Serine protease inhibitors prevent alcoholic liver injury]

The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially characterized. It now appears that Kupffer cell derived TNF-alpha participates in several aspects of alcoholic liver injury. On the other hand, protease inhibitors have been used successfully for treatment of intractable diseases in which TNF-alpha is involved in the pathogenesis, including ulcerative colitis and Crohn's disease. Here, we will review new evidence for the proposal that serine protease inhibitors prevents alcoholic liver injury via mechanisms dependent on Kupffer cell derived TNF-alpha.     

Malignant B-lymphoid cells with bone lesions express receptor activator of nuclear factor-kappaB ligand and vascular endothelial growth factor to enhance osteoclastogenesis.

PURPOSE: Receptor activator of nuclear factor-kappaB ligand (RANKL) is a key mediator of osteoclastogenesis. Because certain types of tumor cells aberrantly express RANKL, and because bone destruction also develops in B-cell lymphomas of bone origin, we investigated RANKL expression and the mechanisms of osteoclastogenesis in B-lymphoid neoplasms. EXPERIMENTAL DESIGN AND RESULTS: Immunohistochemistry of bone specimens resected from patients with primary B-cell lymphoma of bone with bone destruction revealed that lymphoma cells express RANKL as well as vascular endothelial cell growth factor (VEGF). The tumor cells isolated from the bone specimens enhanced osteoclastogenesis in vitro. In contrast, B-cell lymphoma infiltrating to the bone marrow without bone destruction did not express RANKL. Both RANKL and VEGF were expressed by a portion of B-lymphoid cell lines, including Daudi and IM-9. These RANKL-expressing tumor cells enhanced osteoclastogenesis from RAW264.7 cells and human monocyte-derived preosteoclasts in the absence of stromal cells/osteoblasts in a RANKL-dependent manner. Furthermore, conditioned media from Daudi cells enhanced transmigration of preosteoclasts that was inhibited by anti-VEGF antibody, suggesting that tumor cell-derived VEGF mediates recruitment of osteoclast precursors. Moreover, cocultures of B-lymphoid cell lines with osteoclasts enhanced the growth of B-lymphoid cells. CONCLUSIONS: Some malignant B cells aberrantly express functional RANKL as well as VEGF to enhance osteoclastogenesis. The coexpression of RANKL and VEGF may also contribute to the close cellular interactions with osteoclastic cells, thereby forming a vicious cycle between osteoclastic bone destruction and tumor expansion in bone.     

Gender difference in alcoholic liver injury]

Gender differences of alcoholic liver injury have been described previously, but mechanisms have only partially characterized. For example, it is known that females develop alcoholic liver injury more rapidly and to a greater extent than males. It now appears that estrogen participates in several aspects of this phenomenon. On the other hand, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cell and alcohol-induced liver injury.     

Fetal facial expressions in small-for-gestational-age and growth-restricted fetuses

Objective: To evaluate the frequencies of fetal facial expressions among appropriate-for-gestational-age (AGA), small-for-gestational-age (SGA), and growth-restricted (FGR) fetuses.

Methods: Four-dimensional (4D) ultrasound was used to examine the facial expressions of 50 AGA, 25 SGA, and six FGR fetuses between 28 and 35 weeks of gestation. The frequencies of seven facial expressions during 15-minute recordings were assessed. Comparison of facial expressions among the three groups was performed.

Results: Mouthing was the commonest facial expression at 28–35 weeks, and the frequency of mouthing was significantly higher than those of the other six facial expressions in AGA fetuses. Mouthing was the most frequent facial expression, but there was no significant difference in the frequency among mouthing, smiling and blinking in SGA fetuses. Moreover, mouthing displayed a significantly higher frequency than the other facial expressions, except for yawning, smiling, and blinking in FGR fetuses. However, there was no significant difference in the frequency of each facial expression among the three groups.

Conclusions: Our results suggest that the frequencies of fetal facial expressions are not decreased in either SGA or FGR pregnancies. The absence of a decrease in the frequency of each fetal expression in FGR fetuses may be due to increased brain blood flow because of the brain-sparing effect. Moreover, accelerated maturation and development of the brain function, especially the central dopamine system, might be suspected in SGA and FGR fetuses.     

Metabolomic approach to oral biofilm characterization—A future direction of biofilm research

Research approaches to biofilm are stratified by a series of analyses: (1) microbial number and species; (2) microbial proteins, such as enzymes; and (3) microbial activity, such as metabolic activity. On the other hand, the hierarchical structure of biology includes the genome, proteome, and metabolome, in which the metabolome is the final output of biological function. Metabolome analysis is the comprehensive analysis of the metabolome, a new strategy for biological research in the 21st century. The stratified structure of biofilm research corresponds to the biological hierarchy, and the analysis of microbial activity, especially metabolic activity, is comparable to metabolome analysis; however, oral biofilm samples are too small to analyze the metabolome by conventional methods. Recently, a new device involving capillary electrophoresis (CE) and time-of-flight mass spectrometry (MS) has been developed, facilitating metabolomic investigation of the central carbon metabolic pathways (i.e., the EMP pathway, pentose phosphate pathway, and TCA cycle) in oral biofilm. Using CE–MS, we analyzed metabolome profiles of oral biofilm after oral rinsing with glucose in vivo and evaluated the effects of oral rinsing with fluoride and xylitol on the metabolome profiles of oral biofilm. The results were somewhat consistent with previous in vitro data obtained from single bacterial strains, namely, Streptococcus and Actinomyces; however, new information describing the metabolic properties of oral biofilm was also obtained. This metabolomic approach will reveal the functional characteristics of oral biofilm in vivo, potentially providing new insights into the nature of oral biofilm in health and disease.