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Characterization of C-C motif chemokine ligand 4 in the porcine endometrium during the presence of the maternal-fetal interface.

Chemokines and their receptors play a crucial role in embryo implantation at the maternal-fetal interface during pregnancy. In this study, w … n addition, CCL4 recovered the endoplasmic-reticulum stress-reduced proliferation and decreased the unfolded protein response in pLE cells. Besides, the lipopolysaccharide-activated NF-κB pathway was suppressed in response to CCL4 in pLE cells. Inhibition of CCR5 decreased the proliferation of pLE cells and activation of the PI3K and MAPK pathways by CCL4. Furthermore, CCL …

Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells.

Endoplasmic reticulum (ER) stress is associated with chronic pulmonary inflammatory diseases. We hypothesized that the combined activation o … on, and pharmacological inhibition of these kinases could inhibit the boosting effect. Knockdown of unfolded protein response signaling indicated that mainly PERK and ATF6 were responsible for the synergistic activity. Specifically, PERK and ATF6 mediated increased MAPK activation, which is needed for effective cytokine secretion. We conclude that within airway epithelial …

Endoplasmic reticulum stress: implications for inflammatory bowel disease pathogenesis.

PURPOSE OF REVIEW: To provide an overview of the emerging role of cellular stress responses in inflammatory bowel disease (IBD). RECENT FINDINGS: The unfolded protein response (UPR) is a primitive cellular pathway that is engaged when responding to endoplasmic reticulum stress and regulates autophagy. Highly secretory cells such as Paneth cells and goblet cells in the intestines are particularly susceptible to endoplasmic reticulum stress and are exceedingly dependent upon a properly functioning UPR to maintain cellular viability and homeostasis. Primary genetic abnormalities within the compo…

Werner syndrome exonuclease promotes gut regeneration and causes age-associated gut hyperplasia in Drosophila.

Human Werner syndrome (adult progeria, a well-established model of human aging) is caused by mutations in the Werner syndrome (WRN) gene. Ho … a WRN homologue (WRNexo) binds to Heat shock 70-kDa protein cognate 3 (Hsc70-3/Bip) to regulate the unfolded protein response of the endoplasmic reticulum (UPRER). Activation of the WRNexo-mediated UPRER in ISCs is required for ISC proliferation during injury repair. However, persistent DNA damage during aging leads to chronic upregulation of WRNexo in ISCs, where excessiv …

UPRmt-regulated mitokines: novel strategies for myocardial injury repair.

Cardiac mitochondria generate ATP, via oxidative phosphorylation (OXPHOS) to sustain continuous and forceful myocardial contraction, thereby meeting systemic metabolic demands. Mitochondrial biogenesis and energy metabolism depend on proteostasis, which can be disrupted by stressors such as hypoxia, leading to impaired cardiac function. As a result, the study of mitochondrial energy metabolism and proteostasis under stress has become a key focus in cardiovascular research. The mitochondrial unfolded protein response (UPRmt) plays a "double-edged sword" role-either protective or detrimental-dep…

Sephin1 reduces TDP-43 cytoplasmic mislocalization and improves motor neuron survival in ALS models.

A pathological hallmark of ALS is the abnormal accumulation of misfolded proteins (e.g., TDP-43) and enlarged endoplasmic reticulum (ER), indicating ER stress. To resolve this stress, cells initiate the Unfolded Protein Response (UPR). However, unresolved stress leads to apoptosis. In ALS, UPR activation fails to resolve proteostasis impairment. UPR activation modulators, among them Sephin1, reduce protein aggregates and improve motor neuron survival in ALS models. We demonstrate that following glutamate intoxication, Sephin1 increases motor neuron survival by reducing mitochondria ROS product…

Brucella abortus induces dynamin-related protein 1 (DRP1)-dependent mitochondrial fission in infected macrophages via stress sensor IRE1α altering metabolic function.

Brucella abortus exploits the endoplasmic reticulum as a site for replication, triggering the unfolded protein response (UPR). While various pathogens have developed strategies to manipulate mitochondrial dynamics, the mechanisms underlying bacterial infection and mitochondrial dynamics interactions remain poorly understood. Here, we demonstrate that B. abortus induces mitochondrial fragmentation via IRE1α. Our findings reveal that Brucella-induced mitochondrial fission is mediated by dynamin-related protein 1 (DRP1), a pivotal regulator of mitochondrial fission. Moreover, we have demonstrated…

Широкие повреждения обода являются новым патологическим и визуализированным биомаркером для быстрого развития заболеваний в множестве склерозов.

Текущее несколько методов лечения склероза (MS) сокращают активность рецидивов, но оказывают ограниченное воздействие на прогрессию заболеваний. Клинические испытания, ориентированные на прогресс, часто не дают результатов из-за недостаточного понимания его основополагающих механизмов. В этом исследовании анализировалась клинически хорошо известная когорта вскрытия MS из банка мозга Негерланда (186 человек), из которого мы отобрали доноров, проявляющих противоположные траектории заболеваний медленных и быстрых темпов развития. Мы провели обширную непредвзятую гистологию и пространственную тран

Совпадение в аннотации оригинала
Current multiple sclerosis (MS) treatments reduce relapse activity but have limited impact on disease progression. Clinical trials targeting … lular and transcriptional signatures of innate immune activation, inflammatory cytokine production, unfolded protein response and apoptosis. Presence of this particular lesion type was linked to rapid disease progression. An independent translocator protein 18-kDa positron emission tomography study (114 individuals) validates the association between lesions with a broad my …

Tumor necrosis factor-stimulated gene-6 inhibits endoplasmic reticulum stress in the ischemic mouse kidney.

Kidney tissue injury in renal artery stenosis (RAS) involves inflammation, endoplasmic reticulum stress (ERS), and mitochondria damage. Tumo … -related molecules were downregulated after TSG-6 treatment, while most indicators of mitochondrial unfolded protein response remained unaltered. Therefore, TSG-6 alleviates inflammation, ERS, apoptosis, and fibrosis in the post-stenotic mouse kidney. These observations position TSG-6 as a potential therapeutic tool in RAS.

The endoplasmic reticulum stress sensor IRE1 regulates collagen secretion through the enforcement of the proteostasis factor P4HB/PDIA1 contributing to liver damage and fibrosis.

Collagen is one the most abundant proteins and the main cargo of the secretory pathway, contributing to hepatic fibrosis and cirrhosis due to excessive deposition of extracellular matrix. Here we investigated the possible contribution of the unfolded protein response, the main adaptive pathway that monitors and adjusts the protein production capacity at the endoplasmic reticulum, to collagen biogenesis and liver disease. Genetic ablation of the ER stress sensor IRE1 reduced liver damage and diminished collagen deposition in models of liver fibrosis triggered by carbon tetrachloride (CCl 4 ) ad…

Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies.

Endemic Burkitt lymphoma (BL) is a childhood cancer in sub-Saharan Africa characterized by Epstein-Barr virus and malaria-associated aberran … model exhibiting direct sensitivity, characterized by apoptotic gene expression counterbalanced by unfolded protein response and mTOR pro-survival pathways. In rituximab-unresponsive tumors, we observed an IFN-α signature confirmed by the expression of IRF7 and ISG15. Our results demonstrate significant inter-patient tumor variation and heterogeneity, and that contemporar …

GJA8 missense mutation disrupts hemichannels and induces cell apoptosis in human lens epithelial cells.

Autosomal dominant congenital cataract (ADCC), the most common hereditary disease, is a major cause of eye disease in children. Due to its h … enging by inhibiting G6PD expression and thus induces cell apoptosis via aberrant activation of the unfolded protein response (UPR). In conclusion, we report a novel GJA8 heterozygous mutation in a Chinese family with a vital role in ADCC, broadening the genetic spectrum of this disease.

Lafora Disease: A Ubiquitination-Related Pathology.

Lafora disease (LD, OMIM254780) is a rare and fatal form of progressive myoclonus epilepsy (PME). Among PMEs, LD is unique because of the ra … athways, such as intracellular protein degradation, oxidative stress, and the endoplasmic reticulum unfolded protein response. In this work we review the possible cellular functions of laforin and malin with a special focus on their role in the ubiquitination of specific substrates. We also discuss here the pathological consequences of defects in laforin or malin functions …

The effect of Tmem135 overexpression on the mouse heart.

Tissues with high-energy demand including the heart are rich in the energy-producing organelles, mitochondria, and sensitive to mitochondria … ation and hypertrophy. The gene expression analysis showed that genes associated with ER stress and unfolded protein response, and especially the pathway involving activating transcription factor 4, are upregulated in the heart of Tmem135 transgenic mice. It also showed that gene expression changes in the heart of Tmem135 transgenic mice significantly overlap with those of …

Two novel mutations identified in ADCC families impair crystallin protein distribution and induce apoptosis in human lens epithelial cells.

Congenital cataract (CC) is a clinical and genetically heterogeneous eye disease that primarily causes lens disorder and even amblyopic blin … erdispersion of CRYAA. Furthermore, these two crystallin mutations result in aberrant expression of unfolded protein response (UPR) marker genes as well as apoptosis in HLEpiCs. Collectively, these findings broaden the genetic spectrum of ADCC.

The Sec domain protein Scfd1 facilitates trafficking of ECM components during chondrogenesis.

Chondrogenesis in the developing skeleton requires transformation of chondrocytes from a simple mesenchymal condensation to cells with a hig … was found to hinder ER to Golgi transport of ECM proteins and is accompanied with activation of the unfolded protein response in chondrocytes. We further demonstrate a conserved role for Scfd1 in differentiation of mammalian chondrocytes, in which loss of either SCFD1 or STX18, a SLY1 interacting t-SNARE, severely impair transport of type II collagen. These results show th …

Physiological roles of regulated Ire1 dependent decay.

Inositol-requiring enzyme 1 (Ire1) is an important transducer of the unfolded protein response (UPR) that is activated by the accumulation of misfolded proteins in the endoplamic reticulum (ER stress). Activated Ire1 mediates the splicing of an intron from the mRNA of Xbp1, causing a frame-shift during translation and introducing a new carboxyl domain in the Xbp1 protein, which only then becomes a fully functional transcription factor. Studies using cell culture systems demonstrated that Ire1 also promotes the degradation of mRNAs encoding mostly ER-targeted proteins, to reduce the load of inc…

Rheb and mammalian target of rapamycin in mitochondrial homoeostasis.

Mitochondrial dysfunction has been associated with various diseases, such as cancer, myopathies, neurodegeneration and obesity. Mitochondria … signalling to adapt metabolic processes, and highlight how mTORC1 signalling is integrated with the unfolded protein response in mitochondria, which in Caenorhabditis elegans is mediated via transcription factors such as DVE-1/UBL-5 and ATFS-1.

Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives.

Mitochondrial translation is crucial for maintaining cellular respiration, energy balance, calcium signaling, apoptosis, immune surveillance, and the regulation of inflammatory responses. This specialized process, involving mitochondrial rRNAs, tRNAs, mitoribosomes, and nuclear-encoded translation factors, ensures the synthesis of mitochondrially encoded proteins that support oxidative phosphorylation. The mitochondrial translation cycle is tightly regulated by RNA-binding proteins, mitochondrial unfolded protein response, and stress-responsive pathways such as mTOR, particularly during metabo…

Characterization, Formation Mechanism, and Curcumin Delivery of Buckwheat Peptide-Based Emulsion Gels.

This study aimed to construct a natural peptide-based emulsion gel (PG) using small peptides (∼2.2 kDa) by mild enzymatic hydrolysis of buckwheat proteins. The obtained PG presented a porous and tight texture and solid-gel viscoelasticity compared with its parent protein-based emulsion gel. Meanwhile, it exhibited good resistance against heating and freeze-thawing. Furthermore, peptide-oil interaction analysis revealed that the gel matrix was enhanced by the hydrophobic aggregation between peptides and oil molecules, H-bonding interaction of peptide molecules, and peptide-oil aggregate repulsi