Fibroblast Proliferation Research Articles

Naltrexone accelerated oral traumatic ulcer healing and downregulated TLR-4/NF-kB pathway in Wistar rats

ObjectiveTo assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DesignWistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily. ResultsThe 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01). ConclusionNaltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats.

Effects of Non-Thermal Dielectric Barrier Discharge Plasma on Human Fibroblasts: A Narrative Review.

Objectives: Fibroblasts are among the most critical connective tissue cells in almost all tissues and organs. Enhancement of fibroblast differentiation, proliferation, and morphogenesis is of paramount importance in tissue regeneration and wound healing. The non-thermal dielectric barrier discharge (DBD) plasma technology has recently gained interest due to its extensive applications and multiple biological effects. This review article outlines the applications of DBD plasma in dentistry, and its biological effects on human fibroblasts. Materials and Methods: Relevant keywords were searched in PubMed, Ovid, and Google Scholar online databases. The search strategy resulted in selection of 7 studies according to the eligibility criteria. Results: Most studies reported increased cell proliferation and viability after the application of DBD plasma. Four studies that focused on the development of adhesion-related appendages examined the morphology of fibroblast cells, including the creation of vinculin, protrusion, and actin cytoskeleton. Expression of cyclin D1/P27 genes and genes associated with adhesion and cell attachments was also reported in two studies. Conclusion: This narrative review discussed the effects of DBD plasma technology on proliferation and behavior of human fibroblasts, and reviewed the available articles in this regard. More in vivo studies are required to understand the exact effects of this emerging technology on human mesenchymal tissues.

152 Three-Dimensional Printing Bespoke Polycaprolactone Tracheal Splint for Treatment of Tracheomalacia

Abstract Aim Tracheomalacia can be a fatal airway disease with limited treatment options. Three-dimensional (3D) printing has led to various patient-specific tracheal stents and splints. However, these are limited by mismatched stiffness and resulting granulation tissue formation and fibrosis. We aimed to develop a non-toxic and biodegradable polycaprolactone expandable tracheal splint by 3D printing. By fine-tuning mechanical properties, we hypothesised that the splint would match the native trachea and accommodate tracheal growth in tracheomalacia patients. Method We designed splints consisting of concave topological patterns with varying angles and aspect ratios. Fabrication occurred using polycaprolactone filaments in a 3D fuse deposition modelling printer. Uniaxial tensile studies were performed on splints to assess Young’s Modulus, Toughness, Ultimate strain, Strength, and Poisson ratio. Splints displaying optimal mechanical properties were tested for human lung fibroblast cell viability, proliferation, and morphology. Results On a mechanical testing rig, uniaxial tensile studies confirmed that splint designs with smaller angles and negative Poisson ratios of up to strains of 25%, better mimicked mechanical properties of native human trachea, accommodating tracheal growth. In vitro studies using these tracheal splints demonstrated successful human lung cell proliferation with low cell toxicity. Conclusions This study characterised 3D printed bespoke tracheal splints with various 2D structures, showing mechanical properties that match the native trachea. However, in vivo studies investigating cellular interactions on our splint must be performed to further evaluate the ability for endogenous tissue formation.

Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches.

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin's and non-Hodgkin's lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury.

Fibroblasts activation by embryonic signal switching: A novel mechanism of placental growth factor-induced cardiac remodeling

IntroductionCardiac remodeling is defined as cellular interstitial changes that lead dysfunction of the heart after injury. Placental growth factor (PlGF), a member of the VEGF family, has been reported to regulate cardiac hypertrophy in hemodynamic state.We therefore analyze the function of PlGF during cardiac remodeling using cardiac cells and fibroblasts, under Angiotensin II (AngII) stimulation. MethodsPlGF overexpressed mouse embryonic fibroblasts derived from C57BL/6 mice, were made by deficient retrovirus vector, designated as C57/PlGF. Only retrovirus vector introduced C57 cells (C57/EV) were used as control.After AngII stimulation, wound scratching assay and MTT proliferation assay with or without p38 MAPK inhibitor, SB205580 were performed in retrovirally-introduced C57 cells. Reactive oxygen species (ROS) production, NF-kB activation, IL-6 and TNF-α production were also measured. Then we assessed AngII-induced cell proliferation of mouse cardiac fibroblasts (CFs) and rat primary cardiomyocytes incubating with C57/PlGF conditioned-medium. ResultsThe PlGF production in C57/PlGF were confirmed by ELISA (1093.48 ± 3.5 pg/ml, ±SE). AngII-induced cell migration, proliferation and H2O2 production were increased in C57/PlGF compared with C57/EV. SB205580 inhibited the AngII-induced cell proliferation in C57/PlGF. In C57/PlGF cells, NF-kB activation was higher, followed by up-regulation of IL-6 and TNF-α production. CFs and cardiomyocytes proliferation increased when stimulated with C57/PlGF conditioned-medium. DiscussionThe activation of fibroblast is stimulated by PlGF signaling via p38 MAPK/NF-kB pathway accompanied by elevation of ROS and inflammatory response. Furthermore, these signals stimulate the activation of CFs and cardiomyocytes, indicating that high circulating level of PlGF have a potential to regulate cardiac remodeling.

The role of glycerol in manufacturing freeze-dried chitosan and cellulose foams for mechanically stable scaffolds in skin tissue engineering

Various strategies have extensively explored enhancing the physical and biological properties of chitosan and cellulose scaffolds for skin tissue engineering. This study presents a straightforward method involving the addition of glycerol into highly porous structures of two polysaccharide complexes: chitosan/carboxymethyl cellulose (Chit/CMC) and chitosan/oxidized cellulose (Chit/OC); during a one-step freeze-drying process. Adding glycerol, especially to Chit/CMC, significantly increased stability, prevented degradation, and improved mechanical strength by nearly 50%. Importantly, after 21 days of incubation in enzymatic medium Chit/CMC scaffold has almost completely decomposed, while foams reinforced with glycerol exhibited only 40% mass loss. It is possible due to differences in multivalent cations and polymer chain contraction, resulting in varied hydrogen bonding and, consequently, distinct physicochemical outcomes. Additionally, the scaffolds with glycerol improved the cellular activities resulting in over 40% higher proliferation of fibroblast after 21 days of incubation. It was achieved by imparting water resistance to the highly absorbent material and aiding in achieving a balance between hydrophilic and hydrophobic properties. This study clearly indicates the possible elimination of additional crosslinkers and multiple fabrication steps that can reduce the cost of scaffold production for skin tissue engineering applications while tailoring mechanical strength and degradation.

Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics

Exudates of non-healing wounds contain drivers of pathogenicity. We utilized >800 exudates from non-healing and healing wounds of diverse etiologies, collected by three different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to a) to differentiate between healing and non-healing wounds, b) follow the healing process of individual patients, and c) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically non-healing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo non-healing wound exudates revealed an induction of inflammatory cytokine- and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of non-healing wounds. Testing the wound therapeutics platelet derived growth factor and silver sulfadiazine yielded responses in line with clinical experience and indicate the usefulness of the assay to search for and profile new therapeutics.

SIRT6 Inhibits the Proliferation and Collagen Synthesis of Keloid Fibroblasts through MAPK/ERK Pathway.

Keloid, a fibroproliferative disorder, significantly impacts patients' quality of life, yet effective therapies remain elusive. This study explored the role of silent information regulator 6 (SIRT6) in modulating the proliferation, invasion, and collagen synthesis of keloid fibroblasts. Keloid and normal skin specimens were collected, and fibroblasts were isolated from the keloid tissue. SIRT6 recombinant adenovirus (Ad) was constructed to infect keloid fibroblasts to overexpress SIRT6. This study entails three groups: Control group, adenovirus-Negative Control (Ad-NC) group, and Ad-SIRT6 group. SIRT6 protein and mRNA levels were measured via Western blotting and Quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Cell viability was determined using 5-ethynyl-2'-deoxyuridine (EdU) assay. Flow cytometry was exploited to measure cell apoptosis. To investigate cell migration, wound healing assay and Transwell assay were employed. Western blotting was also utilized to study the expression levels of apoptotic proteins, collagen deposition-related proteins, and Mitogen-Activated Protein Kinases (MAPK)/extracellular regulated protein kinases (ERK) pathway-related proteins. Compared to the control and Ad-NC groups, the Ad-SIRT6 group exhibited significantly elevated SIRT6 level; diminished cell proliferation, migration and invasion; reduced protein levels of α-smooth muscle actin (α-SMA), collagen I, collagen III, phospho SMAD Family Member 3 (p-Smad3), transforming growth factor-β 1 (TGF-β1), and MAPK/ERK pathway proteins (phospho extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phospho MAP kinase-ERK kinase (p-MEK) and phospho-c-Raf (p-c-Raf)). Treatment with epidermal growth factor (EGF), an MAPK/ERK pathway agonists, reversed the inhibitory effect of SIRT6 on cell activity and inhibited apoptosis in keloid fibroblasts. SIRT6 overexpression in keloid fibroblasts attenuates proliferation, invasion, and collagen synthesis, while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity. This suggests a potential therapeutic target for keloid treatment.

Proteomics analysis of deep fascia in acute compartment syndrome.

Acute compartment syndrome (ACS) is a syndrome in which local circulation is affected due to increased pressure within the compartment. We previously found in patients with calf fractures, the pressure of fascial compartment could be sharply reduced upon the appearance of tension blisters. Deep fascia, as the important structure for compartment, might play key role in this process. Therefore, the aim of the present study was to examine the differences in gene profile in deep fascia tissue in fracture patients of the calf with or without tension blisters, and to explore the role of fascia in pressure improvement in ACS. Patients with lower leg fracture were enrolled and divided into control group (CON group, n = 10) without tension blister, and tension blister group (TB group, n = 10). Deep fascia tissues were collected and LC-MS/MS label-free quantitative proteomics were performed. Genes involved in fascia structure and fibroblast function were further validated by Western blot. The differentially expressed proteins were found to be mainly enriched in pathways related to protein synthesis and processing, stress fiber assembly, cell-substrate adhesion, leukocyte mediated cytotoxicity, and cellular response to stress. Compared with the CON group, the expression of Peroxidasin homolog (PXDN), which promotes the function of fibroblasts, and Leukocyte differentiation antigen 74 (CD74), which enhances the proliferation of fibroblasts, were significantly upregulated (p all <0.05), while the expression of Matrix metalloproteinase-9 (MMP9), which is involved in collagen hydrolysis, and Neutrophil elastase (ELANE), which is involved in elastin hydrolysis, were significantly reduced in the TB group (p all <0.05), indicating fascia tissue underwent microenvironment reconstruction during ACS. In summary, the ACS accompanied by blisters is associated with the enhanced function and proliferation of fibroblasts and reduced hydrolysis of collagen and elastin. The adaptive alterations in the stiffness and elasticity of the deep fascia might be crucial for pressure release of ACS.

Sulfenylation of ERK1/2: A novel mechanism for SO2-mediated inhibition of cardiac fibroblast proliferation

BackgroundEndogenous sulfur dioxide (SO2) plays a crucial role in protecting heart from myocardial fibrosis by inhibiting the excessive growth of cardiac fibroblasts. This study aimed to investigate potential mechanisms by which SO2 suppressed myocardial fibrosis. Methods and resultsMouse model of angiotensin II (Ang II)-induced cardiac fibrosis and cell model of Ang II-stimulated cardiac fibroblast proliferation were employed. Our findings discovered that SO2 mitigated the aberrant phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) induced by Ang II, leading to a reduction of fibroblast proliferation. Mechanistically, for the first time, we found that SO2 sulfenylated ERK1/2, and inhibited ERK1/2 phosphorylation and cardiac fibroblast proliferation, while a sulfhydryl reducing agent dithiothreitol (DTT) reversed the above effects of SO2. Furthermore, mutant ERK1C183S (cysteine 183 to serine) abolished the sulfenylation of ERK by SO2, thereby preventing the inhibitory effects of SO2 on ERK1 phosphorylation and cardiac fibroblast proliferation. ConclusionOur study suggested that SO2 inhibited cardiac fibroblast proliferation by sulfenylating ERK1/2 and subsequently suppressing ERK1/2 phosphorylation. These new findings might enhance the understanding of the mechanisms underlying myocardial fibrosis and emphasize the potential of SO2 as a novel therapeutic target for myocardial fibrosis.

POST-TRAUMATIC BRACHIAL ARTERY PSEUDOANEURYSM (CLINICAL CASE)

We present a clinical case of treatment of pseudoaneurysm of the right brachial artery. The cause of the pseudoaneurysm was a gunshot wound to the right shoulder. An aneurysmectomy, endarterectomy, and autovenous prosthetic repair of the right brachial artery were performed. Histological examination revealed thrombotic masses, a fragment of the vessel wall with fibroblast proliferation, hemorrhages, focal hemosiderosis, and moderate lymphocytic infiltration. 6 months after surgery, limb function was completely restored. Autovenous prosthetic repair of a section of the brachial artery with a pseudoaneurysm due to a gunshot wound is an effective surgical method of treatment and restoration of blood flow.

Rhizoma coptidis can inhibit the excessive proliferation, inflammation, and transformation of lung fibroblasts into myofibroblasts.

Pulmonary fibrosis (PF) is a chronic, progressive, and irreversible heterogeneous disease of lung interstitial tissue. To combat progression of PF, new drugs are required to be developed. Rhizoma coptidis (COP), one of the main alkaloids of Coptis chinensis, is a traditional herbal medicine used to treat various inflammatory diseases. To investigate the possible effects of Coptisine (Cop) on the growth, inflammation, as well as FMT of TNF-β1-induced HFL1 cells and uncover the mechanism. Human fetal lung fibroblast 1 (HFL1) was induced using 6ng/mL TGF-β1 as a model of pulmonary fibrosis. CCK-8, Brdu, and transwell assays indicated the effects on cell growth as well as motility. qPCR and the corresponding kits indicted the effects on cell inflammation. Immunoblot showed the effects on FMT and further confirmed the mechanism. Coptisine inhibits excessive growth as well as motility of TNF-β1-induced HFL1 cells. It further inhibits inflammation and ROS levels in TNF-β1-induced HFL1 cells. Coptisine inhibits the FMT process of TNF-β1-induced HFL1 cells. Mechanically, coptisine promotes the Nrf2/HO-1 pathway. Coptisine can inhibit the excessive growth, inflammation as well as FMT of lung fibroblasts into myofibroblasts. It could serve as a promising drug of PF.

Enhancing cellular affinity for skin disorders: Electrospun polyurethane/collagen nanofiber mats coated with phytoceramides

Although the use of thermoplastic polyurethane (Tpu) nanofiber mats as wound dressings is of great interest due to their mechanical properties, they are hindered by their poor wettability and bioavailability. In this study, we aimed to improve the cellular affinity of Tpu nanofiber mats for skin disorders by incorporating extracted collagen (Col) from tendons and physically mixed with a layer of phytoceramides (Phyto) to produce TpuCol@X-Phyto mats in which the weight % of Phyto relatively to the weight of the solution was X = 0.5, 1.0, or 1.5 wt% via facile electrospinning approach. The collective observations strongly indicate the successful incorporation and retention of Phyto within the TpuCol architecture. An increase in the Phyto concentration decreased the water contact angle from 69.4° ± 3.47° to 57.9° ± 2.89°, demonstrating improvement in the hydrophilicity of Tpu and binary blend TpuCol nanofiber mats. The mechanical property of 1.0 wt% Phyto aligns with practical requirements owing to the presence of two hydroxyl groups and the amide linkage likely contributing to various hydrogen bonds, providing mechanical strength to the channel structure and a degree of rigidity essential for transmitting mechanical stress. The proliferation of human skin fibroblast (HSF) peaked significantly 100 % with TpuCol@X-Phyto mats coated for X =1.0 and 1.5 wt% of Phyto. Electrospun scaffolds with the highest Phyto content have shown the lowest degree of hemolysis, demonstrating the high level of compatibility between them and blood. The TpuCol@1.5Phyto mat also demonstrated higher efficacy in antibacterial and antioxidant activities, achieving a rate of DPPH radical scavenging of 83.3 % for this latter property. The most notable wound closure among all tested formulations was attributed to higher Phyto. Thus, the developed TpuCol@1.5Phyto nanofiber formula exhibited enhanced healing in an in vitro epidermal model.

Benign Fibrous Histiocytoma of Gingiva: A Rare Case Report

Abstract Fibrous histiocytoma is a benign soft-tissue neoplasm that commonly involves the dermis. It is rare in the oral cavity. This lesion creates a diagnostic dilemma due to its nonspecific clinical appearance and microscopic similarities with other benign fibrous tissue lesions. Microscopically, it shows the proliferation of both spindle-shaped fibroblasts and histiocytes. Surgical excision is the treatment of choice with a good prognosis. The purpose of this paper is to report a rare case of gingival benign fibrous histiocytoma occurring in an 11-year-old female patient. The diagnosis of this lesion is based on combined clinical, histopathological, and immunohistochemical features.

Development of mADM-collagen wound dressings for mimicking native skin architecture to enhance skin wound healing

Acellular dermal matrix (ADM) is one of the most promising scaffold materials due to its ability to retain natural extracellular matrix structure. Micronized acellular dermal matrix (mADM) was prepared with no intact cell nuclei and preserved growth factors by High Hydrostatic Pressure (HHP) approach. And mADM-collagen wound dressings were developed with different proportion of type I collagen and recombinant humanized type III collagen. The porous structure of the mADM-collagen wound dressings made them a good candidate for preventing excessive fluid accumulation, while the collagens with gel-like texture combined with mADM powder to form pasty texture wound dressing, which preserving the moisture at the wound site. Moreover, the paste texture of the mADM-collagen wound dressing was easy to reshape to conform any wound shapes and body contours. Furthermore, the resulted mADM-collagen wound dressings showed good biocompatibility by supporting fibroblasts adhesion and proliferation in vitro. Subsequently, a murine model of full-thickness skin wounds was employed to assess its effects on wound healing. Notably, mADM-75% Col-I exhibited superior effects throughout the wound healing process, specifically it promoted neovascularization, skin appendage growth and new skin regeneration. This formulation closely mimicked the collagen ratio found in healthy skin, facilitating the favorable wound repair. These results indicated the superior performance of this mADM-collagen wound dressing providing an optimal environment for wound healing.Graphical

Molecular insight into the role of isoflavones targeting estrogen β receptor in diabetic wound healing pathway: A computational and in-vitro studies

This study aims to investigate the modulation of ER-β by phytoestrogens (isoflavones) in target diabetic wound healing using computational tools and in vitro studies. One of the primary limitations associated with delayed wound healing is inhibiting antioxidant pathways mediated by estrogen receptor-β (ER-β). In this study, we screened 50 isoflavones against the active pocket of ER-β (5TOA.pdb). Through the XP docking score, we evaluated the binding pattern and dynamic changes of the top 5 isoflavones having the highest docking scores, binding energy, and interactions with ER-β. Further, in vitro, MTT assay was performed on the L929 cell line, followed by scratch assay, DPPH assay and glucose uptake assay. The XP (Extra precision) docking score of the top 5 isoflavones were S-Equol −9.90, Genistein −9.71, Icaritin (ICT) −9.92, Biochanin A −8.97, and Formononetin −8.87 respectively when compared with standard estradiol −10.61 when docked with ER-β. The binding free energy values (ΔG bind) of the top 5 isoflavones were S-Equol (−27.15 kcal/mol), Genistein (−41.49 kcal/mol), ICT (−46.56 kcal/mol) Biochanin A (−37.01 kcal/Mol) and Formononetin (−42.96 kcal/Mol) respectively when compared with standard estradiol (−97.15 kcal/mol). Based on the XP glide score and free binding energy calculations, ICT was subjected to 100 ns MD simulation, confirming the stability of ICT with ER-β. The in-vitro results showed no cytotoxicity found up to 125 µM concentration, revealing normal proliferation of fibroblasts reduced total ROS production and prevented cell glucose uptake. These results highlighted the interaction potential of ICT for targeting ER-β, antioxidant, and anti-diabetic activity for diabetic wound healing.

Dual-wavelength dye laser combined with betamethasone injection for treatment of keloids: protocol of a randomised controlled trial

IntroductionKeloids, benign fibroproliferative tumours characterised by excessive fibroblast proliferation and over-deposition of extracellular matrix, pose a therapeutic challenge with high recurrence rates. Betamethasone (diprospan) injection (BI) is one of the...

Targeting the Epigenome Reduces Keloid Fibroblast Cell Proliferation, Migration, and Invasion

Keloids are pathological fibroproliferative scars resulting from abnormal collagen deposition within and beyond the margins of the initial cutaneous insult. Keloids negatively impact quality of life functionally and cosmetically, with current treatment modalities unsatisfactory. Recent studies indicate that epigenetic dysregulation is central to the development and progression of keloids. Here we evaluate the functional significance of epigenetic targeting strategies in vitro using patient-derived keloid fibroblasts treated with small molecule inhibitors of HDACs, LSD1, CoREST and p300, as potential therapies for keloids. We find that both the dual-acting CoREST inhibitor, corin, and the HDAC inhibitor, entinostat, reduce fibroblast proliferation more than the LSD1 inhibitor, GSK-LSD1; additionally, corin was the most effective inhibitor of migration and invasion across keloid fibroblasts. RNA-seq analysis of keloid fibroblasts treated with corin demonstrates coordinate upregulation of many genes including key mediators of cell adhesion such as claudins. Corin also downregulates gene sets involved in cell cycle progression, including reduced expression of cyclins A1 and B2 compared to DMSO. These results highlight a significant role for epigenetic regulation of pathologic mediators of keloidal scarring and suggest that inhibitors of the epigenetic CoREST repressor complex may prove beneficial in the prevention and/or treatment of keloidal scarring in patients.

Acceleration of wound healing using adipose mesenchymal stem cell secretome hydrogel on partial-thickness cutaneous thermal burn wounds: An in vivo study in rats.

The intricate healing process involves distinct sequential and overlapping phases in thermal injury. To maintain the zone of stasis in Jackson's burn wound model, proper wound intervention is essential. The extent of research on the histoarchitecture of thermal wound healing and the application of mesenchymal stem cell (MSC)-free-based therapy is limited. This study aimed to assess the efficacy of MSC-secretome-based hydrogel for treating partial-thickness cutaneous thermal burn wounds. Eighteen male Wistar rats were divided into three groups, namely the hydrogel base (10 mg), hydrogel secretome (10 mg) and Bioplacenton™ (10 mg) treatment groups. All groups were treated twice a day (morning and evening) for 7 days. Skin tissue samples from the animals were processed for histological evaluation using the formalin-fixed paraffin-embedded method on days 3 and 7. This study's findings showed that secretome hydrogel expedited thermal burn wound healing, decreasing residual burn area, boosting collagen deposition and angiogenesis, guiding scar formation, and influencing the inflammation response facilitated by polymorphonuclear leukocytes and macrophages. The secretome hydrogel significantly improves healing outcomes in partial-thickness cutaneous thermal burn wounds. The administration of secretome hydrogel accelerates the reduction of the residual burn area and promotes fibroblast proliferation and collagen density. The repairment of histo-architecture of the damaged tissue was also observed such as the reduction of burn depth, increased angiogenesis and epidermal scar index while the decreased dermal scar index. Furthermore, the secretome hydrogel can modulate the immunocompetent cells by decreasing the polymorphonuclear and increasing the mononuclear cells. Thus, it effectively and safely substitutes for thermal injury stem cell-free therapeutic approaches. The study focuses on the microscopical evaluation of secretome hydrogel; further research to investigate at the molecular level may be useful in predicting the beneficial effect of secretome hydrogel in accelerating wound healing.

Advanced Delivery Strategies of Nintedanib for Lung Disorders and Beyond: A Comprehensive Review.

Nintedanib, a primary treatment for lung fibrosis, has gathered substantial attention due to its multifaceted potential. A tyrosine kinase inhibitor, nintedanib, inhibits multiple signalling receptors, including endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) and ultimately inhibits fibroblast proliferation and differentiation. Therefore, nintedanib has been studied widely for other ailments like cancers and hepatic fibrosis, apart from lung disorders. Commercially, nintedanib is available as soft gelatin capsules for treatment against idiopathic pulmonary fibrosis. Since it has very low oral bioavailability (4.7%), high doses of a drug, such as 100-150mg, are administered, which can cause problems of gastrointestinal irritation and hepatotoxicity. The article begins with exploring the mechanism of action of nintedanib, elucidating its complex interactions within cellular pathways that govern fibrotic processes. It also emphasizes the pharmacokinetics of nintedanib, clinical trial insights, and the limitations of conventional formulations. The article mainly focuses on the emerging landscape of nanoparticle-based carriers such as hybrid liposome-exosome, nano liquid crystals, discoidal polymeric, and magnetic systems, offering promising avenues to optimize drug targeting, address its efficacy issues and minimise adverse effects. However, none of these delivery systems are commercialised, and further research is required to ensure safety and effectiveness in clinical settings. Yet, as research progresses, these advanced delivery systems promise to revolutionise the treatment landscape for various fibrotic disorders and cancers, potentially improving patient outcomes and quality of life.