Graphene Oxide/Gelatin Nanofibrous Scaffolds Loaded with N-Acetyl Cysteine for Promoting Wound Healing.

Purpose: We aimed to develop an antioxidant dressing material with pro-angiogenic potential that could promote wound healing. Gelatin (Gel) was selected to improve the biocompatibility of the scaffolds, while graphene oxide (GO) was added to enhance their mechanical property. The loaded N-Acetyl cysteine (NAC) was performing the effect of scavenging reactive oxygen species (ROS) at the wound site. Materials and Methods: The physicochemical and mechanical properties, NAC releases, and biocompatibility of the NAC-GO-Gel scaffolds were evaluated in vitro. The regeneration capability of the scaffolds was systemically investigated in vivo using the excisional wound-splinting model in mice. Results: The NAC-GO-Gel scaffold had a stronger mechanical property and sustainer NAC release ability than the single Gel scaffold, which resulted in a better capacity for cell proliferation and migration. Mice wound-splinting models revealed that the NAC-GO-Gel scaffold effectively accelerated wound healing, promoted re-epithelialization, enhanced neovascularization, and reduced scar formation. Conclusion: The NAC-GO-Gel scaffold not only promotes wound healing but also reduces scar formation, showing a great potential application for the repair of skin defects.

Circ-FAT1 Up-Regulates FOSL2 Expression by Sponging miR-619-5p to Facilitate Colorectal Cancer Progression.

Circular RNA FAT atypical cadherin 1 (circ-FAT1) has been reported to play roles in colorectal cancer (CRC) development. Here, the purpose of this study was to investigate the function and mechanism of circ-FAT1 in CRC tumorigenesis and its potential value in the clinic. Levels of genes and proteins were examined by quantitative real-time polymerase chain reaction and Western blot. In vitro assays were conducted using cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, transwell assay, and tube formation assay, respectively. The target relationship between miR-619-5p and circ-FAT1 or FOS-like antigen 2 (FOSL2) was verified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was performed using a mouse subcutaneous xenograft model. Circ-FAT1 and FOSL2 were highly expressed in CRC tissues and cells. Functionally, knockdown of circ-FAT1 or FOSL2 suppressed CRC cell apoptosis, migration, invasion, and angiogenesis, but induced cell apoptosis in vitro. Mechanistically, circ-FAT1 acted as a sponge for miR-619-5p to up-regulate the expression of FOSL2, which was confirmed to be a target of miR-619-5p. A series of rescue experiments demonstrated that miR-619-5p inhibition or FOSL2 overexpression reversed the inhibitory action of circ-FAT1 silencing on CRC cell malignant phenotypes mentioned above. Pre-clinically, lentivirus-mediated circ-FAT1 knockdown inhibited the tumorigenesis of CRC xenografts in nude mice via regulating miR-619-5p and FOSL2. Circ-FAT1 knockdown repressed FOSL2 expression by sponging miR-619-5p to suppress CRC tumorigenesis, providing a potential approach for CRC therapeutics.

Exosomes Derived by SIRT1-Overexpressing Bone Marrow Mesenchymal Stem Cells Improve Pubococcygeus Muscle Injury in Rats.

BACKGROUND AND OBJECTIVES: To evaluate the effect of exosomes (Exos) derived from silent mating type information regulation 2 homolog 1 (SIRT1)-overexpressing human bone marrow mesenchymal stem cells (BMSCs) on the recovery of pubococcygeus muscle Injury. METHODS AND RESULTS: Exos isolated from SIRT1-overexpressing BMSCs (SIRT1/exos) were injected into a vaginal dilation-induced rat model of Stress urinary incontinence (SUI). The efficacy of Exos treatment on SUI was evaluated by determining the values of urodynamic parameters. The proliferation and differentiation of satellite cells (SCs) were examined by CCK-8 assay, Western blotting, and immunofluorescence staining. The mRNA and protein expression of molecules related to SC differentiation were detected by RT-qPCR and Western blotting, respectively. Treatment with SIRT1/exos significantly improved the values of abdominal leak point pressure (ALPP), maximum bladder volume (MBV), and estimated marginal mean in rats of SUI. Exposure of SIRT1/exos enhanced the proliferation, differentiation, and activation of SCs. Moreover, SIRT1/exos exhibited their positive effect on BMSCs by activating the ERK signaling. CONCLUSIONS: Our findings demonstrated that SIRT1/exos meliorated pubococcygeus muscle injury in rats by promoting ERK pathway, which may provide a novel cell-free therapeutic strategy for SUI.

First known case of successful pressure ulcer treatment in a lung transplant patient with post-COVID-19 pneumonia.

Given the current COVID-19 crisis, multiple clinical manifestations and related complications of COVID-19 disease, especially in lung transplant patients following post-COVID-19 pneumonia, are a major challenge. Herein, we report the therapeutic course of the first reported case of sacrococcyx pressure ulcers (PU) in a 65-year-old male COVID-19 patient who underwent lung transplantation and developed a PU following surgery. We used a combination of regulated negative pressure-assisted wound therapy system (RNPT, six treatment courses, five days per treatment course), a skin tension-relief system (an intraoperative aid in minimising wounds caused by sacrococcygeal PUs) and a gluteus maximus myocutaneous flap to repair sacrococcygeal wounds. This successfully treated case provides a reference point for the treatment of similar cases.

Adipose-derived mesenchymal stem cells from obese mice prevent body weight gain and hyperglycemia.

Changes that occur to the stem cell microenvironment with disease are a major consideration that may affect the behavior and potential therapeutic efficacy of mesenchymal stem cells (MSCs). The purpose of this study is to evaluate the effects of adipose-derived MSCs (ADSCs) from obese mice with hyperglycemia on body weight and glucose homeostasis. After 10 weeks of high-fat diet, mice were injected with phosphate-buffered saline (PBS) and ADSCs derived from normal mice (N-ADSCs) or obese mice (O-ADSCs), respectively. Mice fed with standard rodent chow were injected with PBS and served as normal controls. Obese mice treated with O-ADSCs showed less body weight gain than those receiving PBS or N-ADSCs. The mice that received ADSCs, especially O-ADSCs, also showed improvement in obesity-related hyperglycemia. In particular, the inguinal fat was reduced in obese mice receiving O-ADSCs compared with other groups, probably caused by the increased lipolysis of inguinal fat. Moreover, ADSC infusion restored insulin receptor (INSR) expression in the muscle of obese mice. Differential expression of the CD90 surface marker was slightly increased, while monocyte chemoattractant protein 1 (MCP-1) was reduced in O-ADSCs compared to N-ADSCs. These data provide a theoretical basis that autologous ADSCs from obese individuals may be more effective for treating obesity and related hyperglycemia.

Human umbilical cord mesenchymal stem cell-derived and dermal fibroblast-derived extracellular vesicles protect dermal fibroblasts from ultraviolet radiation-induced photoaging in vitro.

Ultraviolet B (UVB) radiation is a major cause of aging in dermal fibroblasts. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show antioxidant activity. In this study, the anti-aging effects of MSC-EVs on dermal fibroblast photoaging induced by UVB radiation were evaluated, and the effects of extracellular vesicles derived from dermal fibroblasts (Fb-EVs) were compared. Human umbilical cord mesenchymal stem cells and human dermal fibroblasts were cultured, and MSC-EVs and Fb-EVs were isolated and characterized. Human dermal fibroblasts were cultured in the absence or presence of different concentrations of EVs 24 hours prior to UVB radiation exposure. Cell proliferation and cell cycle were evaluated, and senescent cells and intracellular ROS were detected. The expressions of matrix metalloproteinase-1 (MMP-1), extracellular matrix protein collagen type 1 (Col-1), and antioxidant proteins such as glutathione peroxidase 1 (GPX-1), superoxide dismutase (SOD), and catalase were also analyzed. Pretreatment with MSC-EVs or Fb-EVs significantly inhibited the production of ROS induced by UVB radiation, increased dermal fibroblast proliferation, protected cells against UVB-induced cell death and cell cycle arrest, and remarkably decreased the percentage of aged cells. Pretreatment with MSC-EVs or Fb-EVs promoted the expressions of GPX-1 and Col-1 and decreased the expression of MMP-1. Both MSC-EVs and Fb-EVs protected dermal fibroblasts from UVB-induced photoaging, likely through their antioxidant activity.

Cell-free fat extract promotes tissue regeneration in a tissue expansion model.

BACKGROUND: Tissue expansion techniques play an important role in plastic surgery. How to improve the quality of the expanded skin and shorten the expansion period are still worth investigating. Our previous studies found that a cell-free fat extract (CEFFE) possessed pro-angiogenic and pro-proliferative activities. However, the role of CEFFE on tissue expansion has remained unclear. The purpose of this study was to evaluate the effect of CEFFE on tissue expansion. METHODS: A rat tissue expansion model was used. Animals were treated with CEFFE by subcutaneous injection. After 4 weeks of tissue expansion, the skin necrosis and retraction rates were evaluated, the thicknesses of the epidermis and dermis were determined by histological analyses, blood vessel density was measured by anti-CD31 staining, cell proliferation was assessed by proliferating cell nuclear antigen staining, and the expression of specific proteins was evaluated by western blot analyses. In addition, the effects of CEFFE on the proliferation and cell cycle of cultured HaCaT cells were evaluated in vitro. RESULTS: CEFFE treatment significantly decreased the necrosis rate and retraction of the expanded skin. The thickness of the epidermal and dermal layers was higher in CEFFE-treated compared to untreated skin. The density of blood vessels and cell proliferation in the epidermis of the expanded skin was improved by CEFFE treatment. In addition, CEFFE treatment significantly increased the expression of the vascular endothelial growth factor receptor, epidermal growth factor receptor, collagen type 1, and collagen type 3. CEFFE also increased the proliferation of HaCaT cells in culture. CONCLUSIONS: CEFFE improves the quality of the expanded skin by promoting angiogenesis and cell proliferation. It could be potentially used clinically for augmenting tissue expansion.

Cell-Free Fat Extract Increases Dermal Thickness by Enhancing Angiogenesis and Extracellular Matrix Production in Nude Mice.

BACKGROUND: Although adipose-derived stem cells (ADSCs) and nanofat exert antiaging effects on skin, they contain cellular components that have certain limitations in clinical practice. Cell-free fat extract (Ceffe) is a fraction purified from nanofat through removal of cellular components and lipid remnants that contains various growth factors. OBJECTIVES: The purpose of this study was to evaluate the effects of Ceffe on cultured human dermal fibroblasts in vitro and on the dermis of nude mice in vivo. METHODS: In the in vitro study, human dermal fibroblasts were cultured with Ceffe for 72 hours, followed by flow cytometry measurement of cell proliferation and cell cycle. In the in vivo study, different concentrations of Ceffe were injected into the dorsal skin of nude mice for 4 weeks. The thickness of the dermis; proliferation of cells; density of the capillary; and expressions of type I and III collagen (Col-1 and Col-3), matrix metalloproteinase-1, matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-3 were measured through histologic and Western blot analyses. RESULTS: Ceffe significantly increased cell proliferation in cultured dermal fibroblasts. In the mouse skin, Ceffe significantly increased the thickness of the dermis, number of proliferating cells, density of the capillary, and expressions of Col-1 and Col-3. CONCLUSIONS: Ceffe increased the dermal thickness of nude mice, possibly by enhancing angiogenesis and extracellular matrix production, and can therefore be used for skin rejuvenation.

Characterization and identification of human immortalized granulosa cells derived from ovarian follicular fluid.

Follicular fluid serves a crucial role in follicular development and oocyte maturation. Increasing evidence indicates that follicular fluid is rich in proteins and functional cells. In addition to oocyte cells, follicular fluid contains granulosa, thecal and ovarian surface epithelial cells. Granulosa cells (GCs) represent the predominant somatic cell type of the ovarian follicle and are involved in steroidogenesis and folliculogenesis. However, the long-term culture of GCs in vitro remains challenging. The present study aimed to extend the culture of GCs in vitro. Human GCs were collected from the follicular fluid of patients included in an in vitro fertilization program and cultured in the presence of conditioned medium obtained from mouse embryonic fibroblasts. GCs were cultured for over a year and 130 passages, and the population doubling time was ~22 h. Cells presented epithelial-like morphology and a cobblestone-like appearance when they reached confluence. Flow cytometric analysis demonstrated that cells expressed CD29, CD166 and CD49f but not CD31, CD34, CD45, CD90, CD105 or CD13. Immunofluorescence staining revealed that cells expressed follicle stimulating hormone receptor, luteinizing hormone receptor and cytochrome P450 aromatase, which was confirmed by reverse transcription-quantitative polymerase chain reaction. In the presence of androstenedione, cells secreted estradiol. In addition, estradiol level was further stimulated by dibutyryl cAMP treatment. In addition, intracellular cAMP and progesterone expression levels were upregulated by follicle stimulating hormone and/or human chorionic gonadotropin. Furthermore, cells survived in severe combined immunodeficiency mice following intra-ovarian injection. Histological analysis revealed that certain cells formed follicle-like structures. The results from the present study suggested that immortalized GCs may be a useful tool for further research on GC and improve the clinical application of drugs such as follicle-stimulating hormone or human chorionic gonadotropin.

Cell-mediated delivery of VEGF modified mRNA enhances blood vessel regeneration and ameliorates murine critical limb ischemia.

Synthetic chemically modified mRNAs (modRNA) encoding vascular endothelial growth factor (VEGF) represents an alternative to gene therapy for the treatment of ischemic cardiovascular injuries. However, novel delivery approaches of modRNA are needed to improve therapeutic efficacy in the diseased setting. We hypothesized that cell-mediated modRNA delivery may enhance the in vivo expression kinetics of VEGF protein thus promoting more potent angiogenic effects. Here, we employed skin fibroblasts as a "proof of concept" to probe the therapeutic potential of a cell-mediated mRNA delivery system in a murine model of critical limb ischemia (CLI). We show that fibroblasts pre-treated with VEGF modRNA have the potential to fully salvage ischemic limbs. Using detailed molecular analysis we reveal that a fibroblast-VEGF modRNA combinatorial treatment significantly reduced tissue necrosis and dramatically improved vascular densities in CLI-injured limbs when compared to control and vehicle groups. Furthermore, fibroblast-delivered VEGF modRNA treatment increased the presence of Pax7+ satellite cells, indicating a possible correlation between VEGF and satellite cell activity. Our study is the first to demonstrate that a cell-mediated modRNA therapy could be an alternative advanced strategy for cardiovascular diseases.

Fat extract improves fat graft survival via proangiogenic, anti-apoptotic and pro-proliferative activities.

BACKGROUND: Our previous study proved that nanofat could enhance fat graft survival by promoting neovascularization. Fat extract (FE), a cell-free component derived from nanofat, also possesses proangiogenic activity. OBJECTIVES: The aim of this study was to investigate whether FE could improve fat graft survival and whether FE and nanofat could work synergistically to promote fat graft survival. The underlying mechanism was also investigated. METHODS: In the first animal study, human macrofat from lipoaspirate was co-transplanted into nude mice with FE or nanofat. The grafts were evaluated at 2, 4 and 12 weeks post-transplantation. In the second animal study, nude mice were transplanted with a mixture of macrofat and nanofat, followed by intra-graft injection of FE at days 1, 7, 14, 21 and 28 post-transplantation. The grafts were evaluated at 12 weeks post-transplantation. To detect the mechanism by which FE impacts graft survival, the proangiogenic, anti-apoptotic and pro-proliferative activities of FE were analysed in grafts in vivo and in cultured human vascular endothelial cells (HUVECs), adipose-derived stem cells (ADSCs) and fat tissue in vitro. RESULTS: In the first animal study, the weights of the fat grafts in the nanofat- and FE-treated groups were significantly higher than those of the fat grafts in the control group. In addition, higher fat integrity, more viable adipocytes, more CD31-positive blood vessels, fewer apoptotic cells and more Ki67-positive proliferating cells were observed in the nanofat- and FE-treated groups. In the second animal study, the weights of the fat grafts in the nanofat+FE group were significantly higher than those of the fat grafts in the control group. In vitro, FE showed proangiogenic effects on HUVECs, anti-apoptotic effects on fat tissue cultured under hypoxic conditions and an ability to promote ADSC proliferation and maintain their multiple differentiation capacity. CONCLUSIONS: FE could improve fat graft survival via proangiogenic, anti-apoptotic and pro-proliferative effects on ADSCs. FE plus nanofat-assisted fat grafting is a new strategy that could potentially be used in clinical applications.

Numerical optimal control of a size-structured PDE model for metastatic cancer treatment.

In this paper, we propose a unified size-structured PDE model for the growth of metastatic tumors, which extends a well-known coupled ODE-PDE dynamical model developed and studied in the literature. A treatment model based on the proposed unified PDE model is investigated via optimal control theory, where its first-order necessary optimality system characterizing the optimal control is derived. We prove that the uniqueness of the optimal control depends on the chosen objective functional, and the optimal control is of bang-bang type when it is unique. For obtaining its efficient numerical solutions, a projection gradient descent algorithm based on the characteristic scheme is developed for solving the established optimal treatment model. Several numerical examples are provided to validate our mathematical analysis and numerical algorithm, and also illustrate the biologically interesting treatment outcomes of different models and control strategies. Our simple model reveals that: (i) only the total drug dosage matters if one just cares about the final treatment output; (ii) given the same total drug dosage, the optimal bang-bang treatment plan outperforms the others in the sense that it maximally reduces the total tumor sizes during the whole period of treatment, although their final tumor sizes are the same.

Fat Extract Improves Random Pattern Skin Flap Survival in a Rat Model.

BACKGROUND: Adipose tissue and its derivatives, including adipose-derived stem cells, stromal vascular fraction (SVF), and SVF-gel, have been utilized in the treatment of many ischemic disorders. However, the utilization of these products is limited in clinical applications by concerns related to the presence of cells in these derivatives. OBJECTIVES: This study aimed to isolate a cell-free fat extract (FE) from fat tissue and to evaluate its proangiogenic ability in vitro as well as its protective effects on skin flap survival in vivo. METHODS: FE was isolated from human fat via a mechanical approach. The concentrations of several growth factors in the FE were determined by enzyme-linked immunosorbent assay. The proangiogenic ability of FE was evaluated utilizing assays of the proliferation, migration, and tube formation in human umbilical vein endothelial cells in vitro. The protective effects of FE on the survival of random pattern skin flaps were investigated by subcutaneous injection into rats. RESULTS: Enzyme-linked immunosorbent assay results revealed that FE contained proangiogenic growth factors that promoted proliferation, migration, and tube formation in human umbilical vein endothelial cells in vitro. In addition, FE reduced skin flap necrosis and increased survival, as demonstrated by macroscopic measurements and blood flow analysis. Histological analysis revealed that FE treatment increased the capillary density. CONCLUSIONS: FE is a cell-free, easy-to-prepare, and growth-factor-enriched liquid derived from human adipose tissue that possesses proangiogenic activity and improves skin flap survival by accelerating blood vessel formation. FE may be potentially used for treating ischemic disorders.

Fat extract promotes angiogenesis in a murine model of limb ischemia: a novel cell-free therapeutic strategy.

BACKGROUND: The proangiogenic capacity of adipose tissue and its derivatives has been demonstrated in a variety of studies. The paracrine mechanism of the cellular component is considered to play a critical role in the regenerative properties of these tissues. However, cell-based therapy for clinical application has been hindered by limitations such as safety, immunogenicity issues, and difficulties in cell preservation, transportation, and phenotype control. In the current study, we aimed to produce a cell-free extract directly from human fat tissue and evaluate its potential therapeutic efficacy. METHODS: We developed a novel physical approach to produce a cell-free aqueous extract from human fat tissue (fat extract (FE)). The therapeutic potential of FE was investigated in the ischemic hindlimb model of nude mice. After establishment of hindlimb ischemia with ligation of the left femoral artery and intramuscular injection of FE, blood perfusion was monitored at days 0, 7, 14, 21, and 28. Tissue necrosis and capillary density were evaluated. Enzyme-linked immunosorbent assay was used to analyze the growth factors contained in FE. Moreover, the proliferation, migration, and tube formation ability were tested on human umbilical vein endothelial cells (HUVECs) in vitro when treated with FE. The proangiogenic ability of FE was further assessed in an in-vivo Matrigel plug assay. RESULTS: FE was prepared and characterized. The intramuscular injection of FE into the ischemic hindlimb of mice attenuated severe limb loss and increased blood flow and capillary density of the ischemic tissue. Enzyme-linked immunosorbent assay showed that FE contained high levels of various growth factors. When added as a cell culture supplement, FE promoted HUVEC proliferation, migration, and tube formation ability in a dose-dependent manner. The subcutaneous injection of Matrigel infused with FE enhanced vascular formation. CONCLUSIONS: We developed a novel cell-free therapeutic agent, FE, produced from human adipose tissue. FE was able to attenuate ischemic injury and stimulate angiogenesis in ischemic tissues. This study indicates that FE may represent a novel cell-free therapeutic agent in the treatment of ischemic disorders.

Co-Transplantation of Nanofat Enhances Neovascularization and Fat Graft Survival in Nude Mice.

BACKGROUND: Autologous fat grafting is commonly used for soft-tissue augmentation and reconstruction. However, this technique is limited by a high rate of graft absorption. Thus, approaches to improve fat graft survival that promote neovascularization are of great interest. Nanofat has several beneficial features that may render it more suitable for clinical applications than other stem-cell based approaches. OBJECTIVES: We aimed to determine whether nanofat could enhance new vessel formation and improve the long-term retention of fat grafts. METHODS: Nanofat was processed via mechanical emulsification and filtration. Fat grafts were transplanted subcutaneously under the scalps of nude mice with different nanofat volumes or without nanofat. The grafted fat was dissected 12 weeks after transplantation. Graft weight and volume were measured, and histological evaluations, including capillary density measurement, were performed. RESULTS: The co-transplantation of fat with nanofat showed higher graft weight and volume retention, better histological structure, and higher capillary density compared to that in controls. However, there were no significant differences between the two nanofat volumes utilized. CONCLUSIONS: Nanofat can enhance neovascularization and improve fat graft survival, providing a potential clinically viable approach to fat graft supplementation in plastic and reconstructive surgery.

Bone marrow mesenchymal stem cell­derived extracellular vesicles improve the survival of transplanted fat grafts.

Autologous fat grafting is a promising surgical technique for soft tissue augmentation, reconstruction and rejuvenation. However, it is limited by the low survival rate of the transplanted fat, due to the slow revascularization of such grafts. Previous studies have demonstrated that bone marrow mesenchymal stem cell­derived extracellular vesicles (BMSC­EVs) are proangiogenic. The present study aimed to investigate whether BMSC­EVs could improve the survival of transplanted fat grafts. Extracellular vesicles were isolated from the supernatant of cultured rat bone marrow mesenchymal stem cells, and characterized by flow cytometry and scanning electron microscopy. Their proangiogenic potential was measured in vitro using tube formation and cell migration assays. Subsequently, human fat tissue grafts, alongside various concentrations of BMSC­EVs, were subcutaneously injected into nude mice. A total of 12 weeks following transplantation, the mice were sacrificed and the grafts were harvested. The grafts from the experimental group had a higher survival rate and an increased number of vessels compared with grafts from the control group, as demonstrated by tissue volume, weight and histological analyses. Reverse transcription­quantitative polymerase chain reaction analysis indicated that the expression levels of proangiogenic factors were increased in the experimental group compared with in the control group, thus suggesting that BMSC­EVs may promote neovascularization by stimulating the secretion of proangiogenic factors. The present study is the first, to the best of our knowledge, to demonstrate that supplementation of fat grafts with BMSC­EVs improves the long­term retention and quality of transplanted fat.

Expansion of CD26 positive fibroblast population promotes keloid progression.

BACKGROUND: Keloid is a skin fibrosis disease that characterised by invasive growth of fibroblasts and aberrant deposition of extracellular matrix. Studies indicated that keloid fibroblasts (KFs) is a class of 'activated' fibroblasts, which show accelerated proliferation and excessive extracellular matrix formation as compared with normal fibroblasts (NFs). However, the mechanism underlying keloid fibroblasts dysfunction is still unknown. OBJECTIVE: To verify CD26 expression difference between KFs and NFs, and investigate the function of CD26 positive fibroblasts in keloid progression. METHODS: KFs and NFs were isolated from Keloid tissues and normal skin tissues respectively. Flow cytometry was performed to isolate CD26+/CD26- fibroblasts from KFs and NFs. Proliferation of different fibroblasts were analyzed by CCK8 assay and Ki 67 straining. Profibrotic phenotype difference was detected by qRT-PCR, western blot, ELISA and immunofluorescence. Scratching experiment and transwell assay were used to assess invasion ability of CD26+/CD26- fibroblasts. Diprotin A was used as a CD26 inhibitor to further investigated the function of CD26 fibroblasts in keloid disease. RESULT: CD26 expression was increased in KFs, and the proportion of CD26+ fibroblasts was significantly increased in KFs. Cell viability analysis showed that CD26+ fibroblasts was more active in proliferation. Furthermore, the expression of profibrotic genes were increased in CD26+ fibroblasts, including TGF-ß1, IGF-1, IL6, collagen 1, collagen 3 and fibronectin. And meanwhile, CD26+ fibroblasts showed stronger invasion ability as compared to CD26- fibroblasts. Moreover, Diprotin A significantly suppressed proliferation and extracellular matrix secretion of CD26+ fibroblasts isolated from keloid tissues. CONCLUSION: Our findings suggest that CD26+ fibroblasts possess proliferation advantage in compare to CD26- fibroblasts, and the advantage caused expansion of CD26 positive fibroblast population promotes keloid progression.

pH-sensitive Au-BSA-DOX-FA nanocomposites for combined CT imaging and targeted drug delivery.

Albumin-based nanoparticles (NPs) as a drug delivery system have attracted much attention owing to their nontoxicity, non-immunogenicity, great stability and ability to bind to many therapeutic drugs. Herein, bovine serum albumin (BSA) was utilized as a template to prepare Au-BSA core/shell NPs. The outer layer BSA was subsequently conjugated with cis-aconityl doxorubicin (DOX) and folic acid (FA) to create Au-BSA-DOX-FA nanocomposites. A list of characterizations was undertaken to identify the successful conjugation of drug molecules and targeted agents. In vitro cytotoxicity using a cell counting kit-8 (CCK-8) assay indicated that Au-BSA NPs did not display obvious cytotoxicity to MGC-803 and GES-1 cells in the concentration range of 0-100 µg/mL, which can therefore be used as a safe drug delivery carrier. Furthermore, compared with free DOX, Au-BSA-DOX-FA nanocomposites exhibited a pH-sensitive drug release ability and superior antitumor activity in a drug concentration-dependent manner. In vivo computed tomography (CT) imaging experiments showed that Au-BSA-DOX-FA nanocomposites could be used as an efficient and durable CT contrast agent for targeted CT imaging of the folate receptor (FR) overexpressed in cancer tissues. In vivo antitumor experiments demonstrated that Au-BSA-DOX-FA nanocomposites have selective antitumor activity effects on FR-overexpressing tumors and no adverse effects on normal tissues and organs. In conclusion, the Au-BSA-DOX-FA nanocomposite exhibits selective targeting activity, X-ray attenuation activity and pH-sensitive drug release activity. Therefore, it can enhance CT imaging and improve the targeting therapeutic efficacy of FR-overexpressing gastric cancers. Our findings suggest that Au-BSA-DOX-FA nanocomposite is a novel drug delivery carrier and a promising candidate for cancer theranostic applications.

Association of the CCDC26 rs4295627 polymorphism with the risk of glioma: Evidence from 7,290 cases and 11,630 controls.

Published data on the association between the coiled-coil domain-containing 26 (CCDC26) rs4295627 polymorphism and the risk of glioma have been inconclusive. To further investigate this association, a meta-analysis was performed. By a comprehensive literature search using PubMed and EMBASE databases, a total of 16 case-control studies were identified for inclusion in the meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess this association. Our results confirmed that the risk with allele G was higher compared with that with allele T for glioma. The results indicated that the allele G of rs4295627 polymorphism in the CCDC26 gene was associated with increased risk of glioma in the homozygote model (GG vs. TT, OR=1.936, 95 %CI: 1.500-2.658, P<0.001), the heterozygote model (GT vs. TT, OR=1.323, 95% CI: 1.241-1.412, P=0.206), the dominant model (GG+GT vs. TT, OR=1.375, 95% CI: 1.256-1.505, P=0.026), the recessive model (GG vs. GT+TT, OR=1.769, 95% CI: 1.302-2.403, P<0.001) and the allele model (G vs. T, OR=1.310, 95% CI: 1.185-1.448, P<0.001). Current evidence suggests that the rs4295627 polymorphism in the CCDC26 gene may contribute to glioma susceptibility. However, further case-control studies are required to confirm our results.

Serum endocan levels are correlated with the presence and severity of coronary artery disease in patients with hypertension.

BACKGROUND: Endothelial dysfunction is one of the most important early indicators of atherosclerosis in hypertension (HT) patients. Endocan has been reported to play a role in the pathophysiology of endothelial dysfunction. OBJECTIVE: We sought to assess whether serum endocan levels are correlated with the presence and severity of coronary artery disease (CAD) in patients with HT. METHODS: We measured endocan levels in 164 patients with HT and in 55 controls. The severity of CAD was assessed by the coronary atherosclerosis index scores. RESULTS: Serum endocan levels were independently correlated with the presence and severity of CAD in HT patients. CONCLUSION: Endocan might function as a useful biomarker for monitoring the development and progression of CAD in HT patients.