Background: Gut microbiota, which plays a crucial role in inflammatory bowel diseases (IBD), might have therapeutic benefits for ulcerative colitis or Crohn's disease. Targeting gut microbiota represents a new treatment strategy for IBD patients. Rhein is one of the main components of rhubarb and exhibits poor oral bioavailability but still exerts anti-inflammatory effects in some diseases. Therefore, we investigated the effect of rhein on colitis and studied its possible mechanisms. Methods: The chronic mouse colitis model was induced by four rounds of 2% dextran sulfate sodium (DSS) treatment. The mice were treated with 50 mg/kg and 100 mg/kg rhein daily, body weight, colon length, histological score, inflammatory cytokines in serum or intestine, and fecal lipocalin 2 concentration were determined. Th17 cell, Th1 cell and Th2 cell infiltration in the mesenteric lymph node were analyzed by flow cytometry. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 4.0. We also assessed intestinal barrier permeability and performed 16s rDNA sequencing. Lactobacillus sp. was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate the contribution of gut microbiota. Results: Rhein could significantly alleviate DSS-induced chronic colitis. Uric acid was identified as a crucial modulator of colitis and rhein treatment led to decreased uric acid levels. We determined that rhein changed purine metabolism indirectly, while the probiotic Lactobacillus was involved in the regulation of host metabolism. Uric acid resulted in a worsened intestinal barrier, which could be rescued by rhein. We further confirmed that rhein-treated gut microbiota was sufficient to relieve DSS-induced colitis by FMT. Conclusion: We showed that rhein could modulate gut microbiota, which indirectly changed purine metabolism in the intestine and subsequently alleviated colitis. Our study has identified a new approach to the clinical treatment of colitis.
Our results indicate that photosensitizer entrapped in micelle exert similar or better PDI efficacy than that of liposome, which indicates this formulation may be useful for the treatment of local infections in the future.
ABSTRACT. Virilization, including penile enlargement and growth of pubic hair and facial acne, developed in a 2-year-old boy over a period of months. This sexual development was induced by incidental and unintentional dermal exposure to a testosterone cream that was applied to his father's arm and back as a part of body building regimen. Except for penile size, the other signs of virilization diminished several months after the exposure was discontinued. Pediatrics 1999;104(2). URL: http://www.pediatrics.org/cgi/content/full/104/2/e23; testosterone, sexual development, childhood, topical exposure.ABBREVIATIONS. T, testosterone; BA, bone age; DHT, dihydrotestosterone.V irilization in boys before puberty caused by exposure to exogenous androgens is rarely reported. We have evaluated a 2-year-old boy who developed androgenization, including progressive penile enlargement and development of pubic hair and facial acne, over a period of months. We discovered dermal exposure to exogenous androgens and ruled out the other causes of androgenization. Here, we discuss the differential diagnosis, laboratory testing, and outcome of this patient. Given the widespread availability of androgens in our society, we suspect that this is not an isolated event. CASE PRESENTATIONA 2.7-year-old boy presented to our pediatric endocrine clinic for evaluation of his sexual development. Over the past 4 to 5 months, he developed progressive enlargement of his penis. Over 1 to 2 months before this visit, he also developed facial acne and pubic hair. The patient was otherwise healthy and active. No change in behavior was noticed. There was no history of accidental ingestion of any medications. However, during approximately the past year, his father had been applying a topical cream containing 50 g of testosterone (T) per ounce to his arms and back (4 oz/day) as a part of a body building regimen. Although the cream was not applied directly to the boy, he had close contact with his father, as well as with his father's body building equipment and mats, which were smeared with the T cream.The patient was born at 31 weeks' gestation and subsequently was diagnosed with congenital hypothyroidism. He had been receiving thyroid replacement therapy successfully since 1 month of age. He had demonstrated a remarkable catch-up growth since birth, and his height crossed the 5th percentile at 21 months of age. He was seen in our pediatric endocrine clinic at 2 years of age. At that time, he was clinically and biochemically euthyroid and had no abnormalities of sexual development.The family history is unremarkable. His father measures 5 feet 7 inches, and his mother measures 5 feet 5 inches. There is no known family history of any causes of abnormal sexual development such as precocious puberty, intracranial tumor, or adrenal abnormalities.Physical examination revealed a very active, playful, and healthy boy. Vital signs were normal for his age. His standing height was 90.6 cm (15th percentile), and his weight was 12.2 kg (15th percentile). His height growt...
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