Cellular Aspects Research Articles

Homeopathic Medicines Influence Fungal Adhesion and Cellular Oxygen Metabolism of MDCK and MA104 Cell Lines

Background: Fungal and viral infections constitute a serious public health problem, because morbidity and mortality rates of these diseases have been increasing in the last decades [1,2]. The resistance to antifungal and antiviral agents [3,4] currently available in the pharmaceutical market motivates the development of new therapies, including complementary and alternative health practices [5,6]. In this context, our research group has deepened the knowledge about the therapeutic potential of homeopathy using different models [7-9]. Homeopathic medicines undergo a process of serial dilution whereby the final remedy contains extremely low amounts of the active substance, with pharmacological action, and, consequently, cannot be considered merely placebos [10]. Aims: In the present study, we evaluated the potential of two different homeopathic medicines, named Influenzinum RC (compounded with influenza A virus) and Candida albicans RC (compounded with Candida albicans yeasts), which are prepared according to Brazilian homeopathic procedures [11]. Methodology: The biotherapics (12x, 30x) were prepared from Candida albicans yeasts [7, 11] and from influenza A (H3N2) viruses [6,11]. The cellular parameters evaluated after biotherapic treatments were: cytotoxicity by MTT assay; PFK-1 activity; and maximum respiratory capacity. Results: Our results showed that Influenzinum RC did not cause cytotoxic effects but induced morphological alterations, increased (p < 0.05) mitochondrial respiration, and significantly modified (p < 0.05) PFK-1 activity of MDCK cells. Additionally, using high-resolution respirometry we could detect an increase in the maximum respiratory capacity when these cells were treated with Influenzinum RC, despite a well-preserved ultrastructure of their mitochondrial organelles. In contrast, when MA104 cells were treated with Candida albicans RC, a significant decrease in cellular respiratory capacity as well as in yeasts adhesion rate was detected. Conclusions: These results indicate that homeopathic medicines modify important cellular and metabolic aspects of mammalian cells and these alterations should be responsible for the therapeutic potential of these drugs.

The Effects of Stromal Vascular Fraction Administration in Stimulating Graft Healing Process after Anterior Cruciate Ligament Reconstruction Surgery in Rattus norvegicus

Introduction: Ligament injuries commonly occur in the knee region, and the anterior cruciate ligament (ACL) being the most usually injured. Currently, autograft or allograft is the most common material used for ACL reconstruction surgery. The result of the ACL reconstruction depends on the healing process of the graft or ligamentization between graft and bone tunnel. This study aims to evaluate the effect of Stromal Vascular Fraction (SVF) intratunnel injection to stimulates graft healing following ACL reconstruction surgery, as measured by histology examination.
 Method: This study was an experimental laboratory study with a post-test-only control group design using male Rattus novergicus. A random sampling procedure was used to choose the sample, which was then divided into two groups. The two groups consist of the control group that only had ACL reconstruction surgery and the treatment group that had reconstruction surgery with SVF administration.
 Result: This study used Advanced Ligament Maturity Index (LMI) score and showed a significant improvement of graft healing in the treatment group compared to the control group. The measurement is based on the cellular, collagen, and vascular aspect testing with P < 0,05 for each subscore.
 Conclusion: SVF intratunnel injection stimulates graft healing after ACL reconstruction surgery and causes a significant increase in cellular, collagen, and vascular aspects in the graft.

Functional importance and structure of small ribosomal protein RACK1

The Receptor for Activated C Kinase 1 (RACK1) protein is one of the ribosomal proteins that is located in the small subunit which is maintained across most of the eukaryotes and functions as a flexible scaffold protein involved in multiple signaling pathways. It is considered as a highly conserved protein that found in a wide range of tryptophan-aspartate (WD40) repeat proteins of eukaryotic organisms, from Chlamydomonas to plants and mammals. RACK1 adopts a propeller structure with seven blades structures, enabling the binding capability of the protein. RACK1 participates in shuttling and anchoring of proteins around the cells at certain positions and it stabilizes protein production during translation. RACK1 is a member of the protein family WD repeat that consists of seven-bladed β- propeller structure which shares important homology to the G-proteins (Gb) β-subunit. It interacts with the ribosomal machinery, multiple receptors of the cell surface and the nuclear proteins. RACK1 is a key mediator of different pathways and contributes to a variety of cellular functional aspects. This review discusses the main function of RACK1 protein in eukaryotes including animals and plants. Furthermore, we will show the recent study on RACK1 function in different organisms.

Comparison of myonuclear domain in phylogenetically paired tropical and temperate bird species

The life‐history theory of evolution posits that organisms are maximized for reproductive success through the processes of natural selection. Though believed to impact nearly every aspect of an organism, the life‐history theory of evolution shines little attention on the cellular aspects of organismal physiology. Tropical bird species, compared with temperate birds, are typically placed on the ‘slow' pace‐of‐life spectrum, and demonstrate a ‘slow' pace of life across every level of organization. Previously, we demonstrated that phylogenetically paired tropical birds have significantly smaller muscle fiber diameters than their temperate counterparts. No other muscle‐related properties have been addressed and correlated to life‐histories in the literature. Myonuclear domain (MND), the cytoplasmic volume that each myonucleus serves, is an under‐appreciated skeletal muscle property that has been largely ignored in bird muscle literature. Here, we measured MND in muscle cross‐sections in phylogenetically paired species of tropical and temperate birds. We found that tropical bird species had significantly higher numbers of nuclei per mm of fiber as compared with temperate bird species. This may be due to the fact that tropical birds could have a higher population of slow‐ oxidative fiber and/or due to developing in warmer climates, as compared with temperate birds. In both tropical and temperate birds, we found significantly positive associations between muscle fiber diameter and MND and between muscle cross‐sectional areas and number of nuclei per mm of fiber in tropical birds and temperate birds, as previously noted in other bird species.

Evaluating the influence of Human Umbilical Cord Mesenchymal Stem Cells-derived exosomes loaded with miR-3182 on metastatic performance of Triple Negative Breast Cancer cells

AimsDeregulation of microRNA (miRNA) function has been linked to numerous human cancers, such as Triple Negative Breast Cancer (TNBC). Exosomes, a subgroup of extracellular vehicles (EVs), can efficiently deliver many different cargo types to the target cell and have an extensive role in delivering therapeutic cargo for treatment. The present study intended to interrogate the effects of exosomal delivery of miR-3182 on TNBC cellular processes. Main methodsHuman Umbilical Cord Mesenchymal Stem Cells (HUCMSCs) were cultured and exosomes were isolated and characterized using TEM, SEM, DLS, and Western blot. Exosomes were transfected with miR-3182 and added to the treatment groups. The expression level of miR-3182 and their target genes including mTOR and S6KB1 were evaluated using RT-qPCR. The effects of miR-3182 loaded HUCMSC-exosomes treatment on the cellular aspect of MDA-MB-231 cells including their viability, migration potency, cell cycle status and apoptosis were investigated. Key findingsAccording to the results, exosomal miR-3182 significantly abolished cell proliferation and migration (P < 0.05). miR-3182 loaded exosomes also induced apoptosis in TNBC cells by down-regulating mTOR and S6KB1 genes (P < 0.05). SignificanceIn nutshell, miR-3182-loaded HUCMSC-exosomes can suppress TNBC invasion, suggesting that exosomes containing miR-3182 could be a reliable therapeutic paradigm in TNBC therapy.

Claudin-5: A Pharmacological Target to Modify the Permeability of the Blood-Brain Barrier.

Claudin-5 is the dominant tight junction protein in brain endothelial cells and exclusively limits the paracellular permeability of molecules larger than 400 Da across the blood-brain barrier (BBB). Its pathological impairment or sustained down-regulation has been shown to lead to the progression of psychiatric and neurological disorders, whereas its expression under physiological conditions prevents the passage of drugs across the BBB. While claudin-5 enhancers could potentially act as vascular stabilizers to treat neurological diseases, claudin-5 inhibitors could function as delivery systems to enhance the brain uptake of hydrophilic small-molecular-weight drugs. Therefore, the effects of claudin-5 manipulation on modulating the BBB in different neurological diseases requires further examination. To manipulate claudin-5 expression levels and function, several claudin-5 modulating molecules have been developed. In this review, we first describe the molecular, cellular and pathological aspects of claudin-5 to highlight the mechanisms of claudin-5 enhancers/inhibitors. We then discuss recently developed claudin-5 enhancers/inhibitors and new methods to discover these molecules.

A Multiscale View of the Mechanisms Underlying Ketamine's Antidepressant Effects: An Update on Neuronal Calcium Signaling.

Major depressive disorder (MDD) is a debilitating disease characterized by depressed mood, loss of interest or pleasure, suicidal ideation, and reduced motivation or hopelessness. Despite considerable research, mechanisms underlying MDD remain poorly understood, and current advances in treatment are far from satisfactory. The antidepressant effect of ketamine is among the most important discoveries in psychiatric research over the last half-century. Neurobiological insights into the ketamine’s effects have shed light on the mechanisms underlying antidepressant efficacy. However, mechanisms underlying the rapid and sustained antidepressant effects of ketamine remain controversial. Elucidating such mechanisms is key to identifying new therapeutic targets and developing therapeutic strategies. Accumulating evidence demonstrates the contribution of the glutamatergic pathway, the major excitatory neurotransmitter system in the central nervous system, in MDD pathophysiology and antidepressant effects. The hypothesis of a connection among the calcium signaling cascade stimulated by the glutamatergic system, neural plasticity, and epigenetic regulation of gene transcription is further supported by its associations with ketamine’s antidepressant effects. This review briefly summarizes the potential mechanisms of ketamine’s effects with a specific focus on glutamatergic signaling from a multiscale perspective, including behavioral, cellular, molecular, and epigenetic aspects, to provide a valuable overview of ketamine’s antidepressant effects.

Viruses Run: The Evasion Mechanisms of the Antiviral Innate Immunity by Hantavirus.

Hantavirus can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in America, with high mortality and unknown mechanisms. Innate immunity is the host’s first-line defense to bridge the acquired immunity against viral infections. However, hantavirus has evolved various strategies in both molecular and cellular aspects to evade the host’s natural immune surveillance. The Interferon-I (IFN-I) signaling pathway, a central link of host defense, induces various antiviral proteins to control the infection. This paper summarizes the molecular mechanisms of hantavirus evasion mechanisms of the IFN signaling pathway and cellular processes such as regulated cell death and cell stress. Besides, hantavirus could also evade immune surveillance evasion through cellular mechanisms, such as upregulating immune checkpoint molecules interfering with viral infections. Understanding hantavirus’s antiviral immune evasion mechanisms will deepen our understanding of its pathogenesis and help us develop more effective methods to control and eliminate hantavirus.

Substrate stiffness modulates endothelial cell function via the YAP-Dll4-Notch1 pathway

Endothelial cells adapt their functions as a consequence of sensing extracellular substrate stiffness; these alterations allow them to maintain their vascular structure and function. Substrate stiffness-mediated yes-associated protein 1 (YAP) activation plays an important role in mechano-transduction and pro-angiogenic phenotype of endothelial cells, and Delta-like ligand 4 (Dll4)-Notch1 signaling is closely related to angiogenesis; however, the impact of substrate stiffness-mediated interrelation of these pathways on endothelial cell functions remains elusive. We confirmed that endothelial cells on softer substrates not only elongate cellular aspects but also attenuate YAP activation compared to cells on stiffer substrates. Endothelial cells on softer substrates also upregulate the vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 mRNA expression that is enhanced by VEGF stimulation. We determined that endothelial cells on softer substrates increased Dll4 expression, but not Notch1 expression, via YAP signaling. Moreover, endothelial cells on soft substrates induced not only VEGFRs upregulation but also suppression of pro-inflammatory interleukin-6 and plasminogen activator inhibitor-1 mRNA expression and the facilitation of anti-coagulant thrombomodulin and pro-coagulant tissue factor mRNA expression. Our results suggest that endothelial cells activate the YAP-Dll4-Notch signaling pathway in response to substrate stiffness and dictate cellular function.

Sudden infant death syndrome: Melatonin, serotonin, and CD34 factor as possible diagnostic markers and prophylactic targets.

Sudden infant death syndrome (SIDS) is one of the primary causes of death of infants in the first year of life. According to the WHO’s data, the global infant mortality rate is 0.64–2 per 1,000 live-born children. Molecular and cellular aspects of SIDS development have not been identified so far. The purpose of this paper is to verify and analyze the expression of melatonin 1 and 2 receptors, serotonin (as a melatonin precursor), and CD34 molecules (as hematopoietic and endothelial markers of cardiovascular damage) in the medulla, heart, and aorta in infants who died from SIDS. An immunohistochemical method was used to investigate samples of medulla, heart, and aorta tissues of infants 3 to 9 months of age who died from SIDS. The control group included children who died from accidents. It has been shown that the expression of melatonin receptors as well as serotonin and CD34 angiogenesis markers in tissues of the medulla, heart, and aorta of infants who died from SIDS is statistically lower as compared with their expression in the same tissues in children who died from accidents. The obtained data help to clarify in detail the role of melatonin and such signaling molecules as serotonin and CD34 in SIDS pathogenesis, which can open new prospects for devising novel methods for predictive diagnosis of development and targeted prophylaxis of SIDS.

Aplastic anemia, cellular and molecular aspects.

Aplastic anemia (AA) is an autoimmune disorder characterized by bone marrow and peripheral blood pancytopenia. Different environmental and genetical conditions could be effective in an outbreak of this disease. The exact pathogenesis of this disease, however, is still idiopathic. The present study is based on Pubmed database information (2002-2021) using the words "Aplastic Anemia," "Hematopoietic Stem Cells niche," "Signaling pathway," "Cytokines," and "Immuno cells." In this disease, both hematopoietic stem cells and mesenchymal stromal cells are impaired, which is associated with impaired hematopoiesis and decreased hematopoietic cells. Inflammatory cytokines increase, which changes the ratio of T lymphocytes and leads to disease progression. In addition, the most common mechanism of AA is damage by the immune system, which leads to increased apoptosis in progenitor cells. We have shown in this review that the disease involves quantitative defects in stem cell numbers and qualitative abnormalities in the function of these cells and the activity of many different cellular and molecular factors can damage hematopoietic cells and the protective substrate of these cells in this disease.

RIP1/RIP3/MLKL Mediates Myocardial Function Through Necroptosis in Experimental Autoimmune Myocarditis.

Cardiomyopathy often leads to dilated cardiomyopathy (DCM) when caused by viral myocarditis. Apoptosis is long considered as the principal process of cell death in cardiomyocytes, but programmed necrosis or necroptosis is recently believed to play an important role in cardiomyocyte cell death. We investigated the role of necroptosis and its interdependency with other processes of cell death, autophagy, and apoptosis in a rat system of experimental autoimmune myocarditis (EAM). We successfully created a rat model system of EAM by injecting porcine cardiac myosin (PCM) and showed that in EAM, all three forms of cell death increase considerably, resulting in the deterioration of cardiac conditions with an increase in inflammatory infiltration in cardiomyocytes. To explore whether necroptosis occurs in EAM rats independent of autophagy, we treated EAM rats with a RIP1/RIP3/MLKL kinase-mediated necroptosis inhibitor, Necrostatin-1 (Nec-1). In Nec-1 treated rats, cell death proceeds through apoptosis but has no significant effect on autophagy. In contrast, autophagy inhibitor 3-Methyl Adenine (3-MA) increases necroptosis, implying that blockage of autophagy must be compensated through necroptosis. Caspase 8 inhibitor zVAD-fmk blocks apoptosis but increases both necroptosis and autophagy. However, all necroptosis, apoptosis, and autophagy inhibitors independently reduce inflammatory infiltration in cardiomyocytes and improve cardiac conditions. Since apoptosis or autophagy is involved in many important cellular aspects, instead of suppressing these two major cell death processes, Nec1 can be developed as a potential therapeutic target for inflammatory myocarditis.

Plant Growth-Promoting Microbe Mediated Uptake of Essential Nutrients (Fe, P, K) for Crop Stress Management: Microbe–Soil–Plant Continuum

The indiscriminate and intensive use of agrochemicals in developing nations to enhance crop productivity has posed an alarming threat to soil quality, fertility, biodiversity, food safety, agricultural sustainability, and groundwater quality, thus critically affecting planetary health and food productivity. Additionally, both abiotic and biotic stresses and developmental disorders, i.e., disease susceptibility, hormonal imbalance, and nutritional deficiency, are the major constraints on crop productivity. In this context, the use of soil–plant associated microbiomes “phytomicrobiome,” especially rhizospheric microbiota, in combination with agronomic practices (nutrient, water, and resource management, as integrated management options: INM/IPM/IWM) is the most promising alternative for managing soil health and crop productivity. The global recognition of plant/soil-associated microbiome has generated substantial investment of public and private bodies to grow microbe-based food products. However, understanding the molecular, genetic, physiological, and ecological aspects of phytomicrobiome toward sustainable agriculture would require broad attention along with associated environmental/physico-chemical control points. The underpinning mechanisms of plant–microbe interactions are of immense significance for strategizing host selection (single culture/consortia) and its field application. Taxa such asRhizobium, Pseudomonas, Alcaligenes, Burkholderia, Sphingomonas, Stenotrophomonas, Arthrobacter, Bacillus, andRhodococcushave emerged as promising plant growth-promoting (PGP) candidates with diverse beneficial traits, such as, producing phyto-hormones, volatile organics, antibiotics for disease suppression, N2-fixation, Fe uptake, and extracellular enzymes, but several physico-chemical constraints/extremities limit the field application (on-site) of such microbes. Hence, a detailed overview on genomic, physiological, metabolic, cellular, and ecological aspects is necessitated. Thorough insights into nutrient acquisition (especially limiting nutrients like Fe and P) during abiotic stress are still under-studied, so the use OMICS, robust bioinformatics pipeline/tools, might greatly revolutionize the field of PGP microbial ecology (complex plant–microbe interactions) for application in agricultural sustainability, nutritional security, and food safety. This review focusses on critical aspects of mechanisms of Fe and P transport-uptake (nutrient acquisition) by various PGP microbes, and their metabolism, genetics, and physiology relevant for managing stress and better crop production.

May the Force Be with You (Or Not): The Immune System under Microgravity.

All terrestrial organisms have evolved and adapted to thrive under Earth’s gravitational force. Due to the increase of crewed space flights in recent years, it is vital to understand how the lack of gravitational forces affects organisms. It is known that astronauts who have been exposed to microgravity suffer from an array of pathological conditions including an impaired immune system, which is one of the most negatively affected by microgravity. However, at the cellular level a gap in knowledge exists, limiting our ability to understand immune impairment in space. This review highlights the most significant work done over the past 10 years detailing the effects of microgravity on cellular aspects of the immune system.

High-Energy Phosphates and Ischemic Heart Disease: From Bench to Bedside.

The purpose of this review is to bridge the gap between clinical and basic research through providing a comprehensive and concise description of the cellular and molecular aspects of cardioprotective mechanisms and a critical evaluation of the clinical evidence of high-energy phosphates (HEPs) in ischemic heart disease (IHD). According to the well-documented physiological, pathophysiological and pharmacological properties of HEPs, exogenous creatine phosphate (CrP) may be considered as an ideal metabolic regulator. It plays cardioprotection roles from upstream to downstream of myocardial ischemia through multiple complex mechanisms, including but not limited to replenishment of cellular energy. Although exogenous CrP administration has not been shown to improve long-term survival, the beneficial effects on multiple secondary but important outcomes and short-term survival are concordant with its pathophysiological and pharmacological effects. There is urgent need for high-quality multicentre RCTs to confirm long-term survival improvement in the future.

Changes in \u03b3\u03b4T Cells in Peripheral Blood of Patients with Ulcerative Colitis Exacerbations

The role of γδT cells in ulcerative colitis (UC) is well confirmed in experimental animals and demonstrated in many clinical observations. Recent investigations have indicated that UC is associated with several forms of immune imbalance, such as an imbalance between effector T cells and regulatory T cells. However, little is known about the cellular aspect of clinical colitis exacerbations. We observed 140 patients with histologically confirmed UC over the course of 8 years. We investigated the percentage of γδT and αβT cells in peripheral blood of patients and also the expression of various surface markers (CD25, CD54, CD62L). Patients were assembled into stable colitis and exacerbated colitis groups. The percentage of γδT and αβT cells was evaluated by Ortho Cytorone Absolute flow cytometer. In patients with exacerbated colitis we observed a decrease of γδT cells in peripheral blood and an increased ratio of αβT/γδT. Additionally, we found that exacerbation results in a significant increase of percentage of γδTCD25, γδTCD54 and γδTCD62L lymphocytes in peripheral blood when compared to patients with stable colitis. Exacerbation of ulcerative colitis results in a decreased percentage of γδT cells in peripheral blood with increase of CD25, CD54 and CD62L expressing γδT cells. This may represent the effect of cell activation and migration, similar to that observed after the surgical trauma. We hope that this observation may help to predict exacerbations in colitis patients.

Characterization of laryngeal motor neuron properties in the American bullfrog, Lithobates catesbieanus

Motor neurons represent the final output from the central respiratory network. American bullfrogs, Lithobates catesbieanus, have provided insight into development and plasticity of the breathing control system, yet cellular aspects of bullfrog motor neurons are not well-described. In this study, we characterized properties of laryngeal motor neurons that produce motor outflow to the glottal dilator, a muscle that gates airflow to the lungs of anurans. To this end, we measured several intrinsic membrane properties of labeled laryngeal motor neurons in brain slices. Using unsupervised clustering analyses, we identified two broad classes of motor neurons: those with high firing rates and strong adaptation (∼70 %), and those with lower firing rates and less adaptation (∼30 %). These results suggest that two neuronal cell types innervate the glottal dilator, roughly aligning with the composition of fast and slower twitch fibers of this muscle. In sum, these data reinforce the need to consider cell-type when assessing motor neuron function in the respiratory network.

Viscum album homeopathic tinctures: phytochemical profile and antiproliferative activity

Background: The mistletoe Viscum album L. (Santalaceae) is a semi-parasitic plant that grows on different host trees. Although V. album antitumor activity is mainly associated with aqueous preparations, recently we showed antitumoral effects of homeopathic V. album tinctures containing also the ethanolic soluble compounds [1]. &#x0D; Aims: to analyze the phytochemical profile of different Viscum album homeopathic tinctures as well as their in vitro effects in tumoral cells. &#x0D; Methodology: The Viscum album samples (leaves, stems and berries) were collected in 2016 and 2017 (summer), and in 2018 (winter) at different locations in Switzerland. After harvest, they were immediately submitted to ethanolic extraction (45% V/V) using homeopathic methodology [2, 3]. The following mother tinctures (MT) were prepared: V. album ssp. album growing on Malus domestica, Quercus sp. and Ulmus sp., V. album ssp. austriacum from Pinus sylvestris, and V. album ssp. abietis from Abies alba. The homeopathic dynamizations (1-3dH; 6, 12, 30dH) were prepared with the respective MT. The phytochemical profiles were analysed by High Performance Liquid Chromatography tandem Mass Spectroscopy, HPLC and Thin Layer Chromatography. MT prepared in 2016 were also submitted to the Pfeiffer’s circular chromatography (PCC) [4]. The proliferation assay was performed by WST-1 [5] after incubation of tumoral cells (Yoshida and Molt-4) with non-dynamized (0.5 to 0.05% v/v) and dynamized MT. Apoptosis/necrosis was measured by flow cytometer (FACS) using Annexin V-FITC [5], and the cellular morphological aspects were analysed by light microscope. &#x0D; Results and Discussion: The chemical analyses of MT identified the presence of phenolic acids, flavonoids, lignans, as principal compounds. Besides, the HPLC indicated higher viscotoxin concentration in the summer harvest of Abies alba, Malus domestica and Quercus (897, 475, 219 ?g/mL), respectively. The PCC methodology permitted the MT differentiation. The higher levels of cellular mortality were attribute to Abies alba, Malus domestica and Quercus (p

Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma.

Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA-sequencing. Rhinovirus-derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B-cell differentiation in response rhinovirus stimulation. Protein expression of pro-inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN-alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co-stimulation with rhinovirus and IFN-alpha upregulated pro-inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. These findings add to the understanding of systemic effects of rhinovirus infections on B-cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses.

Physiology and Pathophysiology of Oxygen Sensitivity.

Oxygen is an essential requirement for metabolism in mammals and many other animals. Therefore, pathways that sense a reduction in available oxygen are critical for organism survival. Higher mammals developed specialized organs to detect and respond to changes in O2 content to maintain gas homeostasis by balancing oxygen demand and supply. Here, we summarize the various oxygen sensors that have been identified in mammals (carotid body, aortic bodies, and astrocytes), by what mechanisms they detect oxygen and the cellular and molecular aspects of their function on control of respiratory and circulatory O2 transport that contribute to maintaining normal physiology. Finally, we discuss how dysregulation of oxygen availability leads to elevated signalling sensitivity in these systems and may contribute to the pathogenesis of chronic cardiovascular and respiratory diseases and many other disorders. Hence, too little oxygen, too much oxygen, and a malfunctioning sensitivity of receptors/sensors can create major pathophysiological problems for the organism.