Cancer AND Apoptosis AND shear

BACKGROUND: Heart failure (HF) is the end stage of the development of heart disease, whose prognosis is poor. The previous research of our team indicated that the formulae containing Aconiti Lateralis Radix Praeparata and Lepidii Semen Descurainiae Semen (ALRP-LSDS) could inhibit myocardial hypertrophy, inhibit cardiomyocyte apoptosis, delay myocardial remodeling (REM), and improve the prognosis of patients with HF effectively. In order to explore the mechanism of ALRP-LSDS for the treatment of HF, a combined approach of network pharmacology and molecular docking was conducted...

Background: Gastric cancer (GC) is a common type of gastrointestinal tumor in the world. Transfer RNA (tRNA) derived fragments (tsRNAs) implicate various cancers, but their roles in GC remain unclear. Our study aimed to investigate the potential biological functions and molecular mechanisms of tsRNAs in GC. Methods: Differentially expressed tsRNAs were identified using high-throughput sequencing. The expression levels of tsRNAs were validated in 62 paired GC tissues and adjacent normal tissues using RT-qPCR...

At present, it is commonly believed that tRFs and tiRNAs are formed by the specific and selective shear of tRNAs under certain pressure stimulation, rather than by random degradation of tRNA. tRFs and tiRNAs have been reported to contribute to the biological process of a variety of human cancers. However, the evidence for the mechanisms of tRFs and tiRNAs in the occurrence and development of gastric cancer (GC) is still insufficient. Here, we aimed to explore the carcinogenic roles of tRFs and tiRNAs in GC with RNA-sequencing technique, and found a novel 3'tRNA-derived fragment tRF-Val was significantly upregulated in GC tissues and cell lines...

The mechanisms controlling the aggressiveness and survival of cervical SCC cells remain unclear. We investigated how the physical and biological microenvironments regulate the growth, apoptosis and invasiveness of cervical cancer cells. Dynamic flow and air exposure were evaluated as physical microenvironmental factors, and stromal fibroblasts were evaluated as a biological microenvironmental factor. To investigate any regulatory effects of these microenvironmental factors, we established a new culture model which concurrently replicates fluid streaming, air exposure and cancer-stromal interactions...

PURPOSE: There is a clinical need to better non-invasively characterize the tumor microenvironment in order to reveal evidence of early tumor response to therapy and to better understand therapeutic response. The goals of this work are first to compare the sensitivity to modifications occurring during tumor growth for measurements of tumor volume, immunohistochemistry parameters, and emerging ultrasound parameters (Shear Wave Elastography (SWE) and dynamic Contrast-Enhanced Ultrasound (CEUS)), and secondly, to study the link between the different parameters...

Until recently, necrosis is generally regarded as traumatic cell death due to mechanical shear stress or other physicochemical factors, while apoptosis is commonly thought to be programmed cell death, which is silent to immunological response. Actually, multiple modalities of cell death are programmed to maintain systematic immunity. Programmed necrosis, such as necrosis, pyroptosis, and ferroptosis, are inherently more immunogenic than apoptosis. Programmed necrosis leads to the release of inflammatory cytokines, defined as danger-associated molecular patterns (DAMPs), resulting in a necroinflammatory response, which can drive the proinflammatory state under certain biological circumstances...

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and ranks third in cancer-related deaths worldwide. This study was conducted to identify novel biomarkers related to the pathogenesis of CRC based upon a bioinformatics analysis, and further verify the biomarkers in clinical tumor samples and CRC cell lines. METHODS: A series of bioinformatics analyses were performed using datasets from NCBI-GEO and constructed a protein-protein interaction (PPI) network...

Oral squamous cellular carcinoma (OSCC) is considered a life-threatening disease with detection in late stages, which forces us to opt for dangerous treatment with a combination of chemotherapy and radiotherapy. Herbal components such as piperine and quercetin are derived from edible sources, proving their anticancer potential against oral cancer cells in vitro. Encapsulation into lipid matrix-mediated nanostructured lipid carriers (NLCs) can make both drugs bio-accessible. NLCs were synthesised using the high shear homogenisation method and characterised for their physicochemical properties, followed by in vitro cellular evaluation in FaDu oral cancer cells...

Teucrium polium extract (TPE) is a natural product with potent anticancer activity because of its terpenoid and flavonoid content. The aim of this study was to synthesize solid lipid nanoparticles (SLN) containing T. polium extract (TPE-SLNs) and to evaluate its anti-cancer effect. Formulations of TPE-SLNs were prepared using high-shear homogenization followed by the ultra-sonication technique. Then the TPE-SLNs were characterized by dynamic light scattering (DLS), Zetasizer and field-emission scanning electron microscopy (FESEM), and Fourier transform infrared spectroscopy methods...

To characterize transcriptomic changes in endothelial cells (ECs) infected by coronaviruses, and stimulated by DAMPs, the expressions of 1311 innate immune regulatomic genes (IGs) were examined in 28 EC microarray datasets with 7 monocyte datasets as controls. We made the following findings: The majority of IGs are upregulated in the first 12 hours post-infection (PI), and maintained until 48 hours PI in human microvascular EC infected by middle east respiratory syndrome-coronavirus (MERS-CoV) (an EC model for COVID-19)...

OBJECTIVE: To analyze the pharmacological mechanism of the treatment of dry age-related macular degeneration (dry AMD) based on a network pharmacological approach of Shuang Di Shou Zhen Tablets (SDSZT) and to provide a new reference for the current lack of effective treatment of dry AMD. METHODS: The main chemical constituents and their targets of Rehmanniae Radix Praeparata, Ligustrum lucidum, Mori Fructus, Paeonia albiflora, Rhizoma Dioscoreae, Alisma orientale, Schisandra chinensis, Radix Polygoni Multiflori Preparata, Ophiopogon japonicus, and Radix Rehmanniae were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID)...

Metastasis of cancer is the main cause of death in many types of cancer. Acute shear stress (ASS) is an important part of tumor micro-environment, it plays a crucial role in tumor invasion and spread. However, less is known about the role of ASS in tumorigenesis and metastasis of NSCLC. In this study, NSCLC cells were exposed to ASS (10 dyn/cm2 ) to explore the effect of ASS in regulation of autophagy and exosome mediated cell survival. Finally, the influence of SIRT2 on NSCLC cell metastasis was verified in vivo ...

All life forms have evolved under the constant force of gravity on Earth and developed ways to counterbalance acceleration load. In space, shear forces, buoyance-driven convection, and hydrostatic pressure are nullified or strongly reduced. When subjected to microgravity in space, the equilibrium between cell architecture and the external force is disturbed, resulting in changes at the cellular and sub-cellular levels (e.g., cytoskeleton, signal transduction, membrane permeability, etc.). Cosmic radiation also poses great health risks to astronauts because it has high linear energy transfer values that evoke complex DNA and other cellular damage...

BACKGROUND: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. OBJECTIVE: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs...

Circulating tumor cells (CTCs) are cancer cells that detach from the primary site and travel in the blood stream. A higher number of CTCs increases the risk of breast cancer metastasis, and it is inversely associated with the survival rates of patients with breast cancer. Although the numbers of CTCs are generally low and the majority of CTCs die in circulation, the survival of a few CTCs can seed the development of a tumor at a secondary location. An increasing number of studies demonstrate that CTCs undergo modification in response to the dynamic biophysical environment in the blood due in part to fluid shear stress...

Breast cancer is the most common cancer among women in the United States, with late stages associated with the lowest survival rates. The latest stage, defined as metastasis, accounts for 90% of all cancer-related deaths. There is a strong need to develop antimetastatic therapies. TRAIL, or TNF-related apoptosis inducing ligand, has been used as an antimetastatic therapy in the past, and conjugating TRAIL to nanoscale liposomes has been shown to enhance its targeting efficacy. When circulating tumor cells (CTCs) released during metastasis are exposed to TRAIL-conjugated liposomes and physiologically relevant fluid shear stress, this results in rapid cancer cell destruction into cell fragments...

Ubiquitin is a small molecule protein consisting of 76 amino acids,widely found in eukaryotic cells. The process by which ubiquitin binding to a specific protein is called ubiquitination. Deubiquitination is the reversed process of ubiquitination. Ubiquitination stimulates downstream signal,including complex assembly,protein conformation and activity changes,proteolysis,autophagy,guilt,chromatin remodeling,and DNA repair. More than 80% of eukaryotic protein degradation is mediated by the ubiquitination system,and ubiquitin-dependent proteolysis is an extremely complex process involving many biomolecular processes...

Severe forms of pulmonary arterial hypertension (PAH) are most frequently the consequence of a lumen-obliterating angiopathy. One pathobiological model is that the initial pulmonary vascular endothelial cell injury and apoptosis is followed by the evolution of phenotypically altered, apoptosis-resistant, proliferating cells and an inflammatory vascular immune response. Although there may be a vasoconstrictive disease component, the increased pulmonary vascular shear stress in established PAH is caused largely by the vascular wall pathology...

TRAIL specifically induces apoptosis in cancer cells without affecting healthy cells. However, TRAIL's cancer cytotoxicity was insufficient in clinical trials. Circulatory-shear stress is known to sensitize cancer cells to TRAIL. In this study, we examine the mechanism of this TRAIL sensitization with the goal of translating it to static conditions. GsMTx-4, a Piezo1 inhibitor, was found to reduce shear stress-related TRAIL sensitization, implicating Piezo1 activation as a potential TRAIL-sensitizer. The Piezo1 agonist Yoda1 recreated shear stress-induced TRAIL sensitization under static conditions...

Cell-surface receptors (e.g., EGFR and integrin) and their interactions play determining roles in signal transduction and cytoskeletal activation, which affect cell attachment/detachment, invasion, motility, metastasis (intracellular), and cell-cell signaling. For instance, the interactions between the EGFR and integrin (α6β4) may cause increased mechanical force and shear stress via enhanced cytoskeleton activation. Here, we design a DNA nanodevice (DNA-ND) that can simultaneously target the EGFR and integrin receptors on the caveolae...