scholarly journals Targeting the toll-like receptor pathway as a therapeutic strategy for neonatal infection

2021 ◽  
Author(s):  
Maria L Dias ◽  
Karen M O'Connor ◽  
Eugene Dempsey ◽  
Ken D. O'Halloran ◽  
Fiona Brigid McDonald
Keyword(s):  
Early Stage ◽  
Neonatal Infection ◽  
Adaptor Proteins ◽  
Toll Like Receptors ◽  
Transmembrane Receptors ◽  
Response To Stress ◽  
And Function ◽  
Tlr Signalling

Toll-like receptors (TLRs) are crucial transmembrane receptors that form part of the innate immune response. They play a role in the recognition of various microorganisms and their elimination from the host. TLRs have been proposed as vital immunomodulators in the regulation of multiple neonatal stressors that extend beyond infection such as oxidative stress and pain. The immune system is immature at birth and takes some time to become fully established. As such, babies are especially vulnerable to sepsis at this early stage of life. Findings suggest a gestational age-dependent increase in TLR expression. TLRs engage with accessory and adaptor proteins to facilitate recognition of pathogens and their activation of the receptor. TLRs are generally upregulated during infection and promote the transcription and release of proinflammatory cytokines. Several studies report that TLRs are epigenetically modulated by chromatin changes and promoter methylation upon bacterial infection which have long-term influences on immune responses. TLR activation is reported to modulate cardiorespiratory responses during infection and may play a key role in driving homeostatic instability observed during sepsis. Although complex, TLR signalling and downstream pathways are potential therapeutic targets in the treatment of neonatal diseases. By reviewing the expression and function of key toll-like receptors, we aim to provide an important framework to understand the functional role of these receptors in response to stress and infection in premature infants.

Targeting Toll like Receptors in Cancer: Role of TLR Natural and Synthetic Modulators

2020 ◽  
Vol 26 (39) ◽  
pp. 5040-5053 ◽  
Author(s):  
Arunaksharan Narayanankutty ◽  
Aswathi Sasidharan ◽  
Joice T. Job
Keyword(s):  
Immune Response ◽  
Web Of Science ◽  
Broad Class ◽  
The Body ◽  
Toll Like Receptors ◽  
Transmembrane Receptors ◽  
Molecular Patterns ◽  
Tlr Signalling ◽  
Detailed Outline

Background: Toll like receptors (TLRs) are a group of transmembrane receptors belonging to the broad class pattern recognition receptors (PRR), involved in recognition of Pathogen Associated Molecular Patterns (PAMPs) thereby inducing an immune response. Apart from these exogenous PAMPs, numerous endogenous PAMPs are also ligands for various TLRs thereby activating the TLR dependent immune response, subsequently leading to the onset of an inflammatory response. Prolonged activation of TLR by these endogenous PAMPs leads to chronic inflammatory insults to the body and which in turn alters the proliferative patterns of the cells, which ultimately leads to the development of cancer. Objectives: The present review aims to provide a detailed outline of the differential roles of various TLRs in cancer and the possible use of them as a therapeutic target. Methods: Data were collected from PubMed/Sciencedirect/Web of Science database and sorted; the latest literature on TLRs was incorporated in the review. Results: Among the different TLRs, few are reported to be anti-neoplastic, which controls the cell growth and multiplication in response to the endogenous signals. On the contrary, numerous studies have reported the procarcinogenic potentials of TLRs. Hence, TLRs have emerged as a potential target for the prevention and treatment of various types of cancers. Several molecules, such as monoclonal antibodies, small molecule inhibitors and natural products have shown promising anticancer potential by effectively modulating the TLR signalling. Conclusion: Toll-like receptors play vital roles in the process of carcinogenesis, hence TLR targeting is a promising approach for cancer prevention.

scholarly journals Fetal Neurology: The Role of Fetal Stress

2015 ◽  
Vol 9 (1) ◽  
pp. 30-39 ◽  
Author(s):  
Aida Salihagic Kadic
Keyword(s):  
Fetal Development ◽  
Behavioral Alterations ◽  
Intrauterine Environment ◽  
Cardiometabolic Disorders ◽  
The Central Nervous System ◽  
Response To Stress ◽  
And Function ◽  
Fetal Response

ABSTRACT Fetal development and growth, as well as the timing of birth is influenced by the intrauterine environment. Many environmental factors causing the fetal stress can interfere with fetal development and leave long-term and profound consequences on health. Fetal glucocorticoid overexposure has primarily significant consequences for the development of the central nervous system. In response to an adverse intrauterine conditions, the fetus is able to adapt its physiology to promote survival. However, these adaptations can result in permanent changes in tissue and organ structure and function that directly ‘program’ predisposition to disease. Cardiometabolic disorders, behavioral alterations and neuropsychiatric impairments in adulthood and/ or childhood may have their roots in the fetal period of life. Fetal response to stress and its prenatal and lifelong consequences are discussed in this review. How to cite this article Kadić AS. Fetal Neurology: The Role of Fetal Stress. Donald School J Ultrasound Obstet Gynecol 2015;9(1):30-39.

Expression and function of decapentaplegic and thick veins during the differentiation of the veins in the Drosophila wing

Development ◽  
1997 ◽  
Vol 124 (5) ◽  
pp. 1007-1018 ◽  
Author(s):  
J.F. Celis de
Keyword(s):  
Imaginal Disc ◽  
Signal Transduction Pathways ◽  
Pupal Development ◽  
Transmembrane Receptors ◽  
Notch Ligand ◽  
Regulatory Interactions ◽  
Drosophila Wing ◽  
Signalling Molecule ◽  
And Function

The differentiation of the veins in the Drosophila wing involves the coordinate activities of several signal transduction pathways, including those mediated by the transmembrane receptors Torpedo and Notch. In this report, the role of the signalling molecule Decapentaplegic during vein differentiation has been analysed. It is shown that decapentaplegic is expressed in the pupal veins under the control of genes that establish vein territories in the imaginal disc. Decapentaplegic, acting through its receptor Thick veins, activates vein differentiation and restricts expression of both veinlet and the Notch-ligand Delta to the developing veins. Genetic combinations between mutations that increase or reduce Notch, veinlet and decapentaplegic activities suggest that the maintenance of the vein differentiation state during pupal development involves cross-regulatory interactions between these pathways.

scholarly journals The Intricate Role of p53 in Adipocyte Differentiation and Function

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2621
Author(s):  
Yun Kyung Lee ◽  
Yu Seong Chung ◽  
Ji Hye Lee ◽  
Jin Mi Chun ◽  
Jun Hong Park
Keyword(s):  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Metabolic Stress ◽  
Health Concern ◽  
Metabolic Dysfunction ◽  
Direct Role ◽  
Proliferation And Apoptosis ◽  
Response To Stress ◽  
And Function

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.

TLR4 signalling in the intestine in health and disease

2007 ◽  
Vol 35 (6) ◽  
pp. 1473-1478 ◽  
Author(s):  
M. Fukata ◽  
M.T. Abreu
Keyword(s):  
Mammalian Cells ◽  
Metabolic Energy ◽  
Short Term ◽  
Receptor Signalling ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Term Benefit ◽  
Tlr Signalling

The colonic epithelium is lined along its apical membrane with ∼1014 bacteria/g of tissue. Commensal bacteria outnumber mammalian cells in the gut severalfold. The reason for this degree of commensalism probably resides in the recent recognition of the microbiome as an important source of metabolic energy in the setting of poorly digestible nutrients. As in many themes in biology, the host may have sacrificed short-term benefit, i.e. nutritional advantages, for long-term consequences, such as chronic inflammation or colon cancer. In the present review, we examine the role of TLR (Toll-like receptor) signalling in the healthy host and the diseased host. We pay particular attention to the role of TLR signalling in idiopathic IBD (inflammatory bowel disease) and colitis-associated carcinogenesis. In general, TLR signalling in health contributes to homoeostatic functions. These include induction of antimicrobial peptides, proliferation and wound healing in the intestine. The pathogenesis of IBD, ulcerative colitis and Crohn's disease may be due to increased TLR or decreased TLR signalling respectively. Finally, we discuss the possible role of TLR signalling in colitis-associated neoplasia.

Regulation of gastric carcinoma development in gastric adenoma/dysplasia by crebzf inhibition via miRNA-421.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 410-410 ◽  
Author(s):  
Yu Jin Kim ◽  
Won Shik Kim ◽  
Sang Woo Kim ◽  
Woon Yong Jung
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Early Stage ◽  
Gastric Adenoma ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
And Migration ◽  
Gastric Cancer Patients ◽  
And Function

410 Background: In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. Methods: We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. Results: We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. Conclusions: This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.

scholarly journals What We have Learned from Fetal Neurophysiology?

2012 ◽  
Vol 6 (2) ◽  
pp. 179-188 ◽  
Author(s):  
Aida Salihagic-Kadic ◽  
Maja Predojevic
Keyword(s):  
Nervous System ◽  
Obstet Gynecol ◽  
Sensory Development ◽  
Brain Structure And Function ◽  
The Central Nervous System ◽  
Response To Stress ◽  
And Function ◽  
Fetal Response

ABSTRACT The nervous system is one of the earliest emerging systems in fetal development. Due to progress of modern imaging technologies, such as ultrasound, a growing pool of information on the development of the central nervous system (CNS) and fetal behavioral patterns has been made available. The major events in the development of the CNS, fetal motor and sensory development as well as fetal response to stress are discussed in this review. The fetus is not entirely protected from harmful influence of the external factors. Postnatal follow-up studies have showed that many environmental influences causing the fetal stress can interfere with the fetal neurodevelopment and leave long-term and profound consequences on brain structure and function. How to cite this article SalihagićKadić A, Predojevic M. What We have Learned from Fetal Neurophysiology? Donald School J Ultrasound Obstet Gynecol 2012;6(2):179-188.

scholarly journals Transition in successors’ behavior and mindset while managing long-lived small and medium-sized manufacturing enterprises: a qualitative study

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 285
Author(s):  
Hiroo Suzuki ◽  
Yasunobu Kino
Keyword(s):  
Early Stage ◽  
Manufacturing Companies ◽  
Structured Interviews ◽  
Manufacturing Enterprises ◽  
Double Loop Learning ◽  
Initial Stage ◽  
Core Category ◽  
Stable Employment

Background: There have been many studies conducted on succession, which can be considered as the most important issue in family businesses. However, most of these previous studies have focused only on the early stage of succession, uncovering the role of the predecessor and the successor. Only a few studies have made efforts to examine the total lifecycle of succession. The purpose of this study is to explore the process of the transition in successors' behavior and mindset while managing long-lived small and medium-sized manufacturing enterprises throughout the lifecycle of succession. Methods: Semi-structured interviews were conducted with six successors of small and medium-sized manufacturing companies who are more than half a century old. Their answers were analyzed using the Modified-GTA method to construct a hypothetical model. Results: In total, 46 concepts, four categories, 17 subcategories, and one core category were generated. An analysis result diagram using all concepts and categories was formed. From the observation of this diagram, the successors gained confidence in management through the dilemma between autonomy and constraint in the early stage of succession, which was found in previous research. Following the initial stage, the successors responded to the crisis caused by market constraints and created autonomous strategies in their businesses. Conclusions: By experiencing repetitive crises, the successors tend to acquire new perspectives toward the naturally occurring crises. This change of premise by the successors is considered as the process of double-loop learning. Relationships inside and outside the company influence the generation of this viewpoint. From a long-term perspective, a sense of unity with employees, stable employment, and the pursuit of enjoyment constitute the successors' own values in this model.

scholarly journals Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease

2007 ◽  
Vol 193 (3) ◽  
pp. 323-330 ◽  
Author(s):  
Jane A Mitchell ◽  
Mark J Paul-Clark ◽  
Graham W Clarke ◽  
Shaun K McMaster ◽  
Neil Cartwright
Keyword(s):  
Germ Line ◽  
Critical Role ◽  
Adaptor Proteins ◽  
Lipoteichoic Acid ◽  
Host Cells ◽  
Toll Like Receptors ◽  
Specific Pathogen ◽  
Toll Receptor ◽  
Leucine Rich Repeats

Pathogens are sensed by pattern recognition receptors (PRRs), which are germ line-encoded receptors, including transmembrane Toll-like receptors (TLRs) and cytosolic nucleotide oligomerisation domain (NOD) proteins, containing leucine-rich repeats (NLRs). Activation of PRRs by specific pathogen-associated molecular patterns (PAMPs) results in genomic responses in host cells involving activation transcription factors and the induction of genes. There are now at least 10 TLRs in humans and 13 in mice, and 2 NLRs (NOD1 and NOD2). TLR signalling is via interactions with adaptor proteins including MyD88 and toll-receptor associated activator of interferon (TRIF). NOD signalling is via the inflammasome and involves activation of Rip-like interactive clarp kinase (RICK). Bacterial lipopolysaccharide (LPS) from Gram-negative bacteria is the best-studied PAMP and is activated by or ‘sensed’ by TLR4. Lipoteichoic acid (LTA) from Gram-positive bacteria is sensed by TLR2. TLR4 and TLR2 have different signalling cascades, although activation of either results in symptoms of sepsis and shock. This review describes the rapidly expanding field of pathogen-sensing receptors and uses LPS and LTA as examples of how these pathways parallel and diverge from each other. The role of pathogen-sensing pathways in disease is also discussed.

scholarly journals Involvement of Cholinergic, Adrenergic, and Glutamatergic Network Modulation with Cognitive Dysfunction in Alzheimer’s Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2283
Author(s):  
Yu-Jung Cheng ◽  
Chieh-Hsin Lin ◽  
Hsien-Yuan Lane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Early Stage ◽  
Amyloid Β ◽  
Tau Proteins ◽  
And Oxidative Stress

Alzheimer’s disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. The number of AD cases has been rapidly growing worldwide. Several the related etiological hypotheses include atypical amyloid β (Aβ) deposition, neurofibrillary tangles of tau proteins inside neurons, disturbed neurotransmission, inflammation, and oxidative stress. During AD progression, aberrations in neurotransmission cause cognitive decline—the main symptom of AD. Here, we review the aberrant neurotransmission systems, including cholinergic, adrenergic, and glutamatergic network, and the interactions among these systems as they pertain to AD. We also discuss the key role of N-methyl-d-aspartate receptor (NMDAR) dysfunction in AD-associated cognitive impairment. Furthermore, we summarize the results of recent studies indicating that increasing glutamatergic neurotransmission through the alteration of NMDARs shows potential for treating cognitive decline in mild cognitive impairment or early stage AD. Future studies on the long-term efficiency of NMDA-enhancing strategies in the treatment of AD are warranted.

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