Stress Protection Research Articles

Neurons of the central nucleus of the amygdala that express angiotensin type 2 receptors couple lowered blood pressure with anxiolysis in male mice.

Relief from psychological stress confers cardio-protection by altering brain activity and lowering blood pressure; however, the neuronal circuits orchestrating these effects are unknown. Here, we used male mice to discern neuronal circuits conferring stress relief and reduced blood pressure. We found that neurons residing in the central nucleus of the amygdala (CeA) expressing angiotensin type 2 receptors (AT2R), deemed CeAAT2R, innervate brain nuclei regulating stress responding. In vivo optogenetic excitation of CeAAT2R lowered blood pressure and this effect was abrogated by systemic hexamethonium or antagonism of GABA receptors within the CeA. Intriguingly, in vivo optogenetic excitation of CeAAT2R was also potently anxiolytic. Delivery of an AT2R agonist into the CeA recapitulated the hypotensive and anxiolytic effects, but ablating AT2R(s) from the CeA was anxiogenic. The results suggest that the excitation of CeAAT2R couples lowered blood pressure with anxiolysis. The implication is that therapeutics targeting CeAAT2R may provide stress relief and protection against cardiovascular disease.Significance statement There is increasing appreciation that brain-to-body communication promotes susceptibility or resiliency to cardiovascular disease. Here, we present preclinical research that discerns a neural circuit that orchestrates brain-to-body communication and provides relief from mental stress. We discover that neurons within the central nucleus of the amygdala that express angiotensin type 2 receptors (hereafter referred to as CeAAT2R) are potent mediators of blood pressure and anxiolysis. The implication is that CeAAT2R or their angiotensin type 2 receptors can be targeted to protect against stress-induced cardiovascular disease.

Redox proteomics reveal a role for peroxiredoxinylation in stress protection.

The redox state of proteins is essential for their function and guarantees cell fitness. Peroxiredoxins protect cells against oxidative stress, maintain redox homeostasis, act as chaperones, and transmit hydrogen peroxide signals to redox regulators. Despite the profound structural and functional knowledge of peroxiredoxins action, information on how the different functions are concerted is still scarce. Using global proteomic analyses, we show here that the yeast peroxiredoxin Tsa1 interacts with many proteins of essential biological processes, including protein turnover and carbohydrate metabolism. Several of these interactions are of a covalent nature, and we show that failure of peroxiredoxinylation of Gnd1 affects its phosphogluconate dehydrogenase activity and impairs recovery upon stress. Thioredoxins directly remove TSA1-formed mixed disulfide intermediates, thus expanding the role of the thioredoxin-peroxiredoxin redox cycle pair to buffer the redox state of proteins.

Biomimetic bioreactor for potentiated uricase replacement therapy in hyperuricemia and gout.

Uricase replacement therapy is a promising approach for managing hyperuricemia and gout but is hindered by challenges such as short blood circulation time, reduced catalytic activity, and excessive hydrogen peroxide (H2O2) production. These limitations necessitate innovative strategies to enhance therapeutic efficacy and safety. We designed and synthesized RBC@SeMSN@Uri, a red blood cell-coated biomimetic self-cascade bioreactor, which encapsulates uricase (Uri) and a selenium-based nano-scavenger (SeMSN) within RBC membranes. This design aims to reduce immunogenicity, extend systemic circulation, and maintain enzymatic activity. In vitro assays were conducted to evaluate biocompatibility, anti-inflammatory effects, and oxidative stress protection. In vivo experiments in hyperuricemia and gout models assessed therapeutic efficacy, biodistribution, and biosafety. RBC@SeMSN@Uri effectively degraded uric acid (UA) into allantoin and converted H2O2 into water, preventing oxidative damage and inflammation. In vitro assays demonstrated excellent biocompatibility and reduced H2O2-induced inflammatory responses compared to free uricase. In vivo, the bioreactor prolonged circulation time, significantly reduced uric acid levels, alleviated kidney damage, and mitigated symptoms of hyperuricemia and gout. It also targeted inflamed joints, reducing swelling and inflammation in gouty arthritis models. This study presents RBC@SeMSN@Uri as a novel biomimetic strategy for enzyme replacement therapy in hyperuricemia and gout. By integrating uricase and selenium-based nano-scavenger within RBC membranes, the bioreactor addresses key limitations of traditional therapies, offering enhanced stability, reduced immunogenicity, and superior therapeutic efficacy. This platform holds potential for broader applications in protein or antibody delivery for enzyme replacement therapies in other diseases.

Comprehensive Anti-Stress Protection of Grain Crops under Contrasting Weather Conditions

The article presents the results of stress protection of seeds and plants of spring wheat and barley of zoned varieties for the 3rd agro-climatic zone of the Russian Federation. The research was carried out in 2018–2022 in 2 stages: the first was a series of laboratory experiments at the departments of breeding, seed production and Agrotechnology of the Federal State Budgetary Educational Institution of Higher Education, the second was field experiments on gray forest soils of average fertility in an agricultural enterprise named after him. Krupskaya Ryazan region. The algorithm of complex stress protection included a sequential cascade of interrelated agrotechnological techniques: a) a method for selecting the most resistant batches of seeds to ethylene stress for sowing purposes, b) a method for stress protection and increasing the germination of these seeds during post-harvest storage, c) pre-sowing seed treatment and d) plants IV-V stages of organogenesis with multifunctional growth regulators with anti-stress properties (Albite, TPS; Zircon,R; Epin-Extra,R), prolonging the effect of plant protection in critical phases of plant growth and development. During all 5 years of research, which were contrasting in meteorological conditions, the use of seeds with increased stress resistance and functional activity for sowing contributed, on average, to a stable increase in field germination of spring wheat by 2.8–10.6%, barley – 4.2–7.2%, increased shoot formation in the tillering phase of spring wheat by 0.12–0.23 and barley 0.16–0.25% of plants. These processes were most pronounced in spring wheat, in years with increased drought. The plant variants of complex stress protection were characterized by higher photosynthesis productivity, leaf surface index and terrestrial phytomass. A set of techniques that block the development of stress from the initial stages of ontogenesis to the formation of reproductive organs intensified plant growth, provided a higher level of accumulation of productivity resources, contributed to an increase in grain yields of spring wheat and barley, depending on the experimental options, by 0.48–0.62 t/ha and 0.31–0.39 t/ha, respectively. The increase in yield in all the years of the study, when using anti-stress protection, was due to an increase in the number of productive stems, a higher full-weight ear and a weight of 1000 grains. The applied stress protection methods fully meet the requirements of the production of environmentally friendly products and can be used as an element of technology in the production of organic crop products.

Isoquinolinequinone N-oxides with diverging mechanisms of action induce collateral sensitivity against multidrug resistant cancer cells.

Multidrug resistance (MDR) is a major challenge in cancer research. Collateral sensitizers, compounds that exploit the enhanced defense mechanisms of MDR cells as weaknesses, are a proposed strategy to overcome MDR. Our previous work reported the synthesis of two novel Isoquinolinequinone (IQQ) N-oxides that induce collateral sensitivity in MDR ABCB1-overexpressing non-small cell lung cancer (NSCLC) and colorectal cancer cells. Herein, we aimed to investigate underlying mechanisms of antitumor and collateral sensitivity activity of these compounds. We evaluated their effect on cancer cell viability, proliferation, cell cycle profile, and studied their cytotoxicity in non-tumorigenic cells. Their antitumor effect was further studied using NSCLC and colorectal cancer MDR spheroids. To understand underlying collateral sensitivity mechanisms, we assessed the effect on rhodamine-123 accumulation, ROS production, GSH/GSSG balance and expression of key proteins associated with metabolism and redox balance. Both compounds reduced the viability of MDR cells, as 2D cultures or as spheroids, without decreasing the growth of a human nontumorigenic cell line, and increased rhodamine-123 accumulation in MDR NCI-H460/R cells. Moreover, RK2 increased ROS, disrupted GSH balance, and altered expression of proteins associated with oxidative stress protection, particularly in NCI-H460/R cells. The collateral sensitivity effect of RK3 could not be attributed to redox balance disruption, but increased IDH1 expression following treatment suggests a potential metabolic shift in MDR cells. These findings highlight RK2 and RK3 as promising candidates for next stages of drug development. Their distinct mechanisms of action could lead to therapeutic solutions for MDR-related cancers, specifically linked to ABCB1 overexpression.

Anthocyanin-rich black wheat as a functional food for managing type 2 diabetes mellitus: a study on high fat diet-streptozotocin-induced diabetic rats.

Background: Type 2 Diabetes Mellitus (T2DM) is associated with insulin resistance, hyperglycemia, and hyperlipidemia. Anthocyanins, which are natural antioxidants, have been reported to manage T2DM-related complications. However, the potential of anthocyanin-rich black wheat as a functional food for managing diabetes remains unexplored. Aim: This study aimed to investigate the effects of anthocyanin-rich black wheat on glucose metabolism, insulin sensitivity, lipid profile, oxidative stress, inflammation, and organ protection in high fat diet-streptozotocin (HFD-STZ) induced T2DM rats. Methods: T2DM was induced in rats using HFD-STZ. The rats were fed with either white wheat or anthocyanin-rich black wheat chapatti. Glucose metabolism, insulin sensitivity, lipid profile, antioxidant enzymes, inflammatory markers, and glucose transporters were assessed. Histopathological analysis of the liver, kidneys, and spleen was performed. Results: Compared to white wheat chapatti, black wheat chapatti exhibited higher α-amylase and α-glucosidase inhibitory activities. Black wheat chapatti consumption significantly reduced blood glucose and HbA1c levels, and improved insulin sensitivity, oral glucose tolerance, and insulin tolerance. Antioxidant enzyme (superoxide dismutase and catalase) activities were enhanced. Atherogenic dyslipidemia was attenuated, with improved high-density lipoprotein cholesterol levels. Inflammatory markers (TNF-α, IL-1β, leptin, resistin and cortisol) were reduced, while adiponectin (Acrp-30) levels increased. Black wheat chapatti activated adiponectin-AMPK and PI3K-AKT pathways, upregulating glucose transporters (GLUT-2 and GLUT-4). Histopathology revealed protective effects on the liver, kidneys, and spleen. Conclusions: Anthocyanin-rich black wheat chapatti ameliorates insulin resistance and associated complications in HFD-STZ-induced T2DM rats. It modulates key signaling pathways and glucose transporters, demonstrating its potential as a functional food for managing T2DM and its complications.

Proteomic Insights into the Regulatory Mechanisms of the Freezing Response in the Alpine Subnivale Plant Chorispora bungeana.

Freezing temperatures impose significant constraints on plant growth and productivity. While cold tolerance mechanisms have been extensively studied in model species, the molecular basis of freezing tolerance in naturally adapted plants remains underexplored. Chorispora bungeana, an alpine plant with a strong freezing tolerance, provides a valuable model for investigating these adaptive mechanisms. In this study, we used Tandem Mass Tag (TMT)-based quantitative proteomics to analyze C. bungeana seedlings subjected to freezing stress (-6 °C) at 6 and 30 h, identifying 302 differentially expressed proteins (DEPs) compared with controls. Our findings capture the dynamic proteomic landscape of C. bungeana under freezing stress, revealing distinct early and prolonged responses. Early responses featured upregulated proteins involved in signaling and stress protection, with no clear involvement of the ICE1-CBF pathway (ICE1: Inducer of CBF Expression 1; CBF: C-repeat Binding Factor) found in cold-acclimating plants, while calcium signaling and epigenetic modifications enabled a rapid response. Extended exposure involved DEPs in RNA modification, glutamine metabolism, and biosynthesis of polysaccharides and flavonoids, highlighting metabolic adjustments crucial for long-term adaptation. By combining protein-protein interaction (PPI) networks and functional analysis, we identified 54 key proteins validated by qRT-PCR. These findings provide comprehensive insight into freezing tolerance mechanisms, identifying candidate proteins for enhancing cold resilience in crops and mitigating agricultural cold stress impacts.

Synthetic inhibition of SREBP2 and the mevalonate pathway blocks rhabdomyosarcoma tumor growth invitro and invivo and promotes chemosensitization.

By analyzing RNA datasets from rhabdomyosarcoma (RMS), a soft tissue tumor with a prevalence in young people, we found upregulation of sterol regulatory element-binding protein 2 (SREBP2) and mevalonate pathway (MVP) genes, including 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), farnesyl-diphosphate synthase (FDPS), squalene epoxidase (SQLE), which correlated with worse overall patient survival and predicted statin sensitivity. In human RD and RH30 lines, treatment with 0.01-1μM doses of fatostatin (SREBP2 inhibitor), lovastatin and simvastatin (HMGCR inhibitors), and zoledronic acid (FDPS inhibitor) impaired cell growth and migration, which were conversely stimulated by 50-100μM cholesterol (CHO) supplementation. Treatment of RMS lines with higher doses of SREBP2 and MVP inhibitors (5-50μM) promoted oxidative cell death and chemosensitization in combination with actinomycin D. Administration of lovastatin or fatostatin to RD and RH30 cells produced a rapid attenuation of Erk1/2 and Akt1 phosphorylation, detectable after 4h of treatment. Furthermore, tumor mass growth of xenografted RD cells in NOD/SCID mice was reduced by oral administration of lovastatin. Lastly, we found the forced Akt1 activation in RD cells was sufficient to drive SREBP2, HMGCR and SQLE protein expression and enhance cell death susceptibility to MVP inhibitors. Taken together, these data suggest that the axis formed by Akt1, SREBP2 and MVP is critical for RMS tumor growth, migration, and oxidative stress protection mainly through the maintenance of CHO levels that ensure proper intracellular signaling. Therefore, targeting CHO levels by SREBP2 and MVP inhibition may represent a viable option to improve the combination therapy protocol in RMS.

Conversion of Kappaphycus alvarezii macroalgae biomass enriched with fulvic acid into a foliar biostimulant for plant (Oryza sativa L.) growth and stress protection

BackgroundThe incorporation of circular economy into agricultural processes is necessary to improve the efficiency of agronomic practices in the future. The biomass of macroalgae as well as humic substances is sustainable options for stimulating the efficient use of nutrients in plants. This study aimed to evaluate the modes of action of a potential plant biostimulant composed of an aqueous extract of Kappaphycus alvarezii seaweed plus fulvic acid (KAF) applied to rice (Oryza sativa L.) leaves. The aqueous extract was obtained from the fresh biomass of the macroalga Kappaphycus alvarezii and the fulvic acid was extracted from a cattle manure vermicompost (FAVC). Both fractions (KAlv-sap and FAVC) were characterized using 1H NMR. The bioactivity of KAF was evaluated in experiments with four treatments: control (foliar application of water), FAVC (foliar application of FAVC), KAlv-sap (foliar application of seaweed extract), and KAF (foliar application of FA + KAlv-sap). In rice, the expression of genes related to K+ and N transport, plasma membrane H+-ATPases, and oxidative stress defense enzymes were evaluated. Metabolites and N, K, and P contents, as well as photosynthetic efficiency and root morphology, were quantified.ResultsThe 1H-NMR spectra showed that KAF is rich in organic fragments such as sugars, nitrogenous, aromatic, and aliphatic compounds in general. Foliar application of KAF resulted in a 7.1% and 19.04% increase in the dry mass of roots and leaves, respectively. These plants had 19% more roots and 11% more total root length. The application of KAF increased in the plant sheaths the N and K contents by up to 50% and 14%, respectively.ConclusionsThe mechanism of action by which KAF triggered these changes seemed to start with an improvement in the photosynthetic efficiency of plants and regulation through increased expression and suppression of genes related to K+, N, H+-ATPase transporters, and oxidative metabolism. KAF might become a sustainable plant biostimulant that promotes plant growth, development, and defense against abiotic stresses.Graphical

An updated reference genome sequence and annotation reveals gene losses and gains underlying naked mole-rat biology.

The naked mole-rat (NMR; Heterocephalus glaber ) is a eusocial subterranean rodent with a highly unusual set of physiological traits that has attracted great interest amongst the scientific community. However, the genetic basis of most of these traits has not been elucidated. To facilitate our understanding of the molecular mechanisms underlying NMR physiology and behaviour, we generated a long-read chromosomal-level genome assembly of the NMR. This genome was subsequently annotated and incorporated into multiple whole genome alignments in the Ensembl database. Our long-read assembly identified thousands of repeats and genes that were previously unassembled in the NMR and improved the results of routinely used short-read sequencing-based experiments such as RNA-seq, snRNA-seq, and ATAC-seq. We identified several spermatozoa related gene losses that may underlie the unique degenerative sperm phenotype in NMRs ( IRGC , FSCB , AKAP3 , MROH2B , CATSPER1 , DCDC2C , ATP1A4 , TEKT5 , and ZAN ), and an additional gene loss related to the established NK-cell absence in NMRs (PILRB). We resolved several tandem duplications in genes related to pathways underlying unique NMR adaptations including hypoxia tolerance, oxidative stress, and nervous system protection ( TINF2 , TCP1 , KYAT1 ). Lastly, we describe our ongoing efforts to generate a reference telomere-to-telomere assembly in the NMR which includes the resolution of complex gene families. This new reference genome should accelerate the discovery of the genetic underpinnings of NMR physiology and adaptation.

Root hair developmental regulators orchestrate drought triggered microbiome changes and the interaction with beneficial Rhizobiaceae

Drought is one of the most serious abiotic stresses, and emerging evidence suggest plant microbiome affects plant drought tolerance. However, there is a lack of genetic evidence regarding whether and how plants orchestrate the dynamic assembly of the microbiome upon drought. By utilizing mutants with enhanced or decreased root hair densities, we find that root hair regulators also affect drought induced root microbiome changes. Rhizobiaceae is a key biomarker taxa affected by root hair related mutants. We isolated and sequenced 1479 root associated microbes, and confirmed that several Rhizobium strains presented stress-alleviating activities. Metagenome, root transcriptome and root metabolome studies further reveal the multi-omic changes upon drought stress. We knocked out an ornithine cyclodeaminase (ocd) gene in Rhizobium sp. 4F10, which significantly dampens its stress alleviating ability. Our genetic and integrated multi-omics studies confirm the involvement of host genetic effects in reshaping a stress-alleviating root microbiome during drought, and provide mechanistic insights into Rhizobiaceae mediated abiotic stress protection.

ОСОБЛИВОСТІ ПСИХОЛОГІЧНОГО ІМУНІТЕТУ УКРАЇНСЬКИХ КОМБАТАНТІВ ТА ЧЛЕНІВ ЇХНІХ РОДИН: ТЕОРЕТИЧНІ АСПЕКТИ

The article is devoted to the analysis of the problem of psychological immunity of active Ukrainian military personnel and their families. The psychological immune system is a multidimensional but integrated unit of personal resources of resilience and adaptive capacities, also called "psychological antibodies", which provide immunity against stress and traumatic events. Under martial law, the Ukrainian military is the most important asset in countering armed aggression. Their psychological immunity can ensure effective stress management and protect them from possible psychopathology. Promotion of resources (psychological antibodies) will help active military personnel, as well as their family members, to use and overcome their traumatic experiences, stress and negative influences in a useful and productive way, including creating support networks, learning new skills, and achieving combatant goals during combat missions. It is justified that the return of a vital sense of security for successful recovery and functioning depends on the presence of psychological immunity not only among servicemen, but also among their families as a center of rehabilitation potential. The three-component structure of psychological immunity according to A.Olakh is described, which includes: the approach-conviction subsystem, the monitoring-creation-execution subsystem and the self-regulation subsystem. These subsystems make it possible to recognize one's environment, search for and activate the necessary resources for constructive interaction with it, and maintain emotional equanimity. Based on the experience of communicating with active military personnel, veterans, and members of their families, the authors propose to add a fourth component to the existing structural model - the spiritual and value subsystem. The allocation of this component is due to the peculiarities of Ukrainian identity and the specifics of the Russian-Ukrainian war. This component includes the spiritual self, the values of patriotism, moral qualities and religiosity (as an internal need to believe).

Mental Health Risk and Protection Among First-Generation Latinx Immigrant Youth: A Latent Profile Analysis.

First-generation Latinx immigrant youth from the Northern Triangle (NT; El Salvador, Guatemala, and Honduras) face unique risks for experiencing stressors across the phases of migration, which could exacerbate their mental health. This study aimed to (a) identify and characterize unique latent profile groups based on response patterns to immigrant minority stress and psychosocial protective factor items and (b) examine the associations of latent profile membership with depression and anxiety symptoms among NT immigrant youth, controlling for study covariates (i.e., postmigration victimization and forced immigration-related family separation). Primary surveys assessing immigrant minority stress and psychosocial protective factors (i.e., ethnic identity importance, and family, peer, and school support) were administered (N = 172, age range = 14-21, 63% female). Latent profile analysis (Aim 1) and multiple linear regression (Aim 2) were conducted to examine the study aims. A three latent profile model was identified: (a) moderate immigrant minority stress and low psychosocial protection (weak resources), (b) moderate immigrant minority stress and moderate psychosocial protection (average resources), and (c) low immigrant minority stress and high psychosocial protection (strong resources) during postmigration. Multiple linear regression demonstrated that latent profile membership was significantly associated with mental health. Protective associations with mental health were consistently present among the strong resources group. Detrimental associations with mental health were consistently present among the weak resources group. The average resources group demonstrated both protective and detrimental associations with mental health. Postmigration victimization and forced immigration-related family separation covariates were significantly associated with mental health. Findings provide a foundation for further mental health prevention research with NT immigrant youth.

The master regulator OxyR orchestrates bacterial oxidative stress response genes in space and time

Bacteria employ diverse gene regulatory networks to survive stress, but deciphering the underlying logic of these complex networks has proved challenging. Here, we use time-resolved single-cell imaging to explore the functioning of the E.coli regulatory response to oxidative stress. We observe diverse gene expression dynamics within the network. However, by controlling for stress-induced growth-rate changes, we show that these patterns involve just three classes of regulation: downregulated genes, upregulated pulsatile genes, and gradually upregulated genes. The two upregulated classes are distinguished by differences in the binding of the transcription factor, OxyR, and appear to play distinct roles during stress protection. Pulsatile genes activate transiently in a few cells for initial protection of a group of cells, whereas gradually upregulated genes induce evenly, generating a lasting protection involving many cells. Our study shows how bacterial populations use simple regulatory principles to coordinate stress responses in space and time. A record of this paper's transparent peer review process is included in the supplemental information.

Ascophyllum nodosum Extract Improves Olive Performance Under Water Deficit Through the Modulation of Molecular and Physiological Processes.

The olive tree is well adapted to the Mediterranean climate, but how orchards based on intensive practices will respond to increasing drought is unknown. This study aimed to determine if the application of a commercial biostimulant improves olive tolerance to drought. Potted plants (cultivars Arbequina and Galega) were pre-treated with an extract of Ascophyllum nodosum (four applications, 200 mL of 0.50 g/L extract per plant), and were then well irrigated (100% field capacity) or exposed to water deficit (50% field capacity) for 69 days. Plant height, photosynthesis, water status, pigments, lipophilic compounds, and the expression of stress protective genes (OeDHN1-protective proteins' dehydrin; OePIP1.1-aquaporin; and OeHSP18.3-heat shock proteins) were analyzed. Water deficit negatively affected olive physiology, but the biostimulant mitigated these damages through the modulation of molecular and physiological processes according to the cultivar and irrigation. A. nodosum benefits were more expressive under water deficit, particularly in Galega, promoting height (increase of 15%) and photosynthesis (increase of 34%), modulating the stomatal aperture through the regulation of OePIP1.1 expression, and keeping OeDHN1 and OeHSP18.3 upregulated to strengthen stress protection. In both cultivars, biostimulant promoted carbohydrate accumulation and intrinsic water-use efficiency (iWUE). Under good irrigation, biostimulant increased energy availability and iWUE in Galega. These data highlight the potential of this biostimulant to improve olive performance, providing higher tolerance to overcome climate change scenarios. The use of this biostimulant can improve the establishment of younger olive trees in the field, strengthen the plant's capacity to withstand field stresses, and lead to higher growth and crop productivity.

Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Diabetic Retinopathy: An Attractive but Elusive Choice for Drug Development.

Owing to its promiscuous roles, poly (ADP-ribose) polymerase-1 (PARP-1) is involved in various neurological disorders including several retinal pathologies. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus affecting the retina. In the present review, we highlight the importance of PARP-1 participation in pathophysiology of DR and discuss promising potential inhibitors for treatment. A high glucose level enhances PARP-1 expression; PARP inhibitors have gained attention due to their potential therapeutic effects in DR. They target different checkpoints (blocking nuclear transcription factor (NF-κB) activation; oxidative stress protection, influence on vascular endothelial growth factor (VEGF) expression, impacting neovascularization). Nowadays, there are several improved clinical PARP-1 inhibitors with different allosteric effects. Combining PARP-1 inhibitors with other compounds is another promising option in DR treatments. Besides pharmacological inhibition, genetic disruption of the PARP-1 gene is another approach in PARP-1-initiated therapies. In terms of future treatments, the limitations of single-target approaches shift the focus onto combined therapies. We emphasize the importance of multi-targeted therapies, which could be effective not only in DR, but also in other ischemic conditions.

Elucidation of Spartina dimethylsulfoniopropionate synthesis genes enables engineering of stress tolerant plants

The organosulfur compound dimethylsulfoniopropionate (DMSP) has key roles in stress protection, global carbon and sulfur cycling, chemotaxis, and is a major source of climate-active gases. Saltmarshes are global hotspots for DMSP cycling due to Spartina cordgrasses that produce exceptionally high concentrations of DMSP. Here, in Spartina anglica, we identify the plant genes that underpin high-level DMSP synthesis: methionine S-methyltransferase (MMT), S-methylmethionine decarboxylase (SDC) and DMSP-amine oxidase (DOX). Homologs of these enzymes are common in plants, but differences in expression and catalytic efficiency explain why S. anglica accumulates such high DMSP concentrations and other plants only accumulate low concentrations. Furthermore, DMSP accumulation in S. anglica is consistent with DMSP having a role in oxidative and osmotic stress protection. Importantly, administration of DMSP by root uptake or over-expression of Spartina DMSP synthesis genes confers plant tolerance to salinity and drought offering a route for future bioengineering for sustainable crop production.

Gene Regulatory Network Analysis of Decidual Stromal Cells and Natural Killer Cells.

Human reproductive success relies on the proper differentiation of the uterine endometrium to facilitate implantation, formation of the placenta, and pregnancy. This process involves two critical types of decidual uterine cells: endometrial/decidual stromal cells (dS) and uterine/decidual natural killer (dNK) cells. To better understand the transcription factors governing the in vivo functions of these cells, we analyzed single-cell transcriptomics data from first-trimester terminations of pregnancy, and for the first time conducted gene regulatory network analysis of dS and dNK cell subpopulations. Our analysis revealed stromal cell populations that corresponded to previously described in vitro decidualized cells and senescent decidual cells. We discovered new decidualization driving transcription factors of stromal cells for early pregnancy, including DDIT3 and BRF2, which regulate oxidative stress protection. For dNK cells, we identified transcription factors involved in the immunotolerant (dNK1) subpopulation, including IRX3 and RELB, which repress the NFKB pathway. In contrast, for the less immunotolerant (dNK3) population we predicted TBX21 (T-bet) and IRF2-mediated upregulation of the interferon pathway. To determine the clinical relevance of our findings, we tested the overrepresentation of the predicted transcription factors target genes among cell type-specific regulated genes from pregnancy disorders, such as recurrent pregnancy loss and preeclampsia. We observed that the predicted decidualized stromal and dNK1-specific transcription factor target genes were enriched with the genes downregulated in pregnancy disorders, whereas the predicted dNK3-specific targets were enriched with genes upregulated in pregnancy disorders. Our findings emphasize the importance of stress tolerance pathways in stromal cell decidualization and immunotolerance promoting regulators in dNK differentiation.

Chronic Kidney Disease and Oxidative Stress

Abstract Disturbance of the balance between production of oxygen free radicals (or some other radical species) and activity of antioxidative system of protection causes the so called oxidative stress Protection of an organism from oxygen free radicals implies activity of enzymatic (catalase, SOD, glutathione peroxidase, glutathione reductase etc.) and nonenzymatic (vitamin E. vitamin C. glutathione, uric acid etc.) systems of protection. An organism can tolerate a mild oxidative stress but a higher disturbance between the production of free radicals and the activity of the antioxidative protection results in lipid protein and DNA as well as numerous diseases. In this article we analyze oxidative stress role as an important cofactor contributing to endothelial dysfunction, inflammation, atherosclerosis, glomerulosclerosis, anemia, tubulointerstitial nephritis and ischemia-reperfusion injury to chronic kidney disease patients.

Analyzing thermal‐moisture comfort and thermal protective performance of phase change materials dripped protective clothing

AbstractThe objective of the study was to alleviate the thermal‐moisture comfort (TMC) of phase change material (PCM) thermal protective clothing, while simultaneously enhancing thermal protective performance (TPP) by a drip molding process. Nine types of PCM dripped fabrics were prepared by the drip molding process and served as comfort layers of thermal protective clothing. The TMC and TPP of the fabric systems were measured. A new method was proposed to balance the TMC and TPP of thermal protective clothing. The results demonstrated that the drip molding process marginally weakened the TMC while substantially enhancing the TPP of fabric systems. But the TMCs of the PCM dripped fabrics were far larger than the PCM coated fabric. Specifically, an increase in droplet diameter led to a decline in TMC and an improvement in TPP, whereas an increase in droplet interval resulted in an enhancement in TMC and a decrease in TPP. The findings obtained in this study can be used to engineer fabric systems that provide better protection for heat stress and skin burns.