Advances in exercise-induced vascular adaptation: mechanisms, models, and methods

Insufficient physical activity poses a significant risk factor for cardiovascular diseases. Exercise plays a crucial role in influencing the vascular system and is essential for maintaining vascular health. Hemodynamic stimuli generated by exercise, such as shear stress and circumferential stress, directly impact vascular structure and function, resulting in adaptive changes. In clinical settings, incorporating appropriate exercise interventions has become a powerful supplementary approach for treating and rehabilitating various cardiovascular conditions. However, existing models for studying exercise-induced vascular adaptation primarily rely on in vivo animal and in vitro cellular models, each with its inherent limitations. In contrast, human research faces challenges in conducting mechanistic analyses due to ethics issues. Therefore, it is imperative to develop highly biomimetic in vitro/ex vivo vascular models that can replicate exercise stimuli in human systems. Utilizing various vascular assessment techniques is also crucial to comprehensively evaluate the effects of exercise on the vasculature and uncover the molecular mechanisms that promote vascular health. This article reviews the hemodynamic mechanisms that underlie exercise-induced vascular adaptation. It explores the advancements in current vascular models and measurement techniques, while addressing their future development and challenges. The overarching goal is to unravel the molecular mechanisms that drive the positive effects of exercise on the cardiovascular system. By providing a scientific rationale and offering novel perspectives, the aim is to contribute to the formulation of precise cardiovascular rehabilitation exercise prescriptions

IgA-Targeted Lactobacillus jensenii Modulated Gut Barrier and Microbiota in High-Fat Diet-Fed Mice

IgA-coated Lactobacillus live in the mucous layer of the human or mammalian intestine in close proximity to epithelial cells. They act as potential probiotics for functional food development, but their physiological regulation has not yet been studied. We isolated IgA-targeted (Lactobacillus jensenii IgA21) and lumen lactic acid bacterial strains (Pediococcus acidilactici FS1) from the fecal microbiota of a healthy woman. C57BL/6 mice were fed a normal (CON) or high fat diet (HFD) for 6 weeks and then treated with IgA21 or FS1 for 4 weeks. HFD caused dyslipidemia, mucosal barrier damage, and intestinal microbiota abnormalities. Only IgA21 significantly inhibited dyslipidemia and gut barrier damage. This was related to significant up-regulation of mucin-2, PIgR mRNA expression, and colonic butyrate production (P < 0.05 vs. HFD). Unlike IgA21, FS1 caused a more pronounced gut dybiosis than did HFD, and, in particular, it induced a significant decrease in the Bacteroidales S24-7 group and an increase in Desulfovibrionaceae (P < 0.05 vs. CON). In conclusion, IgA-coated and non-coated lactic acid bacteria of gut have been demonstrated to differentially affect the intestinal barrier and serum lipids. This indicates that IgA-bound bacteria possess the potential to more easily interact with the host gut to regulate homeostasis

Transcription and splicing regulation in human umbilical vein endothelial cells under hypoxic stress conditions by exon array

<p>Abstract</p> <p>Background</p> <p>The balance between endothelial cell survival and apoptosis during stress is an important cellular process for vessel integrity and vascular homeostasis, and it is also pivotal in angiogenesis during the development of many vascular diseases. However, the underlying molecular mechanisms remain largely unknown. Although both transcription and alternative splicing are important in regulating gene expression in endothelial cells under stress, the regulatory mechanisms underlying this state and their interactions have not yet been studied on a genome-wide basis.</p> <p>Results</p> <p>Human umbilical vein endothelial cells (HUVECs) were treated with cobalt chloride (CoCl₂) both to mimic hypoxia and to induce cell apoptosis and alternative splicing responses. Cell apoptosis rate analysis indicated that HUVECs exposed to 300 μM CoCl₂for 24 hrs were initially counterbalancing apoptosis with cell survival. We therefore used the Affymetrix exon array system to determine genome-wide transcript- and exon-level differential expression. Other than 1583 differentially expressed transcripts, 342 alternatively spliced exons were detected and classified by different splicing types. Sixteen alternatively spliced exons were validated by RT-PCR. Furthermore, direct evidence for the ongoing balance between HUVEC survival and apoptosis was provided by Gene Ontology (GO) and protein function, as well as protein domain and pathway enrichment analyses of the differentially expressed transcripts. Importantly, a novel molecular module, in which the heat shock protein (HSP) families play a significant role, was found to be activated under mimicked hypoxia conditions. In addition, 46% of the transcripts containing stress-modulated exons were differentially expressed, indicating the possibility of combinatorial regulation of transcription and splicing.</p> <p>Conclusion</p> <p>The exon array system effectively profiles gene expression and splicing on the genome-wide scale. Based on this approach, our data suggest that transcription and splicing not only regulate gene expression, but also carry out combinational regulation of the balance between survival and apoptosis of HUVECs under mimicked hypoxia conditions. Since cell survival following the apoptotic challenge is pivotal in angiogenesis during the development of many vascular diseases, our results may advance the knowledge of multilevel gene regulation in endothelial cells under physiological and pathological conditions.</p

Maternal exercise represses Nox4 via SIRT1 to prevent vascular oxidative stress and endothelial dysfunction in SHR offspring

Maternal exercise during pregnancy has emerged as a potentially promising approach to protect offspring from cardiovascular disease, including hypertension. Although endothelial dysfunction is involved in the pathophysiology of hypertension, limited studies have characterized how maternal exercise influences endothelial function of hypertensive offspring. In this study, pregnant spontaneously hypertensive rats and Wistar-Kyoto rats were assigned either to a sedentary lifestyle or to swimming training daily, and fetal histone deacetylase-mediated epigenetic modification and offspring vascular function of mesenteric arteries were analyzed. Maternal exercise ameliorated the impairment of acetylcholine-induced vasodilation without affecting sodium nitroprusside-induced vasodilation in mesenteric arteries from the hypertensive offspring. In accordance, maternal exercise reduced NADPH oxidase-4 (Nox4) protein to prevent the loss of nitric oxide generation and increased reactive oxygen species production in mesenteric arteries of hypertensive offspring. We further found that maternal exercise during pregnancy upregulated vascular SIRT1 (sirtuin 1) expression, leading to a low level of H3K9ac (histone H3 lysine 9 acetylation), resulting in the transcriptional downregulation of Nox4 in mesenteric arteries of hypertensive fetuses. These findings show that maternal exercise alleviates oxidative stress and the impairment of endothelium-dependent vasodilatation via SIRT1-regulated deacetylation of Nox4, which might contribute to improved vascular function in hypertensive offspring

Financial Volatility Forecasting: A Sparse Multi-Head Attention Neural Network

Accurately predicting the volatility of financial asset prices and exploring its laws of movement have profound theoretical and practical guiding significance for financial market risk early warning, asset pricing, and investment portfolio design. The traditional methods are plagued by the problem of substandard prediction performance or gradient optimization. This paper proposes a novel volatility prediction method based on sparse multi-head attention (SP-M-Attention). This model discards the two-dimensional modeling strategy of time and space of the classic deep learning model. Instead, the solution is to embed a sparse multi-head attention calculation module in the network. The main advantages are that (i) it uses the inherent advantages of the multi-head attention mechanism to achieve parallel computing, (ii) it reduces the computational complexity through sparse measurements and feature compression of volatility, and (iii) it avoids the gradient problems caused by long-range propagation and therefore, is more suitable than traditional methods for the task of analysis of long time series. In the end, the article conducts an empirical study on the effectiveness of the proposed method through real datasets of major financial markets. Experimental results show that the prediction performance of the proposed model on all real datasets surpasses all benchmark models. This discovery will aid financial risk management and the optimization of investment strategies

Reducing Exchange Rate Risks in International Trade: A Hybrid Forecasting Approach of CEEMDAN and Multilayer LSTM

In international trade, it is common practice for multinational companies to use financial market instruments, such as financial derivatives and foreign currency debt, to hedge exchange rate risks. Making accurate predictions and decisions on the direction and magnitude of exchange rate movements is a more direct way to reduce exchange rate risks. However, the traditional time series model has many limitations in forecasting exchange rate, which is nonlinear and nonstationary. In this paper, we propose a new hybrid model of complete ensemble empirical mode decomposition (CEEMDAN) based multilayer long short-term memory (MLSTM) networks. It overcomes the shortcomings of the classic methods. CEEMDAN not only solves the mode mixing problem of empirical mode decomposition (EMD), but also solves the residue noise problem which is included in the reconstructed data of ensemble empirical mode decomposition (EEMD) with less computation cost. MLSTM can learning more complex dependences from exchange rate data than the classic model of time series. A lot of experiments have been conducted to measure the performance of the proposed approach among the exchange rates of British pound, the Australian dollar, and the US dollar. In order to get an objective evaluation, we compared the proposed method with several standard approaches or other hybrid models. The experimental results show that the CEEMDAN-based MLSTM (CEEMDAN&ndash;MLSTM) goes on better than some state-of-the-art models in terms of several evaluations

Redox regulation of Tobacco Rubisco activase mediated by thioredoxin-<i>f</i>

We measured the activation activities of RCA from spinach,arabidopsis,tobacco and tomato under different redox states in the presence of Trx-f from spinach and tobacco,respectively.The results showed that the activity of RCA from spinach and Arabidopsis was regulated by different redox states in the presence of Trx-f from spinach,and the activity of RCA from tobacco and tomato was regulated by different redox states in the presence of Trx-f from tobacco.It demonstrated that that both the activity of RCA consisted of two isoforms and only one isoform (like tobacco) can be regulated by changes in the redox states,which mediated by the Trx-f.Furthermore,we also suggested changes in the redox state of RCA mediated by Trx-f are species dependent

The Role of Pannexin3-Modified Human Dental Pulp-Derived Mesenchymal Stromal Cells in Repairing Rat Cranial Critical-Sized Bone Defects

Background/Aims: Human dental pulp-derived mesenchymal stromal cells (hDPSCs) are promising seed cells for tissue engineering due to their easy accessibility and multi-lineage differentiation. Pannexin3 (Panx3) plays crucial roles during bone development and differentiation. The aim of the present study was to investigate the effect of Panx3 on osteogenesis of hDPSCs and the underlying mechanism. Methods: Utilizing qRT-PCR, Western blot, and immunohistochemistry, we explored the change of Panx3 during osteogenic differentiation of hDPSCs. Next, hDPSCs with loss (Panx3 knockdown) and gain (Panx3 overexpression) of Panx3 function were developed to investigate the effects of Panx3 on osteogenic differentiation of hDPSC and the underlying mechanism. Finally, a commercial β-TCP scaffold carrying Panx3-modified hDPSCs was utilized to evaluate bone defect repair. Results: Panx3 was upregulated during osteogenic differentiation in a time-dependent manner. Panx3 overexpression promoted osteogenic differentiation of hDPSCs, whereas depletion of Panx3 resulted in a decline of differentiation, evidenced by upregulated expression of mineralization-related markers, increased alkaline phosphatase (ALP) activity, and enhanced ALP and Alizarin red staining. Panx3 was found to interact with the Wnt/β-catenin signaling pathway, forming a negative feedback loop. However, Wnt/β-catenin did not contribute to enhancement of osteogenic differentiation as observed in Panx3 overexpression. Moreover, Panx3 promoted osteogenic differentiation of hDPSCs via increasing ERK signaling pathway. Micro-CT and histological staining results showed that Panx3-modified hDPSCs significantly improved ossification of critical-sized bone defects. Conclusion: These findings suggest that Panx3 is a crucial modulator of hDPSCs differentiation