The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma

Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death. However, the prognostic role of concordant overexpression of synthetic lethality genes in protein level rather than a combination of mutations is not clear. In this study, we explore the prognostic role of combined overexpression of paired genes in lung adenocarcinoma. We used immunohistochemical staining to investigate 24 paired genes in 93 lung adenocarcinoma patients and Kaplan-Meier analysis and Cox proportional hazards models to evaluate their prognostic roles. Among 24 paired genes, only FEN1 (Flap endonuclease 1) and RAD54B (RAD54 homolog B) were overexpressed in lung adenocarcinoma patients with poor prognosis. Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis (HR = 2.35, P = 0.0230). These results suggest that intensive follow up and targeted therapy might improve clinical outcome for patients who show expression of both FEN1 and RAD54B.     

<Emphasis Type="Italic">Trichophyton erinacei</Emphasis> Infection from a Hedgehog: A Case Report from Taiwan

Trichophyton erinacei is a fungus affecting hedgehogs. As these animals have become popular as exotic pets, human infections with this organism have been documented in many countries. In Taiwan, a 36-year-old woman developed tinea lesions at multiple sites after carrying a sick hedgehog. The animal subsequently lost its quills and died. On culture of the patient’s skin scrapings, the pathogen was identified mycologically as Trichophyton erinacei, which was confirmed by sequencing of the internal transcribed spacers of the fungal nuclear ribosomal DNA. The same fungus was isolated from the sawdust bed previously used by the diseased hedgehog. A careful contact history is important for identifying this emerging zoonosis.     

Enhancing antimicrobial activity of mastoparan-B by amino acid substitutions

This study evaluated antimicrobial and hemolytic activities of mastoparan-B (MP-B) isolated from the venom of the hornet, Vespa basalis, and its analogs after substituting certain amino acid (aa) residues. MP-B exhibited significantly different antimicrobial activities against bacteria species/strains tested, especially two Escherichia coli strains, Staphylococcus xylosus and Citrobacter koseri at low dosages, and was non-specific against certain Gram-positive and -negative bacteria. Our results indicated that hydrophobicity modification by single aa substitution may enhance their antimicrobial activities. An aa substituted MP-B, viz., MP-B-1, in which Trp substituted for Leu³, became more effective than the original peptide at inhibiting or killing the bacterial species tested, especially Klebsiella pneumonia, Salmonella typhimurium, and Salmonella Cholerasuis, and even up to 8 times more effective in some cases. However, MP-B-2 was virtually similar to MP-B against each bacterial species assayed, while MP-B-3 reduced its effectiveness greatly compared to others. On the other hand, MP-B and its analogs were not effective against the beneficial probiotics and they were not hemolytic to erythrocytes at the dosages tested. Our results suggested that MP-B becomes more potent against specific pathogenic bacteria and safe to the probiotics after undergoing appropriate amino acid substitutions.     

High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma

PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit.     

Fisetin Inhibits Migration and Invasion of Human Cervical Cancer Cells by Down-Regulating Urokinase Plasminogen Activator Expression through Suppressing the p38 MAPK-Dependent NF-κB Signaling Pathway

Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.     

Modulation of membrane rigidity by the human vesicle trafficking proteins Sar1A and Sar1B

The sculpting of membranes into highly curved vesicles is central to intracellular cargo trafficking, yet the mechanical activities of trafficking proteins remain poorly understood. Using an optical trap based assay that measures in vitro membrane response to imposed deformations, we examined the behavior of the two human paralogs of Sar1, a key component of the COPII family of vesicle coat proteins. Like their yeast counterpart, the human Sar1 proteins can lower the mechanical rigidity of the membranes to which they bind. Unlike the yeast Sar1, the rigidity is not a monotonically decreasing function of concentration. At high concentrations, we find increased bending rigidity and decreased protein mobility. These features imply a model in which protein clustering governs membrane mechanical properties.     

Proteomic Profiling of Rabbit Embryonic Stem Cells Derived from Parthenotes and Fertilized Embryos

Rabbit embryonic stem (rES) cells can be derived from various sources of embryos. However, understanding of the gene expression profile, which distincts embryonic stem (ES) cells from other cell types, is still extremely limited. In this study, we compared the protein profiles of three independent lines of rabbit cells, i.e., fibroblasts, fertilized embryo-derived stem (f-rES) cells, and parthenote-derived ES (p-rES) cells. Proteomic analyses were performed using two-dimensional gel electrophoresis (2-DE) and mass spectrometry. Collectively, the expression levels of 100 out of 284 protein spots differed significantly among these three cell types (p<0.05). Of those differentially expressed spots, 91% were identified in the protein database and represented 63 distinct proteins. Proteins with known identities are mainly localized in the cytoplasmic compartments (48%), nucleus (14%), and cytoskeletal machineries (13%). These proteins were majorly involved in biological functions of energy and metabolic pathways (25%), cell growth and maintenance (25%), signal transduction (14%), and protein metabolisms (10%). When protein expression levels among cell types were compared, six proteins associated with a variety of cellular activities, including structural constituents of the cytoskeleton (tubulins), structural molecule (KRT8), catalytic molecules (α-enolase), receptor complex scaffold (14-3-3 protein sigma), microfilament motor proteins (Myosin-9), and heat shock protein (HSP60), were found highly expressed in p-rES cells. Two proteins related to HSP activity and structural constituent of cytoskeleton in f-rES cells, and one structural molecule activity protein in fibroblasts showed significantly higher expression levels (p<0.05). Marker protein expressions in f-rES and p-rES cells were further confirmed by Western blotting and immunocytochemical staining. This study demonstrated unique proteomic profiles of the three rabbit cell types and revealed some novel proteins differentially expressed between f-rES and p-rES cells. These analyses provide insights into rES cell biology and would invite more in-depth studies toward rES cell applications.     

Household extension and reproductive behaviour in Taiwan

The inflence of household type on reproductive behavior is examined for a national probability sample of Taiwanese women. Data were derived from a 1980 national household survey of the labor force in Taiwan, focusing on 10,624 couples. Reproductive variables include measures of current and prospective fertility as well as cumulative fertility. In spite of remarkable social and economic development over the past 3 decades, extended families are still widely found in Taiwan. Women in extended households have only slightly higher fertility preferences and current fertility than women in nuclear families once marital duration is controlled. Although women in extended households marry earlier and receive more family help with child care than women in nuclear families, such factors are no longer considered sufficient to produce major differentials in reproductive behavior. Residence and husband's class of work are the strongest correlates of whether a household is currently extended or nuclear. In general, the husband's characteristics are more strongly related to family type than the wife's. Findings suggest that preferences for smaller families and low fertility need not await a transformation to a nuclear family structue.