Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation: Challenges and Perspectives.

During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation.

Anti-Cancer Properties of Flaxseed Proteome.

Flaxseed has been recognized as a valuable source of nutrients and bioactive compounds, including proteins that possess various health benefits. In recent years, studies have shown that flaxseed proteins, including albumins, globulins, glutelin, and prolamins, possess anti-cancer properties. These properties are attributed to their ability to inhibit cancer cell proliferation, induce apoptosis, and interfere with cancer cell signaling pathways, ultimately leading to the inhibition of metastasis.

Encapsulation and adhesion of nanoparticles as a potential biomarker for TNBC cells metastatic propensity.

Metastasis is the main cause of cancer-related mortality; therefore, the ability to predict its propensity can remarkably affect survival rate. Metastasis development is predicted nowadays by lymph-node status, tumor size, histopathology, and genetic testing. However, all these methods may have inaccuracies, and some require weeks to complete.

Proteomic Markers for Mechanobiological Properties of Metastatic Cancer Cells.

The major cause (more than 90%) of all cancer-related deaths is metastasis, thus its prediction can critically affect the survival rate. Metastases are currently predicted by lymph-node status, tumor size, histopathology and genetic testing; however, all these are not infallible, and obtaining results may require weeks. The identification of new potential prognostic factors will be an important source of risk information for the practicing oncologist, potentially leading to enhanced patient care through the proactive optimization of treatment strategies.

Recent advances in therapeutic strategies for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC) with a poor prognosis. Current treatment options are limited to surgery, adjuvant chemotherapy and radiotherapy; however, a proportion of patients have missed the surgical window at the time of diagnosis. TNBC is a highly heterogeneous cancer with specific mutations and aberrant activation of signaling pathways.

Emerging mechanisms of pyroptosis and its therapeutic strategy in cancer.

Pyroptosis, a type of inflammatory programmed cell death, is triggered by caspase cleavage of gasdermin family proteins. Based on accumulating evidence, pyroptosis is closely associated with tumour development, but the molecular mechanism underlying pyroptosis activation and the signalling pathways regulated by pyroptosis remain unclear. In this review, we first briefly introduce the definition, morphological characteristics, and activation pathways of pyroptosis and the effect of pyroptosis on anticancer immunity.

Rapid, quantitative prediction of tumor invasiveness in non-melanoma skin cancers using mechanobiology-based assay.

Non-melanoma skin cancers, including basal and squamous cell carcinomas (BCC and SCC), are the most common malignancies worldwide. BCC/SCC cancers are generally highly localized and can be surgically excised; however, invasive tumors may be fatal. Current diagnosis of skin cancer and prognosis of potential invasiveness are based mainly on clinical-pathological factors of the biopsied lesions.

Actin as a Target to Reduce Cell Invasiveness in Initial Stages of Metastasis.

We demonstrate the relative roles of the cell cytoskeleton, and specific importance of actin in facilitating mechanical aspects of metastatic invasion. A crucial step in metastasis, the typically lethal spread of cancer to distant body-sites, is cell invasion through dense tissues composed of extracellular matrix and various non-cancerous cells. Cell invasion requires cell-cytoskeleton remodeling to facilitate dynamic morphological changes and force application.

Lung mechanics modifications facilitating metastasis are mediated in part by breast cancer-derived extracellular vesicles.

Tumor microenvironment-mechanics greatly affect tumor-cell characteristics such as invasion and proliferation. We and others have previously shown that after chemotherapy, tumor cells shed more extracellular vesicles (EVs), leading to tumor growth and even spread, via angiogenesis and the mobilization of specific bone-marrow-derived cells contributing to metastasis. However, physical, mechanobiological and mechanostructural changes at premetastatic sites that may support tumor cell seeding, have yet to be determined.

Rapid Cancer Diagnosis and Early Prognosis of Metastatic Risk Based on Mechanical Invasiveness of Sampled Cells.

We provide an innovative, bioengineering, mechanobiology-based approach to rapidly (2-h) establish the in vivo metastatic likelihood of patient tumor-samples, where results are in direct agreement with clinical histopathology and patient outcomes. Cancer-related mortality is mostly due to local recurrence or to metastatic disease, thus early prediction of tumor-cell-fate may critically affect treatment protocols and survival rates. Metastasis and recurrence risks are currently predicted by lymph-node status, tumor size, histopathology and genetic testing, however, these are not infallible and results may require days/weeks.

Proximity of Metastatic Cells Enhances Their Mechanobiological Invasiveness.

A critical step in metastases formation is cancer-cell invasion through tissue. During invasion, cells change morphology and apply forces to their surroundings. We have previously shown that single, metastatic breast-cancer cells will mechanically indent a synthetic, impenetrable polyacrylamide gel with physiological-stiffness in attempted invasion; benign breast cells do not indent the gels.

Prolyl hydroxylation in elastin is not random.

Background: This study aimed to investigate the prolyl and lysine hydroxylation in elastin from different species and tissues.

Methods: Enzymatic digests of elastin samples from human, cattle, pig and chicken were analyzed using mass spectrometry and bioinformatics tools.

Results: It was confirmed at the protein level that elastin does not contain hydroxylated lysine residues regardless of the species.

Injectable hydrogels with high fixed charge density and swelling pressure for nucleus pulposus repair: biomimetic glycosaminoglycan analogues.

The load-bearing biomechanical role of the intervertebral disc is governed by the composition and organization of its major macromolecular components, collagen and aggrecan. The major function of aggrecan is to maintain tissue hydration, and hence disc height, under the high loads imposed by muscle activity and body weight. Key to this role is the high negative fixed charge of its glycosaminoglycan side chains, which impart a high osmotic pressure to the tissue, thus regulating and maintaining tissue hydration and hence disc height under load.

Advances in the diagnosis of degenerated lumbar discs and their possible clinical application.

Purpose: One possible source of chronic low back pain is a degenerated intervertebral disc. In this review, various diagnostic methods for the assessment of the presence of degenerative changes are described. These include clinical MRI, a number of novel MRI techniques and nuclear magnetic resonance spectroscopy.

Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc.

Background: The intervertebral disc (IVD) is a complex cartilaginous structure which functions to resist biomechanical loads during spinal movement. It consists of the highly viscous cartilaginous nucleus pulposus, which is surrounded laterally by a thick outer ring of fibrous cartilage-the annulus fibrosus-and sandwiched inferiorly and superiorly by the cartilage end-plates. The main extracellular matrix molecules of the disc are collagens, proteoglycans, glycoproteins and elastin.

A needle micro-osmometer for determination of glycosaminoglycan concentration in excised nucleus pulposus tissue.

Purpose: Aggrecan is one of the major macromolecular components of the intervertebral disc (IVD) and its loss is an early sign of degeneration. Restoration of aggrecan, and hence of biomechanical properties, is a major objective of biological therapies. At present, assessment of aggrecan concentration via its glycosaminoglycan (GAG) content is accomplished using biochemical and histological methods which require sacrifice of tissue.

Normal and shear interactions between hyaluronan-aggrecan complexes mimicking possible boundary lubricants in articular cartilage in synovial joints.

Using a surface force balance, normal and shear interactions have been measured between two atomically smooth surfaces coated with hyaluronan (HA), and with HA/aggrecan (Agg) complexes stabilized by cartilage link protein (LP). Such HA/Agg/LP complexes are the most abundant mobile macromolecular species permeating articular cartilage in synovial joints and have been conjectured to be present as boundary lubricants at its surface. The aim of the present study is to gain insight into the extremely efficient lubrication when two cartilage surfaces slide past each other in healthy joints, and in particular to elucidate the possible role in this of the HA/Agg/LP complexes.

Longevity of elastin in human intervertebral disc as probed by the racemization of aspartic acid.

Background: Aging and degeneration of human intervertebral disc (IVD) are associated with biochemical changes, including racemization and glycation. These changes can only be counteracted by protein turnover. Little is known about the longevity of IVD elastin in health or disease.

Articular cartilage proteoglycans as boundary lubricants: structure and frictional interaction of surface-attached hyaluronan and hyaluronan--aggrecan complexes.

Mammalian synovial joints are extremely efficient lubrication systems reaching friction coefficient μ as low as 0.001 at high pressures (up to 100 atm) and shear rates (up to 10(6) to 10(7) Hz); however, despite much previous work, the exact mechanism responsible for this behavior is still unknown. In this work, we study the molecular mechanism of synovial joint lubrication by emulating the articular cartilage superficial zone structure.

Liposomes act as effective biolubricants for friction reduction in human synovial joints.

Phospholipids (PL) form the matrix of biological membranes and of the lipoprotein envelope monolayer, and are responsible for many of the unique physicochemical, biochemical, and biological properties of these supermolecular bioassemblies. It was suggested that phospholipids present in the synovial fluid (SF) and on the surface of articular cartilage have major involvement in the low friction of cartilage, which is essential for proper mobility of synovial joints. In pathologies, such as impaired biolubrication (leading to common joint disorders such as osteoarthritis), the level of phospholipids in the SF is reduced.

Are disc pressure, stress, and osmolarity affected by intra- and extrafibrillar fluid exchange?

Because extrafibrillar water content dictates extrafibrillar osmolarity, we aimed to determine the influence of intra- and extrafibrillar fluid exchange on intradiscal pressures and stresses. As experimental results showed that extrafibrillar osmolarity affects intervertebral disc cell gene expression and crack propagation, quantification of the effects of changes in intra- and extrafibrillar fluid exchange is physiologically relevant. Therefore, our 3D osmoviscoelastic finite element (FE) model of the intervertebral disc was extended to include the intra- and extrafibrillar water differentiation.

Correlation of swelling pressure and intrafibrillar water in young and aged human intervertebral discs.

Fluid balance in the intervertebral disc under applied load is determined primarily by its swelling pressure, that is, the external pressure at which it neither loses nor gains water. This depends on the composition of the tissue, in particular on its proteoglycan concentration. Proteoglycans develop a high osmotic pressure due to their fixed negatively charged groups.