Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia

Critical limb ischemia (CLI) constitutes the most severe form of peripheral arterial disease (PAD), it is characterized by progressive blockade of arterial vessels, commonly correlated to atherosclerosis. Currently, revascularization strategies (bypass grafting, angioplasty) remain the first option for CLI patients, although less than 45% of them are eligible for surgical intervention mainly due to associated comorbidities. Moreover, patients usually require amputation in the short-term. Angiogenic cell therapy has arisen as a promising alternative for these “no-option” patients, with many studies demonstrating the potential of stem cells to enhance revascularization by promoting vessel formation and blood flow recovery in ischemic tissues. Herein, we provide an overview of studies focused on the use of angiogenic cell therapies in CLI in the last years, from approaches testing different cell types in animal/pre-clinical models of CLI, to the clinical trials currently under evaluation. Furthermore, recent alternatives related to stem cell therapies such as the use of secretomes, exosomes, or even microRNA, will be also described.     

Role of Receptor Protein Tyrosine Phosphatases (RPTPs) in Insulin Signaling and Secretion

Changes in lifestyle in developed countries have triggered the prevalence of obesity and type 2 diabetes mellitus (T2DM) in the latest years. Consequently, these metabolic diseases associated to insulin resistance, and the morbidity associated with them, accounts for enormous costs for the health systems. The best way to face this problem is to identify potential therapeutic targets and/or early biomarkers to help in the treatment and in the early detection. In the insulin receptor signaling cascade, the activities of protein tyrosine kinases and phosphatases are coordinated, thus, protein tyrosine kinases amplify the insulin signaling response, whereas phosphatases are required for the regulation of the rate and duration of that response. The focus of this review is to summarize the impact of transmembrane receptor protein tyrosine phosphatase (RPTPs) in the insulin signaling cascade and secretion, and their implication in metabolic diseases such as obesity and T2DM.     

Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10⁻⁵, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10⁻⁵, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10⁻⁵, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10⁻⁵, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10⁻⁵, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10⁻², p = 5.1 × 10⁻³, p = 1.2 × 10⁻², respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.     

Basic Methods for Preparation of Liposomes and Studying Their Interactions with Different Compounds,with the Emphasis on Polyphenols

Studying the interactions between lipid membranes and various bioactive molecules (e.g., polyphenols) is important for determining the effects they can have on the functionality of lipid bilayers. This knowledge allows us to use the chosen compounds as potential inhibitors of bacterial and cancer cells, for elimination of viruses, or simply for keeping our healthy cells in good condition. As studying those effect can be exceedingly difficult on living cells, model lipid membranes, such as liposomes, can be used instead. Liposomal bilayer systems represent the most basic platform for studying those interactions, as they are simple, quite easy to prepare and relatively stable. They are especially useful for investigating the effects of bioactive compounds on the structure and kinetics of simple lipid membranes. In this review, we have described the most basic methods available for preparation of liposomes, as well as the essential techniques for studying the effects of bioactive compounds on those liposomes. Additionally, we have provided details for an easy laboratory implementation of some of the described methods, which should prove useful especially to those relatively new on this research field.     

Anti-Inflammatory Activity of Oat Beta-Glucans in a Crohn’s Disease Model: Time- and Molar Mass-Dependent Effects

Background: The incidence of Crohn’s disease (CD) is increasing worldwide, and it has currently become a serious public health issue in society. The treatment of CD continues throughout a patient’s lifetime, and therefore, it is necessary to develop new, effective treatment methods, including dietotherapy. The present study aimed to determine the effects of consumption of oat beta-glucans with different molar mass on colon inflammation (colitis) in the early stages of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD in an animal model. Methods: Sprague–Dawley rats (control and TNBS-induced CD) were divided into three dietary groups and fed for 3 days (reflecting acute inflammation) or 7 days (reflecting remission) with a feed containing 1% low (βGl) or high (βGh) molar mass oat beta-glucan or a feed without this polysaccharide. The level of colon inflammatory markers and the expression of cytokines and their receptor genes were measured by ELISA and RT-PCR methods, respectively. Results: Acute inflammation or remission (3 or 7 days after TNBS administration, respectively) stages of experimentally induced CD were characterized by an increase in the level of inflammatory markers (IL-1, IL-6, IL-10, IL-12, TNF-α, CRP, MPO, COX, and PGE2) and the disruption of some cytokine signaling pathways as well as macro- and microscopic changes of colon tissue. The consumption of oat beta-glucans reduced the level of inflammatory markers and recovered the signaling pathways and histological changes, with stronger effects of βGl after 7 days of colitis. Conclusions: Dietary oat beta-glucans can reduce colitis at the molecular and organ level and accelerate CD remission.     

Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women. Its early diagnosis seems to have a significant impact on the developing fetus, the course of delivery, and the neonatal period. It may also affect the later stages of child development and subsequent complications in the mother. Therefore, the crux of the matter is to find a biopredictor capable of singling out women at risk of developing GDM as early as the very start of pregnancy. Apart from the well-known molecules with a proven and clear-cut role in the pathogenesis of GDM, e.g., adiponectin and leptin, a potential role of newer biomolecules is also emphasized. Less popular and less known factors with different mechanisms of action include: galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, fatty acid-binding protein 4 (FABP4), fibroblast growth factor 21, and lipocalin-2. The aim of this review is to present the potential and significance of these 13 less known biomolecules in the pathogenesis of GDM. It seems that high levels of FABP4, low levels of irisin, and high levels of under-carboxylated osteocalcin in the serum of pregnant women can be used as predictive markers in the diagnosis of GDM. Hopefully, future clinical trials will be able to determine which biomolecules have the most potential to predict GDM.     

The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown. In this review, we outline the role of the immune system in promoting cancer development in chronic inflammatory diseases such as IBD, with a specific focus on the anti-inflammatory mechanisms and suppressive immune cells that may play a role in IBD-associated tumorigenesis.     

Pitting corrosion behaviour of PM austenitic stainless steels sintered in nitrogen-hydrogen atmosphere

PM 304L and 316L stainless steel have been compacted at 400, 600 and 800 MPa and sintered in vacuum and in nitrogen-hydrogen atmosphere. Postsintered heat treatments (annealing solution and ageing at 375, 675 and 875 °C) have been applied. Pitting corrosion resistance has been studied using anodic polarization measurements and the ferric chloride test. Anodic polarization curves reveal that densities and atmospheres are relevant on anodic behaviour. Pitting resistance is higher for PM 316L and for higher densities and vacuum as sintered atmosphere. Ageing heat treatments at medium and high temperatures are detrimental to passivity although susceptibility to pitting corrosion barely changes. But heat treatments at 375 °C even show certain improvement in pitting corrosion resistance. The results were correlated to the presence of precipitates and mainly to the lamellar constituent which appears in some samples sintered in nitrogen-hydrogen atmosphere. The role of nitrogen on the samples sintered under nitrogen-hydrogen atmosphere and its relation to the microstructural features was described.     

自治式水下监测机器人的动态性能分析

文章介绍了两种自治式水下监测机器人:垂直运动水下机器人和滑翔运动水下机器人,讨论了它们各自的特点与工作方式.结合水下监测机器人的试验模型,该文对其沉浮阶段的运动过程进行了动力学分析,讨论了它们在垂直剖面上的运动情况,推导了动力学方程.这些对于确定水下监测机器人的各项参数和设计控制器与观测器具有重要的指导价值.