Bone marrow-derived cells contribute to cerulein-induced pancreatic fibrosis in the mouse.

Bone marrow (BM) cells may transdifferentiate into circulating fibrocytes and myofibroblasts in organ fibrosis. In this study, we investigated the contribution and functional roles of BM-derived cells in murine cerulein-induced pancreatic fibrosis. C57/BL6 female mice wild-type (WT) or Col 1α1(r/r) male BM transplant, received supraphysiological doses of cerulein to induce pancreatic fibrosis. The CD45(+)Col 1(+) fibrocytes isolated from peripheral blood (PB) and pancreatic tissue were examined by in situ hybridization for Y chromosome detection. The number of BM-derived myofibroblasts, the degree of Sirius red staining and the levels of Col 1α1 mRNA were quantified. The Y chromosome was detected in the nuclei of PB CD45(+)Col 1(+) fibrocytes, confirming that circulating fibrocytes can be derived from BM. Co-expression of α-smooth muscle actin illustrated that fibrocytes can differentiate into myofibroblasts. The number of BM-derived myofibroblasts, degree of collagen deposition and pro-collagen I mRNA expression were higher in the mice that received Col 1α1(r/r) BM, (cells that produce mutated, collagenase-resistant collagen) compared to WT BM, indicating that the genotype of BM cells can alter the degree of pancreatic fibrosis. Our data indicate that CD45(+)Col 1(+) fibrocytes in the PB can be BM-derived, functionally contributing to cerulein-induced pancreatic fibrosis in mice by differentiating into myofibroblasts.

ERK activation induced by selenium treatment significantly downregulates beta/gamma-secretase activity and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M.

Selenium reportedly contribute to the modulation process of protein phosphorylation to regulate various cellular functions including growth, differentiation, proliferation and development. The aim of this study was to investigate whether selenium and Selenoprotein M (SelM) affects the mechanism of Alzheimer's disease. To achieve this, we determined the change of the MAPK pathway, secretase activity, and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M. Based on these results, we concluded that, i) CMV/GFP-hSelM Tg rats showed a high activity level of antioxidant enzyme in the brain tissues, ii) in response to selenium treatment, the ERK signaling pathway was significantly increased in Tg rats, but did not change in wild-type rats, iii) the activation of the ERK pathway by selenium treatment and SelM overexpression induced the inhibition of the alpha/gamma-secretase activity related to the protection of Abeta-42 production, iv) the activation of the ERK pathway by selenium treatment and SelM overexpression inhibited the phosphorylation in several sites of Tau protein. Therefore, these results provide strong evidence that selenium treatment and SelM activate the ERK pathway to attenuate alpha/gamma-secretase-mediated proteolysis and Tau phosphorylation to protect brain function.

A Missed Late Presentation of a Congenital Pulmonary Airway Malformation as a Large Infected Bulla.

A congenital pulmonary airway malformation (CPAM) is a rare cystic anomaly that may occur during development of the fetal airways. The vast majority of CPAMs are detected in neonates; as such, it is unusual for diagnosis to occur in adulthood. We report a 21-year-old male patient who presented to the emergency department of the Hospital Ampang, Kuala Lumpur, Malaysia, in 2015 with chest pain, breathlessness and tachypnoea. Based on an initial chest X-ray, the patient was misdiagnosed with pneumothorax and underwent urgent chest tube insertion; however, his condition deteriorated over the course of the next three days. Further imaging was suggestive of infected bullae or an undiagnosed CPAM. The patient therefore underwent video-assisted thoracoscopic surgery, during which a large infected bulla was resected. A diagnosis of an infected CPAM was confirmed by histopathological examination. Following the surgery, the patient recovered quickly and no bullae remnants were found at a one-month follow-up.

Isolated crypts form spheres prior to full intestinal differentiation when grown as xenografts: an in vivo model for the study of intestinal differentiation and crypt neogenesis, and for the abnormal crypt architecture of juvenile polyposis coli.

We describe a model system in which single crypts, isolated from newborn rats, were embedded in a type I collagen gel and subcutaneously grafted to the flanks of nude mice, whereupon they underwent full intestinal morphogenesis. Small fragments of small intestine and colon were incubated with the divalent cation chelator EDTA, resulting in the release of crypts and villi. Released crypts were then suspended sparsely in type I collagen gel. Segments of gel containing a single crypt were grafted subcutaneously into a nude mouse. Grafts were harvested at weekly intervals. By 2 days, the mouth of the crypts had joined to seal the crypt and, within 1 week, the structure ballooned to form a spherical cystic structure lined by flattened epithelial cells showing no evidence of cytodifferentiation. After 2 weeks, host stromal cells had invaded the collagen and settled around this spherical crypt. At points where stromal cells appeared in contact with the crypt, the epithelium exhibited a more columnar phenotype. By 4 weeks, the 'crypt sphere' was surrounded by stroma expressing alpha-smooth muscle actin and, at this time, multiple buds appeared that gave rise to new crypts. By 5 weeks, villi had formed and cell lineages associated with the small intestine and colon were present; the original single crypt had transformed into a functional intestinal unit. Therefore, we have shown that a single crypt has the potential to grow, give rise to other crypts and dependent structures such as villi. This model has considerable potential for use in gene transfer experiments in the study of intestinal differentiation, and for the analysis of crypt neogenesis via crypt fission. Moreover, the appearances showed a close resemblance to those seen in juvenile polyposis syndrome (JPS), where the budding and fission of single crypts isolated by stromal overgrowth offers an alternative explanation for the histogenesis of JPS.