Mechanobiology in Medicine最新文献

Coronavirus disease-19 (COVID-19) is the ongoing pandemic affecting millions of people worldwide. Several vaccine candidates have been designed and developed for the causative virus, SARS-CoV-2. However high mutation rate in the viral genome and the emergence of new variants have challenged the effectiveness of these vaccines developed for previous strains. Hence, screening and identification of anti-SARS-CoV-2 agents having multi-target potency would be more impactful in the prevention of the disease. Epicatechin gallate (ECG) is a green tea polyphenol having various medicinal properties, including anti-oxidative and anti-inflammatory effects. However its role as anti-SARS-CoV-2 agent is not clear. Hence the present in silico study aims to investigate the binding potential of ECG with several proteins which are critical to SARS-CoV-2 entry and replication within the host cell. Molecular docking analyses have revealed that ECG could potentially block several amino acid residues of entry factors in host cells, spike protein, and many non-structural proteins through Hydrogen bonds and hydrophobic interactions. Such interactions with vital proteins could inhibit SARS-CoV-2 entry and its subsequent replication into the host. Therefore, ECG could be a potential therapeutic agent for the prevention of COVID-19. However, the findings of the present study demand further validation in animal models.

Cell migration is an important biological process regulated by mechanical stimulation, which leads to intracellular calcium response. Cell migration are dependent on the distribution and dynamic changes of intracellular calcium concentration. However, the temporal relation among mechanical stimulation, cell migration, and intracellular calcium distribution remains unclear. In this study, unidirectional flow and oscillatory flow were applied on osteoclast precursor RAW264.7 cells. The parameters of cell migration under fluid flow and intracellular calcium distribution along the migration or flow direction were calculated. Experimental results suggest the cells to adjust the [Ca²⁺]_i distribution in the migration direction is independent of flow application or the reverse of flow direction, but the [Ca²⁺]_i distribution in the flow direction is determined by the [Ca²⁺]_i distribution-adjusting ability of cells and flow stimulation. Blocking calcium signaling pathways, namely, mechanosensitive cation-selective channels, phospholipase C, and endoplasmic reticulum, and removing extracellular calcium inhibited cell migration along the flow direction and the gradient distribution of intracellular calcium. This study provided insights into the mechanism of flow-induced cell migration and quantitative data for the recruitment of osteoclast precursors targeting the location of bone resorption.

Increased matrix stiffness is a common phenomenon in solid tumor tissue and is regulated by both tumor and mesenchymal cells. The increase in collagen and lysyl oxidase family proteins in the extracellular matrix leads to deposition, contraction, and crosslinking of the stroma, promoting increased matrix stiffness in tumors. Matrix stiffness is critical to the progression of various solid tumors. As a mechanical factor in the tumor microenvironment, matrix stiffness is involved in tumor progression, promoting biological processes such as tumor cell proliferation, invasion, metastasis, angiogenesis, drug resistance, and immune escape. Reducing tissue stiffness can slow down tumor progression. Therefore targeting matrix stiffness is a potential option for tumor therapy. This article reviews the detailed mechanisms of matrix stiffness in different malignant tumor phenotypes and potential tumor therapies targeting matrix stiffness. Understanding the role and mechanisms of matrix stiffness in tumors could provide theoretical insights into the treatment of tumors and assist in the clinical development of new drug therapies.

Tumor state transitions between the excited (high-concentration) and nonexcited (low-concentration) basins under the Gaussian white noise and non-Gaussian colored noise are investigated via the most probable steady states (MPSS) and the first escape probability (FEP)-based stochastic basin of attraction (SBA), respectively. Reducing the non-Gaussian colored noise and then utilizing the unified colored noise approximation (UCNA), the Markov system is derived. The extremal controlling equation of stationary probability density function (SPDF) is derived to analyze the impacts of noise on transitions in terms of MPSS. The existence of the ‘color’ of the non-Gaussian colored noise induces the reappearance of the uncorrelated additive white noise parameter that had vanished from the extremal controlling equation, completely reversing the inability of the uncorrelated additive Gaussian white noise to operate on transitions. The FEP-dependent SBA characterizing the excited basin stability is performed to further analyze the role of noise on the likelihood of escaping to the nonexcited state. Results show that the cross-correlated noises play a dual role in regulating SBA. The increased SBA indicating more difficulty to escape to the nonexcited state reflects a worse therapeutic effect. Therefore, enhancing the negatively correlated noise intensities and augmenting the non-Gaussian noise correlation time is essential for destabilizing the excited basin and achieving optimal therapeutic efficacy.