Mitochondrial dysfunction, UPRmt signaling, and targeted therapy in metastasis tumor

In modern research, mitochondria are considered a more crucial energy plant in cells. Mitochondrial dysfunction, including mitochondrial DNA (mtDNA) mutation and denatured protein accumulation, is a common feature of tumors. The dysfunctional mitochondria reprogram molecular metabolism and allow tumor cells to proliferate in the hostile microenvironment. One of the crucial signaling pathways of the mitochondrial dysfunction activation in the tumor cells is the retrograde signaling of mitochondria-nucleus interaction, mitochondrial unfolded protein response (UPRmt), which is initiated by accumulation of denatured protein and excess ROS production. In the process of UPRmt, various components are activitated to enhance the mitochondria-nucleus retrograde signaling to promote carcinoma progression, including hypoxia-inducible factor (HIF), activating transcription factor ATF-4, ATF-5, CHOP, AKT, AMPK. The retrograde signaling molecules of overexpression ATF-5, SIRT3, CREB, SOD1, SOD2, early growth response protein 1 (EGR1), ATF2, CCAAT/enhancer-binding protein-d, and CHOP also involved in the process. Targeted blockage of the UPRmt pathway could obviously inhibit tumor proliferation and metastasis. This review indicates the UPRmt pathways and its crucial role in targeted therapy of metastasis tumors.

The Effect of Protein Structure and Concentration on Tribocorrosion and Film Formation on CoCrMo Alloys

The formation of tribochemical reaction layers, better known as tribofilms, on cobalt-chromium-molybdenum (CoCrMo) alloys commonly used in orthopaedic applications has been hypothesized to reduce degradation owing to wear and corrosion. However, the mechanisms and pathways influencing tribofilm formation remain largely unknown. This study aims to develop a clearer understanding of the role of protein structures and its concentration on tribocorrosion and surface tribofilms formed on CoCrMo alloys during boundary regime sliding. A reciprocating tribometer with a three-electrode electrochemical cell was employed to simulate and monitor the tribocorrosion of CoCrMo in situ. As-received Foetal Bovine Serum (as-FBS) and pre-heated FBS at 70 °C for 1 h (de-FBS) were diluted with saline (0.9% NaCl) at different concentrations (25% and 75% v/v) and utilized as electrolytes during the tribocorrosion tests. The result shows that the denatured protein structure in electrolyte tends to reduce the volume losses due to wear and corrosion on the CoCrMo samples with an appreciation of the protein tribofilms. On the other hand, an increased protein concentration increased the total volume loss due to corrosive processes. A novel finding revealed in this study is that the tribocorrosion mechanism of the CoCrMo surface is dependent on the protein structure, concentration and sliding duration due to the change in surface condition.

SIMPLE ASSAY FOR ADSORPTION OF PROTEINS TO THE AIR-WATER INTERFACE

A rapid assay is described, based upon the Marangoni effect, which detects the formation of a denatured-protein film at the air-water interface (AWI) of aqueous samples. This assay requires no more than a 20 microliter aliquot of sample, at a protein concentration of no more than 1 mg/ml, and it can be performed with any buffer that is used to prepare grids for electron cryo-microscopy (cryo-EM). In addition, this assay provides an easy way to estimate the rate at which a given protein forms such a film at the AWI. Use of this assay is suggested as a way to pre-screen the effect of various additives and chemical modifications that one might use to optimize the preparation of grids, although the final proof of optimization still requires further screening of grids in the electron microscope. In those cases when the assay establishes that a given protein does form a sacrificial, denatured-protein monolayer, it is suggested that subsequent optimization strategies might focus on discovering how to improve the adsorption of native proteins onto that monolayer, rather than to prevent its formation. A second alternative might be to bind such proteins to the surface of rationally designed affinity grids, in order to prevent their diffusion to, and unwanted interaction with, the AWI.

Fabrication of a Novel Protein Sponge with Dual-Scale Porosity and Mixed Wettability Using a Clean and Versatile Microwave-Based Process

An open-porous protein sponge with mixed wettability is presented made entirely from whey proteins and with promising applications in biomedicine, pharmaceutical, and food industry. The fabrication relies on an additive-free, clean and scalable process consisting of foaming followed by controlled microwave-convection drying. Volumetric heating throughout the matrix induced by microwaves causes fast expansion and elongation of the foam bubbles, retards crust formation and promotes early protein denaturation. These effects counteract collapse and shrinkage typically encountered in convection drying of foams. The interplay of high protein content, tailored gas incorporation and controlled drying result in a dried structure with dual-scale porosity composed of open macroscopic elongated foam bubbles and microscopic pores in the surrounding solid lamellae induced by water evaporation. Due to the insolubility and mixed wettability of the denatured protein network, polar and non-polar liquids are rapidly absorbed into the interconnected capillary system of the sponge without disintegrating. While non-watery liquids penetrate the pores by capillary suction, water diffuses also into the stiff protein matrix, inducing swelling and softening. Consequently, the water-filled soft sponge can be emptied by compression and re-absorbs any wetting liquid into the free capillary space.

REVISITING THE ECOTOXICITY AND EFFICIENCY OF DIFFERENT CLASSES OF INDUSTRIAL NONIONIC SURFACES USED FOR CLEANING METAL SURFACES IN THE PROCESS OF CAPILLARY CONTROL OF DETAILS OF THE AVIATION TECHNOLOGY (review)

A review of modern classes of nonionic surfactants used for cleaning metal surfaces is carried out. The following aspects are considered: efficiency of cleaning metal surfaces, ecotoxicity, biodegradability, impact on human health. The most promising class of surfactants – alkyl polyglycosides (APG) – for cleaning metal surfaces, including in the process of capillary control, has been determined. It is noted that APGs have shown high efficiency in removing even such contaminants as denatured protein and burnt corn starch from metal surfaces. In addition, APGs have the highest emulsifying ability among industrial surfactants, which effectively affects the reduction in surfactant consumption when cleaning the surfaces.

One-pot synthesis of high-concentration mixed-shell polymeric micelles as nanochaperones for renaturation of bulk proteins

Refolding denatured protein into its native form and stabilizing its structure are significant in the production and storage of protein products. The self-assembled mixed-shell polymeric micelle (MSPM) based nanochaperone closely...

Analytical Estimation of Temperature in Living Tissues Using the TPL Bioheat Model with Experimental Verification

The aim of this study is to propose the analytical method associated with Laplace transforms and experimental verification to estimate thermal damages and temperature due to laser irradiation by utilizing measurement information of skin surface. The thermal damages to the tissues are totally estimated by denatured protein ranges using the formulations of Arrhenius. By using Laplace transformations, the exact solution of all physical variables is obtained. Numerical results for the temperature and thermal damage are presented graphically. Furthermore, the comparisons between the numerical calculations with experimental verification show that the three-phase lag bioheat mathematical model is an efficient tool for estimating the bioheat transfer in skin tissue.