Production Of Collagen Fibers Research Articles

Radiofrequency Treatment Attenuates Age-Related Changes in Dermal-Epidermal Junctions of Animal Skin.

The dermal-epidermal junction (DEJ) is essential for maintaining skin structural integrity and regulating cell survival and proliferation. Thus, DEJ rejuvenation is key for skin revitalization, particularly in age-related DEJ deterioration. Radiofrequency (RF) treatment, known for its ability to enhance collagen fiber production through thermal mechanisms and increase heat shock protein (HSP) expression, has emerged as a promising method for skin rejuvenation. Additionally, RF activates Piezo1, an ion channel implicated in macrophage polarization toward an M2 phenotype and enhanced TGF-β production. This study investigated the impact of RF treatment on HSP47 and HSP90 expression, known stimulators of DEJ protein expression. Furthermore, using in vitro and aged animal skin models, we assessed whether RF-induced Piezo1 activation and the subsequent M2 polarization could counter age-related DEJ changes. The RF treatment of H2O2-induced senescent keratinocytes upregulated the expression of HSP47, HSP90, TGF-β, and DEJ proteins, including collagen XVII. Similarly, the RF treatment of senescent macrophages increased Piezo1 and CD206 (M2 marker) expression. Conditioned media from RF-treated senescent macrophages enhanced the expression of TGF-β and DEJ proteins, such as nidogen and collagen IV, in senescent fibroblasts. In aged animal skin, RF treatment increased the expression of HSP47, HSP90, Piezo1, markers associated with M2 polarization, IL-10, and TGF-β. Additionally, RF treatment enhanced DEJ protein expression. Moreover, RF reduced lamina densa replication, disrupted lesions, promoted hemidesmosome formation, and increased epidermal thickness. Overall, RF treatment effectively enhanced DEJ protein expression and mitigated age-related DEJ structural changes by increasing HSP levels and activating Piezo1.

Expression analysis of leptin in nephrogenesis and renal carcinogenesis

The complex phenomenon of renal development involves several signaling molecules. Any alteration in the developmental process could largely influence the organogenesis, thus predisposing to several adulthood diseases. Leptin is a pleiotropic gene secreted by adipose cells. However, the purview of its actions is much beyond merely the extent of human adipose reserve. It regulates several cellular mechanisms such as cell proliferation, inflammation, vasculogenesis, and the production of collagen fibres. Further leptins are thought to play a putative role in embryogenesis and tumorigenesis. The aim of thIS study was to investigate the localization of the protein in fetal and cancer kidney in an attempt to understand the role of the protein in fetal kidney development and in renal cancer. Leptin expression was evaluated by subjecting tissue sections from paraffin-embedded blocks of renal tissues (fetal, adult and cancer) to immunohistochemistry staining. The tissues were scored based on the staining pattern and percentage of immunoreactive cells. The tissues were subjected to haematoxylin and eosin stain before performing immunohistochemistry. The images were analyzed and photographed. Mild staining for leptin was observed in the tubules of fetal and adult kidneys. Mild to moderate staining was seen in membranes of renal cell carcinoma tissues. It appears such that leptin may not be a key factor or rather a temporary factor in the developmental process of the kidney. The low levels of leptin in normal adult renal tissues may be physiologically significant. The role of leptin in the renal cell carcinoma progression is sceptible.

Modified Zhenwu Tang delays chronic renal failure progression by modulating oxidative stress and hypoxic responses in renal proximal tubular epithelial cells

BackgroundTubulointerstitial fibrosis (TIF) is a critical pathological feature of chronic renal failure (CRF), with oxidative stress (OS) and hypoxic responses in renal proximal tubular epithelial cells playing pivotal roles in disease progression. This study explores the effects of Modified Zhenwu Tang (MZWT) on these processes, aiming to uncover its potential mechanisms in slowing CRF progression. MethodsWe used adenine (Ade) to induce CRF in rats, which were then treated with benazepril hydrochloride (Lotensin) and MZWT for 8 weeks. Assessments included liver and renal function, electrolytes, blood lipids, renal tissue pathology, OS levels, the hypoxia-inducible factor (HIF) pathway, inflammatory markers, and other relevant indicators. In vitro, human renal cortical proximal tubular epithelial cells were subjected to hypoxia and lipopolysaccharide for 72 h, with concurrent treatment using MZWT, FM19G11, and N-acetyl-l-cysteine. Measurements taken included reactive oxygen species (ROS), HIF pathway activity, inflammatory markers, and other relevant indicators. ResultsAde treatment induced significant disruptions in renal function, blood lipids, electrolytes, and tubulointerstitial architecture, alongside heightened OS, HIF pathway activation, and inflammatory responses in rats. In vivo, MZWT effectively ameliorated proteinuria, renal dysfunction, lipid and electrolyte imbalances, and renal tissue damage; it also suppressed OS, HIF pathway activation, epithelial-mesenchymal transition (EMT) in proximal tubular epithelial cells, and reduced the production of inflammatory cytokines and collagen fibers. In vitro findings demonstrated that MZWT decreased apoptosis, reduced ROS production, curbed OS, HIF pathway activation, and EMT in proximal tubular epithelial cells, and diminished the output of inflammatory cytokines and collagen. ConclusionOS and hypoxic responses significantly contribute to TIF development. MZWT mitigates these responses in renal proximal tubular epithelial cells, thereby delaying the progression of CRF.

Hyaluronidase inhibits TGF-β-mediated rat periodontal ligament fibroblast expression of collagen and myofibroblast markers: An in vitro exploration of periodontal tissue remodeling

ObjectiveTo determine the effect of hyaluronic acid (HA) degradation by hyaluronidase (HYAL) in inhibiting collagen fiber production by rat periodontal ligament cells (rPDLCs). DesignPrimary rPDLCs were isolated from the euthanized rats and used for in vitro experiments. The appropriate HYAL concentration was determined through CCK-8 testing for cytotoxicity detection and Alizarin red staining for mineralization detection. RT-qPCR and western blot assays were conducted to assess the effect of HYAL, with or without TGF-β, on generation of collagen fiber constituents and expression of actin alpha 2, smooth muscle (ACTA2) of rPDLCs. ResultsNeither cell proliferation nor mineralization were significantly affected by treatment with 4 U/mL HYAL. HYAL (4 U/mL) alone downregulated type I collagen fiber (Col1a1 and Col1a2) and Acta2 mRNA expression; however, ACTA2 and COL1 protein levels were only downregulated by HYAL treatment after TGF-β induction. ConclusionsTreatment of rPDLCs with HYAL can inhibit TGF-β-induced collagen matrix formation and myofibroblast transformation.

Evaluation of the wound healing efficacy of new antibacterial polymeric nanofiber based on polyethylene oxide coated with copper nanoparticles and defensin peptide: An in-vitro to in-vivo assessment

ObjectiveToday, designing nanofibers with antibacterial properties using electrospinning technology is one of the attractive approaches for wound healing. Methods& analysis: This study aims to fabricate a nanocomposite from polyethylene oxide (PEO) coated with copper nanoparticles (NPs) and defensin peptide with wound healing and antimicrobial properties in different ratios of CuNPs/defensin (2/0 mg), (1.5/0.5 mg), and (1/1 mg) in the fixed contain polymer (98 mg). Then, the nanofiber properties were investigated by SEM, tensile, DSC, and BET analysis. Also, the antibacterial properties against S. aureus and E. coli, antioxidant, and in-vivo wound healing effects and histological analysis of the designed nanocomposites were evaluated in rat models. ResultsOur SEM images showed that CuNPs and defensin were properly coated on the PEO surface. According to the tensile, DSC, and antibacterial analysis results, the most appropriate feature was related to CuNPs/defensin (1.5/0.5 mg), with maximum elasticity, heat resistance, and antibacterial activity. Furthermore, the designed nanocomposites showed the best performance as a wound closure agent by increasing dermis and epidermis volume density, stimulating fibroblast cells and collagen fiber production, and improving skin vessels. ConclusionAccording to our results, PEO nanofibers loaded with CuNPs and defensin have the best potential for wound healing, and they can be used as antibacterial materials in the textile, drug, and medical industries.

Ginsenoside Rh4 alleviates idiopathic pulmonary fibrosis by enhancing the CXCL9–CXCR3 axis

AbstractIdiopathic pulmonary fibrosis (IPF), often likened to a “tumor‐like disease,” proves more lethal than several malignancies. Although prior studies have demonstrated the lung‐protective efficacy of ginsenosides, the precise mechanism underlying their alleviative effect on IPF remains elusive. In this study, we validated the efficacy of the ginsenoside Rh4 in alleviating IPF and delved into the underlying mechanisms. Our data showed that Rh4 intervention significantly reduced mortality and hydroxyproline (HYP) content in mice. It also alleviated the pathological process of IPF by ameliorating phenomena such as alveolar wall thickening induced by IPF. In addition, in vitro cellular experiments confirmed that ginsenoside Rh4 was effective in alleviating transforming growth factor‐β1‐induced IPF model. Further analysis showed that ginsenoside Rh4 significantly reduced collagen fiber production and deposition while inhibiting the coagulation cascade signaling pathway. In addition, ginsenoside Rh4 inhibited the epithelial‐mesenchymal transition(EMT) pathway by promoting the CXCR3‐CXCL9 axis, which ultimately alleviated IPF. In conclusion, our data strongly suggest that ginsenoside Rh4 has the potential to be an innovative prophylactic drug against IPF.

Ellagic acid protected the gingival tissue via fibroblast and epidermal growth factors in rats.

To investigate the effect of ellagic acid (EA) in gingival tissues injury in rats. Twenty rats were categorized into two groups. In burn group, an excisional wound area was created by removing a 4-mm diameter flap from the left molar region in the mucoperiosteal region of the gingiva. In burn + ellagic acid group, 1.2mg/mL EA was administered as irrigation for one week. Animals was sacrificed under anesthesia at the end of experiment. Malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) level were measured. Hematoxylin and eosin, fibroblast growth factor (FGF) and epidermal growth factor (EGF) immunostainings were applied to tissues. MDA, MPO, inflammation and leukocyte infiltration were high in burn group. Degeneration epithelium, edema and inflammatory cell infiltration in connective tissue areas, and dilatation and congestion in blood vessels were observed in burn group. In burn + EA group, the gingival epithelium improved, collagen fiber production increased and organized dermis were observed. After burn injury, FGF and EGF activity was increased in EA treated groups. We suggest that EA have the potential for better healing outcomes in oral wounds. EA seems to have promising therapeutic efficacy to enhance oral wound healing.

Inflammation-related signaling pathways in tendinopathy.

Tendon is a connective tissue that produces movement by transmitting the force produced by muscle contraction to the bones. Most tendinopathy is caused by prolonged overloading of the tendon, leading to degenerative disease of the tendon. When overloaded, the oxygen demand of tenocytes increases, and the tendon structure is special and lacks blood supply, which makes it easier to form an oxygen-deficient environment in tenocytes. The production of reactive oxygen species due to hypoxia causes elevation of inflammatory markers in the tendon, including PGE2, IL-1β, and TNF-α. In the process of tendon healing, inflammation is also a necessary stage. The inflammatory environment formed by cytokines and various immune cells play an important role in the clearance of necrotic material, the proliferation of tenocytes, and the production of collagen fibers. However, excessive inflammation can lead to tendon adhesions and hinder tendon healing. Some important and diverse biological functions of the body originate from intercellular signal transduction, among which cytokine mediation is an important way of signal transduction. In particular, NF-κB, NLRP3, p38/MAPK, and signal transducer and activator of transcription 3, four common signaling pathways in tendinopathy inflammatory response, play a crucial role in the regulation and transcription of inflammatory factors. Therefore, summarizing the specific mechanisms of inflammatory signaling pathways in tendinopathy is of great significance for an in-depth understanding of the inflammatory response process and exploring how to inhibit the harmful part of the inflammatory response and promote the beneficial part to improve the healing effect of the tendon.

Ellagic acid loaded nanospheres/biodegradable PVA‐sodium alginate hydrogel for wound healing application

AbstractIn the present study, a novel polyvinyl alcohol‐sodium alginate hydrogel was prepared using ellagic acid loaded nanospheres in its structure. Ellagic acid was loaded into polymeric nanospheres using a double‐emulsion solvent evaporation technique. Obtained nanospheres were dispersed in a polyvinyl alcohol‐sodium alginate hydrogel, prepared using freeze–thaw method followed by freeze‐drying. Ellagic acid loaded nanospheres and the final hydrogel preparation were characterized using scanning electron microscopy, dynamic light scattering, and Fourier transformation infrared spectroscopy, and investigated for ellagic acid content, and release profile. MTT assays were conducted to measure the viability of cells after treatment with the hydrogel, and wound healing activity was investigated through in vivo studies on open wounds of an animal model. Results showed formation of nanospheres with average diameter of 241.5 nm and prolonged‐release profile of ellagic acid during 48 h. MTT assays showed a significant increase in cell proliferation upon treatment of NIH3T3 cells with the hydrogel. The hydrogel also significantly increased the rate of wound closure through improved epithelialization and production of collagen fibers. It can be concluded that the hydrogel containing ellagic acid‐loaded nanospheres prepared in this study can be designated as a biocompatible dressing to accelerate the wound healing process.

Use of retinoids in the treatment of skin lesions and prevention of signs of skin aging - a systematic review

Retinoids are a group of substances that include vitamin A and its natural and synthetic derivatives. They are used in the treatment of various skin diseases, such as: rosacea, acne vulgaris, psoriasis. In addition, recently there is a lot of information about the action of preventing photoaging. Oral retinoids have been proven to be the most effective treatment for acne of various severity available today. Through their comprehensive action, affecting the four main factors associated with the pathogenesis of acne, they significantly reduce skin changes. Externally applied retinoids regulate the renewal of epidermal cells, stimulate the production of collagen fibers, increase the production of elastin, and lead to an increase in the number and activity of fibroblasts. Therefore, more and more people are using preparations containing retinoids to prevent skin aging. It has been proven that this procedure leads to shallower wrinkles and slows down the appearance of new ones, and evens out the skin tone. Retinoids are effective substances, but their use is associated with the risk of various side effects, the most common of which are: skin irritation, photosensitisation, headaches, muscle and joint pain, and teratogenicity.

Carbon dioxide-induced decrease in extracellular pH enhances the production of extracellular matrix components by upregulating TGF-β1 expression via CREB activation in human dermal fibroblasts.

Mild acidification caused by transcutaneous administration of carbon dioxide (CO2 ) has been reported to improve some epidermal skin impairments, such as desquamation and inflammation; however, its effects on dermal tissue remain unclear. Here, we examined the effect and mechanism of mild acidity on extracellular matrix (ECM) protein production in normal human dermal fibroblasts (NHDFs). To achieve this, the skin permeability of CO2 and its effect on intradermal pH were evaluated by treating reconstructed human skin equivalents (HSEs) with a CO2 -containing formulation. Additionally, NHDFs were cultured in a pH-adjusted medium (pH 6.5). CO2 successfully permeated HSEs and reduced the intradermal pH. Decreased extracellular pH activated CREB, upregulated TGF-β1 expression, promoted the production of elastic and collagen fibres, and increased hyaluronan concentration in NHDFs. Additionally, the low pH-induced increase in TGF-β1 expression was attenuated via the RNAi-mediated suppression of the expression of CREB1 and proton-sensing G protein-coupled receptors (GPCRs), including GPR4 and GPR65. Moreover, low pH-induced CREB activation was suppressed by the inhibition of the cAMP/PKA and PLC/PKC signalling pathways. Taken together, a CO2 -induced decrease in intradermal pH may promote ECM production in NHDFs via the upregulation of TGF-β1 expression, which was mediated by the activation of the GPCR signalling pathway and CREB, indicating that CO2 could be used to treat ultraviolet radiation-induced photoaging, intrinsic ageing and ECM deterioration.

Wound Healing Properties of Pelargonium Graveolens L'Hér Extract Lipogel: In-Vivo Evaluation in an Animal Burn Model.

Pelargonium graveolens L'Hér has traditionally been used to reduce skin inflammation, and recent studies have confirmed antioxidant compounds in the plant's extract. The present study aimed to prepare a lipogel formulation from P. graveolens hydroalcoholic extract and evaluate its efficacy on the wound healing process in an animal model. The aerial part extract of P. graveolens was prepared through percolation. Additionally, plastibase was prepared by mixing 5% of low-molecular-weight polyethylene with hot mineral oil (130°C). The extract (5%) was levigated in the mineral oil (5-15%) and dispersed in the cooled plastibase. The physical properties of the lipogel, thermal stability, and microbial limits were tested. Further, the effect of the lipogel in the wound healing rate was examined among male Wistar rats, and skin tissue samples were assessed histologically. The results represented the best rheological and thermal stability characteristics in the formulation with 5% mineral oil (as the levigator). The lipogel-treated group had the least burn area compared to the silver sulfadiazine and negative control groups (p<0.05). The microscopic examination of tissue samples revealed increased collagen fiber production and maturation and significantly also faster epithelial repair among lipogel-treated rats than in the other two groups(p<0.05). The results indicated the significant therapeutic effects of P. graveolens lipogelon burn healing. The suitable physicochemical properties and the low lipogel production cost facilitate further scale-up studies.

Luteolin improves nephropathy in hyperglycemic rats through anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms

Hyperglycemia can also induce the production of free radicals and the progression of inflammatory reactions. The aim of this study is to explore the potential anti-oxidant and anti-inflammatory mechanisms of luteolin in the treatment of diabetic nephropathy.Luteolin significantly reduced blood glucose and BUN levels in streptozotocin-induced diabetic rats and increased serum sodium and chloride levels. Histopathological staining of the kidney showed that luteolin effectively inhibits glycoprotein deposition and production of collagen fibers in the kidney. On Western blotting, luteolin increased anti-oxidant enzymes in the kidney by up-regulating NF-E2-related factor 2 (Nrf2). In DML rats, the expression of inflammatory cytokines decreased significantly with down-regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In addition, luteolin inhibited the activation of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and the expressions of its downstream apoptosis-related proteins.In conclusion, luteolin slows the progression of nephropathy through anti-hyperglycemic, anti-inflammatory, anti-oxidant, and anti-apoptotic mechanisms.

The role of the retinoids in topical treatment of skin diseases - the review of the literature

INTRODUCTION: Retinoids are a broad group of natural and synthetic compounds derived from vitamin A. Many studies have shown strong anti-aging effects, and they have also been shown to have therapeutic effects on acne vulgaris or psoriasis. Vitamin A and its derivatives make the skin more elastic and smooth, cause a decrease in fine wrinkles and cause an increase in fibroblast activity and collagen fiber production. Retinoid compounds regulate biological processes of the skin such as immune processes, angiogenesis, proliferation and differentiation. THE AIM OF STUDY: The purpose of this paper is to discuss the effects of retinoids and the use of the substances in skin diseases. MATERIALS AND METHOD: Literature review of PubMed, Google Scholar and Science Direct and evaluation of available randomized controlled trials using retinoids in terms of treatment effectiveness in terms of skin quality, anti-aging benefits use in dermatology. CONCLUSIONS: Vitamin A and its derivatives plays an important role in anty-aging prevention and treatment of skin diseases, such as acne vulgaris, psoriasis and photo-aging. There are still many ongoing studies and not known opportunities of its use to treat other skin diseases that we should be aware of and keep track of new papers that indicate such.

Polyacrylamide Hydrogel Containing Calendula Extract as a Wound Healing Bandage: In Vivo Test.

Hydrogel is a biomaterial widely used in several areas of industry due to its great biocompatibility and adaptability to biological tissues. In Brazil, the Calendula plant is approved by the Ministry of Health as a medicinal herb. It was chosen to be incorporated in the hydrogel formulation because of its anti-inflammatory, antiseptic and healing effects. This study synthesized polyacrylamide hydrogel containing calendula extract and evaluated its efficiency as a bandage for wound healing. The hydrogels were prepared using free radical polymerization and characterized by Scanning Electron Microscopy, swelling analysis and mechanical properties by texturometer. The morphology of the matrices showed large pores and foliaceous structure. In vivo testing, as well as the evaluation of acute dermal toxicity, was conducted using male Wistar rats. The tests indicated efficient collagen fiber production, improved skin repair and no signs of dermal toxicity. Thus, the hydrogel presents compatible properties for the controlled release of calendula extract used as a bandage to promote cicatrization.

Preparation of polyvinyl alcohol hydrogel containing chlorogenic acid microspheres and its evaluation for use in skin wound healing.

Chlorogenic acid (CGA) is a phenolic compound widely found in plants. Several studies have shown that CGA possesses antioxidant, antibacterial, anti-inflammatory and wound healing properties. Because of their three-dimensional structure, good permeability, excellent biocompatibility and moisturizing properties, hydrogels are ideal candidates for wound dressing. The aim of the present study was to preparation and characterization of Polyvinyl alcohol (PVA) hydrogel containing CGA microspheres and evaluation its wound healing activity. The double-emulsion solvent evaporation technique was applied for preparing the CGA containing microspheres. The microspheres were characterized using scanning electron microscopy (SEM) and Fourier transformation infrared spectroscopy (FTIR) and subsequently incorporated in the structure of a PVA hydrogel. The effects of prepared hydrogel on NIH3T3 cell line viability were evaluated using MTT method and wound healing activity was investigated in full thickness wound model in rabbit. SEM images showed formation of homogenous CGA microspheres with diameters in the range of 1-2μm, embedded in the porous structure of the hydrogel. Infra-red results indicated successful incorporation of CGA microspheres into PVA hydrogel. The NIH3T3 cell viability percentage in CGA 2.5% hydrogel treated group significantly (p < .05) increased after 24 h and 48 h comparing to control group. In vivo studies showed that CGA hydrogel significantly (p < .001) stimulated the rate of wounds closures. Histological studies revealed that administration of CGA hydrogel significantly increased epithelialization and production of collagen fibers compared to the control group. It can be concluded that the CGA microsphere loaded PVA hydrogel has the potential for wound healing.

Mitochondria and light: An overview of the pathways triggered in skin and retina with incident infrared radiation.

Slightly more than half of the solar radiation that passes through the atmosphere and reaches the Earth's surface is infrared. Over the past few years, many papers have been published on the possible positive effects of receiving this part of the electromagnetic spectrum. In this article we analyse the role of mitochondria in the supposed effects of infrared light based on the published literature. It is claimed that ATP synthesis is stimulated, which has a positive effect on the skin by increasing fibroblast proliferation, anchorage and production of collagen fibres, procollagen, and various cytokines responsible for the wound healing process, such as keratinocyte growth factor. Currently there are infrared light emitting equipment whose manufacturers and the centres where this service or treatment is offered claim that they are used for skin rejuvenation among other positive effects. Based on the literature review, it is necessary to deepen the scientific study of the mechanism of absorption of infrared radiation through the skin to better understand its possible positive effects, the risks of overexposure and to improve consumer health protection.

Experimental Study of Using Aloe Vera Gel to Treat Diabetic Chronic Cutaneous Ulcers in Bama Miniature Pigs

To investigate the efficacy, safety, and mechanism of topical application of aloe vera gel (AVG) to treat diabetic chronic cutaneous ulcers in Bama miniature pigs. The Bama miniature pig model of diabetic chronic skin wounds was constructed and the model pigs were randomly assigned to AVG daily administration group (AVG QD), aloe vera gel every-other-day administration group (AVG QOD), and diabetic control group (DC). A non-diabetic chronic skin wounds model pig was set as the non-diabetic control group (NDC). Treatment efficacy was evaluated based on the amount of time needed for complete healing of the wounds, healing rates, granulation growth rates, and skin histopathological changes. Safety was evaluated according to whether adverse reactions were observed. In addition, the dynamic changes of the relative expression levels of miR21, miR29a, miR126, miR146a, miR155, and miR210 in wound granulation tissues were examined. 1) Efficacy and safety: The amount of time needed for complete healing of the wounds was shorter in the NDC group than those of the three other groups, DC group, AVG QD group, and AVG QOD group (all P<0.05). The amount of time needed for complete healing of the wounds was shorter in the AVG QD group and AVG QOD group than that of DC group (all P<0.05). The amount of time needed for complete healing of the wounds was shorter in the AVG QOD group than that of AVG QD group (all P<0.05). No adverse reactions were detected in the whole process of AVG topical treatment. The granulation growth rate of NDC group was higher than those of DC group, AVG QD group, and AVG QOD group (all P<0.05). The wound healing rate of NDC group was higher than those of DC group, AVG QD group, and AVG QOD group (all P<0.05); the wound healing rate of AVG QOD group was higher than those of DC group and AVG QD group (all P<0.05). 2) Histopathology: The results of HE staining light microscopy showed that collagen fiber production increased, and that microvascular formation with slight inflammatory cell infiltration was observed in the dermal interstitium at the initial stage of wound healing after AVG treatment. One year of after complete healing, pathological examination results of wound healing skin showed that the epidermal keratinization was complete, that collagen was arranged neatly and orderly, and that many microvessels were found in the interstitium. The results of picric acid celestite scarlet staining showed that, after AVG treatment, type Ⅰ collagen mainly increased in the initial stage of wound healing, type Ⅲ collagen gradually increased when the wound healed completely, and the collagen was arranged neatly during the whole process. 3) The relative expression of microRNAs: The relative expression of miR21, miR126, and miR210 in NDC group, AVG QD group, and AVG QOD group were higher than that in DC group (all P<0.05). The relative expression of miR29a and miR155 in NDC group, AVG QD group, and AVG QOD group was lower than that in DC group (all P<0.05). The relative expression of miR146a in NDC group was higher than that in DC group ( P<0.05). AVG topical application can shorten the time needed for complete healing of diabetic chronic wounds in Bama minipigs. The wound healing speed of the alternate-day treatment group was faster than that of the daily treatment group. No adverse reactions were observed over the course of the treatment. The mechanism may be related to the up-regulation of the expressions of miR21, miR126, and miR210 and the down-regulation of miR29a and miR155 in wound granulation tissue.

Role of TGF-β3 and bone marrow mesenchymal stem cells on regeneration of myometrial injury in rats

ObjectiveThis study aimed to explore therapeutic effect of bone marrow mesenchymal stem cells (BMSCs) and TGF-β3 in regenerative injuries in the myometrium of the uterus in rats. MethodsTwenty-four pregnant rats were randomly assigned into four groups and their pregnancy was terminated on day 19 of pregnancy: 1. Blank scar uterus control group injected with the physiological saline, 2. TGF-β3 group injected with TGF-β3, 3. BMSCs group injected with BMSCs, 4. BMSCS + TGF-β3 injected with TGF-β3 and BMSCs. ResultsMSCs expressing specific surface antigens had multidirectional differentiation potential and showed a tendency to home to the site of injury, and the macroscopic appearance of the cell-treated uterus was smoother and tougher in the three groups than in the control group. The uterus improved by the TGF-β3+MSCs group had the best recovery showing significant glandular and vascular nature, with better repair effect and promoted endometrial cell proliferation. Proteins related to endometrial cell proliferation showed that the expression of Ki-67 was significantly increased in three intervention groups, and a positive signal of waveform protein was observed in the uterine stromal cells. The levels of waveform protein and CK-19 protein were significantly lower in the control group compared to their levels in the three interventional groups. Injection of BMSCs and TGF-β3 resulted in the repair of whole damaged myometrium and significant improvement in function compared to other groups, whereas TGF-β3 significantly reduced collagen fiber production. ConclusionsBMSCs can differentiate into uterine smooth muscle cells, repair uterine scar tissue and promote uterine scar healing.

Liposomal stem cell extract formulation from Coffea canephora shows outstanding anti-inflammatory activity, increased tissue repair, neocollagenesis and neoangiogenesis.

Coffea canephora plant stem cells can have bioactive compounds with tissue repairing and anti-inflammatory action. This study aimed to develop a liposomal stem cell extract formulation obtained from the leaves of C. canephora (LSCECC) and to investigate its capacity to contribute to the dynamic mechanisms of tissue repair. The liposome cream was developed and characterized through the dynamic light scattering technique, atomic force microscopy, and transmission electron microscopy. The excisional full-thickness skin wound model was used and daily topically treated with the LSCECC formulation or vehicle control. On days 2, 7, 14, and 21 after wounding, five rats from each group were euthanized and the rates of wound closure and re-epithelialization were evaluated using biochemical and histological tests. LSCECC resulted in faster re-epithelialization exhibiting a significant reduction in wound area of 36.4, 42.4, and 87.5% after 7, 10, and 14days, respectively, when compared to vehicle control. LSCECC treated wounds exhibited an increase in granular tissue and a proper inflammatory response mediated by the reduction of pro-inflammatory cytokines like TNF-α and IL-6 and an increase of IL-10. Furthermore, wounds treated with LSCECC showed an increase in the deposition and organization of collagen fibers at the wound site and improved scar tissue quality due to the increase in transforming growth factor-beta and vascular endothelial growth factor. Our data showed that LSCECC improves wound healing, the formation of extracellular matrix, modulates inflammatory response, and promotes neovascularization being consider a promising bioactive extract to promote and support healthy skin. The graphical presents the action of LSCECC in all four phases of wound healing and tissue repair. The LSCECC can reduce the inflammatory infiltrate in the inflammatory phase by decreasing the pro-inflammatory cytokines like IL-6 and TNF-α, in addition to maintaining this modulation through lesser activation and recruitment of macrophages. The LSCECC can also increase the release of IL-10, an anti-inflammatory cytokine, decreasing local edema. The increase in VEGF provides neovascularization and the supply of nutrients to newly repaired tissue. Finally, signaling via TGF-β increases the production and organization of collagen fibers in the remodeling phase.