Combined Catalpol and Tetramethylpyrazine Promote Axonal Plasticity in Alzheimer's Disease by Inducing Astrocytes to Secrete Exosomes Carrying CDK5 mRNA and Regulating STAT3 Phosphorylation.

Alzheimer's disease (AD) is a common progressive degenerative disease of the central nervous system in aging populations. This study aimed to investigate the effects of combined catalpol and tetramethylpyrazine (CT) in promoting axonal plasticity in AD and the potential underlying mechanism. Astrocytes were treated with different concentrations of compatible CT. Exosomes were collected and subjected to sequencing analysis, which was followed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. Amyloid precursor protein/presenilin 1 (APP/PS1) double-transfected male mice were used as the in vivo AD models. Astrocyte-derived exosomes that were transfected with cyclin-dependent kinase 5 (CDK5) or CT treatment were injected into the tail vein of mice. The levels of CDK5, synaptic plasticity marker protein neurofilament 200 (NF200), and growth-associated protein 43 (GAP-43) in the hippocampus of mice were compared in each group. Immunofluorescence staining was used to detect the localization of STAT3 and to visualize synaptic morphology via ß-tubulin-III (TUBB3). Astrocyte-derived exosomes transfected with siCDK5 or treated with CT were co-cultured with HT-22 cells, which were untransfected or silenced for signal transducer and activator of transcription 3 (STAT3). Amyloid ß-protein (Aß)1-42 was induced in the in vitro AD models. The viability, apoptosis, and expression levels of NF200 and GAP-43 proteins in the hippocampal neurons of each group were compared. In total, 166 differentially expressed genes in CT-induced astrocyte-derived exosomes were included in the KEGG analysis, and they were found to be enriched in 12 pathways, mainly in axon guidance. CT treatment significantly increased the level of CDK5 mRNA in astrocyte-derived exosomes-these exosomes restored CDK5 mRNA and protein levels in the hippocampus of the in vivo AD model mice and the in vitro AD model; promoted p-STAT3 (Ser727), NF200 and GAP-43 proteins; and promoted the regeneration and extension of neuronal synapses. Silencing of CDK5 blocked both neuronal protection as well as induction of axonal plasticity in AD by CT-treated exosomes in vitro and in vivo. Moreover, silencing of STAT3 blocked both neuronal protection as well as induction of axonal plasticity in AD caused by CDK5 overexpression or CT-treated astrocyte-induced exosomes. CT promotes axonal plasticity in AD by inducing astrocytes to secrete exosomes carrying CDK5 mRNA and regulating STAT3 (Ser727) phosphorylation.

Effects of TCM on polycystic ovary syndrome and its cellular endocrine mechanism.

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease characterized by menstrual disorders, infertility, and obesity, often accompanied by insulin resistance and metabolic disorders. The pathogenesis of PCOS is relatively complex and has a certain relationship with endocrine disorders. The increase of androgen and luteinizing hormone (LH) is the main cause of a series of symptoms. Traditional Chinese medicine (TCM) has obvious advantages and significant curative effects in the treatment of this disease. It can effectively reduce the insulin level of PCOS patients, regulate lipid metabolism, and increase ovulation rate and pregnancy rate and has fewer side effects. This article reviews the efficacy and safety of Chinese herbs and other TCM (such as acupuncture) in the treatment of PCOS and its complications in recent years, as well as the effect and mechanism on cellular endocrine, in order to provide a new clinical idea for the treatment of PCOS.

Association of choline and betaine with the risk of cardiovascular disease and all-cause mortality: Meta-analysis.

BACKGROUND: This study aimed to systematically evaluate the role of circulating levels of choline and betaine in the risk of cardiovascular disease (CVD) and all-cause mortality by comprehensively reviewing observational studies. METHODS: This study was conducted according to PRISMA 2020 statement. Six electronic databases, including PubMed, Embase and China National Knowledge Infrastructure (CNKI), were searched for cohort studies and derivative research design types (nested case-control and case-cohort studies) from the date of inception to March 2022. We pooled relative risk (RR) and 95% confidence interval (CI) of the highest versus lowest category and per SD of circulating choline and betaine concentrations in relation to the risk of CVD and all-cause mortality. RESULTS: In the meta-analysis, 17 studies with a total of 33,009 participants were included. Random-effects model results showed that highest versus lowest quantile of circulating choline concentrations were associated with the risk of CVD (RR = 1.29, 95% CI: 1.04-1.61) and all-cause mortality (RR = 1.62, 95% CI: 1.12-2.36). We also observed the risk of CVD were increased 13% (5%-22%) with per SD increment. Furthermore, highest versus lowest quantile of circulating betaine concentrations were not associated with the risk of CVD (RR = 1.07, 95% CI: 0.92-1.24) and all-cause mortality (RR = 1.39, 95% CI: 0.96-2.01). However, the risk of CVD was increased 14% (5%-23%) with per SD increment. CONCLUSIONS: Higher levels of circulating choline were associated with a higher risk of CVD and all-cause mortality.

Prevalence and correlators of burnout among health professionals during different stages of the COVID-19 pandemic in China.

Background: Persistently increased workload and stress occurred in health professionals (HPs) during the past 3 years as the COVID-19 pandemic continued. The current study seeks to explore the prevalence of and correlators of HPs' burnout during different stages of the pandemic. Methods: Three repeated online studies were conducted in different stages of the COVID-19 pandemic: wave 1: after the first peak of the pandemic, wave 2: the early period of the zero-COVID policy, and wave 3: the second peak of the pandemic in China. Two dimensions of burnout, emotional exhaustion (EE) and declined personal accomplishment (DPA), were assessed using Human Services Survey for Medical Personnel (MBI-HSMP), a 9-item Patient Health Questionnaire (PHQ-9), and a 7-item Generalized Anxiety Disorder (GAD-7) to assess mental health conditions. An unconditional logistic regression model was employed to discern the correlators. Results: There was an overall prevalence of depression (34.9%), anxiety (22.5%), EE (44.6%), and DPA (36.5%) in the participants; the highest prevalence of EE and DPA was discovered in the first wave (47.4% and 36.5%, respectively), then the second wave (44.9% and 34.0%), and the third wave had the lowest prevalence of 42.3% and 32.2%. Depressive symptoms and anxiety were persistently correlated with a higher prevalence risk of both EE and DPA. Workplace violence led to a higher prevalence risk of EE (wave 1: OR = 1.37, 95% CI: 1.16-1.63), and women (wave 1: OR = 1.19, 95% CI: 1.00-1.42; wave 3: OR =1.20, 95% CI:1.01-1.44) and those living in a central area (wave 2: OR = 1.66, 95% CI: 1.20-2.31) or west area (wave 2: OR = 1.54, 95% CI: 1.26-1.87) also had a higher prevalence risk of EE. In contrast, those over 50 years of age (wave 1: OR = 0.61, 95% CI: 0.39-0.96; wave 3: OR = 0.60, 95% CI: 0.38-0.95) and who provided care to patients with COVID-19 (wave 2: OR = 0.73, 95% CI: 0.57-0.92) had a lower risk of EE. Working in the psychiatry section (wave 1: OR = 1.38, 95% CI: 1.01-1.89) and being minorities (wave 2: OR = 1.28, 95% CI: 1.04-1.58) had a higher risk of DPA, while those over 50 years of age had a lower risk of DPA (wave 3: OR = 0.56, 95% CI: 0.36-0.88). Conclusion: This three-wave cross-sectional study revealed that the prevalence of burnout among health professionals was at a high level persistently during the different stages of the pandemic. The results suggest that functional impairment prevention resources and programs may be inadequate and, as such, continuous monitoring of these variables could provide evidence for developing optimal strategies for saving human resources in the coming post-pandemic era.

Catalpol Mitigates Alzheimer's Disease Progression by Promoting the Expression of Neural Stem Cell Exosomes Released miR-138-5p.

Alzheimer's disease (Alzheimer's disease, AD) is a neurodegenerative disease characterized by senile plaque deposition and neurofibrillary tangles. The pathogenesis of AD is complicated and the drugs used to treat AD are single-targeted drugs, which can only improve or alleviate the symptoms of patients, but cannot delay or prevent the progress of the disease. Because of its ability to act on multiple targets, multiple systems, multiple links, and multiple pathways, Chinese herbal compound prescriptions have shown unique advantages in the research and treatment of AD. Our previous study has demonstrated the protect role of the Chinese medicine Rehmannia in AD. However, the underlying mechanism remains unclear. In the present study, both in vitro and vivo experiments were employed, and we found Catalpol (Ca), the main extract of Rehmannia, could mitigate AD progression both in vitro and in vivo by promoting miR-138-5p level in neural stem cell secreted exosomes.

Tetramethylpyrazine ameliorates systemic streptozotocin-induced Alzheimer-like pathology.

Diabetes mellitus (DM) and its complications are the main threats to the global disease burden. DM-related cognitive dysfunction is a progressive neurodegenerative disease, similar to Alzheimer's disease (AD). The underlying pathophysiology remains unclear, and an effective treatment is unavailable. Tetramethylpyrazine (TMP) is a bioactive ingredient extracted from the plant Ligusticum wallichii, which has anti-diabetic and neuroprotective properties. In this study, streptozotocin (STZ) injection was used to establish a mouse STZ-AD model, and TMP was administered through the lateral ventricle (ICV) to evaluate the effects of TMP on cognitive ability and neurochemical changes and to explore the underlying cellular and molecular mechanisms. Using MWM and Y-maze behavioral paradigms, we observed that TMP protected against STZ-induced learning and memory impairment. STZ promoted the deposition of amyloid plaques, activation of glial cells, loss of neurons and synapses, and reduction of synaptic plasticity. In contrast, TMP restored these aberrations and improved cognitive deficits in STZ-induced diabetic animals. Moreover, TMP attenuated hippocampal mitochondrial dysfunction and oxidative stress through modulation of the SIRT1/Nrf2/ HO-1 pathway. This evidence shows that TMP exerts its therapeutic effects through multiple pathways. Our study provides new insights into the neuroprotective effects of TMP for the treatment of diabetes-related cognitive failure.

Research Progress of Targeting Neuro-Immune Inflammation in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by extracellular senile plaques and the formation of intracellular neurofibrillary tangles. The accumulation of toxic beta-amyloid (Aß) induces the overproduction of reactive oxygen species (ROS), nitric oxide (NO) and pro-inflammatory cytokines. Accumulating studies suggest that neuroinflammatory mechanism plays an important role in the occurrence and development of AD. Microglia, astrocytes, macrophages, mast cells and T cells are involved in the pathogenesis of AD through neuroimmune mechanisms and inflammatory reactions. In recent years, many new drugs have been developed for the treatment of AD targeting neuroimmune and inflammatory mechanisms. Although some drugs failed in the Ⅲ phase of clinical trial, they made sense on subsequent research. This paper mainly discusses the positive effects on AD according to immunotherapy, anti-inflammatory treatment and regulation of immune inflammation by traditional Chinese medicine, in order to benefit for prevention or treatment of AD in the future.

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment.

The incidence of sporadic Alzheimer's disease (AD) is increasing in recent years. Studies have shown that in addition to some genetic abnormalities, the majority of AD patients has a history of long-term exposure to risk factors. Neuroendocrine related risk factors have been proved to be strongly associated with AD. Long-term hormone disorder can have a direct detrimental effect on the brain by producing an AD-like pathology and result in cognitive decline by impairing neuronal metabolism, plasticity and survival. Traditional Chinese Medicine(TCM) may regulate the complex process of endocrine disorders, and improve metabolic abnormalities, as well as the resulting neuroinflammation and oxidative damage through a variety of pathways. TCM has unique therapeutic advantages in treating early intervention of AD-related neuroendocrine disorders and preventing cognitive decline. This paper reviewed the relationship between neuroendocrine and AD as well as the related TCM treatment and its mechanism. The advantages of TCM intervention on endocrine disorders and some pending problems was also discussed, and new insights for TCM treatment of dementia in the future was provided.

Association between dietary intake of one-carbon metabolism nutrients and hyperglycemia in coal-burning fluorosis areas of Guizhou, China.

Background and aims: There are limited studies describing the association between dietary intake of one-carbon metabolism nutrients and hyperglycemia. The present study aimed to investigate the association of habitual dietary intake of one-carbon metabolism nutrients with hyperglycemia in a fluorosis area in China, and explored the interaction between these nutrients and fluorosis related to hyperglycemia. Method: In a cross-sectional study, we recruited 901 villagers, ages ranging from 18-75, in Guizhou Province. Dietary data and other covariate data were obtained through an interviewer-administered questionnaire. We collected venous blood samples from participants who had fasted for one night to obtain fasting blood glucose levels and we categorized dietary intake of betaine, total choline, methionine, folate, vitamins B6 and B12, and choline subclasses into quartiles (Q1-Q4). The lowest quartile (Q1) served as the reference group. An unconditional logistic regression model was used to evaluate the protective effects of a dietary intake of one-carbon nutrients against hyperglycemia. We calculated Odds Ratios (ORs) with 95% confidence intervals (CIs). A presence or absence of fluorosis subgroup analysis was performed to determine the potential effect of fluorosis on hyperglycemia. Result: After adjusting for potential confounding factors, we found that a greater intake of dietary vitamin B6, total choline and methyl-donor index was inversely associated with the occurrence of hyperglycemia (P-trend <0.05). However, there were no significant associations between hyperglycemia and the dietary intake of folate, vitamin B12, methionine, and betaine. As for the choline subgroups, it showed that the dietary intake of free choline, phosphatidylcholine, and glycerol phosphatidylcholine was negatively correlated with the occurrence of hyperglycemia (P < 0.05). In contrast, there was no statistical association between dietary phosphatidylcholine and sphingomyelin and hyperglycemia (all P > 0.05). The results of subgroup analysis showed that dietary intake of folate, vitamin B6, total choline, free choline, glycerol phosphorylcholine, and phosphocholine had a protective effect against the occurrence of hyperglycemia in the non-fluorosis subgroup, although no effects were observed in the fluorosis subgroup. There were significant interactions between these nutrients and fluorosis (P = 0.010-0.048). Conclusion: The study demonstrated that higher dietary intake of vitamin B6, total choline, methyl-donor index, free choline, glycerol phosphorylcholine, and phosphocholine in choline compounds were associated with a lower incidence of hyperglycemia. Moreover, the associations were modified by the presence or absence of fluorosis. Further investigation is needed to test the association in large-scale follow-up studies.

Potential cellular endocrinology mechanisms underlying the effects of Chinese herbal medicine therapy on asthma.

Asthma is a complex syndrome with polygenetic tendency and multiple phenotypes, which has variable expiratory airflow limitation and respiratory symptoms that vary over time and in intensity. In recent years, continuous industrial development has seriously impacted the climate and air quality at a global scale. It has been verified that climate change can induce asthma in predisposed individuals and that atmospheric pollution can exacerbate asthma severity. At present, a subset of patients is resistant to the drug therapy for asthma. Hence, it is urgent to find new ideas for asthma prevention and treatment. In this review, we discuss the prescription, composition, formulation, and mechanism of traditional Chinese medicine monomer, traditional Chinese medicine monomer complex, single herbs, and traditional Chinese patent medicine in the treatment of asthma. We also discuss the effects of Chinese herbal medicine on asthma from the perspective of cellular endocrinology in the past decade, emphasizing on the roles as intracellular and extracellular messengers of three substances-hormones, substances secreted by pulmonary neuroendocrine cells, and neuroendocrine-related signaling protein-which provide the theoretical basis for clinical application and new drug development.

Therapeutic Effects and Metabolic Spectrum of Traditional Chinese Medicine Hengqing II Prescription on Alzheimer's Disease.

Alzheimer's disease (AD) seriously damages elders' social and daily abilities around the world. Traditional Chinese medicine (TCM), a rich drug resource bank, could help research AD. In order to explore the role of TCM in AD treatment, 86 AD patients were recruited from the hospital, then treated with Hengqing II prescription and donepezil hydrochloride. The cognitive and serum lipid levels were investigated before and after treatment. The patient's urine was collected after three months of treatment. Metabolites in the urine samples were extracted with methanol and detected on the UHPLC-MS platform. Results proved that Hengqing II can improve cognitive levels and reduce the levels of Hcy, D-D, FIB, Apo B, TC, and LDL-C compared with donepezil hydrochloride (P < 0.05). The results of multivariate statistical analysis revealed that the metabolism of HQII was significantly different compared with Control groups. A total of 66 differential metabolites were found in this comparison (50 were down-regulated and 16 were up-regulated). Four amino acid pathways and one linoleic acid pathway were found through these metabolites. After receiver operating characteristic analysis, it was suggested that palmitic acid, palmitoleic acid, linoleic acid, oleic acid, SAH, and methionine can be used as biomarkers for treating AD, while the effects of daidzein, genistein, and naringenin on the treatment of AD need to be further studied.

Effects of Catalpol on Alzheimer's Disease and Its Mechanisms.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by memory loss and cognitive dysfunction. With the increasing aging of the population, the incidence of AD and the number of patients are also increasing year by year, causing more and more heavy burdens to the family and society. Catalpol, an iridoid glycoside compound, is one of the main active components of Rehmannia glutinosa. At present, a large number of experimental studies in vivo and in vitro have confirmed that catalpol has antioxidant, anti-inflammatory, antiapoptotic, and other neuroprotective effects, and it plays a significant role in the prevention and treatment of AD, with very small side effects and high safety. Therefore, it may be an ideal drug for the treatment of AD. Based on this, the role and mechanism of catalpol in AD will be comprehensively reviewed in the following.

Gastrodin and Vascular Dementia: Advances and Current Perspectives.

Gastrodia elata, a traditional Chinese medicine, has been widely used since ancient times to treat diseases such as dizziness, epilepsy, stroke, and memory loss. Gastrodin, one of the active components of Gastrodia elata, has been used in the treatment of migraine, epilepsy, Parkinson's disease, dementia, and depression in recent years. It can improve cognitive function and related neuropsychiatric symptoms through various effects and is considered as a promising treatment for dementia. Vascular dementia is a kind of severe cognitive impairment syndrome caused by vascular factors, and it is the dementia syndrome with the largest number of patients besides Alzheimer's disease. Although there is still a lack of evidence-based explorations, the paper reviewed the mechanism and methods of gastrodin in the treatment of vascular dementia, providing a reference for clinical therapy.

Multiple Roles of Paeoniflorin in Alzheimer's Disease.

Alzheimer's disease (AD) is a geriatric disease with the morbidity and mortality continuing to grow, partly due to the aging of the world population. As one of the most common types of primary neurodegenerative dementia, it is mainly due to environmental, epigenetic, immunological, and genetic factors. Paeoniflorin (PF), the main component of paeony extract, plays a more and more important role in the prevention and treatment of AD, including regulating protein, anti-inflammation, antioxidation, and antiapoptosis, protecting glial cells, regulating neurotransmitters and related enzymes and receptors, and inhibiting or activating related signal pathways. This article summarizes the latest researches on the multiple effects and the mechanisms of PF in the treatment to cure AD, providing new insights and research basis for further clinical application of traditional Chinese medicine (TCM) in the treatment of AD.

Metabolomics Deciphering the Potential Biomarkers of Hengqing I Prescription against Vascular Dementia.

With the aging of population, vascular dementia (VaD) seriously threatens people's health and quality of life. It is of great significance to explore biomarkers of VaD from the perspective of metabolomics and traditional Chinese medicine (TCM). Therefore, VaD was divided into kidney deficiency and blood stasis syndrome (KDBS) and non-KDBS according to TCM. Then, some patients received the treatment of Hengqing I (HQI) prescription. The urine of six groups (VaD group, normal group, KDBS group, non-KDBS group, HQI group, and control group) was detected on LC-MS/MS. Multivariate statistical analysis showed that the metabolic profiles of the three comparisons were significantly different. The top analysis-ready molecules of downregulated histamine and upregulated biotin, methionine, pantothenic acid, SAH, histidine, and kaempferol may be the most related metabolites. These putative biomarkers play an important role in the regulation of key metabolic processes linked to VaD. Additionally, pathway analysis showed aminoacyl-tRNA biosynthesis, and amino acids metabolic pathways were highly correlated with the occurrence of VaD. In this present paper, vitamins, amino acids, and their derivatives were selected as the basis for VaD diagnosis and treatment monitoring, and the significance of TCM classification and Hengqing I prescription in the treatment of VaD was discussed.

The Roles of Tetramethylpyrazine During Neurodegenerative Disease.

With the aging of the world population, neurodegenerative diseases are considered crippling diseases, which seriously affect the quality of life and are an increasing burden on society and the economy. As a major alkaloid in Ligusticum chuanxiong Hort, tetramethylpyrazine (TMP) plays an increasingly significant role during neurodegenerative diseases, including roles as an anti-inflammatory, antioxidative, antiplatelet citatory poisoning, and anti-inflammation. This review focuses on the latest advances in the roles and mechanisms of action of TMP in neurodegenerative diseases to stimulate new concepts and methods for the prevention and treatment of neurodegenerative diseases.