Selenochemical modification of low molecular weight polysaccharides from Grifola frondosa and the mechanism of their inhibitory effects on gastric cancer cells.

An important micronutrient involved in immune response and antitumor is selenium. LMW-GFP, a polysaccharide extracted from Grifola frondosa seed bodies, has a relatively weak antitumor effect on BGC-823 and MFC cells in vitro, whereas selenium binding to LMW-GFP can significantly increase the in vitro antitumor activity of LMW-GFP. In this study, Se-LMW-GFP was prepared by the HNO3-Na2SeO3 method, and the structures of LMW-GFP and Se-LMW-GFP were characterized by UV-visible spectroscopy of absorption, FTIR spectroscopy, and electron scanning microscopy, and these structural analyses showed that selenium was successfully complexed to LMW-GFP. The selenium content of Se-LMW-GFP was measured to be 2.08 % ± 0.08 % by ICP-MS. The anti-tumor activity of LMW-GFP before and after selenium modification was compared by cellular experiments, and the findings indicated that the anti-tumor activity of Se-LMW-GFP was considerably improved over that of LMW-GFP, and inhibited the proliferation of BGC-823 cells and MFC cells through a combination of the Fas/FasL-mediated exogenous death receptor pathway as well as the endogenous mitochondrial pathway. Our results suggest that Se-LMW-GFP not only has great potential for natural health food and anti-gastric cancer drug development but is also a good selenium supplement.

Quantifying chemical correlations between fruits and processed fruit products: A non-targeted analysis approach.

Juices and beverages are produced by industry for long-distance distribution and shelf-stability, providing valuable nutrients. However, their nutritional value is often underestimated due to insufficient analytical methods. We have employed non-targeted analysis through a standardized analytical protocol, taking advantage of Data Independent Acquisition (DIA) technique and a novel Chromatographic Retention Behavior (CRB) data deconvolution algorithm. After analyzing 9 fruits and their products, correlations between fruits and their juices are accurately digitalized by similarities of their LC-MS fingerprints. We also specify non-targeted molecules primarily associate with nutrient loss in these analyzed juice products, including nitrogenous nutrients, flavonoids, glycosides, and vitamins. Moreover, we unveiled previously unreported fruit-characteristic metabolites, of which reconstituted-from-concentrate (RFC) juices contain over 40% of the content found in their fresh counterparts. Conclusively, our method establishes a quantitative benchmark for rational selection of RFC juices to substitute natural fruits.

Hypericum perforatum L. protects against renal function decline in ovariectomy rat model by regulating expressions of NOS3 and AKT1 in AGE-RAGE pathway.

BACKGROUND: Hypericum perforatum L. (HPL) is a potential traditional Chinese medicine. It could promotes menopausal 'kidney-yin deficiency syndrome' that characterized by renal function decline. However, its potential pharmacological effect and mechanism remains unknown. OBJECTIVE: The aim of this study was to investigate whether HPL can improve menopausal renal function decline and to explore its mechanism of action. METHODS: The mainly ingredients of HPL were identified using UPLC-Q-TOF-MS/MS approach, and the potential therapeutic targets of HPL for renal function decline were chose via network pharmacology technique. The key therapeutic metabolites were selected through non-targeted metabolomic and chemometric methods. Then, the network were constructed and the key targets and metabolites were screened. At last, the validation experiments and mechanism exploring were adopted by using Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting assays. RESULTS: mainly ingredients of HPL were identified and determined 17 compounds and 29 targets were chose as mainly active compounds and potential therapeutic targets. Based on OVX induced renal decline rat model, after chemometric analysis, 59 endo-metabolites were selected as key therapeutic metabolites, and AGE-RAGE signal pathway in diabetes complications was enriched as the key pathway. By constructing a "disease-component-target" network, Hyperoside, Quercetrin, and quinic were selected as the key therapeutic compounds, and the AKT1 and NOS3 were selected as the key therapeutic targets. The results of ELISA, RT-PCR and western blot experiments indicated that HPL could rescue the abnormal expressions both of AKT1 and NOS3, as well as their related metabolites distortion. CONCLUSION: Our findings indicated that HPL regulated expression of AKT1 and NOS3 through modulating AGE-RAGE signaling pathway in OVX stimulated rats` renal dysfunction, implicating the potential values of HPL in menopause syndromes therapy.

Hypothetical chloroplast reading frame 51 encodes a photosystem I assembly factor in cyanobacteria.

Hypothetical chloroplast open reading frames (ycfs) are putative genes in the plastid genomes of photosynthetic eukaryotes. Many ycfs are also conserved in the genomes of cyanobacteria, the presumptive ancestors of present-day chloroplasts. The functions of many ycfs are still unknown. Here, we generated knock-out mutants for ycf51 (sll1702) in the cyanobacterium Synechocystis sp. PCC 6803. The mutants showed reduced photoautotrophic growth due to impaired electron transport between photosystem II (PSII) and PSI. This phenotype results from greatly reduced PSI content in the ycf51 mutant. The ycf51 disruption had little effect on the transcription of genes encoding photosynthetic complex components and the stabilization of the PSI complex. In vitro and in vivo analyses demonstrated that Ycf51 cooperates with PSI assembly factor Ycf3 to mediate PSI assembly. Furthermore, Ycf51 interacts with the PSI subunit PsaC. Together with its specific localization in the thylakoid membrane and the stromal exposure of its hydrophilic region, our data suggest that Ycf51 is involved in PSI complex assembly. Ycf51 is conserved in all sequenced cyanobacteria, including the earliest branching cyanobacteria of the Gloeobacter genus, and is also present in the plastid genomes of glaucophytes. However, Ycf51 has been lost from other photosynthetic eukaryotic lineages. Thus, Ycf51 is a PSI assembly factor that has been functionally replaced during the evolution of oxygenic photosynthetic eukaryotes.

[Mechanism of Wuling Capsules against hepatic fibrosis based on network pharmacology and animal experiments].

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.

Synthesis of Spirocyclopropane-Containing 4H-Pyrazolo[1,5-a]indoles via Alkylative Dearomatization and Intramolecular N-Imination of an Indole-O-(Methylsulfonyl)oxime.

In this paper, we report the synthesis of spirocyclopropane-containing 4H-pyrazolo[1,5-a]indoles 6a-e via alkylative dearomatization and intramolecular N-imination of indole-O-(methylsulfonyl)oxime 11. Starting materials tryptophol (7) and 2-bromocyclopetanone (8) were reacted in the presence of HBF4·OEt2, providing 1,2,3,5,6,11-hexahydrocyclopenta[2,3]oxepino[4,5-b]indole (9) in a 63% yield. Compound 9 was reacted with hydroxylamine hydrochloride to afford oxime 10 (65% yield), which was subsequently bis-methanesulfonated to form 11 in a 85% yield. Heating 11 with various alcohols in the presence of N,N-diisopropylethylamine (DIPEA) triggered the alkylative dearomatization and intramolecular N-imination, forming the spirocyclopropane and 4H-pyrazolo[1,5-a]indole structures in the targets 6a-e with 67-84% yields.

Fushenmu treatment ameliorates RyR2 with related metabolites in a zebrafish model of barium chloride induced arrhythmia.

BACKGROUND: Fushenmu (Pini Radix in Poria, FSM) is a folk parasitic herb that has been mainly used for palpitation and amnesiain in traditional Chinese medicine (TCM). Recently, as an individual herb or a component of formulations, Fushenmu exhibits therapeutic potential for the treatment of cardiac arrhythmias. Yet, how specific targets or pathways of Fushenmu inhibit arrhythmia has not yet been reported. METHODS: Here, based on clinical functional genomics, metabolomics and molecular biologic technologies, a network construction strategy was adopted to identify FSM therapeutic targets and biomarkers that might explore its functions. RESULTS: In this study, it was found that FSM recovered arrhythmia-associated heart failure in barium chloride (BaCl2) induced arrhythmic zebrafish embryos, as was evidenced by the shortened cardiac sinus venosus-bulbus arteriosus (SV-BA) distance, smaller cardiovascular bleeding areas, and reduced cardiomyocyte apoptosis. Moreover, analysis via ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-QTOF-ESI-MS/MS) components identification and network pharmacology prediction showed that 11 main active components of FSM acted on 33 candidate therapeutic targets. Metabolomic analysis also suggested that FSM could rescue 242 abnormal metabolites from arrhythmic zebrafish embryos. Further analysis based on the combination of target prediction and metabolomic results illustrated that FSM down-regulated Ryanodine Receptor 2 (RyR2) expressions, inhibited adrenaline and 3',5'-Cyclic AMP (cAMP) levels in a dose-dependent manner, which was confirmed by metabolites quantification and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. CONCLUSION: In summary, this study revealed that FSM mitigated BaCl2 induced cardiac damage caused by arrhythmia by suppressing RyR2 expressions, decreasing adrenaline and cAMP through the adrenergic signalling pathway.

Research on the improvement effect of Saposhnikovia divaricata (Trucz.) Schischk on rheumatoid arthritis based on the "component-target-pathway" association.

OBJECTIVE: To investigate the therapeutic effect and mechanism of the traditional Chinese medicine Saposhnikovia divaricata (Trucz.) Schischk in rats with complete Freund's adjuvant-induced rheumatoid arthritis (RA). METHODS: The chemical targets and RA targets of Saposhnikovia divaricata (Trucz.) Schischk were acquired by the network pharmacological method. The complete Freund's adjuvant-induced rat RA model was used to further explore the mechanism of Saposhnikovia divaricata (Trucz.) Schischk in improving RA. Pathological changes in the volume of toes, body weight and synovial tissues of joints as well as serum inflammatory factor levels before and after the intervention of Saposhnikovia divaricata (Trucz.) Schischk were investigated. The key metabolic pathways were screened by correlations between metabolites and key targets. Finally, a quantitative analysis of key targets and metabolites was experimentally validated. RESULTS: Saposhnikovia divaricata (Trucz.) Schischk administration increased body weight, mitigated foot swelling and downregulated inflammatory cytokine levels in model rats. The histopathology showed that treatment with Saposhnikovia divaricata (Trucz.) Schischk can induce inflammatory cell infiltration and synovial hyperplasia and obviously reduce cartilage injuries, thus improving arthritis symptoms in rats. According to the network pharmacology-metabonomics association analysis results, the purine metabolic signaling pathway might be the key pathway for RA intervention with Saposhnikovia divaricata (Trucz.) Schischk. Targeted metabonomics, Western blotting (WB) and reverse transcription-polymerase chain reaction (RT‒PCR) assays showed that the recombinant adenosine deaminase (ADA) mRNA expression level and metabolic level of inosine in Saposhnikovia divaricata (Trucz.) Schischk administration group were lower than those of the model group. This reflected that Saposhnikovia divaricata (Trucz.) Schischk could improve RA by downregulating ADA mRNA expression levels and the metabolic level of inosine in the purine signaling pathway. CONCLUSION: Based on the "component-disease-target" association analysis, this study concludes that Saposhnikovia divaricata (Trucz.) Schischk improves complete Freund's adjuvant-induced RA symptoms in rats mainly by downregulating ADA mRNA expression levels in the purine metabolic signaling pathway, mitigating foot swelling, improving the levels of serum inflammatory factors (IL-1ß, IL-6 and TNF-α), and decreasing the ADA protein expression level to intervene in purine metabolism.

Biogenic Solution Map Based on the Definition of the Metabolic Correlation Distance between 4-Dimensional Fingerprints.

Accurate discrimination and classification of unknown species are the basis to predict its characteristics or applications to make correct decisions. However, for biogenic solutions that are ubiquitous in nature and our daily lives, direct determination of their similarities and disparities by their molecular compositions remains a scientific challenge. Here, we explore a standard and visualizable ontology, termed "biogenic solution map", that organizes multifarious classes of biogenic solutions into a map of hierarchical structures. To build the map, a novel 4-dimensional (4D) fingerprinting method based on data-independent acquisition data sets of untargeted metabolomics is developed, enabling accurate characterization of complex biogenic solutions. A generic parameter of metabolic correlation distance, calculated based on averaged similarities between 4D fingerprints of sample groups, is able to define "species", "genus", and "family" of each solution in the map. With the help of the "biogenic solution map", species of unknown biogenic solutions can be explicitly defined. Simultaneously, intrinsic correlations and subtle variations among biogenic solutions in the map are accurately illustrated. Moreover, it is worth mentioning that samples of the same analyte but prepared by alternative protocols may have significantly different metabolic compositions and could be classified into different "genera".

[Determination of 10 mycotoxins in Hippophae Fructus medicinal and edible products by ultra-performance liquid chromatography- tandem mass spectrometry].

An analytical method for 10 mycotoxins in Hippophae Fructus medicinal and edible products was established in this study, and the contamination of their mycotoxins was analyzed. First of all, the mixed reference solution of ten mycotoxins such as aflatoxin, ochratoxin, zearalenone, and dexoynivalenol was selected as the control, and the Hippophae Fructus medicinal and edible products were prepared. Secondly, based on the ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) technology, 10 mycotoxins in Hippophae Fructus medicinal and edible products were quantitatively investigated and their content was determined. Finally, the contamination of mycotoxins was analyzed and evaluated. The optimal analysis conditions were determined, and the methodological inspection results showed that the 10 mycotoxins established a good linear relationship(r>0.99). The method had good repeatability, test sample specificity, stability, and instrument precision. The average recovery rates of 10 mycotoxins in Hippophae Fructus medicinal products, edible solids, and edible liquids were 90.31%-109.4%, 87.86%-107.8%, and 85.61%-109.1%, respectively. Relative standard deviation(RSD) values were 0.22%-10%, 0.75%-13%, and 0.84%-8.5%, repsectively. Based on UPLC-MS/MS technology, the simultaneous determination method for the limits of 10 mycotoxins established in this study has fast detection speed, less matrix interference, high sensitivity, and accurate results, which is suitable for the limit examination of 10 mycoto-xins in Hippophae Fructus medicinal and edible products.

Rheum officinale Baill. Treats zebrafish embryo thrombosis by regulating NOS3 expression in the arginine biosynthesis pathway.

BACKGROUND: Rheum officinale Baill. (ROB), as one of the traditional Chinese medicines for promoting blood circulation and removing blood stasis, has a wide range of pharmacological effects, such as cardiovascular protection, and has become a common drug in the clinical care of thrombosis. OBJECTIVE: Although there are some pharmacological studies on ROB in the treatment of thrombotic diseases, the mechanism and material basis are still unclear. Based on the arginine biosynthesis signalling pathway, this research explored the target proteins and metabolites related to the intervention of ROB in thrombosis and expounded on the antithrombotic mechanism of ROB from the comprehensive perspectives of target prediction, intermediate metabolites and potential metabolic pathways. METHODS: In this research, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology was used to qualitatively detect the chemical compounds of ROB, and the antithrombotic activity of ROB was evaluated by establishing a zebrafish model. The target function was predicted by network pharmacology, and differential metabolites were screened by metabolomics and multivariate statistical analysis methods. Correlation analysis of network pharmacology and metabolomics screening results was conducted to identify the potential pathway of ROB intervention in thrombosis, and the prediction results were further verified. RESULTS: ROB significantly reduced the reactive oxygen species (ROS) staining intensity in zebrafish induced by phenylhydrazine (PHZ) and improved the inhibition rate of thrombosis. By constructing the "herb-disease-component-target" network, it was concluded that the active ingredients of ROB in treating thrombosis involved emodin, aloe-emodin and physcion, and the key targets included nitric oxide synthase 2 (NOS2) and nitric oxide synthase 3 (NOS3). A total of 341 differential metabolites in zebrafish with thrombosis were screened by partial least squares discriminant analysis (PLS-DA). The results of reverse transcription-polymerase chain reaction (RT-PCR) experiments and targeted metabolomics verification showed that ROB was mainly involved in improving thrombosis by upregulating the expression of NOS3 mRNA and regulating the levels of arginine, glutamate and glutamine in the arginine biosynthesis pathway. CONCLUSIONS: ROB improved thrombosis by regulating the expression of NOS3 mRNA and the contents of arginine, glutamate and glutamine in the arginine biosynthesis signalling pathway.

Poria cum Radix Pini Rescues Barium Chloride-Induced Arrhythmia by Regulating the cGMP-PKG Signalling Pathway Involving ADORA1 in Zebrafish.

The traditional Chinese medicine Poria cum Radix Pini (PRP) is a fungal medicinal material that has been proven to play an important role in the treatment of arrhythmia. However, the mechanism of its effect on arrhythmia is still unclear. In this study, network pharmacology and metabolomics correlation analysis methods were used to determine the key targets, metabolites and potential pathways involved in the effects of PRP on arrhythmia. The results showed that PRP can significantly improve cardiac congestion, shorten the SV-BA interval and reduce the apoptosis of myocardial cells induced by barium chloride in zebrafish. By upregulating the expression of the ADORA1 protein and the levels of adenosine and cGMP metabolites in the cGMP-PKG signalling pathway, PRP can participate in ameliorating arrhythmia. Therefore, we believe that PRP shows great potential for the treatment of arrhythmia.

Hypericum perforatum L. Regulates Glutathione Redox Stress and Normalizes Ggt1/Anpep Signaling to Alleviate OVX-Induced Kidney Dysfunction.

Menopause and associated renal complications are linked to systemic redox stress, and the causal factors remain unclear. As the role of Hypericum perforatum L. (HPL) in menopause-induced kidney disease therapy is still ambiguous, we aim to explore the effects of HPL on systemic redox stress under ovariectomy (OVX)-induced kidney dysfunction conditions. Here, using combined proteomic and metabolomic approaches, we constructed a multi-scaled "HPL-disease-gene-metabolite" network to generate a therapeutic "big picture" that indicated an important link between glutathione redox stress and kidney impairment. HPL exhibited the potential to maintain cellular redox homeostasis by inhibiting gamma-glutamyltransferase 1 (Ggt1) overexpression, along with promoting the efflux of accumulated toxic amino acids and their metabolites. Moreover, HPL restored alanyl-aminopeptidase (Anpep) expression and metabolite shifts, promoting antioxidative metabolite processing, and recovery. These findings provide a comprehensive description of OVX-induced glutathione redox stress at multiple levels and support HPL therapy as an effective modulator in renal tissues to locally influence the glutathione metabolism pathway and subsequent redox homeostasis.

Plastic bronchitis associated with Botrytis cinerea infection in a child: A case report.

BACKGROUND: Plastic bronchitis (PB) frequently occurs in children after the surgical repair of congenital cardiac defects or in the presence of inflammatory or allergic diseases of the lung. Accurate epidemiological data of this condition are still lacking. CASE SUMMARY: A 5-year-old boy, with a clear medical history, presented to our hospital with persistent cough and pneumonia with segmental atelectasis on chest computerized tomography. He showed no significant improvement after 1 wk of amoxicillin-clavulanate potassium treatment. Bronchial casts were extracted using flexible bronchoscopy. Pathological examination of the dendritic cast confirmed the diagnosis of type I PB. Botrytis cinerea was detected by next-generation sequencing of the bronchoalveolar lavage fluid. After the removal of the airway obstruction and fluconazole treatment, the patient recovered and was discharged 14 d after admission without the recurrence of cough. CONCLUSION: Botrytis cinerea pneumonia should be considered in children with PB who still have prolonged cough and atelectasis after a regular course of antibiotic therapy. Flexible bronchoscopy and etiological examination should be performed in a timely manner to determine the diagnosis, clear the airway obstruction, and target etiological treatment.

Research on the mechanism of Chinese herbal medicine Radix Paeoniae Rubra in improving chronic pelvic inflammation disease by regulating PTGS2 in the arachidonic acid pathway.

Radix Paeoniae Rubra (RPR) is a traditional Chinese medicine with anti-inflammatory effects that has been used in chronic pelvic inflammation disease (CPID) therapy. However, research on the mechanism of RPR in CPID therapy is lacking. Here, we used a network pharmacology method to screen targets and found that the PTGS2 target in the arachidonic acid (AA) pathway was significantly related to CPID. Then, regarding the molecular mechanism, it was further confirmed that RPR may reduce the development of CPID by regulating the PTGS2 target. The CPID rat model was established by mixed bacterial infection. We verified the expression of PTGS2 by immunohistochemical analysis, western blotting assays to detect the expression of PTGS2 protein, and polymerase chain reaction detection of PTGS2 mRNA expression. It was observed that the PTGS2 target decreased significantly after RPR administration at different doses. It is suggested that RPR can reverse the abnormal expression of PTGS2 in CPID rats. We believe that RPR is effective in the treatment of CPID, and RPR can reduce the inflammatory symptoms of CPID by regulating the level of PTGS2 in the AA pathway.

Taoren-dahuang herb pair reduces eicosanoid metabolite shifts by regulating ADORA2A degradation activity in ischaemia/reperfusion injury rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peach kernel (taoren: TR) is the dried mature seed of peach, Prunus persica (L.) Batsch, which belongs to the Rosaceae family. Rhubarb (dahuang: DH) is the dried root and rhizome of rhubarb (Rheum palmatum L., Rheum officinale Baill., or Rheum tanguticum Maxim. ex Balf.). TR-DH (TD) is a traditional Chinese medicine herb pair that promotes blood circulation and removes blood stasis. In recent years, TD has shown definite benefits in the cardio-cerebrovascular system, but its specific mechanism is not very clear. AIM OF STUDY: The purpose of this study was to explore the mechanism by which TD affects cerebral ischaemia/reperfusion (I/R) injury and to optimize the mixture ratio. METHODS: The affected metabolic pathways in rat brain tissues after I/R were analysed by network pharmacology and verified with animal pharmacological experiments. RESULTS: TD had a certain therapeutic effect on cerebral I/R injury. TD with a TR:DH ratio of 1:1 had the best therapeutic effect. Metabolic pathway analysis showed that the protective mechanism of TD against I/R injury involves mainly regulation of brain tissue ADORA2A protein levels and action on the arachidonic acid (AA) pathway. CONCLUSION: TD can ameliorate cerebral I/R injury by regulating ADORA2A degradation in the AA metabolic pathway to attenuate AA metabolic dysfunction and the inflammatory response.

ER-depletion lowering the 'hypothalamus-uterus-kidney' axis functions by perturbing the renal ERß/Ptgds signalling pathway.

Researchers have long assumed that systematic estrogen fading might contribute to the sustained progression of menopausal degenerate syndromes, although definitive evidence has not been presented. Whether such findings represent a causal contribution or are the result of opportunistic messengers sent from the reproductive system to the brain is also a vital question. We constructed a multiscale network of the ovariectomy (OVX) induced estrogen receptors depletion (ER-depletion) model and integrated targeted proteomic, targeted lipidomic, cytochemical, and histopathological data across three tissues from the ovariectomy rodent model. We found that compared to control rats, OVX rats showed increased renal and uterine prostaglandin D2 synthase (Ptgds) expression and decreased hypothalamic Ptgds expression, abnormal Ptgds metabolites, the degenerate renal function profiles and decreased cognitive ability (learning and memory) in Morris water maze test. Importantly, we observed a regulatory relationship among ER (particularly ERß), the degree of the pathological phenotype, learning behavior test and the 'hypothalamus-uterus-kidney (HUK) axis functions. Collectively, this study elucidates that ER depletion promoted HUK aging is mostly attributed to a renal ERß/Ptgds signalling imbalance.

[Quantitative determination of nine furanocoumarins for quality evaluation of Angelica dahurica from different habitats].

A UPLC method has been developed for simultaneous determination of nine furanocoumarins of Angelica dahurics,and was used for quality evaluation of A. dahurica from different habitats. ACQUITY UPLC BEH C18 chromatographic column was employed,the separation was performed with the mobile phase consisting of acetonitrile and water,and the detection wavelength was set at254 nm. This method was used to simultaneously determine the content of xanthotoxol,oxypeucedaninhydrate,byak-angelicin,psoralen,xanthotoxin,bergapten,oxypeucedanin,imperatorin and isoimperatorin in A. dahurica from different habitats. Then,the further quality assessment of the drug was carried out by similarity evaluation,cluster analysis( CA),principal component analysis( PCA),and orthogonal partial least squares discriminant analysis( OPLS-DA). The content order of measured furanocoumarins from high to low was: oxypeucedanin>imperatorin>isoimperatorin>oxypeucedaninhydrate>bergapten>byak-angelicin>xanthotoxin>xanthotoxol>psoralen,with the mean content 2. 844,1. 277,0. 649 2,0. 216 2,0. 129 8,0. 062 68,0. 052 68,0. 019 30,0. 018 19 mg·g-1,respectively. There were difference between the batches of the drug,and the quality was influenced by smouldering sulphur based on the results of chemical pattern recognition and content determination. Finally,six active ingredients were recognized as the quality makers using OPLS-DA method. The validated UPLC fingerprint combined with chemical pattern recognition method can be used in the quality control and evaluation of A. dahurica.

LC-MS guided isolation of gracilistones A and B, a pair of diastereomeric sesquiterpenoids with an unusual tetrahydrofuran-fused tricyclic skeleton from Acanthopanax gracilistylus and their potential anti-inflammatory activities.

Gracilistones A (1) and B (2), two new eudesmane-type sesquiterpenoids with an unusual tetrahydrofuran-fused 6/6/5 tricyclic ring system, were obtained from Acanthopanax gracilistylus under the guidance of LC-MS investigation. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and quantum calculation methods. Compounds 1 and 2 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, compared with the positive control L-NMMA. In addition, compounds 1 and 2 were also evaluated for their antioxidant (DPPH• and ABTS•+) and xanthine oxidase (XO) inhibitory activities, and they exhibited weak inhibitory effects at 100 µM.

Micelle Structure in a Deep Eutectic Solvent for the Electrochemical Preparation of Nanomaterials.

The self-aggregation of a surfactant in a deep eutectic solvent (DES) for electrodeposition is reported. The physical properties and electrochemical behavior of an anionic surfactant, sodium dodecyl sulfate (SDS), in a widely used DES, a choline chloride-urea mixture (ChCl-urea), were investigated. On the basis of surface tension and the conductivity measurements, the SDS micelles that were formed in the ChCl-urea system remained stable at higher temperatures, that is, 90 °C. Cyclic voltammetric and chronoamperometric data indicate that the addition of SDS to the DES may alter the nucleation and the growth processes that occur in the electrodeposition process. Scanning electron microscopy images show that the SDS adsorption prevents dendrite formation during the electrodeposition process. A simple mechanism for the formation of the SDS micelles in the DES system for electrodeposition is proposed.