Cell Biology International最新文献

Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig-2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig-2 positive cells count in hippocampi of chronic stress-exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig-2 proteins. This work underscores the amelioration of the stress-induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.

Lung cancer is one of the most prevalent human cancers with a high lethality rate worldwide. In this study, we demonstrated that GSE1 (genetic suppressor element 1) expression is aberrantly upregulated in lung adenocarcinoma and that GSE1 depletion inhibits the proliferation and migration of both A549 and H1299 cells. Immunoprecipitation assays demonstrated that GSE1 interacts with histone deacetylase 1 (HDAC1) and other BRAF–HDAC complex (BHC) components in cells. The transcriptome of GSE1-knockdown A549 cells indicated that 207 genes were upregulated and 159 were downregulated based on a p-value < .05 and fold change ≥ 1.5. Bioinformatics analysis suggested that 140 differentially expressed genes harbor binding sites for HDAC1, including the tumor suppressor gene KLF6 (Kruppel-like factor 6). Indeed, quantitative reverse-transcription polymerase chain reaction and western blot analysis revealed that GSE1 could inhibit the transcription of KLF6 in lung cancer cells. In conclusion, GSE1 cooperates with HDAC1 to promote the proliferation and metastasis of non-small cell lung cancer cells through the downregulation of KLF6 expression.

ErbB3-binding protein 1(Ebp1) has two isoforms, p42 Ebp1 and p48 Ebp1, both of which can regulate cell growth and differentiation. But these isoforms often have opposite effects, including contradictory roles in regulation of cell growth in different tissues and cells. P48 Ebp1 belongs to the full-length sequence, while conformational changes in the crystal structure of p42 Ebp1 reveals a lack of an α helix at the amino terminus. Due to the differences in the structures of these two isoforms, they have different binding partners and protein modifications. Ebp1 can function as both an oncogene and a tumor suppressor factor. However, the underlying mechanisms by which these two isoforms exert opposite functions are still not fully understood. In this review, we summarize the genes and the structures of protein of these two isoforms, protein modifications, binding partners and the association of different isoforms with diseases.

RETRACTION: W. Xi, X. Zhao, M. Wu, W. Jia, and H. Li, “Lack of MicroRNA-155 Ameliorates Renal Fibrosis by Targeting PDE3A/TGF-β1/Smad Signaling in Mice with Obstructive Nephropathy”, Cell Biology International 42, no. 11 (2018): 1523-1532. https://doi.org/10.1002/cbin.11038

The above article, published online on 6 August 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Sergio Schenkman; the International Federation for Cell Biology; and John Wiley & Sons Ltd.

The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Several flaws and inconsistencies between results presented and experimental methods described were found. Furthermore, several image elements in Figure 2 A were found to have been published previously in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. The authors have been informed of the decision of retraction but were not available for a final confirmation.

Platelets are essential component of circulation that plays a major role in hemostasis and thrombosis. During activation and its demise, platelets release platelet-derived microvesicles, with lysophosphatidylcholine (LPC) being a prominent component in their lipid composition. LPC, an oxidized low-density lipoprotein, is involved in cellular metabolism, but its higher level is implicated in pathologies like atherosclerosis, diabetes, and inflammatory disorders. Despite this, its impact on platelet function remains relatively unexplored. To address this, we studied LPC's effects on washed human platelets. A multimode plate reader was employed to measure reactive oxygen species and intracellular calcium using H₂DCF-DA and Fluo-4-AM, respectively. Flow cytometry was utilized to measure phosphatidylserine expression, mitochondrial membrane potential (ΔΨm), and mitochondrial permeability transition pore (mPTP) formation using FITC-Annexin V, JC-1, and CoCl₂/calcein-AM, respectively. Additionally, platelet morphology and its ultrastructure were observed via phase contrast and electron microscopy. Sonoclot and light transmission aggregometry were employed to examine fibrin formation and platelet aggregation, respectively. The findings demonstrate that LPC induced oxidative stress and increased intracellular calcium in platelets, resulting in increased phosphatidylserine expression and reduced ΔΨm. LPC triggered caspase-independent platelet death and mPTP opening via cytosolic and mitochondrial calcium, along with microvesiculation and reduced platelet counts. LPC increased the platelet's size, adopting a balloon-shaped morphology, causing membrane fragmentation and releasing its cellular contents, while inducing a pro-coagulant phenotype with increased fibrin formation and reduced integrin αIIbβ3 activation. Conclusively, this study reveals LPC-induced oxidative stress and calcium-mediated platelet death, necrotic in nature with pro-coagulant properties, potentially impacting inflammation and repair mechanisms during vascular injury.

Ferroptosis is a novel form of programmed cell death and is considered to be a druggable target for colorectal cancer (CRC) therapy. However, the role of ferroptosis in CRC and its underlying mechanism are not fully understood. In the present study we found that a protein enriched in the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3), was overexpressed in human CRC tissue and in several CRC cell lines. The expression of GOLPH3 was significantly correlated with the expression of ferroptosis-related genes in CRC. The overexpression of GOLPH3 in Erastin-induced Caco-2 CRC cells reduced ferroptotic phenotypes, whereas the knockdown of GOLPH3 potentiated ferroptosis in HT-29 CRC cells. GOLPH3 induced the expression of prohibitin-1 (PHB1) and prohibitin-2 (PHB2), which also inhibited ferroptosis in Erastin-treated CRC cells. Moreover, GOLPH3 interacted with PHB2 and nuclear factor erythroid 2-related factor 2 (NRF2) in Caco-2 cells. These observations indicate that GOLPH3 is a negative regulator of ferroptosis in CRC cells. GOLPH3 protects these cells from ferroptosis by inducing the expression of PHB1 and PHB2, and by interacting with PHB2 and NRF2.

It was imperative to identify latent biomarkers pertinent to malignancies, given the pivotal role targeted molecular therapies play in tumor treatment investigations. This study aimed to assess the validity of HAUS1 as an indicator for survival prognosis and immune responses in prostate adenocarcinoma (PRAD) via single-cell and bulk RNA-sequencing. Related data on HAUS1 expression in PRAD were obtained from online databases, followed by comprehensive analyses to delineate its associations with survival prognosis, implicated pathways, and immune responses. Besides, the expression pattern of HAUS1 in PRAD was also verified in vitro, by using qRT-PCR, Western blot analysis, and immunohistochemistry. We found HAUS1 was downregulated in PRAD compared with normal tissues, as verified in vitro by qRT-PCR, Western blot, and immunohistochemistry (p < 0.05). Single-cell RNA-sequencing analysis indicated that HAUS1 had relatively higher expressions in B cells, Mono/Macro cells, and Endothelial cells compared with other cell types. Cox regression analysis revealed HAUS1 could serve as an independent indicator for the overall survival prognosis of PRAD (p < 0.05). Spearman correlation analyses revealed HAUS1 was closely related to the tumor microenvironment, immune cell infiltration levels, immune checkpoints, and immune cell pathways (p < 0.05). Furthermore, HAUS1 expression was found to be closely related to the immunotherapeutic response of patients receiving clinical intervention (p < 0.05). Collectively, our findings underscored the significant role of HAUS1 in PRAD prognosis and immune response, thereby presenting a novel and promising avenue for investigating the clinical utility of immunotherapy in PRAD.

Type 2 diabetes mellitus (T2DM) is an immensely debilitating chronic disease that progressively undermines the well-being of various bodily organs and, indeed, most patients succumb to the disease due to post-T2DM complications. Although there is evidence supporting the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway by insulin, which is essential in regulating glucose metabolism and insulin resistance, the significance of this pathway in T2DM has only been explored in a few studies. The current review aims to unravel the mechanisms by which different classes of PI3Ks control the metabolism of glucose; and also to discuss the original data obtained from international research laboratories on this topic. We also summarized the role of the PI3K/Akt signaling axis in target tissues spanning from the skeletal muscle to the adipose tissue and liver. Furthermore, inquiries regarding the impact of disrupting this axis on insulin function and the development of insulin resistance have been addressed. We also provide a general overview of the association of impaired PI3K/Akt signaling pathways in the pathogenesis of the most prevalent diabetes-related complications. The last section provides a special focus on the therapeutic potential of this axis by outlining the latest advances in active compounds that alleviate diabetes via modulation of the PI3K/Akt pathway. Finally, we comment on the future research aspects in which the field of T2DM therapies using PI3K modulators might be developed.

Aldehyde dehydrogenase 1 (ALDH1), a crucial aldehyde metabolizing enzyme, has six family members. The ALDH1 family is expressed in various tissues, with a significant presence in the liver. It plays a momentous role in several pathophysiological processes, including aldehyde detoxification, oxidative stress, and lipid peroxidation. Acetaldehyde detoxification is the fundamental function of the ALDH1 family in participating in vital pathological mechanisms. The ALDH1 family can catalyze retinal to retinoic acid (RA) that is a hormone-signaling molecule and plays a vital role in the development and adult tissues. Furthermore, there is a need for further and broader research on the role of the ALDH1 family as a signaling molecule. The ALDH1 family is widely recognized as a cancer stem cell (CSC) marker and plays a significant role in the proliferation, invasion, metastasis, prognosis, and drug resistance of cancer. The ALDH1 family also participates in other human diseases, such as neurodegenerative diseases, osteoarthritis, diabetes, and atherosclerosis. It can inhibit disease progression by inhibiting/promoting the expression/activity of the ALDH1 family. In this review, we comprehensively analyze the tissue distribution, and functions of the ALDH1 family. Additionally, we review the involvement of the ALDH1 family in diseases, focusing on the underlying pathological mechanisms and briefly talk about the current status and development of ALDH1 family inhibitors. The ALDH1 family presents new possibilities for treating diseases, with both its upstream and downstream pathways serving as promising targets for therapeutic intervention. This offers fresh perspectives for drug development in the field of disease research.

Trichloroethylene (TCE) is a commonly used organic solvent in industry. Our previous studies have found that TCE can cause liver injury accompanied by macrophage polarization, but the specific mechanism is unclear. The epigenetic regulation of macrophage polarization is mainly focused on histone modification. Histone lysine demethylase 4A (KDM4A) is involved in the activation of macrophages. In this study, we used a mouse model we investigated the role of KDM4A in the livers of TCE-drinking mice and found that the expression of KDM4A, M1-type polarization indicators, and related inflammatory factors in the livers of TCE-drinking mice. In the study, BALB/c mice were randomly divided into four groups: 2.5 mg/mL TCE dose group and 5.0 mg/mL TCE dose group, the vehicle control group, and the blank control group. We found that TCE triggered M1 polarization of mouse macrophages, characterized by the expression of CD11c and robust production of inflammatory cytokines. Notably, exposure to TCE resulted in markedly increased expression of KDM4A in macrophages. Functionally, the increased expression of KDM4A significantly impaired the expression of H3K9me3 and H3K9me2 and increased the expression of H3K9me1. In addition, KDM4A potentially represents a novel epigenetic modulator, with its upregulation connected to β-catenin activation, a signal critical for the pro-inflammatory activation of macrophages. Furthermore, KDM4A inhibitor JIB-04 treatment resulted in a decrease in β-catenin expression and prevented TCE-induced M1 polarization and the expression of the pro-inflammatory cytokines TNF-α and IL-1β. These results suggest that the association of KDM4A and Wnt/β-catenin cooperatively establishes the activation and polarization of macrophages and global changes in H3K9me3/me2/me1. Our findings identify KDM4A as an essential regulator of the polarization of macrophages and the expression of inflammatory cytokines, which might serve as a potential target for preventing and treating liver injury caused by TCE.