Purpose: We previously reported that activated T cells accumulate in the perihematomal regions after Intracerebral hemorrhage (ICH) and aggravate hemorrhagic brain injury. However, brain-infiltrating T cells precise activation mechanisms and resulting pathological impacts remain largely unexplored. This study aims to address these knowledge gaps. Methodology: ICH was induced via standard collagenase injection in male C57BL/6J mice (10 weeks old). Activation pathways of T cells were analyzed through single-cell RNA data (GSE230414). We assessed T cell receptor (TCR) activation, pro-inflammatory cytokines expression, and immune cell infiltration via flow cytometry and immunostaining at 1- and 3-days post-ICH. Neurobehavioral evaluations were conducted at 1-, 3-, 7-, and 14-days post-ICH. TCR activation was pharmacologically inhibited using the TCR-specific inhibitor AX-024, administered (10 mg/kg, i.p.) one hour after ICH. Results: Single-cell transcriptomic analysis revealed an upregulation of the TCR pathway in activated T cells following ICH in mice. Flow cytometry and immunostaining validated TCR activation markers (p-CD3, p-Zap70) in ICH mouse models. These findings suggest that TCR activation likely plays a central role in the activation of brain-infiltrating T cells. In the subsequent experiment, we explored the pathological implications of TCR activation on T cell activation, leukocyte brain infiltration, and neurological outcomes post-ICH. We found that administration of AX-024 substantially inhibited TCR activation (CD69 expression) and expression of pro-inflammatory cytokines (IL-17, IL-1β) in brain-infiltrating T cells at 1- and 3-days post-ICH. Notably, AX-024 administration also significantly decreased the infiltration of other leukocytes and remarkably enhanced long-term sensorimotor and cognitive function up to 14 days after ICH. Discussion: This study underscores TCR activation as a pivotal mechanism driving activation of brain-infiltrating T cells following ICH. Inhibiting TCR activation through AX-024 proves beneficial for improving neurological outcomes after ICH. However, further investigations are warranted to comprehensively elucidate the intricate underlying pathological mechanisms.
To investigate the tomographic characteristics of corneas with excessive thickness and to explore their potential impact on the assessment of candidates for refractive surgery. One hundred and two eyes from 102 patients with the thinnest pachymetry (TP) < 500 μm, 100 eyes from 100 patients with TP ranging from 500 to 580 μm, and 102 eyes from 102 subjects with TP ≥ 580 μm were included. Pentacam ectasia indices were compared among these different groups. When compared to eyes with TP between 500 and 580 μm, significantly higher values in anterior radius of curvature (ARC), anterior corneal astigmatism (KAp), back elevation at the thinnest pachymetry (BE), deviation of normality of the back elevation (Db), and a more negative Q value for the back surface (Qback) were observed in eyes with TP ≥ 580 μm (Mann-Whitney U test: P < 0.001). No significant differences were observed in the indices for the anterior cornea (Mann-Whitney U test: index of height decentration, P = 0.348; inferior-superior value, P = 0.334; keratoconus percentage index, P = 0.077; deviation of normality of the front elevation, P = 0.891). The proportion of abnormalities was highest in eyes with TP ≥ 580 μm for BE (16.7%, Chi-square test: P < 0.001) and Db (20.6%, Chi-square test: P = 0.001). The tomography of thick corneas reveals greater BE and Db, as well as a more negative Qback while no significant disparities emerged in the anterior corneal indices.
Abstract The overall survival of patients with hepatocellular carcinoma (HCC) remains poor, and the molecular pathogenesis remains incompletely defined in HCC. Here we report that increased expression of αB-Crystallin in human HCC predicts poor survival and disease recurrence after surgery. Multivariate analysis identifies αB-Crystallin expression as an independent predictor for postoperative recurrence and overall survival. We show that elevated expression of αB-Crystallin promotes HCC progression in vivo and in vitro . We demonstrate that αB-Crystallin overexpression fosters HCC progression by inducing epithelial-mesenchymal transition (EMT) in HCC cells through activation of the extracellular-regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. αB-Crystallin complexes with and elevates 14-3-3ζ protein, leading to up-regulation of ERK1/2 activity. Moreover, overexpression of αB-Crystallin in HCC cells induces EMT progression through an ERK1/2/Fra-1/slug signaling pathway. Clinically, our data reveal that overexpression of both αB-Crystallin and 14-3-3ζ correlates with the HCC poorest survival outcomes, and sorafenib response is impaired in patients with αB-Crystallin overexpression. Conclusion: These data suggest that the αB-Crystallin-14-3-3ζ complex acts synergistically to promote HCC progression by constitutively activating ERK signaling. This study reveals αB-Crystallin as a potential therapeutic target for HCC and a biomarker for predicting sorafenib treatment response.
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
An entry from the Inorganic Crystal Structure Database, the world’s repository for inorganic crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the joint CCDC and FIZ Karlsruhe Access Structures service and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Polymorphs of ZnHPO3·2H2O with both centrosymmetry (Cmcm) and noncentrosymmetry (C2) structures were successfully prepared by modified solution evaporation and seed-crystals induced secondary nucleation methods. In Cmcm-ZnHPO3·2H2O, the zinc atoms are only octahedrally coordinated, while in C2-ZnHPO3·2H2O, they feature both tetrahedral and octahedral coordination. As a result, Cmcm-ZnHPO3·2H2O features a 2D layered structure with lattice water molecules located in the interlayer space, while C2-ZnHPO3·2H2O features a 3D electroneutral framework of tfa topology connected by Zn(1)O4, Zn(2)O6 and HPO3 units. The UV-Visible diffuse-reflectance spectra associated with Tauc’s analyses give a direct bandgap of 4.24 and 4.33 eV for Cmcm-ZnHPO3·2H2O and C2-ZnHPO3·2H2O, respectively. Moreover, C2-ZnHPO3·2H2O exhibits a week second harmonic generation (SHG) response and a moderate birefringence for phase matching, indicating its potential as a nonlinear optical material. Detailed dipole moment calculation and analysis confirmed that the SHG response mainly derived from the HPO3 pseudo-tetrahedra.
Abstract To determine whether positive or negative DWI TIA patients could get benefits from HST we conducted a cohort study which data from the prospective, hospital-based, TIA database of the First Affiliated Hospital of Zhengzhou University. The end-point was 7-day and 90-day incidence of stroke. Cox proportional hazard regression models were used to analyze the association between end-points and high-intensity statin treatment in TIA patients with positive and negative DWI. A total of 987 eligible TIA patients were analyzed. The stroke risk of patients with positive DWI was about a four-fold increase compared to that with negative DWI (7 d, 10.9 versus 1.8, p < 0.001 and 90 d, 18.3 versus 4.2, p < 0.001). After adjusting confounding factors, HST significantly improved both 7-day (HR 0.331, 95% CI 0.165–0.663; p = 0.002) and 90-day (HR 0.480, 95% CI 0.288–0.799; p = 0.005) outcomes in positive DWI patients. As a conclusion, high-intensity statin use reduces the 90 days’ recurrent stroke risk in DWI-positive TIA patients but not in DWI-negative patients.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)