- Research Article
- 10.1016/j.neulet.2026.138580
The role of IRF5 in Microglia-Mediated neuroinflammation in ALS.
- Apr 01, 2026
- Neuroscience letters
- Lu Yang + 7 more +7
Publications from 2021 to 2026
Showing 10 of 61 papers
The role of IRF5 in Microglia-Mediated neuroinflammation in ALS.
Transcriptome analysis identifies EDA1 variants disrupt FOSB-mediated regulation of odontogenic epithelial cell behaviors during dental germ development
Here, we systematically investigated the effects of EDA1 variants on apoptosis, migration, and adhesion in ameloblast-like LS8 cells and identified downstream effectors of the EDA-NF-κB pathway through RNA sequencing (RNA-seq) combined with in vivo and in vitro validation. LS8 cells were transiently transfected with four constructs: wild-type (Wt) EDA1, nonsyndromic tooth agenesis-associated EDA1 variant (EDA1-A259E), X-linked hypohidrotic ectodermal dysplasia-associated EDA1 variant (EDA1-H252L), or empty vector control (pCMV-C-FLAG). We used flow cytometry, wound-healing assay, and cell counting kit 8 assay to assess cell apoptosis, migration, and adhesion, respectively. High-throughput RNA-seq was used to identify differentially expressed genes, which were subsequently validated through quantitative polymerase chain reaction and immunoblotting. Spatiotemporal Fosb expression patterns were comparatively analyzed in Wt and Tabby mouse tooth germs through in situ hybridization by using RNAscope. Wt EDA1 transiently enhances cellular migratory capacity, a function compromised in the pathogenic EDA1 variants. The EDA-NF-κB pathway operates through FOSB-mediated transcriptional regulation, as evidenced by coordinated suppression of Fosb expression at transcriptional and translational levels in the mutant models. Therefore, FOSB is a candidate downstream effector in EDA1-mediated odontogenesis. These results provide mechanistic insights into ectodermal dysplasia pathogenesis.
Read moreNAT10 inhibits ferroptosis and promotes the progression of renal clear cell carcinoma by regulating the NFE2L1-GPX4 signaling pathway
ObjectiveClear cell renal cell carcinoma (ccRCC) is a prevalent pathological subtype of renal cell carcinoma that arises from renal tubular epithelial cells. ccRCC has long been characterized by high mortality, and at present, surgical resection is the only curative treatment, but its effectiveness is low and survival rates are low. N-acetyltransferase 10 (NAT10) is a protein that acts as an acetyltransferase, has distinct catalytic and regulatory functions, and is involved in the progression of various cancers such as bladder cancer, hepatocellular carcinoma, and multiple myeloma. Ferroptosis is a novel form of programmed cell death that is iron-dependent and distinct from apoptosis, necrosis, and autophagy. Therefore, this study aimed to investigate the potential functions of NAT10 in this context, with a particular focus on its interactions and mechanisms involving ferroptosis.MethodsIn this study, immunohistochemistry, immunofluorescence, and Western blotting were utilized to evaluate the changes of NAT10 and ferroptosis-related marker proteins. Plasmid vectors were utilized to establish stable ccRCC cell lines with NAT10 overexpression and knockdown. Cell proliferation, scratch, and invasion assays were conducted to assess the impact of NAT10 modification on cell proliferation and migration capabilities. Meanwhile, remodelin hydrobromide (HBr) treatment was given to ccRCC cells to observe the variations in cell proliferation ability and ferroptosis marker proteins.ResultsOur study demonstrated that NAT10 can enhance the malignant biological behavior of ccRCC, while simultaneously inhibiting markers associated with ferroptosis.ConclusionsTherefore, this study suggests that NAT10 may exert a pro-cancer effect by modulating the nuclear factor erythroid-2, like-1(NFE2L1)-glutathione peroxidase-4(GPX4)signaling pathway in ccRCC, indicating its potential as a new therapeutic target for this malignancy.
Read moreA machine learning model for predicting the risk of diabetic nephropathy in individuals with type 2 diabetes mellitus
IntroductionDiabetic kidney disease (DKD) represents the predominant form of chronic kidney disease (CKD) linked with diabetes mellitus. The application of artificial intelligence holds promise for delaying renal deterioration and decreasing treatment expenses by facilitating early detection and intervention. This is contingent upon the development of an efficient and user-friendly model for predicting DKD risk in diabetic individuals. In this study, leveraging extensive clinical datasets, we sought to develop and validate a predictive model employing machine learning techniques to assess the risk of DKD in patients with type 2 diabetes mellitus (T2DM).Research design and methodsWe conducted a retrospective collection of clinical data from 10,057 patients diagnosed with T2DM at Shijiazhuang Second Hospital. A random selection of 15% of these patients (n=1,508) was utilized for external validation. The remaining 8,549 patients were divided into a training set (n = 5,985) and a validation set (n = 2,564) using a simple random sampling method in a 7:3 ratio. Subsequently, we employed LASSO regression to identify variables significantly associated with DKD in T2DM patients. These variables were incorporated into eight distinct predictive models: Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), Gaussian Naive Bayes (GNB), KNeighbors Classifier (KNN), Gradient Boosting Classifier (GBM), AdaBoost Classifier (AdaBoost), and Extreme Gradient Boosting (XGBoost). The models’ predictive performance was assessed using metrics such as the area under the curve (AUC), accuracy, F1 score, and Brier score. Finally, we developed an online calculator to estimate DKD risk in T2DM patients.ResultsFifteen features—namely gender, age, systolic blood pressure (SBP), blood urea nitrogen (BUN), creatinine (Cr), BUN/Cr ratio, uric acid (UA), hemoglobin A1c (HbA1c), microalbuminuria, presence of diabetic retinopathy (DR), hypertension, coronary heart disease (CHD), history of cerebral infarction, family history of diabetes, and family history of CHD-associated with DKD were selected using LASSO regression. Among eight evaluated models, the XGBoost algorithm demonstrated superior performance on both training and validation datasets, with an AUCof 0.932 (95%CI: 0.926-0.938) and 0.930, (95%CI: 0.920-0.939), respectively. The model achieved an accuracy of 0.845 and 0.844, sensitivity of 0.834 and 0.850, specificity of 0.857 and 0.837, F1 score of 0.847 and 0.848, and a Brier score of 0.167 and 0.166, respectively. Decision curve analysis (DCA) further validated the superiority of the XGBoost model over other models across a range of clinically relevant risk thresholds, yielding the highest net benefits. Finally, an online predictive calculator for the occurrence of DKD was developed based on the XGBoost model, utilizing a cut-off value of 50.7%.ConclusionsThe developed XGBoost model demonstrated optimal predictive accuracy for the occurrence of DKD in patients with T2DM. This model facilitated the construction of an online prediction calculator, offering an accessible and practical tool for both patients and clinicians.
Read moreCharacteristics and outcomes of electric bicycle-related canalicular lacerations in a tertiary hospital in North China.
The purpose of this study was to describe the demographics and outcomes of patients treated for electric bicycle (EB)-related canalicularlacerations. We performed a retrospective review of 116 patients who had suffered EB-related canalicularlacerations, and got referral to Hebei Eye Hospital in North China from 1 January 2013 to 31 December 2019. The demographic data including age, gender,injury laterality,injury location, associatedinjuries andsurgicalrepair results were all recorded. A total of 116 patients who had EB-related canalicularlacerations and met the inclusion criteria were enrolled in the study. The average age of the 116 patients was 46.9years (ranging from 15 to 79years), including 74 (63.8%) males and 42 (36.2%) females. Among the patients, 108 (93.1%) were farm workers, 3 (2.6%) were industrial workers, 5 (4.3%) were students. The most frequency associated injuries was fracture, and a total of 57 (49.1%) fractures were discovered, and the most common fractures sites were medial orbital wall, accounting for 25 (21.6%) patients. The functional success rate was 87.1%. High speeding was identified as the primary cause of injuries, followed by using motor vehicle lanes, carrying goods or children while riding the EB, failing to obey traffic signals, helmet wearing and evenings during rush hour. EB-related canalicular lacerations may lead to severe consequences. Therefore, to improve safety awareness, put forward policies and suggestions, strengthen the publicity of laws and regulations, and regulate the use of electric bicycles, in order to improve safety and prevent injuries.
Read moreApplication of intraorbital magnets in the removal of magnetic intraorbital foreign bodies
BackgroundTo explore a new surgical method for treating intraorbital foreign bodies.Materials and methodsFrom January 2015 to December 2023, 35 patients with magnetic intraorbital foreign bodies, representing 35 affected eyes, were admitted to the Department of Ocular Trauma of Hebei Eye Hospital; these patients included 32 males and 3 females aged from 2 to 63 years (average: 36.97 ± 14.28 years). In the preoperative examinations and postoperative routine follow-ups, the basic conditions of the patients’ eyes were ascertained through visual acuity examination using an international standard chart, slit‒lamp microscopic examination, anterior- and posterior-segment examinations with anterior slit‒lamp lenses, and intraocular pressure measurements. The foreign bodies were properly localized on axial and coronal CT scans. All patients had deep, orbital, magnetic foreign bodies and underwent extraction using a strong magnet.ResultsAmong the 35 patients (35 eyes), the foreign body was successfully removed from 34 eyes, with a success rate of 97.1%. In one patient, the foreign body had been retained in the posterior location of the orbit for nearly 30 years, with organizational encapsulation, and was not removed, considering the risk of damaging the globe and optic nerves. None of the patients experienced postoperative complications, such as decreased visual acuity, excessive intraorbital haemorrhage, aggravated limitation of eye movement, or intraorbital infection.ConclusionForeign body removal using a strong magnet is the optimal surgical procedure for treating deep intraorbital metallic foreign bodies.
Read moreTHE QUANTITATIVE CONE BEAM-COMPUTED TOMOGRAPHY STUDY OF THE THERAPEUTIC EFFECT OF PULP BLOOD FLOW RECONSTRUCTION IN ENDODONTIC DISEASE
The quality of dental pulp cone beam computed tomography (CBCT) images significantly impacts the accuracy of disease diagnosis. However, existing CBCT images often suffer from deficiencies such as artifacts, noise, resolution limitations and data processing issues, which frequently lead to misdiagnoses and missed diagnoses. This study aims to construct a highly accurate dental pulp CBCT image segmentation model based on the pulse-coupled neural network (PCNN) approach. By optimizing the PCNN model, this work sought to enhance the segmentation accuracy of dental pulp CBCT images and to evaluate the clinical efficacy of dental pulp revascularization surgery through quantitative analysis of the CBCT images, thereby improving the diagnostic accuracy of imaging data and the reliability of treatment outcome assessments. To achieve this, a cross-entropy thresholding method was introduced to optimize the PCNN model, establishing the Otsu-PCNN model for CBCT pulp segmentation. The model performance was evaluated using accuracy, sensitivity, positive predictive value (PPV) and the area under the receiver operating characteristic curve (ROC). The study involved 43 patients with pulp diseases who underwent dental pulp revascularization, with follow-ups conducted preoperatively and at 3, 6, 9, 12 and 18 months postoperatively. Changes in root image area (RIA), tooth root length (TRL) and apical diameter (AHd) were recorded, along with the classification of root development types. The results showed that the sensitivity and PPV of the Otsu-PCNN model were significantly higher than those of the optimized PCNN model ([Formula: see text]). The detection time for the Otsu-PCNN model was 13.80 s, with an ROC area of 0.93. The overall effective treatment rate for all patients was 100%. RIA, TRL and AHd increased from 30.55%, 2.58% and 19.95% at 3 months postoperatively to 84.85%, 25.18% and 51.62% at 18 months, respectively. Of the roots examined, 22 (48.84%) exhibited Type I root development. This study demonstrates that the optimization of the PCNN model significantly enhances the segmentation accuracy of dental pulp CBCT images, and that dental pulp revascularization surgery can effectively improve root development, yielding significant results in the treatment of pulp diseases.
Read moreThe inhibitory effects of Cucurbitacin B on hypopharyngeal cancer cell malignant behaviors were investigated based on network pharmacology and molecular docking
Hypopharyngeal cancer is a metastatic squamous cell carcinoma of the head and neck (SCCHN), and the early symptoms are not obvious. Cucurbitacin B (Cu-B) is the most abundant member of the Cucurbitacin family and has a wide range of pharmacological activities, but its effect on hypopharyngeal cancer is not very clear. The cell functions were detected by the cell counting kit-8 (CCK-8), colony formation assay, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, wound healing, transwell, and tube formation assays. The Gene Expression Omnibus (GEO), Comparative Toxicogenomics Database (CTD), SwissTargetPrediction, and GeneCards databases were applied to identify the targets of Cu-B in hypopharyngeal cancer. What’s more, the protein-protein interaction (PPI) network was constructed using the String database, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed employing the DAVID database. The TOP 10 hub genes were screened adopting the Cytoscape software and the gene expression was predicted or determined by the GEO and Gene Expression Profiling Interactive Analysis (GEPIA) databases or quantitative reverse transcription PCR (qRT-PCR) and western blot. The molecular docking was executed in the Autodock Vina software. Cellular functional assays (cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, wound healing, transwell, and tube formation) were conducted. Network pharmacology integrating the Gene Expression Omnibus (GEO), Comparative Toxicogenomics Database (CTD), SwissTargetPrediction, and GeneCards databases identified potential Cu-B targets. Protein-protein interaction (PPI) network (String), Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis (DAVID), and molecular docking (Autodock Vina) were performed. Hub gene validation employed quantitative reverse transcription PCR (qRT-PCR), western blot, and rescue experiments. Cu-B dose-dependently restrained the malignant behaviors of FaDu cells. Bioinformatics analysis prioritized transforming growth factor beta 1 (TGFB1) as a core target, confirmed by its overexpression in hypopharyngeal cancer. Molecular docking revealed strong Cu-B-TGFB1 binding. Meanwhile, Cu-B retarded FaDu cell malignant behaviors by repressing TGFB1 expression. The network pharmacology along with bioinformatics analysis and molecular docking confirm that Cu-B may combine with TGFB1 to confine the malignant progression of hypopharyngeal cancer.
Read moreEfficacy of Combined Conjoint Fascial Sheath and Levator Muscle Composite Flap Suspension for Recurrent Severe Ptosis
BackgroundConjoint fascial sheath (CFS) and levator muscle (LM) composite flap suspension has been gradually accepted for the treatment of congenital severe blepharoptosis in recent years. This study is to evaluate the clinical efficacy of conjoint fascial sheath with levator muscle (CFS + LM) suspension in the treatment of recurrent severe ptosis.MethodsA total of 45 patients (51 eyes) with recurrent severe ptosis admitted to our hospital between February 2018 and October 2022 were treated with CFS + LM suspension. The surgical efficacy was evaluated by recording and analyzing the distance (in millimeters) from the pupillary reflex on the patient’s cornea to the upper eyelid margin (MRD1), palpebral fissure height (PFH), lagophthalmos (LAG), degree of satisfaction and complications.ResultsA total of 45 patients (51 eyes) with recurrent severe ptosis were included in this study, including 26 males and 19 females, with an average age of 23.16 ± 10.68 years. The average levator function was 1.98 ± 1.35 mm, and the average postoperative follow-up time was 19.71 ± 13.77 month. The preoperative MRD1 and PFH were − 0.18 ± 1.03 mm and 3.90 ± 0.88 mm, respectively. Postoperative follow-up was conducted at least 6 months, and the MRD1 and PFH values were 2.25 ± 0.77 mm and 7.04 ± 0.82 mm at the last follow-up, respectively; the differences with the corresponding preoperative values were significant (p< 0.05). All the operated eyes had different degrees of LAG, which also stabilized 6 months after surgery. The treatment was considered curative for 30 eyes (58.82%), to have made improvement in 11 eyes (21.57%), and ineffective for 10 eyes (19.61%). The overall effectiveness (curative + improvement) rate was 80.39%, and the total degree of satisfaction reached 77.78%. After surgery, conjunctival prolapse occurred in 3 patients, 2 of whom recovered after placement of fornix sutures. Conjunctival prolapse in 1 patient disappeared after conservative treatment. Exposure keratitis occurred in 1 patient and improved after drug treatment. No other complications occurred.ConclusionsCFS + LM suspension technique for correcting recurrent severe ptosis is easy to perform, causes minimal trauma, and results in good therapeutic effects and few complications. We recommend popularizing this technique in clinical practice.Level of Evidence IIThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Read moreZonular ligament abnormalities intermingled in acute primary angle closure: A diagnostic and therapeutic challenge