Organic–Inorganic Surface Modifications for Titanium Implant Surfaces

This paper reviews current physicochemical and biochemical coating techniques that are investigated to enhance bone regeneration at the interface of titanium implant materials. By applying coatings onto titanium surfaces that mimic the organic and inorganic components of living bone tissue, a physiological transition between the non-physiological titanium surface and surrounding bone tissue can be established. In this way, the coated titanium implants stimulate bone formation from the implant surface, thereby enhancing early and strong fixation of bone-substituting implants. As such, a continuous transition from bone tissue to implant surface is induced. This review presents an overview of various techniques that can be used to this end, and that are inspired by either inorganic (calcium phosphate) or organic (extracellular matrix components, growth factors, enzymes, etc.) components of natural bone tissue. The combination, however, of both organic and inorganic constituents is expected to result into truly bone-resembling coatings, and as such to a new generation of surface-modified titanium implants with improved functionality and biological efficacy

Robust metabolic transcriptional components in 34,494 patient-derived cancer-related samples and cell lines

BACKGROUND: Patient-derived bulk expression profiles of cancers can provide insight into the transcriptional changes that underlie reprogrammed metabolism in cancer. These profiles represent the average expression pattern of all heterogeneous tumor and non-tumor cells present in biopsies of tumor lesions. Hence, subtle transcriptional footprints of metabolic processes can be concealed by other biological processes and experimental artifacts. However, consensus independent component analyses (c-ICA) can capture statistically independent transcriptional footprints of both subtle and more pronounced metabolic processes. METHODS: We performed c-ICA with 34,494 bulk expression profiles of patient-derived tumor biopsies, non-cancer tissues, and cell lines. Gene set enrichment analysis with 608 gene sets that describe metabolic processes was performed to identify the transcriptional components enriched for metabolic processes (mTCs). The activity of these mTCs was determined in all samples to create a metabolic transcriptional landscape. RESULTS: A set of 555 mTCs was identified of which many were robust across different datasets, platforms, and patient-derived tissues and cell lines. We demonstrate how the metabolic transcriptional landscape defined by the activity of these mTCs in samples can be used to explore the associations between the metabolic transcriptome and drug sensitivities, patient outcomes, and the composition of the immune tumor microenvironment. CONCLUSIONS: To facilitate the use of our transcriptional metabolic landscape, we have provided access to all data via a web portal (www.themetaboliclandscapeofcancer.com). We believe this resource will contribute to the formulation of new hypotheses on how to metabolically engage the tumor or its (immune) microenvironment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-021-00272-7

Increased glycation and oxidative damage to apolipoprotein B100 of LDL cholesterol in patients with type 2 diabetes and effect of metformin

OBJECTIVE The aim of this study was to investigate whether apolipoprotein B100 of LDL suffers increased damage by glycation, oxidation, and nitration in patients with type 2 diabetes, including patients receiving metformin therapy. RESEARCH DESIGN AND METHODS For this study, 32 type 2 diabetic patients and 21 healthy control subjects were recruited; 13 diabetic patients were receiving metformin therapy (median dose: 1.50 g/day). LDL was isolated from venous plasma by ultracentrifugation, delipidated, digested, and analyzed for protein glycation, oxidation, and nitration adducts by stable isotopic dilution analysis tandem mass spectrometry. RESULTS Advanced glycation end product (AGE) content of apolipoprotein B100 of LDL from type 2 diabetic patients was higher than from healthy subjects: arginine-derived AGE, 15.8 vs. 5.3 mol% (P < 0.001); and lysine-derived AGE, 2.5 vs. 1.5 mol% (P < 0.05). Oxidative damage, mainly methionine sulfoxide residues, was also increased: 2.5 vs. 1.1 molar equivalents (P < 0.001). 3-Nitrotyrosine content was decreased: 0.04 vs. 0.12 mol% (P < 0.05). In diabetic patients receiving metformin therapy, arginine-derived AGE and methionine sulfoxide were lower than in patients not receiving metformin: 19.3 vs. 8.9 mol% (P < 0.01) and 2.9 vs. 1.9 mol% (P < 0.05), respectively; 3-nitrotyrosine content was higher: 0.10 vs. 0.03 mol% (P < 0.05). Fructosyl-lysine residue content correlated positively with fasting plasma glucose. Arginine-derived AGE residue contents were intercorrelated and also correlated positively with methionine sulfoxide. CONCLUSIONS Patients with type 2 diabetes had increased arginine-derived AGEs and oxidative damage in apolipoprotein B100 of LDL. This was lower in patients receiving metformin therapy, which may contribute to decreased oxidative damage, atherogenicity, and cardiovascular disease

Unraveling the Formation of Gelatin Nanospheres by Means of Desolvation

Gelatin nanoparticles (GNPs) have been widely studied for a plethora of biomedical applications, but their formation mechanism remains poorly understood, which precludes precise control over their physicochemical properties. This leads to timeconsuming parameter adjustments without a fundamental grasp of the underlying mechanism. Here, we analyze and visualize in a timeresolved manner the mechanism by which GNPs are formed during desolvation of gelatin as a function of gelatin molecular weight and type of desolvating agent. Through various analytical and imaging techniques, we unveil a multistage process that is initiated by the formation of primary particles that are ∼18 nm in diameter (wet state). These primary particles subsequently assemble into colloidally stable GNPs with a raspberry-like structure and a hydrodynamic diameter of ∼300 nm. Our results create a basic understanding of the formation mechanism of gelatin nanoparticles, which opens new opportunities for precisely tuning their physicochemical and biofunctional properties.Radboud University Medical Cente

Usefulness of preclinical models for assessing the efficacy of late-life interventions for sarcopenia

Caloric restriction and physical exercise have proven beneficial against age-associated changes in body composition and declining physical performance; however, little is known regarding what benefit these interventions might have when initiated late in life. The study of mimetics of diet and exercise and the combination thereof may provide additional treatments for a vulnerable elderly population; however, how and when to initiate such interventions requires consideration in developing the most safe and efficacious treatment strategies. In this review, we focus on preclinical late-life intervention studies, which assess the relationship between physical function, sarcopenia, and body composition. We provide a conceptual framework for the ever-changing definition of sarcopenia and a rationale for the use of an appropriate rodent model of this condition. We finish by providing our perspective regarding the implications of this body of work and future areas of research that may also contribute to the ultimate goal of extending healthspan. © 2011 The Author

Mitochondrial-derived vesicles in skeletal muscle remodeling and adaptation

Mitochondrial remodeling is crucial to meet the bioenergetic demand to support muscle contractile activity during daily tasks and muscle regeneration following injury. A set of mitochondrial quality control (MQC) processes, including mitochondrial biogenesis, dynamics, and mitophagy, are in place to maintain a well-functioning mitochondrial network and support muscle regeneration. Alterations in any of these pathways compromises mitochondrial quality and may potentially lead to impaired myogenesis, defective muscle regeneration, and ultimately loss of muscle function. Among MQC processes, mitophagy has gained special attention for its implication in the clearance of dysfunctional mitochondria via crosstalk with the endo-lysosomal system, a major cell degradative route. Along this pathway, additional opportunities for mitochondrial disposal have been identified that may also signal at the systemic level. This communication occurs via inclusion of mitochondrial components within membranous shuttles named mitochondrial-derived vesicles (MDVs). Here, we discuss MDV generation and release as a mitophagy-complementing route for the maintenance of mitochondrial homeostasis in skeletal myocytes. We also illustrate the possible role of muscle-derived MDVs in immune signaling during muscle remodeling and adaptation