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The endoplasmic reticulum (ER) is an organelle equipped with mechanisms for proper protein folding, trafficking, and degradation to maintain protein homeostasis in the secretory pathway. As a defense mechanism, perturbation of ER proteostasis by ER stress agents activates a cascade of signaling pathways from the ER to the nucleus known as unfolded protein response (UPR). The primary goal of UPR is to induce transcriptional and translational programs to restore ER homeostasis for cell survival. As such, defects in UPR signaling have been implicated as a key contributor to multiple diseases including metabolic diseases, degenerative diseases, inflammatory disorders, and cancer. Growing evidence support the critical role of ER stress in regulating the fate as well as the magnitude of the immune response. Moreover, the availability of multiple UPR pharmacological inhibitors raises the hope that targeting UPR can be a new strategy for immune modulation and immunotherapy of diseases. This paper reviews the principal mechanisms by which ER stress affects immune cell biology and function, with a focus of discussion on UPR-associated immunopathology and the development of potential ER stress-targeted therapeutics. [ABSTRACT FROM AUTHOR]

The paper examines the effects of the antimicrobial agent triclosan on the functioning of the liver mitochondria of marsh frog (Pelophylax ridibundus (Pallas, 1771)). It was established that triclosan inhibits DNP-stimulated respiration of mitochondria and decreases respiratory control ratio. In addition, triclosan causes the collapse of the mitochondrial membrane potential on both types of substrates. Such an action of triclosan can be mediated by both a protonophore effect and suppression of the activity of complex II and combined activity of complexes II + III (and, to a lesser degree, the combined activity of complexes I + III) of the mitochondrial respiratory chain. It is shown that high concentrations of triclosan enhance the production of hydrogen peroxide during the oxidation of substrates of the complex I by mitochondria, and decrease it in the case of succinate oxidation. It is found that triclosan is able to induce nonspecific permeability of the liver mitochondria of these amphibians, as well as the plasma membrane of erythrocytes. The possible mechanisms of triclosan effect on marsh frog liver mitochondria and red blood cells are discussed. [ABSTRACT FROM AUTHOR]

In this paper, a high-voltage driver with a switch-capacitor cell and a current-sensing resistor for implementing the functions of zero-voltage switching (ZVS) and overcurrent protection is proposed. It has the following advantages: (1) By using a switch-capacitor cell for implementing the function of ZVS, we can reduce the switching losses of active switches. (2) By using a voltage-doubler circuit, we can easily obtain a high voltage (8 kV). (3) By incorporating a sensing resistor and a logic circuit, we can sense overcurrent conditions to achieve the function of protection. Therefore, the proposed high-voltage driver can increase efficiency and safety. To verify its performance, a prototype of the proposed high-voltage driver is built. The experimental results have confirmed that the proposed high-voltage driver with a switch-capacitor cell and a current-sensing resistor for implementing the functions of ZVS and overcurrent protection is suitable for application to air cleaners. [ABSTRACT FROM AUTHOR]

In vitro gametogenesis (IVG) might offer numerous research and clinical benefits. Some potential clinical applications of IVG, such as allowing opposite‐sex couples experiencing infertility to have genetically related children, have attracted support. Others, such as enabling same‐sex reproduction and solo reproduction, have attracted significantly more criticism. In this paper, we examine how different ethical principles might help us to draw lines and distinguish between ethically desirable and undesirable uses of IVG. We discuss the alleged distinction between therapeutic and non‐therapeutic uses of assisted reproduction in the context of IVG, and show how it is both problematic to apply in practice and theoretically dubious. We then discuss how the ethical principles of reproductive justice and beneficence apply to IVG for opposite‐sex reproduction, same‐sex reproduction, and solo reproduction. We suggest that these principles generate strong reasons for the use of IVG for opposite‐sex and same‐sex reproduction, but not for solo reproduction. [ABSTRACT FROM AUTHOR]

Lasers have wide applications in the treatment and diagnosis of diseases and various medical fields. Laser therapy like the other methods has advantages and disadvantages. Some risks such as bleeding, pain, and infection are created after laser therapy. Explanation and evaluation of laser effects on cell function, tissue, and the body are the aims of this study. We reviewed papers available from 1986 to 2019 about the effects of lasers on cells and tissue. An online search of PubMed, Science Direct and Google scholar using such keywords as "laser", "cell", "tissue", "body" and "side effects" was performed. The laser photons are absorbed by chromophores, resulting in the target heating and localized damage. Laser irradiation alters cellular metabolism and cellular functions. These alterations may be accompanied by undesired side effects which can be monitored via metabolites level change in the body. Based on this finding, laser therapy may be associated with several side effects and complications; therefore, before treatment, the determination of laser types and their properties is necessary to avoid creating side effects. The advantages and disadvantages of the treatment type should be considered in order to choose the best treatment with the least side effects. The patients' awareness of possible side effects before treatment and also an effective follow-up and management of patients after action are two important points in laser therapy. Training curriculum definition should be determined for laser applicant qualifications in different medical fields. [ABSTRACT FROM AUTHOR]

Most scientists assume that thought is a mental process closely associated to the nervous systems and brain. This paper points to the possibility that thought might be a much more fundamental biological phenomenon associated with the cells of an organism. The idea is that every cell has thoughts that can be energized and fixed, dependent on the conditions. From this follows that cells can be conditioned. Structure, function, and behavior of the cells can change by learning on the level of cell-consciousness. The understanding of cell-thought might give us a better understanding of the process of healing in holistic medicine, holistic sexology and holistic psychiatry. [ABSTRACT FROM AUTHOR]

In vitro biological experiments and in silico individual-based computational models are widely used to understand the low-level behavior of cells and cellular functions. Many of these functions can not be directly observed, however, may be deduced from other properties that can be well measured and modeled. In this paper, we present a procedure to evaluate synthetic cell colony formation generated by an off-lattice individual-based model. The calculated shape features of the artificial cell aggregates can be related to the parameter values of the simulated agents, therefore this data can be used to quantify properties of real-life cells such as motility or binding affinity that can not be easily determined otherwise. Our experiments showed that only a few of these parameters are responsible for the difference in shape features of the colonies. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) is the major cause of seasonal epidemics and flu outbreaks worldwide. Given that interleukin 16 (IL16) can regulate T cell function and is one of the signature markers for virus infection including IAV infection, the impact of IL16 on IAVinduced T cell immune response hasn't been elucidated yet. In this paper, we infected wild type and IL16 knockout (KO) mice with IAV and analyzed the immunity of mice by flow cytometry. We observed an increase in the percentage of T helper (Th) 1 cells in the spleens of IL16 KO mice and elevation of IFN-α and TNF-α secretion from CD8+ T cells in the lungs and spleens of IL16 KO mice in response to IAV infection. Moreover, the expression of major histocompatibility complex II which represents the maturation of dendritic cells (DCs) was upregulated in the lungs of IL16 KO mice. Taken together, our study suggests that IL16 deficiency enhanced Th1 and cytotoxic T lymphocyte response as well as DC maturation upon IAV infection, which provides new insight into the host regulation of T cell immune responses during IAV infection. [ABSTRACT FROM AUTHOR]

The involvement of the apoptosis signal-regulating kinase 1 (ASK1)-related signalling pathway in the control of reproduction is unknown. This study aimed to investigate the role of ASK-1 in the control of basic ovarian functions (proliferation, apoptosis and hormone release) and its response to ovarian hormonal regulators (leptin and FSH). We compared the accumulation of ASK-1, proliferation marker proliferating cell nuclear antigen (PCNA), apoptosis marker Bax and apoptosis and proliferation regulating transcription factor p53 and the release of progesterone (P4), oxytocin (OT), insulin-like growth factor I (IGF-I) and prostaglandins F (PGF) and E (PGE) using cultured porcine ovarian granulosa cells transfected with ASK-1 cDNA and cultured with leptin or FSH. This study is the first to demonstrate that ASK-1 does not affect cell apoptosis and viability in ovarian cells, but promotes cell proliferation, suppresses p53, alters the release of ovarian hormones (P4, OT, IGF-I, PGF and PGE) and defines their response to the upstream hormonal regulators leptin and FSH. Therefore, ASK-1 can be considered a new and important regulator of multiple ovarian functions. This paper describes a new regulator of female reproduction – the intracellular apoptosis signal-regulating kinase 1. It can promote proliferation and alter the release of hormones and the response of porcine ovarian cells to the upstream hormonal regulators leptin and FSH. Therefore, this kinase and its regulators could be a new tool to control multiple ovarian functions. [ABSTRACT FROM AUTHOR]

Background: In the past, the airway epithelium was thought to be primarily an inert physical barrier. We now know that the upper airway epithelium plays a critical role in both innate and adaptive immunity, and that epithelial dysfunction is strongly associated with inflammatory airway disease. The pathogenesis of chronic rhinosinusitis is poorly understood, but growing evidence supports a key role for the airway epithelium in the pathophysiology of the disease. Objective: The purpose of this study is to explore our current understanding of how dysfunction in human sinonasal epithelial cells (HSNECs) contributes to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and to examine how current and developing therapies affect epithelial cell functions. Methods: A literature review of papers published in English pertaining to epithelial cell dysfunction in patients with CRSwNP was performed using the PubMed database. The search utilized combinations of the following key words: sinusitis, polyps, epithelium, pathophysiology, barrier function, dendritic cells, eosinophils, T cells, complement, mucociliary clearance, vitamin D, cytokines, chemokines, taste receptors, steroids, saline, and therapy. Results: HSNEC mucociliary clearance, barrier function, secretion of cytokines, influence on dendritic cells, influence on T-cells, regulation of eosinophils, vitamin D metabolism, complement production, and taste receptor function are altered in patients with CRSwNP and contribute to the pathogenesis of the disease. Current therapies utilized to manage CRSwNP counteract the effects of HSNEC dysfunction and relieve key symptoms of the disease. Conclusion: HSNECs are key players in both innate and adaptive immunity, and altered epithelial functions are closely intertwined with the pathogenesis of CRSwNP. Our review supports further investigation of altered HSNEC function in patients with CRSwNP and supports development of novel epithelial-targeted therapies for its management. [ABSTRACT FROM AUTHOR]

Cell is the structural and functional unit of life. The manipulation of fluids and cells is of vital importance in biotechnology, chemistry and biomedical areas. Microfluidics has provided a relatively simple, low-cost, and cell manipulation method. Different microfluidic technologies offer a variety of functions in the process of cell manipulation process, such as, cell separation, single cell trapping, single cell analysis. In this paper, we review emerging tools enabled by microfluidic technologies for cell manipulation including sorting and single cell trapping, and even single cell characterization. We summarized recent advance in the development of different methods for cell sorting, and single cell isolation. Focus was then put on electric field, mechanical, and fluorescence-based methods for single cell analysis and characterization, as well as the integrated microfluidic devices. We further discussed future commercialization and research prospects, highlight current bottlenecks and provide out perspective on the prospects for microfluidic cell manipulation. • Development of different methods for cell sorting, and single cell isolation are summarized. • Integrated microfluidic devices are highlighted. • Future commercialization, research prospects and current bottlenecks are discussed. [ABSTRACT FROM AUTHOR]

Pre-eclampsia affects 4-5% of pregnancies worldwide and leads to increased maternal and fetal morbidity and mortality.2 Although the exact mechanisms for developing pre-eclampsia are unclear, placental ischaemia is central in its pathogenesis. Furthermore, those patients with SCD who developed pre-eclampsia had a higher proportion with >=1 VOC/year during their pregnancy compared those that did not have pre-eclampsia (78% vs. 48%). In their paper Boudhabhay I et al i . investigate risk factors and consequences of pre-eclampsia on pregnancy outcomes and kidney function in patients with sickle cell disease (SCD).1 They report that pre-eclampsia: (i) was independently associated with higher body mass index, increased haemolysis and >=1 vaso-occlusive crisis (VOC) requiring hospitalisation; (ii) led to poor maternal and neonatal outcomes and (iii) predicted a more rapid decline in kidney function and greater risk of developing chronic kidney disease (CKD) on longitudinal follow-up. [Extracted from the article]

Discrete tissue niches are emerging as essential prerequisites enabling cell communication and function in both homeostasis and disease. In a recent Cell paper, Di Pilato et al. identify a unique dendritic cell-cytotoxic T cell crosstalk within the perivascular space that facilitates T cell survival and proliferation and drives anti-tumor activity. [ABSTRACT FROM AUTHOR]

Microglia are brain resident immune cells with multiple functions. However, little is known about microglia-vascular interactions. In a recent paper published in Nature Communications, Bisht et al. identify a signalling mechanism that attracts and maintains microglia at the capillary wall. Moreover, they show that microglia regulate capillary vascular tone, playing a more significant role in blood flow regulation than previously thought. [ABSTRACT FROM AUTHOR]

The way in which biological cells function is of prime importance, and the determination of such knowledge is highly dependent on probes that can extract information from within the cell. Probing deep inside the cell at high resolutions however is not easy: optical microscopy is limited by fundamental diffraction limits, electron microscopy is not able to maintain spatial resolutions inside a whole cell without slicing the cell into thin sections, and many other new and novel high resolution techniques such as atomic force microscopy (AFM) and near field scanning optical microscopy (NSOM) are essentially surface probes. In this paper we show that microscopy using fast ions has the potential to extract information from inside whole cells in a unique way. This novel fast ion probe utilises the unique characteristic of MeV ion beams, which is the ability to pass through a whole cell while maintaining high spatial resolutions. This paper first addresses the fundamental difference between several types of charged particle probes, more specifically focused beams of electrons and fast ions, as they penetrate organic material. Simulations show that whereas electrons scatter as they penetrate the sample, ions travel in a straight path and therefore maintain spatial resolutions. Also described is a preliminary experiment in which a whole cell is scanned using a low energy (45 keV) helium ion microscope, and the results compared to images obtained using a focused beam of fast (1.2 MeV) helium ions. The results demonstrate the complementarity between imaging using low energy ions, which essentially produce a high resolution image of the cell surface, and high energy ions, which produce an image of the cell interior. The characteristics of the fast ion probe appear to be ideally suited for imaging gold nanoparticles in whole cells. Using scanning transmission ion microscopy (STIM) to image the cell interior, forward scattering transmission ion microscopy (FSTIM) to improve the contrast of the gold nanoparticles, and Rutherford Backscattering Spectrometry (RBS) to determine the depth of the gold nanoparticles in the cell, a 3D visualization of the nanoparticles within the cell can be constructed. Finally a new technique, proton induced fluorescence (PIF), is tested on a cell stained with DAPI, a cell-nucleic acid stain that exhibits a 20-fold increase in fluorescence when binding to DNA. The results indicate that the technique of PIF, although still at an early stage of development, has high potential since there does not seem to be any physical barrier to develop simultaneous structural and fluorescence imaging at sub 10 nm resolutions. [ABSTRACT FROM AUTHOR]

In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell's multi-objective topology formed by temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organize in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly progressing, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organized into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organization, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modeling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterizes the properties and constraints that are consequential to the adaptive dynamics in biological cells. [ABSTRACT FROM AUTHOR]

Several cytoskeleton proteins interact with raft proteins to form raft-cytoskeleton binding protein complexes (RCPCs) that control cell migration and adhesion. The purpose of this paper is to review the latest research on the modes and mechanisms by which a RCPC controls different cellular functions. This paper discusses RCPC composition and its role in cytoskeleton reorganization, as well as the latest developments in molecular mechanisms that regulate cell adhesion and migration under normal conditions. In addition, the role of some external stimuli (such as stress and chemical signals) in this process is further debated, and meanwhile potential mechanisms for RCPC to regulate lipid raft fluidity is proposed. Thus, this review mainly contributes to the understanding of RCPC signal transduction in cells. Additionally, the targeted signal transduction of RCPC and its mechanism connection with cell behaviors will provide a logical basis for the development of unified interventions to combat metastasis related dysfunction and diseases. [ABSTRACT FROM AUTHOR]

Background. Primo vascular system is a new anatomical structure whose research results have reported the possibility of a new circulatory system similar to the blood vascular system and cells. Electrophysiology, which measures and analyzes bioelectrical signals tissues and cells, is an important research area for investigating the function of tissues and cells. The bioelectrical study of the primo vascular system has been reported by using modern techniques since the early 1960s by Bonghan Kim. This paper reviews the research result of the electrophysiological study of the primo vascular system for the discussion of the circulatory function. We hope it would help to study the electrophysiology of the primo vascular system for researchers. This paper will use the following exchangeable expressions: Kyungrak system = Bonghan system = Bonghan circulatory system = primo vascular system = primo system; Bonghan corpuscle = primo node; Bonghan duct = primo vessel. We think that objective descriptions of reviewed papers are more important than unified expressions when citing the papers. That said, this paper will unify the expressions of the primo vascular system. [ABSTRACT FROM AUTHOR]

Copyright of Epistemologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Cell-seeded collagen and fibrin gels represent excellent assays for studying interactions between adherent interstitial cells and the three-dimensional extracellular matrix in which they reside. Over one hundred papers have employed the free-floating collagen gel assay alone since its introduction in 1979 and much has been learned about mechanobiological responses of diverse types of cells. Yet, given that mechanobiology is the study of biological responses by cells to mechanical stimuli that must respect the basic laws of mechanics, we must quantify better the mechanical conditions that are imposed on or arise in cell-seeded gels. In this paper, we suggest that cell responses and associated changes in matrix organization within the classical free-floating gel assay are highly restricted by the mechanics. In particular, many salient but heretofore unexplained or misinterpreted observations in free-floating gels can be understood in terms of apparent cell-mediated residual stress fields that satisfy quasi-static equilibria and continuity of tractions. There is a continuing need, therefore, to bring together the allied fields of mechanobiology and biomechanics as we continue to elucidate cellular function within both native connective tissues and tissue equivalents that are used in basic scientific investigations or regenerative medicine. [Copyright &y& Elsevier]

Recent experimental observations suggest that cells can show relatively precise and reliable responses to external signals even though substantial noise is inevitably involved in the signals. An intriguing question is the way how cells can manage to do it. One possible way to realize such response for a cell is to evolutionary develop and optimize its intra-cellular signaling pathways so as to extract relevant information from the noisy signal. We recently demonstrated that certain intracellular signaling reactions could actually conduct statistically optimal information processing. In this paper, we clarify that such optimal reaction operates near bifurcation point. This result suggests that critical-like phenomena in the single-cell level may be linked to efficient information processing inside a cell. In addition, improving the performance of response in the single-cell level is not the only way for cells to realize reliable response. Another possible strategy is to integrate information of individual cells by cell-to-cell interaction such as quorum sensing. Since cell-to-cell interaction is a common phenomenon, it is equally important to investigate how cells can integrate their information by cell-to-cell interaction to realize efficient information processing in the population level. In this paper, we consider roles and benefits of cell-to-cell interaction by considering integrations of obtained information of individuals with the other cells from the viewpoint of information processing. We also demonstrate that, by introducing cell movement, spatial organizations can spontaneously emerge as a result of efficient responses of the population to external signals. [ABSTRACT FROM AUTHOR]

Fungal biofilm infections have become increasingly recognised as a significant clinical problem. One of the major reasons behind this is the impact that these have upon treatment, as antifungal therapy often fails and surgical intervention is required. This places a large financial burden on health care providers. This paper aims to illustrate the importance of fungal biofilms, particularly Candida albicans, and discusses some of the key fungal biofilm resistance mechanisms that include, extracellular matrix (ECM), efflux pump activity, persisters, cell density, overexpression of drug targets, stress responses, and the general physiology of the cell. The paper demonstrates the multifaceted nature of fungal biofilm resistance, which encompasses some of the newest data and ideas in the field. [ABSTRACT FROM AUTHOR]

This paper describes the effect of increased expression of HO-1 protein and increased levels of HO activity on differentiation of bone-marrow-derived human MSCs. MSCs are multipotent cells that proliferate and differentiate into many different cell types including adipocytes and osteoblasts. HO, the rate-limiting enzyme in heme catabolism, plays an important role during MSCs differentiation. HO catalyzes the stereospecific degradation of heme to biliverdin, with the concurrent release of iron and carbon monoxide. Upregulation of HO-1 expression and increased HO activity are essential for MSC growth and differentiation to the osteoblast lineage consistent with the role of HO-1 in hematopoietic stem cell differentiation. HO-1 participates in the MSC differentiation process shifting the balance of MSC differentiation in favor of the osteoblast lineage by decreasing PPARγ and increasing osteogenic markers such as alkaline phosphatase and BMP-2. In this paper, we define HO-1 as a target molecule in the modulation of adipogenesis and osteogenesis from MSCs and examine the role of the HO system in diabetes, inflammation, osteoporosis, hypertension, and other pathologies, a burgeoning area of research. [ABSTRACT FROM AUTHOR]

Cancer is becoming an increasingly common disease in which abnormal cells aggressively grow, invade, and metastasize. In this paper, we review the biological functions of PEDF (pigmented epithelium-derived factor) against cancer, with a focus on a particular type of bone cancer called osteosarcoma. PEDF is a 50 kDa glycoprotein and is a potent inhibitor of angiogenesis, via its ability to decrease proliferation and migration of endothelial cells. This paper critically examines the anticancer activities of PEDF via its role in antiangiogenesis, apoptosis-mediated tumor suppression, and increased tumor cell differentiation. Recently, an orthotopic model of osteosarcoma was used to show that treatment with PEDF had the greatest impact on metastases, warranting an evaluation of PEDF efficacy in other types of cancers. [ABSTRACT FROM AUTHOR]

In this paper, a novel high-order three-scale (HOTS) computational method is presented to analyze the dynamic thermo-mechanical performance of composite structures with multiple spatial scales. The heterogeneities of composite structures are taken into account by periodic distributions of representative unit cells on the mesoscale and microscale. By virtue of multiscale asymptotic analysis, a new unified micro-meso-macro HOTS approximate solutions are successfully constructed for these multiscale problems. Two classes of auxiliary cell functions are established on the mesoscale and microscale, respectively. Also, two kinds of equivalent material parameters are calculated by up-scaling procedure on the mesoscale and microscale, and the homogenization problems are subsequently defined on global structure. Then, the comparisons of approximate performance are obtained in the pointwise sense for the conventional two-scale solutions, low-order three-scale (LOTS) solutions and HOTS solutions, which illustrate the necessity of developing HOTS solutions for simulating the dynamic thermo-mechanical performances of composite structures with multiple spatial scales. Furthermore, the corresponding HOTS numerical algorithm based on finite element method (FEM) and Finite difference method (FDM) is brought forward in details. Finally, some numerical examples are reported to demonstrate the usability of our HOTS computational method to simulate the dynamic thermo-mechanical behaviors of composite structures with multiple spatial scales. This study offers a unified three-scale computational framework that enables the simulation and analysis of dynamic thermo-mechanical problems of composite structures with multiple spatial scales. [ABSTRACT FROM AUTHOR]

Objectives: The discovery of alternative and well-tolerated anti-arthritic drugs, especially from natural products, is becoming an area of active research. Pedunculoside (PE) is a novel triterpene saponin extracted from the dried bark of Ilex rotunda Thunb. Limited published papers have reported its pharmacological properties, including anti-inflammatory, anti-myocardial ischaemia, anti-liver injury, and hypocholesterolaemic activities. However, the effect of PE on rheumatoid arthritis (RA) remains unknown. Here, we investigated the anti-arthritic effect of PE in both in vitro and in vivo models. Method: The inhibitory effects of PE on proliferation, migration, and production of inflammatory mediators in primary fibroblast-like synoviocytes (FLSs) were examined by a 5-ethynyl-2'-deoxyuridine incorporation assay, wound-healing assay, and real-time polymerase chain reaction, respectively. Cellular signalling mechanisms were analysed by Western blot. The in vivo studies were performed using a collagen-induced arthritis (CIA) rat model. Multiple methods, including arthritis scoring, enzyme-linked immunoassay, radiography, and histopathological assessment, were used to evaluate the therapeutic effects of PE on CIA rats. Results: The in vitro studies revealed that PE significantly inhibited proliferation and migration of FLSs. PE also decreased the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, and tumour necrosis factor-α (TNF-α). Western blot results suggested that PE suppressed TNF-α-stimulated activation of p38 and extracellular signal-regulated kinase. The in vivo studies showed that PE treatment significantly inhibited synovial inflammation and bone destruction in CIA rats. Conclusion: These results demonstrate that PE exerts an inhibitory role in FLSs and CIA rats, and therefore may have therapeutic value for the treatment of RA. [ABSTRACT FROM AUTHOR]

This paper reports on the two‐scale fractal structure of chromatin organization in the nucleus of the HeLa cell. Two neutron scattering methods, small‐angle neutron scattering (SANS) and spin‐echo SANS, are used to unambiguously identify the large‐scale structure as being a logarithmic fractal with the correlation function γ(r) ∼ ln(r/ξ). The smaller‐scale structural level is shown to be a volume fractal with dimension DF = 2.41. By definition, the volume fractal is self‐similar at different scales, while the logarithmic fractal is hierarchically changed upon scaling. As a result, the logarithmic fractal is more compact than the volume fractal but still has a rather high surface area, which provides accessibility at all length scales. Apparently such bi‐fractal chromatin organization is the result of an evolutionary process of optimizing the compactness and accessibility of gene packing. As they are in a water solution, the HeLa nuclei tend to agglomerate over time. The large‐scale logarithmic fractal structure of chromatin provides the HeLa nucleus with the possibility of penetrating deeply into the adjacent nucleus during the agglomeration process. The interpenetration phenomenon of the HeLa nuclei shows that the chromatin‐free space of one nucleus is not negligible but is as large as the volume occupied by chromatin itself. It is speculated that it is the logarithmic fractal architecture of chromatin that provides a comfortable compartment for this most important function of the cell. [ABSTRACT FROM AUTHOR]

Melatonin (N-acetyl-5-methoxytryptamine), secreted by the pineal gland is known to perform multiple functions including, antioxidant, anti-hypertensive, anti-cancerous, immunomodulatory, sedative and tranquilizing functions. Melatonin is also known to be involved in the regulation of body mass index, control the gastrointestinal system and play an important role in cardioprotection, thermoregulation, and reproduction. Recently, several studies have reported the efficacy of Melatonin in treating various pain syndromes. The current paper reviews the studies on Melatonin and its analogs, particularly in Neuropathic pain. Here, we first briefly summarized research in preclinical studies showing the possible mechanisms through which Melatonin and its analogs induce analgesia in Neuropathic pain. Second, we reviewed research indicating the role of Melatonin in attenuating analgesic tolerance. Finally, we discussed the recent studies that reported novel Melatonin agonists, which were proven to be effective in treating Neuropathic pain. [ABSTRACT FROM AUTHOR]

As antimicrobial resistance increases, it is crucial to develop new treatment strategies to counter the emerging threat. In this paper, we consider combination therapies involving conventional antibiotics and debridement, coupled with a novel anti-adhesion therapy, and their use in the treatment of antimicrobial resistant burn wound infections. Our models predict that anti-adhesion–antibiotic–debridement combination therapies can eliminate a bacterial infection in cases where each treatment in isolation would fail. Antibiotics are assumed to have a bactericidal mode of action, killing bacteria, while debridement involves physically cleaning a wound (e.g. with a cloth); removing free bacteria. Anti-adhesion therapy can take a number of forms. Here we consider adhesion inhibitors consisting of polystyrene microbeads chemically coupled to a protein known as multivalent adhesion molecule 7, an adhesin which mediates the initial stages of attachment of many bacterial species to host cells. Adhesion inhibitors competitively inhibit bacteria from binding to host cells, thus rendering them susceptible to removal through debridement. An ordinary differential equation model is developed and the antibiotic-related parameters are fitted against new in vitro data gathered for the present study. The model is used to predict treatment outcomes and to suggest optimal treatment strategies. Our model predicts that anti-adhesion and antibiotic therapies will combine synergistically, producing a combined effect which is often greater than the sum of their individual effects, and that anti-adhesion–antibiotic–debridement combination therapy will be more effective than any of the treatment strategies used in isolation. Further, the use of inhibitors significantly reduces the minimum dose of antibiotics required to eliminate an infection, reducing the chances that bacteria will develop increased resistance. Lastly, we use our model to suggest treatment regimens capable of eliminating bacterial infections within clinically relevant timescales. [ABSTRACT FROM AUTHOR]

The subset of pro-inflammatory B cells, called late memory, tissue-like or double negative (DN), accumulates in the blood of elderly individuals. Here we show that DN B cells do not proliferate and do not make antibodies to influenza antigens, but they secrete antibodies with autoimmune reactivity, in agreement with their membrane phenotype (CD95+CD21-CD11c+) and their spontaneous expression of the transcription factor T-bet. These cells also increase in the blood of individuals with obesity and autoimmune diseases, but causative mechanisms and signaling pathways involved are known only in part. In the present paper we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and the subcutaneous adipose tissue (SAT) of individuals with obesity. Results show that DN B cells from young individuals have minimal metabolic requirements, DN B cells from elderly and obese individuals utilize higher amounts of glucose to perform autoimmune antibody production and enroll in aerobic glycolysis to support their function. DN B cells from the SAT have the highest metabolic requirements as they activate oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. DN B cells from the SAT also show the highest levels of ROS and the highest levels of phosphorylated AMPK (5’-AMP activated kinase) and Sestrin 1, both able to mitigate stress and cell death. This metabolic advantage drives DN B cell survival and function (secretion of autoimmune antibodies). [ABSTRACT FROM AUTHOR]

The conduction of electrical signals through cardiac tissue is essential for maintaining the function of the heart, and conduction abnormalities are known to potentially lead to life-threatening arrhythmias. The properties of cardiac conduction have therefore been the topic of intense study for decades, but a number of questions related to the mechanisms of conduction still remain unresolved. In this paper, we demonstrate how the so-called EMI model may be used to study some of these open questions. In the EMI model, the extracellular space, the cell membrane, the intracellular space and the cell connections are all represented as separate parts of the computational domain, and the model therefore allows for study of local properties that are hard to represent in the classical homogenized bidomain or monodomain models commonly used to study cardiac conduction. We conclude that a non-uniform sodium channel distribution increases the conduction velocity and decreases the time delays over gap junctions of reduced coupling in the EMI model simulations. We also present a theoretical optimal cell length with respect to conduction velocity and consider the possibility of ephaptic coupling (i.e. cell-to-cell coupling through the extracellular potential) acting as an alternative or supporting mechanism to gap junction coupling. We conclude that for a non-uniform distribution of sodium channels and a sufficiently small intercellular distance, ephaptic coupling can influence the dynamics of the sodium channels and potentially provide cell-to-cell coupling when the gap junction connection is absent. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is one of the most common single gene hereditary disease caused by mutation of DMD gene. How to replace the mutated gene has been greatly concerned until now. The continuous progress of gene therapy on DMD has focusing on constructing the micro - dystrophin and choosing a vector to transfer it through the whole body. Adeno - associated virus (AAV) has been widely used in this study because of its less pathogenicity, low immunogenicity and long - term expression in nondividing cells. This paper discussed the research progress of AAV micro - dystrophin gene therapy in DMD from the aspects of construction of AAV micro - dystrophin, animal models and clinical trials. In a conclusion, there is a long way to explore the clinical use of AAV micro - dystrophin on DMD patients, but it probably would be the most potential one we should pay more attention to. [ABSTRACT FROM AUTHOR]

With the increasing amount of digital journal submissions, there is a need to deploy new scalable computational methods to improve information accessibilities. One common task is to identify useful information and named entity from text documents such as journal article submission. However, there are many technical challenges to limit applicability of the general methods and lack of general tools. In this paper, we present domain informational vocabulary extraction (DIVE) project, which aims to enrich digital publications through detection of entity and key informational words and by adding additional annotations. In a first of its kind to our knowledge, our system engages authors of the peer-reviewed articles and the journal publishers by integrating DIVE implementation in the manuscript proofing and publication process. The system implements multiple strategies for biological entity detection, including using regular expression rules, ontology, and a keyword dictionary. These extracted entities are then stored in a database and made accessible through an interactive web application for curation and evaluation by authors. Through the web interface, the authors can make additional annotations and corrections to the current results. The updates can then be used to improve the entity detection in subsequent processed articles in the future. We describe our framework and deployment in details. In a pilot program, we have deployed the first phase of development as a service integrated with the journals Plant Physiology and The Plant cell published by the American Society of Plant Biologists (ASPB). We present usage statistics to date since its production on April 2018. We compare automated recognition results from DIVE with results from author curation and show the service achieved on average 80% recall and 70% precision per article. In contrast, an existing biological entity extraction tool, a biomedical named entity recognizer (ABNER), can only achieve 47% recall and return a much larger candidate set. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Preserving survival and function of beta cells is the logical management of diabetes. • Flavonoids are natural phenolic compounds, which are found in vegetables and fruits. • Flavonoids stimulate survival pathways and inhibit apoptotic signals in beta cells. • Flavonoids preserve the triggering and amplifying pathways of insulin secretion. Abstract Although the currently available antidiabetic medications are effective in managing hyperglycemia, vascular complications are common in diabetic patients. Cohort studies have shown preserved beta cell function has a protective role against the development of diabetic complications. Accordingly, beta cell mass and function are important pharmacological targets in the field of diabetes. Growing number of evidence supports the efficacy of flavonoids (e.g., quercetin, kaempferol, luteolin, and epicatechin) for prevention and attenuation of diabetes consequences. The focus of this paper is to give an overview regarding the effects of flavonoids on pancreatic beta cells. Experiments on insulin-releasing cell lines, isolated pancreatic islets, and diabetic animal models have shown that flavonoids strengthen the survival processes and insulin secretory capacity of beta cells. The proposed mechanisms by which flavonoids preserve beta cells survival (against cytokines, glucotoxicity, and lipotoxicity) include inhibition of NF-κB signaling, activation of PI3K/Akt pathway, inhibition of nitric oxide generation, and decrease of reactive oxygen species levels. Improving mitochondrial bioenergetic function and stimulating pathways of insulin secretion (e.g., PLC/PKC and/or cAMP/PKA signaling) are mechanisms by which flavonoids improve the secretory capacity of beta cells. These beneficial effects of flavonoids are of great importance because may protect beta cells of diabetic patients before dramatic dysfunction and degeneration. [ABSTRACT FROM AUTHOR]

Photovoltaic cells are optoelectronic devices for converting light energy into electrical energy. This work studies the effect of the active layer thickness on the performances of the inverted organic solar cells. The structures of the devices manufactured are Glass/ITO/ZnO NPS/P3HT:PCBM/PEDOT(FO10)/Ag. The active layer based on a blend of poly (3-hexylthiophene) and fullerene with a ratio of 1:0.8 is spin-coating at different speeds in order to obtain different thicknesses. ZnO NPS (30 nm) were used to improve electron transport between ITO and the active layer. PEDOT (F010) (40 nm) were used as a hole transport layer. The commercial ITO used in this study has a sheet resistance of 7 Ω/□ for a thickness of 110 nm. The fabrication and the characterization of the cells as well as the optical properties of materials used and the photovoltaic parameters of the solar cells are reported in the paper. A direct relation between the active layer thickness and efficiency of the inverted organic solar cells is proved. An efficiency of 4.36 % is obtained for 200 nm of P3HT:PCBM. The effect of light intensity and the thermal annealing on the performances of photovoltaic cells are discussed. The characterizations of the cells show that the luminous intensity influences the electrical and optical parameters of organic solar cells [ABSTRACT FROM AUTHOR]

Farnesol, the sesquiterpenoid precursor of insect juvenile hormones (JH) that itself has JH activity, existed already long before animals and their hormones came into being. Although it is omnipresent in all eukaryotes, this molecule remains a "noble unknown" in cell physiology. It is neither documented as a hormone nor as another type of signaling molecule. To date, its function as an intermediate in the synthesis of squalene-cholesterol-steroids in chordates/vertebrates, and of the insect/arthropod JHs, esters of farnesol, in the mevalonate biosynthetic pathway is assumed to be the only one. This assumption neglects that already two decades ago, farnesol has been shown to be a potent endogenous inhibitor of N-type voltage-gated Ca2+ channels in some mammalian cell types. The tandem mevalonate pathway and Ca2+ channels originated early in eukaryotic evolution, and has since been well conserved, "promoting" it as a ubiquitous player in Ca2+ homeostasis in all eukaryotes. This paper accentuates how this drastic change in thinking gained momentum after the discovery by Paroulek and Sláma that the huge amounts of JH I in male accessory glands of the Cecropia moth, are actually synthesized in these glands themselves and not in the corpora allata, the hitherto assumed unique synthesis site of such compounds. In addition, MAG-JHs have no hormonal- but an exocrine function. Here we hypothesize that MAG-JHs may function in protecting the spermatozoa against toxic Ca2+ concentrations, and in enabling their flagellum to undulate. They may do so by acting through membrane receptors. Our novel paradigm assigns to farnesol/JHs a function of flexible hydrophobic molecular valves for restricting untimely Ca2+-passage through some types of canonical Ca2+channels, using covalently bound farnesyl- or geranyl-geranyl group attachment as well as GPCRs-G proteins all containing a prenyl group. The high rotatable bond count, and their horseshoe-shape are instrumental to their valve function. In our paradigm, Met/Tai and Gce, to date generally thought to be the (only) functional (nuclear) receptors for JHs, are classified as probable Ca2+-sensitive transcription factors. Some theoretical and practical considerations for possible applications in a medical context will be discussed. [ABSTRACT FROM AUTHOR]

Ghrelin is a protein hormone secreted from the gastric mucosa, but is also expressed in a variety of tissues. The biological function of ghrelin is widely known, including regulation of food intake, body weight, gastrointestinal, cardiovascular, reproductive, immune functions, cell proliferation and hormone secretion. The growth hormone secretagogue receptor (GHS-R) mediates the effect of ghrelin. Depending on cell type, ghrelin either induces apoptosis or has anti-apoptotic effect. Apoptosis is a physiological process that plays an important role in many biological actions such as proliferation, development or differentiation and regulation of physiological function in many cells. Dysfunction or dysregulation of apoptosis leads to pathology conditions. The action of ghrelin on cell apoptosis is reviewed in this paper. [ABSTRACT FROM AUTHOR]

Metabolic models can estimate intrinsic product yields for microbial factories, but such frameworks struggle to predict cell performance (including product titer or rate) under suboptimal metabolism and complex bioprocess conditions. On the other hand, machine learning, complementary to metabolic modeling necessitates large amounts of data. Building such a database for metabolic engineering designs requires significant manpower and is prone to human errors and bias. We propose an approach to integrate data-driven methods with genome scale metabolic model for assessment of microbial bio-production (yield, titer and rate). Using engineered E. coli as an example, we manually extracted and curated a data set comprising about 1200 experimentally realized cell factories from ~100 papers. We furthermore augmented the key design features (e.g., genetic modifications and bioprocess variables) extracted from literature with additional features derived from running the genome-scale metabolic model iML1515 simulations with constraints that match the experimental data. Then, data augmentation and ensemble learning (e.g., support vector machines, gradient boosted trees, and neural networks in a stacked regressor model) are employed to alleviate the challenges of sparse, non-standardized, and incomplete data sets, while multiple correspondence analysis/principal component analysis are used to rank influential factors on bio-production. The hybrid framework demonstrates a reasonably high cross-validation accuracy for prediction of E.coli factory performance metrics under presumed bioprocess and pathway conditions (Pearson correlation coefficients between 0.8 and 0.93 on new data not seen by the model). [ABSTRACT FROM AUTHOR]

In this paper, we further study the dynamics of the Kyrtsou model composed of heterogeneous nonlinear feedback rules. For various levels and types of underlying nonlinearity, we analyze the resulting time series by means of the largest Lyapunov exponent. Our results highlight that the observed interaction among feedback mechanisms cannot lead to a univocal interpretation of system complexity. [ABSTRACT FROM AUTHOR]

Homeostatic model of assessment (HOMA) is a statistical method for assessing pancreatic β - cell function (HOMA - β) and insulin resistance (HOMA - IR). Both are calculated using fasting plasma glucose (FPG) and insulin but with different formulae. A modified form of HOMA is emerging using Connective Peptide (C - Peptide) concentration, but studies based on this have been very limited. More than 500 research papers have been published about the use of HOMA to assess Diabetes Mellitus (DM) and Cardiovascular Disease (CVD), but the main area of its application is in the field of DM. HOMA - IR has been diagnostically more useful in all types of DM and obesity, in assessing prediabetes and detecting DM in the elderly. It has also been found to be useful during the gestational period. HOMA indices have been widely used along with Glycosylated Hemoglobin (HbA1c), but good standardization is very important for better clinical use of HOMA. This review article has given condensed highlights on the clinical usefulness of HOMA in monitoring the control of DM at various stages using simple formulae to calculate HOMA indices. The parameters used were FPG and insulin. HOMA indices were also compared with other parameters such as HbA1c and two emerging parameters Obstatin and Visfatin, but very few studies have been reported about their clinical usefulness. The contents of this review articles can be very useful for future researchers to expand the application of HOMA indices to the other diseases induced by the uncontrolled DM. [ABSTRACT FROM AUTHOR]

The biological effects of low frequency magnetic fields (LF MF) at high flux densities are well known and the underlying mechanism is established. In contrast, health associated effects at lower flux densities, which can be found in the human environment, are controversial, and no accepted interaction mechanism has been presented. Here we present a hypothesis regarding the biological aspect of interaction between LF MF and cells. We suggest that the endoplasmic reticulum (ER) membrane protein STIM1, which functions as a sensor for several cellular conditions (low Ca2+ levels, temperature increase, increased levels of oxygen radicals, hypoxia), is a candidate LF MF sensor. Such a sensor function can be either direct (via local temperature increase caused by intracellularly induced electric fields), or indirect due to responses to increased reactive oxygen species (ROS) levels. Activated STIM1 leads to downstream effects by activation of signal transduction processes and changes in gene expression leading to secondary events. The nature of these changes would be dependent on both cell type and the particular physiological state the cell displays at the time of STIM1 activation. Results from testing of this hypothesis, as suggested in this paper, would greatly assist in understanding of the possible health-related effects of low-level LF MF. This would benefit both safety assessments regarding MF exposure as well as possible use of MF in medicine. A better understanding of the biological mechanisms underpinning MF exposure effects of living matter allows the targeted use of the fields in medical applications. There are several examples already in use based on empiric and not on mechanistic knowledge. Knowledge generated from our hypothesis testing makes it possible for MF based medical applications to be optimized. [ABSTRACT FROM AUTHOR]

Necrosis in heart muscles can permanently hinder the natural healthy rhythm of heart pumping mechanism. The damaged muscular tissues are replaced by scar tissues and burdens the healthy muscles resulting in further attenuated functioning of heart. Since, human heart muscles cannot regenerate naturally or it has been thought so, pharmacological procedures such as using a heart assist device are followed to restore the lost function of heart. Stem cell engineering and cardiac patches offers promising prospects with their cutting edge research reports. Cardiac patches offers a viable solution as they can also function as an implant to assist in offering the mechanical support the damaged muscles were capable of. Designing cardiac patches to suit multiple functions is not only challenging but also perilous due to the target organ with which it will be interfaced. Sensor based, electrically active, miniaturized circuitry etc., poses a huge threat to the individual in whom the device/patch is implanted. In this paper, we propose a hypothesis on choosing β-PVDF based nanocomposites as the inimitable material for designing implantable cardiac patches. β-PVDF based nanocomposite materials is expected to exhibit piezoelectric effect and contribute to the adherence, proliferation and maturation of stem cells. Physico-chemical characterizations followed by in vitro cell line studies were performed in ought to confirm the same. The results revealed that the β-PVDF based nanocomposite material was mechanically stable and supportive in cardiomyocyte adherence and differentiation when compared to standard non piezoelectric scaffolds (control). Hence, an implantable β-PVDF based novel electrospun nanocomposite scaffold is hypothesized to be the hour of need in conjugation with stem cell engineering for repairing damaged heart muscles. [ABSTRACT FROM AUTHOR]

The prevalence of adult and childhood obesity are increasing. Most of the human newborn's body fat accumulates in the last half of intrauterine life. Fat in the fetus was thought to be mostly synthesized from glucose, but now it is commonly accepted that the bulk of it is the product of placental transfer of maternal fatty acids. Transported fatty acids originate in maternal plasma "free" fatty acids, fatty acids hydrolyzed from maternal plasma triglycerides, and the poly-unsaturated fatty acid component of maternal phospholipids. Glucose remains an important precursor of alpha-glycerol phosphate, to which most transported fatty acids are eventually esterified. Maternal plasma lipids are elevated in late pregnancy and even more in obese and diabetic pregnant women. This accelerates the placental transport of fatty acids. The hypothesis presented in this paper rests on the observations that the exponential increase in fat tissue in the human embryo's body occurs in time to parallel the increase of lipids in the mother's blood and depends on the chemical affinity of the transcription factor PPAR gamma to fatty acids and on fatty acid stimulation of adipocyte generation from precursor cells. The hypothesis asserts that transported maternal fatty acids activate the transcription factors in the fetus and initiate conversion of the mesenchymal stem cells into adipocytes. In obese and diabetic mothers, the higher plasma lipids facilitate increased placental fatty acid transfer. This will increase adipocyte generation and, through this, the prevalence of babies with increased fat cell size and number. Babies born with increased adipose tissue cellularity will have greater probability of growing up to become obese adolescents and adults. These newborns, whose obesity is hyperplastic as well as hypertrophic, as adults will have difficulty losing weight through diet and exercise or will regain the lost weight more quickly than others without these characteristics. Accordingly, increased placental fatty acid transfer and accelerated adipocyte generation may explain not only neonatal obesity, but some aspects of the adult obesity epidemic also. It is therefore recommended that prevention of fetal fat cell hyperplasia, by lowering maternal plasma lipids in mid and late pregnancy, should be attempted in pregnancies at risk for macrosomia. [ABSTRACT FROM AUTHOR]

Members of the large superclass of P-loop GTPases share a core domain with a conserved three-dimensional structure. In eukaryotes, these proteins are implicated in various crucial cellular processes, including translation, membrane trajficking, cell cycle progression, and membrane signaling. As targets of mutation and toxins, GTPases are involved in the pathogenesis of cancer and infectious diseases. In prokaryotes also, it is hard to overestimate the importance of GTPases in cell physiology. Numerous papers have shed new light on the role of bacterial GTPases in cell cycle regulation, ribosome assembly, the stress response, and other cellular processes. Moreover, bacterial GTPases have been identified as high-potential drug targets. A key paper published over 2 decades ago stated that, "It may never again be possible to capture [GTPases] in a family portrait" (H. R. Bourne, D. A. Sanders, and F. McCormick, Nature 348:125-132, 1990), and indeed, the last 20 years have seen a tremendous increase in publications on the subject. Sequence analysis identified 13 bacterial GTPases that are con- served in at least 75% of all bacterial species. We here provide an overview of these 13 protein subfamifies, covering their cellular functions as well as cellular localization and expression levels, three-dimensional structures, biochemical properties, and gene organization. Conserved roles in eukaryotic homologs will be discussed as well. A comprehensive overview summarizing current knowledge on prokalyotic GTPases will aid in further elucidating the function of these important proteins. [ABSTRACT FROM AUTHOR]

Survival of mammalian cells is achieved by tight control of cell volume, while transmembrane potential has been known to control many cellular functions since the seminal work of Hodgkin and Huxley. Regulation of cell volume and transmembrane potential have a wide range of implications in physiology, from neurological and cardiac disorders to cancer and muscle fatigue. Therefore, understanding the relationship between transmembrane potential, ion fluxes, and cell volume regulation has become of great interest. In this paper we derive a system of differential equations that links transmembrane potential, ionic concentrations, and cell volume. In particular, we describe the dynamics of the cell within a few seconds after an osmotic stress, which cannot be done by the previous models in which either cell volume was constant or osmotic regulation instantaneous. This new model demonstrates that both membrane potential and cell volume stabilization occur within tens of seconds of changes in extracellular osmotic pressure. When the extracellular osmotic pressure is constant, the cell volume varies as a function of transmembrane potential and ion fluxes, thus providing an implicit link between transmembrane potential and cell volume. Experimental data provide results that corroborate the numerical simulations of the model in terms of time-related changes in cell volume and dynamics of the phenomena. This paper can be seen as a generalization of previous electrophysiological results, since under restrictive conditions they can be derived from our model. [ABSTRACT FROM AUTHOR]

A growing number of laboratory and clinical studies over the past 10 years have shown that low-level laser stimulation (633 or 670 nm) at extremely low power densities (about 0.15 mW/cm(2)), when administered through a particular emission mode, is capable of eliciting significant biological effects. Studies on cell cultures and animal models as well as clinical trials give support to a novel therapeutic modality, which may be referred to as ultra low level laser therapy (ULLLT). In cultured neural cells, pulsed irradiation (670 nm, 0.45 mJ/cm(2)) has shown to stimulate NGF-induced neurite elongation and to protect cells against oxidative stress. In rats, anti-edema and anti-hyperalgesia effects following ULLL irradiation were found. Clinical studies have reported beneficial effects (also revealed through sonography) in the treatment of musculoskeletal disorders. The present paper reviews the existing experimental evidence available on ULLLT. Furthermore, the puzzling issue of the biophysical mechanisms that lie at the basis of the method is explored and some hypotheses are proposed. Besides presenting the state-of-the-art about this novel photobiostimulation therapy, the present paper aims to open up an interdisciplinary discussion and stimulate new research on this subject. [ABSTRACT FROM AUTHOR]

Motivation Transcriptomics and proteomics data have been integrated into constraint-based models to influence flux predictions. However, it has been reported recently for Escherichia coli and Saccharomyces cerevisiae, that model predictions from parsimonious flux balance analysis (pFBA), which does not use expression data, are as good or better than predictions from various algorithms that integrate transcriptomics or proteomics data into constraint-based models. Results In this paper, we describe a novel constraint-based method called Linear Bound Flux Balance Analysis (LBFBA), which uses expression data (either transcriptomic or proteomic) to predict metabolic fluxes. The method uses expression data to place soft constraints on individual fluxes, which can be violated. Parameters in the soft constraints are first estimated from a training expression and flux dataset before being used to predict fluxes from expression data in other conditions. We applied LBFBA to E.coli and S.cerevisiae datasets and found that LBFBA predictions were more accurate than pFBA predictions, with average normalized errors roughly half of those from pFBA. For the first time, we demonstrate a computational method that integrates expression data into constraint-based models and improves quantitative flux predictions over pFBA. Availability and implementation Code is available in the Supplementary data available at Bioinformatics online. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Osteogenic differentiation of cells has considerable clinical significance in bone defect treatment, and cell behavior is linked to extracellular matrix stiffness. This study aimed to determine how matrix stiffness affects cell morphology and subsequently regulates the osteogenic phenotype of osteogenesis precursor cells. Four PDMS substrates were prepared with stiffness corresponding to the elastic modulus ranging from 0.6 MPa to 2.7 MPa by altering the Sylgard 527 and Sylgard 184 concentrations. MC3T3-E1 cells were cultured on the matrices. Cell morphology, vinculin expression, and key osteogenic markers, Col I, OCN, OPN, and calcium nodule, were examined. The activity and expression level of Yes-associated protein (YAP) were evaluated. Results showed that cell spreading exhibited no correlation with the stiffness of matrix designed in this paper, but substratum stiffness did modulate MC3T3-E1 osteogenic differentiation. Col I, OPN, and OCN proteins were significantly increased in cells cultured on soft matrices compared with stiff matrices. Additionally, cells cultured on the 1:3 ratio matrices had more nodules than those on other matrices. Accordingly, cells on substrates with low stiffness showed enhanced expression of the osteogenic markers. Meanwhile, YAP expression was downregulated on soft substrates although the subcellular location was not affected. Our results provide evidence that matrix stiffness (elastic modulus ranging from 0.6 MPa to 2.7 MPa) affects the osteogenic differentiation of MC3T3-E1, but it is not that “the stiffer, the better” as showed in some of the previous studies. The optimal substrate stiffness may exist to promote osteoblast differentiation. Cell differentiation triggered by the changes in substrate stiffness may be independent of the YAP signal. This study has important implications for biomaterial design and stem cell-based tissue engineering. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Upon investigation, it was discovered that 5 figures contain fabrication. Figures 1C, 3D, 5C, 5D, and 6G contain manipulated and/or duplicated data. The authors requested a corrigendum be published, however, due to the large number of corrections applied (figures 3, 6, 7, 8 and S3), it cannot be concluded that these changes would not alter the conclusions of the paper. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. [ABSTRACT FROM AUTHOR]