with swept-source optical coherence tomography at 3 months after treatment. Three-dimensional (3D) choroidal vessel and stromal volumes in each area of the central 1.5-mm-diameter circle, the torus-shaped area with 6-mm-diameter circle excluding the area of the central 1.5-mm-diameter circle, and the treated area of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid centered at the fovea were analyzed using a deep learning-based method. Changes in volume at baseline and 1 and 3 months after treatment were compared. The mean patient age was 49.3 ± 10.5 years. In the central 1.5-mm-diameter circle, the mean vessel and stromal volume rates significantly decreased after the treatment in both the PDT and PC groups (P = 0.00029 and P = 0.0014, respectively), and significant differences between the PDT and PC groups of continuous variables within times were observed in both volumes (P = 0.024 and P = 0.037, respectively). In the torus-shaped area and treated area, the PDT and PC groups both showed similar decreases in vessel and stromal volume over time. In the 3D optical coherence tomography volumetric analysis, both PDT and focal PC reduced choroid vessel volume in eyes with CSCR. This new finding is useful in elucidating the pathogenesis and healing mechanisms of CSCR.

Controllably Self-Assembled Antibacterial Nanofibrils Based on Insect Cuticle Protein for Infectious Wound Healing.

Developing self-assembled biomedical materials based on insect proteins is highly desirable due to their advantages of green, rich, and sustainable characters as well as excellent biocompatibility, which has been rarely explored. Herein, salt-induced controllable self-assembly, antibacterial performance, and infectious wound healing performance of an insect cuticle protein (OfCPH-2) originating from the Ostrinia furnacalis larva head capsule are investigated. Interestingly, the addition of salts could trigger the formation of beaded nanofibrils with uniform diameter, whose length highly depends on the salt concentration. Surprisingly, the OfCPH-2 nanofibrils not only could form functional films with broad-spectrum antibacterial abilities but also could promote infectious wound healing. More importantly, a possible wound healing mechanism was proposed, and it is the strong abilities of OfCPH-2 nanofibrils in promoting vascular formation and antibacterial activity that facilitate the process of infectious wound healing. Our exciting findings put forward instructive thoughts for developing innovative bioinspired materials based on insect proteins for wound healing and related biomedical fields.

The Role of Collagen in The Mechanisms of Chronic Wound Healing for Diabetic Foot Syndrome

The review of the world literature, is devoted to the role of collagen in the process of wound healing. The problems of epidemiology of chronic wounds and ulcers of various genesis, physiology and pathophysiology of wound healing phases are considered. The pathogenetic role of different types of collagen, as well as the mechanisms of collagen, macrophage, fibroblasts, matrix metalloproteinases and other cytokines in healing ulcers are discussed. The prospects of development and use of medical products and preparations based on collagen in the treatment of patients with chronic wounds and ulcers are shown. The results of clinical studies on the effectiveness of collagen with preserved (native) and unsaved (fractionated) structure are presented. The advantages of using native collagen in the treatment of diabetic foot syndrome are demonstrated

Hypoxia endothelial cells-derived exosomes facilitate diabetic wound healing through improving endothelial cell function and promoting M2 macrophages polarization

It is imperative to develop and implement newer, more effective strategies to address refractory diabetic wounds. As of now, there is currently no optimal solution for these wounds. Hypoxic human umbilical vein endothelial cells (HUVECs)-derived exosomes have been postulated to promote diabetic wound healing, however, its effect and molecular mechanism need further study. In this study, we aimed to investigate whether hypoxic exosomes enhance wound healing in diabetics. Based on our high-throughput sequencing, differentially expressed lncRNAs (including 64 upregulated lncRNAs and 94 downregulated lncRNAs) were found in hypoxic exosomes compared to normoxic exosomes. Interestingly, lncHAR1B was one of the prominently upregulated lncRNAs in hypoxic exosomes, showing a notable correlation with diabetic wound healing. More specifically, hypoxic exosomes were transmitted to surrounding cells, which resulted in a significant increase in lncHAR1B level, thereby relieving the dysfunction of endothelial cells and promoting the switch from M1 to M2 macrophages under high glucose conditions. Mechanistically, lncHAR1B directly interacted with the transcription factor basic helix-loop-helix family member e23 (BHLHE23), which subsequently led to its binding to the KLF transcription factor 4 (KLF4) and promoted KLF4 expression. In our in vivo experiments, the use of hypoxic exosomes-loaded HGM-QCS hydrogels (Gel-H-Exos) resulted in rapid wound healing compared to that of normoxic exosomes-loaded HGM-QCS hydrogels (Gel-N-Exos) and diabetic groups. Consequently, our study provides potentially novel therapeutic approaches aimed at accelerating wound healing and developing a practical exosomes delivery platform.

Myocardial fibrosis activity following ST-segment elevation myocardial infarction

Abstract Background Myocardial fibrosis following myocardial infarction (MI) is a key healing mechanism and involves widespread fibroblast activation. Once activated, fibroblasts express fibroblast activation protein (FAP) (1). Hybrid positron emission tomography (PET) imaging of radiolabelled fibroblast activation protein inhibitor (FAPI) fused with cardiovascular magnetic resonance (68Ga-FAPI PET/MR) is an emerging method for assessing myocardial fibrosis activity that may provide additional insights into the recovery of the heart following MI. Methods Forty patients with acute (&amp;lt;4 weeks), 19 with recent (12 weeks), and 19 with prior established ST-segment elevation MI (&amp;gt;12 months), and 20 healthy volunteer participants underwent 68Ga-FAPI PET/MR. Participants were imaged 30 min after administration of 100-200 MBq 68Ga-FAPI-04. Image analysis was performed using FusionQuant (Cedars Sinai, Los Angeles, California). 68Ga-FAPI uptake was quantified by maximum standardised uptake value (SUVmax) and tissue-to-background ratio (TBRmax) correcting for blood-pool activity in the left ventricle. Comparisons between were assessed with one-way ANOVA with Tukey-Kramer post-hoc testing where significant differences were detected. A 2-sided p-value of &amp;lt;0.05 denoted statistical significance. Results Participants were predominantly middle-aged men with similar sized infarcts (peak plasma cardiac troponin concentrations and post-MI left ventricular ejection fraction) (Table). Blood pool tracer activity was also similar between groups. Focal myocardial 68Ga-FAPI uptake localised to areas of the infarct and peri-infarct zones on magnetic resonance late gadolinium enhancement imaging (Figure). Both myocardial SUVmax and TBRmax varied between infarcts of different ages, being highest in acute (TBRmax 4.1±1.2) and lowest in those with prior established MI (2.1±0.7, Table and Figure). Conclusions Fibrosis activity is greatest in the immediate aftermath of acute MI with a step-wise reduction in the weeks and years that follow. Fibrosis activity continues for many months and years after acute infarction.FigureTable

Ozonated saline intradermal injection: promising therapy for accelerated cutaneous wound healing in diabetic rats.

The use of ozonized water is gaining importance in medicine due to its effects on hyperglycemia and wound healing mechanisms. This experiment was conducted to assess the impacts of intradermal administration of ozonated water on acute skin wound healing in a diabetic rat model. Sixty-four adult male Wistar rats were randomly divided into two groups: an ozonated water group (O3W) and a control group (CG). Experimental diabetes was chemically induced in the rats by the intraperitoneal administration of 60 mg/kg streptozotocin. One week later, full-thickness skin surgical wounds (1 cm2) were created between the two shoulders of the rats under general anesthesia. The wounds were then daily irrigated with normal saline (CG) or intradermally injected with 1 mL of ozonated water at 10 mg/L O3W. Wound healing was evaluated through macroscopic analysis, measuring wound size, diameter, and percentage of contraction rate before wounding and at 3, 7, 9, 12, 14, 18, 21, 24, and 28 days post-wounding. On days 7, 14, 21, and 28 after induction of the wounds, the body weights and blood glucose levels of rats (8 per group) were measured before the rats were euthanized. Moreover, the morphological structure of the tissue, vascular endothelial and transforming growth factor (VEGF and TGF) affinity and gene expression were examined. The O3W group had significantly lower blood glucose levels and wound size and gained body weight. Additionally, epithelial vascularization, stromal edema, TGF, and VEGF gene expression significantly improved in the O3W group. Therefore, ozonated water has the potential to enhance and promote cutaneous wound healing in diabetic rats.