Ziyuglycoside II attenuated OVX mice bone loss via inflammatory responses and regulation of gut microbiota and SCFAs.

BACKGROUND AND PURPOSE: Osteoporosis (OP) is a frequent clinical problem for the elderly. Traditional Chinese Medicine (TCM) has achieved beneficial results in the treatment of OP. Ziyuglycoside II (ZGS II) is a major active compound of Sanguisorba officinalis L. that has shown anti-inflammation and antioxidation properties, but little information concerning its anti-OP potential is available. Our research aims to investigate the mechanism of ZGS II in ameliorating bone loss by inflammatory responses and regulation of gut microbiota and short chain fatty acids (SCFAs) in ovariectomized (OVX) mice. METHODS: We predicted the mode of ZGS II action on OP through network pharmacology and molecular docking, and an OVX mouse model was employed to validate its anti-OP efficacy. Then we analyzed its impact on bone microstructure, the levels of inflammatory cytokines and pain mediators in serum, inflammation in colon, intestinal barrier, gut microbiota composition and SCFAs in feces. RESULTS: Network pharmacology identified 55 intersecting targets of ZGS II related to OP. Of these, we predicted IGF1 may be the core target, which was successfully docked with ZGS II and showed excellent binding ability. Our in vivo results showed that ZGS II alleviated bone loss in OVX mice, attenuated systemic inflammation, enhanced intestinal barrier, reduced the pain threshold, modulated the abundance of gut microbiota involving norank_f__Muribaculaceae and Dubosiella, and increased the content of acetic acid and propanoic acid in SCFAs. CONCLUSIONS: Our data indicated that ZGS II attenuated bone loss in OVX mice by relieving inflammation and regulating gut microbiota and SCFAs.

Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota.

Objective: Eleutheroside E (EE) is an anti-inflammatory natural compound derived from the edible medicinal herb Acanthopanax senticosus. This study aims to investigate the underlying mechanism of the anti-osteoporosis action of EE through network pharmacology, molecular docking and gut microbiota. Materials and methods: Network pharmacology was used to explore the potential core targets and main pathways mediated by EE in osteoporosis (OP) treatment. Molecular docking was exploited to investigate the interactions between the active anti-OP compounds in EE and the potential downstream targets. Following the multi-approach bioinformatics analysis, ovariectomy (OVX) model was also established to investigate the in vivo anti-OP effects of EE. Results: The top 10 core targets in PPI network were TP53, AKT1, JUN, CTNNB1, STAT3, HIF1A, EP300, CREB1, IL1B and ESR1. Molecular docking results that the binding energy of target proteins and the active compounds was approximately between -5.0 and -7.0 kcal/mol, which EE has the lowest docking binding energy with HIF1A. Enrichment analysis of GO and KEGG pathways of target proteins indicated that EE treatment could potentially alter numerous biological processes and cellular pathways. In vivo experiments demonstrated the protective effect of EE treatment against accelerated bone loss, where reduced serum levels of TRAP, CTX, TNF-α, LPS, and IL-6 and increased bone volume and serum levels of P1NP were observed in EE-treated mice. In addition, changes in gut microbiota were spotted by 16S rRNA gene sequencing, showing that EE treatment increased the relative abundance of Lactobacillus and decreased the relative abundance of Clostridiaceae. Conclusion: In summary, these findings suggested that the characteristics of multi-target and multi-pathway of EE against OP. In vivo, EE prevents the onset of OP by regulating gut microbiota and inflammatory response and is therefore a potential OP drug.

Chemical constituents from Eupatorium fortunei and their anti-inflammatory evaluation by in silico and experimental approaches.

The well-known aromatic and medicinal plant Eupatorium fortunei Turcz. is widely cultivated in China, and previous studies on its bioactive constituents mainly focus on the essential oil ingredients especially thymol derivatives. However, reports on other type of constituents and the potential application are lacking. In the present project, an intensive chemical fractionation on the aerial part extract of E. fortunei led to the isolation and identification of a series of fatty acid derivatives (lipids, 1a/1b-19) including seven pairs of previously undescribed enantiomers (1a/1b-7a/7b), as well as a lignan (brachangobinan A (BBA), 20) and two monoterpenes (8S/8R-9-hydroxythymol, 21a/21b). A preliminary biological evaluation of these compounds in a NO production inhibitory assay model demonstrated compound BBA as the most active one. Network pharmacology analysis was used to predict and explore the possible anti-inflammatory targets and mechanism of BBA, which revealed some potential inflammation-related proteins and signaling pathways. Further experimental investigations validated that the anti-inflammatory effect of BBA could be achieved by suppressing pro-inflammatory factors and blocking the activation of NF-κB signaling pathway. Taken together, our work shows that E. fortunei can serve as a potential resource of lipids and anti-inflammatory agents.

Effect of an Online Mindfulness-Based Stress Reduction Intervention on Postpandemic Era Nurses' Subjective Well-being, Job Burnout, and Psychological Adaptation.

This study explores the effects of an online mindfulness-based stress reduction intervention on postpandemic era nurses' subjective well-being, job burnout, and psychological adaptation. Previous studies on the psychological adaptability of nurses mainly focused on investigation rather than intervention. Ninety nurses were randomly classified into an intervention or control group. The intervention group received weekly online mindfulness-based stress reduction training for 8 weeks. The Subjective Well-being, Job Burnout, and Psychological Use scales were administered pre- and postintervention. Postintervention, nurses' positive emotions and life satisfaction significantly improved. Nurses' psychological adaptation was significantly higher postintervention than preintervention. The total scores for negative emotion, low personal accomplishment, and job burnout were significantly lower postintervention than preintervention. The scores for positive emotion and life satisfaction in the intervention group were significantly higher than those in the control group, and the scores for low personal accomplishment in the intervention group were significantly lower than those in the control group. Online mindfulness-based stress reduction interventions can improve nurses' subjective well-being, reduce job burnout, and improve their level of psychological adaptability. Moreover, it could promote nurses' ability to communicate mindfully with patients and their families. This intervention could help promote the development of mindfulness in the nursing field.

Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.

Serum Essential Elements and Survival after Cancer Diagnosis.

In a prospective study, we measured the associations between three serum elements (Se, Zn and Cu) and the prognosis of 1475 patients with four different types of cancer (breast, prostate, lung and larynx) from University Hospitals in Szczecin, Poland. The elements were measured in serum taken after diagnosis and prior to treatment. Patients were followed from the date of diagnosis until death from any cause or until the last follow-up date (mean years of follow-up: 6.0-9.8 years, according to site). Kaplan-Meier curves were constructed for all cancers combined and for each cancer separately. Age-adjusted hazard ratios (HRs) were estimated using Cox regression. The outcome was all-cause mortality. A Se level in the highest quartile was also associated with a reduced mortality (HR = 0.66; 95%CI 0.49-0.88; p = 0.005) in all-cause mortality for all cancers combined. Zn level in the highest quartile was also associated with reduced mortality (HR = 0.55; 95%CI 0.41-0.75; p = 0.0001). In contrast, a Cu level in the highest quartile was associated with an increase in mortality (HR = 1.91; 95%CI 1.56-2.08; p = 0.0001). Three serum elements-selenium, zinc and copper-are associated with the prognosis of different types of cancer.

Effects of dietary phosphorus deficiency on the growth performance, hepatic lipid metabolism, and antioxidant capacity of Yellow River Carp Cyprinus carpio haematopterus.

OBJECTIVE: The study aimed to evaluate the effects of phosphorus (P) deficiency in diets on growth performance, hepatic lipid metabolism, and antioxidant capacity in Yellow River Carp Cyprinus carpio haematopterus. METHODS: In this study, 72 healthy experimental fish (initial weight = 12.0 ± 0.1 g [mean ± SE]) were randomly selected and distributed to two groups, with three replicates in each group. The groups were fed either a P-sufficient diet or a P-deficient diet for 8 weeks. RESULT: The P-deficient feed significantly decreased the specific growth rate, feed efficiency, and condition factor of Yellow River Carp. Fish that were fed the P-deficient feed demonstrated higher contents of triglyceride, total cholesterol (T-CHO), and low-density lipoprotein cholesterol in the plasma and a higher T-CHO content in the liver compared to the P-sufficient diet group. In addition, the P-deficient diet significantly reduced the catalase activity level, decreased the glutathione content, and increased the malondialdehyde content in the liver and in the plasma. Furthermore, P deficiency in the diet significantly downregulated the messenger RNA expression of nuclear erythroid 2-related factor 2 and peroxisome proliferator-activated receptor α, whereas it upregulated the messenger RNA expression of tumor necrosis factor α and fatty acid synthase in the liver. CONCLUSION: Dietary P deficiency reduced fish growth performance, induced fat deposition and oxidative stress, and impaired liver health.

The Efficacy and Safety of Manual Therapy for Symptoms Associated with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: Multiple sclerosis (MS) is a chronic neurological autoimmune disease, affecting the psychological and physical health of patients. Manual therapies have been proven to relieve pain, strengthen muscles, and improve bladder and bowel problems with a high safety and low adverse event profile. Previous studies have reported the results of manual therapy in alleviating symptoms associated with MS, but the conclusions were controversial. Objective: The purpose of this meta-analysis is to comprehensively analyze and determine the efficacy and safety of manual therapy in relieving symptoms associated with MS. Methods: Eight electronic databases were searched from inception of the database to April 30, 2021. Randomized controlled trials (RCTs) using manual therapy in patients to relieve symptoms associated with MS were considered eligible for this study. Two reviewers independently extracted data using pre-established standards. Results: Finally, 10 eligible RCTs with 631 subjects were included in this meta-analysis. These data establish that massage therapy can significantly ameliorate fatigue, pain, and spasms, while reflexology was only effective in relieving pain in MS patients. No adverse events were reported in eligible RCTs. Conclusions: The present study provides strong evidence that massage therapy could alleviate fatigue, pain, and spasms in MS patients, while reflexology plays a positive role in relieving pain. Physicians could consider massage therapy or reflexology as a safe and effective complementary and alternative treatment. Larger RCTs with higher methodological quality are needed in the future, which aim to provide more meaningful evidence for further proof of efficacy.

Efficacy of astragalus in the treatment of radiation-induced lung injury based on traditional Chinese medicine: A systematic review and meta-analysis of 25 RCTs.

BACKGROUND: Astragalus (Hedysarum Multijugum Maxim., Huangqi) is a Chinese herbal medicine, and according to the theory of traditional Chinese medicine (TCM), Chinese medicinal preparations containing astragalus can be used clinically to treat radiation-induced lung injury (RILI). To systematically review the efficacy and safety of Chinese medicinal preparations containing astragalus in the prevention and treatment of RILI by means of meta-analysis. METHODS: A systematic literature on randomized controlled trials (RCTs) of prescriptions containing astragalus in the treatment of RILI by Pubmed, Embase, Web of Science, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, WANFANG Database. The retrieval time is from the establishment of the database to January 18, 2022. Meta-analysis, heterogeneity test and sensitivity analysis were performed on eligible RCTs using Revman 5.4 software and STATA 17.0 software, and a "funnel plot" was used to analyze potential publication bias. RESULTS: A total of 25 RCTs were included, including 1762 patients, and the most widely used drugs were heat-clearing and detoxifying, yin-nourishing and qi-nourishing. The prescriptions containing astragalus can significantly reduce the total incidence of RILI (P < .01), improve the total effective rate and cure rate of RILI (P < .01), improve the quality of life of patients, alleviate breathing difficulties and reduce the expression of inflammatory factors (P < .01), and no adverse reactions related to TCM treatment were reported. CONCLUSION: The traditional Chinese medicinal preparation containing astragalus can effectively alleviate the clinical symptoms of RILI, reduce the toxic side effects, and is safe to use in clinic.

Berberine inhibited the formation of metastasis by intervening the secondary homing of colorectal cancer cells in the blood circulation to the lung and liver through HEY2.

BACKGROUND: Metastasis is the leading cause of death in patients with colorectal cancer (CRC). The 5-year survival rate of CRC patients in whom the cancer has spread to distant sites is 13.5%. The most common sites of CRC metastasis are liver and lung. The principal therapies for CRC metastatic disease are surgery, but its benefits are limited. PURPOSE: This study aimed to reveal the regulatory mechanism of berberine on secondary homing of CRC cells to form metastatic focus. This was more valuable than the previous direct study of the migration and metastasis characteristics of CRC cells. METHODS: In this study, we used the functional enrichment analysis of differentially expressed genes after berberine treatment and investigated co-expression modules related with CRC metastasis by WGCNA. PPI and survival analyses of significant modules were also conducted. The biological functions of berberine in CRC lung and liver metastasis were investigated by a series of in vitro and in vivo experiments: MTT, colony formation and mouse tail vein injection. And we scanned through the entire extracellular domain of HEY2 protein for autodocking analysis with berberine. RESULTS: We found the differentially expressed genes (DEGs) after berberine treatment were related with cancer progression and metastasis related pathways. Through WGCNA analysis, four cancer progression and metastasis related modules were detected. After PPI and survival analysis, we identified and validated HEY2 as a hub gene, high expression and poor survival at the metastatic stage. Functionally, berberine inhibited the survival, invasion and migration of CRC cells in vitro and in vivo. Mechanistically, berberine treatment down-regulated the expression of HEY2, metastasis related protein E-cadherin, ß-catenin and Cyclin D1 during Mesenchymal epithelial transformation (MET). Berberine and HEY2 showed a significant interaction, and berberine binded to HEY2 protein at the residue HIS-99 interface with a hydrogen-bond distance of 1.9A. CONCLUSIONS: We revealed that berberine could significantly inhibit the expression of hub gene HEY2 and metastasis related proteins E-cadherin and ß-catenin and Cyclin D1 during MET in CRC lung and liver metastases. In total, HEY2 was a promising candidate biomarker for prognosis and molecular characteristics in CRC metastasis.

Effects of Insulin Combined with Traditional Chinese Medicine Assisted Comprehensive Nursing Intervention on Oxidative Stress State, Cell Adhesion Factor, and Pregnancy Outcome of Patients with Gestational Diabetes Mellitus.

Objectives: The changes of oxidative stress state, cell adhesion factor (sICAM-1) level, blood glucose, and blood lipid of patients with gestational diabetes mellitus (GDM) assisted by insulin combined with traditional Chinese medicine (TCM) prescription were detected to explore the effect of TCM treatment on maternal and infant outcomes of GDM. Methods: A total of 60 patients diagnosed with GDM from January 2019 to December 2019 were selected. Among them, 30 patients were treated with insulin combined with TCM prescription (control group), and 30 patients were treated with nursing intervention based on control group (study group). Serum of maternal vein and fetal umbilical vein was collected. The contents of superoxide dismutase (SOD) and lipid oxide (MDA) were determined. The content of intercellular adhesion factor (ICAM-1) was measured, and the differences of fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), cholesterol (CHO) and low density lipoprotein (LDL-C) between 2 groups were compared. The incidence of maternal and infant adverse outcomes was assessed. Results: After treatment, blood glucose indexes in 2 groups were decreased, and the study group was lower than the control group. After treatment, LDL-C, TC and TG in 2 groups were lower than before, and the study group was lower than the control group. HDL-C was higher than before treatment, and the study group was higher than the control group. After treatment, oxidation-related substances SOD and GSH-Px in 2 groups were higher than before, and those in study group were higher than those in control group. ROS and MDA were lower than before treatment, and the level of sICAM-1 in the study group was significantly higher than that in the control group. Clinical application of insulin combined with TCM prescription assisted comprehensive nursing intervention in the treatment of gestational diabetes, pregnancy outcome is improved. Conclusions: Oxidative stress imbalance exists in GDM and the causes of adverse pregnancy outcomes are closely related to oxidative stress and vascular endothelial injury. TCM can improve the oxidative stress imbalance and the pregnancy outcome of patients with GDM from the perspective of reducing vascular endothelial injury. Comprehensive nursing intervention for pregnant women with GDM can optimize the outcome of pregnancy and is worthy of clinical application.

Response of cyanobacterial bloom risk to nitrogen and phosphorus concentrations in large shallow lakes determined through geographical detector: A case study of Taihu Lake, China.

Understanding the sensitivity of the response of chlorophyll (Chla) to nutrients (e.g., nitrogen and phosphorus) concentrations is important for predicting cyanobacterial bloom risk. However, the processes by which nutrients in lake that affect cyanobacterial growth and outbreaks are nonlinear, gradual and spatially and temporally heterogeneous, and the single response thresholds of concentrations between nutrients and the Chla proposed in current studies maybe hardly reflect these characteristics. Due to three decades of rapid regional socio-economic development, the eutrophication in Taihu Lake of China is serious and there are cyanobacterial blooms every year. In this study, we quantified the interaction effects of different forms of nitrogen and phosphorus on Chla concentrations in lake water and sediment pore water. And a refined response threshold range with continuous variation was proposed to characterize the relationship between the Chla concentration and the NH4-N, total nitrogen (TN) and total phosphorus (TP) concentrations. The results showed that TP was the dominant factor influencing the spatial variation of cyanobacteria blooms in most areas of Taihu Lake, followed by TN. TP should therefore be the highest priority for future pollution load reduction in Taihu Lake. The effects of the interactions between the pollution factors were greater than the sum of them individually. NH4-N and dissolved inorganic phosphorus (DIP) are likely to be preferentially consumed by algae for growth and should be the focus of nutrient control efforts in Taihu Lake. For cyanobacterial risk prediction, prevention and control, NH4-N, TN and TP concentrations of 0.06 mg/L, 2.89 mg/L and 0.06 mg/L, respectively, can be used to indicate the beginning of cyanobacterial blooms in Taihu Lake, and concentrations of 0.34 mg/L, 4.67 mg/L and 0.11 mg/L, respectively, can be used as reference thresholds to indicate serious cyanobacterial blooms.

[Clinical efficacy of Longjintonglin Capsules on chronic prostatitis with damp-heat stasis syndrome Re-evaluation based on multicenter real-world study].

OBJECTIVE: To re-evaluate the clinical efficacy of Longjintonglin Capsules (LJTL) in the treatment of chronic prostatitis with damp-heat stasis syndrome. METHODS: This multicenter real-world study included 1 352 cases of chronic prostatitis with damp-heat and stagnation syndrome treated with LJTL (3 capsules once, tid, 30 minutes after meals, for 2 four-week courses) in addition to routine treatment. Before and after treatment, we analyzed the NIH-CPSI scores, the scores of Chinese medicine symptom quantitative classification and changes in individual symptom scores, and observed adverse reactions to medication. RESULTS: The total effectiveness rate of LJTL was 93.64%. Compared with the baseline, the NIH-CPSI scores were significantly decreased after treatment (ï¼»24.27 ± 6.04ï¼½ vs ï¼»8.17 ± 4.21ï¼½, P < 0.05), and so were the scores on the pain symptoms (ï¼»9.63 ± 3.65ï¼½ vs ï¼»3.02 ± 2.23ï¼½, P < 0.05), voiding symptoms (ï¼»5.65 ± 2.15ï¼½ vs ï¼»1.62 ± 1.36) and quality of life (ï¼»8.96 ± 2.32ï¼½ vs ï¼»3.16 ± 1.89ï¼½, P < 0.05). The effectiveness rate of LJTL was 95.9% on the Chinese medicine symptom frequent urination, 90.4% on painful urination, and 91.4% scanty dark urine, with a total effectiveness rate of 82.4% － 95.9%, all with statistically significant difference in comparison with the baseline (P < 0.05). CONCLUSION: Longjintonglin Capsules combined with routine treatment can significantly improve the clinical symptoms of chronic prostatitis with damp-heat stasis syndrome, especially effective on the symptoms of frequent urination, painful urination and scanty dark urine. Besides, it recommendable for its antidepressant and antianxiety effects, and the effect of improving the quality of life of the chronic prostatitis patients with damp-heat stasis.

Network pharmacology-based strategy to investigate the active ingredients and molecular mechanisms of Scutellaria Barbata D. Don against radiation pneumonitis.

INTRODUCTION: Herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (RP), and the Scutellaria barbata D. Don (SBD) is a perennial herb that has been reported to protect against radiation-induced pneumonitis. However, the exact molecular mechanism is not known. The objective of this research was to investigate the against radiation pneumonitis ingredients and their functional mechanisms in SBD. METHODS: Based on the network pharmacology approaches, we collected active ingredients and target genes in SBD against RP through Traditional Chinese Medicine System Pharmacology (TCMSP) Database, and the "Herb-Ingredients-Target Genes-Disease" Network was constructed by using of Cytoscape. STRING analysis was performed to reveal the protein-protein interactions, and then we applied enrichment analysis on these target proteins, gene function, and pathways. RESULTS: A total of 18 ingredients in SBD regulate 65 RP related target proteins, which show that quercetin, luteolin, baicalein, wogonin may be the key active ingredients, while IL6, AKT1, VEGFA, MMP9, CCL2, prostaglandin-endoperoxide synthase 2 (PTGS2) (cyclooxygenase-2 [COX-2]), CXCL8, IL1B, mitogen-activated protein kinase (MAPK1), and IL10 were identified as critical targets. Besides, the results of Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that predicted targets of SBD are mostly associated with the pathological process of oxidative stress and inflammation. AGE- Receptor of Advanced Glycation Endproducts (RAGE) signaling pathway in diabetic complications, IL-17 signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, NF-kappa B signaling pathway might serve as the principal pathways for RP treatment. CONCLUSION: In our study, the pharmacological and molecular mechanism of SBD against RP was predicted from a holistic perspective, and the results provided theoretical guidance for researchers to explore the mechanism in further research.

12-Deoxyphorbol 13-acetate inhibits RANKL-induced osteoclastogenesis via the attenuation of MAPK signaling and NFATc1 activation.

Osteoporosis, characterized by bone loss and microstructure damage, occurs when osteoclast activity outstrips osteoblast activity. Natural compounds with inhibitory effect on osteoclast differentiation and function have been evidenced to protect from osteoporosis. After multiple compounds screening, 12-deoxyphorbol 13-acetate (DPA) was found to decline RANKL-induced osteoclastogenesis dose-dependently by attenuating activities of NFATc1 and c-Fos, followed by decreasing the level of osteoclast function-associated genes and proteins including Acp5, V-ATPase-d2 and CTSK. Mechanistically, we found that DPA suppressing RANKL-induced downstream signaling pathways, including MAPK signaling pathway and calcium oscillations. Furthermore, the in vivo efficacy of DPA was further confirmed in an OVX-induced osteoporosis mice model. Collectively, the results in our presentation reveal that DPA might be a promising compound to manage osteoporosis.

Tanshinones inhibit NLRP3 inflammasome activation by alleviating mitochondrial damage to protect against septic and gouty inflammation.

Tanshinones, the active ingredients derived from the roots of Salvia miltiorrhiza, have been widely used as traditional medicinal herbs for treating human diseases. Although tanshinones showed anti-inflammatory effects in many studies, large knowledge gaps remain regarding their underlying mechanisms. Here, we identified 15 tanshinones that suppressed the activation of NLRP3 inflammasome and studied their structure-activity relationships. Three tanshinones (tanshinone IIA, isocryptotanshinone, and dihydrotanshinone I) reduced mitochondrial reactive-oxygen species production in lipopolysaccharide (LPS)/nigericin-stimulated macrophages and correlated with altered mitochondrial membrane potentials, mitochondria complexes activities, and adenosine triphosphate and protonated-nicotinamide adenine dinucleotide production. The tanshinones may confer mitochondrial protection by promoting autophagy and the AMP-activated protein kinase pathway. Importantly, our findings demonstrate that dihydrotanshinone I improved the survival of mice with LPS shock and ameliorated inflammatory responses in septic and gouty animals. Our results suggest a potential pharmacological mechanism whereby tanshinones can effectively treat inflammatory diseases, such as septic and gouty inflammation.

Characterization of functional chocolate formulated using oleogels derived from ß-sitosterol with γ-oryzanol/lecithin/stearic acid.

With an aim to prepare the functional chocolate, corn oil was used as the base oil and ß-sitosterol was combined with oryzanol/stearic acid/lecithin to prepare respective oleogels (GO, SO, and LO). Oleogels (12%) were prepared by adding compound oleogelators at different ratios [GO-2:3, SO-1:4, and LO-4:1 (w/w)] in corn oil. The microstructure, interaction, thermodynamic, crystalline, and rheological behavior of formulated oleogels were studied by microscopic observation, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rotational rheometer, respectively. The results showed that GO had the strongest gel forming ability and the densest gel crystallization network. Moreover, chocolate prepared with GO (cocoa butter and oleogels-1:1) had the similar texture, crystal structure, rheological, and sensory properties to that of dark chocolate. This study provides the possibility for the wider application of oleogel prepared with lower saturated and trans-fatty acids in the chocolate industry.

In Silico Network Analysis of Ingredients of Cornus officinalis in Osteoporosis.

BACKGROUND Cornus officinalis (CO), also known as 'Shanzhuyu', is one of the most common traditional Chinese herbs used against osteoporosis. Although previous studies have found that CO has beneficial effects in alleviating osteoporosis, its mechanisms remain unclear. MATERIAL AND METHODS In this study, we applied system bioinformatic approaches to investigate the possible therapeutic mechanisms of CO against osteoporosis. We collected the active ingredients of CO and their targets from the TCMSP, BATMAN-TCM, and ETCM databases. Next, we obtained the osteoporosis targets from differentially expressed mRNAs from the Gene Expression Omnibus (GEO) gene series (GSE35958). Next, the shared genes of the CO pharmacological targets and osteoporosis-related targets were selected to construct the protein-protein interaction network, based on the results from the STRING database. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out by using the clusterProfiler package in R software. RESULTS In all, there were 58 unique CO compounds and 518 therapeutic targets. Based on the GO and KEGG enrichment results of 98 common genes, we selected the top 25 terms, based on the terms' P values. We found that the anti-osteoporotic effect of CO may mostly involve the regulation of calcium metabolism and reactive oxygen species, and the estrogen signaling pathway and osteoclast differentiation pathway. CONCLUSIONS We found the possible mechanisms of CO in treating osteoporosis may be based on multiple targets and pathways. We also provided a theoretical basis and promising direction for investigating the exact anti-osteoporotic mechanisms of CO.

Physiological and Transcriptomic Analysis Provide Insight into Low Temperature Enhancing Hypericin Biosynthesis in Hypericum perforatum.

Hypericin (Hyp), well-known as an antidepressant, is mainly extracted from Hypericum perforatum. Although Hyp accumulation and biomass are greater at lower compared to higher temperature, the regulation mechanism has not been reported. Here, the physiological characteristics and transcriptome of H. perforatum grown at 15 and 22 °C were determined and analyzed by HPLC and de novo sequencing. The results showed that the stomatal density and opening percentages were 1.1- and 1.4-fold more, and the Hyp content was 4.5-fold greater at 15 °C compared to 22 °C. A total of 1584 differentially expressed genes (DEGs) were observed at 15 versus 22 °C, with 749 characterized genes, 421 upregulated (UR) and 328 downregulated (DR). Based on biological functions, 150 genes were associated with Hyp biosynthesis, plant growth and the stress response, including photosynthesis, carbohydrate metabolism, fatty acids metabolism, cytochrome P450 (CYPs), morpho-physiological traits, heat shock proteins (HSPs), cold-responsive proteins (CRPs) and transcription factors (TFs). The differential expression levels of the master genes were confirmed by qRT-PCR and almost consistent with their Reads Per kb per Million (RPKM) values. This physiological and transcriptomic analyses provided insight into the regulation mechanisms of low temperature enhancing Hyp biosynthesis in H. perforatum.

Cellulose accumulation in the secondary cell walls is negatively correlated with the tenderness of new shoots in Camellia sinensis.

Tea, which is usually made from the new shoots of tea plants (Camellia sinensis), is one of the most popular and healthy beverages. The tenderness of new shoots plays a critical role in the production of high-quality tea; however, the factors affecting the tenderness of the new shoots of tea have not been extensively studied. Here, we show that cellulose accumulation is negatively correlated with the tenderness of new shoots, including leaves and stems, by characterizing the cellulose content and visualizing cellulose in the new shoots of two cultivars ("Huangjinya" and "Yujinxiang") via toluidine blue staining. We further found that the number of cells with secondary cell walls (SCWs) and the thickness of SCWs increased with the maturity degree of stems in both cultivars. Because cellulose is the most abundant polymer in SCW, we next identified three cellulose synthase CsCesAs, CsCesA4, 7, and 8A, through homologous alignment with Arabidopsis AtCesAs. Protein sequence analysis revealed that these proteins were closely related based on the phylogenetic analysis. We finally showed that the gene expression of the three CsCesAs was positively correlated with the maturity degree and cellulose content of the new shoots. Thus, our data suggest that cellulose accumulation, especially in the SCWs, is negatively correlated with the tenderness of new shoots in tea plants.