Attribution of lake eutrophication risk to anthropogenic forcing adjacent to the agriculture areas: a case study of Chagan Lake.

Lake eutrophication, exacerbated by high-intensity anthropogenic forcing, threatens water ecological security and the sustainable development of fisheries. Accurately evaluating lake eutrophication is the basis for effective management of the water environment. This study aimed to study eutrophication and its anthropogenic forcing in Chagan Lake, which is surrounded by agricultural areas with irrigation discharge as the primary water source. The spatiotemporal evolution characteristics of lake eutrophication and the anthropogenic forcing factors were analyzed based on the long-series multi-source data and modified eutrophication index. The results showed that (1) the average trophic state of Chagan Lake was eutrophic according to the modified eutrophication index (TLI = 58.31) and the nutrient level was higher in summer, reaching hypertrophy (TLI 61.49); (2) the maximum pollution footprint affecting the lake reached 34.7 km2, with a maximum buffer zone radius of 1 km; (3) the gross domestic product of primary industry, total sown area, and rice field area were the main anthropogenic factors leading to the lake eutrophication, with contribution rates of 64.43%, 13.09%, and 10.23%, respectively. Multidimensional management strategies for maximum pollution footprint, buffer zone radius, and contribution of anthropogenic factors were used to improve the water quality of the lake. The findings provided scientific support for the management of water environment of Chagan Lake and guided the formulation of "one lake, one policy."

Fast Inspection of Quality of Indigo Naturalis by Multiple Light Scattering.

Quality control of Chinese herbal medicine is a crucial component of Chinese herbal medicine research and development. Faced with the challenges of modernization and internationalization of Chinese herbal medicine, it is urgent to establish thorough and effective procedures for quality identification of Chinese herbal medicine, and there is an urgent need for new analytical and testing techniques that are efficient, accurate, and environmentally friendly. Multiple light scattering is a cutting-edge and analytical method that can accurately and rapidly assess the quality of Chinese herbal medicine without altering the nature or state of the sample or using organic reagents. Indigo Naturalis is considered a good remedy for pediatric hyperthermia, psoriasis, leukemia, and ulcerative colitis. In this study, the process of addition of Indigo Naturalis powder in water was recorded precisely using a multiple light scattering instrument. The qualitative and quantitative measurements of the instrument can be used to accurately capture the overall trajectory and sinking behavior of Indigo Naturalis powder into water and to establish a rapid evaluation method for the quality of Indigo Naturalis with the transmission and backscattering spectrograms of the sample as qualitative indicators and stability index as a quantitative indicator. The analytical technique based on multiple light scattering provides a fast, accurate, green, and environmentally friendly method for the quality evaluation of Indigo Naturalis and supports the development and transformation of high-quality Indigo Naturalis.

Tai Chi as a complementary exercise for pulmonary rehabilitation in chronic obstructive pulmonary disease: A randomised controlled trial.

OBJECTIVES: With the characteristics of mindfulness and breathing techniques, Tai Chi has been recommended with therapeutic values in chronic obstructive pulmonary disease (COPD). However, its strengths as a complementary exercise for conventional pulmonary rehabilitation (PR) remain unclear. DESIGN AND SETTING: This single-blinded randomised controlled trial recruited patients with mild to severe stable COPD. Eligible participants were randomly assigned to the group with usual care (control), total body recumbent stepper (TBRS) exercise, Tai Chi (TC), or combined TBRS exercise and Tai Chi (TBRS-TC). Patients received a two-month hospital-based supervised exercise, followed by a ten-month community- or home-based rehabilitation program. RESULTS: A total of 120 participants were recruited, and 102 were included in the per-protocol analysis. The mean changes in St George's Respiratory Questionnaire (SGRQ) total score from baseline to the post-hospital exercise in the control group, TBRS group, TC group, and TBRS-TC group was 2.62 (95 % CI -8.99 to 8.99), -9.28 (95 % CI -13.96 to -4.60), -10.19 (95 % CI -13.72 to -6.67), and -16.75 (95 % CI -20.25 to -13.24), respectively, with a statistically significant difference between groups in favor of the TBRS-TC exercise (P < 0.001). The remarkable effect of TBRS-TC exercise in improving the quality of life maintained until the end of the community- or home-based rehabilitation training (P < 0.001). Besides, a statistically better effect with the TBRS-TC exercise was also observed in the outcomes regarding exercise capacity, pulmonary function, symptom burden, and systemic inflammation after the whole process of 12-month integrative PR exercise programme. CONCLUSIONS: Based on the results, a novel integrated exercise modality combining Tai Chi and conventional pulmonary rehabilitation was developed. It might contribute to more positive effects in patients with stable COPD. REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-15006874) prior to commencing recruitment.

Efficacy and safety of herbal medicine (Binafuxi granules) for the common cold with fever: A multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial.

Background: Binafuxi granules are a traditional Uighur medicine (TUM) for treating the common cold with fever. However, high-quality clinical studies supporting its efficacy and safety are lacking. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial, patients with common cold and fever were randomly assigned to a high-dose group, low-dose group, and placebo group in a 1:1:1 ratio. Outcomes were time to fever relief, time to fever clearance, proportion of afebrile patients, time to symptom disappearance, rate of symptom disappearance, effective rate, emergency drug usage and safety assessment. Results: A total of 235 patients were recruited. Of these, 234 were included in the full analysis set (FAS), and 217 were included in the per-protocol set (PPS). In the FAS analysis, the median time to fever relief was 6.00 h, 5.54 h and 10.65 h (P = 0.31) in the high-dose group, low-dose group and placebo group, respectively. The median time to fever clearance was 18.29 h, 20.08 h and 25.00 h (P = 0.0018), respectively, and the proportion of afebrile patients was 92.4%, 89.7% and 71.4% (P = 0.0002), respectively. There was a significant difference in the disappearance time and disappearance rate of all symptoms and of individual symptoms. No serious adverse events were found. Conclusions: Binafuxi granules can dose-dependently shorten the fever course and improve clinical symptoms in patients suffering from the common cold with fever. Trial Registration: This trial was registered at Chinese Clinical Trial Registry (ChiCTR-IIR-17013379).

Expression of the Populus Orthologues of AtYY1, YIN and YANG Activates the Floral Identity Genes AGAMOUS and SEPALLATA3 Accelerating Floral Transition in Arabidopsis thaliana.

YIN YANG 1 (YY1) encodes a dual-function transcription factor, evolutionary conserved between the animal and plant kingdom. In Arabidopsis thaliana, AtYY1 is a negative regulator of ABA responses and floral transition. Here, we report the cloning and functional characterization of the two AtYY1 paralogs, YIN and YANG (also named PtYY1a and PtYY1b) from Populus (Populus trichocarpa). Although the duplication of YY1 occurred early during the evolution of the Salicaceae, YIN and YANG are highly conserved in the willow tree family. In the majority of Populus tissues, YIN was more strongly expressed than YANG. Subcellular analysis showed that YIN-GFP and YANG-GFP are mainly localized in the nuclei of Arabidopsis. Stable and constitutive expression of YIN and YANG resulted in curled leaves and accelerated floral transition of Arabidopsis plants, which was accompanied by high expression of the floral identity genes AGAMOUS (AG) and SEPELLATA3 (SEP3) known to promote leaf curling and early flowering. Furthermore, the expression of YIN and YANG had similar effects as AtYY1 overexpression to seed germination and root growth in Arabidopsis. Our results suggest that YIN and YANG are functional orthologues of the dual-function transcription factor AtYY1 with similar roles in plant development conserved between Arabidopsis and Populus.

A systematic pharmacology-based in vivo study to reveal the effective mechanism of Yupingfeng in asthma treatment.

BACKGROUND: The clinical effect of Yupingfeng (YPF) has been confirmed in asthma patients, however, it lacks a study to verify its pharmacological mechanism. HYPOTHESIS/PURPOSE: To reveal the molecular basis and potential pharmacological mechanism of YPF in the treatment of asthma. STUDY DESIGN AND METHODS: First, a systems pharmacology-based method integrating pharmacokinetic screening, target prediction, network analyses, GO and KEGG analyses were used for the systematic deciphering of the mechanism of YPF in asthma. Second, differentially expressed genes (DEGs) between asthma patients and healthy controls were identified by GEO2R online tool. Third, based on systems pharmacology and DEGs results, molecular docking was performed utilizing the Discovery Studio 2020 Client version to detect the binding capacity between compounds and targets. Finally, ovalbumin (OVA)-challenged C57BL/6 mice were treated with YPF or its effective compound to assess the predictions. RESULTS: A total of 35 active compounds were filtered out, with 87 potential targets being identified for further analysis after target fishing and matching. Quercetin, kaempferol, and wogonin were identified as the main ingredients in YPF. The signaling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), tumor necrosis factor (TNF) and IL-17 were identified as the top signaling pathways in KEGG enrichment analysis. GEO2R tools of NCBI discovered five DEGs that overlapped with the therapeutic targets of YPF. Wogonin was proven to be the top active compound in YPF through the results of molecular docking. In vivo experiments indicated that YPF and wogonin significantly attenuated airway resistance and lung inflammation by decreasing the levels of inflammatory cytokines and key factors in PI3K/AKT, IL-17, and TNF signaling pathways. CONCLUSIONS: YPF and its main active compound wogonin may exert some therapeutic effects on asthma inflammation through multiple molecular targets and signaling pathways including PI3K/AKT, IL-17 and TNF-α.

Dopamine relieves inflammatory responses through the D2 receptor after electroacupuncture at ST36 in a mouse model of chronic obstructive pulmonary disease.

OBJECTIVE: To detect the role of dopamine in the anti-inflammatory effect of electroacupuncture (EA) at ST36 in a mouse model of chronic obstructive pulmonary disease (COPD). METHODS: Twenty-eight male BALB/c mice were randomly divided into the control group, model group, sham EA (sham) group or ST36 EA (ST36) group in a 1:1:1:1 ratio (n = 7 each). The COPD mouse model was established through cigarette smoke (CS) exposure for 12 weeks. During the last 2 weeks, EA was applied at a sham point location or ST36 before CS exposure. Lung function, histopathological changes, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), inflammatory cytokines in BALF, plasma, lung tissue homogenate (LTH), and plasma dopamine levels were detected in the different groups. Furthermore, the role of different dopamine receptors was explored through intraperitoneal injections of non-specific dopamine receptor antagonist chlorpromazine, specific dopamine D1 receptor antagonist SCH 23390 and specific dopamine D2 receptor antagonist eticlopride hydrochloride prior to ST36 EA and CS exposure. RESULTS: EA at ST36 improved lung function, alleviated lung and systemic inflammatory responses by reducing inflammatory cells and cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-8 and IL-1ß in BALF, plasma and lung tissue in this COPD mouse model. Plasma dopamine was greatly increased after EA at ST36, negatively correlated with lung histological lesions and inflammatory cytokine levels, and positively correlated with mice body weight and lung function indicators. Chlorpromazine and eticlopride hydrochloride inhibited the anti-inflammatory effect of EA at ST36, while SCH 23390 showed no neutralizing effect. CONCLUSION: EA at ST36 could alleviate inflammation in this mouse model of COPD through the dopamine D2 receptor pathway.

A cross-sectional study on the tea consumption effects of ankle-brachial index.

OBJECTIVES: This thesis aims to explore the relationship between tea consumption and ankle-brachial index (ABI) and further studies the relationship between tea consumption and lower extremity atherosclerosis. METHODS: This is a cross-sectional, epidemiological survey of 17,373 subjects selected from the staff of Kailuan Group who had come to Kailuan General Hospital for a health examination from January 2016 to December 2017. Tea consumption was obtained by questionnaires. ABI was measured using an automated analyzer. The other data, such as age, gender, body mass index (BMI), and so on, was collected on the same day of the health examination results. The relationship between tea drinking habits and ABI was studied using logistic regression and multivariate linear regression analysis. RESULTS: Among the 17,373 analyzed subjects, the difference in age, gender, BMI, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), uric acid (UA), C-reactive protein (CRP), fasting blood-glucose (Fbg), and ABI was statistically significant in the tea-drinking group and the nontea-drinking group (p < 0.05). Multiple logistic regression models revealed that tea consumption was a positive predictor for ABI (odds ratio (OR) = 0.782, confidence interval (CI), 0.615-0.994) (p < 0.05). Multivariate linear regression analysis of the ABI value showed that frequent tea-drinking has a positive correlation with the ABI value (p < 0.05). CONCLUSIONS: The higher tea consumption is significantly associated with higher ABI which means less risk for lower extremity atherosclerosis.

[Secondary metabolites of endophyte fungi Xylaria sp. from Coptis chinensis].

Two new polyketides, lasobutone A(1) and lasobutone B(2), along with three known compounds, guignardianone C(3), guignardic acid(4), and 4-hydroxy-17R-methylincisterol(5), were isolated from the endophytic fungi Xylaria sp. by silica gel, MCI, and preparative HPLC, which was separated from the Chinese medicinal material Coptis chinensis and cultivated through solid fermentation with rice. Their structures were elucidated on the basis of spectroscopic methods, such as MS, NMR, IR, UV, and ECD. Compounds 2 and 4 showed inhibitory activities against the nitric oxide(NO) production in the LPS-induced macrophage RAW264.7 with IC_(50) values of 58.7 and 42.5 µmol·L~(-1) respectively, while compound 5 exhibited cytotoxic activities against HT-29 with IC_(50) value of 14.3 µmol·L~(-1).

A simple method for Ce-Nd separation using nano-NaBiO3: Application in the isotopic analysis of U, Sr, Pb, Nd, and Hf in uranium ores.

U, Sr, Pb, Nd, and Hf isotope ratios can provide basic and important information of nuclear materials. We established a simple and efficient column chemistry method using nano-NaBiO3, as both oxidizer and adsorbent, to completely separate Ce from rare earth elements (REEs). This new method exhibited a high decontamination (Ce/Nd < 10-5) ability and was easy to conducted, thereby providing clear advantages compared to traditional liquid-liquid and solid phase micro-extraction techniques. Additionally, a rapid four-column separation procedure, based on Sr, TUR, Ln resins and nano-NaBiO3, was developed to isolate U, Sr, Pb, Nd, and Hf in ore samples. The entire procedure could be completed in 4-5 hrs. The robustness of the proposed method was demonstrated by analyzing the 235U/238U, 87Sr/86Sr, 206Pb/204Pb, 207Pb/204Pb, 208Pb/204Pb, 142Nd/144Nd, 143Nd/144Nd, and 176Hf/177Hf isotopic ratios of two certified reference materials (CRMs). The analytical results obtained using this method showed good agreement with previously published data. The feasibility of this method was extended to the determination of isotope ratios in uranium ores. The results obtained from the two samples with different regions indicated that they have different isotopic ratios information. These findings indicate the potential for the use of this new method in nuclear forensic science.

The source of the fat significantly affects the results of high-fat diet intervention.

High-fat diet (HFD) is widely used in animal models of many diseases, it helps to understand the pathogenic mechanism of related diseases. Several dietary fats were commonly used in HFD, such as corn oil, peanut oil, soybean oil, sunflower oil, and lard. However, it was reported that different dietary fat could have completely different effects on physiological indicators and the gut microbiome, and the sources of dietary fat used in high-fat diet research have not been comprehensively compared. In this research, we conduct comparative experiments on various sources of dietary fats to test their different effects during the high-fat diet intervention. We investigated the effects of twelve common dietary fats in high-fat diet intervention of mice, body/liver weight changes, four blood lipid indices, and gut microbiome were analyzed. Our results showed that the source of dietary fat used in high-fat diet significantly affects the changes of body/liver weight and triglyceride (TRIG) in the blood. Furthermore, the intervention of canola oil increased the alpha diversity of gut microbiota, and lard has decreased diversity compared with the control group. The composition of saturated fatty acid (SFA) in fat has the most significant effects on the gut microbiome. All dietary fats treatments have an increasing Firmicutes abundance and a reduced Bacteroidetes abundance in gut microbiome, while the canola oil has a slight variation compared to other intervention groups, and the lard group has the largest changes. This study showed that different types of dietary fat have different effects on the body indicators and intestinal microbiota of mice, and canola oil produced less disturbance than other types of dietary fats in high-fat diet.

Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway after ischemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmannioside A is derived from Rehmannia glutinosa Libosch, which is widely used as an important ingredient in diverse traditional Chinese medicines to treat diseases caused by "kidney deficiency" such as cerebral arteriosclerosis, aging-related stroke and dementia in China. Recent studies have proved that Rehmannia glutinosa Libosch and Rehmannioside A can improve memory capability and recover nerve damage. AIM OF THE STUDY: To investigate the effect of Rehmannioside A on cognitive impairment after ischemia in rats and SH-SY5Y cells, and further evaluate the anti-oxidative and anti-ferroptosis mechanisms. MATERIALS AND METHODS: Differentially expressed proteins (DEPs) in patients after cerebral ischemic stroke were revealed by a RayBio protein array. Cognitive impairment model was established by middle cerebral artery occlusion and reperfusion (MCAO) 14 days in rats. Rehmannioside A was administered intraperitoneally injection at dose of 80 mg/kg. The SH-SY5Y cells were exposed to H2O2 for 24 h and treated with Rehmannioside A (80 µM) for 24 h. The neuroprotecion of Rehmannioside A were evaluated by infarct volume (TTC), neurological defects (Garcia score) and learning memory (Morris water maze test) in vivo, and cell viability (CCK-8 or LDH) in vitro. Superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO) activity of rats, glutathione (GSH), oxidized glutathione (GSSG) and nicotinamide adenine dinucleotide phosphate (NADPH) of cells were detected by biochemical assay. Intracellular reactive oxygen species (ROS) were measured by DCFH-DA assay. Myeloperoxidase (MPO), PI3 kinase (PI3K), p-PI3K, Akt, p-Akt, heme oxygenase-1 (HO-1), nuclear factor-E2-related factor 2 (Nrf2), SLC7A11, glutathione peroxidase 4 (GPX4) of the cerebral cortex in rats or SH-SY5Y cells were examined by western blotting. RESULTS: Compared with model group, the cognitive impairment and neurological deficits of Rehmannioside A group were significantly improved, and the cerebral infarction was reduced in MCAO rats. Moreover, the cell viability obviously increased and the H2O2-induced toxicity was reduced in Rehmannioside A group. Further research indicated that the expression of p-PI3K, p-Akt, nuclear Nrf2, HO-1 and SLC7A11 in Rehmannioside A group was significantly higher than model group. CONCLUSION: Rehmannioside A has neuroprotection effect and improves cognitive impairment after cerebral ischemia by inhibiting ferroptosis and activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway. These findings provide valuable insight into the pathogenesis and therapeutic target of ischemic stroke.

Music therapy effect on anxiety reduction among patients with cancer: A meta-analysis.

Introduction: The study aimed to investigate the effect of music therapy on anxiety alleviation among cancer patients. Methods: A comprehensive literature research was performed in four electronic databases (PubMed, Embase, Cochrane Library, and Web of Science). Fifteen randomized controlled trials (RCTs) were included. The risk of bias for the RCTs was evaluated by the Cochrane Risk of Bias tool. Anxiety levels were extracted to synthesize the combined effect by using meta-analysis. All analyses were performed using R version 4.0.4. Results: In total, 15 RCTs met the inclusion criteria involving 1320 cancer patients (662 patients in the experimental group and 658 patients in the controlled group). The majority of interventions were performed with recorded music lasting for 15-60 minutes. Compared with standard care, music intervention had a moderate superiority of anxiety alleviation (SMD: -0.54, 95% CI: [-0.92, -0.16]). Discussion: Music intervention could reduce cancer-related anxiety moderately. Nevertheless, the result should be interpreted with caution as high heterogeneity in this pooled study. Well-designed trials with higher quality were still warranted in the future.

Effects and Mechanism of Zishen Jiangtang Pill on Diabetic Osteoporosis Rats Based on Proteomic Analysis.

OBJECTIVE: To explore the effect and mechanism of ZJP on DOP rats by proteomic analysis. MATERIALS AND METHODS: After the establishment of diabetes model by Streptozocin (STZ, 60 mg/kg), 40 Wistar rats were equally divided into normal group, model group (diabetic rats), high-dose group (3.0 g/kg/d ZJP), and low-dose group (1.5 g/kg/d ZJP) and received treatment for 3 months. Histological changes in bone and pancreas tissues were observed by hematoxylin and eosin staining, electron microscopy, and immunofluorescence. Proteomic and bioinformatic analyses were performed to identify the differentially expressed proteins. The fingerprint and active ingredients of ZJP were identified via high-performance liquid chromatography (HPLC). RESULTS: Compared with the model group, ZJP could rescue the weight, fasting blood glucose, and fasting insulin of rats in both high-dose and low-dose group. ZJP could also improve the microstructures of pancreatic islet cells, bone mass, and trabecular and marrow cavities in DOP rats. Bioinformatic analysis suggested that ZJP might influence DOP via multiple pathways, mainly including ribosomes, vitamin digestion and absorption, and fat digestion and absorption. The primary active ingredients, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, icariin, and ginsenoside Rb1, were detected. CONCLUSION: ZJP could significantly improve the histomorphology and ultrastructure of bone and islets tissues and might serve as an effective alternative medicine for the treatment of DOP.

Study on the Mechanism of Prunella Vulgaris L on Diabetes Mellitus Complicated with Hypertension Based on Network Pharmacology and Molecular Docking Analyses.

The role of traditional Chinese medicine Prunella vulagaris L in the treatment of tumors and inflammation has been widely confirmed. We found that some signaling pathways of Prunella vulgaris L action can also regulate diabetes and hypertension, so we decided to study the active ingredients, potential targets and signaling pathway of Prunrlla vulgaris L, and explore the "multi-target, multi-pathway" molecular mechanism of Prunella vulgaris L on diabetes mellitus complicated with hypertension(DH). Methods. Based on TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and CNKI(China National Knowledge Infrastructure), the components and action targets related to Prunella vulgaris L were screened. The OMIM(Online Mendelian Inheritance in Man) and GeneCards (The human gene database) were used to search for targets related to DH. The "gene - drug - disease" relationship map was drawn by Cytoscape_v3.7.2 plug-in. The target was amplified by the STRING platform, and the "protein - protein" interaction relationship (PPI) network of the interacting target was obtained by the STRING online analysis platform and the Cytoscape_v3.7.2 plug-in. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were conducted on David and Metascape platform to study the co-acting targets. Results. 11 active components, 41 key targets and 16 significant signaling pathways were identified from Prunella vulgaris L. The main active components of Prunella vulgaris L against DH were quercetin and kaumferol, etc, and potential action targets were IL-6 and INS, etc and signaling pathways were AGE-RAGE signaling pathway, TNF signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, etc. It involves in biological processes such as cell proliferation, apoptosis and inflammatory response. Conclusions. The main molecular mechanism of Prunella vulgaris L against DH is that sterols and flavonoids play an active role by affecting TNF signaling pathway, AGE-RAGE signaling pathway, MAPK pathway, PI3K-Akt pathway related targets such as IL-6 and INS.

Exploring the Molecular Mechanism of Liuwei Dihuang Pills for Treating Diabetic Nephropathy by Combined Network Pharmacology and Molecular Docking.

BACKGROUND: Diabetic nephropathy (DN) is a common and serious complication of diabetes, but without a satisfactory treatment strategy till now. Liuwei Dihuang pills (LDP), an effective Chinese medicinal formula, has been used to treat DN for more than 1000 years. However, its underlying mechanism of action is still vague. METHODS: Active compounds and corresponding targets of LDP were predicted from the TCMSP database. DN disease targets were extracted from the OMIM, GeneCards, TTD, DisGeNET, and DrugBank databases. Subsequently, the "herbal-compound-target" network and protein-protein interaction (PPI) network were constructed and analyzed via the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Molecular docking utilized AutoDock Vina and PyMOL software. RESULTS: 41 active components and 186 corresponding targets of LDP were screened out. 131 common targets of LDP and DN were acquired. Quercetin, kaempferol, beta-sitosterol, diosgenin, and stigmasterol could be defined as five crucial compounds. JUN, MAPK8, AKT1, EGF, TP53, VEGFA, MMP9, MAPK1, and TNF might be the nine key targets. The enrichment analysis showed that common targets were mainly associated with inflammation reaction, oxidative stress, immune regulation, and cell apoptosis. AGE-RAGE and IL-17 were the suggested two significant signal pathways. Molecular docking revealed that the nine key targets could closely bind to their corresponding active compounds. CONCLUSION: The present study fully reveals the multicompound's and multitarget's characteristics of LDP in DN treatment. Furthermore, this study provides valuable evidence for further scientific research of the pharmacological mechanisms and broader clinical application.

Sinomenine Attenuated Capsaicin-Induced Increase in Cough Sensitivity in Guinea Pigs by Inhibiting SOX5/TRPV1 Axis and Inflammatory Response.

BACKGROUND: Chronic cough is a common complaint which affects a large number of patients worldwide. Increased cough sensitivity is a very important cause of chronic persistent cough. However, there are limited clinical diagnosis and treatment for increased cough sensitivity. Transient receptor potential vanilloid-1 (TRPVl) is a member of the transient receptor potential (TRP) family of channels which is very closely associated with respiratory diseases. However, the mechanism through which TRPV1 that influences downstream events is still poorly understood. RESULTS: Capsaicin induced increase in cough sensitivity by upregulating the protein level of TRPV1, leading to the secretions of Substance P and neurokinin A which stimulated neurogenic inflammation. However, sinomenine, a component of traditional Chinese medicine, significantly attenuated the capsaicin-induced cough by inhibiting the expression of TRPV1 in guinea pigs. In addition, capsaicin increased the expression of SOX5 which mediated the transcriptional upregulation of TRPV1. However, pretreatment with sinomenine reduced the expression of SOX5. CONCLUSION: These results indicate that capsaicin induced increase in cough sensitivity by activating neurogenic inflammation, while sinomenine attenuated the increase in cough sensitivity by inhibiting the expressions of SOX5 and TRPV1 in guinea pigs. This finding may provide a novel target for the treatment of aggravated cough sensitivity.

Curcumin modulates gut microbiota and improves renal function in rats with uric acid nephropathy.

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 µmol/L vs. 325.60 ± 18.65 µmol/L, p < 0.001), serum creatinine (66.20 ± 11.88 µmol/L vs. 182.20 ± 8.87 µmol/L, p < 0.001) and BUN level (13.33 ± 3.16 mmol/L vs. 36.04 ± 6.60 mmol/L, p < 0.001). The treatment group also displayed attenuated renal pathological lesions and metabolic endotoxemia (25.60 ± 5.90 ng/mL vs. 38.40 ± 4.98 ng/mL, p < 0.01), and improved tightly linked proteins expression. Besides, curcumin altered the gut microbiota structure in UAN rats. More specifically, curcumin treatment protected against the overgrowth of opportunistic pathogens in UAN, including Escherichia-Shigella and Bacteroides, and increased the relative abundance of bacteria producing short-chain fatty acids (SCFAs), such as Lactobacillus and Ruminococcaceae. These results suggest that curcumin could modulate gut microbiota, fortify the intestinal barrier, attenuate metabolic endotoxemia, and consequently protect the renal function in UAN rats.

Pharmacokinetics of five phthalides in volatile oil of Ligusticum sinense Oliv.cv. Chaxiong, and comparison study on physicochemistry and pharmacokinetics after being formulated into solid dispersion and inclusion compound.

BACKGROUNDS: The dried rhizome of Ligusticum sinense Oliv.cv. Chaxiong has been used to treat cardiovascular and cerebrovascular diseases, atherosclerosis, anemia and stroke. A high purity extract from chaxiong (VOC, brownish yellow oil) was extracted and separated. Its main components were senkyunolide A (SA, 33.81%), N-butylphthalide (NBP, 1.38%), Neocnidilide (NOL, 16.53%), Z-ligustilide (ZL, 38.36%), and butenyl phthalide (BP, 2.48%), respectively. Little is known about the pharmacokinetics of these phthalides in Chaxiong, and different preparations to improve the physicochemistry and pharmacokinetics of VOC have not been investigated. METHODS: At different predetermined time points after oral administration or intravenous administration, the concentrations of SA, NBP, NOL, ZL and BP in the rat plasma were determined using LC-MS/MS, and the main PK parameters were investigated. VOC-P188 solid dispersion and VOC-ß-CD inclusion compound were prepared by melting solvent method and grinding method, respectively. Moreover, the physicochemical properties, dissolution and pharmacokinetics of VOC-P188 solid dispersion and VOC-ß-CD inclusion compound in rats were assessed in comparison to VOC. RESULTS: The absorptions of SA, NBP, NOL, ZL and BP in VOC were rapid after oral administration, and the absolute bioavailability was less than 25%. After the two preparations were prepared, dissolution rate was improved at pH 5.8 phosphate buffer solution. Comparing VOC and physical mixture with the solid dispersion and inclusion compound, it was observed differences occurred in the chemical composition, thermal stability, and morphology. Both VOC-P188 solid dispersion and VOC-ß-CD inclusion compound had a significantly higher AUC and longer MRT in comparison with VOC. CONCLUSION: SA, NBP, NOL, ZL and BP in VOC from chaxiong possessed poor absolute oral bioavailability. Both VOC-P188 solid dispersion and VOC-ß-CD inclusion compound could be prospective means for improving oral bioavailability of SA, NBP, NOL, ZL and BP in VOC.

[Pharmacokinetic study on five components in phthalide target areas of Chaxiong and its ß-CD inclusion compounds based on UPLC-MS/MS].

This study aims to establish a method for the determination of the concentration of five main components of phthalide target areas of Chaxiong(CPTA) and its inclusion of ß-CD in the plasma of rats, and determine the pharmacokinetic parameters, absolute bioavailability and relative bioavailability of CPTA/ß-CD inclusion compound in vivo. The plasma concentrations of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide were determined with UPLC-MS/MS. The content determination was conducted at the chromatographic conditions as follows: Shim-pack GIST C_(18)-AQ HP column(2.1 mm×100 mm, 3 µm), mobile phase of 0.1% formic acid solution(A)-acetonitrile(B), gradient elution, flow rate of 0.3 mL·min~(-1), column temperature of 35 ℃ and injection volume of 2 µL. The mass spectra were obtained with electrospray ion source(ESI), positive ion mode and multi reaction monitoring. CPTA/ß-CD inclusion compound was prepared by grinding method, DAS 2.0 software was used to model the data, and the absolute bioavailability of CPTA and relative bioavailability of inclusion compound were calculated. Finally, the methods for the determination of five components of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide in CPTA, were successfully established. The linear relationship among the five components was good within their respective ranges, r>0.99. The absolute bioavailability of the five components in rats was 22.30%, 16.32%, 21.90%, 10.16% and 12.43%, respectively. After CPTA/ß-CD inclusion was prepared, the relative bioavailability of the five components was 138.69%, 198.39%, 218.01%, 224.54% and 363.55%, respectively, significantly improved. This method is rapid, accurate and sensitive, so it is suitable for the pharmacokinetic study of extracts in traditional Chinese medicine and their preparations.