• Genomics & Informatics
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• v.21 no.1
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• pp.2.1-2.14
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• 2023

Microglia, similar to peripheral macrophages, are the primary immune cells of the central nervous system (CNS). Microglia exist in the resting state in the healthy CNS, but can be activated and polarized into either M1 or M2 subtypes for immune defense and the maintenance of CNS homeostasis by multiple stimuli. Several long noncoding RNAs (lncRNAs) mediate human inflammatory diseases and neuropathologies by regulating their target genes. However, the function of common lncRNAs that contribute to microglial activation remains unclear. Thus, we used bioinformatic approaches to identify common lncRNAs involved in microglial activation in vitro. Our study identified several lncRNAs as common regulators of microglial activation. We identified 283 common mRNAs and 53 common lncRNAs during mouse M1 microglial activation processes, whereas 26 common mRNAs and five common lncRNAs were identified during mouse M2 microglial activation processes. A total of 648 common mRNAs and 274 common lncRNAs were identified during the activation of human M1 microglia. In addition, we identified 1,920 common co-expressed pairs in mouse M1 activation processes and 25 common co-expressed pairs in mouse M2 activation processes. Our study provides a comprehensive understanding of common lncRNA expression profiles in microglial activation processes in vitro. The list of common lncRNAs identified in this study provides novel evidence and clues regarding the molecular mechanisms underlying microglial activation.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.5.1-5.15
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• 2020

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

• Journal of Microbiology and Biotechnology
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• v.34 no.10
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• pp.2091-2099
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• 2024

Probiotics, when consumed in adequate amounts, can promote the health of the host and beneficially modulate the host's immunity. Particularly during the host's early life, the gut intestine undergoes a period of epithelial maturation in which epithelial cells organize into specific crypt and villus structures. This process can be mediated by the gut microbiota. Recent studies have reported that the administration of probiotics can further promote intestinal maturation in the neonatal intestine. Therefore, in this study, we investigated the effects of extracellular vesicles derived from the Limosilactobacillus fermentum SLAM 216 strain, which is an established probiotic with known immune and anti-aging effects on intestinal epithelial maturation and homeostasis, using mouse small intestinal organoids. As per our findings, treatment with L. fermentum SLAM 216-derived LF216EV (LF216EV) has significantly increased the bud number and size of organoid buds. Furthermore, extracellular vesicle (EV) treatment upregulated the expression of maturation-related genes, including Ascl2, Ephb2, Lgr5, and Sox9. Tight junctions are known to have an important role in the intestinal immune barrier, and EV treatment has significantly increased the expression of genes associated with tight junctions, such as Claudin, Muc2, Occludin, and Zo-1, indicating that it can promote intestinal development. This was supported by RNA sequencing, which revealed the upregulation of genes associated with cAMP-mediated signaling, which is known to regulate cellular processes including cell differentiation. Additionally, organoids exposed to LF216EV exhibited upregulation of genes associated with maintaining brain memory and neurotransmission, suggesting possible future functional implications.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7069-7074
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• 2013

Programmed cell death is a basic cellular process that is critical to maintaining tissue homeostasis. In contrast to apoptosis, necrosis was previously regarded as an unregulated and uncontrollable process. However, as research has progressed, necrosis, also known as necroptosis or programmed necrosis, is drawing increasing attention, not least becasu of its possible impications for cancer research. Necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinases 1 and 3 (RIP1 and RIP3), mixed lineage kinase domain-like (MLKL), and phosphoglycerate mutase 5 (PGAM5) and can be specifically inhibited by necrostatins. Not only does necroptosis serve as a backup cell death program when apoptosis is inhibited, but it is now recognized to play a pivotal role in regulating various physiological processes and the pathogenesis of a variety of human diseases such as ischemic brain injury, immune system disorders and cancer. The control of necroptosis by various defined trigger factors and signaling pathways now offers the opportunity to target this cellular process for therapeutic purposes. The purpose of this paper is to review current findings concerning the connections between various trigger factors and the RIP1/RIP3 signaling pathway as it relates to necroptosis.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.46 no.4
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• pp.359-364
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• 2013

Inordinate stress causes disorders of various systems in humans and activates defense mechanisms to maintain homeostasis in the body. Sleep is a vital, highly organized process regulated by complex systems of neuronal networks and neurotransmitters. Sleep is an essential biological process whose underlying regulating involves numerous anatomical structures and biochemical substances that can be compromised by stress and by the immune system. Gamma-amino butyric acid (GABA) is the main inhibitory neurotransmitter of the central nervous system, and activation of GABAA receptors is known to favor sleep. This study was conducted to evaluate the possible application of Lactobacillus brevis BJ20 fermentation to improve the functional qualities of sea tangle Saccharina japonica and oyster Crassostrea gigas. Antioxidant activity was determined by assaying levels of radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide. L. brevis BJ20 fermentation of sea tangle and oyster enhanced both antioxidant and antiinflammatory activities. These results suggested that L. brevis BJ20 fermented sea tangle and oyster could be used for alleviation of stress and to promote sleep.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.5
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• pp.1180-1186
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• 1999

A wide ranges of chemicals released into the environment have potential to interfere with physiological and development process by disrupting endocrine pathways. Endocrine system embraces a multitude of mechanisms of action, including effect on growth, behavior, reproduction and immune function. These environmental endocrine disruptors are present in environment and pose potential health consequences to human and wildlife. The best known form in endocrine distruptors involves substances which mimic or block the action of natural hormone in the body. Endocrine disruptor have been variously defined as exogenous agents that interfere with the synthesis, secretion, transport, metabolism, binding action or elimination of the natural hormones in the body which are responsible for the maintenance of homeostasis, reproduction developmental and/or behavior. Many compounds polluted into the environment by human activity are capable of disrupting the endocrine system of animals, including fish, wildlife, and humans. Among these chemicals are pesticides, industrial chemicals, and other anthropogenic products. It has been alleged that several adverse effects on human health are linked with exposure to chemicals which are claimed to be endocrine disrupters, that is, increased incidence of testicular, prostate and female breast cancer, time dependent reductions in sperm quality and quantity, increased incidence of cryptorchidism (undescended testicles) and hypospadias(malformation of the penis), altered physical and mental de velopment in children. This observation is currently the only example of chemically mediated endocrine disruption which has resulted in a clear effect at the population level.

• BMB Reports
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• v.49 no.10
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• pp.529-535
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• 2016

The NLRP3 inflammasome is activated by a variety of external or host-derived stimuli and its activation initiates an inflammatory response through caspase-1 activation, resulting in inflammatory cytokine IL-1β maturation and secretion. The NLRP3 inflammasome activation is a kind of innate immune response, most likely mediated by myeloid cells acting as a host defense mechanism. However, if this activation is not properly regulated, excessive inflammation induced by overactivated NLRP3 inflammasome can be detrimental to the host, causing tissue damage and organ dysfunction, eventually causing several diseases. Previous studies have suggested that mitochondrial damage may be a cause of NLRP3 inflammasome activation and autophagy, which is a conserved self-degradation process that negatively regulates NLRP3 inflammasome activation. Recently, mitochondria-selective autophagy, termed mitophagy, has emerged as a central player for maintaining mitochondrial homeostasis through the elimination of damaged mitochondria, leading to the prevention of hyperinflammation triggered by NLRP3 inflammasome activation. In this review, we will first focus on the molecular mechanisms of NLRP3 inflammasome activation and NLRP3 inflammasome-related diseases. We will then discuss autophagy, especially mitophagy, as a negative regulator of NLPP3 inflammasome activation by examining recent advances in research.

• Fisheries and Aquatic Sciences
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• v.18 no.2
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• pp.173-181
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• 2015

We identified the $Na^+-K^+-2Cl^-$ cotransporter 2 (NKCC2) cDNA isoform from starry flounder, Platichthys stellate. The NKCC2 cDNA encoded a polypeptide of 1,043 amino acids representing 12 putative transmembrane domains based on the bioinformatic topology prediction. In addition, starry flounder NKCC2 possessed highly conserved residues within transmembrane domain 4, known as an essential site for its function. End-point reverse transcription-polymerase chain reaction analysis revealed that the NKCC2 transcript was moderately expressed only in the anterior and posterior intestines and the rectum. The NKCC2 mRNA level in the rectum, but not in other segments, was significantly induced 3 days post Streptococcus parauberis challenge, indicating that excess salt may be transported into the rectum. Taken together, our data indicate that an S. parauberis infection could tip the intestinal fluid balance in favor of fluid accumulation, indicating that bacterial pathogens can interfere with intestinal osmotic balance and normal mucosal immune homeostasis.

• Journal of Ginseng Research
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• v.31 no.3
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• pp.127-136
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• 2007

Ginseng, the root of Panax species, is a well-known herbal medicine. It has been used as traditional medicine in Korea, China and Japan for thousands of years and now is a popular and worldwide natural medicine. The active principles of ginseng are ginsenosides which are also called ginseng saponins. Traditionally ginseng has been used primarily as a tonic to invigorate weak body functions and help the restoration of homeostasis. Current in vivo and in vitro studies demonstrate its beneficial effects in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency and hepatotoxicity. Moreover, recent research indicates that some of ginseng's active ingredients exert beneficial actions on aging and neurodegenerative disorders such as Parkinson´s disease. Essentially, antioxidant, antiinflammatory, anti-apoptotic and immunostimulant activities are mostly underlying the postulated ginseng-mediated protective mechanisms. Next to animal studies, data from neural cell cultures contribute to the understanding of these mechanisms which involve decreasing nitric oxide, scavenging of free radicals and counteracting excitotoxicity. This paper focuses on own and other neuroprotective data on ginseng for dopaminergic neurons and intends to show aspects where neuroprotection e.g. by ginsenosides, additionally or preceding standard Parkinson therapy, could come about as a valuable contribution to slow neurodegenerative processes.

• Journal of Ginseng Research
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• v.31 no.3
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• pp.117-126
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• 2007

Ginseng, the root of Panax species, a well-known herbal medicine has been used as a traditional medicine for thousands of years and is now a popular and worldwide used natural medicine. Ginseng has been used primarily as a tonic to invigorate weak bodies to help the restoration of homeostasis in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency and hepatotoxicity. Although conclusive clinical data in humans is still missing, recent research results have suggested that some of the active ingredients ginseng exert beneficial effects on central nervous system (CNS) disorders and neurodegenerative diseases, suggesting it could be used in treatment of psychotic disorders. Data from neural cell cultures and animal studies contribute to the understanding of these mechanisms that involve inhibitory effects on stress-induced corticosterone level increasing and modulating of neurontransmitters, reducing $Ca^{2+}$ over-influx, scavenging of free radicals and counteracting excitotoxicity. In this review, we focused on recently reported medicinal effects of ginseng and summarized the possibility of its applications on psychotic disorders.