Tetrandrine exerts antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis.

Klebsiella pneumoniae is the most common pathogen of community-acquired meningitis in Taiwan. However, the lack of a physiologically relevant meningitis model for K. pneumoniae has impeded research into its pathogenesis mechanism. Based on the core genome MLST analyses, the hypervirulent K1 K. pneumoniae strains, which are etiologically implicated in adult meningitis, mostly belong to a single clonal complex, CC23. Some K1 CC23 K. pneumoniae strains carry a gene cluster responsible for colibactin production. Colibactin is a small genotoxic molecule biosynthesized by an NRPS-PKS complex, which is encoded by genes located on the pks island. Compared to other hypervirulent K. pneumoniae which primarily infect the liver, the colibactin-producing (pks+) K1 CC23 strains had significant tropism toward the brain of BALB/c mice. We aimed in this study to develop a physiologically relevant meningitis model with the use of pks+ K1 CC23 K. pneumoniae. Acute meningitis was successfully induced in adult BALB/c male mice through orogastric, intranasal, and intravenous inoculation of pks+ K1 CC23 K. pneumoniae. Besides the typical symptoms of bacterial meningitis, severe DNA damages, and caspase 3-independent cell death were elicited by the colibactin-producing K1 CC23 K. pneumoniae strain. The deletion of clbA, which abolished the production of colibactin, substantially hindered K. pneumoniae hypervirulence in the key pathogenic steps toward the development of meningitis. Our findings collectively demonstrated that colibactin was necessary but not sufficient for the meningeal tropism of pks+ K1 CC23 K. pneumoniae, and the mouse model established in this study can be applied to identify other virulence factors participating in the development of this life-threatening disease.

Hypotheses. Epithelial-mesenchymal transition (EMT) and invasion play a critical role in cancer progression and metastasis. We have shown that low E-cadherin and high Twist expression are significantly correlated with prognostic survival prediction in oral squamous cell carcinoma (OSCC). This study aimed to determine the anti-invasive effect of curcumin on the expression of matrix metalloproteinases (MMPs) and of EMT regulators in OSCC. Methods. SCC-25 cells were treated with curcumin, and cell proliferation, invasion, and expression of MMPs and EMT regulators were assessed for cell viability by trypan blue exclusion, for invasion by Matrigel invasion chamber, and for EMT regulators and MMP changes in the levels of proteins by immunoblotting. Results. Our data showed that curcumin treatment not only decreased the expression of MMP-2 and MMP-9 to inhibit invasiveness in oral cancer but also modulated the expression of EMT markers, such as Snail, Twist, and E-cadherin, and induced p53 expression that is crucial to EMT repression. Conclusion. Curcumin has the potential to become an adjunctive regimen for the prevention of cancer progression and metastasis in oral cancer.

Immune escape is a characteristic of cancer progression, but its underlying molecular mechanism is still poorly understood. An immunomodulatory protein, indoleamide 2,3-dioxygenase (IDO), is induced by gamma-interferon (IFN-gamma) in several immune cells; those cells are observed in cancer cell microenvironment and can enhance immune escape. Previous studies show that IDO is expressed in the process of tumor formation and associated with cancer cell immune tolerance. By locally degrading tryptophan, IDO inhibits the proliferation of T lymphocytes and induces T cell apoptosis, leading to suppression of T cell response. In this study, (-)-epigallocatechin-3-gallate (EGCG), the major constituent of green tea, is found to significantly inhibit the expression of IDO in human oral cancer cell lines. EGCG suppresses the induction of IDO at transcriptional level. Activation of STAT1 is discovered to play an important role in regulating IDO expression by IFN-gamma. The study results demonstrate that EGCG can inhibit translocation of STAT1 into nucleus in IFN-gamma-stimulated human oral cancer cells. In addition, both tyrosine and serine phosphorylation of STAT1 are revealed to be suppressed by EGCG. Moreover, phosphorylation of PKC-delta, JAK-1, and JAK-2, which are the upstream event for the activation of STAT1, are also inhibited by EGCG in IFN-gamma-stimulated human oral cancer cells. These data show that EGCG inhibited IDO expression by blocking the IFN-gamma-induced JAK-PKC-delta-STAT1 signaling pathway. This study indicates that EGCG is a potential drug for immune and target therapy to enhance cancer therapy by increasing antitumor immunity.

Shewanella algae is a rod-shaped Gram-negative marine bacterium frequently found in nonhuman sources such as aquatic ecosystems and has been shown to be the pathogenic agent in various clinical cases due to the ingestion of raw seafood. The results of this study showed that S. algae was present in approximately one in four samples, including water and shellfish samples. Positive reactions (API systems) in S. algae strains were seen for gelatinase (gelatin); however, negative reactions were found for indole production (tryptophan). S. algae is adapted to a wide range of temperatures (4°C, 25°C, 37°C, and 42°C) and salinity. Temperature is a key parameter in the pathogenicity of S. algae as it appears to induce hemolysis at 25°C and 37°C. S. algae exhibits pathogenic characteristics at widely varying temperatures, which suggests that it may have the ability to adapt to climate change.

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Optimal conditions required for the creation of an iatrogenic chorioretinal venous anastomosis in the dog using argon green laser photocoagulation.

Trypanosoma (subgenus Megatrypanum) theileri was first identified over one hundred years ago, and is a widespread parasite in cattle. Its life cycle within the mammalian host has rarely been reported. Whether there is an intracellular stage in tissues is unknown and such a stage has not been demonstrated experimentally. Intriguingly, using Giemsa staining with light microscopy and transmission electron microscopy examination, we found that the parasite was able not only to attach to cells but also to invade several phagocytic and non-phagocytic mammalian cells. Based on these findings, we conducted further investigations using a special antibody in immunofluorescence confocal images. Moreover, we examined a series of possible events of cell invasion in T. theileri. The results revealed that GM1, a marker of membrane rafts, was implicated in the mechanism of entry by this parasite. After incubation with tissue culture trypomastigotes, the gelatinolytic activity was significantly increased and accumulated at the attachment sites. Using ultrastructural localization detection by CytoTracker live imaging and confocal immunofluorescence microscopy, we found that lysosome fusion and the autophagy pathway were engaged in invaginating processes. T. theileri amastigotes also invaded cells and were enclosed by the lysosomes. Furthermore, tissue-cultured trypomastigotes were found to be capable of triggering intracellular free Ca(2+) transients and TGF-β-signaling. Our findings that intracellular amastigote stages exist in mammalian cells infected with T. theileri and that the invasion processes involved various host cell components and cell signalings were extremely surprising and warrant further investigation.