Amphiphilic Dendrimer Doping Enhanced pH-Sensitivity of Liposomal Vesicle for Effective Co-delivery toward Synergistic Ferroptosis-Apoptosis Therapy of Hepatocellular Carcinoma.

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxides, has emerged as an attractive strategy to reverse drug resistance. Of particular interest is the ferroptosis-apoptosis combination therapy for cancer treatment. Herein, a nanoplatform is reported for effective co-delivery of the anticancer drug sorafenib (S) and the ferroptosis inducer hemin (H), toward synergistic ferroptosis-apoptosis therapy of advanced hepatocellular carcinoma (HCC) as a proof-of-concept study. Liposome is an excellent delivery system; however, it is not sufficiently responsive to the acidic tumor microenvironment (TME) for tumor-targeted drug delivery. The pH-sensitive vesicles are therefore developed (SH-AD-L) by incorporating amphiphilic dendrimers (AD) into liposomes for controlled and pH-stimulated release of sorafenib and hemin in the acidic TME, thanks to the protonation of numerous amine functionalities in AD. Importantly, SH-AD-L not only blocked glutathione synthesis to disrupt the antioxidant system, but also increased intracellular Fe2+ and ·OH concentrations to amplify oxidative stress, both of which contribute to enhanced ferroptosis. Remarkably, high levels of ·OH also augmented sorafenib-mediated apoptosis in tumor cells. This study demonstrates the efficacy of ferroptosis-apoptosis combination therapy, as well as the promise of the AD-doped TME-responsive vesicles for drug delivery in combination therapy to treat advanced HCC.

Successful treatment of immune-related cystitis by Chai-Ling-Tang (Sairei-To) in a gastric carcinoma patient: Case report and literature review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have changed the landscape of advanced cancer treatment. However, immune checkpoint inhibitors can trigger effector T cells against self-antigens as well as tumor antigens, resulting in immune-related toxicities in normal organs, referred to as immune-related adverse events (irAEs). CASE SUMMARY: A 56-year-old man with undifferentiated gastric carcinoma received sintilimab plus paclitaxel and tegafur therapy. After five cycles of treatment, the patient was referred to the hospital for sudden onset urinary frequency, micturition pain, and urinary incontinence. Cystoscopy revealed the entire bladder mucosa was red and edematous but there was no evidence of tumor. Oral administration of Chai-Ling-Tang (Sairei-To) alleviated lower urinary tract symptoms (LUTS). Histological analysis revealed numerous infiltrates of CD3-positive and CD8-positive cells into the urothelium but no atypia, indicating a diagnosis of immune-related cystitis. Interestingly, the urothelial epithelium infiltrated by lymphocytes and subepithelial inflammatory cells strongly expressed cell boundary PD-L1. The dose of Chai-Ling-Tang was maintained and stopped 2 months later without recurrence of LUTS. Since recovering from cystitis, the patient remains alive with no disease progression. CONCLUSION: This report shows that Chai-Ling-Tang is safe and effective for treating immune-related cystitis. The detailed mechanism of action requires further investigation.

Misdiagnosis of primary mucosa-associated lymphoid tissue lymphoma of the pleura: case report and literature review.

Background: Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B cell lymphoma. Its occurrence in the pleura is rare, with atypical clinical manifestations. MALT of the pleura is easily misdiagnosed. This is the first case report of pleural MALT lymphoma in China. Case Description: We report the case of a 54-year-old Chinese man with no notable medical history who complained of cough, sputum, and shortness of breath for 3 months. He had a positive purified protein derivative (PPD) test. An initial misdiagnosis of pleural tuberculosis was corrected, after 3 thoracoscopic biopsies and tests, to primary pleural MALT lymphoma. He received treatments of R-CHOP (rituximab, cyclophosphamide, epirubicin, vindesine and prednisolone) and traditional Chinese medicine. The patient was followed for 3 years until June 2022, with no obvious respiratory symptoms. Pleural MALT lymphoma is extremely rare, with only a few cases reported. This article describes our case, and includes an overview of 15 previously reported cases to summarize the characteristics, treatments, and prognosis of primary pleural MALT lymphoma. Conclusions: Pleural MALT lymphoma is rare, and a correct diagnosis depends on tissue biopsy, immunohistochemical staining, and detection of gene rearrangement. Thoracoscopy is important to diagnose this disease. Multiple thoracoscopic biopsies may be necessary.

Network Pharmacology Analysis of the Identification of Phytochemicals and Therapeutic Mechanisms of Paeoniae Radix Alba for the Treatment of Asthma.

BACKGROUND: Paeoniae Radix Alba (PRA), the root of the plant Paeonia lactiflora Pall., has been suggested to play an important role for the treatment of asthma. A biochemical understanding of the clinical effects of Paeoniae Radix Alba is needed. Here, we explore the phytochemicals and therapeutic mechanisms via a systematic and comprehensive network pharmacology analysis. METHODS: Through TCMSP, PubChem, GeneCards database, and SwissTargetPrediction online tools, potential targets of active ingredients from PRA for the treatment of asthma were obtained. Cytoscape 3.7.2 was used to determine the target of active ingredients of PRA. Target protein interaction (PPI) network was constructed through the STRING database. The Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genes (KEGG) pathway enrichment analysis were analyzed through the biological information annotation database (DAVID). RESULTS: Our results indicate that PRA contains 21 candidate active ingredients with the potential to treat asthma. The enrichment analysis of GO and KEGG pathways found that the treatment of asthma by PRA may be related to the process of TNF (tumor necrosis factor) release, which can regulate and inhibit multiple signaling pathways such as ceramide signaling. CONCLUSIONS: Our work provides a phytochemical basis and therapeutic mechanisms of PRA for the treatment of asthma, which provides new insights on further research on PRA.

Phlorizin ameliorates obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity.

Phlorizin (PHZ) is one of phytonutrients in apples that contributes to the health-promoting effect implicated by the saying, 'an apple a day keeps the doctor away'. PHZ was firstly identified as a competitive inhibitor of sodium-glucose co-transporters-2 (SGLT2); however, its low bioavailability makes it hard to fully explain its pharmacological mechanisms. This study aimed to investigate the ameliorating effect of PHZ on high-fat diet (HFD)-induced obesity via modulating the "gut microbiota-barrier axis". Firstly, C57BL/6 J mice were fed a normal chow diet (NCD) or HFD coadministered with or without PHZ for 12 weeks. Our results showed that PHZ supplementation significantly reduced HFD-induced body weight gain (P < .001), alleviated metabolic disorders (MDs) like insulin resistance (P < .001) and elevation of serum lipopolysaccharides (LPS) (P < .001), attenuated HFD-induced gut microbiota alterations, enhanced short-chain fatty acids (SCFAs) production (P < .001), and inhibited fecal LPS production (P < .001). To investigate the role of the fecal microbiota in the observed beneficial effects, a fecal microbiota transplantation (FMT) experiment was performed by transplanting the feces of the four groups of mice (as donor mice) daily collected from the fourth week to a new batch of acclimatized HFD-fed mice. Our results confirmed that feeding the gut contents of the PHZ-modulated mice could attenuate HFD-induced MDs, accompanied by enhanced glucagon-like peptide 2 (GLP-2) secretion (P < .001) and restoration of HFD-induced damage in the gut epithelial barrier. This study has provided evidence that the "gut microbiota-barrier axis" was an alternative target for the anti-obesity effect of PHZ. This work has also provided an explanation for the high efficacy of PHZ despite the low bioavailability, and PHZ holds great potential to be developed as a functional food ingredient.

Combined effect of n-3 fatty acids and phytosterol esters on alleviating hepatic steatosis in non-alcoholic fatty liver disease subjects: a double-blind placebo-controlled clinical trial.

The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver-spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-ß (TGF-ß) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-ß was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.

On Variation in Mindfulness Training: A Multimodal Study of Brief Open Monitoring Meditation on Error Monitoring.

A nascent line of research aimed at elucidating the neurocognitive mechanisms of mindfulness has consistently identified a relationship between mindfulness and error monitoring. However, the exact nature of this relationship is unclear, with studies reporting divergent outcomes. The current study sought to clarify the ambiguity by addressing issues related to construct heterogeneity and technical variation in mindfulness training. Specifically, we examined the effects of a brief open monitoring (OM) meditation on neural (error-related negativity (ERN) and error positivity (Pe)) and behavioral indices of error monitoring in one of the largest novice non-meditating samples to date (N = 212). Results revealed that the OM meditation enhanced Pe amplitude relative to active controls but did not modulate the ERN or behavioral performance. Moreover, exploratory analyses yielded no relationships between trait mindfulness and the ERN or Pe across either group. Broadly, our findings suggest that technical variation in scope and object of awareness during mindfulness training may differentially modulate the ERN and Pe. Conceptual and methodological implications pertaining to the operationalization of mindfulness and its training are discussed.

Identification of Sinapine-Derived Choline from a Rapeseed Diet as a Source of Serum Trimethylamine N-Oxide in Pigs.

Choline and its metabolites have diverse and important functions in many physiological processes, especially for anabolic metabolism in growth and reproduction. Besides endogenous biosynthesis and direct choline supplement, choline esters in the diet are another source of choline in the body. Phenolic choline esters are a group of unique dietary choline esters rich in the seeds of Brassicaceae plants, among which sinapine is a choline ester of sinapic acid abundant in rapeseed. In this study, 40 nursery pigs were fed with rapeseed-derived feed ingredients (RSF) or soybean meal for 3 weeks (20 pigs/diet). The metabolic fate of sinapine-derived choline in RSF was examined by comparing the distribution of choline and its metabolites in digesta, liver, and serum samples by liquid chromatography-mass spectrometry analysis. The results showed that choline was released from extensive hydrolysis of sinapine in the small intestine. However, sinapine-derived choline did not increase the levels of choline and its major metabolites, including betaine, phosphocholine, and glycerophosphocholine, in the liver and serum. Instead, RSF feeding increased trimethylamine (TMA), the microbial metabolite of choline, in the large intestine and further increased trimethylamine N-oxide (TMAO), the oxidation metabolite of TMA, in the liver and serum. Overall, these results suggested that sinapine-derived choline from rapeseed feeding had limited influences on the post-absorption choline pool as a result of its low bioavailability but may serve as a major source of TMAO through microbial metabolism in nursery pigs. Improving the bioavailability of sinapine-derived choline might have the potential to modify the nutritional values and functionalities of rapeseed meal in swine feeding.

Effects of Tao-Hong-Si-Wu decoction on acute blood stasis in rats based on a LC-Q/TOF-MS metabolomics and network approach.

A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of Tao-Hong-Si-Wu decoction (THSWD) on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice-cold water following two injections with epinephrine. The hemorheological indicators [whole blood viscosity (WBV) and plasma viscosity (PV)] and the blood coagulation indicators [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved 10 pathways and five hub metabolites, namely, l-glutamate, l-phenylalanine, N-acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted to close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped to evaluate the effects of THSWD on acute blood stasis.

Traditional herbal formula Sini Powder extract produces antidepressant-like effects through stress-related mechanisms in rats.

Sini Powder (SP), a traditional Chinese herbal formula, has long been used to treat depression in patients, although the underlying mechanisms remain to be elucidated. In the present study, we found that rats treated with SP extract for 7 days showed a significant increase in swimming time and reduction in immobility time in forced swimming test in a dose-dependent manner, without changes in locomotion. These effects could be attributed to SP's modulation of the hypothalamus-pituitary-adrenal axis, because a single pretreatment of SP extract could rescue increased serum corticosterone and plasma adrenocorticotropin levels induced by acute elevated platform stress. A single pretreatment of SP extract could also elevate the mRNA expression of hippocampal glucocorticoid receptors. In conclusion, our results suggest that SP extract may act as an anti-stress medication to produce antidepressant-like effects.

Urine metabonomic study for blood-replenishing mechanism of Angelica sinensis in a blood-deficient mouse model.

This study aimed at determining the effects of Angelica sinensis (AS) on urinary metabolites in blood deficiency mice and exploring its replenishing blood mechanism. Gas chromatography-mass spectrometry (GC-MS) was applied to detect metabolites in the urine samples in different collection periods. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to investigate the differences in metabolic profiles among control group (CG), blood deficiency model group (MG), AS groups, and Colla Corii Asini group (CCAG). The potential biomarkers were identified based on the variable importance in the projection (VIP), T-test, and National Institute of Standards and Technology (NIST) and mass spectra library. The metabolites were analyzed using metabolomics pathway analysis (MetPA) to build the metabolic pathways. Our results indicated that, on the seventh day, the levels of glucose, lactic acid, pyruvic acid, alanine, acetoacetic acid, and citric acid changed significantly in blood deficiency mice. However, these metabolic deviations came to closer to normal levels after AS intervention. The reversing blood-deficiency mechanism of AS might involve regulating synthesis and degradation of ketone bodies, Pyruvate metabolism, TCA cycle, and Glycolysis/Gluconeogenesis. In conclusion, metabonomics is a robust and promising means for the identification of biomarkers and elucidation of the mechanisms of a disease, thereby highlighting its importance in drug discovery.

[Metabolomic evaluation for anti-inflammatory effect of volatile oils from different preparations of Angelicae Sinensis Radix].

To evaluate the anti-acute inflammation effects of volatile oils from different processed products of Angelicae Sinensis Radix(AS) in the rat model of acute inflammation established by the metabolomic method. Volatile oil of charred AS (C-VOAS), wine-processed AS (J-VOAS), locally processed AS (T-VOAS) and oil-process AS (Y-VOAS) were applied to intervene the rat acute paw swelling inflammation model induced by Carrageenan. Changes in serum HIS, 5-HT, PGE2 and TNF-α content in rats were detected. Gas chromatography-mass spectrometry was used to detect the metabolites in plasma. Potential biomarkers were investigated according to principal component analysis method and partial least-squares discriminant analysis. According to the results, C-VOAS and J-VOAS could significantly inhibit inflammatory mediators Histamine, 5-hydroxytryptamine, prostaglandin-E2 and cytokine tumor necrosis factor-alpha (P<0.01), and T-VOAS and Y-VOAS also showed a significantly inhibitory effect (P<0.05). Compared with the normal group, 14 endogenous metabolite biomarkers showed metabolic disturbance in plasma (P<0.05 or P<0.01). Compared with acute inflammation model group, C-VOAS and J-VOAS could better recover the levels of the endogenous metabolites (P<0.05 or P<0.01) than T-VOAS and Y-VOAS (P<0.05 or P<0.01). This study suggests that C-VOAS and J-VOAS show a better anti-inflammatory effect than T-VOAS and Y-VOAS. Therefore, the metabolomic method could be used to expound the anti-inflammatory mechanism of volatile oils from different processed products of AS, and provide a theoretical basis for clinical application of VOAS.

Urine metabonomic study for blood-replenishing mechanism of Angelica sinensis in a blood-deficient mouse model / 中国天然药物

This study aimed at determining the effects of Angelica sinensis (AS) on urinary metabolites in blood deficiency mice and exploring its replenishing blood mechanism. Gas chromatography-mass spectrometry (GC-MS) was applied to detect metabolites in the urine samples in different collection periods. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to investigate the differences in metabolic profiles among control group (CG), blood deficiency model group (MG), AS groups, and Colla Corii Asini group (CCAG). The potential biomarkers were identified based on the variable importance in the projection (VIP), T-test, and National Institute of Standards and Technology (NIST) and mass spectra library. The metabolites were analyzed using metabolomics pathway analysis (MetPA) to build the metabolic pathways. Our results indicated that, on the seventh day, the levels of glucose, lactic acid, pyruvic acid, alanine, acetoacetic acid, and citric acid changed significantly in blood deficiency mice. However, these metabolic deviations came to closer to normal levels after AS intervention. The reversing blood-deficiency mechanism of AS might involve regulating synthesis and degradation of ketone bodies, Pyruvate metabolism, TCA cycle, and Glycolysis/Gluconeogenesis. In conclusion, metabonomics is a robust and promising means for the identification of biomarkers and elucidation of the mechanisms of a disease, thereby highlighting its importance in drug discovery.

Metabolomics study of hematopoietic function of Angelica sinensis on blood deficiency mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (AS) has been used in traditional Chinese medicine for thousands of years to enrich and invigorate blood. In this study, the aim is to investigate the influence of AS on metabolism of blood deficiency mice model and to explore its anti-blood deficiency mechanism. MATERIALS AND METHODS: The blood deficiency mice model was induced by being hypodermically injected with N-acetyl phenylhydrazine (APH) and being intraperitoneally injected with cyclophosphamide (CTX). Gas chromatography-mass spectrometry (GC-MS), principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to identify potential biomarkers in plasma and splenic tissue. RESULTS: The levels of white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and platelet (PLT) showed a trend to return to control group after administrating with AS, while the dose of 10g/kg showed the best effect. Potential metabolite biomarkers (nine in the plasma and nine in the spleen homogenates) were identified in this study. These biomarkers were mainly related to five metabolic pathways, such as arachidonic acid metabolism, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, arginine and proline metabolism and TCA cycle. CONCLUSION: Metabolomics was used to reflect an organism׳s physiological and metabolic state comprehensively, indicating that metabolomics was a potentially powerful tool to reveal the anti-blood deficiency mechanism of AS.

[Comparative metabonomics study on urine in rat treated by Angelica sinensis volatile oil].

Metabonomics was employed to investigate the effect of Angelica sinensis volatile oil (ASVO) to the endogenous metabolites of normal rats, and to reveal the possible ways of metabolism in rats caused by ASVO. The fifty male Waster rats were randomly divided into five groups (each consists of 10 rats), such as control group, high dose group of ASVO, middle dose group of ASVO, low dose group of ASVO, and Aspirin group. They were given 0.9% saline, 0.352 mL x kg(-1) ASVO, 0.176 mL x kg(-1) ASVO, 0.088 mL x kg(-1) ASVO and ASP respectively with the equal volume of 0.2 mL. Drugs and vehicle were given for 3 successive days. The urine was collected at 12, 24, 36, 48 h after modeling with metabolic cages. Rat urine metabolic fingerprint in different stages was analyzed using GC-MS, based on which the principal component analysis (PCA)and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were established for metabonomic analysis. Potential biomarkers were screened by using variable importance in the projection (VIP) and T test. It was revealed that the middle dose of ASVO at 36 h induces a substantial change in rat urine. Compared with control group, seven kinds of endogenous metabolites in ASP group and ASVO group change significantly (P < 0.05), among which aconitic acid, succinic acid, citric acid, alpha-ketone glutaric acid, glycine and malic acid content had an upward trend (P < 0.05) and prostaglandin content had a downward trend (P < 0.01). The mechanism of ASVO and ASP have the similarity. It is likely that ASVO intervenes the metabolic process by affecting the energy, amino acid and lipid metabolism. Our work also indicates that rats administrated with ASVO can increase the energy metabolism of the body, induce the production of inflammatory substances and strengthen the body's immune ability. The result has also provide a proof for futher interpret ASVO pharmacological effects.

Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo.

UNLABELLED: Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here we show an innovative RNA-based targeted approach to enhance endogenous albumin production while reducing liver tumor burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBPα (CCAAT/enhancer-binding protein-α), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBPα-saRNA transfected HepG2 cells. Intravenous injection of C/EBPα-saRNA in a cirrhotic rat model with multifocal liver tumors increased circulating serum albumin by over 30%, showing evidence of improved liver function. Tumor burden decreased by 80% (P = 0.003) with a 40% reduction in a marker of preneoplastic transformation. Since C/EBPα has known antiproliferative activities by way of retinoblastoma, p21, and cyclins, we used messenger RNA (mRNA) expression liver cancer-specific microarray in C/EBPα-saRNA-transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis, and metastasis. Up-regulated genes were enriched for tumor suppressors and positive regulators of cell differentiation. A quantitative polymerase chain reaction (PCR) and western blot analysis of C/EBPα-saRNA-transfected cells suggested that in addition to the known antiproliferative targets of C/EBPα, we also observed suppression of interleukin (IL)6R, c-Myc, and reduced STAT3 phosphorylation. CONCLUSION: A novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumor burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model.

Comparative metabonomics study on urine in rat treated by Angelica sinensis volatile oil / 中国中药杂志

Metabonomics was employed to investigate the effect of Angelica sinensis volatile oil (ASVO) to the endogenous metabolites of normal rats, and to reveal the possible ways of metabolism in rats caused by ASVO. The fifty male Waster rats were randomly divided into five groups (each consists of 10 rats), such as control group, high dose group of ASVO, middle dose group of ASVO, low dose group of ASVO, and Aspirin group. They were given 0.9% saline, 0.352 mL x kg(-1) ASVO, 0.176 mL x kg(-1) ASVO, 0.088 mL x kg(-1) ASVO and ASP respectively with the equal volume of 0.2 mL. Drugs and vehicle were given for 3 successive days. The urine was collected at 12, 24, 36, 48 h after modeling with metabolic cages. Rat urine metabolic fingerprint in different stages was analyzed using GC-MS, based on which the principal component analysis (PCA)and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were established for metabonomic analysis. Potential biomarkers were screened by using variable importance in the projection (VIP) and T test. It was revealed that the middle dose of ASVO at 36 h induces a substantial change in rat urine. Compared with control group, seven kinds of endogenous metabolites in ASP group and ASVO group change significantly (P < 0.05), among which aconitic acid, succinic acid, citric acid, alpha-ketone glutaric acid, glycine and malic acid content had an upward trend (P < 0.05) and prostaglandin content had a downward trend (P < 0.01). The mechanism of ASVO and ASP have the similarity. It is likely that ASVO intervenes the metabolic process by affecting the energy, amino acid and lipid metabolism. Our work also indicates that rats administrated with ASVO can increase the energy metabolism of the body, induce the production of inflammatory substances and strengthen the body's immune ability. The result has also provide a proof for futher interpret ASVO pharmacological effects.

Two novel saponins of 20, 26-epoxy derivatives of pseudojujubogenin from the seeds of Hovenia trichocarpa.

Two new saponins of 20, 26-epoxy derivatives of pseudojujubogenin, hoduloside XI (1) and hoduloside XII (2) were isolated from the seeds of Hovenia trichocarpa. The structures of the new compounds were established by extensive NMR experiments and chemical methods. Hoduloside XI was confirmed to be 3-O-{ß-D-glucopyranosyl(1→3)-[ß-D-xylopyranosyl(1→2)]-α-L-arabinopyranosyl}-20, 26-epoxypseudojujubogenin. Hoduloside XII was identified as 3-O-{ß-D-xylopyranose(1→2)glucopyranosyl(1→3)[rhamnopyranose(1→2)]ß-D-glucopyranosyl}-20, 26-epoxypseudojujubogenin. The in vitro cytotoxic activity of compounds 1 and 2 was assayed. They displayed inhibitive activities against human cancer cell lines HL60 and K562.

Prophylactic pyridoxine was not able to reduce the incidence of capecitabine-induced hand-foot syndrome: A meta-analysis.

Hand-foot syndrome (HFS) is a dose-limiting adverse event of capecitabine, which commonly leads to early discontinuation of capecitabine-based therapy in the palliative and adjuvant settings. Although pyridoxine has been used for the prevention of capecitabine-associated HFS, its efficacy is controversial. The aim of this study was to evaluate whether prophylactic pyridoxine reduces the incidence of capecitabine-associated HFS by performing a meta-analysis of the literature involving available studies. Systematic searches for trials were undertaken through PubMed, Embase, Web of Science, the Cochrane Library, the American Society of Clinical Oncology (ASCO) and the ASCO Gastrointestinal Cancers Symposium, updated to March, 2013, to identify relevant studies. A meta-analysis was conducted with eligible studies that evaluated the efficacy of the prophylactic use of pyridoxine against capecitabine-induced HFS. We performed a meta-analysis of five studies (n=793 patients) that evaluated the efficacy of the prophylactic use of pyridoxine in cancer patients treated with capecitabine. The odds ratio (OR) comparing prophylactic pyridoxine to placebo was 0.91 [95% confidence interval (CI): 0.67-1.24] for HFS of all grades; OR=1.17 (95% CI: 0.82-1.67) for HFS ≥ grade 2 and OR=1.05 (95% CI: 0.60-1.85) for HFS ≥ grade 3. Based on our meta-analysis, prophylactic pyridoxine did not appear to reduce the incidence of HFS in patients receiving capecitabine.

Antitumor activities of dammarane triterpene saponins from Bacopa monniera.

Bioassay-guided methods were used to test the antitumor activity of methanol extract of the whole plant of Bacopa monniera (L.) Wettst. and four different fractions (petroleum ether, CHCl(3), EtOAc, and n-BuOH fractions) of the methanol extract. Among the five crude samples, n-BuOH fraction was noted to have the highest antitumor activity. The dammarane triterpene saponins isolated from n-BuOH fraction, bacopaside E (1) and bacopaside VII (3), had potential antitumor effect. 1 and 3 showed cytotoxicity of all the tested human tumor cell lines MDA-MB-231, SHG-44, HCT-8, A-549 and PC-3M in MTT assay in vitro, and showed 90.52 % and 84.13 % inhibition in mouse implanted with sarcoma S180 in vivo at the concentration of 50 micromol/kg, respectively. The remaining two compounds, bacopaside II (2) and bacopasaponin C (4) were found to be much less potent compared with 1 and 3. 1 and 3 significantly inhibited human breast cancer cell line MDA-MB-231 adhesion, migration and Matrigel invasion in vitro at the concentration of 50 micromol/L. Since no antitumor activities about the monomers from Bacopa monniera (L.) Wettst. have been reported, these results indicate that the mechanism of action of 1 and 3 needs further study.