Search Results (27)

Vital pulp therapy with calcium hydroxide or mineral trioxide aggregate (MTA) rapidly induces dystrophic calcification and promotes the accumulation of two members of small integrin-binding ligand N-linked glycoproteins: osteopontin (OPN) and dentin matrix protein-1 (DMP1). However, the precise relationship between these initial events and their roles in reparative dentinogenesis remain unclear. This study aimed to clarify the relationship between dystrophic calcification, OPN and DMP1 accumulation, and reparative dentin formation. Pulpotomy was performed on rat molars using MTA or zirconium oxide (ZrO₂). ZrO₂ was used as a control to assess pulp healing in the absence of dystrophic calcification. Pulpal responses were evaluated from 3 h to 7 days postoperatively via elemental mapping, micro-Raman spectroscopy, and histological staining. In the MTA-treated group, a calcium-rich dystrophic calcification zone containing calcite and hydroxyapatite was observed at 3 h after treatment; OPN and DMP1 accumulated under the dystrophic calcification zone by day 3; reparative dentin formed below the region of OPN and DMP1 accumulation by day 7. In contrast, these reactions did not occur in the ZrO₂-treated group. These results suggest that dystrophic calcification serves as a key trigger for OPN and DMP1 accumulation and plays a pivotal role in reparative dentinogenesis. Full article

The structural and electrical properties of double perovskite compounds SrLaFe_1−xMn_xTiO_6−δ (x = 0, 0.33, 0.67, and 1.0) were studied using X-ray diffraction (XRD) and dielectric impedance measurements. The reparation of perovskite compounds was successfully achieved through the precursor solid-state reaction in air at 1250 °C. The purity phase and crystal structures of perovskite compounds were determined by means of the standard Rietveld refinement method using the FullProf suite. The best fitting results showed that SrLaFeTiO_6−δ was orthorhombic with space group Pnma, and both SrLaFe_0.67Mn_0.33TiO_6−δ and SrLaFe_0.33Mn_0.67TiO_6−δ were cubic structures with space group Fm3m, while SrLaMnTiO_6−δ was tetragonal with a I/4m space group. The charge density maps obtained for these structures indicated that the compounds show an ionic and mixed ionic–electronic conduction. The dielectric impedance measurements were carried out in the range of 20 Hz to 1 MHz, and the analysis showed that there is more than one relaxation mechanism of Debye type. Doping with Mn was found to reduce the dielectric impedance of the samples, and the major contribution to the dielectric impedance was established to change from a capacitive for SrLaFeTiO_6−δ to a resistive for SrLaMnTiO_6−δ. The fall in values of electrical resistance may be related to the possible occurrence of the double exchange (DEX) mechanism among the Mn ions, provided there is oxygen deficiency in the samples. DC-resistivity measurements revealed that SrLaFeTiO_6−δ was an insulator while SrLaMnTiO_6−δ was showing a semiconductor–metallic transition at ~250 K, which is in support of the DEX interaction. The dielectric impedance of SrLaFe_0.67Mn_0.33TiO_6−δ was found to be similar to that of (La,Sr)(Co,Fe)O_3-δ, the mixed ionic–electronic conductor (MIEC) model. The occurrence of a mixed ionic–electronic state in these compounds may qualify them to be used in free lead solar cells and energy storage technology. Full article

Prolonged sun exposure disrupts the skin’s structural, mechanical, and functional properties, accelerating aging and contributing to skin disorders. To counteract these effects, we developed a formulation containing potent antioxidant, anti-inflammatory, moisturizing, and reparative ingredients to protect and repair sun-damaged skin. The efficacy of the formulation was evaluated through in vitro, ex vivo, and in vivo studies. Results demonstrated that the formulation reduced oxidative stress and suppressed the production of pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), as well as lactate dehydrogenase (LDH) secretion, in a photodamaged skin model, nearly reaching levels observed in undamaged skin. It also restored collagen levels, improving structural integrity. In vivo, no adverse reactions were observed when used for 28 or 56 days. The formulation improved skin hydration by up to 46%, reduced transepidermal water loss by 20%, increased luminosity by 70%, and reduced hyperpigmented spots by 14%. It also enhanced skin firmness and elasticity by 30% and reduced wrinkle volume and density by up to 53% and 19%, respectively. These findings demonstrate that the formulation’s active ingredients effectively target the pathways altered by UV exposure, offering considerable potential for preventing and reversing sun-induced skin damage while improving both the appearance and functionality of the skin. Full article

Disturbance or insufficiency of the tear film challenges the regulatory systems of the ocular surfaces. The reaction of the surfaces includes temporary mechanisms engaged in the preservation of homeostasis. However, strong or persisting challenges can lead to the potential exhaustion of the coping capacity. This again activates the vicious circle with chronic inflammation and autocatalytic deterioration. Hence, the factors challenging the homeostasis should be addressed in time. Amongst them are a varying osmolarity, constant presence of small lesions at the epithelium, acidification, attrition with mechanical irritation, and onset of pain and discomfort. Each of them and, especially when occurring simultaneously, impose stress on the coping mechanisms and lead to a stress response. Many stressors can culminate, leading to an exhaustion of the coping capacity, outrunning normal resilience. Reaching the limits of stress tolerance leads to the manifestation of a lubrication deficiency as the disease we refer to as dry eye disease (DED). To postpone its manifestation, the avoidance or amelioration of stress factors is one key option. In DED, this is the target of lubrication therapy, substituting the missing tear film or its components. The latter options include the management of secondary sequelae such as the inflammation and activation of reparative cascades. Preventive measures include the enhancement in resilience, recovery velocity, and recovery potential. The capacity to handle the external load factors is the key issue. The aim is to guard homeostasis and to prevent intercellular stress responses from being launched, triggering and invigorating the vicious circle. Considering the dilemma of the surface to have to cope with increased time of exposure to stress, with simultaneously decreasing time for cellular recovery, it illustrates the importance of the vicious circle as a hub for ocular surface stress. The resulting imbalance triggers a continuous deterioration of the ocular surface condition. After an initial phase of the reaction and adaption of the ocular surface to the surrounding challenges, the normal coping capacity will be exhausted. This is the time when the integrated stress response (ISR), a protector for cellular survival, will inevitably be activated, and cellular changes such as altered translation and ribosome pausing are initiated. Once activated, this will slow down any recovery, in a phase where apoptosis is imminent. Premature senescence of cells may also occur. The process of prematurization due to permanent stress exposures contributes to the risk for constant deterioration. The illustrated flow of events in the development of DED outlines that the ability to cope, and to recover, has limited resources in the cells at the ocular surface. The reduction in and amelioration of stress hence should be one of the key targets of therapy and begin early. Here, lubrication optimization as well as causal treatment such as the correction of anatomical anomalies (leading to anatomical dry eye) should be a prime intent of any therapy. The features of cellular stress as a key hub for the vicious circle will be outlined and discussed. Full article

Fracture healing is a complex series of events that requires a local inflammatory reaction to initiate the reparative process. This inflammatory reaction is important for stimulating the migration and proliferation of mesenchymal progenitor cells from the periosteum and surrounding tissues to form the cartilaginous and bony calluses. The proinflammatory cytokine interleukin (IL)-17 family has gained attention for its potential regenerative effects; however, the requirement of IL-17 signaling within mesenchymal progenitor cells for normal secondary fracture healing remains unknown. The conditional knockout of IL-17 receptor a (Il17ra) in mesenchymal progenitor cells was achieved by crossing Il17ra^F/F mice with Prx1-cre mice to generate Prx1-cre; Il17ra^F/F mice. At 3 months of age, mice underwent experimental unilateral mid-diaphyseal femoral fractures and healing was assessed by micro-computed tomography (µCT) and histomorphometric analyses. The effects of IL-17RA signaling on the osteogenic differentiation of fracture-activated periosteal cells was investigated in vitro. Examination of the intact skeleton revealed that the conditional knockout of Il17ra decreased the femoral cortical porosity but did not affect any femoral trabecular microarchitectural indices. After unilateral femoral fractures, Il17ra conditional knockout impacted the cartilage and bone composition of the fracture callus that was most evident early in the healing process (day 7 and 14 post-fracture). Furthermore, the in vitro treatment of fracture-activated periosteal cells with IL-17A inhibited osteogenesis. This study suggests that IL-17RA signaling within Prx1+ mesenchymal progenitor cells can influence the early stages of endochondral ossification during fracture healing. Full article

Mobilization of CTCs after various types of therapy, such as radiation therapy, has been reported, but systematic study of CTCs after chemotherapy remained quite limited. In this study, we sequentially examined CTC numbers after single-dose and repetitive-dose chemotherapy, including FORFIRINOX (FFX) and Gemcitabine and nab-Paclitaxel (GnP) using two pancreatic cancer xenograft models. CTC was detected by the immunocytology-based microfluidic platform. We further examined the dynamic change in the histology of primary tumor tissues during chemotherapy. We confirmed a transient increase in CTCs 1–2 weeks after single-dose and repetitive-dose of FFX/GnP chemotherapy. Histological examination of the primary tumors revealed that the peak period of CTC at 1–2 weeks after chemotherapy corresponded to the maximal destructive phase consisting of cell cycle arrest, apoptosis of tumor cells, and blood vessel destruction without secondary reparative tissue reactions and regeneration of tumor cells. These findings indicate that mobilization of CTCs early after chemotherapy is mediated by the shedding of degenerated tumor cells into the disrupted blood vessels driven by the pure destructive histological changes in primary tumor tissues. These results suggest that sequential CTC monitoring during chemotherapy can be a useful liquid biopsy diagnostic tool to predict tumor chemosensitivity and resistance in preclinical and clinical settings. Full article

Ursula Le Guin’s The Word for World is Forest emerged as a reaction to the Vietnam War, which ravaged human and nonhuman lifeworlds. Le Guin offers two competing discursive systems through which to interpret human and nonhuman alterity—Terran industrial capitalism, grounded in physical and symbolic violence, and Athshean ecosocialism, rooted in an ethics of non-violence and forest-centred nominalism. Le Guin appears to suggest that both “readings” of Athshea are locked in an intractable, adversarial logic, typical of the “paranoid” reading practices that Eve Sedgwick would theorise twenty-five years later. In its sensitivity to the spectrum of negative affect covering anticipatory anxiety about forestalling pain, symmetrical suspicion, and fear of humiliation, the novella offers an uncanny prefiguration of paranoid practices. Le Guin suggests that the way out of the paranoid clash of civilisations can be found in two “reparative” reading stances—Selver’s reinterpretation and rearrangement of components of the oppressor’s culture into new, unexpected wholes (hermeneutic reassemblage) and the alien observers’ valorisation of disinterested curiosity over action as a categorical imperative (cerebral equivocity). Le Guin thus seems to offer a reparative poetics avant la lettre. Full article

Incisional hernia is a frequent complication after abdominal surgery. A previous study on rats evaluated the use of a Pectin–Honey Hydrogel (PHH)-coated polypropylene (PP) mesh for the healing of acute hernias. However, there are no studies investigating the use of PHH in association with PP mesh in chronic contaminated hernia. The aims of this study are to assess the effectiveness of PHH in promoting abdominal hernia repaired with PP mesh and in counteracting infection. Twenty Sprague Dawley male rats were enrolled and a full thickness defect was made in the abdominal wall. The defect was repaired after 28 days using a PP mesh, and a culture medium (Tryptone Soy Broth, Oxoid) was spread onto the mesh to contaminate wounds in both groups. The rats were randomly assigned to a treated or untreated group. In the treated group, a PHH was applied on the mesh before skin closure. At euthanasia—14 days after surgery—macroscopical, microbiological and histopathological evaluations were performed, with a score attributed for signs of inflammation. An immunohistochemical investigation against COX-2 was also performed. Adhesions were more severe (p = 0.0014) and extended (p = 0.0021) in the untreated group. Bacteriological results were not significantly different between groups. Both groups showed moderate to severe values (score > 2) in terms of reparative and inflammatory reactions at histopathological levels. The use of PHH in association with PP mesh could reduce adhesion formation, extension and severity compared to PP mesh alone. No differences in terms of wound healing, contamination and grade of inflammation were reported between groups. Full article

Introduction: The effect of high temperatures on the properties of endodontic sealers during warm compaction of gutta-percha may be a matter of concern. This study aimed to evaluate the effect of heat on the biocompatibility and bioactivity of EndoSequence BC Sealer HiFlow (ESHF; Brasseler, Savannah, GA, USA) and AH Plus (AHPS; Dentsply, De Trey, Konstanz, Germany) when implanted into the bone tissue of rat tibias. Methods: Medical-grade silicone tubes containing freshly prepared ESHF or AHPS were heated to 100 °C and then cooled down to 65 °C before being implanted in the tibias of 24 Wistar rats. The outer walls of the tubes served as controls. After 10, 30 and 90 days, the animals were euthanized and the implants and their surrounding tissues were dissected, fixed in formalin, and processed for microscopic evaluation. Results: After 10 days postoperatively, a severe inflammatory reaction without reactionary bone formation was observed in contact with ESHF and AHPS. The severity of the reaction had decreased at the 30-day observation period for both sealers but only ESHF samples showed new bone formation adjacent to the sealer. After 90 days, no inflammatory cells were found in contact with ESHF, while a thin fibrous tissue capsule and complete bone reparation of the surrounding areas were observed in contact with the material. For AH Plus, a fibrous connective tissue containing scarce remaining inflammatory cells could be observed in most of the samples, however, in the absence of new bone formation. No significant differences (p > 0.05) between ESHF and AHPS were found at the 10-day observation period. At the 30 and 90-day, significant differences (p < 0.05) between both materials were observed. The reaction to the controls showed significant differences with ESHF and AHPS for all experimental periods. Significant differences (p < 0.05) for the total effect of time were also found between both sealers (p < 0.05). Conclusions: At the end of the experiment, heated ESHF reacted as a biocompatible/bioactive material and stimulated continued development of new healthy bone. Although AHPS was tolerated well by the surrounding tissues, the sealer did not promote new reparative bone formation. Full article

We are not entirely able to understand, assess, and modulate the functioning of the immune system in clinical situations that lead to a systemic inflammatory response. In the search for diagnostic and treatment strategies (which are still far from perfect), it became very important to study the pathogenesis and participation of endogenous inflammation mediators. This study attempts to more precisely establish the role of neutrophils in individual phenomena occurring during an inflammatory and anti-inflammatory reaction, taking into account their cidal, immunoregulatory, and reparative abilities. Pro- and anticoagulatory properties of endothelium in systemic inflammatory response syndrome (SIRS) are emphasised, along with the resulting clinical implications (the application of immunotherapy using mesenchymal stem/stromal cells (MSCs) or IL-6 antagonists in sepsis and COVID-19 treatment, among others). Special attention is paid to reactive oxygen species (ROS), produced by neutrophils activated during “respiratory burst” in the course of SIRS; the protective and pathogenic role of these endogenous mediators is highlighted. Moreover, clinically useful biomarkers of SIRS (neutrophil extracellular traps, cell-free DNA, DAMP, TREMs, NGAL, miRNA, selected cytokines, ROS, and recognised markers of endothelial damage from the group of adhesins by means of immunohistochemical techniques) related to the neutrophils are presented, and their role in the diagnosing and forecasting of sepsis, burn disease, and COVID-19 is emphasised. Finally, examples of immunomodulation of sepsis and antioxidative thermal injury therapy are presented. Full article

Control over endogenous reparative mechanisms is the future of regenerative medicine. The rabbit ear defect is a rare model which allows the observation of the epimorphic regeneration of elastic cartilage. However, the mechanisms of phenotypical restoration of this highly differentiated tissue have not been studied. We modelled circular ear defects of different sizes (4, 6, and 8 mm in diameter) in 12 laboratory rabbits, and observed them during 30, 60, 90, and 120 day periods. Excised tissues were processed and analyzed by standard histological methods and special histochemical reactions for senescence associated-β-galactosidase and lectin markers. We demonstrated that larger defects caused significant elevation of senescence associated-β-galactosidase in chondrocytes. The fullness of epimorphic regeneration of elastic cartilage depended on the activation of cellular senescence and synthesis of elastic fibers. Further investigation into the role of cells with senescence-associated secretory phenotype in damaged tissues can present new targets for controlled tissue regeneration. Full article

There are well-established links between acute inflammation and successful tissue repair across evolution. Innate immune reactions contribute significantly to pathogen clearance and activation of subsequent reparative events. A network of molecular and cellular regulators supports antimicrobial and tissue repair functions throughout the healing process. A delicate balance must be achieved between protection and the potential for collateral tissue damage associated with overt inflammation. In this review, we summarize the contributions of key cellular and molecular components to the acute inflammatory process and the effective and timely transition toward activation of tissue repair mechanisms. We further discuss how the disruption of inflammatory responses ultimately results in chronic non-healing injuries. Full article

In recent years, the application of mesenchymal stem cells (MSCs) has been recognized as a promising method for treatment of different diseases associated with inflammation and sclerosis, which include nephrotuberculosis. The aim of our study is to investigate the effectiveness of MSCs in the complex therapy of experimental rabbit kidney tuberculosis and to evaluate the effect of cell therapy on the reparative processes. Methods: To simulate kidney tuberculosis, a suspension of the standard strain Mycobacterium tuberculosis H37Rv (10⁶ CFU) was used, which was injected into the cortical layer of the lower pole parenchyma of the left kidney under ultrasound control in rabbits. Anti-tuberculosis therapy (aTBT) was started on the 18th day after infection. MSCs (5 × 10⁷ cells) were transplanted intravenously after the start of aTBT. Results: 2.5 months after infection, all animals showed renal failure. Conducted aTBT significantly reduced the level of albumin, ceruloplasmin, elastase and the severity of disorders in the proteinase/inhibitor system and increased the productive nature of inflammation. A month after MSC transplantation, the level of inflammatory reaction activity proteins decreased, the area of specific and destructive inflammation in kidneys decreased and the formation of mature connective tissue was noted, which indicates the reparative reaction activation. Full article

The C-C chemokine motif ligand 5 (CCL5) and its receptors have recently been thought to be substantially involved in the development of obesity-associated adipose tissue inflammation and insulin resistance. However, the respective contributions of tissue-derived and myeloid-derived CCL5 to the etiology of obesity-induced adipose tissue inflammation and insulin resistance, and the involvement of monocytic myeloid-derived suppressor cells (MDSCs), remain unclear. This study used CCL5-knockout mice combined with bone marrow transplantation (BMT) and mice with local injections of shCCL5/shCCR5 or CCL5/CCR5 lentivirus into bilateral epididymal white adipose tissue (eWAT). CCL5 gene deletion significantly ameliorated HFD-induced inflammatory reactions in eWAT and protected against the development of obesity and insulin resistance. In addition, tissue (non-hematopoietic) deletion of CCL5 using the BMT method not only ameliorated adipose tissue inflammation by suppressing pro-inflammatory M-MDSC (CD11b⁺Ly6G⁻Ly6C^hi) accumulation and skewing local M1 macrophage polarization, but also recruited reparative M-MDSCs (CD11b⁺Ly6G⁻Ly6C^low) and M2 macrophages to the eWAT of HFD-induced obese mice, as shown by flow cytometry. Furthermore, modulation of tissue-derived CCL5/CCR5 expression by local injection of shCCL5/shCCR5 or CCL5/CCR5 lentivirus substantially impacted the distribution of pro-inflammatory and reparative M-MDSCs as well as macrophage polarization in bilateral eWAT. These findings suggest that an obesity-induced increase in adipose tissue CCL5-mediated signaling is crucial in the recruitment of tissue M-MDSCs and their trans-differentiation to tissue pro-inflammatory macrophages, resulting in adipose tissue inflammation and insulin resistance. Full article

Background: Titanium trabecular cages (TTCs) are emerging implants designed to achieve immediate and long-term spinal fixation with early osseointegration. However, a clear radiological and clinical demonstration of their efficacy has not yet been obtained. The purpose of this study was to evaluate the reactive bone activity of adjacent plates after insertion of custom-made titanium trabecular cages for the lumbar interbody with positron emission tomography (PET)/computed tomography (CT) 18F sodium fluoride (18F-NaF). Methods: This was an observational clinical study that included patients who underwent surgery for degenerative disease with lumbar interbody fusion performed with custom-made TTCs. Data related to the metabolic-reparative reaction following the surgery and its relationship with clinical follow-up from PET/CT performed at different weeks were evaluated. PET/CTs provided reliable data, such as areas showing abnormally high increases in uptake using a volumetric region of interest (VOI) comprising the upper (UP) and lower (DOWN) limits of the cage. Results: A total of 15 patients was selected for PET examination. Timing of PET/CTs ranged from one week to a maximum of 100 weeks after surgery. The analysis showed a negative correlation between the variables SUVmaxDOWN/time (r = −0.48, p = 0.04), ratio-DOWN/time (r = −0.53, p = 0.02), and ratio-MEAN/time (r = −0.5, p = 0.03). Shapiro−Wilk normality tests showed significant results for the variables ratio-DOWN (p = 0.002), ratio-UP (0.013), and ratio-MEAN (0.002). Conclusions: 18F-NaF PET/CT has proven to be a reliable tool for investigating the metabolic-reparative reaction following implantation of TTCs, demonstrating radiologically how this type of cage can induce reparative osteoblastic activity at the level of the vertebral endplate surface. This study further confirms how electron-beam melting (EBM)-molded titanium trabecular cages represent a promising material for reducing hardware complication rates and promoting fusion. Full article