Frontiers in Cell and Developmental Biology最新文献

The liver possesses an impressive capability to regenerate following various injuries. Given its profound implications for the treatment of liver diseases, which afflict millions globally, liver regeneration stands as a pivotal area of digestive organ research. Zebrafish (Danio rerio) has emerged as an ideal model organism in regenerative medicine, attributed to their remarkable ability to regenerate tissues and organs, including the liver. Many fantastic studies have been performed to explore the process of liver regeneration using zebrafish, especially the extreme hepatocyte injury model. Biliary-mediated liver regeneration was first discovered in the zebrafish model and then validated in mammalian models and human patients. Considering the notable expansion of biliary epithelial cells in many end-stage liver diseases, the promotion of biliary-mediated liver regeneration might be another way to treat these refractory liver diseases. To date, a comprehensive review discussing the current advancements in zebrafish liver regeneration models is lacking. Therefore, this review aims to investigate the utility of different zebrafish models in exploring liver regeneration, highlighting the genetic and cellular insights gained and discussing the potential translational impact on human health.

Chronic kidney disease (CKD) is the progressive loss of kidney function/structure over a period of at least 3 months. It is characterised histologically by the triad of cell loss, inflammation and fibrosis. This literature review focuses on the forms of cell death that trigger downstream inflammation and fibrosis, collectively called regulated cell death (RCD) pathways. Discrete forms of RCD have emerged as central mediators of CKD pathology. In particular, pathways of regulated necrosis - including mitochondrial permeability transition pore (mPTP)-mediated necrosis, necroptosis, ferroptosis and pyroptosis - have been shown to mediate kidney pathology directly or through the release of danger signals that trigger a pro-inflammatory response, further amplifying tissue injury in a cellular process called necroinflammation. Despite accumulating evidence in pre-clinical models, no clinical studies have yet targeted these RCD modes in human CKD. The review summarizes recent advances in our understanding of RCD pathways in CKD, looks at inter-relations between the pathways (with the emphasis on propagation of death signals) and the evidence for therapeutic targeting of molecules in the RCD pathways to prevent or treat CKD.

Hepatocyte transplantation (HTx) has been a novel cell-based therapy for severe liver diseases, as the donor livers for orthotopic liver transplantation are of great shortage. However, HTx has been confronted with two main hurdles: limited high-quality hepatocyte sources and low cell engraftment and repopulation rate. To cope with, researchers have investigated on various strategies, including small molecule drugs with unique advantages. Small molecules are promising chemical tools to modulate cell fate and function for generating high quality hepatocyte sources. In addition, endothelial barrier, immune responses, and low proliferative efficiency of donor hepatocytes mainly contributes to low cell engraftment and repopulation rate. Interfering these biological processes with small molecules is beneficial for improving cell engraftment and repopulation. In this review, we will discuss the applications and advances of small molecules in modulating cell differentiation and reprogramming for hepatocyte resources and in improving cell engraftment and repopulation as well as its underlying mechanisms.

DNA plays an indispensable role in ensuring the perpetuation of life and safeguarding the genetic stability of living organisms. The emergence of diseases linked to a wide spectrum of responses to DNA damage has garnered increasing attention within the scientific community. There is growing evidence that patterns of DNA damage response in the lungs are associated with the onset, progression, and treatment of chronic lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and bronchopulmonary dysplasia (BPD). Currently, some studies have analyzed the mechanisms by which environmental factors induce lung DNA damage. In this article, we summarize inducible factors of lung DNA damage, current indicators, and methods for diagnosing DNA damage in chronic lung diseases and explore repair mechanisms after DNA damage including nonhomologous end-joining and homology-directed repair end joining pathways. Additionally, drug treatments that may reduce DNA damage or promote repair after it occurs in the lungs are briefly described. In general, more accurate assessment of the degree of lung DNA damage caused by various factors is needed to further elucidate the mechanism of lung DNA damage and repair after damage, so as to search for potential therapeutic targets.

In this study, we identify and characterize new molecular determinants that optimize human capillary tube network assembly. Our lab has previously reported a novel, serum free-defined 3D co-culture model using human endothelial cells (ECs) and human pericytes whereby EC-lined tubes form and co-assemble with pericytes, but when these cultures are maintained at or beyond 5 days, tubes become progressively wider and unstable. To address this issue, we generated novel human pericytes that carry a tissue inhibitor of metalloproteinase (TIMP)-3 transgene which can be upregulated following doxycycline addition. EC-pericyte co-cultures established in the presence of doxycycline demonstrated marked enhancement of capillary network assembly including dramatic narrowing of capillary tube widths to an average of 8 µm (physiologic capillary tube width), increased tube lengths, increased tube branching, and robust stimulation of basement membrane matrix assembly, particularly with collagen type IV and fibronectin deposition compared to controls. These substantial changes depend not only on induction of pericyte TIMP-3, but also on recruitment of pericytes to EC tubes. Blockade of pericyte recruitment prevents these dramatic capillary network alterations suggesting that EC-pericyte interactions and induction of pericyte TIMP-3 are necessary together to coordinate and facilitate capillary assembly and maturation. Overall, this work is critical for our basic understanding of capillary formation, but also for the ability to reproducibly generate stabilized networks of capillary tubes.

STK11 (serine-threonine kinase 11), also known as LKB1 (liver kinase B1) is a highly conserved master kinase that regulates cellular metabolism and polarity through a complex signaling network involving AMPK and 12 other AMPK-related kinases. Germline mutations in LKB1 have been causatively linked to Peutz-Jeghers Syndrome (PJS), an autosomal dominant hereditary disease with high cancer susceptibility. The identification of inactivating somatic mutations in LKB1 in different types of cancer further supports its tumor suppressive role. Deleterious mutations in LKB1 are frequently observed in patients with epithelial ovarian cancer. However, its inconsistent effects on tumorigenesis and cancer progression suggest that its functional impact is genetic context-dependent, requiring cooperation with other oncogenic lesions. In this review, we summarize the pleiotropic functions of LKB1 and how its altered activity in cancer cells is linked to oncogenic proliferation and growth, metastasis, metabolic reprogramming, genomic instability, and immune modulation. We also review the current mechanistic understandings of this master kinase as well as therapeutic implications with particular focus on the effects of LKB1 deficiency in ovarian cancer pathogenesis. Lastly, we discuss whether LKB1 deficiency can be exploited as an Achilles heel in ovarian cancer.

Aim: This study aimed to predict the formation of OBL during femtosecond laser SMILE surgery by employing deep learning technology.

Methods: This was a cross-sectional, retrospective study conducted at a university hospital. Surgical videos were randomly divided into a training (3,271 patches, 73.64%), validation (704 patches, 15.85%), and internal verification set (467 patches, 10.51%). An artificial intelligence (AI) model was developed using a SENet-based residual regression deep neural network. Model performance was assessed using the mean absolute error (E _MA ), Pearson's correlation coefficient (r), and determination coefficient (R ² ).

Results: Four distinct types of deep neural network models were established. The modified deep residual neural network prediction model with channel attention built on the PyTorch framework demonstrated the best predictive performance. The predicted OBL area values correlated well with the Photoshop-based measurements (E _MA = 0.253, r = 0.831, R ² = 0.676). The ResNet (E _MA = 0.259, r = 0.798, R ² = 0.631) and Vgg19 models (E _MA = 0.31, r = 0.758, R ² = 0.559) both displayed satisfactory predictive performance, while the U-net model (E _MA = 0.605, r = 0.331, R ² = 0.171) performed poorest.

Conclusion: We used a panoramic corneal image obtained before the SMILE laser scan to create a unique deep residual neural network prediction model to predict OBL formation during SMILE surgery. This model demonstrated exceptional predictive power, suggesting its clinical applicability across a broad field.

Background: Lacrimal gland enlargement is a common pathological change in patients with thyroid eye disease (TED). Tear fluid has emerged as a new source of diagnostic biomarkers, but tear-based diagnostic biomarkers for TED with high efficacy are still lacking.

Objective: We aim to investigate genes associated with TED-associated lacrimal gland lesions. Additionally, we seek to identify potential biomarkers for diagnosing TED in tear fluid.

Methods: We obtained two expression profiling datasets related to TED lacrimal gland samples from the Gene Expression Omnibus (GEO). Subsequently, we combined the two separate datasets and conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on the obtained integrated dataset. The genes were employed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The genes were intersected with the secretory proteins profile to get the potential proteins in the tear fluid. Machine learning techniques were then employed to identify optimal biomarkers and develop a diagnostic nomogram for predicting TED. Finally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted on screened hub genes to further elucidate their potential mechanisms in TED.

Results: In our analysis of the integrated TED dataset, we identified 2,918 key module genes and 157 differentially expressed genes and finally obtained 84 lacrimal-associated key genes. Enrichment analysis disclosed that these 84 genes primarily pertain to endoplasmic reticulum organization. After intersecting with the secretory proteins, 13 lacrimal gland-associated secretory protein genes (LaSGs) were identified. The results from machine learning indicated the substantial diagnostic value of dyslexia associated gene (KIAA0319) and peroxiredoxin4 (PRDX4) in TED-associated lacrimal gland lesions. The two hub genes were chosen as candidate biomarkers in tear fluid and employed to establish a diagnostic nomogram. Furthermore, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in the lacrimal gland of TED, with KIAA0319 and PRDX4 showing significant associations with infiltrating immune cells.

Conclusions: We uncovered the distinct pathophysiology of TED-associated lacrimal gland enlargement compared to TED-associated orbital adipose tissue enlargement. We have demonstrated the endoplasmic reticulum-related pathways involved in TED-associated lacrimal gland lesions and established a diagnostic nomogram for TED utilizing KIAA0319 and PRDX4 through integrated bioinformatics analysis. This contribution offers novel insights for non-invasive, prospective diagnostic approaches in the context of TED.

This review delves into the pivotal role of circulating tumor cells (CTCs) in colorectal cancer (CRC) metastasis, focusing on their biological properties, interactions with the immune system, advanced detection techniques, and clinical implications. We explored how metastasis-competent CTCs evade immune surveillance and proliferate, utilizing cutting-edge detection and isolation technologies, such as microfluidic devices and immunological assays, to enhance sensitivity and specificity. The review highlights the significant impact of CTC interactions with immune cells on tumor progression and patient outcomes. It discusses the application of these findings in clinical settings, including non-invasive liquid biopsies for early diagnosis, prognosis, and treatment monitoring. Despite advancements, challenges remain, such as the need for standardized methods to consistently capture and analyze CTCs. Addressing these challenges through further molecular and cellular research on CTCs could lead to improved interventions and outcomes for CRC patients, underscoring the importance of unraveling the complex dynamics of CTCs in cancer progression.