small vs WBbt:0004017

The arginine-dependent production of nitric oxide (NO), which is strongly inhibited by methylarginines, serves as a protective small molecule against oxidative stress in eukaryotic cells.

Anti-alpha4 antibody but not anti-beta7 antibody treatment also induced a small but significant decrease in the numbers of mast cells in tongue tissue.

Interestingly, the DB(1) and DB(3) to a small extent stimulate the proliferation of HeLa and F-977 cells, respectively.

This biosensor was successfully applied to screen a library of small chemical compounds leading to discovery of a family of quinacridine analogs, which potently inhibit cancer cell proliferation, and promote accumulation of cells in S phase and G2.

Here in this study, we report that emetine inhibits migration and invasion of human non-small-cell lung cancer (NSCLC) cells.

In the current study, EGFR, IL-6, and glycoprotein 130 (GP130) were highly expressed in non-small cell lung cancer (NSCLC) tissue samples and were associated with clinicopathological features and poor prognosis of patients with NSCLC.

Here, we have shown that a nano-formulated bioactive small molecule inhibitor Quinacrine (NQC) caused apoptosis in oral cancer stem cells (OCSCs; isolated from different oral cancer cells and oral cancer patient derived primary cells) by down regulating WNT-β catenin and HH-GLI components through activation of GSK3β.

The small molecules, natural antioxidant Caffeic Acid (trans-3,4-Dihydroxycinnamic acid CA) and anti-diabetic drug Metformin (Met), activate 5′-adenosine monophosphate-activated protein kinase (AMPK) and interfere with metabolic reprogramming in human cervical squamous carcinoma cells.

Moreover, knockdown of CD10 expression by CD10 small interfering RNA in HCC cells suppressed cell migratory/invasive abilities and overexpression of CD10 relieved the migration inhibition induced by niclosamide.

Using structure-guided design, we discovered small molecules that increase nucleotide exchange on RAS in vitro at submicromolar concentrations, bind to SOS1 with low double-digit nanomolar affinity, rapidly enhance cellular RAS-GTP levels, and invoke biphasic signaling changes in phosphorylation of ERK 1/2.

Silencing of SHP-1 gene by small interfering RNA (siRNA) reversed the ABZ-promoted attenuation of STAT3 as well as STAT5 activation and cellular apoptosis.

Currently, a broad array of small-molecule drugs is known that specifically inhibit protein synthesis in eukaryotic cells.

A series of mutations of the TTT have been identified that cause disease syndrome with neurodevelopmental defects, and misregulation of the TTT has been shown to contribute to myeloma, colorectal, and non-small-cell lung cancers.

Furthermore, we evaluated the therapeutic potential of plumbagin in non-small cell lung cancer (NSCLC), and found that Kelch-like ECH-associated protein 1 (KEAP1)-mutant NSCLC cells, which possess constitutive nuclear factor erythroid 2-related factor 2 (NRF2) activity, were insensitive to plumbagin; however, inhibition of glucose transporter 1 (GLUT1) by small-molecule BAY-876 or inhibiting glucose-6-phosphate dehydrogenase (G6PD) by 6-aminonicotinamide (6-AN) overcame the plumbagin-resistance of KEAP1-mutant NSCLC cells.

NPD689 suppressed the transcriptional activity of TEAD and reduced the viability of human malignant pleural mesothelioma and non-small cell lung cancer cells but not the viability of normal human mesothelial cells.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide.

In non-small cell lung cancer (NSCLC), M2-polarized tumor-associated macrophages (TAMs) induce T cell dysfunction and correlate with poor clinical outcomes.

Transmittance increases induced by hypo-osmotic artificial cerebrospinal fluid or 10 microM kainate were small in the CA1 cell body region compared to dendritic regions.

At the lower concentrations tested, suramin stimulated proliferation of the two small cell lung cancer cell lines, NCI-H187 and NCI-N417.

Suramin inhibits the growth of non-small cell lung cancer (NSCLC) and breast cancer in vitro by blocking the action of most known growth factors.

In the present investigation we evaluated the ability of suramin to induce cross-linked envelope (CLE) formation, as a common marker for squamous differentiation and apoptosis, in three representative human non-small cell lung cancer cell lines: NCI-H226 (squamous), NCI-H358 (bronchoalveolar [adenocarcinoma]), and NCI-H596 (adenosquamous).

Use of a small-molecule, cell-permeable dimerizer to control the interaction of a transcription activation domain and a DNA-binding domain allows the level of expression of a target gene to be regulated by the concentration of dimerizer.

We found that at 5 h in vitro only a small number of cells took up Co(2+) upon stimulation with 100 microM kainate or other AMPA receptor agonists, in the presence of cyclothiazide (CTZ), to inhibit desensitisation.

Here it is shown that small molecule aptamers also bound their ligand in vivo, enabling development of a method for controlling gene expression in living cells.

The RNA interference (RNAi) phenomenon is a recently observed process in which the introduction of a double-stranded, small interfering RNA (siRNA) into a cell causes the specific degradation of a homologous single-stranded RNA.

Small interfering RNAs lowered NRF2 expression in HepG2 cells and prevented the up-regulation of BSEP by oltipraz.

Results revealed a unique profile of small numbers of equivalently up- and down-regulated genes with biological functions that included transport and localization, ubiquitin metabolism, apoptosis and cell cycle control.

Depletion of 14-3-3 zeta levels using small interfering RNA induced both ER stress proteins and death of granule cells.

MicroRNAs (miRNAs) are a highly conserved group of small non-coding RNAs (18-25 nucleotides), instrumental in modulating the expression of target genes associated with various biological and cellular processes including cellular senescence.

Concurrently, small molecules that suppress senescent phenotypes without causing cell death are known as senomorphics.

This article focuses on the prospects of small-molecule-induced cell reprogramming for anti-aging, covering its mechanisms, applications, current limitations, and future directions to facilitate clinical translation and breakthroughs in human healthspan extension.

Increasingly, the role of genomic non-protein coding small regulatory RNAs, in particular the microRNAs (miRNAs), in regulating cellular pathways controlling fundamental functions in the nervous system and in neurodegenerative disease is being appreciated.

Angiostrongylus cantonensis causes eosinophilic meningitis and eosinophilic pleocytosis in humans and is of significant socio-economic importance globally. microRNAs (miRNAs) are endogenous small non-coding RNAs that play crucial roles in gene expression regulation, cellular function and defense, homeostasis and pathogenesis.

However, PPNs have evolved specialized effector proteins (small, secreted molecules, typically proteins, that enter host cells to directly suppress immunity and manipulate host processes), which they secrete into host tissues and cells to interfere with ROS production and signaling.

Recently, we identified a small heat shock protein expressed by Brugia malayi (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines.

Smaller increases were observed with repeated injections of mitogen-stimulated spleen lymphocyte supernatants, with L-cell supernatants, and with fibroblast growth factor.

Small interfering RNA-mediated knockdown of the cytoplasmic HSP90 alpha isoform 2 (Smp_072330) also attenuated stem cell proliferation and restricted schistosomulum growth, supporting the importance of this isoform. 17-AAG and EC-144 attenuated the phosphorylation of schistosomula Akt/protein kinase B, extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, suggesting HSP90 regulates core 'system-based' signalling pathways in the parasite; glucose uptake was also reduced.

The present investigation was undertaken to determine whether reserpine-induced increase in the sulphation of the small intestinal goblet cell mucins of rats affects the establishment of intestinal helminths.

In snails maintained at LC25, showed significantly higher percentages of small round cells than controls, 56.2% & 9.2% respectively.

Here we show that both excretory-secretory products (E-S) and extract of T. spiralis can stimulate the release of the cytokine interleukin 25 (IL-25) from the mouse small intestinal villi and evoke calcium responses from tuft cells in the intestinal organoids, which can be blocked by a bitter-taste receptor inhibitor, allyl isothiocyanate.

Inhibition of the NLRP3 inflammasome by small interfering RNA (siRNA) blocked extracellular secretory proteins (ESPs) stimulated COX-2, mPGES-1 and PGE-2 in microglia.

These small RNAs form complex networks that regulate cell differentiation, development and homeostasis.

The relatively small concentrations required for in vivo bioactivity of diterpene ester skin irritants and promoters (approximately 10 nmol per animal; approximately 10 nM in cell cultures) has discouraged studies of EPR spectra of bioactive, TPA-analogous, spin-labeled phorbol-12,13-diesters [(n,m)PA] bound to their membrane receptors, protein kinases C (PKC).

Helminths secrete small regulatory microRNA (miRNAs), which can interact with host cells.

These findings therefore identify a novel small-molecule-activated GATA factor that is required to regulate the cell type-specific effects of DIF.

CLEs are small non-cell autonomous signalling peptides that regulate cell division rate and orientation in a variety of developmental contexts.

These small RNAs guide animal development by regulating temporal transitions in gene expression involved in cell fate choices and transitions between pluripotency and differentiation.

MicroRNAs (miRNAs) are small (20-24 nucleotides), non-coding ribonucleid acids, which regulate gene expression on the post-transcriptional level, thus influencing physiological processes including cellular growth, differentiation and apoptosis.

Overall, our results indicated that T. spiralis induced autophagy of host small intestinal cells, and its TsSPIs play an important role in enhancing autophagy flux by affecting autophagy-related pathways.

The origin and fate of small "oval" cells expressing different immunohistologic phenotypes and ultrastructural appearance were examined in livers of Syrian hamsters during cholangiocarcinogenesis induced by dimethylnitrosamine and promoted by Clonorchis sinensis infection.

It appears that C. sinensis infection stimulates proliferation and differentiation of small ductular or periductal cells (primitive oval cells) into either hepatocyte-like oval cells, which mature into hepatocytes without malignant transformation, or into ductular-like oval cells.

Small activating RNAs (saRNAs) involved in RNAa have been successfully used to activate gene expression in cultured cells, and thereby this emergent technique might allow us to develop various biotechnological applications, without the need to synthesize hazardous construct systems harboring exogenous DNA sequences.

GJ proteins form plasma membrane channels that facilitate passage of small molecules across cells and modulate signaling pathways and cellular behavior in different tissues.

Endogenous small non-coding RNAs play important roles in many biological processes such as protection against foreign pathogens, cell differentiation, and chromosomal stability by regulating target gene expression at the transcriptional and post-transcriptional levels.

Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated.

Herein, we show that Ago1 and Ago4, which encode key components of the small RNA-induced silencing complex (RISC), were up-regulated in murine macrophage RAW264.7 cells transfected by Echinococcus multilocularis miR-71 (emu-miR-71) mimics.

CLE peptides are small extracellular proteins important in regulating plant meristematic activity through the CLE-receptor kinase-WOX signalling module.

In the in vitro assay, rNAPc2 obviously inhibited the invasive ability of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner.

PIWI-interacting RNAs (piRNAs) are genome-encoded small RNAs that regulate germ cell development and maintain germline integrity in many animals.

Similar to classic hormonal signalling, small RNAs also play a critical role in regulating development and behaviour in a cell non-autonomous fashion.

I will then define the core molecular mechanisms - the Par/Crb/Scrib polarity complexes, small GTPases, the actin and microtubule cytoskeletons, and phosphoinositides/PI3K signaling - that are required for asymmetric cell division, apico-basal and front-rear polarity in model systems, including C elegans zygote, Drosophila embryos and cultured mammalian cells.

Recently, stimulated Raman scattering (SRS) microscopy has emerged as a powerful tool to visualize small biological molecules tagged with alkyne (C≡C) or carbon-deuterium (C-D) bonds in the cell-silent region.

MANF is a small, soluble, endoplasmic-reticulum (ER)-resident protein that is secreted upon ER stress and promotes survival of target cells such as neurons.

These approaches can be employed to screen drugs and small molecules that can interact with the biogenesis and dynamics of formation of tau aggregates and to analyze their interactions with other cellular proteins.

Post-translational modification by small ubiquitin-related modifier (SUMO) is a key regulator of cell physiology, modulating protein-protein and protein-DNA interactions.

Here we report that a small protein, SrpA, controls core cellular processes in response to phage infection and environmental signals in Pseudomonas aeruginosa.

The small GTPase Rab11 dynamically changes its location to regulate various cellular processes such as endocytic recycling, secretion, and cytokinesis.

RhoGEF proteins activate the Rho family of small GTPases and thus play a key role in regulating fundamental cellular processes such as cell morphology and polarity, cell cycle progression and gene transcription.

Although non-small cell lung carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to these drugs.

Chemical genomics combines chemistry with molecular biology as a means of exploring the function of unknown proteins or identifying the proteins responsible for a particular phenotype induced by a small cell-permeable bioactive molecule.

The mechanisms regulating the extension of small unicellular tubes remain poorly defined.

Rab GTPase-activating protein, RabGAP, acts as a negative regulator of Rab small GTPases, which orchestrate the intracellular membrane trafficking involved in cell proliferation.

The complexity increases with the dynamic delay induced by other small molecules involved in gene regulation, and noisy cellular environment.

Using a functional siRNA (small interfering RNA) screen in HeLa cells, we identified Roquin-2 (also called RC3H2) as an E3 ubiquitin ligase required for ROS-induced ubiquitination and degradation of ASK1.

RNA sequencing of mRNAs and small RNAs in the 1-cell hybrid embryo revealed that about one hundred sixty paternal mRNAs are reproducibly expressed in the embryo and that about half of all assayed endogenous siRNAs and piRNAs are also of paternal origin.

Small RNAs recognize, bind, and regulate other complementary cellular RNAs.

Subsequent studies from our lab also revealed that PAX5 transcription factor is preferentially expressed in small cell lung cancer (SCLC) and promotes MET transcription.

We propose that TOE-2 ensures an apoptotic fate for the small Q.a daughter by promoting asymmetry in the daughter cell sizes of the Q.a neuroblast division but by a mechanism that is independent of cell size in the Q.p division.

Signaling pathways and small RNAs direct diverse cellular events, but few examples are known of defined signaling pathways directly regulating small RNA biogenesis.

Management of ROS to prevent potential damage, yet enabling its signalling function is achieved through numerous enzyme systems e.g. peroxidases, superoxide dismutases etc. and small molecules e.g. glutathione that collectively form the cellular anti-oxidant system.

Small guanosine triphosphatases of the Rab family regulate intracellular vesicular trafficking.

MicroRNA are small noncoding transcripts involved in many cellular mechanisms, including tumorigenesis. miR-210, in particular, is induced by hypoxia and correlates with adverse outcomes in certain cancers.

We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency.

Originally discovered in C. elegans, microRNAs (miRNAs) are small RNAs that regulate fundamental cellular processes in diverse organisms.

Further elucidation of how miRNAs and other small RNAs interact with known and yet-to-be identified gene regulatory pathways in the cell should provide us with a more in-depth understanding of the mechanisms regulating cellular function and differentiation, and facilitate the application of small RNA technology in disease control and treatment.

MicroRNAs (miRNAs) are small, abundant transcripts that can bind partially homologous target messages to inhibit their translation in animal cells. miRNAs have been shown to affect a broad spectrum of biological activities, including developmental fate determination, cell signaling and oncogenesis.

P21 activated kinases (PAKs) are major downstream effectors of rac-related small GTPases that regulate various cellular processes.

The small G protein Cdc42 also functions in cell polarity and has been shown in some cases to act by regulating the Par3 complex.

Our goal was to identify and characterize new XSEs and further analyze known XSEs to understand the principles by which a small difference in the concentration of an intracellular signal is amplified to induce dramatically different developmental fates.

Thus, specific Argonaute proteins can transport specific classes of small regulatory RNAs to distinct cellular compartments to regulate gene expression.

In a parallel fashion, we detect hScrt expression in lung cancers with NE features, especially small cell lung cancer. hScrt shares the capacity of other Snail family members to bind to E-box enhancer motifs, which are targets of basic helix--loop--helix (bHLH) transcription factors.

Small interfering RNAs regulate gene expression in diverse biological processes, including heterochromatin formation and DNA elimination, developmental regulation, and cell differentiation.

Small regulatory RNAs have crucial roles in the timing mechanism, and the cellular machinery required for production of these RNAs intersects with that used to process double-stranded RNAs during RNA interference.

We also found that CrkL-induced activation of small guanine triphosphatase (GTPase) Rac1 was significantly inhibited by the DOCK2-dCS mutant in 293T cells.

Family B (the secretin-receptor family or 'family 2') of the GPCRs is a small but structurally and functionally diverse group of proteins that includes receptors for polypeptide hormones, molecules thought to mediate intercellular interactions at the plasma membrane and a group of Drosophila proteins that regulate stress responses and longevity.

The family of Rac small GTPases including Rac1, Rac2 and Rac3 regulate numerous cellular processes.

Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference.

Small RNA technology is both extremely versatile, because virtually any expressed gene can be inhibited, and effective, because it exploits natural cellular machinery that evolved to use small RNAs to regulate gene expression.

First discovered in plants the nematode Caenorhabditis elegans, the production of small interfering RNAs (siRNAs) that bind to and induce the degradation of specific endogenous mRNAs is now recognized as a mechanism that is widely employed by eukaryotic cells to inhibit protein production at a post-transcriptional level.

The mechanisms that regulate the small GTPase Ras as well as the downstream kinases MEK and extracellular signal regulated kinase (ERK) are well understood.

In vivo HsEg5 is reversibly inhibited by monastrol, a small cell-permeable molecule that causes cells to be arrested in mitosis.

Calmodulin (CaM), a small calcium-binding protein, is the key mediator of numerous calcium-induced changes in cellular activity.

We found that two small coexpressed groups of genes regulated by the Mcm1-Fkh2-Ndd1 transcription regulatory complex are sufficient to account for the difference in the effects of HP and MD on the progress of the cell cycle, namely, G1 arrest with MD and an S phase delay followed by a G2/M arrest with HP.

Thioredoxins are a class of small proteins that play a key role in regulating many cellular redox processes.

The small GTP-binding protein family regulates various cell functions in mammalian and yeast cells.

First, studies with the small nematode Caenorhabditis elegans have identified a number of apoptosis regulating genes--the first evidence that cell death is an active process under genetic control.

Small changes of extracellular pH activate depolarizing inward currents in most nociceptive neurons.

From a high-content screen, we identified loperamide as a small molecule that can prevent FoxO inhibitor-induced glucagon expression and further stimulate insulin protein processing and secretion by altering calcium levels, intracellular pH, and FoxO1 localization.

Many proteins required for the biogenesis and function of silencing small RNAs (sRNAs) enrich in nuage, and it is often assumed that nuage is the cellular site where sRNAs are synthesized and encounter target transcripts for silencing.

The natural small molecules can inhibit protein aggregation and underlying cellular pathogenesis of neurodegenerative diseases involving multi-factorial mechanisms of action.

Small-molecule drugs were designed to target and stabilize G4 structures, thereby blocking replication and transcription, resulting in cancer cell death.

Here, we present a series of small-molecule compounds based on bis(phenylmethylen)cycloalkanones and their heterocyclic analogues, identified via targeted library screening, that can induce NRF1-dependent downstream events, such as proteasome synthesis, heat shock response, and autophagy, in both model cell lines and Caenorhabditis elegans strains.

Dicer proteins also produce microRNAs (miRNAs), a class of endogenous small non-coding RNAs that regulate essential cellular functions through post-transcriptional mechanisms.

We discovered pyrvinium, a small-molecule inhibitor of GIC self-renewal in vitro and in vivo, in part through inhibition of Wnt/β-catenin signaling and other essential stem cell regulatory pathways.

Targeting these structures by small compounds shows promise in the selective suppression of cell growth, opening up novel possibilities for anticancer treatment.

These results indicate that DEX-treatment delayed the rejection of E. trivolvis from the small intestine of SCID mice in association with the suppression of goblet cell hyperplasia.

These results indicate that dexamethasone treatment delayed the expulsion of E. trivolvis from the small intestine of the host mouse in association with the suppression of goblet cell hyperplasia and increase in the number of mast cells and eosinophils.

In the small intestine, chemosensing by epithelial tuft cells results in the activation of group 2 innate lymphoid cells (ILC2s), which subsequently drive increased tuft cell frequency.

MicroRNAs (miRNAs) are a class of small (∼22 nucleotides), non-coding, highly conserved single-stranded RNAs with posttranscriptional regulatory features, including the regulation of cell proliferation, differentiation, survival, and apoptosis.

Small-molecule ligands of nuclear hormone receptors (NHRs) govern the transcriptional regulation of metazoan development, cell differentiation, and metabolism.

The small ubiquitin-like modifier (SUMO), initially characterized as a suppressor of a mutation in the gene encoding the centromeric protein MIF2, is involved in many aspects of cell cycle regulation.

The small nematode Caenorhabditis elegans is an excellent model system to study the regulation of cell division in a multicellular organism, and is poised to make important contributions to this field.

The small Ras-like GTPase Rap1 has been identified as a regulator of integrin activation and cadherin-mediated cell-cell contacts.

Foremost is our current inability to restrict the activity of small regulatory RNA to this RNA cleavage pathway which leads to the activation of other cellular regulations some of which have a lower level of sequence specificity than RNA interference.

RNA duplexes of 21 - 23 nucleotides (nts), with approximately 2 nt 3' overhangs (called small interfering RNAs or siRNAs), have recently been shown to mediate sequence-specific inhibition of gene expression in mammalian cells via a post-transcriptional gene silencing (PTGS) mechanism termed RNA interference (RNAi).

The major objective of this work was to explore the possibility of identifying a small molecule inhibitor of the dengue virus protease and assessing its ability to suppress viral replication in cultured cells.

Because monomeric TCTP (mTCTP) and dTCTP share a high topological similarity, we hypothesized that small molecules interacting with mTCTP would also bind to dTCTP and interfere with dTCTP-based cellular processes.

This might be because the small number of chromosomes in the genome predisposes aneuploid cells to an imbalance of genes carrying out the basic activities required for cell division and cell survival.

Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research.

Trichinella spiralis excretory/secretory proteins may inhibit apoptosis of NCI-H446 small-cell lung cancer cells by reducing the apoptosis protein C-myc and Bcl-2 mRNA levels, and causing the increase of Fas/Fasl mRNA ratio.

Focal application of small doses of the putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA) onto the somata of pyramidal cells caused a conductance increase and hyperpolarization.

After early surface ectodermal expression, the anterior and central class genes are expressed in small domains of putative neural precursor cells co-expressing ClSoxB1, suggesting an evolutionary early function of Hox genes in patterning parts of the nervous system.

The smaller genome size of wBm, relative to wMel, may reflect the loss of genes required for infecting host cells and avoiding host defense systems.

Our data suggest that Z granules coordinate small RNA-based gene regulation to promote germ cell function and that ZSP-1 helps/is need to maintain Z granule morphology and liquidity.

These defects correlate with the altered abundance and distribution of a number of chromatin modifications, all of which can be corrected by disabling components of the endogenous small RNA pathway, suggesting that AMPK regulates germ cell integrity by targeting an RNA interference (RNAi)-like pathway during dauer.

We show that ZYG11A/B subunit knockdown, or broad cullin-RING ubiquitin ligase inactivation with the small molecule MLN4924, inhibits mitotic slippage in human cells, suggesting the potential for antimitotic combination therapy.

This small amount of newly generated CD8α+ DCs might contribute to enhanced activation of CD8+T cells via cross-presentation and activation which then attenuate hepatic pathological damage found in Batf3 -/- mice.

Taken together, our data suggest that isoharringtonine is a potential natural product for treatment of non-small cell lung cancers, and inhibition of NR4A1 sensitizes cancer cells to anti-cancer treatment.