Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

Validation of a Numerical Model of Skeletal Muscle Compression With MR Tagging: A Contribution to Pressure Ulcer Research

2008 ◽  
Vol 130 (6) ◽  
Author(s):  
K. K. Ceelen ◽  
A. Stekelenburg ◽  
J. L. J. Mulders ◽  
G. J. Strijkers ◽  
F. P. T. Baaijens ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Animal Studies ◽  
Tissue Injury ◽  
Element Model ◽  
Tissue Deformation ◽  
Deep Tissue ◽  
Deep Tissue Injury ◽  
Muscle Tissues

Sustained tissue compression can lead to pressure ulcers, which can either start superficially or within deeper tissue layers. The latter type includes deep tissue injury, starting in skeletal muscle underneath an intact skin. Since the underlying damage mechanisms are poorly understood, prevention and early detection are difficult. Recent in vitro studies and in vivo animal studies have suggested that tissue deformation per se can lead to damage. In order to conclusively couple damage to deformation, experiments are required in which internal tissue deformation and damage are both known. Magnetic resonance (MR) tagging and T2-weighted MR imaging can be used to measure tissue deformation and damage, respectively, but they cannot be combined in a protocol for measuring damage after prolonged loading. Therefore, a dedicated finite element model was developed to calculate strains in damage experiments. In the present study, this model, which describes the compression of rat skeletal muscles, was validated with MR tagging. Displacements from both the tagging experiments and the model were interpolated on a grid and subsequently processed to obtain maximum shear strains. A correlation analysis revealed a linear correlation between experimental and numerical strains. It was further found that the accuracy of the numerical prediction decreased for increasing strains, but the positive predictive value remained reasonable. It was concluded that the model was suitable for calculating strains in skeletal muscle tissues in which damage is measured due to compression.

scholarly journals Continuous Delivery of Stromal Cell-Derived Factor-1 from Alginate Scaffolds Accelerates Wound Healing

2010 ◽  
Vol 19 (4) ◽  
pp. 399-408 ◽  
Author(s):  
Sina Y. Rabbany ◽  
Joseph Pastore ◽  
Masaya Yamamoto ◽  
Tim Miller ◽  
Shahin Rafii ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stromal Cell ◽  
Wound Closure ◽  
Tissue Injury ◽  
Unmet Need ◽  
Novel Therapy ◽  
Yorkshire Pigs ◽  
Stromal Cell Derived Factor

Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo Kd 0.55 days) than SDF-1 plasmid (in vivo Kd 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein ( n = 10) and plasmid ( n = 6) loaded patches healed faster than sham ( n = 4) or control ( n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 ± 14.3% healed) compared to nontreated controls (8.2 ± 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.

scholarly journals l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiangbing Mao ◽  
Rui Sun ◽  
Qingxiang Wang ◽  
Daiwen Chen ◽  
Bing Yu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Activity Index ◽  
Control Diet ◽  
Average Daily Gain ◽  
Disease Activity Index ◽  
Inflammatory Cells ◽  
Feed Conversion ◽  
Enterocyte Apoptosis

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P &lt;0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P &lt;0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P &lt;0.05), shortened colonic length (P &lt;0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P &lt;0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P &lt;0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P &lt;0.05), DAI (P &lt;0.05), colonic length and enterocyte apoptosis (P &lt;0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P &lt;0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

Synthesis of Novel Derivatives of Quinazoline Schiff base Compound Promotes Epithelial Wound Healing

2018 ◽  
Vol 24 (13) ◽  
pp. 1395-1404
Author(s):  
Elham Bagheri ◽  
Kamelia Saremi ◽  
Fatemeh Hajiaghaalipour ◽  
Fadhil Lafta Faraj ◽  
Hapipah Mohd Ali ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Biological Activities ◽  
Inflammatory Cells ◽  
Negative Control ◽  
High Dose ◽  
Sprague Dawley ◽  
Wound Tissue

Quinazoline is an aromatic bicyclic compound exhibiting several pharmaceutical and biological activities. This study was conducted to investigate the potential wound healing properties of Synthetic Quinazoline Compound (SQC) on experimental rats. The toxicity of SQC was determined by MTT cell proliferation assay. The healing effect of SQC was assessed by in vitro wound healing scratch assay on the skin fibroblast cells (BJ-5ta) and in vivo wound healing experiment of low and high dose of SQC on adult Sprague-Dawley rats compared with negative (gum acacia) and positive control (Intrasite-gel). Hematoxylin and Eosin (H&E), Masson’s Trichrome (MT) staining and immunohistochemistry analysis were performed to evaluate the histopathological alterations and proteins expression of Bax and Hsp70 on the wound tissue after 10 days. In addition, levels of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase), and malondialdehyde (MDA) were measured in wound tissue homogenates. The SQC significantly enhanced BJ-5ta cell proliferation and accelerated the percentage of wound closure, with less scarring, increased fibroblast and collagen fibers and less inflammatory cells compared with the negative control. The compound also increases endogenous enzymes and decline lipid peroxidation in wound homogenate.

Snail1 transcription factor is a critical mediator of hepatic stellate cell activation following hepatic injury

2011 ◽  
Vol 300 (2) ◽  
pp. G316-G326 ◽  
Author(s):  
Melania Scarpa ◽  
Alessia R. Grillo ◽  
Paola Brun ◽  
Veronica Macchi ◽  
Annalisa Stefani ◽  
...  
Keyword(s):  
Wound Healing ◽  
Transcription Factor ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Mrna Expression ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Qrt Pcr

Following liver injury, the wound-healing process is characterized by hepatic stellate cell (HSC) activation from the quiescent fat-storing phenotype to a highly proliferative myofibroblast-like phenotype. Snail1 is a transcription factor best known for its ability to trigger epithelial-mesenchymal transition, to influence mesoderm formation during embryonic development, and to favor cell survival. In this study, we evaluated the expression of Snail1 in experimental and human liver fibrosis and analyzed its role in the HSC transdifferentiation process. Liver samples from patients with liver fibrosis and from mice treated by either carbon tetrachloride (CCl4) or thioacetamide (TAA) were evaluated for mRNA expression of Snail1. The transcription factor expression was investigated by immunostaining and real-time quantitative RT-PCR (qRT-PCR) on in vitro and in vivo activated murine HSC. Snail1 knockdown studies on cultured HSC and on CCl4-treated mice were performed by adenoviral delivery of short-hairpin RNA; activation-related genes were quantitated by real-time qRT-PCR and Western blotting. Snail1 mRNA expression resulted upregulated in murine experimental models of liver injury and in human hepatic fibrosis. In vitro studies showed that Snail1 is expressed by HSC and that its transcription is augmented in in vitro and in vivo activated HSC compared with quiescent HSC. At the protein level, we could observe the nuclear translocation of Snail1 in activated HSC. Snail1 knockdown resulted in the downregulation of activation-related genes both in vitro and in vivo. Our data support a role for Snail1 transcription factor in the hepatic wound-healing response and its involvement in the HSC transdifferentiation process.

scholarly journals Effect ofAngelica sinensisPolysaccharides on OsteoarthritisIn VivoandIn Vitro: A Possible Mechanism to Promote Proteoglycans Synthesis

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Jun Qin ◽  
Yan-song Liu ◽  
Jun Liu ◽  
Jing Li ◽  
Yang Tan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Articular Chondrocytes ◽  
Interleukin 1 ◽  
Knee Joints ◽  
Protective Effects ◽  
Interleukin 1 Beta ◽  
Degrading Enzymes ◽  
Matrix Degrading Enzymes

This study investigated the effect ofAngelica sinensispolysaccharides (APS-3c) on rat osteoarthritis (OA) modelin vivoand rat interleukin-1-beta- (IL-1β-) stimulated chondrocytesin vitro. APS-3c was administrated into rat OA knee joints and had protective effects on rat OA cartilagein vivo. Primary rat articular chondrocytes were cotreated with APS-3c and IL-1β  in vitro. 2~50 μg/mL APS-3c had no effect on chondrocytes viability, whereas it increased the proteoglycans (PGs) synthesis inhibited by IL-1β. Microarray analysis showed that the significant changes were concentrated in the genes which were involved in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1βbut did not affect the mRNA expression of matrix-degrading enzymes. These results indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA modelin vivoand IL-1β-stimulated chondrocytesin vitro, which is due to the promotion of the expression of aggrecan and GTs involved in PGs synthesis but not the inhibition of the expression of matrix-degrading enzymes. Our findings suggest the clinical relevance of APS-3c in the prospective of future alternative medical treatment for OA.

scholarly journals L-arginine suppresses lipopolysaccharide-induced expression of RANTES in glomeruli.

1998 ◽  
Vol 9 (2) ◽  
pp. 203-210 ◽  
Author(s):  
U Haberstroh ◽  
K Stilo ◽  
J Pocock ◽  
G Wolf ◽  
U Helmchen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Northern Blotting ◽  
No Synthase ◽  
In Vivo Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Cell Infiltrate ◽  
Beneficial Effects

Endotoxemia leads to the infiltration of inflammatory cells in glomeruli and the tubulointerstitium of the kidney. The ultimate mechanisms for this infiltration, however, are not entirely clear. In this study, the glomerular formation of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) was examined in an in vivo model of endotoxemia to evaluate the role the local release of chemokines might play in the regulation of this inflammatory cell infiltrate. Since the beneficial effects of nitric oxide (NO) on immune-mediated tissue injury have been reported, we also examined possible interactions between the chemokine RANTES and the L-arginine/NO pathway. To induce endotoxemia, rats were injected intraperitoneally with lipopolysaccharide (LPS). Glomeruli were isolated over a 24-h time period, and RANTES was assessed by Northern blotting, a chemotactic assay, and a specific enzyme-linked immunosorbent assay. The chemokine release was associated with increased glomerular infiltration of monocytes/macrophages. LPS also stimulated the mRNA expression of inducible NO synthase and increased the release of nitrite into the supernatants of isolated glomeruli. Supplementation of L-arginine intake increased the release of glomerular nitrite and reduced glomerular RANTES expression after the injection of LPS. Inhibition of the L-arginine/NO pathway by the unspecific NO synthase inhibitor N(G)-nitro-L-arginine methylester significantly increased glomerular RANTES mRNA expression and the number of infiltrating glomerular macrophages. These data demonstrate that L-arginine suppresses glomerular RANTES formation and suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS-induced endotoxemia can be modulated by the L-arginine/NO pathway.

scholarly journals Omeprazole increases survival via different mechanisms in two rat models of liver injury

2021 ◽  
Author(s):  
Masaya Kotsuka ◽  
Yuki Hashimoto ◽  
Richi Nakatake ◽  
Tetsuya Okuyama ◽  
Masahiko Hatta ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mrna Expression ◽  
Rat Hepatocytes ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Beneficial Effects ◽  
Factor Alpha ◽  
Oxide Synthase

Abstract Omeprazole (OMZ) is a proton pump inhibitor (PPI) that is used to reduce gastric acid secretion, but little is known about its possible liver protective effects. This study investigated whether OMZ has beneficial effects in rat septic models of lipopolysaccharide (LPS)-induced liver injury after D-galactosamine (GalN) treatment and 70% hepatectomy (PH), and to determine the mechanisms of OMZ in an in vitro model of liver injury. In the in vivo models, the effects of OMZ were examined 1 h before treatment. OMZ increased survival and decreased tumor necrosis factor-alpha, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant 1, interleukin (IL)-6, and IL-1β mRNA expression, and increased IL-10 mRNA expression in the livers of both GaIN/LPS- and PH/LPS-treated rats. Necrosis and apoptosis were inhibited by OMZ in GaIN/LPS rats, but OMZ had no effects on necrosis in PH/LPS rats. Primary rat hepatocytes were treated with IL1-β in the presence or absence of OMZ (in vitro model). OMZ inhibited iNOS induction partially through suppression of NF-κB signaling in hepatocytes. Furthermore, OMZ inhibited the induction of several inflammatory mediators, resulting in the prevention of LPS-induced liver injury after GalN liver failure and PH, although OMZ showed different doses and mechanisms in the two models.

scholarly journals Normal gonadotropin production and fertility in gonadotrope-specific Bmpr1a knockout mice

2016 ◽  
Vol 229 (3) ◽  
pp. 331-341 ◽  
Author(s):  
Xiang Zhou ◽  
Ying Wang ◽  
Luisina Ongaro ◽  
Ulrich Boehm ◽  
Vesa Kaartinen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Knockout Mice ◽  
Reproductive Organ ◽  
Normal Serum ◽  
Receptor Protein ◽  
Pcr Analysis ◽  
Type I ◽  
Pituitary Cells

Pituitary follicle-stimulating hormone (FSH) synthesis is regulated by transforming growth factorβsuperfamily ligands, most notably the activins and inhibins. Bone morphogenetic proteins (BMPs) also regulate FSHβ subunit (Fshb) expression in immortalized murine gonadotrope-like LβT2 cells and in primary murine or ovine primary pituitary cultures. BMP2 signals preferentially via the BMP type I receptor, BMPR1A, to stimulate murine Fshb transcription in vitro. Here, we used a Cre–lox approach to assess BMPR1A’s role in FSH synthesis in mice in vivo. Gonadotrope-specific Bmpr1a knockout animals developed normally and had reproductive organ weights comparable with those of controls. Knockouts were fertile, with normal serum gonadotropins and pituitary gonadotropin subunit mRNA expression. Cre-mediated recombination of the floxed Bmpr1a allele was efficient and specific, as indicated by PCR analysis of diverse tissues and isolated gonadotrope cells. Furthermore, BMP2 stimulation of inhibitor of DNA binding 3 expression was impaired in gonadotropes isolated from Bmpr1a knockout mice, confirming the loss of functional receptor protein in these cells. Treatment of purified gonadotropes with small-molecule inhibitors of BMPR1A (and the related receptors BMPR1B and ACVR1) suppressed Fshb mRNA expression, suggesting that an autocrine BMP-like molecule might regulate FSH synthesis. However, deletion of Bmpr1a and Acvr1 in cultured pituitary cells did not alter Fshb expression, indicating that the inhibitors had off-target effects. In sum, BMPs or related ligands acting via BMPR1A or ACVR1 are unlikely to play direct physiological roles in FSH synthesis by murine gonadotrope cells.

scholarly journals In vitro evaluation of chitosan-DNA plasmid complex encoding Jembrana disease virus Env-TM protein as a vaccine candidate

2019 ◽  
Vol 63 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Januar Ishak ◽  
Lalu Unsunnidhal ◽  
Ronny Martien ◽  
Asmarani Kusumawati
Keyword(s):  
Mrna Expression ◽  
Dna Vaccine ◽  
Hela Cells ◽  
Restriction Analysis ◽  
Initial Study ◽  
Pcr Analysis ◽  
Colony Pcr ◽  
Dna Complex

AbstractIntroduction:The development of Jembrana disease vaccine is an important effort to prevent losses in the Bali cattle industry in Indonesia. This study aims to prepare a Jembrana DNA vaccine encoding the transmembrane portion of the envelope protein in pEGFP-C1 and test the success of its delivery in culture cells using a chitosan-DNA complex.Material and Methods:Cloning of the DNA vaccine was successfully performed onE. coliDH5α and confirmed by colony PCR, restriction analysis and sequencing. The plasmids were prepared as a chitosan complex using the complex coacervation method and physicochemically characterised using a particle size analyser. A transfection assay was performed in HeLa cells with 4 h exposure, and mRNA expression was assessed at 24 h post transfection.Results:With a 1:2 (wt./wt.) ratio of DNA and chitosan, the complexes have a mean diameter of 236 nm, zeta potential value of + 17.9 mV, and showed no high toxicity potential in the HeLa cells. This complex successfully delivered the DNA into cells, as shown by the presence of a specific RT-PCR product (336 bp). However, the real-time PCR analysis showed that the delivery with chitosan complex resulted in lower target mRNA expression when compared with a commercial transfecting agent.Conclusion:pEGFP-env-tm JDV as a candidate vaccine can be delivered as the chitosan-DNA complex and be expressed at the transcription levelin vitro. This initial study will be used for further improvement and evaluationin vivo.

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