Targeting cellular senescence in senile osteoporosis: therapeutic potential of traditional Chinese medicine.

Senile osteoporosis (SOP) is a prevalent manifestation of age-related bone disorders, resulting from the dysregulation between osteoblast (OB)-mediated bone formation and osteoclast (OC)-mediated bone resorption, coupled with the escalating burden of cellular senescence. Traditional Chinese medicine (TCM) herbs, renowned for their remarkable attributes encompassing excellent tolerability, low toxicity, heightened efficacy, and minimal adverse reactions, have gained considerable traction in OP treatment. Emerging evidence substantiates the therapeutic benefits of various TCM formulations and their active constituents, including Zuogui wan, Fructus Ligustri Lucidi, and Resveratrol, in targeting cellular senescence to address SOP. However, a comprehensive review focusing on the therapeutic efficacy of TCM against SOP, with a particular emphasis on senescence, is currently lacking. In this review, we illuminate the pivotal involvement of cellular senescence in SOP and present a comprehensive exploration of TCM formulations and their active ingredients derived from TCM, delineating their potential in SOP treatment through their anti-senescence properties. Notably, we highlight their profound effects on distinct aging models that simulate SOP and various senescence characteristics. Finally, we provide a forward-looking discussion on utilizing TCM as a strategy for targeting cellular senescence and advancing SOP treatment. Our objective is to contribute to the unveiling of safer and more efficacious therapeutic agents for managing SOP.

Mechanisms of action and synergetic formulas of plant-based natural compounds from traditional Chinese medicine for managing osteoporosis: a literature review.

Osteoporosis (OP) is a systemic skeletal disease prevalent in older adults, characterized by substantial bone loss and deterioration of microstructure, resulting in heightened bone fragility and risk of fracture. Traditional Chinese Medicine (TCM) herbs have been widely employed in OP treatment owing to their advantages, such as good tolerance, low toxicity, high efficiency, and minimal adverse reactions. Increasing evidence also reveals that many plant-based compounds (or secondary metabolites) from these TCM formulas, such as resveratrol, naringin, and ginsenoside, have demonstrated beneficial effects in reducing the risk of OP. Nonetheless, the comprehensive roles of these natural products in OP have not been thoroughly clarified, impeding the development of synergistic formulas for optimal OP treatment. In this review, we sum up the pathological mechanisms of OP based on evidence from basic and clinical research; emphasis is placed on the in vitro and preclinical in vivo evidence-based anti-OP mechanisms of TCM formulas and their chemically active plant constituents, especially their effects on imbalanced bone homeostasis regulated by osteoblasts (responsible for bone formation), osteoclasts (responsible for bone resorption), bone marrow mesenchymal stem cells as well as bone microstructure, angiogenesis, and immune system. Furthermore, we prospectively discuss the combinatory ingredients from natural products from these TCM formulas. Our goal is to improve comprehension of the pharmacological mechanisms of TCM formulas and their chemically active constituents, which could inform the development of new strategies for managing OP.

AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.

Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1ß. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP.

Effect of iron cyclic transformation on the natural purification of antimony in contaminated reservoirs of mines.

To further understand the purification mechanism of antimony (Sb) in reservoirs, samples of stratified water and bottom interface sediment were collected in this study. The cross-flow ultrafiltration technique was used to separate the truly dissolved (<1 kDa) and colloidal (1 kDa-0.45 µm) phases of water, and two modified sequential extraction techniques were used to determine the Sb and Fe mineral forms in sediment, respectively. The results showed that the total Sb concentration could decrease from 142.2 µg/L in surface water to 98.6 µg/L at 16 m; this was contributed to by the removal of truly dissolved Sb. In comparison to particulate Sb (>0.45 µm), the formation of colloidal Sb played a greater role in the purification process. There was a positive correlation between Sb and Fe in the colloidal phase (r = 0.45, P < 0.05). The generation of colloidal Fe could be promoted by higher temperatures, pH values, DO, and DOC in the upper layer (0-5 m). However, the complexation of DOC with colloidal Fe inhibited the adsorption of truly dissolved Sb. After entering the sediment, the secondary release of Sb could not increase the Sb concentration in the lower layer obviously, while the supplementation of Fe(III) could further enhance Sb natural purification.

Endoscopic Submucosal Dissection and Teprenone for Early Gastric Cancer, With Evaluation of eCura Scoring System.

Context: Early gastric cancer is a common, malignant, tumor disease. Compared with traditional surgical methods, endoscopic mucosal dissection (ESD) is a minimally invasive surgery; however, in practice, it still carries some surgical risks. Teprenone is a common drug that protects the gastric mucosa and promotes the recovery of gastric mucosal and gastrointestinal function. Objective: The study intended to investigate the clinical efficacy of endoscopic mucosal dissection combined with teprenone for early gastric cancer, including an evaluation of the combined treatment using the eCura scoring system, with a view to providing the results as a reference for the choice of treatment modality for early gastric cancer. Design: The research team performed a prospective controlled study. Setting: The study took place in the Department of General Surgery, Huidong, at Zigong Fourth People's Hospital in Zigong, China. Participants: Participants were patients with early gastric cancer, 58 who were admitted to the hospital between January 2019 and June 2020 and 58 who were admitted between July 2020 and December 2021. Intervention: The research team assigned: (1) the 58 patients in the earlier group to the control group, and they received treatment using endoscopic mucosal dissection; and (2) the 58 patients in the latter group to be the intervention group, and they received treatment using endoscopic mucosal dissection combined with teprenone. Outcome Measures: The research team examined participants' postoperative: (1) abdominal pain scores; (2) size of ulcer wound area, (3) complications-delayed bleeding, ulcer perforation, fever, or abdominal pain; (4) risk as measured by the eCura scoring system-low, medium, or high risk; and (5) survival rates of those assessed at different risks under the eCura scoring systems. Results: Postoperatively, the intervention group's abdominal pain scores on days 3 and 5 and the size of the groups' ulcer areas at days 7 and 14 were significantly lower than those of the control group (all P < .001). The intervention group's total incidence of postoperative complications, at 3.45%, was significantly lower than that in the control group, at 20.69% (P = .004). The number of participants low risk was 39 (67.25%), as assessed by eCura scoring system, which was significantly higher than that of the control group, at 22 participants (37.93%). The intervention groups' overall survival rate, at 98.28%, was significantly higher than that of the control group, at 69.49% (P < .001). Conclusions: Endoscopic mucosal dissection combined with teprenone as a treatment for early gastric cancer can achieve a significantly better therapeutic effect than can endoscopic mucosal dissection only. It can reduce the risk of postoperative complications and improve the assessment of risk found with the eCura scoring system. It can have an important role in improving the postoperative survival rate of patients with early gastric cancer and is worthy of clinical application.

M13, an anthraquinone compound isolated from Morinda officinalis promotes the osteogenic differentiation of MSCs by targeting Wnt/ß-catenin signaling.

BACKGROUND: Morinda officinalis (MO) is a herb used in Traditional Chinese Medicine (TCM) for the treatment of osteoporosis. M13, a MO-based anthraquinone compound is known to suppress osteoclast activity. However, whether M13 promotes MSCs osteogenic differentiation and its potential mechanism remains unknown. PURPOSE: To examine the influence of M13 on MSCs proliferation and osteogenic differentiation and elucidate the underlying mechanism. METHODS/STUDY DESIGNS: The effect of M13 exposure on MSCs proliferation was assessed via CCK8 assay, clone formation assay, immunofluorescence, RT-qPCR, and Western blot. The M13-mediated osteogenesis in vitro and ex vivo were evaluated via ALP and Alizarin red S staining, osteogenesis-associated gene (Runx2, Col1a1 and Opn) expression, and fetal limb explants culture. Molecular docking was employed for target signal pathway screening. The potential signaling mechanisms of M13-promoted MSCs osteogenic differentiation were analyzed by introducing XAV939 (Wnt/ß-catenin signaling inhibitor). RESULTS: M13 induced certain obvious positive effects on MSCs proliferation and osteogenic differentiation. Treatment with M13 enhanced MSCs viability and clone numbers. Meanwhile, M13 promoted osteogenic gene expression, enhanced ALP intensity and Alizarin red S staining in MSCs. In terms of mechanism, M13 strongly interacted with the docking site of the WNT signaling complex, thereby activating the Wnt/ß-catenin pathway. Furthermore, the M13-mediated osteogenic effect was partially inhibited by XAV939 both in vitro and ex vivo, which confirmed that the Wnt/ß-catenin axis is a critical regulator of M13-induced osteogenic differentiation of MSCs. CONCLUSION: Our study elucidated for the first time that M13 significantly promoted osteogenic differentiation of MSCs via stimulation of the Wnt/ß-catenin pathway in vitro and ex vivo.Our findings offered new additional evidence to support the MO or M13-based therapy of osteoporosis.

Health-related quality of life in breast cancer patients in Asia: A meta-analysis and systematic review.

Objectives: The primary purposes of this meta-analysis and systematic review were to evaluate the health-related quality of life (HRQoL) of Asian breast cancer (BC) patients to understand their holistic HRQoL level and provide medical and nursing recommendations to improve and preserve their quality of life. Methods: A comprehensive literature search was conducted to find cross-sectional studies published in Chinese and English concerning HRQoL in BC patients from the inceptions of databases to 14 March 2022. The databases consulted were PubMed, Web of Science, Embase, Cochrane, PsyclNFO, CINAHL, and CNKI. Literature screening, data extraction, risk bias assessment, and data synthesis were independently carried out by two researchers. The Endnote X9 and Stata 15.0 software programs were used during the meta-analysis process. Results: Out of the 8,563 studies identified, 23 cross-sectional studies involving 3,839 Asian BC patients were included in this meta-analysis. Two tools, namely, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and Quality of Life Questionnaire Breast Cancer module 23 (EORTC QLQ-BR23)-were used to evaluate the HRQoL of BC patients in Asia. The pooled mean of the global health status of Asian BC patients was 58.34 (95% confidence interval [CI]: 53.66-63.02). According to functional subscales of EORTC QLQ-C30 and EORTC QLQ-BR23, Asian BC patients suffered from the worst emotional functioning (pooled mean=66.38; 95% CI: 59.66-73.11) and sexual enjoyment (pooled mean=49.31; 95% CI: 31.97-63.36). In addition, fatigue (pooled mean=42.17; 95% CI: 34.46-49.88) and being upset by hair loss (pooled mean=48.38; 95% CI: 36.64-60.12) were the most obvious symptoms that Asian BC patients experienced according to the meta-analysis results of the EORTC QLQ-C30 and EORTC QLQ-BR23 symptom subscales. Conclusion: Asian BC patients experience a relatively low HRQoL due to the prominent decline in their body functions, as well as the unpleasant experiences caused by their symptoms. It is suggested that timely, appropriate, and targeted intervention should be provided in relation to the physical, psychological, and social aspects of Asian BC patients' lives to enhance their ability to function, relieve them of adverse symptoms, and improve their overall HRQoL. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022321165.

Risk control and assessment of sulfide-rich sediment remediation by controlled-release calcium nitrate.

Nitrate stimulation is widely used in sediment remediation to eliminate sulfides, degrade organic pollutants and immobilize phosphorus. However, the environmental risks of nitrate escape and the subsequent release of pollutants (e.g. nitrite, ammonium and trace metals) to water bodies during its application has received less attention. In this study, controlled-release nitrate pellets (SedCaN pellets) were manufactured and applied at different sediment depths to examine their effectiveness in controlling the risk of nitrate escape and subsequent pollutant release. The germination of submerged plant was also analyzed to assess the ecological risks associated with the remediated sediment. The results showed that the SedCaN pellets slowly released calcium nitrate, which led to denitrifying sulfide oxidation, organic matter degradation and the immobilization of phosphorus as a calcium-bound species. Gas production by denitrification increased the sediment porosity (0.3-2.2%) and led to the concomitant release of nitrite, ammonium, and heavy metals, creating secondary risks. Application of the SedCaN pellets at depth decreased the nitrate escape and the secondary risks, presumably by means of a capping effect of the upper sediment. The release of nitrate, ammonium, Ni and Cu were partially limited by 91.6%, 19.0%, 61.6% and 57.4% when SedCaN pellets were incorporated into deeper sediments (7-9 cm). Moreover, the range of sulfide oxidation extended to the upper and lower sediments in the profile (column), while the sulfide oxidation efficiency reached 85.9-95.0%. Finally, increased germination of Bacopa monnieri (20.0-26%) demonstrated that in comparison to reference materials the ecological risks of the treated sediments was reduced and the habitat function of sediment was restored after nitrate-stimulating remediation. The results of this study provide valuable guidelines for nitrate-stimulating remediation of sulfide-rich (black-odor) sediments.

Pyridoxine-responsive KCNQ2 epileptic encephalopathy: Additional cases and literature review.

BACKGROUND: Typical patients with KCNQ2 (OMIM# 602235) epileptic encephalopathy present early neonatal-onset intractable seizures with a burst suppression EEG pattern and severe developmental delay or regression, and those patients always fail first-line treatment with sodium channel blockers. Vitamin B6, either pyridoxine or pyridoxal 50-phosphate, has been demonstrated to improve seizure control in intractable epilepsy. METHODS: Here, we collected and summarized the clinical data for four independent cases diagnosed with pyridoxine-responsive epileptic encephalopathy, and their exome sequencing data. Moreover, we reviewed all published cases and summarized the clinical features, genetic variants, and treatment of pyridoxine-responsive KCNQ2 epileptic encephalopathy. RESULTS: All four cases showed refractory seizures during the neonatal period or infancy, accompanied by global development delay. Four pathogenetic variants of KCNQ2 were uncovered and confirmed by Sanger sequencing: KCNQ2 [NM_172107.4: c.2312C > T (p.Thr771Ile), c.873G > C (p.Arg291Ser), c.652 T > A (p.Trp218Arg) and c.913-915del (p. Phe305del)]. Sodium channel blockers and other anti-seizure medications failed to control their seizures. The frequency of seizures gradually decreased after treatment with high-dose pyridoxine. In case 1, case 2, and case 4, clinical seizures relapsed when pyridoxine was withdrawn, and seizures were controlled again when pyridoxine treatment was resumed. CONCLUSION: Our study suggests that pyridoxine may be a promising adjunctive treatment option for patients with KCNQ2 epileptic encephalopathy.

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration.

PURPOSE: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation. METHODS: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology. RESULTS: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1ß, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1ß, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD. CONCLUSION: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.

Xiaochaihu decoction for nonalcoholic fatty liver disease: A protocol for a systematic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by excessive deposition of fat in hepatocytes except for alcohol and other specific hepatic factors. Xiaochaihu decoction (XD) has been widely used to treat NAFLD in China. However, there is no systematic review found. In order to evaluate the efficacy and safety of XD in the treatment of NAFLS, we need to conduct a meta-analysis and systematic evaluation. METHODS: There are enrolled randomized controlled trials (RCTs) evaluating the effectiveness and safety of XD in the treatment of NAFLD. Data come mainly from 4 Chinese databases (CNKI, CBM, Wanfang, and VIP Database) and 4 English databases (Pubmed, Embase, Cochrane Library, and Web of science). The enrollment of RCTs is from the starting date of database establishment till September 30, 2021. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software. RESULTS: This study will provide high-quality evidence for the effectiveness and safety of XD in the treatment of NAFLD. CONCLUSION: The results of the study will help us determine whether XD can effectively treat NAFLD. ETHICS AND DISSEMINATION: This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/A5XEM.

L-carnitine suppresses transient receptor potential vanilloid type 1 activity and myofibroblast transdifferentiation in human corneal keratocytes.

Corneal stromal wound healing is a well-balanced process promoted by overlapping phases including keratocyte proliferation, inflammatory-related events, and tissue remodeling. L-carnitine as a natural antioxidant has shown potential to reduce stromal fibrosis, yet the underlying pathway is still unknown. Since transient receptor potential vanilloid 1 (TRPV1) is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing, we investigated if L-carnitine can mediate inhibition of the fibrotic response through suppression of TRPV1 activation in human corneal keratocytes (HCK). We determined TRPV1-induced intracellular calcium transients using fluorescence calcium imaging, channel currents by planar patch-clamping, and cell migration by scratch assay for wound healing. The potential L-carnitine effect on TRPV1-induced myofibroblast transdifferentiation was evaluated by immunocytochemical detection of alpha smooth muscle actin. RT-PCR analysis confirmed TRPV1 mRNA expression in HCK. L-carnitine (1 mmol/l) inhibited either capsaicin (CAP) (10 µmol/l), hypertonic stress (450 mOsmol/l), or thermal increase (>43 °C) induced Ca2+ transients and corresponding increases in TRPV1-induced inward and outward whole-cell currents. This was accompanied by suppression of injury-induced increases in myofibroblast transdifferentiation and cell migration. In conclusion, L-carnitine contributes to inhibit stromal scarring through suppressing an injury-induced intrinsic TRPV1 activity that is linked with induction of myofibroblast transdifferentiation in HCK cells.

Ascorbate-induced oxidative stress mediates TRP channel activation and cytotoxicity in human etoposide-sensitive and -resistant retinoblastoma cells.

There are indications that pharmacological doses of ascorbate (Asc) used as an adjuvant improve the chemotherapeutic management of cancer. This favorable outcome stems from its cytotoxic effects due to prooxidative mechanisms. Since regulation of intracellular Ca2+ levels contributes to the maintenance of cell viability, we hypothesized that one of the effects of Asc includes disrupting regulation of intracellular Ca2+ homeostasis. Accordingly, we determined if Asc induced intracellular Ca2+ influx through activation of pertussis sensitive Gi/o-coupled GPCR which in turn activated transient receptor potential (TRP) channels in both etoposide-resistant and -sensitive retinoblastoma (WERI-Rb1) tumor cells. Ca2+ imaging, whole-cell patch-clamping, and quantitative real-time PCR (qRT-PCR) were performed in parallel with measurements of RB cell survival using Trypan Blue cell dye exclusion. TRPM7 gene expression levels were similar in both cell lines whereas TRPV1, TRPM2, TRPA1, TRPC5, TRPV4, and TRPM8 gene expression levels were downregulated in the etoposide-resistant WERI-Rb1 cells. In the presence of extracellular Ca2+, 1 mM Asc induced larger intracellular Ca2+ transients in the etoposide-resistant WERI-Rb1 than in their etoposide-sensitive counterpart. With either 100 µM CPZ, 500 µM La3+, 10 mM NAC, or 100 µM 2-APB, these Ca2+ transients were markedly diminished. These inhibitors also had corresponding inhibitory effects on Asc-induced rises in whole-cell currents. Pertussis toxin (PTX) preincubation blocked rises in Ca2+ influx. Microscopic analyses showed that after 4 days of exposure to 1 mM Asc cell viability fell by nearly 100% in both RB cell lines. Taken together, one of the effects underlying oxidative mediated Asc-induced WERI-Rb1 cytotoxicity stems from its promotion of Gi/o coupled GPCR mediated increases in intracellular Ca2+ influx through TRP channels. Therefore, designing drugs targeting TRP channel modulation may be a viable approach to increase the efficacy of chemotherapeutic treatment of RB. Furthermore, Asc may be indicated as a possible supportive agent in anti-cancer therapies.

Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis.

Osteoporosis (OP) is a common skeletal disease, characterized by decreased bone formation and increased bone resorption. As a novel Chinese medicine formula, Zhuanggu Busui formula (ZGBSF) has been proved to be an effective prescription for treating OP in clinic, however, the pharmacological mechanisms underlying the beneficial effects remain obscure. In this study, we explored the pharmacological mechanisms of ZGBSF against OP via network pharmacology analysis coupled with in vivo experimental validation. The results of the network pharmacology analysis showed that a total of 86 active ingredients and 164 targets of ZGBSF associated with OP were retrieved from the corresponding databases, forming an ingredient-target-disease network. The protein-protein interaction (PPI) network manifested that 22 core targets, including Caspase-3, BCL2L1, TP53, Akt1, etc, were hub targets. Moreover, functional enrichment analyses revealed that PI3K-Akt and apoptosis signalings were significantly enriched by multiple targets and served as the targets for in vivo experimental study validation. The results of animal experiments revealed that ZGBSF not only reversed the high expression of Caspase-3, Bax, Prap, and low expression of Bcl-2 in osteoblasts of the OP mouse model but also contributed to the phosphorylation of Akt1 and expression of PI3K, thereby promoting osteogenesis and ameliorating the progression of OP. In conclusion, this study systematically and intuitively illustrated that the possible pharmacological mechanisms of ZGBSF against OP through multiple ingredients, targets, and signalings, and especially the inhibition of the apoptosis and the activation of PI3K-Akt signaling.

Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Our previous studies showed that Yougui pills and Bushenhuoxue formula, both TCM prescriptions containing Corni Fructus (CF), have protective effects on osteoarthritis (OA). However, the underlying detailed components in both TCM prescriptions that play therapeutic roles have not been fully defined. Morroniside is a major iridoid glycoside and one of the quality control metrics of CF, but the effects of morroniside on OA remain largely elusive. AIM OF THE STUDY: The study aims to assess the therapeutic effects of morroniside on cartilage degeneration using a mouse model of OA. MATERIAL AND METHODS: 8-week-old male C57BL/6J mice were randomly divided into 4 groups: Sham, destabilization of the medial meniscus (DMM)-treated with vehicle, DMM-treated with low dose morroniside and DMM-treated with high dose morroniside. Histological staining, immunostaining, and TUNEL staining were conducted to detect changes in tissue morphology, expression of key molecules in chondrocytes, and chondrocyte apoptosis, respectively. Osteophyte formation, meniscus calcification, and subchondral sclerosis were quantitated using micro-CT. The expression of chondrocyte markers was also analyzed by Western blot in primary chondrocytes derived from mice treated with morroniside. RESULTS: Morroniside attenuated the progression of OA in mice, resulting in substantially reduced osteophyte formation and subchondral sclerosis and lower OARSI scores. Specifically, morroniside significantly promoted cartilage matrix synthesis by increasing collagen type II expression and suppressing chondrocyte pyroptosis. Morroniside administration led to inhibition of matrix metalloproteinase-13 (MMP13), Caspase-1 and nod-like receptor protein-3 (NLRP3) expression in DMM mice and IL-1ß-stimulated chondrocytes. In addition, morroniside attenuated the progression of OA by enhancing chondrocyte proliferation and inhibiting chondrocyte apoptosis. Morroniside also attenuated the progression of OA by inhibiting nuclear factor-κB (NF-κB) signaling. CONCLUSION: Morroniside was protective against cartilage matrix degradation and reduced DMM-induced chondrocyte pyroptosis and apoptosis by the inhibition of NF-κB signaling.

Mental operations in rhythm: Motor-to-sensory transformation mediates imagined singing.

What enables the mental activities of thinking verbally or humming in our mind? We hypothesized that the interaction between motor and sensory systems induces speech and melodic mental representations, and this motor-to-sensory transformation forms the neural basis that enables our verbal thinking and covert singing. Analogous with the neural entrainment to auditory stimuli, participants imagined singing lyrics of well-known songs rhythmically while their neural electromagnetic signals were recorded using magnetoencephalography (MEG). We found that when participants imagined singing the same song in similar durations across trials, the delta frequency band (1-3 Hz, similar to the rhythm of the songs) showed more consistent phase coherence across trials. This neural phase tracking of imagined singing was observed in a frontal-parietal-temporal network: the proposed motor-to-sensory transformation pathway, including the inferior frontal gyrus (IFG), insula (INS), premotor area, intra-parietal sulcus (IPS), temporal-parietal junction (TPJ), primary auditory cortex (Heschl's gyrus [HG]), and superior temporal gyrus (STG) and sulcus (STS). These results suggest that neural responses can entrain the rhythm of mental activity. Moreover, the theta-band (4-8 Hz) phase coherence was localized in the auditory cortices. The mu (9-12 Hz) and beta (17-20 Hz) bands were observed in the right-lateralized sensorimotor systems that were consistent with the singing context. The gamma band was broadly manifested in the observed network. The coherent and frequency-specific activations in the motor-to-sensory transformation network mediate the internal construction of perceptual representations and form the foundation of neural computations for mental operations.

Erchen decoction for hyperlipemia: Protocol for a systematic review and meta-analysis.

BACKGROUND: Hyperlipidemia is a metabolic disease characterized by elevated levels of blood lipids and lipoproteins and a major pathogenic factor of atherosclerosis. In China, Erchen decoction (ECD) has been widely used to treat hyperlipidemia. However, there is no systematic review found. In order to evaluate the efficacy and safety of ECD in the treatment of hyperlipidemia, we need to conduct a meta-analysis and systematic evaluation. METHODS: We will enroll the randomized controlled trials (RCTs) evaluating the effectiveness and safety of ECD in the treatment of hyperlipidemia. Data come mainly from 4 Chinese databases (China national knowledge infrastructure, Wanfang, Chinese biomedical literature database, and VIP Database) and 4 English databases (Pubmed, Embase excerpt medica database, Cochrane Library, and Web of science). The enrollment of RCTs is from the starting date of database establishment till September 30, 2020. Low density lipoprotein cholesterol is considered as the main indicator of the dyslipidemia, while the serum concentrations of total cholesterol, triglyceride, high density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B are regarded as the secondary indicators. There are Safety indicators including liver enzyme, kidney function and fasting blood glucose. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software. RESULTS: This study will provide high-quality evidence for the effectiveness and safety of ECD in the treatment of hyperlipidemia. CONCLUSION: The results of the study will help us determine whether ECD can effectively treat hyperlipidemia. ETHICS AND DISSEMINATION: This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/GZ69F.

Shengyang Yiwei Decoction for the treatment of chronic gastritis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Chronic gastritis is a very common chronic gastric mucosal inflammatory disease in China. Long-term chronic inflammation will aggravate the disease and develop towards gastric cancer. Clinically, infection with Helicobacter pylori (H pylori) is a common cause. The application of antibiotics to eradicate H pylori has been reported to have produced drug resistance. However, the application of Shengyang Yiwei Decoction(SYD) in traditional Chinese medicine has resulted in significant clinical effects and small side effects. It is used for the treatment of chronic gastritis and other diseases, but there is a lack of systematic reviews on the treatment of chronic gastritis by SYD. This article reviews the efficacy and safety of SYD in the treatment of chronic gastritis. METHODS: The registration date for the randomized controlled trials is set by the database to October 15, 2020. Through searching the following 8 Chinese and English electronic databases: Cochrane Library, Embase, PubMed, Science Net, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Science Journal Database and Wanfang Database to analyze. The main results were clinical efficacy, H pylori infection clearance rate, symptom score and quality of life, and 1-year recurrence rate. Finally, Stata 15 was used for meta-analysis. RESULTS: This study will provide the latest evidence for the treatment of chronic gastritis by SYD in the following aspects: clinical efficacy, H pylori infection clearance rate, quality of life, symptom score, and 1-year recurrence rate. CONCLUSION: The results of this study will provide evidence for evaluating the effectiveness of SYD in chronic gastritis treatment. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/AZKUQ.

Prior Knowledge Guides Speech Segregation in Human Auditory Cortex.

Segregating concurrent sound streams is a computationally challenging task that requires integrating bottom-up acoustic cues (e.g. pitch) and top-down prior knowledge about sound streams. In a multi-talker environment, the brain can segregate different speakers in about 100 ms in auditory cortex. Here, we used magnetoencephalographic (MEG) recordings to investigate the temporal and spatial signature of how the brain utilizes prior knowledge to segregate 2 speech streams from the same speaker, which can hardly be separated based on bottom-up acoustic cues. In a primed condition, the participants know the target speech stream in advance while in an unprimed condition no such prior knowledge is available. Neural encoding of each speech stream is characterized by the MEG responses tracking the speech envelope. We demonstrate that an effect in bilateral superior temporal gyrus and superior temporal sulcus is much stronger in the primed condition than in the unprimed condition. Priming effects are observed at about 100 ms latency and last more than 600 ms. Interestingly, prior knowledge about the target stream facilitates speech segregation by mainly suppressing the neural tracking of the non-target speech stream. In sum, prior knowledge leads to reliable speech segregation in auditory cortex, even in the absence of reliable bottom-up speech segregation cue.

[Effect of vitamin D supplementation and outdoor time on the 25(OH)D level in adolescents].

OBJECTIVE: To assess the effect of vitamin D( VD) supplementation and outdoor time intervention on the 25( OH) D level in adolescents. METHODS: In April2015, participants from three classes in a college of North Anhui were randomly assigned to VD supplementation group( receive oral vitamin D3 of 800 IU/d for 4 weeks, n = 55), outdoor time intervention group( more than 30 min/d of outdoor between 9 am and 15 pm for 4 weeks, n = 52) and control group( no any intervention, n = 63). The data on demographic characteristics, behavior related to vitamin D and life style were evaluated by using questionnaire. 25( OH) D level in finger-tip blood was measured by using LC-MS/MS. The differences of 25( OH) D levels among 3 groups over 4 weeks were compared. RESULTS: On baseline, there was no significant difference( F = 0. 77, P = 0. 464) on the25( OH) D level among VD supplementation group( 15. 5 nmol/L, 95% CI 14. 3- 16. 6nmol/L), outdoor time intervention group( 16. 5nmol/L, 95% CI 15. 2- 17. 8 nmol/L)and control group( 16. 0 nmol/L, 95% CI 14. 9- 17. 1 nmol/L). However, the 25( OH)D level of VD supplementation group( 56. nmol/L, 95% CI 52. 0- 61. 6 nmol/L) and outdoor time intervention group( 54. 3 nmol/L, 95% CI 49. 4- 59. 3 nmol/L) were significantly higher( F = 4. 40, P = 0. 014) than that of the control group( 47. 2 nmol/L, 95% CI 42. 7- 51. 7 nmol/L) 4 weeks later. All participants among 3 group were all in VD deficiency( < 50 nmol/L) on baseline. After 4 weeks, the prevalence of VD deficiency among 3 group reduced to 40. 0%( 95% CI 27. 7%- 53. 2%), 48. 1%( 95%CI 34. 8%- 61. 5%) and 65. 1%( 95% CI 52. 9%- 76. 1%), respectively. Compared with the control, the risk of VD deficiency in VD supplementation group significantly decreased( RRadj= 0. 33, 95% CI 0. 15- 0. 72, P = 0. 005), and the risk in the outdoor time intervention group also obviously decreased( RRadj= 0. 48, 95% CI 0. 22- 1. 05, P = 0. 065), but did not reach statistical significance. CONCLUSION: The 25( OH) D level of adolescents could be significantly improved through oral vitamin D3 supplementation of800 IU/d or more than 30 min/d of outdoor.