Translational research : the journal of laboratory and clinical medicine
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Randomized Controlled Trial
Antioxidant supplementation reduces endometriosis-related pelvic pain in humans.
We previously suggested that women with endometriosis have increased oxidative stress in the peritoneal cavity. To assess whether antioxidant supplementation would ameliorate endometriosis-associated symptoms, we performed a randomized, placebo-controlled trial of antioxidant vitamins (vitamins E and C) in women with pelvic pain and endometriosis. Fifty-nine women, ages 19 to 41 years, with pelvic pain and history of endometriosis or infertility were recruited for this study. ⋯ In the placebo group, dysmenorrhea-associated pain decreased in 4 patients and no change was seen in chronic pain or dyspareunia. There was a significant decrease in peritoneal fluid inflammatory markers, regulated upon activation, normal T-cell expressed and secreted (P ≤ 0.002), interleukin-6 (P ≤ 0.056), and monocyte chemotactic protein-1 (P ≤ 0.016) after antioxidant therapy compared with patients not taking antioxidants. The results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers in the peritoneal fluid.
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Fatty acids are carboxylic acids with aliphatic tails of different lengths, where short chain fatty acids (SCFAs) typically refer to carboxylic acids with aliphatic tails less than 6 carbons. In humans, SCFAs are derived in large part from fermentation of carbohydrates and proteins in the colon. By this process, the host is able to salvage energy from foods that cannot be processed normally in the upper parts of the gastrointestinal tract. ⋯ These receptors, free fatty acid receptor-2 and -3 (FFAR2 and FFAR3), are expressed not only in the gut epithelium where SCFAs are produced, but also at multiple other sites considered to be metabolically important, such as adipose tissue and pancreatic islets. Because of these relatively recent findings, studies examining the role of these receptors, FFAR2 and FFAR3, and their ligands, SCFAs, in metabolism are emerging. This review provides a critical analysis of SCFAs, their recently identified receptors, and their connection to metabolism.
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A major mechanism of DNA repair related to homologous recombination is the Fanconi anemia (FA) pathway. FA genes collaborate with BRCA genes to form foci of DNA repair on chromatin after DNA damage or during the S phase of the cell cycle. Our goal was to develop a method capable of evaluating the functional status of the pathway in patients' tumor tissue, which could also be practically incorporated into large-scale screening. ⋯ The ratios of FANCD2 foci-negative tumors in ovarian, lung, and breast tumor samples were 21%, 20%, and 29.4%, respectively. Our studies have led to the development of a suitable method for screening, capable of identifying tumors with somatic functional defects in the FA pathway. The use of paraffin-embedded tissues renders the reported method suitable for large-scale screening to select patients for treatment with DNA interstrand crosslinking agents, poly ADP-ribose polymerase inhibitors, or their combination.
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A plethora of somatic mutations and germline variations in mitochondrial DNA (mtDNA) have been increasingly reported in numerous cancer entities including osteosarcoma. However, it remains largely unclear whether mtDNA copy number changes occur during the multistep process of osteosarcoma carcinogenesis. For this purpose, we determined quantitative mtDNA levels in 31 primary osteosarcoma specimens and 5 normal bone tissue samples using a real-time polymerase chain reaction assay. ⋯ Tumors carrying somatic D-loop mutations, at the polycytidine stretch between nucleotide positions 303 and 309 or close to the replication origin sites of the heavy strand, had significantly lowered mtDNA levels in comparison with those without mutations. Taken together, these results provide evidence for the first time that reduced mtDNA content may be critically implicated in the development and/or progression of osteosarcoma. Somatic D-loop mutation is likely one key factor among others leading to altered mtDNA amount in osteosarcoma.