• Allergy, Asthma & Immunology Research
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• 제10권6호
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• pp.575-590
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• 2018

The prevalence of allergic disorders has dramatically increased over the past decade, particularly in developed countries. Apart from gastrointestinal disorders, neoplasia, genital and dermatological diseases etc., dysregulation of gut microbiota (dysbiosis) has also been found to be associated with increased risk of allergies. Probiotics are increasingly being employed to correct dysbiosis and, in turn, to modulate allergic diseases. However, several factors like strain variations and effector metabolites or component of them in a bacterial species can affect the efficacy of those as probiotics. On the other hand, host variations like geographical locations, food habits etc. could also affect the expected results from probiotic usage. Thus, there is a glaring deficiency in our approach to establish probiotics as an irrefutable treatment avenue for suitable disorders. In this review, we explicate on the reported probiotics and their effects on certain allergic diseases like atopic dermatitis, food allergy and asthma to establish their utility. We propose possible measures like elucidation of effector molecules and functional mechanisms of probiotics towards establishing probiotics for therapeutic use. Certain probiotics studies have led to very alarming outcomes which could have been precluded, had effective guidelines been in place. Thus, we also propose ways to secure the safety of probiotics. Overall, our efforts tend to propose necessary discovery and quality assurance guidelines for developing probiotics as potential immunomodulatory 'Pharmabiotics.'

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.10.1-10.11
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• 2018

Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.621-629
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• 2021

Shigella flexneri is a facultative intracellular pathogen that causes bacillary dysentery in humans. Infection with S. flexneri can result in more than a million deaths yearly and most of the victims are children in developing countries. Therefore, identifying novel and unique drug targets against this pathogen is instrumental to overcome the problem of drug resistance to the antibiotics given to patients as the current therapy. In this study, a comparative analysis of the metabolic pathways of the host and pathogen was performed to identify this pathogen's essential enzymes for the survival and propose potential drug targets. First, we extracted the metabolic pathways of the host, Homo sapiens, and pathogen, S. flexneri, from the KEGG database. Next, we manually compared the pathways to categorize those that were exclusive to the pathogen. Further, all enzymes for the 26 unique pathways were extracted and submitted to the Geptop tool to identify essential enzymes for further screening in determining the feasibility of the therapeutic targets that were predicted and analyzed using PPI network analysis, subcellular localization, druggability testing, gene ontology and epitope mapping. Using these various criteria, we narrowed it down to prioritize 5 novel drug targets against S. flexneri and one vaccine drug targets against all strains of Shigella. Hence, we suggest the identified enzymes as the best putative drug targets for the effective treatment of S. flexneri.

• Genomics & Informatics
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• 제19권1호
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• pp.4.1-4.9
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• 2021

Lip and oral cavity cancer, which can occur in any part of the mouth, is the 11th most common type of cancer worldwide. The major obstacles to patients' survival are the poor prognosis, lack of specific biomarkers, and expensive therapeutic alternatives. This study aimed to identify the main genes and pathways associated with lip and oral cavity carcinoma using network analysis and to analyze its molecular mechanism and prognostic significance further. In this study, 472 genes causing lip and oral cavity carcinoma were retrieved from the DisGeNET database. A protein-protein interaction network was developed for network analysis using the STRING database. VEGFA, IL6, MAPK3, INS, TNF, MAPK8, MMP9, CXCL8, EGF, and PTGS2 were recognized as network hub genes using the maximum clique centrality algorithm available in cytoHubba, and nine potential drug candidates (ranibizumab, siltuximab, sulindac, pomalidomide, dexrazoxane, endostatin, pamidronic acid, cetuximab, and apricoxib) for lip and oral cavity cancer were identified from the DGIdb database. Gene enrichment analysis was also performed to identify the gene ontology categorization of cellular components, biological processes, molecular functions, and biological pathways. The genes identified in this study could furnish a new understanding of the underlying molecular mechanisms of carcinogenesis and provide more reliable biomarkers for early diagnosis, prognostication, and treatment of lip and oral cavity cancer.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 춘계학술대회
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• pp.93-93
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on GSK3${\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• 동의생리병리학회지
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• 제33권1호
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• pp.31-38
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• 2019

Cheongpyesagan-tang (CP) is one of the traditional medicinal prescription to treat Taeumin (太陰人)'s disease. It has been commonly used for the treatment of stroke, arthritis, diabetes and obesity. In this study, we investigated an anti-inflammatory potential of CP water extract. We examined the effects of CP on the lipopolysarccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). We also examined the levels of protein or mRNA of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and proinflammatory cytokines in RAW 264.7 cells. CP inhibited NO and $PGE_2$ production in a dose dependent manner and decreased the protein and mRNA expression of iNOS and COX-2. Also, CP decreased the mRNA expression of interleukin-6 (IL-6), interleukin-$1{\beta}$ (IL-$1{\beta}$), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). These results suggest that CP has potential as anti-inflammatory therapeutic medicine.

• Genomics & Informatics
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• 제16권4호
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• pp.25.1-25.5
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• 2018

Coronary artery disease (CAD) is one of the leading causes of death and disability all around the world. Recent studies have revealed that aberrantly regulated long non-coding RNA (lncRNA) as one of the main classes of cellular transcript plays a key regulatory role in transcriptional and epigenetic pathways. Recent reports have demonstrated that circulating lncRNAs in the blood can be potential biomarkers for CAD. HOTAIR is one of the most cited lncRNAs with a critical role in the initiation and progression of the gene expression regulation. Recent research on the role of the HOTAIR in cardiovascular disease lays the basis for the development of new studies considering this lncRNA as a potential biomarker and therapeutic target in CAD. In this study, we aimed to compare the expression of HOTAIR lncRNA in the blood samples of patients with CAD and control samples. The expression level was examined by semi-quantitative reverse transcriptase polymerase chain reaction technique. Our data shows that expression of HOTAIR is up-regulated in blood samples of patients with CAD.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.257-264
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• 2022

Colorectal cancer (CRC) is one of the most common malignant tumor. 5-FU is commonly used for the treatment of CRC. However, the development of drug resistance in tumor chemotherapy can seriously reduce therapeutic efficacy of 5-FU. Recent data show that FoxM1 is associated with 5-FU resistance in CRC. FoxM1 plays a critical role in the carcinogenesis and drug resistance of several malignancies. It has been reported that urushiol V isolated from the cortex of Rhus verniciflua Stokes is cytotoxic to several types of cancer cells. However, the underlying molecular mechanisms for its antitumor activity and its potential to attenuate the chemotherapeutic resistance in CRC cells remain unknown. Here, we found that urushiol V could inhibit the cell proliferation and induced S-phase arrest of SW480 colon cancer cells. It inhibited protein expression level of FoxM1 through activation of AMPK. We also investigated the combined effect of urushiol V and 5-FU. The combination treatment reduced FoxM1 expression and consequently reduced cell growth and colony formation in 5-FU resistant colon cancer cells (SW480/5-FUR). Taken together, these result suggest that urushiol V from Rhus verniciflua Stokes can suppress cell proliferation by inhibiting FoxM1 and enhance the antitumor capacity of 5-FU. Therefore, urushiol V may be a potential bioactive compound for CRC therapy.

• BMB Reports
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• 제55권1호
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• pp.39-47
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• 2022

Adoptive cell transfer (ACT), a form of cell-based immunotherapy that eliminates cancer by restoring and strengthening the body's immune system, has revolutionized cancer treatment. ACT entails intravenous transfer of either tumor-resident or peripheral blood-modified immune cells into cancer patients to mediate anti-tumor response. Although these immune cells control and eradicate cancer via enhanced cytotoxicity against specific tumor antigens, several side effects have been frequently reported in clinical trials. Recently, exosomes, potential cell-free therapeutics, have emerged as an alternative to cell-based immunotherapies, due to their higher stability under same storage condition, lower risk of GvHD and CRS, and higher resistance to immunosuppressive tumor microenvironment. Exosomes, which are nano-sized lipid vesicles, are secreted by living cells, including immune cells. Exosomes contain proteins, lipids, and nucleic acids, and the functional role of each exosome is determined by the specific cargo derived from parental cells. Exosomes derived from cytotoxic effectors including T cells and NK cells exert anti-tumor effects via proteins such as granzyme B and FasL. In this mini-review, we describe the current understanding of the ACT and immune cell-derived exosomes and discuss the limitations of ACT and the opportunities for immune cell-derived exosomes as immune therapies.

• Annals of Clinical Neurophysiology
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• 제23권2호
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• pp.69-81
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• 2021

Cortico-cortical evoked potential (CCEP) mapping is a rapidly developing method for visualizing the brain network and estimating cortical excitability. The CCEP comprises the early N1 component the occurs at 10-30 ms poststimulation, indicating anatomic connectivity, and the late N2 component that appears at < 200 ms poststimulation, suggesting long-lasting effective connectivity. A later component at 200-1,000 ms poststimulation can also appear as a delayed response in some studied areas. Such delayed responses occur in areas with changed excitability, such as an epileptogenic zone. CCEP mapping has been used to examine the brain connections causally in functional systems such as the language, auditory, and visual systems as well as in anatomic regions including the frontoparietal neocortices and hippocampal limbic areas. Task-based CCEPs can be used to measure behavior. In addition to evaluations of the brain connectome, single-pulse electrical stimulation (SPES) can reflect cortical excitability, and so it could be used to predict a seizure onset zone. CCEP brain mapping and SPES investigations could be applied both extraoperatively and intraoperatively. These underused electrophysiologic tools in basic and clinical neuroscience might be powerful methods for providing insight into measures of brain connectivity and dynamics. Analyses of CCEPs might enable us to identify causal relationships between brain areas during cortical processing, and to develop a new paradigm of effective therapeutic neuromodulation in the future.