Organoids in recapitulating tumorigenesis driven by risk factors: Current trends and future perspectives

Environmental and exogenous/ endogenous factors, in a setting of individual genetic predisposition, contribute to the cancer development. Over the years, epidemical evidence increasingly highlights the correlations of multiple cancer incentives and genetic alterations with cancer incidence. Unraveling the pivotal carcinogenesis events prompted by particular risk factors remarkably advances early surveillance and oncogenesis intervening. Traditional cell-based models and animal-based models are unrealistic and unreliable for translational study, respectively ascribing to the limited tumor heterogeneity and species-related variation. Organoid emerged as a fidelity model that well preserves the properties of its origin. With inherent quality of holistic perspective, organoid is therefore ideally suited for delineating the carcinogenesis under risk exposure, in favor of understanding pathogen-host interactions and alleviating cancer initiation. In this review, we have summarized the organoid model-based evidence that identified or validated carcinogenic risks, mainly including diet, aging, microbial infection, and chemical exposure. In addition, we envisioned the exciting prospect of organoid model in screening promising treatment and/or prevention during tumorigenesis. As a robust 3D in vitro system, organoid has been widespread applied in basial and clinical cancer research, which may elucidate crucial mechanisms of oncogenesis and develop novel targeting strategies.     

Phylogenetic analysis of the fecal flora of the wild pygmy loris

The bacterial diversity in fecal samples from the wild pygmy loris was examined with a 16S rDNA clone library and restriction fragment length polymorphism analysis. The clones were classified as Firmicutes (43.1%), Proteobacteria (34.5%), Actinobacteria (5.2%), and Bacteroidetes (17.2%). The 58 different kinds of 16S rDNA sequences were classified into 16 genera and 20 uncultured bacteria. According to phylogenetic analysis, the major genera within the Proteobacteria was Pseudomonas, comprising 13.79% of the analyzed clone sequences. Many of the isolated rDNA sequences did not correspond to known microorganisms, but had high homology to uncultured clones found in human feces. Am. J. Primatol. 72:699–706, 2010. © 2010 Wiley‐Liss, Inc.     

Evidence for the intertwined dimer of the cytochrome bc(1) complex in solution

To confirm that the cytochrome bc(1) complex exists as a dimer with intertwining Rieske iron-sulfur proteins in solution, four Rhodobacter sphaeroides mutants expressing His-tagged cytochrome bc(1) complexes containing two pairs of cysteine substitutions, one in the interface between the head domain of iron-sulfur protein (ISP) and cytochrome b and the other between the tail domain of ISP and cytochrome b, were generated and characterized. They are: K70C(ISP)/A185C(cytb).P33C(ISP)/G89C(cytb), K70C(ISP)/A185C(cytb).P33C(ISP)/M92C (cytb), K70C (ISP)/A185C(cytb).L34C(ISP)/V64C(cytb), and K70C(ISP)/A185C(cytb).N36C(ISP)/G89C(cytb). The K70C(ISP)/A185C(cytb) cysteine pair cross-links the head domain of ISP and cytochrome b; the P33C(ISP)/G89C(cytb), P33C(ISP)/M92C (cytb), L34C(ISP)/V64C(cytb), and N36C(ISP)/G89C(cytb) cysteine pairs cross-link the tail domain of ISP and cytochrome b. An adduct protein with an apparent molecular mass of 128 kDa containing two cytochrome b and two ISP proteins is detected in the K70C(ISP)/A185C(cytb).P33C(ISP)/G89C(cytb) and K70C(ISP)/A185C(cytb).N36C(ISP)/G89C(cytb) mutant complexes, confirming that the bc(1) complex exists as a dimer with intertwining ISPs. The loss of activity in these two double-cysteine-pair mutant complexes was attributed to the disulfide bond between the head domain of ISP and cytochrome b and not the one between the tail domain of ISP and cytochrome b.     

Molecular and phylogenetic characterisation of Cryptosporidium from birds

Avian isolates of Cryptosporidium species from different geographic locations were sequenced at two loci, the 18S rRNA gene and the heat shock gene (HSP-70). Phylogenetic analysis of the sequence data provided support for the existence of a new avian species of Cryptosporidium infecting finches and a second species infecting a black duck. The identity of Cryptosporidium baileyi and Cryptosporidium meleagridis as valid species was confirmed. Also, C. baileyi was identified in a number of isolates from the brown quail extending the host range of this species.     

High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion

High density lipoprotein (HDL) mediates reverse transport of cholesterol from atheroma foam cells to the liver, but the mechanisms of hepatic uptake and trafficking of HDL particles are poorly understood. In contrast to its accepted role as a cell surface receptor, scavenger receptor class B type 1 (SR-BI) is shown to be an endocytic receptor that mediates HDL particle uptake and recycling, but not degradation, in both transfected Chinese hamster ovary cells and hepatocytes. Confocal microscopy of polarized primary hepatocytes shows that HDL particles enter both the endocytic recycling compartment and the apical canalicular region paralleling the movement of SR-BI. In polarized epithelial cells (Madin-Darby canine kidney) expressing SR-BI, HDL protein and cholesterol undergo selective sorting with recycling of HDL protein from the basolateral membrane and secretion of HDL-derived cholesterol through the apical membrane. Thus, HDL particles, internalized via SR-BI, undergo a novel process of selective transcytosis, leading to polarized cholesterol transport. A distinct process not mediated by SR-BI is involved in uptake and degradation of apoE-free HDL in hepatocytes.     

Inhibition kinetics of green crab (Scylla serrata) alkaline phosphatase by zinc ions: a new type of complexing inhibition

The Tsou method was used to study the kinetic course of inactivation of green crab alkaline phosphatase by zinc ions. The results show that the enzyme was inactivated by a complexing scheme which has not been previously identified. The enzyme first reversibly and quickly binds Zn(2+) and then undergoes a slow reversible course to inactivation and slow conformational change. The inactivation reaction is a single molecule reaction and the apparent inactivation rate constant is for a saturated reaction being independent of Zn(2+) concentration if the concentration is sufficiently high. The microscopic rate constants of inactivation and the association constant were determined from the measurements.