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Journal of Molecular Biology Mar 2022An effective innate antiviral response is critical for the mitigation of severe disease and host survival following infection. In vivo, the innate antiviral response is... (Review)
Review
An effective innate antiviral response is critical for the mitigation of severe disease and host survival following infection. In vivo, the innate antiviral response is triggered by cells that detect the invading pathogen and then communicate through autocrine and paracrine signaling to stimulate the expression of genes that inhibit viral replication, curtail cell proliferation, or modulate the immune response. In other words, the innate antiviral response is complex and dynamic. Notably, in the laboratory, culturing viruses and assaying viral life cycles frequently utilizes cells that are derived from tissues other than those that support viral replication during natural infection, while the study of viral pathogenesis often employs animal models. In recapitulating the human antiviral response, it is important to consider that variation in the expression and function of innate immune sensors and antiviral effectors exists across species, cell types, and cell differentiation states, as well as when cells are placed in different contexts. Thus, to gain novel insight into the dynamics of the host response and how specific sensors and effectors impact infection kinetics by a particular virus, the model system must be selected carefully. In this review, we briefly introduce key signaling pathways involved in the innate antiviral response and highlight how these differ between systems. We then review the application of tissue-engineered or 3D models for studying the antiviral response, and suggest how these in vitro culture systems could be further utilized to assay physiologically-relevant host responses and reveal novel insight into virus-host interactions.
Topics: Animals; Host-Pathogen Interactions; Immunity, Innate; Signal Transduction; Virus Replication; Viruses
PubMed: 34863779
DOI: 10.1016/j.jmb.2021.167374 -
Phytomedicine : International Journal... Jan 2024Traditional Chinese medicine prescription sini decoction (SND) can alleviate inflammation, improve microcirculation, and modulate immune status in sepsis patients....
BACKGROUND
Traditional Chinese medicine prescription sini decoction (SND) can alleviate inflammation, improve microcirculation, and modulate immune status in sepsis patients. However, its underlying mechanisms remain unclear, and therapeutic effects may vary among individuals.
PURPOSE
Through a comprehensive and systematic network pharmacology analysis, the purpose of this study is to investigate the therapeutic mechanisms of SND in treating sepsis.
METHODS
An analysis of WGCNA identified CX3CR1 as a key gene influencing sepsis prognosis. A drug-active component-target network for SND was created using the traditional Chinese medicine systems pharmacology (TCMSP) database and Cytoscape software. Shared targets between SND and CX3CR1 high-expression gene modules were found through the GEO database. Gene module functionality was analyzed using GO, KEGG, GSEA, and GSVA. Unsupervised clustering of sepsis patients was performed based on the ferroptosis gene set, and immune cell interactions and mechanisms were explored using CIBERSORT, single-cell sequencing, and intercellular communication analysis.
RESULTS
This study demonstrates that high expression of CX3CR1 improves survival rates in sepsis patients and is associated with immune cell signaling pathways. SND contains 116 active components involved in oxidative stress and lipid metabolism pathways. HMOX1, a co-expressed gene in SND and CX3CR1 high-expression gene module, plays a crucial role in sepsis survival. Unsupervised clustering analysis classified sepsis patients into three clusters based on the ferroptosis gene set, revealing differences in immune cell expression and involvement in heme metabolism pathways. Notably, intercellular interactions among immune cells primarily occur through paracrine and autocrine mechanisms in MIF, GALECTIN, and IL16 signaling pathways, modulating the immune-inflammatory microenvironment in sepsis.
CONCLUSIONS
This study identifies CX3CR1 as a crucial molecule impacting sepsis prognosis through WGCNA analysis. It reveals that SND's active component, quercetin and kaempferol, target HMOX1 via related pathways to regulate heme metabolism, reduce inflammation, inhibit ferroptosis, and improve immune function, ultimately improving sepsis prognosis. These findings offer a solid pharmacological foundation and potential therapeutic targets for SND in treating sepsis.
Topics: Humans; Network Pharmacology; Multiomics; Drugs, Chinese Herbal; Sepsis; Inflammation; Heme; Molecular Docking Simulation
PubMed: 38029626
DOI: 10.1016/j.phymed.2023.155212 -
International Journal of Molecular... Jun 2020Somatostatin is a peptide hormone, which most commonly is produced by endocrine cells and the central nervous system. In mammals, somatostatin originates from... (Review)
Review
Somatostatin is a peptide hormone, which most commonly is produced by endocrine cells and the central nervous system. In mammals, somatostatin originates from pre-prosomatostatin and is processed to a shorter form, i.e., somatostatin-14, and a longer form, i.e., somatostatin-28. The two peptides repress growth hormone secretion and are involved in the regulation of glucagon and insulin synthesis in the pancreas. In recent years, the processing and secretion of somatostatin have been studied intensively. However, little attention has been paid to the regulatory mechanisms that control its expression. This review provides an up-to-date overview of these mechanisms. In particular, it focuses on the role of enhancers and silencers within the promoter region as well as on the binding of modulatory transcription factors to these elements. Moreover, it addresses extracellular factors, which trigger key signaling pathways, leading to an enhanced somatostatin expression in health and disease.
Topics: Animals; Autocrine Communication; Enhancer Elements, Genetic; Feedback, Physiological; Gene Expression Regulation; Humans; Promoter Regions, Genetic; Somatostatin; Transcription Factors
PubMed: 32545257
DOI: 10.3390/ijms21114170 -
Frontiers in Neural Circuits 2021Here, we present and discuss the characteristics and properties of neurotransmitter segregation, a subtype of neurotransmitter cotransmission. We review early evidence... (Review)
Review
Here, we present and discuss the characteristics and properties of neurotransmitter segregation, a subtype of neurotransmitter cotransmission. We review early evidence of segregation and discuss its properties, such as plasticity, while placing special emphasis on its probable functional implications, either in the central nervous system (CNS) or the autonomic nervous system. Neurotransmitter segregation is a process by which neurons separately route transmitters to independent and distant or to neighboring neuronal processes; it is a plastic phenomenon that changes according to synaptic transmission requirements and is regulated by target-derived signals. Distant neurotransmitter segregation in the CNS has been shown to be related to an autocrine/paracrine function of some neurotransmitters. In retinal amacrine cells, segregation of acetylcholine (ACh) and GABA, and glycine and glutamate to neighboring terminals has been related to the regulation of the firing rate of direction-selective ganglion cells. In the rat superior cervical ganglion, segregation of ACh and GABA to neighboring varicosities shows a heterogeneous regional distribution, which is correlated to a similar regional distribution in transmission strength. We propose that greater segregation of ACh and GABA produces less GABAergic inhibition, strengthening ganglionic transmission. Segregation of ACh and GABA varies in different physiopathological conditions; specifically, segregation increases in acute sympathetic hyperactivity that occurs in cold stress, does not vary in chronic hyperactivity that occurs in hypertension, and rises in early ages of normotensive and hypertensive rats. Given this, we propose that variations in the extent of transmitter segregation may contribute to the alteration of neural activity that occurs in some physiopathological conditions and with age.
Topics: Acetylcholine; Amacrine Cells; Animals; Glutamic Acid; Neurotransmitter Agents; Rats; Synaptic Transmission
PubMed: 34720888
DOI: 10.3389/fncir.2021.738516 -
MMW Fortschritte Der Medizin Jul 2023Myokines discharged from working muscles are intensively researched in view of rising importance of preventive and secondary preventive effects of the autocrine,... (Review)
Review
BACKGROUND
Myokines discharged from working muscles are intensively researched in view of rising importance of preventive and secondary preventive effects of the autocrine, paracrine and endocrine functions.
OBJECTIVES
Recording of the current state of knowledge on the paracrine and endocrine effects of myokines and evaluation of training measures to optimize myokine concentration.
METHOD
A selective database-driven literature search was carried out on myostatin, interleukin-6 (IL-6), interleukin-15 (IL-15), irisin, cathepsin B, brain-derived neurotrophic factor (BDNF), meteorin-like and kynurenine for the period 2011 until June 2021. The paracrine and endocrine effects of the myokines are analyzed. Their release after acute physical stress and training is described.
RESULTS
IL-6 and IL-15 act in lipid metabolism and carbohydrate metabolism, IL-6 also in the brain and immune system. Irisin produces a conversion of white to brown adipose tissue ("browning"), so does meteorin-like. Cathepsin B has a central effect. Kynurenine acts indirectly via kynurenic acid in the brain. The secretion of myokines depends on the intensity of physical stress and is modified by training. Prevention of vascular and neurologic diseases, cognitive enhancement and increased immunological function can be reached by setting free myokines during physical activity. Therapeutical use by technologically modified myokines is proposed in metabolic and neurological diseases, immobilization and sarcopenia.
CONCLUSIONS
The current research situation on myokines gives reason to recommend regular muscular activity in addition to the previously evidence-based benefits of sport in order to achieve preventive and therapeutic effects.
Topics: Humans; Interleukin-6; Muscle, Skeletal; Interleukin-15; Cathepsin B; Fibronectins; Kynurenine
PubMed: 37415033
DOI: 10.1007/s15006-023-2493-z -
International Journal of Molecular... Aug 2019Atrial natriuretic peptide (ANP) is a cardiac hormone belonging to the family of natriuretic peptides (NPs). ANP exerts diuretic, natriuretic, and vasodilatory effects... (Review)
Review
Atrial natriuretic peptide (ANP) is a cardiac hormone belonging to the family of natriuretic peptides (NPs). ANP exerts diuretic, natriuretic, and vasodilatory effects that contribute to maintain water-salt balance and regulate blood pressure. Besides these systemic properties, ANP displays important pleiotropic effects in the heart and in the vascular system that are independent of blood pressure regulation. These functions occur through autocrine and paracrine mechanisms. Previous works examining the cardiac phenotype of loss-of-function mouse models of ANP signaling showed that both mice with gene deletion of ANP or its receptor natriuretic peptide receptor A (NPR-A) developed cardiac hypertrophy and dysfunction in response to pressure overload and chronic ischemic remodeling. Conversely, ANP administration has been shown to improve cardiac function in response to remodeling and reduces ischemia-reperfusion (I/R) injury. ANP also acts as a pro-angiogenetic, anti-inflammatory, and anti-atherosclerotic factor in the vascular system. Pleiotropic effects regarding brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were also reported. In this review, we discuss the current evidence underlying the pleiotropic effects of NPs, underlying their importance in cardiovascular homeostasis.
Topics: Animals; Cardiovascular System; Humans; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptides; Reperfusion Injury; Vascular Remodeling; Ventricular Remodeling
PubMed: 31398927
DOI: 10.3390/ijms20163874 -
Molecular Biology Reports Jun 2020Prostanoids are short-lived autocrine and paracrine signaling molecules involved in a wide range of biological functions. They have been shown to be intimately involved... (Review)
Review
Prostanoids are short-lived autocrine and paracrine signaling molecules involved in a wide range of biological functions. They have been shown to be intimately involved in many different disease states when their regulation becomes dysfunctional. In order to fully understand the progression of any disease state or the biological functions of the well state, a complete evaluation of the genomics, proteomics, and metabolomics of the system is necessary. This review is focused on the enzymology for the enzymes involved in the synthesis of the prostanoids (prostaglandins, prostacyclins and thromboxanes). In particular, the isolation and purification of the enzymes, their enzymatic parameters and catalytic mechanisms are presented.
Topics: Humans; Prostaglandins; Prostaglandins I; Signal Transduction; Thromboxanes
PubMed: 32430846
DOI: 10.1007/s11033-020-05526-z -
Experimental Neurology Sep 2022Neural stem cell (NSC) based therapies are at the forefront of regenerative medicine strategies to combat illness and injury of the central nervous system (CNS). In... (Review)
Review
Neural stem cell (NSC) based therapies are at the forefront of regenerative medicine strategies to combat illness and injury of the central nervous system (CNS). In addition to their ability to produce new cells, NSCs secrete a variety of products, known collectively as the NSC secretome, that have been shown to ameliorate CNS disease pathology and promote recovery. As pre-clinical and clinical research to harness the NSC secretome for therapeutic purposes advances, a more thorough understanding of the endogenous NSC secretome can provide useful insight into the functional capabilities of NSCs. In this review, we focus on research investigating the autocrine and paracrine functions of the endogenous NSC secretome across life. Throughout development and adulthood, we find evidence that the NSC secretome is a critical component of how endogenous NSCs regulate themselves and their niche. We also find gaps in current literature, most notably in the clinically-relevant domain of endogenous NSC paracrine function in the injured CNS. Future investigations to further define the endogenous NSC secretome and its role in CNS tissue regulation are necessary to bolster our understanding of NSC-niche interactions and to aid in the generation of safe and effective NSC-based therapies.
Topics: Central Nervous System; Neural Stem Cells; Secretome; Stem Cell Niche
PubMed: 35709983
DOI: 10.1016/j.expneurol.2022.114142 -
Advances in Cancer Research 2022In most solid tumors, malignant cells coexist with non-cancerous host tissue comprised of a variety of extracellular matrix components and cell types, notably... (Review)
Review
In most solid tumors, malignant cells coexist with non-cancerous host tissue comprised of a variety of extracellular matrix components and cell types, notably fibroblasts, immune cells, and endothelial cells. It is becoming increasingly evident that the non-cancerous host tissue, often referred to as the tumor stroma or the tumor microenvironment, wields tremendous influence in the proliferation, survival, and metastatic ability of cancer cells. The tumor stroma has an active biological role in the transmission of signals, such as growth factors and chemokines that activate oncogenic signaling pathways by autocrine and paracrine mechanisms. Moreover, the constituents of the stroma define the mechanical properties and the physical features of solid tumors, which influence cancer progression and response to therapy. Inspired by the emerging importance of tumor-stroma crosstalk and oncogenic physical forces, numerous biosensors, or advanced imaging and analysis techniques have been developed and applied to investigate complex and challenging questions in cancer research. These techniques facilitate measurements and biological readouts at scales ranging from subcellular to tissue-level with unprecedented level of spatial and temporal precision. Here we examine the application of biosensor technology for studying the complex and dynamic multiscale interactions of the tumor-host system.
Topics: Biosensing Techniques; Chemokines; Endothelial Cells; Humans; Neoplasms; Signal Transduction; Stromal Cells; Tumor Microenvironment
PubMed: 35459472
DOI: 10.1016/bs.acr.2022.01.001 -
Biomolecules Sep 2023Endometriosis (EMs) is a common disease among women whose pathogenesis is still unclear, although there are various hypotheses. Recent studies have considered... (Review)
Review
Endometriosis (EMs) is a common disease among women whose pathogenesis is still unclear, although there are various hypotheses. Recent studies have considered macrophages the key part of the immune system in developing EMs, inducing inflammation, the growth and invasion of the ectopic endometrium, and angiogenesis. Extracellular vesicles (EVs) as novel intercellular vesicle traffic, can be secreted by many kinds of cells, including macrophages. By carrying long non-coding RNA (lncRNA), microRNA (miRNA), or other molecules, EVs can regulate the biological functions of macrophages in an autocrine and paracrine manner, including ectopic lesion growth, immune dysfunction, angiogenesis, and can further accelerate the progression of EMs. In this review, the interactions between macrophages and EVs for the pathogenesis of EMs are summarized. Notably, the regulatory pathways and molecular mechanisms of EVs secreted by macrophages during EMs are reviewed.
PubMed: 37759776
DOI: 10.3390/biom13091376