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Allergy is an acquired hypersensitivity reaction of the immune system mediated by IgE‑induced mast cell degranulation. In China, bacillus Calmette‑Guerin extract (BCGE) has been shown to be clinically effective for regulating immunity, which enhances the resistance of the body to anaphylactic disease, infectious diseases and cancer. However, the mechanisms remain to be fully elucidated. The present study investigated the potential anti‑allergic effects of BCGE in animal models of mast cell‑dependent anaphylaxis and mechanisms of BCGE in mast cells. Anti‑allergic actions of BCGE were evaluated in passive cutaneous anaphylaxis, dextran T40‑induced scratching behavior mouse models, and in ovalbumin (OVA)‑induced contraction of intestinal tube isolated from OVA‑sensitized guinea pigs. Direct mast cell‑stabilizing effects of BCGE were examined in mast cells from the abdominal cavity of OVA‑sensitized rats. Anti‑allergic signaling mechanisms of BCGE in mast cells were investigated by detection of cyclic adenosine monophosphate levels and protein kinase A expression in mast cells. It was observed that BCGE prevented OVA‑induced cutaneous vascular hyperpermeability, skin itching, elevation in plasma histamine levels and abdominal cavity fluid mast cell degranulation in animal models, in a dose‑dependent manner. BCGE also suppressed OVA‑mediated guinea pig intestinal tube contraction in vitro. In addition, BCGE was found to increase the levels of interferon‑γ, and reduce the levels of interleukin‑4 and OVA‑sIg E levels in OVA‑sensitized rats. BCGE also increased levels of cyclic adenosine monophosphate and the expression of protein kinase A in mast cells separated from the abdominal cavity fluid of OVA‑sensitized rats. In conclusion, the results suggested that BCGE possesses anti‑allergic activity by inhibiting IgE‑induced mast cell degranulation, providing a foundation for the development of BCGE for the treatment of mast cell‑mediated allergic disorders. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) have been suggested to serve an important role in tumor recurrence and metastasis in breast cancer. The hedgehog (Hh) signaling pathway is essential for the maintenance of breast CSCs. The present study used immunohistochemistry to investigate the expression of Patched (PTCH) and Gli1, which are the main components of the Hh signaling pathway, as well as the expression of cluster of differentiation (CD)44/CD24, which are markers for breast CSCs, in 266 patients with breast cancer. The combined expression of PTCH and Gli1 was significantly associated with larger tumors (>2.0 cm; P=0.001), lymph node metastasis (P=0.003), invasive lobular carcinoma (P=0.016) and Grade II-III tumors (P<0.001). In addition, PTCH and Gli1 expression was associated with lymph node metastasis (P=0.005 and P=0.001) and Grade II-II tumors (P=0.020 and P=0.033) in breast cancer patients with the CD44+/CD24- phenotype. The expression of PTCH and Gli1 was also associated with significantly shorter overall survival and disease-free survival (DFS) in breast cancer patients with the CD44+/CD24- phenotype. Multivariate Cox regression analysis demonstrated that PTCH expression and the CD44+/CD24- phenotype were independent prognostic factors for decreased DFS in patients with breast cancer. These findings suggest that the Hh signaling pathway in breast CSCs may contribute to the poor outcome of patients with breast cancer. [ABSTRACT FROM AUTHOR]

Laminar cooling technology is widely used in hot rolling process, especially, the ultra-fast cooling and dense cooling technologies play an important role in high strength steel strip production. Research on temperature and stress coupled model in the process of hot rolling laminar cooling is of positive significance for solving strip uneven transverse cooling, uneven stress and buckling. By using finite element method, temperature and stress coupled model of laminar cooling on hot strip mill is established, and the coupling calculation of temperature, phase transformation and stress is realized. Temperature test material microstructure test and stress test are used for model validation. The result shows that strip transverse initial temperature difference and edge masking are significant to reduce residual stress. In this paper, an example is given to improve the strip residual stress by improving the initial temperature difference distribution, and the correctness of the proposed method and conclusion is verified. [ABSTRACT FROM AUTHOR]

BCSCs (breast cancer stem cells) have been shown to be resistant to chemotherapy. However, the mechanisms underlying BCSC-mediated chemoresistance remain poorly understood. The Hh (Hedgehog) pathway is important in the stemness maintenance of CSCs. Nonetheless, it is unknown whether the Hh pathway is involved in BCSC-mediated chemoresistance. In the present study, we cultured breast cancer MCF-7 cells in suspension in serum-free medium to obtain BCSC-enriched MCF-7 MS (MCF-7 mammosphere) cells. We showed that MCF-7 MS cells are sensitive to salinomycin, but not paclitaxel, distinct from parent MCF-7 cells. The expression of the critical components of Hh pathway, i.e. PTCH (Patched), SMO (Smoothened), Gli1 and Gli2, was significantly up-regulated in MCF-7 MS cells; salinomycin, but not paclitaxel, treatment caused a remarkable decrease in expression of those genes in MCF-7 MS cells, but not in MCF-7 cells. Salinomycin, but not paclitaxel, increased apoptosis, decreased the migration capacity of MCF-7 MS cells, accompanied by a decreased expression of c-Myc, Bcl-2 and Snail, the target genes of the Hh pathway. The salinomycin-induced cytotoxic effect could be blocked by Shh (Sonic Hedgehog)-mediated Hh signalling activation. Inhibition of the Hh pathway by cyclopamine could sensitize MCF-7 MS cells to paclitaxel. In addition, salinomycin, but not paclitaxel, significantly reduced the tumour growth, accompanied by decreased expression of PTCH, SMO, Gli1 and Gli2 in xenograft tumours. Furthermore, the expression of SMO and Gli1 was positively correlated with the expression of CD44+/CD24-, and the expression of SMO and Gli1 in CD44+/CD24- tissues was associated with a significantly shorter OS (overall survival) and DFS (disease-free survival) in breast cancer patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

The breast cancer susceptibility gene 1 (BRCA1) inactivation in sporadic epithelial ovarian carcinoma (EOC) is common and low BRCA1 expression is associated with promoter hypermethylation. The clinical validation of BRCA1 methylation as a prognostic marker in EOC remains unresolved. The aim of the present study was to determine the aberrant promoter methylation of BRCA1 in benign and malignant ovarian tumor tissues, to establish the association with the clinicopathological significance and the prognostic value. Additionally, the contribution of DNA methyltransferase (DNMT) expression to BRCA1 promoter hypermethylation was determined. The rate of BRCA1 methylation was observed to be 35.2% (50/142) in the EOCs; however, no methylation (0/32) was observed in the benign tumors. BRCA1 methylation was significantly associated with the downregulation of BRCA1 expression (P<0.001) and the frequency of BRCA1 methylation was greater in the carcinomas of patients whose tumor was bilateral than that of patients with a unilateral carcinoma (P=0.015). BRCA1 methylation was significantly associated with the preoperative serum carbohydrate antigen-125 level (P=0.013), improved overall survival (P=0.005) and disease-free survival (P=0.007). In addition, a significant correlation was observed between the co-expression of DNMTs and the methylation status of BRCA1. Thus, the present study provided support for BRCA1 promoter hypermethylation as a prognostic marker for survival in sporadic EOC, and co-expression of DNMTs was observed to contribute to BRCA1 promoter hypermethylation. [ABSTRACT FROM AUTHOR]

Bacillus Calmette-Guerin extract (BCGE) has been proven to be clinically effective for anaphylactic disease, infectious diseases and cancer. In this study, we investigated the effect of the intramuscular application of BCGE on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). We established an AD model in BALB/c mice by repeated local exposure of DNCB to the ear and dorsal skin. Following intramuscular application of BCGE, the ear thickness, mast cell infiltration, serum total immunoglobulin E (IgE) and histamine level were measured. In addition, levels of interleukin (IL)-4, IL-13, interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the ears were assayed. BCGE reduced AD symptoms based on ear thickness, dermatitis score, histopathological analysis and serum IgE levels. In addition, BCGE inhibited mast cell infiltration into the ear and elevation of serum histamine, increased IFN-γ level and suppressed IL-4, IL-13 and TNF-α levels in the ears. Furthermore, BCGE attenuated the NF-κBp65 expression in the nuclear extract of the ear tissue. Taken together, our results demonstrated that intramuscular application of BCGE exerts beneficial effects on the symptoms of AD suggesting that BCGE may be a candidate for the treatment of AD. [ABSTRACT FROM AUTHOR]

Altered DNA methylation of tumor suppressor gene promoters plays a role in human carcinogenesis and DNA methyltransferases (DNMTs) are responsible for it. This study aimed to determine aberrant expression of DNMT1, DNMT3a, and DNMT3b in benign and malignant ovarian tumor tissues for their association with clinicopathological significance and prognostic value. A total of 142 ovarian cancers and 44 benign ovarian tumors were recruited for immunohistochemical analysis of their expression. The data showed that expression of DNMT1, DNMT3a, and DNMT3b was observed in 76 (53.5%), 92 (64.8%) and 79 (55.6%) of 142 cases of ovarian cancer tissues, respectively. Of the serious tumors, DNMT3a protein expression was significantly higher than that in benign tumor samples (P = 0.001); DNMT3b was marginally significant down regulated in ovarian cancers compared to that of the benign tumors (P = 0.054); DNMT1 expression has no statistical difference between ovarian cancers and benign tumor tissues (P = 0.837). Of the mucious tumors, the expression of DNMT3a, DNMT3b, and DNMT1 was not different between malignant and benign tumors. Moreover, DNMT1 expression was associated with DNMT3b expression (P = 0.020, r = 0.195). DNMT1 expression was associated with age of the patients, menopause status, and tumor localization, while DNMT3a expression was associated with histological types and serum CA125 levels and DNMT3b expression was associated with lymph node metastasis. In addition, patients with DNMT1 or DNMT3b expression had a trend of better survival than those with negative expression. Co-expression of DNMT1 and DNMT3b was significantly associated with better overall survival (P = 0.014). The data from this study provided the first evidence for differential expression of DNMTs proteins in ovarian cancer tissues and their associations with clinicopathological and survival data in sporadic ovarian cancer patients. [ABSTRACT FROM AUTHOR]