Activating transcription factor 3 (ATF3) regulates cell growth, apoptosis, invasion and collagen synthesis in keloid fibroblast through transforming growth factor beta (TGF-beta)/SMAD signaling pathway.

The successful treatment of keloids is a great challenge in the plastic surgery field. Activating transcription factor 3 (ATF3) is discovered as an adaptive responsive gene, which plays a critical role in fibroblast activation. This study aimed to investigate the expression and biological role of ATF3 in the pathogenesis of keloids. ATF3 expression in normal skins and keloids was evaluated by real-time PCR, western blot and immunohistochemistry. Effects of ATF3 on cell growth, apoptosis, invasion and collagen production were evaluated in keloid fibroblast cells overexpressing or downregulating ATF3. ATF3 expression was significantly elevated in keloid tissues when compared with that of normal skins and parakeloidal skin tissues. Moreover, ATF3 promoted cell proliferation and collagen production in keloid fibroblast cells. Conversely, transfection with siRNA targeting ATF3 led to decreased cell viability and collagen synthesis via inhibiting transforming growth factor-ß1 (TGF-ß1) and fibroblast growth factor 2/8 (FGF2/8) production in keloid fibroblasts. ATF3 could reduce the apoptosis rate of keloid fibroblast cells. Molecularly, we found that ATF3 promoted BCL2 level and inhibit the expression of BCL2 associated agonist of cell death (Bad), Caspase3 and Caspase9 in keloid fibroblast cells. ATF3 also enhanced the invasive potential via upregulating the expression of Matrix Metalloproteinases (MMP) family members (MMP1, MMP2, MMP9 and MMP13). ATF3 could induce activation of TGF-ß/Smad signaling pathway in fibroblasts. Collectively, ATF3 could promote growth and invasion, and inhibit apoptosis via TGF-ß/Smad pathway in keloid fibroblast cells, suggesting that ATF3 might be considered as a novel therapeutic target for the management of keloid.

Effects of the portage early education program on Chinese children with global developmental delay.

Children with global developmental delay (GDD) were trained with the Portage Guide to Early Education (PGEE) program.In the treatment group, the PGEE program was performed on children with GDD (45 cases) through a combination of family and hospital interventions, in a 1-to-1 ratio. The Gesell Infant Development Scale (GESELL) developmental quotient (DQ) and social adaptability were measured before and 6 months after PGEE implementation in the treatment group. These parameters were also evaluated in a control group (30 cases) during an initial visit and 6 months later.Before the PGEE intervention, no significant differences were observed between the general characteristics of children in the control and treatment groups. Six months after the PGEE intervention, the DQ values of the children with GDD in the treatment group (64.7 ±â€Š9.5) were significantly higher than those before treatment (54.6 ±â€Š9.3) and those of the control group (58.3 ±â€Š10.2) (P < .05). The PGEE intervention significantly increased the DQ values on 5 aspects, including gross motor, fine motor, adaptability, language, and personal social activity abilities, and the scores on the Infants-Junior Middle School Students' Social-Life Abilities Scales (SM scales), as compared with the control group (P < .05).The PGEE program improves the DQ, social adaptability, and prognosis of children with GDD.

Effects of endoplasmic reticulum stress on the expression of inflammatory cytokines in patients with ulcerative colitis.

AIM: To explore the changes of X-box binding protein 1 splicing (XBP1s) and inflammatory cytokine expression in patients with ulcerative colitis (UC) in response to endoplasmic reticulum stress (ERS). METHODS: Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction were performed to detect the forms of XBP1s and the expression of interleukin (IL)-2, interferon (IFN)-γ, and IL-17α. Differences between patients with UC and normal subjects were then determined. RESULTS: Mononuclear cells of the peripheral blood of normal subjects and UC patients with were stimulated with no drugs (control), phytohemagglutinin (PHA), thapsigargin (TG), or both PHA and TG. XBP1s in patients with UC exhibited splicing, which was greater with co-stimulation than single stimulation. Co-stimulation increased the expression level of IL-2, IFN-γ, and IL-17α. CONCLUSION: The T lymphocytes of both normal subjects and patients with UC responded to ERS by activating the XBP1s-mediated signalling pathway, upregulating the expression of inflammatory cytokines, and increasing the occurrence of inflammation. The mononuclear cells in the peripheral blood of patients with UC were more sensitive to ERS than those in the peripheral blood of normal subjects.

Aloe vera and Vitis vinifera improve wound healing in an in vivo rat burn wound model.

Aloe vera and Vitis vinifera have been traditionally used as wound healing agents. The present study aimed to investigate the effects of aloe emodin and resveratrol in the burn wound healing procedure. Burn wounds are common in developed and developing countries, however, in developing countries, the incidence of severe complications is higher and financial resources are limited. The results of the present study demonstrated that neither aloe emodin or resveratrol were cytotoxic to THP-1 macrophages at concentrations of 1, 100 and 500 ng/ml. A significant increase in wound-healing activity was observed in mice treated with the aloe emodin and resveratrol, compared with those which received control treatments. The levels of IL-1ß in the exudates of the burn wound area of the treated mice increased in a time-dependent manner over 7 days following burn wound injury. At 10 days post-injury, steady and progressive wound healing was observed in the control animals. The present study confirmed that increased wound healing occurs following treatment with aloe emodin,, compared with resveratrol, providing support for the use of Aloe vera plants to improve burn wound healing.

A New Infracture Technique for Reduction Malarplasty with an L-Shaped Osteotomy Line.

BACKGROUND: Reduction malarplasty is one of the most common surgical procedures performed in the Asian population for aesthetic purposes. Although multiple methods have been developed for reduction malarplasty, including a variety of infracture techniques, most of the current procedures have limitations. In the current study we created a new infracture method to circumvent these shortcomings. MATERIAL AND METHODS: Between January 2004 and October 2013, we applied this novel infracture technique in 700 patients. The highest area of the zygomatic body was marked pre-operatively and ground intra-operatively through an intraoral incision. An L-shaped incomplete osteotomy of the zygomatic body was performed with a reciprocating saw, and then a complete perpendicular osteotomy (1 cm anterior to the articular tubercle of the zygomatic arch) was made through a pre-auricular incision. Light pressure on the posterior part of the arch produced a greenstick fracture of the anterior osteotomy site, resulting in posterior-inward repositioning of the malar complex. Internal fixation was not required. RESULTS: Satisfactory aesthetic results and good post-operative stability were achieved. Three months post-operatively, the bone around the zygomatic arc osteotomy line was remodeled. The bone posterior to the articular tubercle of the zygomatic arch was partially absorbed, leading to a depression of the root of the arc and a natural transition on both sides of the osteotomy line, making the midface more slender. Instead, the anterior bone presented with new bones, making the malar complex more stable. CONCLUSIONS: This new method has multiple advantages, including simple manipulation, no need for internal fixation, short operative and recovery times, and few complications. X-ray images showing the bony changes demonstrated that the infracture technique is an effective and ideal method for reduction malarplasty.

Isolation and characterization of a novel lectin with mitogenic activity from Pleurotus ferulae.

Lectins are the tools for the determination of sugar chain structure. Recently, lectin arrays have become a popular new technology; therefore, lectins with specific sugar-binding properties are required. The objective of the study was to isolate a novel lectin from Pleurotus ferulae mushrooms and characterize its various biological activities. A novel lectin was extracted with deionized water, precipitated from the aqueous extract using 75% saturated (NH4)2SO4, and subjected on DEAE-cellulose followed by affinity chromatography on sepharose-6B. The activity was tested using hemagglutination assays, and carbohydrate-binding specificity was determined by glycan microarray analysis. Its effects on the mitogenic activity of mouse splenocytes were determined by MTT assay. The novel lectin was adsorbed on ion-exchange chromatography DEAE-cellulose and shown as a band with the molecular mass of 17.5 kDa on a SDS-PAGE and as a single 35.0-kDa peak in gel filtration on Superdex G-75. The hemagglutinating activity of the lectin was inhibited by D-glucose, lactose, D-galactose, and galactosamine. The lectin was stable on 60°C. The hemagglutinating activity of lectin was reduced by 50% at 70°C. At 80°C, it was further reduced to 6.25% of its original activity. The hemagglutinating activity was the highest at pH 6-9. Moreover, its hemagglutinating activity was inhibited by Mg2+ and Ca2+ ions. The lectin isolated from P. ferulae in the current study possessed highly potent hemagglutinating and proliferative activities toward mouse splenocytes.

Interaction of manganese(II) complex with apotransferrin and the apotransferrin enhanced anticancer activities.

Apotransferrin could bind a number of metal ions besides Fe, which makes it an attractive delivery vehicle for metal-based medicines. In order to evaluate whether anticancer Mn(II) complex of [(Adpa)Mn(Cl)(H(2)O)] Adpa=bis(2-pyridylmethyl)amino-2-propionic acid) (AdpaMn) could be transported by apotransferrin, we investigated its interaction with human apotransferrin by fluorescence and circular dichroism spectroscopy (CD). The association dynamics show that AdpaMn could bind to apotransferrin spontaneously in Hepes buffer. Synchronous fluorescence spectroscopy and CD spectroscopy show that the conjugation of AdpaMn and apotransferrin by hydrophobic interactions induces the change of the microenvironment and conformation of apotransferrin. The reversible binding and release of AdpaMn was studied with fluorescence titration method. The AdpaMn complex can be released from the AdpaMn-apotransferrin entity in weak acid environments. MTT assay in vitro confirms that apotransferrin can enhance the inhibition rate of AdpaMn on the proliferation of HepG-2 cells, so we deduce that AdpaMn could be transported by apotransferrin in vivo.

ErbB4 in parvalbumin-positive interneurons is critical for neuregulin 1 regulation of long-term potentiation.

Neuregulin 1 (NRG1) is a trophic factor that acts by stimulating ErbB receptor tyrosine kinases and has been implicated in neural development and synaptic plasticity. In this study, we investigated mechanisms of its suppression of long-term potentiation (LTP) in the hippocampus. We found that NRG1 did not alter glutamatergic transmission at SC-CA1 synapses but increased the GABA(A) receptor-mediated synaptic currents in CA1 pyramidal cells via a presynaptic mechanism. Inhibition of GABA(A) receptors blocked the suppressing effect of NRG1 on LTP and prevented ecto-ErbB4 from enhancing LTP, implicating a role of GABAergic transmission. To test this hypothesis further, we generated parvalbumin (PV)-Cre;ErbB4(-/-) mice in which ErbB4, an NRG1 receptor in the brain, is ablated specifically in PV-positive interneurons. NRG1 was no longer able to increase inhibitory postsynaptic currents and to suppress LTP in PV-Cre;ErbB4(-/-) hippocampus. Accordingly, contextual fear conditioning, a hippocampus-dependent test, was impaired in PV-Cre;ErbB4(-/-) mice. In contrast, ablation of ErbB4 in pyramidal neurons had no effect on NRG1 regulation of hippocampal LTP or contextual fear conditioning. These results demonstrate a critical role of ErbB4 in PV-positive interneurons but not in pyramidal neurons in synaptic plasticity and support a working model that NRG1 suppresses LTP by enhancing GABA release. Considering that NRG1 and ErbB4 are susceptibility genes of schizophrenia, these observations contribute to a better understanding of how abnormal NRG1/ErbB4 signaling may be involved in the pathogenesis of schizophrenia.

[Effects of STI571 combined with As2O3 on proliferation, apoptosis and caspase 3, Bcl-xL expression of K562 cells].

This study was aimed to explore the effects of STI571 alone or with As2O3 on proliferation, apoptosis and caspase 3, bcl-xL mRNA expression of K562 cells, and the molecular mechanism of As2O3 enhancing the anti-leukemia effect of STI571 so as to provide the scientific basis for clinical treatment of chronic myeloid leukemia. The effect of drugs on proliferation of K562 cells was assayed by MTT method, the apoptosis rate of K562 cells was detected by flow cytometry with Annexin V/PI double staining, the caspase 3, bcl-xL mRNA expressions of K562 cells were determined by real time quantitative PCR. The results showed that STI571 alone or with As2O3 both could inhibit the proliferation of K562 cells. OD value in test groups reduced along with prolonging of action times, the OD values between different time points were significantly different (p < 0.05), furthermore the OD values at 72 hours in test groups were lowest, while as compared with control group, OD values at same time points in test groups all gradually decreased, among which decrease of OD value in test 5 group was most significant. The flow cytometric detection indicated that along with time prolonging, the apoptotic rate in control group not obviously changed, but the apoptotic rate in test groups gradually increased, the difference between time points was significant (p < 0.05), moreover apoptotic rate increased most obviously at 72 hours, while as compared with control group, apoptotic rate at same time points in test groups was gradually enhanced (p < 0.05), among which the apoptotic rate in test 5 group was highest. The real time qPCR assay revealed that as compared with control group, the bcl-xL mRNA expression in test groups reduced with decrease of 2-ΔΔCT value, furthermore the decrease of expression level in test 3 group was higher than that in test 2 group (p < 0.05), while the caspase 3 mRNA expression in test groups was enhanced with increase of 2-ΔΔCT value, moreover the increase of expression level in test 3 group was higher than that in test 2 group (p < 0.05). It is concluded that the STI571 can inhibit the proliferation of K562 cells, accelerate the apoptosis of K562 cells. The STI571 combined with As2O3 can enhance these two effects, increase the expression of caspase-3 mRNA and decrease the expression of bcl-xL mRNA. Therefore, the effect of STI571 combined with As2O3 on expression of caspase 3 and bcl-xL mRNA may be one of molecular mechanisms underlying their synergic antileukemia efficacy.

[Perfusion-weighted magnetic resonance imaging for monitoring vascularization in tissue-engineered bone in rhesuses].

OBJECTIVE: To assess the value of perfusion-weighted magnetic resonance (MR) imaging (PWMRI) in monitoring vascularization in tissue-engineered bone graft. METHODS: Tibial diaphyseal defect of 20 mm was induced in 25 lower limbs of 13 rhesuses and fixed with an AO reconstruction plate with 7 holes. The monkeys were randomized into 5 groups according to the materials used for defect filling: group A, with beta-tricalcium phosphate (beta-TCP), bone marrow stromal cells (BMSCs) and blood vessel bundles; group B, with beta-TCP and blood vessel bundles; group C, with beta-TCP and BMSCs; group D, with beta-TCP, and group E without filling. PWMRI, X-ray, and radionuclide imaging were carried out at weeks 4, 8, 12 postoperatively. The maximum slope rates of the single intensity-time curve (SS(max)) and the baseline values (SI(baseline)) on the same time points were calculated. Transmittances on the X-ray films and isotope counts in the region of interest (ROI) were assessed and calculated. RESULTS: Compared with other groups, group A showed the highest SS(max) at weeks 4, 8, and 12 postoperatively, and its SS(max) at week 8 was significantly higher than that at week 4 (P=0.003). The SS(max) was positively related to isotope counts in ROI at week 8 after operation (r(s)=0.899, P=0.038), and inversely related to transmittance on X-ray films at week 12 (r(s)=-0.892, P=0.042). CONCLUSION: The SS(max) of the single intensity-time curve can accurately reflect the vascularization of the tissue-engineered bone graft, and PWMRI allows sensitive, quantitative, noninvasive and radiation-free vascularization monitoring.