A 16-Year-Old Girl with Sinonasal Cutaneous Fistula Following Excision and Radiotherapy for Rhabdomyosarcoma Requiring Reconstructive Surgery Using an Expanded Forehead Flap.

BACKGROUND Sinonasal rhabdomyosarcoma (RMS) is a rare malignancy in children and adolescents. It is aggressive and locally invasive, and can require local postoperative radiotherapy. This report presents the case of a 16-year-old girl with a sinonasal-cutaneous fistula following excision and radiotherapy for rhabdomyosarcoma, which required reconstructive surgery using an expanded forehead flap. CASE REPORT We report the case of a16-year-old girl who was referred to our clinic with sinonasal-cutaneous fistula. Prior to presentation at our department, she presented with bilateral intermittent nasal congestion 3 years ago. At a local hospital, orbital computed tomography and nasal endoscopic biopsy revealed an embryonal rhabdomyosarcoma (ERMS). One month later, skull base tumor resection, nasal cavity and sinus tumor resection, and low-temperature plasma ablation were performed at a local hospital. Two weeks after the operation, the patient received intensity-modulated radiation therapy for a total of 50 Gy. Chemotherapy started 15 days after radiotherapy, using a vincristine, dactinomycin, and cyclophosphamide (VAC) regimen. Approximately 1 month later, an ulcer appeared at the nasal root and the lesion gradually expanded. The patient was referred to our hospital due to the defect. Firstly, a tissue expander was implanted at the forehead for 7 months. Then, the skin around the defect was trimmed and forehead flap was separated to repair the lining and external skin. The flap survived well 1-year after the operation. CONCLUSIONS This report highlights the challenges of post-radiation reconstructive surgery and describes how an expanded forehead flap can achieve an acceptable cosmetic outcome in a patient with a sinonasal-cutaneous fistula.

IOX1 epigenetically enhanced photothermal therapy of 3D-printing silicene scaffolds against osteosarcoma with favorable bone regeneration.

Osteosarcoma (OS) is the third most common malignancy in adolescence. Currently, the treatments of OS confront great obstacles of tumor recurrence and critical bone defects after surgery, severely affecting the survival rates and living qualities of patients. Hence, it is urged to develop distinct biomaterials with both efficient tumor therapeutic and osteogenic functions. Although photothermal therapy (PTT) has aroused expanding interest, characterizing negligible invasiveness and high spatiotemporal adjustment, few studies discussed its drawbacks, such as thermal injury to adjacent normal tissue and exceeded laser power density, implying that focusing on sensitizing OS to PTT instead of simply elevating the laser power density may be a fresh way to enhance the PTT efficacy and attenuate the side/adverse effects. Herein, we successfully constructed 3D-printing silicene bioactive glass scaffolds with preferable PTT efficacy at the second near-infrared (NIR-II) biowindow and outstanding osteogenic biofunctions owing to the release of bioactive elements during degradation. Impressively, a histone demethylase inhibitor, IOX1, was introduced before PTT to sensitize OS to thermal therapy and minimize the side/adverse effects. This work offered a distinctive paradigm for optimizing the PTT efficacy of osteogenic scaffolds against OS with epigenetic modulation agents.

Hybrid Autologous Costal Cartilage Grafting for Augmentation Rhinoplasty in Asian Patients.

BACKGROUND: Autologous costal cartilage has been used for augmentation rhinoplasty in Asia for many years. This study aimed to assess the effectiveness and safety of hybrid grafting of costal cartilage for dorsal augmentation, septal reconstruction, and tip augmentation for Asian patients. METHODS: A surgical technique was introduced and patients having rhinoplasty using this technique from April 2020 to March 2021 were retrospectively studied. In this technique, costal cartilage was meticulously carved or diced and grafted in various ways mainly based on the anatomic characteristics of nasal skin and subcutaneous soft tissues as well as bone and cartilage framework. The surgical outcomes, patient satisfaction, and complications retrieved from the documented medical records were reviewed and analyzed. RESULTS: Twenty-five patients having rhinoplasty with the proposed technique were followed up from 6 months to 12 months. As for cosmetic outcomes, 21 patients were graded as good, 3 patients were graded as fair, and only 1 patient was graded as poor. Those patients who were not graded as good had over-rotated tips, insufficient dorsal augmentation, or asymmetry of nostrils and soft tissue contracture. The overall patient satisfaction was as high as 96.0%. Local infection occurred in 1 patient and hematoma was not observed. Warping and visibility of costal cartilage were not observed in any patients. Slight displacement of diced cartilages was found in 2 patients near the radix 1 week postoperatively. CONCLUSIONS: Hybrid autologous costal cartilage grafts can be used for both tip refinement and dorsal augmentation for East Asian patients and achieve an outcome of a natural-looking nose with minimal complications. LEVEL OF EVIDENCE: Level IV.

The efficacy and safety of epirubicin and cyclophosphamide combined with pyrotinib in neoadjuvant treatment for HER2-positive breast cancer: A real-world study.

Purpose: Long-term survival benefit of anthracyclines for human epidermal growth factor receptor 2 (HER2)-positive breast cancer is clear. In the neoadjuvant treatment, compared with the monoclonal antibody such as trastuzumab and pertuzumab, the clinical benefit of pyrotinib, a new small-molecule tyrosine kinase inhibitor (TKI), as the main anti-HER2 strategy currently requires more research to determine. Our real-world study is the first prospective observational study in China to evaluate the efficacy and safety of epirubicin (E) and cyclophosphamide (C) with pyrotinib as anti-HER2 therapy in the neoadjuvant setting of patients with stage II-III HER2-positive breast cancer. Methods: From May 2019 to December 2021, 44 untreated patients with HER2-positive nonspecific invasive breast cancer who received 4 cycles of neoadjuvant EC with pyrotinib. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included the overall clinical response, breast pathological complete response rate (bpCR), the rate of axillary lymph nodes pathological negativity and adverse events (AEs). Other objective indicators were the rate of surgical breast-conserving, the negative conversion ratios of tumor markers. Results: Thirty-seven (84.1%) of 44 patients completed this neoadjuvant therapy, and 35 (79.5%) had surgery and were included in the primary endpoint assessment. The objective response rate (ORR) of 37 patients was 97.3%. Two patients reached clinical complete response, 34 obtained clinical partial response, 1 sustained stable disease, and no one had progressive disease. Eleven (31.4%) of 35 patients who had surgery achieved bpCR and the rate of axillary lymph nodes pathological negativity was 61.3%. The tpCR rate was 28.6% (95% CI: 12.8-44.3%). Safety was evaluated in all 44 patients. Thirty-nine (88.6%) had diarrhea, and 2 developed grade 3 diarrhea. Four (9.1%) patients had grade 4 leukopenia. All grade 3-4 AEs could be improved after symptomatic treatment. Conclusion: The regimen of 4 cycles of EC combined with pyrotinib presented some feasibility in the neoadjuvant setting for HER2-positive breast cancer with manageable safety. New regimens with pyrotinib should be evaluated for higher pCR in future. Trial registration: chictr.org Identifier: ChiCTR1900026061.

Ferroptosis regulator SLC7A11 is a prognostic marker and correlated with PD-L1 and immune cell infiltration in liver hepatocellular carcinoma.

Background: Liver hepatocellular carcinoma (LIHC) is a complicated disease with poor survival and lack of viable treatment options. The roles of ferroptosis and immunotherapy in LIHC are increasingly prominent, but the interplay of ferroptosis with the tumor microenvironment (TME) in LIHC is currently under-investigated. Methods: In this study, we analyzed normal liver tissues and tumor tissues from the TCGA and GTEx databases to obtain differentially expressed ferroptosis-related genes (FRGs). We then clustered LIHC based on the expression levels of selected FRGs and acquired distinct subtypes with significant heterogeneity regarding survival prognoses, PD-L1 expression, and immune cell infiltration. The correlation of those FRGs with TME in LIHC and pan-cancer analysis was also investigated. GO functional annotations and KEGG pathway analyses were performed to investigate the potential reactions of the obtained differentially expressed genes (DEGs). Further external validation was performed using microarrays on the GEO database and the key ferroptosis regulator SLC7A11 expression between LIHC and normal cells was detected by Western blotting. Results: A large proportion of genes were upregulated in the LIHC group. Among three clusters, cluster 3 had the worst prognosis combined with the highest PD-L1 expression and was positively correlated with various immune cells. Subsequently, survival analysis and Cox regression analysis screened out SLC7A11 as an independent prognostic factor in LIHC featured strong PD-L1 expression and unfavorable survival time. We filter out SLC7A11 as an independent prognostic signature in LIHC patients with strongly associated PD-L1 expression and unfavorable survival probability. In the pan-cancer analysis, high expression of SLC7A11 showed poor overall survival in seven cancers, while the correlation between immune checkpoints (ICs) and SLC7A11 varied by cancer type, indicating the potential therapeutic effects of SLC7A11 in cancers other than LIHC. Western blot was further employed to verify the expression of SLC7A11 in LIHC in vitro. Conclusion: Ferroptosis and TME synergistically play key roles in oncogenesis and progression of LIHC, and SLC7A11 can be used as a predictive biomarker for customized immunotherapy.

Association of novel MUC16, MAP3K15 and ABCA1 mutation with giant congenital melanocytic nevus.

BACKGROUND: Giant congenital melanocytic nevus (GCMN) is the benign nevomelanocytic proliferation. Mutations in NRAS have been previously detected in GCMN, but mutations in BRAF are generally lacking in the Chinese population. Mutated genes in this disease can estimate the risk of malignant transformation in GCMN. Therefore, it is worth investigating the genetic information of GCMN. METHODS: Here, we presented two cases of GCMN of the upper extremities. The clinical and histological data were analyzed. The whole exome sequencing (WES) was performed to investigate the mutational profile of peripheral venous blood (PB), normal skin (NS), small melanocytic nevus (SMN), deep penetrating and non-penetrating GCMN (dPGCMN and nPGCMN). RESULTS: We showed a reduction in the circumference of involved upper extremities in both patients. The clinical and histopathological data indicated the reduction of adipose tissue associated with the invasion of GCMN. The WES data revealed that MUC16, MAP3K15 and ABCA1 were novel potential candidate genes for the disease as well as biomarkers for predicting malignant transformation. CONCLUSION: The MUC16, MAP3K15 and ABCA1 may serve as novel biomarkers for predicting malignant transformation and targets for the diagnoses and therapy for the GCMN.

Investigating the Reliability of Novel Nasal Anthropometry Using Advanced Three-Dimensional Digital Stereophotogrammetry.

Three-dimensional surface imaging systems (3DSI) provide an effective and applicable approach for the quantification of facial morphology. Several researchers have implemented 3D techniques for nasal anthropometry; however, they only included limited classic nasal facial landmarks and parameters. In our clinical routines, we have identified a considerable number of novel facial landmarks and nasal anthropometric parameters, which could be of great benefit to personalized rhinoplasty. Our aim is to verify their reliability, thus laying the foundation for the comprehensive application of 3DSI in personalized rhinoplasty. We determined 46 facial landmarks and 57 anthropometric parameters. A total of 110 volunteers were recruited, and the intra-assessor, inter-assessor, and intra-method reliability of nasal anthropometry were assessed through 3DSI. Our results displayed the high intra-assessor reliability of MAD (0.012-0.29, 0.003-0.758 mm), REM (0.008-1.958%), TEM (0-0.06), rTEM (0.001-0.155%), and ICC (0.77-0.995); inter-assessor reliability of 0.216-1.476, 0.003-2.013 mm; 0.01-7.552%, 0-0.161, and 0.001-1.481%, 0.732-0.985, respectively; and intra-method reliability of 0.006-0.598°, 0-0.379 mm; 0 0.984%, 0-0.047, and 0-0.078%, 0.996-0.998, respectively. This study provides conclusive evidence for the high reliability of novel facial landmarks and anthropometric parameters for comprehensive nasal measurements using the 3DSI system. Considering this, the proposed landmarks and parameters could be widely used for digital planning and evaluation in personalized rhinoplasty, otorhinolaryngology, and oral and maxillofacial surgery.

[Treatment of extensive cervicomandibular scar in children and adolescent patients with bilateral expanded scapular flaps: report of 7 consecutive cases].

PURPOSE: To explore the feasibility of applying bilateral free expanded scapular flaps to treat extensive cervicomandibular scar in children and adolescents. METHODS: This study reviewed 7 children and adolescent patients who received bilateral expanded scapular flaps to treat extensive cervicomandibular scars in the Pediatric Plastic Surgery Ward from August 2018 to December 2020. The scars in all patients involved neck, mandible, and anterior chest. The cervical scars involved the anterior neck and one or both sides of the lateral neck, and there were varying degrees of cervical dysfunction and mandibular dysplasia. The operation was completed into two stages. In the first stage, the expanded circumflex scapular artery perforator flaps were designed on both sides of the back and soft tissue expanders were implanted. The expansion process lasted for 6-14 months. In the second stage, the scar tissue was removed and contracture was released, and the expanded flaps were harvested. The cervical wound was repaired with free flap transplantation by anastomosing the facial artery and vein with the circumflex scapular artery and vein. The donor sites were closed directly. RESULTS: In this series of 7 patients, one patient had poorly healed incision after the expander was implanted. One expanded flap ruptured before the second-stage surgery, which was successfully treated by secondary surgery. One patient had expansion problem due to the blockage of the internally placed injection bottle, which was treated by placing the injection bottle externally. One patient developed a small area of ischemic necrosis at the distal end of the flap after transplantation, which was treated conservatively with dressing change. The postoperative follow-up was 6 months to 2 years. The cervico-mandibular angle restored to normal range, the cervical extension, flexion, and rotation were significantly improved. Two patients underwent flap thinning and scar releasing. CONCLUSIONS: The route of the circumflex scapular artery is constant. Bilateral expanded scapular flap transplantation can be used to repair extensive cervicomandibular scar in children and adolescent patients. The flap donor site is concealed and secondary damage is minimal.

HOXA5 counteracts the function of pathological scar-derived fibroblasts by partially activating p53 signaling.

The inactivation of p53 can lead to the formation of pathological scars, including hypertrophic scars and keloids. HOXA5 has been reported to be a critical transcription factor in the p53 pathway in cancers. However, whether HOXA5 also plays a role in pathological scar progression through activating p53 signaling remains unknown. In this study, we first demonstrated that HOXA5 overexpression in hypertrophic scar-or keloids-derived fibroblasts decreased cell proliferation, migration and collagen synthesis, whereas increased cell apoptosis. Furthermore, the results of luciferase activity assays and ChIP PCR assays indicated that HOXA5 transactivated p53 by binding to the ATTA-rich core motif in the p53 promoter. HOXA5 also increased the levels of p21 and Mdm2, which are downstream targets of p53. Interestingly, silencing p53 in these pathological scar-derived fibroblasts partially attenuated HOXA5-mediated growth inhibition effect and HOXA5-induced apoptosis. In addition, 9-cis-retinoic acid augmented the expression of HOXA5 and promoted the effects of HOXA5 on pathological scar-derived fibroblasts, and these effects could be suppressed by HOXA5 knockdown. Thus, our study reveals a role of HOXA5 in mediating the cellular processes of pathological scar-derived fibroblasts by transcriptionally activating the p53 signaling pathway, and 9-cis-retinoic acid may be a potential therapy for pathological scars.

LncRNA FLVCR1-AS1 accelerates osteosarcoma cells to proliferate, migrate and invade via activating wnt/ß-catenin pathway.

PURPOSE: To clarify the biological function of long non-coding RNA (lncRNA) FLVCR1-AS1 in the progression of osteosarcoma. METHODS: The correlation between FLVCR1-AS1 level and pathological indexes of osteosarcoma patients was analyzed by chi-square test. Subsequently, the regulatory effects of FLVCR1-AS1 on the proliferative, migratory and invasive abilities of osteosarcoma cells were evaluated. Moreover, the relative levels of CTNNB1, SOX4, CCND1, CCND2 and MYC in osteosarcoma cells regulated by FLVCR1-AS1 were detected by qRT-PCR. Finally, rescue experiments were conducted to verify the role of wnt/ß-catenin in osteosarcoma progression. RESULTS: LncRNA FLVCR1-AS1 was upregulated in osteosarcoma, which was positively correlated to tumor size, WHO grade and distant metastasis, but negatively correlated to survival of osteosarcoma patients. Overexpression of FLVCR1-AS1 markedly suppressed osteosarcoma cells to proliferate, migrate and invade. Relative levels of CTNNB1, SOX4, CCND1, CCND2, MYC and nucleus ß-catenin were upregulated in U2OS and MG63 cells overexpressing FLVCR1-AS1. Finally, CTNNB1 knockdown was identified to reverse the influence of overexpressed FLVCR1-AS1 of osteosarcoma cells. CONCLUSIONS: FLVCR1-AS1 accelerates the progression of osteosarcoma via activating wnt/ß-catenin pathway.

Cloning and Functional Characterization of Putative Escherichia coli ABC Multidrug Efflux Transporter YddA.

A putative multidrug efflux gene, yddA, was cloned from the Escherichia coli K-12 strain. A drugsensitive strain of E. coli missing the main multidrug efflux pump AcrB was constructed as a host and the yddA gene was knocked out in wild-type (WT) and drug-sensitive E. coliΔacrB to study the yddA function. Sensitivity to different substrates of WT E.coli, E. coliΔyddA, E. coliΔacrB and E. coliΔacrBΔyddA strains was compared with minimal inhibitory concentration (MIC) assays and fluorescence tests. MIC assay and fluorescence test results showed that YddA protein was a multidrug efflux pump that exported multiple substrates. Three inhibitors, ortho-vanadate, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and reserpine, were used in fluorescence tests. Ortho-vanadate and reserpine significantly inhibited the efflux and increased accumulation of ethidium bromide and norfloxacin, while CCCP had no significant effect on YddA-regulated efflux. The results indicated that YddA relies on energy released from ATP hydrolysis to transfer the substrates and YddA is an ABC-type multidrug exporter. Functional study of unknown ATP-binding cassette (ABC) superfamily transporters in the model organism E. coli is conducive to discovering new multidrug resistance-reversal targets and providing references for studying other ABC proteins of unknown function.

Estrogen accelerates heart regeneration by promoting the inflammatory response in zebrafish.

Sexual differences have been observed in the onset and prognosis of human cardiovascular diseases, but the underlying mechanisms are not clear. Here, we found that zebrafish heart regeneration is faster in females, can be accelerated by estrogen and is suppressed by the estrogen-antagonist tamoxifen. Injuries to the zebrafish heart, but not other tissues, increased plasma estrogen levels and the expression of estrogen receptors, especially esr2a. The resulting endocrine disruption induces the expression of the female-specific protein vitellogenin in male zebrafish. Transcriptomic analyses suggested heart injuries triggered pronounced immune and inflammatory responses in females. These responses, previously shown to elicit heart regeneration, could be enhanced by estrogen treatment in males and reduced by tamoxifen in females. Furthermore, a prior exposure to estrogen preconditioned the zebrafish heart for an accelerated regeneration. Altogether, this study reveals that heart regeneration is modulated by an estrogen-inducible inflammatory response to cardiac injury. These findings elucidate a previously unknown layer of control in zebrafish heart regeneration and provide a new model system for the study of sexual differences in human cardiac repair.

Circ_ANKIB1 stabilizes the regulation of miR-19b on SOCS3/STAT3 pathway to promote osteosarcoma cell growth and invasion.

Osteosarcoma is a highly malignant tumor. The molecular mechanism of its occurrence and development has not yet been clarified. Current studies have found that noncoding RNAs, such as circular RNAs (circRNAs) and microRNAs (miRNAs), play important regulatory roles in the progression of diseases. Our previous studies have shown that miR-19b is an oncogene in osteosarcoma. Further studies have shown that circ_ANKIB1 has binding sites for miR-19b, and both molecules were generally upregulated in osteosarcoma cells. RIP assay, RNA pull down, and dual-luciferase reporter gene assay showed that circ_ANKIB1 could directly bind to miR-19b and act as an miR-19b sponge in osteosarcoma cells. Circ_ANKIB1 promoted miR-19b expression, inhibited the expression of the downstream target gene SOCS3, and then activated the STAT3 pathway. When cotransfected with circ_ANKIB1 siRNA, and miR-19b mimics, the expression of SOCS3 and the phosphorylation level of STAT3 did not change significantly. Continuous detection of cell growth and invasion showed that the downregulation of circ_ANKIB1 or miR-19b significantly inhibited cell proliferation and invasion, but increased the apoptotic level. When cotransfected with circ_ANKIB1 siRNA and miR-19b mimics or SOCS3 siRNA, the cell proliferation, apoptosis, and invasion levels did not change significantly, suggesting that circ_ANKIB1 could affect the STAT3 pathway and osteosarcoma cell growth and invasion by enhancing the regulation of miR-19b on the downstream target gene SOCS3. These findings suggest that circRNAs stabilize miRNA functions, and further studies on this new function of circRNAs will provide a meaningful reference for the diagnosis and treatment of tumors and other diseases.

Blockade of lncRNA-ASLNCS5088-enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation.

In hypertrophic scar (HS) formation, the type 2 immune response induces the alternatively activated macrophages (M2), which manipulate fibroblasts to differentiate into myofibroblasts with active biologic functions and proliferation. Myofibroblasts express α-smooth muscle actin (α-SMA) and synthesize and produce additional collagen type I and collagen type III, inducing HS formation. However, studies on the mechanism of M2 macrophage modulation are only based on the recognition of profibrotic factors such as TGF-ß1 secreted by macrophages. The influence of exosomes from M2 macrophages on scar formation is still unknown. Both M2 macrophages and myofibroblasts highly express glutaminases (GLSs). GLS is a critical enzyme in glutaminolysis and is important for M2 macrophage and fibroblast polarization. In this study, we found that in a TGF-ß1-stimulated coculture system, a long noncoding RNA (lncRNA) named lncRNA-ASLNCS5088 was enriched in M2 macrophage-derived exosomes. This lncRNA could be transferred with high efficiency to fibroblasts and acted as an endogenous sponge to adsorb microRNA-200c-3p, resulting in increased GLS and α-SMA expression. Pretreatment with GW4869, which impairs M2 macrophage exosome synthesis, ameliorated these pathologic changes in fibroblasts in vitro. Local injection in the late scar formation period with GW4869 reduced α-SMA+ fibroblasts and alleviated the fibrosis of tissue after wound healing in vivo.-Chen, J., Zhou, R., Liang, Y., Fu, X., Wang, D., Wang, C. Blockade of lncRNA-ASLNCS5088-enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation.

Modification of the plasma complement protein profile by exogenous estrogens is indicative of a compromised immune competence in marine medaka (Oryzias melastigma).

Growing evidence suggests that the immune system of teleost is vulnerable to xenoestrogens, which are ubiquitous in the marine environment. This study detected and identified the major circulatory immune proteins deregulated by 17α-ethinylestradiol (EE2), which may be linked to fish susceptibility to pathogens in the marine medaka, Oryzias melastigma. Fish immune competence was determined using a host resistance assay to pathogenic bacteria Edwardsiella tarda. Females were consistently more susceptible to infection-induced mortality than males. Exposure to EE2 could narrow the sex gap of mortality by increasing infection-induced death in male fish. Proteomic analysis revealed that the major plasma immune proteins of adult fish were highly sexually dimorphic. EE2 induced pronounced sex-specific changes in the plasma proteome, with the male plasma composition clearly becoming "feminised". Male plasma was found to contain a higher level of fibrinogens, WAP63 and ependymin-2-like protein, which are involved in coagulation, inflammation and regeneration. For the first time, we demonstrated that expression of C1q subunit B (C1Q), an initiating factor of the classical complement pathway, was higher in males and was suppressed in both sexes in response to EE2 and bacterial challenge. Moreover, cleavage and post-translational modification of C3, the central component of the complement system, could be altered by EE2 treatment in males (C3dg down; C3g up). Multiple regression analysis indicated that C1Q is possibly an indicator of fish survival, which warrants further confirmation. The findings support the potential application of plasma immune proteins for prognosis/diagnosis of fish immune competence. Moreover, this study provides the first biochemical basis of the sex-differences in fish immunity and how these differences might be modified by xenoestrogens.

Tanshinone IIA Inhibits Proliferation and Induces Apoptosis Through the Downregulation of Survivin in Keloid Fibroblasts.

Keloids are considered benign dermal fibroproliferative tumors. Keloid fibroblasts (KFs) persistently proliferate and fail to undergo apoptosis, and no treatment is completely effective against these lesions. Tanshinone IIA induces apoptosis and inhibits the proliferation of various tumor cell types. In this study, we investigated the effect of tanshinone IIA on the regulation of proliferation, cell cycle, and apoptosis in KFs, and investigated potential mechanisms involved in the effects. First, KFs and normal skin fibroblasts (NSFs) were treated with various concentrations of tanshinone IIA. Cell counting kit-8 (CCK-8) was used to assess the proliferative activity of KFs and NSFs, and flow cytometry was used to investigate the cell cycle and apoptosis in KFs. We found that the proliferation of all tanshinone IIA-treated KFs was significantly decreased after treatment for 72 hours (P < 0.001). Also, NSFs treated with tanshinone IIA did not exhibit noticeable effects compared with KFs. In addition, the percentages of G0/G1 cells in all tanshinone IIA-treated KFs were significantly increased after treatment for 72 hours (P < 0.001). And the percentages of cells undergoing early apoptosis in all tanshinone IIA-treated KFs were significantly increased after treatment for 120 hours (P < 0.001). Furthermore, the apoptosis antibody array kit and Western blot analysis revealed that tanshinone IIA decreased survivin expression in KFs (P < 0.001). In conclusion, tanshinone IIA downregulates survivin and deactivates KFs, thus suggesting that tanshinone IIA could serve as a potential clinical keloid treatment.

Oxidative Degradation of the Monolayer of 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphocholine (POPC) in Low-Level Ozone.

Ambient ozone is a common pollutant in the atmosphere that has an extremely high oxidative ability, can dramatically change the structure and functionality of biomolecules, and is harmful to public health. However, the knowledge about the influence of low-level ozone is still very limited at a molecular level. In the present study, the monolayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC, 16:0-18:1 PC) as well as its binary mixed monolayer with 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC, 16:0 PC), which are widely found in many biological systems, have been systematically investigated in a low-level ozone environment (20 ± 10 ppb), by π-A isotherm, sum frequency generation (SFG) vibrational spectroscopy, and atomic force microscopy (AFM). Our results demonstrate that the POPC monolayer is unstable and the C═C moieties in the oleyl chain are selectively oxidized by the low-level ozone. The oxidized lipids from POPC initially remain and reorientate the hydrophilic portion to the water surface and gradually dissolve into the aqueous solution. One should take great caution when using unsaturated lipid molecules to avoid their possible oxidation in the ambient environment. The present study expands and deepens our insights into the oxidation mechanism of unsaturated lipids at a molecular level.

Synthesis and antitumor activity of a series of osmium(VI) nitrido complexes bearing quinolinolato ligands.

A series of osmium(VI) nitrido complexes supported by quinolinolato ligands have been prepared and they exhibit promising in vitro anti-cancer activities. These results establish that Os(VI)≡N is a potentially versatile and promising platform for the design of a variety of high-valent anti-cancer drugs.

Adipose tissue-derived stem cells (ADSCs) transplantation promotes regeneration of expanded skin using a tissue expansion model.

Transplantation of adipose tissue-derived stem cells (ADSCs) is a promising method that has been used in regenerative medicine because it has shown the capacity to accelerate wound healing. However, roles of ADSCs transplantation in expanded-skin regeneration have remained unknown. To clarify the roles, a tissue expansion model was used in this study. The study comprised three groups of 13 rats in each group: the ADSCs group, the fibroblast (FB) group, and the control group. The skin regeneration in the ADSCs group was enhanced, as evidenced by increased cell proliferation and a higher hydroxyproline content and degree of neovascularization, all with p < 0.05, when compared with both the FB group and the control group. Consistent with enhanced cell proliferation and neovascularization, the regenerated skin in the ADSCs group was much thicker, which further reduced the retraction ratio of the expanded skin. Four weeks after operation, 5'-bromo-2'-deoxyuridine-labeled ADSCs appeared in subcutaneous tissue, vascular vessels, and hair follicles. The up-regulation of protein expression, such as epidermal growth factor and vascular endothelial growth factor, primarily emerged in the ADSC group, with the up-regulated basic fibroblast growth factor appearing in the FB group. Collectively, these results suggest that the transplantation of ADSCs could enhance the regeneration of expanded skin by participating in skin structures and up-regulating the secretion of epidermal growth factor and vascular endothelial growth factor.