The efficacy and safety of MARS-PD: Meridian activation remedy system for Parkinson's disease-A single-center, assessor and statistician-blinded, parallel-group randomized, controlled trial protocol.

BACKGROUND: Parkinson's disease (PD) patients face a substantial unmet need for disease-modifying interventions. Potential approaches such as exercise and acupuncture have been investigated to slow PD progression. To address this unmet need, we developed a novel therapeutic approach that integrates acupuncture and exercise: the Meridian Activation Remedy System for PD patients (MARS-PD). Building upon promising outcomes observed in our preliminary pilot study, where MARS-PD exhibited a large clinically important difference on the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III), we embark on a randomized controlled trial with the primary objective of examining the efficacy, safety, and economic impact of MARS-PD. METHODS: In this single-center, assessor and statistician-blinded, parallel-group randomized controlled trial, we aim to investigate the clinical efficacy of MARS-PD through 16 interventions administered over 8 weeks in 88 PD patients. Participants will be randomly assigned to the experimental (n = 44) or control (n = 44) groups. The experimental group will receive MARS-PD intervention alongside standard care, while the control group will solely receive standard care. The intervention period spans 8 weeks, followed by a 12-week post-intervention follow-up. The primary endpoint is the change in MDS-UPDRS Part III score from baseline to the conclusion of the 8-week intervention. Secondary outcomes encompass various assessments, including MDS-UPDRS, International Physical Activity Questionnaire Short Form, Parkinson Self Questionnaire, Parkinson's Disease Sleep Scale, Timed Up and Go test, GAITRite metrics, Functional Near-Infrared Spectroscopy measurements, smart band outcomes, gut microbiome analysis results, and iris connective tissue texture. DISCUSSION: Previous studies by the authors have indicated MARS-PD's safety and benefits for PD patients. Building upon this foundation, our current study aims to provide a more comprehensive and detailed confirmation of the efficacy of MARS-PD. TRIAL REGISTRATION: cris.nih.go.kr KCT0006646 -First posted on 7 October 2021; ClinicalTrials.gov NCT05621772 -First posted on 11 November 2022.

Effectiveness and Safety of Meridian Activation Remedy System for Alleviating Motor Symptoms in Parkinson's Disease: an Observational Study.

Background: Parkinson's disease (PD) lacks disease-modifying drugs or sustainable interventions, creating an unmet treatment need. Investigating complementary and alternative medicines aims to improve PD patients' quality of life by alleviating symptoms and delaying the course of the disease. Objectives: In this single-center, prospective, observational, single-arm study, we aimed to assess the effectiveness and safety of acupuncture combined with exercise therapy and the Meridian Activation Remedy System (MARS). Methods: From March to October 2021, 13 PD patients with Hoehn and Yahr stages 1 to 3 were recruited. For 8 weeks, MARS intervention was carried out twice a week. T-statistics were used to evaluate functional near-infrared spectroscopy (fNIRS) and GAITRite outcomes. All of the remaining outcome variables were evaluated using the Wilcoxon signed-rank test. Results: The MARS intervention significantly reduced PD patients' Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDSUPDRS) Part III score (from 20.0 ± 11.8 to 8.8 ± 5.5, p = 0.003), 10-meter walk test speed (from 9.5 ± 1.8 to 8.7 ± 1.3 seconds, p = 0.040), and timed up and go time (from 9.8 ± 1.8 to 8.9 ± 1.4 seconds, p = 0.040). Moreover, the MDS-UPDRS Part II, fNIRS hemodynamics, 360-degree turn test, fall efficacy scale, and Parkinson's Disease Questionnaire 39 scores improved but not significantly. All participants completed the 8-week intervention without any adverse reactions. Conclusion: An 8-week MARS intervention improved motor symptoms in PD patients. In particular, improvements in UPDRS Part III scores exhibited large clinically important differences. The findings are encouraging, and a randomized controlled trial will be conducted to determine the efficacy and cost-effectiveness of MARS intervention.

Characteristics of insulin resistance in Korean adults from the perspective of circadian and metabolic sensing genes.

BACKGROUND: The biological clock allows an organism to anticipate periodic environmental changes and adjust its physiology and behavior accordingly. OBJECTIVE: This retrospective cross-sectional study examined circadian gene polymorphisms and clinical characteristics associated with insulin resistance (IR). METHODS: We analyzed data from 1,404 Korean adults aged 30 to 55 with no history of cancer and cardio-cerebrovascular disease. The population was classified according to sex and homeostasis model assessment of insulin resistance (HOMA-IR) values. Demographics, anthropometric and clinical characteristics, and single nucleotide polymorphisms (SNPs) were analyzed with respect to sex, age, and HOMA-IR values. We used association rule mining to identify sets of SNPs from circadian and metabolic sensing genes that may be associated with IR. RESULTS: Among the subjects, 15.0% of 960 women and 24.3% of 444 men had HOMA-IR values above 2. Most of the parameters differed significantly between men and women, as well as between the groups with high and low insulin sensitivity. Body fat mass of the trunk, which was significantly higher in insulin-resistant groups, had a higher correlation with high sensitivity C-reactive protein and hemoglobin levels in women, and alanine aminotransferase and aspartate aminotransferase levels in men. Homozygous minor allele genotype sets of SNPs rs17031578 and rs228669 in the PER3 gene could be more frequently found among women with HOMA-IR values above 2 (p = .014). CONCLUSION: Oxidative stress enhanced by adiposity and iron overload, which may also be linked to NRF2 and PER3-related pathways, is related to IR in adulthood. However, due to the small population size in this study, more research is needed.

Modern concepts and biomarkers of blood stasis in cardio- and cerebrovascular diseases from the perspectives of Eastern and Western medicine: a scoping review protocol.

OBJECTIVE: The objective of this review is to provide a modern definition and identify potential biomarkers of blood stasis in cardio- and cerebrovascular diseases by mapping, comparing, and combining Eastern and Western concepts. INTRODUCTION: Blood stasis is a pathological concept found in both Eastern and Western medical literature. In traditional East Asian medicine, blood stasis is a differential syndrome characterized by stagnant blood flow in various parts of the body. Similarly, in Western medicine, various diseases, especially cardio- and cerebrovascular diseases, are known to be accompanied by blood stasis. Numerous scientific studies on blood stasis have been conducted over the last decade, and there is a need to synthesize those results. INCLUSION CRITERIA: We will use the keywords "blood stasis," "blood stagnation," "blood stagnant," and "blood congestion" in 3 electronic databases: PubMed, Cochrane CENTRAL, and Google Scholar. In addition, we will use the keywords "어혈" and "혈어" in 4 Korean electronic databases (ie, NDSL, OASIS, KISS, and DBpia). Peer-reviewed articles published from 2010 to the present that focus on blood stasis in cardio- and cerebrovascular diseases in human subjects according to the International Classification of Diseases 11 th revision categories BA00-BE2Z, 8B00-8B2Z, 8E64, and 8E65 will be included. Reviews, opinion articles, in vivo, in vitro, and in silico preclinical studies will be excluded. METHODS: We will follow the frameworks by Arksey and O'Malley and Levac et al. as well as JBI guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Two reviewers will independently search and screen titles and abstracts followed by full-text screening of eligible studies. If there are discrepancies between the 2 reviewers, a third reviewer will be consulted to make the final decision. We will use descriptive narrative, tabular, and graphical displays, and content analysis to present the results. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/gv4ym.

Pharmacological Properties of Jaeumgeonbi-Tang on Redox System and Stress-Related Hormones in Chronic Subjective Dizziness: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial.

Jaeumgeonbi-Tang (JGT), a traditional herbal medicine, has been used to treat dizziness and vertigo in Korea and China for hundreds of years. The purpose of this study was to evaluate the pharmacological properties of JGT in chronic subjective dizziness (CSD) patients. A randomized, double-blind, parallel-group and placebo-controlled trial was performed with a total of 50 CSD patients. The patients were randomly assigned to one of two groups: JGT or placebo (n = 25 for each). All participants received the treatment (placebo or JGT, 24 g/day) for 4 weeks. We analyzed the serum levels of oxidative stressors, antioxidants, and stress hormones. Serum levels of lipid peroxidation, but not nitric oxide, were significantly decreased in the JGT group. JGT not only prevented the decline of serum total glutathione contents and total antioxidant capacity, but it also increased superoxide dismutase and catalase activities. Serum levels of stress hormones including cortisol, adrenaline, and serotonin were notably normalized by JGT treatment, but noradrenaline levels were not affected. Regarding the safety and tolerability of JGT, we found no allergic, adverse, or side effects in any of the participants. JGT showed beneficial effects on CSD patients by improving redox status and balancing psycho-emotional stress hormones.

Pharmacological Effects of Gami-Yukmijihwang-Tang on the Lipopolysaccharide-Induced Hippocampus Oxidation and Inflammation via Regulation of Sirt6.

Yukmijihwang-Tang is widely used in traditional Korean medicine to treat age-related disorders. In the present study, we re-prescribed Gami-Yukmijihwang-Tang (YJT), which is slightly modified from Yukmijihwang-Tang by adding more medicinal plants to evaluate its pharmacological effects on underlying mechanisms against repeated lipopolysaccharide (LPS)-injection-induced neuroinflammation in the hippocampus regions. C57BL/6J male mice (16-24 weeks old) were divided into six groups: (1) the control group (DW with 0.9% saline injection), (2) LPS group (DW with LPS injection), YJT groups ((3) 100, (4) 200, or (5) 400 mg/kg of YJT with LPS injection), and (6) glutathione (GSH) group (100 mg/kg of GSH with LPS injection), respectively. Mice were orally administrated with various doses of YJT or glutathione (GSH) for the first five days. Neuroinflammation in the hippocampus region was induced by repeated injection of LPS during the last three days. As predicted, LPS not only increased oxidative stress-related markers including malondialdehyde, 4-hydroxynonenal, nitrotryptophan, and hydrogen peroxide, but also drastically enhanced inflammatory reactions including nitric oxide, inducible nitric oxide synthase, p65, and toll-like receptor 4, respectively. YJT administration, on the other hand, notably decreased the above pathological alterations by enhancement of antioxidant capacities such as superoxide dismutase and catalase activities. To explain the underlying pharmacological actions of YJT, we focused on a representative epigenetic regulator, a nicotinamide adenine dinucleotide + (NAD+)-dependent chromatin enzyme, Sirtuin 6 (Sirt6). Neuroinflammation in hippocampus regions depleted Sirt6 at the protein level and this alteration directly affected the nuclear factor erythroid 2-related factor (Nrf2)/hemeoxygenase (HO)-1 signaling pathway in the LPS group; however, YJT significantly recovered the Sirt6 protein levels, and it could recover the abnormal status of Nrf2/HO-1 signaling pathways in the hippocampus regions. Additionally, Sirt6 led to the up-regulation of GSH sub-enzymes of mRNA expression and protein levels of total GSH content. These findings suggest that YJT can protect against LPS-induced neuroinflammation and oxidative stress by regulating the Sirt6-related pathways and normalizing the GSH redox cycle.