Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray.

Galanin receptor1 (GalR1) transcript levels are elevated in the rat ventral periaqueductal gray (vPAG) after chronic mild stress (CMS) and are related to depression-like behavior. To explore the mechanisms underlying the elevated GalR1 expression, we carried out molecular biological experiments in vitro and in animal behavioral experiments in vivo. It was found that a restricted upstream region of the GalR1 gene, from -250 to -220, harbors an E-box and plays a negative role in the GalR1 promoter activity. The transcription factor Scratch2 bound to the E-box to down-regulate GalR1 promoter activity and lower expression levels of the GalR1 gene. The expression of Scratch2 was significantly decreased in the vPAG of CMS rats. Importantly, local knockdown of Scratch2 in the vPAG caused elevated expression of GalR1 in the same region, as well as depression-like behaviors. RNAscope analysis revealed that GalR1 mRNA is expressed together with Scratch2 in both GABA and glutamate neurons. Taking these data together, our study further supports the involvement of GalR1 in mood control and suggests a role for Scratch2 as a regulator of depression-like behavior by repressing the GalR1 gene in the vPAG.

[Comparative study on excretion of Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats].

Scutellariae Radix extract is one of the important components in Shuganning Injection. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for simultaneously determining five components in Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats, so as to reveal the difference in the excretion process of Shuganning Injection and Scutellariae Radix extract in rats and explore the law of the excretion process of the five components in vivo before and after the compatibility of Scutellariae Radix. Rats were injected with Shuganning Injection and Scutellariae Radix extract(4.2 mL·kg~(-1)), respectively, and the excretion of baicalin, baicalein, oroxylin A, oroxylin A-7-O-ß-D-glucuronide, and scutellarin in bile, urine, and feces of rats in 24 h was observed. The results showed that except for baicalin, the other four index components were excreted as prototype components in a high proportion after intravenous injection of Shuganning Injection and Scutellariae Radix extract in rats, respectively. The excretion of each component was relatively high in urine and less in feces and bile. After the compatibility of Scutellariae Radix extract, the accumulative excretion of five index components in rats all decreased. Among them, the cumulative excretion of baicalein in bile, urine, and feces significantly decreased by 26.67%, 48.11%, and 31.01%. The cumulative excretion of baicalin in bile, urine, and feces decreased significantly by 70.69%, 19.43%, and 31.22%. The result showed that the five index components in Scutellariae Radix extract were mainly excreted by the kidneys, and other components in Shuganning Injection delayed the excretion process and prolonged the residence time. This study is of great significance for elucidating the compatibility rationality of Shuganning Injection.

In vitro antifungal susceptibility profile and genotypic characterization of clinical Aspergillus isolates in Eastern China on behalf of Eastern China Invasive Fungi Infection Group.

Aspergillus species is a widespread environmental mould that can cause aspergillosis. The purpose of this study was to investigate the antifungal susceptibility profile and genotypic characterization of clinical Aspergillus isolates from different provinces in Eastern China. The data included the antifungal susceptibility distributions with eight common antifungal drugs, cyp51A gene mutations of triazole-resistant Aspergillus fumigatus sensu stricto, and the genotypic relationships among the A. fumigatus sensu stricto isolates based on microsatellite typing. A. fumigatus sensu lato was the most common clinical Aspergillus species (n = 252), followed by A. flavus (n = 169), A. terreus (n = 37), A. niger (n = 29), and A. nidulans (n = 4). The modal minimum effective concentration values of micafungin and anidulafungin were lower than those of caspofungin for all Aspergillus species. The in vitro efficacy of isavuconazole was similar to that of voriconazole against most Aspergillus species. Sequencing revealed cyp51A gene mutations TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A in four triazole-resistant A. fumigatus sensu stricto. Phylogenetic analyses using microsatellite markers of A. fumigatus sensu stricto revealed that 211 unique genotypes clustered into two clades. The data demonstrate the diversity of clinically relevant Aspergillus species in Eastern China. Routine antifungal susceptibility testing should be performed to monitor the antifungal resistance and guide clinical therapy.

The 6-year multicenter study collected a total of 491 Aspergillus isolates from Eastern China to investigate the in vitro antifungal susceptibility to eight antifungal drugs, the cyp51A gene mutations of triazole-resistant A. fumigatus sensu stricto, and the genetic relatedness through microsatellite typing.

Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options.

Urinary tract infections (UTIs) are common bacterial infections that represent a severe public health problem. They are often caused by Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumonia), Proteus mirabilis (P. mirabilis), Enterococcus faecalis (E. faecalis), and Staphylococcus saprophyticus (S. saprophyticus). Among these, uropathogenic E. coli (UPEC) are the most common causative agent in both uncomplicated and complicated UTIs. The adaptive evolution of UPEC has been observed in several ways, including changes in colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. While antibiotic therapy has historically been very successful in controlling UTIs, high recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly reduce the efficacy of these treatments. Furthermore, the gradual global emergence of multidrug-resistant UPEC has highlighted the need to further explore its pathogenesis and seek alternative therapeutic and preventative strategies. Therefore, a thorough understanding of the clinical status and pathogenesis of UTIs and the advantages and disadvantages of antibiotics as a conventional treatment option could spark a surge in the search for alternative treatment options, especially vaccines and medicinal plants. Such options targeting multiple pathogenic mechanisms of UPEC are expected to be a focus of UTI management in the future to help combat antibiotic resistance.

Anti-Rheumatoid Arthritis Pharmacodynamic Substances Screening of Periploca forrestii Schltr.: Component Analyses In Vitro and In Vivo Combined with Multi-Technical Metabolomics.

The purpose of this study was to elucidate the metabolic action patterns of P. forrestii against rheumatoid arthritis (RA) using metabolomics, and to obtain its potential effective substances for treating RA. First, the therapeutic effects of P. forrestii against RA were confirmed; second, the chemical composition of P. forrestii was analyzed, and 17 prototypes were absorbed into blood; subsequently, plasma metabolomics studies using UPLC-Triple-TOF-MS/MS and GC-MS were performed to disclose the metabolomics alterations in groups, which revealed 38 altered metabolites after drug intervention. These metabolites were all associated with the arthritis pathophysiology process (-log(p) > 1.6). Among them, sorted by variable important in projection (VIP), the metabolites affected (VIP ≥ 1.72) belonged to lipid metabolites. Finally, Pearson's analysis between endogenous metabolites and exogenous compounds was conducted to obtain potential pharmacological substances for the P. forrestii treatment of RA, which showed a high correlation between five blood-absorbed components and P. forrestii-regulated metabolites. This information provides a basis for the selection of metabolic action modes for P. forrestii clinical application dosage, and potential pharmacological substances that exerted anti-RA effects of P. forrestii were discovered. The study provided an experimental basis for further research on pharmacoequivalence, molecular mechanism validation, and even the development of new dosage forms in the future.

Polygonum orientale L. Alleviates Myocardial Ischemia-Induced Injury via Activation of MAPK/ERK Signaling Pathway.

Although Polygonum orientale L. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.

[Simultaneous determination of eleven volatile components in Cinnamomi Oleum by GC-MS].

A gas chromatography-triple quadrupole mass spectrometry(GC-MS) method was established for the simultaneous determination of eleven volatile components in Cinnamomi Oleum and the chemical pattern recognition was utilized to evaluate the quality of essential oil obtained from Cinnamomi Fructus medicinal materials in various habitats. The Cinnamomi Fructus medicinal materials were treated by water distillation, analyzed using GC-MS, and detected by selective ion monitoring(SIM), and the internal standards were used for quantification. The content results of Cinnamomi Oleum from various batches were analyzed by hierarchical clustering analysis(HCA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) for the statistic analysis. Eleven components showed good linear relationships within their respective concentration ranges(R~2>0.999 7), with average recoveries of 92.41%-102.1% and RSD of 1.2%-3.2%(n=6). The samples were classified into three categories by HCA and PCA, and 2-nonanone was screened as a marker of variability between batches in combination with OPLS-DA. This method is specific, sensitive, simple, and accurate, and the screened components can be utilized as a basis for the quality control of Cinnamomi Oleum.

[Content determination of seven active components of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats by UPLC-MS/MS].

In the present study, the contents of seven active components [genipinic acid(GA), protocatechuic acid(PCA), neochlorogenic acid(NCA), chlorogenic acid(CA), cryptochlorogenic acid(CCA),(+)-pinoresinol di-O-ß-D-glucopyranosid(PDG), and(+)-pinoresinol 4'-O-ß-D-glucopyranoside(PG)] of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats(SHR) were simultaneously determined by ultra-high liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The qualified SHR models were selected. The primary aortic endothelial cells(VECs) of rats were separated and cultured by ligation and adherence, followed by subculture. After successful identification, an UPLC-MS/MS method for simultaneously determining the contents of GA, PCA, NCA, CA, CCA, PDG, PG in seven components of Eucommiae Cortex in VECs was established, including specificity, linearity, matrix effect, recovery, accuracy, precision and stability. The established method had the lo-west limit of quantification of 0.97-4.95 µg·L~(-1), accuracy of 87.26%-109.6%, extraction recovery of 89.23%-105.3%, matrix effect of 85.86%-106.2%, and stability of 86.00%-112.5%. Therefore, the established accurate UPLC-MS/MS method could rapidly and simultaneously determine the contents of the seven active components of Eucommiae Cortex in VECs of SHRs, which provided a refe-rence for the study of cellular pharmacokinetics of active components of Eucommiae Cortex extract.

Enhancement of Visible-Light-Driven Hydrogen Evolution Activity of 2D π-Conjugated Bipyridine-Based Covalent Organic Frameworks via Post-Protonation.

Photocatalytic hydrogen (H2 ) evolution represents a promising and sustainable technology. Covalent organic frameworks (COFs)-based photocatalysts have received growing attention. A 2D fully conjugated ethylene-linked COF (BTT-BPy-COF) was fabricated with a dedicated designed active site. The introduced bipyridine sites enable a facile post-protonation strategy to fine-tune the actives sites, which results in a largely improved charge-separation efficiency and increased hydrophilicity in the pore channels synergically. After modulating the degree of protonation, the optimal BTT-BPy-PCOF exhibits a remarkable H2 evolution rate of 15.8 mmol g-1 h-1 under visible light, which surpasses the biphenyl-based COF 6 times. By using different types of acids, the post-protonation is proved to be a potential universal strategy for promoting photocatalytic H2 evolution. This strategy would provide important guidance for the design of highly efficient organic semiconductor photocatalysts.

The association between serum selenium level and gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: The relationship between serum selenium level and gestational diabetes mellitus (GDM) is controversial. The purpose is to update and summarize previous studies to understand the relationship in more detail. METHODS: PubMed, The Cochrane Library, EMBASE, Web of science, CNKI, WANFANG DATA and Cqvip were searched for studies published up to 3 September 2021. The random-effects model was used to measure the combined estimation. The overall effect was reported in a standard mean difference (SMD) and 95% confidence interval (95% CI). All data were analysed by Review Manager 5.4. RESULTS: Twenty-seven studies involving 1588 patients with GDM and 2450 healthy pregnant women contributed to this meta-analysis. Selenium level was significantly lower in women with GDM than those without GDM (SMD = -1.29; 95% CI: -1.60 to -0.97, p < 0.00001). Subgroup analyses showed that such trend was consistent within the non-European population (Asia: SMD = -1.44; 95% CI: -1.79 to -1.08, p < 0.00001; Africa: SMD = -2.62; 95% CI: -4.50 to -0.74, p = 0.006) and in the second and third trimesters (the second trimester: SMD = -1.41; 95% CI: -1.82 to -0.99, p < 0.00001; the third trimester: SMD = -1.54; 95% CI: -2.09 to -0.98, p < 0.00001), but not within the European population (SMD = -0.47; 95% CI: -1.09 to 0.16, p = 0.14) or in the first trimester (SMD = -0.52; 95% CI: -1.13 to 0.10, p = 0.10). CONCLUSIONS: This meta-analysis showed that the serum selenium level of patients with GDM was lower than that in healthy pregnant women, especially within the non-European population and in the second and third trimesters.

Protective effects on ovalbumin-induced mouse asthma models and qualitative and quantitative analysis of multiple compounds in Gerberae Piloselloidis Herba.

Gerberae Piloselloidis Herba is widely used to treat cough and asthma in China. However, its effects on allergic asthma as related to its chemical compositions have not been fully elucidated, and there is a scarcity of methods to determine multi-component contents for quality control. In this study, protective effects of Gerberae Piloselloidis Herba on ovalbumin-induced asthma models were investigated, while qualitative and quantitative analyses of multiple constituents in Gerberae Piloselloidis Herba were conducted by using an ultrahigh-performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry and an ultrahigh-performance liquid chromatography-photodiode array detection. The results showed that Gerberae Piloselloidis Herba could significantly mitigate asthma symptoms, reduce eosinophils counts in the bronchoalveolar lavage fluid, as well as decrease IgE, IL-5, and IL-13 concentration, and inflammatory cellular infiltration in lung tissues. A total of 51 compounds were tentatively identified, in which the content of 10 representative compounds was determined in 24 batches of Gerberae Piloselloidis Herba by using an ultrahigh-performance liquid chromatography method with good linearity, precision, repeatability, accuracy, and stability. This research presents a comprehensive strategy combining biological activity evaluation with chemical profiling, providing a useful and comprehensive reference for further application and quality control of Gerberae Piloselloidis Herba.

Chemical profiling and quantification of multiple components in Jin-Gu-Lian capsule using a multivariate data processing approach based on UHPLC-Orbitrap Exploris 240 MS and UHPLC-MS/MS.

The Jin-Gu-Lian capsule, a Chinese Miao herbal compound, is widely used to treat rheumatoid arthritis. In this study, a rapid, selective, and sensitive UHPLC-Orbitrap Exploris 240 MS method was developed to analyze the chemical composition of Jin-Gu-Lian capsules. A total of 88 compounds were identified, including 23 flavonoids, 23 organic acids, 14 phenylpropanoids, 12 phenols, eight alkaloids, four terpenes, three quinones, and one ketone. Among these, 21 compounds were clearly detected based on a comparison with reference standards and selected as quality control markers. Thereafter, these compounds were simultaneously determined in the Jin-Gu-Lian capsules. The established method was successfully validated and applied for the simultaneous determination of 21 biologically active compounds in Jin-Gu-Lian capsules of 27 sample batches. Quantitative data of the analytes were analyzed using multivariate statistical analysis to determine the quality of the Jin-Gu-Lian capsules. Four compounds (JGLC6 [salidroside], JGLC8 [chlorogenic acid], JGLC12 [liriodendrin], JGLC19 [quercetin]) were identified as chemical markers for quality control of Jin-Gu-Lian capsules. Altogether, the established method was validated as a novel and efficient tool, that can be used for rapid analysis of Jin-Gu-Lian capsules. Accordingly, this study serves as a reference for scientific research on traditional Chinese and ethnic medicine.

Pharmacokinetics Study of Jin-Gu-Lian Prescription and Its Core Drug Pair (Sargentodoxa cuneata (Oliv.) Rehd. et W and Alangium chinense (Lour.) Harms) by UPLC-MS/MS.

Jin-Gu-Lian (JGL) is traditionally used by Miao for the treatment of rheumatism arthralgia. At the same time, the combination of Sargentodoxa cuneata (Oliv.) Rehd. et W (SC) and Alangium chinense (Lour.) Harms (AC), the core drug pair (CDP) in the formula of JGL, is used at high frequencies in many Miao medicine prescriptions for rheumatic diseases. However, previous research lacks the pharmacokinetic study of JGL, and study on the compatibility of its CDP with other medicinal herbs in the formula is needed. This study aims to establish a simple, rapid, and sensitive Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous determination of four main bioactive components of JGL in rat plasma, including Salidroside (Sal), Anabasine (Ana), Chlorogenic Acid (CA), and Protocatechuic Acid (PCA), and compare the pharmacokinetic properties of two groups of rats after being orally administrated with JGL and its CDP extracts, respectively. The results showed that area under the plasma concentration-time curve (AUC), mean retention time (MRT), and clearance rate (CL), of Sal, Ana, CA and PCA in the two groups of rats were changed in different degrees. The CDP combined with other drugs could significantly increase the absorption of Sal and Ana, prolong its retention time in vivo, and may accelerate the absorption rate of CA and PCA. This indicated that the combination of CDP and other herbs may affect the pharmacokinetics process of active components in vivo, increase the exposure and bioavailability of compounds in the JGL group, and prolong the retention time, which may be the reason why JGL has a better inhibitory effect on inflammatory cytokines, providing a viable orientation for the compatibility investigation of herb medicines.

Quality Control of Oleum Cinnamomi Assisted by Network Pharmacology Strategy.

Oleum Cinnamomi is a traditional medicine used by the Hmong, the essential oil obtained from Fructus Cinnamomi, for the treatment of coronary heart disease. Information regarding the efficient quality control markers of it is lacking, which has become a bottleneck restricting its development and utilization. Here, an integrated qualitative analysis approach based on a GC-MS and network pharmacology strategy was applied to explore quality control markers for the assessment of Oleum Cinnamomi. Firstly, the compounds of Oleum Cinnamomi were detected by GC-MS. In total, 57 chemical components were identified, mainly monoterpenes and sesquiterpenes, accounting for 83.05% of total essential oil components. Secondly, network pharmacology was adopted to explore the compounds linked to target genes of coronary heart disease. Fifty-two compounds were found, indicating the effectiveness of Oleum Cinnamomi in the treatment of coronary heart disease. Among them, 10 compounds, including eucalyptol, were chosen as potential effective compounds in Oleum Cinnamomi. Thirdly, an established GC-MS SIM method was validated and applied for the simultaneous determination of the contents of these 10 compounds using 20 sample batches of Oleum Cinnamomi. It was preliminarily found that the contents of these 10 compounds differed in Oleum Cinnamomi from different origins. Finally, quantitative analyte data were analyzed using multivariate statistical analysis to determine Oleum Cinnamomi quality. Four compounds (eucalyptol, p-cymene, sabinene, ß-pinene) were identified as chemical markers for quality control. Accordingly, this study provides new strategies to explore the quality control markers and develops a novel method for the quality assessment of Oleum Cinnamomi.

A Network-Pharmacology-Combined Integrated Pharmacokinetic Strategy to Investigate the Mechanism of Potential Liver Injury due to Polygonum multiflorum.

Polygonum multiflorum (PM) has been used as a tonic and anti-aging remedy for centuries in Asian countries. However, its application in the clinic has been hindered by its potential to cause liver injury and the lack of investigations into this mechanism. Here, we established a strategy using a network pharmacological technique combined with integrated pharmacokinetics to provide an applicable approach for addressing this issue. A fast and sensitive HPLC-QQQ-MS method was developed for the simultaneous quantification of five effective compounds (trans-2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside, emodin-8-O-ß-d-glucoside, physcion-8-O-ß-d-glucoside, aloe-emodin and emodin). The method was fully validated in terms of specificity, linearity, accuracy, precision, extraction recovery, matrix effects, and stability. The lower limits of quantification were 0.125-0.500 ng/mL. This well-validated method was successfully applied to an integrated pharmacokinetic study of PM extract in rats. The network pharmacological technique was used to evaluate the potential liver injury due to the five absorbed components. Through pathway enrichment analysis, it was found that potential liver injury is primarily associated with PI3K-Akt, MAPK, Rap1, and Ras signaling pathways. In brief, the combined strategy might be valuable in revealing the mechanism of potential liver injury due to PM.

Identification of Protosappanoside D from Caesalpinia decapetala and Evaluation of Its Pharmacokinetic, Metabolism and Pharmacological Activity.

Protosappanoside D (PTD) is a new component isolated from the extract of Caesalpinia decapetala for the first time. Its structure was identified as protosappanin B-3-O-ß-D-glucoside by 1H-NMR, 13C-NMR, 2D-NMR and MS techniques. To date, the pharmacological activities, metabolism or pharmacokinetics of PTD has not been reported. Therefore, this research to study the anti-inflammatory activity of PTD was investigated via the LPS-induced RAW264.7 cells model. At the same time, we also used the UHPLC/Q Exactive Plus MS and UPLC-MS/MS methods to study the metabolites and pharmacokinetics of PTD, to calculate its bioavailability for the first time. The results showed that PTD could downregulate secretion of the pro-inflammatory cytokines. In the metabolic study, four metabolites were identified, and the primary degradative pathways in vivo involved the desaturation, oxidation, methylation, alkylation, dehydration, degradation and desugarization. In the pharmacokinetic study, PTD and its main metabolite protosappanin B (PTB) were measured after oral and intravenous administration. After oral administration of PTD, its Tmax was 0.49 h, t1/2z and MRT(0-t) were 3.47 ± 0.78 h and 3.06 ± 0.63 h, respectively. It shows that PTD was quickly absorbed into plasma and it may be eliminated quickly in the body, and its bioavailability is about 0.65%.

Assessing potential liver injury induced by Polygonum multiflorum using potential biomarkers via targeted sphingolipidomics.

CONTEXT: Polygonum multiflorum Thunb. (Polygonaceae) (PM) can cause potential liver injury which is typical in traditional Chinese medicines (TCMs)-induced hepatotoxicity. The mechanism involved are unclear and there are no sensitive evaluation indicators. OBJECTIVE: To assess PM-induced liver injury, identify sensitive assessment indicators, and screen for new biomarkers using sphingolipidomics. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were randomly divided into four groups (control, model with low-, middle- and high-dose groups, n = 6 each). Rats in the three model groups were given different doses of PM (i.g., low/middle/high dose, 2.7/8.1/16.2 g/kg) for four months. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and liver were quantitatively analyzed. Fixed liver tissue sections were stained with haematoxylin and eosin and examined under a light microscope. The targeted sphingolipidomic analysis of plasma was performed using high-performance liquid chromatography tandem mass spectrometry. RESULTS: The maximal tolerable dose (MTD) of PM administered intragastrically to mice was 51 g/kg. Sphingolipid profiling of normal and PM-induced liver injury SD rats revealed three potential biomarkers: ceramide (Cer) (d18:1/24:1), dihydroceramide (d18:1/18:0)-1-phosphate (dhCer (d18:1/18:0)-1P) and Cer (d18:1/26:1), at 867.3-1349, 383.4-1527, and 540.5-658.7 ng/mL, respectively. A criterion for the ratio of Cer (d18:1/24:1) and Cer (d18:1/26:1) was suggested and verified, with a normal range of 1.343-2.368 (with 95% confidence interval) in plasma. CONCLUSIONS: Three potential biomarkers and one criterion for potential liver injury caused by PM that may be more sensitive than ALT and AST were found.

[SAPHO Syndrome Complicated with Ulcerative Colitis:Report of One Case].

Synovitis,acne,pustulosis,hyperostosis,and osteitis (SAPHO) syndrome is a rare disease. The previous literature demonstrated that about 10% of the patients with SAPHO syndrome were complicated with inflammatory bowel disease.So far,few cases of SAPHO syndrome complicated with inflammatory bowel disease have been reported in China.Herein,we reported a SAPHO syndrome case complicated with ulcerative colitis. The patient suffered from recurrent attacks of colitis following treatment of SAPHO syndrome with etanercept.

[Simultaneous determination of content of eight components in Caesalpinia decapetala by UPLC-MS/MS].

The present study established the ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of the content of eight major active components in Caesalpinia decapetala and performed the quality evaluation of C. decapetala from different habitats with the chemical pattern recognition. The analysis was carried out on a Waters BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) at 40 ℃, with the mobile phase of water containing 0.1% formic acid(A) and acetonitrile containing 0.1% formic acid under gradient elution, the flow rate of 0.3 mL·min~(-1), and the injection volume of 1 µL. The electrospray ionization(ESI) source in the negative mode and multiple reaction monitoring(MRM) were used for MS quantitative analysis. The content results were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) for the evaluation of the quality difference. Eight components showed good linear relationships within their respective concentration ranges(r>0.999), with the average recoveries of 96.85%-103.4% and RSD of 0.52%-2.8%. The analysis results showed that the quality of samples from different batches was different. The samples were classified into three clusters by HCA and PCA. The method is simple, sensitive, accurate, and efficient, and can be used for the quality evaluation of C. decapetala.