• Title/Summary/Keyword: Preclinical

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Current Status of Stem Cell Treatment for Type I Diabetes Mellitus

  • Kakkar, Anupama;Sorout, Ashima;Tiwari, Mahak;Shrivastava, Pallavi;Meena, Poonam;Kumar Saraswat, Sumit;Srivastava, Supriya;Datt, Rajan;Pandey, Siddharth
    • Tissue Engineering and Regenerative Medicine
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    • v.15 no.6
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    • pp.699-709
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    • 2018
  • BACKGROUND: Diabetes mellitus is a major health concern in current scenario which has been found to affect people of almost all ages. The disease has huge impact on global health; therefore, alternate methods apart from insulin injection are being explored to cure diabetes. Therefore, this review mainly focuses on the current status and therapeutic potential of stem cells mainly mesenchymal stem cells (MSCs) for Type 1 diabetes mellitus in preclinical animal models as well as humans. METHODS: Current treatment for Type 1 diabetes mellitus mainly includes use of insulin which has its own limitations and also the underlying mechanism of diseases is still not explored. Therefore, alternate methods to cure diabetes are being explored. Stem cells are being investigated as an alternative therapy for treatment of various diseases including diabetes. Few preclinical studies have also been conducted using undifferentiated MSCs as well as in vitro MSCs differentiated into ${\beta}$ islet cells. RESULTS: These stem cell transplant studies have highlighted the benefits of MSCs, which have shown promising results. Few human trials using stem cells have also affirmed the potential of these cells in alleviating the symptoms. CONCLUSION: Stem cell transplantation may prove to be a safe and effective treatment for patients with Type 1 diabetes mellitus.

Suggestions for Potentially Useful Herbal Medicines for Treating Insomnia in COVID-19 Era: A Mini-Review

  • Suh, Hyo-Weon;Kwon, Chan-Young;Kim, Jong Woo
    • Journal of Oriental Neuropsychiatry
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    • v.32 no.2
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    • pp.95-109
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    • 2021
  • Objectives: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Mental sequelae occurring in patients with COVID-19 and the general population are important concerns. In Korea, herbal medicine is used nationwide to respond to this pandemic. It can be prescribed by COVID-19 telemedicine center of Korean medicine (KM). Among some herbal medicines, Gamiguibi-tang is the only herbal medicine prescribed for individuals with mental health, especially for those with insomnia. In this mini-review, the objective of this study was to summarize the evidence of some promising herbal medicines available for treating primary insomnia based on existing clinical and preclinical studies. Methods: A research team was formed for KM clinical practice guidelines for insomnia (version 1.0). Team members were provided with a list of references of relevant herbal medicines for insomnia. To gather evidence from clinical studies with appropriate sample sizes, among the list of references, randomized controlled trials for primary insomnia that included 50 subjects or more per arm and used herbal medicine were included in the final analysis. Moreover, pre-clinical studies examining the mechanism of action of each herbal medicine and studies on herb-drug interactions, were searched and summarized. Results: Four herbal medicines (Ondam-tang, Sanjoin-tang, Guibi-tang, and Hyeolbuchugeo-tang) were reviewed based on existing clinical and preclinical studies. Based on findings of existing studies, some suggestions of herbal medicines for insomnia in the COVID-19 era in Korea were suggested. Conclusions: Data of this study could be used to prepare a future revision of the manual of COVID-19 telemedicine center of KM.

Clinical assessment and grading of back pain in horses

  • Mayaki, Abubakar Musa;Razak, Intan Shameha Abdul;Adzahan, Noraniza Mohd;Mazlan, Mazlina;Rasedee, Abdullah
    • Journal of Veterinary Science
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    • v.21 no.6
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    • pp.82.1-82.10
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    • 2020
  • Background: The clinical presentation of horses with back pain (BP) vary considerably with most horse's willingness to take part in athletic or riding purpose becoming impossible. However, there are some clinical features that are directly responsible for the loss or failure of performance. Objectives: To investigate the clinical features of the thoracolumbar region associated with BP in horses and to use some of the clinical features to classify equine BP. Methods: Twenty-four horses comprised of 14 with BP and 10 apparently healthy horses were assessed for clinical abnormality that best differentiate BP from normal horses. The horses were then graded (0-5) using the degree of pain response, muscular hypertonicity, thoracolumbar joint stiffness and overall physical dysfunction of the horse. Results: The common clinical features that significantly differentiate horses with BP from non-BP were longissimus dorsi spasm at palpation (78.6%), paravertebral muscle stiffness (64.3%), resist lateral bending (64.3%), and poor hindlimb impulsion (85.7%). There were significantly (p < 0.05) higher scores for pain response to palpation, muscular hypertonicity, thoracolumbar joint stiffness and physical dysfunction among horses with BP in relation to non-BP. A significant relationship exists between all the graded abnormalities. Based on the cumulative score, horses with BP were categorized into mild, mild-moderate, moderate and severe cases. Conclusions: BP in horse can be differentiated by severity of pain response to back palpation, back muscle hypertonicity, thoracolumbar joint stiffness, physical dysfunctions and their cumulative grading score is useful in the assessment and categorization of BP in horses.

Trends of Studies in Journal of Korean Medicine Rehabilitation: Focused on Diseases and Treatment for Recent 10 years (한방재활의학과학회지의 연구동향: 최근 10년간의 연구들을 질환과 치료법 중심으로)

  • Ji-Hong Jeong;Hong-Ryoul Yoon;Soon-Joong Kim
    • Journal of Korean Medicine Rehabilitation
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    • v.33 no.1
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    • pp.61-75
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    • 2023
  • Objectives The purpose of this study is to find out what diseases or treatments the Korean Medicine Rehabilitation department is dealing with. Methods For data collection, papers published from 2012 to 2021 were searched and collected on the website of the Korean Society of Rehabilitation Medicine (https://www.ormkorea.org/). After that, reconfirmed data at the Oriental Medicine Advanced Searching Integrated System (OASIS) Traditional Medicine Portal (https://oasis.kiom.re.kr/). The searched papers were classified by year and classified according to format based on thesis and abstract. In addition, the papers were classified by subject, focusing on diseases and treatments. Results Total 557 studies were classified. The format of a total of 557 papers was distributed in 129 preclinical studies (23.2%), 136 literature studies (24.4%), 153 clinical studies (27.5%), 112 case reports (20.1%), and 27 other studies (4.8%). While preclinical studies and clinical studies are gradually decreasing over the years, case reports and literature studies are gradually increasing. Conclusions The number of papers in Journal of Korean Medicine Rehabilitation is gradually decreasing. Papers on more diverse topics is needed for the qualitative growth of journals and Department of Korean Medicine Rehabilitation.

Therapeutic Potential of Active Components from Acorus gramineus and Acorus tatarinowii in Neurological Disorders and Their Application in Korean Medicine

  • Cheol Ju Kim;Tae Young Kwak;Min Hyeok Bae;Hwa Kyoung Shin;Byung Tae Choi
    • Journal of Pharmacopuncture
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    • v.25 no.4
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    • pp.326-343
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    • 2022
  • Neurological disorders represent a substantial healthcare burden worldwide due to population aging. Acorus gramineus Solander (AG) and Acorus tatarinowii Schott (AT), whose major component is asarone, have been shown to be effective in neurological disorders. This review summarized current information from preclinical and clinical studies regarding the effects of extracts and active components of AG and AT (e.g., α-asarone and β-asarone) on neurological disorders and biomedical targets, as well as the mechanisms involved. Databases, including PubMed, Embase, and RISS, were searched using the following keywords: asarone, AG, AT, and neurological disorders, including Alzheimer's disease, Parkinson's disease, depression and anxiety, epilepsy, and stroke. Meta-analyses and reviews were excluded. A total of 873 studies were collected. A total of 89 studies were selected after eliminating studies that did not meet the inclusion criteria. Research on neurological disorders widely reported that extracts or active components of AG and AT showed therapeutic efficacy in treating neurological disorders. These components also possessed a wide array of neuroprotective effects, including reduction of pathogenic protein aggregates, antiapoptotic activity, modulation of autophagy, anti-inflammatory and antioxidant activities, regulation of neurotransmitters, activation of neurogenesis, and stimulation of neurotrophic factors. Most of the included studies were preclinical studies that used in vitro and in vivo models, and only a few clinical studies have been performed. Therefore, this review summarizes the current knowledge on AG and AT therapeutic effects as a basis for further clinical studies, and clinical trials are required before these findings can be applied to human neurological disorders.

Muscimol as a treatment for nerve injury-related neuropathic pain: a systematic review and meta-analysis of preclinical studies

  • Hamzah Adel Ramawad;Parsa Paridari;Sajjad Jabermoradi;Pantea Gharin;Amirmohammad Toloui;Saeed Safari;Mahmoud Yousefifard
    • The Korean Journal of Pain
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    • v.36 no.4
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    • pp.425-440
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    • 2023
  • Background: Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical studies aimed at summarizing the evidence regarding the efficacy of muscimol administration in the amelioration of nerve injury-related neuropathic pain. Methods: Two independent researchers performed the screening process in Medline, Embase, Scopus and Web of Science extracting data were extracted into a checklist designed according to the PRISMA guideline. A standardized mean difference (SMD [95% confidence interval]) was calculated for each. To assess the heterogeneity between studies, 2 and chi-square tests were utilized. In the case of heterogeneity, meta-regression and subgroup analyses were performed to identify the potential source. Results: Twenty-two articles met the inclusion criteria. Pooled data analysis showed that the administration of muscimol during the peak effect causes a significant reduction in mechanical allodynia (SMD = 1.78 [1.45-2.11]; P < 0.0001; I2 = 72.70%), mechanical hyperalgesia (SMD = 1.62 [1.28-1.96]; P < 0.0001; I2 = 40.66%), and thermal hyperalgesia (SMD = 2.59 [1.79-3.39]; P < 0.0001; I2 = 80.33%). This significant amendment of pain was observed at a declining rate from 15 minutes to at least 180 minutes post-treatment in mechanical allodynia and mechanical hyperalgesia, and up to 30 minutes in thermal hyperalgesia (P < 0 .0001). Conclusions: Muscimol is effective in the amelioration of mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia, exerting its analgesic effects 15 minutes after administration for up to at least 3 hours.

Preclinical evaluation using functional SPECT imaging of 123I-metaiodobenzylguanidine (mIBG) for adrenal medulla in normal mice

  • Yiseul Choi;Hye Kyung Chung;Sang Keun Woo;Kyo Chul Lee;Seowon Kang;Seowon Kang;Joo Hyun Kang;Iljung Lee
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.7 no.2
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    • pp.93-98
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    • 2021
  • meta-iodobenzylguanidine is one of the norepinephrine analogs and reuptakes together with norepinephrine with norepinephrine transporter. The radioiodinated ligand, 123I-meta-iodobenzylguanidine, is the most widely used for single photon emission computed tomography imaging to diagnose functional abnormalities and tumors of the sympathetic nervous system. In this study, we performed cellular uptake studies of 123I-meta-iodobenzylguanidine in positive- and negative-norepinephrine transporter cells in vitro to verify the uptake activity for norepinephrine transporter. After 123I-meta-iodobenzylguanidine was injected via a tail vein into normal mice, Single photon emission computed tomography/computed tomography images were acquired at 1 h, 4 h, and 24 h post-injection, and quantified the distribution in each organ including the adrenal medulla as a norepinephrine transporter expressing organ. In vitro cell study showed that 123I-meta-iodobenzylguanidine specifically uptaked via norepinephrine transporter, and significant uptake of 123I-meta-iodobenzylguanidine in the adrenal medulla in vivo single photon emission computed tomography images. These results demonstrated that single photon emission computed tomography imaging with 123I-meta-iodobenzylguanidine were able to quantify the biodistribution in vivo in the adrenal medulla in normal mice.

Network pharmacological analysis for identifying herbal medicine candidate for cerebral infarction focusing on Gardeniae Fructus (뇌경색 전임상 연구 후보 약재 선정을 위한 네트워크 약리학 분석법의 활용과 치자(梔子)의 적용 가능성 검토)

  • Jung Joohyun;Park Heejun;Lim Sehyun;Cho Suin
    • Herbal Formula Science
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    • v.31 no.3
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    • pp.145-156
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    • 2023
  • Objectives : This study aimed to select candidate herbal medicines to be used in preclinical studies of cerebral infarction using the network pharmacology research method. Methods : Oral bioavailability (OB), drug likeness (DL), Caco-2, and blood-brain barrier (BBB) permeability were employed in this study's network pharmacology analysis method to choose compounds with potential efficacy. The following formulas were utilized for the values of each variable used in this study: OB ≥ 20%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ -0.3. The relationships between target proteins and diseases that are assumed to be involved in the chosen bioavailable chemicals were built in a network manner using the aforementioned factors, and proteins thought to play a significant role were identified. Results : Sudan III was obtained as a result of selecting compounds related to ischemic stroke in consideration of pharmacokinetic characteristics such as digestion and absorption and practicality using the TCMSP database. Medicinal herbs Gardeniae Fructus (GF) contains sudan III, and it was confirmed that compounds in GF were highly related to brain diseases, and the mechanism involved through the KEGG pathway was confirmed. GF, which has sudan III related to ischemic stroke and is also involved in other neurological diseases, is expected to be used for ischemic stroke treatment. Conclusions : GF has been predicted to have potential for ischemic stroke treatment, and can be used for future preclinical studies.

Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis

  • Rui Chen;Mengting Wang;Qiaoling Qi;Yanli Tang;Zhenzhao Guo;Shuai Wu;Qiyan Li
    • Journal of Periodontal and Implant Science
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    • v.53 no.1
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    • pp.20-37
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    • 2023
  • Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

Whole genome sequence analyses of thermotolerant Bacillus sp. isolates from food

  • Phornphan Sornchuer;Kritsakorn Saninjuk;Pholawat Tingpej
    • Genomics & Informatics
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    • v.21 no.3
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    • pp.35.1-35.12
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    • 2023
  • The Bacillus cereus group, also known as B. cereus sensu lato (B. cereus s.l.), is composed of various Bacillus species, some of which can cause diarrheal or emetic food poisoning. Several emerging highly heat-resistant Bacillus species have been identified, these include B. thermoamylovorans, B. sporothermodurans, and B. cytotoxicus NVH 391-98. Herein, we performed whole genome analysis of two thermotolerant Bacillus sp. isolates, Bacillus sp. B48 and Bacillus sp. B140, from an omelet with acacia leaves and fried rice, respectively. Phylogenomic analysis suggested that Bacillus sp. B48 and Bacillus sp. B140 are closely related to B. cereus and B. thuringiensis, respectively. Whole genome alignment of Bacillus sp. B48, Bacillus sp. B140, mesophilic strain B. cereus ATCC14579, and thermophilic strain B. cytotoxicus NVH 391-98 using the Mauve program revealed the presence of numerous homologous regions including genes responsible for heat shock in the dnaK gene cluster. However, the presence of a DUF4253 domain-containing protein was observed only in the genome of B. cereus ATCC14579 while the intracellular protease PfpI family was present only in the chromosome of B. cytotoxicus NVH 391-98. In addition, prophage Clp protease-like proteins were found in the genomes of both Bacillus sp. B48 and Bacillus sp. B140 but not in the genome of B. cereus ATCC14579. The genomic profiles of Bacillus sp. isolates were identified by using whole genome analysis especially those relating to heat-responsive gene clusters. The findings presented in this study lay the foundations for subsequent studies to reveal further insights into the molecular mechanisms of Bacillus species in terms of heat resistance mechanisms.