Stress-related Processes Research Articles

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress.

Apelin is an endogenous ligand for the G protein-coupled receptor APJ and has multiple biological activities in human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. This article reviews the crucial role of apelin in regulating oxidative stress-related processes by promoting prooxidant or antioxidant mechanisms. Following the binding of APJ to different active apelin isoforms and the interaction with several G proteins according to cell types, the apelin/APJ system is able to modulate different intracellular signaling pathways and biological functions, such as vascular tone, platelet aggregation and leukocytes adhesion, myocardial activity, ischemia/reperfusion injury, insulin resistance, inflammation, and cell proliferation and invasion. As a consequence of these multifaceted properties, the role of the apelinergic axis in the pathogenesis of degenerative and proliferative conditions (e.g., Alzheimer's and Parkinson's diseases, osteoporosis, and cancer) is currently investigated. In this view, the dual effect of the apelin/APJ system in the regulation of oxidative stress needs to be more extensively clarified, in order to identify new potential strategies and tools able to selectively modulate this axis according to the tissue-specific profile.

Redox-Reversible Near-Infrared Fluorescent Probe for Imaging of Acute Kidney Oxidative Injury and Remedy.

Drug-induced acute kidney injury (DIAKI) is associated with high morbidity and mortality. It remains a diagnostic and therapeutic dilemma due to failure of providing unambiguous real-time feedback on nephrotoxicity, which is regarded as a serious problem in clinics. Herein, we report a reversible fluorescence probe, NRN, to monitor the ONOO-/GSH in an acute kidney injury model. The NRN near-infrared fluorescent probe features a big Stokes shift (83 nm), which was oxidized by ONOO- and reduced by succussive glutathione (GSH) with excellent selectivity and good sensitivity (detection limit: 418 nM and 0.28 mM, respectively). Taking the reversibility of NRN toward ONOO- and GSH, real-time evaluations in vivo with cisplatin (CP) alone and CP combined with acetaminophen-stimulated acute kidney injury and the following remedy process with l-carnitine were realized for the first time. The experiments revealed that acute kidney injury caused by combined drugs might be more serious and irreversible under certain conditions. Therefore, NRN could act as a potential tool for understanding oxidative stress-related DIAKI disease processes.

Genome-Wide Identification Analysis of the R2R3-MYB Transcription Factor Family in Cymbidium sinense for Insights into Drought Stress Responses

Cymbidium sinense represents a distinctive Orchidaceae plant that is more tolerant than other terrestrial orchids. Studies have shown that many members of the MYB transcription factor (TF) family, especially the R2R3-MYB subfamily, are responsive to drought stress. This study identified 103 CsMYBs; phylogenetic analysis classified these genes into 22 subgroups with Arabidopsis thaliana. Structural analysis showed that most CsMYB genes contained the same motifs, three exons and two introns, and showed a helix-turn-helix 3D structure in each R repeat. However, the members of subgroup 22 contained only one exon and no intron. Collinear analysis revealed that C. sinense had more orthologous R2R3-MYB genes with wheat than A. thaliana and rice. Ka/Ks ratios indicated that most CsMYB genes were under purifying negative selection pressure. Cis-acting elements analysis revealed that drought-related elements were mainly focused on subgroups 4, 8, 18, 20, 21, and 22, and Mol015419 (S20) contained the most. The transcriptome analysis results showed that expression patterns of most CsMYB genes were upregulated in leaves in response to slight drought stress and downregulated in roots. Among them, members in S8 and S20 significantly responded to drought stress in C. sinense. In addition, S14 and S17 also participated in these responses, and nine genes were selected for the real-time reverse transcription quantitative PCR (RT-qPCR) experiment. The results were roughly consistent with the transcriptome. Our results, thus, provide an important contribution to understanding the role of CsMYBs in stress-related metabolic processes.

Effects of non-invasive vagus nerve stimulation on cognitive and autonomic correlates of perseverative cognition.

Perseverative cognitions can provoke psychophysiological stress in the absence of an actual stressor and are considered important transdiagnostic vulnerability factors for several (mental) health issues. These stress-related cognitive processes are reflected by both cognitive (assessed by self-reports) and autonomic inflexibility (assessed by heart rate variability; HRV), with a key role attributed to the vagus nerve. Interestingly, modulation of the afferent branches of the vagus can be achieved with transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive technique that employs a low-intensity electrical current applied to the ear. In a sample of healthy individuals, we investigated the effects of taVNS of the left concha, compared to sham (earlobe) stimulation, on the cognitive and autonomic correlates of perseverative cognition following a psychosocial stress task. Interestingly, taVNS significantly reduced cognitive rigidity, reflected by reduced subjective perseverative thinking after psychosocial stress. Although there were no direct effects on autonomic correlates of perseverative cognition, individual differences in perseverative thinking after the stressor significantly affected the effects of taVNS on HRV. Specifically, more autonomic inflexibility during the stress task (i.e., reduced HRV) was associated with increases in perseverative thinking afterward for the sham condition, but not the active taVNS condition. Additional exploratory analyses revealed no significant moderation of stimulation intensity. Overall, the study findings endorse the association between perseverative cognitions and vagus nerve functioning.

Free Radicals Mediated Redox Signaling in Plant Stress Tolerance.

Abiotic and biotic stresses negatively affect plant cellular and biological processes, limiting their growth and productivity. Plants respond to these environmental cues and biotrophic attackers by activating intricate metabolic-molecular signaling networks precisely and coordinately. One of the initial signaling networks activated is involved in the generation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS). Recent research has exemplified that ROS below the threshold level can stimulate plant survival by modulating redox homeostasis and regulating various genes of the stress defense pathway. In contrast, RNS regulates the stress tolerance potential of crop plants by modulating post-translation modification processes, such as S-nitrosation and tyrosine nitration, improving the stability of protein and DNA and activating the expression of downstream stress-responsive genes. RSS has recently emerged as a new warrior in combating plant stress-induced oxidative damage by modulating various physiological and stress-related processes. Several recent findings have corroborated the existence of intertwined signaling of ROS/RNS/RSS, playing a substantial role in crop stress management. However, the molecular mechanisms underlying their remarkable effect are still unknown. This review comprehensively describes recent ROS/RNS/RSS biology advancements and how they can modulate cell signaling and gene regulation for abiotic stress management in crop plants. Further, the review summarizes the latest information on how these ROS/RNS/RSS signaling interacts with other plant growth regulators and modulates essential plant functions, particularly photosynthesis, cell growth, and apoptosis.

Co-Expression of ZmVPP1 with ZmNAC111 Confers Robust Drought Resistance in Maize.

Drought is a primary environmental factor limiting maize production globally. Although transferring a single gene to maize can enhance drought resistance, maize response to water deficit requires further improvement to accommodate the steadily intensifying drought events worldwide. Here, we generated dual transgene lines simultaneously overexpressing two drought-resistant genes, ZmVPP1 (encoding a vacuolar-type H+ pyrophosphatase) and ZmNAC111 (encoding a NAM, ATAF, and CUC (NAC)-type transcription factor). Following drought stress, survival rates of the pyramided transgenic seedlings reached 62-66%, while wild-type and single transgene seedling survival rates were 23% and 37-42%, respectively. Maize seedlings co-expressing ZmVPP1 and ZmNAC111 exhibited higher photosynthesis rates, antioxidant enzyme activities, and root-shoot ratios than the wild type, and anthesis-silking intervals were shorter while grain yields were higher under water deficit conditions in field trials. Additionally, RNA-sequencing analysis confirmed that photosynthesis and stress-related metabolic processes were stimulated in the dual transgene plants under drought conditions. The findings in this work illustrate how high co-expression of different drought-related genes can reinforce drought resistance over that of individual transgene lines, providing a path for developing arid climate-adapted elite maize varieties.

Corticotropin-Releasing Hormone: Biology and Therapeutic Opportunities.

In 1981, Wylie Vale, Joachim Spiess, Catherine Rivier, and Jean Rivier reported on the characterization of a 41-amino-acid peptide from ovine hypothalamic extracts with high potency and intrinsic activity stimulating the secretion of adrenocorticotropic hormone and β-endorphin by cultured anterior pituitary cells. With its sequence known, this neuropeptide was determined to be a hormone and consequently named corticotropin-releasing hormone (CRH), although the term corticotropin-releasing factor (CRF) is still used and preferred in some circumstances. Several decades have passed since this seminal contribution that opened a new research era, expanding the understanding of the coding of stress-related processes. The characterization of CRH receptors, the availability of CRH agonists and antagonists, and advanced immunocytochemical staining techniques have provided evidence that CRH plays a role in the regulation of several biological systems. The purpose of this review is to summarize the present knowledge of this 41-amino-acid peptide.

New insights into extracellular and intracellular redox status in COVID-19 patients

BackgroundThe imbalance of redox homeostasis induces hyper-inflammation in viral infections. In this study, we explored the redox system signature in response to SARS-COV-2 infection and examined the status of these extracellular and intracellular signatures in COVID-19 patients. MethodThe multi-level network was constructed using multi-level data of oxidative stress-related biological processes, protein-protein interactions, transcription factors, and co-expression coefficients obtained from GSE164805, which included gene expression profiles of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and healthy controls. Top genes were designated based on the degree and closeness centralities. The expression of high-ranked genes was evaluated in PBMCs and nasopharyngeal (NP) samples of 30 COVID-19 patients and 30 healthy controls. The intracellular levels of GSH and ROS/O2• − and extracellular oxidative stress markers were assayed in PBMCs and plasma samples by flow cytometry and ELISA. ELISA results were applied to construct a classification model using logistic regression to differentiate COVID-19 patients from healthy controls. ResultsCAT, NFE2L2, SOD1, SOD2 and CYBB were 5 top genes in the network analysis. The expression of these genes and intracellular levels of ROS/O2• − were increased in PBMCs of COVID-19 patients while the GSH level decreased. The expression of high-ranked genes was lower in NP samples of COVID-19 patients compared to control group. The activity of extracellular enzymes CAT and SOD, and the total oxidant status (TOS) level were increased in plasma samples of COVID-19 patients. Also, the 2-marker panel of CAT and TOS and 3-marker panel showed the best performance. ConclusionSARS-COV-2 disrupts the redox equilibrium in immune cells and the upper respiratory tract, leading to exacerbated inflammation and increased replication and entrance of SARS-COV-2 into host cells. Furthermore, utilizing markers of oxidative stress as a complementary validation to discriminate COVID-19 from healthy controls, seems promising.

Impact of acute stress on neural indices of positive and negative reinforcement processing in cannabis users.

Chronic cannabis use is maintained in part through dysregulated stress and reward response systems. Specifically, stress-related negative affect is thought to act as a salient motivator for chronic substance use. Models of addiction posit that the transition from positive to negative reinforcement motives for substance use is a key mechanism of disordered use. However, research in substance-using samples has not assessed stress-related neural processing of both positive and negative reinforcement. Therefore, the present study utilized laboratory stress induction to examine how stress affects the reward positivity, an event-related potential sensitive to both positive (RewP) and negative (relief-RewP) reinforcement, in 87 cannabis users (58.10% female, Mage = 19.40) varying in cannabis use disorder (CUD) severity and, as part of larger study aims, history of traumatic brain injury (TBI). We predicted greater CUD severity would be associated with a blunted RewP and enhanced relief-RewP, particularly after stress induction, independent of TBI status. Findings indicated that CUD severity was not associated with RewP/relief-RewP amplitude regardless of acute stress. Exploratory analyses revealed, however, that among those with history of TBI +, CUD severity was associated with greater stress-elicited blunting of the RewP and enhancement of the relief-RewP. Although initial findings contradict current allostatic models of addiction, exploratory findings suggest that history of TBI, and potentially other confounding variables related to increased risk of TBI experience, may influence the extent to which stressful experiences modulate the neurophysiology of both positive and negative reinforcement reward processing in CUD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Binding of the transcription factor MYC2-like to the ABRE of the OsCYP2 promoter enhances salt tolerance in Oryza sativa.

Cyclophilins, a type of peptidyl-prolyl cis-trans isomerase, function as important molecular chaperones in a series of biological processes. However, the expression pattern and signal transduction pathway of cyclophilins are still unclear. Here, we showed that the promoter of OsCYP2 could function as a tissue-specific promoter by GUS staining. Moreover, we found that the promoter sequence contained not only core elements but also inducible elements. Then, the ABA-responsive element was used for cDNA library screening, and the transcription factor MYC2-like was identified by a yeast one-hybrid assay and confirmed through an electrophoretic mobility shift assay. Furthermore, the relative expression showed that MYC2-like was induced by abscisic acid. In addition, MYC2-like overexpression enhanced salt tolerance in transformants and partially restored the cyp2-RNAi line. In summary, we explored a novel transcriptional signal mediated by MYC2-like, a potential regulator of salt stress-related physiological processes in rice.

Regulatory Role of PFC Corticotropin-Releasing Factor System in Stress-Associated Depression Disorders: A Systematic Review.

Stress has a substantial role in formation of psychiatric disorders especially depression. Meanwhile, impairment of the prefrontal cortex (PFC) is connected to the executive and cognitive deficits induced by the stress. Given the involvement of the corticotropin-releasing factor (CRF) in stress-related processes and knowing the fact that PFC hosts a lot of CRF receptors and CRF neurotransmissions, it can worth to look at the CRF as a potential treatment for the regulation of depression disorders induced by stress within PFC region. Here, for the first time we aimed to systematically review the effectiveness of intra-PFC CRF system in the modulation of depression dysfunction caused by the stress in clinical and preclinical models/studies. Qualified researches were combined utilizing a comprehensive search of six databases including Scopus, Pubmed, Web of Science, Sciencedirect, APA PsycNet, and Embase in April 2021 and were evaluated through proper methodological quality assessment tools. Results indicate that PFC has a remarkable role in the modulation for stress-induced depression and intra-PFC CRF receptors agonist and antagonist are very considerable for regulating these types of impairments. Specifically, elevation of both CRF immunoreactivity and gene expression were observed in human studies. In the animal studies, mostly immunoreactivity or excitatory/inhibitory currents of CRF within the PFC regulated depression dysfunction. In conclusion, reviewed studies show a positive attitude toward the CRF system in regulation of the stress-induced depression; however, obviously further investigations are required to get closer to the best treatment. Prefrontal cortex corticotropin-releasing factor system regulates stress-induced depression. CRFR1, Corticotropin-releasing factor receptor of type1; PFC, Prefrontal cortex; Minus (-) and Plus (+) signs, dysregulation and upregulation, respectively.

The Relationship Between Negative Affect, State Mindfulness, and the Role of Personality.

ObjectivesAre affective states influencing state mindfulness and can this explain the link between personality and mindfulness? Mindfulness is commonly thought to decrease negative affect, but a number of studies have reported reductions in mindfulness in negative affect situations. This highlights a potential mechanism explaining previously observed negative relationships between individual differences such as Neuroticism and mindfulness, via their shared relationship with negative affect.MethodsIn an experiment, 331 participants were exposed to a negative affect stimulus to investigate whether previously established relationships between Neuroticism, Behavioral Inhibition, and Mindfulness are due to differences in negative affect reactivity. It was expected that participants high on Neuroticism and Behavioral Inhibition to show greater negative affect reactivity which in turn would reduce their state Non-Judgmental Acceptance and Acting with Awareness.ResultsWhile change in negative affect was related to lower Non-Judgmental Acceptance and Acting with Awareness, negative affect reactivity did not mediate the relationship between Neuroticism/BIS and these state mindfulness facets. Importantly, only Non-Judgmental Acceptance and Acting with Awareness facets of mindfulness were affected by negative affect change, but not Attention. This indicates that greater negative affect might require allocation of cognitive resources to stress-related processes such as threat monitoring, reducing mindful emotion processing but not attention.ConclusionsThe current study found that situational mindfulness might be influenced by state affect highlighting the need to more strongly consider the environmental factors which can shape affect in mindfulness interventions.Trial RegistrationOpen Science Framework (https://osf.io/kmyh2).

The Response of the Human Umbilical Vein Endothelial Cell Transcriptome to Variation in Magnesium Concentration.

Vascular endothelial cells have a critical role in the maintenance of cardiovascular function. Evidence suggests that endothelial function may be compromised under conditions of magnesium deficiency, which increases vulnerability to inflammation. Whole genome transcription analysis was used to explore the acute (24 h) effects of magnesium on human umbilical vascular endothelial cells (HUVEC) cultured in low (0.1 mM) or high (5 mM) concentrations. With low magnesium 2728 transcripts were differentially expressed compared to the 1 mM control cultures and 3030 were differentially expressed with high magnesium. 615 transcripts were differentially expressed under both conditions, of which only 34 showed a concentration-dependent response. Analysis indicated that cellular organisation and biogenesis and key cellular processes such as apoptosis were impacted by both low and high conditions. High magnesium also influenced protein binding functions, intracellular signal transduction, metabolic and catalytic processes. Both conditions impacted on stress-related processes, in particular the inflammatory response. Key mediators of calcium-dependent regulation of gene expression were responsive to both high and low magnesium conditions. The HUVEC transcriptome is highly sensitive to acute changes in the concentration of magnesium in culture medium. The findings of this study support the view that whilst inflammation is an important process that is responsive to magnesium, the function of the endothelium may be impacted by other magnesium-induced changes including maintenance of cellular integrity, receptor expression and metabolic functions. The high proportion of transcripts that did not show a concentration-dependent response suggests variation in magnesium may elicit indirect changes, possibly mediated by other ions.

Analysis of ceRNA networks during mechanical tension-induced osteogenic differentiation of periodontal ligament stem cells.

The molecular mechanisms underlying osteogenic differentiation of periodontal ligament stem cells (PDLSCs) under mechanical tension remain unclear. This study aimed to identify a potential long non-coding ribonucleic acids (lncRNAs)/circular RNAs (circRNAs)-microRNAs (miRNAs)-messenger RNAs (mRNAs) network in mechanical tension-induced osteogenic differentiation of PDLSCs. PDLSCs were isolated from the healthy human periodontal ligament, identified, cultured, and exposed to tensile force. The expression of osteogenic markers was examined, and whole transcriptome sequencing was performed to identify the expression patterns of lncRNA, circRNA, miRNAs, and mRNAs. Enrichment analyses were also performed. Candidate targets of differentially expressed non-coding RNAs (ncRNAs) were predicted, and potential competitive endogenous RNA (ceRNA) networks were constructed by Cytoscape. We found that the osteogenic differentiation of PDLSCs was significantly enhanced under dynamic tension (magnitude: 12%, frequency: 0.7Hz). Overall, 344 lncRNAs, 57 miRNAs, 41 circRNAs, and 70mRNAs were differentially expressed in the tension group and the control group. Functional enrichment analysis showed that differentially expressed mRNAs were mainly enriched in osteogenesis-related and mechanical stress-related biological processes and signal transduction pathways (e.g., tumor necrosis factor [TNF] and Hippo signaling pathways). The lncRNA/circRNA-miRNA-mRNA networks were depicted, and potential key ceRNA networks were identified. Our findings may help to further explore the underlying regulatory mechanism of osteogenic differentiation of PDLSCs under mechanical tensile stress.

The Role of Boundary in Deterring Burnout Among Perfectionists in the Work–Family Interface

The purpose of this study is to investigate the role of the boundary and its effects on the perfectionism–burnout relationship in the work–family interface. Previous studies on perfectionism have mostly focused on a single domain, and little research has tapped into work–family interactions. Additionally, in regard to perfectionism–burnout research, much attention has been placed on the resources consumed to burn out (e.g., motivation and perceived stress). However, we seek to study the situational component for activating the stress-related process. That is, we adopt boundary characteristics—forming distance between roles—to secure personal well-being from going through stress patterns. Drawing on conservation of resources and boundary theory, we argue that perfectionists with weaker boundaries have a higher risk of burnout than employees with stronger boundaries because they have difficulty maintaining their focus on a single domain. Further, we attempt to unveil the mechanism between perfectionism and burnout by the serial mediators (i.e., work telepressure and work–family conflict). We propose in particular a mediated moderation model, hypothesizing that perfectionism with a weaker boundary can be a predictor for work telepressure, work–family conflict, and burnout, serially. Our findings suggest that the hypotheses are all supported. The present study verifies that the role of a boundary as a protector can substantially secure the well-being of employees.

Potential Utility of Natural Products against Oxidative Stress in Animal Models of Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune-mediated degenerative disease of the central nervous system (CNS) characterized by immune cell infiltration, demyelination and axonal injury. Oxidative stress-induced inflammatory response, especially the destructive effect of immune cell-derived free radicals on neurons and oligodendrocytes, is crucial in the onset and progression of MS. Therefore, targeting oxidative stress-related processes may be a promising preventive and therapeutic strategy for MS. Animal models, especially rodent models, can be used to explore the in vivo molecular mechanisms of MS considering their similarity to the pathological processes and clinical signs of MS in humans and the significant oxidative damage observed within their CNS. Consequently, these models have been used widely in pre-clinical studies of oxidative stress in MS. To date, many natural products have been shown to exert antioxidant effects to attenuate the CNS damage in animal models of MS. This review summarized several common rodent models of MS and their association with oxidative stress. In addition, this review provides a comprehensive and concise overview of previously reported natural antioxidant products in inhibiting the progression of MS.

Identification of Microproteins in Saccharomyces cerevisiae under Different Stress Conditions.

Small open reading frame-encoded peptides (SEPs) are microproteins with a length of 100 amino acids or less, which may play a critical role in maintaining cell homeostasis under stress. Therefore, we used mass spectrometry-based proteomics to explore microproteins potentially involved in cellular stress responses in Saccharomyces cerevisiae. A total of 225 microproteins with 1920 unique peptides were identified under six culture conditions: normal, oxidation, starvation, ultraviolet radiation, heat shock, and heat shock with starvation. Among these microproteins, we found 70 SEPs with 75 unique peptides. The annotated microproteins are involved in stress-related processes, such as cell redox reactions, cell wall modification, protein folding and degradation, and DNA damage repair. It suggests that SEPs may also play similar functions under stress conditions. For example, SEP IP_008057, translated from a short coding sequence of YJL159W, may play a role in heat shock. This study identified stress-responsive SEPs in S. cerevisiae and provided valuable information to determine the functions of these proteins, which enrich the genome and proteome of S. cerevisiae and show clues to improving the stress tolerance of S. cerevisiae.

Molecular Cloning, Characterization, and Expression Analysis of SIMILAR TO RCD-ONE (SRO) Family Genes Responding to Abiotic and Biotic Stress in Cucumber

SIMILAR TO RCD-ONE (SRO) is a plant-specific small protein family that controls many biological processes including physiological development and stress responses. The SRO gene family has been studied in several plant species, but no detailed characterization and expression profiles of this important gene family were performed in cucumber. In this study, we characterize the SRO genes in cucumber, and determined their transcript levels in various tissues and under exposure to diverse biotic and abiotic stressors. Four SRO genes (named as CsSRO1–CsSRO4) were identified and isolated, which were distributed on three different chromosomes. Gene duplication analysis showed that only one pair of segmental duplication event was identified, but no tandem duplication events were detected. All CsSROs consist of the PARP domain and a C-terminal RST domain, while the N-terminal WWE domain was only present in CsSRO2 and CsSRO4. SROs from 15 plant species are divided into two groups (I and II), and group I can be further divided into four subgroups (Ia to Id) according to the phylogenetic tree. The conserved motif and gene structure analyses showed that SROs within the same branch of the phylogenetic tree have analogous conserved motifs configuration and gene structures. However, SRO genes possessed variable numbers of introns in different subgroups, which may affect the evolution of new family members. RNA-Seq data and qRT-PCR results showed that the four CsSRO genes have distinct expression pattern in various tissues and under diverse stresses, suggesting their multiple functions in plant growth and stress responses. The findings provide a basis for further research aiming at functional characterization of the regulatory mechanism to reveal the roles of CsSRO genes in developmental and stress-related processes of cucumber.

Ablation of Carotenoid Cleavage Enzymes BCO1 & BCO2 Alters Gut Microbial and Plasma Metabolomic Profiles in High Refined Carbohydrate Diet-Fed Mice

Objectivesβ-Carotene-15,15′-oxygenase (BCO1) and β-carotene-9′,10′-oxygenase (BCO2) cleave carotenoids to form vitamin A or apo-carotenoid species. Beyond these roles, BCO1 and BCO2 have been implicated in modulating lipid, cholesterol, and oxidative stress-related processes, yet less is known about their combined influence on shaping gut microbial and plasma metabolic profiles. Current intake of refined carbohydrates and added sugars exceeds the recommendations within the Dietary Guidelines for Americans, which may contribute to the development of nonalcoholic fatty liver disease (NAFLD). In the present study, we aimed to uncover whether mice with systemic ablation of BCO1-/-/BCO2-/- (DKO) display distinctive phenotypes in response to a high refined carbohydrate diet (HRCD) model of NAFLD. MethodsMale, six-week-old C57BL/6J wild type mice (WT) and DKO mice were fed a chow diet or a HRCD (66.5% carbs including sucrose) for 24 weeks. We used fecal and plasma samples to respectively perform 16S rDNA sequencing, and both targeted and untargeted metabolomics using our UHPLC-QTOF-MS platform, a targeted Biocrates MxP Quant 500 kit, and a complimentary untargeted analysis of phospholipids from the METLIN database. Data were analyzed using QIIME2-DEseq2, MetaboAnalyst 5.0, MassHunter Qualitative Analysis, and MicrobiomeAnalyst. ResultsHRCD-fed WT and DKO mice developed similar levels of hepatic steatosis although DKO mice had significantly higher hepatic levels of malondialdehyde (MDA). Interestingly, in both chow-fed and HRCD-fed DKO mice, plasma adiponectin and hepatic bile acids were significantly lower compared to respective WT groups. Our metabolomics data revealed that DKO mice displayed significant alterations in ceramide, cholesterol ester, triglyceride, and phospholipid classes under both chow and HRCD conditions. Additionally, when compared to HRCD-fed WT mice, HRCD-fed DKO mice displayed significantly reduced alpha diversity and possessed significant compositional differences based on Bray Curtis dissimilarity measures. ConclusionsBCO1/BCO2 DKO mice display altered metabolomic and gut microbial profiles. Carotenoid cleavage enzymes affect diverse physiological processes, which involve lipid metabolism and the gut microbiome. Funding SourcesUSDA/ARS and NIFA/AFRI.

Excitatory neurons in paraventricular hypothalamus contributed to the mechanism underlying acupuncture regulating the swallowing function

Paraventricular hypothalamus (PVH) is demonstrated to regulate stress, feeding behaviors, and other related homeostatic processes. However, no direct evidence has been investigated for the role of PVH in swallowing function. Acupuncture therapy at Lianquan (CV23) acupoint has been reported to improve the swallowing function in clinical trials, but its underlying mechanism still needs to be uncovered. Thus, we aimed to explore whether PVH involved the acupuncture mediated regulating swallowing function. Chemogenetics, electromyography (EMG) recording, and immunofluorescence staining methods were combined to demonstrate that neurons in PVH could be activated by electroacupuncture (EA) stimulation at CV23, and this neuronal cluster was represented as excitatory neurons. Furthermore, we mapped both the inputs and outputs of PVH neurons using viral tracing. The neurons in PVH projected with the brain regions, including parabrachial nucleus (PBN) and the solitary tract nucleus (NTS), which both participated in the swallowing process. The EA function regulating the swallowing was attenuated after inhibiting the neurons in PVH in the post stroke dysphagia. In conclusion, this study suggested that EA at CV23 could regulate swallowing function involving the excitatory neurons in PVH.