• 제목/요약/키워드: therapeutic evidence

검색결과 629건 처리시간 0.025초

Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells

  • Kang, Sun Kyoung;Bae, Hyun Joo;Kwon, Woo Sun;Che, Jingmin;Kim, Tae Soo;Chung, Hyun Cheol;Rha, Sun Young
    • Genomics & Informatics
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    • 제18권4호
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    • pp.37.1-37.11
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    • 2020
  • BET inhibitor, as an epigenetic regulator inhibitor, reduces the expression of oncogenes such as Myc and Bcl-2, which affects cancer growth and development. However, it has modest activity because of the narrow therapeutic index. Therefore, combination therapy is necessary to increase the anti-tumor effect. Paclitaxel, an anti-mitotic inhibitor, is used as second-line therapy for gastric cancer (GC) as a monotherapy or combination. In this study, we performed RNA sequencing of GC cells treated with iBET-151 and/or paclitaxel to identify the differentially expressed genes associated with possible mechanisms of synergistic effect. We also performed Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses to determine the most enriched terms and pathways of upregulated and downregulated genes. We found 460 genes in which iBET-151 and paclitaxel combination treatment changed more than single-treatment or no-treatment. Thus, additional functional studies are needed, but our results provide the first evidence of the synergistic effect between iBET-151 and paclitaxel in regulating the transcriptome of GC cells.

Induction of Apoptosis by Ethyl Acetate Fraction of Astragalus membranaceus in Human Non-small Cell Lung Cancer Cells - Apoptosis Induction by Astragalus membranaceus -

  • Park, Hyun-Ji;Park, Shin-Hyung
    • 대한약침학회지
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    • 제21권4호
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    • pp.268-276
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    • 2018
  • Objectives: The purpose of this study is to investigate the anti-cancer effects of different fractions of Astragalus membranaceus (AM) in human non-small cell lung cancer (NSCLC) cells. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AM. The cell death was examined by MTT assay and trypan blue exclusion assay. Apoptosis was detected by DAPI staining, annexin V-PI double staining and cell cycle analysis. The expression of apoptosis-related proteins and mitogen-activated protein kinases (MAPKs) was examined by western blot. Results: Among various fractions of AM, the ethyl acetate fraction of AM (EAM) showed the strongest cytotoxic effect in NSCLC cells. EAM reduced the cell proliferation in a time- and dose-dependent manner in NSCLC cells. In addition, EAM induced the chromatin condensation, and increased the population of sub-G1 phase and annexin V-positive cells in a time-dependent manner, indicating that EAM induced apoptosis in NSCLC cells. Consistently, EAM enhanced the expression of cleaved caspase-8 and -9, and induced the accumulation of cleaved- poly (ADP-ribose) polymerase (PARP). Among MAPK proteins, only ERK was dephosphorylated by EAM, suggesting that ERK might be related with EAM-induced apoptosis. Conclusion: Our results clearly demonstrate that EAM exhibited anti-cancer effects in NSCLC cells by induction of apoptosis. We provide a valuable evidence which suggests that AM could be a desirable therapeutic option for treatment of NSCLC.

Interventions to Reduce the Problems of Abused Children and Adolescents in Residential Facilities in South Korea: An Integrative Review

  • Kim, Sungjae;Bang, Kyung-Sook;Lee, Gumhee;Song, Min Kyung;Jeong, Yeseul
    • Child Health Nursing Research
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    • 제25권3호
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    • pp.273-289
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    • 2019
  • Purpose: The purpose of this study was to review the literature on intervention studies for abused children and adolescent in residential facilities in South Korea (ACARF-K). The goal was to understand the problems they experience, to evaluate the content and effectiveness of interventions applied to them, and to develop evidence-based nursing intervention programs. Methods: We used four electronic databases to search for relevant articles. 18 studies according to Whittemore and Knafl's integrative review method to synthesize the literature. Results: The ACARF-K experienced problems in biophysical, psychological, and sociocultural domains related to attachment impairment. Effective intervention strategies were building trust through empathy and fulfillment of needs, encouraging ACARF-K to express themselves and helping them to clarify emotions in an unthreatening environment, and improving their self-concept through activities in which they experienced achievement. Conclusion: Interventions are needed to help restore attachment damage among ACARF-K. The interventions in this study utilized emotional, cognitive, relational, and behavioral therapeutic tools to improve their psychological and social capacities. Future intervention programs for ACARF-K should include these key elements.

Xanthone attenuates mast cell-mediated allergic inflammation

  • AYE, AYE;Jeon, Yong-Deok;Song, Young-Jae;Jin, Jong-Sik
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2019년도 춘계학술대회
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    • pp.123-123
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    • 2019
  • Xanthone is a kind of polyphenolic compounds that contain a distinctive chemical structure with a tricyclic aromatic ring found in a few higher plant families e.g. gentian root. This compound had a variety of biological activity, for instance antioxidant, antibacterial, anti-inflammatory, and anticancer effects. However, the effect of xanthone on mast cell-mediated allergic inflammation and its associated mechanism have not been elucidated. Therefore, the aim of this study was to elucidate the anti-allergic inflammatory effects and the underlying molecular mechanism of xanthone in PMACI-stimulated human mast cells-1 (HMC-1). In this result, xanthone treatment decreased the production of histamine, pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-${\alpha}$), IL-6, and IL-8 and expressions of TSLP in PMACI-stimulated HMC-cells. In addition, xanthone significantly suppressed the phosphorylation of MAPKs and the activation of NF-${\kappa}B$ signal pathway in activated mast cells. Furthermore, xanthone inhibited the activation of caspase-1, an IL-$1{\beta}$ converting enzyme, in PMACI-stimulated HMC-1 cells. These findings provide evidence that xanthone could be a potential therapeutic agent for allergy-related inflammatory disorders.

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Anti-Inflammatory Role of TAM Family of Receptor Tyrosine Kinases Via Modulating Macrophage Function

  • Lee, Chang-Hee;Chun, Taehoon
    • Molecules and Cells
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    • 제42권1호
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    • pp.1-7
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    • 2019
  • Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.

The impacts of exercise on pediatric obesity

  • Headid, Ronald J. III;Park, Song-Young
    • Clinical and Experimental Pediatrics
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    • 제64권5호
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    • pp.196-207
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    • 2021
  • Over the last few decades, the rates of pediatric obesity have more than doubled regardless of sociodemographic categorization, and despite these rates plateauing in recent years there continues to be an increase in the severity of obesity in children and adolescents. This review will discuss the pediatric obesity mediated cardiovascular disease (CVD) risk factors such as attenuated levels of satiety and energy metabolism hormones, insulin resistance, vascular endothelial dysfunction, and arterial stiffness. Additionally, early intervention to combat pediatric obesity is critical as obesity has been suggested to track into adulthood, and these obese children and adolescents are at an increased risk of early mortality. Current suggested strategies to combat pediatric obesity are modifying diet, limiting sedentary behavior, and increasing physical activity. The effects of exercise intervention on metabolic hormones such as leptin and adiponectin, insulin sensitivity/resistance, and body fat in obese children and adolescents will be discussed along with the exercise modality, intensity, and duration. Specifically, this review will focus on the differential effects of aerobic exercise, resistance training, and combined exercise on the cardiovascular risks in pediatric obesity. This review outlines the evidence that exercise intervention is a beneficial therapeutic strategy to reduce the risk factors for CVD and the ideal exercise prescription to combat pediatric obesity should contain both muscle strengthening and aerobic components with an emphasis on fat mass reduction and long-term adherence.

Can Myofascial Release Techniques Reduce Stress Hormones in the Subject of Short Hamstring Syndrome? A Pilot Study

  • Cho, Sunghak
    • 국제물리치료학회지
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    • 제11권4호
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    • pp.2237-2243
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    • 2020
  • Background: The myofascial release technique is known to be an effective technique for increasing posterior fascia flexibility in short hamstring syndrome (SHS) subjects. But therapeutic mechanism of myofascial relaxation remains unclear. Recently, the theory of autonomic nervous system domination has been raised, however, a proper study to test the theory has not been conducted. Objectives: To investigate whether the application of the myofascial release technique can induce changes in the autonomic nervous system and affect the secretion of stress hormones and myofascial relaxation. Design: Quasi-experimental study. Methods: Twenty-four subjects with SHS were randomly divided into two groups. In the experimental group, the suboccipital muscle inhibition (SMI) technique was applied to the subjects for 4 min in supine position, and in the control group, the subjects were lying in the supine position only. A forward flexion distance (FFD) was conducted, blood pressure, heart rate, and cortisol levels were measured before and after the intervention and 30 min after intervention to determine myofascial relaxation and stress hormone levels. The evaluation was conducted separately in blind by an evaluator. Results: A FFD decreased in the experimental group, no change in cortisol was observed. On the contrary, a decrease in cortisol appeared in the control group after 30 minutes. Conclusion: The myofascial release technique is an effective treatment to increase the range of motion through posterior superior myofascial chain, but there is no evidence that myofascial release technique can control the autonomic nervous system.

Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases

  • Durnaoglu, Serpen;Lee, Sun-Kyung;Ahnn, Joohong
    • Molecules and Cells
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    • 제44권12호
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    • pp.861-878
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    • 2021
  • The human genome contains many retroviral elements called human endogenous retroviruses (HERVs), resulting from the integration of retroviruses throughout evolution. HERVs once were considered inactive junk because they are not replication-competent, primarily localized in the heterochromatin, and silenced by methylation. But HERVs are now clearly shown to actively regulate gene expression in various physiological and pathological conditions such as developmental processes, immune regulation, cancers, autoimmune diseases, and neurological disorders. Recent studies report that HERVs are activated in patients suffering from coronavirus disease 2019 (COVID-19), the current pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In this review, we describe internal and external factors that influence HERV activities. We also present evidence showing the gene regulatory activity of HERV LTRs (long terminal repeats) in model organisms such as mice, rats, zebrafish, and invertebrate models of worms and flies. Finally, we discuss several molecular and cellular pathways involving various transcription factors and receptors, through which HERVs affect downstream cellular and physiological events such as epigenetic modifications, calcium influx, protein phosphorylation, and cytokine release. Understanding how HERVs participate in various physiological and pathological processes will help develop a strategy to generate effective therapeutic approaches targeting HERVs.

Potential application of biomimetic exosomes in cardiovascular disease: focused on ischemic heart disease

  • Kang, In Sook;Kwon, Kihwan
    • BMB Reports
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    • 제55권1호
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    • pp.30-38
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    • 2022
  • Cardiovascular disease, especially ischemic heart disease, is a major cause of mortality worldwide. Cardiac repair is one of the most promising strategies to address advanced cardiovascular diseases. Despite moderate improvement in heart function via stem cell therapy, there is no evidence of significant improvement in mortality and morbidity beyond standard therapy. The most salutary effect of stem cell therapy are attributed to the paracrine effects and the stem cell-derived exosomes are known as a major contributor. Hence, exosomes are emerging as a promising therapeutic agent and potent biomarkers of cardiovascular disease. Furthermore, they play a role as cellular cargo and facilitate intercellular communication. However, the clinical use of exosomes is hindered by the absence of a standard operating procedures for exosome isolation and characterization, problems related to yield, and heterogeneity. In addition, the successful clinical application of exosomes requires strategies to optimize cargo, improve targeted delivery, and reduce the elimination of exosomes. In this review, we discuss the basic concept of exosomes and stem cell-derived exosomes in cardiovascular disease, and introduce current efforts to overcome the limitations and maximize the benefit of exosomes including engineered biomimetic exosomes.

Stimulant Induced Movement Disorders in Attention Deficit Hyperactivity Disorder

  • Nam, Seok-Hyun;Lim, Myung Ho;Park, Tae Won
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • 제33권2호
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    • pp.27-34
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    • 2022
  • Stimulants, such as amphetamine and methylphenidate, are one of the most effective treatment modalities for attention deficit hyperactivity disorder (ADHD) and may cause various movement disorders. This review discusses various movement disorders related to stimulant use in the treatment of ADHD. We reviewed the current knowledge on various movement disorders that may be related to the therapeutic use of stimulants in patients with ADHD. Recent findings suggest that the use of stimulants and the onset/aggravation of tics are more likely to be coincidental. In rare cases, stimulants may cause stereotypies, chorea, and dyskinesia, in addition to tics. Some epidemiological studies have suggested that stimulants used for the treatment of ADHD may cause Parkinson's disease (PD) after adulthood. However, there is still a lack of evidence that the use of stimulants in patients with ADHD may cause PD, and related studies are only in the early stages. As stimulants are one of the most commonly used medications in children and adolescents, close observations and studies are necessary to assess the effects of stimulants on various movement disorders, including tic disorders and Parkinson's disease.