Mccurdymackenzie1223
Cox risk model regression analysis showed that age ≥60 years, IPI 3-5 points,
gene mutation and extranodal organ invasion suggested poor prognosis. Finally, we constructed an OS predict model of PT-DLBCL patients using above factors with a high accuracy.
In conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of
was an independent factor predicting a poor prognosis.
In conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of BTG2 was an independent factor predicting a poor prognosis.Vascular endothelial cells (ECs), derived from the mesoderm, form a single layer of squamous cells that covers the inner surface of blood vessels. In addition to being regulated by chemical signals from the extracellular matrix (ECM) and blood, ECs are directly confronted to complex hemodynamic environment. These physical inputs are translated into biochemical signals, dictating multiple aspects of cell behaviour and destination, including growth, differentiation, migration, adhesion, death and survival. Mechanosensors are initial responders to changes in mechanical environments, and the overwhelming majority of them are located on the plasma membrane. Physical forces affect plasma membrane fluidity and change of protein complexes on plasma membrane, accompanied by altering intercellular connections, cell-ECM adhesion, deformation of the cytoskeleton, and consequently, transcriptional responses in shaping specific phenotypes. Among the diverse forces exerted on ECs, shear stress (SS), defined as tangential friction force exerted by blood flow, has been extensively studied, from mechanosensing to mechanotransduction, as well as corresponding phenotypes. However, the precise mechanosensors and signalling pathways that determine atheroprone and atheroprotective phenotypes of arteries remain unclear. Moreover, it is worth to mention that some established mechanosensors of atheroprotective SS, endothelial glycocalyx, for example, might be dismantled by atheroprone SS. Therefore, we provide an overview of the current knowledge on mechanosensors in ECs for SS signals. We emphasize how these ECs coordinate or differentially participate in phenotype regulation induced by atheroprone and atheroprotective SS.
Aggressive phenotype and abnormal glycolytic metabolism of fibroblast-like synoviocytes (FLSs) are essential to joint inflammation and damage in rheumatoid arthritis (RA). Eukaryotic elongation factor-2 kinase (eEF2K) is a negative regulator of protein synthesis and has been shown to play an important role in regulating various cellular processes and promoting glycolysis in tumor cells. However, the role of eEF2K in regulating the pathogenic FLS behaviors is unknown.
A specific inhibitor of eEF2K, NH125, and siRNA were used to evaluate the role of eEF2K on RA FLSs in vitro. Collagen-induced arthritis (CIA) mice were used to evaluate the in vivo effect of eEF2K. Cell migration, invasion of RA FLSs were assessed by transwell or wound healing assays. Relative changes of cytokines were analyzed by quantitative real-time PCR, western blot and ELISA.
Herein, we found an increased expression of eEF2K in synovial tissues and FLSs of RA patients. eEF2K knockdown by siRNA or treatment with NH125, an inhibitor of eEF2K, significantly reduced inflammation, migration/invasion, glucose uptake and lactate productions. eEF2K knockdown suppressed TNF-α-induced activation of NF-κB and AKT pathways in RA FLSs. Lactate reversed the inhibitory effect of eEF2K knockdown on inflammation and migration of RA FLSs. Moreover, lactate was also involved in eEF2K-mediated activation of NF-κB and AKT. NH125 treatment attenuated the severity of arthritis in collagen-induced arthritis mice.
eEF2K inhibition suppressed glycolysis and aggressive behaviors of RA FLS, which indicated that targeting eEF2K may be a new strategy for the treatment of RA.
eEF2K inhibition suppressed glycolysis and aggressive behaviors of RA FLS, which indicated that targeting eEF2K may be a new strategy for the treatment of RA.
The goal of this study was to identify the crucial autophagy-related genes (ARGs) in periodontitis and construct mRNA-miRNA-lncRNA networks to further understand the pathogenesis of periodontitis.
We used the Gene Expression Omnibus (GEO) database and Human Autophagy Database (HADb) to identify differentially expressed mRNAs, miRNAs, and ARGs. These ARGs were subjected to Gene Ontology (GO), KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, and PPI (protein-protein interaction) network analysis. Two databases (miRDB and StarBase v2.0) were used to reverse-predict miRNAs while the miRNA-lncRNA interaction was predicted using the StarBase v2.0 and LncBase Predicted v.2 databases. After excluding the lncRNAs only present in the nucleus, a competing endogenous RNA (ceRNA) network was built. Finally, we used quantitative real-time PCR (qRT-PCR) to confirm the levels of mRNA expression in the ceRNA network.
The differential expression analysis revealed 10 upregulated and 10 downregulated differentially expressed ARGs. After intersecting the reverse-predicted miRNAs with the differentially expressed miRNAs, a ceRNA network consisting of 4 mRNAs (LAMP2, NFE2L2, NCKAP1, and EGFR), 3 miRNAs (hsa-miR-140-3p, hsa-miR-142-5p, and hsa-miR-671-5p), and 30 lncRNAs was constructed. In addition, qRT-PCR results revealed that EGFR expression was downregulated in diseased gingival tissue of periodontitis patients.
Four autophagy-related genes, especially EGFR, may play a key role in periodontitis progression. The novel ceRNA network may aid in elucidating the role and the mechanism of autophagy in periodontitis, which could be important in developing new therapeutic options.
Four autophagy-related genes, especially EGFR, may play a key role in periodontitis progression. The novel ceRNA network may aid in elucidating the role and the mechanism of autophagy in periodontitis, which could be important in developing new therapeutic options.
To investigate the differential clinical and computed tomography (CT) characteristics of pulmonary nonabsorbable inflammatory and malignant subsolid nodules (SSNs) with a solid component ≤5 mm.
We retrospectively analyzed 576 consecutive patients who underwent surgical resection and had SSNs with a solid component ≤5 mm on CT images. These patients were divided into inflammatory and malignant groups according to pathology. Their clinical and imaging data were analyzed and compared. Multiple logistic regression analysis was used to identify independent prognostic factors differentiating inflammatory from malignant SSNs. Furthermore, 146 consecutive patients were included as internal validation cohort to test the prediction efficiency of this model.
Significant differences in 11 clinical characteristics and CT features were found between both groups (
< 0.05). Presence of respiratory symptoms, distribution of middle/lower lobe, irregular shape, part-solid nodule (PSNs), CT value of ground-glass opacity (GGO) areas <-657 Hu, presence of abnormal intra-nodular vessel sign, and interlobular septal thickening were the most effective factors for diagnosing nonabsorbable inflammatory SSNs, with an AUC (95% CI), accuracy, sensitivity, and specificity of 0.843 (95% CI 0.811-0.872), 89.76%, 72.86%, and 81.23%, respectively. The internal validation cohort obtained an AUC (95% CI), accuracy, sensitivity, and specificity of 0.830 (95% CI 0.759-0.887), 83.56%, 73.91%, and 76.42%, respectively.
Nonabsorbable inflammatory and malignant SSNs with a solid component ≤5 mm exhibited different clinical and imaging characteristics.
Nonabsorbable inflammatory and malignant SSNs with a solid component ≤5 mm exhibited different clinical and imaging characteristics.
Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and stool irregularity. However, its pathophysiological mechanisms, which trigger intestinal motility disorders and diarrhea leading to diarrhea-predominant IBS (D-IBS), remain largely unknown.
In the present study, we established a D-IBS rat model by mother-infant separation combined with restraint stress. Then we exposed the modelled rats to suberoylanilide hydroxamic acid (SAHA) treatment, followed by determination of their visceral sensitivity. Toluidine blue staining served to reveal the effects of SAHA treatment on mast cells of D-IBS model rats. Then we measured the expression of serotonin (5-hydroxytryptamine; 5-HT) and its receptors by ELISA.
Construction of short hairpin RNA (sh)-serotonin transporter (SERT) lentivirus vectors verified the regulation of the 5-HT signaling pathway by phosphorylated (p)-STAT/SERT. SAHA treatment of D-IBS model rats reduced the fecal water content, electromyography integral change rate, abdominal withdrawal reflex score, and number of mast cells, as well as the expression of 5-HT type 3A (5-HT3AR), 3B receptor (5-HT3BR), and 4 receptor (5-HT4R) receptors. The treatment also elevated the expression of signal transducer and activator for transcription 3 (STAT3) and SERT. Activation of p-STAT3 may reverse the inhibitory effect of SAHA on the elevated visceral sensitivity of D-IBS model rats. Moreover, SAHA promoted the transcription of SERT through repression of the p-STAT3/5-HT signaling, thereby inhibiting the visceral sensitivity of D-IBS model rats.
This study highlights that SAHA treatment can alleviate D-IBS through regulation of the p-STAT3/SERT/5-HT signaling pathway.
This study highlights that SAHA treatment can alleviate D-IBS through regulation of the p-STAT3/SERT/5-HT signaling pathway.
Mannan-binding lectin (MBL) is a key molecule in innate immunity and activates the lectin complement pathway, which plays an important role in resisting
(
) infection. However, the underlying mechanism of this resistance to infection remains unclear.
In this study, we investigated how MBL regulates the differentiation of CD4
T cells into T helper type 17 (Th17) and T regulatory (Treg) cells against
in mice, as well as the underlying mechanisms. We generated MBL double-knockout (KO) mice and infected them with
by intraperitoneal injection.
Compared with that in wild-type (WT) mice, the percentage of Th17 cells increased in MBL-null mice, whereas Treg cells decreased, indicating that MBL might regulate the Th17/Treg balance. click here In addition, in MBL-null mice, the expression levels of interleukin (IL)-17A, IL-21, and the master transcription factor of Th17 cells, RORγt, significantly increased. Conversely, IL-10, IL-2, and the Treg-specific transcription factor, Foxp3, decreased. Moreover, we found that the levels of TGF-β and IL-6 upregulated in MBL-null mice. Mechanistically, we found that MBL regulated the TGF-β/SMAD pathway through the inhibition of p-SMAD2 and promotion of p-SMAD3, and mediated the JAK/STAT pathway through the inhibition of p-JAK2 and p-STAT3 and promotion of p-JAK3 and p-STAT5. MBL double-KO mice showed a more severe inflammatory response and significantly lower survival rates with
infection.
These results suggest that MBL regulates the Th17/Treg cell balance to inhibit inflammatory responses, possibly via IL-6- and TGF-β-mediated JAK/STAT and TGF-β/SMAD signaling, and play an important role in anti-
infection.
These results suggest that MBL regulates the Th17/Treg cell balance to inhibit inflammatory responses, possibly via IL-6- and TGF-β-mediated JAK/STAT and TGF-β/SMAD signaling, and play an important role in anti-C. albicans infection.
