Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

Despite the important role that the growth hormone (GH)/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium is considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effects, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy is described. All the elements that trigger the local and systemic production of GH/IGF-I, as well as their possible roles both in physiological and pathological conditions are analyzed. All of the evidence is combined with important data from the GHAS trial, in which GH or a placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of ischemic disease

The Role of Growth Hormone on Ovarian Functioning and Ovarian Angiogenesis

Although not yet well-understood, today it is clear that Growth Hormone (GH) exerts a relevant role in the regulation of ovulation and fertility; in fact, fertility is lower in women with GH deficiency (GHD), and GH receptors (GHR) and GH mRNA have been found in the ovary since the onset of follicular development in humans. However, despite the strong evidence of GH in the regulation of fertility, many aspects of GH actions at this level are still not well-established, and it is likely that some controversial data depend on the species analyzed, the dose of the hormone and the duration of use of GH. Folliculogenesis, ovulation, and corpus luteum formation and maintenance are processes that are critically dependent on angiogenesis. In the ovary, new blood vessel formation facilitates oxygen, nutrients, and hormone substrate delivery, and also secures transfer of different hormones to targeted cells. Some growth factors and hormones overlap their actions in order to control the angiogenic process for fertility. However, we still know very little about the factors that play a critical role in the vascular changes that occur during folliculogenesis or luteal regression. To promote and maintain the production of VEGF-A in granulosa cells, the effects of local factors such as IGF-I and steroids are needed; that VEGF-A-inducing effect cannot be induced by luteinizing hormone (LH) or chorionic gonadotropin (CG) alone. As a result of the influences that GH exerts on the hypothalamic-pituitary-gonadal axis, facilitating the release of gonadotropins, and given the relationship between GH and local ovarian factors such as VEGF-A, FGF-2, IGF-1, or production of sex steroids, we assume that GH has to be a necessary factor in ovarian angiogenesis, as it happens in other vascular beds. In this review we will discuss the actions of GH in the ovary, most of them likely due to the local production of the hormone and its mediators

The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the “Warburg Effect”. However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Melatonin Exerts Anti-Inflammatory, Antioxidant, and Neuromodulatory Effects That Could Potentially Be Useful in the Treatment of Vertigo

The acute phase of vertigo involves multiple neurotransmitters, inflammatory mediators, and products of oxidative stress. The vestibular pathway has multiple melatonin receptors distributed along its path, both centrally and peripherally. In addition, melatonin has been shown to be a powerful antioxidant and anti-inflammatory agent against factors related to vertigo, such as Bax/caspases, interleukins, and chemokines. Likewise, it exerts central GABAergic, antidopaminergic, and anti-migraine functions and regulates sympathetic activity in a similar way to the drugs classically used in acute vestibular crisis. In this review, the role of melatonin as a potential treatment of the acute phase of vertigo is discussed

Spanish hotel industry: indebtedness determinants

This article analyses the indebtedness of the companies belonging to the Spanish hotel industry. The internationalization process of Spanish hotel companies requires a new approach to their financial strategies. The form of expansion chosen in this process has an impact on the pace and volume of the funds needed for it. Other items are incorporated to observe different behaviour among hotel companies in relation with their indebtedness process. Among analysed factors, we can observe the importance of solvency, liquidity, and asset structure. The hotel industry's means to explain individual indebtedness is also relevant, demonstrating the fact that firms usually follow the sector's benchmark when determining the level of indebtedness. Studies such those of Grinblatt and Titman (2003) or Frank and Goyal (2009) confirm this same hypothesis.

Facilitation of arthroscopic visualization and treatment of meniscal tears using a stifle joint distractor in the dog

Abstract Background Stifle arthroscopy has been described to have high sensitivity and specificity in the evaluation of menisci in dogs, particularly for the medial meniscus. However, the visualization of menisci can be difficult. The use of femoral distractors in human medicine has been described to simplify demanding surgical procedures, such as meniscus transplantation. In veterinary medicine, stifle distraction has been reported to facilitate access to the joint and visualization of intra-articular structures, but there are no studies reporting the use of a stifle distraction technique while performing challenging surgical procedures, such as meniscal suture, in clinical patients. The objective of this study was to evaluate the feasibility, effectiveness and safety of stifle distraction to achieve consistent visualization of menisci and to facilitate performing arthroscopic procedures in clinical patients with stifle disease. Initial arthroscopic evaluation of the stifle joint was performed without distraction in the study population consisting of 13 dogs with naturally occurring stifle disease. The criteria for inclusion was prospectively set as the observation of a frank disease or anomaly of the menisci that could not be further treated or clarified without the risk of damaging the joint cartilage due to the requested manoeuvres. After the first examination, distraction was applied in order to complete the assessment of menisci. After achieving an accurate diagnosis, partial meniscectomy or meniscal repair was performed as needed while maintaining the distraction. Results Complete visualization and assessment of menisci were achieved thanks to the use of distraction. This manoeuvre facilitated access to the required area of the involved meniscus, and meniscal treatment could be successfully performed without damaging the articular cartilage. During the follow-up period, no postoperative complication related to the distraction or to the arthroscopic procedure was observed. Conclusions Stifle joint distraction during arthroscopy in dogs improves visualization of both menisci, and particularly the caudal horn of the medial meniscus. Despite being a subjective assessment, it is the authors’ opinion that this procedure also increases the ease of performing challenging procedures like meniscal suture, as it enlarges the space available to reach the correct working angulations

iSanXoT: A standalone application for the integrative analysis of mass spectrometry-based quantitative proteomics data.

Many bioinformatics tools are available for the quantitative analysis of proteomics experiments. Most of these tools use a dedicated statistical model to derive absolute quantitative protein values from mass spectrometry (MS) data. Here, we present iSanXoT, a standalone application that processes relative abundances between MS signals and then integrates them sequentially to upper levels using the previously published Generic Integration Algorithm (GIA). iSanXoT offers unique capabilities that complement conventional quantitative software applications, including statistical weighting and independent modeling of error distributions in each integration, aggregation of technical or biological replicates, quantification of posttranslational modifications, and analysis of coordinated protein behavior. iSanXoT is a standalone, user-friendly application that accepts output from popular proteomics pipelines and enables unrestricted creation of quantification workflows and fully customizable reports that can be reused across projects or shared among users. Numerous publications attest the successful application of diverse integrative workflows constructed using the GIA for the analysis of high-throughput quantitative proteomics experiments. iSanXoT has been tested with the main operating systems. Download links for the corresponding distributions are available at https://github.com/CNIC-Proteomics/iSanXoT/releases.This study was supported by competitive grants from the Spanish Ministry of Science, Innovation and Universities (PGC2018–097019-BI00, PID2021–122348NB-I00, PLEC2022–009235 and PLEC2022–009298), the Instituto de Salud Carlos III (Fondo de Investigacion ´ Sanitaria grant PRB3 (PT17/0019/0003- ISCIII-SGEFI / ERDF, ProteoRed), Comunidad de Madrid (IMMUNO-VAR, P2022/BMD7333), the Spanish Ministry of Education, Culture and Sports (FPU18/ 03882, FPU20/03365 and PRE2019-090019), and the “la Caixa” Banking Foundation (project codes HR17–00247 and HR22–00253). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovacion ´ (MCIN), and the Pro CNIC Foundation) and is a Severo Ochoa Center of Excellence (grant CEX2020–001041-S funded by MICIN/AEI/10.13039/501100011033).S

Influence of the Particle Size on the Electrical, Magnetic and Biological Properties of the Bioglass® Containing Iron Oxide

Bioglasses have been used throughout the past century as a biomaterial in the bone regeneration field. However, recent studies have attempted to use them as a therapeutic material as well, mainly in the treatment of osteosarcomas. The most widely recognized bioglass is the 45S5 Bioglass, invented by Larry Hench et al., which presents higher bioactivity. A possible application of this bioglass in the treatment of osteosarcomas can be accomplished by adding specific ions, such as iron, that will allow the use of magnetic hyperthermia and Fenton reaction as therapeutic mechanisms. In this study, a 45S5 Bioglass containing 10%mol of Fe2O3 was produced using the melt-quenching method. A group of samples was prepared by changing the overall ball milling time, from 1 h up to 48 h, to analyze the effects of iron in the bioactive glass matrix and evaluate the influence of particle size on their physical and biological properties. The studied bioglasses showed no evidence of changes in the amorphous structural nature compared to the 45S5 Bioglass. The data of the impedance spectroscopy study revealed that the addition of Fe2O3 can increase the standard rate constant of the Electro-Fenton reaction, with the sample milled for 12 h showing the most promising results. The reduction in the particle size influenced the cytotoxicity and the bioactivity. The samples with lower particle sizes showed a higher level of cytotoxicity