Natural Mediterranean Spotted Fever Foci, Qingdao, China.

We sequenced DNA from spleens of rodents captured in rural areas of Qingdao, East China, during 2013-2015. We found 1 Apodemus agrarius mouse infected with Rickettsia conorii, indicating a natural Mediterranean spotted fever foci exists in East China and that the range of R. conorii could be expanding.

Effect of TP53 rs1042522 on the susceptibility of patients to oral squamous cell carcinoma and oral leukoplakia: a meta-analysis.

BACKGROUND: There are different and inconsistent conclusions regarding the genetic relationship between the human tumor suppressor p53 (TP53) rs1042522 polymorphism and the risk of oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL). Therefore, the aim of the study was to comprehensively reassess this association through the performance of an updated meta-analysis. METHODS: After searching the available databases, we systematically screened and included the eligible case-control studies, which contain the full genotype frequency data of the TP53 rs1042522 polymorphism for both OSCC/OL patients and the negative control groups. PA (P-value of the association test) and ORs (odd ratios) with their corresponding 95% CIs (confidence intervals) were calculated to quantitatively evaluate the influence of TP53 rs1042522 on the susceptibility of patients to OSCC or OL. RESULTS: In total, twenty eligible case-control articles were finally enrolled. Compared with the controls, no increased or decreased risk of OSCC was observed in the cases for six genetic models including allele C vs. G (PA = 0.741), carrier C vs. G (PA = 0.853), homozygote CC vs. GG (PA = 0.085), heterozygote GC vs. GG (PA = 0.882), dominant GC + CC vs. GG (PA = 0.969), and recessive CC vs. GG + GC (PA = 0.980). Furthermore, no statistically significant difference between the cases and controls was detected in most subgroup meta-analyses (PA > 0.05). For the risk of OL, we did not observe the difference between the cases and controls for most genetic models in the overall meta-analysis and subsequent subgroup analysis (PA > 0.05). Begg's test and Egger's test excluded the large risk of publication bias within the included studies in the meta-analysis of OSCC. The sensitivity analysis indicated the above relatively stable results. CONCLUSIONS: Our updated meta-analysis (based on the current evidence) shows that TP53 rs1042522 may not confer susceptibility to OSCC. In addition, for the first time, we provided evidence regarding the negative association between TP53 rs1042522 and OL risk.

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity.

Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014's activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014's anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors.

The therapeutic effects of tectorigenin on chemically induced liver fibrosis in rats and an associated metabonomic investigation.

The aim of this study was to investigate the effects of tectorigenin on chemically induced liver fibrosis in rats. Liver fibrosis was induced in rats with carbon tetrachloride, a diet high in fat, cholesterol and alcohol in the drinking water. Our results indicate that tectorigenin treatment significantly inhibited the increases in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the increases in the serum levels of hyaluronate (HA), laminin (LN) and procollagen III N-terminal peptide (PIIIP); tectorigenin treatment also significantly inhibited the increases in the amount of collagen in the livers of the fibrogenic rats. Chemically induced liver fibrosis caused a drop in the serum albumin concentration and a decrease in the ratio of albumin to globulin (A/G). Tectorigenin caused a remarkable increase at a dose of 30 mg/kg, but only a slight increase at the lower doses. Tectorigenin was also able to inhibit the increase in the liver lipid peroxidation (LPO), as well as the decrease in the activities of liver superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), caused by liver fibrosis. In addition, we present a related metabolic profile determined, using a (1)H NMR spectroscopy and multivariate pattern recognition techniques. The results were consistent with the pathological examination, liver function analysis and liver fibrosis marker analysis. Furthermore, tectorigenin does not cause acute toxicity.

[Comparative study of clinical efficacy between surgery by intraoperative MRI navigation versus traditional surgical resection for malignancy of parapharyngeal space].

OBJECTIVE: To investigate the clinical efficacy between mobile intraoperative magnetic resonance imaging (iMRI) navigation with a high field strength and routine surgical resection for malignancy of parapharyngeal space. METHODS: The surgical efficacy indexes of patients at our hospital during the time range from February 2010 to February 2011 were compared between two groups consisting of 29 or 42 individuals undergoing surgery with the assistance of the technique of iMRI navigation with a high field strength 1.5T or routine operation. RESULTS: No difference existed between two groups in terms of age, gender, maximal diameter of tumors, tumor stages, surgical approach or pathologic diagnosis (P > 0.05). The operative duration of the group by iMRI navigation was more than the group of routine operation ((3.1 ± 0.6) h vs (2.7 ± 0.7) h, P < 0.05). And the hemorrhagic loss ((185 ± 20) ml vs (230 ± 22) ml), the volume of drainage in 72 hours, the positive rate of initial surgical margins, the postoperative hospital stay ((9.1 ± 2.1) d vs (10.3 ± 2.3) d) and the complication incidence rate (3.4% vs 9.5%) were less (all P < 0.05). CONCLUSION: The operation by the iMRI navigation offers a much better clinical efficacy than the traditional surgery in the resection of malignancy of parapharyngeal space.

Polo-like kinase 1 is overexpressed in colorectal cancer and participates in the migration and invasion of colorectal cancer cells.

BACKGROUND: Polo-like kinase 1 (PLK1) is an important molecule in proliferation of many human cancers. The aim of study is to clarify the expression patterns and potential function of PLK1 in colorectal cancers. MATERIAL/METHODS: Fifty-six colorectal cancers samples were collected and arranged onto a tissue array and the expression of PLK1 were detected by immunohistochemistry and correlated with clinico-pathological characteristics and expression of PCNA. Expression of PLK1 in 9 colorectal cancer cells lines was investigated by RT-PCR and Western blot, then SW1116 cells lines were treated with PLK1 siRNA and the efficiency was examined by Western blot. Transwell test was applied to detect the migration and invasion capability of cancer cells by counting the number of cells passing through the membranes. Cell proliferation and apoptosis were examined by Cell Counting Kit-8 (CCK-8) and Annexin-V Kit. RESULTS: PLK1 was positively expressed in 73.2% (41/56) of colorectal cancers tissues, but in only 3.6% (2/56) of normal tissues, and was associated with Duke's stage (P<0.01), tumor size (P<0.01), invasion extent (P<0.05) and lymphatic metastasis (P<0.01). The expression of PLK1 was correlated with expression of PCNA (R=0.553, P<0.01). PLK1 was inhibited in SW1116 cells by treating with PLK1 siRNA oligos, which resulted in a decreased number of cells passing through the membrane as compared with control groups (P<0.01) at 24 hours after transfection. Cell proliferation was inhibited from 48 hours after transfection, while cells apoptosis was induced from 72 hours after transfection. CONCLUSIONS: PLK1 could be a progression marker for colorectal cancer patients and PLK1 depletion can inhibit migration and invasion capability of colorectal cancer cells SW1116, suggesting that PLK1 might be involved in metastasis and invasion of colorectal cancer. Therapeutic strategies targeting PLK1 may be a new approach to colorectal cancer.

Neuraminidase inhibitory polyketides from the marine-derived fungus Phoma herbarum.

Two new polyketides, arthropsadiol C (1) and massarilactone H (2), together with six known derivatives (3-8) were isolated from the culture broth of the marine-derived fungus Phoma herbarum. Their structures were elucidated on the basis of spectroscopic methods, including 2D NMR techniques. Compounds 2, 4, 5, and 8 showed moderate neuraminidase inhibitory activity with IC(50) values ranging from 4.15 to 9.16 µM.

[The preliminary study of the use of MRI navigation in identifying the safe surgical margin of the maxillofacial malignancy].

OBJECTIVE: To evaluate the feasibility of MRI navigation in identifing the safe surgical margin of the maxillofacial malignancy. METHODS: The pathology results of the surgical margin identified by the technique of MRI navigation form 20 patients with maxillofacial malignancy were compared with those of 45 patients with maxillofacial malignancy who underwent the routine operation without MRI navigation. RESULTS: There was no difference between the two groups of patients in age, sex, size of tumor, tumor stages, pathologic diagnosis (P > 0.05). The negative rate of the surgical margin of the lesions treated by surgery with the technique of MRI navigation was significantly lower than that of the lesions treated without MRI navigation (P = 0.007) and highly correspondent with the pathology results. CONCLUSIONS: MRI navigation was helpful in identifying the safe surgical margin of the maxillofacial malignancy.

Trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway.

Trichothecin, one of fungal toxins which were encountered in food and in the environment, seriously threatens human and animal health. It has been shown that trichothecin changed the morphology of cellular mitochondria. However, the molecular mechanism remains unknown. Here we found that cell viability was attenuated by trichothecin. Features of apoptosis such as homosomal condensation and inter nucleosomal fragmentation were observed. In consistence with the elevated apoptosis rate, expression of anti-apoptotic protein Bcl-2 was diminished and expression of proapoptotic protein Bax was enhanced at mRNA levels. Furthermore, expression of caspase-9 and activity of caspase-3 were increased after the treatment of trichothecin. Accordingly, the mitochondrial membrane potential (∆Ψm) was decreased in a dose-dependent manner. And Ca(2+) overload was induced by trichothecin, followed by the generation of reactive oxygen species (ROS). Collectedly, our results suggested that apoptosis induced by trichothecin is mediated by caspase-9 activation and the decrement of mitochondrial function resulted from the overloaded calcium and ROS production.

Fully substituted unsaturated lactones from endophytic Myrothecium sp.

Two new α,ß-unsaturated γ-lactones, myrolactones A (1) and B (2), were characterized from the culture broth of the Myrothecium sp. IFB-E106 isolated from the roots of Vatica mangachapoi Blauco. The absolute configuration was determined by the computational electronic circular dichroism approach. Myolactone B showed neuraminidase inhibitory activity with the IC(50) value of 13.95 µM.

N-(3,5-Dimeth-oxy-phen-yl)benzamide.

The title compound, C(15)H(15)NO(3), was prepared by stirring benzoyl chloride with 3,5-dimeth-oxy-aniline in dioxane at ambient temperature. The dimeth-oxy-phen-yl-amide segment of the mol-ecule is almost planar, with a C-N-C=O torsion angle of -4.1 (4)°. The two benzene rings are inclined at an angle of 76.66 (13)°. In the crystal, inter-molecular N-H⋯O inter-actions generate centrosymmetric dimers..

Neuraminidase inhibitory terpenes from endophytic Cochliobolus sp.

The chemical study of endophytic fungus of Cochliobolus led to the isolation of 10 terpenes (1-10), including one new compound named isocochlioquinone B (1). Their structures were elucidated on the basis of spectroscopic methods, including 2D NMR techniques. Compounds 5-7 showed significant neuraminidase inhibitory activity with IC(50) values of 0.79-1.75 µM.

[Influence of silencing Polo-like kinase 1 on migration and invasion of colorectal cancer cells].

OBJECTIVE: To examine the role of Polo-like kinase 1(PLK1) in the migration and invasiveness of human colorectal cancer cells. METHODS: Nine colorectal cancer cell lines were cultured. Cell lines with the highest level of PLK1 expression was selected by PCR and Western blot. Three siRNA oligo segments targeting PLK1 were designed and selected cell lines transfected. Successful transfection was confirmed using real-time PCR and Western blot. Changes in migration and invasiveness of the selected cell line were evaluated by Transwell test. RESULTS: Colorectal cancer cell line SW1116 was selected with the highest expression of PLK1 at both mRNA level and protein level. The expression of PLK1 in SW1116 was reduced by the three siRNA oligo segments to varying degrees, and the No.1 siRNA oligo segment was the most efficient. In migration test, the number of cells crossing through chambers in PLK1-siRNA group was 44 ± 14, which was lower than that in the negative control group (242 ± 40) and in blank control group(240 ± 38). In invasion test, the number of cells crossing through chambers in PLK1-siRNA group was 62 ± 3, which was lower than that in negative control group (207 ± 12) and in blank control group (211 ± 15). These differences were statistically significant(P<0.01). CONCLUSION: PLK1 silencing by siRNA may inhibit the migration and invasiveness of colorectal cancer cells, suggesting that PLK1 might play an important role in the infiltration and metastasis of colorectal cancer.

Bioactive alkaloids from the plant endophytic fungus Aspergillus terreus.

One new alkaloid, named 16 alpha-hydroxy-5 N-acetylardeemin ( 1), along with seven known metabolites ( 2- 8) was isolated from the fermentation broth of an endophytic fungus, ASPERGILLUS TERREUS. The structures of these metabolites were assigned on the basis of detailed spectroscopic analysis and by comparing spectroscopic data with those in the literature. Compound 1 displayed an inhibitory effect against acetylcholinesterase. Compounds 1- 8 also showed moderate or weak cytotoxic activity against KB and HSC-T6 cell lines.