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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-β1 (TGF-β1) 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-β/Smad signaling pathway in fibroblasts. Collectively, ATF3 could promote growth and invasion, and inhibit apoptosis via TGF-β/Smad pathway in keloid fibroblast cells, suggesting that ATF3 might be considered as a novel therapeutic target for the management of keloid., GRAPHICAL ABSTRACT

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 ± 9.5) were significantly higher than those before treatment (54.6 ± 9.3) and those of the control group (58.3 ± 10.2) (P

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)(H2O)] 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.

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 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-1β 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.

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 (p0.05), 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 (p0.05), 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 (p0.05), 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 (p0.05), 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 (p0.05). 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.