Stress Stimuli Research Articles

BAG3 protects chondrocytes against lumbar facet joint osteoarthritis by regulating autophagy and apoptosis.

Bcl2-associated athanogene3 (BAG3) protein, mainly induced by stressful stimuli, has been confirmed to participate in apoptosis and autophagy. In recent studies, BAG3 has gradually become a key molecule in tumors. However, the role of BAG3 in the progression of lumbar facet joint osteoarthritis (FJOA) and whether it can regulate chondrocyte apoptosis and autophagy are still unknown. In both human and FJOA rat models, we observed an upregulation of BAG3 and apoptosis and autophagy-related proteins compared with healthy tissues. Then, we established the chondrocytes injury model in vitro by using IL-1β to stimulate human SW1353 cells. Western blot analysis data showed significant expression of BAG3, apoptosis, and autophagy-related proteins in SW1353 cells. Finally, by knocking down and overexpressing BAG3, we discovered possible anti-apoptotic and autophagy-promoted effects of BAG3 in FJOA through various experimental methods. This study demonstrated that BAG3 actively participates in regulating chondrocyte apoptosis and autophagy in FJOA and may be a highly interesting targetfor pharmacological interventions.

Insights into the novel magnetoelectric coupling mechanism in soft materials due to Maxwell interactions

This study models the novel ME coupling mechanism in soft materials that are inherently non-magnetoelectric (NME). First, the central physical concept for developing ME coupling in soft NME materials is explained. Following this, the stretch of soft materials under magnetic and stress stimuli is solved by using the obtained Euler–Lagrange equations. Finally, the ME coefficients for various operating modes are analytically derived. The numerical results obtained for the ME coefficients of a ME electret system are in good agreement with the experimental data. The nonlinear interplay between the stress, magnetic field, and ME response is investigated. In addition, the key factors for maximizing the ME coupling are discussed. Based on the proposed model, we present physical insights to support the prospects of achieving magnetic energy harvesting and revealing the physical mechanisms of animals' magnetoreception. This work may provide a simple basis to further create soft ME-like materials with good flexibility and strong ME coupling.

Dynamics of T-Cell Intracellular Antigen 1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy under Oxidative Stress.

T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is primarily involved in the post-transcriptional regulation of cellular RNAs. Furthermore, it is a key component of stress granules (SGs), RNA, and protein aggregates that are formed in response to stressful stimuli to reduce cellular activity as a survival mechanism. TIA1 p.E384K mutation is the genetic cause of Welander distal myopathy (WDM), a late-onset muscular dystrophy whose pathogenesis has been related to modifying SG dynamics. In this study, we present the results obtained by analyzing two specific aspects: (i) SGs properties and dynamics depending on the amino acid at position 384 of TIA1; and (ii) the formation/disassembly time-course of TIA1WT/WDM-dependent SGs under oxidative stress. The generation of TIA1 variants—in which the amino acid mutated in WDM and the adjacent ones were replaced by lysines, glutamic acids, or alanines—allowed us to verify that the inclusion of a single lysine is necessary and sufficient to alter SGs dynamics. Moreover, time-lapse microscopy analysis allowed us to establish in vivo the dynamics of TIA1WT/WDM-dependent SG formation and disassembly, after the elimination of the oxidizing agent, for 1 and 3 h, respectively. Our observations show distinct dynamics between the formation and disassembly of TIA1WT/WDM-dependent SGs. Taken together, this study has allowed us to expand the existing knowledge on the role of TIA1 and the WDM mutation in SG formation.

Lactato y catecolaminas: respuesta fisiológica en el paciente crítico

Lactate is a highly dynamic metabolite that is produced, under anaerobic conditions, due to hypoxia or ischemia. Under aerobic conditions, it is synthesized by a mechanism driven by the stimulation of the β2 adrenergic receptor, which increases the activity of the sodium-potassium pump, and by a state of accelerated aerobic glycolysis. This metabolite is capable of being exchanged between different producing and consuming cells, ensuring the raw material for energy production.The sympathetic nervous system responds to stress stimuli through the release of catecholamines, which act as hormones and neurotransmitters in various tissues of the body, allowing an increase in metabolism that raises glucose and available oxygen levels.There is a physiological dependence between catecholamine levels and lactate production, predisposing the body to respond effectively to a stressful situation. However, an exacerbated adrenergic response may cause exaggerated effects on sensitive tissues that increase the probability of failure. Based on the knowledge of these mechanisms, therapeutic strategies focused on regulating the sympathetic activity are proposed.

Fos response of the tail of the ventral tegmental area to food restriction entails a prediction error processing

The tail of the ventral tegmental area (tVTA) or rostromedial tegmental nucleus (RMTg) receives lateral habenula inputs and projects heavily to midbrain dopamine neurons. Midbrain dopamine and lateral habenula neurons participate in learning processes predicting the outcomes of actions, placing the tVTA in a critical location into prediction error pathways. tVTA GABA neurons show electrophysiological inhibition or activation after reward and aversive stimuli, respectively, and their predictive cues. tVTA molecular recruitment, however, is not elicited by all aversive stimuli. Indeed, precipitated opioid withdrawal, repeated footshocks or food restriction raise tVTA Fos expression, whereas various other unpleasant, stressful or painful stimuli does not elicit that molecular response. However, the basis of that difference remains unknown. In the present study, we tried to disentangle whether the tVTA c-Fos induction observed after food restriction was due to the aversive state of food restriction or to procedure-related reward prediction error. To this end, male Sprague-Dawley rats were food-restricted for 7–8 days. During this period, animals were handled and weighed every day before feeding. On the test day, rats underwent several behavioral procedures to explore the impact of food restriction and food-predictive cue exposure on tVTA c-Fos expression. We showed that food restriction per se was not able to recruit c-Fos in the tVTA. On the contrary, the food-predicting cues induced c-Fos locally in the absence of feeding, whereas the food-predicting cues followed by feeding evoked lower c-Fos expression. Overall, our results support the proposed involvement of the tVTA in reward prediction error.

Emerging Role of Oxidative Stress on EGFR and OGG1-BER Cross-Regulation: Implications in Thyroid Physiopathology.

Thyroid diseases have a complex and multifactorial aetiology. Despite the numerous studies on the signals referable to the malignant transition, the molecular mechanisms concerning the role of oxidative stress remain elusive. Based on its strong oxidative power, H2O2 could be responsible for the high level of oxidative DNA damage observed in cancerous thyroid tissue and hyperactivation of mitogen-activated protein kinase (MAPK) and PI3K/Akt, which mediate ErbB signaling. Increased levels of 8-oxoG DNA adducts have been detected in the early stages of thyroid cancer. These DNA lesions are efficiently recognized and removed by the base excision repair (BER) pathway initiated by 8-oxoG glycosylase1 (OGG1). This study investigated the relationships between the EGFR and OGG1-BER pathways and their mutual regulation following oxidative stress stimulus by H2O2 in human thyrocytes. We clarified the modulation of ErbB receptors and their downstream pathways (PI3K/Akt and MAPK/ERK) under oxidative stress (from H2O2) at the level of gene and protein expression, according to the mechanism defined in a human non-pathological cell system, Nthy-ori 3-1. Later, on the basis of the results obtained by gene expression cluster analysis in normal cells, we assessed the dysregulation of the relationships in a model of papillary thyroid cancer with RET/PTC rearrangement (TPC-1). Our observations demonstrated that a H2O2 stress may induce a physiological cross-regulation between ErbB and OGG1-BER pathways in normal thyroid cells (while this is dysregulated in the TPC-1 cells). Gene expression data also delineated that MUTYH gene could play a physiological role in crosstalk between ErbB and BER pathways and this function is instead lost in cancer cells. Overall, our data on OGG1 protein expression suggest that it was physiologically regulated in response to oxidative modulation of ErbB, and that these might be dysregulated in the signaling pathway involving AKT in the progression of thyroid malignancies with RET/PTC rearrangements.

Mitochondrial Dysfunction: An Emerging Link in the Pathophysiology of Cardiorenal Syndrome.

The crosstalk between the heart and kidney is carried out through various bidirectional pathways. Cardiorenal syndrome (CRS) is a pathological condition in which acute or chronic dysfunction in the heart or kidneys induces acute or chronic dysfunction of the other organ. Complex hemodynamic factors and biochemical and hormonal pathways contribute to the development of CRS. In addition to playing a critical role in generating metabolic energy in eukaryotic cells and serving as signaling hubs during several vital processes, mitochondria rapidly sense and respond to a wide range of stress stimuli in the external environment. Impaired adaptive responses ultimately lead to mitochondrial dysfunction, inducing cell death and tissue damage. Subsequently, these changes result in organ failure and trigger a vicious cycle. In vitro and animal studies have identified an important role of mitochondrial dysfunction in heart failure (HF) and chronic kidney disease (CKD). Maintaining mitochondrial homeostasis may be a promising therapeutic strategy to interrupt the vicious cycle between HF and acute kidney injury (AKI)/CKD. In this review, we hypothesize that mitochondrial dysfunction may also play a central role in the development and progression of CRS. We first focus on the role of mitochondrial dysfunction in the pathophysiology of HF and AKI/CKD, then discuss the current research evidence supporting that mitochondrial dysfunction is involved in various types of CRS.

A positive feedback circuit comprising p21 and HIF-1α aggravates hypoxia-induced radioresistance of glioblastoma by promoting Glut1/LDHA-mediated glycolysis.

The radioresistance induced by hypoxia is the major obstacle in the successful treatment of cancer radiotherapy. p21 was initially identified as a widespread inhibitor of cyclin-dependent kinases, through which mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. In this study, we discovered a novel function of p21, which participated in the regulation of metabolic pathways under hypoxia. We found that p21 was upregulated in glioblastoma (GBM) cells under hypoxic conditions, which enhanced the radioresistance of GBM cells. In principle, HIF-1α is bound directly to the hypoxia response elements (HREs) of the p21 promoter to enhance its transcription activity, in turn, p21 also promoted the transcription of HIF-1α at the mRNA level and maintained HIF-1α function under oxygen deficiency. The positive correlation between p21 and HIF-1α augmented Glut1/LDHA-mediated glycolysis and aggravated the radioresistance of GBM cells. Thus, our results constructed a positive feedback circuit comprising p21/HIF-1α that might play a key role in enhancing the radioresistance of GBM under hypoxia.

CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.

Cellular senescence is characterized by cell cycle arrest and senescence-associated secretory phenotypes. Cellular senescence can be caused by various stress stimuli such as DNA damage, oxidative stress, and telomere attrition and is related to several chronic diseases, including atherosclerosis, Alzheimer's disease, and osteoarthritis. Chromobox homolog 4 (CBX4) has been shown to alleviate cellular senescence in human mesenchymal stem cells and is considered a possible target for senomorphic treatment. Here, we explored whether CBX4 expression is associated with replicative senescence in WI-38 fibroblasts, a classic human senescence model system. We also examined whether and how regulation of CBX4 modifies the senescence phenotype and functions as an antisenescence target in WI-38. During the serial culture of the WI-38 primary fibroblast cell line to a senescent state, we found increased expression of senescence markers, including senescence β-galactosidase (SA-βgal) activity, protein expression of p16, p21, and DPP4, and decreased proliferation marker EdU; moreover, CBX4 protein expression declined. With knockdown of CBX4, SA-βgal activity and p16 protein expression increased, and EdU decreased. With the activation of CBX4, SA-βgal activity, p16, and DPP4 protein decreased. In addition, CBX4 knockdown increased, while CBX4 activation decreased, gene expression of both CDKN2A (encoding the p16 protein) and DPP4. Genes related to DNA damage and cell cycle pathways were regulated by CBX4. These results demonstrate that CBX4 can regulate replicative senescence in a manner consistent with a senomorphic agent.

Cardiovascular Reactivity to a Novel Stressor: Differences on Susceptible and Resilient Rats to Social Defeat Stress.

Prolonged and heightened responses to stress are known factors that influence the development of mood disorders and cardiovascular diseases. Moreover, the coping strategies related to the experience of adverse events, i.e., resilience or the susceptibility to stress, are determinants for the individual risk of developing such diseases. Susceptible rats to the social defeat stress (SDS), identified by the social interaction test (SIT), show behavioral and cardiovascular alterations after SDS exposure that are not found in resilient rats. However, it is not elucidated yet how the cardiovascular system of susceptible and resilient phenotypes responds to a new stressor after SDS exposure. Thus, using the SDS exposure followed by the SIT, we evaluated heart rate, blood pressure (BP), tail skin temperature, and circulating corticosterone responses to an acute session of restraint stress in susceptible and resilient rats to SDS. Susceptible rats showed resting tachycardia and exaggerated BP response to restraint stress, while resilient rats did not present such alterations. In contrast, both phenotypes showed increased plasma corticosterone and a drop in tail skin temperature to restraint stress, which was similar to that observed in control animals. Our results revealed an increased cardiovascular reactivity in response to a new stressful stimulus in susceptible rats, which might be related to a greater risk for the development of cardiovascular diseases.

Physiology of Plant Responses to Water Stress and Related Genes: A Review

Drought and waterlogging seriously affect the growth of plants and are considered severe constraints on agricultural and forestry productivity; their frequency and degree have increased over time due to global climate change. The morphology, photosynthetic activity, antioxidant enzyme system and hormone levels of plants could change in response to water stress. The mechanisms of these changes are introduced in this review, along with research on key transcription factors and genes. Both drought and waterlogging stress similarly impact leaf morphology (such as wilting and crimping) and inhibit photosynthesis. The former affects the absorption and transportation mechanisms of plants, and the lack of water and nutrients inhibits the formation of chlorophyll, which leads to reduced photosynthetic capacity. Constitutive overexpression of 9-cis-epoxydioxygenase (NCED) and acetaldehyde dehydrogenase (ALDH), key enzymes in abscisic acid (ABA) biosynthesis, increases drought resistance. The latter forces leaf stomata to close in response to chemical signals, which are produced by the roots and transferred aboveground, affecting the absorption capacity of CO2, and reducing photosynthetic substrates. The root system produces adventitious roots and forms aerenchymal to adapt the stresses. Ethylene (ETH) is the main response hormone of plants to waterlogging stress, and is a member of the ERFVII subfamily, which includes response factors involved in hypoxia-induced gene expression, and responds to energy expenditure through anaerobic respiration. There are two potential adaptation mechanisms of plants (“static” or “escape”) through ETH-mediated gibberellin (GA) dynamic equilibrium to waterlogging stress in the present studies. Plant signal transduction pathways, after receiving stress stimulus signals as well as the regulatory mechanism of the subsequent synthesis of pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) enzymes to produce ethanol under a hypoxic environment caused by waterlogging, should be considered. This review provides a theoretical basis for plants to improve water stress tolerance and water-resistant breeding.

Circulating Tumor Cells in Breast Cancer Patients: A Balancing Act between Stemness, EMT Features and DNA Damage Responses.

Simple SummaryCirculating tumor cells dissociate from the primary tumor, enter the bloodstream and travel to distant sites where they seed metastases. To endow these tumor cells with the features necessary for this journey, they must undergo dramatic shape changes, acquire migratory potential, alter their metabolism, and quickly adapt to insults in each new environment. To permit such phenotypic changes in multiple directions, they often acquire a more primitive state reminiscent of stem cells in the embryo. These changes are coupled with altered capacities and qualities to remove DNA lesions such as those induced by a metabolic shift or an immune cell attack. Defects in DNA repair cause mutations, leading to hereditary breast cancer and accelerating progression. Enhanced DNA repair causes resistance to chemotherapeutic treatment. Therefore, it is of utmost interest to understand the choreography of these functions in circulating tumor cells at the molecular level, because they represent targets to fight chemoresistant metastases.Circulating tumor cells (CTCs) traverse vessels to travel from the primary tumor to distant organs where they adhere, transmigrate, and seed metastases. To cope with these challenges, CTCs have reached maximal flexibility to change their differentiation status, morphology, migratory capacity, and their responses to genotoxic stress caused by metabolic changes, hormones, the inflammatory environment, or cytostatic treatment. A significant percentage of breast cancer cells are defective in homologous recombination repair and other mechanisms that protect the integrity of the replication fork. To prevent cell death caused by broken forks, alternative, mutagenic repair, and bypass pathways are engaged but these increase genomic instability. CTCs, arising from such breast tumors, are endowed with an even larger toolbox of escape mechanisms that can be switched on and off at different stages during their journey according to the stress stimulus. Accumulating evidence suggests that DNA damage responses, DNA repair, and replication are integral parts of a regulatory network orchestrating the plasticity of stemness features and transitions between epithelial and mesenchymal states in CTCs. This review summarizes the published information on these regulatory circuits of relevance for the design of biomarkers reflecting CTC functions in real-time to monitor therapeutic responses and detect evolving chemoresistance mechanisms.

The role of oxidative and nitrosative stress and the tryptophan catabolites pathway in the pathogenesis of depression

Depression is the most common mental illness, affecting approximately 350 million people around the world. Despite numerous studies, the etiology of this disease remains unclear. Previous studies suggest the involvement of interrelated biochemical pathways, i.e. oxidative and nitrative stress as well as abnormalities of the tryptophan catabolites pathway (TRYCATs) in the depression development. Therefore, the aim of this study was to explain the role of oxidative and nitrative stress as well as disorders in the course of the TRYCATs pathway in the molecular basis of depression. In this study, an attempt was made to determine the effect of single nucleotide polymorphisms, located in genes, encoding enzymes involved in oxidative and nitrative stress, and the TRYCATs pathway on the incidence of depression. Moreover, using an in vivo model of depression, the impact of chronic mild stress stimuli on mRNA expression and protein amount as well as the degree of methylation of the promoter regions of genes encoding enzymes involved in the studied pathways was assessed. The obtained results clearly confirmed the studied biochemical pathways are involved in the development of depression at the molecular level.

The Expression and Regulatory Roles of Long Non-Coding RNAs in Periodontal Ligament Cells: A Systematic Review.

Periodontal ligament (PDL) cells play a pivotal role in periodontal and bone homeostasis and have promising potential for regenerative medicine and tissue engineering. There is compelling evidence that long non-coding RNAs (lncRNAs) are differentially expressed in PDL cells compared to other cell types and that these lncRNAs are involved in a variety of biological processes. This study systematically reviews the current evidence regarding the expression and regulatory functions of lncRNAs in PDL cells during various biological processes. A systematic search was conducted on PubMed, the Web of Science, Embase, and Google Scholar to include articles published up to 1 July 2021. Original research articles that investigated the expression or regulation of lncRNAs in PDL cells were selected and evaluated for a systematic review. Fifty studies were ultimately included, based on our eligibility criteria. Thirteen of these studies broadly explored the expression profiles of lncRNAs in PDL cells using microarray or RNA sequencing. Nineteen studies investigated the mechanisms by which lncRNAs regulate osteogenic differentiation in PDL cells. The remaining 18 studies investigated the mechanism by which lncRNAs regulate the responses of PDL cells to various stimuli, namely, lipopolysaccharide-induced inflammation, tumor necrosis factor alpha-induced inflammation, mechanical stress, oxidative stress, or hypoxia. We systematically reviewed studies on the expression and regulatory roles of lncRNAs in diverse biological processes in PDL cells, including osteogenic differentiation and cellular responses to inflammation, mechanical stress, and other stimuli. These results provide new insights that may guide the development of lncRNA-based therapeutics for periodontal and bone regeneration.

Interaction of transcription factor FoxO3 with histone acetyltransferase complex subunit TRRAP modulates gene expression and apoptosis

Forkhead box O (FoxO) transcription factors are conserved proteins involved in the regulation of life span and age-related diseases, such as diabetes and cancer. Stress stimuli or growth factor deprivation promotes nuclear localization and activation of FoxO proteins, which—depending on the cellular context—can lead to cell cycle arrest or apoptosis. In endothelial cells (ECs), they further regulate angiogenesis and may promote inflammation and vessel destabilization implicating a role of FoxOs in vascular diseases. In several cancers, FoxOs exert a tumor-suppressive function by regulating proliferation and survival. We and others have previously shown that FoxOs can regulate these processes via two different mechanisms: by direct binding to forkhead-responsive elements at the promoter of target genes or by a poorly understood alternative process that does not require direct DNA binding and regulates key targets in primary human ECs. Here, we performed an interaction study in ECs to identify new nuclear FoxO3 interaction partners that might contribute to FoxO-dependent gene regulation. Mass spectrometry analysis of FoxO3-interacting proteins revealed transformation/transcription domain–associated protein (TRRAP), a member of multiple histone acetyltransferase complexes, as a novel binding partner of FoxO family proteins. We demonstrate that TRRAP is required to support FoxO3 transactivation and FoxO3-dependent G1 arrest and apoptosis in ECs via transcriptional activation of the cyclin-dependent kinase inhibitor p27kip1 and the proapoptotic B-cell lymphoma 2 family member, BIM. Moreover, FoxO–TRRAP interaction could explain FoxO-induced alternative gene regulation via TRRAP-dependent recruitment to target promoters lacking forkhead-responsive element sequences.

High, in Contrast to Low Levels of Acute Stress Induce Depressive-like Behavior by Involving Astrocytic, in Addition to Microglial P2X7 Receptors in the Rodent Hippocampus.

Extracellular adenosine 5′-triphosphate (ATP) in the brain is suggested to be an etiological factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also possess P2X7Rs. In order to elucidate the possible involvement of the MDD-relevant hippocampal astrocytes in the development of a depressive-like state, we used various behavioral tests (tail suspension test [TST], forced swim test [FST], restraint stress, inescapable foot shock, unpredictable chronic mild stress [UCMS]), as well as fluorescence immunohistochemistry, and patch-clamp electrophysiology in wild-type (WT) and genetically manipulated rodents. The TST and FST resulted in learned helplessness manifested as a prolongation of the immobility time, while inescapable foot shock caused lower sucrose consumption as a sign of anhedonia. We confirmed the participation of P2X7Rs in the development of the depressive-like behaviors in all forms of acute (TST, FST, foot shock) and chronic stress (UCMS) in the rodent models used. Further, pharmacological agonists and antagonists acted in a different manner in rats and mice due to their diverse potencies at the respective receptor orthologs. In hippocampal slices of mice and rats, only foot shock increased the current responses to locally applied dibenzoyl-ATP (Bz-ATP) in CA1 astrocytes; in contrast, TST and restraint depressed these responses. Following stressful stimuli, immunohistochemistry demonstrated an increased co-localization of P2X7Rs with a microglial marker, but no change in co-localization with an astroglial marker. Pharmacological damage to the microglia and astroglia has proven the significance of the microglia for mediating all types of depression-like behavioral reactions, while the astroglia participated only in reactions induced by strong stressors, such as foot shock. Because, in addition to acute stressors, their chronic counterparts induce a depressive-like state in rodents via P2X7R activation, we suggest that our data may have relevance for the etiology of MDD in humans.

Genome-Wide Evolution and Comparative Analysis of Superoxide Dismutase Gene Family in Cucurbitaceae and Expression Analysis of Lagenaria siceraria Under Multiple Abiotic Stresses.

Superoxide dismutase (SOD) is an important enzyme that serves as the first line of defense in the plant antioxidant system and removes reactive oxygen species (ROS) under adverse conditions. The SOD protein family is widely distributed in the plant kingdom and plays a significant role in plant growth and development. However, the comprehensive analysis of the SOD gene family has not been conducted in Cucurbitaceae. Subsequently, 43 SOD genes were identified from Cucurbitaceae species [Citrullus lanatus (watermelon), Cucurbita pepo (zucchini), Cucumis sativus (cucumber), Lagenaria siceraria (bottle gourd), Cucumis melo (melon)]. According to evolutionary analysis, SOD genes were divided into eight subfamilies (I, II, III, IV, V, VI, VII, VIII). The gene structure analysis exhibited that the SOD gene family had comparatively preserved exon/intron assembly and motif as well. Phylogenetic and structural analysis revealed the functional divergence of Cucurbitaceae SOD gene family. Furthermore, microRNAs 6 miRNAs were predicted targeting 3 LsiSOD genes. Gene ontology annotation outcomes confirm the role of LsiSODs under different stress stimuli, cellular oxidant detoxification processes, metal ion binding activities, SOD activity, and different cellular components. Promoter regions of the SOD family revealed that most cis-elements were involved in plant development, stress response, and plant hormones. Evaluation of the gene expression showed that most SOD genes were expressed in different tissues (root, flower, fruit, stem, and leaf). Finally, the expression profiles of eight LsiSOD genes analyzed by qRT-PCR suggested that these genetic reserves responded to drought, saline, heat, and cold stress. These findings laid the foundation for further study of the role of the SOD gene family in Cucurbitaceae. Also, they provided the potential for its use in the genetic improvement of Cucurbitaceae.

Differential roles of prelimbic and infralimbic cholinergic neurotransmissions in control of cardiovascular responses to restraint stress in rats

Previous studies showed a prominent role of the medial prefrontal cortex (mPFC), especially the prelimbic (PL) and infralimbic (IL) subregions, in behavioral and physiological responses to stressful stimuli. Nevertheless, the local neurochemical mechanisms involved are not completely understood. In this sense, previous studies identified cholinergic terminals within the mPFC, and stressful stimuli increased local acetylcholine release. Despite these pieces of evidence, the specific role of cholinergic neurotransmission in different subregions of the mPFC controlling the cardiovascular responses to stress has never been systematically evaluated. Therefore, the purpose of this study was to investigate the involvement of cholinergic neurotransmission present within PL and IL in cardiovascular responses to an acute session of restraint stress in rats. For this, rats received bilateral microinjection of the choline uptake inhibitor hemicholinium-3 before exposure to restraint stress. The arterial pressure and heart rate (HR) increases and the decrease in tail skin temperature as an indirect measurement of sympathetically-mediated cutaneous vasoconstriction were recorded throughout the restraint stress session. The results showed that the depletion of acetylcholine within the PL caused by local microinjection of hemicholinium-3 decreased the tachycardia to restraint stress, but without affecting the pressor response and the drop in tail skin temperature. Conversely, IL treatment with hemicholinium-3 decreased the restraint-evoked pressor response and the sympathetically-mediated cutaneous vasoconstriction without interfering with the HR response. Taken together, these results indicate functional differences of cholinergic neurotransmission within the PL and IL in control of cardiovascular and autonomic responses to stressful stimuli.

Plant Responses Underlying Timely Specialized Metabolites Induction of Brassica Crops.

A large subset of plant stress-signaling pathways, including those related with chemical defense production, exhibit diurnal or circadian oscillations. However the extent to which diurnal or circadian time influences the stress mediated accumulation of plant specialized metabolites remains largely unknown. Because plant responses to physical stress (e.g., wounding) is considered a common component of mounting a response against a broad range of environmental stresses, including herbivory, we have utilized mechanical wounding as the stress stimulus to determine the direct contribution of time of day on the induced defenses of Brassica crops. We analyzed glucosinolates (GSLs) from leaves of broccoli (Brassica oleracea) and turnip greens (Brassica rapa) following exposure to mechanical wounding at dawn (ZT0), mid-day (ZT4), and dusk (ZT8). Several GSLs differentially accumulated and their changes depended upon the time of day at wounding was performed. This response varied considerably between species. In a parallel experiment, we investigated whether diurnal activation of Brassica phytochemicals in response to wounding might prime plants against herbivore attack. Results showed that maximal response of plant chemical defense against larvae of the generalist pest Mamestra brassicae occurred at ZT0 in broccoli and ZT8 in turnip greens. Metabolome analysis for global trends of time dependent compounds showed that sulfur-containing phytochemicals, GSL hydrolysis products, auxin-signaling components, and other metabolites activators of plant disease resistance (nicotinamide and pipecolate) had important contributions to the responses of M. brassicae feeding behavior in broccoli at morning. Overall, the findings in this study highlight a significant role for time of day in the wound stress responsive metabolome, which can in turn affect plant-herbivore interactions.

Intra-CA1 injection of orexin receptors antagonism attenuates the stress-induced analgesia in a rat acute pain model

Orexins or hypocretins are excitatory neuropeptides predominantly produced by neuronal clusters in the lateral hypothalamus. The orexinergic system's involvement in pain modulation makes it a candidate for pain control alternative to the opioid system. Moreover, orexin-1 and orexin -2 receptors (OX1r and OX2r, respectively) play a role in responsiveness to stressful stimuli. Some evidence indicates that the Cornu Ammonis 1 (CA1) region of the hippocampus potentially participates in the modulation of both pain and stress. In quest of better understanding the interaction between orexin receptors and stress-induced analgesia (SIA), The present study examined the involvement of OX1r and OX2r within the CA1 in response to acute pain after exposure to forced swim stress (FSS) for a 6-min period. Adult male Wistar rats received different doses of OX1r antagonist (SB334867; 1, 3, 10, and 30 nmol), OX2r antagonist (TCS OX2 29; 3, 10, 30 and 100 nmol), or vehicle (0.5 μl DMSO) through an implanted cannula. After that, animals individually experienced acute pain by performing the tail-flick test. Results indicated that FSS produces antinociceptive responses in the tail-flick test. Blockade of both orexin receptors within the CA1 region attenuated the analgesic effect of FSS. The antinociceptive effect of swim stress was prevented by lower doses of SB334867 than TCS OX2 29. These findings show that the orexinergic system might be partially involved in the SIA via the OX1 and OX2 receptors in the hippocampal CA1 region.