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In this study, we investigated how Roux-en-Y gastric bypass (RYGB) enhances glucagon-like peptide 1 (GLP-1) response in GK rats and explored the potential link between RYGB-stimulated BAs/FXR signalling and GLP-1R-linked signalling in β-cells, a key pathway that regulates glucose-stimulated insulin secretion (GSIS). Here we show that RYGB restores GLP-1R expression in GK rat islets. This involves increased total BAs as well as chenodeoxycholic acid (CDCA), leading to FXR activation, increasing FXR binding to the promoter of Glp-1r and enhancing occupancy of histone acetyltransferase steroid receptor coactivator-1 (SRC1), thus increasing histone H3 acetylation at the promoter. These coordinated events bring about increased GLP-1R expression, resulting in greater GLP-1 response in β-cells. Moreover, ablation of FXR suppressed the stimulatory effects of GLP-1. Thus, this study unravels the crucial role of the BAs/FXR/SRC1 axis-controlled GLP-1R expression in β-cells, which results in enhanced incretin effect and normalized blood glucose of GK rats after RYGB.We investigated whether horses trained in moderate and mild hypoxia demonstrate greater improvement in performance and aerobic capacity compared to horses trained in normoxia and whether the acquired training effects are maintained after 2 weeks of post-hypoxic training in normoxia. Seven untrained Thoroughbred horses completed 4 weeks (3 sessions/week) of three training protocols, consisting of 2-min cantering at 95% maximal oxygen consumption V ˙ O 2 max under two hypoxic conditions (H16, FI O2 = 16%; H18, FI O2 = 18%) and in normoxia (N21, FI O2 = 21%), followed by 2 weeks of post-hypoxic training in normoxia, using a randomized crossover study design with a 3-month washout period. Incremental treadmill tests (IET) were conducted at week 0, 4, and 6. The effects of time and groups were analyzed using mixed models. Run time at IET increased in H16 and H18 compared to N21, while speed at V ˙ O 2 max was increased significantly only in H16. V ˙ O 2 max in all groups and cardiac output at exhaustion in H16 and H18 increased after 4 weeks of training, but were not significantly different between the three groups. In all groups, run time, V ˙ O 2 max , V V ˙ O 2 max , Q ˙ max , and lactate threshold did not decrease after 2 weeks of post-hypoxic training in normoxia. These results suggest that 4 weeks of training in moderate (H16), but not mild (H18) hypoxia elicits greater improvements in performance and running economy than normoxic training and that these effects are maintained for 2 weeks of post-hypoxic training in normoxia.Blind snakes (Typhlopidae) are an enigmatic group of small burrowing snakes whose anatomy, phylogenetics, and biodiversity remain poorly known. Madatyphlops comorensis (Boulenger, 1889), endemic to the Comoros Archipelago in the Western Indian Ocean, is one of many species whose phylogenetic placement and generic assignment is unclear. We used DNA barcoding, external morphological examination, and osteological data from 3D reconstruction with micro-CT to study specimens of Madatyphlops from the Comoros Archipelago. Our results support the placement of M. comorensis in Madatyphlops and the recognition of the specimens from Mayotte Island as a closely related but distinct species, which we describe as Madatyphlops eudelini sp. nov. In this context, we present the first detailed osteological descriptions of any species of Madatyphlops, which we hope will serve as groundwork for further osteological studies in this genus and contribute to our limited but growing understanding of the osteology of typhlopid snakes.Excessive post-epidural fibrosis is a common cause of recurrent back pain after spinal surgery. Though various treatment methods have been conducted, the safe and effective drug for alleviating post-epidural fibrosis remains largely unknown. Metformin, a medicine used in the treatment of type 2 diabetes, has been noted to relieve fibrosis in various organs. In the present study, we aimed to explore the roles and mechanisms of metformin in scar formation in a mouse model of laminectomy. Post-epidural fibrosis developed in a mouse model of laminectomy by spinous process and the T12-L2 vertebral plate with a rongeur. With the administration of metformin, post-epidural fibrosis was reduced, accompanied with decreased collagen and fibronectin in the scar tissues. Mechanistically, metformin decreased fibronectin and collagen deposition in fibroblast cells, and this effect was dependent on the HMGB1/TLR4 and TGF-β1/Smad3 signalling pathways. In addition, metformin influenced the metabolomics of the fibroblast cells. Taken together, our study suggests that metformin may be a potential option to mitigate epidural fibrosis after laminectomy.
Retinopathy of prematurity (ROP), one of the leading causes of childhood blindness, is a complex condition in which various antenatal and neonatal factors participate at different stages of the disease. This meta-analysis was conducted to investigate whether pregnancy-induced hypertension (PIH) was associated with ROP by summarizing all available evidence.
PubMed, EMBASE, Web of Science, EBSCO and SCOPUS databases were searched for all relevant studies published from inception to April 2020. this website Studies investigating the association between PIH and ROP were included.
A total of 29 studies were finally included for the meta-analysis after study selection. The results showed there are both no significant association between PIH and the occurrence of ROP in case-control studies (OR 0.91, 95%CI 0.59 to 1.40, I
=81%, p=0.67) and cohort studies (OR 1.32, 95%CI 0.89 to 1.98, I
=93%, p=0.17). The conclusion was same between pre-eclampsia and ROP (OR 0.82, 95%CI 0.50 to 1.35, I
=83%, p=0.43 in case-control studies and OR 1.70, 95%CI 0.82 to 3.50, I
=95%, p=0.15 in cohort studies).
In summary, this meta-analysis did not reveal a consistent result, the conclusion remains inconclusive, and further studies will be needed to come to a conclusion for the effect of maternal PIH on ROP and foster a better understanding of the prevention of ROP.
In summary, this meta-analysis did not reveal a consistent result, the conclusion remains inconclusive, and further studies will be needed to come to a conclusion for the effect of maternal PIH on ROP and foster a better understanding of the prevention of ROP.
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