Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) are chronic long-lasting inflammatory diseases with yet unknown etiology. Recent advancement revealed that both diseases are associated with genetic predisposition and environmental factors such as luminal microorganisms and antigens. Crohn’s disease is associated with histopathologic features such as granuloma formation and longitudinal ulceration. In this article we describe the role of granuloma in the immunopathogenesis of Crohn’s disease. Granuloma of Crohn’s disease may play crucial roles as antigen-presenting cites to memory type T cells, which leads to activation and proliferation of T cells. Antigens presented at granuloma may be closely related to the disease.
Metformin is a metabolic disruptor, and its efficacy and effects on metabolic profiles under different oxygen and nutrient conditions remain unclear. Therefore, the present study examined the effects of metformin on cell growth, the metabolic activities and consumption of glucose, glutamine, and pyruvate, and the intracellular ratio of nicotinamide adenine dinucleotide (NAD+) and reduced nicotinamide adenine dinucleotide (NADH) under normoxic (21% O2) and hypoxic (1% O2) conditions. The efficacy of metformin with nutrient removal from culture media was also investigated. The results obtained show that the efficacy of metformin was closely associated with cell types and environmental factors. Acute exposure to metformin had no effect on lactate production from glucose, glutamine, or pyruvate, whereas long-term exposure to metformin increased the consumption of glucose and pyruvate and the production of lactate in the culture media of HeLa and HaCaT cells as well as the metabolic activity of glucose. The NAD+/NADH ratio decreased during growth with metformin regardless of its efficacy. Furthermore, the inhibitory effects of metformin were enhanced in all cell lines following the removal of glucose or pyruvate from culture media. Collectively, the present results reveal that metformin efficacy may be regulated by oxygen conditions and nutrient availability, and indicate the potential of the metabolic switch induced by metformin as combinational therapy.
Sclerosing pneumocytoma is a rare tumor of the lung, commonly affecting middle-aged women, and is mostly isolated. Although this tumor is thought to be derived from primitive respiratory epithelial cells, the characteristics of the precursor cells are still unknown. A 19-year-old woman presented with multiple nodules in the right lung. Partial resection of the right middle lobe was performed, and seven sclerosing pneumocytomas, including four that were microscopic, were detected. The latter showed a simple papillary pattern, and three of them consisted of only round cell-like cells (single population). Interestingly, these round cell-like cells were positive for both p63 and TTF-1, but totally negative for SP-A. On the other hand, the tumor cells of the other four sclerosing pneumocytomas showing a papillary pattern with a dual population, were diffusely positive for TTF-1 and focally positive for SP-A (only in surface cells), but negative or very focally positive for p63. It has been reported that p63-positive stem cell-like cells are present in the distal airway and have potential to differentiate into type II pneumocytes. The immunohistochemical features of these multiple microscopic lesions suggest that the p63-TTF-1 double-positive cells are candidate precursor cells of sclerosing pneumocytoma.
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