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Open AccessArticle
Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia
by , , , , , , , , , and
Cells 2020, 9(3), 570; https://doi.org/10.3390/cells9030570 (registering DOI) - 28 Feb 2020
Abstract
Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not [...] Read more.
Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not understood. Here, we aimed to study whether mitochondrial dysfunction is a distinctive characteristic of CLI myopathy by assessing mitochondrial respiration in gastrocnemius muscle from 14 CLI patients (65.3 ± 7.8 y) and 15 matched control patients (CON) with a similar comorbidity risk profile and medication regimen but without peripheral ischemia (67.4 ± 7.4 y). Furthermore, we studied potential structural and molecular mechanisms of mitochondrial dysfunction by measuring total, sub-population, and fiber-type-specific mitochondrial volumetric content and cristae density with transmission electron microscopy and by assessing mitophagy and fission/fusion-related protein expression. Finally, we asked whether commonly used biomarkers of mitochondrial content are valid in patients with cardiovascular disease. CLI patients exhibited inferior mitochondrial respiration compared to CON. This respiratory deficit was not related to lower whole-muscle mitochondrial content or cristae density. However, stratification for fiber types revealed ultrastructural mitochondrial alterations in CLI patients compared to CON. CLI patients exhibited an altered expression of mitophagy-related proteins but not fission/fusion-related proteins compared to CON. Citrate synthase, cytochrome c oxidase subunit IV (COXIV), and 3-hydroxyacyl-CoA dehydrogenase (β-HAD) could not predict mitochondrial content. Mitochondrial dysfunction is a distinctive characteristic of CLI myopathy and is not related to altered organelle content or cristae density. Our results link this intrinsic mitochondrial deficit to dysregulation of the mitochondrial quality control system, which has implications for the development of therapeutic strategies. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Metabolic Disease)
Open AccessArticle
Human IgA Monoclonal Antibodies That Neutralize Poliovirus, Produced by Hybridomas and Recombinant Expression
by , , , , , , , and
Antibodies 2020, 9(1), 5; https://doi.org/10.3390/antib9010005 (registering DOI) - 28 Feb 2020
Abstract
Poliovirus (PV)-specific intestinal IgAs are important for cessation of PV shedding in the gastrointestinal tract following an acute infection with wild type or vaccine-derived PV strains. We sought to produce IgA monoclonal antibodies (mAbs) with PV neutralizing activity. We first performed de novo [...] Read more.
Poliovirus (PV)-specific intestinal IgAs are important for cessation of PV shedding in the gastrointestinal tract following an acute infection with wild type or vaccine-derived PV strains. We sought to produce IgA monoclonal antibodies (mAbs) with PV neutralizing activity. We first performed de novo IgA discovery from primary human B cells using a hybridoma method that allows assessment of mAb binding and expression on the hybridoma surface: On-Cell mAb Screening (OCMS™). Six IgA1 mAbs were cloned by this method; three potently neutralized type 3 Sabin and wt PV strains. The hybridoma mAbs were heterogeneous, expressed in monomeric, dimeric, and aberrant forms. We also used recombinant methods to convert two high-potency anti-PV IgG mAbs into dimeric IgA1 and IgA2 mAbs. Isotype switching did not substantially change their neutralization activities. To purify the recombinant mAbs, Protein L binding was used, and one of the mAbs required a single amino acid substitution in its κ LC in order to enable protein L binding. Lastly, we used OCMS to assess IgA expression on the surface of hybridomas and transiently transfected, adherent cells. These studies have generated potent anti-PV IgA mAbs, for use in animal models, as well as additional tools for the discovery and production of human IgA mAbs. Full article
(This article belongs to the Special Issue Development of Therapeutic Antibodies against Toxins and Pathogens)
Open AccessArticle
Effect of Crack Initiation and Life Prediction of Polyacrylonitrile-Reinforced Gussasphalt Surfacing over Steel Bridge Deck under Fiber Content Variation
by , , , , and
Crystals 2020, 10(3), 155; https://doi.org/10.3390/cryst10030155 (registering DOI) - 28 Feb 2020
Abstract
The crack initiation and life prediction of fiber-reinforced asphalt concrete (FRAC) surfacing for steel bridge decks under a cyclic vehicle load are analyzed from the perspective of damage mechanics. The damage field and the stress and strain field evolution rule of a composite [...] Read more.
The crack initiation and life prediction of fiber-reinforced asphalt concrete (FRAC) surfacing for steel bridge decks under a cyclic vehicle load are analyzed from the perspective of damage mechanics. The damage field and the stress and strain field evolution rule of a composite beam in fatigue test are studied, and a fatigue failure criterion is proposed for steel deck FRAC surfacing. Bending fatigue tests are performed on composite beams composed of a steel deck and polyacrylonitrile (PAN)-fiber-reinforced Gussasphalt (GA), i.e., GA-PAN, concrete surfacing under different fiber content and temperature conditions. The damage evolution characteristics of GA-PAN concrete surfacing over the steel deck with different fiber lengths and volume ratios are predicted by analyzing the fatigue life equations. The results show that the steel bridge deck FRAC surfacing model can reflect the comprehensive influence of the fiber content and length on the fatigue performance of steel bridge AC. Specifically, a lower temperature results in the fiber more synergistically affecting the fatigue resistance of AC. Theoretically, the service performance of asphalt concrete increases with the increase of fiber length and content. The optimum fiber length and volume ratio of GA-PAN are found to be 9 mm and 0.46%–0.48%, respectively, considering the construction workability. Full article
(This article belongs to the Section Crystalline Materials)
Open AccessArticle
Metabolite Profiling and Distribution of Militarine in Rats Using UPLC-Q-TOF-MS/MS
by , , , and
Molecules 2020, 25(5), 1082; https://doi.org/10.3390/molecules25051082 (registering DOI) - 28 Feb 2020
Abstract
Militarine, a natural glucosyloxybenzyl 2-isobutylmalate, isolated from Bletilla striata, was reported with a prominent neuroprotective effect recently. The limited information on the metabolism of militarine impedes comprehension of its biological actions and pharmacology. This study aimed to investigate the metabolite profile and [...] Read more.
Militarine, a natural glucosyloxybenzyl 2-isobutylmalate, isolated from Bletilla striata, was reported with a prominent neuroprotective effect recently. The limited information on the metabolism of militarine impedes comprehension of its biological actions and pharmacology. This study aimed to investigate the metabolite profile and the distribution of militarine in vivo, which help to clarify the action mechanism further. A total of 71 metabolites (57 new metabolites) in rats were identified with a systematic method by ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The proposed metabolic pathways of militarine include hydrolyzation, oxidation, glycosylation, esterification, sulfation, glucuronidation and glycine conjugation. Militarine and its metabolites were distributed extensively in the treated rats. Notably, six metabolites of militarine were identified in cerebrospinal fluid (CSF), which were highly consistent with the metabolites after oral administration of gastrodin in rats. Among the metabolites in CSF, five of them were not reported before. It is the first systematic metabolic study of militarine in vivo, which is very helpful for better comprehension of the functions and the central nervous system (CNS) bioactivities of militarine. The findings will also provide an essential reference for the metabolism of other glucosylated benzyl esters of succinic, malic, tartaric and citric acids. Full article
Open AccessReview
The Beast of Beauty: Environmental and Health Concerns of Toxic Components in Cosmetics
by , and
Cosmetics 2020, 7(1), 13; https://doi.org/10.3390/cosmetics7010013 (registering DOI) - 28 Feb 2020
Abstract
Cosmetic products are used in large quantities across the world. An increasing number of chemical compounds are being added to the formulation of cosmetic products as additives, fragrances, preservatives, stabilizers, surfactants, dye and shine to potentiate their quality, property and shelf life. Owing [...] Read more.
Cosmetic products are used in large quantities across the world. An increasing number of chemical compounds are being added to the formulation of cosmetic products as additives, fragrances, preservatives, stabilizers, surfactants, dye and shine to potentiate their quality, property and shelf life. Owing to their widespread use, active residues of cosmetic products are continuously introduced into the environment in several ways. Many of these chemicals are bioactive and are characterized by potential bioaccumulation ability and environmental persistence, thus exerting a major risk to humans and the health of ecosystems. Hence, the indiscriminate consumption of cosmetics may present a looming issue with significant adverse impacts on public health. This review intends to spotlight a current overview of toxic ingredients used in formulating cosmetics such as parabens, triclosan, benzalkonium chloride, 1,4-dioxane, plastic microbeads, formaldehyde, diazolidinyl urea, imidazolidinyl urea, sunscreen elements (organic and inorganic UV filters) and trace metals. Specific focus is given to illustrate the biological risks of these substances on human health and aquatic system in terms of genotoxicity, cytotoxicity, neurotoxicity mutagenicity, and estrogenicity. In addition to conclusive remarks, future directions are also suggested. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2020)
Open AccessArticle
Experimental and Computational Analyses of Temperature Distributions in Slope-Type Thin-Film Thermoelectric Generators at Different Slope Angles and Evaluation of Their Thermoelectric Performance
by , , and
Coatings 2020, 10(3), 214; https://doi.org/10.3390/coatings10030214 (registering DOI) - 28 Feb 2020
Abstract
Thin-film thermoelectric generators are not widely used mainly because it is difficult to provide a temperature difference (T) within the generators. To solve this problem, in our previous study, we prepared slope-type thin-film thermoelectric generators (STTEGs) using electrodeposition and transferred processes [...] Read more.
Thin-film thermoelectric generators are not widely used mainly because it is difficult to provide a temperature difference (T) within the generators. To solve this problem, in our previous study, we prepared slope-type thin-film thermoelectric generators (STTEGs) using electrodeposition and transferred processes (Yamamuro et al., Coatings 2018, 8, 22) [1]. A thin-film generator including n-type Bi2Te3 and p-type Sb2Te3 thin films was attached on slope blocks made of polydimethylsiloxane. In this study, the slope angle of STTEGs was optimized based on experimental results and computational analyses using computational fluid dynamics (CFD). With the increase in the slope angle, the T began increasing and became saturated at a slope angle of 58°, and this trend was also confirmed by experimental measurements. When the heat source temperature was set at 65 °C, theT computationally reached 26 K at a slope angle of 58°, and the maximum output power was 46.1 nW. Therefore, we demonstrated that the highest performance of STTEGs with an optimal slope angle can be estimated by combining the experimental results and computational analyses. Full article
(This article belongs to the Section Thin Films)
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Open AccessArticle
Extent of Food Processing and Risk of Prostate Cancer: The PROtEuS Study in Montreal, Canada
by , and
Nutrients 2020, 12(3), 637; https://doi.org/10.3390/nu12030637 (registering DOI) - 28 Feb 2020
Abstract
We studied the association between food intake, based on the extent of processing, and prostate cancer risk in a population-based case-control study conducted in Montreal, Canada in 2005-2012. Incident prostate cancer cases (n = 1919) aged ≤75 years were histologically confirmed. Population [...] Read more.
We studied the association between food intake, based on the extent of processing, and prostate cancer risk in a population-based case-control study conducted in Montreal, Canada in 2005-2012. Incident prostate cancer cases (n = 1919) aged ≤75 years were histologically confirmed. Population controls (n = 1991) were randomly selected from the electoral list and frequency-matched to cases by age (±5 years). A 63-item food frequency questionnaire focusing on the two years prior to diagnosis/interview was administered by interviewers. The NOVA classification was used to categorize foods based on processing level. Unconditional logistic regression estimated the association between food intake and prostate cancer risk, adjusting for age, education, ethnicity, family history, and timing of last prostate cancer screening. Consumption of unprocessed or minimally processed foods showed a slight, inverse association (Odd ratio [OR] 0.86, 95% confidence interval [CI] 0.70-1.07; highest vs. lowest quartile) with prostate cancer. An increased risk was observed with higher intake of processed foods (OR 1.29, 95%CI 1.05-1.59; highest vs. lowest quartile), but not with consumption of ultra-processed food and drinks. The associations with unprocessed/minimally processed foods and processed foods were slightly more pronounced for high-grade cancers (ORs 0.80 and 1.33, respectively). Findings suggest that food processing may influence prostate cancer risk. Full article
(This article belongs to the Special Issue Nutrition and Prostate Cancer)
Open AccessReview
Exosomes are the Driving Force in Preparing the Soil for the Metastatic Seeds: Lessons from the Prostate Cancer
by , , , , , and
Cells 2020, 9(3), 564; https://doi.org/10.3390/cells9030564 (registering DOI) - 28 Feb 2020
Abstract
Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have [...] Read more.
Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients. Full article
(This article belongs to the Section Cellular Pathology)
Open AccessReview
Cross-Presenting XCR1+ Dendritic Cells as Targets for Cancer Immunotherapy
by , and
Cells 2020, 9(3), 565; https://doi.org/10.3390/cells9030565 (registering DOI) - 28 Feb 2020
Abstract
The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies [...] Read more.
The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies following the remarkable patient responses observed with novel checkpoint blockade therapies, due to the potential for synergistic treatment. Cross-presenting DCs are recognized for their ability to prime CD8+ T cell responses to directly induce tumor death. Consequently, they are an attractive target for next-generation DC-based strategies. In this review, we define the universal classification system for cross-presenting DCs, and the vital role of this subset in mediating anti-tumor immunity. Furthermore, we will detail methods of targeting these DCs both ex vivo and in vivo to boost their function and drive effective anti-tumor responses. Full article
(This article belongs to the Special Issue Dendritic Cells in Immunity and Inflammation)
Open AccessReview
Alternative Cell Sources for Liver Parenchyma Repopulation: Where Do We Stand?
by , and
Cells 2020, 9(3), 566; https://doi.org/10.3390/cells9030566 (registering DOI) - 28 Feb 2020
Abstract
Acute and chronic liver failure is a highly prevalent medical condition with high morbidity and mortality. Currently, the therapy is orthotopic liver transplantation. However, in some instances, chiefly in the setting of metabolic diseases, transplantation of individual cells, specifically functional hepatocytes, can be [...] Read more.
Acute and chronic liver failure is a highly prevalent medical condition with high morbidity and mortality. Currently, the therapy is orthotopic liver transplantation. However, in some instances, chiefly in the setting of metabolic diseases, transplantation of individual cells, specifically functional hepatocytes, can be an acceptable alternative. The gold standard for this therapy is the use of primary human hepatocytes, isolated from livers that are not suitable for whole organ transplantations. Unfortunately, primary human hepatocytes are scarcely available, which has led to the evaluation of alternative sources of functional hepatocytes. In this review, we will compare the ability of most of these candidate alternative cell sources to engraft and repopulate the liver of preclinical animal models with the repopulation ability found with primary human hepatocytes. We will discuss the current shortcomings of the different cell types, and some of the next steps that we believe need to be taken to create alternative hepatocyte progeny capable of regenerating the failing liver. Full article
(This article belongs to the Special Issue Recent Advances in Liver Repair Strategies)
Open AccessReview
Advances in Research on the Bioactivity of Alginate Oligosaccharides
by , , , , , , and
Mar. Drugs 2020, 18(3), 144; https://doi.org/10.3390/md18030144 (registering DOI) - 28 Feb 2020
Abstract
Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely [...] Read more.
Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely related to the diversity of their structures. AOS with a specific structure and distinct applications can be obtained by different methods of alginate degradation. This review focuses on recent advances in the biological activity of alginate and its derivatives, including their anti-tumor, anti-oxidative, immunoregulatory, anti-inflammatory, neuroprotective, antibacterial, hypolipidemic, antihypertensive, and hypoglycemic properties, as well as the ability to suppress obesity and promote cell proliferation and regulate plant growth. We hope that this review will provide theoretical basis and inspiration for the high-value research developments and utilization of AOS-related products. Full article
(This article belongs to the collection Marine Polysaccharides) Printed Edition available
Open AccessArticle
Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment
by , , , , , and
Pharmaceutics 2020, 12(3), 206; https://doi.org/10.3390/pharmaceutics12030206 (registering DOI) - 28 Feb 2020
Abstract
Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure [...] Read more.
Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure in safety/efficacy studies. Drug repurposing (i.e., investigating FDA-approved drug molecules for use against new indications) provides an opportunity to shorten the drug development cycle. In this project, we propose to repurpose pirfenidone (PFD), an anti-fibrotic drug, for NSCLC treatment by encapsulation in a cationic liposomal carrier. Liposomal formulations were optimized and evaluated for their physicochemical properties, in-vitro aerosol deposition behavior, cellular internalization capability, and therapeutic potential against NSCLC cell lines in-vitro and ex-vivo. Anti-cancer activity of PFD-loaded liposomes and molecular mechanistic efficacy was determined through colony formation (1.5- to 2-fold reduction in colony growth compared to PFD treatment in H4006, A549 cell lines, respectively), cell migration, apoptosis and angiogenesis assays. Ex-vivo studies using 3D tumor spheroid models revealed superior efficacy of PFD-loaded liposomes against NSCLC, as compared to plain PFD. Hence, the potential of inhalable liposome-loaded pirfenidone in NSCLC treatment has been established in-vitro and ex-vivo, where further studies are required to determine their efficacy through in vivo preclinical studies followed by clinical studies. Full article
(This article belongs to the Special Issue Advances in Pulmonary Drug Delivery)
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Open AccessCommunication
Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study
by , , , , , and
Mar. Drugs 2020, 18(3), 143; https://doi.org/10.3390/md18030143 (registering DOI) - 28 Feb 2020
Abstract
Fucoidans are a class of fucose-rich sulfated polysaccharides derived from brown macroalgae that exert a range of biological activities in vitro and in vivo. To generate an unbiased assessment of pathways and processes affected by fucoidan, a placebo-controlled double-blind pilot study was performed [...] Read more.
Fucoidans are a class of fucose-rich sulfated polysaccharides derived from brown macroalgae that exert a range of biological activities in vitro and in vivo. To generate an unbiased assessment of pathways and processes affected by fucoidan, a placebo-controlled double-blind pilot study was performed in healthy volunteers. Blood samples were taken immediately before and 24 h after ingestion of a single dose of 1 g of Undaria pinnatifida fucoidan (UPF) or placebo. Levels of isolated miRNAs were analyzed using Taqman Open Array Human MicroRNA panels. Out of 754 miRNAs screened, UPF affected a total of 53 miRNAs. Pathway analysis using the TALOS data analysis tool predicted 29 different pathways and processes that were largely grouped into cell surface receptor signaling, cancer-related pathways, the majority of which were previously associated with fucoidans. However, this analysis also identified nine pathways and processes that have not been associated with fucoidans before. Overall, this study illustrates that even a single dose of fucoidans has the potential to affect the expression of genes related to fundamental cellular processes. Moreover, it confirms previous data that fucoidans influence immunity, cancer cells, inflammation, and neurological function. Full article
Open AccessArticle
Administration of Steamed and Freeze-Dried Mature Silkworm Larval Powder Prevents Hepatic Fibrosis and Hepatocellular Carcinogenesis by Blocking TGF-β/STAT3 Signaling Cascades in Rats
by , , , , and
Cells 2020, 9(3), 568; https://doi.org/10.3390/cells9030568 (registering DOI) - 28 Feb 2020
Abstract
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide and the majority of HCC patients occur with a background of hepatic fibrosis and cirrhosis. We have previously reported the hepatoprotective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in [...] Read more.
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide and the majority of HCC patients occur with a background of hepatic fibrosis and cirrhosis. We have previously reported the hepatoprotective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in a chronic ethanol-treated rat model. Here, we assessed the anti-fibrotic and anti-carcinogenic effects of SMSP on diethylnitrosamine (DEN)-treated rats. Wistar rats were intraperitoneally injected with DEN once a week for 12 or 16 weeks with or without SMSP administration (0.1 and 1 g/kg). SMSP administration significantly attenuated tumor foci formation and proliferation in the livers of the rats treated with DEN for 16 weeks. SMSP administration also inhibited hepatic fibrosis by decreasing the levels of collagen fiber and the expression of pro-collagen I and alpha-smooth muscle actin (α-SMA). Moreover, SMSP supplementation improved the major parameters of fibrosis such as transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and collagen type I (Col1A1) in the livers from the rats treated with DEN for 16 weeks. As s possible mechanisms, we investigated the effects of SMSP on the TGF-β and signal transducer and activator of transcription 3 (STAT3)-mediated signaling cascades, which are known to promote hepatic fibrosis. We found that SMSP treatment inhibited the activation of TGF-β and the phosphorylation of STAT3 pathway in DEN-treated rats. Moreover, SMSP administration suppressed the expressions of the target genes of TGF-β and STAT3 induced by DEN treatment. Our findings provide experimental evidences that SMSP administration has inhibitory effects of hepatic fibrosis and HCC induced by DEN in vivo and could be a promising strategy for the prevention or treatment of hepatic fibrosis and hepatocellular carcinogenesis. Full article
(This article belongs to the Special Issue Role of STAT3 Signaling Pathway in Cancer)
Open AccessArticle
Personalized Indicator Thrombocytosis Shows Connection to Staging and Indicates Shorter Survival in Colorectal Cancer Patients with or without Type 2 Diabetes
by , , , and
Cancers 2020, 12(3), 556; https://doi.org/10.3390/cancers12030556 (registering DOI) - 28 Feb 2020
Abstract
Background: Pre- and postoperative thrombocytosis was reported to have significant effect on patient survival. However, the definition of thrombocytosis throughout the literature is not unified. Methods: A retrospective longitudinal observational study has been conducted with the inclusion of 150 colorectal cancer (CRC) patients [...] Read more.
Background: Pre- and postoperative thrombocytosis was reported to have significant effect on patient survival. However, the definition of thrombocytosis throughout the literature is not unified. Methods: A retrospective longitudinal observational study has been conducted with the inclusion of 150 colorectal cancer (CRC) patients and 100 control subjects. A new measure of platelet changes at an individual level, named personalized indicator thrombocytosis (PIT) was defined, including 4 anemia adjusted variants. Results: In concordance with the literature, PIT values of control subjects showed a slow decrease in platelet counts, while PIT values of CRC patients were significantly higher (p < 0.0001). More advanced staging (p < 0.0001) and both local (p ≤ 0.0094) and distant (p ≤ 0.0440) metastasis are associated with higher PIT values. Higher PIT values suggested shorter survival times (p < 0.0001). Compared to conventional, a PIT-based definition resulted in approximately 3-times more patients with thrombocytosis. 28% and 77% of the deceased patients had conventional- and PIT-based thrombocytosis, respectively. Conclusions: Compared to conventional thrombocytosis, as an individual metric, PIT values may indicate the condition of patients more precisely. Possible future applications of PIT may include its usage in therapy decision and early cancer detection; therefore, further investigations are recommended. Full article
(This article belongs to the Special Issue Platelets and Cancer)
Open AccessArticle
The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats
by , , and
Nutrients 2020, 12(3), 636; https://doi.org/10.3390/nu12030636 (registering DOI) - 28 Feb 2020
Abstract
High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy [...] Read more.
High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism. Full article
(This article belongs to the Special Issue High-Fat High-Saturated Diet)
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