Stress-induced Effects Research Articles

Investigation of the inflammatory and oxidative stress-inducing effects of deoxynivalenol and T-2 toxin exposure in non-tumorigenic human intestinal cell model

Fungi in the Fusarium genus produce trichothecene mycotoxins including deoxynivalenol (DON) and T-2 toxin which may elicit their damaging effects on the gastrointestinal tract following the consumption of contaminated cereal-based foods. The aim of our study was to evaluate the effects of these commonly occurring fusarotoxins alone and in combination using the human, non-cancerous intestinal epithelial cell line HIEC-6. Based on our experimental data, 24 h after treatment with fusarotoxins, hydrogen peroxide levels, intracellular oxidative stress and the amounts of inflammatory interleukins IL-6 and IL-8 significantly increased. Cell membrane localization of the tight junction protein claudin-1 decreased, whereas distribution of occludin remained unchanged. Taken together, the HIEC-6 cell line appears to be a suitable experimental model for monitoring the combined effects of mycotoxins at the cellular level including changes in the redox states of cells.

Numerical simulation of stress field distribution before re-fracturing treatment

Due to the first fracturing failure at the middle and final stages of oil and gas field development, re-fracturing technology has become a key method to increase production in oilfield. So, stress field distribution should be the key successful factor to impact re-fracturing technology after the initial fracturing in reservoir. In order to accurately describe the initial stress field distribution of reservoir after fracturing and provide theoretical basis for subsequent re-fracturing, this paper with theory of rock fracture mechanics and fluid-solid coupling equation had built several ABAQUS numerical model of hydraulic fracturing according to the basic theory of XFEM, to analyses the stress influence by horizontal stress difference, rock elastic modulus, Poisson’s ratio and production time before re-fracturing. Numerical simulation results show that due to the initial crack and the change of pore pressure in the process of production, the direction and size of the original stress field change a lot, which lead a stress field redirection; Reservoir and rock physical mechanical parameters bring a significantly change of reservoir stress field distribution; with the difference of horizontal stress, rock elastic modulus and oil field production time increasing, induced stress effect and stress redirection area decrease; the greater of Poisson’s ratio, the induced stress effect and redirection area is smaller.

Stimulation of myogenesis by ascorbic acid and capsaicin

Myogenesis is a complex process regulated by several factors. This study evaluated the functional interaction between vitamin C and a high dose of capsaicin (a potential endoplasmic reticulum (ER) stress inducer) on myogenesis. After the induction of differentiation, treatment with ascorbic acid or ascorbic acid phosphate (AsAp) alone had minimal effects on myogenesis in C2C12 cells. However, treatment with capsaicin (300 μM) in undifferentiated C2C12 cells increased the expression levels of genes related to ER stress as well as oxidative stress. Myogenesis was effectively enhanced in C2C12 cells treated with a combination of capsaicin (300 μM) for one day before differentiation stimulation and AsAp for four days post-differentiation; subsequently, thick and long myotubes formed, and the expression levels of myosin heavy chain (MYH) 1/2 and Myh1, Myh4, and Myh7 increased. Considering that mild ER stress stimulates myogenesis, AsAp may elicit myogenesis through the alleviation of oxidative stress-induced negative effects in capsaicin-pretreated cells. The enhanced expression of Myh1 and Myh4 coincided with the expression of Col1a1, a type I collagen, suggesting that the fine-tuning of the myogenic cell microenvironment is responsible for efficient myogenesis. Our results indicate that vitamin C is a potential stimulator of myogenesis in cells, depending on the cell context.

Nelfinavir Blocks Export of Newly Synthesized Protein from the ER and Interacts with ER-Resident and Mitochondrial Proteins in an Activity-Dependent Fashion

The majority of multiple myeloma (MM) patients initially respond to proteasome inhibitor (PI)-based therapy, but later develop PI resistance and ultimately dies from PI-refractory MM. PI sensitivity of MM cells correlates with the activation status of the unfolded protein response (UPR) and its major activating axis IRE1/XBP1. PI-refractory MM cells downregulate IRE1/XBP1, and high IRE1/XBP1 expression correlates with clinical sensitivity to PI treatment. The anti-HIV drug nelfinavir induces IRE1/XBP1 and overcomes PI-resistance of MM in vitro . Nelfinavir showed unprecedented clinical activity in PI-refractory, heavily pretreated MM with ORR 65% in combination with bortezomib and dexamethasone. The molecular target of nelfinavir and its mechanism of action in MM cells are unknown. We synthesized structurally modified nelfinavir analogues equipped with a covalently protein-binding, photo-reactive moiety and functional groups that allow affinity purification of the nelfinavir analogue bound to its interacting cellular protein (SC-441), together with appropriate controls where the active center of nelfinavir was sterically occupied (SC-451). Isolation and identification of nelfinavir-interacting proteins in AMO-1 MM cells and cells adapted to carfilzomib (AMO-CFZ) was achieved with these tools by photoactivation in living cells, affinity purification and tandem mass spectrometry. We identified a small set of proteins that specifically bound to active nelfinavir. The majority of these were endoplasmic reticulum (ER)-resident proteins involved in protein quality control and transport from ER to Golgi apparatus. In addition, individual proteins from mitochondria or the nucleus were identified. We thus hypothesized that nelfinavir interferes with intracellular protein transport, in line with its UPR-activating properties. Using a construct of ST-SBP-TNFa-EGFP engineered with an ER-retention signal (KDEL) that can be released upon biotin treatment of cells (RUSH-system), in conjunction with confocal microscopy and flow cytometry in U2OS cells, we show that nelfinavir, but not its analogue SC-451, which lacks proteasome inhibitor-sensitizing activity, retains TNFa-EGFP in the ER and prevents its transport to the Golgi and into the extracellular space. We confirmed in MM cells that active nelfinavir, but not SC-451, likewise retains newly synthesized IgA by preventing its secretion, and similarly decreases MHC class I export to the cell surface.Functionally depletion of the putative ER-targets of nelfinavir by siRNA in U2OS cells sensitized cells to nelfinavir and proteasome inhibitors. The mitochondrial targets of nelfinavir were identified as constituents of the mitochondria permeability transition pore (mPTP), a multimeric protein complex that regulates the permeability of mitochondrial membranes. The formation of reactive oxygen species (ROS) and inhibition of ABCB1 efflux, known for nelfinavir, can be functionally linked to mPTP modulation.In conclusion, we demonstrate that nelfinavir blocks export of newly synthetized protein from the ER, consistent with its activity-dependent binding to ER proteins. The block in protein export from the ER by nelfinavir is consistent with its ER stress-inducing, IRE1/XBP1-activating, and PI-sensitizing effect in the clinic. We further identify mPTP as an additional protein target of nelfinavir, consistent with its ROS-inducing and ABCB1-modulating activity. The block in ER protein export represents a novel mechanism of action to sensitize MM cells for proteasome inhibitor treatment. DisclosuresNo relevant conflicts of interest to declare.

Managing Water Stress by Potassium Fertilizer in Legumes for Sustainable Agricultural Intensification: A Review

Water stress has become the most uncontrolled and unpredictable factor, which is continuously limiting production in crops. Legumes are the major source of protein and are well-recognized for their nutritional benefits as well as their impact on the sustainability of agricultural systems are well known. Leguminous crops are severely affected by water stress causing alterations in various development processes. Proper nutrient management helps in attaining economical legume yields from drought-prone lands. The protective role of potassium in plants suffering from water stress has been documented and it positively influences plant capacity to adjust water stress conditions. This review compromises the information on the water stress-induced harmful effects on legumes growth, nitrogen fixation, gaseous exchange and mineral uptake parameters and proposes appropriate management by potassium application to alleviate the severity of water stres on above mentioned parameters. Application of potassium proved to meet higher yield from legume on cultivation under low/residual soil moisture availability conditions.

Warm perches: a novel approach for reducing cold stress effect on production, plasma hormones, and immunity in laying hens

Cold temperature is a common environmental stressor that induces pathophysiological stress in birds with profound economic losses. Current methods used for preventing cold stress, such as reducing ventilation and using gas heaters, are facing challenges due to poor indoor air quality and deleterious effects on bird and caretaker health. The aim of this study was to examine if the novel designed warmed perch system, as a thermal device, can reduce cold stress-associated adverse effects on laying hens. Seventy-two 32-week-old DeKalb hens were randomly assigned to 36 cages arranged to 3 banks. The banks were assigned to 1 of 3 treatments: cages with warmed perches (WP; perches with circulating water at 30°C), air perches (AP, regular perches only), or no perches (NP) for a 21-d trial. The room temperature was set at 10°C during the entire experimental period. Rectal temperature and body weight were measured from the same bird of each cage at d 1, 8, 15, and 21 during the cold exposure. Egg production was recorded daily. Feed intake, egg and eggshell quality were determined during the 1st and 3rd wk of cold stress. Plasma levels of corticosterone, thyroid hormones (3, 3’, 5-triiodothyronine and thyroxine), interleukin (IL)-6 and IL-10, were determined after 1 d and 21 d of cold exposure. Compared to both AP and NP hens, WP hens were able to maintain their body temperature without increasing feed intake and losing BW. The eggs from WP hens had thicker eggshell during the 3rd wk of cold exposure. Warmed perch hens also had a lower thyroxine conversion rate (3, 3’, 5-triiodothyronine/thyroxine) at d 1, while higher plasma concentrations of IL-6 at d 21. Plasma levels of corticosterone, 3, 3’, 5-triiodothyronine, and IL-10 were not different among treatments. Our results indicate that the warmed perch system can be used as a novel thermal device for preventing cold stress-induced negative effects on hen health and welfare through regulating immunity and metabolic hormonal homeostasis.

Bacillus subtilis-Based Probiotic Improves Skeletal Health and Immunity in Broiler Chickens Exposed to Heat Stress.

Simple SummaryHigh ambient temperature is a major environmental stressor affecting the physiological and behavioral status of animals, increasing stress susceptibility and immunosuppression, and consequently increasing intestinal permeability (leaky gut) and related neuroinflammation. Probiotics, as well as prebiotics and synbiotics, have been used to prevent or decrease stress-associated detrimental effects on physiological and behavioral homeostasis in humans and various animals. The current data indicate that a dietary probiotic supplement, Bacillus subtilis, reduces heat stress-induced abnormal behaviors and negative effects on skeletal health in broilers through a variety of cellular responses, regulating the functioning of the microbiota–gut–brain axis and/or microbiota-modulated immunity during bone remodeling under thermoneutral and heat-stressed conditions.The elevation of ambient temperature beyond the thermoneutral zone leads to heat stress, which is a growing health and welfare issue for homeothermic animals aiming to maintain relatively constant reproducibility and survivability. Particularly, global warming over the past decades has resulted in more hot days with more intense, frequent, and long-lasting heat waves, resulting in a global surge in animals suffering from heat stress. Heat stress causes pathophysiological changes in animals, increasing stress sensitivity and immunosuppression, consequently leading to increased intestinal permeability (leaky gut) and related neuroinflammation. Probiotics, as well as prebiotics and synbiotics, have been used to prevent or reduce stress-induced negative effects on physiological and behavioral homeostasis in humans and various animals. The current data indicate dietary supplementation with a Bacillus subtilis-based probiotic has similar functions in poultry. This review highlights the recent findings on the effects of the probiotic Bacillus subtilis on skeletal health of broiler chickens exposed to heat stress. It provides insights to aid in the development of practical strategies for improving health and performance in poultry.

New Insights on Hemp Oil Enriched in Cannabidiol: Decarboxylation, Antioxidant Properties and In Vitro Anticancer Effect.

This study aimed to obtain and characterize extracted hemp oil enriched in cannabidiol (CBD) by decarboxylation of cannabidiolic acid (CBDA) and to give new insights into its antioxidant and anticancer effects. Optimization of CBDA decarboxylation in hemp oil was performed, and CBD and CBDA contents and purities were determined by flash chromatography, 1H- and 13C-NMR. The antioxidant properties of CBD-enriched oil were investigated by Fe2+ chelating activity, Fe3+ reducing antioxidant power assay, O2●− scavenging activity, HO● scavenging ability and lipid peroxidation inhibitory assay, and its cytotoxicity, apoptosis- and oxidative stress-inducing effects on NHDF, MeWo, HeLa, HepG2 and HOS cells were determined. The CBD concentration in hemp oil was increased by CBDA soft decarboxylation optimized at 90 °C, for 1 h and the resulting oil was capable of reducing iron, scavenging free radicals and inhibiting lipid peroxidation in cell-free oxidative conditions. CBD-enriched oil promoted NHDF proliferation at up to 15 µg CBD/mL, while inducing apoptosis and ROS production and modulating antioxidant enzymes’ gene expression in cancer cells, being selective for osteosarcoma cells, and induced apoptosis by p53- and ROS-independent mechanisms. CBD-enriched hemp oil demonstrated antioxidant properties in oxidative conditions and promoted normal fibroblasts’ proliferation, while inducing apoptosis and ROS production in cancer cells.

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise. Toxin-mediated ablation of lysozyme M+ (LysM+) myeloid cells was performed in LysMCreiDTR mice carrying a cre-inducible diphtheria toxin receptor. In the last 4d of toxin treatment, the animals were exposed to noise at maximum and mean sound pressure levels of 85 and 72 dB(A), respectively. Flow cytometry analysis revealed accumulation of CD45+, CD11b+, F4/80+, and Ly6G−Ly6C+ cells in the aortas of noise-exposed mice, which was prevented by LysM+ cell ablation in the periphery, whereas brain infiltrates were even exacerbated upon ablation. Aircraft noise-induced increases in blood pressure and endothelial dysfunction of the aorta and retinal/mesenteric arterioles were almost completely normalized by ablation. Correspondingly, reactive oxygen species in the aorta, heart, and retinal/mesenteric vessels were attenuated in ablated noise-exposed mice, while microglial activation and abundance in the brain was greatly increased. Expression of phagocytic NADPH oxidase (NOX-2) and vascular cell adhesion molecule-1 (VCAM-1) mRNA in the aorta was reduced, while NFκB signaling appeared to be activated in the brain upon ablation. In sum, we show dissociation of cerebral and peripheral inflammatory reactions in response to aircraft noise after LysM+ cell ablation, wherein peripheral myeloid inflammatory cells represent a dominant part of the pathomechanism for noise stress-induced cardiovascular effects and their central nervous counterparts, microglia, as key mediators in stress responses.

Antioxidant Nanomedicine Significantly Enhances the Survival Benefit of Radiation Cancer Therapy by Mitigating Oxidative Stress-Induced Side Effects.

Oxidative stress-induced off-target effects limit the therapeutic window of radiation therapy. Although many antioxidants have been evaluated as radioprotective agents, none of them are in widespread clinical use, owing to the side effects of the antioxidants themselves and the lack of apparent benefit. Aiming for a truly effective radioprotective agent in radiation cancer therapy, the performance of a self-assembling antioxidant nanoparticle (herein denoted as redox nanoparticle; RNP) is evaluated in the local irradiation of a subcutaneous tumor-bearing mouse model. Since RNP is covered with a biocompatible shell layer and possesses a core-shell type structure of several tens of nanometers in size, its lifetime in the systemic circulation is prolonged. Moreover, since 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), one of the most potent antioxidants, is covalently encapsulated in the core of RNP, it exerts intense antioxidant activity and induces fewer adverse effects by avoiding leakage of the TEMPO molecules. Preadministration of RNP to the mouse model effectively mitigates side effects in normal tissues and significantly extends the survival benefit of radiation cancer therapy. Moreover, RNP pretreatment noticeably increases the apoptosis/necrosis ratio of radiation-induced cell death, a highly desirable property to reduce the chronic side effects of ionizing irradiation.

Variable Compensation and Salesperson Health

Positive effects of incentives on salespeople’s motivation, effort, and performance are well-established in literature. This article takes a novel look at their influence on salespeople’s health. The results of four empirical studies, including more than 1,400 salespeople, suggest that an increasing variable compensation share (i.e., greater pay-for-performance component in salespeople’s compensation plans) increases salespeople’s stress, resulting in emotional exhaustion and more sick days. These outcomes are more likely for salespeople with lower personal ability and fewer social resources. The harmful effects of the variable compensation share on salespeople’s health reduce the positive effects of this incentive on sales performance. To practice better marketing for a better world, if variable compensation is used, the authors recommend that managers screen new hires for job-related resources and help their existing staff build such resources. In addition, companies may personalize incentive schemes and sensitize managers to the stress-inducing effects of variable compensation shares.

Single cell spectroscopy of red blood cells in intravenous crystalloid fluids

Crystalloid fluids, a subset of intravenous (IV) fluid solutions are commonly used in clinical settings. The influence of these fluids on the functions of blood components are least explored. Raman spectroscopy combined with optical trapping has been widely used to evaluate the impact of external stress agents on red blood cells. The present study investigates the impact of commonly used crystalloid fluids on red blood cells in comparison with that of blood plasma using Raman Tweezers spectroscopy. The red blood cells suspended in crystalloid fluids undergo deoxygenation readily than that in blood plasma. In addition, cells in blood plasma were able to withstand laser induced deoxygenation comparatively better than that in crystalloid fluids at higher laser powers. Principle component analysis of the Raman spectral data has clearly demonstrated the discrimination of cells in plasma with that of crystalloid fluids demonstrating the effect of external induced stress on RBCs.

Stress-derived reactive oxygen species enable hemocytes to release activator of growth blocking peptide (GBP) processing enzyme

Insect cytokine growth blocking peptide (GBP) is synthesized as an inactive precursor, termed proGBP, that is normally present in a significant concentration in the hemolymph of non-stressed animals (Hayakawa, 1990, 1991). Under stress conditions, proGBP is instantly processed to active GBP by a serine protease and this is thought to be an important initial step for insects to cope with stress-induced adverse effects via GBP-induced physiological changes. However, the detailed mechanism underlying proteolytic processing of hemolymph proGBP in insects under stress conditions remains unknown. Here we demonstrated that proGBP processing requires ROS-induced release of a proteinaceous factor from hemocytes that activates the inactive proGBP processing enzyme. The release of the activator protein from hemocytes is initiated by an elevation of the cytoplasmic Ca2+ concentration induced by ROS. Therefore, we concluded that stress-induced activation of proGBP requires ROS-dependent stimulation of an intracellular calcium signaling pathway in hemocytes, followed by release of the hemocyte proteinaceous factor that specifically activates the proGBP processing enzyme.

Overexpression of SmZIP plays important roles in Cd accumulation and translocation, subcellular distribution, and chemical forms in transgenic tobacco under Cd stress

Plant ZIP genes represent an important transporter family and may be involved in cadmium (Cd) accumulation and Cd resistance. In order to explore the function of SmZIP isolated from Salix matsudana, the roles of SmZIP in Cd tolerance, uptake, translocation, and distribution were determined in the present investigation. The transgenic SmZIP tobacco was found to respond to external Cd stress differently from WT tobacco by exhibiting a higher growth rate and more vigorous phenotype. The overexpression of SmZIP in tobacco resulted in the reduction of Cd stress-induced phytotoxic effects. Compared to WT tobacco, the Cd content of the root, stem, and leaf in the transgenic tobacco increased, and the zinc, iron, copper, and manganese contents also increased. The assimilation factor, translocation factor and bioconcentration factor of Cd were improved. The scanning electron microscopy and energy dispersive X-ray analysis results of the root maturation zone exposed to Cd for 24 h showed that Cd was transferred through the root epidermis, cortex, and vascular cylinder and migrated to the aboveground parts via the vascular cylinder, resulting in the transgenic tobacco accumulating more Cd than the WT plants. Based on the transverse section of the leaf main vein and leaf blade, Cd was transported through the vascular tissues to the leaves and accumulated more greatly in the leaf epidermis, but less in the leaf mesophyll cells, following the overexpression of SmZIP to reduce the photosynthetic toxicity. The overexpression of SmZIP resulted in the redistribution of Cd at the subcellular level, a decrease in the percentage of Cd in the cell wall, and an increase of the Cd in the soluble fraction in both the roots and leaves. It also changed the percentage composition of different Cd chemical forms by elevating the proportion of Cd extracted using 2% HAc and 0.6 mol/L HCl, but lowering that of the Cd extracted using 1 mol/L NaCl in both the leaves and roots under 10 and 100 μmol/L Cd stress for 28 d. The results implied that SmZIP played important roles in advancing Cd uptake, accumulation, and translocation, as well as in enhancing Cd resistance by altering the Cd subcellular distribution and chemical forms in the transgenic tobacco. The study will be useful for future phytoremediation applications to clean up Cd-contaminated soil.

The effect of hydrogen sulfide on growth, yield and biochemical responses of strawberry (Fragaria × ananassa cv. Paros) leaves under alkalinity stress

Plant stress caused by alkalinity in irrigation water can significantly limit the growth and development of plants. Emerging evidence suggests that hydrogen sulfide (H2S), as a versatile signal molecule, can ameliorate stress-induced adverse effects. The objective of this study was to determine the effects of sodium hydrosulfide (NaHS) application on growth, fruit yield and biochemical responses of strawberry plants exposed to alkalinity stress under greenhouse conditions. Strawberry plants were grown hydroponically under three levels (0, 15 and 30 mM) of alkalinity stress (induced using sodium bicarbonate and sodium carbonate) along with three levels of foliar application (0, 0.2 and 0.5 mM) of the H2S donor, NaHS. The results showed that compared to the control conditions, alkalinity stress reduced plant biomass, fruit yield, maximum quantum efficiency of photosystem II (Fv/Fm) and chlorophyll SPAD value. Oxidative stress was induced, which was measured, as accumulation of reactive oxygen species (ROS). On the other hand, when alkalinity stress was mitigated with the application of NaHS, the recovery of photosynthetic activity, a decrease in ROS and an improvement in antioxidative defense system were observed. Overall, NaHS treatments had the best results on lower level (15 mM) of alkalinity stress compared to the 30 mM alkalinity stress. These findings indicate possible role for H2S for improving strawberry plant growth and yield under non-stress conditions and moderate alkalinity stress.

Revealing Subtle Changes in Cardiac Function using Transthoracic Dobutamine Stress Echocardiography in Mice.

Left ventricular (LV) dysfunction paves the final pathway for a multitude of cardiac disorders. With the non-invasive high-frequency transthoracic dobutamine stress echocardiography in humans, a reductionist investigation approach to unmask subtle changes in cardiac function has become possible. Here, we provide a protocol for using this technique in mice to facilitate expanded analysis of LV architecture and function in physiology and pathology enabling the observation of alterations in models of cardiac disease hidden in unstressed hearts. This investigation can be performed in one and the same animal and allows both, basal and pharmacologically stress-induced measurements. We outline detailed criteria for appropriate anesthesia, imaging-based LV analysis, consideration of intra- and interobserver variability, and obtaining positive inotrope response that can be attained in mice after intraperitoneal injection of dobutamine under near physiological conditions. To recapitulate the characteristics of human physiology and disease in small animal models, we highlight critical pitfalls in evaluation, e.g., a pronounced Bowditch effect in mice. To further meet translational objectives, we compare stress-induced effects in humans and mice. When used in translational studies, attention must be paid to physiological differences between mice and human. Experimental rigor dictates that some parameters assessed in patients can only be used with caution due to restrictions in spatial and temporal resolution in mouse models.

Alteration of lipid metabolism, autophagy, apoptosis and immune response in the liver of common carp (Cyprinus carpio) after long-term exposure to bisphenol A

Bisphenol A (BPA), as a phenolic compound, is harmful to human health, and its residue in the aquatic environment also threatens the health of aquatic animals. In this research, the toxicity effects of BPA on liver tissues were evaluated in common carp (Cyprinus carpio) after long-term exposure. Fish were exposed to five concentrations of BPA (0, 0.01, 0.1, 0.5 and 2 mg/L) for 30 days. The blood and liver tissues were gathered to analyze biochemical indices and genes transcription levels. The data related to lipid metabolism showed that BPA exposure increased serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) levels, upregulated the expressions of fatp1, pparγ, fas, atgl, hsl, pparα, cpt1b, acox-1, and downregulated the expression of dgat1 in liver. Antioxidative parameters displayed a reduced antioxidant ability and increased lipid peroxidation after BPA exposure. Meanwhile, the upregulations of nrf2, ho-1, cyp1a and cyp1b genes revealed an adaptive response mechanism against oxidative stress-induced adverse effects. After 30 days of exposure, BPA induced apoptosis and endoplasmic reticulum stress (ERS) via upregulating the expression levels of apoptosis and ERS-related genes and increasing Ca2+ concentration in liver. Moreover, the downregulation of mtor and the upregulation of atg3, atg7, tfeb, uvrag and mcoln1 indicated that BPA could influence the normal process of autophagy. Furthermore, BPA exposure activated toll like receptors (TLRs) pathway to mediate the inflammatory response. Our results demonstrated that BPA exposure disturbed lipid metabolism, and induced oxidative stress, ERS, apoptosis, autophagy and inflammatory response in the liver of common carp. These findings contributed to the understanding of hepatotoxicity mechanism induced by BPA in fish.

Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis

Alcohol use disorders are associated with altered stress responses, but the impact of stress or stress hormones on alcohol-associated tissue injury remain unknown. We evaluated the effects of chronic restraint stress on alcohol-induced gut barrier dysfunction and liver damage in mice. To determine whether corticosterone is the stress hormone associated with the stress-induced effects, we evaluated the effect of chronic corticosterone treatment on alcoholic tissue injury at the Gut-Liver-Brain (GLB) axis. Chronic restraint stress synergized alcohol-induced epithelial tight junction disruption and mucosal barrier dysfunction in the mouse intestine. These effects of stress on the gut were reproduced by corticosterone treatment. Corticosterone synergized alcohol-induced expression of inflammatory cytokines and chemokines in the colonic mucosa, and it potentiated the alcohol-induced endotoxemia and systemic inflammation. Corticosterone also potentiated alcohol-induced liver damage and neuroinflammation. Metagenomic analyses of 16S RNA from fecal samples indicated that corticosterone modulates alcohol-induced changes in the diversity and abundance of gut microbiota. In Caco-2 cell monolayers, corticosterone dose-dependently potentiated ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. These data indicate that chronic stress and corticosterone exacerbate alcohol-induced mucosal barrier dysfunction, endotoxemia, and systemic alcohol responses. Corticosterone-mediated promotion of alcohol-induced intestinal epithelial barrier dysfunction and modulation of gut microbiota may play a crucial role in the mechanism of stress-induced promotion of alcohol-associated tissue injury at the GLB axis.

Hydrogen sulfide priming can enhance the tolerance of artichoke seedlings to individual and combined saline-alkaline and aniline stresses

Regulatory roles of hydrogen sulfide (H2S) under saline-alkaline and/or aniline stress have not been studied yet. In this study, we investigated the insights into saline-alkaline and/or aniline stresses-induced toxicity in artichoke plants and its alleviation by H2S priming. Individual saline-alkaline or aniline stress and their combination reduced plant growth and photosynthetic pigments. Principal component analysis (PCA) revealed that these detrimental impacts were caused by the higher oxidative damage and disruption of osmolyte homeostasis. Interestingly, only aniline stress (25 mg L−1) caused neither oxidative nor osmotic stress thus almost slight growth retarding effects had ensued. On the other hand, the presence of aniline in saline-alkaline conditions exacerbated stress-induced deleterious effects on plants, as evidenced by PCA and heatmap. However, H2S priming markedly eased the stress-induced deleteriousness as evident by enhanced chlorophyll, soluble proteins, soluble carbohydrates and up-regulated water relation in H2S-primmed plants compared with only stressed plants resulting in improved plant phenotypic features. Furthermore, H2S priming enhanced endogenous H2S content, phenylalanine ammonia-lyase, non-enzymatic antioxidants (ascorbic acid, flavonoids, glutathione, α-tocopherol, and anthocyanins) and enzymatic antioxidants (superoxide dismutase, catalase, and ascorbate peroxidase), whereas reduced oxidative stress markers (superoxide, hydrogen peroxide, hydroxyl radical, malondialdehyde, and methylglyoxal) compared with only stressed plants, indicating a protective function of H2S against oxidative damage. The PCA also clarified that H2S-mediated saline-alkaline and/or aniline stress tolerance strongly connected with the improved antioxidant system. Overall, our finding proposed that H2S priming could be an effective technique to mitigate saline-alkaline and/or aniline stress in artichoke, and perhaps in other crop plants.

Impact of bifrontal transcranial Direct Current Stimulation on decision-making and stress reactivity. A pilot study

Stress is an adaptive response with repercussions on the human health. The dorsolateral prefrontal cortex (DLPFC) is thought to be involved in stress regulation by contributing to limit its biological and behavioral pejorative consequences. Here, to investigate the contribution of the DLPFC in stress response, we applied transcranial Direct Current Stimulation (tDCS) over the DLPFC during acute stress exposure in healthy participants. We hypothesized that active tDCS compared to sham would impact top-down control of the DLPFC on goal-directed behavior and hypothalamo–pituitary–adrenal (HPA) axis activity.In a double-blind sham-controlled study, 30 healthy subjects were randomly allocated to receive either active (2 mA, n = 15) or sham tDCS (n = 15) with the anode over the left DLPFC and the cathode over the right DLFPC. During the 30-min stimulation period, participants faced an experimental acute stress paradigm. Changes in goal-directed behavior were measured with a decision-making task. HPA axis reactivity was assessed by repeated measures of salivary cortisol.Acute stress decreased appetite for immediate reward in the sham group (mean - 4.40%; p = 0.017) whereas no significant effect of stress was observed in the active group. During stress exposure, we observed a significant larger elevation of salivary cortisol (p = 0.045; Cohen's d = 0.431) in the sham tDCS group (+179.8%; Standard error of the mean (SEM) = 20.6) than in the active group (+138.5%; SEM = 14.2).Stimulating the DLPFC using bifrontal tDCS may prevent stress-induced acute effects on both biological and behavioral outcomes.