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1.
Braz. arch. biol. technol ; 64(spe): e21200772, 2021. tab, graf
Article in English | LILACS | ID: biblio-1278459

ABSTRACT

Abstract Eucalyptus species possess anti-inflammatory, antifungal, antibacterial, and insecticidal properties. In this study, the chemical composition and biological activities of Eucalyptus cinerea essential oil (EO) and the leaf and stem anatomy were investigated. EO was extracted by Clevenger apparatus and the compounds were identified by GC/MS. The antioxidant activity was evaluated by DPPH, ABTS, and reducing phosphomolybdenum complex. Broth microdilution was used to determine antimicrobial activity. Cytotoxicity was verified against HeLa, HRT-18, and Calu-3 cells by MTT assay. The cytotoxic mechanism was studied by cell DNA content, cell cycle, and DNA fragmentation. The microscopic analyzes of the leaves and the stems were performed by light microscopy, field emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The main constituent of the EO was 1,8-cineole (55.24%). The EO showed low antioxidant and antimicrobial activities. Calu-3 cells showed a significant reduction in viability with IC50 of 689.79 ± 29.34 μg/mL. EO at 1000 μg/mL decreased the DNA content in Jurkat cells. In general, EO increased cell percentage in sub-G0 and S phases with concomitant reduction of cell percentage in G0/G1 and G2/M phases and provided DNA fragmentation of 29.73%. Anatomical and micromorphological features of the leaves and stems can help in the species identification and its differentiation from other Eucalyptus species.


Subject(s)
Terpenes , Biological Phenomena , Oils, Volatile , Myrtaceae , Microscopy
2.
Rev. Ateneo Argent. Odontol ; 63(2): 39-54, nov. 2020. ilus
Article in Spanish | LILACS | ID: biblio-1150748

ABSTRACT

La búsqueda por encontrar métodos para acortar la duración de los tratamientos de ortodoncia tiene un pasado reciente, un presente y un futuro. Las fuerzas ortodóncicas que se ejercen sobre la membrana periodontal producen movimientos dentarios por modificaciones histológicas y biomoleculares. El conocimiento de los procesos biológicos da lugar a implementar cambios para favorecer la aceleración de los procesos resortivos y neoformativos. El objetivo de esta publicación es hacer una breve síntesis de lo acontecido con este tema y exponer el procedimiento de las micro-osteoperforaciones (MOPs) como una opción complementaria al tratamiento de ortodoncia convencional. Aún no existe suficiente apoyo de ensayos clínicos en humanos para aseverar su éxito. Más aún, distintos autores publican conclusiones contradictorias. Es de esperar que, en breve, nuevas investigaciones contribuyan a respaldarlo o desestimarlo (AU)


The quest to find methods to shorten the duration of orthodontic treatments has a recent past, a present, and a future. Orthodontic forces exerted on the periodontal membrane produce tooth movements by histological and biomolecular modifications. Knowledge of biological processes results in changes to promote the acceleration of spring and neoformative processes. The objective of this publication is to make a brief synthesis of what happened with this topic and expose the micro-osteoperforations (MOPs) procedure as a complementary option to conventional orthodontic treatment. There is not yet enough support from human clinical trials to assert its success. Moreover, different authors publish conflicting conclusions. It is to be expected that, shortly, further investigations will help to support or dismiss it (AU)


Subject(s)
Humans , Tooth Movement Techniques/methods , Biological Phenomena , Oral Surgical Procedures , Microsurgery , Osteotomy/methods , Bone Resorption/physiopathology , Low-Level Light Therapy , RANK Ligand , Duration of Therapy
4.
J. venom. anim. toxins incl. trop. dis ; 26: e20190067, 2020. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1135161

ABSTRACT

Extracellular vesicles (EVs) are small membrane-bound vesicles of growing interest in vetetinary parasitology. The aim of the present report was to provide the first isolation, quantification and protein characterization of EVs from buffalo (Bubalus bubalis) sera infected with Theileria spp. Methods: Infected animals were identified through optical microscopy and PCR. EVs were isolated from buffalo sera by size-exclusion chromatography and characterized using western blotting analysis, nanoparticle tracking analysis and transmission electron microscopy. Subsequently, the proteins from isolated vesicles were characterized by mass spectrometry. Results: EVs from buffalo sera have shown sizes in the 124-140 nm range and 306 proteins were characterized. The protein-protein interaction analysis has evidenced biological processes and molecular function associated with signal transduction, binding, regulation of metabolic processes, transport, catalytic activity and response to acute stress. Five proteins have been shown to be differentially expressed between the control group and that infected with Theileria spp., all acting in the oxidative stress pathway. Conclusions: EVs from buffaloes infected with Theileria spp. were successfully isolated and characterized. This is an advance in the knowledge of host-parasite relationship that contributes to the understanding of host immune response and theileriosis evasion mechanisms. These findings may pave the way for searching new EVs candidate-markers for a better production of safe biological products derived from buffaloes.(AU)


Subject(s)
Animals , Buffaloes/microbiology , Communicable Diseases , Theileria , Nanoparticles , Extracellular Vesicles , Biological Phenomena , Proteomics
5.
Article in Chinese | WPRIM | ID: wpr-827537

ABSTRACT

Lysophosphatidic acid (LPA) is a small phospholipid that is present in all eukaryotic tissues and blood plasma. As an extracellular signaling molecule, LPA mediates many cellular functions by binding to six known G protein-coupled receptors and activating their downstream signaling pathways. These functions indicate that LPA may play important roles in many biological processes that include organismal development, wound healing, and carcinogenesis. Recently, many studies have found that LPA has various biological effects in different kinds of bone cells. These findings suggest that LPA is a potent regulator of bone development and remodeling and holds promising application potential in bone tissue engineering. Here, we review the recent progress on the biological regulatory function of LPA in bone tissue cells.


Subject(s)
Biological Phenomena , Bone and Bones , Lysophospholipids , Receptors, Lysophosphatidic Acid
6.
Article in English | WPRIM | ID: wpr-719647

ABSTRACT

BACKGROUND: Single nucleotide polymorphisms (SNPs) can modulate various biological processes by influencing microRNA (miRNA) biogenesis and altering target selection. Common SNPs may alter the processing of miRNA and may be associated with hepatocellular carcinoma (HCC). We investigated the relationship between miR-499A>G, miR-149C>T, miR-196a2T>C, and miR-146aG>C and HCC susceptibility, examining the interaction of the miRNAs with hepatitis B virus (HBV). METHODS: We evaluated the associations of miR-499A>G (rs3746444), miR-149C>T (rs2292832), miR-196a2T>C (rs11614913), and miR-146aG>C (rs2910164) with HCC susceptibility in 100 HCC patients (70 males and 30 females) and 120 healthy controls (70 males and 50 females), using the PCR-restriction fragment length polymorphism method. RESULTS: For miR-499A>G, the frequencies of the AG genotype and G allele were higher in female HCC patients than in female controls (P=0.02 and 0.045, respectively). The frequency of the A allele was higher in HBV-positive HCC patients than in controls (P=0.019). For miR-149C>T, the frequency of the CC genotype was higher in female HCC patients than in female controls (P=0.009). For miR-196a2T>C, the frequencies of the CT and CC genotypes and the C allele were higher in HBV-positive HCC patients than in controls (P C polymorphisms did not differ between HCC patients and controls. CONCLUSIONS: miR-499A>G, miR-149C>T, and miR-196a2T>C were associated with the development of HCC in women and/or that of HBV-related HCC. They can be considered genetic risk factors for the development of HCC among Iranians.


Subject(s)
Alleles , Biological Phenomena , Carcinoma, Hepatocellular , Female , Genotype , Hepatitis B virus , Humans , Male , Methods , MicroRNAs , Polymorphism, Single Nucleotide , Risk Factors
7.
Article in English | WPRIM | ID: wpr-719642

ABSTRACT

Reactive oxygen species (ROS) are widely generated in biological processes such as normal metabolism and response to xenobiotic exposure. While ROS can be beneficial or harmful to cells and tissues, generation of ROS by diverse anti-cancer drugs or phytochemicals plays an important role in the induction of apoptosis. We recently identified a derivative of naphthalene, MS-5, that induces apoptosis of an ovarian cell, CAOV-3. Interestingly, MS-5 induced apoptosis by down-regulating the ROS. Cell viability was evaluated by water-soluble tetrazolium salt (WST-1) assay. Apoptosis was evaluated by flow cytometry analysis. Intracellular ROS (H₂O₂), mitochondrial superoxide, mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was assessed by western blotting. The level of ATP was measured using ATP Colorimetric/Fluorometric Assay kit. MS-5 inhibited growth of ovarian cancer cell lines, CAOV-3, in a concentration- and time-dependent manner. MS-5 also induced G1 cell cycle arrest in CAOV-3 cells, while MS-5 decreased intracellular ROS generation. In addition, cells treated with MS-5 showed the decrease in MMP and ATP production. In this study, we found that treatment with MS-5 in CAOV-3 cells induced apoptosis but decreased ROS level. We suspect that MS-5 might interfere with the minimum requirements of ROS for survival. These perturbations appear to be concentration-dependent, suggesting that MS-5 may induce apoptosis by interfering with ROS generation. We propose that MS-5 may be a potent therapeutic agent for inducing apoptosis in ovarian cancer cell through regulation of ROS.


Subject(s)
Adenosine Triphosphate , Apoptosis , Biological Phenomena , Blotting, Western , Cell Line , Cell Survival , Flow Cytometry , G1 Phase Cell Cycle Checkpoints , Membrane Potential, Mitochondrial , Metabolism , Ovarian Neoplasms , Phytochemicals , Reactive Oxygen Species , Superoxides
8.
Asia Pacific Allergy ; (4): e4-2019.
Article in English | WPRIM | ID: wpr-750170

ABSTRACT

Food allergy is a growing global public health concern. As treatment strategies are currently limited to allergen avoidance and emergency interventions, there is an increasing demand for appropriate models of food allergy for the development of new therapeutics. Many models of food allergy rely heavily on the use of animals, and while useful, many are unable to accurately reflect the human system. In order to bridge the gap between in vivo animal models and clinical trials with human patients, human models of food allergy are of great importance. This review will summarize the commonly used human ex vivo and in vitro models of food allergy and highlight their advantages and limitations regarding how accurately they represent the human in vivo system. We will cover biopsy-based systems, precision cut organ slices, and coculture systems as well as organoids and organ-on-a-chip. The availability of appropriate experimental models will allow us to move forward in the field of food allergy research, to search for effective treatment options and to further explore the cause and progression of this disorder.


Subject(s)
Allergens , Anaphylaxis , Animals , Biological Phenomena , Coculture Techniques , Emergencies , Food Hypersensitivity , Humans , In Vitro Techniques , Models, Animal , Models, Theoretical , Organoids , Public Health
9.
Yonsei Medical Journal ; : 319-325, 2019.
Article in English | WPRIM | ID: wpr-742552

ABSTRACT

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and its high rates of relapse and metastasis are associated with a poor prognosis. Despite extensive research, the underlying regulatory mechanisms of CRC remain unclear. Long noncoding RNAs (lncRNAs) are a major type of noncoding RNAs that have received increasing attention in the past few years, and studies have shown that they play a role in many biological processes in CRC. Here, we summarize recent studies on lncRNAs associated with CRC and the signaling pathways and mechanisms underlying this association. We show that dysregulated lncRNAs may be new prognostic and diagnostic biomarkers or therapeutic targets for clinical application. This review contributes not only to our understanding of CRC, but also suggests novel signaling pathways associated with lncRNAs that can be targeted to block or eradicate CRC.


Subject(s)
Biological Phenomena , Biomarkers , Colon , Colonic Neoplasms , Colorectal Neoplasms , Neoplasm Metastasis , Prognosis , Recurrence , RNA, Long Noncoding , RNA, Untranslated
10.
Article in English | WPRIM | ID: wpr-740165

ABSTRACT

We discuss recent advances in Gd-based T₁-weighted MR contrast agents for the mapping of cellular pH. The pH plays a critical role in various biological processes. During the past two decades, several MR contrast agents of strategic importance for pH-mapping have been developed. Some of these agents shed light on the pH fluctuation in the tumor microenvironment. A pH-responsive self-assembled contrast agent facilitates the visualization of tumor size as small as 3 mm³. Optimization of various parameters is crucial for the development of pH-responsive contrast agents. In due course, the new contrast agents may provide significant insight into pH fluctuations in the human body.


Subject(s)
Biological Phenomena , Contrast Media , Human Body , Hydrogen-Ion Concentration , Tumor Microenvironment
11.
Experimental Neurobiology ; : 172-182, 2019.
Article in English | WPRIM | ID: wpr-739545

ABSTRACT

Rheb (Ras homolog enriched in the brain) is a small GTPase protein that plays an important role in cell signaling for development of the neocortex through modulation of mTORC1 (mammalian-target-of-rapamycin-complex-1) activity. mTORC1 is known to control various biological processes including axonal growth in forming complexes at the lysosomal membrane compartment. As such, anchoring of Rheb on the lysosomal membrane via the farnesylation of Rheb at its cysteine residue (C180) is required for its promotion of mTOR activity. To test the significance of Rheb farnesylation, we overexpressed a farnesylation mutant form of Rheb, Rheb C180S, in primary rat hippocampal neurons and also in mouse embryonic neurons using in utero electroporation. Interestingly, we found that Rheb C180S maintained promotional effect of axonal elongation similar to the wild-type Rheb in both test systems. On the other hand, Rheb C180S failed to exhibit the multiple axon-promoting effect which is found in wild-type Rheb. The levels of phospho-4EBP1, a downstream target of mTORC1, were surprisingly increased in Rheb C180S transfected neurons, despite the levels of phosphorylated mTOR being significantly decreased compared to control vector transfectants. A specific mTORC1 inhibitor, rapamycin, also could not completely abolish axon elongation characteristics of Rheb C180S in transfected cells. Our data suggests that Rheb in a non-membrane compartment can promote the axonal elongation via phosphorylation of 4EBP1 and through an mTORC1-independent pathway.


Subject(s)
Animals , Axons , Biological Phenomena , Cysteine , Electroporation , GTP Phosphohydrolases , Hand , Membranes , Mice , Neocortex , Neurons , Phosphorylation , Prenylation , Protein Prenylation , Rats , Sirolimus , TOR Serine-Threonine Kinases
12.
Article in English | WPRIM | ID: wpr-786461

ABSTRACT

Owing to its highly biocompatible property as naturally produced nanoscale particle and drug carrying ability, exosome has attracted much interest in the biomedical area. Versatile functions of exosome in biological system play an important role in elucidating mysterious and unknown biological processes and pathological disease progression. For usage of exosome as brain disease therapeutics, even though the ability of exosomes crossing blood brain barrier (BBB) is not well clearly proven, the small size and their own characteristics possessing cell-derived molecular contents may provide great and beneficial tools for brain delivery and brain-associated disease therapy. A variety of trials related to bioapplications using stem cell-derived exosome in regenerative therapy or autologous exosome shuttling inhibitor targeting brain disease-associated protein marker enhance possibility of exosome toward clinical application. The radionuclide PETor SPECT imaging of radiolabeled exosome will be clearly able to provide accurate clues for analyzing their whole body distribution, targeting efficacy, and the degree of non-specific tissue uptake. In this perspective, the practical information on thranostics of exosome for brain delivery and therapy is offered and radionuclide-based exosome applicability will be dealt with.


Subject(s)
Biological Phenomena , Blood-Brain Barrier , Brain Diseases , Brain , Disease Progression , Exosomes , Lifting , Radionuclide Imaging , Theranostic Nanomedicine , Tomography, Emission-Computed, Single-Photon
13.
Article in English | WPRIM | ID: wpr-788781

ABSTRACT

The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.


Subject(s)
Biological Phenomena , Brain , Drug Resistant Epilepsy , Epilepsies, Partial , Epilepsy , Eukaryotic Cells , Humans , Intercellular Signaling Peptides and Proteins , Malformations of Cortical Development , Nervous System , Oxygen , Sirolimus
14.
Journal of Breast Cancer ; : 219-236, 2019.
Article in English | WPRIM | ID: wpr-764267

ABSTRACT

PURPOSE: Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. METHODS: We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. RESULTS: A total of 68 miRNAs showed significantly different expression patterns between the groups (p < 0.001), and 13 of these miRNAs were significantly associated with poor survival (p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. CONCLUSION: The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.


Subject(s)
Apoptosis , Biological Phenomena , Biological Phenomena , Biomarkers , Breast Neoplasms , Breast , Diagnosis , Female , Gene Ontology , Genome , Humans , In Vitro Techniques , Kaplan-Meier Estimate , MicroRNAs , ROC Curve , Sensitivity and Specificity
15.
Article in English | WPRIM | ID: wpr-764074

ABSTRACT

BACKGROUND AND OBJECTIVES: There have been contradictory reports on the pro-cancer or anti-cancer effects of mesenchymal stem cells. In this study, we investigated whether conditioned medium (CM) from hypoxic human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) (H-CM) showed enhanced anti-cancer effects compared with CM from normoxic hUC-MSCs (N-CM). METHODS AND RESULTS: Compared with N-CM, H-CM not only strongly reduced cell viability and increased apoptosis of human cervical cancer cells (HeLa cells), but also increased caspase-3/7 activity, decreased mitochondrial membrane potential (MMP), and induced cell cycle arrest. In contrast, cell viability, apoptosis, MMP, and cell cycle of human dermal fibroblast (hDFs) were not significantly changed by either CM whereas caspase-3/7 activity was decreased by H-CM. Protein antibody array showed that activin A, Beta IG-H3, TIMP-2, RET, and IGFBP-3 were upregulated in H-CM compared with N-CM. Intracellular proteins that were upregulated by H-CM in HeLa cells were represented by apoptosis and cell cycle arrest terms of biological processes of Gene Ontology (GO), and by cell cycle of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In hDFs, negative regulation of apoptosis in biological process of GO and PI3K-Akt signaling pathway of KEGG pathways were represented. CONCLUSIONS: H-CM showed enhanced anti-cancer effects on HeLa cells but did not influence cell viability or apoptosis of hDFs and these different effects were supported by profiling of secretory proteins in both kinds of CM and intracellular signaling of HeLa cells and hDFs.


Subject(s)
Activins , Hypoxia , Apoptosis , Biological Phenomena , Cell Cycle , Cell Cycle Checkpoints , Cell Survival , Culture Media, Conditioned , Fibroblasts , Gene Ontology , Genome , HeLa Cells , Humans , Insulin-Like Growth Factor Binding Protein 3 , Membrane Potential, Mitochondrial , Mesenchymal Stem Cells , Tissue Inhibitor of Metalloproteinase-2 , Uterine Cervical Neoplasms
16.
Article in English | WPRIM | ID: wpr-763360

ABSTRACT

OBJECTIVE: Vitamin D-binding protein (VDBP) mediates various biological processes in humans. The goal of this study was to investigate whether VDBP gene polymorphisms could predispose Korean women to endometriosis. METHODS: We prospectively enrolled women with endometriosis (n = 16) and healthy controls (n = 16). Total serum 25-hydroxyl vitamin D (25(OH)D) concentrations were measured using an Elecsys vitamin D total kit. Levels of bioavailable and free 25(OH)D were calculated. Concentrations of VDBP were measured using a vitamin D BP Quantikine ELISA kit. DNA was extracted using a DNeasy blood & tissue kit. Two single-nucleotide polymorphisms (SNPs; rs4588 and rs7041) in GC, the gene that codes for VDBP, were analyzed using a TaqMan SNP genotyping assay kit. The functional variant of VDBP was determined based on the results of the two SNPs. RESULTS: Gravidity and parity were significantly lower in the endometriosis patients than in the control group, but serum CA-125 levels and the erythrocyte sedimentation rate were significantly higher. Total serum 25(OH)D levels in the endometriosis patients were significantly lower than in the control group. However, serum bioavailable 25(OH)D, free 25(OH)D, and VDBP levels did not differ significantly between the endometriosis and control groups. The genotypes and allele frequencies of GC were similar in both groups. CONCLUSION: Korean women with endometriosis had lower total serum 25(OH)D concentrations than controls. Neither serum VDBP concentrations nor polymorphisms in the gene coding for VDBP were associated with endometriosis. Further studies are needed to investigate the pathophysiology and clinical implications of 25(OH)D and VDBP in endometriosis.


Subject(s)
Biological Phenomena , Blood Sedimentation , Clinical Coding , DNA , Endometriosis , Enzyme-Linked Immunosorbent Assay , Female , Gene Frequency , Genotype , Gravidity , Humans , Parity , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Prospective Studies , Vitamin D , Vitamin D-Binding Protein , Vitamins
17.
Article in English | WPRIM | ID: wpr-763014

ABSTRACT

Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and


Subject(s)
Antigen Presentation , Biological Phenomena , Cell Adhesion , Cell Line , Cell Movement , Classification , Collagen , Drug Resistance , Extracellular Matrix , Gene Expression , Gene Ontology , Melanoma , Osteoblasts , Proto-Oncogene Proteins c-akt
18.
Article in English | WPRIM | ID: wpr-765353

ABSTRACT

The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.


Subject(s)
Biological Phenomena , Brain , Drug Resistant Epilepsy , Epilepsies, Partial , Epilepsy , Eukaryotic Cells , Humans , Intercellular Signaling Peptides and Proteins , Malformations of Cortical Development , Nervous System , Oxygen , Sirolimus
19.
Natural Product Sciences ; : 215-221, 2019.
Article in English | WPRIM | ID: wpr-760570

ABSTRACT

Inflammation is the crucial biological process of immune system which acts as body's defense and protective response against the injuries or infection. However, the systemic inflammation devotes the adverse effects such as multiple inflammation associated diseases. One of the best ways to treat this entity is by blocking the tumor necrosis factor alpha (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) to avoid the proinflammation cytokines production. Thus, this study aims to evaluate the potency of Sambucus bioactive compounds as anti-inflammation through in silico approach. In order to assess that, molecular docking was performed to evaluate the interaction properties between the TNF-α or TRAIL with the ligands. The 2D structure of ligands were retrieved online via PubChem and the 3D protein modeling was done by using SWISS Model. The prediction results of the study showed that caffeic acid (−6.4 kcal/mol) and homovanillic acid (−6.6 kcal/mol) have the greatest binding affinity against the TNF-α and TRAIL respectively. This evidence suggests that caffeic acid and homovanillic acid may potent as anti-inflammatory agent against the inflammation associated diseases. Finally, this study needs further examination and evaluation to validate the potency of Sambucus bioactive compounds.


Subject(s)
Biological Phenomena , Computational Biology , Computer Simulation , Cytokines , Homovanillic Acid , Immune System , Inflammation , Ligands , Plants , Sambucus , TNF-Related Apoptosis-Inducing Ligand , Tumor Necrosis Factor-alpha
20.
Article in English | WPRIM | ID: wpr-728013

ABSTRACT

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a , Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.


Subject(s)
Animals , Biological Phenomena , Chemotaxis , Classification , Cytokines , Dermatitis, Contact , Gene Expression , Gene Ontology , Genome , Hypersensitivity , Immune System , Interleukin-6 , Mice , Models, Animal , Neutrophils , Pruritus , RNA , Sensation , Sequence Analysis, RNA , Signal Transduction , Skin , Transcriptome , Transient Receptor Potential Channels , Up-Regulation , Wound Healing
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