• Title/Summary/Keyword: Therapeutic mechanism

Search Result 898, Processing Time 0.022 seconds

Autophagy and Digestive Disorders: Advances in Understanding and Therapeutic Approaches

  • Thein, Wynn;Po, Wah Wah;Choi, Won Seok;Sohn, Uy Dong
    • Biomolecules & Therapeutics
    • /
    • v.29 no.4
    • /
    • pp.353-364
    • /
    • 2021
  • The gastrointestinal (GI) tract is a series of hollow organs that is responsible for the digestion and absorption of ingested foods and the excretion of waste. Any changes in the GI tract can lead to GI disorders. GI disorders are highly prevalent in the population and account for substantial morbidity, mortality, and healthcare utilization. GI disorders can be functional, or organic with structural changes. Functional GI disorders include functional dyspepsia and irritable bowel syndrome. Organic GI disorders include inflammation of the GI tract due to chronic infection, drugs, trauma, and other causes. Recent studies have highlighted a new explanatory mechanism for GI disorders. It has been suggested that autophagy, an intracellular homeostatic mechanism, also plays an important role in the pathogenesis of GI disorders. Autophagy has three primary forms: macroautophagy, microautophagy, and chaperone-mediated autophagy. It may affect intestinal homeostasis, host defense against intestinal pathogens, regulation of the gut microbiota, and innate and adaptive immunity. Drugs targeting autophagy could, therefore, have therapeutic potential for treating GI disorders. In this review, we provide an overview of current understanding regarding the evidence for autophagy in GI diseases and updates on potential treatments, including drugs and complementary and alternative medicines.

A Review on the Correlation between the Pathology of Alzheimer's Disease and microRNA

  • Kim, Soo-Jung;Cho, Hyun-Jeong
    • Biomedical Science Letters
    • /
    • v.27 no.4
    • /
    • pp.208-215
    • /
    • 2021
  • The purpose of this study was to explain the pathology of Alzheimer's disease (AD) and to investigate the correlation between AD and microRNA. AD is the most common type of dementia, accounting for about 80% of all types of dementia, causing dysfunction in various daily activities such as memory loss, cognitive impairment, and behavioral impairment. The typical pathology of AD is explained by the accumulation of beta-amyloid peptide plaques and neurofibrillary tangles containing hyperphosphorylated tau protein. On the other hand, microRNA is small non-coding RNA 22~23 nucleotides in length that binds to the 3' untranslated region of messenger RNA to inhibit gene expression. Many reports explain that microRNAs found in circulating biofluids are abundant in the central nervous system, are involved in the pathogenic mechanism of AD, and act as important factors for early diagnosis and therapeutic agents of AD. Therefore, this paper aims to clarify the correlation between AD and microRNA. In this review, the basic mechanism of miRNAs is described, and the regulation of miRNAs in the pathological processes of AD are highlighted. Furthermore, we suggest that miRNA-based system in development of therapeutic and diagnostic agents of AD can be a promising tool.

The Role of Autophagy in Eosinophilic Airway Inflammation

  • Jinju Lee;Hun Sik Kim
    • IMMUNE NETWORK
    • /
    • v.19 no.1
    • /
    • pp.5.1-5.12
    • /
    • 2019
  • Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.

Mizoribine Inhibits Production of Pro-inflammatory Cytokines and $PGE_2$ in Macrophages

  • Han, Shin-Ha;Kim, Kwang-Hee;Kim, Hyun-Yul;Kwon, Jeung-Hak;Han, Nam-Joo;Lee, Chong-Kil;Kim, Kyung-Jae
    • IMMUNE NETWORK
    • /
    • v.7 no.1
    • /
    • pp.31-38
    • /
    • 2007
  • Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

Review of Experimental Researches on Gastrointestinal Activity of Agastache rugosa (Fisch. & C. A. Mey.) Kuntze and Pogostemon cablin (Blanco) Benth. (곽향(藿香) 및 광곽향(廣藿香)의 위장관 효능에 대한 실험연구 고찰)

  • Jerng, Ui Min;Oh, Yong Taek;Kim, Jung Hoon
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.31 no.2
    • /
    • pp.138-144
    • /
    • 2017
  • The pharmacological rationale of Agastache rugosa (AR) or Pogostemon cablin (PC), which have been used in traditional Korean medicine to treat dampness pattern or syndrome in gastrointestinal tract, was investigated on the gastrointestinal disorders. In-vivo model studies that examined the effect on the gastrointestinal disorders of AR or PC were collected. They were classified into disease-induced in-vivo models or non-disease in vivo models. The target disease, animal species, induction method, administration, and outcomes (changes in morphological and histological parameter, or blood and fluid) of each study were analyzed. The therapeutic mechanism of AR or PC extract was evaluated by the induced diseases and the changes in outcomes. There were contradictory reports on gastrointestinal motility of AR or PC in disease non-disease in-vivo model. AR or PC inhibited gastrointestinal motility in disease model of increased gastrointestinal motility, while promoted motility in disease model of decreased gastrointestinal motility. AR or PC also inhibited inflammatory changes in gastrointestinal inflammation model. These results suggest that the bidirectional regulation of gastrointestinal motility and the improvement of gastrointestinal inflammatory disorders might underpin traditional therapeutic effect of AR or PC, that is effect to resolve dampness of gastrointestinal tract.

Therapeutic Effects of Cheonggisan Extract on Th2 cell differentiation and $NF-kB$ p65 activation (청기산(淸肌散)이 Th2 세포 분화와 염증에 미치는 영향)

  • Ku, Young-Hui;Hong, Seung-Ug
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
    • /
    • v.20 no.3
    • /
    • pp.63-70
    • /
    • 2007
  • Objectives : Atopic dermatitis is a recurrent or chronic eczematous skin disease with severe pruritus. Although the pathogenic mechanisms of atopic dermatitis are yet unknown, recently hyperresponsive Th2 cells in the acute phase are reported as the important mechanisms. Cheonggisan(CGS) is used in oriental clinics for curing acute skin lesions of eczema, atopic dermatitis or urticaria. There have been no studies on the therapeutic mechanism of CGS for curing atopic dermatitis. We aimed to find out the therapeutic mechanism of CGS on atopic dermatitis, so we observed Th2 cell differentiation in EL 4 cells and $NF-kB$ p65 activation in RAW 264.7 cells. Materials and Methods : EL 4 cells were induced the increase of IL-4 mRNA expression by phorbol-12-myristate-13-acetate(PMA) and 4-tert-Octylphenol(OP) and treated with CGS extract. RAW 264.7 cells were induced the increase of cyclooxygenase(COX)-2 mRNA expression by lipopolysaccharide(LPS) and treated with CGS extract. Results : The PMA and OP induced IL-4 mRNA expression was dose-dependantly decreased in CGS treated EL 4 cells. The LPS-induced COX-2 mRNA expression was dose-dependantly decreased in CGS treated RAW 264.7 cells. Conclusion : The results may suggest that the CGS inhibits Th2 cell differentiation in EL 4 cells and inhibits $NF-kB$ p65 activation in RAW 264.7 cells.

  • PDF

Candidacidal Effects of Rev (11-20) Derived from HIV-1 Rev Protein

  • Lee, Juneyoung;Lee, Dong Hwan;Lee, Dong Gun
    • Molecules and Cells
    • /
    • v.28 no.4
    • /
    • pp.403-406
    • /
    • 2009
  • Rev is an essential regulatory protein for HIV-1 replication. Rev (11-20) is known as the significant region regarding the function of a nuclear entry inhibitory signal (NIS) of Rev. In this study, anticandidal effects and mechanism of action of Rev (11-20) were investigated. The result exhibited that Rev (11-20) contained candidacidal activities. To understand target site(s) of Rev (11-20), the intracellular localization of the peptide was investigated. The result showed that Rev (11-20) rapidly accumulated in the fungal cell surface. The cell wall regeneration test also indicated that Rev (11-20) exerted its anticandidal activity to fungal plasma membrane rather than cell wall. The fluorescent study using 1,6-diphenyl-1,3,5-hexatriene (DPH) further confirmed the membrane-disruption mechanism(s) of Rev (11-20). The present study suggests that Rev (11-20) possesses significant potential regarding therapeutic agents for treating fungal diseases caused by Candida species in humans.

Inhibitory Effects of Harmine on Migration and Invasion of Human Breast Cancer Cells by Regulating Notch Signaling (Harmine의 Notch 신호전달 조절에 의한 유방암세포주 이동 및 침윤 억제 효과)

  • Yun, Jieun
    • Korean Journal of Pharmacognosy
    • /
    • v.49 no.4
    • /
    • pp.285-290
    • /
    • 2018
  • Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala has been reported as a promising drug candidate for cancer therapy. However, the effect of harmine on breast cancer remains still unclear. In this study, the effect of harmine on the cell proliferation, migration, and invasion of breast cancer MDA-MB231 cells and the underlying mechanism were investigated. The results indicated that harmine inhibited the proliferation MDA-MB231 cells in a dose-dependent manner and markedly suppressed migration and invasion of MDA-MB231 cells. The mechanism involved in part through Notch signaling. The Notch activity was significantly inhibited by harmine treatment and harmine suppressed the expression of Jagged1 which is a key ligand to activate Notch signaling. These findings suggest a novel mechanism of harmine on anti-cancer activity and harmine may act as a potential therapeutic drug for breast cancer treatment.

Study on the Treatment Mechanism of Back-Shu Points for Organ Dysfunction (배수혈의 내장기 치료 기전에 관한 연구)

  • Hwang, Man-Suk
    • Korean Journal of Acupuncture
    • /
    • v.33 no.3
    • /
    • pp.95-101
    • /
    • 2016
  • Objectives : This study aims to overview the therapeutic mechanism of back-shu points in terms of sympathetic visceral motor nervous system. Methods : Studies about autonomic nervous system, and studies and ancient texts about back-shu points were reviewed. We interpreted possible mechanism of back-shu points considering similarities of anatomical and physiological characteristics of back-shu points and visceral motor nervous system. Results : Afferent signals for organ lesions that can develop the symptoms of autonomic neurological symptoms, pain, hyperalgesia through the skin segment. Through a physical examination of the myotome and dermatome, it is possible to diagnose segmental disorders. Treatment stimulation of the thick fibers of the disorder segment skin can reduce abnormal autonomic influence over the sympathetic reflex mechanism. In addition, if spinal muscles are relaxed, the pressure on the nerve roots could be reduced and consequently the hyperactivity of the sympathetic visceral motor signal would be suppressed. Conclusions : The back-shu points treatments work through the mechanism of the sympathetic nervous reflex. Moreover, segmental acupuncture can reduce tension of the spinal muscles, thereby improving pathological conditions of the sympathetic nervous system.

A Study on the Therapeutic Mechanism of Line Drawing's Movement in Art Therapy (미술치료에서 선화(Line Drawing)의 운동성이 갖는 치료적 메커니즘 고찰)

  • Lee, Hyun-Jee;Chung, Yeo-Ju
    • The Journal of the Korea Contents Association
    • /
    • v.22 no.9
    • /
    • pp.497-509
    • /
    • 2022
  • Lines are the oldest visual elements in human history and are closely related to human life and drawings and symbols drawn with lines on cave paintings and rocks have existed as alternative images for human survival. In arts the line reveals the core of the object within a short period of time and in art therapy it becomes a medium that can diagnose the client's psychological state and intervene therapeutically. However although line drawing has therapeutic importance in the process as well as diagnosis studies on its effectiveness and therapeutic characteristic have not been actively conducted. Therefore in this study the characteristics related to line art in art therapy are first derived through 'Triangular Verification of Theory', 'Qualitative Content Analysis', and 'Finding Common Parts' in domestic and foreign literature. As a result I will examine the Movement which is a key therapeutic element of line drawing in connection with the brain structure. Through this I will examine the therapeutic mechanisms that affect the body, brain and mind of the movement of line drawing and examine and suggest how it can be used in art therapy.