The systemic inflammation indexes after admission predict in-hospital mortality in patients with extensive burns.

PURPOSE: To explore the clinical value of various complete blood count (CBC)-derived inflammation indicators to predict in-hospital mortality in patients with extensive burns. METHODS: Systemic inflammation indexes, including lymphocyte-platelet ratio (LPR), neutrophil-lymphocyte ratio (NLR), neutrophil-monocyte ratio (NMR), monocyte-lymphocyte ratio (MLR), neutrophil-to-lymphocyte * platelet (NLPR), systemic inflammation index (SII), and systemic inflammation response index (SIRI) on days 1, 3, and 7 after admission were calculated in 135 patients with extensive burns. RESULTS: We included 135 patients with extensive burns, including 97 survivors and 38 non-survivors. After adjusting for confounders, only the LPR on day 1, NLPR on days 3 and 7 were significantly associated with survival (OR= 1.237, 1.097, 1.104; 95 % CI: 1.055-1.451, 1.002-1.202, 1.005-1.212; respectively) in the analysis of multivariate logistic regression. The optimum cutoff values of the LPR on day 1 and NLPR on day 3 were 6.37 and 8.06, and the area under the curves (AUC) were 0.695 and 0.794, respectively. The AUC of NLPR on day 7 had the highest value, 0.814, and the optimum cut-off value was 3.84. The efficacy of LPR on day 1, NLPR on days 3 and 7 combined with the burn prognostic score index in predicting the prognosis of patients was higher than that of the burn index alone, and the three composite inflammatory indexes combined with PBI had the highest efficacy in predicting the prognosis (AUC = 0.994). Kaplan-Meier survival analysis showed poor prognosis in patients with higher LPR on day 1 and higher NLPR on days 3 and 7 (log-rank χ2 =9.623,31.564, 20.771, respectively; P < 0.01). CONCLUSIONS: LPR on day 1 and NLPR on days 3 and 7 after admission are reliable predictors of prognosis in patients with severe extensive burns. The combination of the burn prognostic score index, LPR on day 1, and NLPR on days 3 and 7 was superior to the burn indexes alone in predicting a patient's prognosis.

[Retracted] Downregulation of let­7b promotes COL1A1 and COL1A2 expression in dermis and skin fibroblasts during heat wound repair.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the western blotting data shown in Figs. 4B and 5 and the H&E immunostaining data shown in Fig 1A were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time.  Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 2683-2688, 2016; DOI: 10.3892/mmr.2016.4877].

MicroRNA-9 inhibits the proliferation and migration of malignant melanoma cells via targeting sirituin 1.

[This retracts the article DOI: 10.3892/etm.2017.4595.].

The antimicrobial peptides and their potential clinical applications.

Nowadays, the bacterial drug resistance leads to serious healthy problem worldwide due to the long-term use and the abuse of traditional antibiotics result in drug resistance of bacteria. Finding a new antibiotic is becoming more and more difficult. Antimicrobial peptides (AMPs) are the host defense peptides with most of them being the cationic (positively charged) and amphiphilic (hydrophilic and hydrophobic) α-helical peptide molecules. The membrane permeability is mostly recognized as the well-accepted mechanism to describe the action of cationic AMPs. These cationic AMPs can bind and interact with the negatively charged bacterial cell membranes, leading to the change of the electrochemical potential on bacterial cell membranes, inducing cell membrane damage and the permeation of larger molecules such as proteins, destroying cell morphology and membranes and eventually resulting in cell death. These AMPs have been demonstrated to have their own advantages over the traditional antibiotics with a broad-spectrum of antimicrobial activities including anti-bacteria, anti-fungi, anti-viruses, and anti-cancers, and even overcome bacterial drug-resistance. The natural AMPs exist in a variety of organisms and are not stable with a short half-life, more or less toxic side effects, and particularly may have severe hemolytic activity. To open the clinical applications, it is necessary and important to develop the synthetic and long-lasting AMP analogs that overcome the disadvantages of their natural peptides and the potential problems for the drug candidates.

Study of Promoter Methylation Patterns of HOXA2, HOXA5, and HOXA6 and Its Clinicopathological Characteristics in Colorectal Cancer.

Research on DNA methylation offers great potential for the identification of biomarkers that can be applied for accurately assessing an individual's risk for cancer. In this article, we try to find the ideal epigenetic genes involved in colorectal cancer (CRC) based on a CRC database and our CRC cohort. The top 20 genes with an extremely high frequency of hypermethylation in CRC were identified in the latest database. Remarkably, 3 HOXA genes were included in this list and ranked at the top. The percentage of methylation in the HOXA5, HOXA2, and HOXA6 genes in CRC were up to 67.62, 58.36, and 31.32%, respectively, and ranked first in CRC among all human tumor tissues. Paired colorectal tumor samples and adjacent non-tumor colorectal tissue samples and four CRC cell lines were selected for MethylTarget™ assays. The results demonstrated that CRC tissues and cells had a stronger methylation status around the 3 HOXA gene promoter regions compared with adjacent non-tumor colonic tissue samples. The Receiver operator characteristic curve (ROC) curves for HOXA genes show excellent diagnostic ability in distinguishing tissue from healthy individuals and CRC patients, especially for Stage I patients (AUC = 0.9979 in HOXA2, 0.9309 in HOXA5, and 0.8025 in HOXA6). An association analysis between the methylation pattern of HOXA genes and clinical indicators was performed and found that HOXA2 methylation was significantly associated with age, N, stage, M, lymphovascular invasion, perineural invasion, lymph node number. HOXA5 methylation was associated with age, T, M, stage, and tumor status, and HOXA6 methylation was associated with age and KRAS mutation. Notably, we found that the highest methylation of HOXA5 and HOXA2 occurs in the early stages of colorectal cancer tissues such as stage I, N0, MO, and non-invasive tissues. The methylation levels declined as tumors progressed. However, methylation level at any stage of the tumor was still significantly higher than in normal tissues (p < 0.0001). The mRNA of the 3 HOXA genes was downregulated in early tumor stages due to hypermethylation of CpG islands adjacent to the promoters of the genes. In addition, hypermethylation of HOXA5 and HOXA6 mainly occurred in patients < 60 years old and with MSI-L, MSS, CIMP.L and non-CIMP tumors. Together, this suggests that epigenetic silencing of 3 adjacent HOXA genes may be an important event in the progression of colorectal cancer.

Application of animated cartoons in reducing the pain of dressing changes in children with burn injuries.

BACKGROUND: Nonpharmacological management remains one of the central pain interventional therapies in the burn unit. VR and other distraction treatments for adults have achieved great advantages in pain relief. METHODS: A within-subject study was conducted to evaluate 54 participants aged from 3 to 7. In the control group, a standard analgesic, ibuprofen, was used over the period of dressing change, whereas animated cartoons were played simultaneously in the intervention-group condition. We adopted the Wong-Baker faces pain rating scale, COMFORT scale, FLACC scale and POCIS to assess the pain rating 5 min before, during and 5 min after dressing changes, respectively. RESULTS: Compared with the control group, FLACC scale and POCIS scores in the intervention group were not significantly different (P>0.05) throughout the observation period; outcomes measured using the Wong-Baker faces pain rating scale and COMFORT scale 5 min before and during dressing changes were also not different between the groups (P>0.05). Nevertheless, 5 min after that period, subjects in the intervention group had reduced pain behavior according to scores on the Wong-Baker faces pain rating scale (control-group scores: 7.231±0.403; intervention-group scores: 6.026±0.501, P<0.05) and COMFORT scale (control-group scores: 21.602±1.316; intervention-group scores: 19.040±1.204, P<0.05). CONCLUSION: This study supports that watching animated cartoons appears to be a practical way to ease the pain behavior of children in the burn unit after replacing wound dressings, although its effectiveness remains insufficient before and during the dressing change procedure. SIGNIFICANCE: Conducting a thorough study and exploring the efficacy of animated cartoons in reducing the pain of dressing changes for pediatric patients may surely result in practical value, especially in developing countries.

E2F3 promotes cancer growth and is overexpressed through copy number variation in human melanoma.

INTRODUCTION: Melanoma is a malignant tumor that seriously affects patients. The pathogenesis of malignant melanoma is complex, and the cell cycle is closely related to tumor progression. Based on the catalog of cancer somatic mutations, we found that overexpression of the E2F3 gene ranked first in percentage increase in not only melanoma but also in all human cancer tissues. However, there are few studies on the high expression of E2F3 and its carcinogenic mechanism in melanoma. METHODS AND RESULTS: We found that E2F3 showed extensive copy number amplification that was positively correlated with the expression level. Patients with high copy number had a significantly poorer prognosis. We also found that E2F3 levels were significantly negatively correlated with promoter methylation. However, we showed that the E2F3 promoter region is hypomethylated, and in normal cells or tumor cells, the methylation level did not correlate with expression. Finally, we knocked down the E2F3 gene in melanoma cells by shRNA. Colony formation, anchorage-dependent growth, and EdU cell proliferation experiments showed a significant decrease in proliferation. Flow cytometry showed a significant increase in the G0/G1 ratio. CONCLUSION: It can be speculated that copy number amplification and other mechanisms result in the high expression of E2F3 in melanoma, which promotes tumor progression by involving the cell cycle. E2F3 is a good target for the treatment of melanoma.

HDAC inhibitors suppressed small cell lung cancer cell growth and enhanced the suppressive effects of receptor-targeting cytotoxins via upregulating somatostatin receptor II.

Small cell lung cancer (SCLC) is a malignant human cancer and patients have very limited benefit from traditional anticancer treatments, with a poor five-year survival rate being 10% less. In present study, we observed that Notch signalling activation induced SCLC cell growth suppression via overexpressing Notch active fragments (ICN1, ICN2, ICN3 and ICN4), implying its tumor suppressive role. The histone deacetylase (HDAC) inhibitors also displayed their suppressive effects. Valproic acid (VPA) as a HDAC inhibitor was found to suppress SCLC cell growth and cell cycle arrest at phase G1, and observed to decrease HDAC4 and increase acetylation of histone H4 (AcH4) while activating Notch signalling with an increase of Notch1, Notch target gene HES1 and p21. Meanwhile, we also observed that VPA greatly stimulated the expression of somatostatin receptor type II (SSTR2) that is usually overexpressed in many cancer cells and is used as a target for anticancer drug development, providing a combination therapy with VPA and the SSTR2-targeting cytotoxins. Thus, VPA was investigated in combination with SSTR2-targeted cytotoxins captothecine-somatostatin conjugate (CPT-SST) and colchicine-somatostatin conjugate (COL-SST). Our assays showed that these combination treatments strongly led to a greater suppression as compared to each alone. In conclusion, we found that VPA suppressed SCLC cell growth and increased the expression of SSTR2. These may provide a novel clinical opportunity for enhanced anticancer therapy using the combination strategy of Notch signalling regulator and SSTR2-targeting cytotoxins in SCLC treatments.

MicroRNA-9 inhibits the proliferation and migration of malignant melanoma cells via targeting sirituin 1.

MicroRNA (miR) are a class of small non-coding RNA that are able to inhibit gene expression by directly binding to the 3' untranslated region (UTR) of their target mRNA and thus promote translational repression or mRNA degradation. Recently, miR-9 was reported to have a suppressive role in malignant melanoma; however, the underlying mechanism remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to examine the mRNA and protein expression levels in malignant melanoma tissues and cell lines. The MTT assay and wound healing assay were used to examine the cell viability, proliferation and migratory capacities. Bioinformatics prediction and luciferase reporter assay were performed to investigate the relationship between miR-9 and its potential target gene. The present data revealed that miR-9 expression was significantly downregulated in malignant melanoma tissues when compared with their matched adjacent non-tumor tissues. Furthermore, the expression levels of miR-9 were reduced in malignant melanoma cell lines when compared with human normal skin HACAT cells. Moreover, the ectopic expression of miR-9 significantly suppressed the proliferation and migration of malignant melanoma cells, accompanied with a remarkable decrease in the protein expression levels of sirtuin 1 (SIRT1), which were markedly upregulated in malignant melanoma tissues and cell lines. Additionally, restoration of SIRT1 reversed the suppressive effects of miR-9 on the proliferation and migration of malignant melanoma cells. Luciferase reporter assay data further identified SIRT1 as a direct target gene of miR-9. To conclude, the present findings indicate that miR-9 has a suppressive role in malignant melanoma cell viability and migration, at least in part, via directly inhibiting the protein expression of its target gene, SIRT1. Therefore, miR-9 may serve as a potential candidate for the treatment of malignant melanoma.

Identification of a missense HOXD13 mutation in a Chinese family with syndactyly type I-c using exome sequencing.

Syndactyly is one of the most common hereditary limb malformations, and is characterized by the fusion of specific fingers and/or toes. Syndactyly type I­c is associated with bilateral cutaneous or bony webbing of the third and fourth fingers and occasionally of the third to fifth fingers, with normal feet. The aim of the present study was to identify the genetic basis of syndactyly type I­c in four generations of a Chinese Han family by exome sequencing. Exome sequencing was conducted in the proband of the family, followed by direct sequencing of other family members of the same ancestry, as well as 100 ethnically­matched, unrelated normal controls. A missense mutation, c.917G>A (p.R306Q), was identified in the homeobox D13 gene (HOXD13). Sanger sequencing verified the presence of this mutation in all of the affected family members. By contrast, this mutation was absent in the unaffected family members and the 100 ethnically­matched normal controls. The results suggest that the c.917G>A (p.R306Q) mutation in the HOXD13 gene, may be responsible for syndactyly type I­c in this family. Exome sequencing may therefore be a powerful tool for identifying mutations associated with syndactyly, which is a disorder with high genetic and clinical heterogeneity. The results provide novel insights into the etiology and diagnosis of syndactyly, and may influence genetic counseling and the clinical management of the disease.

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling.

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our homemade device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)­1ß expression, and downregulating IL­10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)­ß and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen â…  and â…¢ were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)­13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)­1 and TIMP­2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP­1 and TIMP­2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD­induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue.

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1.

MicroRNAs (miRs) are a class of small noncoding RNAs that negatively regulate the gene expression by directly binding to the 3' untranslated region of their target mRNA, thus resulting in mRNA degradation or translational repression. miR-9 has recently been demonstrated to play a role in the development and progression of malignant melanoma (MM), but the regulatory mechanism of miR-9 in the malignant phenotypes of MM still remains largely unknown. In this study, a total of 73 pairs of MM tissues and adjacent normal tissues were collected. Real-time reverse transcription polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of miR-9. MTT assay, wound healing assay, and transwell assay were conducted to determine the cell proliferation, migration, and invasion. Luciferase reporter assay was used to determine the targeting relationship between miR-9 and NRP1. Our data demonstrated that miR-9 expression was significantly downregulated in MM tissues compared with that in adjacent normal tissues. The decreased miR-9 level was significantly associated with the tumor stage and metastasis of MM. We also found that the expression level of miR-9 was decreased in MM cell lines (G361, B16, A375, and HME1) compared with normal skin HACAT cells. Ectopic expression of miR-9 led to a significant decrease in the ability of proliferation, migration, and invasion in A375 cells. NRP1 was further identified as a direct target gene of miR-9, and the protein expression of NRP1 was negatively regulated by miR-9 in A375 cells. Furthermore, overexpression of NRP1 reversed the suppressive effects of miR-9 on the malignant phenotypes of A375 cells. In vivo study revealed that miR-9 overexpression decreased the tumor growth, while overexpression of NRP1 increased MM growth. In summary, our findings suggest that the miR-9/NRP1 axis may serve as a potential target for the treatment of MM.

Emodin­8­O­glucuronic acid, from the traditional Chinese medicine qinghuobaiduyin, affects the secretion of inflammatory cytokines in LPS­stimulated raw 264.7 cells via HSP70.

Qinghuobaiduyin (QHBDY) is a traditional Chinese medicine, which has an opsonization effect on the immune system. However, which chemical compound in QHBDY underlies the therapeutic effect remains to be elucidated. The present study was designed to investigate the effect of emodin­8­O­glucuronic acid, a chemical compound isolated from QHBDY, on the secretion of inflammatory cytokines in lipopolysaccharide (LPS)­stimulated Raw 264.7 cells. The compound was isolated from QHBDY and identified as emodin­8­O­glucuronic acid using liquid chromatography­mass spectrometryn. The results obtained from an ELISA assay showed that emodin­8­O­glucuronic acid inhibited the elevated expression levels of tumor necrosis factor­α (TNF­α), interleukin (IL)­1ß and IL­10 in the LPS­stimulated Raw 264.7 cells, which occurred in a dose­dependent manner. In addition, emodin­8­O­glucuronic acid induced the expression of heat shock protein 70 (HSP70) in the LPS­stimulated Raw 264.7 cells, as demonstrated using western blot analysis. The effect of emodin­8­O­glucuronic acid on the secretion of TNF­α, IL­1ß and IL­10 was attenuated by the knockdown of HSP70. In conclusion, the present study demonstrated that emodin­8­O­glucuronic acid effectively suppressed LPS­induced inflammatory cytokine secretion, and this effect was attained by the increased expression of HSP70.

miR-199a-5p induces cell invasion by suppressing E-cadherin expression in cutaneous squamous cell carcinoma.

A growing quantity of evidence exists to suggest that microRNAs are significant regulators of multiple cellular processes. When expressed aberrantly in different types of cancer, including cutaneous squamous cell carcinoma (cSCC), they play key roles in tumorigenesis and progression. The aberrant expression of miR-199a-5p has been observed to contribute to carcinogenesis in various types of cancer. However, the role of miR-199a-5p in the progression of cSCC metastasis remains largely unknown. In this study, we determined that miR-199a-5p was the upstream regulator of CDH1 (E-cadherin) and that it could suppress the expression of E-cadherin in cSCC cells. In addition, miR-199a-5p mimics significantly induced cell invasion and the activity of matrix metalloproteinase (MMP)2 and MMP9 in cSCC cells. In conclusion, these results are likely to aid in elucidating the molecular mechanisms of cSCC progression. In addition, the findings provide a new theoretical basis to further investigate miR-199a-5p as a potential biomarker and a promising approach in cSCC treatment.

Downregulation of let-7b promotes COL1A1 and COL1A2 expression in dermis and skin fibroblasts during heat wound repair.

MicroRNAs (miRs), a class of non­coding RNAs 18­25 nucleotides in length, generally serve suppressive role in the regulation of gene expression via directly binding to the 3'­untranslated region (UTR) of their target mRNA. Previous studies have identified several miRs to be involved in thermal injury repair. However, the role of miR let­7b during the recovery of thermal injury, in addition to the underlying mechanisms, has not previously been studied. In the present study, the expression of let­7b was observed to be significantly increased in skin tissue shortly following thermal injury, however, gradually reduced during the recovery of thermal injury. Notably, similar findings were observed in heat­denatured skin fibroblasts. Furthermore, collagen, type I, alpha 1 (COL1A1) and collagen, type I, alpha 2 (COL1A2), which are associated with the synthesis of type I collagen, were identified as two targets of let­7b in skin fibroblasts. The overexpression of let­7b was observed to upregulate the protein expression levels of COL1A1 and COL1A2, while knockdown of let­7b reduced the levels of COL1A1 and COL1A2 in skin fibroblasts. Furthermore, COL1A1 and COL1A2 were significantly downregulated shortly following thermal injury, while gradually upregulated during healing, in heat­damaged skin tissue and skin fibroblasts, with the expression profiles opposite to that of let­7b. Taken together, this suggests that the downregulation of let­7b in heat­damaged dermis promotes the synthesis of type I collagen and thus aids in burn wound repair.

miR-33a functions as a tumor suppressor in melanoma by targeting HIF-1α.

BACKGROUND: Our previous findings showed that miR-33 expressed abnormally in clinical specimens of melanoma, but the exact molecular mechanism has not been elucidated. OBJECT: To determine miR-33's roles in melanoma and confirm whether HIF-1α is a direct target gene of miR-33a. METHODS: First miR-33a/b expression levels were detected in HM, WM35, WM451, A375 and SK-MEL-1. Then lentiviral vectors were constructed to intervene miR-33a expression in melanoma cells. Cell proliferation, invasion and metastasis were detected. A375 cells mice model was performed to test the tumorigenesis of melanoma in vivo. Finally the dual reporter gene assay was carried out to confirm whether HIF-1α is a direct target gene of miR-33a. RESULTS: MiR-33a/b exhibited a lower expression in WM35, WM451, A375 and SK-MEL-1 of the metastatic skin melanoma cell lines than that in HM. Then inhibition of miR-33a expression in WM35 and WM451 cell lines could promote cell proliferation, invasion and metastasis. Conversely, increased expression of miR-33a in A375 cells could inhibit cellproliferation, invasion and metastasis. In vivo tests also confirmed that overexpression of miR-33a in A375 cells significantly inhibited melanoma tumorigenesis. Finally, we confirmed that HIF-1α is a direct target gene of miR-33a. CONCLUSION: The newly identified miR-33a/HIF-1α axis might provide a new strategy for the treatment of melanoma.

Diagnostic and prognostic potential of serum angiopoietin-2 expression in human breast cancer.

BACKGROUND: Accumulating evidence demonstrated a link of increased expression of Angiopoietin-2 (Ang-2) with invasive and metastatic phenotypes of various types of human cancers. However, until now, the serum level and its diagnostic and prognostic potential in breast cancer have not been investigated. METHODS: Enzyme-linked immunosorbent assays were used to measure the levels of Ang-2. Sensitivity, specificity and area under curve (AUC) for serum Ang-2 levels were determined using receiver operator characteristic (ROC) analysis. Survival curves were plotted using the Kaplan-Meier method and differences in survival rates were analyzed using the log-rank test. Prognostic relevance of each variable to overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox regression model. RESULTS: Serum expression of Ang-2 in patients with breast cancer was significantly higher than healthy control group (3171 ± 1024 vs. 1800 ± 874 pg/ml, P < 0.0001). ROC curve analysis showed that at the optimal cut-off (2558.5 pg/ml), serum level of Ang-2 had a sensitivity of 78.3% and a specificity of 77.0% for distinguishing breast cancer patients from healthy controls with an area under the curve (AUC) of 0.836 (P < 0.001, 95% confidence interval: 0.787-0.885). The 5-year OS of high Ang-2 expression group was significantly shorter than that of low Ang-2 expression group (55.9% vs. 80.3%; P = 0.018). Moreover, the 5-year DFS of high Ang-2 expression group was also significantly shorter than that of low Ang-2 expression group (46.0% vs. 68.7%; P = 0.029). CONCLUSIONS: Our data indicate that serum Ang-2 level has potential value for early detection of breast cancer. Furthermore, Ang-2 has prognostic value in patients with breast cancer.

Differentially expressed miRNAs in acute wound healing of the skin: a pilot study.

The aim of the present study was to compare expression of microRNAs (miRNAs) from scar and normal skin areas in patients who suffered acute injuries in the skin. A total of 9 patients with acute injuries in the skin who received surgical treatment from December 2012 to March 2013 were included in this pilot study. Specimens from the hypertrophic scar and normal skin areas were obtained from the same patient during surgery. To screen for differentially expressed miRNAs, we applied 3 statistical methods, namely the traditional t test, the false discovery rate (FDR), and a novel sure independence screening procedure based on the distance correlation (DC-SIS). We examined the functional trends and metabolic and regulatory pathways for the target genes of the identified miRNAs, and explored interaction of these miRNAs in the implication of scar healing using Ingenuity Pathway Analysis. DC-SIS identified 18 differentially expressed miRNAs, 4 of which (miR-149, miR-203a, miR-222, miR-122) were also identified by FDR. The target genes of the 4 miRNAs exhibit a variety of biological functions, and are involved in various pathways such as mitogen-activated protein kinase, Wnt signaling, and focal adhesion. We identified 1 network in which 14 out of the 18 differentially expressed miRNAs were involved. Many of the miRNAs in the network target genes were involved in cell proliferation and apoptosis.In this pilot study, we identified several miRNAs exhibiting differential expression in patients who suffered acute injuries in the skin. Further studies on these miRNAs are needed to validate our findings and explore their roles in the wound healing process of the skin.

Recent Advance in Drug Development of Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) has a high worldwide incidence that is commonly seen as head and neck cancers, esophageal cancers, and non-small cell lung cancers. There is a poor prognosis for SCC due to potential recurrence and its metastatic tendency so the 5-year survival rate is very low. Target therapy is a novel and promising treatment strategy exhibiting great anti-tumor effects and survival benefits in SCC. This review summarizes current treatment strategies from clinical and experimental studies, including the agents targeting epidermal growth factor receptors, RNA polymerase, toll-like receptors, p38α MAPK, CXCR, and the related combination therapy regimens. However, there are still many challenges we have to face. It is a burning need to improve the development and availability of drug formulations.

MiR-199a inhibits the ability of proliferation and migration by regulating CD44-Ezrin signaling in cutaneous squamous cell carcinoma cells.

Cutaneous squamous cell carcinoma (cSCC), the second most common form of human cancer, is an epithelial skin tumor, which can result in metastasis with lethal consequences accounting for about 20% of all skin cancer-related deaths. The metastasis is the main reason for cSCC-related deaths with an overall 5-year survival rate < 30% in cases that spread systemically. The role of miRNAs has been involved in SCC of different origins. Recent data have revealed that the expression of miRNA-199a was changed in many human cancers. In this study, we found that miR-199a was significantly decreased in cSCC tissues, which had an inverse relationship with CD44. MiR-199a specifically regulated the expression of CD44 at mRNA and protein levels, and the interaction between CD44 and Ezrin in cSCC cells. Moreover, the suppressive role of miR-199a in cell migration in cSCC cells was also associated with the activity of MMP2 and MMP9. Taken together, our data indicated that increased expression of endogenous mature miR-199a might prevent the growth and migration of human cSCC via decreasing the expression of CD44 and regulating the interaction between CD44 and Ezrin, which may provide a potentially important therapeutic target for human cSCC.