RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins, cellular morphology, and migration along with various proliferation and transcriptional activity in cells. RhoA ...activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the guanine nucleotide dissociation factor (GDI). The RhoA‐RhoGDI complex exists in the cytosol and the active GTP‐bound form of RhoA is located to the membrane. GDI displacement factors (GDFs) including IκB kinase γ (IKKγ) dissociate the RhoA‐GDI complex, allowing activation of RhoA through GEFs. In addition, modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156 phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA‐RhoGDI complex. The expression of RhoA is regulated through transcriptional factors such as c‐Myc, HIF‐1α/2α, Stat 6, and NF‐κB along with several reported microRNAs. As the role of RhoA in regulating actin‐filament formation and myosin‐actin interaction has been well described, in this review we focus on the transcriptional activity of RhoA and also the regulation of RhoA message itself. Of interest, in the cytosol, activated RhoA induces transcriptional changes through filamentous actin (F‐actin)‐dependent (“actin switch”) or—independent means. RhoA regulates the activity of several transcription regulators such as serum response factor (SRF)/MAL, AP‐1, NF‐κB, YAP/TAZ, β‐catenin, and hypoxia inducible factor (HIF)‐1α. Interestingly, RhoA also itself is localized to the nucleus by an as‐yet‐undiscovered mechanism.
We descibed the regulation of RhoA activity and expression levels. In addition, we described transcription factors which are regulated by RhoA.
Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of ...mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions.
Pyruvate kinase M2 (PKM2) is crucial for cell proliferation in embryonic and cancer cells. PKM2 has a novel function as protein kinase and transcription factor. In nucleus, PKM2 has a variety of binding proteins to regulate the expression of specific genes.
Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding ...of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis.
The present communication addresses the removal of toxic lead, cadmium, and arsenic using iron oxide modified clay-activated carbon composite beads from aqueous solutions. The SEM-EDX analysis was ...conducted to study the heterogeneity of the surface and the elemental composition of the composite beads. The specific surface area of the composite beads was found to be 433 m2/g. Furthermore, the XRD pattern indicates the intercalation of iron particles between the layers of bentonite clay. The FT-IR analysis suggests that the hydroxyl, carboxyl, and Fe-O were the major functional groups responsible for the removal of lead, cadmium, and arsenic. The Langmuir monolayer sorption capacity of Pb(II), Cd(II) and As(V) were observed to be 74.2, 41.3 and 5.0 mg/g respectively. Kinetic studies indicate that intra-particle diffusion plays a significant role in the removal of these three toxic pollutants. In addition, the composite beads were applied for the adsorption of a ternary mixture of subjected pollutants at low concentrations and found efficient to remove these pollutants up to an acceptable permissible limit of drinking water. The significances of this study propose the potential of composite beads for purifying the water containing toxic pollutants, viz., lead, cadmium, and arsenic.
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•Reasonable preparation of Fe-modified bentonite-activated carbon alginate beads•Beads enhance the handling efficiency and applied as a multifunctional adsorbent•Developed beads showed better sorption efficiency for single and mixed toxic ions•Maximum sorption efficiency for Pb(II):74.2, Cd(II):41.3 and As(V):5.0 mg/g beads•Molded adsorbent for trace level toxic ions removal from ternary mixture system.
infection is one of the most common infectious diseases worldwide. Although the prevalence of
is gradually decreasing, approximately half of the world's population still becomes infected with this ...disease.
is responsible for substantial gastrointestinal morbidity worldwide, with a high disease burden. It is the most common cause of gastric and duodenal ulcers and gastric cancer. Since the revision of the
clinical practice guidelines in 2013 in Korea, the eradication rate of
has gradually decreased with the use of a clarithromycin-based triple therapy for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of
and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance, especially from clarithromycin. The clinical practice guidelines for the treatment of
were updated according to evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after an expert consensus on three recommendations regarding the indication for treatment and eight recommendations for the treatment itself. These guidelines were designed to provide clinical evidence for the treatment (including primary care treatment) of
infection to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards and will be revised if more evidence emerges in the future.
In the tumor microenvironment (TME), communication between cancer cells and tumor-associated macrophages (TAMs) through secreted extracellular proteins promotes cancer progression. Here, we observed ...that co-culturing cancer cells (4T1) and macrophage cells (Raw264.7) significantly enhanced superoxide production in both cell types. Using MALDI-TOF, we identified PKM2 as a highly secreted protein by Raw264.7 cells and bone marrow-derived monocytes. The extracellular recombinant PKM2 protein not only enhanced cancer cell migration and invasion but also increased superoxide production. Additionally, PKM2 was found to associate with the cell surface, and its binding to integrin α5/β1 receptor was inhibited by antibodies specifically targeting it.
Furthermore, we investigated downstream signaling pathways involved in PKM2-induced superoxide production. We found that knock-down of RhoA and p47phox using siRNAs effectively abolished superoxide generation in response to extracellular PKM2. Notably, extracellular PKM2 triggered the phosphorylation of p47phox at Ser345 residue and RhoA at Tyr42 residue (p-Tyr42 RhoA). Moreover, extracellular PKM2 exerted regulatory control over the expression of key epithelial-mesenchymal transition (EMT) markers, including ZEB1, Snail1, vimentin, and E-cadherin. Interestingly, p-Tyr42 RhoA translocated to the nucleus, where it bound to the ZEB1 promoter region. In light of these findings, we propose that extracellular PKM2 within the TME plays a critical role in tumorigenesis by promoting cancer cell migration and invasion through RhoA/p47phox signaling pathway.
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•Extracellular PKM2 secreted from macrophages stimulates superoxide production in cancer cells.•Superoxide production is regulated by p-Tyrosine42 RhoA and p-p47phox.•p-Tyrosine42 RhoA translocates to the nucleus, where it binds to the promoter of ZEB1 and induces its expression.•Extracellular PKM2 binds to integrin α5β1 and phosphoenol pyruvate (PEP) inhibits PKM2 binding to the integrin α5β1.
Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of ...fexuprazan in patients with acute or chronic gastritis.
In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events.
Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups. No significant difference was noted in the incidence of adverse drug reactions.
Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).
Early detection is crucial for improving the prognosis of gastric cancer, but there are no non-invasive markers for the early diagnosis of gastric cancer in real clinical settings. Recently, ...bacteria-derived extracellular vesicles (EVs) emerged as new biomarker resources. We aimed to evaluate the microbial composition in gastric cancer using bacteria-derived EVs and to build a diagnostic prediction model for gastric cancer with the metagenome data. Stool, urine, and serum samples were prospectively collected from 453 subjects (gastric cancer, 181; control, 272). EV portions were extracted from the samples for metagenome analysis. Differences in microbial diversity and composition were analyzed with 16S rRNA gene profiling, using the next-generation sequencing method. Biomarkers were selected using logistic regression models based on relative abundances at the genus level. The microbial composition of healthy groups and gastric cancer patient groups was significantly different in all sample types. The compositional differences of various bacteria, based on relative abundances, were identified at the genus level. Among the diagnostic prediction models for gastric cancer, the urine-based model showed the highest performance when compared to that of stool or serum. We suggest that bacteria-derived EVs in urine can be used as novel metagenomic markers for the non-invasive diagnosis of gastric cancer by integrating the liquid biopsy method and metagenome analysis.
In this study, verification was conducted through experiments to identify problems caused by traditional attachment methods in order to highlight the need for a suitable attachment method for new ...tile types according to changes in materials, production technology, and demand. The stability of adhesion strength was evaluated by subdividing the size of the adhesion area and adhesion strength measurement method for the country-type attachment method. The adhesion area on the back of the tile was divided into 60% and 80%, and the test specimens used in the experiment were tested for partial adhesion strength (Ta-1), overall adhesion strength (Ta-2), and adhesion strength after splitting (Ta-3), and the results were derived. As a result of conducting the adhesion test presented in the current national building standard tile specification (KCS 41 48 01) for 80% of the backfill area, the average adhesive strength was 0.85 N/mm2, and the standard strength was 0.39 N/mm2. However, as a result of the arithmetic average test of the adhesive strength of all tiles or cutting of the entire tile, rather than the partial adhesion test method of the mortar-attached part, it was confirmed that the adhesive strength was about −20% less than the current KCS 0.39 N/mm2.
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