ABSTRACT
MicroRNAs (miRNAs) are involved in the pathogenesis of several cancers including skin squamous cell carcinoma (sSCC), and miR-134 is reported to possess tumor inhibition properties. The present study is an attempt to study the mechanistic role and antitumor property of miR-134 in sSCC. For this purpose, α-tocopherol PEG 1000 succinate (TPGS)-based PEGylated liposome was formulated and encapsulated with miR-134 (TP-miR-LP). CCK-8 assay results showed that miR-134 exhibited a concentration-dependent decrease in the cell viability of A-431 cells. Importantly, TPGS-based TP-miR-LP showed significantly (p < 0.05) lower cell viability compared with that of miR-134-loaded PEGylated liposome (miR-LP). Western blot analysis clearly indicates the specific targeting ability of miR-134 (TP-miR-LP) towards the Forkhead Box M1 (FOXM1) in the cancer cells. The apoptosis rate of the cells was significantly increased in TP-miR-LP (~ 38%) than that of miR-LP (~ 15%), respectively with significant inhibition of cell migration. Importantly, tumors treated with TP-miR-LP grew significantly slower compared with that of any other formulation group in the xenograft animal model. Present results clearly demonstrate the tumor suppressive effect of miR-134 through the downregulation of FOXM1 which subsequently blocks the downstream signaling pathways. These findings suggest the translational potential of miR-134 towards designing formulation strategies for sSCC treatment. Graphical abstract.
Subject(s)
Carcinoma, Squamous Cell , MicroRNAs , Animals , Apoptosis , Carcinoma, Squamous Cell/drug therapy , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Liposomes , MicroRNAs/genetics , MicroRNAs/metabolism , Polyethylene Glycols/pharmacology , alpha-TocopherolABSTRACT
Objective To evaluate the relationship between the change rate of regional cerebral ox-ygen saturation ( rSO2 ) and early postoperative cognitive function during laparoscopic surgery in elderly pa-tients. Methods Fifty American Society of Anesthesiologists physical status Ⅰ-Ⅱ patients, aged 65-80 yr, scheduled for elective laparoscopic radical resection for colorectal cancer under general anesthesia, were enrolled in this study. rSO2 was recorded at 5 min before anesthesia induction ( T0 ) , 5 min after tra-cheal intubation ( T1 ) , 5 min after changing position ( T2 ) , 1 h after changing position ( T3 ) , 5 min after stopping pneumoperitoneum ( T4 ) , and 5 min after changing to supine position at the end of pneumoperito-neum ( T5 ) . The change rate of rSO2 was calculated at T3 . Mini-Mental State Examination scores were per-formed at 1 day before surgery and 3 days after surgery. The patients were divided into cognitive disorder group and non-cognitive disorder group. Results Compared with non-cognitive disorder group, rSO2 was significantly increased at T2-5 , and the change rate of rSO2 was enlarged in cognitive disorder group ( P<0. 05) . The change rate of intraoperative rSO2 was negatively correlated with Mini-Mental State Examination scores at 3 days after surgery (r=-0. 516, P<0. 01). Conclusion The increased change rate of rSO2 during laparoscopic surgery may be related to the development of early postoperative cognitive dysfunction in elderly patients.
ABSTRACT
There are many superiorities of multimedia in the practice of dermatovenerology teaching and also some disadvantages.And some improvement measures are also suggested.
ABSTRACT
To investigate the expression of Toll-like receptor (TLR) 2 and 4 mRNA in local tissues of model of oropharyngeal candidiasis in mice and to explore the potential role of TLR2 and TLR4 in earlier period of immune response, a murine model of oropharyngeal candidiasis inoculated by cotton wool balls saturated with Candida albicans was established. Mice were sacrificed at the indicated time points and the oropharyngeal tissues were excised. The expression of TLR2 and TLR4 mRNA was detected by RT-PCR. The results showed that low level of TLR2/4 mRNA could be detected in oropharyngeal tissues, but they were markedly up-regulated 6 h after inoculation, peaking after 12-24 h. Tissue TLR4 mRNA was gradually down-regulated 24-48 h, while TLR2 mRNA levels remained high up to the 72nd h. These data suggested that oropharyngeal infection of Candida albicans could result in up-regulation of TLR2/4 mRNA expression in local tissues, which might play important roles in earlier period of immune response.
Subject(s)
Candidiasis/metabolism , Candidiasis, Oral/metabolism , Mouth Mucosa/metabolism , Pharyngitis/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Random Allocation , Toll-Like Receptor 2/biosynthesis , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/biosynthesis , Toll-Like Receptor 4/geneticsABSTRACT
To investigate the expression of Toll-like receptor (TLR) 2 and 4 mRNA in local tissues of model of oropharyngeal candidiasis in mice and to explore the potential role of TLR2 and TLR4 in earlier period of immune response, a murine model of oropharyngeal candidiasis inoculated by cotton wool balls saturated with Candida albicans was established. Mice were sacrificed at the indicated time points and the oropharyngeal tissues were excised. The expression of TLR2 and TLR4 mRNA was detected by RT-PCR. The results showed that low level of TLR2/4 mRNA could be detected in oropharyngeal tissues, but they were markedly up-regulated 6 h after inoculation, peaking after 12-24 h. Tissue TLR4 mRNA was gradually down-regulated 24-48 h, while TLR2 mRNA levels remained high up to the 72nd h. These data suggested that oropharyngeal infection of Candida albicans could result in up-regulation of TLR2/4 mRNA expression in local tissues, which might play important roles in earlier period of immune response.