Cutaneous Regeneration Mechanism of ß-Sheet Silk Fibroin in a Rat Burn Wound Healing Model.

Therapeutic dressings to enhance burn wound repair and regeneration are required. Silk fibroin (SF), a natural protein, induces cell migration and serves as a biomaterial in various dressings. SF dressings usually contain α-helices and ß-sheets. The former has been confirmed to improve cell proliferation and migration, but the wound healing effect and related mechanisms of ß-sheet SF remain unclear. We investigated the effects of ß-sheet SF in vivo and in vitro. Alcohol-treated α-helix SF transformed into the ß-sheet form, which promoted granulation formation and re-epithelialization when applied as lyophilized SF dressing (LSFD) in a rat burn model. Our in vitro results showed that ß-sheet SF increased human dermal fibroblast (HDF) migration and promoted the expression of extracellular matrix (ECM) proteins (fibronectin and type III collagen), matrix metalloproteinase-12, and the cell adhesion molecule, integrin ß1, in rat granulation tissue and HDFs. This confirms the role of crosstalk between integrin ß1 and ECM proteins in cell migration. In summary, we demonstrated that ß-sheet SF facilitates tissue regeneration by modulating cell adhesion molecules in dermal fibroblasts. LSFD could find clinical application for burn wound regeneration. Moreover, ß-sheet SF could be combined with anti-inflammatory materials, growth factors, or antibiotics to develop novel dressings.

Pre-clinical assessment of chimeric antigen receptor t cell therapy targeting CD19+ B cell malignancy.

BACKGROUND: Autologous chimeric antigen receptor (CAR) T cell therapy is a promising therapeutic strategy for treating hematologic malignancies. A spectrum of serious complications caused by CAR-T cells has caught great attention. We developed a novel CAR against CD19 namely UWC19, consisting anti-CD19 single-chain variable fragment (scFv) hinged with 4-1BB and CD3z signaling domains. In this study, preclinical assessments of UWC19 were conducted to evaluate the safety and efficacy in vitro and in vivo. METHODS: To evaluate the binding activity of UWC19 cells to CD19, we measured the saturation degree of CAR with human CD19 molecules using flow cytometry in vitro. The antitumor efficacy of UWC19 cells was determined by in vitro cytotoxicity assay against CD19 positive cells and in vivo using a xenograft mouse model. Cross tissue reactivity of UWC19 cells was examined by co-culturing with cell lines from difference human tissues. Tumorigenicity was determined by subcutaneously injecting UWC19 in immunodeficient mice. Persistence was analyzed using quantitative PCR. RESULTS: We showed that UWC19 CAR T cells exerted highly specific binding affinity and cytotoxicity against CD19+ cells in vitro. In vivo, UWC19 CAR T cells are able to fully control disease progression in a Raji-xenografted immunodeficient mouse model. UWC19 exerted no obvious effects on the mean body mass and graft versus host disease were observed in surviving mice. We showed that UWC19 cells specifically recognized and eliminated CD19 positive cells, whereas CD19 negative cells were much less affected. No tumorigenicity of UWC19 in immunodeficient mice was observed. CONCLUSIONS: UWC19 treatment effectively eliminated CD19 positive tumor cells with favorable toxicity profile. The findings suggest encouraging clinical prospects for its use in patients with CD19 positive B cell malignancies. Our study presented an alternative evaluation strategy for CAR-T cell products.

EFLA 945 restricts AIM2 inflammasome activation by preventing DNA entry for psoriasis treatment.

Psoriasis is a chronic inflammatory skin disease that affects about 2% of the general population. Activation of the Absent in Melanoma 2 (AIM2) inflammasome is crucial for immune defense, but it can also cause inflammatory and autoimmune diseases, including psoriasis. We currently lack an AIM2 inflammasome inhibitor that could be used therapeutically. Here, we show that EFLA 945, a safe product of red grape vine leaf extracts, can restrict AIM2 inflammasome activation. Mechanistically, EFLA945 prevents DNA entry into THP-1-derived macrophages, and thereby inhibits cytoplasmic DNA-dependent apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, caspase-1 activation, and the secretion of interleukin (IL)-1ß and IL-18. The major phytochemicals of EFLA 945, resveratrol and peonidin 3-O-glucoside (P3G), appear to be the potential bioactive compounds responsible for its ability to restrict AIM2-dependent IL-1ß secretion. Importantly, in an in vivo mouse model, EFLA 945 attenuates imiquimod (IMQ)-induced psoriasis-related pro-inflammatory responses in topical psoriatic skin, including caspase-1 activation, IL-1ß maturation, and IL-17 production, and decreases the severity of psoriasis. Together, these results demonstrate that the safe natural product, EFLA 945, can restrict the AIM2 inflammasome activation through preventing DNA entry and may prove beneficial for treating psoriasis.

Adjuvant chemotherapy with tegafur/uracil for more than 1 year improves disease-free survival for low-risk Stage II colon cancer.

BACKGROUND: It is uncertain whether adjuvant chemotherapy (CMT) improves survival in patients with low-risk Stage II colon cancer. We aimed to determine the disease-free survival (DFS) and 5-year overall survival (OS) of low-risk Stage II colon cancer patients treated with adjuvant tegafur/uracil (UFUR). METHODS: From January 2004 to December 2011, the follow-up status of 278 low-risk Stage II colon cancer patients who underwent surgery in a single medical center was retrospectively analyzed. These patients were divided into three groups based on whether they received adjuvant CMT with UFUR, adjuvant CMT with 5-fluorouracil, or surgery alone. DFS and 5-year OS curves were calculated using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: In the study population, including 278 low-risk Stage II colon cancer patients with a mean age of 68.28 ± 13.01 years, 132 (47.5%) received adjuvant CMT with UFUR, 49 (17.6%) received adjuvant CMT with 5-fluorouracil, and 97 (34.9%) underwent radical surgery alone. At 5 years, the adjusted DFS and OS of low-risk Stage II colon cancer patients were 85.5% and 81.8%, respectively, in the surgery alone group and 97.9% and 96.2%, respectively, in the surgery plus UFUR > 12 months group (p = 0.004 and p = 0.098, respectively). In multivariate analysis, CMT with UFUR for more than 12 months increased DFS over surgery alone. There was no statistical difference in the 5-year OS. CONCLUSION: Adjuvant CMT treatment of low-risk Stage II colon cancer patients with UFUR for more than 12 months following surgery improves DFS over surgery alone.

Is preoperative bowel preparation necessary for gynecological oncology surgery?

OBJECTIVE: We investigated the necessity of preoperative bowel preparation for gynecological oncology surgery. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent gynecological oncology surgery with simultaneous colon or rectal resection between April 2005 and September 2014 at the Tri-Service General Hospital, Taipei, Taiwan. Patients were divided into two groups based on whether preoperative mechanical bowel preparation (MBP) was performed. Patient characteristics, including duration of antibiotic treatment, surgical procedures, and occurrence of surgical and nonsurgical complications, were compared. RESULTS: We enrolled 124 patients who underwent gynecological oncology surgery with simultaneous colon or rectal resection, of whom 76 received MBP and 48 did not receive mechanical bowel preparation. On comparison between the two groups, no significant differences were noted in the assessed patient characteristics, including mean age (p = 0.61), Federation of Gynecology and Obstetrics stage (p = 0.9), American Society of Anesthesiologists grade (p = 0.9), body mass index (p = 0.8), and residual tumor size (p = 0.86). Furthermore, duration of antibiotic treatment (p = 0.97), surgical procedures (p = 0.99), and total hospital days (p = 0.75), were not different between groups. The risk of surgical (p = 0.78) or nonsurgical (p = 1.0) complications was not significantly higher in the non-MBP group than in the MBP group. CONCLUSION: MBP provides no significant benefit during gynecological oncology surgery. Thus, preoperative MBP is not essential before gynecological oncology surgery and can be omitted.

Spontaneous bilateral extrapleural hematoma: a case report.

Extrapleural hematoma (EPH) is a rare condition characterized by the accumulation of blood in the extrapleural space. EPH is generally identified by computed tomography (CT), which shows an inward displacement of extrapleural fat due to intrathoracic peripheral fluid accumulation (Ann Ital Chir 75(83): 5, 2004; J Korean Radiol Soc 49: 89-97, 2003; Monaldi Arch Chest Dis 63(3): 166-169, 2005). EPH has been reported to be associated with chest trauma and injuries. However, the correlation between hemodialysis and EPH has not yet been reported. The causes of EPH in a hemodialysis patient have been postulated, which include high venous flow through the arteriovenous fistula that results in an increase in venous pressure stenosis and/or thrombosis of the brachiocephalic and/or subclavian veins. These conditions thereby induce an increase in venous pressure in the intercostals and bronchial veins of the chest. Pleural fluid resorption is rare and excess pleural fluid formation commonly occurs (J Thoracic Imaging 26(3): 218-223, 2011). The occurrence of pleuritis with fusion of the two pleuric layers results in hematoma development in the extrapleural space instead of the pleural space. We present a chronic hemodialysis patient with spontaneous unilateral EPH. The progression to bilateral EPH was noted after VATS procedure. Awareness of EPH and the use of conservative management are key points for the treatment of this rare clinical condition.