Tetraspanin 1 regulates papillary thyroid tumor growth and metastasis through c-Myc-mediated glycolysis.

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer and is characterized by its tendency for lymphatic metastasis, leading to a poor prognosis. Tetraspanin 1 (TSPAN1) is a member of the tetra-transmembrane protein superfamily and has been implicated in tumorigenesis and cancer metastasis in various studies. However, the role of TSPAN1 in PTC tumor development remains unclear. In this study, we aimed to investigate the impact of TSPAN1 on PTC cell behavior. Our results demonstrate that knockdown of TSPAN1 inhibits PTC cell proliferation, migration, and invasion, while overexpression of TSPAN1 has the opposite effect. These findings suggest that TSPAN1 might play a role in the tumorigenesis and invasiveness of PTC. Mechanistically, we found that TSPAN1 activates the ERK pathway by increasing its phosphorylation, subsequently leading to upregulated expression of c-Myc. Additionally, we observed that TSPAN1-ERK-c-Myc axis activation promotes glycolytic activity in PTC cells, as evidenced by the upregulation of glycolytic genes such as LDHA. Taken together, our findings indicate that TSPAN1 acts as an oncogene in PTC by regulating glycolytic metabolism. This discovery highlights the potential of TSPAN1 as a promising therapeutic target for PTC treatment. Further research in this area could provide valuable insights into the development of targeted therapies for PTC patients.

Application of secondary sentinel lymph node biopsy in cn1a papillary thyroid carcinoma surgery: a lesson from athletic players

Objective: This study aims to evaluate the efficacy of secondary sentinel lymph node (SLN) biopsy in cN1a papillary thyroid carcinoma (PTC) surgery, drawing parallels to strategic approaches akin to those employed by athletic players.Methods: We selected eleven patients diagnosed with suspected cN1a PTC from January 2020 to July 2020. Carbon nanoparticles were utilized to mark lymph nodes, analogous to strategic marking in athletic games, ensuring precise identification during surgery. The secondary SLN biopsy technique was implemented, reflecting the precision and planning seen in athletic strategies.Results: The average tumor size was 12.64±5.63 mm. Notably, 2 patients exhibited extrathyroidal spread, 3 had thyroiditis, and all had neck metastases. The SLN identification rate stood at 100%, mirroring the accuracy expected in athletic performance. Out of the group, 3 patients had sentinel lymph node metastasis, with additional metastasis in non-SLN areas in 1 patient. The detection rate, false-negative rate, and overall accuracy paralleled the high performance and reliability seen in athletic endeavors. A total of 42 lateral SLNs were identified, with the majority being grade IV. This strategic identification is akin to an athlete's ability to focus on key areas during play (AU)

Utility of video-assisted method for identifying and preserving the external branch of the superior laryngeal nerve during thyroidectomy.

Background: The EBSLN is vulnerable to damage during thyroidectomy, results in voice related complications, negatively affect patient quality of life, routine identification of the EBSLN prior to surgical manipulation is necessary for a complication-free thyroidectomy. We aimed to validate a video-assisted procedure for identifying and preserving the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy and analyze the EBSLN Cernea classification and the localization of the nerve entry point (NEP) from the insertion of the sternothyroid muscle. Methods: A prospective descriptive study was performed; 134 patients, who scheduled for lobectomy with an intraglandular tumor max diameter ≤ 4 cm and without extrathyroidal extension, were randomly divided into the video-assisted surgery (VAS) and conventional open surgery (COS) groups. We used the video-assisted surgical procedure for visually identifying the EBSLN directly, and compared the differences in the visual identification rate and total identification rate of the two groups. We also measured the localization of the NEP using the insertion of the sternothyroid muscle as a reference. Results: There was no statistically significant difference in clinical characteristics between the two groups. The visual identification rate and total identification rate were significantly higher in the VAS group than the COS group (91.04% vs. 77.61%, 100% vs. 89.6%). The EBSLN injury rate was 0 in both groups. The mean vertical distance (VD) of the NEP from the sternal thyroid insertion was 1.18 mm (SD 1.12 mm, range, 0-5 mm), with approximately 88.97% of the results occurring within the 0-2 mm range. The mean horizontal distance (HD) was 9.33 mm (SD 5.03 mm, range, 0-30 mm), with over 92.13% of the results occurring within the 5-15 mm range. Conclusion: Both the visual and total identification rates of the EBSLN were significantly higher in the VAS group. This method provided a good visual exposure rate of the EBSLN, aiding in identifying and protecting the EBSLN during thyroidectomy.

Optimal range of lymph node dissection in patients with unilateral papillary thyroid carcinoma with lateral cervical lymph node metastasis.

Background: Whether patients with unilateral papillary thyroid carcinoma (PTC) with lateral cervical lymph node metastasis (LLNM) require prophylactic central regional lymph node dissection (CLND) remains unclear. Herein, we investigated the independent risk factors associated with contralateral central lymph node metastasis (cCLNM) in unilateral PTC with LLNM and analyzed the optimal extent of lymph node dissection by comparing the 5-year recurrence-free survival rates. Materials and methods: We retrospectively analyzed 695 patients with unilateral papillary thyroid carcinoma and lateral cervical lymph node metastasis. Factors including sex, age, multifocal, location of primary tumor, tumor diameter, capsule invasion, thyroid nodular goiter, Hashimoto thyroiditis, ipsilateral central lymph node metastasis(iCLNM), and lateral cervical lymph node metastasis were analyzed using univariate and multivariate logistic regression analyses to explore the independent risk factors of cCLNM. Propensity scores were matched to compare the 5-year recurrence-free survival rates in patients divided by different lymph node metastases and dissections. Results: Of all patients who underwent bilateral (b)CLND, 52% (149/286) had cCLNM. Receiver operating characteristic (ROC) curve analysis was performed on 286 patients who underwent bCLND, for which a tumor diameter of 20.5 mm and number of LLNM of 3.5 were used as the thresholds for predicting cCLNM. The 5-year recurrence-free survival (RFS) rates in the cCLN-negative and cCLN-positive groups were 98.6% and 91.2%, with statistically significant differences (P=0.034). The 5-year RFS rates showed no significant difference between the ipsilateral (i)CLND and bCLND groups (P=0.235). Multifactorial regression analysis showed that tumor diameter >2 cm, presence of iCLNM, and number of LLNM >3 were independent risk factors of cCLNM.But male sex, young age (<45 years), multifocality, location of primary tumor, capsule invasion, thyroid nodular goiter, and Hashimoto thyroiditis were not associated with cCLNM. Conclusion: Not all unilateral PTC with LLNM require prophylactic cCLND; however, prophylactic cCLND is necessary in cases which display high-risk factors for cCLNM, including primary diameter >2 cm, iCLNM, and number of LLNM >3.

Case report: Balloon compression for cervical chyle leakage post neck dissection.

Postoperative chyle leakage (CL) is a rare but severe complication after neck dissection, and most patients with this complication can be treated conservatively. However, in patients with high-flow leakage, efficient and well-tolerated conservative treatment options are still lacking, and the treatments can be complicated. In this study, we report a case with CL of 1100 ml/day after neck dissection that was successfully treated by balloon compression.

Circular RNA circ_0000644 promotes papillary thyroid cancer progression via sponging miR-1205 and regulating E2F3 expression.

The dysregulation of circular RNAs (circRNAs) facilitates the tumorigenesis of papillary thyroid carcinoma (PTC). This study was targeted at determining the functions and mechanism of circ_0000644 in regulating PTC development. Circ_0000644, microRNA-1205 (miR-1205) and E2F transcription factor 3 (E2F3) expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Actinomycin D (ActD) and Ribonuclease R (RNase R) assays were used to verify the circular characteristic of circ_0000644. After circ_0000644 was knocked down, PTC cell growth, migration, invasion and apoptosis were assessed by cell counting kit-8 (CCK-8) assay, Transwell assay and flow cytometry analysis, respectively. The regulating relationships among circ_0000644, E2F3 and miR-1205 were confirmed through RNA immunoprecipitation (RIP) assay and dual-luciferase reporter assay. Besides, the regulatory effects of circ_0000644 on the protein level of E2F3 was analyzed via Western blot. In PTC, circ_0000644 was highly expressed, and it was located mainly in the cytoplasm, and it had stable structure. The knockdown of circ_0000644 repressed PTC cell growth, migration, and invasion, and facilitated apoptosis. Circ_0000644 could directly interact with miR-1205 to repress the expression of miR-1205, and it served as a miR-1205 sponge to modulate E2F3 expression in PTC cells. Circ_0000644 up-regulates E2F3 expression via sponging miR-1205 to promote PTC progression.

Thyroid hormone postconditioning protects hearts from ischemia/reperfusion through reinforcing mitophagy.

Triiodothyronine (T3), the biologically active form of thyroid hormone, was reported to protect myocardium from ischemia/reperfusion (I/R) injury when given before sustained ischemia, but its cardioprotective effects when given at the onset of reperfusion (postconditioning), a protocol with more clinical impact is unknown. Therefore, the present study was designed to determine whether T3 postconditioning (THPostC) is able to protect the heart from reperfusion injury and its underlying mechanisms. Isolated Sprague-Dawley rat hearts were subjected to 30 min ischemia/45 min reperfusion, triiodothyronine was delivered at the first 5 min of reperfusion. Our data shown that T3 from 1 to 10 µM during the first 5-min of reperfusion concentration-dependently improved post-ischemic myocardial function. A similar protection was observed in isolated rat cardiomyocytes characterized by the alleviation of I/R-induced loss of mitochondrial membrane potential and exacerbated cell death. Moreover, mitophagy (selectively recognize and remove damaged mitochondria) was significantly stimulated by myocardial I/R, which was enhanced with THPostC. Meanwhile, we found that THPostC stimulated PINK1/Parkin pathway, a critical regulator for mitophagy. Then, adenoviral knockdown of PINK1 and Parkin conformed its roles in the THPostC-mediated cardioprotection. Our results suggest that THPostC confers cardioprotection against I/R injury at least in part by reinforcing PINK1-dependent mitophagy. These findings reveal new roles and mechanisms of triiodothyronine in the cardioprotection against I/R injury.

miR-215 suppresses papillary thyroid cancer proliferation, migration, and invasion through the AKT/GSK-3ß/Snail signaling by targeting ARFGEF1.

The incidence of papillary thyroid cancer (PTC) has been rapidly increasing in recent years. PTC is prone to lymph node metastasization, which further increases the recurrence rate and mortality of thyroid cancer. However, the underlying mechanisms of this process remain elusive. Several reports have shown that the microRNA miR-215 plays an important role in cancer metastasis. Here, we investigated, for the first time, the potential association between miR-215 and metastasis in PTC. The results of qPCR analysis demonstrated that miR-215 was downregulated in PTC cell lines and tissues, and lower levels of miR-215 correlated with lymph node metastasis of PTC. In vitro and in vivo assays revealed that restoration of miR-215 dramatically inhibited PTC cell proliferation and metastasis. We identified ADP ribosylation factor guanine nucleotide-exchange factor 1 (ARFGEF1) as the target, which mediated the function of miR-215. The expression of ARFGEF1 was inhibited by miR-215, and the effects of miR-215 were abrogated by re-expression of ARFGEF1. Moreover, we found that miR-215 suppressed PTC metastasis by modulating the epithelial-mesenchymal transition via the AKT/GSK-3ß/Snail signaling. In summary, our study proves that miR-215 inhibits PTC proliferation and metastasis by targeting ARFGEF1 and indicates miR-215 as a biomarker for PTC prognosis.

KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. The poor survival may be due to a high proportions of tumor recurrence and metastasis. Kinesin family member C1 (KIFC1) is highly expressed in a variety of neoplasms and is a potential marker for non-small cell lung cancer or ovarian adenocarcinoma metastasis. Nevertheless, the role of KIFC1 in HCC metastasis remains obscure. We investigated this in the present study using HCC cell lines and clinical specimens. Our results indicated that increased levels of KIFC1 were associated with poor prognosis and metastasis in HCC. In addition, KIFC1 induced epithelial-to-mesenchymal transition (EMT) and HCC metastasis both in vitro and in vivo. This tumorigenic effect depended on gankyrin; inhibiting gankyrin activity reversed EMT via activation of protein kinase B (AKT)/Twist family BHLH transcription factor 1 (AKT/TWIST1). We also found that KIFC1 was directly regulated by the microRNA miR-532-3p, whose downregulation was associated with metastatic progression in HCC. These results denote that a decrease in miR-532-3p levels results in increased KIFC1 expression in HCC, leading to metastasis via activation of the gankyrin/AKT/TWIST1 signaling pathway.

CircRNA circRNA_102171 promotes papillary thyroid cancer progression through modulating CTNNBIP1-dependent activation of ß-catenin pathway.

BACKGROUND: As a type of recently discovered noncoding RNA, circular RNAs (circRNAs) exert pivot biological functions in diverse cancers. However, the role of circRNA_102171 in papillary thyroid cancer (PTC) has not been investigated. Our study was focused on the functional investigation toward circRNA_102171 in PTC progression. And we also aimed to reveal its potential molecular mechanism. METHODS: The expression pattern of circRNA_102171 was determined using quantitative polymerase chain reaction (qPCR) in PTC samples and cell lines. Cell proliferation was examined utilizing CCK8, colony formation and EdU incorporation assays. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. Cell migration and invasion was measured using Transwell assay. Tumor growth in vivo was determined through a xenograft assay. RNA-pulldown, RNA-IP (RIP) and RNA-EMSA were used to analyze the interaction between circRNA_102171 and CTNNBIP1. RESULTS: CircRNA_102171 expression was upregulated in tumor tissues and cell lines. CircRNA_102171 silencing suppressed PTC cell proliferation, migration and invasion while promoting apoptosis. CircRNA_102171 knockdown inhibited PTC growth in vivo. CircRNA_102171 interacted with CTNNBIP1 to block its interaction with the ß-catenin/TCF3/TCF4/LEF1 complex, leading to activation of Wnt/ß-catenin pathway. CONCLUSIONS: CircRNA_102171 overexpression promotes PTC progression through activating Wnt/ß-catenin pathway in a CTNNBIP1-dependent way.

Targeted delivery of adipose-derived stem cells via acellular dermal matrix enhances wound repair in diabetic rats.

Cell-based therapeutic intervention has emerged as a new approach to accelerate wound closure. Adipose-derived stem cells (ASCs), as a fascinating cell source, have received much attention in tissue repair and regeneration. In this study we evaluated the potential of acellular dermal matrix (ADM) scaffold serving as a carrier for the delivery of ASCs and investigated its therapeutic effects on wound healing. First, ASCs were isolated and characterized for multidifferentiation potential. ASCs-ADM grafts were then prepared, and ADM scaffold was shown to support the in vitro growth and proliferation of ASCs. Next, we analysed paracrine factors in conditioned medium and found that ASCs-ADM grafts secreted various cytokines, including VEGF, HGF, TGFß and bFGF. Moreover, ASCs-ADM conditioned medium notably stimulated the migration and proliferation of fibroblasts. In vivo, we established an excisional wound model in diabetic rats which received phosphate-buffered saline (PBS), ADM or ASCs-ADM grafts, respectively. Our results demonstrated that implantation of ASCs-ADM significantly enhanced tissue regeneration and increased epithelialization, resulting in accelerated wound closure. Immunofluorescence analysis further indicated that capillary density was evidently increased in the ASCs-ADM group compared with the control or ADM group. In addition, western blot analysis showed that ASCs-ADM significantly increased the expression of angiogenic factors, which was consistent with in vitro data. Taken together, our results suggest that targeted delivery of ASCs via ADM scaffold accelerate diabetic wound healing through a paracrine mechanism, with enhanced granulation tissue formation and increased re-epithelialization and neovascularization.

Thyrotropin-releasing hormone and its analogs accelerate wound healing.

BACKGROUND: Thyrotropin-releasing hormone (TRH) is a classical hormone that controls thyroid hormone production in the anterior pituitary gland. However, recent evidence suggested that TRH is expressed in nonhypothalamic tissues such as epidermal keratinocytes and dermal fibroblasts, but its function is not clear. This study aimed to investigate the effects of TRH and its analogs on wound healing and explore the underlying mechanisms. MATERIALS AND METHODS: A stented excisional wound model was established, and the wound healing among vehicle control, TRH, and TRH analog taltirelin treatment groups was evaluated by macroscopic and histologic analyses. Primary fibroblasts were isolated from rat dermis and treated with vehicle control, TRH or taltirelin, cell migration, and proliferation were examined by scratch migration assay, MTT, and 5-ethynyl-2'- deoxyuridine (EdU) assay. The expression of α-Smooth muscle actin in fibroblasts was detected by Western blot and immunocytochemical analysis. RESULTS: TRH or taltirelin-treated wounds exhibited accelerated wound healing with enhanced granulation tissue formation and increased re-epithelialization and tissue formation. Furthermore, TRH or taltirelin promoted the migration and proliferation of fibroblasts and induced the expression of α-Smooth muscle actin in fibroblasts. CONCLUSIONS: TRH is important in upregulating the phenotypes of dermal fibroblasts and plays a role in accelerating wound healing.

Shorter distance between the nodule and capsule has greater risk of cervical lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: The purpose of this study was to assess the relationship between different sonographic features of papillary thyroid carcinoma (PTC) on high-frequency ultrasound and cervical lymph node metastasis (CLNM). MATERIALS AND METHODS: We enrolled 548 patients who underwent initial surgery for PTC between May 2011 and December 2012 in our hospital at diagnosis. The sonographic features of 513 PTC nodules in 513 eligible patients, who had single PTC nodules in their thyroid glands, were retrospectively investigated. All patients with a suspect malignant nodule (d<0.5cm) among multiple nodules were initially diagnosed by fine-needle aspiration biopsy (FNAB) to ascertain if the suspect nodule was PTC. The final diagnosis of all the thyroid nodules and existence of CLNM were based on postoperative pathology. Patients were divided into two groups: a positive group with CLNM (224 nodules) and a negative group without CLNM (289 nodules). The following factors were investigated: gender, age, echogenicity, echotexture, size, shape, location, margin, contour, calcification morphology, distance between the nodule and pre- or post-border of the thyroid capsule, vascularity and the differences between the two groups. RESULTS: Correlation analysis showed that shorter distances between the nodule and pre- or post- border of thyroid capsule resulted in greater risk of CLNM (Spearman correlation coefficient=-0.22, p<0.0001). The significant factors in multivariate analysis were age<45yrs, larger size (d>1cm), "wider than tall" shape, extrathyroid extension and mixed flow (internal and peripheral) (p<0.05, OR=0.406, 2.093, 0.461, 1.610, 1.322). CONCLUSIONS: Significant sonographic features of PTC nodules in preoperative high-frequency ultrasound are crucial for predicting CLNM.

The fetal porcine aorta and mesenteric acellular matrix as small-caliber tissue engineering vessels and microvasculature scaffold.

BACKGROUND: The extracellular matrix (ECM) is characterized by not only well-preserved scaffolds of organs and vascularized tissues, but also by extremely low immunogenicity during allo- or xeno-implantation. This study aimed to establish a model of a composite microvasculature network scaffold with a small-caliber-dominant vascular pedicle by decellularizing fetal porcine aorta and the conterminous mesentery. METHODS: The aorta and the conterminous mesenteric vascular system originating from the inferior mesenteric artery were harvested from fetal pigs at late gestation. All of the cellular components were removed by sequential treatment with Triton X-100 and sodium dodecyl sulfate. After the degree of decellularization was assessed, the fetal porcine aorta and mesenteric acellular matrix (FPAMAM) were transplanted into dogs. RESULTS: Gross and histologic examination demonstrated the removal of cellular constituents with preservation of ECM architecture, including macrochannels and microchannels. The residual DNA content in the FPAMAM was less than 2 %. The aorta and microchannels were perfused well, and the fetal porcine aorta had good patency for more than 3 months. CONCLUSIONS: The integrity of the FPAMAM provided a scaffold for the reconstruction of a rich vascular network with numerous segmentally radiating branches. Decellularized fetal porcine vascular tissue might be a potential alternative for xenogeneic transplantation based on its optimized properties and low immunogenicity. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Deferoxamine enhances neovascularization and accelerates wound healing in diabetic rats via the accumulation of hypoxia-inducible factor-1α.

AIMS: Hypoxia-inducible factor (HIF)-1α plays a pivotal role during the process of wound healing. Previous studies reported that deferoxamine (DFO) could increase HIF-1α stability. This study aimed to investigate the effects of DFO on wound healing in diabetic rats and explore the underlying mechanism both in vivo and in vitro. METHODS: An excisional diabetic wound model was established and the wound healing among vehicle control, DFO and vascular endothelial growth factor (VEGF) treatment groups was evaluated by macroscopy, histology and Western blot analysis. Human umbilical vein endothelial cells (HUVECs) were treated with DFO or HIF-1α siRNA, and then endothelial tube formation, cell proliferation and migration were examined. RESULTS: DFO-treated wounds exhibited accelerated wound healing with enhanced granulation formation and increased re-epithelialization. Compared to the vehicle or VEGF treatment, DFO significantly increased neovascularization through up-regulation of HIF-1α and target genes including VEGF and stromal cell-derived factor-1α (SDF-1α). DFO failed to stimulate the expression of VEGF and SDF-1α in HUVECs depleted of HIF-1α. In addition, DFO promoted the angiogenic-associated processes of endothelial tube formation, cell proliferation and migration in HIF-1α dependent manner. CONCLUSIONS: DFO enhances neovascularization and accelerates diabetic wound healing through the accumulation of HIF-1α and the regulation of endothelial cell function.

Hypoxia preconditioning enhances the viability of ADSCs to increase the survival rate of ischemic skin flaps in rats.

UNLABELLED: Use of a skin flap has been a common technique in reconstructive surgery for more than five decades. However, partial necrosis of its distal end is still a serious postoperative complication. Many theories about this problem have been proposed, including deficient blood supply, which is the most accepted theory. In this study we demonstrated that hypoxic preconditioning enhanced the viability of adipose-derived stem cells (ADSCs) in vivo and improved their ability to increase the survival rate of ischemic skin flaps in rats. Seven days after flap elevation, the flap survival rate in the hypoxic preconditioned ADSC group was higher than that in the control group. Moreover, histological examination showed that more ADSCs survived in flaps treated by hypoxic preconditioning. Vascular density in the hypoxic preconditioned ADSC group was 30-90 % greater than that in the control group. In addition, the expressions of vascular endothelial growth factor and hypoxia inducible factor-1α (HIF-1α) were higher in the hypoxic preconditioned ADSC group than in the control group (p < 0.05). This enhancive phenomenon reached its highest level at the precondition times of 3 and 7 days in the hypoxic preconditioned ADSC group. We conclude that hypoxia preconditioning effectively enhances the viability of ADSCs to increase the survival rate of ischemic skin flaps. Furthermore, 3 days is the optimal preconditioning time point. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Controlled release of transforming growth factor-beta receptor kinase inhibitor from thermosensitive Chitosan-based hydrogel: application for prevention of capsular contracture.

BACKGROUND: Capsular contracture has become the most common complication associated with breast implant. Transforming growth factor-beta (TGF-ß) is well known for a prominent role in fibrotic diseases. Due to the critical role of TGF-ß in pathogenesis of capsular formation, we utilized thermosensitive C/GP hydrogel to controlled release of TGF-ß receptor kinase inhibitor (SD208) and investigated their effects on capsular contracture. METHODS: In vitro degradation and drug release of C/GP hydrogel were performed. Twenty-four rabbits underwent subpanniculus implantation with 30 ml smooth silicone implants and were randomly divided into four groups as follows: Group 1 received saline solution; Group 2 received SD208; Group 3 received SD208-C/GP; Group 4 received C/GP. At 8 weeks, the samples of capsular tissues were analyzed by hematoxylin and eosin and immunohistological staining. The mRNA expression of collagen III and TGF-ß1 was detected by RT-PCR assay. RESULTS: C/GP hydrogel could be applied as an ideal drug delivery vehicle which supported the controlled release of SD208. SD208-C/GP treatment showed a significant reduction in capsule thickness with fewer vessels. The histological findings confirmed that the lower amounts of inflammatory cells and fibroblasts infiltrate in SD208-C/GP group. In contrast, typical capsules with more vessel predominance were developed in control group. We did not observe the same inhibitory effect of SD208 or C/GP treatment on capsular contracture. Moreover, SD208-C/GP therapy yielded an evident down-regulation of collagen III and TGF-ß1 mRNA expression. CONCLUSIONS: This study demonstrated that controlled release of TGF-ß receptor kinase inhibitor from thermosensitive C/GP hydrogel could significantly prevent capsule formation after mammary implants.

Medial plantar artery perforator flap for soft-tissue reconstruction of the heel.

Soft-tissue wounds of the foot and especially the heel are challenging problems for reconstructive surgeons. An important principle that guides heel reconstruction is to provide sensate skin with a similar thickness to resurface the weight-bearing heel and avoid late flap ulceration. Among various techniques to achieve this result, the sensate medial plantar perforator flap is an excellent option, which provides durability to friction, a cushioning effect, and sensation. An anatomic study was performed to clarify the anatomy of the cutaneous perforators of the medial plantar artery and to determine the optimal method of medial plantar artery perforator flap harvest. Fifteen cases of heel reconstruction with the sensate medial plantar perforator flap are presented. The outcome of surgery at a mean follow-up of 12 months is reported. The indications for surgery, operative procedures, advantages and disadvantages, and results are presented. Satisfactory results were obtained with a good color and texture match for heel repair and a good sensory recovery. No functional deficit was found at the donor site.

Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis.

Despite advances in wound closure techniques and devices, there is still a critical need for new methods of enhancing the healing process to achieve optimal outcomes. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. Adipose-derived stem cells (ASCs) hold great promise for wound healing, because they are multipotential stem cells capable of differentiation into various cell lineages and secretion of angiogenic growth factors. The aim of this study was to evaluate the benefit of ASCs on wound healing and then investigate the probable mechanisms. ASCs characterized by flow cytometry were successfully isolated and cultured. An excisional wound healing model in rat was used to determine the effects of locally administered ASCs. The gross and histological results showed that ASCs significantly accelerated wound closure in normal and diabetic rat, including increased epithelialization and granulation tissue deposition. Furthermore, we applied GFP-labeled ASCs on wounds to determine whether ASCs could differentiate along multiple lineages of tissue regeneration in the specific microenvironment. Immunofluorescent analysis indicated that GFP-expressing ASCs were costained with pan-cytokeratin and CD31, respectively, indicating spontaneous site-specific differentiation into epithelial and endothelial lineages. These data suggest that ASCs not only contribute to cutaneous regeneration, but also participate in new vessels formation. Moreover, ASCs were found to secret angiogenic cytokines in vitro and in vivo, including VEGF, HGF, and FGF2, which increase neovascularization and enhance wound healing in injured tissues. In conclusion, our results demonstrate that ASC therapy could accelerate wound healing through differentiation and vasculogenesis and might represent a novel therapeutic approach in cutaneous wounds.