Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulated temporary hypoxia triggers the release of CD31+/Annexin+ endothelial microparticles: A prospective pilot study in humans.

INTRODUCTION Endothelial microparticles (EMP) are small membrane vesicles that originate from activated or apoptotic endothelial cells. Although the exact mechanism of EMP function is still relatively unknown, it has been shown that they modulate inflammatory processes, coagulation and vascular function. In this study we hypothesized that transient hypoxia may act as a trigger for the release of EMP into circulation. MATERIALS AND METHODS Fourteen healthy volunteers were subjected to transient normobaric hypoxia in an air-conditioned chamber simulating an oxygen concentration of a height of up to 5500 meters. Blood samples were evaluated for EMP using flow cytometry. RESULTS During the experiment oxygen concentration was adjusted to a value equivalent to a height of 5500 meters to achieve hypoxic conditions. Oxygen saturation decreased to 78% . At the final height a significant increase of CD31+/Annexin+ EMP levels was evident (increase from 0.03% ± 0.01% SEM to 0.12% ± 0.04% SEM, p = 0.0188). CONCLUSIONS These experimental results show that temporary hypoxic conditions can trigger the release of CD31+/ Annexin+ EMP also in healthy volunteers. In our previous studies we have shown that apoptotic bodies can confer pro-survival signals to cardiomyocytes during myocardial ischemia. Based on the experimental results of this current study we believe that the release of CD31+/Annexin+ EMP during hypoxia might act as an endogenous survival signal.
Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1α,25‐dihydroxyvitamin D3 and cytokines

The effects of lα,25‐dihydroxyvitamin D3/caldtriol on the expression of Fc receptors (FcR) for IgA (FcαR), IgE (FcRII), and IgG (FcγR) on human peripheral blood monocytes and the cell lines U937, THP‐1, and Mono Mac‐6, in combination with various cytoldnes, was examined by flow cytometry. On both monocyte‐derived macrophages and the myelomonocytic cell lines, FcαR/CD89 expression was induced by caldtriol alone and additively in combination with tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), and granulocyte‐macrophage colony‐stimulating factor. Constitutive and mterleukin‐4 (IL‐4)‐driven FcRD/CD23 expression was markedly diminished on caldtriol‐treated U937 cells and monocytes. FcRII was also triggered by IFN‐γ, TNF‐α, and IL‐6 on all the cell lines, an effect blocked by caldtriol. On monocytes, the basal level and IFN‐γ‐induced FcγRI/CD64 expression was down‐regulated by caldtriol and IL‐4. The expression of FcγRII/CD32 on monocytes was strongly suppressed by caldtriol. Transforming growth factor‐β induced FcγRIII/CD16 on monocytes, an effect opposed by caldtriol. The ability of caldtriol‐treated monocytes to phagocytose IgG‐sensitized ox erythrocytes was diminished. Our results demonstrate that caldtriol, alone or in combination with cytokines, modulates FcαR, FcRII, FcγRI, and FcγRII expression on human mononudear phagocytes, as well as FcγR‐mediated phagocytosis. J. Leukoc. Biol. 58: 256–262; 1995.
Lentivirus Vectors Using Human and Simian Immunodeficiency Virus Elements

ABSTRACT Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1) constitute a recent development in the field of gene therapy. A key property of HIV-1-derived vectors is their ability to infect nondividing cells. Although high-titer HIV-1-derived vectors have been produced, concerns regarding safety still exist. Safety concerns arise mainly from the possibility of recombination between transfer and packaging vectors, which may give rise to replication-competent viruses with pathogenic potential. We describe a novel lentivirus vector which is based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived genome is encapsidated by SIVmac core particles. These core particles are pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV-1 and SIVmac is low, the likelihood of recombination between vector elements should be reduced. In addition, the packaging construct (SIVpack) for this lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus, the potential for pathogenicity with this vector system is minimal. The transduction ability of HIV/SIVpack/G was demonstrated with immortalized human lymphocytes, human primary macrophages, human bone marrow-derived CD34+ cells, and primary mouse neurons. To our knowledge, these experiments constitute the first demonstration that the HIV-1-derived genome can be packaged by an SIVmac capsid. We demonstrate that the lentivirus vector described here recapitulates the biological properties of HIV-1-derived vectors, although with increased potential for safety in humans.
Antiinflammatory Effect of Oldenlandia diffusa and its Constituent, Hentriacontane, through Suppression of Caspase‐1 Activation in Mouse Peritoneal Macrophages

Oldenlandia diffusa (OD) has been used as a natural drug for the treatment of cancer in Asia and specifically in Korea. However, the antiinflammatory mechanisms employed by OD have yet to be completely understood. This study attempted to determine the effects of OD and hentriacontane, one of the constituent compounds of OD, on lipopolysaccharide (LPS)‐induced inflammatory responses in mouse peritoneal macrophages. The findings of this study showed that OD inhibited the production of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6 and prostaglandin E2 (PGE2). The OD inhibited the enhanced levels of cyclooxygenase (COX)‐2 and inducible nitric oxide synthase (iNOS) induced by LPS. It was shown that the antiinflammatory effect of OD occurs via the regulation of the activation of nuclear factor (NF)‐κB and caspase‐1. Moreover, hentriacontane was shown to ameliorate the expression of inflammatory mediators (TNF‐α, IL‐6, PGE2, COX‐2 and iNOS) and the activation of NF‐κB and caspase‐1 in LPS‐stimulated peritoneal macrophages. These results provide novel insights into the pharmacological actions of OD as a potential candidate for the development of new drugs for the treatment of inflammatory diseases. Copyright © 2011 John Wiley & Sons, Ltd.
RGMa inhibits neurite outgrowth of neuronal progenitors from murine enteric nervous system via the neogenin receptor in vitro

The enteric nervous system (ENS) in vertebrate embryos is formed by neural crest‐derived cells. During development, these cells undergo extensive migration from the vagal and sacral regions to colonize the entire gut, where they differentiate into neurons and glial cells. Guidance molecules like netrins, semaphorins, slits, and ephrins are known to be involved in neuronal migration and axon guidance. In the CNS, the repulsive guidance molecule (RGMa) has been implicated in neuronal differentiation, migration, and apoptosis. Recently, we described the expression of the subtypes RGMa and RGMb and their receptor neogenin during murine gut development. In the present study, we investigated the influence of RGMa on neurosphere cultures derived from fetal ENS. In functional in vitro assays, RGMa strongly inhibited neurite outgrowth of differentiating progenitors via the receptor neogenin. The repulsive effect of RGMa on processes of differentiated enteric neural progenitors could be demonstrated by collapse assay. The influence of the RGM receptor on ENS was also analyzed in neogenin knockout mice. In the adult large intestine of mutants we observed disturbed ganglia formation in the myenteric plexus. Our data indicate that RGMa may be involved in differentiation processes of enteric neurons in the murine gut.
One more health benefit of blood donation: reduces acute-phase reactants, oxidants and increases antioxidant capacity

Abstract Background: One of the most important problems in finding blood donors is the inadequacy of volunteer number. To overcome this problem, one of the solutions we suggest is innovating new health benefits of blood donation. The aim of the present study is to investigate the effects of blood donation on oxidative status markers and acute-phase reactants. Methods: A total of 96 healthy volunteers were recruited into the study. Blood samples were withdrawn 5 min before and 24 h after the blood donation. Serum nitric oxide, malondialdehyde levels, and activity of superoxide dismutase and myeloperoxidase were measured spectrophotometrically. Serum levels of high-sensitive C-reactive protein and pentraxin-3 as acute-phase reactants were measured by enzyme-linked immunosorbent assay kits. Results: We found statistically significant lower pentraxin-3 and high-sensitive C-reactive protein levels and higher superoxide dismutase activity and nitric oxide level 24 h after blood donation in serum of blood donor when compared with before blood donation. Conclusions: These findings suggest that blood donation affected oxidative status and acute-phase reactants in donors. Blood donation removes oxidants and decreases oxidative stress by elevating antioxidant enzyme such as superoxide dismutase. This is one more health benefit or reason why we should donate blood. Further large-scale studies should evaluate this mechanism and compare the same effect of wet cupping therapy.
[Impulsivity and mental disorders].

OBJECTIVE Although there are several studies revealing the role of impulsivity in mental disorders, debates in the literature about how to define and determine impulsivity continue. Being a measurable feature of behaviour, impulsivity is defined as the failure to resist a drive or stimulus or as a personality dimension as the inability to resist the desire to harm one's self or others. Besides this negative definition, however, impulsivity is also defined as independent dysfunctional and functional concepts having both positive and negative consequences. It can be a psychopathological structural part of many mental disorders, but it can be a characteristic of normal behaviour as well. Although not defined in detail in DSM-IV, it is mentioned as a diagnostic criterion in several mental disorders like impulse control disorders (pathological gambling, intermittent explosive disorder, pyromania, kleptomania and trichotillomania), impulsive aggressive disorders of personality (borderline, antisocial, histrionic and narcissistic), manic episodes of bipolar disorder, attention deficit hyperactivity disorder (ADHD), neurological disorders with behavioural disinhibition and substance abuse. Studies have revealed impulsivity to be more common in subjects with conduct disorders, attention deficit hyperactivity disorder, disorders of personality, substance and alcohol abuse, psychotic disorders, bipolar disorders, eating disorders and dementia compared to healthy subjects in control groups. The aim of the present paper is to define impulsivity as a concept and symptom, to discuss its relation to mental disorders, to show the biological basis of this relationship and to review the literature relating to this issue.
Sub-Saharan Africa’s Brain Drain of Medical Doctors to the United States

Many studies prove that the migration of health workers, especially physicians, and nurses from developing countries is a major global health problem (Dovlo, 2005; Cooper et al., 2006; Mullan, 2005; Hagopian et al., 2004). A report on brain drain in Africa illustrates the size of this problem: Kenya loses on average 20 medical doctors each month. Ghana had lost 60 percent of its medical doctors in the 1980s; a figure that represents 50 percent of the total population of doctors in Ghana. In Zambia, only 10 percent of the physicians trained between 1977 and 2000 remain in the public health sector, and in Malawi there is one physician per 16,000 persons (Cooper et al., 2006). Brain drain includes individuals who study abroad and do not return to their home country upon completion of their studies as well as those who emigrate from their home countries to other countries with higher and better opportunities (Kana, 2009).
Proteomic Signature Reveals Modulation of Human Macrophage Polarization and Functions Under Differing Environmental Oxygen Conditions*

Macrophages are innate immune cells which can react to a large number of environmental stimuli thanks to a high degree of plasticity. These cells are involved in a variety of tissue functions in homeostasis, and they play essential roles in pathological contexts. Macrophages' activation state, which determines their functional orientation, is strongly influenced by the cellular environment. A large body of macrophage literature is devoted to better defining polarizations from a molecular viewpoint. It is now accepted that a multidimensional model of polarization is needed to grasp the broad phenotype repertoire controlled by environmental signals. The study presented here aimed, among other goals, to provide a molecular signature of various polarizations in human macrophages at the protein level to better define the different macrophage activation states. To study the proteome in human monocyte-derived macrophages as a function of their polarization state, we used a label-free quantification approach on in-gel fractionated and LysC/Trypsin digested proteins. In total, 5102 proteins were identified and quantified for all polarization states. New polarization-specific markers were identified and validated. Because oxygen tension is an important environmental parameter in tissues, we explored how environmental oxygen tension, at either atmospheric composition (18.6% O2) or “tissue normoxia” (3% O2), affected our classification of macrophage polarization. The comparative results revealed new polarization-specific makers which suggest that environmental oxygen levels should be taken into account when characterizing macrophage activation states. The proteomic screen revealed various polarization-specific proteins and oxygen sensors in human macrophages. One example is arachidonate 15-lipoxygenase (ALOX15), an IL4/IL13 polarization-specific protein, which was upregulated under low oxygen conditions and is associated with an increase in the rate of phagocytosis of apoptotic cells. These results illustrate the need to consider physicochemical parameters like oxygen level when studying macrophage polarization, so as to correctly assess their functions in tissue.
The CCL3 Family of Chemokines and Innate Immunity Cooperate In Vivo in the Eradication of an Established Lymphoma Xenograft by Rituximab1

The therapeutic mAb rituximab induced the expression of the CCL3 and CCL4 chemokines in the human lymphoma line BJAB following binding to the CD20 Ag. Induction of CCL3/4 in vitro was specific, was observed in several cell lines and freshly isolated lymphoma samples and also took place at the protein level in vitro and in vivo. To investigate the role of these β-chemokines in the mechanism of action of rituximab, we synthesized a N-terminally truncated CCL3 molecule CCL3(11–70), which had antagonist activity on chemotaxis mediated by either CCL3 or BJAB supernatant. We also set up an established s.c. BJAB tumor model in athymic mice. Rituximab, given weekly after tumors had reached 250 mm2, led to complete disappearance of the lymphoma within 2–3 wk. Treatment of mice with cobra venom factor showed that complement was required for rituximab therapeutic activity. Treatment of BJAB tumor bearing mice every 2 days with the CCL3(11–70) antagonist, starting 1 wk before rituximab treatment, had no effect on tumor growth by itself, but completely inhibited the therapeutic activity of the Ab. To determine whether CCL3 acts through recruitment/activation of immune cells, we specifically depleted NK cells, polymorphonuclear cells, and macrophages using mAbs, clodronate treatment, or Rag2−/−cγ−/− mice. The data demonstrated that these different cell populations are involved in BJAB tumor eradication. We propose that rituximab rapidly activates complement and induces β-chemokines in vivo, which in turn activate the innate immunity network required for efficient eradication of the bulky BJAB tumor.
Molecular evolution of types in non-polio enteroviruses.

Non-polio enteroviruses are a ubiquitous and divergent group of non-enveloped RNA viruses. Novel types are reported regularly in addition to over 100 known types; however, mechanisms of emergence of novel types remain obscure. Here, the 33 most common types represented by 35-629 non-redundant partial VP1 sequences in GenBank were studied in parallel using Bayesian coalescent molecular clock analysis to investigate common evolutionary trends among enterovirus types. Inferred substitution rates were in the range of 0.41×10-2 to 3.07×10-2 substitutions per site per year. The most recent common ancestors of known isolates of each type presumably existed between 55 and 200 years ago. Phylogenetic analysis results suggested that global type populations underwent bottlenecks that could repeatedly reset the common ancestor dates. Nevertheless, species-level analysis suggested that the contemporary enterovirus types emerged within the last millennium. Analysis of 2657 complete VP1 sequences of the 24 most common types indicated that the type criterion based upon 75 % nucleotide sequence identity remains generally valid, despite exponential growth of the number of known sequences and a high rate of mutation fixation. However, in few types there was evidence that enteroviruses can drift slightly beyond the type threshold, up to 73 % identity, and both amino acid and nucleotide sequences should be considered for type identification. Analysis of sequence distances within types implied that sequence-identity-based identification of genotypes is rational within some, but not all, types and distinct genotype cut-offs (9-20 %) may be useful for different types.
Construction of an expression vector containing a β-actin promoter region for gene transfer by microinjection in red sea bream Pagrus major

Transgenic technology has been widely applied to a variety of freshwater fish species. However there are few reports on the use of this technology in commercially important marine species. In this study, the construction of expression vectors containing the β-actin promoter region for use in the red sea bream Pagrus major, a species of considerable importance to the aquaculture industry in Japan is reported. The β-actin gene was cloned from a red sea bream genomic DNA library. Recombinant plasmids were constructed by linking the 5′ flanking region of the β-actin gene to the green fluorescent protein reporter gene, followed by the poly A signal sequence of simian virus 40 or the 3′ flanking region the β-actin gene. Expression of these constructs was examined following microinjection into zebrafish and red sea bream embryos, and compared to that of the expression vector pXI-GFP driven by the Xenopus elongation factor 1α. The results indicated that the construct consisting of the β-actin 5′-and 3′ flanking regions was the most efficacious. In future studies, it is planned to investigate the efficient condition for integration into chromosomes of the transgene.
Walking Pattern Classification and Walking Distance Estimation Algorithms Using Gait Phase Information

This paper presents a walking pattern classification and a walking distance estimation algorithm using gait phase information. A gait phase information retrieval algorithm was developed to analyze the duration of the phases in a gait cycle (i.e., stance, push-off, swing, and heel-strike phases). Based on the gait phase information, a decision tree based on the relations between gait phases was constructed for classifying three different walking patterns (level walking, walking upstairs, and walking downstairs). Gait phase information was also used for developing a walking distance estimation algorithm. The walking distance estimation algorithm consists of the processes of step count and step length estimation. The proposed walking pattern classification and walking distance estimation algorithm have been validated by a series of experiments. The accuracy of the proposed walking pattern classification was 98.87%, 95.45%, and 95.00% for level walking, walking upstairs, and walking downstairs, respectively. The accuracy of the proposed walking distance estimation algorithm was 96.42% over a walking distance.
Differentiation of glioblastoma multiforme stem-like cells leads to downregulation of EGFR and EGFRvIII and decreased tumorigenic and stem-like cell potential

Glioblastoma multiforme (GBM) is the most common and devastating primary brain tumor among adults. Despite recent treatment progress, most patients succumb to their disease within 2 years of diagnosis. Current research has highlighted the importance of a subpopulation of cells, assigned brain cancer stem-like cells (bCSC), to play a pivotal role in GBM malignancy. bCSC are identified by their resemblance to normal neural stem cells (NSC), and it is speculated that the bCSC have to be targeted in order to improve treatment outcome for GBM patients. One hallmark of GBM is aberrant expression and activation of the epidermal growth factor receptor (EGFR) and expression of a deletion variant EGFRvIII. In the normal brain, EGFR is expressed in neurogenic areas where also NSC are located and it has been shown that EGFR is involved in regulation of NSC proliferation, migration, and differentiation. This led us to speculate if EGFR and EGFRvIII are involved in the regulation of bCSC. In this study we use GBM neurosphere cultures, known to preserve bCSC features. We demonstrate that EGFR and EGFRvIII are downregulated upon differentiation and moreover that when EGFR signaling is abrogated, differentiation is induced. Furthermore, we show that differentiation leads to decreased tumorigenic and stem cell-like potential of the neurosphere cultures and that by specifically inhibiting EGFR signaling it is possible to target the bCSC population. Our results suggest that differentiation therapy, possibly along with anti-EGFR treatment would be a feasible treatment option for patients with GBM, by targeting the bCSC population.
Time‐dependent biodistribution and excretion of silver nanoparticles in male Wistar rats

Silver nanoparticles (AgNPs) are the most commonly used nanoparticles owing to their antimicrobial properties. The motivation of the present study was (1) to analyze the effect of silver particle size on rat tissue distribution at different time points, (2) to determine the accumulation of AgNPs in potential rat target organs, (3) to analyze the intracellular distribution of AgNPs and (4) to examine the excretion of AgNPs by urine and feces. AgNPs were characterized by dynamic light scattering (DLS), zeta potential measurements, BET surface area measurements, transmission and scanning electron microscopy. AgNPs (20 and 200 nm) were administered intravenously (i.v.) to male Wistar rats at a dose of 5 mg kg–1 of body weight. Biological material was sampled 24 h, 7 and 28 days after injection. Using inductively coupled plasma‐mass spectrometry (ICP‐MS) and transmission electron microscopy (TEM) it was observed that AgNPs translocated from the blood to the main organs and the concentration of silver in tissues was significantly higher in rats treated with 20 nm AgNPs as compared with 200 nm AgNPs. The highest concentration of silver was found in the liver after 24 h. After 7 days, a high level of silver was observed in the lungs and spleen. The silver concentration in the kidneys and brain increased during the experiment and reached the highest concentration after 28 days. Moreover, the highest concentration of AgNPs was observed in the urine 1 day after the injection, maintained high for 14 days and then decreased. The fecal level of silver in rats was the highest within 2 days after AgNPs administration and then decreased. Copyright © 2012 John Wiley & Sons, Ltd.