The cardiac neural stem cell phenotype is compromised in streptozotocin‐induced diabetic cardiomyopathy

Neural stem cells were identified in the rat heart and during scar formation and healing participated in sympathetic fiber sprouting and angiogenesis. In the setting of diabetes, impaired wound healing represents a typical pathological feature. These findings provided the impetus to test the hypothesis that experimental diabetes adversely influenced the phenotype of cardiac neural stem cells. Streptozotocin (STZ)‐induced diabetic rats were associated with elevated plasma glucose levels, significant loss of body weight and left ventricular contractile dysfunction. In the heart of STZ‐diabetic rats, the density of nestin immunoreactive processes emanating from cardiac neural stem cells were reduced. The latter finding was reaffirmed as nestin protein expression was significantly decreased in the heart of STZ‐diabetic rats and associated with a concomitant reduction of nestin mRNA. Employing the TUNEL assay, the loss of nestin expression in STZ‐diabetic rats was not attributed to widespread cardiac neural stem cell apoptosis. Insulin administration to STZ‐diabetic rats with established hyperglycaemia led to a modest recovery of nestin protein expression in cardiac neural stem cells. By contrast, the administration of insulin immediately after STZ injection improved plasma glucose levels and significantly attenuated the loss of nestin protein expression. These data highlight the novel observation that nestin protein expression in cardiac neural stem cells was significantly reduced in STZ‐induced type I diabetic rats. The aberrant cardiac neural stem cell phenotype may compromise their biological role and predispose the diabetic heart to maladaptive healing following ischemic injury. J. Cell. Physiol. 220: 440–449, 2009. © 2009 Wiley‐Liss, Inc.     

Effect of novel curcumin‐encapsulated chitosan–bioglass drug on bone and skin repair after gamma radiation: experimental study on a Wistar rat model

Radiation therapy contributes to a significant increase in bone osteoporosis and skin loss. Various natural health products might be beneficial to reduce bone and skin alterations. Curcumin (CUR) medicines derived from natural plants have played an important role in health care. This study aims at synthesizing and evaluating the performance therapy of CUR‐encapsulated bioglass–chitosan (CUR–BG–CH). In vitro, the antioxidant assay was evaluated by using 1,1‐diphenyl‐2‐picrylhydrazyl free‐radical (DPPH) scavenging and the nitroblue tetrazolium reduction. The CUR–BG–CH antimicrobial effects were tested in liquid media. In vivo, after rat ⁶⁰Co γ‐radiation, the tissue wound‐healing process was studied by grafting CUR and CUR–BG–CH in femoral condyle and dorsal skin rat tissue. The antioxidant studies indicated that CUR–BG–CH quenches free radicals more efficiently than unmodified CUR and had effective DPPH (91%) and superoxide anion (51%) radical scavenging activities. The CUR–BG–CH biomaterial exhibited an important antimicrobial activity against Staphylococcus aureus. The histomorphometric parameters showed amelioration in CUR–BG–CH‐treated rats. An improved mechanical property was noticed (33.16 ± 5.0 HV) when compared with that of unmodified CUR group (23.15 ± 4.9 HV). A significant decrease in tumour necrosis factor‐α cytokine production was noted in the CUR–BG–CH rats (90 pg/ml) as compared with that of unmodified CUR group (240 pg/ml). The total amount of hydroxyproline was significantly enhanced (33.5%) in CUR–BG–CH group as compared with that of control. Our findings suggested that CUR–BG–CH might have promising potential applications for wound healing. Copyright © 2015 John Wiley & Sons, Ltd.     

Pulsed electromagnetic fields accelerate wound healing in the skin of diabetic rats

Delayed wound healing is a common complication in diabetes mellitus. From this point of view, the main purpose of the present study is to investigate the effect of extremely low frequency pulsed electromagnetic fields (ELF PEMFs) on skin wound healing in diabetic rats. In this study, diabetes was induced in male Wistar rats via a single subcutaneous injection of 65 mg/kg streptozocin (freshly dissolved in sterile saline, 0.9%). One month after the induction of diabetes, a full‐thickness dermal incision (35 mm length) was made on the right side of the paravertebral region. The wound was exposed to ELF PEMF (20 Hz, 4 ms, 8 mT) for 1 h per day. Wound healing was evaluated by measuring surface area, percentage of healing, duration of healing, and wound tensile strength. Obtained results showed that the duration of wound healing in diabetic rats in comparison with the control group was significantly increased. In contrast, the rate of healing in diabetic rats receiving PEMF was significantly greater than in the diabetic control group. The wound tensile strength also was significantly greater than the control animals. In addition, the duration of wound healing in the control group receiving PEMF was less than the sham group. Based on the above‐mentioned results we concluded that this study provides some evidence to support the use of ELF PEMFs to accelerate diabetic wound healing. Further research is needed to determine the PEMF mechanisms in acceleration of wound healing in diabetic rats. Bioelectromagnetics 31:318–323, 2010. © 2010 Wiley‐Liss, Inc.     

The neuropeptide Gonadotropin-releasing hormone modifies the spontaneous muscular contraction in the earthworm: <Emphasis Type="Italic">Eisenia foetida</Emphasis>

We investigated whether the Gonadotropin-releasing hormone affects the spontaneous muscular contraction in the earthworm Eisenia foetida. In addition, we investigated the presence of Gonadotropin-releasing hormone receptor in ventral nerve cord by immunohistochemistry and polymerase chain reaction. Gonadotropin-releasing hormone induced a significant increase on both amplitude and muscular tone and decrease in the frequency of spontaneous muscular contraction. We found the presence of immunoreactive material to Gonadotropin-releasing hormone receptor in the ventral nerve cord, likewise the Gonadotropin-releasing hormone receptor mRNA expression. In conclusion, the Gonadotropin-releasing hormone modifies the spontaneous muscular contraction in E. foetida and these effects can be due to the activation of the Gonadotropin-releasing hormone receptor.     

Stimulation of growth factor synthesis in skin wounds using tissue extract (G-90) from the earthworm Eissenia foetida

Growth factors are biologically-active mediators that bind to specific receptors on target cells and regulate genes involved in cell growth, wound healing and regeneration. In the case of wound healing, a proper wound dressing is needed to cover the wound area, protect the damaged tissue, and if possible to activate cell proliferation and stimulate the healing process. In this study we examined the efficacy of a glycolipoprotein tissue homogenate extract from Eisenia foetida (G-90) to activate signal transduction pathways, leading to wound healing. We measured the activation of EGF and FGF in healthy skin, in wounds with physiological healing and in wounds treated with G-90. The activation of EGF and FGF was measured during the first 24 h of wound healing under both physiological conditions and treatment with G-90. In both cases an increased concentration of EGF and FGF was observed 6 h after wounding. In comparison with healthy skin, the concentration of EGF increased 10-fold and FGF five-fold in wounds treated with G-90 (10 ng ml(-1)). Healing in physiological conditions resulted in a two-fold increase of EGF and 1.5-fold of FGF.     

Investigating the healing mechanisms of an angiogenesis‐promoting topical treatment for diabetic wounds using multimodal microscopy

Impaired skin wound healing is a significant comorbid condition of diabetes that is caused by poor microcirculation, among other factors. Studies have shown that angiogenesis, a critical step in the wound healing process in diabetic wounds, can be promoted under hypoxia. In this study, an angiogenesis‐promoting topical treatment for diabetic wounds, which promotes angiogenesis by mimicking a hypoxic environment via inhibition of prolyl hydroxylase resulting in elevation or maintenance of hypoxia‐inducible factor, was investigated utilizing a custom‐built multimodal microscopy system equipped with phase‐variance optical coherence tomography (PV‐OCT) and fluorescence lifetime imaging microscopy (FLIM). PV‐OCT was used to track the regeneration of the microvasculature network, and FLIM was used to assess the in vivo metabolic response of mouse epidermal keratinocytes to the treatment during healing. Results show a significant decrease in the fluorescence lifetime of intracellular reduced nicotinamide adenine dinucleotide, suggesting a hypoxic‐like environment in the wounded skin, followed by a quantitative increase in blood vessel density assessed by PV‐OCT. Insights gained in these studies could lead to new endpoints for evaluation of the efficacy and healing mechanisms of wound‐healing drugs in a setting where delayed healing does not permit available methods for evaluation to take place.      

Adipose tissue‐derived mesenchymal stem cells and keratinocytes co‐culture on gelatin/chitosan/β‐glycerol phosphate nanoscaffold in skin regeneration

Using cell‐based engineered skin is an emerging strategy for treating difficult‐to‐heal wounds. To date, much endeavor has been devoted to the fabrication of appropriate scaffolds with suitable biomechanical properties to support cell viability and growth in the microenvironment of a wound. The aim of this research was to assess the impact of adipose tissue‐derived mesenchymal stem cells (AD‐MSCs) and keratinocytes on gelatin/chitosan/β‐glycerol phosphate (GCGP) nanoscaffold in full‐thickness excisional skin wound healing of rats. For this purpose, AD‐MSCs and keratinocytes were isolated from rats and GCGP nanoscaffolds were electrospun. Through an in vivo study, the percentage of wound closure was assessed on days 7, 14, and 21 after wound induction. Samples were taken from the wound sites in order to evaluate the density of collagen fibers and vessels at 7 and 14 days. Moreover, sampling was done on days 7 and 14 from wound sites to assess the density of collagen fibers and vessels. The wound closure rate was significantly increased in the keratinocytes‐AD‐MSCs‐scaffold (KMS) group compared with other groups. The expressions of vascular endothelial growth factor, collagen type 1, and CD34 were also significantly higher in the KMS group compared with the other groups. These results suggest that the combination of AD‐MSCs and keratinocytes seeded onto GCGP nanoscaffold provides a promising treatment for wound healing.     

Migration‐ and Proliferation‐Promoting Activities in Human Keratinocytes of Zea mays Flower Absolute and Its Chemical Composition

Zea mays L. (ZM) has cytotoxic and anti‐inflammatory activities, but its biological activities such as skin regeneration and wound healing in human skin have not been reported. In the present study, we tested the effects of ZM flower (ZMF) absolute on proliferation and migration of human keratinocytes (HaCaTs) and identified its components by using gas chromatography/mass spectrometry (GC/MS) analysis. GC/MS analysis revealed that the ZMF absolute contained 13 constituents, and it increased HaCaT proliferation and migration. The ZMF absolute enhanced the phosphorylation levels of serine/threonine‐specific protein kinase (Akt), p38 mitogen‐activated protein kinase (MAPK), and extracellular signal‐regulated kinase1/2 in HaCaTs. In addition, the absolute induced an increase in sprout outgrowth of HaCaTs. The present study reports for the first time that ZMF absolute may promote skin wound healing and/or skin regeneration by stimulating proliferative and migratory activities in dermal keratinocytes through the Akt/MAPK pathway. Therefore, ZMF absolute may be a promising natural material for the use in skin regeneration and/or wound healing applications.     

Monotropein promotes angiogenesis and inhibits oxidative stress‐induced autophagy in endothelial progenitor cells to accelerate wound healing

Attenuating oxidative stress‐induced damage and promoting endothelial progenitor cell (EPC) differentiation are critical for ischaemic injuries. We suggested monotropein (Mtp), a bioactive constituent used in traditional Chinese medicine, can inhibit oxidative stress‐induced mitochondrial dysfunction and stimulate bone marrow‐derived EPC (BM‐EPC) differentiation. Results showed Mtp significantly elevated migration and tube formation of BM‐EPCs and prevented tert‐butyl hydroperoxide (TBHP)‐induced programmed cell death through apoptosis and autophagy by reducing intracellular reactive oxygen species release and restoring mitochondrial membrane potential, which may be mediated viamTOR/p70S6K/4EBP1 and AMPK phosphorylation. Moreover, Mtp accelerated wound healing in rats, as indicated by reduced healing times, decreased macrophage infiltration and increased blood vessel formation. In summary, Mtp promoted mobilization and differentiation of BM‐EPCs and protected against apoptosis and autophagy by suppressing the AMPK/mTOR pathway, improving wound healing in vivo. This study revealed that Mtp is a potential therapeutic for endothelial injury‐related wounds.     

HORMAD2 methylation‐mediated epigenetic regulation of gene expression in thyroid cancer

This study is aimed to investigate the methylation level of candidate genes and its impact on thyroid carcinoma (THCA) development. Infinium Human Methylation 450 BeadChip Arrays by Illumina (Illumina HM450K) was the most popular CpG microarray platform widely used in biological and medical research. The methylation level of differentially expressed genes and their corresponding CpG sites were analysed by R programme. The expression of HORMAD2 was evaluated by qRT‐PCR and Western blot, while the methylation level was examined via methylation‐specific PCR. Cell viability, metastasis, cell cycle and apoptosis were detected by MTT assay, transwell and wound healing assay and flow cytometry, respectively, after treatment with 5‐aza‐2′‐deoxycytidine (5‐Aza). Tumour formation assay was used to analyse thyroid tumour growth in nude mice in vivo. The methylation levels of all 116 differentially expressed genes were analysed. HORMAD2 was significantly hypermethylated and its mRNA expression was inhibited in THCA cells. After treatment with 5‐Aza, HORMAD2 expression was up‐regulated in THCA cells and its overexpression can suppress thyroid cancer cell viability, mobility and invasiveness remarkably. Up‐regulation of HORMAD2 in THCA cells could prolong G0/G1 phase and shorten S phase to impede cell mitosis as well as promote thyroid cancer cells apoptosis. Furthermore, tumour formation assay showed that increased HORMAD2 level impeded tumour growth in vivo. Hypermethylation of HORMAD2 could induce THCA progression, while hypomethylation of HORMAD2 retard cell growth and mobility and facilitate apoptosis through increasing its mRNA expression.     

Application of platelet derived growth factor-BB and diabetic wound healing: the relationship with oxidative events

The reasons that cause delay in wound healing in diabetes are a decrease in the level of growth factors secretion, an increase in the destruction of growth factors and in oxidative stress. Platelet derived growth factor (PDGF) is one of the important growth factors that play a role in all phases of wound healing. This study investigates time-dependent effects of topically PDGF-BB administration on oxidative events on the healing of dorsolateral-excisional wounds in diabetic rats. Forty-two female Wistar-albino rats with streptozotocin-induced diabetes were divided into four groups: control group, untreated group, chitosan-treated group, chitosan?+?PDGF-BB-treated group. Two identical full-thickness excisional skin wounds were made under anaesthesia in all rats except for the control group. In the PDGF-BB-treated and chitosan-treated groups, the wounds were treated topically PDGF-BB (7?ng/mL, single daily dose) and blank chitosan gel (equal amount) after wounding, respectively. After these administrations, on day 3 and day 7 of wound healing, rats were sacrificed. Thiobarbituric acid reactive substances, glutathione, nitric oxide, ascorbic acid levels, and superoxide dismutase activity in wound tissues were spectrophotometrically measured. PDGF-BB administration significantly increased TBARS levels and non-enzymatic antioxidant levels in early phase of diabetic wound healing. PDGF-BB dramatically reduced NO_x levels on day 3 and sharply increased NO_x levels on day 7 of wound healing. Consequently, PDGF-BB administration can be effective on oxidative balance in the early phase of diabetic wound healing.     

D‐dopachrome tautomerase in adipose tissue inflammation and wound repair

D‐dopachrome tautomerase (D‐DT/MIF‐2) is a member of the macrophage migration inhibitory factor (MIF) cytokine superfamily, and a close structural homolog of MIF. MIF and D‐DT have been reported to be involved in obesity, but there is little known about the regulation of D‐DT in adipose tissue inflammation and wound healing. Subcutaneous adipose tissue was collected from 54 healthy donors and 28 donors with acutely inflamed wounds undergoing wound debridement. In addition, epididymal fat pads of mice were injected with lipopolysaccharide to study receptor expression and cell migration in vivo. D‐DT protein levels and mRNA expression were significantly decreased in subcutaneous adipose tissue adjacent to acutely inflamed wounds. D‐DT improved fibroblast viability and increased proliferation in vitro. While D‐DT alone did not have a significant effect on in vitro fibroblast wound healing, simultaneous addition of neutralizing MIF antibody resulted in a significant improvement of fibroblast wound healing. Interestingly, expression of the MIF and D‐DT receptor CD74 was down‐regulated while the MIF receptors CXCR2 and CXCR4 were up‐regulated primarily on macrophages indicating that the MIF‐CXCR2/4 axis may promote recruitment of inflammatory cells into adipose tissue. Our results describe a reciprocal role of D‐DT to MIF in inflamed adipose tissue, and indicate that D‐DT may be beneficial in wound repair by improving fibroblast survival and proliferation.     

Design,Synthesis, Biological Evaluation and Molecular Docking Studies of Quercetin-Linker-H2S Donor Conjugates for the Treatment of Diabetes and Wound Healing**

Based on the use of quercetin for treating diabetes and H₂S for promoting wound healing, a series of three quercetin-linker-H₂S donor conjugates was designed, synthesized and characterized by ¹H-NMR, ¹³C-NMR and MS. Meanwhile, in vitro evaluation of these compounds was also researched by IR-HepG2 treatment experiment, MTT assay, scratch test and tubule formation experiment. The three compounds could be used to treat insulin resistance induced by high glucose and promote the proliferation of human umbilical vein endothelial cells, wound healing, and the formation of tubules in vitro under a high-glucose environment. Our results illustrate that these compounds could be used to treat diabetes and promote wound healing at the same time. Furthermore, molecular docking study results of the compounds were consistent with the evaluated biological activity. In vivo research of compounds is underway.     

Novel 14S,21‐dihydroxy‐docosahexaenoic acid rescues wound healing and associated angiogenesis impaired by acute ethanol intoxication/exposure

Acute ethanol intoxication and exposure (AE) has been known to impair wound healing and associated angiogenesis. Here, we found that AE diminished the formation of novel reparative lipid mediator 14S,21‐dihydroxy‐docosa‐4Z,7Z,10Z,12E,16Z,19Z‐hexaenoic acid (14S,21‐diHDHA) and its biosynthetic intermediate 14S‐hydroxy‐DHA (14S‐HDHA) from docosahexaenoic acid (DHA) in murine wounds. However, AE did not reduce the formation of DHA and the intermediate 21‐HDHA. These results indicate that in the biosynthetic pathways of 14S,21‐diHDHA in wounds, AE suppresses the 14S‐hydroxy‐generating activity of 12‐lipoxygenase‐like (LOX‐like), but does not suppress the 21‐hydroxy‐generating activity of cytochrome P450 and DHA‐generating activities. The AE‐suppression of 12‐LOX‐like activity was further confirmed by the diminished formation of 12‐hydroxy‐eicosatetraenoic acid in wounds under AE. Supplementing 14S,21‐diHDHA to wounds rescued the AE‐impaired healing and vascularization. 14S,21‐diHDHA restored AE‐impaired processes of angiogenesis in vitro: endothelial cell migration, tubulogenesis, and phosphorylation of p38 mitogen‐activated protein kinase (MAPK). Taken together, the suppression of 14S,21‐diHDHA formation is responsible, at least partially, for the AE‐impairment of cutaneous wound healing and angiogenesis. Supplementing 14S,21‐diHDHA to compensate its deficit in AE‐impaired wounds rescues the healing and angiogenesis. These results provide a novel mechanistic insight for AE‐impaired wound healing that involves the necessary roles of 14S,21‐diHDHA. They also offer leads for developing 14S,21‐diHDHA‐related therapeutics to ameliorate AE‐impairment of wound healing. J. Cell. Biochem. 111: 266–273, 2010. © 2010 Wiley‐Liss, Inc.     

The wound inflammatory response exacerbates growth of pre‐neoplastic cells and progression to cancer

There is a long‐standing association between wound healing and cancer, with cancer often described as a “wound that does not heal”. However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of Ras^G12V‐driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre‐neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre‐neoplastic cells and these interactions lead to increased proliferation of the pre‐neoplastic cells. One of the wound‐inflammation‐induced trophic signals is prostaglandin E₂ (PGE₂). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome.     

Association of the CPT1B Gene with Skeletal Muscle Fat Infiltration in Afro‐Caribbean Men

Skeletal muscle fat is greater in African ancestry individuals compared with whites, is associated with diabetes, and is a heritable polygenic trait. However, specific genetic factors contributing to skeletal muscle fat in humans remain to be defined. Muscle carnitine palmitoyltransferase‐1B (CPT1B) is a key enzyme in the regulation of skeletal muscle mitochondrial β‐oxidation of long‐chain fatty acids, and as such is a reasonable biological candidate gene for skeletal muscle fat accumulation. Therefore, we examined the association of three nonsynonymous coding variants in CPT1B (G531L, I66V, and S427C; a fourth, A320G, could not be genotyped) and quantitative computed tomography measured tibia skeletal muscle composition and BMI among 1,774 Afro‐Caribbean men aged ≥40, participants of the population‐based Tobago Health Study. For all variants, no significant differences were observed for BMI or total adipose tissue. Among individuals who were homozygous for the minor allele at G531L or I66V, intermuscular adipose tissue (IMAT) was 87% (P = 0.03) and 54% lower (P = 0.03), respectively. In contrast, subcutaneous adipose tissue (SAT) was 11% (P = 0.017) and 7% (P = 0.049) higher, respectively, than among individuals without these genotypes. These associations were independent of age, body size, and muscle area. Finally, no individuals with type 2 diabetes were found among those who were homozygous for the minor allele of either at G531L and I66V whereas 14–18% of men with the major alleles had type 2 diabetes (P = 0.03 and 0.007, respectively). Our results suggest a novel association between common nonsynonymous coding variants in CPT1B and ectopic skeletal muscle fat among middle‐aged and older African ancestry men.     

Fluorescence and ultrastructural localization of aminergic neurons in the nerve cord of Eisenia foetida (Annelida—Oligochaeta)

Summary The aminergic nature of the CV neurons present in the genital segments of the nerve cord of Eisenia foetida is demonstrated by fluorescence microscopy and by the chromaffin reaction modified for electron microscopy.     

Bisindole‐oxadiazole hybrids,T3P®‐mediated synthesis,and appraisal of their apoptotic,antimetastatic, and computational Bcl‐2 binding potential

In the pursuit of novel anticancer leads, new bisindole‐oxadiazoles were synthesized using propyl phosphonic anhydride as a mild and efficient reagent. The molecule, 3‐[5‐(1H‐indol‐3‐ylmethyl)‐1,3,4‐oxadiazol‐2‐yl]‐1H‐indole ( 3a ) exhibited selective cytotoxicity to MCF‐7 cells with a cell cycle arrest in the G1 phase. The mechanism of cytotoxicity of 3a involved caspase‐2‐dependent apoptotic pathway with characteristic apoptotic morphological alterations as observed in acridine orange/ethidium bromide and Hoechst staining. The wound healing migratory assay exhibited an intense impairment in the motility of MCF‐7 cells on incubation with 3a . Docking simulations with anti‐apoptotic protein Bcl‐2, which is also involved in cancer metastasis displayed good affinity and high binding energy of 3a into the well characterized BH3 binding site. The positive correlation between the Bcl‐2 binding studies and the results of in vitro investigations exemplifies compound 3a as a lead molecule exhibiting MCF‐7 differential cytotoxicity via apoptotic mode of cell death in addition to its anti‐metastatic activity.     

Superpulsed (Ga‐As, 904 nm) low‐level laser therapy (LLLT) attenuates inflammatory response and enhances healing of burn wounds

Low‐level laser therapy (LLLT) using superpulsed near‐infrared light can penetrate deeper in the injured tissue and could allow non‐pharmacological treatment for chronic wound healing. This study investigated the effects of superpulsed laser (Ga‐As 904 nm, 200 ns pulse width; 100 Hz; 0.7 mW mean output power; 0.4 mW/cm² average irradiance; 0.2 J/cm² total fluence) on the healing of burn wounds in rats, and further explored the probable associated mechanisms of action. Irradiated group exhibited enhanced DNA, total protein, hydroxyproline and hexosamine contents compared to the control and silver sulfadiazine (reference care) treated groups. LLLT exhibited decreased TNF‐α level and NF‐kB, and up‐regulated protein levels of VEGF, FGFR‐1, HSP‐60, HSP‐90, HIF‐1α and matrix metalloproteinases‐2 and 9 compared to the controls. In conclusion, LLLT using superpulsed 904 nm laser reduced the inflammatory response and was able to enhance cellular proliferation, collagen deposition and wound contraction in the repair process of burn wounds.

Photomicrographs showing no, absence inflammation and faster wound contraction in LLLT superpulsed (904 nm) laser treated burn wounds as compared to the non‐irradiated control and silver sulfadiazine (SSD) ointment (reference care) treated wounds     

MiR‐129‐5p inhibits glioma cell progression in vitro and in vivo by targeting TGIF2

This study purposed to explore the correlation between miR‐129‐5p and TGIF2 and their impacts on glioma cell progression. Differentially expressed miRNA was screened through microarray analysis. MiR‐129‐5p expression levels in glioma tissues and cells were measured by qRT‐PCR. CCK‐8 assay, flow cytometer, transwell assay and wound‐healing assay were employed to detect cell proliferation, apoptosis and cycle, invasiveness and migration, respectively. Dual‐luciferase reporting assay was performed to confirm the targeted relationship between miR‐129‐5p and TGIF2. The effects of TGIF2 expression on cell biological functions were also investigated using the indicated methods. Tumour xenograft was applied to explore the impact of miR‐129‐5p on tumorigenesis in vivo. MiR‐129‐5p expression was down‐regulated in both glioma tissues and glioma cells, while TGIF2 expression was aberrantly higher than normal level. Dual‐luciferase reporter assay validated the targeting relation between miR‐129‐5p and TGIF2. Overexpression of miR‐129‐5p or down‐regulation of TGIF2 inhibited the proliferation, invasion and migration capacity of glioma cells U87 and U251, and meanwhile blocked the cell cycle as well as induced cell apoptosis. MiR‐129‐5p overexpression repressed the tumour development in vivo. MiR‐129‐5p and TGIF2 had opposite biological functions in glioma cells. MiR‐129‐5p could inhibit glioma cell progression by targeting TGIF2, shining light for the development of target treatment for glioma.