The role of LncRNA‐regulated autophagy in AKI

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The role of LncRNA-regulated autophagy in AKI

The relationship between lncRNA, autophagy, and AKI. The role of lncRNA-regulated autophagy in AKI.


Abstract

Acute kidney injury (AKI) is a complex clinical syndrome involving a series of pathophysiological processes regulated by multiple pathways at the molecular and cellular level. Long noncoding RNAs (lncRNAs) play an important role in the regulation of epigenetics, and their regulation of autophagy-related genes in AKI has attracted increasing attention. However, the role of lncRNA-regulated autophagy in AKI has not been fully elucidated. Evidence indicated that lncRNAs play regulatory roles in most factors that induce AKI. LncRNAs can regulate autophagy in AKI via a complex network of regulatory pathways to affect the development and prognosis of AKI. This article reviewed and analyzed the pathways of lncRNA regulation of autophagy in AKI in recent years. The results provide new ideas for further study of the pathophysiological process and targeted therapy for AKI.

Skincare potential of a sustainable postbiotic extract produced through sugarcane straw fermentation by Saccharomyces cerevisiae

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Skincare potential of a sustainable postbiotic extract produced through sugarcane straw fermentation by Saccharomyces cerevisiae

Production of a postbiotic extract using sugarcane straw as substrate of fermentation process and Saccharomyces cerevisiae as fermentative microorganism. The extract obtained showed antioxidant and anti-inflammatory activities in skin cells, as well as beneficial for skin microbiota modulation applications. This sustainable produced postbiotic extract can be used for cosmetic and skincare ingredients development


Abstract

Postbiotics are defined as a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.” They can be produced by fermentation, using culture media with glucose (carbon source), and lactic acid bacteria of the genus Lactobacillus, and/or yeast, mainly Saccharomyces cerevisiae as fermentative microorganisms. Postbiotics comprise different metabolites, and have important biological properties (antioxidant, anti-inflammatory, etc.), thus their cosmetic application should be considered. During this work, the postbiotics production was carried out by fermentation with sugarcane straw, as a source of carbon and phenolic compounds, and as a sustainable process to obtain bioactive extracts. For the production of postbiotics, a saccharification process was carried out with cellulase at 55°C for 24 h. Fermentation was performed sequentially after saccharification at 30°C, for 72 h, using S. cerevisiae. The cells-free extract was characterized regarding its composition, antioxidant activity, and skincare potential. Its use was safe at concentrations below ~20 mg mL−1 (extract's dry weight in deionized water) for keratinocytes and ~ 7.5 mg mL−1 for fibroblasts. It showed antioxidant activity, with ABTS IC50 of 1.88 mg mL−1, and inhibited elastase and tyrosinase activities by 83.4% and 42.4%, respectively, at the maximum concentration tested (20 mg mL−1). In addition, it promoted the production of cytokeratin 14, and demonstrated anti-inflammatory activity at a concentration of 10 mg mL−1. In the skin microbiota of human volunteers, the extract inhibited Cutibacterium acnes and the Malassezia genus. Shortly, postbiotics were successfully produced using sugarcane straw, and showed bioactive properties that potentiate their use in cosmetic/skincare products.

Promotion of degradative autophagy by 6‐bromoindirubin‐3′‐oxime attenuates neuropathy

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Promotion of degradative autophagy by 6-bromoindirubin-3′-oxime attenuates neuropathy

Tunicamycin increases peripheral neuropathy subsequently treatment with 6-BIO reduces peripheral neuropathy and increases degradative autophagy and reduces secretory autophagy.


Abstract

Damage to the central or peripheral nervous system causes neuropathic pain. Endoplasmic reticulum (ER) stress plays a role in peripheral neuropathy. Increase in ER stress is seen in diabetic neuropathy. Inducers of ER stress also give rise to peripheral neuropathy. ER stress leads to the formation of autophagosome but as their degradation is also stalled during ER stress accumulation of autophagosomes is seen. Accumulation of autophagosomes has deleterious effects on cells. In the present study, we show that treatment with tunicamycin (TM) (ER stress inducer) in mice leads to peripheral neuropathy as assessed by Von Frey and Hot plate method. Administration of a promoter of autophagy viz. 6-bromoindirubin-3′-oxime (6-BIO) subsequent to ER stress induced by TM exhibits a decrease in peripheral neuropathy. 6-BIO was also effective in reducing diabetic peripheral neuropathy. To understand the type of autophagy activated, SH-SY5Y cells were treated with 6-BIO after TM treatment. Levels of cathepsin D (CTSD), a marker for degradative autophagy was higher in cells treated with 6-BIO after TM treatment compared to only TM-treated SH-SY5Y cells while levels of Rab8A,—a marker for secretory autophagy was reduced. Furthermore, in parallel during ER stress secretory, we noted increased levels of lysozyme in autophagosomes destined for secretion. Cells treated with 6-BIO showed reduction of lysozyme in secretory autophagosomes. This shows that 6-BIO increased degradative autophagy and reduced the secretory autophagy. 6-BIO also reduced the caspase-3 activity in 6-BIO-treated cells. Thus, 6-BIO reduced neuropathy in animals by activating degradative autophagy and reducing the secretory autophagy.

Stachydrine, N‐acetylornithine and trimethylamine N‐oxide levels as candidate milk biomarkers of maternal consumption of an obesogenic diet during lactation

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Stachydrine, N-acetylornithine and trimethylamine N-oxide levels as candidate milk biomarkers of maternal consumption of an obesogenic diet during lactation

Reverting to a healthy maternal diet during lactation normalizes the altered milk metabolome found in obese rats. Stachydrine, N-acetylornithine and TMAO levels are proposed as candidate biomarkers of maternal consumption of an obesogenic diet during lactation.


Abstract

We aimed to evaluate whether improving maternal diet during lactation in diet-induced obese rats reverts the impact of western diet (WD) consumption on the metabolome of milk and offspring plasma, as well as to identify potential biomarkers of these conditions. Three groups of dams were followed: control-dams (CON-dams), fed with standard diet (SD); WD-dams, fed with WD prior and during gestation and lactation; and reversion-dams (REV-dams), fed as WD-dams but moved to SD during lactation. Metabolomic analysis was performed in milk at lactation days 5, 10, and 15, and in plasma from their male and female offspring at postnatal day 15. Milk of WD-dams presented, throughout lactation and compared to CON-dams, altered profiles of amino acids and of the carnitine pool, accompanied by changes in other polar metabolites, being stachydrine, N-acetylornithine, and trimethylamine N-oxide the most relevant and discriminatory metabolites between groups. The plasma metabolome profile was also altered in the offspring of WD-dams in a sex-dependent manner, and stachydrine, ergothioneine and the acylcarnitine C12:1 appeared as the top three most discriminating metabolites in both sexes. Metabolomic changes were largely normalized to control levels both in the milk of REV-dams and in the plasma of their offspring. We have identified a set of polar metabolites in maternal milk and in the plasma of the offspring whose alterations may indicate maternal intake of an unbalanced diet during gestation and lactation. Levels of these metabolites may also reflect the beneficial effects of implementing a healthier diet during lactation.

Including genomic information in the genetic evaluation of production and reproduction traits in South African Merino sheep

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Abstract

Genomic selection (GS) has become common in sheep breeding programmes in Australia, New Zealand, France and Ireland but requires validation in South Africa (SA). This study aimed to compare the predictive ability, bias and dispersion of pedigree BLUP (ABLUP) and single-step genomic BLUP (ssGBLUP) for production and reproduction traits in South African Merinos. Animals in this study originated from five research and five commercial Merino flocks and included between 54,072 and 79,100 production records for weaning weight (WW), yearling weight (YW), fibre diameter (FD), clean fleece weight (CFW) and staple length (SL). For reproduction traits, the dataset included 58,744 repeated records from 17,268 ewes for the number of lambs born (NLB), number of lambs weaned (NLW) and the total weight weaned (TWW). The single-step relationship matrix, H, was calculated using PreGS90 software combining 2811 animals with medium density (~50 K) genotypes and the pedigree of 88,600 animals. Assessment was based on single-trait analysis using ASREML V4.2 software. The accuracy of prediction was evaluated according to the ‘LR-method’ by a cross-validation design. Validation candidates were assigned according to Scenario I: born after a certain time point; and Scenario II: born in a particular flock. In Scenario I, the genotyping rate for the reference population between 2006 and the 2013 cut-off point approached 7% of animals with phenotypes and 20% of their sires. For reproduction traits, about 20% of ewes born between 2006 and 2011 cut-off were genotyped, along with 15% of their sires. Genotyping rates in the validation set of Scenario I were 3.7% (production) and 11.4% (reproduction) for candidates and 35% of their sires. Sires were allowed to have progeny in both the reference and validation set. In Scenario I, ssGBLUP increased the accuracy of prediction for all traits except NLB, ranging between +8% (0.62–0.67) for FD and +44% (0.36–0.52) for WW. This showed a promising gain in accuracy despite a modestly sized reference population. In the ‘across flock validation’ (Scenario II), overall accuracy was lower, but with greater differences between ABLUP and ssGBLUP ranging between +17% (0.12–0.14) for TWW and +117% (0.18–0.39) for WW. There was little indication of severe bias, but some traits were prone to over dispersion and the use of genomic information did not improve this. These results were the first to validate the benefit of genomic information in South African Merinos. However, because production traits are moderately heritable and easy to measure at an early age, future research should be aimed at best exploiting GS methods towards genetic prediction of sex-limited and/or lowly heritable traits such as NLW. GS methods should be combined with dedicated efforts to increase genetic links between sectors and improved phenotyping by commercial flocks.

Performance and bone characteristics of broilers fed diets supplemented with vitamin A at different concentrations

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Abstract

This work evaluated the influence of vitamin A on performance, organ weight, and bone and skin characteristics in broilers (Cobb 500) at 21 and 42 days of age. A total of 1920 chickens were distributed in a randomised design, considering six vitamin A supplementation levels (0, 6000, 16,000, 26,000, 36,000, and 46,000 IU kg−1), with 16 replicates and 20 chickens per experimental unit, established due to rising the range of vitamin levels observed in the literature to evaluate the effect of vitamin A on broilers. At 22 days, half of the replicates from each treatment continued receiving the initial diet, and the other eight repetitions received diets without vitamin A (0 IU kg−1) until 42 days. The level of vitamin A influenced feed intake (FI) and body weight gain (BWG) until 21 days for all treatments. Broilers at 21 days of age had a more significant BWG at a vitamin A supplementation level of 28,209 IU kg−1. At 42 days, vitamin A influenced the BWG and FI of broilers at treatments that were not supplemented after 21 days. Treatments supplemented up to 42 days showed quadratic responses to vitamin A for BWG, FI, and feed conversion. The vitamin A levels influenced the relative weights of the small intestine, pancreas, gizzard, abdominal fat, Seedor index, and breaking strength at 42 days, where the adequate supplementation of vitamin A improved these characteristics in broilers. Vitamin A supplementation from 22 to 42 days old did not affect broiler performance. An increased BWG was obtained when vitamin A supplementation occurred until 42 days, with supplementation of 29,375 IU kg−1 and a lower response of feed conversion with the addition of 27,775 IU kg−1.