Hepatic bile acids and bile acid-related gene expression in pregnant and lactating rats

Background. Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats.Materials and Methods. Livers from timed pregnant SD rats were collected on gestational days (GD) 10, 14 and 19, and postnatal days (PND) 1, 7, 14 and 21. Total bile acids were determined by the enzymatic method, total RNA was isolated and subjected to real time RT-PCR analysis. Liver protein was extracted for western-blot analysis.Results. Under physiological conditions hepatic bile acids were not elevated during pregnancy but increased during lactation in rats. Bile acid synthesis rate-limiting enzyme Cyp7a1 was unchanged on gestational days, but increased on PND14 and 21 at mRNA and protein levels. Expression of Cyp8b1, Cyp27a1 and Cyp7b1 was also higher during lactation. The mRNA levels of small heterodimer partner (SHP) and protein levels of farnesoid X receptor (FXR) were increased during pregnancy and lactation. Bile acid transporters Ntcp, Bsep, Mrp3 and Mrp4 were lower at gestation, but increased during lactation. Hepatic Oatp transporters were decreased during pregnancy and lactation.Conclusion. Hepatic bile acid homeostasis is maintained during normal pregnancy in rats, probably through the FXR-SHP regulation. The expression of bile acid synthesis genes and liver bile acid accumulation were increased during lactation, together with increased expression of bile acid efflux transporter Bsep, Mrp3 and Mrp4

Activation of an AMP-activated protein kinase is involved in post-diapause development of Artemia franciscana encysted embryos

<p>Abstract</p> <p>Background</p> <p>Cysts of <it>Artemia </it>can remain in a dormant state for long periods with a very low metabolic rate, and only resume their development with the approach of favorable conditions. The post-diapause development is a very complicated process involving a variety of metabolic and biochemical events. However, the intrinsic mechanisms that regulate this process are unclear.</p> <p>Results</p> <p>Herein we report the specific activation of an AMP-activated protein kinase (AMPK) in the post-diapause developmental process of <it>Artemia</it>. Using a phospho-AMPKα antibody, AMPK was shown to be phosphorylated in the post-diapause developmental process. Results of kinase assay analysis showed that this phosphorylation is essential for AMPK activation. Using whole-mount immunohistochemistry, phosphorylated AMPK was shown to be predominantly located in the ectoderm of the early developed embryos in a ring shape; however, the location and shape of the activation region changed as development proceeded. Additionally, Western blotting analysis on different portions of the cyst extracts showed that phosphorylated AMPKα localized to the nuclei and this location was not affected by intracellular pH. Confocal microscopy analysis of immunofluorescent stained cyst nuclei further showed that AMPKα localized to the nuclei when activated. Moreover, cellular AMP, ADP, and ATP levels in developing cysts were determined by HPLC, and the results showed that the activation of <it>Artemia </it>AMPK may not be associated with cellular AMP:ATP ratios, suggesting other pathways for regulation of <it>Artemia </it>AMPK activity.</p> <p>Conclusion</p> <p>Together, we report evidence demonstrating the activation of AMPK in <it>Artemia </it>developing cysts and present an argument for its role in the development-related gene expression and energy control in certain cells during post-diapause development of <it>Artemia</it>.</p

Comparison analysis of full-spectrum metabolomics revealed on the variation of potential metabolites of unscented, Chloranthus spicatus scented, and Osmanthus fragrans (Thunb.) Lour. scented Congou black teas

IntroductionIn recent years, scented black tea has attracted much attention due to its pleasant floral aroma and mellow flavor, but little research has been carried out on its flavor metabolic profile.MethodsIn this study, the flavor metabolic profiles of unscented, Chloranthus spicatus scented, and Osmanthus fragrans (Thunb.) Lour. scented Congou black teas were investigated using full-spectrum metabolomics analysis method, the first time that the flavor profiles of scented black tea were characterized in detail.Results and DiscussionThe results revealed that a total of 3,128 metabolites were detected in the three teas. Based on the criteria of variable importance in the project &gt;1 and fold change ≥2 or ≤  0.5, 761 non-volatile metabolites and 509 volatile metabolites were filtered as differential metabolites. Many differential non-volatile metabolites belonged to flavonoids, phenolic acids, and terpenoids. Floral, fruity and herbaceous volatile metabolites were significantly up-regulated in Chloranthus spicatus scented Congou black tea while sweet and fruity volatile metabolites were significantly down-regulated in Osmanthus fragrans (Thunb.) Lour. scented Congou black tea. The results contribute to a better understanding of the scenting techniques on the flavor quality of scented black teas and provide some information on the flavor chemistry theory of scented black teas

MTHFR Polymorphism and Folic Acid Supplementation Influence Serum Homocysteine Levels in Psoriatic Patients Treated with Methotrexate.

BACKGROUND Hyperhomocysteinemia has been reported in psoriasis. We investigated the effect of methylenetetrahydrofolate reductase (MTHFR), polymorphism and folic acid supplementation on serum homocysteine levels in psoriasis. METHODS Serum homocysteine levels were detected at baseline and at week 12 in 201 patients who were genotyped with MTHFR rs1801133 without and 93 psoriatic patients with folate supplement. RESULTS TT genotype carriers of MTHFR rs1801133 had significantly higher serum homocysteine levels at baseline and at week 12, a better PASI 75 response rate at week 8, and a higher PASI 90 response rate at week 12 than the CT and CC genotype carriers. Multiple regression analysis demonstrated that serum homocysteine concentration at baseline was significantly associated with sex, weight, PASI score at baseline, and the rs1801133 genotype. The significant upregulation of serum homocysteine levels after treatment with methotrexate (MTX) was only observed in male CT and CC genotype carriers and female CC genotype carriers. In contrast, folic acid supplementation significantly decreased serum homocysteine levels after MTX treatment but only in male psoriatic patients. CONCLUSIONS The effect of MTX on serum homocysteine levels was associated with the polymorphism of MTHFR rs1801133 and sex. Folic acid supplementation only decreased serum homocysteine levels in male psoriatic patients

MTHFR Gene Polymorphism Association With Psoriatic Arthritis Risk and the Efficacy and Hepatotoxicity of Methotrexate in Psoriasis.

Aims To assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population. Methods This prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed. Results The rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04). Conclusions This study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation

Depositional evolution and models for a deep-lacustrine gravity flow system in a half-graben rifted sag, Beibuwan Basin, South China Sea

Acknowledgement. The authors thank the Scientific Research Fund of the Institute of Seismology, CEA, and the National Institute of Natural Hazards, Ministry of Emergency Management of China (Grant No.IS201626261), for funding this study and allowing its publication. In addition, the China Southern Petroleum Exploration & Development Corporation is thanked for allowing publication of the well log and seismic data. The authors also thank Professor Hua Wang and Professor R.W.C. Arnott for providing instruction and discussion, as well as Laura Rincón, Daniel Ariztegui, and Ovie Emmanuel Eruteya for providing constructive and comprehensive reviews that helped to improve this manuscript. We thank International Science Editing for editing this manuscript.The Paleogene Liushagang Formation is part of the Fushan Sag, a continental lacustrine basin located at the Southeastern margin of the Beibuwan Basin, South China Sea. Further understanding of the deep-water gravity flow deposits in this formation will be conducive to lithologic reservoir exploration in the sag. In this study, three members of the Liushagang Formation, SQEls3 SQEls2 and SQEls1, from old to young, are used with core observation, well log data, and three-dimensional seismic data to identify four deep-lacustrine gravity flow lithofacies including their vertical and lateral relationships within the depositional system. The results are then used to establish a deep-water gravity flow depositional model. Four types of gravity flow lithofacies developed in the sag: sandy debrite, turbidite, sandy slump, and bottom-current deposits. Sand-rich sub-lacustrine fan deposits with typical turbidite channels were developed mainly in the western depression, whereas distal isolated lobes formed by sandy debrite flow deposits occurred mainly in the eastern depression. The results obtained in this study will be helpful in the research of gravity flows in similar continental lacustrine environments

Gut microbiota-derived metabolite Trimethylamine-N-oxide (TMAO) and multiple health outcomes:an umbrella review and updated meta-analysis

BACKGROUND: Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced from dietary nutrients. Many studies have discovered that circulating TMAO levels are linked to a wide range of health outcomes. OBJECTIVES: This study aimed to summarize health outcomes related to circulating TMAO levels. METHODS: We searched Embase, Medline, Web of Science and Scopus databases from inception to 15 February 2022 to identify and update meta-analyses examining the associations between TMAO and multiple health outcomes. For each health outcome, we estimated the summary effect size, 95% prediction confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate the evidence credibility of the identified associations. RESULTS: This umbrella review identified 24 meta-analyses that investigated the association between circulating TMAO levels and health outcomes including all-cause mortality, cardiovascular diseases, diabetes mellitus, cancer, and renal function. We updated these meta-analyses by including a total of 82 individual studies in 18 unique health outcomes. Among them, 14 associations were nominally significant. After evidence credibility assessment, we found six (33%) associations (i.e., all-cause mortality, cardiovascular disease mortality, major adverse cardiovascular events, hypertension, diabetes mellitus, and glomerular filtration rate) to present highly suggestive evidence. CONCLUSIONS: TMAO might be a novel biomarker related to human health conditions including all-cause mortality, hypertension, cardiovascular disease, diabetes, cancer and kidney function. Further studies are needed to investigate whether circulating TMAO levels could be an intervention target for chronic disease

Comparison of the efficacy of steroid-free versus classic steroid-containing regimens in primary membranous nephropathy

Objective: To compare the efficacy of a steroid-free regimen with steroid-based treatment in managing primary membranous nephropathy (PMN) and investigate the potential benefits of steroid-free regimens in PMN therapy.Methods: This was a single-centre prospective cohort study. A total of 81 patients were divided into two groups according to their medication regimen: a rituximab (RTX)/tacrolimus (TAC) group (low-dose RTX combined with low-dose TAC group, without steroids, n = 31) and a prednisone (P)/TAC group (P combined with TAC group, n = 61). The changes in 24-h urine protein quantification, levels of blood albumin, blood creatinine, total cholesterol, triglyceride and fasting blood glucose as well as anti-phospholipase A2 receptor antibody titres were observed in both groups before treatment and after 1, 3, 6 and 12 months of treatment. Clinical remission (complete and partial remission), serological remission and recurrence were assessed in both groups after treatment, and the occurrence of adverse reactions was observed.Results: 1) Before treatment, there was no significant difference in baseline values between the two groups (p &gt; 0.05). 2) After 12 months of treatment, the 24-h proteinuria and total cholesterol levels in the RTX/TAC group were significantly lower than those in the P/TAC group (p &lt; 0.05). 3) After 6 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p &lt; 0.05). After 12 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p &lt; 0.05). (4) After 3, 6 and 12 months of treatment, serological remission rates in the RTX/TAC group were significantly higher than those in the P/TAC group (p &lt; 0.05). During treatment, the anti-PLA2R antibody titres in the RTX/TAC group remained lower than those in the P/TAC group (p &lt; 0.05).Conclusion: The low-dose RTX combined with low-dose TAC steroid-free regimen induces serological remission in patients with PMN earlier than the classic regimen of P combined with TAC, and there was no significant difference in adverse effects between the two groups. Besides, the long-term clinical remission effect of low-dose RTX combined with low-dose TAC is better than that of P combined with TAC