Category Archives: RESEARCH ARTICLE

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.

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.

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.

Torpor‐responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

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Torpor-responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

Monito del monte (Dromiciops gliroides) undergoes metabolic rate depression to conserve energy during torpor. Differential microRNA expression plays a key role in metabolic reorganization by regulating key signaling and metabolic pathways.


Abstract

The marsupial Monito del monte (Dromiciops gliroides) utilizes both daily and seasonal bouts of torpor to preserve energy and prolong survival during periods of cold and unpredictable food availability. Torpor involves changes in cellular metabolism, including specific changes to gene expression that is coordinated in part, by the posttranscriptional gene silencing activity of microRNAs (miRNA). Previously, differential miRNA expression has been identified in D. gliroides liver and skeletal muscle; however, miRNAs in the heart of Monito del monte remained unstudied. In this study, the expression of 82 miRNAs was assessed in the hearts of active and torpid D. gliroides, finding that 14 were significantly differentially expressed during torpor. These 14 miRNAs were then used in bioinformatic analyses to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were predicted to be most affected by these differentially expressed miRNAs. Overexpressed miRNAs were predicted to primarily regulate glycosaminoglycan biosynthesis, along with various signaling pathways such as Phosphoinositide-3-kinase/protein kinase B and transforming growth factor-β. Similarly, signaling pathways including phosphatidylinositol and Hippo were predicted to be regulated by the underexpression of miRNAs during torpor. Together, these results suggest potential molecular adaptations that protect against irreversible tissue damage and enable continued cardiac and vascular function despite hypothermia and limited organ perfusion during torpor.

miR‐34a/SIRT1/HIF‐1α axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise

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miR-34a/SIRT1/HIF-1α axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise

Sodium butyrate and treadmill exercise, alone or together, significantly reduced the blood glucose levels in type 2 diabetic rats. Combination of sodium butyrate and treadmill exercise, improved oral glucose tolerance test in type 2 diabetic rats. Diabetes increased miR-34a expression and FOXO1 levels, and decreased SIRT1 and HIF-1α levels that were measured by real-time PCR and ELISA method. A combination of sodium butyrate and treadmill exercise significantly decreased miR-34a expression and FOXO1 levels, and improved SIRT1 and HIF-1α levels in the heart tissue of diabetic rats. Sodium butyrate and treadmill exercises, alone or together, increased angiogenesis in the heart tissue of diabetic rats. So, those may be useful in the treatment of diabetes through the mir-34a/SIRT1/FOXO1-HIF-1α pathway.


Abstract

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders worldwide. Recent research has indicated that sodium butyrate (NaB) affects glucose metabolism and exercise has an anti-hyperglycemic effect in diabetes. This study aimed to evaluate the effects of NaB and treadmill exercise on heart angiogenesis through the miR-34a/SIRT1/FOXO1-HIF-1α pathway. Diabetic animals received NaB (400 mg/kg daily, orally) and treadmill exercise for 6 weeks. The effect of NaB and treadmill exercise, alone or combined, on miR-34a expression, SIRT1, FOXO1, HIF-1α levels, and angiogenesis in diabetic heart tissue was measured. Diabetes caused increased miR-34a (p < 0.01) and FOXO1 (p < 0.001) expression levels. Also, SIRT1 (p < 0.001) and HIF-1α (not significant) expression levels were reduced in diabetic rats. NaB and treadmill exercise decreased miR-34a (respectively p < 0.05 and not significant) and FOXO1 (both p < 0.001) expression levels and improved SIRT1 (both not significant) and HIF-1α (respectively p < 0.01 and p < 0.001) levels. Also, NaB combined with treadmill exercise decreased miR-34a (p < 0.001) and FOXO1 (p < 0.001) expression levels, and elevated SIRT1 (p < 0.05) and HIF-1α (p < 0.001) levels in comparison with the diabetic group. NaB and treadmill exercises modulate the expression of miR-34a and the levels of SIRT1, FOXO1, and HIF-1α proteins, thus increasing angiogenesis in the heart tissue of diabetic rats. It can be concluded that NaB and treadmill exercise, alone or combined, may be useful in the treatment of diabetes through the miR-34a/SIRT1/FOXO1-HIF-1α pathway.

The structure of a Lactobacillus helveticus chlorogenic acid esterase and the dynamics of its insertion domain provide insights into substrate binding

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The structure of a Lactobacillus helveticus chlorogenic acid esterase and the dynamics of its insertion domain provide insights into substrate binding

Chlorogenic acid esterases are biotechnologically useful enzymes that hydrolyze unwanted chlorogenic acid in foods, thereby improving their sensory properties. This work determines how two residues on hairpin loops above the active site influence substrate binding and turnover in a bacterial chlorogenic acid esterase.


Chlorogenic acid esterases (ChlEs) are a useful class of enzymes that hydrolyze chlorogenic acid (CGA) into caffeic and quinic acids. ChlEs can break down CGA in foods to improve their sensory properties and release caffeic acid in the digestive system to improve the absorption of bioactive compounds. This work presents the structure, molecular dynamics, and biochemical characterization of a ChlE from Lactobacillus helveticus (Lh). Molecular dynamics simulations suggest that substrate access to the active site of LhChlE is modulated by two hairpin loops above the active site. Docking simulations and mutational analysis suggest that two residues within the loops, Gln145 and Lys164, are important for CGA binding. Lys164 provides a slight substrate preference for CGA, whereas Gln145 is required for efficient turnover. This work is the first to examine the dynamics of a bacterial ChlE and provides insights on substrate binding preference and turnover in this type of enzyme.

Characterization the prognosis role and effects of snoRNAs in melanoma patients

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Abstract

Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.

The anticancer/cytotoxic effect of a novel gallic acid derivative in non‐small cell lung carcinoma A549 cells and peripheral blood mononuclear cells from healthy individuals and lung cancer patients

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The anticancer/cytotoxic effect of a novel gallic acid derivative in non-small cell lung carcinoma A549 cells and peripheral blood mononuclear cells from healthy individuals and lung cancer patients

This article presents a series of novel derivatives from gallic acid with antioxidant / anticancer properties. These compounds were studied on lymphocytes from healthy individuals and lung cancer patients. Also, gallic acid and its derivatives were examined on non-small cell carcinoma cell line. The anticancer effect of these compounds was revealed which should be confirmed with further future investigations.


Abstract

Gallic acid (GA) is a naturally occurring polyphenol with a strong antioxidant capacity. GA stimulates the apoptosis of cancer cells, thereby suppressing cancer cell invasion. However, the low oral permeability of GA limits its therapeutic use. In order to enhance the antioxidant capacity and oral permeability of GA, a series of compounds analogous to GA were synthesized: 4-methoxybenzenesulfonamide (MBS), 3,4-dimethoxybenzenesulfonamide (DMBS) and 3,4,5-trimethoxybenzenesulfonamide (TMBS). In the new compounds, hydroxyl groups were replaced with various numbers of methoxy groups (stronger electron-donating groups), to increase hydrophobicity and oral permeability compared to GA. In addition, the carboxylic group was replaced with a sulfonyl group (a stronger electron-withdrawing group), to increase the molecular polarity and antioxidative activities of the compounds. The cell counting kit-8 (CCK-8) assay was used to detect the effect of GA, MBS, DMBS, and TMBS on cell proliferation and apoptosis in peripheral blood mononuclear cells (PBMCs) from healthy individuals and non-small cell lung carcinoma A549 cells. Additionally, the comet assay was used to assess the genotoxicity of these compounds in PBMCs from healthy individuals, lung cancer patients, and A549 cells. Compared to untreated cells, TMBS reduced DNA damage more effectively than GA in PBMCs from lung cancer patients and healthy donors. Furthermore, in comparison to GA, TMBS was more cytotoxic in A549 cells. Moreover, TMBS was not cytotoxic in healthy PBMCs, suggesting that TMBS demonstrates therapeutic potential in cancer.

Insights into the antiosteoporotic mechanism of the soy‐derived isoflavone genistein: Modulation of the Wnt/beta‐catenin signaling

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Insights into the antiosteoporotic mechanism of the soy-derived isoflavone genistein: Modulation of the Wnt/beta-catenin signaling

Glucocorticoid-induced osteoporosis (GIO) reduces bone formation, osteoblasts differentiation and function, and accelerates osteoblast and osteocyte apoptosis. Genistein induces bone remodeling through Wnt/β-catenin pathway activation in osteoblast and osteocytes. Genistein could represent an interesting new therapeutic approach for the management of GIO patients.


Abstract

Bone remodeling is a process that involves osteoblasts, osteoclasts, and osteocytes, and different intracellular signaling, such as the canonical Wnt/β-catenin pathway. Dysregulations of this pathway may also occur during secondary osteoporosis, as in the case of glucocorticoid-induced osteoporosis (GIO), which accelerates osteoblast and osteocyte apoptosis by reducing bone formation, osteoblast differentiation and function, accelerates in turn osteoblast, and osteocyte apoptosis. Genistein is a soy-derived nutrient belonging to the class of isoflavones that reduces bone loss in osteopenic menopausal women, inhibiting bone resorption; however, genistein may also favor bone formation. The aim of this study was to investigate whether estrogen receptor stimulation by genistein might promote osteoblast and osteocyte function during glucocorticoid challenge. Primary osteoblasts, collected from C57BL6/J mice, and MLO-A5 osteocyte cell line were used to reproduce an in vitro model of GIO by adding dexamethasone (1 μM) for 24 h. Cells were then treated with genistein for 24 h and quantitative Polymerase Chain Reaction (qPCR) and western blot were performed to study whether genistein activated the Wnt/β-catenin pathway. Dexamethasone challenge reduced bone formation in primary osteoblasts and bone mineralization in osteocytes; moreover, canonical Wnt/β-catenin pathway was reduced following incubation with dexamethasone in both osteoblasts and osteocytes. Genistein reverted these changes and this effect was mediated by both estrogen receptors α and β. These data suggest that genistein could induce bone remodeling through Wnt/β-catenin pathway activation.

Should sons breed independently or help? Local relatedness matters

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Should sons breed independently or help? Local relatedness matters

Why do some younger individuals breed themselves, whereas other counterparts help? This question is addressed using 15 years of data from a Tibetan bird. The finding—kin neighbourhoods facilitate younger males to acquire a territory and breed independently—explains how the kin-based, facultative cooperative societies form in vertebrates. (Illustration: Y. Chen; Photo: D. Ke).


Abstract

In cooperatively breeding birds, why do some individuals breed independently but others have to help at home? This question has been rarely addressed despite its fundamental importance for understanding the evolution of social cooperation. We address it using 15 years of data from Tibetan ground tits Pseudopodoces humilis where helpers consist of younger males. Since whether younger males successfully breed depends critically on their chances to occupy territories nearby home, our analytic strategy is to identify the determinants of individual differences in gaining territory ownership among these ready-to-breed males. Across widowed, last-year helper and yearling males, an age advantage was evident in inheriting resident territories, occupying adjacent vacancies and budding off part of adjacent territories, which left some last-year helpers and most yearling males to take the latter two routes. These males were more likely to acquire a territory if they were genetically related to the previous or current territory owners; otherwise they remained on natal territories as helpers. The relatedness effect can arise from the prior residence advantage established in the preceding winter when younger males followed their parents to perform kin-directed off-territory forays. Our research highlights the key role of local kinship in determining younger males' territory acquisition and thus their fate in terms of independent reproduction versus help. This finding provides insight into the formation of kin-based, facultative cooperative societies prevailing among vertebrates.

摘要

在合作繁殖鸟类中，为什么一些性成熟的个体独立繁殖，而其它被迫留家帮助?尽管这一问题对于理解社会进化至关重要，但迄今没有得到充分回答。 我们使用来自青藏高原特有物种地山雀15年的野外数据，企图回答这一问题。研究种群中，帮助者都是年轻的雄性。这些个体的繁殖成功，取决于其是否能在家族领域附近获得自己的领域。因此，我们的分析策略就是识别决定繁殖雄性个体获得领域的关键因素。 在继承领域、占据相邻空缺领域和瓜分相邻领域方面，丧偶雄性、上年帮助者和一龄雄性的优势依次降低。这使得一些上年帮助者和大多数一龄雄性不得不采取后两种获得领域的途径。我们发现，如果这些年轻雄性与相邻空缺的前任、或被挤占领域的现任拥有者为亲属，他们就更可能获得领域而独立繁殖；否则便沦为留家的帮助者。这种亲属效应来自冬季年轻雄性跟随父亲频繁访问相邻亲属领域而预先建立的对潜在未来领域的熟悉性。 我们的研究凸显了邻里亲缘关系在决定年轻雄性能否获得领域、进而独立繁殖或成为帮助者的关键作用。该发现增进了人们对普遍存在于脊椎动物中以亲缘关系为基础的兼性合作社会形成机制的理解。