Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of hemolysis-induced gallstones was studied in mice with a hereditary hemolytic disease called normoblastic anemia (genotype nb/nb) and in their normal controls (genotype +/+). Infrared spectroscopy demonstrated that spontaneously formed gallstones from nb/nb mice were nearly identical to stones from patients with chronic hemolysis as the result of sickle cell disease, and both mouse and human stones strikingly resembled synthetic calcium bilirubinate. 57% of 115 nb/nb mice, but none of 109 control mice, developed calcium bilirubinate pigment gallstones (P < 0.001). The incidence of luminal gallstones in nb/nb mice was both sex and age dependent. Female nb/nb mice formed stones twice as frequently as male nb/nb mice (P < 0.001). Before 6 mo of age neither sex developed stones, but thereafter the incidence of stones increased with age. Neither hematocrit, reticulocyte count, nor total plasma bilirubin values, were useful in distinguishing between nb/nb mice with or without gallstones. In gallbladder bile, nb/nb mice with gallstones had higher concentrations of hydrogen ion, total bilirubin, calcium, and bile acids than nb/nb mice without stones. Although total unconjugated bilirubin was similar in both nb/nb groups, the ionized fraction of unconjugated bilirubin was higher in bile from nb/nb mice without stones than those with stones. In nb/nb mice, neutral mucin plugs and pigment concentrations were observed histologically in the glandular crypts of the gallbladder in 33% of nb/nb mice without stones and in 80% of nb/nb mice with luminal stones. This suggested that luminal pigment stone disease in mice with hemolysis may be preceded by microscopic precipitation of calcium bilirubinate in the glandular crypts of the gallbladder. These precipitates may then migrate into the lumen and grow by accretion.
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PMID:Studies on the pathogenesis of pigment gallstones in hemolytic anemia: description and characteristics of a mouse model. 741 May 45

Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity. Here we identify an on-demand mechanism that clears erythrocytes and recycles iron. We show that monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 (LY6C1, also known as Ly-6C) ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1 (FPN1, encoded by SLC40A1)-expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1(+)Tim-4(neg) macrophages are transient, reside alongside embryonically derived T cell immunoglobulin and mucin domain containing 4 (Timd4, also known as Tim-4)(high) Kupffer cells (KCs), and depend on the growth factor Csf1 and the transcription factor Nrf2 (encoded by Nfe2l2). The spleen, likewise, recruits iron-loaded Ly-6C(high) monocytes, but these do not differentiate into iron-recycling macrophages, owing to the suppressive action of Csf2. The accumulation of a transient macrophage population in the liver also occurs in mouse models of hemolytic anemia, anemia of inflammation, and sickle cell disease. Inhibition of monocyte recruitment to the liver during stressed erythrocyte delivery leads to kidney and liver damage. These observations identify the liver as the primary organ that supports rapid erythrocyte removal and iron recycling, and uncover a mechanism by which the body adapts to fluctuations in erythrocyte integrity.
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PMID:On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver. 2742

High fructose (HF) diet-induced liver steatosis is associated with intestinal microbiota dysbiosis. The aim of this study was to assess the modulatory effects of Artemisia sphaerocephala Krash seed polysaccharide (ASKP) on fatty acid metabolism and intestinal microbiota in mice fed with HF water. Administration of HF-fed mice with ASKP prevented fat accumulation and blunted metabolic inflammation and endotoxaemia. ASKP-treated mice displayed improved glucose tolerance and fully exhibited protection against hepatic steatosis. Besides, ASKP was effective in improving the changes in the composition of liver fatty acids via modulating hepatic SREBP-1c, SCD-1, ACC and FAS expressions. 16S rRNA gene sequencing showed that ASKP treatment modified the gut microbial species at the phylum level with a decrease of Firmicutes and a slight increase of Bacteroidetes (p > 0.05). Interestingly, ASKP markedly increased the proportion of the mucin-degrading bacterium Akkermansia at the genus level in HF-fed mice. These findings support the beneficial metabolic effects of ASKP through amelioration of the HF-induced features of liver steatosis, which is associated with health maintenance of the intestinal microecosystem.
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PMID:Artemisia sphaerocephala Krasch polysaccharide prevents hepatic steatosis in high fructose-fed mice associated with changes in the gut microbiota. 3174 83