Sevoflurane and isoflurane preconditioning ameliorates inflammation, cerebral lipid peroxidation, and histologic injury. Downregulation of proapoptotic molecules and upregulation of antiapoptotic molecules may be associated with this effect.

Interactions with stromal components influence the growth, survival, spread, and colonization capacities of tumor cells. Fibroblasts and macrophages which are responsible for the stroma production and maintenance are of the basic elements found in tumor microenvironment. Cellular density and ratio of stromal cells to tumor cells can also have modulatory effects in cancer. Here, the contribution of fibroblast and/or macrophage cells on the malignant behavior of breast cancer cells was modeled in co-culture systems. Co-cultures were established at different cell densities and ratios with 4T1 breast cancer, NIH/3T3 or 3T3-L1 fibroblast, and J774A.1 monocyte/macrophage cell lines. Flow cytometry-based proliferation, 3D growth on alginate matrix, and matrigel invasion assays were performed to determine the change in the malignant assets of tumor cells. The data were also supported by immunocytochemical and morphological analyses. Co-culturing with fibroblasts (especially, NIH/3T3 cells) significantly supported the proliferation, scattering, and invasiveness of 4T1 cells whereas inclusion of macrophages disrupted this positive influence. On the other hand, the invasion capacity of 4T1 cells was not enhanced in the co-cultures with fibroblasts whose motility were inhibited with pertussis toxin pretreatment. Particularly at low-density seeding in 3D cultures, 4T1 cells could form substantially more spheroids than that of in the co-cultures with fibroblasts. Only, increasing the amount of fibroblasts could restore the 3D-growth. Intriguingly, co-existence of macrophage, fibroblast, and tumor cells in 3D cultures provided a convenient stroma sustaining the spheroid formation and growth. In conclusion, fibroblasts can form a favorable environment for tumor cells' spread and motility whereas restricting their 3D-growth capacity. On the other hand, presence of macrophages may disrupt the influence of fibroblasts and enhance the spheroid formation by the tumor cells.

Despite advances in the diagnosis and management of idiopathic non-cirrhotic portal hypertension (INCPH), its pathogenesis remains elusive. Insight may be gained from study of early onset familial INCPH, in which Mendelian mutations may account for disease. We performed exome sequencing of 8 subjects from 6 kindreds with onset of portal hypertension of indeterminate etiology during infancy or childhood. Three subjects from two consanguineous families shared the identical rare homozygous p.N46S mutation in DGUOK, a deoxyguanosine kinase required for mitochondrial DNA replication; haplotype sharing demonstrated the mutation in the two families was inherited from a remote common ancestor. All three affected subjects had stable portal hypertension with non-cirrhotic liver disease for 6–16 years of follow-up. This mutation impairs ATP binding and reduces catalytic activity. Loss-of-function mutations in DGUOK have previously been implicated in cirrhosis and liver failure but not in isolated portal hypertension. Interestingly, treatment of patients with HIV infection with the nucleoside analog didanosine is known to cause portal hypertension in a subset of patients and lowers deoxyguanosine kinase levels in vitro; the current findings implicate these effects on deoxyguanosine kinase in the causal mechanism. CONCLUSION: Our findings provide new insight into the mechanisms mediating inherited and acquired non-cirrhotic portal hypertension, expand the phenotypic spectrum of DGUOK deficiency, and provide a new genetic test for a specific cause of INCPH.

The hypothesis of this study was that the extent of bone regeneration could be enhanced by using scaffolds with appropriate geometry, and that such an effect could be further increased by mimicking the natural timing of appearance of bone morphogenetic proteins BMP-2 and BMP-7 after fracture. Bioplotted poly(ε-caprolactone) (PCL) disks with four different fibre organizations were used to study the effect of 3D scaffold architecture on the healing of bone defects in a rat pelvis model. Moreover, one PCL construct was further modified by introducing a nanoparticulate sequential BMP-2/BMP-7 delivery system into this scaffold. Scaffolds and functionalized construct along with free nanocapsules were implanted using a rat iliac crest defect model. Six weeks post-implantation, the defects were evaluated by CT scan and histology. Analysis revealed that the basic architecture, having the highest pore volume for tissue ingrowth, presented the highest bone formation as determined by the bone mineral density (BMD) within the defect (144.2 ± 7.1); about four-fold higher than that of the empty defect (34.9 ± 10.7). It also showed the highest histological analysis scores with a high amount of bone formation within the defect, within the scaffold pores and along the outer surfaces of the scaffold. The basic scaffold carrying the BMP-2/BMP-7 delivery system showed significantly higher bone formation than the growth factor-free basic scaffold at 6 weeks (BMD 206.8 ± 15.7). Histological analysis also revealed new bone formation in close to or in direct contact with the construct interface. This study indicates the importance of open and interconnecting pore geometry on the better healing of bone defects, and that this effect could be further increased by supplying growth factors, as is the case in nature.

Resveratrol supplementation considerably restored hepatic changes induced by HFCS. The improvement of hepatic insulin signaling and activation of SIRT1 by resveratrol may be associated with decreased triglyceride content and expression levels of the lipogenic genes of the liver.