Cell Biology International

doi: 10.1002/cbin.11641pmid: N/A

Wang, Chenyang; Cheng, Dating; Pan, Chenglong; Wang, Chunyan; Nie, Zhi

doi: 10.1002/cbin.11740pmid: 34882895

The spindle assembly checkpoint (SAC) is a highly conserved monitoring system that ensures a fidelity of chromosome segregation during mitosis. Bub3, a mitotic Checkpoint Protein, is a member of the Bub protein family, and an important factor in the SAC. Abnormal expression of Bub3 results in mitotic defects, defective spindle gate function, chromosomal instability and the development of aneuploidy cells. Aneuploidy is a state of abnormal karyotype that has long been considered as a marker of tumorigenesis. Karyotypic heterogeneity in tumor cells, known as “chromosomal instability” (CIN), can be used to distinguish cancerous cells from their normal tissue counterpart. In this review, we summarize the expression and clinical significance of Bub3 in a variety of tumors and suggest that it has potential in the treatment of cancer.

Zhang, Mengdi; Seitz, Clayton; Chang, Garrick; Iqbal, Fadil; Lin, Hua; Liu, Jing

doi: 10.1002/cbin.11762pmid: 35032142

The emergence of labeling strategies and live cell imaging methods enables the imaging of chromatin in living cells at single digit nanometer resolution as well as milliseconds temporal resolution. These technical breakthroughs revolutionize our understanding of chromatin structure, dynamics and functions. Single molecule tracking algorithms are usually preferred to quantify the movement of these intranucleus elements to interpret the spatiotemporal evolution of the chromatin. In this review, we will first summarize the fluorescent labeling strategy of chromatin in live cells which will be followed by a systematic comparison of live cell imaging instrumentation. With the proper microscope, we will discuss the image analysis pipelines to extract the biophysical properties of the chromatin. Finally, we expect to give practical suggestions to broad biologists on how to select methods and link to the model properly according to different investigation purposes.

Barreto e Barreto, Laylla; Rattes, Isadora C.; Costa, Aline V.; Gama, Patrícia

doi: 10.1002/cbin.11764pmid: 35032139

The small intestine mucosa is lined by specialized cells that form the crypt‐villus axis, which expands its surface. Among the six intestinal epithelial cell types, the Paneth cell is located at the base of the crypt, and it contains numerous granules in its cytoplasm, composed of antimicrobial peptides, such as defensins and lysozyme, and growth factors, such as epidermal growth factor, transforming growth factor‐α, and Wnt ligands. Together, these elements act in the defense against microorganisms, regulation of intestinal microbiota, maintenance, and regulation of stem cell identity. Pathologies that target Paneth cells can disturb such defense activity, but they also affect the maintenance of the stem cell niche. In that way, Crohn's disease, necrotizing enterocolitis, and graft‐versus‐host disease promote a reduction of Paneth cell population, and, consequently, secretion of their products into the lumen of the crypts, making the affected organism predisposed to infections and dysbiosis. Additionally, the emergence of new intestinal cells is also decreased. This review aims to address the main characteristics of Paneth cells, highlighting their multiple functions and the importance of their preservation to ensure bowel homeostasis.

Peng, Liming; Long, Tianyi; Li, Fei; Xie, Qiying

doi: 10.1002/cbin.11773pmid: 35114043

Cardiovascular diseases (CVDs) contribute to the leading cause of death worldwide. Despite significant improvements in CVDs diagnosis and treatment, a continued effort to explore novel therapeutic strategies is urgently need. N6‐methyladenosine (m6A) RNA methylation, well known as the most prevalent type of RNA modifications, involved in RNA stability, nuclear exports, translation, and decoy, plays a crucial role in the pathogenesis of a variety of diseases, including CVDs, cancer, and drug resistance. Here, our article summarizes cellular functions of m6A modulators and recent research progress concerning the functions and mechanisms of m6A methylation in CVDs, in hope of providing references for exploring novel therapeutic approaches and potential biomarkers in the treatment of CVDs.

Cao, Guangying; Yang, Chao; Jin, Zhitao; Wei, Hanwen; Xin, Chao; Zheng, Chengrong; Xu, Jibing; Huang, Qing; Zhang, Zheng; Hu, Taohong

doi: 10.1002/cbin.11763pmid: 35032153

Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. Ferroptosis, a novel form of cell death, has been found to play critical roles under ischemic conditions. Recently, several studies have shown that fibronectin type III domain‐containing 5 (FNDC5) and its cleaved form, irisin, protect the heart against injury. However, its protective effect on ferroptosis and mitochondrial impairments is still unclear. Thus, our aim was to investigate the role of irisin in ferroptosis and mitochondrial dysfunction in cardiomyocytes under hypoxic conditions. Cardiomyocytes were treated with FNDC5 overexpression and/or irisin under normoxic and hypoxic conditions. Cell viability was assessed by Cell Counting Kit‐8 assay. Reactive oxygen species production was evaluated by dihydroethidium staining. In addition, the intracellular ferrous iron level (Fe2+) and the relative concentration of malondialdehyde and ATP content were determined using an Iron Assay Kit, Lipid Peroxidation Assay Kit, and ATP Bioluminescent Assay Kit. The superoxide dismutase level in cells was measured using an Enzyme‐Linked Immunosorbent Assay Kit. Furthermore, an immunoblotting assay was used to determine ferroptosis‐related mitochondrial proteins. Hypoxia promoted cell death, increased ferroptosis, and caused mitochondrial dysfunction in cardiomyocytes. Interestingly, FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO‐1 axis in hypoxic cardiomyocytes. Thus, we have demonstrated that FNDC5/irisin plays a protective role in ferroptosis and mitochondrial dysfunction in hypoxia‐induced cardiomyocytes.

Kim, Sun Hye; Rodriguez, Liliana R. L.; Macias, Everardo; Rodriguez‐Puebla, Marcelo L.

doi: 10.1002/cbin.11765pmid: 35032143

Hair follicles regenerate periodically by spontaneously undergoing cycles of growth, regression, and relative quiescence. During the hair cycle, follicle stem cells residing in a specialized niche remain quiescent, and they are stimulated to proliferate throughout the growth phase of the hair follicle. Although cell cycle regulators play a prominent role during the activation of hair follicle stem cells, the identity and the role of these regulators have not been confirmed. Herein, we reported that stem cells located in the bulge region of the HF (BuSCs) express high levels of cyclin‐dependent kinase 4 (CDK4) through the quiescent phase of the hair cycle. Using gain‐ and loss‐of‐function studies, we have determined that the CDK4 protein level affects the number of BuSCs. Transgenic expression of CDK4 in the bulge region of the hair follicles reduces the number of BuSCs, whereas CDK4 ablation resulted in an increasing number of BuSCs. These results suggest that deregulation of CDK4 protein levels contributes to distorting the self‐renewal/proliferation balance and, in turn, altering the number of BuSCs.

Pang, Ji; Li, Guorui; Qian, Hai; Wu, Yan; Chen, Yongchang

doi: 10.1002/cbin.11766pmid: 35066967

The study of secretory protein kinase is an emergent research field in recent years. The secretion phenomenon of type II cGMP‐dependent protein kinase (PKG II) was found in our latest research and our previous study confirmed that PKG II inhibited platelet‐derived growth factor receptor β (PDGFRβ) activation induced by platelet‐derived growth factor BB (PDGF‐BB) within the gastric cancer cells. Thus, this study was designed to investigated effect of secretory PKG II on PDGFRβ. Transwell assay and CCK8 assay indicated that secretory PKG II reversed PDGF‐BB‐induced cell migration, invasion, and proliferation. Immunoprecipitation, GST pull down and Western blotting results showed that secretory PKG II combined with extracellular domains of PDGFRβ and phosphorylated it, and thereby inhibited PDGF‐BB‐induced activation of PDGFRβ, and downstream PI3K/Akt and MAPK/ERK pathways. Mutation at Ser254 of PDGFRβ to alanine abolished the above inhibitory effects of secretory PKG II on PDGFRβ, indicating that Ser254 was the specific site phosphorylated by secretory PKG II. In conclusion, secretory PKG II inhibited PDGFRβ activation via Ser254 site.

Shu, Futing; Gao, Haojie; Wu, Wenfeng; Yu, Shaoshuo; Zhang, Lianjie; Liu, Huazhen; Xiao, Shichu; Xia, Zhaofan; Zheng, Yongjun

doi: 10.1002/cbin.11771pmid: 35077602

Human amniotic epithelial cells (hAECs), one of the stem cells identified from the human placenta, possess numerous advantages and have been considered as an attractive and available cell source for regenerative medicine. Accumulating evidence has showed that cellular senescence was one of the pathogenic hubs of diabetic wound chronicity. Keratinocytes and fibroblasts are the primary cells involved in wound healing. Therefore, in this study, we aimed to investigate the anti‐senescence effects of hAECs on keratinocytes and fibroblasts in diabetic wounds. Sustained hyperglycemia impaired cell function and accelerated senescence in vitro. However, this phenotype was rescued by hAECs‐conditioned medium (hAECs‐CM), with increased migration and proliferation in keratinocytes and fibroblasts and enhanced collagen synthesis and α‐smooth muscle actin (α‐SMA) production in fibroblasts. In addition, hAECs‐CM dramatically inhibited intracellular reactive oxygen species (ROS) and senescence‐associated β‐galactosidase (SA‐β‐gal) in keratinocytes and fibroblasts under high‐glucose (HG) condition. Moreover, hAECs‐CM could downregulate the increased RAGE and P21 induced by continuous HG stimulation. Intradermal injection of hAECs in diabetic wounds promoted re‐epithelialization and granulation tissue formation, accompanied by decreased P21+ cells and increased PCNA+ cells in epidermis and dermis, as well as promoted collagen deposition and α‐SMA expression. Furthermore, CM‐Dil‐labeled hAECs survived to Day 5 but disappeared by Day 10 in diabetic wounds. These findings indicated that hAECs could inhibit diabetes‐induced premature senescence and enhance the function of keratinocytes and fibroblasts via paracrine effects, partly by inhibiting RAGE/P21 signaling pathway. Thus, hAECs targeting cellular senescence induced by a hyperglycemic environment may be a new strategy for the treatment of diabetic wounds.

Sudhakaran, Gokul; Prathap, Pandurangan; Guru, Ajay; Rajesh, Ravi; Sathish, Sruthy; Madhavan, Thirumurthy; Arasu, Mariadhas V.; Al‐Dhabi, Naif A.; Choi, Ki Choon; Gopinath, Pushparathinam; Arockiaraj, Jesu