Cell Biology International最新文献

Pulmonary fibrosis (PF), particularly idiopathic pulmonary fibrosis, is a chronic and fatal disease. However, the precise pathogenic mechanisms underlying this condition remain elusive. We employed LASSO regression and random forest analyses, combined with expression profiling in TGFβ1-induced MRC-5 cells and bleomycin-induced PF mouse models, to identify differentially expressed genes. These analyses revealed that cytoplasmic carboxypeptidase 1 (CCP1) was significantly downregulated in fibrotic conditions. Relevant signaling pathways were further identified through RNA sequencing (RNA-seq). Subsequent functional studies were conducted using qRT-PCR, western blot, hematoxylin and eosin (HE) staining, Masson's trichrome staining, immunohistochemistry (IHC), immunofluorescence, scratch assays, EdU assays, RNA interference, and co-immunoprecipitation (co-IP). Functional studies revealed that CCP1 knockdown promoted cell migration, proliferation, and the transformation of MRC-5 cells into a fibrotic phenotype, as evidenced by increased expression of fibrosis-associated markers (FN1, COL 1α1, and ACTA2) and dysregulated expression of apoptosis-related markers (BCL2 and BAX). Conversely, CCP1 overexpression inhibited these processes. CCP1 was discovered to inhibit the PI3K/AKT signaling pathway by binding to eukaryotic initiation factor 4B (EIF4B). Overexpression of EIF4B activated the fibrotic process and interacted with c-Myc. In vivo studies further demonstrated that CCP1 inhibited PF by suppressing EIF4B to inhibit the PI3K/AKT signaling pathway. In summary, our results demonstrate that CCP1 inhibits the development of PF by suppressing the EIF4B/PI3K/AKT axis. This study offers new perspectives into the pathogenesis of PF and underscores CCP1 as a potential therapeutic target for managing this condition.

Gastrointestinal (GI) cancers represent a major global health burden, significantly impacts the digestive system. Recent research has focused on the relationship between interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) to deepen understanding of GI cancer—including esophageal, gastric, pancreatic, hepatobiliary, and colorectal cancers—pathogenesis and to enhance diagnostic and therapeutic strategies. Elevated levels of IL-6, IL-10, and CRP have been associated with advanced disease stages and poor prognosis, underscoring their potential utility as biomarkers for disease progression and outcome prediction. Moreover, these markers appear to modulate the sensitivity of GI cancer cells to chemotherapy, suggesting that their assessment in serum and tissue samples could aid therapeutic decision-making and predict treatment responses. In addition to their diagnostic and prognostic value, IL-6, IL-10, and CRP are being investigated as targets for preventive strategies. These findings highlight the potential role of anti-inflammatory interventions in chemoprevention. Overall, studying the interplay among IL-6, IL-10, and CRP has yielded valuable insights into the molecular mechanisms driving GI cancer development and progression. Continued research is essential to fully elucidate these complex interactions and to translate these findings into effective clinical applications for the management of GI malignancies.

Benign prostatic hyperplasia (BPH), a prevalent age-related condition in men, is increasingly linked to metabolic syndrome (MetS) and gut microbiota dysbiosis. This study reveals how Firmicutes-dominant microbial imbalance drives BPH progression via IGF-1 signaling and identifies the green tea polyphenol epigallocatechin-3-gallate (EGCG) as a dual-action therapeutic. Using MetS-BPH mouse models and human prostate cell lines, we demonstrated that BPH-associated gut microbiota—particularly elevated Firmicutes and an increased Firmicutes/Bacteroidetes ratio—promotes prostate hyperplasia by upregulating IGF-1. Both BPH mice and recipient mice transplanted with BPH microbiota showed elevated serum and prostate IGF-1 levels, mirroring findings in human BPH patients. Mechanistically, IGF-1 stimulated prostate cell proliferation (RWPE-1/WPMY-1) and suppressed apoptosis via PI3K/AKT/mTOR activation, while the IGF-1 antagonist Linsitinib reversed these effects. EGCG emerged as a potent modulator of this gut-prostate axis: it selectively reduced Firmicutes overgrowth in BPH mice, normalized IGF-1 levels, and inhibited downstream PI3K/AKT/mTOR signaling. In fecal microbiota transplantation experiments, EGCG counteracted IGF-1-driven prostate enlargement and microbial dysbiosis, underscoring its dual role in rebalancing gut flora and blocking growth factor pathways. Our findings position EGCG as a promising intervention for MetS-associated BPH, simultaneously targeting microbial dysbiosis and IGF-1 signaling. This study not only elucidates the Firmicutes–IGF-1 axis in BPH pathogenesis but also highlights the therapeutic potential of dietary polyphenols in metabolic urological disorders.

Atherosclerosis (AS) is a chronic and progressive inflammatory condition affecting arterial walls. It is widely accepted that the deposition of low-density lipoprotein (LDL) and its adverse impact on endothelial cells (ECs) play a pivotal role in the development of AS. Specifically, oxidized LDL (ox-LDL) has been validated as a trigger for inducing pyroptosis in ECs, thereby contributing significantly to intima inflammation and AS progression. However, the underlying molecular mechanisms require further investigation. In this study, we demonstrated that ox-LDL significantly upregulates the expression of pyrin domain-containing 3 (NLRP3) protein levels in ECs. This upregulation is associated with increased caspase-1 cleavage, interleukin-1β (IL-1β) maturation, and lactate dehydrogenase (LDH) release. Moreover, ox-LDL also upregulates the expression of ASC, caspase-1, GSDMD, IL-1β, and IL-18 proteins. The inhibition of NLRP3-specific inhibitor MCC950 or caspase-1-specific inhibitor VX-765 effectively suppressed the expression of cellular pyroptosis-associated proteins. Our findings highlight the crucial role of Tangzhi Qing (TZQ) in regulating ox-LDL-induced pyroptosis and inflammation through the activation of the NLRP3 inflammasome. This suggests that NLRP3 inflammasome could serve as a promising therapeutic target for mitigating diseases associated with atherosclerosis.

Endothelial dysfunction is a critical contributor to atherosclerosis and cardiovascular diseases, driven by oxidative stress and inflammation induced by oxidized low-density lipoprotein (oxLDL). This study investigates the protective effects of reduced glutathione (GSH) against oxLDL-induced endothelial dysfunction using human umbilical vein endothelial cells (HUVECs) as an in vitro model. Our findings demonstrate that oxLDL exposure significantly reduces cell viability, induces oxidative stress, and promotes endothelial injury by upregulating LOX-1 expression, decreasing nitric oxide (NO) production, and impairing endothelial nitric oxide synthase (eNOS) activity. Pretreatment with GSH effectively restores cell viability, reduces ROS generation, suppresses LOX-1 expression, and preserves NO bioavailability by maintaining eNOS activity. Additionally, GSH enhances the antioxidant defense system by increasing superoxide dismutase, catalase, and glutathione peroxidase levels while reducing lipid peroxidation, as indicated by lower malondialdehyde content. Beyond its antioxidative properties, GSH exhibits antiapoptotic effects by restoring the Bax/Bcl-2 balance, inhibiting cytochrome C release, and suppressing caspase-3 activation, thereby preventing mitochondrial membrane depolarization. Furthermore, GSH mitigates endothelial inflammation by downregulating intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. These findings highlight GSH's potential as a therapeutic agent for protecting endothelial cells against oxLDL-induced dysfunction by alleviating oxidative stress, apoptosis, and inflammation, ultimately contributing to the prevention of atherosclerosis progression.

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC) are chronic recurrent nonspecific intestinal disease. Current IBD therapeutics cannot fundamentally change the natural course of IBD. Therefore, it is of great significance to find new treatment strategies for IBD. Preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising therapeutic approach. However, the mechanism by which MSCs alleviate colitis and how MSCs affect intestinal mucosal barrier is still unclear. LPS-exposed human colonic epithelial cancer cell lines Caco2 and HT29. Dextran sulfate sodium (DSS)-induced IBD mouse were treated with MenSCs. We found that LPS downregulates intercellular junction proteins and induces the production of inflammatory cytokines in intestinal epithelial cells. MenSCs reduced paracellular permeability and restored barrier integrity in Caco2 cells. In Vivo, MenSCs mitigated DSS-induced colitis in mice by reducing body weight loss, colonic shortening, and disease activity index scores and by inhibiting the expressions of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. MenSCs increased the expression of TJ proteins, improved the destruction of tight junction (TJ) structures, and reduced intestinal epithelial permeability. Furthermore, MenSCs could inhibit NF-κB p65 phosphorylation and the expression of Snail and prevent Snail nuclear localization, thereby maintaining tight and adherens junctions. Our findings demonstrate that MenSCs alleviate intestinal inflammation and enhance barrier function by suppressing the NF-κB/Snail signaling axis, offering a promising therapeutic strategy for inflammatory bowel diseases.

Hypoxic-ischemic encephalopathy (HIE) represents a leading cause of morbidity and mortality among neonates. However, the underlying molecular mechanisms of HIE remain largely elusive. A HIE animal model was established, and neural stem cells (NSCs) underwent oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic HIE in vitro. The HIE-induced brain injury was evaluated using a battery of assessments, including the Morris water maze test, wire hanging test, cylinder test, TTC, TUNEL, IHC, and IF staining. Subsequently, the expressions of budding uninhibited by benzimidazoles related 1 (BUBR1) and signal transducer and activator of transcription 3 (STAT3) were examined using immunoblotting and qRT-PCR. Furthermore, the interaction between BUBR1 and STAT3 was confirmed through co-immunoprecipitation assays. BUBR1 was observed to be downregulated in both the HIE model and in NSCs subjected to OGD/R. Notably, the restoration of BUBR1 expression was found to alleviate the detrimental effects of HIE, primarily by facilitating nerve regeneration. Further investigation revealed that BUBR1 also mitigated OGD/R-induced apoptosis in NSCs. Mechanistically, BUBR1 was shown to regulate the phosphorylation of STAT3, a crucial transcription factor involved in cell survival and regeneration. Moreover, BUBR1 alleviated OGD/R-induced apoptosis of NSCs and promoted nerve regeneration to protect HIE by regulating STAT3 phosphorylation. BUBR1 facilitated nerve regeneration by modulating STAT3 phosphorylation, thereby alleviating HIE.

Alopecia represents a global therapeutic challenge, with the challenge of achieving de novo folliculogenesis in alopecic regions rather than reactivating telogen-phase hair follicles to enhance hair density. The successful in vitro cultivation of hair follicle organoids (HFOs) and the effective enhancement of HFOs sprouting rates are critical advancements in addressing this problem. While R-spondin1 (RSPO1) demonstrates in vivo efficacy in activating quiescent follicular stem cells and enhancing hair density, its capacity to augment HFOs sprouting efficiency remains to be elucidated. In this study, we regulate the growth microenvironment of HFOs using RSPO1, enhancing the HFOs sprouting rate and exploring its mechanism. HFO-induced dermal papilla cells (DPCs) induction was quantified via alkaline phosphatase (ALP) assay, with RSPO1-mediated hair-regenerative gene/protein modulation assessed through triple-method analysis (qPCR/WB/IF). Sequencing delineated RSPO1-affected molecular pathways. Our study demonstrates that RSPO1 significantly promotes HFOs sprouting rate and upregulates the gene/protein expression of DPCs. Furthermore, RSPO1 not only potentiates Wnt/β-catenin-mediated organoid patterning but also coordinates a signaling triad involving PI3K-Akt, Rap1 and NF-κB to drive synchronized hair follicle sprouting and stratified pilogenic differentiation. Our 3D organoid-based expansion strategy enables definitive treatment of alopecia through in vitro hair follicle expansion, achieving functional hair neogenesis in patients with baldness.