Quercetin in Osteoporosis Treatment: A Comprehensive Review of Its Mechanisms and Therapeutic Potential.

PURPOSE OF REVIEW: This review aims to provide a theoretical basis and insights for quercetin's clinical application in the prevention and treatment of osteoporosis (OP), analyzing its roles in bone formation promotion, bone resorption inhibition, anti-inflammation, antioxidant effects, and potential mechanisms. RECENT FINDINGS: OP, a prevalent bone disorder, is marked by reduced bone mineral density and impaired bone architecture, elevating the risk of fractures in patients. The primary approach to OP management is pharmacotherapy, with quercetin, a phytochemical compound, emerging as a focus of recent interest. This natural flavonoid exerts regulatory effects on bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts and promotes bone health and metabolic equilibrium via anti-inflammatory and antioxidative pathways. Although quercetin has demonstrated significant potential in regulating bone metabolism, there is a need for further high-quality clinical studies focused on medicinal quercetin.

The effect of the ageing process on the desorption of nonylphenol in black carbon-sediment systems: a kineto-mechanistic and modeling investigation.

Black carbon (BC) exhibits promising potential as a sediment amendment owing to its commendable adsorption capacity for hydrophobic organic contaminants (HOCs), thereby resulting in HOC-laden sediments. Desorption kinetic studies play a crucial role in comprehending the release potential of HOCs from BC-sediment systems. Although the adsorption capacity of BC for HOCs has been found to decrease with aging, there is limited research on its impact on HOC desorption kinetics. In this study, BCs derived from agricultural waste (rice straw carbon, RC) and industrial waste (fly ash carbon, FC), respectively, were used to investigate the desorption kinetics of nonylphenol (NP). Additionally, a predictive model was established using the fitting parameters obtained from the modified two-domain model. The results showed that desorption of NP was divided into three fractions: rapid fraction (Frap), slow fraction (Fslow) and resistant fraction (Fr). BCs significantly decreased, while ageing increased the desorption amount and rate of NP. The performance of RC in controlling NP release was superior to that of FC. The predicted values calculated by the established model exhibit significant positive correlations with the measured values (p < 0.01). Additionally, the correlation analysis between sorption sites and desorption fractions revealed that the concentration of NP in the desorbing fraction was nearly equivalent to that of NP in partition sites within aged sediment/FC-sediment systems. However, the aged RC-sediment systems do not conform well to this rule. In other words, the estimation of NP release risk from sediments with a strong adsorbent would be overestimated, if Frap + Fsolw is considered equivalent to the desorbing fraction.

A Cross-Sectional Survey on Psychological Health and Influencing Factors Among 2628 Asymptomatic and Mild COVID-19 Patients in Fangcang Shelter Hospital.

Purpose: The Coronavirus disease 2019 (COVID-19) remains a global public health concern. Many people have been forced to change their lifestyles, which has led to psychological and sleep problem. This study aims to investigate the psychological health problems and factors among patients in the Fangcang Shelter Hospital (FSH) during the COVID-19 pandemic. Patients and Methods: A Cross-Sectional survey was conducted to investigate the sleep, anxiety, depression and stress disorders of 2628 asymptomatic and mild patients treated in FSH of Zhengzhou, Henan Province, from 30 October to 6 December 2022, by scanning a WeChat two-dimensional code. Sociodemographic data and influencing factors in FSH were collected, Insomnia Severity Index (ISI), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Impact of Event Scale-Revised (IES-R) were administered. Descriptive statistics, t-tests or analysis of variance, Spearman or Pearson correlation analysis, and multivariate regression analysis were used to explore the relationships between different variables and their impact on psychological health indicators. Results: The proportions of patients with insomnia, depressive disorder, anxiety, and stress disorders were 33.49%, 35.80%, 31.74%, and 43.57%, respectively. Spearman correlation analysis demonstrated that factors such as gender, higher education level, positive nucleic acid test results, longer illness duration, underlying diseases, and extended electronic device use were associated with elevated psychological distress scores. Notably, within FSH, extended exposure to light, a noisy environment, and sleep schedule management significantly impacted the prevalence of insomnia, depression, anxiety, and stress disorders (p<0.01). Multivariable binary logistic regression analysis identified higher education level, light exposure, noisy environment, sleep management, and electronic device usage as the primary risk factors for psychological distress. Conclusion: Patients in FSH face psychological distress influenced by sociodemographic factors, environment, and lifestyle, highlighting the need for integrated psychological support in healthcare, particularly in temporary medical facilities during crises.

Exploring the mechanism of atherosclerosis and the intervention of traditional Chinese medicine combined with mesenchymal stem cells based on inflammatory targets.

Atherosclerosis (AS) is a chronic inflammatory vascular disease, which is the common pathological basis of cardiovascular and cerebrovascular diseases. The immune inflammatory response throughout the course of AS has been evidenced by studies, in which a large number of immune cells and inflammatory factors play a crucial role in the pathogenesis of AS. The inflammation related to AS is mainly mediated by inflammatory cytokines (IL-1ß, IL-6, IL-18, TNF-α, hs-CRP, SAA), inflammatory enzymes (Lp-PLA2, sPLA2-IIA, MMPs), and inflammatory signaling pathways (P38 MAPK signaling pathway, NF-κB signaling pathway, TLR2/4 signaling pathway). It is involved in the pathophysiological process of AS, and the degree of inflammation measured by it can be used to evaluate the risk of progression of AS plaque instability. In recent years, traditional Chinese medicine (TCM) has shown the advantage of minimal side effects in immune regulation and has made some progress in the prevention and treatment of AS. Mesenchymal stem cells (MSCs), as self-renewal, highly differentiated, and pluripotent stem cells with anti-inflammatory properties and immune regulation, have been widely used for AS treatment. They also play an important inflammation-immune regulatory function in AS. Notably, in terms of regulating immune cells and inflammatory factors, compared with TCM and its compound, the combination therapy has obvious anti-inflammatory advantages over the use of MSCs alone. It is an important means to further improve the efficacy of AS and provides a new way for the prevention and treatment of AS.

[Research progress on traditional Chinese medicine in treatment of neurodegenerative diseases by delaying neurovascular unit aging].

Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.

Metabolic engineering of oleaginous yeast in the lipogenic phase enhances production of nervonic acid.

Insufficient biosynthesis efficiency during the lipogenic phase can be a major obstacle to engineering oleaginous yeasts to overproduce very long-chain fatty acids (VLCFAs). Taking nervonic acid (NA, C24:1) as an example, we overcame the bottleneck to overproduce NA in an engineered Rhodosporidium toruloides by improving the biosynthesis of VLCFAs during the lipogenic phase. First, evaluating the catalytic preferences of three plant-derived ketoacyl-CoA synthases (KCSs) rationally guided reconstructing an efficient NA biosynthetic pathway in R. toruloides. More importantly, a genome-wide transcriptional analysis endowed clues to strengthen the fatty acid elongation (FAE) module and identify/use lipogenic phase-activated promoter, collectively addressing the stagnation of NA accumulation during the lipogenic phase. The best-designed strain exhibited a high NA content (as the major component in total fatty acid [TFA], 46.3%) and produced a titer of 44.2 g/L in a 5 L bioreactor. The strategy developed here provides an engineering framework to establish the microbial process of producing valuable VLCFAs in oleaginous yeasts.

Potential regulatory effects of stem cell exosomes on inflammatory response in ischemic stroke treatment.

The high incidence and disability rates of stroke pose a heavy burden on society. Inflammation is a significant pathological reaction that occurs after an ischemic stroke. Currently, therapeutic methods, except for intravenous thrombolysis and vascular thrombectomy, have limited time windows. Mesenchymal stem cells (MSCs) can migrate, differentiate, and inhibit inflammatory immune responses. Exosomes (Exos), which are secretory vesicles, have the characteristics of the cells from which they are derived, making them attractive targets for research in recent years. MSC-derived exosomes can attenuate the inflammatory response caused by cerebral stroke by modulating damage-associated molecular patterns. In this review, research on the inflammatory response mechanisms associated with Exos therapy after an ischemic injury is discussed to provide a new approach to clinical treatment.

Study on the Composition and Mechanism of Santiao Decoction in Treating Insomnia Based on UPLC and Network Pharmacology and Molecular Docking Technology.

OBJECTIVE: To identify the chemical components of Santiao Decoction (STD) using Ultra Performance Liquid Chromatography (UPLC) and to conduct a network pharmacological study of STD for the treatment of insomnia based on this technique. METHODS: An ACQUITY UPLC BEH C18 column (2.1 mm×100 mm, 1.7 µm) was used to identify the chemical components of STD by relative molecular weight, mass spectrometry information, and comparison with the control. The active ingredients of the formula and their corresponding gene targets and targets for insomnia were retrieved from several databases, and a visual network diagram of "drug-active ingredient-target-disease" was constructed using Cytoscape 3.8.2 software, and GO functional annotation and KEGG pathway enrichment analysis were performed using various databases such as DAVID. RESULTS: Five active ingredients were identified from STD by UPLC technique, 268 active ingredients of STD were screened from the TCMSP database, and 109 genes related to STD for insomnia were screened by network pharmacology, among which IL6, MMP9, VEGFA, IL10, CCL2 may be the key targets of STD for insomnia. KEGG pathway analysis showed that STD acts on membrane rafts, plasma membrane micro-regions, and other related pathways, such as Toll-like receptor signaling pathway, prolactin signaling pathway, dopaminergic synapse, relaxin signaling pathway, ErbB signaling pathway, steroid hormone biosynthesis and NF-kappa B signaling pathway for regulation. CONCLUSION: The active ingredients in STD, such as (+)-catechin, Swertisin, quercetin, baicalein, and wogonin, may act on IL6, CCL2, VEGFA, MMP9, and other targets to regulate Toll-like receptor signaling pathway, ErbB signaling pathway, NF-kappa B and other signaling pathways, and exert certain therapeutic effects on insomnia, which provide a reference and basis for further research on the mechanism of action of STD.

Microstructure and Mechanical Properties of Magnesium Matrix Composites Reinforced by In Situ Reduced Graphene Oxide.

Due to their excellent mechanical properties and large specific surface area, graphene and its derivatives are widely used in metal matrix composites as reinforcements. In this study, the thermal reduction behavior of large-size graphene oxide are investigated systematically, and reduced graphene oxide (RGO) with few residual oxygen groups and good structural integrity is obtained. ZK61 matrix composites with varying content of in situ RGO are fabricated using the semi-powder metallurgy method. The results reveal that the addition of RGO can cause the refinement of the grains and the second phase, which is attributed to the uniform distribution of the RGO throughout the matrix. The formation of nano-MgO particles is beneficial in increasing the interfacial bonding strength between the RGO and the matrix, resulting in simultaneous increments in yield strength and elongation in the RGO/ZK61 composites. The composite containing 0.6 wt.% RGO shows a superior mechanical property, including microhardness of 79.9 HV, yield strength of 203 MPa and excellent elongation of 17.5%, with increases of 20.9%, 8.6% and 7.4%, respectively, when compared with the ZK61 alloy. Quantitative analysis indicates that the main strengthening mechanisms of RGO-reinforced magnesium matrix composites are load transfer strengthening and grain refinement strengthening.

Occurrence and exposure risk assessment of organochlorine pesticides in two waterbird species from Honghu Lake Wetland, Central China.

Monitoring and evaluating bird exposure to hazardous pollutants in wetlands are receiving considerable attention. In this study, the occurrence of 18 organochlorine pesticides (OCPs) in the muscle of bean geese (Anser fabalis) and common teals (Anas crecca) collected from Honghu Lake Wetland (HLW), Central China was studied. Additionally, an exposure risk assessment model was applied to obtain risk levels of OCPs to these birds through three oral routes (food intake, water drinking and soil ingestion). The results suggested that the most abundant OCPs detected in the muscle of waterbirds were DDTs (7.68-602 ng/g lipid weight), followed by HCHs (1.39-89.8 ng/g lipid weight). A significant difference (p < 0.05) existed between two species, but most of OCPs exhibited no statistically relationship with age or gender (p > 0.05). The compositional patterns of OCPs combined with ratios of certain metabolites to their parent compounds indicated that all OCPs in the HLW were largely from historical usage except heptachlor. The exposure risk assessment revealed that common teals with lighter weight had greater exposure risks than bean geese. Of the OCPs analyzed, DDTs could probably cause harm to target birds studied here. Exposure via food intake was identified to be significant while soil ingestion and water drinking contributed least, but they should still be concerned.

The Advancements and Prospects of Nervonic Acid Production.

Nervonic acid (NA) is a monounsaturated very long-chain fatty acid (VLCFA) and has been identified with critical biological functions in medical and health care for brain development and injury repair. Yet, the approaches to producing NA from the sources of plants or animals continue to pose challenges to meet increasing market demand, as they are generally associated with high costs, a lack of natural resources, a long life cycle, and low production efficiency. The recent technological advance in metabolic engineering allows us to precisely engineer oleaginous microbes to develop high-content NA-producing strains, which has the potential to provide a possible solution to produce NA on a commercial fermentation scale. In this Review, the biosynthetic pathway, natural sources, and metabolic engineering of NA are summarized. The strategies of metabolic engineering that could be adopted to modify oleaginous yeast to produce NA are discussed in detail, providing the prospecting views for the microbial cells producing NA.

Product Processing Quality Classification Model for Small-Sample and Imbalanced Data Environment.

With the rapid development of machine learning technology, how to use machine learning technology to empower the manufacturing industry has become a research hotspot. In order to solve the problem of product quality classification in a small sample data and imbalanced data environment, this paper proposes a data generation model called MSMOTE-GAN, which is based on Mahalanobis Synthetic Minority Oversampling Technology (MSMOTE) and Generative Adversarial Network (GAN). Among them, MSMOTE is proposed to solve the problem of the sample biased to the majority class expanded by methods such as GAN in a sample imbalanced environment. Based on the traditional SMOTE method, the sample distance measurement method is modified from Euclidean distance to Mahalanobis distance, taking into account the correlation between attributes and the influence of dimensions on the sample distance. In the data generation model, MSMOTE is used to balance the positive and negative samples in the data. GAN generates fake data with the same distribution as the original data based on a balanced data set and expands the sample size to solve the problems of overfitting and insufficient model expression ability that occur when the sample size is too small. The quality classification framework of water heater liner based on the data generation model and Random Forest is constructed, and the process of the quality classification of water heater liner under the environment of small sample data and imbalanced data is fully described. This paper compares the MSMOTE-GAN model, Bootstrap, and tableGAN on the water heater liner production line data set and the public data set. The experimental result shows that the expanded data set of the MSMOTE-GAN model can effectively improve the performance of the classification model.

Zuogui Wan improves trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats by regulating orexin-A and orexin receptor.

OBJECTIVE: To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model. METHODS: Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17ß-estradiol (E2, 50 µg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17ß-estrogen (17ß-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis. RESULTS: Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17ß-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01). CONCLUSION: ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.

High-level soluble expression of phospholipase D from Streptomyces chromofuscus in Escherichia coli by combinatorial optimization

BACKGROUND: Phospholipase D (PLD) is used as the biocatalyst for phosphatidylserine (PS) production. In general, PLD was expressed in insoluble form in Escherichia coli. High-level soluble expression of PLD with high activity in E. coli is very important for industrial production of PLD. RESULTS: Streptomyces chromofuscus PLD coding gene was codon-optimized, cloned without signal peptide, and expressed in E. coli. The optimal recombinant E. coli pET-28a+PLD/BL21(DE3) was constructed with pET-28a without His-tag. The highest PLD activity reached 104.28 ± 2.67 U/mL in a 250-mL shake flask after systematical optimization. The highest PLD activity elevated to 122.94 ± 1.49 U/mL by feeding lactose and inducing at 20 C after scaling up to a 5.0-L fermenter. Substituting the mixed carbon source with 1.0 % (w/v) of cheap dextrin and adding a feeding medium could still attain a PLD activity of 105. 81 ± 2.72 U/mL in a 5.0-L fermenter. Fish peptone from the waste of fish processing and dextrin from the starch are both very cheap, which were found to benefit the soluble PLD expression. CONCLUSIONS: After combinatorial optimization, the high-level soluble expression of PLD was fulfilled in E. coli. The high PLD activity along with cheap medium obtained at the fermenter level can completely meet the requirements of industrial production of PLD.

Combination of Adsorption and Cellulose Derivative Membrane Coating for Efficient Immobilization of Laccase.

Immobilization of enzyme based on combination of adsorption and cellulose derivative membrane coating was established in this work for the first time. Laccase, a commonly used enzyme in varied fields, was chosen as the model enzyme to demonstrate this method. After investigating operational conditions, the optimal process was obtained as follows: diatomite or HPD-417 as the adsorption carrier, 0.5% (w/v) methylcellulose (40,000~50,000) acetone solution as the coating solution, 0.75% (w/v) polyethylene glycol or maltose as the protective agent, and drying at 4 °C for 9 h. Under the optimal conditions, the residual activities of diatomite and HPD-417 immobilized laccase reached 99.33% and 94.15%, respectively. The study on properties showed that the immobilized laccases held high pH tolerance and thermal stability. The immobilized laccases were further applied to the indigo decolorization and 2, 4-dichlorophenol degradation. They showed high catalytic efficiency and could be reused for several batches. On the whole, the immobilization method developed in this work can effectively avoid the inactivation of laccase during immobilization and improve the stability of immobilized laccase. The laccase immobilized by this method shows obvious potential for environmental governance.

Facile One-Pot Solvothermal Synthesis of the RGO/MWCNT/Fe3O4 Hybrids for Microwave Absorption.

How to effectively regulate the electromagnetic parameters of magnetic composites to achieve better microwave absorption (MA) performances is still a serious challenge. Herein, we constructed nanocomposites composed of magnetic constituents and carbon materials to obtain high-efficiency electromagnetic wave absorbers. Self-assembled, multi-interfacial, and porous RGO/MWCNT/Fe3O4 hybrids (GMFs) were synthesized via in situ one-pot solvothermal method. The growth mechanism of the GMFs would be that the defects on reduced graphene oxide (RGO) provide sites for the crystallization of Fe3O4. Also, the RGO and Fe3O4 were further linked by the cross-connection of multiwalled carbon nanotubes (MWCNTs), which acted as a bridge. The MA mechanism of GMFs was studied while considering the synergistic effects between the three components (RGO, MWCNT, and raspberry-shaped Fe3O4) and their multi-interfacial and porous structure. Also, the MA performance of the GMFs was conducted. The GMFs exhibited a maximum reflection loss (RL) value of -61.29 dB at 10.48 GHz with a thickness of 2.6 mm when the contents of RGO and MWCNT were 6.3 and 1.3 wt %, respectively. The RL values (≤-10 dB) were observed to be in the range of 8.96-12.32 GHz, and the effective microwave absorption bandwidth was tunable from 3.52 to 18 GHz by changing the sample thickness. The results revealed that the multi-interfacial and porous structure of the GMFs is beneficial to MA performance by inducing multiscatterings. Since no toxic solvents were used, this method is environmentally friendly and has potential for large-scale production. The prepared GMFs may have a wide range of applications in MA materials against electromagnetic interference pollution.

Identification of core genes and prediction of miRNAs associated with osteoporosis using a bioinformatics approach.

Osteoporosis (OP) is an age-related disease, and osteoporotic fracture is one of the major causes of disability and mortality in elderly patients (>70 years old). As the pathogenesis and molecular mechanism of OP remain unclear, the identification of disease biomarkers is important for guiding research and providing therapeutic targets. In the present study, core genes and microRNAs (miRNAs) associated with OP were identified. Differentially expressed genes (DEGs) between human mesenchymal stem cell specimens from normal osseous tissues and OP tissues were detected using the GEO2R tool of the Gene Expression Omnibus database and Morpheus. Network topological parameters were determined using NetworkAnalyzer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, and ClueGO. Cytoscape with the Search Tool for the Retrieval of Interacting Genes and Molecular Complex Detection plug-in was used to visualize protein-protein interactions (PPIs). Additionally, miRNA-gene regulatory modules were predicted using CyTargetLinker in order to guide future research. In total, 915 DEGs were identified, including 774 upregulated and 141 downregulated genes. Enriched GO terms and pathways were determined, including 'nervous system development', 'regulation of molecular function', 'glutamatergic synapse pathway' and 'pathways in cancer'. The node degrees of DEGs followed power-law distributions. A PPI network with 541 nodes and 1,431 edges was obtained. Overall, 3 important modules were identified from the PPI network. The following 10 genes were identified as core genes based on high degrees of connectivity: Albumin, PH domain leucine-rich repeat-containing protein phosphatase 2 (PHLPP2), DNA topoisomerase 2-α, kininogen 1 (KNG1), interleukin 2 (IL2), leucine-rich repeats and guanylate kinase domain containing, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG), leptin, transferrin and RNA polymerase II subunit A (POLR2A). Additionally, 15 miRNA-target interactions were obtained using CyTargetLinker. Overall, 7 miRNAs co-regulated IL2, 3 regulated PHLPP2, 3 regulated KNG1, 1 regulated PIK3CG and 1 modulated POLR2A. These results indicate potential biomarkers in the pathogenesis of OP and therapeutic targets.

The blockade of lipophagy pathway is necessary for docosahexaenoic acid to regulate lipid droplet turnover in hepatic stellate cells.

Hepatic stellate cell (HSC) activation is treated as a dominator segment in hepatic fibrosis, which is accompanied by significant loss of lipid droplets (LDs). However, the regulatory network of LD disappearance is still unclear. It has been reported that lipophagy activation contributed to LD loss by upregulating RAB25 expression. In the present study, we sought to determine the regulation of docosahexaenoic acid (DHA) on LD disappearance, and to further examine potential molecular mechanisms. Interestingly, DHA treatment completely impaired LD disappearance during HSC activation. Moreover, treatment with DHA evidently promoted LD regeneration in activated HSCs that displayed matrix-producing myofibroblasts. Attractively, DHA-induced LD regeneration was coupled with the inhibition of lipophagy signaling. DHA treatment increased autophagosome generation and autophagic flux, but inhibited the target recognition of lipophagy for LDs by inhibiting RAB25 expression. Importantly, up-regulation of RAB25 expression, using RAB25 plasmid, completely blocked DHA-induced LD regeneration in activated HSCs. Noteworthy, treatment of DHA prominently alleviated murine liver fibrosis by reversing HSC lipocyte phenotype. HSC-specific overexpression of RAB25 impaired DHA-induced LD regeneration of activated HSCs, and in turn abolished anti-hepatic fibrosis effect of DHA in murine liver fibrosis. Overall, these results showed that DHA induced LD regeneration by inhibiting lipophagy signaling in activated HSCs, and also identified RAB25 dependent lipophagy as an important target for the prevention of hepatic fibrosis.

[Analysis of anti-fatigue mechanism and potential targets of ginseng].

Ginseng has effects in reinforcing vital energy,invigorating health effectively and relieving fatigue symptoms,and ginsenoside( GS) is the main component of its anti-fatigue effect. Totally 17 active components and 92 drug targets of ginseng compounds were screened from Traditional Chinese Medicine Systems Pharmacology; and 78 intersecting genes of diseases and drug targets were obtained based on R Language Technology. The protein-protein interaction( PPI) network was constructed by STRING 11. 0 software,and Matthews Correlation Coefficient( MCC) algorithm was used to screen core target genes. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the major genes and their roles in regulatory networks. The results indicated that ginseng could regulate the core target genes,including AKT serine/threonine kinase( AKT1),interleukin-1ß,Toll-like receptor binding molecule 1( ICAM1),mitogen-activated protein kinase 8( MAPK8),AP-1 transcription factor subunit( JUN),transducer and activator of transcription 1( STAT1) and prostaglandin peroxidase synthase 2( PTGS2). It could participate in the functions of cytokine receptor binding,cell adhesion molecule binding and tumor necrosis factor receptor superfamily binding,and also regulate the signal pathways of tumor necrosis factor,interleukin 17 and c-type lectin receptor,so as to exert an anti-fatigue effect. Based on the results of network analysis,32 four-week-old male SPFACR mice were randomly divided into control group,low-dose ginsenoside group,middle-dose ginsenoside group and high-dose ginsenoside group. The corresponding drugs were administrated for 3 weeks. The results showed that GS could significantly up-regulate the expressions of STAT1 and AKT1( P<0. 01,P<0. 05),and downregulate the expressions of PTGS2 and JUN( P<0. 01). However,there was no significant effect on MAPK8,IL-1ß and ICAM1. Ginseng's anti-fatigue regulation network was constructed through network pharmacology,and the results were verified by experiments,in order to reveal the anti-fatigue mechanism of ginseng and provide scientific basis for its clinical application.

Effect of Zuoguiwan on osteoporosis in ovariectomized rats through RANKL/OPG pathway mediated by ß2AR.

ETHNOPHARMACOLOGICAL RELEVANCE: The deficiency of kidney Yin is the main pathogenesis of postmenopausal osteoporosis (PMOP) according to traditional Chinese medicine (TCM). Zuoguiwan (ZGW) is among the classical prescriptions in TCM and has been applied to various diseases that are due to deficiency of kidney Yin, including osteoporosis, fractures, menopausal syndromes. However, the underlying mechanism of ZGW in treating PMOP remains poorly understood. AIM OF THE STUDY: ZGW, a traditional Chinese prescription, has been used to nourish Yin and reinforce the kidney since ancient times. The investigation aimed to explore the mechanism of ZGW via the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway as mediated by the ß2-adrenergic receptor (ß2AR) in an osteoporosis rat model. MATERIALS AND METHODS: An osteoporosis model induced by ovariectomy was established in rats. A total of 40 female Sprague-Dawley rats were randomly assigned into bilateral ovariectomy group (OVX), sham operated group (Sham), 17ß-estradiol-treated positive group (E2, 25 µg/kg/d), ZGW low-dose group (ZGW-L, 2.3 g/kg/d lyophilized powder) and ZGW high-dose group (ZGW-H, 4.6 g/kg/d lyophilized powder). The serum markers of bone turnover were measured using enzyme-linked immunosorbent assay (ELISA). The morphological structure changes in bones were detected through H&E staining. Local bone mineral density (BMD) and trabecular bone microarchitecture of the right distal femur were measured and evaluated by using micro-CT. Furthermore, the mRNA and protein expressions levels of ß2AR, OPG and RANKL were measured by qPCR and Western blot analysis. RESULTS: Compared with the OVX group, ZGW groups showed significantly reduced levels of serum tartrate-resistant acid phosphatase 5b (TRACP-5b) and ß-cross-linked c-telopeptide of type I collagen (ß-CTX) (P ＜ 0.01), increased levels of serum bone-specific alkaline phosphatase (BALP) (P ＜ 0.01) and OPG (P ＜ 0.05), prevention of OVX-induced bone loss, and improved microarchitecture of the trabecular bone of distal femur. Moreover, ZGW mediated the osteoporosis syndrome by reducing the empty bone lacunae, promoting the ordered arrangement of trabeculae structure, and increasing the trabeculae structure thickness. Furthermore, in ZGW groups, the protein expression of OPG in the tibia was notably up-regulated (P ＜ 0.01), whereas the mRNA and protein expression of ß2AR in the hippocampus (P ＜ 0.01), and the protein expressions levels of ß2AR (P ＜ 0.01) and RANKL (P ＜ 0.05) in the tibia were down-regulated compared with OVX group. CONCLUSIONS: ZGW through its protective effects, stimulates bone formation and suppresses bone resorption. The underlying mechanism of ZGW in improving perimenopausal syndrome and increasing bone mass might be attributed to the regulation of RANKL/OPG, as mediated by ß2AR. Therefore, ZGW may be used as an alternative treatment for PMOP.