Introduction to Cellular Response

GB004 is a small molecule that stabilizes hypoxia inducible factor (HIF-1α), a key transcription factor involved in the cellular responses at the intersection of hypoxia and inflammation.

In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions.

These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.

The cellular response to misfolded proteins is well-known as the unfolded protein response (UPR) and it is partially concomitant with the response to lipid peroxidation.

G protein-coupled receptors (GPCR) are seven-transmembrane domain receptors that initiate various cellular responses and regulate homeostasis.

In the 35+ years since cysteinyl-LTs were reported to mediate antigen-induced constriction of bronchi in tissue from asthma patients, numerous cellular responses evoked by the LTs, such as chemoattraction and G protein-coupled receptor (GPCR) activation, have been elucidated and revealed a potential for 5-lipoxygenase (5-LOX) as a promising drug target that goes beyond asthma.

As a protective cellular response, DNA breaks result in p53-mediated cell cycle arrest and activation of cell death programs4,5.

Treatment with AMG232 upregulated both cell cycle arrest and apoptotic cellular responses, as measured by annexin V/PI staining and immunoblotting.

These results suggest that viperin is required to enhance the antiviral cellular response with a possible role to position the peroxisome at the mitochondrial/MAM MAVS signaling synapse, furthering our understanding of the importance of multiple organelles driving the innate immune response against viral infection.

Altered molecules were discovered to be enriched in the apoptotic process, innate immune response, and NF-κB transcription factor activity in BZ, as well as chemical synaptic transmission, axon, collagen binding, cell adhesion, response to carbohydrate, laminin binding, and cellular response to nitric oxide in the hippocampus.

Components of the kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway, which regulates cellular response to oxidative stress, are mutated in approximately 30% of non-small-cell lung cancers (NSCLC); therefore, we tested the hypothesis that KEAP1 is required for artesunate sensitivity in NSCLC.

Main body Two of the main players in the molecular and cellular response to OS are NRF2, the transcription nuclear factor erythroid 2-related factor 2, and its principal negative regulator, KEAP1, Kelch-like ECH (erythroid cell-derived protein with CNC homology)-associated protein 1.

Some G protein alpha subunits contain a mitogen-activated protein kinase (MAPK) docking motif (D-motif) near the amino terminus that can impact cellular responses to external signals.

Phosphorylated mitogen-activated protein kinase is the last component of the cascade pathway and activates cellular responses.

It also may has cellular response to tumor necrosis factor (GO:0071356).

Tumor necrosis factor (TNF-α) is a representative cytokine family known to induce multiple signaling cascades leading to various cellular responses, such as cell death, survival, and differentiation.

Functional enrichment analysis showed that biological processes such as cellular response to drugs and pathways such as bladder cancer were mainly regulated by the Salvia miltiorrhiza active ingredient targets.

Functional enrichment analysis showed that resistant genes mainly involved in cellular response to oxygen-containing compound and regulation of cell proliferation, while sensitive genes mainly involved in positive regulation of macromolecule biosynthetic process and regulation of apoptotic process.

Recent studies have profiled the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggest that cellular responses to viral challenge may affect disease severity.

A novel coronavirus related to a condition known as a severe acute respiratory syndrome (SARS) was termed as SARS Coronavirus-19 (SARS-CoV-2 or COVID-19), which has caused an unprecedented global pandemic While the mode of COVID-19 infection, its structural configuration, and multiple mechanisms of action including the critical roles of spike proteins have been substantially explored, elucidation of signaling pathways regulating its cellular responses is yet to be fully determined Among major signaling cascades, phosphoinositide 3-kinases (PI3K) and its downstream pathways have been exploited as the potential therapeutic targets for COVID-19, and its activation induces the release of cytokines such as interleukin-8 (IL-8) To that end, the current studies were sought to determine SARS-CoV-2 spike S1 subunit protein (referred to as COVID-19) on PI3K agonist, phorbol myristate acetate (PMA)-mediated IL-8 release Given that multiple cell types including epithelial lining of the nasal, bronchial and alveolar cells have been found to be primarily affected by COVID-19, we used nasopharyngeal carcinoma, KBP and non-small cell lung cancer, A549 cell lines for our studies We observed that treatments with only PMA but not COVID-19 were able to induce dose-dependent IL-8 release from both KBP and A549 cell lines Our next studies determined the effects of COVID-19 pretreatment with PMA and vice versa to evaluate if any of this combination would exert synergistic effect on IL-8 release We observed no significant differences in IL-8 release with either of these combinations when compared with PMA-alone group However, significantly increased IL-8 release was noticed by PMA + COVID-19 combination when compared with COVID-19-alone group Overall, these studies indicate that PI3K signaling does not directly mediate COVID-19-induced IL-8 release in these cellular models.

Six functional co-expression modules were enriched in various biological processes, such as cell adhesion, regulation of cell motility and cellular response to vascular endothelial growth factor stimulus.

We identified several differentially expressed angiogenesis pathways, including artery morphogenesis, regulation of endothelial cell chemotaxis, and cellular response to vascular endothelial growth factor stimulus.

Different cells, including bone forming osteoblasts, express multiple P2 receptors; however, how P2X and P2Y receptors interact in generating cellular responses to various doses of [ATP] remains poorly understood.

Serine contributes to various cellular responses, but the role in inflammatory responses remains poorly understood.

In this study, an anti-receptor binding domain (RBD) antibody assay and an INFγ-release assay (IGRA) were used to detect humoral and cellular responses to the Pfizer-BioNTech BNT162b2 vaccine in three separate cohorts of COVID-19-naïve patients: 108 healthcare workers (HCWs), 15 elderly people, and 5 autoimmune patients treated with immunosuppressive agents.

Here, we present a new nanovaccine that comprising the Receptor-Binding Domain (RBD) of spike protein and the manganese nanoadjuvant (MnARK), which induces humoral and cellular responses.

The GO enrichment analysis results showed that the BXD anti-cancer and anti-inflammatory mechanism mainly involves cellular response to organic cyclic compound, response to toxic substance, response to oxidative stress, cellular response to nitrogen compound, response to inorganic substance, and others.

GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity and other functions.

Methods SARS-CoV-2-specific humoral and cellular responses were assessed in convalescent coronavirus disease 2019 (COVID-19) patients at one-year post-infection.

METHODS In a prospective cohort of 100 SARS-CoV-2 naïve healthcare professionals who received two doses of CoronaVac, we analyzed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8-10 weeks post the booster dose (T4).

The post-myocardial infarction scar environment is an example of note where mechanically insufficient collagen can result in impaired cardiac function and possibly tissue rupture due to post-MI cellular response and matrix interactions.

The post-myocardial infarction scar environment is an example of note where mechanically insufficient collagen can result in impaired cardiac function and possibly tissue rupture due to post-MI cellular response and matrix interactions.

Gene Ontology (GO) analysis indicated that the target genes for the screened lncRNAs were most enriched in three-terms: regulation of protein serine/threonine kinase activity, pertussis, and cellular response to LPS.

The ATM protein is a serine/threonine kinase and plays a central role in the cellular response to DNA damage, particularly DNA double-strand breaks.

Results Among the upregulated different acetylation proteins (DAPs), the biological process of GO analysis was closely related to cellular response to regulation of apoptotic process, and regulation of programmed cell death.

For Pingan 8, lower expression of TaNramp6 and Cd-induced programmed cell death in cortex lead to its weaker Cd uptake capacity; while for Bainong 160, there are stronger positive cellular responses to Cd stress, including severe lignification in cortex cell, casparian strip formation, increment of both GSH and phytochelatins, and significant increased expression of TaHMA3 and repressed expression of TaHMA2, which together result in its stronger Cd retention in root and so as to inhibit Cd root-to-shoot transfer.

Enrichment analyses found different signaling pathways: immediate changes including cell response to heat, regulation of cellular response to stress, heat shock protein binding, chaperon-mediated protein folding, and sterol biosynthetic process, but prolonged changes mainly involving cell cycle, regulation of apoptotic process/cell proliferation, reproductive process, P53, PI3K-Akt and Glycolysis/Gluconeogenesis.

The induction of highly conserved heat shock protein 70 (HSP70) is often related to a cellular response due to harmful stress or adverse life conditions.

Here, we derive human brain organoids with innately developing microglia to investigate the cellular responses to SARS-CoV-2 infection on a single cell level.

Thus, our findings suggest that DoNick-seq facilitates high-throughput functional dissection of complex cellular responses at the single-cell level and increases the accuracy of CRISPR single-cell transcriptomics.

Simple Summary The transcription factor p53 is a crucial tumor suppressor that regulates diverse cellular responses to protect against cancer development.

As a key tumor suppressor and transcription factor, p53 responds to a wide variety of stress signals, including hypoxia, and selectively transcribes its target genes to regulate various cellular responses to exert its function in tumor suppression.

AMP-activated protein kinase (AMPK) plays a key role in the cellular response to low energy stress and has emerged as an attractive therapeutic target for tackling metabolic diseases.

Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.

As this process generates a significant amount of pathogen-associated molecular patterns, this phylum of viruses can result in a robust induction of the intrinsic host cellular response.

These cellular responses are initiated when conserved pathogen components, known as pathogen-associated molecular patterns (PAMPs), are recognized by pattern-recognition receptors (PRRs), which include members of the C-type lectin receptor (CLR) family that are able to bind to fungal cell wall-derived carbohydrates.

The upregulated 108 genes were significantly enriched in the cell adhesion, cellular response to interleukin-1, positive regulation of transcription from DNA/RNA, and transcription, extracellular matrix/region, anchored membrane component, cell junction and golgi membrane, sequence-specific DNA binding, transcription factor activity, RNA polymerase II regulatory region, and DNA binding.

GO results showed that cellular response to drug, response to oxygen levels, response lipopolysaccharide, and response to molecule of bacterial origin in biological process (BP) category; membrane, transcription regulator complex, nuclear chromatin, postsynaptic membrane, and vesicle lumen in cellular component (CC) category; DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA-binding transcription activator activity, and cytokine receptor binding in molecular function (MF) terms.

Ca2+-based second messenger signaling is used by many signal perception mechanisms to modulate specific cellular responses.

In this review, multiple modes of endothelium-derived blood flow regulation will be discussed, including chemical control of vascular tone, heterotypic and homotypic cell-cell interactions, second messenger signaling and cellular response to physical forces and inflammatory mediators.

The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that multiple biological pathways, including immune response, inflammatory response and cellular response to interleukin-1, as well as signaling pathways, such as tumor necrosis factor signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway and nuclear factor kappa B signaling pathway were implicated in the TBI.

The DE mRNAs were significantly enriched in immune response, inflammatory response, leukocyte migration, cell cycle, cellular response to interleukin-1, IL-17 signalling pathway, cytokine–cytokine receptor interaction and Toll-like receptor signalling pathway.

We chose seven significant pathways (Cellular response to interleukin-1, Chemokine-mediated signaling pathway, Chemokine signaling pathway, Cytokine-cytokine receptor interaction, Inflammatory response, Immune response, TNF signaling pathway) for downstream analysis.

In addition, most of the DEGs were found to be significantly enriched in the GO terms cellular response to extracellular stimulus, response to extracellular stimulus, auxin mediated signaling pathway, cellular response to chemical stimulus and response to oxidative stress through GO enrichment analysis.

With regard to the intestinal barrier’s cellular response to oxidative stress, the activity of the antioxidant gene SOD1 was decreased in a dose-dependent manner.

Wnt gradients elicit distinct cellular responses, such as proliferation, specification, differentiation and survival in a dose-dependent manner.

The up-regulated expressed genes were analyzed through GO and the results demonstrated that biological processes of the up-regulated expressed genes included apoptotic process, cellular response to DNA damage stimulus, aging, and protein ubiquitination; the cellular component of the up-regulated expressed genes included cytoplasm, cytoskeleton, and nucleus; and the molecular function of the up-regulated expressed genes included ubiquitin-protein transferase activity and hydrolase activity.

Based on RNA-seq results, CCFM1148 and CCFM1147 inhibited TNF-α-induced activation of the nuclear factor kappa-B (NF-κB) signaling pathway and altered the cellular response to interleukin (IL)-8, while the two control strains did not.

Parvovirus B19 virus-like particles (B19-VLPs) formed of VP2 protein had been shown to be an effective multi-neoepitope delivery system capable of inducing specific cellular responses towards coupled antigens and reducing tumour growth and lung metastases in triple negative breast cancer mouse model.

tuberculosis-specific cellular responses due to dynamic changes of latent TB infection during pregnancy.

G protein-coupled receptors (GPCR) are seven-transmembrane domain receptors that initiate various cellular responses and regulate homeostasis.

Tumor necrosis factor (TNF-α) is a representative cytokine family known to induce multiple signaling cascades leading to various cellular responses, such as cell death, survival, and differentiation.

We discuss how SWEET17 activity integrates drought-induced cellular responses into fructose signaling necessary for modulation of the root system and maximal drought tolerance.

These data show that TNBC models with wild type versus mutant BRCA1 exhibit differences in CDDP-induced cellular response pathways, however, the CDDP-induced signaling responses remain stable across the isogenic models of OlaR from the same lineage.

This kinase forms the central core of two distinct complexes, mTORC1 and mTORC2, which share the ability of integrating environmental, nutritional, and hormonal cues but which regulate separate molecular pathways that result in different cellular responses.

In summary, our findings suggested that sequential order and effective dose of drug administration in VPA-ETO combination therapy could induce different cellular responses in melanoma cells.

The p75 neurotrophin receptor (p75NTR) is a multifunctional protein that regulates cellular responses to pathological conditions in specific regions of the nervous system.

Human adenosine deaminase acting on RNA 1 (ADAR1) catalyzes adenosine-to-inosine deamination reactions on double-stranded RNA molecules to regulate cellular responses to endogenous and exogenous RNA.

pylori induces a strong host cellular response represented by induction of a set of molecular signaling pathways, expression of proinflammatory cytokines and changes in proliferation.

The PGRS domains of these proteins have been hypothesized to consist of Ca2+ binding motifs that help these intrinsically disordered proteins to modulate the host cellular responses.

Finally, we have investigated how re-stretch of a fibril affects cellular response.

Extracellular reactive oxygen and nitrogen species (RONS) in plasma-activated solutions are key factors for the anti-tumor effects, and amino acid modifications by LTP may affect cellular responses.

Conclusions: In the bloodstream, EchA can mediate cellular responses, act as a radical scavenger, and activate the glutathione pathway.

Current knowledge on how hypoxia levels are sensed by cancer cells and mediate cellular responses that promote treatment resistance is comprehensive.

We focus here on MAPK ERK1/2 signaling that accounts for diverse cellular responses such as cell cycle progression, proliferation, differentiation, senescence, migration, formation of GAP junctions, cell adhesion, cell motility, survival and apoptosis.

New insights from these studies suggest that STING functions as a hub that converts multiple environmental cues into diverse cellular responses rather than acts as a simple IFN-producing machine.

These distinct cellular responses generate a system-scale signaling network that helps in generating a specific organ phenotype.

ABSTRACT Upon activation by different transmembrane receptors, the same signaling protein can induce distinct cellular responses.

These findings suggest a role for Panx3 in mediating the adaptive cellular responses to altered mechanical stress in the IVD, which may buffer aberrant loads transferred to adjacent motion segments.

Mitogen activated protein kinase (MAPK) signaling pathways execute essential functions in eukaryotic organisms by transducing extracellular stimuli into adaptive cellular responses.

More recently, the three-dimensional (3-D) chromatin organization was found to be important for determining genome functionality, finely tuning physiological processes for appropriate cellular responses.

This is a particularly acute challenge to the lungs, where differences in the partial pressure of oxygen (PO2) in the circulation and inspired air must be integrated to ensure appropriate cellular responses and maintain tissue homeostasis.

Disruption of this mechanical homeostasis by tissue injury elicits multiple cellular responses leading to pathological matrix deposition and tissue stiffening, and consequent evolution toward pro-inflammatory/pro-fibrotic phenotypes, leading to tissue/organ fibrosis.

By exposing live cells cultured on a plasmonic metasurface to chemical compounds, we show that MEIRS can be used as a label-free phenotypic assay for detecting multiple cellular responses to external stimuli: changes in cell morphology, adhesion, lipid composition of the cellular membrane, as well as intracellular signaling.

Ca2+ is a versatile intracellular messenger involved in sensing a wide variety of stresses and regulating the subsequent cellular responses.

ABSTRACT Vitamin D is known to elicit many biological effects in diverse tissue types and is thought to act almost exclusively upon its canonical receptor within the nucleus, leading to gene transcriptional changes and the subsequent cellular response.

Glucocorticoids are stress hormones that elicit cellular responses by binding to the glucocorticoid receptor (GR), a ligand-activated transcription factor.

Employing genome-wide cross-linking immunoprecipitation (CLIP) sequencing and a functional CRISPRi screen, we find that ERα-associated mRNAs sustain cancer cell fitness and elicit cellular responses to stress.

Here we established an Axon-on-a-Chip (AoC) model for mimicking DAI and investigating its early cellular responses.

Therefore, early cellular response to seizures in the brain includes induction of the Ntrk2 , Ntrk3 , Ngfr , miRNA-9, and miRNA-29a expression, as well as activation of Bcl-2 and Bax signaling pathways, which may characterize them as important mediators of neuronal adaptation and survival upon induction of the generalized brain activity.

In these 15 years, researches to control cellular responses by light have flourished dramatically to establish "optogenetics" as a research field.

We performed proteomic analysis of rat serum proteins adsorbed on hydroxyapatite (HAp) and α-alumina (α-Al2O3) in order to identify proteins that specifically adsorb onto HAp and control cellular responses.

Nucleocytoplasmic transport of signaling modulators is essential for regulating cellular responses to extracellular stimulation and stress, as well as pathogen infection.

Based on these findings, we propose that substrate stiffness plays a central role in cilia positioning, regulating cellular response to external forces, and may be a key driver of mechanosignalling-associated diseases.

These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.

Our study has provided evidence that neuronal SH-SY5Y cells displayed unique cellular responses upon KSHV infection.

MV, released into the extracellular space, exert paracrine regulation by modulating cellular responses after interaction with near and far target cells.

By modulating cellular responses after injury, it is possible to create local environments that promote wound healing and tissue repair mechanisms.