• Title/Summary/Keyword: Therapeutic mechanism

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Understanding the Unfolded Protein Response (UPR) Pathway: Insights into Neuropsychiatric Disorders and Therapeutic Potentials

  • Pitna Kim
    • Biomolecules & Therapeutics
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    • v.32 no.2
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    • pp.183-191
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    • 2024
  • The Unfolded Protein Response (UPR) serves as a critical cellular mechanism dedicated to maintaining protein homeostasis, primarily within the endoplasmic reticulum (ER). This pathway diligently responds to a variety of intracellular indicators of ER stress with the objective of reinstating balance by diminishing the accumulation of unfolded proteins, amplifying the ER's folding capacity, and eliminating slow-folding proteins. Prolonged ER stress and UPR irregularities have been linked to a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. This review offers a comprehensive overview of the UPR pathway, delineating its activation mechanisms and its role in the pathophysiology of neuropsychiatric disorders. It highlights the intricate interplay within the UPR and its profound influence on brain function, synaptic perturbations, and neural developmental processes. Additionally, it explores evolving therapeutic strategies targeting the UPR within the context of these disorders, underscoring the necessity for precision and further research to effective treatments. The research findings presented in this work underscore the promising potential of UPR-focused therapeutic approaches to address the complex landscape of neuropsychiatric disorders, giving rise to optimism for improving outcomes for individuals facing these complex conditions.

Extracellular Vesicles Derived from Mesenchymal Stem Cells as Cell-Free Therapy for Intrauterine Adhesion

  • Chao Li;Yuanjing Hu
    • International Journal of Stem Cells
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    • v.16 no.3
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    • pp.260-268
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    • 2023
  • Intrauterine adhesion (IUA) can occur after trauma to the basal layer of the endometrium, contributing to severe complications in females, such as infertility and amenorrhea. To date, the proposed therapeutic strategies are targeted to relieve IUA, such as hysteroscopic adhesiolysis, Foley catheter balloon, and hyaluronic acid injection have been applied in the clinic. However, these approaches showed limited effects in alleviating endometrial fibrosis and thin endometrium. Mesenchymal stem cells (MSCs) can offer the potential for endometrium regeneration owing to reduce inflammation and release growth factors. On this basis, MSCs have been proposed as promising methods to treat intrauterine adhesion. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles released by stem cells is raising increasing interest. The paracrine effect, mediated by MSCs derived extracellular vehicles (MSC-EVs), has recently been suggested as a mechanism for their therapeutic properties. Here, we summarizes the main pathological mechanisms involved in intrauterine adhesion, the biogenesis and characteristics of extracellular vesicles, explaining how these vesicles could provide new opportunities for MSCs.

Diagnostic and Therapeutic Laparoscopy for Abdominal Trauma: A Single Surgeon's Experience at a Level I Trauma Center

  • Jo, Hancheol;Kim, Dong Hun
    • Journal of Trauma and Injury
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    • v.34 no.4
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    • pp.248-256
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    • 2021
  • Purpose: Laparoscopy has various advantages over laparotomy in terms of postoperative recovery. The number of surgeons using laparoscopy as a diagnostic and therapeutic tool in abdominal trauma patients is increasing, whereas open conversion is becoming less common. This report summarizes a single surgeon's experience of laparoscopy at a level I trauma center and evaluates the feasibility of laparoscopy as a diagnostic and therapeutic tool for abdominal trauma patients. Methods: In total, 30 abdominal trauma patients underwent laparoscopy by a single surgeon from October 2014 to May 2020. The purpose of laparoscopy was categorized as diagnostic or therapeutic. Patients were classified into three groups by type of surgery: total laparoscopic surgery (TLS), laparoscopy-assisted surgery (LAS), or open conversion (OC). Univariate analysis was performed to determine the advantages and disadvantages. Results: The mechanism of injury was blunt in 19 (63.3%) and penetrating in 11 patients (36.7%). Eleven (36.7%) and 19 patients (63.3%) underwent diagnostic and therapeutic laparoscopy, respectively. The hospital stay was shorter for patients who underwent diagnostic laparoscopy than for those who underwent therapeutic laparoscopy (5.0 days vs. 13.0 days), but no other surgical outcomes differed between the groups. TLS, LAS, and OC were performed in 12 (52.2%), eight (34.8%), and three patients (13.0%), respectively. There was no significant difference in morbidity and mortality among the three groups. Conclusions: Laparoscopic surgery for selected cases of abdominal trauma may be feasible and safe as a diagnostic and therapeutic tool in hemodynamically stable patients due to the low OC rate and the absence of fatal morbidity and mortality.

Pathogenesis and Mechanism of Obstructive Sleep Apnea (폐쇄성 수면 무호흡증의 병인 및 기전)

  • Choi, Ji-Ho;Lee, Seung-Hoon;Shin, Chol
    • Sleep Medicine and Psychophysiology
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    • v.12 no.2
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    • pp.105-110
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    • 2005
  • The pathogenesis and mechanism of obstructive sleep apnea (OSA) has been under investigation for over 25 years, but its etiology and mechanism remains elusive. Skeletal (maxillary and/or mandibular hypoplasia or retrodisplacement, inferior displacement of hyoid) and soft tissue (increased volume of soft tissue, adenotonsillar hypertrophy, macroglossia, thickened lateral pharyngeal walls) factors, pharyngeal compliance (increased), pharyngeal muscle factors (impaired strength and endurance of pharyngeal dilators and fixators), sensory factors (impaired mechanoreceptor sensitivity, impaired pharyngeal dilator reflexes), respiratory control system factors (unstable respiratory control) and so on facilitate collapse upper airway. Therefore, OSA may be a heterogeneous disorder, rather than a single disease entity and various pathogenic factors contribute to the OSA varies person to person. As a result, patients may respond to different therapeutic approaches based on the predominant abnormality leading to the sleep-disordered breathing.

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A Study on the Literature Therapy Using Sijo (시조를 통한 문학치료 연구)

  • Park, Inkwa
    • The Journal of the Convergence on Culture Technology
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    • v.1 no.1
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    • pp.37-64
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    • 2015
  • This technical research paper attempts to examine literature therapeutic significance of Sijo. This research analyzes how the therapeutic mechanisms of literature or sentence can be physiologically applied to human nerve system. To study such interactions between therapeutic mechanisms of literature and human physiological mechanisms, diverse on- and offline Sijo activities, such as a Facebook group "Sijoya Nolja", were studied, as well as various publications in literature and medicine. For the three years this research was being conducted, 27 out of 488 Sijo poets debuted through Sinchunmunye, and many have gone professional through various contests. 19 of them became members of Sijo Poet Associations of Korea, with globalization of Sijo in mind. Their aggressive activity proves that the quality of live was elevated through literature therapy. The therapeutic effects are especially dramatic for older authors, and authors with traumatic experience. Through this research, Sijo turned out to be a form of literature with the quickest effect on elevating quality of life. To solve problems such as depression, emotional isolation, and other mental conditions, literature therapy through Sijo should be implemented, and therapeutic approach of literature should be more professionalized.

RECENT ADVANCES IN HEPATOTOXICITY STUDIES

  • Satoh, Tetsuo
    • Toxicological Research
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    • v.7 no.2
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    • pp.113-128
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    • 1991
  • Hepatotoxicity has many facets. Those to be discussed in this review include the mechanism for the hepatotoxic effects, nature of the injury, and animal models of hepatotoxicity suitable for the detection of chemical injury. Some therapeutic drugs used for treatment of hepatitis are also presented. In addition, as an important and serious problem in future, alternative toxicity testing is discussed.

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Proteomic analysis for the effects of non-saponin fraction with rich polysaccharide from Korean Red Ginseng on Alzheimer's disease in a mouse model

  • Sujin Kim;Yunkwon Nam;Min-jeong Kim;Seung-hyun Kwon;Junhyeok Jeon;Soo Jung Shin;Soyoon Park;Sungjae Chang;Hyun Uk Kim;Yong Yook Lee;Hak Su Kim;Minho Moon
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.302-310
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    • 2023
  • Background: The most common type of dementia, Alzheimer's disease (AD), is marked by the formation of extracellular amyloid beta (Aβ) plaques. The impairments of axons and synapses appear in the process of Aβ plaques formation, and this damage could cause neurodegeneration. We previously reported that non-saponin fraction with rich polysaccharide (NFP) from Korean Red Ginseng (KRG) showed neuroprotective effects in AD. However, precise molecular mechanism of the therapeutic effects of NFP from KRG in AD still remains elusive. Methods: To investigate the therapeutic mechanisms of NFP from KRG on AD, we conducted proteomic analysis for frontal cortex from vehicle-treated wild-type, vehicle-treated 5XFAD mice, and NFP-treated 5XFAD mice by using nano-LC-ESI-MS/MS. Metabolic network analysis was additionally performed as the effects of NFP appeared to be associated with metabolism according to the proteome analysis. Results: Starting from 5,470 proteins, 2,636 proteins were selected for hierarchical clustering analysis, and finally 111 proteins were further selected for protein-protein interaction network analysis. A series of these analyses revealed that proteins associated with synapse and mitochondria might be linked to the therapeutic mechanism of NFP. Subsequent metabolic network analysis via genome-scale metabolic models that represent the three mouse groups showed that there were significant changes in metabolic fluxes of mitochondrial carnitine shuttle pathway and mitochondrial beta-oxidation of polyunsaturated fatty acids. Conclusion: Our results suggested that the therapeutic effects of NFP on AD were associated with synaptic- and mitochondrial-related pathways, and they provided targets for further rigorous studies on precise understanding of the molecular mechanism of NFP.

Influence of Daejowhan-gamibang on Antioxidative Effects and Apoptosis Induction in Neuronal Cells

  • Lee Young Chan;Choi Ho Seung;Lee Jun;Jeon Byung Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1881-1891
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    • 2004
  • Daejowhan-gamibang(DJG) is used to prevention and treatment of cerebrovascular disease, heart disease, dementia, hyperlipdemia circulatory disturbance. Korean traditional herbal prescriptions and herb medicines in neuronal cells, which have been used for the treatment of stroke and brain diseases in Korean traditional medicine were screened to study the antioxidant effects and its mechanism. Daejowhan-gamibang water extract(DJGWE) was tested on their antioxidant activity using radical scavenging effects against ABTS. It showed significant antioxidant capacities at 50㎍ concentration. The antioxidant activity of DJGWE was determined in the different concentration (10㎍, 50 ㎍, and 100㎍). At the same time, the antiperoxidation effects was determined. Lipid peroxidation in brain homogenates induced by NADPH and ADP-Fe/sup 2+/ was significantly inhibited by DJGWE in vitro. DJGWE showed a potent antioxidant and antiperoxidative activity, further investigation, in vitro and in vivo, will be needed for the confirm of possibility as an antioxidant therapeutic agents and their optimal treatment of brain diseases in human. In searching the mechanism of antioxidant effects of DJGWE, it showed the inhibition of activity of JNK, p38, ERK and caspase 3 induced by hypoxia. So, DJGWE should be surveyed for the use of the potential therapeutic prescription for stroke and brain degenerative diseases such as pakinson's disease, dementia.

Suppression of Human Fibrosarcoma Cell Metastasis by Phyllanthus emblica Extract in Vitro

  • Yahayo, Waraporn;Supabphol, Athikom;Supabphol, Roongtawan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6863-6867
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    • 2013
  • Phyllanthus emblica (PE) is known to exhibit various pharmacological properties. This study aimed to evaluate the antimetastatic potential of a PE aqueous extract. Cytotoxicity to human fibrosarcoma cells, HT1080, was determined by viability assay using the 3-(4,5-dimethylthiazol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Cell migration and invasion were investigated using chemotaxis chambers containing membranes precoated with collagen IV and Matrigel, respectively. Cell attachment onto normal surfaces of cell culture plates was tested to determine the cell-adhesion capability. The molecular mechanism of antimetastatic activity was assessed by measuring the gene expression of matrix metalloproteinases, MMP2, and MMP9, using reverse transcription-polymerase chain reaction (RT-PCR) assay. The mRNA levels of both genes were significantly down-regulated after pretreatment with PE extract for 5 days. Our findings show the antimetastatic function of PE extract in reducing cell proliferation, migration, invasion, and adhesion in both dose- and time-dependent manners, especially growth arrest with low $IC_{50}$ value. A decrease in the expression of both MMP2 and MMP9 seems to be the cellular mechanism for antimetastasis in this case. There is a high potential to use PE extracts clinically as an optional adjuvant therapeutic drug for therapeutic intervention strategies in cancer therapy or chemoprevention.