Diffuse malignant peritoneal mesothelioma: A review

Diffuse malignant peritoneal mesothelioma (DMPM) is an unusual and life-threatening locally invasive tumor. The morbidity and mortality of the disease are associated with progressive local effects in the abdominal cavity, such as abdominal distention, painful sensations, and early saturation with reduced oral intake, which eventually lead to intestinal obstruction and cachexia. Computed tomography (CT) has been widely used as a first-line diagnostic tool for DMPM. In addition, the most sensitive immunohistochemical markers of DMPM include WT 1, D2-40, and calmodulin. This paradigm has altered with the advancements in the immunohistochemical analysis of BRCA1-Associated Protein 1 (BAP1) the lack of BAP1 expression shows the diagnosis of malignancy. DMPM is resistant to conventional chemotherapies. Therefore, the gold standard for the treatment of DMPM is the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The overexpression of the phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase 1 (AKT)/mammalian target of rapamycin (mTOR) signaling pathway drives the malignant phenotype of DMPM, thereby showing promising potential for the treatment of DMPM. The coordinated activities among multiple RTKs are directly involved in the biological processes of DMPM, suggesting that the combined inhibition of the PI3K and mTOR signaling pathways might be an effective measure. This treatment strategy can be easily implemented in clinical practice. However, the combined inhibition of ERBB1(HER1)/ERBB2 (HER2) and ERBB3 (HER3) requires further investigations. Thus, based on these, the discovery of novel targeted therapies might be crucial to improving the prognosis of DMPM patients

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

Background/Aims: The present study was aimed at examining Ezrin expression in human colorectal cancer (CRC) tissues and elucidating the influence of baicalein on the proliferation of HCT116 cells. Methods: The expression of Ezrin was determined by qRT-PCR and immunohistochemistry. HCT116 cells were divided into four groups－ baicalein groups with various concentrations, pcDNA3.1-Ezrin group, si-Ezrin group and dual inhibitory group (baicalein + si-Ezrin). CCK-8 assay and flow cytometry (FCM) were employed to assess cell proliferation and to detect the distribution of cell cycle respectively. The expression levels of Ezrin protein and cell cycle-associated proteins were detected by using western blot. The proliferation ability of CRC cells was also evaluated in vivo. Results: Ezrin expression in CRC tissues was observably higher than that in adjacent colorectal tissues. With drug concentration and action time of baicalein increasing, the cell propagation capacity of HCT116 cells was decreased and the cell cycle progression was arrested. Ezrin expression was inhibited by the administration of baicalein in a dose-dependent way. The levels of CyclinD1 and CDK4 were also significantly decreased, but the expression of P53 pathway proteins P53 and P21 was markedly upregulated. Conclusion: Baicalein repressed proliferation of human colorectal cancer cells HCT116 and blocked cell cycle through downregulating Ezrin and upregulating P53 pathway-related proteins

Neural Mechanisms With Respect to Different Paradigms and Relevant Regulatory Factors in Empathy for Pain

Empathy for pain is thought to activate the affective-motivational components of the pain matrix, which includes the anterior insula and middle and anterior cingulate cortices, as indicated by functional magnetic resonance imaging and other methodologies. Activity in this core neural network reflects the affective experience that activates our responses to pain and lays the neural foundation for our understanding of our own emotions and those of others. Furthermore, although picture-based paradigms can activate somatosensory components of directly experienced pain, cue-based paradigms cannot. In addition to this difference, the two paradigms evoke other distinct neuronal responses. Although the automatic “perception-action” model has long been the dominant theory for pain empathy, a “bottom-up, top-down” mechanism seems to be more comprehensive and persuasive. Indeed, a variety of factors can regulate the intensity of empathy for pain through “top-down” processes. In this paper, we integrate and generalize knowledge regarding pain empathy and introduce the findings from recent studies. We also present ideas for future research into the neural mechanisms underlying pain empathy

The Role of KLF4 in Alzheimer’s Disease

Krüppel-like factor 4 (KLF4), a member of the family of zinc-finger transcription factors, is widely expressed in range of tissues that play multiple functions. Emerging evidence suggest KLF4’s critical regulatory effect on the neurophysiological and neuropathological processes of Alzheimer’s disease (AD), indicating that KLF4 might be a potential therapeutic target of neurodegenerative diseases. In this review, we will summarize relevant studies and illuminate the regulatory role of KLF4 in the neuroinflammation, neuronal apoptosis, axon regeneration and iron accumulation to clarify KLF4’s status in the pathogenesis of AD

Stress in Regulation of GABA Amygdala System and Relevance to Neuropsychiatric Diseases

The amygdala is an almond-shaped nucleus located deep and medially within the temporal lobe and is thought to play a crucial role in the regulation of emotional processes. GABAergic neurotransmission inhibits the amygdala and prevents us from generating inappropriate emotional and behavioral responses. Stress may cause the reduction of the GABAergic interneuronal network and the development of neuropsychological diseases. In this review, we summarize the recent evidence investigating the possible mechanisms underlying GABAergic control of the amygdala and its interaction with acute and chronic stress. Taken together, this study may contribute to future progress in finding new approaches to reverse the attenuation of GABAergic neurotransmission induced by stress in the amygdala

Role of Leptin in Mood Disorder and Neurodegenerative Disease

The critical regulatory role of leptin in the neuroendocrine system has been widely reported. Significantly, leptin can improve learning and memory, affect hippocampal synaptic plasticity, exert neuroprotective efficacy and reduce the risk of several neuropsychiatric diseases. In terms of depression, leptin could modulate the levels of neurotransmitters, neurotrophic factors and reverse the dysfunction in the hypothalamic-pituitary-adrenal axis (HPA). At the same time, leptin affects neurological diseases during the regulation of metabolic homeostasis. With regards to neurodegenerative diseases, leptin can affect them via neuroprotection, mainly including Alzheimer’s disease and Parkinson’s disease. This review will summarize the mechanisms of leptin signaling within the neuroendocrine system with respect to these diseases and discuss the therapeutic potential of leptin

The PFILSTM model: a crack recognition method based on pyramid features and memory mechanisms

Crack detection is a crucial task for the structural health diagnosis of buildings. The current widely used manual inspection methods have inherent limitations and safety hazards, while traditional digital image processing methods require manual feature extraction and also have substantial limitations. In this paper, we propose a crack recognition method based on pyramid features and memory mechanisms that leverages a U-shaped network, long short-term memory mechanisms, and a pyramid feature design to address the recognition accuracy, robustness, and universality issues with deep learning-based crack detection methods in recent years. Experiments were conducted on four publicly available datasets and one private dataset. Compared with the commonly used FCN8s, SegNet, UNet, and DeepLabv3+ models and other related studies using the same evaluation criteria and datasets, our proposed model shows better overall performance in terms of all metrics evaluated

Effect of Inflammation on the Process of Stroke Rehabilitation and Poststroke Depression

A considerable body of evidence has shown that inflammation plays an important role in the process of stroke rehabilitation and development of poststroke depression (PSD). However, the specific molecular and cellular mechanisms involved remain unclear. In this review, we summarize how neuroinflammation affects stroke rehabilitation and PSD. We mainly focus on the immune/inflammatory response, involving astrocytes, microglia, monocyte-derived macrophages, cytokines (tumor necrosis factor alpha, interleukin 1), and microRNAs (microRNA-124, microRNA 133b). This review provides new insights into the effect of inflammation on the process of stroke rehabilitation and PSD and potentially offer new therapeutic targets of stroke and PSD

A coupled 3D isogeometric and discrete element approach for modelling interactions between structures and granular matters

A three-dimensional (3D) isogeometric/discrete-element coupling method is presented for modelling contact/impact between structures and particles. This method takes advantages of the geometry smoothness and exactness of isogeometric analysis (IGA) for continuous solid media and the effectiveness and flexibility of the discrete element method (DEM) for particulate matters. The coupling procedure for handling interactions between IGA elements and discrete elements (DEs) includes global search, local search and interaction calculation. In the global search, the CGRID method is modified to detect potential contact pairs between IGA elements and DEs based on their bounding box representations. The strong convex hull property of a NURBS control mesh plays an important part in the bounding box representation of IGA elements. In the local search, the proposed approach treats each spherical DE centroid as a slave node and the contact surface of each IGA element as the master surface. The projection of a DE centroid onto an IGA element contact surface is solved by modifying the simplex method and Brent iterations. The contact force between an IGA element and a DE is determined from their penetration by using a (nonlinear) penalty function based method. The whole coupled system is solved by the explicit time integration within a updated Lagrangian scheme. Finally, three impact examples, including the impact of two symmetric bars, a tube onto a footing strip, and an assembly of granular particles to a tailor rolled blank, are simulated in elastic regime to assess the accuracy and applicability of the proposed method