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Fibroblast Growth Factor 21 Drives Dynamics of Local and Systemic Stress Responses in Mitochondrial Myopathy with mtDNA Deletions.

Mitochondrial dysfunction elicits stress responses that safeguard cellular homeostasis against metabolic insults. Mitochondrial integrated stress response (ISRmt) is a major response to mitochondrial (mt)DNA expression stress (mtDNA maintenance, translation defects), but the knowledge of dynamics or interdependence of components is lacking. We report that in mitochondrial myopathy, ISRmt progresses in temporal stages and development from early to chronic and is regulated by autocrine and endocrine effects of FGF21, a metabolic hormone with pleiotropic effects. Initial disease signs induce tran…

A miR65-MsbZIP11 post-transcriptional regulatory module coordinates saline-alkali stress tolerance in alfalfa (Medicago sativa L.).

Integrated multi-omics analyses reveal that novel miR65 represses MsbZIP11 and negatively regulates saline-alkali tolerance in alfalfa by impairing photosynthetic maintenance and disrupting redox homeostasis. MicroRNA-mediated post-transcriptional regulation plays an important role in plant adaptation to saline-alkali stress; however, the underlying regulatory modules remain poorly understood in alfalfa (Medicago sativa L.). Here, integrated profiling of small RNAs, the transcriptome, and degradome identified 175 stress-responsive miRNAs and 418 degradome-supported miRNA-mRNA interactions. We

Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast.

Translational control is essential in response to stress. We investigated the translational programmes launched by the fission yeast Schizosaccharomyces pombe upon five environmental stresses. We also explored the contribution of defence pathways to these programmes: The Integrated Stress Response (ISR), which regulates translation initiation, and the stress-response MAPK pathway. We performed ribosome profiling of cells subjected to each stress, in wild type cells and in cells with the defence pathways inactivated. The transcription factor Fil1, a functional homologue of the yeast Gcn4 and th…

Multi-systemic evaluation of biological and emotional responses to the Trier Social Stress Test: A meta-analysis and systematic review.

Humans experience multiple biological and emotional changes under acute stress. Adopting a multi-systemic approach, we summarized 61 studies on healthy people's endocrinological, physiological, immunological and emotional responses to the Trier Social Stress Test. We found salivary cortisol and negative mood states were the most sensitive markers to acute stress and recovery. Biomarkers such as heart rate and salivary alpha-amylase also showed sensitivity to acute stress, but the numbers of studies were small. Other endocrinological (e.g., dehydroepiandrosterone), inflammatory (C-Reactive Prot

Revealing transcriptomic responses in Escherichia coli during early antibiotic exposure.

The earliest responses of pathogenic bacteria to antibiotics can affect the outcome of an infection. While long-term adaptations have been extensively studied, the immediate transcriptional changes that unfold immediately following antibiotic exposure remain poorly understood. Here, we applied iModulon analysis to time-resolved transcriptomic data from Escherichia coli exposed to subinhibitory concentrations of two antibiotics (ampicillin and ciprofloxacin), capturing transcriptional regulatory changes occurring within the first 30 min of exposure. This analysis proposes an integrated, three-p

Ocular Surface Infection Mediated Molecular Stress Responses: A Review.

Infection mediated ocular surface stress responses are activated as early defense mechanisms in response to host cell damage. Integrated stress responses initiate the host response to different types of infections and modulate the transcription of key genes and translation of proteins. The crosstalk between host and pathogen results in profound alterations in cellular and molecular homeostasis triggering specific stress responses in the infected tissues. The amplitude and variations of such responses are partly responsible for the disease severity and clinical sequelae. Understanding the etiol…

Mutant CHCHD10 causes an extensive metabolic rewiring that precedes OXPHOS dysfunction in a murine model of mitochondrial cardiomyopathy.

Mitochondrial cardiomyopathies are fatal diseases, with no effective treatment. Alterations of heart mitochondrial function activate the mitochondrial integrated stress response (ISRmt), a transcriptional program affecting cell metabolism, mitochondrial biogenesis, and proteostasis. In humans, mutations in CHCHD10, a mitochondrial protein with unknown function, were recently associated with dominant multi-system mitochondrial diseases, whose pathogenic mechanisms remain to be elucidated. Here, in CHCHD10 knockin mutant mice, we identify an extensive cardiac metabolic rewiring triggered by prot…

Acute cold stress leads to zebrafish ovarian dysfunction by regulating miRNA and mRNA.

Temperature is a critical factor that regulates the reproduction processes in teleost. However, the gonadal response mechanism to cold stress in fish remains largely unknown. In the present study, female zebrafish were exposed to different extents of low temperatures at 18 °C and 10 °C for 48 h. The ovarian histology was remarkably damaged after cold stress exposure. Integrated analysis of miRNA-mRNA was used to investigate the ovarian response to acute cold stress. A large number of mRNAs and miRNAs were altered by cold stress, which are involved in extensive biological processes. It is indic

Cellular stress leading to epithelial cell dysfunction in Sjögren's syndrome.

Cells are highly compartmentalized entities composed of membranous and nonmembranous structures, where organelles such as the endoplasmic re … smits the alarm, and effectors execute the adaptive action. One of these adaptive mechanisms is the integrated stress response, which is activated by various stress-inducing factors to adjust protein biosynthetic rates and redirect resources to mitigate stress and restore cellular homeostasis. Another adaptive mechanism is the unfolded protein response, which is activated b …

Seasonal and sex differences in responsiveness to adrenocorticotropic hormone contribute to stress response plasticity in red-sided garter snakes (Thamnophis sirtalis parietalis).

As in many vertebrates, hormonal responses to stress vary seasonally in red-sided garter snakes (Thamnophis sirtalis parietalis). For example, males generally exhibit reduced glucocorticoid responses to a standard stressor during the spring mating season. We asked whether variation in adrenal sensitivity to adrenocorticotropic hormone (ACTH) explains why glucocorticoid responses to capture stress vary with sex, season and body condition in red-sided garter snakes. We measured glucocorticoids at 0, 1 and 4 h after injection with ACTH (0.1 IU g(-1)body mass) or vehicle in males and females durin

Cardiolipin preserves Treg metabolic fitness and immune homeostasis in the gut.

Loss of host-microbiota balance promotes gut inflammation, colitis and inflammatory bowel disease. Yet, whether host or microbial factors ar … stically, the absence of cardiolipin impairs Treg cell metabolic fitness and triggers a maladaptive integrated stress response, which can be reversed pharmacologically or genetically, restoring gut homeostasis and extending lifespan in PTPMT1 ΔT mice. Barth syndrome, a genetic disorder marked by severe cardiolipin deficiency, also exhibits gastrointestinal symptoms and infl …

Mechanisms of formic acid stress response in evolved yeast for microbial-electrocatalytic systems.

Integrated electrocatalytic microbial systems (iEMS) offers a sustainable route for carbon cycling. However, formic acid by-product stress severely hinders microbial conversion. Herein, we reveal the adaptive mechanisms of Saccharomyces cerevisiae under formic acid stress during ethanol cultivation through adaptive laboratory evolution and transcriptomic analysis. Formic acid exposure systematically downregulates central carbon metabolism while upregulating the acetaldehyde branch to replenish carbon skeletons. Concurrently, cell cycle genes are activated via MAPK signaling, and ribosomal biog

Integration of reactive oxygen species and hormone signaling during abiotic stress.

Each year, abiotic stress conditions such as drought, heat, salinity, cold and particularly their different combinations, inflict a heavy toll on crop productivity worldwide. The effects of these adverse conditions on plant productivity are becoming ever more alarming in recent years in light of the increased rate and intensity of global climatic changes. Improving crop tolerance to abiotic stress conditions requires a deep understanding of the response of plants to changes in their environment. This response is dependent on early and late signal transduction events that involve important sign

ATF4 and CHOP coordinate endoplasmic reticulum stress-responsive gene programs through enhancer activation and chromatin looping.

Endoplasmic reticulum (ER) stress triggers transcriptional programs that promote either adaptation or apoptosis, yet the epigenetic mechanisms underlying this response remain incompletely understood. Here, integrated multi-omics analyses of unfolded protein response transcription factor knockout cells identify ATF4 as a dominant regulator of ER stress-responsive enhancer activation and chromatin looping. Loss of ATF4 markedly impairs stress-induced H3K27ac accumulation and enhancer-promoter interactions at ATF4-associated regulatory elements, establishing ATF4 as a central organizer of the str

Service Utilization Patterns as Predictors of Response to Trauma-Informed Integrated Treatment for Women With Co-occurring Disorders.

OBJECTIVE: The current study examined whether clinical responses to an integrated treatment intervention among women with co-occurring disorders and histories of abuse varied according to their service use patterns at baseline. METHODS: Data were from a national, multi-site, integrated treatment intervention study in 1998-2003. Analyses included 999 study participants assigned to the integrated treatment group and who were symptomatic at baseline. Participants' baseline service use activity was characterized according to five distinct baseline service use clusters. Logistic regression models e

Stress-activated pathways mediate PFAS effects on human placental syncytiotrophoblast cells.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants associated with placenta-mediated pregnancy complications … spase-dependent apoptosis. PFAS exposure reduced mitochondrial membrane potential and activated the integrated stress response (ISR), as evidenced by eukaryotic initiation factor 2α phosphorylation, activating transcription factor 4 (ATF4) induction, and increased ATF4 target gene expression. In parallel, c-Jun N-terminal kinase (JNK) signaling was activated, as evidenced b …

CYP51-mediated cholesterol biosynthesis is required for the proliferation of CD4+ T cells in Sjogren's syndrome.

CYtochrome P450, family 51 (CYP51) is an important enzyme for de novo cholesterol synthesis in mammalian cells. In the present study, we fou … ing protein 2 (SREBP2) activation in CD4+ T cells. Additionally, ketoconazole treatment elicited an integrated stress response in T cells that up-regulated activating transcription factor 4 (ATF4) and DNA-damage inducible transcript 3 (DDIT3/CHOP) at the translational level. Furthermore, treatment with ketoconazole significantly decreased the amount of CD4+ T cells infiltra …

FGF21 induced by endoplasmic reticulum stress maintains medullary thymic epithelial cell function and central immune tolerance.

Medullary thymic epithelial cells (mTECs) establish central immune tolerance by expressing diverse tissue-restricted antigens and eliminatin … lly within the mature mTEC compartment as a stress-responsive metabolic regulator downstream of the integrated stress response. By limiting sustained stress and preserving protein homeostasis, FGF21 maintained mTEC integrity and central tolerance. These findings identify FGF21 as a key regulator of thymic immune homeostasis and as a potential therapeutic target for autoimmu …

Stress and Liver Fibrogenesis: Understanding the Role and Regulation of Stress Response Pathways in Hepatic Stellate Cells.

Stress response pathways are crucial for cells to adapt to physiological and pathologic conditions. Increased transcription and translation in response to stimuli place a strain on the cell, necessitating increased amino acid supply, protein production and folding, and disposal of misfolded proteins. Stress response pathways, such as the unfolded protein response (UPR) and the integrated stress response (ISR), allow cells to adapt to stress and restore homeostasis; however, their role and regulation in pathologic conditions, such as hepatic fibrogenesis, are unclear. Liver injury promotes fibr…

СТАТ3 ингибирует инъекцию иммуногенной клеточной смерти в множестве миеломы.

В одном из недавних публикаций, опубликованных в журнале " Blood Science " ( < < Кровные науки > > ), Sha et al., сообщается, что STAT3 ингибирует несколько стволовых клеток, похожих на миелому, и одновременно выявляет признаки смерти иммуногенных клеток. Эти очень интригующие выводы связывают ствол, комплексную реакцию на стресс и иммунитет от антитуманков, однако для того, чтобы эта стратегия могла считаться иммуногенной, по-прежнему необходимо подтвердить в vivo.

Совпадение в аннотации оригинала
In a recent paper published in Blood Science, Sha et al. report that STAT3 inhibition eliminates multiple myeloma stem-like cells while eliciting hallmarks of immunogenic cell death. These highly intriguing findings connect stemness, integrated stress response, and antitumor immunity, yet in vivo validation remains necessary before this strategy can be consi…