lankorean1
lankorean1
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The gut bacterium Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-associated fatty liver disease (MAFLD). However, its underlying mechanism involved in its well-known metabolic actions needs further evaluation. The present study explored the therapeutic effect and mechanism of A. muciniphila in intervening MAFLD by using a high-fat and high-cholesterol (HFC) diet induced obese mice model. Mice treated with A. muciniphila efficiently reversed MAFLD in the liver, such as hepatic steatosis, inflammatory, and liver injury. These therapeutic effects persisted after long-term drug withdrawal and were slightly weakened in the antibiotics-treated obese mice. A. muciniphila treatment efficiently increased mitochondrial oxidation and bile acid metabolism in the gut-liver axis, ameliorated oxidative stress-induced cell apoptosis in gut, leading to the reshaping of the gut microbiota composition. These metabolic improvements occurred with increased L-aspartate levels in the liver that transported from the gut. The administration of L-aspartate in vitro or in mice displayed the similar beneficial metabolic effects mentioned above and efficiently ameliorated MAFLD. selleck chemicals llc Together, these data indicate that the anti-MAFLD activity of A. muciniphila correlated with lipid oxidation and improved gut-liver interactions through regulating the metabolism of L-aspartate. A. muciniphila could be a potential agent for clinical intervention in MAFLD. Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over age 50 in developed countries. Current therapy for nonexudative AMD (neAMD) is aimed at modifying risk factors and vitamin supplementation to slow progression, while intravitreal anti-vascular endothelial factor (VEGF) injections are the mainstay for treatment of choroidal neovascularization in exudative AMD (eAMD). Over the past decade, promising therapies have emerged that aim to improve the current standard of care for both diseases. Clinical trials for neAMD are investigating targets in the complement cascade, vitamin A metabolism, metformin, and tetracycline, whereas clinical trials for eAMD are aiming to decrease treatment burden through novel port delivery systems, increasing drug half-life, and targeting new sites of the VEGF cascade. Stem cell and gene therapy are also being evaluated for treatment of neAMD and eAMD. With an aging population, the need for effective, long term, low burden treatment options for AMD will be in increasingly high demand. Current investigations aim to address the shortcomings of current treatment options with breakthrough treatment approaches. Therapeutics in the pipeline hold promise for improving the treatment of AMD, and are on track for widespread use within the next decade.With an aging population, the need for effective, long term, low burden treatment options for AMD will be in increasingly high demand. Current investigations aim to address the shortcomings of current treatment options with breakthrough treatment approaches. Therapeutics in the pipeline hold promise for improving the treatment of AMD, and are on track for widespread use within the next decade. Pregnancy among women with end-stage renal disease (ESRD) has risen in frequency, which may be attributed to improvements in hemodialysis care. Our objective was to describe baseline characteristics and pregnancy outcomes among women with ESRD on hemodialysis. Using the United States' Healthcare Cost and Utilization Project-Nationwide Inpatient Sample, we created a cohort of women with ESRD on hemodialysis who gave birth between 2005 and 2015. We determined the proportion of adverse maternal and neonatal outcomes among this cohort. Then, we created a composite measure of vascular-mediated adverse pregnancy outcomes. Women who experienced at least one of either preeclampsia, intrauterine growth restriction, or intrauterine fetal death were categorized as having the composite measure. Then, multivariate regression models were used to estimate the associations between maternal baseline demographic and clinical characteristics and the composite measure. Among 8,765,973 deliveries between 2005 and 2015, 307 were to women with ESRD on hemodialysis. Over the study period, the incidence of pregnancies to women with ESRD increased from 0.47 to 5.76/100,000 births. An estimated 28% of pregnancies were complicated by preeclampsia, 8% by placental abruption, 58% delivered by cesarean, and in the postpartum, 28% required blood transfusions and 6% experienced sepsis. About 45% of babies were born preterm and 14% had IUGR. The composite measure of adverse events was not found to be associated with any baseline maternal characteristics. The frequency of pregnant women with ESRD on hemodialysis has risen, with adverse pregnancy complications for both mother and fetus. Transfer to high-risk centers is suggested for women with ESRD.The frequency of pregnant women with ESRD on hemodialysis has risen, with adverse pregnancy complications for both mother and fetus. Transfer to high-risk centers is suggested for women with ESRD.Background Azithromycin maintenance therapy is widely used in cystic fibrosis (CF), but little is known about its long-term safety. We investigated whether chronic azithromycin use is safe regarding renal function, hepatic cell toxicity and QTc-interval prolongation.Methods Adult CF patients (72 patients using azithromycin for a cumulative period of 364.8 years and 19 controls, 108.8 years) from two CF-centers in the Netherlands with azithromycin (non)-use for at least three uninterrupted years were studied retrospectively.Results There was no difference in mean decline of estimated glomerular filtration rate (eGFR), nor in occurrence of eGFR-events. No drug-induced liver injury could be attributed to azithromycin. Of the 39 azithromycin users of whom an ECG was available, 4/39 (10.3%) had borderline and 4/39 (10.3%) prolonged QTc-intervals, with 7/8 patients using other QTc-prolonging medication. Of the control patients 1/6 (16.7%) had a borderline QTc-interval, without using other QTc-prolonging medication.

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