Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective: To study the effects of Porphyromonas gingivalis (P. g) infection with I, II and IV fimA genotypes on the expression of IL-1beta, IL-6 and TNF-alpha in human umbilical vein endothelial cells (HUVECs). Methods : HUVECs infected with different fimA genotypes were divided into the fimA type I stimulation group, fimA type II stimulation group, fimA type IV stimulation group. In addition, a positive control group (E. coli LPS stimulation) and negative control group (cell culture medium only) were included. Cell proliferation was detected by MTT assay, and cell apoptosis was detected by flow cytometry. IL-1β, IL-6, TNF-α levels in the supernatant of HUVECs after P. g stimulation were assessed by ELISA at 2 h, 6 h and 24 h. Results : HUVECs were infected by P. g with fimA type I,fimA type II and LPS for 24 h. Cell proliferation was inhibited compared with the negative control group (P < 0.05), but there was no significant difference in the apoptosis rate between P. g infection and the negative control group. IL-1β levels in cell culture supernatants were higher at 2th than 6 and 24 h after stimulation of HUVECs with different fimA genotypes, while the IL-6 levels were higher at 24 h than the other time, while the TNF-α levels were no significant difference at every time. After fimA type II and IV P. g infection, IL-1β, IL-6, and TNF-α levels were increased compared with fimA type I P. g (P < 0.05). Conclusion Different P. g fimA genotypes have different effects on stimulating HUVECs to induce dysfunction. Here, fimA type II and IV P. g exhibit a strong ability to upregulate the secretion of IL-1β, IL-6 and TNF-alpha.

Aim Toinvestigatewhetherexposureto Sanguinarine (SAN ) can inhibit cell proliferation in human mammary adenocarcinoma cells (MCF-7 ) and thepossiblemechanism.Methods WeexposedMCF-7 to anticancer compound SAN,cell viability was as-sessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT ) reduction assay. ROS was measured using confocal microscopy,expres-sion of caspase-3 ,caspase-8 and caspase-9 were calcu-latedusingchemiluminescencemethod.Results SAN remarkably inhibited growth of human mammary adeno-carcinoma MCF-7 cells by decreasing cell proliferation. ROS release and caspase-3,caspase-8,caspase-9 ex-pression were stimulated by SAN in MCF-7 ,and these changes were abolished by the antioxidant,N-acetyl-cysteine(NAC).Conclusion Regulationofcaspases expression and release from MCF-7 cells are possibly e-voked by SAN through reactive oxygen species.

OBJECTIVE: To explore the role of calpain in pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension and the underlying mechanisms.
 METHODS: Sprague-Dawley rats were randomly divided into the hypoxia group and the normoxia control group. Right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored by a method with right external jugular vein cannula. Right ventricular hypertrophy index was presented as the ratio of right ventricular weight to left ventricular weight (left ventricle plus septum weight). Levels of calpain-1, -2 and -4 mRNA in pulmonary artery were determined by real-time PCR. Levels of calpain-1, -2 and -4 protein were determined by Western blot. Primary rat pulmonary arterial smooth muscle cells (PASMCs) were divided into 4 groups: a normoxia control group, a normoxia+MDL28170 group, a hypoxia group and a hypoxia+MDL28170 group. Cell proliferation was detected by MTS and flow cytometry. Levels of Ki-67 and proliferating cell nuclear antigen (PCNA) mRNA were determined by real-time PCR.
 RESULTS: RVSP, mPAP and right ventricular remodeling index were significantly elevated in the hypoxia group compared to those in the normoxia group. In the hypoxia group, pulmonary vascular remodeling was significantly developed, accompanied by up-regulation of calpain-1, -2 and -4. MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs concomitant with the suppression of Ki-67 and PCNA mRNA expression.
 CONCLUSION Calpain mediates vascular remodeling via promoting proliferation of PASMCs in hypoxia-induced pulmonary hypertension.
Animals ; Calpain ; genetics ; physiology ; Cell Proliferation ; Dipeptides ; physiology ; Hypertension, Pulmonary ; chemically induced ; genetics ; physiopathology ; Hypertrophy, Right Ventricular ; Hypoxia ; Ki-67 Antigen ; drug effects ; Myocytes, Smooth Muscle ; physiology ; Proliferating Cell Nuclear Antigen ; drug effects ; Pulmonary Artery ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Up-Regulation ; Vascular Remodeling ; genetics ; physiology