• Title/Summary/Keyword: therapeutic potential

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Panax ginseng as a potential therapeutic for neurological disorders associated with COVID-19; Toward targeting inflammasome

  • Seo Won Shin;Ik Hyun Cho
    • Journal of Ginseng Research
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    • v.47 no.1
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    • pp.23-32
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    • 2023
  • Coronavirus disease 2019 (COVID-19) is a highly infectious respiratory disease caused by a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). SARS-CoV-2 infection may cause clinical manifestations of multiple organ damage, including various neurological syndromes. There are currently two oral antiviral drugs-Paxlovid and molnupiravir-that are recognized to treat COVID-19, but there are still no drugs that can specifically fight the challenges of SARS-CoV-2 variants. Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome is a multimolecular complex that can sense heterogeneous pathogen-associated molecular patterns associated with neurological disorders. The NLRP3 activation stimulates the production of caspase-1-mediated interleukin (IL)-1β, IL-18, and other cytokines in immune cells. Panax (P.) ginseng is a medicinal plant that has traditionally been widely used to boost immunity and treat various pathological conditions in the nervous system due to its safety and anti-inflammatory/oxidant/viral activities. Several recent reports have indicated that P. ginseng and its active ingredients may regulate NLRP3 inflammasome activation in the nervous system. Therefore, this review article discusses the current knowledge regarding the pathogenesis of neurological disorders related to COVID-19 and NLRP3 inflammasome activation and the possibility of using P. ginseng in a strategy targeting this pathway to treat neurological disorders.

Discovery of 14-3-3 zeta as a potential biomarker for cardiac hypertrophy

  • Joyeta Mahmud;Hien Thi My Ong;Eda Ates;Hong Seog Seo;Min-Jung Kang
    • BMB Reports
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    • v.56 no.6
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    • pp.341-346
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    • 2023
  • Acute myocardial infarction (AMI) is a multifaceted syndrome influenced by the functions of various extrinsic and intrinsic pathways and pathological processes, which can be detected in circulation using biomarkers. In this study, we investigated the secretome protein profile of induced-hypertrophy cardiomyocytes to identify next-generation biomarkers for AMI diagnosis and management. Hypertrophy was successfully induced in immortalized human cardiomyocytes (T0445) by 200 nM ET-1 and 1 μM Ang II. The protein profiles of hypertrophied cardiomyocyte secretomes were analyzed by nano-liquid chromatography with tandem mass spectrometry and differentially expressed proteins that have been identified by Ingenuity Pathway Analysis. The levels of 32 proteins increased significantly (>1.4 fold), whereas 17 proteins (<0.5 fold) showed a rapid decrease in expression. Proteomic analysis showed significant upregulation of six 14-3-3 protein isoforms in hypertrophied cardiomyocytes compared to those in control cells. Multi-reaction monitoring results of human plasma samples showed that 14-3-3 protein-zeta levels were significantly elevated in patients with AMI compared to those of healthy controls. These findings elucidated the role of 14-3-3 protein-zeta in cardiac hypertrophy and cardiovascular disorders and demonstrated its potential as a novel biomarker and therapeutic strategy.

Antibiotic resistance in Neisseria gonorrhoeae: broad-spectrum drug target identification using subtractive genomics

  • Umairah Natasya Mohd Omeershffudin;Suresh Kumar
    • Genomics & Informatics
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    • v.21 no.1
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    • pp.5.1-5.13
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    • 2023
  • Neisseria gonorrhoeae is a Gram-negative aerobic diplococcus bacterium that primarily causes sexually transmitted infections through direct human sexual contact. It is a major public health threat due to its impact on reproductive health, the widespread presence of antimicrobial resistance, and the lack of a vaccine. In this study, we used a bioinformatics approach and performed subtractive genomic methods to identify potential drug targets against the core proteome of N. gonorrhoeae (12 strains). In total, 12,300 protein sequences were retrieved, and paralogous proteins were removed using CD-HIT. The remaining sequences were analyzed for non-homology against the human proteome and gut microbiota, and screened for broad-spectrum analysis, druggability, and anti-target analysis. The proteins were also characterized for unique interactions between the host and pathogen through metabolic pathway analysis. Based on the subtractive genomic approach and subcellular localization, we identified one cytoplasmic protein, 2Fe-2S iron-sulfur cluster binding domain-containing protein (NGFG RS03485), as a potential drug target. This protein could be further exploited for drug development to create new medications and therapeutic agents for the treatment of N. gonorrhoeae infections.

The Effect of Microcurrent Stimulation on Pain and Quality of Life in Women with Primary Dysmenorrhea

  • Minkyoung Kwon;Wonjae Choi
    • Physical Therapy Rehabilitation Science
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    • v.12 no.3
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    • pp.293-299
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    • 2023
  • Objective: This study aimed to investigate the potential benefits of microcurrent stimulation as a non-invasive therapeutic approach for managing pain and improving the quality of life in women suffering from primary dysmenorrhea. Design: A case study. Methods: This study was conducted, involving a cohort of 6 women diagnosed with primary dysmenorrhea, aged between 20 to 30 years. Participants were received microcurrent stimulation using low-intensity microcurrents for 30 minutes every day for 4 weeks. The intensity of microcurrent stimulation was 25 μA and the frequency was 8 Hz. The intervention was administered between the menstruations, with pain intensity and quality of life being assessed at baseline, and then at the end of menstrual cycle. Pain intensity was evaluated using a visual analog scale (VAS) and menstrual symptom questionnaire (MSQ), while the quality of life was assessed through the stress response inventory (SRI), state trait anxiety inventory (STAI), center for epidemiologic studies depression (CES-D), and menstrual distress questionnaire (MEDI-Q). Results: After the intervention, participants demonstrated a statistically significant reduction in pain intensity, as evidenced by improved VAS scores (p<0.05). However, the changes in MSQ scores did not reach statistical significance. Regarding quality of life measures, no statistically significant differences were found in the SRI, STAI, CES-D, and MEDI-Q scores after the intervention (p>0.05). Conclusions: This study suggest that microcurrent stimulation holds promise as a potential treatment option for alleviating pain associated with primary dysmenorrhea.

Evaluation of the inhibitory effect of Gynostemma pentaphyllum extracts on CYP450 enzyme activities using LC-MS/MS

  • Jun Sang Yu;Young Seok Ji;So Young Jo;Xiang-Lan Piao;Hye Hyun Yoo
    • Mass Spectrometry Letters
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    • v.14 no.3
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    • pp.116-119
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    • 2023
  • Gynostemma pentaphyllum (Thunb.) Makino extract, a natural product with a history of traditional use, has gained attention for its potential health benefits. This study aimed to investigate its effects on key cytochrome P450 (CYP) enzymes using LC-MS/MS. Human liver microsomes and cDNA-expressed CYP2C8, CYP2C9, CYP2C19, and CYP3A4 supersomes were employed. Enzyme activity was assessed based on the formation of CYP-specific marker metabolites. The resulting data showed that the extract exhibited inhibitory effects on CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Thus, G. pentaphyllum extract may influence the pharmacokinetics of drugs metabolized by CYP2C8, CYP2C9, CYP2C19, and CYP3A4. These findings emphasize the importance of considering potential herb-drug interactions when incorporating this extract into therapeutic regimens or dietary supplements.

Extracts of Grifola frondosa inhibit the MAPK signaling pathways involved in keratinocyte inflammation and ameliorate atopic dermatitis

  • Eun-Ju Choi;Jin Kyeong Choi
    • Nutrition Research and Practice
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    • v.17 no.6
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    • pp.1056-1069
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    • 2023
  • BACKGROUND/OBJECTIVES: Grifola frondosa, commonly referred to as the maitake mushroom, has been studied extensively to explore its potential health benefits. However, its anti-inflammatory effects in skin disorders have not been sufficiently elucidated. This study aimed to elucidate the anti-inflammatory role of the ethanol extract of G. frondosa in atopic dermatitis (AD) using in vivo and in vitro models. MATERIALS/METHODS: We investigated its impact on skin and spleen inflammatory responses in Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in a mouse model. Additionally, we determined the immunosuppressive response and mechanism of G. frondosa by inducing atopic-like immune reactions in keratinocytes through tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. RESULTS: Our study revealed that G. frondosa ameliorates clinical symptoms in an AD-like mouse model. These effects contributed to the suppression of Th1, Th2, Th17, and Th22 immune responses in the skin and spleen, leading to protection against cutaneous inflammation. Furthermore, G. frondosa inhibited the production of antibodies immunoglobulin (Ig)E and IgG2a in the serum of AD mice. Importantly, the inhibitory effect of G. frondosa on inflammatory cytokines in TNF-α/IFN-γ-stimulated AD-like keratinocytes was associated with the suppression of MAPK (Mitogen Activated Protein Kinase) pathway activation. CONCLUSIONS: Collectively, these findings highlight the potential of G. frondosa as a novel therapeutic agent for AD treatment and prevention.

Tivozanib-induced activation of the mitochondrial apoptotic pathway and suppression of epithelial-to-mesenchymal transition in oral squamous cell carcinoma

  • Nak-Eun Choi;Si-Chan Park;In-Ryoung Kim
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.3
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    • pp.197-207
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    • 2024
  • The potential of tivozanib as a treatment for oral squamous cell carcinoma (OSCC) was explored in this study. We investigated the effects of tivozanib on OSCC using the Ca9-22 and CAL27 cell lines. OSCC is a highly prevalent cancer type with a significant risk of lymphatic metastasis and recurrence, which necessitates the development of innovative treatment approaches. Tivozanib, a vascular endothelial growth factor receptor inhibitor, has shown efficacy in inhibiting neovascularization in various cancer types but has not been thoroughly studied in OSCC. Our comprehensive assessment revealed that tivozanib effectively inhibited OSCC cells. This was accompanied by the suppression of Bcl-2, a reduction in matrix metalloproteinase levels, and the induction of intrinsic pathway-mediated apoptosis. Furthermore, tivozanib contributed to epithelial-to-mesenchymal transition (EMT) inhibition by increasing E-cadherin levels while decreasing N-cadherin levels. These findings highlight the substantial anticancer potential of tivozanib in OSCC and thus its promise as a therapeutic option. Beyond reducing cell viability and inducing apoptosis, the capacity of tivozanib to inhibit EMT and modulate key proteins presents the possibility of a paradigm shift in OSCC treatment.

Ginseng and ginsenosides on cardiovascular and pulmonary diseases; Pharmacological potentials for the coronavirus (COVID-19)

  • Ajay Vijayakumar;Jong-Hoon Kim
    • Journal of Ginseng Research
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    • v.48 no.2
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    • pp.113-121
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    • 2024
  • Since its outbreak in late 2019, the Coronavirus disease 2019 (COVID-19) pandemic has profoundly caused global morbidity and deaths. The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has major complications in cardiovascular and pulmonary system. The increased rate of mortality is due to delayed detection of certain biomarkers that are crucial in the development of disease. Furthermore, certain proteins and enzymes in cellular signaling pathways play an important role in replication of SARS-CoV-2. Most cases are mild to moderate symptoms, however severe cases of COVID-19 leads to death. Detecting the level of biomarkers such as C-reactive protein, cardiac troponin, creatine kinase, creatine kinaseMB, procalcitonin and Matrix metalloproteinases helps in early detection of the severity of disease. Similarly, through downregulating Renin-angiotensin system, interleukin, Mitogen-activated protein kinases and Phosphoinositide 3-kinases pathways, COVID-19 can be effectively controlled and mortality could be prevented. Ginseng and ginsenosides possess therapeutic potential in cardiac and pulmonary complications, there are several studies performed in which they have suppressed these biomarkers and downregulated the pathways, thereby inhibiting the further spread of disease. Supplementation with ginseng or ginsenoside could act on multiple pathways to reduce the level of biomarkers significantly and alleviate cardiac and pulmonary damage. Therefore, this review summarizes the potential of ginseng extract and ginsenosides in controlling the cardiovascular and pulmonary diseases by COVID-19.

BAP1 controls mesenchymal stem cell migration by inhibiting the ERK signaling pathway

  • Seobin Kim;Eun-Woo Lee;Doo-Byoung Oh;Jinho Seo
    • BMB Reports
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    • v.57 no.5
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    • pp.250-255
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    • 2024
  • Due to their stem-like characteristics and immunosuppressive properties, Mesenchymal stem cells (MSCs) offer remarkable potential in regenerative medicine. Much effort has been devoted to enhancing the efficacy of MSC therapy by enhancing MSC migration. In this study, we identified deubiquitinase BRCA1-associated protein 1 (BAP1) as an inhibitor of MSC migration. Using deubiquitinase siRNA library screening based on an in vitro wound healing assay, we found that silencing BAP1 significantly augmented MSC migration. Conversely, BAP1 overexpression reduced the migration and invasion capabilities of MSCs. BAP1 depletion in MSCs upregulates ERK phosphorylation, thereby increasing the expression of the migration factor, osteopontin. Further examination revealed that BAP1 interacts with phosphorylated ERK1/2, deubiquitinating their ubiquitins, and thus attenuating the ERK signaling pathway. Overall, our study highlights the critical role of BAP1 in regulating MSC migration through its deubiquitinase activity, and suggests a novel approach to improve the therapeutic potential of MSCs in regenerative medicine.

Comprehensive overview of the role of mitochondrial dysfunction in the pathogenesis of acute kidney ischemia-reperfusion injury: a narrative review

  • Min-Ji Kim;Chang Joo Oh;Chang-Won Hong;Jae-Han Jeon
    • Journal of Yeungnam Medical Science
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    • v.41 no.2
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    • pp.61-73
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    • 2024
  • Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.