Exploring the adhesion properties of extracellular vesicles for functional assays.

The "stickiness" of extracellular vesicles (EVs) can pose challenges for EV processing and storage, but adhesive properties may also be exploited to immobilize EVs directly on surfaces for various measurement techniques, including super-resolution microscopy. Direct adhesion to surfaces may allow examination of broader populations of EVs than molecular affinity approaches, which can also involve specialized, expensive affinity reagents. Here, we report on the interaction of EVs with borosilicate glass and quartz coverslips and on the effects of pre-coating coverslips with poly-L-lysine (PLL), a reagent commonly used to facilitate interactions between negatively charged surfaces of cells and amorphous surfaces.

The Role of αvβ3 Integrin in Cancer Therapy Resistance.

A relevant challenge for the treatment of patients with neoplasia is the development of resistance to chemo-, immune-, and radiotherapies. Although the causes of therapy resistance are poorly understood, evidence suggests it relies on compensatory mechanisms that cells develop to replace specific intracellular signaling that should be inactive after pharmacological inhibition. One such mechanism involves integrins, membrane receptors that connect cells to the extracellular matrix and have a crucial role in cell migration.

A novel PD-1/PD-L1 pathway-related seven-gene signature for the development and validation of the prognosis prediction model for breast cancer.

Background: Breast cancer (BC/BRCA) is the most common carcinoma in women. The average 5-year survival rate of BC patients with stage IV disease is 26%. A considerable proportion of patients still do not receive effective therapy.

Blockage of αvβ3 integrin in 3D culture of triple-negative breast cancer and endothelial cells inhibits migration and discourages endothelial-to-mesenchymal plasticity.

Breast cancer is a relevant cause of mortality in women and its triple-negative subtype (TNBC) is usually associated with poor prognosis. During tumor progression to metastasis, angiogenesis is triggered by the sprouting of endothelial cells from pre-existing vessels by a dynamic chain of events including VE-cadherin downregulation, actin protrusion, and integrin-mediated adhesion, allowing for migration and proliferation. The binding of tumoral and tumor-associated stromal cells with the extracellular matrix through integrins mediates angiogenic processes and certain integrin subtypes, such as the αβ integrin, are upregulated in hypoxic TNBC models.

3D printed bioabsorbable composite scaffolds of poly (lactic acid)-tricalcium phosphate-ceria with osteogenic property for bone regeneration.

The fabrication of customized implants by additive manufacturing has allowed continued development of the personalized medicine field. Herein, a 3D-printed bioabsorbable poly (lactic acid) (PLA)- β-tricalcium phosphate (TCP) (10 wt %) composite has been modified with CeO nanoparticles (CeNPs) (1, 5 and 10 wt %) for bone repair. The filaments were prepared by melt extrusion and used to print porous scaffolds.

Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness.

Background: Chemotherapy is one of the common treatments for breast cancer. The induction of cancer stem cells (CSCs) is an important reason for chemotherapy failure and breast cancer recurrence. Astragaloside IV (ASIV) is one of the effective components of the traditional Chinese medicine (TCM) , which can improve the sensitivity of various tumors to chemotherapy drugs.

Human HSP70-escort protein 1 (hHep1) interacts with negatively charged lipid bilayers and cell membranes.

Human Hsp70-escort protein 1 (hHep1) is a cochaperone that assists in the function and stability of mitochondrial HSPA9. Similar to HSPA9, hHep1 is located outside the mitochondria and can interact with liposomes. In this study, we further investigated the structural and thermodynamic behavior of interactions between hHep1 and negatively charged liposomes, as well as interactions with cellular membranes.

Effect of Silicon Dioxide and Magnesium Oxide on the Printability, Degradability, Mechanical Strength and Bioactivity of 3D Printed Poly (Lactic Acid)-Tricalcium Phosphate Composite Scaffolds.

Background: Poly (lactic acid) (PLA) is a biodegradable polyester that has been exploited for a variety of biomedical applications, including tissue engineering. The incorporation of β-tricalcium phosphate (TCP) into PLA has imparted bioactivity to the polymeric matrix.

Methods: We have modified a 90%PLA-10%TCP composite with SiO and MgO (1, 5 and 10 wt%), separately, to further enhance the material bioactivity.

Comparison of hydrophilic and hydrophobic nano topographic surfaces of titanium alloys on pre-osteoblastic cell interaction.

This work aimed to assess the influence of different structured substrates with hydrophilic and hydrophobic properties on micro and nano topographies developed on titanium alloys over pre-osteoblastic cell behavior. Nano topography influences small dimension levels of cell morphology by inducing filopodia formation in cell membranes, irrespectively to the wettability behavior of the surface. Therefore, micro and nanostructured surfaces of titanium-based samples using different techniques of surface modification processing, such as chemical treatments, micro-arc anodic oxidation (MAO), and MAO combined to laser irradiation were developed.

Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer.

Human epidermal growth factor receptor-2 (HER2)-targeting therapies provide clinical benefits for patients with HER2-positive breast cancer. However, the resistance to monotherapies invariably develops and leads to disease relapse and treatment failure. Previous studies have demonstrated a link between the potency of HER2-targeting tyrosine kinase inhibitors (TKIs) and their ability to induce an iron-dependent form of cell death called ferroptosis.

Role of resistance training in bone macro and micro damages in an estrogen absence animal model.

Aims: We evaluated the effects of resistance training (RT) on bone properties, morphology, and bone extracellular matrix (ECM) remodeling markers in an ovariectomy (OVX) rat model.

Main Methods: Thirty-six female rats were divided into four groups: sham sedentary, OVX sedentary, sham RT, and OVX RT. Rats performed RT for ten weeks, during which they climbed a ladder with progressive loads attached to the tail.

Small Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells Induce Oxygen-Dependent Cell Invasion.

Hypoxia, a condition of low oxygenation frequently found in triple-negative breast tumors (TNBC), promotes extracellular vesicle (EV) secretion and favors cell invasion, a complex process in which cell morphology is altered, dynamic focal adhesion spots are created, and ECM is remodeled. Here, we investigated the invasive properties triggered by TNBC-derived hypoxic small EV (SEVh) in vitro in cells cultured under hypoxic (1% O) and normoxic (20% O) conditions, using phenotypical and proteomic approaches. SEVh characterization demonstrated increased protein abundance and diversity over normoxic SEV (SEVn), with enrichment in pro-invasive pathways.

Improving 3-hydroxypropionic acid production in E. coli by in silico prediction of new metabolic targets.

3-Hydroxypropionic acid (3-HP) production from renewable feedstocks is of great interest in efforts to develop greener processes for obtaining this chemical platform. Here we report an engineered E. coli strain for 3-HP production through the β-alanine pathway.

Fabrication, morphological, mechanical and biological performance of 3D printed poly(ϵ-caprolactone)/bioglass composite scaffolds for bone tissue engineering applications.

Several techniques, such as additive manufacturing, have been used for the manufacture of polymer-ceramic composite scaffolds for bone tissue engineering. A new extruder head recently developed for improving the manufacturing process is an experimental 3D printer Fab@CTI that enables the use of ceramic powders in the processing of composite materials or polymer blends. Still, the manufacturing process needs improvement to promote the dispersion of ceramic particles in the polymer matrix.

Effects of Moderate-Intensity Physical Training on Skeletal Muscle Substrate Transporters and Metabolic Parameters of Ovariectomized Rats.

A deficit of estrogen is associated with energy substrate imbalance, raising the risk of metabolic diseases. Physical training (PT) is a potent metabolic regulator through oxidation and storage of substrates transported by GLUT4 and FAT CD36 in skeletal muscle. However, little is known about the effects of PT on these carriers in an estrogen-deficit scenario.

New insights into the discovery of drugs for triple-negative breast cancer metastasis.

Introduction: Triple-negative breast cancer (TNBC) is of great concern due to its aggressiveness and lack of targeted therapy. For these reasons, TNBC is one of the main causes of death in women, mainly due to metastases. Tumor dissemination has highlighted a set of possible targets, with extensive research into new single-target drugs, in addition to drug repurposing strategies, being undertaken to discover new classes of potential inhibitors of metastasis.

The Effects of αvβ3 Integrin Blockage in Breast Tumor and Endothelial Cells under Hypoxia In Vitro.

Breast cancer is characterized by a hypoxic microenvironment inside the tumor mass, contributing to cell metastatic behavior. Hypoxia induces the expression of hypoxia-inducible factor (HIF-1α), a transcription factor for genes involved in angiogenesis and metastatic behavior, including the vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and integrins. Integrin receptors play a key role in cell adhesion and migration, being considered targets for metastasis prevention.

Alternagin-C, an alpha2beta1 integrin ligand, attenuates collagen-based adhesion, stimulating the metastasis suppressor 1 expression in triple-negative breast tumor cells.

Triple-negative breast cancer has an aggressive clinical course and its treatment has been challenging due to high metastatic risk. Molecular targets have been sought to provide better strategies for this type of cancer. Integrins are cell adhesion receptors involved in tumor progression and αβ integrin, a collagen receptor, has a key role in breast metastasis.

Resistance training variable manipulations are less relevant than intrinsic biology in affecting muscle fiber hypertrophy.

We aimed to investigate whether muscle fiber cross-sectional area (fCSA) and associated molecular processes could be differently affected at the group and individual level by manipulating resistance training (RT) variables. Twenty resistance-trained subjects had each leg randomly allocated to either a standard RT (RT-CON: without specific variables manipulations) or a variable RT (RT-VAR: manipulation of load, volume, muscle action, and rest interval at each RT session). Muscle fCSA, satellite cell (SC) pool, myonuclei content, and gene expression were assessed before and after training (chronic effect).

Hormetic-like dose-response induced by alternagin-C, a protein isolated from urutu snake (Rhinocerophis alternatus) venom, in fish (Hoplias malabaricus) cardiac contractility.

The aim of this study was to evaluate the effects of different doses of alternagin-C, a disintegrin-like protein from Rhinocerophis alternatus venom, on myocardial contractility of the freshwater fish Hoplias malabaricus, an alternative model to contractile function studies. Alternagin-C treatment exhibited a hormetic-like dose-response curve with a strong positive inotropism and enhanced cardiac pumping capacity at low dose, whereas a modest inotropism and a left shift in the force-frequency relationship was registered at high dose.

Biphasic α2β1 Integrin Expression in Breast Cancer Metastasis to Bone.

Integrins participate in the pathogenesis and progression of tumors at many stages during the metastatic cascade. However, current evidence for the role of integrins in breast cancer progression is contradictory and seems to be dependent on tumor stage, differentiation status, and microenvironmental influences. While some studies suggest that loss of α2β1 enhances cancer metastasis, other studies suggest that this integrin is pro-tumorigenic.

Suturable elastomeric tubular grafts with patterned porosity for rapid vascularization of 3D constructs.

Vascularization is considered to be one of the key challenges in engineering functional 3D tissues. Engineering suturable vascular grafts containing pores with diameter of several tens of microns in tissue engineered constructs may provide an instantaneous blood perfusion through the grafts improving cell infiltration and thus, allowing rapid vascularization and vascular branching. The aim of this work was to develop suturable tubular scaffolds to be integrated in biofabricated constructs, enabling the direct connection of the biofabricated construct with the host blood stream, providing an immediate blood flow inside the construct.

Metabolic engineering of E. coli for pyocyanin production.

Pyocyanin is a secondary metabolite from Pseudomonas aeruginosa that belongs to the class of phenazines, which are aromatic nitrogenous compounds with numerous biological functions. Besides its antifungal and antimicrobial activities, pyocyanin is a remarkable redox-active molecule with potential applications ranging from the pharma industry to the development of microbial fuel cells. Nevertheless, pyocyanin production has been restricted to P.

Resistance Training Modulates the Matrix Metalloproteinase-2 Activity in Different Trabecular Bones in Aged Rats.

Background: Aging decreases osteogenic ability, inducing harmful effects on the bone extracellular matrix (ECM), while exercise training has been indicated as a tool to counteract bone disorders related to advancing age. The modulation of bone ECM is regulated by several types of matrix metalloproteinase (MMP); however, MMP-2 activity in different trabecular bones in response to resistance training (RT) has been neglected. Remodeling differs in different bones under the application of the same mechanical loading.