γδ T cells are a small population of mostly tissue‐resident lymphocytes, with both innate and adaptive properties. These unique features make them particularly attractive candidates for the ...development of new cellular therapy targeted against tumor development. Nevertheless, γδ T cells may play dual roles in cancer, promoting cancer development on the one hand, while participating in antitumor immunity on the other hand. In mice, γδ T‐cell subsets preferentially produce IL‐17 or IFN‐γ. While antitumor functions of murine γδ T cells can be attributed to IFN‐γ+ γδ T cells, recent studies have implicated IL‐17+ γδ T cells in tumor growth and metastasis. However, in humans, IL‐17‐producing γδ T cells are rare and most studies have attributed a protective role to γδ T cells against cancer. In this review, we will present the current knowledge and most recent findings on γδ T‐cell functions in mouse models of tumor development and human cancers. We will also discuss their potential as cellular immunotherapy against cancer.
γδ T cells play crucial roles in antitumor immunity but have been also linked to tumor growth. Due to their innate and adaptive features, γδ T cells also constitute attractive candidates for newly developing cancer immunotherapy. In this review, we discuss the latest findings and future directions of this conflicting but highly promising field.
This systematic review aims to offer an updated understanding of the relationship between gastrointestinal symptoms (GIS) and autism spectrum disorder (ASD) in children and adolescents. The databases ...PsycINFO, Medline, Cinahl, and ERIC were searched using keywords, and relevant literature was hand-searched. Papers (
= 3319) were systematically screened and deemed eligible if they were empirical studies published in English since 2014 and measured the GIS of individuals with ASD who were under 18 years old. Thirty studies were included in the final review. The study findings were synthesized under eight themes, including the prevalence and nature of GIS and their relationship with developmental regression, language and communication, ASD severity, challenging behavior, comorbid psychopathology, sleep problems, and sensory issues. The review found that GIS were common and that there was contradictory evidence concerning their relationship with co-occurring conditions. It also identified evidence of some causal relationships that support the existence of the gut-immune-brain pathways. Future research needs to use large prospective designs and objective and standardized GIS measurements to provide a nuanced understanding of GIS in the context of ASD.
A novel workflow is presented for integrating fiber optic Distributed Temperature Sensor (DTS) data in numerical simulation model for the Cyclic Steam Stimulation (CSS) process, using an intelligent ...optimization routine that automatically learns and improves from experience. As the steam–oil relationship is the main driver for forecasting and decision-making in thermal recovery operations, knowledge of downhole steam distribution across the well over time can optimize injection and production. This study uses actual field data from a CSS operation in a heavy oil field in California, and the value of integrating DTS in the history matching process is illustrated as it allows the steam distribution to be accurately estimated along the entire length of the well. The workflow enables the simultaneous history match of water, oil, and temperature profiles, while capturing the reservoir heterogeneity and the actual physics of the injection process, and ultimately reducing the uncertainty in the predictive models. A novel stepwise grid-refinement approach coupled with an evolutionary optimization algorithm was implemented to improve computational efficiency and predictive accuracy. DTS surveillance also made it possible to detect a thermal communication event due to steam channeling in real-time, and even assess the effectiveness of the remedial workover to resolve it, demonstrating the value of continuous fiber optic monitoring.
The potential for psychedelic molecules in impacting cognitive flexibility has long been supported and acknowledged across scientific reports. In the current study, an approach leveraging ...knowledge-based gene-set information analysis has been adopted to explore the potential impact of psychedelic molecules on both glycosylation, (a post-translational modifications (PTM)) and on neuro-regulatory pathways. Though limitations and restrictions rise from the scarcity of publicly available 'omics' data, targeted analysis enabled us to identify a number of key glycogenes (
,
,
,
,
,
) involved the structural organization of extracellular matrix and neuroprotective factors (
,
,
,
,
,
) which play vital roles in neuron protection, development as well as synaptic stability. In response to psychedelic molecules, we found that these genes and associated pathways are transcriptional altered in rodent models. The approach used indicates the potential to exploit existing datasets for hypothesis generation and testing for the molecular processes which play a role in the physiological response to psychedelic molecule effects. These reported findings, which focused on alterations in glycogenes and neuro-regulatory factors may provide a novel range of biomarkers to track the beneficial, as well as potential toxicological effects of psychedelic molecules.
Glycosylation, being the most abundant post-translational modification, plays a profound role affecting expression, localization and function of proteins and macromolecules in immune response to ...infection. Presented are the findings of a transcriptomic analysis performed using high-throughput functional genomics data from public repository to examine the altered transcription of the human glycosylation machinery in response to SARS-CoV-2 stimulus and infection. In addition to the conventional in silico functional enrichment analysis methods we also present results from the manual analysis of biomedical literature databases to bring about the biological significance of glycans and glycan-binding proteins in modulating the host immune response during SARS-CoV-2 infection. Our analysis revealed key immunomodulatory lectins, proteoglycans and glycan epitopes implicated in exerting both negative and positive downstream inflammatory signaling pathways, in addition to its vital role as adhesion receptors for SARS-CoV-2 pathogen. A hypothetical correlation of the differentially expressed human glycogenes with the altered host inflammatory response and the cytokine storm-generated in response to SARS-CoV-2 pathogen is proposed. These markers can provide novel insights into the diverse roles and functioning of glycosylation pathways modulated by SARS-CoV-2, provide avenues of stratification, treatment, and targeted approaches for COVID-19 immunity and other viral infectious agents.
In addition to the psychological depressive phenotype, major depressive disorder (MDD) patients are also associated with underlying immune dysregulation that correlates with metabolic syndrome ...prevalent in depressive patients. A robust integrative analysis of biological pathways underlying the dysregulated neural connectivity and systemic inflammatory response will provide implications in the development of effective strategies for the diagnosis, management and the alleviation of associated comorbidities. In the current study, focusing on MDD, we explored an integrative network analysis methodology to analyze transcriptomic data combined with the meta-analysis of biomarker data available throughout public databases and published scientific peer-reviewed articles. Detailed gene set enrichment analysis and complex protein-protein, gene regulatory and biochemical pathway analysis has been undertaken to identify the functional significance and potential biomarker utility of differentially regulated genes, proteins and metabolite markers. This integrative analysis method provides insights into the molecular mechanisms along with key glycosylation dysregulation underlying altered neutrophil-platelet activation and dysregulated neuronal survival maintenance and synaptic functioning. Highlighting the significant gap that exists in the current literature, the network analysis framework proposed reduces the impact of data gaps and permits the identification of key molecular signatures underlying complex disorders with multiple etiologies such as within MDD and presents multiple treatment options to address their molecular dysfunction.
Regulatory T-cells (Treg) are essential for maintaining immune homeostasis and tolerance. Surface glycosylation is ubiquitous on mammalian cells and regulates diverse biological processes. While it ...is currently well accepted that surface glycan expression influences multiple aspects of T-cell function, little is known about the relevance of glycosylation to Treg biology. This study aimed to profile the surface glycosylation characteristics of Treg in various lymphoid compartments of mouse and in human peripheral blood with comparison to non-regulatory, conventional CD4
T-cells (Tconv). It also sought to determine the relationship between the surface glycosylation characteristics and suppressive potency of Treg. Lectin-based flow cytometric profiling demonstrated that Treg surface glycosylation differs significantly from that of Tconv in the resting state and is further modified by activation stimuli. In mouse, the surface glycosylation profiles of FoxP3
Treg from spleen and lymph nodes were closely comparable but greater variability was observed for Treg in thymus, bone marrow, and blood. Surface levels of tri/tetra-antennary
glycans correlated with expression of proteins known to be involved in Treg suppressive functions, including GITR, PD-1, PD-L1, CD73, CTLA-4, and ICOS. In coculture experiments involving purified Treg subpopulations and CD4
or CD8
Tconv, higher surface tri/tetra-antennary
glycans was associated with greater Treg suppressive potency. Enzymatic manipulation of mouse Treg surface glycosylation resulting in a temporary reduction of surface
-glycans significantly reduced Treg capacity to suppress Tconv activation through contact-dependent mechanisms. Overall, these findings demonstrate that Treg have distinctive surface glycan characteristics that show variability across anatomical locations and are modulated by activation events. They also provide evidence of an important role for surface glycosylation in determining Treg phenotype and suppressive potency. These insights may prove relevant to the analysis of Treg in disease settings and to the further development of Treg-based immunotherapies.
Glucagon regulates glucose and lipid metabolism and promotes weight loss. Thus, therapeutics stimulating glucagon receptor (GCGR) signaling are promising for obesity treatment; however, the ...underlying mechanism(s) have yet to be fully elucidated. We previously identified that hepatic GCGR signaling increases circulating fibroblast growth factor 21 (FGF21), a potent regulator of energy balance. We reported that mice deficient for liver Fgf21 are partially resistant to GCGR-mediated weight loss, implicating FGF21 as a regulator of glucagon's weight loss effects. FGF21 signaling requires an obligate coreceptor (β-Klotho, KLB), with expression limited to adipose tissue, liver, pancreas, and brain. We hypothesized that the GCGR-FGF21 system mediates weight loss through a central mechanism. Mice deficient for neuronal Klb exhibited a partial reduction in body weight with chronic GCGR agonism (via IUB288) compared with controls, supporting a role for central FGF21 signaling in GCGR-mediated weight loss. Substantiating these results, mice with central KLB inhibition via a pharmacological KLB antagonist, 1153, also displayed partial weight loss. Central KLB, however, is dispensable for GCGR-mediated improvements in plasma cholesterol and liver triglycerides. Together, these data suggest GCGR agonism mediates part of its weight loss properties through central KLB and has implications for future treatments of obesity and metabolic syndrome.
The evolutionary origin of stem cell pluripotency is an unresolved question. In mammals, pluripotency is limited to early embryos and is induced and maintained by a small number of key transcription ...factors, of which the POU domain protein Oct4 is considered central. Clonal invertebrates, by contrast, possess pluripotent stem cells throughout their life, but the molecular mechanisms that control their pluripotency are poorly defined. To address this problem, we analyzed the expression pattern and function of Polynem (Pln), a POU domain gene from the marine cnidarian Hydractinia echinata. We show that Pln is expressed in the embryo and adult stem cells of the animal and that ectopic expression in epithelial cells induces stem cell neoplasms and loss of epithelial tissue. Neoplasm cells downregulated the transgene but expressed the endogenous Pln gene and also Nanos, Vasa, Piwi and Myc, which are all known cnidarian stem cell markers. Retinoic acid treatment caused downregulation of Pln and the differentiation of neoplasm cells to neurosensory and epithelial cells. Pln downregulation by RNAi led to differentiation. Collectively, our results suggest an ancient role of POU proteins as key regulators of animal stem cells.
The field of biosensor development now encompasses several areas specifically geared toward the rapid and sensitive detection, identification, and quantification of target analytes. In contrast to ...the more mature research and development of nucleic acid and protein biosensors, the development of 'glyco-biosensors' for detecting carbohydrates and conjugates of carbohydrates (glycoconjugates) is at a relatively nascent stage. The application of glyco-biosensors aims to open novel analytical and diagnostic avenues, encompassing industrial bioprocesses, biomedical and clinical applications. This area of research has been greatly aided by advancement brought by interdisciplinary mergers of engineering, biology, chemistry and physical sciences and enabling the miniaturization of detection platforms. In this review, we briefly introduce the need for glyco-biosensors, discuss current analytical technologies, and examine advances in glyco-biosensor approaches aimed at the detection and/or quantification of glycoconjugates or carbohydrates derived from glycoconjugates since 2005.
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