Search

Surface engineering of stainless steels using thermochemical treatments at low temperatures has been the subject of intensive research for enhancing the surface hardness of these alloys without impairing their corrosion resistance. By using treatment media rich in nitrogen and/or carbon, it is possible to inhibit chromium compound formation and obtain supersaturated solid solutions, known as expanded phases, such as expanded austenite or S-phase in austenitic stainless steels, expanded ferrite in ferritic grades, and expanded martensite in martensitic grades. These low-temperature treatments produce a significant increase in surface hardness, which improves wear and fatigue resistance. However, the corrosion behavior of the modified surface layers remains of paramount importance. In the international literature, many studies on this topic are reported, but the results are not always univocal, and there are still open questions. In this review, the corrosion behavior of the expanded phases and the modified layers in which they are present is critically analyzed and discussed. The relationships between the phase composition and the microstructure of the modified layers and the corrosion resistance are highlighted while also considering the different test conditions. Furthermore, corrosion test methods are discussed, and suggestions are given for improving the measurements. Finally, perspectives on future directions for investigation are suggested for encouraging further research. [ABSTRACT FROM AUTHOR]

Vitamin E (Vit E) deficiency studies underline the relevance of this vitamin in skeletal muscle (SkM) homeostasis. The knowledge of the effectors and modulators of Vit E action in SkM cells is limited, especially in aging and chronic diseases characterized by a decline in musculoskeletal health. Vit E comprises eight fat-soluble compounds grouped into tocopherols and tocotrienols, which share the basic chemical structure but show different biological properties and potentials to prevent diseases. Vit E has antioxidant and non-antioxidant activities and both favorable and adverse effects depending on the specific conditions and tissues. In this review, we focus on the actual knowledge of Vit E forms in SkM functions and new potential signaling effectors (i.e., bioactive sphingolipids and myokines). The possible advantages of Vit E supplementation in counteracting SkM dysfunctions in sarcopenia and under microgravity will also be discussed. [ABSTRACT FROM AUTHOR]

Transient receptor potential (TRP) channels are broadly implicated in the developmental programs of most tissues. Amongst these tissues, skeletal muscle and adipose are noteworthy for being essential in establishing systemic metabolic balance. TRP channels respond to environmental stimuli by supplying intracellular calcium that instigates enzymatic cascades of developmental consequence and often impinge on mitochondrial function and biogenesis. Critically, aminoglycoside antibiotics (AGAs) have been shown to block the capacity of TRP channels to conduct calcium entry into the cell in response to a wide range of developmental stimuli of a biophysical nature, including mechanical, electromagnetic, thermal, and chemical. Paradoxically, in vitro paradigms commonly used to understand organismal muscle and adipose development may have been led astray by the conventional use of streptomycin, an AGA, to help prevent bacterial contamination. Accordingly, streptomycin has been shown to disrupt both in vitro and in vivo myogenesis, as well as the phenotypic switch of white adipose into beige thermogenic status. In vivo, streptomycin has been shown to disrupt TRP-mediated calcium-dependent exercise adaptations of importance to systemic metabolism. Alternatively, streptomycin has also been used to curb detrimental levels of calcium leakage into dystrophic skeletal muscle through aberrantly gated TRPC1 channels that have been shown to be involved in the etiology of X-linked muscular dystrophies. TRP channels susceptible to AGA antagonism are critically involved in modulating the development of muscle and adipose tissues that, if administered to behaving animals, may translate to systemwide metabolic disruption. Regenerative medicine and clinical communities need to be made aware of this caveat of AGA usage and seek viable alternatives, to prevent contamination or infection in in vitro and in vivo paradigms, respectively. [ABSTRACT FROM AUTHOR]

Evidence is increasing that vitamin D and CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites play a significant antioxidant role beyond its classical functions in bone health and calcium metabolism. Several recent studies have linked these elements to reduced oxidative stress as well as improved immune, cardiovascular, and neurological functions as a result of chronic kidney disease and cancer. Additionally, supplementation with this vitamin has been shown to be one of the most cost-effective micronutrient interventions worldwide, highlighting its potential as a therapeutic approach. The underlying mechanisms and implications of this antioxidant function of vitamin D or CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites are not well understood. This comprehensive and narrative review is aimed at summarizing the current evidence regarding the molecular mechanisms implicated in this antioxidant function of vitamin D, as well as to provide a general overview and to identify key research areas for the future, offering an extensive perspective that can guide both researchers and clinicians in the management of diseases associated with oxidative stress and/or insufficient vitamin D status. [ABSTRACT FROM AUTHOR]

In this work, 2D simulations of stainless steel nitriding through a mask were performed with two configurations: with and without lateral adsorption under the mask, depending on the strength of the mask adhesion. The stress-induced diffusion and trapping–detrapping process are included as the main mechanisms of nitrogen mass transport. The main focus is on the analysis of the swelling process, which affects the expansion of the material. The surface concentration profiles and topographical profiles along the surface are calculated and compared with experimentally registered ones taken from the literature, and they show a good agreement. This allows for estimation of the values of model parameters. Because nitriding processes takes place in vertical and horizontal directions, the anisotropic aspect of nitriding are analyzed. It is shown that the adherence of the mask significantly influences the topographical profile and the anisotropy of nitriding, because in the case of a weakly adhered mask, a lateral adsorption process takes place under the mask. The influence of swelling and anisotropy in the case of pattern nitriding in small dimensions is discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Naturally occurring diabetes mellitus (NODM) is one of the most common endocrine disorders in dogs and is most similar to type 1 diabetes mellitus (T1DM) in human patients. Immune responses in people with T1DM are abnormal and may contribute to a variety of long-term complications. There is very little information regarding immune function in dogs with NODM. Vitamin D deficiency is a relatively frequent finding in diabetic human patients. This is important because vitamin D has several positive effects on the immune system. Therefore, it is unsurprising that some studies demonstrate that vitamin D supplementation is beneficial in people with T1DM. While vitamin D interacts with the immune system in dogs, there have been no studies evaluating its effect in diabetic dogs. Therefore, our study sought to evaluate several components of immune function and the modulatory effects of calcitriol in diabetic dogs. We found that like human patients with T1DM, the diabetic state causes cytokine and phagocytic dysregulation in dogs. Vitamin D affected leukocyte cytokine secretion but not phagocytosis. The level of clinical control in diabetic dogs did not affect the immune function variables investigated in this study. Human patients with type 1 diabetes mellitus (T1DM) are susceptible to several long-term complications that are related to glycemic control and immune dysregulation. Immune function remains relatively unexplored in dogs with naturally occurring diabetes mellitus (NODM). Calcitriol improves various aspects of immune function in a variety of species, but its effect in diabetic dogs remains unexplored. Therefore, the objectives of this study were to (i) evaluate immune function in dogs with NODM and determine if differences exist based on the level of clinical control and (ii) assess the immunomodulatory effects of calcitriol. Twenty diabetic dogs (clinically controlled, n = ten, not controlled, n = ten) and 20 non-diabetic, healthy control dogs were included in this prospective, case–control study. Whole blood was incubated with calcitriol (10−7 M) or negative control, after which the samples were divided for phagocytosis and leukocyte cytokine response experiments. The phagocytosis of opsonized Escherichia coli (E. coli) was evaluated with flow cytometry. The samples for leukocyte cytokine response evaluations were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or phosphate buffer solution (PBS; negative control), and tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured in supernatant using a canine-specific multiplex bead-based assay. The leukocytes from diabetic dogs produced higher concentrations of IL-10 (p = 0.01), IL-6 (p < 0.0001), and IL-8 (p < 0.0001) than the control dogs while controlling for the intervention and stimulant. Calcitriol decreased the supernatant concentrations of TNF-α (p < 0.001) and IL-8 (p = 0.04) with concomitant increases in IL-6 (p = 0.005). Diabetic dogs had a lower percentage of leukocytes undergoing phagocytosis (p < 0.0001) but a higher number of bacteria phagocytized per cell (p = 0.001) when compared to the control dogs. Calcitriol had no effect on phagocytic capacity. Lastly, the status of clinical control in diabetic dogs did not yield differences in immune function. These results support that dogs with NODM exhibit immune dysregulation and warrant additional investigation. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor (HIF)-1α represents an oxygen-sensitive subunit of HIF transcriptional factor, which is usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expressions. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has been observed. Although HIF-1α has been highlighted as a SC function regulator, its spatio-temporal expression and role during myogenic progression remain controversial. Herein, using biomolecular, biochemical, morphological and electrophysiological analyses, we analyzed HIF-1α expression, localization and role in differentiating murine C2C12 myoblasts and SCs under normoxia. In addition, we evaluated the role of matrix metalloproteinase (MMP)-9 as an HIF-1α effector, considering that MMP-9 is involved in myogenesis and is an HIF-1α target in different cell types. HIF-1α expression increased after 24/48 h of differentiating culture and tended to decline after 72 h/5 days. Committed and proliferating mononuclear myoblasts exhibited nuclear HIF-1α expression. Differently, the more differentiated elongated and parallel-aligned cells, which are likely ready to fuse with each other, show a mainly cytoplasmic localization of the factor. Multinucleated myotubes displayed both nuclear and cytoplasmic HIF-1α expression. The MMP-9 and MyoD (myogenic activation marker) expression synchronized with that of HIF-1α, increasing after 24 h of differentiation. By means of silencing HIF-1α and MMP-9 by short-interfering RNA and MMP-9 pharmacological inhibition, this study unraveled MMP-9's role as an HIF-1α downstream effector and the fact that the HIF-1α/MMP-9 axis is essential in morpho-functional cell myogenic commitment. [ABSTRACT FROM AUTHOR]

Ideal regeneration of hard tissue and dental pulp has been reported with the use of a combination of bioactive glass and basic fibroblast growth factor (bFGF). However, no previous study has investigated the molecular mechanisms underlying the processes induced by this combination in dental pulp cells. This study aimed to examine the cellular phenotype and transcriptional changes induced by the combination of bioactive glass solution (BG) and bFGF in dental pulp cells using phase-contrast microscopy, a cell counting kit-8 assay, alkaline phosphatase staining, and RNA sequence analysis. bFGF induced elongation of the cell process and increased the number of cells. Whereas BG did not increase ALP activity, it induced extracellular matrix-related genes in the dental pulp. In addition, the combination of BG and bFGF induces gliogenesis-related genes in the nervous system. This is to say, bFGF increased the viability of dental pulp cells, bioactive glass induced odontogenesis, and a dual stimulation with bioactive glass and bFGF induced the wound healing of the nerve system in the dental pulp. Taken together, bioactive glass and bFGF may be useful for the regeneration of the dentin-pulp complex. [ABSTRACT FROM AUTHOR]

Sphingolipids (SLs) are structural, bioactive molecules with several key cellular roles, whereas 1,25-dihydroxyvitamin D (1,25(OH)D), the active form of vitamin D, is considered the major regulator of calcium homeostasis, although it also exerts other extraskeletal effects. Many studies reported the physiological connection between vitamin D and SLs, highlighting not only the effects of vitamin D on SL metabolism and signaling but also the influence of SLs on vitamin D levels and function, thus strongly suggesting a crosstalk between these molecules. After a brief description of 1,25(OH)D and SL metabolism, this review aims to discuss the preclinical and clinical evidence on the crosstalk between SLs and 1,25(OH)D, with a special focus on cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Muscle function reflects muscular mitochondrial status, which, in turn, is an adaptive response to physical activity, representing improvements in energy production for de novo biosynthesis or metabolic efficiency. Differences in muscle performance are manifestations of the expression of distinct contractile-protein isoforms and of mitochondrial-energy substrate utilization. Powerful contractures require immediate energy production from carbohydrates outside the mitochondria that exhaust rapidly. Sustained muscle contractions require aerobic energy production from fatty acids by the mitochondria that is slower and produces less force. These two patterns of muscle force generation are broadly classified as glycolytic or oxidative, respectively, and require disparate levels of increased contractile or mitochondrial protein production, respectively, to be effectively executed. Glycolytic muscle, hence, tends towards fibre hypertrophy, whereas oxidative fibres are more disposed towards increased mitochondrial content and efficiency, rather than hypertrophy. Although developmentally predetermined muscle classes exist, a degree of functional plasticity persists across all muscles post-birth that can be modulated by exercise and generally results in an increase in the oxidative character of muscle. Oxidative muscle is most strongly correlated with organismal metabolic balance and longevity because of the propensity of oxidative muscle for fatty-acid oxidation and associated anti-inflammatory ramifications which occur at the expense of glycolytic-muscle development and hypertrophy. This muscle-class size disparity is often at odds with common expectations that muscle mass should scale positively with improved health and longevity. Brief magnetic-field activation of the muscle mitochondrial pool has been shown to recapitulate key aspects of the oxidative-muscle phenotype with similar metabolic hallmarks. This review discusses the common genetic cascades invoked by endurance exercise and magnetic-field therapy and the potential physiological differences with regards to human health and longevity. Future human studies examining the physiological consequences of magnetic-field therapy are warranted. [ABSTRACT FROM AUTHOR]

Irisin is a hormone-like myokine produced in abundance by skeletal muscle (SkM) in response to exercise. This myokine, identical in humans and mice, is involved in many signaling pathways related to metabolic processes. Despite much evidence on the regulators of irisin and the relevance of sphingolipids for SkM cell biology, the contribution of these latter bioactive lipids to the modulation of the myokine in SkM is missing. In particular, we have examined the potential involvement in irisin formation/release of sphingosine-1-phosphate (S1P), an interesting bioactive molecule able to act as an intracellular lipid mediator as well as a ligand of specific G-protein-coupled receptors (S1PR). We demonstrate the existence of distinct intracellular pools of S1P able to affect the expression of the irisin precursor FNDC. In addition, we establish the crucial role of the S1P/S1PR axis in irisin formation/release as well as the autocrine/paracrine effects of irisin on myoblast proliferation and myogenic differentiation. Altogether, these findings provide the first evidence for a functional crosstalk between the S1P/S1PR axis and irisin signaling, which may open new windows for potential therapeutic treatment of SkM dysfunctions. [ABSTRACT FROM AUTHOR]

The endothelial glycocalyx (eGC) is a dynamic hair-like layer expressed on the apical surface of endothelial cells throughout the vascular system. This layer serves as an endothelial cell gatekeeper by controlling the permeability and adhesion properties of endothelial cells, as well as by controlling vascular resistance through the mediation of vasodilation. Pathogenic destruction of the eGC could be linked to impaired vascular function, as well as several acute and chronic cardiovascular conditions. Defining the precise functions and mechanisms of the eGC is perhaps the limiting factor of the missing link in finding novel treatments for lifestyle-related diseases such as atherosclerosis, type 2 diabetes, hypertension, and metabolic syndrome. However, the relationship between diet, lifestyle, and the preservation of the eGC is an unexplored territory. This article provides an overview of the eGC's importance for health and disease and describes perspectives of nutritional therapy for the prevention of the eGC's pathogenic destruction. It is concluded that vitamin D and omega-3 fatty acid supplementation, as well as healthy dietary patterns such as the Mediterranean diet and the time management of eating, might show promise for preserving eGC health and, thus, the health of the cardiovascular system. [ABSTRACT FROM AUTHOR]

Low-temperature thermochemical treatments are particularly suitable for use in the surface hardening of austenitic stainless steels without impairing their corrosion resistance. In fact, when using treatment media rich in nitrogen and/or carbon at relatively low temperatures (<450 °C for nitriding, <550 °C for carburizing), it is possible to inhibit the formation of chromium compounds and obtain modified surface layers that consist mainly of a supersaturated solid solution, known as expanded austenite or S-phase. It has been observed that this hard phase allows the enhancement of corrosion resistance in chloride-ion-containing solutions, while the results were contradictory for chloride-free acidic solutions. This overview aims to discuss the corrosion behavior of low-temperature-treated austenitic stainless steels, taking into account the different microstructures and phase compositions of the modified layers, as well as the different test environments and conditions. In particular, the corrosion behavior in both chloride-ion-containing solutions and chloride-free solutions (sulfuric acid, sulfate and borate solutions) is discussed. The analysis of the international literature presents evidence that the microstructure and phase composition of the modified layers have key roles in corrosion resistance, especially in sulfuric acid solutions. [ABSTRACT FROM AUTHOR]

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, βNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The βNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3. [ABSTRACT FROM AUTHOR]

The vitamin D receptor (VDR) belongs to the nuclear receptor superfamily of transcription factors. The VDR is expressed in diverse brain regions and has been implicated in the neuroprotective, antiaging, prosurvival, and anti-inflammatory action of vitamin D. Accordingly, a relationship between vitamin D insufficiency and susceptibility to neurodegenerative diseases has been suggested. However, due to the multitargeted mechanisms of vitamin D and its often overlapping genomic and nongenomic effects, the role of the VDR in brain pathologies remains obscure. In this narrative review, we present progress in deciphering the molecular mechanism of nuclear VDR-mediated vitamin D effects on prosurvival and anti-inflammatory signaling pathway activity within the central nervous system. In line with the concept of the neurovascular unit in pathomechanisms of neurodegenerative diseases, a discussion of the role of the VDR in regulating the immune and vascular brain systems is also included. Next, we discuss the results of preclinical and clinical studies evaluating the significance of vitamin D status and the efficacy of vitamin D supplementation in the treatment of Parkinson's and Alzheimer's diseases, emphasizing the possible role of the VDR in these phenomena. Finally, the associations of some VDR polymorphisms with higher risks and severity of these neurodegenerative disorders are briefly summarized. [ABSTRACT FROM AUTHOR]

Cell mechanotransduction, the ability to detect physical forces and convert them into a series of biochemical events, is important for a wide range of physiological processes. Cells express an array of mechanosensors transducing physical forces into intracellular signaling cascades, including ion channels. Ion channels that can be directly activated by mechanical cues are known as mechanically activated (MA), or stretch-activated (SA), channels. In response to repeated exposures to mechanical stimulation in the form of resistance training, enhanced protein synthesis and fiber hypertrophy are elicited in skeletal muscle, whereas a lack of mechanical stimuli due to inactivity/mechanical unloading leads to reduced muscle protein synthesis and fiber atrophy. To date, the role of MA channels in the transduction of mechanical load to intracellular signaling pathways regulating muscle protein synthesis is poorly described. This review article will discuss MA channels in striated muscle, their regulation, and putative roles in the anabolic processes in muscle cells/fibers in response to mechanical stimuli. [ABSTRACT FROM AUTHOR]

Atherosclerosis lesions are described as the formation of an occlusive wall-vessel plaque that can exacerbate infarctions, strokes, and even death. Furthermore, atherosclerosis damages the endothelium integrity, avoiding proper regeneration after stent implantation. Therefore, we investigate the beneficial effects of TiO2 nanotubes (NTs) in promoting the initial response of detrimental human atherosclerotic-derived endothelial cells (AThEC). We synthesized and characterized NTs on Ti6Al4V by anodization. We isolated AThEC and tested the adhesion long-lasting proliferation activity, and the modulation of focal adhesions conducted on the materials. Moreover, ultrastructural cell-surface contact at the nanoscale and membrane roughness were evaluated to explain the results. Our findings depicted improved filopodia and focal adhesions stimulated by the NTs. Similarly, the NTs harbored long-lasting proliferative metabolism after 5 days, explained by overcoming cell-contact interactions at the nanoscale. Furthermore, the senescent activity detected in the AThEC could be mitigated by the modified membrane roughness and cellular stretch orchestrated by the NTs. Importantly, the NTs stimulate the initial endothelial anchorage and metabolic recovery required to regenerate the endothelial monolayer. Despite the dysfunctional status of the AThEC, our study brings new evidence for the potential application of nano-configured biomaterials for innovation in stent technologies. [ABSTRACT FROM AUTHOR]

Ischemic stroke is one of the major causes of death and permanent disability worldwide. The only efficient treatment to date is anticoagulant therapy and thrombectomy, which enable restitution of blood flow to ischemic tissues. Numerous promising neuroprotectants have failed in clinical trials. Given the complex pathomechanism of stroke, a multitarget pharmacotherapy seems a more rational approach in stroke prevention and treatment than drugs acting on single molecular targets. Recently, vitamin D3 has emerged as a potential treatment adjunct for ischemic stroke, as it interferes with the key prosurvival pathways and shows neuroprotective, anti-inflammatory, regenerative and anti-aging properties in both neuronal and vascular tissue. Moreover, the stimulatory effect of vitamin D3 on brain-derived neurotrophic factor (BDNF) signaling and neuroplasticity may play a role not only in the recovery of neurological functions, but also in ameliorating post-stroke depression and anxiety. This narrative review presents advances in research on the biochemical mechanisms of stroke-related brain damage, and the genomic and non-genomic effects of vitamin D3 which may interfere with diverse cell death signaling pathways. Next, we discuss the results of in vitro and in vivo experimental studies on the neuroprotective potential of 1alpha,25-dihydroxyvitamin D3 (calcitriol) in brain ischemia models. Finally, the outcomes of clinical trials on vitamin D3 efficiency in ischemic stroke patients are briefly reviewed. Despite the mixed results of the clinical trials, it appears that vitamin D3 still holds promise in preventing or ameliorating neurological and psychiatric consequences of ischemic stroke and certainly deserves further study. [ABSTRACT FROM AUTHOR]

The multifaceted activity of vitamin D in patients with inflammatory bowel disease (IBD) presents a challenge for further research in this area. Vitamin D is involved in the regulation of bone mineral metabolism, it participates in the regulation of the immune system, and it is an underlying factor in the pathogenesis of IBD. Additionally, vitamin D affects Th1 and Th2 lymphocytes, influencing the release of cytokines and inhibiting tumor necrosis factor (TNF) expression and the wnt/β-catenin pathway. As far as IBDs are concerned, they are associated with microbiota dysbiosis, abnormal inflammatory response, and micronutrient deficiency, including vitamin D hypovitaminosis. In turn, the biological activity of active vitamin D is regulated by the vitamin D receptor (VDR) which is associated with several processes related to IBD. Therefore, in terms of research on vitamin D supplementation in IBD patients, it is essential to understand the metabolic pathways and genetic determinants of vitamin D, as well as to identify the environmental factors they are subject to, not only in view of osteoporosis prevention and therapy, but primarily concerning modulating the course and supplementation of IBD pharmacotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Childhood cancer cannot generally be prevented or identified through screening. The disease is often diagnosed at advanced stages, and this obviously affects patient outcomes negatively. There is an urgent need for the identification of prognostic and therapeutic biomarkers. In this study, lower vitamin D receptor (VDR) expression was associated with a worse prognosis in various childhood cancer patients (significant correlation, p = 0.0061). The identification of VDR status in various childhood cancers has highlighted potential patient populations that could benefit from the newly identified biomarker. Knowledge of the VDR status in childhood solid tumors provides clinicians with a valuable biomarker and based on this, additional therapy (vitamin D and analogs) to use alongside conventional first-line oncotherapy. Background: Our previous work has shown a correlation between lower vitamin D levels in children with cancer and adverse prognosis. It suggests that supplying vitamin D is reasonable. VDR expression in childhood solid tumors has been linked to tumor characteristics and patient survival in only a few studies. Methods: For this study, 177 children with solid tumors were selected whose biopsies and tumor tissue formalin-fixed, paraffin-embedded tissue blocks were available for immunohistochemical analysis at Semmelweis University, Budapest (Hungary). Results: We found that non-significant VDR expression was associated with a significantly less favorable prognosis (p = 0.0061) in the examined childhood solid tumors. There was a clinically significant association; non-significant VDR expression had more than 14-fold odds of an unfavorable prognosis (OR = 14.74). The rate of VDR expression differed significantly between tumor types (p < 0.0001). Conclusion: In conclusion, VDR expression measured by IHC staining is inversely associated with aggressive characteristics in different childhood cancers. The downregulation of VDR expression in more aggressive childhood cancers suggests that functional vitamin D activity may slow or block cancer progression. [ABSTRACT FROM AUTHOR]

Plasma electrolytic polishing (PEP) is an environment-friendly alternative to the conventional electrochemical polishing (EP), giving optimal surface properties and improved corrosion resistance with minimum energy and time consumption, which leads to both economic and environmental benefits. This paper is focused on the corrosion behavior of PEP treated AISI 316L stainless steel widely used as a biomaterial. Corrosion resistance of plasma electrolytic polished surfaces without/with chemical pretreatment (acid cleaning) is evaluated and compared with original non-treated (as received) surfaces by three independent test methods: electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PP), and exposure immersion test. All corrosion tests are carried out in the 0.9 wt.% NaCl solution at a temperature of 37 ± 0.5 °C to simulate the internal environment of a human body. The quality of tested surfaces is also characterized by optical microscopy and by the surface roughness parameters. The results obtained indicated high corrosion resistance of PEP treated surfaces also without chemical pretreatment, which increases the ecological benefits of PEP technology. [ABSTRACT FROM AUTHOR]

Vitamin A (VA) deficiency and diarrheal diseases are both serious public health issues worldwide. VA deficiency is associated with impaired intestinal barrier function and increased risk of mucosal infection-related mortality. The bioactive form of VA, retinoic acid, is a well-known regulator of mucosal integrity. Using Citrobacter rodentium-infected mice as a model for diarrheal diseases in humans, previous studies showed that VA-deficient (VAD) mice failed to clear C. rodentium as compared to their VA-sufficient (VAS) counterparts. However, the distinct intestinal gene responses that are dependent on the host's VA status still need to be discovered. The mRNAs extracted from the small intestine (SI) and the colon were sequenced and analyzed on three levels: differential gene expression, enrichment, and co-expression. C. rodentium infection interacted differentially with VA status to alter colon gene expression. Novel functional categories downregulated by this pathogen were identified, highlighted by genes related to the metabolism of VA, vitamin D, and ion transport, including improper upregulation of Cl− secretion and disrupted HCO3− metabolism. Our results suggest that derangement of micronutrient metabolism and ion transport, together with the compromised immune responses in VAD hosts, may be responsible for the higher mortality to C. rodentium under conditions of inadequate VA. [ABSTRACT FROM AUTHOR]

Simple Summary: Vitamin D, conventionally considered a nutrient, is a potent hormone regulating many physiological functions. In addition, many studies point to the anticancer activities of calcitriol. However, cancer cells use mechanisms that negate the beneficial effects of calcitriol. Many of these mechanisms control or are controlled by the Hypoxia Inducible transcription Factors (HIFs) that are overexpressed in human cancers due to the development of hypoxia inside the tumors. This review discusses the crosstalk between calcitriol and HIF signaling in order to better understand their relationship to cancer, its prevention, and treatment. Vitamin D is a hormone that, through its action, elicits a broad spectrum of physiological responses ranging from classic to nonclassical actions such as bone morphogenesis and immune function. In parallel, many studies describe the antiproliferative, proapoptotic, antiangiogenic effects of calcitriol (the active hormonal form) that contribute to its anticancer activity. Additionally, epidemiological data signify the inverse correlation between vitamin D levels and cancer risk. On the contrary, tumors possess several adaptive mechanisms that enable them to evade the anticancer effects of calcitriol. Such maladaptive processes are often a characteristic of the cancer microenvironment, which in solid tumors is frequently hypoxic and elicits the overexpression of Hypoxia-Inducible Factors (HIFs). HIF-mediated signaling not only contributes to cancer cell survival and proliferation but also confers resistance to anticancer agents. Taking into consideration that calcitriol intertwines with signaling events elicited by the hypoxic status cells, this review examines their interplay in cellular signaling to give the opportunity to better understand their relationship in cancer development and their prospect for the treatment of cancer. [ABSTRACT FROM AUTHOR]

In this study, an electrochemical anodizing method was applied as surface modification of the 316L biomedical stainless steel (BSS). The surface properties, microstructural characteristics, and biocompatibility responses of the anodized 316L BSS specimens were elucidated through scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffractometry, transmission electron microscopy, and in vitro cell culture assay. Analytical results revealed that the oxide layer of dichromium trioxide (Cr2O3) was formed on the modified 316L BSS specimens after the different anodization modifications. Moreover, a dual porous (micro/nanoporous) topography can also be discovered on the surface of the modified 316L BSS specimens. The microstructure of the anodized oxide layer was composed of amorphous austenite phase and nano-Cr2O3. Furthermore, in vitro cell culture assay also demonstrated that the osteoblast-like cells (MG-63) on the anodized 316L BSS specimens were completely adhered and covered as compared with the unmodified 316L BSS specimen. As a result, the anodized 316L BSS with a dual porous (micro/nanoporous) oxide layer has great potential to induce cell adhesion and promote bone formation. [ABSTRACT FROM AUTHOR]

Sphingolipids, sphingolipid metabolizing enzymes, and their receptors network are being recognized as part of the signaling mechanisms, which govern breast cancer cell growth, migration, and survival during chemotherapy treatment. Approximately 70% of breast cancers are estrogen receptor (ER) positive and, thus, rely on estrogen signaling. Estrogen activates an intracellular network composed of many cytoplasmic and nuclear mediators. Some estrogen effects can be mediated by sphingolipids. Estrogen activates sphingosine kinase 1 (SphK1) and amplifies the intracellular concentration of sphingosine-1-phosphate (S1P) in breast cancer cells during stimulation of proliferation and survival. Specifically, Estrogen activates S1P receptors (S1PR) and induces growth factor receptor transactivation. SphK, S1P, and S1PR expression are causally associated with endocrine resistance and progression to advanced tumor stages in ER-positive breast cancers in vivo. Recently, the network of SphK/S1PR was shown to promote the development of ER-negative cancers and breast cancer stem cells, as well as stimulating angiogenesis. Novel findings confirm and broaden our knowledge about the cross-talk between sphingolipids and estrogen network in normal and malignant cells. Current S1PRs therapeutic inhibition was indicated as a promising chemotherapy approach in non-responsive and advanced malignancies. Considering that sphingolipid signaling has a prominent role in terminally differentiated cells, the impact should be considered when designing specific SphK/S1PR inhibitors. This study analyzes the dynamic of the transformation of sphingolipid axis during a transition from normal to pathological condition on the level of the whole organism. The sphingolipid-based mediation and facilitation of global effects of estrogen were critically accented as a bridging mechanism that should be explored in cancer prevention. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D2 and D3 analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and -secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the -secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention. [ABSTRACT FROM AUTHOR]

Increasing evidence supports the concept that the vitamin D axis possesses immunoregulatory functions, with vitamin D receptor (VDR) status representing the major determinant of vitamin D's pleiotropic effects. Vitamin D promotes the production of anti-microbial peptides, including β-defensins and cathelicidins, the shift towards Th2 immune responses, and regulates autophagy and epithelial barrier integrity. Impairment of vitamin D-mediated pathways are associated with chronic inflammatory conditions, including inflammatory bowel diseases (IBD). Interestingly, inhibition of vitamin D pathways results in dysbiosis of the gut microbiome, which has mechanistically been implicated in the development of IBD. Herein, we explore the role of the vitamin D axis in immune-mediated diseases, with particular emphasis on its interplay with the gut microbiome in the pathogenesis of IBD. The potential clinical implications and therapeutic relevance of this interaction will also be discussed, including optimizing VDR function, both with vitamin D analogues and probiotics, which may represent a complementary approach to current IBD treatments. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of mortality worldwide. Therefore, a better understanding of their pathomechanisms and the subsequent implementation of optimal prophylactic and therapeutic strategies are of utmost importance. A growing body of evidence states that low-grade inflammation is a common feature for most of the cardiovascular diseases in which the contributing factors are the activation of toll-like receptors (TLRs) and vitamin D deficiency. In this article, available data concerning the association of cardiovascular diseases with TLRs and vitamin D status are reviewed, followed by a discussion of new possible approaches to cardiovascular disease management. [ABSTRACT FROM AUTHOR]

P38 mitogen-activated protein kinase (MAPK) is a crucial target for chronic inflammatory diseases. Alzheimer's disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain, as well as neurodegeneration, and there is no known cure. Recent studies on the underlying biology of AD in cellular and animal models have indicated that p38 MAPK is capable of orchestrating diverse events related to AD, such as tau phosphorylation, neurotoxicity, neuroinflammation and synaptic dysfunction. Thus, the inhibition of p38 MAPK is considered a promising strategy for the treatment of AD. In this review, we summarize recent advances in the targeting of p38 MAPK as a potential strategy for the treatment of AD and envision possibilities of p38 MAPK inhibitors as a fundamental therapeutics for AD. [ABSTRACT FROM AUTHOR]

The implantation of biomedical devices, including collagen-based implants, evokes an inflammatory response. Despite inflammation playing an important role in the early stages of wound healing, excessive and non-resolving inflammation may lead to the poor performance of biomaterial implants in some patients. Therefore, steps should be taken to control the level and duration of an inflammatory response. In this study, oxygen and nitrogen gas plasmas were employed to modify the surface of collagen film, with a view to modifying the surface properties of a substrate in order to induce changes to the inflammatory response, whilst maintaining the mechanical integrity of the underlying collagen film. The effects of cold plasma treatment and resultant changes to surface properties on the non-specific inflammatory response of the immune system was investigated in vitro in direct contact cell culture by the measurement of protein expression and cytokine production after one and four days of human peripheral blood mononuclear cell (PBMC) culture. The results indicated that compared to oxygen plasma, nitrogen plasma treatment produced an anti-inflammatory effect on the collagen film by reducing the initial activation of monocytes and macrophages, which led to a lower production of pro-inflammatory cytokines IL-1βand TNFα, and higher production of anti-inflammatory cytokine IL-10. This was attributed to the combination of the amino chemical group and the significant reduction in roughness associated with the introduction of the nitrogen plasma treatment, which had an effect on the levels of activation of the adherent cell population. [ABSTRACT FROM AUTHOR]

Background/Aims: Vitamin D has been investigated for many non-skeletal effects. The objective of this study was to determine whether circulating lipids, systemic inflammation, and biomarkers of endothelial cell activation varied with the vitamin D status of older Australians. Methods: One hundred and one participants were proportionately and randomly sampled across tertiles of 25 hydroxy vitamin D (25(OH)D) from a larger cohort of free living older adults (T1 median = 97; T2 median = 74.5; T3 median = 56.8 nmol/L). Overnight fasting blood samples were assayed for 25(OH)D, parathyroid hormone (PTH), insulin, triacylglycerol (TAG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). Markers of systemic inflammation (high sensitivity C-reactive protein (hsCRP), tumour necrosis factor-a (TNF-a)) and endothelial activation (hepatocyte growth factor (HGF), P-selectin and soluble vascular cell adhesion molecule (sVCAM), soluble intracellular adhesion molecule (sICAM)) were determined. A general linear model multivariate analysis with a backward elimination procedure was performed. Results: Eighty-three participants (48 women, 35 men), aged 65 ± 7.7 years, BMI 28 ± 4.5 kg/m², with complete data were analyzed. The final parsimonious model controlled for age, gender, BMI, and McAuley's index, but excluded season, medications, and PTH. There were significant differences across 25(OH)D tertiles in TC (T1 < T3, p = 0.003; T2 < T3, p = 0.001), LDL-C (T1 < T3, p = 0.005; T2 < T3, p = 0.001), TAG (T2 < T3, p = 0.026), HGF (T1 > T3, p = 0.009) and sVCAM (T1 > T3, P = 0.04). Conclusions: Higher vitamin D status may protect the endothelium through reduced dyslipidaemia and increased HGF. [ABSTRACT FROM AUTHOR]

Polyether ether ketone (PEEK) has been frequently used in spinal surgery with good clinical results. The material has a low elastic modulus and is radiolucent. However, in oral implantology PEEK has displayed inferior ability to osseointegrate compared to titanium materials. One idea to reinforce PEEK would be to coat it with hydroxyapatite (HA), a ceramic material of good biocompatibility. In the present study we analyzed HA-coated PEEK tibial implants via histology and radiography when following up at 3 and 12 weeks. Of the 48 implants, 24 were HA-coated PEEK screws (test) and another 24 implants served as uncoated PEEK controls. HA-coated PEEK implants were always osseointegrated. The total bone area (BA) was higher for test compared to control implants at 3 (p < 0.05) and 12 weeks (p < 0.05). Mean bone implant contact (BIC) percentage was significantly higher (p = 0.024) for the test compared to control implants at 3 weeks and higher without statistical significance at 12 weeks. The effect of HA-coating was concluded to be significant with respect to early bone formation, and HA-coated PEEK implants may represent a good material to serve as bone anchored clinical devices. [ABSTRACT FROM AUTHOR]

The high incidence of cardiovascular disease and vitamin D deficiency in chronic kidney disease patients is well known. Vitamin D activation by omega-3 fatty acid (FA) supplementation may explain the cardioprotective effects exerted by omega-3 FA. We hypothesized that omega-3 FA and 25-hydroxyvitamin D (25(OH)D) supplementation may increase 1,25-dihydroxyvitamin D (1,25(OH)2D) levels compared to 25(OH)D supplementation alone in hemodialysis (HD) patients that have insufficient or deficient 25(OH)D levels. We enrolled patients that were treated for at least six months with 25(OH)D < 30 ng/mL (NCT01596842). Patients were randomized to treatment for 12 weeks with cholecalciferol supplemented with omega-3 FA or a placebo. Levels of 25(OH)D and 1,25(OH)2D were measured after 12 weeks. The erythrocyte membrane FA contents were also measured. Levels of 25(OH)D were increased in both groups at 12 weeks compared to baseline. The 1,25(OH)2D levels at 12 weeks compared to baseline showed a tendency to increase in the omega-3 FA group. The oleic acid and monounsaturated FA content decreased, while the omega-3 index increased in the omega-3 FA group. Omega-3 FA supplementation may be partly associated with vitamin D activation, although increased 25(OH)D levels caused by short-term cholecalciferol supplementation were not associated with vitamin D activation in HD patients. [ABSTRACT FROM AUTHOR]

Low-temperature treatments have become a valuable method for improving the surface hardness of stainless steels, and thus their tribological properties, without impairing their corrosion resistance. By using treatment temperatures lower than those usually employed for nitriding or carburizing of low alloy steels or tool steels, it is possible to obtain a fairly fast (interstitial) diffusion of nitrogen and/or carbon atoms; on the contrary, the diffusion of substitutional atoms, as chromium atoms, has significantly slowed down, therefore the formation of chromium compounds is hindered, and corrosion resistance can be maintained. As a consequence, nitrogen and carbon atoms can be retained in solid solutions in an iron lattice well beyond their maximum solubility, and supersaturated solid solutions are produced. Depending on the iron lattice structure present in the stainless steel, the so-called "expanded austenite" or "S-phase", "expanded ferrite", and "expanded martensite" have been reported to be formed. This review summarizes the main studies on the characteristics and properties of these "expanded" phases and of the modified surface layers in which these phases form by using low-temperature treatments. A particular focus is on expanded martensite and expanded ferrite. Expanded austenite–S-phase is also discussed, with particular reference to the most recent studies. [ABSTRACT FROM AUTHOR]

Adipose tissue plays an important role in systemic metabolism via the secretion of adipocytokines and storing and releasing energy. In obesity, adipose tissue becomes dysfunctional and characterized by hypertrophied adipocytes, increased inflammation, hypoxia, and decreased angiogenesis. Although adipose tissue is one of the major stores of vitamin D, its deficiency is detective in obese subjects. In the presented review, we show how vitamin D regulates numerous processes in adipose tissue and how their dysregulation leads to metabolic disorders. The molecular response to vitamin D in adipose tissue affects not only energy metabolism and adipokine and anti-inflammatory cytokine production via the regulation of gene expression but also genes participating in antioxidant defense, adipocytes differentiation, and apoptosis. Thus, its deficiency disturbs adipocytokines secretion, metabolism, lipid storage, adipogenesis, thermogenesis, the regulation of inflammation, and oxidative stress balance. Restoring the proper functionality of adipose tissue in overweight or obese subjects is of particular importance in order to reduce the risk of developing obesity-related complications, such as cardiovascular diseases and diabetes. Taking into account the results of experimental studies, it seemed that vitamin D may be a remedy for adipose tissue dysfunction, but the results of the clinical trials are not consistent, as some of them show improvement and others no effect of this vitamin on metabolic and insulin resistance parameters. Therefore, further studies are required to evaluate the beneficial effects of vitamin D, especially in overweight and obese subjects, due to the presence of a volumetric dilution of this vitamin among them. [ABSTRACT FROM AUTHOR]

Simple Summary: There are a number of reports in the scientific literature dealing with the implication of ceramide kinase (CERK) and its product, ceramide 1-phosphate (C1P), in the regulation of cell growth and survival, apoptosis, inflammation, and cell migration/invasion. However, no report has so far compiled or put into context the information related to the implication of the CERK/C1P axis in cancer development and metastasis. Hence, the present review highlights the relevance of CERK and C1P in tumorigenesis and tumor dissemination. Whilst CERK produces intracellular C1P, which can act on intracellular targets directly, C1P can also be secreted into the extracellular milieu and interact with sites (possibly receptors) at the plasma membrane of cells. This action can trigger signaling cascades that may end up modulating the expression of specific genes involved in tumor promotion and dissemination. The biology of CERK/C1P in cancer growth and dissemination is herein discussed in detail. Cancer cells rewire their metabolic programs to favor biological processes that promote cell survival, proliferation, and dissemination. Among this relevant reprogramming, sphingolipid metabolism provides metabolites that can favor or oppose these hallmarks of cancer. The sphingolipid ceramide 1-phosphate (C1P) and the enzyme responsible for its biosynthesis, ceramide kinase (CERK), are well established regulators of cell growth and survival in normal, as well as malignant cells through stress-regulated signaling pathways. This metabolite also promotes cell survival, which has been associated with the feedback regulation of other antitumoral sphingolipids or second messengers. C1P also regulates cancer cell invasion and migration of different types of cancer, including lung, breast, pancreas, prostate, or leukemia cells. More recently, CERK and C1P have been implicated in the control of inflammatory responses. The present review provides an updated view on the important role of CERK/C1P in the regulation of cancer cell growth, survival, and dissemination. [ABSTRACT FROM AUTHOR]

Investigations on ion channels in muscle tissues have mainly focused on physiological muscle function and related disorders, but emerging evidence supports a critical role of ion channels and transporters in developmental processes, such as controlling the myogenic commitment of stem cells. In this review, we provide an overview of ion channels and transporters that influence skeletal muscle myoblast differentiation, cardiac differentiation from pluripotent stem cells, as well as vascular smooth muscle cell differentiation. We highlight examples of model organisms or patients with mutations in ion channels. Furthermore, a potential underlying molecular mechanism involving hyperpolarization of the resting membrane potential and a series of calcium signaling is discussed. [ABSTRACT FROM AUTHOR]

The tibia of New Zealand White rabbits was used as a model of critical bone defects to investigate a new design of composite scaffold for bone defects composed of dual materials. The all-in-one design of a titanium alloy (Ti-6Al-4V) scaffold comprised the structure of a bone plate and gradient porosity cage. Hydroxyapatite (HAp), a biodegradable material, was encapsulated in the center of the scaffold. The gradient pore structure was designed with 70%-65%-60%-55%-50% porosity, since the stresses could be distributed more uniformly when the all-in-one scaffold was placed on the bone contact surface. By covering the center of the scaffold with a low strength of HAp to contact the relatively low strength of bone marrow tissues, the excessive stiffness of the Ti-6Al-4V can be effectively reduced and further diminish the incidence of the stress shielding effect. The simulation results show that the optimized composite scaffold for the 3D model of tibia had a maximum stress value of 27.862 MPa and a maximum strain of 0.065%. The scaffold prepared by selective laser melting was annealed and found that the Young's coefficient increased from 126.44 GPa to 131.46 GPa, the hardness increased from 3.9 GPa to 4.12 GPa, and the strain decreased from 2.27% to 1.13%. The result demonstrates that the removal of residual stress can lead to a more stable structural strength, which can be used as a reference for the design of future clinical tibial defect repair scaffolds. [ABSTRACT FROM AUTHOR]

The study aimed to analyze the recovery period of the anodized 316L biomedical stainless steel (BSS) mini-implant through its implantation on femur of rabbit model. The 316L BSS mini-implant was modified by an electrochemical anodization approach with different voltages. The anodized samples were characterized via field-emission scanning electron microscopy, X-ray diffractometry, and X-ray photoelectron spectroscopy. The biocompatibility was assessed by cell culture assay. The anodized mini-implant was implanted on rabbit's femur then evaluated histologically after 4 and 8 weeks. Analytical results indicated that the topography of the anodized mini-implant at 5 V for 5 min consisted of a dual (micro/nano) porous structure. Oxide film of Cr2O3 was formed on the surface of anodized mini-implant after anodizing with 5 V for 5 min. In vitro cell culture assay revealed that fibroblast cells (NIH-3T3) on the anodized samples were more firmly attached as compared with the control sample. Moreover, histological analysis demonstrated that the anodized mini-implant improved bone recovering at 4 weeks after implantation. Thus, this study suggests that the anodized 316L BSS mini-implant could be a potential choice as anchorage device for effective and efficient orthodontic treatment. [ABSTRACT FROM AUTHOR]

Cobalt–chromium (Co-Cr) alloys have been used in a wide variety of biomedical applications, including dental, cardiovascular, and orthopedic devices. In vitro studies have shown that the mineralization of cells involved in osteogenesis is regulated by boron. The development of a new cobalt-chromium-boron (Co-Cr-B) alloy improves the mechanical properties of the metal, such as wear resistance, and meets biocompatibility requirements. Therefore, the objective of this study was to evaluate the osteogenic differentiation and biocompatibility in in vitro assays. Human dental pulp mesenchymal cells (hDPSCs) were isolated from volunteers and then co-cultured with the Co-Cr plus boron alloy from 0.3% to 1% for 15 days, while the formation of calcium deposits was quantified by Alizarin red staining and the expression of genes was related to osteodifferentiation by RT-qPCR. Simultaneously, the cytotoxicity of our alloy was evaluated by MTT assay and the change in the gene expression of cytokines commonly associated with inflammatory processes. The results showed low cytotoxicity when cells were treated with the Co-Cr-B alloy, and no change in the gene expression of IL-1β, TNF-α, IL-6, and IL-8 was observed compared to the untreated control (p > 0.05). The osteoinduction results shown an increase in mineralization in hDPSCs treated with Co-Cr-B alloy with 1.0% B. In addition, a significant increase in mRNA levels for collagen type 1 in with 0.3% boron and alkaline phosphatase and Runx2 with 0.6% boron were observed. The addition of Boron to the ASTM F75 Co-Cr base alloy improves the biocompatible characteristics. No cytotoxicity and any change of the expression of the pro-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-8 in human peripheral blood mononuclear cells treated with the cobalt-chromium-boron alloy was observed in vitro assays. Furthermore, our alloy acts as an osteoinductive in osteogenic differentiation in vitro. Therefore, our results could set the standard for the development of in vivo trials and in the future, it could be considered as an alternative for regenerative therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Skeletal muscle (SkM) represents the largest "organ" in the human body as it constitutes at least 40% of the body mass. SkM mass wasting is a serious conditions since pathological tissue degeneration significantly worsens the prognosis of the associated disease and significantly reduces the quality and life expectancy with an incidence of 10–50% in patients suffering of cancer, chronic infection and inflammation. Therefore, it is urgent to investigate the molecular basis of SkM mass wasting and identify potential therapeutic targets. Apart from cytokines and chemokines, also sphingolipid mediators, particularly sphingosine-1-phosphate and ceramide 1-phosphate (C1P), contribute to cancer and inflammation, however, the contribution of  ceramide kinase (CerK), and its product ceramide 1-phosphate (C1P), to SkM mass wasting in these conditions is missing. The present study was developed using mice bearing the C26, or Lewis lung carcinoma (LLC) tumors, well characterized models of cancer-associated SkM atrophy, and in murine and human myotubes treated with conditioned media obtained from C26 or LLC-cells or with the corticosteroid dexamethasone. The results obtained reveal that CerK protein expression and the Ceramide/C1P axis are markedly impaired in all experimental models, demonstrating that the CerK/C1P axis plays a crucial role as molecular regulator of SkM mass associated to cancer or corticosteroids. Apart from cytokines and chemokines, sphingolipid mediators, particularly sphingosine-1-phosphate (S1P) and ceramide 1-phosphate (C1P), contribute to cancer and inflammation. Cancer, as well as other inflammatory conditions, are associated with skeletal muscle (SkM) atrophy, which is characterized by the unbalance between protein synthesis and degradation. Although the signaling pathways involved in SkM mass wasting are multiple, the regulatory role of simple sphingolipids is limited. Here, we report the impairment of ceramide kinase (CerK), the enzyme responsible for the phosphorylation of ceramide to C1P, associated with the accomplishment of atrophic phenotype in various experimental models of SkM atrophy: in vivo animal model bearing the C26 adenocarcinoma or Lewis lung carcinoma tumors, in human and murine SkM cells treated with the conditioned medium obtained from cancer cells or with the glucocorticoid dexamethasone. Notably, we demonstrate in all the three experimental approaches a drastic decrease of CerK expression. Gene silencing of CerK promotes the up-regulation of atrogin-1/MAFbx expression, which was also observed after cell treatment with C8-ceramide, a biologically active ceramide analogue. Conversely, C1P treatment significantly reduced the corticosteroid's effects. Altogether, these findings provide evidence that CerK, acting as a molecular modulator, may be a new possible target for SkM mass regulation associated with cancer or corticosteroids. [ABSTRACT FROM AUTHOR]

In this paper, fracture behavior of four types of implants with different geometries (pure titanium locking plate, pure titanium femoral implant, Ti-6Al-4V titanium alloy pelvic implant, X2CrNiMo18 14-3 steel femoral implant) was studied in detail. Each implant fractured in the human body. The scanning electron microscopy (SEM) was used to determine the potential cause of implants fracture. It was found that the implants fracture mainly occurred in consequence of mechanical overloads resulting from repetitive, prohibited excessive limb loads or singular, un-intendent, secondary injures. Among many possible loading types, the implants were subjected to an excessive fatigue loads with additional interactions caused by screws that were mounted in their threaded holes. The results of this work enable to conclude that the design of orthopedic implants is not fully sufficient to transduce mechanical loads acting over them due to an increasing weight of treated patients and much higher their physical activity. [ABSTRACT FROM AUTHOR]

Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed to influence membrane properties and to accommodate receptors within themselves by facilitating their interaction with ligands. Over the past decade, technical advances have improved our understanding of lipid rafts as bioactive structures. In this review, we will cover the more recent findings about cholesterol, sphingolipids and lipid rafts located in cellular and nuclear membranes in cancer. Collectively, the data provide insights on the role of lipid rafts as biomolecular targets in cancer with good perspectives for the development of innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

In animals, muscle growth is a quantitative trait controlled by multiple genes. Previously, we showed that the transient receptor potential channel 1 (TRPC1) gene was differentially expressed in muscle tissues between pig breeds with divergent growth traits base on RNA-seq. Here, we characterized TRPC1 expression profiles in different tissues and pig breeds and showed that TRPC1 was highly expressed in the muscle. We found two single nucleotide polymorphisms (SNPs) (C-1763T and C-1604T) in TRPC1 that could affect the promoter region activity and regulate pig growth rate. Functionally, we used RNAi and overexpression to illustrate that TRPC1 promotes myoblast proliferation, migration, differentiation, fusion, and muscle hypertrophy while inhibiting muscle degradation. These processes may be mediated by the activation of Wnt signaling pathways. Altogether, our results revealed that TRPC1 might promote muscle growth and development and plays a key role in Wnt-mediated myogenesis. [ABSTRACT FROM AUTHOR]

Some adipokines, such as adiponectin (ADPN), other than being implicated in the central regulation of feeding behavior, may influence gastric motor responses, which are a source of peripheral signals that also influence food intake. The present study aims to elucidate the signaling pathways through which ADPN exerts its actions in the mouse gastric fundus. To this purpose, we used a multidisciplinary approach. The mechanical results showed that ADPN caused a decay of the strip basal tension, which was abolished by the nitric oxide (NO) synthesis inhibitor, L-NG-nitro arginine (L-NNA). The electrophysiological experiments confirmed that all ADPN effects were abolished by L-NNA, except for the reduction of Ca2+ current, which was instead prevented by the inhibitor of AMP-activated protein kinase (AMPK), dorsomorphin. The activation of the AMPK signaling by ADPN was confirmed by immunofluorescence analysis, which also revealed the ADPN R1 receptor (AdipoR1) expression in glial cells of the myenteric plexus. In conclusion, our results indicate that ADPN exerts an inhibitory action on the gastric smooth muscle by acting on AdipoR1 and involving the AMPK signaling pathway at the peripheral level. These findings provide novel bases for considering AMPK as a possible pharmacologic target for the potential treatment of obesity and eating disorders. [ABSTRACT FROM AUTHOR]

In this paper, 45S5 Bioglass® coatings were elaborated by electrophoretic deposition (EPD) on the titanium alloy Ti6Al4V. An adequate grinding protocol was developed to obtain a stable suspension of submicrometric particles in isopropanol. The voltage and the deposition time of EPD were optimized. An optimal voltage of 30 V and two deposition times (30 and 90 s) were chosen to obtain two different coatings with thicknesses of 21 and 85 µm, respectively. The as-deposited coatings were thermally treated following a two-step protocol: one hour at 120 °C followed by one hour at 450 °C. The surface morphology and the chemical analysis of the 45S5 Bioglass® coatings were assessed, before and after heat treatment, by scanning electron microscopy associated to X-ray microanalysis (SEM-EDXS). Their structural analysis was performed by X-ray diffraction (XRD). A scratch test study was developed for mechanical properties analysis. The obtained results revealed that the obtained coatings were homogeneous, weakly crystallized with an important compactness. An increase in the critical load LC associated with the cohesive limit of the film (from Lc = 3.39 N to Lc = 5.18 N) was observed when the coating thickness was decreased from 85 to 21 µm. After the thermal treatment, the chemical composition of the coatings was not altered, and their mechanical properties were improved. [ABSTRACT FROM AUTHOR]

Vitamin D is widely known to regulate bone health, but there is increasing evidence that it may also ameliorate colitis through inflammation, cell proliferation and apoptosis, and the microbiota. The purpose of this review is to systematically examine the mechanisms by which vitamin D reduces colitis. PubMed and Web of Science were searched for articles published between 2008 and 2019 using key words such as "vitamin D," "colitis," "inflammatory bowel disease," "inflammation," "apoptosis," "cell proliferation," and "gut bacteria". Retrieved articles were further narrowed and it was determined whether their title and abstracts contained terminology pertaining to vitamin D in relation to colitis in human clinical trials, animal studies, and cell culture/biopsy studies, as well as selecting the best match sorting option in relation to the research question. In total, 30 studies met the established criteria. Studies consistently reported results showing that vitamin D supplementation can downregulate inflammatory pathways of COX-2, TNF-α, NF-κB, and MAPK, modify cell kinetics, and alter gut microbiome, all of which contribute to an improved state of colitis. Although vitamin D and vitamin D analogs have demonstrated positive effects against colitis, more randomized, controlled human clinical trials are needed to determine the value of vitamin D as a therapeutic agent in the treatment of colitis. [ABSTRACT FROM AUTHOR]