[Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats].

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Coptis chinensis-Induced Changes in Metabolomics and Gut Microbiota in Rats.

Rhizoma coptidis (CR) is traditionally used for treating gastrointestinal diseases. Wine-processed CR (wCR), zingiber-processed CR (zCR), and evodia-processed CR (eCR) are its major processed products. However, the related study of their specific mechanisms is very limited, and they need to be further clarified. The aim of this study is to compare the intervening mechanism of wCR/zCR/eCR on rats via faecal metabolomics and 16S rDNA gene sequencing analysis. First, faecal samples were collected from the control and CR/wCR/zCR/eCR groups. Then, a metabolomics analysis was performed using UHPLC-Q/TOF-MS to obtain the metabolic profile and significantly altered metabolites. The 16S rDNA gene sequencing analysis was carried out to analyze the composition of gut microbiota and screen out the significantly altered microbiota at the genus level. Finally, a pathway enrichment analysis of the significantly altered metabolites via the KEGG database and a functional prediction of relevant gut microbes based on PICRUSt2 software were performed in combination. Together with the correlation analysis between metabolites and gut microbiota, the potential intervening mechanism of wCR/zCR/eCR was explored. The results suggested that wCR played a good role in maintaining immune homeostasis, promoting glycolysis, and reducing cholesterol; zCR had a better effect on protecting the integrity of the intestinal mucus barrier, preventing gastric ulcers, and reducing body cholesterol; eCR was good at protecting the integrity of the intestinal mucus barrier and promoting glycolysis. This study scientifically elucidated the intervening mechanism of wCR/zCR/eCR from the perspective of faecal metabolites and gut microbiota, providing a new insight into the processing mechanism research of Chinese herbs.

Exploring the efficacy mechanism and material basis of three processed Coptidis Rhizoma via metabolomics strategy.

Wine/zingiberis rhizoma recens/euodiae fructus processed Coptidis Rhizoma (wCR/zCR/eCR) are the major processed products of CR in clinic, and the role of CR is highlighted in different aspects after being processed with different excipients. To explore the mechanism and material basis for the highlighted efficacy of wCR/zCR/eCR, the metabolomics strategy was introduced to the comparative study between wCR/zCR/eCR and CR. Firstly, the metabolomics approach was applied to compare the chemical profiling and differential components between wCR/zCR/eCR and CR extract. Secondly, the rats were treated with CR/wCR/zCR/eCR extracts and a serum metabolomics approach was adopted to compare the metabolic profiling and significantly changed metabolites in CR/wCR/zCR/eCR groups, base on which the metabolic pathways were enriched, the metabolic network was constructed and the highlighted efficacy wCR/zCR/eCR was investigated. Lastly, the pathological and biochemical assessments (VIP, COX, HSL and HMGR) were implemented to validate the results inferred from metabolomics study. In chemical research, 23 differential components between wCR/zCR/eCR and CR extracts were identified. Thereinto, the content of alkaloids and organic acids decreased in wCR extract, the content of partial alkaloids and most organic acids increased in zCR extract, the content of alkaloids decreased, and partial organic acids increased in eCR extract. In serum metabolomics study, wCR had no outstanding effect, zCR played a more prominent role in resisting inflammation of gastrointestinal tissue by interfering with arachidonic acid metabolism, eCR exhibited the hottest drug property and the strongest effect on smoothing the liver and harmonizing the stomach by interfering with of bile acids biosynthesis. Based on the changes in chemical composition and efficacy before and after processing, as well as biochemical validation, it can be concluded that the above activity of zCR might be related to the increased alkaloids and organic acids in zCR extract, and the prominent role of eCR may be related to the increased organic acids in eCR extract. In brief, hot processing excipients could alleviate the cold property of CR, and different excipients have different effects on the chemical composition and efficacy mechanism. The present study fully reflects the advantage of metabolomics and provides guidance for the rational use of CR.

A comparative metabolomics study on dried and processed Rehmannia Radix.

The efficacy of Rehmannia Radix changes after processing. However, the precise effect of processing on the properties of Rehmannia Radix is an intricate topic, as this effect cannot be explained by traditional methods. The purpose of this study was to investigate how processing methods influence the properties of Rehmannia Radix, as well as the changes in body function after administering dried Rehmannia Radix (RR) and processed Rehmannia Radix (PR) using a metabolomics approach. In addition, principal component analysis and orthogonal partial least-squares discriminant analysis models were generated using SIMCA-P 14.0 to evaluate the properties of RR and PR. Potential biomarkers were identified, and associated metabolic networks were established to clarify differences in the properties and efficacies of RR and PR. The results showed that RR and PR have cold and hot properties, respectively. RR can exert a hypolipidaemic effect by regulating nicotinate and nicotinamide metabolism. PR exerts a tonic effect and regulates the body's reproductive function through the regulation of alanine, aspartate and glutamate metabolism, arachidonic acid, pentose and glucuronate metabolism, respectively. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics is a promising approach to determine the cold/hot properties of traditional Chinese medicine formulations.

Characterizing the specific mechanism of series processed Coptidis Rhizoma by multi-organ metabolomics combined with network pharmacology and molecular docking.

BACKGROUND: After being processed with different excipients, the clinical application of Coptidis Rhizoma (CR) is differentially investigated. However, the underlying mechanism and material basis are not clear, and there is a lack of attention to the collaborative working mode of herbal medicine during exploration. PURPOSE: To characterize the specific mechanism of wine/zingiberis rhizoma recens/euodiae fructus processed CR (wCR/zCR/eCR) and to investigate the role of excipients during processing. METHODS: The multi-organ metabolomics approach was employed to explore the target organs of wCR/zCR/eCR and multiple pathways being triggered in each organ. The tissue distribution of CR and wCR/zCR/eCR components was compared to indicate the material basis of efficacy change after processing. Further, the network pharmacology study coupled with experimental validation was conducted to support metabolomic research and predicted active ingredients and core targets, and the molecular docking coupled with binding test was performed to identify the binding between active ingredient and core target. RESULTS: The multi-organ metabolomics and network pharmacology study elucidated the intervening effect of wCR on heart/lung, zCR on stomach/colon, and eCR on liver/colon/stomach. Combined with molecular docking, binding test and tissue distribution studies, the specific mechanism was as follows: the wine made iso-quinoline alkaloids in CR more likely to accumulate in heart/lung, thus triggering the core targets of PTGS2, NOS2, ESR1 and SLC6A4 in heart/lung, and thereby highlighting the detoxifying and cardiopulmonary protective effect of wCR. The zingiberis rhizoma recens and euodiae fructus made organic acids in CR more likely to accumulate in stomach/colon and liver/colon/stomach respectively, thus triggering the core targets of ACTB, TNF and PRKCA in stomach/colon, the core targets of ACTB, TNF, PRKCA and GPT in stomach/colon/liver, and thereby highlighting the improving effect of zCR/eCR on digestive function. CONCLUSION: Iso-quinoline alkaloids were the material basis of CR for anti-inflammation, and organic acids were mainly responsible for regulating gastrointestinal function. Due to the influence of excipients on the accumulation tendency of CR components, the differentially highlighted application of wCR/zCR/eCR was achieved. These findings propose a novel strategy for processing mechanism research.

Protective effects of Descurainia sophia seeds extract and its fractions on pulmonary edema by untargeted urine and serum metabolomics strategy.

Background: Descurainia sophia seeds (DS) is a herbal medicine in traditional Chinese medicine (TCM) for treating lung diseases. We aimed to evaluate the therapeutic effect of DS and five of its fractions upon pulmonary edema (PE) through metabolomics analysis (MA) of urine and serum samples of rats. Methods: A PE model was established by intrathoracic injection of carrageenan. Rats were pretreated with DS extract or its five fractions (polysaccharides (DS-Pol); oligosaccharides (DS-Oli); flavonoid glycosides (DS-FG); flavonoid aglycone (DS-FA); fat oil fraction (DS-FO)) for seven consecutive days. Forty-eight hours after carrageenan injection, lung tissues were subjected to histopathology. MA of urine and serum was done by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, respectively. Principal component analysis and orthogonal partial least squares-discriminant analysis were operated for the MA of rats and potential biomarkers related to treatment. Heatmaps and metabolic networks were constructed to explore how DS and its five fractions act against PE. Results: DS and its five fractions could all attenuate pathologic lung injury to different degrees, and DS-Oli, DS-FG, and DS-FO had a more potent effect compared with DS-Pol and DS-FA. DS-Oli, DS-FG, DS-FA, and DS-FO could regulate the metabolic profiles of PE rats, but DS-Pol was less potent. According to MA, the five fractions could improve PE to some degree due to their anti-inflammatory, immunoregulatory, and renoprotective activities by mediating the metabolism of taurine, tryptophan, and arachidonic acid. However, DS-Oli, DS-FG, and DS-FO had more important roles in edema-fluid reabsorption, and reduction of vascular leakage through regulating the metabolism of phenylalanine, sphingolipid and bile acid. Finally, heatmaps and hierarchical clustering analysis indicated DS-Oli, DS-FG, and DS-FO to be more efficacious than DS-Pol or DS-FA against PE. The five fractions of DS had a synergistic effect on PE from different aspects, thereby constituting the entire efficacy of DS. DS-Oli, DS-FG, or DS-FO could be used as an alternative to DS. Conclusion: MA combined with use of DS and its fractions provided novel insights into the mechanism of action of TCM.

Comparative pharmacokinetic studies of Ephedra herba in common cold and nephrotic syndrome rat models.

Ephedra herba is a conventional Chinese medicine to treat cold, fever, asthma, edema, and lung diseases in the clinic. At present, most pharmacokinetic studies focus on the pharmacokinetic process of alkaloids in normal animals. However, the non-alkaloid components are also active. In addition, the pharmacokinetic studies under pathological state make more sense for clarifying the material basis of efficacy. In this study, a sensitive and rapid ultra-high-performance-tandem mass spectrometry method was developed and applied to determine nine bioactive components (ephedrine, pseudoephedrine, methylephedrine, (+)-catechin, epicatechin, vitexin, vicenin-2, cinnamic acid, and ferulic acid) in normal, common cold and nephrotic syndrome rats after the oral administration of Ephedra herba. Compared to the normal group, except for ferulic acid, the exposure levels of the other eight components were significantly increased and the plasma clearance clearly declined in common cold rats. Similarly, the exposure levels of seven components other than cinnamic acid and ferulic acid were also significantly augmented and the plasma clearance decreased significantly in nephrotic syndrome rats. In brief, the pathological conditions of the common cold and nephrotic syndrome could lead to alterations in the pharmacokinetics profiles of the nine components, which provide a reference for further exploration of the pharmacodynamics basis of Ephedra herba.

Integrated Metabonomic Study on the Relationship between Medicinal Properties and Efficacy of Rehmanniae Radix.

Each Chinese medicine has its own properties and effects. However, the close connection between the medicinal properties and the effects of the medicine remains unclear. To export the scientific connection between the medicinal properties and efficacy of Rehmanniae Radix (RR), this study established a model and evaluated the therapeutic effects of RR on cold-heat syndrome to access the properties of RR, and then established a blood-heat syndrome model through the injection of rats with dry yeast combined with anhydrous ethanol. Related biochemical indicators (coagulation factors and central pyrogenic factor) were measured to assess the efficacy of RR. Finally, metabonomic technology was used to study the blood-cooling mechanism of RR from two aspects: medicinal properties and efficacy. The comprehensive results suggest that RR can significantly reduce the rectal temperature of blood-heat syndrome model rats and increase both the expression levels of coagulation factors (TNF-[Formula: see text], IL-1[Formula: see text], and IL-6) and the central pyrogenic factors (c-AMP, PGE-2). RR also cools the blood through regulating arginine, proline, phenylalanine, taurine, hypotaurine, sulfur, glycerophospholipid, primary bile acid metabolic pathways, and the tricarboxylic acid cycle. Therefore, RR plays the role of cooling blood by virtue of its cold property. The medicinal property of RR has a guiding effect on the clinical application. Moreover, the integrated metabolomic approach is a powerful tool for studying the properties and efficacy of Chinese medicine.

Selenium-containing polysaccharide from Spirulina platensis alleviates Cd-induced toxicity in mice by inhibiting liver inflammation mediated by gut microbiota.

Selenium-containing polysaccharide from Spirulina platensis (Se-SPP) has been demonstrated to help in inhibiting cadmium-induced injury in mice, but the underlying mechanism has not been determined. This study aimed to investigate the beneficial effects of Se-SPP on alleviating Cd-induced toxicity in mice by targeting liver inflammatory and gut microbiota. Se-SPP supplementation for 28 days in Cd-induced toxic mice significantly mitigated liver pathological damage and inflammation, which was correlated to the upregulation of antioxidant enzyme activity. Furthermore, Se-SPP effectively restored Cd-induced disruption of the intestinal barrier compared to model group, as indicated by the depletion of Muribaculaceae and the enrichment of Ruminococcaceae. Spearman's correlation analysis revealed that the Se-SPP-altered microbes were highly correlated with inflammation-related indexes in Cd-induced toxic mice. Noteworthily, the modulation of Se-SPP on the Ruminococcaceae population contributed to the improvement of Cd-induced inflammation-related diseases by downregulating the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the liver. These findings suggested that Se-SPP may act as prebiotics for ameliorating Cd-induced toxicity in mice by inhibiting liver inflammation mediated by gut microbiota, and target-specific microbiota of Cd-induced inflammation-related diseases deserve further attention.

Protective effects of black onion polysaccharide on liver and kidney injury in T2DM rats through the synergistic impact of hypolipidemic and antioxidant abilities.

In this study, the synergistic effects of black onion on the hypolipidemic and antioxidant activities in T2DM rats induced by a high-fat-diet and alloxan were investigated. The results showed that the fasting blood glucose of diabetic rats was significantly decreased after treatment with black onion polysaccharide (p < 0.01). Blood lipid analysis indicated that black onion polysaccharide could significantly improve the abnormal metabolism of blood lipids caused by diabetes. In addition, the MDA and ROS of the diabetic rats treated with black onion polysaccharide were significantly reduced; moreover, SOD was increased, indicating the excellent antioxidant activity of black onion polysaccharide. A histological examination clearly showed that black onion polysaccharide could improve the histological morphology of the liver and kidney. Furthermore, the indices of liver and kidney function were restored. These results indicate that black onion polysaccharide can reduce blood glucose and simultaneously show synergistic effects of hypoglycemic and antioxidant activities in diabetic rats. Therefore, black onion polysaccharide may alleviate liver and kidney function injury by improving the "two-hit" mechanism and can thus be used as a potential functional food to prevent diabetes and its complications.

Enhanced hair growth effects through low-level vortex beams radiation: An experimental animal study.

Photobiomodulation therapy (PBMT) is a non-invasive and pain-less treatment for hair loss. Researches on PBMT rarely considered the impact of different light structures. In this study, we irradiated shaven rats with both 650 nm, m = 32 vortex beams and ordinary Gaussian beams. The laser treatment was performed at 24-hour intervals for 20 days. The energy density was set to 4.25 J/cm2 . The results indicated that low-level vortex beam irradiation led to better stimulation of hair growth than the Gaussian beams, which might be related to deeper penetration. The underlying biological mechanisms are discussed in terms of the activation of Wnt/ß-catenin/sonic hedgehog pathway. Our results suggest that low-level vortex beam irradiation is advantageous to the treatment of hair loss because it is technically feasible, convenient and effective.

Salvianolic Acid Ameliorates Pressure Overload-Induced Cardiac Endothelial Dysfunction via Activating HIF1[Formula: see text]/HSF1/CD31 Pathway.

Pressure overload is a major risk factor for various cardiovascular diseases. Disorders of the endothelium are involved in the pathological mechanisms of pressure, and maintaining endothelial function is a practical strategy to alleviate pressure overload-induced cardiac injury. In this study, we provided evidence that salvianolic acid, the active component of Danshen, a traditional Chinese herb medicine, preserved pressure overload-induced cardiac dysfunction via protecting endothelium. Male C57BL/6J mice were imposed with transverse aortic constriction to mimic pressure overload and treated with salvianolic acid (200[Formula: see text]mg/kg/day) or vehicle for 6 weeks. The hemodynamic and cardiac functional parameters were detected by the cardiac catheter and transthoracic echocardiography. The pathological measurements were conducted by heart hematoxylin-eosin, wheat germ agglutinin staining, Masson's trichrome staining, and immunofluorescence staining. Endothelial cell (EC) proliferation was estimated using the Cell Counting Kit-8, EC migration was evaluated by scratched assay, and EC integrity was observed by electron microscope. Salvianolic acid notably inhibited cardiac chamber enlargement, restrained cardiac contractile dysfunction, and repressed cardiac fibrosis caused by chronic pressure overload. Salvianolic acid maintained endothelial tight junction integrity by boosting the expression of CD31. Furthermore, the endothelial protective effect of salvianolic acid against pressure overload is dependent on the activation of hypoxia-inducible factor 1[Formula: see text], which consequently activated heat shock factor 1 and promoted CD31 expression. Our study uncovered that salvianolic acid protected cardiac ECs against pressure overload via a HIF1[Formula: see text]/HSF1/CD31 pathway, indicating a potential appliance of salvianolic acid in hypertensive heart disease.

Metabolomic strategies and biochemical analysis of the effect of processed Rehmanniae radix extract on a blood-deficient rat model.

BACKGROUND: Rehmanniae Radix (RR), an herb with numerous pharmacological effects, is widely used in traditional Chinese medicine for the treatment of blood deficiency syndrome, either alone or in combination with other herbs. However, the mechanism by which processed Rehmanniae Radix (PRR) improves blood enrichment efficacy has not been clearly defined. METHODS: Ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) and biochemical methods were combined to explore the hematopoietic functional mechanisms of PRR on blood deficiency in a rat model, as well as the potential active ingredient for blood enrichment efficacy. The pharmacological effects of PRR were evaluated on a rat blood deficiency model induced by cyclophosphamide in combination with 1-acetyl-2-phenylhydrazine. The blood routine index, including white blood cell (WBC), red blood cell (RBC), and platelet (PLT) counts, as well as hemoglobin (HGB) level, and the changing metabolite profile based on urine and serum were assessed. Nontargeted metabolomic studies, combined with biochemical analyses, were employed to clarify pharmacological mechanisms. RESULTS: PRR significantly increased the blood routine index levels and reversed the levels of SOD, GSH, and ATP. The PRR group was similar to the control group, as determined from the metabolic profile. All of the 60 biomarkers, representing the typical metabolic characteristics of the blood-deficient rat model, mainly involved energy metabolism dysfunction, the peripheral circulation system, and oxidative damage in the body. This improvement may be attributed to changes in polysaccharide and sixteen non-polysaccharide compounds in PRR, which were caused by processing RR with rice wine. CONCLUSIONS: The strategies of integrated metabolomic and biochemical analyses were combined, revealing the biological function and effective mechanism of PRR.

Total flavonoids of Selaginella tamariscina (P.Beauv.) Spring ameliorates doxorubicin-induced cardiotoxicity by modulating mitochondrial dysfunction and endoplasmic reticulum stress via activating MFN2/PERK.

BACKGROUND: Doxorubicin (DOX) is a highly effective chemotherapeutic that is effective for various tumours. However, the clinical application of DOX has been limited by adverse reactions such as cardiotoxicity and heart failure. Since DOX-induced cardiotoxicity is irreversible, drugs to prevent DOX-induced cardiotoxicity are needed. PURPOSE: This study aimed to investigate the effect of total flavonoids of Selaginella tamariscina (P.Beauv.) Spring (TFST) on doxorubicin-induced cardiotoxicity. METHODS: The present study established DOX-induced cardiotoxicity models in C57BL/6 mice treated with DOX (cumulative dose: 20 mg/kg body weight) and H9c2 cells incubated with DOX (1 µM/l) to explore the intervention effect and potential mechanism of TFST. Echocardiography was performed to evaluate left ventricular functions. Heart tissue samples were collected for histological evaluation. Myocardial injury markers and oxidative stress markers were examined. Mitochondrial energy metabolism pathway associated proteins PPARα/PGC-1α/Sirt3 were detected. We also explored the effects of TFST on endoplasmic reticulum (ER) stress and apoptosis. To further investigate the protective mechanism of TFST, we used the specific small interfering RNA MFN2 (siMFN2) to explore the effect of MFN2 on TFST against DOX-induced cardiotoxicity in vitro. Flow cytometry detected reactive oxygen species, mitochondrial membrane potential and apoptosis. Cell mitochondrial stress was measured by Seahorse XF analyser. RESULTS: Both in vivo and in vitro studies verified that TFST observably alleviated DOX-induced mitochondrial dysfunction and ER stress. However, these effects were reversed after transfected siMFN2. CONCLUSION: Our results indicated that TFST ameliorates DOX-induced cardiotoxicity by alleviating mitochondrial dysfunction and ER stress by activating MFN2/PERK. MFN2/PERK pathway activation may be a novel mechanism to protect against DOX-induced cardiotoxicity.

Modified cystoscopy-assisted laparoscopic Y-V plasty for recalcitrant bladder neck contracture.

BACKGROUND AND AIM: Recalcitrant bladder neck contracture (BNC) is a common complication after transurethral resection of the prostate. Our aim was to show the outcomes of a modified cystoscopy-assisted laparoscopic Y-V plasty for BNC treatments. MATERIAL AND METHODS: We retrospectively evaluated a series of 27 patients who underwent a modified cystoscopy-assisted laparoscopic Y-V plasty for recalcitrant BNC from January 2017 to September 2019. Urinary flow rate, international prostate symptom score (IPSS), international index of erectile function-5 (IIEF-5) and bladder urethral examination by cystoscopy were performed preoperatively and postoperatively, respectively. RESULTS: All patients underwent the procedure successfully and no serious complication occurred. The median surgery time was 68.6 min without massive bleeding. The median follow-up time was 14.2 months and no patients had urinary incontinence. The maximum urine flow rate 3 months after surgery was significantly higher than prior to surgery (17.7 ± 2.1 ml/s vs. 8.2 ± 1.2 ml/s, p < 0.05). The IPSS was significantly decreased compared with the preoperative score (5.7 ± 2.3 vs. 19.2 ± 1.4, p < 0.05). The cystoscopy showed a wide bladder neck and the survival bladder flap in prostate urethral 3 months postoperatively in 92.6% (25/27) patients. CONCLUSIONS: The modified cystoscopy-assisted laparoscopic Y-V plasty is a feasible and effective technique for recalcitrant BNC treatment.

Curcumin inhibits proliferation and invasion of papillary thyroid carcinoma cells by inhibiting the JAK2 / STAT3 pathway.

PURPOSE: The purpose of this study was to analyze the function of curcumin to suppress the proliferative and invasive abilities of papillary thyroid carcinoma (PTC) through inhibiting the JAK2/STAT3 pathway. METHODS: After treatment of different doses of curcumin in TPC-1 and SW1736 cells, changes in viability, clonality, cell cycle, apoptosis, wound healing and invasion were determined. Western blot analyses were performed to detect protein levels of apoptosis-associated genes, JAK2 and STAT3 in TPC-1 and SW1736 cells treated with different doses of curcumin. RESULTS: Curcumin treatment dose-dependently reduced viability, clonality and metastatic ability in TPC-1 and SW1736 cells. After treatment of 10 µM or 20 µM curcumin, PTC cells were blocked in G2/M phase, and their apoptotic rate increased. Curcumin treatment downregulated Bcl-2 and upregulated Bax in PTC cells. In addition, curcumin treatment downregulated p-JAK2 and p-STAT3 in TPC-1 and SW1736 cells. CONCLUSIONS: Curcumin treatment blocks PTC cells to proliferate and invade via inhibiting the JAK2/STAT3 pathway.

A UPLC-Q-TOF/MS-Based Metabolomics Study on the Effect of Corallodiscus flabellatus (Craib) B. L. Burtt Extract on Alzheimer's Disease.

A UPLC-Q-TOF/MS-based metabolomics study was carried out to explore the intervening mechanism of Corallodiscus flabellatus (Craib) B. L. Burtt (CF) extract on Alzheimer's disease (AD). The AD model group consisted of senescence-accelerated mouse prone 8 (SAMP8) mice, and the control group consisted of senescence-accelerated mouse resistant 1 (SAMR1) mice. UPLC-Q-TOF/MS detection, multivariate statistical analysis, and pathway enrichment were jointly performed to research the change in metabolite profiling in the urine of AD mice. The result suggested that the metabolite profiling of SAMP8 mice significantly changed at the sixth month compared with SAMR1 mice of the same age, and the principal component analysis (PCA) score scatter plots of the CF group closely resembled those of the control and positive drug (huperzine A, HA) group. A total of 28 metabolites were considered potential biomarkers associated with the metabolism of beta-alanine, glycine, serine, threonine, cysteine, methionine, arginine, proline, and purines in AD mice. Furthermore, the CF group was clustered with the control and positive group and was clearly separated from the model group in the heat map. In conclusion, significant anti-AD effects were firstly observed in mice after treatment with the CF extract, and the urinary metabolomics approach assisted with dissecting the underlying mechanism.

Correlation analysis between extracts and endogenous metabolites to characterise the influence of salt-processing on compatibility mechanism of 'Psoraleae Fructus & Foeniculi Fructus'.

ETHNOPHARMACOLOGICAL RELEVANCE: 'Salt-processed Psoraleae Fructus & salt-processed Foeniculi Fructus' (sPF&sFF) is a common Chinese medicinal combination for treating diarrhoea. However, it is not clear how sPF and sFF work together, and why salt-processing is necessary. AIM OF THE STUDY: To investigate the compatibility mechanism of sPF&sFF and the influence of salt-processing on it. MATERIALS AND METHODS: Firstly, the metabolomics approach was appliedto screen the differential components between four (s)PF&(s)FF extracts, i.e., sPF&sFF, sPF&FF, PF&sFF, and PF&FF extracts. Then, an in vivo metabolomics study was carried out to filter critical metabolites reflecting the curative effects of (s)PF&(s)FF, and construct a metabolic network. Finally, a correlation analysis between chemical components in extracts and critical metabolites in vivo was performed to find out the synergistic and/or antagonistic effects between herbs as well as the influence of salt-processing. RESULTS: Salt-processing had a direct influence on the contents of chemical components in sPF and sFF extracts, and there existed positive/negative correlations between the content change of chemical components and the effects of critical metabolites. Therefore, salt-processing indirectly affected on these correlations and was (i) conducive to the positive effects of sPF and sFF on bile acids, making sFF play a synergistic role, thereby, sPF&sFF could perform better than sPF and other three combinations and effectively relieve the symptoms of fatty diarrhoea, osmotic diuresis, malnutrition, and weight loss; (ii) conducive to the positive effects of sPF on triacylglycerol, 12(S)-hydroxyeicosatetraenoic acid, cholesterol, and arachidonic acid, and adverse to that of sFF, making sFF play an antagonistic role, thereby, sPF&sFF could prevent a series of side effects caused by over-regulation and suitably relieve the symptoms of osmotic diuresis, polyuria, malnutrition, and weight loss; and (iii) adverse to the positive effects of sPF and sFF on thromboxane A2, sphinganine and sphingosine, making sFF play a synergistic role, thereby, sPF&sFF could prevent a series of side effects and moderately relieve the symptoms of metabolic diarrhoea and polyuria. CONCLUSIONS: Salt-processing indirectly affected on the correlations between chemical components in extracts and critical metabolites in vivo, and exhibited both conducive and adverse effects on the efficacy, making sPF and sFF cooperate with each other to moderately repair the metabolic disorders. Thereby, sPF&sFF could suitably relieve the diarrhoea and polyuria symptoms in the model and exert the most appropriate efficacy. Moreover, this novel strategy provided a feasible approach for further studying the compatibility mechanism of herbs.

Preparation of pH-sensitive food packaging film based on konjac glucomannan and hydroxypropyl methyl cellulose incorporated with mulberry extract.

A pH-sensitive food packaging film was prepared based on konjac glucomannan (KGM) and hydroxypropyl methyl cellulose (HPMC) incorporated with mulberry extracts2 (MBE). FT-IR and XRD analysis revealed that there are good molecular interactions among the three components. The incorporation of MBE into KGM and HPMC (KH) films can significantly improve the mechanical properties and UV resistance. Notably, the KH-MBE-20% film almost completely blocked UV light in the range of 200-600 nm. The best antioxidant and antibacterial properties were obtained when the addition of MBE in the composite film was 20%. In addition, KH-MBE film has good responsiveness to buffers with pH range from 2 to 12. In visual monitoring experiments using the film on fresh fish, the color of the KH-MBE film changed from purple to gray to yellow as the freshness of the fish decreased, and the KH-MBE-20% film had the best color stability. Therefore, intelligent packaging of KH-MBE film has potential applications in real-time monitoring of fish freshness.

Characterization of selenium-containing polysaccharide from Spirulina platensis and its protective role against Cd-induced toxicity.

Herein, selenium-containing polysaccharide from Spirulina platensis (Se-SPP) was prepared and its structural characteristics and protective role against Cd-induced toxicity in vivo and in vitro were investigated. Se-SPP was alkali-extracted from selenium-containing Spirulina platensis which was cultured in Zarrouk medium supplemented with Na2SeO3. The contents of carbohydrate, protein, uronic acid, sulfate and elements (including Se, C, H, O, N, and S) as well as the monosaccharide composition, molecular weight, surface morphology and FT-IR spectra of Se-SPP was compared to that of selenium-free polysaccharide (SPP). The results revealed that SPP and Se-SPP were both high-molecular-weight heteropolysaccharide with similar molecular weight and monosaccharide composition but significantly different selenium content, indicating that the covalently-bonding of a small amount of selenium did not destroy the original structure of polysaccharide. Furthermore, CdCl2 was utilized to build Cd-intoxicated cells model in vitro and rats model in vivo respectively. Then, the protective effect of Se-SPP against cadmium-induced toxicity was assessed. The results demonstrated that Se-SPP treatment provided significant protection against Cd-induced toxicity, which was superior compared to that of SPP or Na2SeO3 alone. The enhancement of protective role may be affected by the covalently-bonding of selenium to polysaccharide.