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.

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].

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).

Comparative Analysis of the Metabolic Profiles of Yellow- versus Black-Seeded Rapeseed Using UPLC-HESI-MS/MS and Transcriptome Analysis.

The high levels of secondary metabolites in rapeseed play important roles in determining the oil quality and feeding value. Here, we characterized the metabolic profiles in seeds of various yellow- and black-seeded rapeseed accessions. Two hundred and forty-eight features were characterized, including 31 phenolic acids, 54 flavonoids, 24 glucosinolates, 65 lipid compounds, and 74 other polar compounds. The most abundant phenolic acids and various flavonoids (epicatechin, isorhamnetin, kaempferol, quercetin, and their derivatives) were widely detected and showed significant differences in distribution between the yellow- and black-seeded rapeseed. Furthermore, the related genes (e.g., BnTT3, BnTT18, BnTT10, BnTT12, and BnBAN) involved in the proanthocyanidin pathway had lower expression levels in yellow-seeded rapeseed, strongly suggesting that the seed coat color could be mainly determined by the levels of epicatechin and their derivatives. These results improve our understanding of the primary constituents of rapeseed and lay the foundation for breeding novel varieties with a high nutritional value.

Genome-Wide Identification and Comparative Expression Profile Analysis of the Long-Chain Acyl-CoA synthetase (LACS) Gene Family in Two Different Oil Content Cultivars of Brassica napus.

Long-chain acyl-CoA synthetase (LACS) is one of the key enzymes involved in fatty acid metabolism, including phospholipid biosynthesis, triacylglycerol (TAG) biosynthesis, and fatty acid ß-oxidation in plants. However, the characterization of LACSs family in seed oil biosynthesis of Brassica napus (B. napus) remains unknown. In the present study, we performed a comprehensive genome-wide analysis of this gene family in B. napus, and 34 B. napus LACS genes (BnaLACSs) were identified. Phylogenetic analysis classified the BnaLACS proteins into four groups (A, B, C, and D), which were supported by highly conserved gene structures and consensus motifs. RNA-Sequencing (RNA-Seq) and qRT-PCR combined analysis revealed that 18 BnaLACSs (BnaLACS1-2, 1-3, 1-4, 1-9, 1-10, 2-1, 2-2, 4-1, 4-2, 6-1, 6-2, 6-4, 7-1, 7-2, 8-1, 8-2, 9-3, and 9-4) were highly expressed in developmental seeds. Comparative expression analysis between extremely high oil content (P1-HO) and low oil content (P2-LO) B. napus cultivars revealed that BnaLACS6-4, BnaLACS9-3, and BnaLACS9-4 may be involved in fatty acid synthesis in chloroplast, and BnaLACS1-10 and 4-1 may play a vital role in lipid biosynthesis in B. napus, which is important for further seed oil accumulation in oilseed rape. The present study provides important information for functional characterization of BnaLACSs in seed oil metabolism in B. napus.

High-voltage electrostatic field-induced oxidative stress: Characterization of the physiological effects in Sitobion avenae (Hemiptera: Aphididae) across multiple generations.

In recent decades, man-made electric fields have greatly increased the intensity of electrostatic fields that are pervasively present in the environment. To better understand the physiological alterations exhibited by herbivorous insects in response to changing electric environments, we determined the activities of anti-oxidative enzymes and the metabolic rate of Sitobion avenae Fabricius (Hemiptera: Aphididae) over multiple generations in response to direct and host-seed exposure to a high-voltage electrostatic field (HVEF) of varying strength for different durations. Under controlled greenhouse conditions, 20-min direct exposure of S. avenae and wheat seeds to a 2- or 4-kV/cm HVEF resulted in significantly increased superoxide dismutase (SOD) activity in the sixth, 11th, 16th, and 21st generations relative to the control activities, whereas significantly decreased SOD activity was detected in the second generation. In addition, the activities of catalase (CAT) and peroxidase (POD) in S. avenae showed significant decreases over multiple generations. We also examined the suppressive effects of the duration of 4-kV/cm treatment on aphid physiology. The results showed that exposure to the 4-kV/cm HVEF for 20 min exerted adverse effects on CAT and POD activities and significantly decreased the metabolic rates of S. avenae, as demonstrated through evaluations of CO2 production rate, and these parameters were not significantly affected by higher HVEF durations. Overall, these findings increase our understanding of plant-pest interactions under novel HVEF environments and provide information that can improve integrated management strategies for S. avenae. Bioelectromagnetics. 40:52-61, 2019. © 2018 Wiley Periodicals, Inc.

Physiological and metabolome changes during anther development in wheat (Triticum aestivum L.).

This study used cytology, cytochemistry, and non-targeted metabolomics to investigate the distribution characteristic of polysaccharides, lipids, and all the metabolites present during five wheat (Triticum aestivum L.) anther developmental stages to provide insights into wheat anther development. Anthers were collected from the tetrad through trinucleate stages, and 1.5% (w/v) acetocarmine and 4',6-diamidino-2-phenylindole staining were used to confirm the developmental stage and visualize the nuclei, respectively. Polysaccharides and lipids were detected by staining with periodic acid-Schiff and Sudan Black B, respectively. The integrated optical density of the tapetum and microspores were calculated using IPP6.0 software. Furthermore, the metabolites were identified by gas chromatograph system coupled with a Pegasus HT time-of-flight mass spectrometer (GC-TOF-MS). The results indicated that the interior and exterior surface cells of anthers are orderly. Pollen was rich in numerous nutrient substances (e.g., lipids, insoluble carbohydrates, and others), and formed a normal sperm cell that contained three nuclei, i.e., one vegetative nuclei and two reproductive nuclei in the mature pollen. Semi-thin sectioning indicated that the tapetum cells degraded progressively from the tetrad to late uninucleate stage and disappeared from the bi-to trinucleate stages. Moreover, nutrient substances (lipids and insoluble carbohydrates) accumulated, were synthesized in the pollen, and gradually increased from the tetrad to trinucleate stages. Finally, the metabolomics results identified that 146 metabolites were present throughout the wheat anther developmental stages. Principal component analysis, hierarchical cluster analysis, and metabolite-metabolite correlation revealed distinct dynamic changes in metabolites. The metabolism of organic acids, amino acids, sugars, fatty acids, amines, polyols, and nucleotides were interrelated and involved in the tricarboxylic acid (TCA) cycle and glycolysis. Furthermore, their interactions were revealed using an integrated metabolic map, which indicated that the TCA cycle and glycolysis were very active during anther development to provide the required energy for anther and pollen development. Our study provides valuable insights into the mechanisms of substance metabolism in wheat anthers and can be used for possible application by metabolic engineers for the improvement of cell characteristics or creating new compounds and molecular breeders in improving pollen fertility or creating the ideal male sterile line, to improve wheat yield per unit area to address global food security.

Comparative Transcriptome Analysis of Recessive Male Sterility (RGMS) in Sterile and Fertile Brassica napus Lines.

The recessive genetic male sterility (RGMS) system plays a key role in the production of hybrid varieties in self-pollinating B. napus plants, and prevents negative cytoplasmic effects. However, the complete molecular mechanism of the male sterility during male-gametogenesis in RGMS remains to be determined. To identify transcriptomic changes that occur during the transition to male sterility in RGMS, we examined the male sterile line WSLA and male fertile line WSLB, which are near-isogenic lines (NILs) differing only in the fertility trait. We evaluated the phenotypic features and sterility stage using anatomical analysis. Comparative RNA sequencing analysis revealed that 3,199 genes were differentially expressed between WSLA and WSLB. Many of these genes are mainly involved in biological processes related to flowering, including pollen tube development and growth, pollen wall assembly and modification, and pollen exine formation and pollination. The transcript profiles of 93 genes associated with pollen wall and anther development were determined by quantitative RT-PCR in different flower parts, and classified into the following three major clades: (1) up-regulated in WSLA plants; (2) down-regulated in WSLA plants; and 3) down-regulated in buds, but have a higher expression in stigmas of WSLA than in WSLB. A subset of genes associated with sporopollenin accumulation were all up-regulated in WSLA. An excess of sporopollenin results in defective pollen wall formation, which leads to male sterility in WSLA. Some of the genes identified in this study are candidates for future research, as they could provide important insight into the molecular mechanisms underlying RGMS in WSLA.