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The theme of the 2022 symposium was 'Cell Diversity in the Cardiovascular System, cell-autonomous and cell-cell signalling'. Keywords: cardiovascular physiology; cell diversity; ion channels; vascular smooth muscle EN cardiovascular physiology cell diversity ion channels vascular smooth muscle 2543 2544 2 07/04/23 20230701 NES 230701 This paper is based on the most recent UC Davis Cardiovascular Research Symposium on Systems Approach to Understanding Cardiovascular Disease and Arrhythmia. Cardiovascular physiology, ion channels, vascular smooth muscle, cell diversity. [Extracted from the article]

The article presents abstracts on medical topics which include the use of cytohistology to increase diagnostic accuracy of atypical glandular cells in cervical cytology, the usability of diagnostic markers to predict progression of cervical dysplasia, and the clinical importance of ASC-H in non menopausal, perimenopausal and postmenopausal women.

The efficiency of antimony selenide (Sb2Se3) solar cells is still limited by significant interface and deep‐level defects, in addition to carrier recombination at the back contact surface. This paper investigates the use of lithium (Li) ions as dopant for Sb2Se3 films, using lithium hydroxide (LiOH) as a dopant medium. Surprisingly, the LiOH solution not only reacts at the back surface of the Sb2Se3 film but also penetrate inside the film along the (Sb4Se6)n molecular chain. First, the Li ions modify the grain boundary's carrier type and create an electric field between p‐type grain interiors and n‐type grain boundary. Second, a gradient band structure is formed along the vertical direction with the diffusion of Li ions. Third, carrier collection and transport are improved at the surface between Sb2Se3 and the Au layer due to the reaction between the film and alkaline solution. Additionally, the diffusion of Li ions increases the crystallinity, orientation, surface evenness, and optical electricity. Ultimately, the efficiency of Sb2Se3 solar cells is improved to 7.57% due to the enhanced carrier extraction, transport, and collection, as well as the reduction of carrier recombination and deep defect density. This efficiency is also a record for CdS/Sb2Se3 solar cells fabricated by rapid thermal evaporation. [ABSTRACT FROM AUTHOR]

Collapsibility is a practical and useful technique for dimension reduction in multidimensional contingency tables. In this paper, we consider marginal log‐linear models for studying collapsibility and related aspects in such tables. These models generalize ordinary log‐linear and multivariate logistic models, besides several others. First, we obtain some characteristic properties of marginal log‐linear parameters. Then we define collapsibility and strict collapsibility of these parameters in a general sense. Several necessary and sufficient conditions for collapsibility and strict collapsibility are derived based on simple functions of only the cell probabilities, which are easily verifiable. These include results for an arbitrary set of marginal log‐linear parameters having some common effects. The connections of strict collapsibility to various forms of independence of the variables are explored. We analyze some real‐life datasets to illustrate the above results on collapsibility and strict collapsibility. Finally, we obtain a result relating parameters with the same effect, but different margins for an arbitrary table, and demonstrate smoothness of marginal log‐linear models under collapsibility conditions. [ABSTRACT FROM AUTHOR]

Objective: This narrative review illuminates on the application of single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics (ST) in periodontitis and highlights the probability of relating cell population and gene signatures to the pathogenesis of the disease for a better diagnosis. Methods: An electronic search of the literature in the PubMed database for the keywords, "single cell sequencing" OR "spatial transcriptomics" and "periodontitis" OR "gingiva" OR "oral mucosa" yielded 486 research articles and reviews. After filtering duplicates and careful curation, 22 papers conducted in humans were retained. Results: The molecular mechanisms underlying periodontitis are complex and involve the interaction of multiple cells and various gene expressions. Most residing cells in periodontal tissues participate in maintaining homeostasis and health, while in addition to infiltrating immune cells contribute to the fight against the bacterial insult. Conclusion: scRNA‐seq and ST have provided new insights into the cellular and molecular changes associated with periodontitis for a better diagnosis and clinical outcome. New functions of cells and genes are revealed with these techniques; however, no cells or gene signatures are attributed to periodontitis so far. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is one of the life‐threatening diseases of the digestive system. MicroRNA has been asserted to be a regulator of AP. This paper explored the miR‐374a‐5p expression in AP patients and investigated the efficacy of AR42J cells. In this study, 60 healthy people, 58 MAP patients and 58 SAP patients were included, and the serum miR‐374a‐5p levels of the subjects were detected by RT‐qPCR technology. The pancreatitis cell model was structured by stimulating AR42J cells with cerulein. Next, cell viability and apoptosis were detected by CCK‐8 assay and flow cytometry. ELISA was used to measure the concentration of cytokines, such as TNF‐α, IL‐6, and IL‐1β. The data showed that miR‐374a‐5p was downregulated in samples from AP patients, while showing discriminative power for AP populations. Attenuated miR‐374a‐5p were negatively bound up with patients' Ranson score and APACHE II score. Besides, miR‐374a‐5p was declined in cerulein‐treated AR42J cells and forced elevation of miR‐374a‐5p was beneficial to increase cell viability, and inhibit cell apoptosis and inflammation. The present study found that miR‐374a‐5p was reduced in AP serum samples, and up‐regulated expression level of miR‐374a‐5p in cell models had a protective effect on cerulein‐induced inhibition of cell function and inflammatory response. [ABSTRACT FROM AUTHOR]

In addition to being an important intermediate in the TCA cycle, L‐malate is also widely used in the chemical and beverage industries. Due to the resulting high demand, numerous studies investigated chemical methods to synthesize L‐malate from petrochemical resources, but such approaches are hampered by complex downstream processing and environmental pollution. Accordingly, there is an urgent need to develop microbial methods for environmentally‐friendly and economical L‐malate biosynthesis. The rapid progress and understanding of DNA manipulation, cell physiology, and cell metabolism can improve industrial L‐malate biosynthesis by applying intelligent biochemical strategies and advanced synthetic biology tools. In this paper, we mainly focused on biotechnological approaches for enhancing L‐malate synthesis, encompassing the microbial chassis, substrate utilization, synthesis pathway, fermentation regulation, and industrial application. This review emphasizes the application of novel metabolic engineering strategies and synthetic biology tools combined with a deep understanding of microbial physiology to improve industrial L‐malate biosynthesis in the future. [ABSTRACT FROM AUTHOR]

The capability to design and manufacture metal lattice structures is today one of the most promising targets of powder bed fusion technologies. Not only additively manufactured lattices offer great lightweighting possibilities but they also open the way to tailored and graded mechanical response. To best capitalize on this opportunity, research effort is first needed to assess the feasibility of reticular structures and to quantify the expected deviations from the nominal geometry, as a function of the cell topology and dimensions. Notwithstanding the inherent suitability of additive processes to complex shapes, this paper proposes a more exact definition of the technological boundaries for body‐centered cubic lattices, showing to what extent specific dimensional ratios, as well as a self‐supporting cell structure, can be favorable to minimize the deviation from the nominal reticulum in terms of dimensions, density, and presence of defects. [ABSTRACT FROM AUTHOR]

Living organisms experience a range of stresses. To cope effectively with these stresses, eukaryotic cells have evolved a sophisticated mechanism involving the formation of stress granules (SGs), which play a crucial role in protecting various types of RNA species under stress, such as mRNAs and long non‐coding RNAs (lncRNAs). SGs are non‐membranous cytoplasmic ribonucleoprotein (RNP) granules, and the RNAs they contain are translationally stalled. Importantly, SGs have been thought to contribute to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). SGs also contain multiple RNA‐binding proteins (RBPs), several of which have been implicated in AD progression. SGs are transient structures that dissipate after stress relief. However, the chronic stresses associated with aging lead to the persistent formation of SGs and subsequently to solid‐like pathological SGs, which could impair cellular RNA metabolism and also act as a nidus for the aberrant aggregation of AD‐associated proteins. In this paper, we provide a comprehensive summary of the physical basis of SG‐enriched RNAs and SG‐resident RBPs. We then review the characteristics of AD‐associated gene transcripts and their similarity to the SG‐enriched RNAs. Furthermore, we summarize and discuss the functional implications of SGs in neuronal RNA metabolism and the aberrant aggregation of AD‐associated proteins mediated by SG‐resident RBPs in the context of AD pathogenesis. Geriatr Gerontol Int 2024; 24: 7–14. [ABSTRACT FROM AUTHOR]

This paper reviews provenance, processing and properties of rooibos (Aspalathus linearis, Brum.f) and its numerous biologically active constituents, as well as the currently available knowledge concerning their physiological and medicinal effects and their possible extra‐ and intracellular mechanisms of action. Search for literature was performed in agreement with the preferred reporting items for systematic review criteria in Cochrane Library, PubMed, Web of Science and SCOPUS databases between the years 2000 and 2021. The limited number of in vitro studies suggests an influence of rooibos on basic ovarian cell functions, as well as its potential applicability to control female reproduction and prevent the effect of environmental contaminants on ovarian functions. Nevertheless, further studies are required for better understanding of the character and mechanisms of action, as well as of rooibos' application in reproductive biology and medicine. [ABSTRACT FROM AUTHOR]

Aim: Endometriosis is a chronic disease of reproductive age, associated with pelvic pain and infertility. Endometriotic cells adapt to changing environments such as oxidative stress and hypoxia in order to survive. However, the underlying mechanisms remain to be fully elucidated. In this review, we summarize our current understanding of the pathogenesis of endometriosis, focusing primarily on the molecular basis of energy metabolism, redox homeostasis, and mitochondrial function, and discuss perspectives on future research directions. Methods: Papers published up to March 31, 2023 in the PubMed and Google Scholar databases were included in this narrative literature review. Results: Mitochondria serve as a central hub sensing a multitude of physiological processes, including energy production and cellular redox homeostasis. Under hypoxia, endometriotic cells favor glycolysis and actively produce pyruvate, nicotinamide adenine dinucleotide phosphate (NADPH), and other metabolites for cell proliferation. Mitochondrial fission and fusion dynamics may regulate the phenotypic plasticity of cellular energy metabolism, that is, aerobic glycolysis or OXPHOS. Endometriotic cells have been reported to have reduced mitochondrial numbers, increased lamellar cristae, improved energy efficiency, and enhanced cell proliferation and survival. Increased mitochondrial fission and fusion turnover by hypoxic and normoxic conditions suggests an activation of mitochondrial quality control mechanisms. Recently, candidate molecules that influence mitochondrial dynamics have begun to be identified. Conclusion: This review suggests that unique energy metabolism and redox homeostasis driven by mitochondrial dynamics may be linked to the pathophysiology of endometriosis. However, further studies are needed to elucidate the regulatory mechanisms of mitochondrial dynamics in endometriosis. [ABSTRACT FROM AUTHOR]

Cellular therapy nowadays includes various products from haematopoietic stem cells (HSC) collected from bone marrow, peripheral blood, and umbilical cord blood to more complex adoptive immune therapy for the treatment of malignant diseases, and gene therapy for inherited immune deficiencies. Broader utilization of cellular therapy requires extensive quality testing of these products that should fulfil the same requirements regarding composition, purity, and potency nevertheless they are manufactured in various centres. Technical improvements of the flow cytometers accompanied by the increased number of available reagents and fluorochromes used to conjugate monoclonal antibodies, enable detailed and precise insight into the function of the immune system and other areas of cell biology, and allows cell evaluation based on size, shape, and morphology or assessment of cell surface markers, as well as cell purity and viability, which greatly contributes to the development and progress of the cell therapy. The aim of this paper is to give an overview of the current use and challenges of flow cytometry analysis in quality assessment of cellular therapy products, with regard to basic principles of determining HSC and leukocyte subpopulation, assessment of cells viability and quality of thawed cryopreserved HSC as well as the importance of validation and quality control of flow cytometry methods according to good laboratory practice. [ABSTRACT FROM AUTHOR]

CDC42 is a member of the Rho‐GTPase family and is involved in a variety of cellular functions including regulation of cell cycle progression, constitution of the actin backbone and membrane transport. In particular, CDC42 plays a key role in the establishment of polarity in female vertebrate oocytes, and essential to this major regulatory role is its local occupation of specific regions of the cell to ensure that the contractile ring is assembled at the right time and place to ensure proper gametogenesis. The multifactor controlled 'inactivation‐activation' process of CDC42 also allows it to play an important role in the multilevel signalling network, and the synergistic regulation of multiple genes ensures maximum precision during gametogenesis. The purpose of this paper is to review the role of CDC42 in the control of gametogenesis and to explore its related mechanisms, with the aim of further understanding the great research potential of CDC42 in female vertebrate germ cells and its future clinical translation. [ABSTRACT FROM AUTHOR]

The article cites key findings from various research papers presented during the international "Mechanisms of Exocytosis 2008" meeting at the Slovenian Academy of Sciences and Arts in Ljubljana, Slovenia from May 22 to 25, 2008. It includes an in-depth analysis of various issues relevant to the physiological process of exocytosis that are discussed by the research papers including intracellular messengers and exocytosis, molecular mechanisms of exocytosis and vesicle dynamics and cell types. Also cited are various leading scientists in the field who presented their research studies during the event.

Patient‐derived organoids (PDOs) are emerging as powerful models to capture the genetic heterogeneity of human tumors. However, the self‐assembling nature of PDOs limits their use in studies of the impact of microenvironmental heterogeneity on tumor cell function. Here, a paper‐based model, the Tissue Roll for Analysis of Cellular Environment and Response (TRACER) is adapted, using patterned polymer infiltration, to enable controlled assembly and disassembly of organoid structures to study the impact of both genetic and microenvironmental heterogeneity on tumor cell behavior. In the adapted platform (TRACER2), pancreatic cancer PDOs establish oxygen gradients across the tissue and in response exhibit graded cell viability, proliferation, hypoxia‐response gene transcription, and response to gemcitabine therapy. Further, PDOs retrieved from the hypoxic regions of the TRACER2 cultures show graded transcriptional changes in immunosuppression‐related genes and upon co‐culture, after TRACER2 disassembly, induce graded functional changes in Jurkat cells and macrophage cells. Therefore, TRACER2 offers a novel platform to dissect the effects of microenvironmental parameters on tumor cell function. [ABSTRACT FROM AUTHOR]

Microglia play a vital role in maintaining brain homeostasis. Their continuous sensing of surrounding micro‐environments is crucial for their activity. Cross talk between specific neurons and microglia might occur through specific neurotransmitter receptors on microglia. Impairment with this interaction might result in pathological activity of microglia against potential insults. The reason for this activity in many neurodegenerative diseases such as Alzheimer's disease (AD) is not known. However, several papers report of the effects of different neurotransmitter agonists on microglial cells function that relate to their activity in AD. This review aims to summarize those works and to raise potential fundamental questions for future research. [ABSTRACT FROM AUTHOR]

This paper aims to emphasize the importance of applying international consensus guidelines to detect qualitative and quantitative abnormalities of megakaryocytes on smears of bone marrow aspirates (BMA) for a shared and harmonized diagnostic path between different laboratories. Careful evaluation of megakaryocytes on BMA smears represents a cornerstone in the diagnosis of most clonal and nonclonal hematological diseases. Images associated with the detailed morphologic description of normal, reactive, abnormal, and dysplastic megakaryocytes are also reported together with examples of similar cells that, if not promptly identified, can lead to a morphological misdiagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Immune cell function assay (ICFA) and CD3 lymphocyte counts have been considered to be useful in discerning the overall intensity of immunosuppression in pediatric orthotopic heart transplant (OHT) recipients. Methods: The aim of this retrospective analysis was to evaluate trends of ICFA and CD3 lymphocyte counts and their association with adverse outcomes post‐OHT. Results: A total of 381 ICFA and 493 CD3 laboratory values obtained in 78 patients within six months post‐OHT were analyzed. There were 14 patients treated for biopsy‐proven acute rejection, four of whom had ISHLT grade 2R/3A rejection. In patients with rejection versus those without, CD3 and ICFA values were 122 (IQR 74.5–308) cells/mm2 and 224.5 (IQR 132–343.5) ng/ml compared to 231.8 (IQR 68–421) cells/m2 and 191 (IQR 81.5–333) ng/mL (p = NS for both). Twenty‐six patients had at least one detectable cytomegalovirus or Epstein‐Barr virus DNAemia within the study timeframe. In patients with viremia versus those without, CD3 and ICFA values were 278.5 (IQR 68–552) cells/mm2 and 130 (IQR 48–284) ng/ml compared to 195 (IQR 74.5–402.5) cells/mm2 and 212 (IQR 89–342) ng/ml (p = NS for both). Conclusions: No association was found between these immune markers and adverse outcomes. In the absence of larger pediatric studies justifying the role of these tests in identifying elevated risk profiles post OHT, we do not recommend their routine use. [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]

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]

In multicellular organisms, stem cells are impacted by microenvironmental resources such as nutrient availability and oxygen tension for their survival, growth, and differentiation. However, the accessibility of these resources in the pericellular environment greatly varies from organ to organ. This divergence in resource availability leads to variations in the potency and differentiation potential of stem cells. This study aimed to explore the distinct effects of glucose and fructose, as well as different oxygen tensions, on the growth dynamics, cytokine production, and differentiation of stem cells. We showed that replacing glucose with fructose subjected stem cells to stress, resulting in increased Hif1α expression and stability, which in turn led to a reduction in cell proliferation, and alterations in cytokine production. However, fructose failed to induce differentiation of human mesenchymal stem cells (hMSCs) as well as mouse fibroblasts into mature adipocytes compared to glucose, despite the upregulation of key markers of adipogenesis, including C/EBPβ, and PPARγ. Conversely, we showed that fructose induced undifferentiated mouse fibroblasts to release cytokines associated with senescence, including IL1α1, IL6, IL8, MCP1, and TNF1α, suggesting that these cells were undergoing lipolysis. Taken together, our results suggest that altering the culture conditions through changes in hexose levels and oxygen tension places considerable stress on stem cells. Additional research is required to further characterize the mechanisms governing stem cell response to their microenvironments. [ABSTRACT FROM AUTHOR]

Adapted immune cells are known to develop memory functions that increase resistance to subsequent infections after initial pathogen exposure, however, it is unclear whether non‐immune cells, like tissue‐resident stem cells, have similar memory functions. Here, it is found that tissue‐resident stem cells crucial for tissue regeneration show diminished adverse effects on diverse stem cell functions against successive exposure to foreign antigen (β‐glucan) to maintain tissue homeostasis and stability both in vitro and in vivo. These data suggest that endometrial stem cells may possess a robust memory function, in contrast, fully differentiated cells like fibroblasts and vesicular cells do not show these memory mechanisms upon consecutive antigen exposure. Moreover, the pivotal role of Angiopoietin‐like 4 (ANGPTL4) in regulating the memory functions of endometrial stem cells is identified through specific shRNA knockdown in vitro and knockout mice in vivo experiments. ANGPTL4 is associated with the alteration of diverse stem cell functions and epigenetic modifications, notably through histone H3 methylation changes and two pathways (i.e., PI3K/Akt and FAK/ERK1/2 signaling) upon consecutive antigen exposure. These findings imply the existence of inherent self‐defense mechanisms through which local stem cells can adapt and protect themselves from recurrent antigenic challenges, ultimately mitigating adverse consequences. [ABSTRACT FROM AUTHOR]

Objective: Unique metabolic requirements accompany the development and functional fates of immune cells. How cellular metabolism is important in natural killer (NK) cells and their memory‐like differentiation in bacterial infections remains elusive. Methods: Here, we utilise our established NK cell memory assay to investigate the metabolic requirement for memory‐like NK cell formation and function in response to the Gram‐negative intracellular bacteria Burkholderia pseudomallei (BP), the causative agent of melioidosis. Results: We demonstrate that CD160+ memory‐like NK cells upon BP stimulation upregulate glucose and amino acid transporters in a cohort of recovered melioidosis patients which is maintained at least 3‐month post‐hospital admission. Using an in vitro assay, human BP‐specific CD160+ memory‐like NK cells show metabolic priming including increased expression of glucose and amino acid transporters with elevated glucose uptake, increased mTOR activation and mitochondrial membrane potential upon BP re‐stimulation. Antigen‐specific and cytokine‐induced IFN‐γ production of this memory‐like NK cell subset are highly dependent on oxidative phosphorylation (OXPHOS) with some dependency on glycolysis, whereas the formation of CD160+ memory‐like NK cells in vitro is dependent on fatty acid oxidation and OXPHOS and further increased by metformin. Conclusion: This study reveals the link between metabolism and cellular function of memory‐like NK cells, which can be exploited for vaccine design and for monitoring protection against Gram‐negative bacterial infection. [ABSTRACT FROM AUTHOR]

Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is a critical regulator of the particularly autophagic degradation of ferritin, a process known as ferritinophagy. Mechanistically, NCOA4‐mediated ferritinophagy performs an increasingly vital role in the maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release as needed. Ferritinophagy is not only involved in iron‐dependent responses but also in the pathogenesis and progression of various human diseases, including metabolism‐related, neurodegenerative, cardiovascular and infectious diseases. Therefore, ferritinophagy is of great importance in maintaining cell viability and function and represents a potential therapeutic target. Recent studies indicated that ferritinophagy regulates the signalling pathway associated with ferroptosis, a newly discovered type of cell death characterised by iron‐dependent lipid peroxidation. Although accumulating evidence clearly demonstrates the importance of the interplay between dysfunction in iron metabolism and ferroptosis, a deeper understanding of the double‐edged sword effect of ferritinophagy in ferroptosis has remained elusive. Details of the mechanisms underlying the ferritinophagy–ferroptosis axis in regulating relevant human diseases remain to be elucidated. In this review, we discuss the latest research findings regarding the mechanisms that regulate the biological function of NCOA4‐mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. The important role of the ferritinophagy–ferroptosis axis in human diseases will be discussed in detail, highlighting the great potential of targeting ferritinophagy in the treatment of diseases. [ABSTRACT FROM AUTHOR]

Autophagy is a self‐recycling machinery to maintain cellular homeostasis by degrading harmful materials in the cell. Autophagy‐related gene 5 (Atg5) is required for autophagosome maturation. However, the role of Atg5 in tumorigenesis under autophagy deficient conditions remains unclear. This study focused on the autophagy‐independent role of Atg5 and the underlying mechanism in tumorigenesis. We demonstrated that knockout of autophagy‐related genes including Atg5, Atg7, Atg9, and p62 in mouse embryonic fibroblast (MEF) cells consistently decreased cell proliferation and motility, implying that autophagy is required to maintain diverse cellular functions. An Atg7 knockout MEF (Atg7−/− MEF) cell line representing deprivation of autophagy function was used to clarify the role of Atg5 transgene in tumorigenesis. We found that Atg5‐overexpressed Atg7−/‐MEF (clone A) showed increased cell proliferation, colony formation, and migration under autophagy deficient conditions. Accordingly, rescuing the autophagy deficiency of clone A by overexpression of Atg7 gene shifts the role of Atg5 from pro‐tumor to anti‐tumor status, indicating the dual role of Atg5 in tumorigenesis. Notably, the xenograft mouse model showed that clone A of Atg5‐overexpressed Atg7−/− MEF cells induced temporal tumor formation, but could not prolong further tumor growth. Finally, biomechanical analysis disclosed increased Wnt5a secretion and p‐JNK expression along with decreased β‐catenin expression. In summary, Atg5 functions as a tumor suppressor to protect the cell under normal conditions. In contrast, Atg5 shifts to a pro‐tumor status under autophagy deprivation conditions. [ABSTRACT FROM AUTHOR]

Introduces articles that focus on the application of microscopic techniques for the analysis of immune cell development and function. Technologies that enable investigators to visualize cognate interactions during immune cell development and activation; Determination of the biochemical events in single cells; Applications and topics which contribute to the understanding of immune system responses.

Abstract: The purpose of this review is to present an update of the main mechanisms involved in the physiological regulation of contraction and relaxation of the human umbilical artery (HUA) smooth muscle cells. A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the regulation of the HUA are presented in this article. The vascular smooth muscle is a highly specialized structure, whose main function is to regulate the vascular tonus. This is controlled by a balance between the cellular signaling pathways that mediate contraction and relaxation. The cells responsible for the contractile property of this muscle are the smooth muscle cells (SMC), and an excellent source of these cells is the HUA, involved in fetoplacental circulation. Since the umbilical blood vessels are not innervated, the HUA tonus is modulated by vasoactive substances that regulate the contractile process. The main vasoactive substances that induce contraction are serotonin, histamine, thromboxane, bradykinin, endothelin 1 and prostaglandin F2α, that are linked to the activation of proteins Gq and Gi/0. On the other hand, the main vasorelaxation mechanisms are the activation of adenyl and guanil cyclases, potassium channels and the inhibition of calcium channels. The SMC from the HUA allow the study of different cellular mechanisms and their functions. Therefore, these cells are an important tool to study the mechanisms regulating the contractility of this artery, allowing to detect potential therapeutic targets to treat HUA disorders (gestational hypertension and pre‐eclampsia). [ABSTRACT FROM AUTHOR]

The Restoring Insulin Secretion ( RISE) study was initiated to evaluate interventions to slow or reverse the progression of β-cell failure in type 2 diabetes ( T2D). To design the RISE study, we undertook an evaluation of methods for measurement of β-cell function and changes in β-cell function in response to interventions. In the present paper, we review approaches for measurement of β-cell function, focusing on methodologic and feasibility considerations. Methodologic considerations included: (1) the utility of each technique for evaluating key aspects of β-cell function (first- and second-phase insulin secretion, maximum insulin secretion, glucose sensitivity, incretin effects) and (2) tactics for incorporating a measurement of insulin sensitivity in order to adjust insulin secretion measures for insulin sensitivity appropriately. Of particular concern were the capacity to measure β-cell function accurately in those with poor function, as is seen in established T2D, and the capacity of each method for demonstrating treatment-induced changes in β-cell function. Feasibility considerations included: staff burden, including time and required methodological expertise; participant burden, including time and number of study visits; and ease of standardizing methods across a multicentre consortium. After this evaluation, we selected a 2-day measurement procedure, combining a 3-hour 75-g oral glucose tolerance test and a 2-stage hyperglycaemic clamp procedure, augmented with arginine. [ABSTRACT FROM AUTHOR]

The physical interactome of a protein can be altered upon perturbation, modulating cell physiology and contributing to disease. Identifying interactome differences of normal and disease states of proteins could help understand disease mechanisms, but current methods do not pinpoint structure-specific PPIs and interaction interfaces proteome-wide. We used limited proteolysis–mass spectrometry (LiP–MS) to screen for structure-specific PPIs by probing for protease susceptibility changes of proteins in cellular extracts upon treatment with specific structural states of a protein. We first demonstrated that LiP–MS detects well-characterized PPIs, including antibody–target protein interactions and interactions with membrane proteins, and that it pinpoints interfaces, including epitopes. We then applied the approach to study conformation-specific interactors of the Parkinson's disease hallmark protein alpha-synuclein (aSyn). We identified known interactors of aSyn monomer and amyloid fibrils and provide a resource of novel putative conformation-specific aSyn interactors for validation in further studies. We also used our approach on GDP- and GTP-bound forms of two Rab GTPases, showing detection of differential candidate interactors of conformationally similar proteins. This approach is applicable to screen for structure-specific interactomes of any protein, including posttranslationally modified and unmodified, or metabolite-bound and unbound protein states. Synopsis: A structural proteomics approach for identifying candidate interactors of any protein within a complex lysate is presented. It is applied to identify conformation-specific interactors of Rab GTPases and of the monomeric and fibrillar forms of the disease-associated protein alpha-synuclein. A method is presented for identifying candidate interactors of any bait protein within a complex lysate. It is applicable to the identification of conformation-specific interactors and pinpoints interaction sites. A resource of candidate interactors of monomeric and fibrillar forms of alpha-synuclein is presented. Candidate interactors of GTP- and GDP-bound forms of Rab GTPases are identified. A structural proteomics approach for identifying candidate interactors of any protein within a complex lysate is presented. It is applied to identify conformation-specific interactors of Rab GTPases and of the monomeric and fibrillar forms of the disease-associated protein alpha-synuclein. [ABSTRACT FROM AUTHOR]

Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of RNA modification regulators operating through various pathways, play pivotal roles in driving the progression of haematological malignancies. Among RNA modifications, N6‐methyladenosine (m6A) RNA modification, the most abundant internal mRNA modification, stands out as the most extensively studied modification. This prominence underscores the crucial role of the layer of epitranscriptomic regulation in controlling haematopoietic cell fate and therefore the development of haematological malignancies. Additionally, other RNA modifications (non‐m6A RNA modifications) have gained increasing attention for their essential roles in haematological malignancies. Although the roles of the m6A modification machinery in haematopoietic malignancies have been well reviewed thus far, such reviews are lacking for non‐m6A RNA modifications. In this review, we mainly focus on the roles and implications of non‐m6A RNA modifications, including N4‐acetylcytidine, pseudouridylation, 5‐methylcytosine, adenosine to inosine editing, 2′‐O‐methylation, N1‐methyladenosine and N7‐methylguanosine in haematopoietic malignancies. We summarise the regulatory enzymes and cellular functions of non‐m6A RNA modifications, followed by the discussions of the recent studies on the biological roles and underlying mechanisms of non‐m6A RNA modifications in haematological malignancies. We also highlight the potential of therapeutically targeting dysregulated non‐m6A modifiers in blood cancer. [ABSTRACT FROM AUTHOR]

High‐resolution spatio‐temporal monitoring of the cell membrane lipid order provides visual insights into the complex and sophisticated systems that control cellular physiological functions. Solvatochromic fluorescent probes are highly promising noninvasive visualization tools for identifying the ordering of the microenvironment of plasma membrane microdomains. However, conventional probes, although capable of structural analysis, lack the necessary long‐term photostability required for live imaging at the cellular level. Here, an ultra‐high‐light‐resistant solvatochromic fluorescence probe, 2‐N,N‐diethylamino‐7‐(4‐methoxycarbonylphenyl)‐9,9‐dimethylfluorene (FπCM) is reported, which enables live lipid order imaging of cell division. This probe and its derivatives exhibit sufficient fluorescence wavelengths, brightness, polarity responsiveness, low phototoxicity, and remarkable photostability under physiological conditions compared to conventional solvatochromic probes. Therefore, these probes have the potential to overcome the limitations of fluorescence microscopy, particularly those associated with photobleaching. FπCM probes can serve as valuable tools for elucidating mechanisms of cellular processes at the bio‐membrane level. [ABSTRACT FROM AUTHOR]

Maternal exercise (ME) has been established as a useful non‐pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to infant tissues (e.g., skeletal muscle), and remain involved in mature tissue maintenance. Importantly, these cells maintain metabolic characteristics of an offspring donor and provide a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC to investigate if ME affects infant MSC mitochondrial function and insulin action, and if these adaptations are associated with lower infant adiposity. We found that infants from exercising mothers have improvements in MSC insulin signaling related to higher MSC respiration and fat oxidation, and expression and activation of energy‐sensing and redox‐sensitive proteins. Further, we found that infants exposed to exercise in utero were leaner at 1 month of age, with a significant inverse correlation between infant MSC respiration and infant adiposity at 6 months of age. These data suggest that infants from exercising mothers are relatively leaner, and this is associated with higher infant MSC mitochondrial respiration, fat use, and insulin action. [ABSTRACT FROM AUTHOR]

Recent developments in single‐cell sequencing technology enable the acquisition of entire transcriptome data. Understanding the underlying mechanism and identifying the driving force of transcriptional regulation governing cell function directly from these data remains challenging. This study reconstructs a continuous vector field of the cell cycle based on discrete single‐cell RNA velocity to quantify the single‐cell global nonequilibrium dynamic landscape‐flux. It reveals that large fluctuations disrupt the global landscape and genetic perturbations alter landscape‐flux, thus identifying key genes in maintaining cell cycle dynamics and predicting associated functional effects. Additionally, it quantifies the fundamental energy cost of the cell cycle initiation and unveils that sustaining the cell cycle requires curl flux and dissipation to maintain the oscillatory phase coherence. This study enables the inference of the cell cycle gene regulatory networks directly from the single‐cell transcriptomic data, including the feedback mechanisms and interaction intensity. This provides a golden opportunity to experimentally verify the landscape‐flux theory and also obtain its associated quantifications. It also offers a unique framework for combining the landscape‐flux theory and single‐cell high‐through sequencing experiments for understanding the underlying mechanisms of the cell cycle and can be extended to other nonequilibrium biological processes, such as differentiation development and disease pathogenesis. [ABSTRACT FROM AUTHOR]

Fracture healing is a complex staged repair process in which the mechanical environment plays a key role. Bone tissue is very sensitive to mechanical stress stimuli, and the literature suggests that appropriate stress can promote fracture healing by altering cellular function. However, fracture healing is a coupled process involving multiple cell types that balance and limit each other to ensure proper fracture healing. The main cells that function during different stages of fracture healing are different, and the types and molecular mechanisms of stress required are also different. Most previous studies have used a single mechanical stimulus on individual mechanosensitive cells, and there is no relatively uniform standard for the size and frequency of the mechanical stress. Analyzing the mechanisms underlying the effects of mechanical stimulation on the metabolic regulation of signaling pathways in cells such as in bone marrow mesenchymal stem cells (BMSCs), osteoblasts, chondrocytes, and osteoclasts is currently a challenging research hotspot. Grasping how stress affects the function of different cells at the molecular biology level can contribute to the refined management of fracture healing. Therefore, in this review, we summarize the relevant literature and describe the effects of mechanical stress on cells associated with fracture healing, and their possible signaling pathways, for the treatment of fractures and the further development of regenerative medicine. [ABSTRACT FROM AUTHOR]

Aims: Peripheral immune cells infiltrating into the brain trigger neuroinflammation after an ischemic stroke. Partial immune cells reprogram their function for neural repair. Which immune cells promote ischemic brain recovery needs further identification. Methods: We performed single‐cell transcriptomic profiling of CD45high immune cells isolated from the ischemic hemisphere at subacute (5 days) and chronic (14 days) stages after ischemic stroke. Results: A subset of phagocytic macrophages was associated with neuron projection regeneration and tissue remodeling. We also identified a unique type of T cells with highly expressed macrophage markers, including C1q, Apoe, Hexb, and Fcer1g, which showed high abilities in tissue remodeling, myelination regulation, wound healing, and anti‐neuroinflammation. Moreover, natural killer cells decreased cytotoxicity and increased energy and metabolic function in the chronic stage after ischemic stroke. Two subgroups of neutrophils upregulated CCL signals to recruit peripheral immune cells and released CXCL2 to keep self‐recruiting at the chronic stage. Conclusions: We identified subsets of peripheral immune cells that may provide potential therapeutic targets for promoting poststroke recovery. [ABSTRACT FROM AUTHOR]

Despite the great body of research done on Alzheimer's disease, the underlying mechanisms have not been vividly investigated. To date, the accumulation of amyloid‐beta plaques and tau tangles constitutes the hallmark of the disease; however, dysregulation of the mammalian target of rapamycin (mTOR) seems to be significantly involved in the pathogenesis of the disease as well. mTOR, as a serine–threonine protein kinase, was previously known for controlling many cellular functions such as cell size, autophagy, and metabolism. In this regard, mammalian target of rapamycin complex 1 (mTORC1) may leave anti‐aging impacts by robustly inhibiting autophagy, a mechanism that inhibits the accumulation of damaged protein aggregate and dysfunctional organelles. Formation and aggregation of neurofibrillary tangles and amyloid‐beta plaques seem to be significantly regulated by mTOR signaling. Understanding the underlying mechanisms and connection between mTOR signaling and AD may suggest conducting clinical trials assessing the efficacy of rapamycin, as an mTOR inhibitor drug, in managing AD or may help develop other medications. In this literature review, we aim to elaborate mTOR signaling network mainly in the brain, point to gaps of knowledge, and define how and in which ways mTOR signaling can be connected with AD pathogenesis and symptoms. [ABSTRACT FROM AUTHOR]

The prevalence of itch is higher in individuals with darker skin types. In this paper, we review the systems involved in the physiology of itch and how they may differ across the races. Current data point out that the differences may be explained by barrier function, mast cell physiology, and itch receptor polymorphisms. [ABSTRACT FROM AUTHOR]

Imaging of actin filaments is crucial due to the integral role that they play in many cellular functions such as intracellular transport, membrane remodelling and cell motility. Visualizing actin filaments has so far relied on fluorescence microscopy and electron microscopy/tomography. The former lacks the capacity to capture the overall local ultrastructure, while the latter requires rigorous sample preparation that can lead to potential artefacts, and only delivers relatively small volumes of imaging data at the thinnest areas of a cell. In this work, a correlative approach utilizing in situ super‐resolution fluorescence imaging and cryo X‐ray tomography was used to image bundles of actin filaments deep inside cells under near‐native conditions. In this case, fluorescence 3D imaging localized the actin bundles within the intracellular space, while X‐ray tomograms of the same areas provided detailed views of the local ultrastructure. Using this new approach, actin trails connecting vesicles in the perinuclear area and hotspots of actin presence within and around multivesicular bodies were observed. The characteristic prevalence of filamentous actin in cytoplasmic extensions was also documented. [ABSTRACT FROM AUTHOR]

Legionella pneumophila is a human pathogen that causes Legionnaires' disease, a severe form of pneumonia. It can be found in various aquatic environments ranging from cooling towers to ponds. In addition to causing disease in humans, it can also infect free‐living amoebae commonly found in various aquatic environments. Once inside a human lung macrophage, it creates a niche called the Legionella‐containing vacuole where it can evade phagolysosomal degradation and replicate. During infection, normal cellular functions are hijacked by proteins that are secreted by the pathogen, called bacterial effectors. Here, the structural characterization of the effector LegA15/AnkD is reported. The protein contains an ankyrin‐repeat domain followed by a cysteine protease‐like (CPL) domain with a putative catalytic triad consisting of His268–Asn290–Cys361. The CPL domain shows similarity to the CE clan in the MEROPS database, which contains ubiquitin‐like hydrolases. The C‐terminal segment of LegA15, including the CPL domain, shows structural similarity to another effector, LegA3/AnkH, while they share only 12% sequence identity. When expressed in mammalian cells, LegA15 is localized within the cytoplasm, in contrast to LegA3, which localizes to the nucleus. [ABSTRACT FROM AUTHOR]

The G1 cyclins, D1, D3 and E, were investigated in 38 lesions of oral epithelial dysplasia from the floor of the mouth or the lateral border of the tongue. Their immunohistochemical expression was observed and compared with that of Ki-67 and with the degree of dysplasia assessed by the semiobjective technique of Smith & Pindborg. Antibody labelled cells were quantified and expressed as a percentage (LI%) of the total nucleated cell population and per mm basement membrane length (LI/mm). The labelling indices of all of the antibodies were high and quantitatively similar. There were no significant correlations with the degree of dysplasia assessed by the atypia scores. There was a correlation between labelling indices for the various antibodies expressed as LI/mm but little correlation between the indices expressed as LI%. The distribution of the D cyclins was similar to that of Ki-67 with relatively few of the basal cells demonstrating immunoreactivity. The reasons for this are discussed in the paper. Some cross-reactivity was observed with the cyclin antibodies. We conclude that the antibodies against the cyclins used in the present study are not a useful adjunct in the study of the cell kinetics of oral epithelial dysplasia. [ABSTRACT FROM AUTHOR]

SUMMARY There is a strong interest in onsite rapid analysis and monitoring of the activity of cells and biological samples. Such analyses contribute not only to the understanding of cell functions, but also to the improvement of point-of-care testing and quality-of-life. In promoting miniaturization and integration of sensing components, electrochemistry is advantageous. By coupling this technique with microfluidic techniques, additional functions that can never be realized with only independent sensors can be realized. In this review paper, we introduce our recent electrochemical devices, particularly focusing on analyses of cell functions and biological samples. [ABSTRACT FROM AUTHOR]

Cancers are usually treated by anticancer agents that are toxic for both normal and cancer cells, so these drugs have major side effects and they are not suitable and enough effective for cancer prevention. Solamargine, a steroidal alkaloid glycoside found in Solanum species such as Solanum nigrum, displayed several therapeutic activities. We aim to review the use of solamargine in experimental cancer studies. Articles published in biology journals between 1975 and 2017 were retrieved from PubMed, Scopus, and Web of Science using relevant keywords. The scientific papers mainly focusing on solamargine with therapeutic efficacies against cancers were identified and tabulated. In addition, the reliability of experimental findings was determined under "Risk of Bias" criteria. The author manually reviewed 33 articles; 27 articles were found concerning the anti-cancer potential in cancer cells. Solamargine has been found to possess anticancer activities via its effect on a variety of biological pathways including cell survival pathways, tumor suppressor pathways, caspase activation pathway, mitochondrial pathways, death receptor pathways, protein kinase pathways, and signal pathways, which promote invasion/migration and multi drug resistance. Solamargine can be an anticancer agent candidate when complementary scientific evidences become available. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective A challenge in studying human salivary glands is to maintain the cells ex vivo in their three-dimensional (3D) morphology with an intact native extracellular matrix ( ECM) environment. This paper established a human salivary 3D organotypic slice culture model that could maintain its physiological functions as well as allowing a direct visualization of the cells. Methods Human salivary biopsies from six patients were embedded in agarose and submerged in cold buffer for thin (50 μm) sectioning using a vibratome. 'Salivary slices' were mechanically supported by a porous membrane insert that allowed an air-liquid interface and cultured in serum-free culture media. Cell viability, proliferation, apoptosis, physiological functions, and gene expression were assessed during 14 days of culture. Results Human salivary slices maintained cell survival (70-40%) and proliferation (6-17%) for 14 days ex vivo. The protein secretory (amylase) function decreased, but fluid (intracellular calcium mobilization) function was maintained. Acinar, ductal, and myoepithelial cell populations survived and maintained their 3D organization within the slice culture model. Conclusion The human salivary slice culture model kept cells alive ex vivo for 14 days as well as maintaining their 3D morphology and physiological functions. [ABSTRACT FROM AUTHOR]

Background: Statins are 3‐Hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors blocking cholesterol biosynthesis in hepatic cells, thereby causing an increase in low‐density lipoprotein (LDL) receptors resulting in enhanced uptake and clearance of atherogenic LDL‐cholesterol (LDL‐C) from the blood. Accordingly, statins decrease the risk of developing atherosclerosis and its acute complications, such as acute myocardial infarction and ischaemic stroke. Besides the LDL‐C‐lowering impact, statins also have other so‐called pleiotropic effects. Among them, the ability to modulate differentiation and function of bone cells and exert direct effects on osteosynthesis factors. Specifically, earlier studies have shown that statins cause in vitro and in vivo osteogenic differentiation. Design: The most relevant papers on the bone‐related 'pleiotropic' effects of statins were selected following literature search in databases and were reveiwed. Results: Statins increase the expression of many mediators involved in bone metabolism including bone morphogenetic protein‐2 (BMP‐2), glucocorticoids, transforming growth factor‐beta (TGF‐β), alkaline phosphatase (ALP), type I collagen and collagenase‐1. As a result, they enhance bone formation and improve bone mineral density by modulating osteoblast and osteoclast differentiation. Conclusion: This review summarizes the literature exploring bone‐related 'pleiotropic' effects of statins and suggests an anabolic role in the bone tissue for this drug class. Accordingly, current knowledge encourages further clinical trials to assess the therapeutic potential of statins in the treatment of bone disorders, such as arthritis and osteoporosis. [ABSTRACT FROM AUTHOR]

Microglia, the major resident immune cells in the central nervous system, serve as the frontline soldiers against cerebral ischemic injuries, possibly along with metabolic alterations. However, signaling pathways involved in the regulation of microglial immunometabolism in ischemic stroke remain to be further elucidated. In this study, using single‐nuclei RNA sequencing, a microglial subcluster up‐regulated in ischemic brain tissues is identified, with high expression of Igf1 and Trem2, neuroprotective transcriptional signature and enhanced oxidative phosphorylation. Microglial depletion by PLX3397 exacerbates ischemic brain damage, which is reversed by repopulating the microglia with high Igf1 and Trem2 phenotype. Mechanistically, Igf1 serves as one of the major down‐stream molecules of Trem2, and Trem2‐Igf1 signaling axis regulates microglial functional and metabolic profiles, exerting neuroprotective effects on ischemic stroke. Overexpression of Igf1 and supplementation of cyclocreatine restore microglial glucometabolic levels and cellular functions even in the absence of Trem2. These findings suggest that Trem2‐Igf1 signaling axis reprograms microglial immunometabolic profiles and shifts microglia toward a neuroprotective phenotype, which has promising therapeutic potential in treating ischemic stroke. [ABSTRACT FROM AUTHOR]

Fatty acid binding proteins (Fabps) are small soluble proteins that are abundant in the cytosol. These proteins are known to bind a myriad of small hydrophobic molecules and have been postulated to serve a variety of roles, yet their precise functions have remained an enigma over half a century of study. Here, we consider recent findings, along with the cumulative findings contributed by many laboratories working on Fabps over the last half century, to synthesize a new outlook for what functions Fabps serve in cells and organisms. Collectively, the findings illustrate that Fabps function as versatile multi‐purpose devices serving as sensors, conveyors and modulators to enable cells to detect and handle a specific class of metabolites, and to adjust their metabolic capacity and efficiency. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age-related diseases in a wide range of animals, including non-human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils. In this paper, we study the effect of these dietary fats on structural and physiological parameters of kidney from mice maintained on 40% CR for 6 and 18 months. Analyses were performed using quantitative electron microcopy techniques and protein expression in Western blots. CR mitigated most of the analyzed age-related parameters in kidney, such as glomerular basement membrane thickness, mitochondrial mass in convoluted proximal tubules and autophagic markers in renal homogenates. The lard group showed improved preservation of several renal structures with aging when compared to the other CR diet groups. These results indicate that dietary fat modulates renal structure and function in CR mice and plays an essential role in the determination of health span in rodents. [ABSTRACT FROM AUTHOR]

The interplay between HIV-1 and epithelial cells represents a critical aspect in mucosal HIV-1 transmission. Epithelial cells lining the oral cavity cover subepithelial tissues, which contain virus-susceptible host cells including CD4+ T lymphocytes, monocytes/macrophages, and dendritic cells. Oral epithelia are among the sites of first exposure to both cell-free and cell-associated virus HIV-1 through breast-feeding and oral-genital contact. However, oral mucosa is considered to be naturally resistant to HIV-1 transmission. Oral epithelial cells have been shown to play a crucial role in innate host defense. Nevertheless, it is not clear to what degree these local innate immune factors contribute to HIV-1 resistance of the oral mucosa. This review paper addressed the following issues that were discussed at the 7th World Workshop on Oral Health and Disease in AIDS held in Hyderabad, India, during November 6-9, 2014: (i) What is the fate of HIV-1 after interactions with oral epithelial cells?; (ii) What are the keratinocyte and other anti- HIV effector oral factors, and how do they contribute to mucosal protection?; (iii) How can HIV-1 interactions with oral epithelium affect activation and populations of local immune cells?; (iv) How can HIV-1 interactions alter functions of oral epithelial cells? [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including a paper by Oda et al. on thyroid function and glucose tolerance, hyperglycemia in pregnancy, and postpartum glucose screening.

Spontaneous subarachnoid hemorrhage (SAH) is one of the most devastating forms of stroke, with limited treatment modalities and poor patient outcomes. Previous studies have proposed multiple prognostic factors; however, relative research on treatment has not yet yielded favorable clinical outcomes. Moreover, recent studies have suggested that early brain injury (EBI) occurring within 72 h after SAH may contribute to its poor clinical outcomes. Oxidative stress is recognized as one of the main mechanisms of EBI, which causes damage to various subcellular organelles, including the mitochondria, nucleus, endoplasmic reticulum (ER), and lysosomes. This could lead to significant impairment of numerous cellular functions, such as energy supply, protein synthesis, and autophagy, which may directly contribute to the development of EBI and poor long‐term prognostic outcomes. In this review, the mechanisms underlying the connection between oxidative stress and subcellular organelles after SAH are discussed, and promising therapeutic options based on these mechanisms are summarized. [ABSTRACT FROM AUTHOR]