Effectiveness of probiotic- and fish oil-loaded water-in-oil-in-water (W1/O/W2) emulsions at alleviating ulcerative colitis.

Ulcerative colitis (UC) is a common chronic inflammatory disease that causes serious harm to human health. Probiotics have the effect of improving UC. This study evaluated the preventative potential of water-in-oil-in-water (W1/O/W2) emulsions containing both probiotics and fish oil on UC and associated anxiety-like behavior using a mice model. UC model was established in mice by administering dextran sulfate sodium salt (DSS). Free probiotics, probiotic-loaded emulsions, or fish oil and probiotic co-loaded emulsions were then orally administered to the mice. Various bioassays, histological studies, 16s rDNA gene sequencing, and behavioral experiments were conducted to assess changes in the intestinal environment, microbiota, and anxiety-like behavior of the mice. The fish oil and probiotic co-loaded emulsions significantly reduced the inflammatory response by enhancing tight junction protein secretion (ZO-1, Occludin, and Claudin-1), inhibiting pro-inflammatory factors (TNF-α, and IL-1ß), and promoting short-chain fatty acids (SCFAs) production. These emulsions also modified the gut microbiota by promoting beneficial bacteria and suppressing pathogenic bacteria, thereby restoring a balanced gut microbiota. Notably, the emulsions containing both probiotics and fish oil also ameliorated anxiety-like behavior in the mice. The co-delivery of probiotics and fish oil using W1/O/W2 emulsions has shown significant promise in relieving UC and its associated anxiety-like behavior. These findings provide novel insights into the development of advanced therapeutic strategies for treating UC.

[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.

An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats.

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

Chaihu Guizhi Ganjiang Decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPARα mediated lipotoxicity.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prominent cause of liver-related death that poses a threat to global health and is characterized by severe hepatic steatosis, lobular inflammation, and ballooning degeneration. To date, no Food and Drug Administration-approved medicine is commercially available. The Chaihu Guizhi Ganjiang Decoction (CGGD) shows potential curative effects on regulation of blood lipids and blood glucose, mitigation of organism inflammation, and amelioration of hepatic function. However, the overall regulatory mechanisms underlying its effects on NASH remain unclear. PURPOSE: This study aimed to investigate the efficiency of CGGD on methionine- and choline-deficient (MCD)-induced NASH and unravel its underlying mechanisms. METHODS: A NASH model of SD rats was established using an MCD diet for 8 weeks, and the efficacy of CGGD was evaluated based on hepatic lipid accumulation, inflammatory response, and fibrosis. The effects of CGGD on the intestinal barrier, metabolic profile, and differentially expressed genes (DEGs) profile were analyzed by integrating gut microbiota, metabolomics, and transcriptome sequencing to elucidate its mechanisms of action. RESULTS: In MCD-induced NASH rats, pathological staining demonstrated that CGGD alleviated lipid accumulation, inflammatory cell infiltration, and fibrosis in the hepatic tissue. After CGGD administration, liver index, liver weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) contents, liver triglycerides (TG), and free fatty acids (FFAs) were decreased, meanwhile, it down-regulated the level of proinflammatory mediators (TNF-α, IL-6, IL-1ß, MCP-1), and up-regulated the level of anti-inflammatory factors (IL-4, IL-10), and the expression of liver fibrosis markers TGFß, Acta2, Col1a1 and Col1a2 were weakened. Mechanistically, CGGD treatment altered the diversity of intestinal flora, as evidenced by the depletion of Allobaculum, Blautia, norank_f_Erysipelotrichaceae, and enrichment of the probiotic genera Roseburia, Lactobacillus, Lachnoclostridium, etc. The colonic histopathological results indicated that the gut barrier damage recovered in the CGGD treatment group, and the expression levels of colonic short-chain fatty acids (SCFAs)-specific receptors FFAR2, FFAR3, and tight junction (TJs) proteins ZO-1, Occludin, Claudin-1 were increased compared with those in the model group. Further metabolomic and transcriptomic analyses suggested that CGGD mitigated the lipotoxicity caused by glycerophospholipid and eicosanoid metabolism disorders by decreasing the levels of PLA2G4A, LPCAT1, COX2, and LOX5. In addition, CGGD could activate the inhibitory lipotoxic transcription factor PPARα, regulate the proteins of FABP1, APOC2, APOA2, and LPL to promote fatty acid catabolism, and suppress the TLR4/MyD88/NFκB pathway to attenuate NASH. CONCLUSION: Our study demonstrated that CGGD improved steatosis, inflammation, and fibrosis on NASH through enhancing intestinal barrier integrity and alleviating PPARα mediated lipotoxicity, which makes it an attractive candidate for potential new strategies for NASH prevention and treatment.

Integration of metabolomics and transcriptomics reveals that Da Chuanxiong Formula improves vascular cognitive impairment via ACSL4/GPX4 mediated ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Da Chuanxiong Formula (DCX) is a traditional herbal compound composed of Gastrodia elata Bl. and Ligusticum chuanxiong Hort, which could significantly enhance blood circulation and neuroprotection, showing promise in treating Vascular Cognitive Impairment (VCI). AIM OF STUDY: This study aims to elucidate the potential of DCX in treating VCI and its underlying mechanism. MATERIALS AND METHODS: Firstly, the cognitive behavior level, blood flow changes, and brain pathology changes were evaluated through techniques such as the Morris water maze, step-down, laser speckle, coagulation analysis, and pathological staining to appraise the DCX efficacy. Then, the DCX targeting pathways were decoded by merging metabolomics with transcriptomics. Finally, the levels of reactive oxygen species (ROS), Fe2+, and lipid peroxidation related to the targeting signaling pathways of DCX were detected by kit, and the expression levels of mRNAs or proteins related to ferroptosis were determined by qPCR or Western blot assays respectively. RESULTS: DCX improved cognitive abilities and cerebral perfusion significantly, and mitigated pathological damage in the hippocampal region of VCI model rats. Metabolomics revealed that DCX was able to call back 33 metabolites in plasma and 32 metabolites in brain samples, and the majority of the differential metabolites are phospholipid metabolites. Transcriptomic analysis revealed that DCX regulated a total of 3081 genes, with the ferroptosis pathway exhibiting the greatest impact. DCX inhibited ferroptosis of VCI rates by decreasing the levels of ferrous iron, ROS, and malondialdehyde (MDA) while increasing the level of superoxide dismutase (SOD) and glutathione (GSH) in VCI rats. Moreover, the mRNA and protein levels of ACSL4, LPCAT3, ALOX15, and GPX4, which are related to lipid metabolism in ferroptosis, were also regulated by DCX. CONCLUSION: Our research findings indicated that DCX could inhibit ferroptosis through the ACSL4/GPX4 signaling pathway, thereby exerting its therapeutic benefits on VCI.

Four new glycosides isolated from Gerbera delavayi Franch.

Phytochemical investigation of the whole plant of Gerbera delavayi afforded four new glycosides including three coumarin glycosides, Gerbelavinside A (1), Gerbelavinside B (2) and Gerbelavinside C (3) and one acetophenone glycoside, Gerbelavinside F (4). The structures of isolated compounds were elucidated by analysis of 1D and 2D NMR, HR-ESI-MS, acid hydrolysis, as well as comparing with the literature. The isolated compounds were examined the effects of nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells, and Gerbelavinside C presented a certain inhibitory activity.

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.

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.

Biancaea decapetala (Roth) O.Deg. extract exerts an anti-inflammatory effect by regulating the TNF/Akt/NF-κB pathway.

BACKGROUND: Biancaea decapetala (Roth) O.Deg. (Fabaceae) is used to treat colds, fever, and rheumatic pain caused by inflammation. However, the mechanism underlying its anti-inflammatory properties remains unclear. PURPOSE: This study aimed to evaluate the anti-inflammatory activity of Biancaea decapetala extract (BDE) in vitro and in vivo and explore the possible underlying mechanism and potential targets. METHODS: The release of nitric oxide (NO) and inflammatory cytokines in LPS-stimulated RAW264.7 cells and rats were measured using Griess reagent and enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was employed to examine the pathology of animal tissues. Transcriptome analysis was performed to screen the pathways related to BDE-mediated inhibition of inflammation, and the expression of related proteins was measured using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, ELISA, and immunofluorescence methods. Surface Plasmon Resonance (SPR) and the Drug Affinity Reaction Target Stability (DARTS) method were used to verify whether BDE binds to TNF-α target protein, while a L929 cell model and NF-κB gene reporter systematic method were used to investigate the inhibitory effect of BDE on the activity of TNF-α protein. RESULTS: BDE inhibited the expression of TNF-α, IL-1ß, IL-6, and NO in RAW264.7 cells and rats, and improved the pathological changes in lung tissue. RNA-seq showed that BDE may regulate the TNF/Akt/NF-κB pathway to inhibit inflammation onset. BDE significantly downregulated the mRNA expression of TNF-α, IL-6, IL-1ß, and that of relevant proteins, including TNF-α, p-p65, p-Akt, p-IκBα. Furthermore, BDE inhibited the nuclear translocation of NF-κB (p65) and the activation of the Akt pathway by SC79. The L929 cell model, luciferase reporter gene analysis, DARTS, and SPR experiments showed that BDE may bind to TNF-α and inhibit the TNF-α-NF-κB pathway. CONCLUSION: BDE may target TNF-α to inhibit the TNF/Akt/NF-κB pathway, thereby attenuating inflammation. These findings reveal the anti-inflammatory effects and mechanisms of BDE and provide a theoretical basis for the further development and utilization of BDE.

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.

[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.

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.

Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease.

Introduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED). Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael's addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction. Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission. Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.

[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.

Polygoni Multiflori Radix interferes with bile acid metabolism homeostasis by inhibiting Fxr transcription, leading to cholestasis.

Objective: To explore the possible mechanisms of cholestasis induced by Polygoni Multiflori Radix (PM). Methods: Low and high doses of water extract of PM were given to mice by gavage for 8 weeks. The serum biochemical indexes of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (GGT) alkaline phosphatase (ALP) and so on were detected in the second, fourth, sixth, and eighth weeks after administration. At the end of the eighth week of administration, the bile acid metabolic profiles of liver and bile were screened by high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS). Liver pathological changes were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA transcription of the target genes and Western blotting (WB) was used to the detect target protein expression. Results: Biochemical tests results showed the values of ALP and GGT were two and three times greater than the normal values respectively, and the value of R was less than 2. Histopathology also showed that PM caused lymphocyte infiltration, a small amount of hepatocyte necrosis and nuclear fragmentation in mouse liver. The proliferation of bile duct epithelial cells was observed in the high group. These results indicated that PM may lead to cholestatic liver injury. HPLC-QQQ-MS/MS analysis with the multivariate statistical analysis revealed significant alterations of individual bile acids in liver and gallbladder as compared to those of the control group. RT-qPCR showed that the transcription of Fxr, Shp, Bsep, Bacs, Mdr2, and Ugt1a1 were downregulated and that of Cyp7a1, Mrp3, and Cyp3a11 was significantly upregulated in the treatment group. WB demonstrated that PM also markedly downregulated the protein expression of FXR, BSEP, and MDR2, and upregulated CYP7A1. Conclusion: PM inhibited the expression of FXR, which reduced the expression of MDR2 and BSEP, leading to the obstruction of bile acids outflow, and increased the expression of CYP7A1, resulting in an increase of intrahepatic bile acid synthesis, which can lead to cholestasis.

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.

Quantification of six volatile oil constituents of Oleum Cinnamomi in rat plasma and multiple tissues using GC-MS and its application to pharmacokinetic and tissue distribution studies.

Oleum Cinnamomi is the essential oil obtained from the herb Fructus Cinnamomi which is used by the Hmong people in traditional medicine for the treatment of various diseases. At present, there are a variety of marketed preparations with it as the main medicine on the market. Information regarding the in vivo process of it is lacking, which has become a bottleneck restricting its development and utilization. In view of this, a GC-MS SIM analysis method was established for the simultaneous determination of six main volatile components [eucalyptol, p-cymene, 4-carvomenthenol, 4-isopropyl-2-cyclohexenone, α-terpineol, and 2-(4-Methylphenyl)-propan-2-ol] in plasma and ten tissues of rats to study their pharmacokinetic and distribution characteristics in vivo. The pharmacokinetic results showed that the t1/2 of each index was 0.41-1.66 h, Tmax was 0.16-0.68 h, Cmax was 13.66-2015.02 ng/mL, AUC0-t was 12.84-4299.00 h·ng/mL, CLZ/F was 1750.93-107013.11 mL/h/kg. This meant that the six components could be absorbed quickly, had a short residence time, and be eliminated quickly in the body. Among them, eucalyptol has the highest degree of absorption and a larger amount of entering the body. Moreover, the Cmax and AUC0-t of the six components increased correspondingly with the increase of the dose, indicating that the concentration of Oleum Cinnamomi in the rat plasma was dose-dependent. At different time points, the six components were widely distributed with uneven characteristics in the body. The six components mainly tend to be distributed in stomach, small intestine, and liver, followed by kidney, spleen, heart, and brain, and to a lesser extent in lung, skin, and muscle. And the six components were eliminated quickly in each tissue. The pharmacokinetic process and tissue distribution characteristics of Oleum Cinnamomi were expounded in this study, which can provide scientific theory for the in-depth development and guidance of clinical drug use of Oleum Cinnamomi, and at the same time provide a medicinal material basis for the in-depth development and utilization of Oleum Cinnamomi.

Four new benzo[d,e]isochromene derivatives from rhizomes of Musa basjoo.

Four new compounds, basjoochromene A (1), basjoochromene B (2), basjoochromene C (3) and basjoochromene D (4) were isolated from the 70% ethanol extract of the rhizomes of Musa basjoo using column chromatography techniques. Their structures were elucidated on the basis of spectroscopic data interpretation, mass spectrometric analyses.