Pulmonary hemodynamics and tissue damage after one lung infusion of Pseudomonas aeruginosa in sheep.

The relative roles of hematogenous mediators and direct bacterial toxicity due to phagocytosis by pulmonary intravascular macrophages were determined by selective bacterial infusion into the left pulmonary artery and comparison of right and left lungs at 24 h. Chronically instrumented sheep received 15-min pulmonary arterial infusions of live Pseudomonas aeruginosa (0.35-2.9 x 10(9), n = 6) or saline (n = 5). The saline group demonstrated stable cardiopulmonary function over time. Left lung blood flow, measured by Doppler flow probe, decreased 15 min into the bacterial infusion, with a concomitant sevenfold increase in left lung pulmonary vascular resistance index. The right lung pulmonary vascular resistance index doubled at 1 h, in association with increased plasma thromboxane B2 levels. An increase in cardiac index and decrease in systemic vascular resistance occurred at 12 h. The wet-to-dry weight ratio of the Pseudomonas-infused left lung was increased compared with that of the sham-infused lung. The tissue count of neutrophils in the lungs was doubled in both sides, but neutrophils on the left were more degranulated. The left lung tissue damage was caused by direct bacterial toxicity, including activation of phagocytic cells. Hematogenous mediators induced pulmonary and systemic hemodynamic changes and right lung neutrophil sequestration, but they did not damage the noninfused lung.     

Epigenetics and mitochondrial dysfunction insights into the impact of the progression of non-alcoholic fatty liver disease

A metabolic problem occurs when regular functions of the body are disrupted due to an undesirable imbalance. Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common in this category. NAFLD is subclassified and progresses from lipid accumulation to cirrhosis before advancing to hepatocellular cancer. In spite of being a critical concern, the standard treatment is inadequate. Metformin, silymarin, and other nonspecific medications are used in the management of NAFLD. Aside from this available medicine, maintaining a healthy lifestyle has been emphasized as a means of combating this. Epigenetics, which has been attributed to NAFLD, is another essential feature of this disease that has emerged as a result of several sorts of research. The mechanisms by which DNA methylation, noncoding RNA, and histone modification promote NAFLD have been extensively researched. Another organelle, mitochondria, which play a pivotal role in biological processes, contributes to the global threat. Individuals with NAFLD have been documented to have a multitude of alterations and malfunctioning. Mitochondria are mainly concerned with the process of energy production and regulation of the signaling pathway on which the fate of a cell relies. Modulation of mitochondria leads to elevated lipid deposition in the liver. Further, changes in oxidation states result in an impaired balance between the antioxidant system and reactive oxygen species directly linked to mitochondria. Hence mitochondria have a definite role in potentiating NAFLD. In this regard, it is essential to consider the role of epigenetics as well as mitochondrial contribution while developing a medication or therapy with the desired accuracy.