The functions of FOXP transcription factors and their regulation by post-translational modifications.

The forkhead box subfamily P (FOXP) of transcription factors, consisting of FOXP1, FOXP2, FOXP3, and FOXP4, is involved in the regulation of multisystemic functioning. Disruption of the transcriptional activity of FOXP proteins leads to neurodevelopmental disorders and immunological diseases, as well as the suppression or promotion of carcinogenesis. The transcriptional activities of FOXP proteins are directly or indirectly regulated by diverse post-translational modifications, including phosphorylation, ubiquitination, SUMOylation, acetylation, O-GlcNAcylation, and methylation.

Implications of ubiquitination and the maintenance of replication fork stability in cancer therapy.

DNA replication forks are subject to intricate surveillance and strict regulation by sophisticated cellular machinery. Such close regulation is necessary to ensure the accurate duplication of genetic information and to tackle the diverse endogenous and exogenous stresses that impede this process. Stalled replication forks are vulnerable to collapse, which is a major cause of genomic instability and carcinogenesis.

Contact Lens Sensor with Anti-jamming Capability and High Sensitivity for Intraocular Pressure Monitoring.

Contact lens sensors provide a noninvasive approach for intraocular pressure (IOP) monitoring in patients with glaucoma. Accurate measurement of this imperceptible pressure variation requires highly sensitive sensors in the absence of simultaneously amplifying IOP signal and blinking-induced noise. However, current noise-reduction methods rely on external filter circuits, which thicken contact lenses and reduce signal quality.

Regulation of ATR-CHK1 signaling by ubiquitination of CLASPIN.

DNA replication forks are frequently forced into stalling by persistent DNA aberrations generated from endogenous or exogenous insults. Stalled replication forks are catastrophic for genome integrity and cell survival if not immediately stabilized. The ataxia-telangiectasia and RAD3-related kinase (ATR)-CLASPIN-checkpoint kinase 1 (CHK1) signaling cascade is a pivotal mechanism that initiates cell-cycle checkpoints and stabilizes stalled replication forks, assuring the faithful duplication of genomic information before entry into mitosis.

TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination.

Expression of the E3 ligase TRIM21 is increased in a broad spectrum of cancers; however, the functionally relevant molecular pathway targeted by TRIM21 overexpression remains largely unknown. Here, we show that TRIM21 directly interacts with and ubiquitinates CLASPIN, a mediator for ATR-dependent CHK1 activation. TRIM21-mediated K63-linked ubiquitination of CLASPIN counteracts the K6-linked ubiquitination of CLASPIN which is essential for its interaction with TIPIN and subsequent chromatin loading.

Determining the Fate of Neurons in SCA3: ATX3, a Rising Decision Maker in Response to DNA Stresses and Beyond.

DNA damage response (DDR) and apoptosis are reported to be involved in the pathogenesis of many neurodegenerative diseases including polyglutamine (polyQ) disorders, such as Spinocerebellar ataxia type 3 (SCA3) and Huntington's disease (HD). Consistently, an increasing body of studies provide compelling evidence for the crucial roles of ATX3, whose polyQ expansion is defined as the cause of SCA3, in the maintenance of genome integrity and regulation of apoptosis. The polyQ expansion in ATX3 seems to affect its physiological functions in these distinct pathways.

Successful application of anti-CD19 CAR-T therapy with IL-6 knocking down to patients with central nervous system B-cell acute lymphocytic leukemia.

Few studies have described chimeric antigen receptor-modified T cell (CAR-T) therapy for central nervous system (CNS) B-cell acute lymphocytic leukemia (B-ALL) patients due to life-threatening CAR-T-related encephalopathy (CRES) safety issues. In this study, CAR-Ts targeting CD19 with short hairpin RNA (shRNA)-IL-6 gene silencing technology (ssCART-19s) were prepared. We conducted a phase 1 clinical trial (ClinicalTrials.

Economic Hardship, Ocular Complications, and Poor Self-reported Visual Function are Predictors of Mental Problems in Patients with Uveitis.

: To characterize the quality of life and mental health status of patients with uveitis and investigate predictors of psychological problems.: A total of 245 patients and 105 controls were enrolled in this cross-sectional study. Quality of life, psychological status, socio-demographic and clinical data were obtained from questionnaires and medical records.

Essential Contribution of Macrophage Tie2 Signalling in a Murine Model of Laser-Induced Choroidal Neovascularization.

Wet age-related macular degeneration (AMD), which can cause progressive blindness, is characterised by choroid neovascularization (CNV) in the macular area. Although close attention has been paid to AMD, and anti-vascular endothelial growth factor (VEGF) drugs are available, its complex pathogenesis is still elusive. Tie2-expressing macrophages (TEMs) have been found to promote angiogenesis in remodel tissues and tumours.

Miro2 supplies a platform for Parkin translocation to damaged mitochondria.

PINK1/Parkin-mediated mitophagy is an important process in selective removal of damaged mitochondria, in which translocation of Parkin to damaged mitochondria is recognized as an initiation step. At present, how the damaged mitochondria are selectively recognized and targeted by Parkin is not fully understood. Here we show that Miro2, an outer mitochondrial membrane protein, undergoes demultimerization from a tetramer to a monomer and alteration in mitochondrial localization upon CCCP treatment, suggesting a CCCP-induced realignment of Miro2.

RNF126 Quenches RNF168 Function in the DNA Damage Response.

DNA damage response (DDR) is essential for maintaining genome stability and protecting cells from tumorigenesis. Ubiquitin and ubiquitin-like modifications play an important role in DDR, from signaling DNA damage to mediating DNA repair. In this report, we found that the E3 ligase ring finger protein 126 (RNF126) was recruited to UV laser micro-irradiation-induced stripes in a RNF8-dependent manner.

RBM45 competes with HDAC1 for binding to FUS in response to DNA damage.

DNA damage response (DDR) is essential for genome stability and human health. Recently, several RNA binding proteins (RBPs), including fused-in-sarcoma (FUS), have been found unexpectedly to modulate this process. The role of FUS in DDR is closely linked to the pathogenesis of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord.

Parkin regulates translesion DNA synthesis in response to UV radiation.

Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation.

Ataxin-3 promotes genome integrity by stabilizing Chk1.

The Chk1 protein is essential for genome integrity maintenance and cell survival in eukaryotic cells. After prolonged replication stress, Chk1 can be targeted for proteasomal degradation to terminate checkpoint signaling after DNA repair finishes. To ensure proper activation of DNA damage checkpoint and DNA repair signaling, a steady-state level of Chk1 needs to be retained under physiological conditions.

Genotype-Phenotype Association Study Reveals CFI-Rs13104777 to be a Protective Genetic Marker Against Acute Anterior Uveitis.

Purpose: To investigate the roles of CFI, genotype-phenotype associations were identified in AAU.

Methods: A case-control study was conducted in a total of 575 subjects consisting of 279 AAU patients and 296 healthy controls. Genotypic analyses were performed using Sequenom MassARRAY technology.

Efficacy of combined administration of 0.2% brimonidine and 0.5% betaxolol in treatment of primary open angle glaucoma and ocular hypertension.

Purpose: To observe the efficacy of combined use of brimonidine and betaxolol in treatment of primary open angle glaucoma (POAG) and ocular hypertension.

Methods: A total of 54 patients (90 eyes) with POAG and ocular hypertension were randomly divided into three groups (receiving betaxolol, brimonidine and combined administration of betaxolol and brimonidine respectively). The administration was given twice daily in all groups (0.

[Eukaryotic expression and biological activity of recombinant human IL-17B protein].

Aim: To construct pCEP4/hIL-17B recombinant expression vector and express it stably in eukaryotic cells and investigate the biological activity in vitro.

Methods: The CDS region of human IL-17B gene was cloned by RT-PCR. After identification by sequencing, the hIL-17B gene was inserted into expression vector of pCEP4 to construct the recombinant vector pCEP4/hIL-17B, then transfected into 293T cells.

Production of interleukin-17 in Behcet's disease is inhibited by cyclosporin A.

Purpose: Behcet's disease (BD) is a systemic inflammatory disease presumably caused by an autoimmune response. Interleukin (IL)-17 has been demonstrated to be involved in the development and maintenance of certain inflammatory diseases, including BD. This study was designed to investigate the influence of cyclosporine A (CsA) on IL-17 production by peripheral blood mononuclear cells (PBMCs) from BD patients in vitro and in vivo.

Upregulated IL-23 and IL-17 in Behçet patients with active uveitis.

Purpose: Behçet disease (BD) is a systemic inflammatory disease presumably caused by an autoimmune response. The interleukin (IL)-23/IL-17 pathway has been demonstrated to be involved in the development and maintenance of certain inflammatory diseases. This study was designed to investigate the role of IL-23 and IL-17 in BD.

CD4+CD25+Tregs express an increased LAG-3 and CTLA-4 in anterior chamber-associated immune deviation.

Background: Regulatory CD4(+)CD25(+) T cells have been proven to be essential for maintenance of peripheral tolerance and autoimmune diseases. ACAID is a model of immune privilege in the eye. Relatively little is known about the role and phenotype of these regulatory CD4(+)CD25(+) T cells in ACAID.

IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease.

Background: Vogt-Koyanagi-Harada (VKH) disease is a systemic refractory autoimmune disease. IL-23 has been thought to play a critical role in autoimmune disease through inducing the development of IL-17-producing CD4(+) T cells.

Objective: To investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in patients with VKH disease.

Expression of Tim-3 is transiently increased before development of anterior chamber-associated immune deviation.

Purpose: To assess the expression of T-cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) in the spleens of BALB/c mice undergoing anterior chamber-associated immune deviation (ACAID).

Methods: ACAID was generated after intracameral (i.c.

Cationic liposome-mediated bcl-xl gene transfection into human keratocytes.

The efficiency and safe range of Lipofectamine2000 (LF2000)/bcl-xl applied in human keratocytes, the optimal ratio of LF2000/bcl-xl and the bcl-xl gene expression in human keratocytes were investiaged. By using trypan-blue staining, the effects of LF2000 and bcl-xl on the survival rate of the cultured human keratocytes were measured respectively. By using semi-quantitative RT-PCR, the efficiency and the expression of LF2000-mediated bcl-xl transfection into keratocytes were examined.