Surgeons usually use synthetic polymer meshes for abdominal wall hernia repair. However, synthetic polymer meshes exhibit a lack of growth and related complications. In this study, we produced a tissue-engineered patch for abdominal hernia repair. Autologous bone-marrow-derived mesenchymal stem cells (BMSCs) were isolated and proliferated in vitro; decellularized dermal scaffolds (DSs) were prepared using enzymatic process; and then BMSCs were seeded onto the DSs for the construction of tissue-engineered patches. Under general anesthesia, rabbits underwent creation of abdominal wall defects and which were repaired with BMSC-seeded DSs, acellular DSs, and skin sutures only, respectively. Animals were sacrificed after 2 months for assessing the histological and gross examination. Abdominal hernias were absent in animals repaired with cell-seeded group, and abdominal hernias or bulges appeared in all animals repaired with acellular group. All the animals that were not repaired died within 10 days. The cell-seeded implants were thicker and indicated good angiogenesis compared with that of the acellular implants, both in histological and gross examination. The tissue-engineered patches prepared with BMSCs seeding on DSs can be used for abdominal wall hernia repair.

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Although therapeutic cellular angiogenesis is effective for chronic ischemia, the optimal mode of cellular administration is still under exploration. This study aimed to develop a cellular delivery system to enhance the perfusion and angiogenesis in the ischemic hind limb. Collagen scaffold (CS) was prepared, and for morphology and toxicity analysis, bone marrow-derived mesenchymal stem cells (BMSCs) were isolated, expanded, filtrated, and seeded onto CS to construct BMSCs-CS. The ischemic hind limbs of rabbit models were implanted with autologous BMSCs-CS, CS, and autologous BMSCs; the untreated ischemic or normal animals were considered as the ischemic or normal control groups. Oxygen saturation parameters were regularly measured to determine the perfusion in the extremities. Histological examinations with hematoxylin and eosin immunostaining against von Willebrand factor and smooth muscle (SM) α-actin were performed for capillary and mature vessel evaluation. CS was a multiporous structure without cytotoxicity. At several intervals, the oxygen saturation ratio (OSR) in normal control was the highest. The OSRs in BMSCs-CS and CS were higher than that in BMSCs and ischemic control (p < 0.05); the OSR in BMSCs-CS group was higher than that in CS at 6 and 8 weeks (p < 0.05). The capillaries in BMSCs-CS and CS were higher than that in CS, BMSCs, and the ischemic or normal control (p < 0.05). The mature vessels in BMSCs-CS were higher than that in CS, BMSCs, and the ischemic or normal control (p < 0.05). The autologous cellular delivery system proved to be an effective approach for improving higher ischemic hind limb perfusion and angiogenesis as opposed to cellular therapy alone.

Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain.

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Chronic itch is clinically correlated with the development of mood disorders such as anxiety and depression. Nonetheless, whether this relevance exists in rodents is unknown, and evidence demonstrating chronic itch can affect mood is lacking. The aim of this study is to characterize the affective consequences of chronic itch, and explore potential mechanisms and interventional strategy. We subjected mice to chronic itch by repetitive cutaneous treatment with acetone and diethylether followed by water (AEW) that models "dry skin." After 3 to 4 weeks AEW treatment, the mice developed behavioral phenotypes of anxiety and depression assessed by a battery of behavioral paradigms, such as light-dark box and forced swim test. These behavioral symptoms of mood disturbance were independent of cutaneous barrier disruption, but correlated well with the degree of the irritating itch sensation. Although AEW mice showed normal circadian hypothalamic-pituitary-adrenal (HPA) axis activity, their neuroendocrine functionality was dampened, including impaired endocrine stress responsivity, altered neuroendocrine-immune interaction, and blunted corticosterone response to both dexamethasone and CRF. Parameters of HPA functionality at the level of mRNA transcripts are altered in stress-related brain regions of AEW mice, implying an overdrive of central CRF system. Remarkably, chronic treatment of AEW mice with antalarmin, a CRFR1 antagonist, ameliorated both their mood impairment and stress axis dysfunction. This is the first evidence revealing mood impairment, HPA axis dysfunction, and potential therapeutic efficacy by CRFR1 antagonist in mice with chronic itch, thus providing a preclinical model to investigate the affective consequence of chronic itch and the underlying mechanisms.

There is an urgent clinical need of tissue-engineering (TE) vascular grafts, so this study was for developing a fast and simple way of producing TE vascular scaffold. The TE vascular scaffold was prepared with pepsin, DNase and RNase enzymatic decellularization and crosslinked with 0.1, 1, 5% glutaraldehyde (GA), respectively. The samples were underwent analyses of burst pressure; suture strength; cytotoxicity; enzymatic degradation in vitro; degradation in vivo; rehydration; biocompatibilities detected with hematoxylin and eosin (H&E), scan electron microscope, immunohistochemistry both in vivo and in vitro; macrophage infiltration and calcification using Von Kossa staining. After being decellularized the scaffold had a complete removal of cellular components, an intact collagen structure. The burst pressure and suture strength were similar to native artery. 0.1% GA crosslinked scaffold showed less cytotoxicity than 1 and 5% GA groups (P < 0.05) and was resistance to enzymatic degradation in vitro. Once being implanted, 0.1% GA group was resistant to degradation and formed endothelium, smooth muscle and adventitia with few macrophages infiltration. However, there appeared calcification in implants compared with that in native artery. This study demonstrated that DVPs producing methods by enzymatic decellularizing and crosslinking with 0.1% GA could be used for clinical TE vascular graft manufacture.

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