The application of organoid models in research into metabolic diseases.

Metabolic diseases have become a major threat to human health worldwide as a result of changing lifestyles. The exploration of the underlying molecular mechanisms of metabolic diseases and the development of improved therapeutic methods have been hindered by the lack of appropriate human experimental models. Organoids are three-dimensional in vitro models of self-renewing cells that spontaneously self-organize into structures similar to the corresponding in vivo tissues, recapitulating the original tissue function. Off-body organoid technology has been successfully applied to disease modelling, developmental biology, regenerative medicine, and tumour precision medicine. This new generation of biological models has received widespread attention. This article focuses on the construction process and research progress with regard to organoids related to metabolic diseases in recent years, and looks forward to their prospective applications.

The regulatory role of m6A methylation modification in metabolic syndrome pathogenesis and progression.

Metabolic syndromes are characterized by various complications caused by disrupted glucose and lipid metabolism, which are major factors affecting the health of a population. However, existing diagnostic and treatment strategies have limitations, such as the lack of early diagnostic and therapeutic approaches, variability in patient responses to treatment, and cost-effectiveness. Therefore, developing alternative solutions for metabolic syndromes is crucial. N6-methyladenosine (m6A) is one of the most abundant modifications that determine the fate of RNA. m6A modifications are closely associated with metabolic syndrome development and present novel prospects for clinical applications. Aberrant m6A modifications have been detected during inflammatory infiltration, apoptosis, autophagy, iron sagging, necrosis, and scorching during metabolic syndrome pathogenesis and progression. However, few reviews have systematically described the correlation between m6A modifications and these factors concerning metabolic syndrome pathogenesis and progression. This study summarizes the m6A methylation regulators and their roles in metabolic syndrome development, highlighting the potential of m6A modification as a biomarker in metabolic disorders.

Zero-shot learning via visual-semantic aligned autoencoder.

Zero-shot learning recognizes the unseen samples via the model learned from the seen class samples and semantic features. Due to the lack of information of unseen class samples in the training set, some researchers have proposed the method of generating unseen class samples by using generative models. However, the generated model is trained with the training set samples first, and then the unseen class samples are generated, which results in the features of the unseen class samples tending to be biased toward the seen class and may produce large deviations from the real unseen class samples. To tackle this problem, we use the autoencoder method to generate the unseen class samples and combine the semantic features of the unseen classes with the proposed new sample features to construct the loss function. The proposed method is validated on three datasets and showed good results.

Neural architecture search based on dual attention mechanism for image classification.

Deep learning neural networks based on the manual design for image classification tasks usually require a large amount of a priori knowledge and experience from experts; thus, research on designing neural network architectures automatically has been widely performed. The neural architecture search (NAS) method based on the differentiable architecture search (DARTS) ignores the interrelationships within the searched network architecture cells. The optional operations in the architecture search space lack diversity, and the large parametric and non-parametric operations in the search space make the search process inefficient. We propose a NAS method based on a dual attention mechanism (DAM-DARTS). An improved attention mechanism module is introduced to the cell of the network architecture to deepen the interrelationships between the important layers within the architecture by enhancing the attention between them, which improves the accuracy of the architecture and reduces the architecture search time. We also propose a more efficient architecture search space by adding attention operations to increase the complex diversity of the searched network architectures and reduce the computational cost consumed in the search process by reducing non-parametric operations. Based on this, we further analyze the impact of changing some operations in the architecture search space on the accuracy of the architectures. Through extensive experiments on several open datasets, we demonstrate the effectiveness of the proposed search strategy, which is highly competitive with other existing neural network architecture search methods.

Identification of key genes and miRNAs related to polycystic ovary syndrome by comprehensive analysis of microarray.

BACKGROUND: We aimed to explore mechanisms of development and progression of polycystic ovary syndrome (PCOS). METHODS: The microRNA expression microarray GSE37914 and gene expression profiles GSE43264 and GSE98421 were downloaded from the Gene Expression Omnibus database. The differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were screened using Limma package. Then, the DEGs and DEmiRNAs were combined to use for the subsequent analysis, including the functional enrichment analysis, protein-protein interaction (PPI) network and module analysis, drug-gene interaction network analysis, and DEmiRNAs-DEGs interactive network construction. RESULTS: A total of 26 DEmiRNAs and 80 DEGs were screened. The PPI network contained 68 nodes and 259 interactions. A significant clustering module with 8 nodes and 25 interactions was obtained. Three PCOS-related overlapping pathways were obtained based on PPI-degree top10 and module genes, including prion diseases, Staphylococcus aureus infection, and Chagas disease (American trypanosomiasis). A total of 44 drug-gene interaction pairs were obtained, which included 2 up-regulated genes (LDLR and VCAM1), 4 down-regulated genes (C1QA, C1QB, IL6 and ACAN) and 26 small molecules drugs. A total of 52 nodes and 57 interactions were obtained in the DEmiRNA-DEGs regulatory network, LDLR was regulated by miR-152-3p, miR-1207-5p, miR-378a-5p and miR-150-5p. CONCLUSIONS: Our research has identified several key genes and pathways related to PCOS. These results can improve our understanding of PCOS and provide new basis for drug target research.

Tumor-derived extracellular vesicles in angiogenesis.

Angiogenesis is crucial for tumor growth and metastasis. Recent studies revealed that tumor cells promote angiogenesis by secreting extracellular vesicles, which can be captured by endothelial cells. These tumor-derived extracellular vesicles carry microRNAs, long non-coding RNAs, and proteins, which activate pro-angiogenic signaling in endothelial cells. In this review, we will summarize the roles of tumor-derived extracellular vesicles in angiogenesis and the underlying molecular mechanisms.

Anti-angiogenic properties of artemisinin derivatives (Review).

Angiogenesis, the process involving the development of new blood vessels from existing capillaries, is critical for growth and wound healing. However, pathological angiogenesis contributes to the pathogeneses of numerous diseases, including cancer, rheumatoid arthritis, diabetic retinopathy and macular degeneration. Hence, the inhibition of angiogenesis is an effective therapeutic approach for these diseases. Apart from its anti-malarial properties, artemisinin and its derivatives also exhibit potent anti-angiogenic properties. The molecular mechanisms underlying their inhibitory effects on angiogenesis have been studied by several groups. These investigations have revealed that artemisinins inhibit angiogenesis via the perturbations of cellular signaling pathways involved in the regulation of angiogenesis. Along with a brief introduction to artemisinin derivatives, this review provides a detailed summary of the effects of artemisinins on the mitogen-activated protein kinase (MAPK) pathway, the nuclear factor-κB (NF-κB) pathway and the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Due to the multiplicity of their actions on relevant signaling pathways, artemisinins are promising candidates with potential for use as anti-angiogenic agents for the treatment of related diseases or disorders.

Dose dependent effects of cadmium on tumor angiogenesis.

Angiogenesis is crucial for tumor growth and metastasis. Cadmium (Cd) exposure is associated with elevated cancer risk and mortality. Such association is, at least in part, attributable to Cd-induced tumor angiogenesis. Nevertheless, the reported effects of Cd on tumor angiogenesis appear to be either stimulatory or inhibitory, depending on the concentrations. Ultra-low concentrations of Cd (<0.5 µM) inhibit endothelial nitric oxide synthase activation, leading to reduced endothelial nitric oxide production and attenuated tumor angiogenesis. In contrast, low-lose Cd (1-10 µM) up-regulates vascular endothelial growth factor (VEGF)-mediated tumor angiogenesis by exerting sub-apoptotic levels of oxidative stress on both tumor cells and endothelial cells (ECs). The consequent activation of protein kinase B/Akt, nuclear factor-κB, and mitogen-activated protein kinase signaling cascades mediate the increased secretion of VEGF by tumor cells and the up-regulated VEGF receptor-2 expression in ECs. Furthermore, Cd in high concentrations (>10 µM) induces EC apoptosis via the activation of caspase-3, resulting in destruction of tumor vasculature. In this review, we summarize the current knowledge concerning the roles of Cd in tumor angiogenesis, with a focus on molecular mechanisms underlying the dose dependent effects of Cd on various EC phenotypes.

The roles of signal transducer and activator of transcription factor 3 in tumor angiogenesis.

Angiogenesis is the development of new blood vessels, which is required for tumor growth and metastasis. Signal transducer and activator of transcription factor 3 (STAT3) is a transcription factor that regulates a variety of cellular events including proliferation, differentiation and apoptosis. Previous studies revealed that activation of STAT3 promotes tumor angiogenesis. In this review, we described the activities of STAT3 signaling in different cell types involved in angiogenesis. Particularly, we elucidated the molecular mechanisms of STAT3-mediated gene regulation in angiogenic endothelial cells in response to external stimulations such as hypoxia and inflammation. The potential for STAT3 as a therapeutic target was also discussed. Overall, this review provides mechanistic insights for the roles of STAT3 signaling in tumor angiogenesis.

Plasmalemma vesicle-associated protein: A crucial component of vascular homeostasis.

Endothelial subcellular structures, including caveolae, fenestrae and transendothelial channels, are crucial for regulating microvascular function. Plasmalemma vesicle-associated protein (PLVAP) is an endothelial cell-specific protein that forms the stomatal and fenestral diaphragms of blood vessels and regulates basal permeability, leukocyte migration and angiogenesis. Loss of PLVAP in mice leads to premature mortality due to disrupted homeostasis. Evidence from previous studies suggested that PLVAP is involved in cancer, traumatic spinal cord injury, acute ischemic brain disease, transplant glomerulopathy, Norrie disease and diabetic retinopathy. Specifically, PLVAP expression has been demonstrated to be upregulated in these diseases, accompanied by pro-angiogenic or pro-inflammatory responses. Therefore, PLVAP is considered a novel therapeutic target, in addition to an endothelial cell marker. The present review summarizes the structure and functions of PLVAP, and its roles in pathophysiological processes.