Therapeutic Potential of Combined Herbal Medicine and Electroacupuncture in Mild Cognitive Impairment Through Cytokine Modulation: An Observational Study.

Purpose: We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action. Patients and Methods: This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively. Results: The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], p < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas. Conclusion: Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.

This was a single-centered study focusing on the therapeutic effect of combined herbal medicine and electroacupuncture in patients with mild cognitive impairment, including a small number of participants, a relatively long treatment intervention of 12 weeks, and a follow-up assessment of 24 weeks. The intervention was a combination of a herbal formula and electroacupuncture treatment customized for each participant. The blood cytokine analyses of the participants were compared with the network analysis of the predicted target organs and pathways for the herbal formulas administered. Because each participant was not given the exact same intervention, we were unable to identify the specific treatment that produced the predicted effect. The observational study design of the study limited the ability to accurately assess causation between intervention and outcome. However, combined traditional medicine has potential therapeutic application in preventing mild cognitive impairment progression to dementia.

Exploring Traditional Medicine Diagnostic Classification for Parkinson's Disease Using Hierarchical Clustering.

INTRODUCTION: Personalized diagnosis and therapy for Parkinson's disease (PD) are needed due to the clinical heterogeneity of PD. Syndrome differentiation (SD) in traditional medicine (TM) is a diagnostic method for customized therapy that comprehensively analyzes various symptoms and systemic syndromes. However, research identifying PD classification based on SD is limited. METHODS: Ten electronic databases were systematically searched from inception to August 10, 2021. Clinical indicators, including 380 symptoms, 98 TM signs, and herbal medicine for PD diagnosed with SD, were extracted from 197 articles; frequency statistics on clinical indicators were conducted to classify several subtypes using hierarchical clustering. RESULTS: Four distinct cluster groups were identified, each characterized by significant cluster-specific clinical indicators with 95% confidence intervals of distribution. Subtype 2 had the most severe progression, longest progressive duration, and highest association with greater late-stage PD-associated motor symptoms, including postural instability and gait disturbance. The action properties of the herbal formula and original SD presented in the data sources for subtype 2 were associated with Yin deficiency syndrome. DISCUSSION/CONCLUSION: Hierarchical clustering analysis distinguished various symptoms and TM signs among patients with PD. These newly identified PD subtypes may optimize the diagnosis and treatment with TM and facilitate prognosis prediction. Our findings serve as a cornerstone for evidence-based guidelines for TM diagnosis and treatment.Eine personalisierte Diagnose und Therapie des Morbus Parkinson (MP) ist angesichts der ausgeprägten klinischen Heterogenität des MP unerlässlich. Die Syndromdifferenzierung (SD) ist in der traditionellen Medizin (TM) eine diagnostische Methode für eine maßgeschneiderte Therapie, bei der verschiedene Symptome und systemische Syndrome umfassend analysiert werden. Es liegen jedoch nur begrenzt Forschungsergebnisse in Bezug auf eine SD-basierte Klassifikation des MP vor.Zehn elektronische Datenbanken wurden systematisch durchsucht, von der Einrichtung bis zum 10. August 2021. Klinische Indikatoren einschließlich von 380 Symptomen, 98 TM-Zeichen sowie pflanzlichen Heilmitteln für mittels SD diagnostiziertem MP wurden aus 197 Artikeln extrahiert, und Häufigkeitsstatistiken der klinischen Indikatoren wurden erstellt, um mittels hierarchischem Clustering eine Reihe von Subtypen zu klassifizieren.Vier verschiedene Cluster-Gruppen wurden identifiziert, die jeweils durch signifikante, Cluster-spezifische klinische Indikatoren mit 95% Konfidenzintervall der Verteilung gekennzeichnet waren. Subtyp 2 hatte den schwersten Verlauf, die längste Progressionsdauer und die stärkste Assoziation mit einem höheren Ausmaß von motorischen Symptomen des MP im Spätstadium, darunter Haltungsinstabilität und Gangstörungen. Die Wirkungseigenschaften der pflanzlichen Formulierung sowie die ursprüngliche SD, die in den Datenquellen für Subtyp 2 genannt wurden, waren mit Yin-Mangel-Syndrom assoziiert.Die hierarchische Clustering-Analyse hob verschiedene Symptome und TM-Zeichen bei Patienten mit MP hervor. Die neu identifizierten MP-Subtypen könnten die Diagnose und Behandlung mittels TM optimieren und zur Prognoseerstellung beitragen. Unsere Ergebnisse sind ein Fundament für eine evidenzbasierte Leitlinie für die TM-Diagnostik und -Therapie.

Traditional Medicine Classification Based on the Nature and Location of Disease in Parkinson's Disease: A Clustering Study Using Pattern Identification Disassemble Presented in Clinical Studies.

Objectives: The purpose of this study was to investigate a traditional medicine (TM) classification based on the nature and location of disease for pattern identification (PI) in Parkinson's disease (PD). This study also aimed to present evidence regarding the pathogenesis of PD and provide a basis for establishment of individualized treatment strategies with TM. Methods: An electronic search was conducted in three core databases, three Korean databases, and four Chinese databases. A hierarchical clustering analysis was conducted based on the nature and location of the disease for PD, and the analysis findings were compared with PI in the existing literature. Results: A total of 79 different types of PI were confirmed in 189 PD cases. Cluster analysis using the nature and location of disease disassembled from PI identified 7 groups: group 1 (wind, blood stasis) comprised 15 studies; group 2 (fire-heat, phlegm-retained fluid) comprised 7 studies; group 3 (liver, Qi stagnation) comprised 5 studies; group 4 (kidney, Yang deficiency) comprised 10 studies; group 5 (liver-kidney, Yin deficiency) comprised 93 studies; group 6 (Qi deficiency, blood deficiency) comprised 18 studies; and group 7 (meridian and collateral) comprised 9 studies. Conclusions: The findings provide evidence for the pathogenesis of PD and have the potential to translate into more specific TM patterns for PD. The authors hope that their study results will be used as a foundation for development of traditional medical diagnostic methods and treatments tailored to PD.

Effects of Corticosterone on Beta-Amyloid-Induced Cell Death in SH-SY5Y Cells.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aß25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aß25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aß25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aß25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1ß. Aß25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aß25-35-induced neurotoxicity and might be used to treat and/or prevent AD.

Literature review on the interdisciplinary biomarkers of multi-target and multi-time herbal medicine therapy to modulate peripheral systems in cognitive impairment.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease characterized by the deposition of amyloid-beta (Aß) peptide and neurofibrillary tangles in the brain. The approved drug for AD has certain limitations such as a short period of cognitive improvement effect; moreover, the development of drug for AD therapeutic single target for Aß clearance in brain ended in failure. Therefore, diagnosis and treatment of AD using a multi-target strategy according to the modulation of the peripheral system, which is not only limited to the brain, is needed. Traditional herbal medicines can be beneficial for AD based on a holistic theory and personalized treatment according to the time-order progression of AD. This literature review aimed to investigate the effectiveness of herbal medicine therapy based on syndrome differentiation, a unique theory of traditional diagnosis based on the holistic system, for multi-target and multi-time treatment of mild cognitive impairment or AD stage. Possible interdisciplinary biomarkers including transcriptomic and neuroimaging studies by herbal medicine therapy for AD were investigated. In addition, the mechanism by which herbal medicines affect the central nervous system in connection with the peripheral system in an animal model of cognitive impairment was reviewed. Herbal medicine may be a promising therapy for the prevention and treatment of AD through a multi-target and multi-time strategy. This review would contribute to the development of interdisciplinary biomarkers and understanding of the mechanisms of action of herbal medicine in AD.

Efficacy of herbal medicine treatment based on syndrome differentiation for Parkinson's disease: A systematic review and meta-analysis of randomized placebo-controlled clinical trials.

Background: Parkinson's disease (PD), the second most common progressive neurodegenerative disease, causes heterogeneous clinical symptoms. Patients experience a range of motor and non-motor symptoms, and personalized diagnosis and treatment are needed. In traditional East Asian medicine, syndrome differentiation (SD) is a diagnostic approach for customized therapy that uses a comprehensive analysis and varies for the same disease. We aimed to evaluate the efficacy of herbal medicine (HM) prescribed according to the SD of PD. Methods: Ten electronic databases were searched from inception to August 2021 without language limitations. All randomized controlled trials (RCTs) involving HM for SD of PD were included. Assessment of Cochrane's risk of bias and meta-analysis and Grading of Recommendations Assessment, Development, and Evaluation was also performed. Effect measurement was summarized using the mean difference (MD) with 95% confidence interval, through a meta-analysis. Results: Thirteen RCTs involving 843 participants were included. The overall risk of bias was either low or unclear. Compared with the placebo, a combined therapy of HM and Western medicine (WM) significantly improved the total Unified Parkinson's Disease Rating Scale (UPDRS) (MD = -8.03, [-10.27, -5.79], p < 0.00001; I2 = 0%) and was more beneficial, as assessed using the UPDRS (I-III), the Parkinson's Disease Questionnaire-39, and the Non-Motor Symptoms Scale. Adverse events did not differ between the groups. Conclusion: The findings suggest that the combined treatment of WM and HM based on SD diagnosis has additional benefits in PD treatment. However, the methodological quality of the included RCTs was suboptimal. Nevertheless, this systematic review is the first to investigate the efficacy of HM treatment according to the SD diagnosis in PD. The clinically meaningful improvement in HM according to SD in PD needs to be tested in further studies with rigorous designs and longer follow-up periods. Systematic Review Registration: [https://inplasy.com/inplasy-2021-10-0020/], identifier [INPLASY2021100020].

α-Pinene Attenuates Methamphetamine-Induced Conditioned Place Preference in C57BL/6 Mice.

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

Effectiveness and Therapeutic Mechanism of Pharmacopuncture for Pain in Parkinson's Disease: A Study Protocol for a Pilot Pragmatic Randomized, Assessor-Blinded, Usual Care-Controlled, Three-Arm Parallel Trial.

Pain in Parkinson's disease (PD) represents a complex phenotype known to decrease quality of life. This pragmatic randomized, controlled clinical trial evaluated the efficacy of pharmacopuncture (PA) for improving pain symptoms and investigated the corresponding therapeutic mechanisms in patients with PD. Ninety patients with PD-related pain were randomly allocated to receive either PA, manual acupuncture, or usual care in a 1:1:1 ratio; sixty healthy controls were included for comparative analysis of brain imaging data. Over 12 weeks, study treatment provided 2 days per week for 8 weeks with a follow-up period of 4 weeks. The primary outcome measure was the King's Parkinson's Disease Pain Scale score for assessing improvement in PD-related pain, including a sub-analysis to investigate the pattern of changes in pain according to a PD-related pain mechanism-based classification. Secondary outcome measures included a numerical rating scale-based assessment of the intensity and location of pain and changes in pain-associated symptoms, such as depression, anxiety, and sleep disorders. Exploratory outcome measures included structural and functional brain patterns on magnetic resonance imaging, blood molecular signature changes, gait analysis, facial expression and movement assessment in response to emotional stimuli, and a traditional Korean medicine syndrome differentiation questionnaire. The trial findings provided important clinical evidence for the effectiveness of PA in the management of PD-related pain and its associated symptoms, and helped elucidate the mechanism of its therapeutic effect on PD-related pain.

Effectiveness of Sopoongsan for chronic upper body pruritus in patients with atopic or seborrheic dermatitis: A pilot study protocol for a randomized, double-blind, placebo-controlled, parallel trial.

INTRODUCTION: Chronic pruritus persists for > 6 weeks and is known to decrease patients' quality of life. Due to the complex pathological mechanism of chronic pruritus, there is still a lack of satisfactory therapeutic agents; therefore, complementary therapies are required to improve itching symptoms. In the Republic of Korea, Sopoongsan, an herbal formula, has been used to treat itching, dizziness, and skin paralysis. To our knowledge, this is the first study to evaluate whether Sopoongsan improves chronic pruritus and to identify Sopoongsan-related changes in the immune response in patients with chronic upper body pruritus. METHODS: A randomized, double-blind, placebo-controlled parallel trial will be conducted to assess 20 patients with chronic upper body pruritus for 3 months who have been diagnosed with allergic atopic dermatitis or seborrheic dermatitis. The patients will be randomly allocated to either the placebo-control (n = 10) or treatment (n = 10) group. The total study period will be 8 weeks (i.e., administration of Sopoongsan or placebo drugs for 4 wk and follow-up for 4 wk). Participants will be allowed to receive external treatment, except for antipruritic medications administered orally, throughout the study period. The primary outcome measure will be the numeric rating scale results for itching, whereas the secondary outcome measures will be questionnaire survey (Dermatological Life Quality Index and Epworth Sleepiness Scale) findings and the immune response index, including interferon gamma, interleukin-4, immunoglobulin E, thymic stromal lymphopoietic protein, and histamine, to investigate the biological mechanisms underlying chronic pruritus. DISCUSSION AND CONCLUSIONS: We expect that the results of this study will provide important clinical evidence regarding the effectiveness of Sopoongsan on itching symptoms, quality of life, sleep disturbance, and changes in the immune response. The findings will help elucidate the mechanism underlying the therapeutic effect of Sopoongsan for chronic pruritus and lay the foundation for further studies in this area.

Protective Role of Corticosterone against Hydrogen Peroxide-Induced Neuronal Cell Death in SH-SY5Y Cells.

Stress breaks body balance, which can cause diverse physiological disorders and worsen preexisting diseases. However, recent studies have reported that controllable stress and overcoming from stress reinforce resilience to resist against more intense stress afterwards. In this study, we investigated the protective effect of corticosterone (CORT), a representative stress hormone against hydrogen peroxide (H2O2)-induced neuronal cell death and its underlying molecular mechanism in SH-SY5Y cells, a human neuroblastoma cell line. The decreased cell viability by H2O2 was effectively restored by the pretreatment with low concentration of CORT (0.03 µM for 72 h) in the cells. H2O2-increased expression of apoptotic markers such as PUMA and Bim was decreased by CORT pretreatment. Furthermore, pretreatment of CORT attenuated H2O2-mediated oxidative damages by upregulation of antioxidant enzymes via activation of nuclear factor erythroid 2-related factor 2 (Nrf2). These findings suggest that low concentration of CORT with eustressed condition enhances intracellular self-defense against H2O2-mediated oxidative cell death, suggesting a role of low concentration of CORT as one of key molecules for resilience and neuronal cell survival.

Ukgansan Protects Dopaminergic Neurons against MPTP-Induced Neurotoxicity via the Nurr1 Signaling Pathway.

Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor that protects dopaminergic neurons and is a promising therapeutic target for Parkinson's disease (PD). Parkinson's disease is a neurodegenerative disorder caused by the destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and the long-term use of conventional dopamine replacement therapies causes many side effects, highlighting the need for new treatments such as complementary and alternative medicine. Ukgansan has been used in East Asia to treat neurological disorders, including neurodegenerative diseases, and has been reported to have strong effects in treating patients with PD. In addition, recent studies have reported that Ukgansan has a neuroprotective potential. However, there are no detailed studies on the mechanism of action of Nurr1. Thus, unlike previous studies, we focused on the Nurr1 pathways. We confirmed neurotoxicity and apoptosis signaling in the differentiated PC12 cells. In addition, to confirm the protective effect of Ukgansan, we conducted behavioral tests (motor coordination and postural balance, and bradykinesia) and tyrosine hydroxylase immunohistochemistry in both the SNpc and striatum. Specifically, this study demonstrated the effect of Ukgansan in protecting dopaminergic neurons and increasing Nurr1 involved in maintaining dopamine levels by activating Nurr1 expression in MPTP-induced PC12 cells and a mouse model of PD. In this mechanism, the loss of dopaminergic neurons and dopamine depletion were suppressed, and motor impairment caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity was improved. These results provide evidence that Ukgansan ameliorates PD's motor symptoms and progression.

Effects of an Exercise Program Combining Aerobic and Resistance Training on Protein Expressions of Neurotrophic Factors in Obese Rats Injected with Beta-Amyloid.

In this study, the effects of a 12-week exercise program combining aerobic and resistance training on high-fat diet-induced obese Sprague Dawley (SD) rats after the injection of beta-amyloid into the cerebral ventricle were investigated. Changes in physical fitness, cognitive function, blood levels of beta-amyloid and metabolic factors, and protein expressions of neurotrophic factors related to brain function such as BDNF (brain-derived neurotrophic factor) in the quadriceps femoris, hippocampus, and cerebral cortex were analyzed. The subjects were thirty-two 10-week-old SD rats (DBL Co., Ltd., Seoul, Korea). The rats were randomized into four groups: ß-Non-Ex group (n = 8) with induced obesity and ßA25-35 injection into the cerebral ventricle through stereotactic biopsy; ß-Ex group (n = 8) with induced obesity, ßA25-35 injection, and exercise; S-Non-Ex group (n = 8) with an injection of saline in lieu of ßA25-35 as the control; and S-Ex group (n = 8) with saline injection and exercise. The 12-week exercise program combined aerobic training and resistance training. As for protein expressions of the factors related to brain function, the combined exercise program was shown to have a clear effect on activating the following factors: PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), FNDC5 (fibronectin type III domain-containing protein 5), and BDNF in the quadriceps femoris; TrkB (Tropomyosin receptor kinase B), FNDC5, and BDNF in the hippocampus; PGC-1α, FNDC5, and BDNF in the cerebral cortex. The protein expression of ß-amyloid in the cerebral cortex was significantly lower in the ß-Ex group than in the ß-Non-Ex group (p < 0.05). The 12-week intervention with the combined exercise program of aerobic and resistance training was shown to improve cardiopulmonary function, muscular endurance, and short-term memory. The results demonstrate a set of positive effects of the combined exercise program, which were presumed to have arisen mainly due to its alleviating effect on ß-amyloid plaques, the main cause of reduced brain function, as well as the promotion of protein expressions of PGC-1α, FNDC5, and BDNF in the quadriceps femoris, hippocampus, and cerebral cortex.

Efficacy of Traditional Herbal Medicine Treatment Based on Pattern Identification for Idiopathic Parkinson's Disease: A Protocol for Systematic Review and Meta-Analysis.

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, is characterized by various clinical symptoms and reduced quality of life. The standard dopaminergic therapy for PD has limitations such as drug wear-off, drug-related side effects, and drug-resistant PD symptoms. Traditional oriental medicine, which is a personalized approach based on pattern identification (PI), has been reported to relieve symptoms, halt disease progression, and improve the quality of life in patients with PD. This comprehensive systematic review will be conducted to gather clinical studies related to complementary traditional herbal therapies based on PI for idiopathic PD and assess its effectiveness. Clinical studies, including randomized controlled trials in English, Korean, and Chinese databases related to the efficacy of herbal medicine based on PI for PD will be searched in computer retrieval. In addition, the subdivided PI for each clinical manifestation of PD will be investigated. Two researchers will independently screen and select studies, extract data, and assess bias risk. The risk of bias will be evaluated using the Cochrane risk-of-bias assessment tool. After screening the studies, a meta-analysis will be performed. The primary outcome will be the unified Parkinson's disease rating scale to measure clinical symptom reduction. Secondary outcomes will consist of other validated scales to evaluate the improvement of PD, including improvement of clinical symptoms and quality of life. The quality of evidence will be evaluated through the Grading of Recommendations, Assessment, Development, and Evaluation pro. Complementary traditional medicine is a personalized medicine that classifies individual states based on PI. We expect that the results of this review will provide evidence for the efficacy of traditional herbal medicine based on PI for the treatment of PD. This protocol has been registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) 2021 (registration number INPLASY2021100020).

Parkinson's Disease Subtyping Using Clinical Features and Biomarkers: Literature Review and Preliminary Study of Subtype Clustering.

The second most common progressive neurodegenerative disorder, Parkinson's disease (PD), is characterized by a broad spectrum of symptoms that are associated with its progression. Several studies have attempted to classify PD according to its clinical manifestations and establish objective biomarkers for early diagnosis and for predicting the prognosis of the disease. Recent comprehensive research on the classification of PD using clinical phenotypes has included factors such as dominance, severity, and prognosis of motor and non-motor symptoms and biomarkers. Additionally, neuroimaging studies have attempted to reveal the pathological substrate for motor symptoms. Genetic and transcriptomic studies have contributed to our understanding of the underlying molecular pathogenic mechanisms and provided a basis for classifying PD. Moreover, an understanding of the heterogeneity of clinical manifestations in PD is required for a personalized medicine approach. Herein, we discuss the possible subtypes of PD based on clinical features, neuroimaging, and biomarkers for developing personalized medicine for PD. In addition, we conduct a preliminary clustering using gait features for subtyping PD. We believe that subtyping may facilitate the development of therapeutic strategies for PD.

Gait Disturbance Improvement and Cerebral Cortex Rearrangement by Acupuncture in Parkinson's Disease: A Pilot Assessor-Blinded, Randomized, Controlled, Parallel-Group Trial.

BACKGROUND: Parkinson's disease (PD) leads to impaired mobility and limited independence. OBJECTIVE: We investigated the effects of acupuncture on gait disturbance and analyzed hemodynamic changes caused by acupuncture in the cerebral cortex of patients with PD. METHODS: Participants (n = 26) with gait disturbance due to PD were randomly assigned to the intervention (acupuncture twice a week for 4 weeks + conventional therapy) or control (conventional therapy) groups. We analyzed gait parameters using the GAITRite system and hemodynamic responses in the cerebral cortices using functional near-infrared spectroscopy, Unified Parkinson's Disease Rating Scale (UPDRS) scores, neurotransmitter levels, as well as the immediate effects of acupuncture in patients with PD. RESULTS: The participants tended to walk with hypometric gait (high cadence, short steps) overground. After acupuncture treatment, those in the intervention group showed a significant reduction in cadence and the UPDRS scores involving "walking and balance" compared with those in the control group (P = .004 and P = .020, respectively); the stride, swing, and single support times were significantly increased (P = .006, P = .001, and P = .001, respectively). Oxyhemoglobin levels in the intervention group while walking on a treadmill were significantly increased in the prefrontal and supplementary motor areas. The oxyhemoglobin levels in the prefrontal cortex and swing time revealed significant positive correlations. CONCLUSIONS: Our findings indicated that acupuncture tended to improve hypometric gait and rearranged activation of the cerebral cortex. Thus, acupuncture may be a useful complementary treatment for gait disturbance, including hypometric gait, in patients with PD. Trial Registration Number. Clinical Research Information Service (KCT0002603), https://cris.nih.go.kr/cris/index.jsp.

Effect of Surface Treatment by O3 and Chemical Activation by Alkali Metal on the Performance of ACFs on Adsorption and Desorption of BTX Gases.

In order to investigate the adsorption characteristics of activated carbon fibers (ACFs) with improved surface morphologies towards volatile organic compounds (VOCs), a commercial low-grade ACF was surface modified by successive surface treatment (ST) and chemical activation (CA) process. O3 was used as an ST agent for the formation of oxygen-containing functional groups on the carbon matrix of ACFs. CA was carried out after ST, using a KOH solution. After the successive ST-CA process, Brunauer-Emmett-Teller (BET) surface area and average pore diameter of ACFs were increased from 1483 m2/g to 2743 m2/g and enlarged from 1.931 nm to 2.512 nm, respectively. The successive ST-CA process also resulted in the adsorption capacities of benzene, toluene, and xylene of the ACFs to increase from 0.22 g-Ben./g-ACFs, 0.18 g-Tol./g-ACFs, and 0.19 g-Xyl/g-ACFs up to 0.37 g-Ben./g-ACFs, 0.35 g-Tol./g-ACFs, and 0.38 g-Xyl/g-ACFs, respectively.

Inhibitory Effects of Myricetin on Lipopolysaccharide-Induced Neuroinflammation.

Microglial activation elicits an immune response by producing proinflammatory modulators and cytokines that cause neurodegeneration. Therefore, a plausible strategy to prevent neurodegeneration is to inhibit neuroinflammation caused by microglial activation. Myricetin, a natural flavanol, induces neuroprotective effects by inhibiting inflammation and oxidative stress. However, whether myricetin inhibits lipopolysaccharide (LPS)-induced neuroinflammation in hippocampus and cortex regions is not known. To test this, we examined the effects of myricetin on LPS-induced neuroinflammation in a microglial BV2 cell line. We found that myricetin significantly downregulated several markers of the neuroinflammatory response in LPS-induced activated microglia, including inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory modulators and cytokines such as prostaglandin E2 (PGE2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). Moreover, myricetin suppressed the expression of c-Jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), which are components of the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, myricetin inhibited LPS-induced macrophages and microglial activation in the hippocampus and cortex of mice. Based on our results, we suggest that myricetin inhibits neuroinflammation in BV2 microglia by inhibiting the MAPK signaling pathway and the production of proinflammatory modulators and cytokines. Therefore, this could potentially be used for the treatment of neuroinflammatory diseases.

Beta wave enhancement neurofeedback improves cognitive functions in patients with mild cognitive impairment: A preliminary pilot study.

BACKGROUND: Mild cognitive impairment (MCI) is a symptom characterizing cognitive decline and a transitional state between normal aging and dementia; however, there is no definitive diagnosis and treatment for MCI. Neurofeedback (NF), which is a training mechanism that employs operant conditioning to regulate brain activity, has been increasingly investigated concerning its beneficial effects for dementia and MCI. METHODS: This study investigated cognitive improvement and hemodynamic changes in the prefrontal cortex (PFC) following NF training in patients with MCI. Five patients with MCI received NF training for enhanced beta band activity in the dorsolateral PFC-16 sessions for 8 weeks-with each session divided into 9 5-minute trials. The primary outcome measure was a cognitive assessment tool: the Korean version of the Montreal Cognitive Assessment. The secondary outcome measures were the Central Nervous System Vital Signs for neurocognitive testing, hemodynamic changes using functional near-infrared spectroscopy in the PFC during a working-memory task, and Beck Depression Inventory scores. RESULTS: After completing the training, patients' cognitive function significantly improved in domains such as composite memory, cognitive flexibility, complex attention, reaction time, and executive function. Increased electroencephalogram beta power was observed over NF training sessions (Spearman rank correlation test: r = 0.746, P = .001). The threshold value for gaining positive feedback from pre-NF baseline on beta power significantly increased (Spearman rank correlation test: r = 0.805, P = .001). Hemodynamic response in PFC changed after NF training, and individual differences were identified. Specifically, hypoactivation of the hemodynamic response by emotional distraction recovered following NF training. CONCLUSION: We suggest that patients' cognitive processing efficiency was improved by the NF training. These beneficial results suggest that NF training may have potential therapeutic applications to prevent the progression from MCI to dementia. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (KCT0003433).

Correction to: Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study.

In the original version of the article titled "Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study", published in 41(5):554-563 (https://doi.org/10.1007/s12272-018-1013-7), unfortunately an important statement was missing in the Clinical study section by the author.