Potential for the development of Taraxacum mongolicum aqueous extract as a phytogenic feed additive for poultry.

Introduction: Taraxacum mongolicum (TM) is a kind of medicinal and edible homologous plant which is included in the catalogue of feed raw materials in China. It is rich in polyphenols, flavonoids, polysaccharides and other active substances, and shows many benefits to livestock, poultry and aquatic products. The study aimed to assess the potential of TM aqueous extract (TMAE) as a substitute for poultry AGPs. Methods: A total of 240 one-day-old Arbor Acker broilers were randomly assigned to four groups and fed a basal diet (Con) supplemented with 500, 1000, and 2000 mg/kg TMAE (Low, Medium, and High groups). The growth performance of the broilers was measured on day 21 and day 42. At the end of the trial, the researchers measured slaughter performance and collected serum, liver, spleen, ileum, and intestinal contents to investigate the effects of TMAE on serum biochemistry, antioxidant capacity, immune function, organ coefficient, intestinal morphology, flora composition, and short-chain fatty acids (SCFAs). Results: The results showed that broilers treated with TMAE had a significantly higher average daily gain from 22 to 42 days old compared to the Con group. Various doses of TMAE resulted in different levels of improvement in serum chemistry. High doses increased serum alkaline phosphatase and decreased creatinine. TMAE also increased the antioxidant capacity of serum, liver, and ileum in broilers. Additionally, middle and high doses of TMAE enhanced the innate immune function of the liver (IL-10) and ileum (Occludin) in broilers. Compared to the control group, the TMAE treatment group exhibited an increase in the ratio of villi length to villi crypt in the duodenum. TMAE increased the abundance of beneficial bacteria, such as Alistipes and Lactobacillus, while reducing the accumulation of harmful bacteria, such as Colidextracter and Sellimonas. The cecum's SCFAs content increased with a medium dose of TMAE. Supplementing broiler diets with TMAE at varying doses enhanced growth performance and overall health. The most significant benefits were observed at a dose of 1000 mg/kg, including improved serum biochemical parameters, intestinal morphology, antioxidant capacity of the liver and ileum, immune function of the liver and ileum, and increased SCFAs content. Lactobacillus aviarius, norank_f_norank_o__Clostridia_UCG-014, and Flavonifractor are potentially dominant members of the intestinal microflora. Conclusion: In conclusion, TMAE is a promising poultry feed additive and 1000 mg/kg is an effective reference dose.

Morusinol Extracted from Morus alba Inhibits Cell Proliferation and Induces Autophagy via FOXO3a Nuclear Accumulation-Mediated Cholesterol Biosynthesis Obstruction in Colorectal Cancer.

The incidence rate of colorectal cancer (CRC) has been increasing significantly in recent years, and it is urgent to develop novel drugs that have more effects for its treatment. It has been reported that many molecules extracted from the root bark of Morus alba L. (also known as Cortex Mori) have antitumor activities. In our study, we identified morusinol as a promising anticancer agent by selecting from 30 molecules extracted from Morus alba L. We found that morusinol treatment suppressed cell proliferation and promoted apoptosis of CRC cells in vitro. Besides this, we observed that morusinol induced cytoprotective autophagy. The GO analysis of differentially expressed genes from RNA-seq data showed that morusinol affected cholesterol metabolism. Then we found that key enzyme genes in the cholesterol biosynthesis pathway as well as the sterol regulatory element binding transcription factor 2 (SREBF2) were significantly downregulated. Furthermore, additional cholesterol treatment reversed the anti-CRC effect of morusinol. Interestingly, we also found that morusinol treatment could promote forkhead box O3 (FOXO3a) nuclear accumulation, which subsequently suppressed SREBF2 transcription. Then SREBF2-controlled cholesterol biosynthesis was blocked, resulting in the suppression of cell proliferation, promotion of apoptosis, and production of autophagy. The experiments in animal models also showed that morusinol significantly impeded tumor growth in mice models. Our results suggested that morusinol may be used as a candidate anticancer drug for the treatment of CRC.

Facile fabrication of Artemisia sphaerocephala krasch gum hydrogels by radiation induced cross-linking polymerization and enhanced ultrahigh adsorption for methylene blue.

Although Artemisia sphaerocephala krasch gum (ASKG) has attracted growing attention in the field of medical engineering and food industries, however, there are few studies on the gelation of ASKG. In this paper, acrylic acid modified ASKG hydrogels were prepared by radiation induced grafting, cross-linking and polymerization technique for the first time. The semi-IPN structure was prepared by the cross-linked ASKG network and poly-AAc dispersed within the network. The effects of the adsorbed dose on the swelling ratio and gel fraction were investigated. The different acrylic acid content modified ASKG hydrogels (ASKGAAc1 and ASKGAAc2) for methyl blue (MB) adsorption were investigated, and the ASKG hydrogels was also studied for comparison. The influence of pH, contact time, initial concentration, temperature, ion strength on MB adsorption were tested. The results showed that acrylic acid can promote the formation of hydrogel and greatly enhanced the adsorption of ASKG. The adsorption isotherms were well obeyed the Langmuir model, and the maximum adsorption capacity for MB of ASKG, ASKGAAc1 and ASKGAAc2 were 571.43, 1517.8 and 1654.9 mg/g, respectively. Moreover, the MB adsorption by ASKG based hydrogels was exothermic, spontaneous, and more favorable at lower temperature. Furthermore, the adsorption-desorption experiments demonstrated a good reusability of these hydrogels.

Morusinol extracted from Morus alba induces cell cycle arrest and apoptosis via inhibition of DNA damage response in melanoma by CHK1 degradation through the ubiquitin-proteasome pathway.

BACKGROUD: Flavonoids have a variety of biological activities, such as anti-inflammation, anti-tumor, anti-thrombosis and so on. Morusinol, as a novel isoprene flavonoid extracted from Morus alba root barks, has the effects of anti-arterial thrombosis and anti-inflammatory in previous studies. However, the anti-cancer mechanism of morusinol remains unclear. PURPOSE: In present study, we mainly studied the anti-tumor effect of morusinol and its mode of action in melanoma. METHODS: The anti-cancer effect of morusinol on melanoma were evaluated by using the MTT, EdU, plate clone formation and soft agar assay. Flow cytometry was used for detecting cell cycle and apoptosis. The É£-H2AX immunofluorescence and the alkaline comet assay were used to detect DNA damage and the Western blotting analysis was used to investigate the expressions of DNA-damage related proteins. Ubiquitination and turnover of CHK1 were also detected by using the immunoprecipitation assay. The cell line-derived xenograft (CDX) mouse models were used in vivo to evaluate the effect of morusinol on tumorigenicity. RESULTS: We demonstrated that morusinol not only had the ability to inhibit cell proliferation, but also induced cell cycle arrest at G0/G1 phase, caspase-dependent apoptosis and DNA damage in human melanoma cells. In addition, morusinol effectively inhibited the growth of melanoma xenografts in vivo. More strikingly, CHK1, which played an important role in maintaining the integrity of cell cycle, genomic stability and cell viability, was down-regulated in a dose- and time-dependent manner after morusinol treatment. Further research showed that CHK1 was degraded by the ubiquitin-proteasome pathway. Whereafter, morusinol-induced cell cycle arrest, apoptosis and DNA damage were partially salvaged by overexpressing CHK1 in melanoma cell lines. Herein, further experiments demonstrated that morusinol increased the sensitivity of dacarbazine (DTIC) to chemotherapy for melanoma in vitro and in vivo. CONCLUSION: Morusinol induces CHK1 degradation through the ubiquitin-proteasome pathway, thereby inducing cell cycle arrest, apoptosis and DNA damage response in melanoma. Our study firstly provided a theoretical basis for morusinol to be a candidate drug for clinical treatment of cancer, such as melanoma, alone or combinated with dacarbazine.

Protective mechanisms of Leontopodium leontopodioides extracts on lipopolysaccharide-induced acute kidney injury viathe NF-κB/NLRP3 pathway / 中国天然药物

Sepsis-induced uncontrolled systemic inflammatory response syndrome (SIRS) is a critical cause of multiple organ failure. Acute kidney injury (AKI) is one of the most serious complications associated with an extremely high mortality rate in SIRS, and it lacked simple, safe, and effective treatment strategies. Leontopodium leontopodioides (Willd.) Beauv (LLB) is commonly used in traditional Chinese medicine for the treatment of acute and chronic nephritis. However, it remains unclear whether lipopolysaccharide (LPS) affects LPS-induced AKI. To identify the molecular mechanisms of LLB in LPS-induced HK-2 cells and mice, LLB was prepared by extraction with 70% methanol, while a lipopolysaccharide (LPS)-induced HK-2 cell model and an AKI model were established in this study. Renal histopathology staining was performed to observe the morphology changes. The cell supernatant and kidney tissues were collected for determining the levels of inflammatory factors and protein expression by ELISA, immunofluorescence, and Western blot. The results indicated that LLB significantly reduced the expression of IL-6 and TNF-α in LPS-induced HK-2 cells, as well as the secretion of IL-6, TNF-α, and IL-1β in the supernatant. The same results were observed in LPS-induced AKI serum. Further studies revealed that LLB remarkably improved oxidative stress and apoptosis based on the content of MDA, SOD, and CAT in serum and TUNEL staining results. Notably, LLB significantly reduced the mortality due to LPS infection. Renal histopathology staining results supported these results. Furthermore, immunofluorescence and Western blot results confirmed that LLB significantly reduced the expression of the protein related to the NF-κB signaling pathway and NLRP3, ASC, and Caspase-1 which were significantly increased through LPS stimulation. These findings clearly demonstrated the potential use of LLB in the treatment of AKI and the crucial role of the NF-κB/NLRP3 pathway in the process through which LLB attenuates AKI induced by LPS.

Exploring the Anti-inflammatory Effects of Protopine Total Alkaloids of Macleaya Cordata (Willd.) R. Br.

Macleaya cordata (Willd). R. Br. is a Chinese medicinal plant commonly used externally to treat inflammatory-related diseases such as arthritis, sores, and carbuncles. This study aimed to evaluate the anti-inflammatory activity of protopine total alkaloids (MPTAs) in Macleaya cordata (Willd.) R. Br. in vivo tests in rats with acute inflammation showed that MPTA (2.54 and 5.08 mg/kg) showed significant anti-inflammatory activity 6 h after carrageenan injection. Similarly, MPTA (3.67 and 7.33 mg/kg) showed significant anti-inflammatory activity in the mouse ear swelling test. In addition, the potential mechanisms of the anti-inflammatory effects of MPTA were explored based on network pharmacology and molecular docking. The two main active components of MPTA, protopine and allocryptopine, were identified, and the potential targets and signaling pathways of MPTA's anti-inflammatory effects were initially revealed using tools and databases (such as SwissTargetPrediction, GeneCards, and STRING) combined with molecular docking results. This study provides the basis for the application of MPTA as an anti-inflammatory agent.

Flavonoids from Rhododendron nivale Hook. f delay aging via modulation of gut microbiota and glutathione metabolism.

BACKGROUND: Rhododendron nivale Hook. f (R.n), one of the four Manna Stash used in Tibetan medicine to delay aging, possesses anti-aging pharmacological activity. However, which R.n ingredients contain anti-aging properties and the underlying mechanisms involved are unclear. HYPOTHESIS/PURPOSE: Based on interactions between gut microbiota and natural medicines and the important role of gut microbiota in anti-aging, the study investigated the hypothesis that R.n possesses anti-aging properties and the interaction of gut microbiota with R.n is responsible for its anti-aging effects. STUDY DESIGN: The primary active ingredients of R.n and their target function and pathway enrichment were explored. An aging mouse model was used to clarify the underlying anti-aging mechanisms of R.n. METHODS: Chromatography, spectroscopy, nuclear magnetic technology, and pharmacology were used to reveal the major active ingredients of ethanol extract residues of R.n (RNEA). The target function and pathway enrichment of these active ingredients were explored. Plasma metabolomics coupled with intestinal flora evaluation and bioinformatics analysis was used to clarify the underlying anti-aging mechanisms of RNEA. RESULTS: Myricetin-3-ß-D-xylopyranoside, hyperin, goospetin-8-methyl ether 3-ß-D-galactoside, and diplomorphanin B were separated and identified from RNEA. The network pharmacology study revealed that the active ingredients' target function and pathway enrichment focused mainly on the glutathione antioxidant system. In a D-galactose-induced mouse model of aging, RNEA was shown to possess suitable anti-aging pharmacological activity, as indicated by the amelioration of memory loss and weakened superoxide dismutase and glutathione peroxidase activities. Plasma metabolomics coupled with intestinal flora examination and bioinformatics analysis revealed that RNEA could regulate the expression of glutathione-related enzymes and ameliorate D-galactose-induced imbalances in methionine, glycine, and serine, and betaine and galactose metabolism. The results showed that RNEA reshaped the disordered intestinal flora and mitigated the D-galactose-mediated decline in glutathione oxidase expression, further confirming that the anti-aging effect of RNEA was closely related to regulation of the glutathione antioxidant system. CONCLUSION: RNEA, consisting of myricetin-3-ß-D-xylopyranoside, hyperin, goospetin-8-methyl ether 3-ß-D-galactoside, and diplomorphanin B, possesses anti-aging activity. The anti-aging effect of RNEA might be due to reshaping intestinal flora homeostasis, increasing the expression of glutathione peroxidase 4 in the intestines and liver, enhancing glutathione peroxidase activity, and reinforcing the glutathione antioxidant system.

Safety assessment of MPTA: An oral acute and 90-day sub-chronic toxicity study in Sprague-Dawley rats.

MPTA is a novel extract product derived from Macleaya cordata (Willd.) R. Br., which has good anti-inflammatory and antioxidant activity. The aim of this study was to investigate the acute oral toxicity and 90-day sub-chronic oral toxicity of MPTA. In the acute toxicity study, 50 SD rats of both sexes were randomly divided into 5 groups and dosed in a gradient from 197.53 mg/kg to 1000.00 mg/kg bw. Toxic effects were observed up to 14 days and LD50 was calculated. In a subchronic toxicity test, male and female SD rats were orally dosed repeatedly with 96.40, 19.28, 3.86 mg/kg bw of MPTA for 90 days. In addition, a control group was set up in the subchronic study. The acute toxicity test showed that the oral LD50 of MPTA was 481.99 mg/kg with a 95% confidence interval of 404.24-574.70 mg/kg. MPTA did not appear to induce toxic effects in the longer term in terms of food and water consumption, weight gain, haematological and clinical biochemical parameters and pathological examination. The first data on the potential toxicity of MPTA was provided to highlight the safety of short-term to longer-term oral administration of MPTA, and the experimental results yield and establish a NOEAL of 96.40 mg/kg/d for MPTA.

Alternation of EEG Characteristics During Transcutaneous Acupoint Electrical Stimulation-Induced Sedation.

Recent studies have shown that applying acupuncture during general anesthesia can reduce the dosage of anesthetics. Hence, it is speculated that acupuncture may have a sedative effect. However, existing studies employed acupuncture in combination with anesthetics, which makes determine acupuncture's role in producing sedation difficult. In this work, we investigated the sedative effect of acupuncture by using transcutaneous acupoint electrical stimulation (TAES) at bilateral Zusanli (ST36), Shenmen (HT7) and Sanyinjiao (SP6). Using a cross-over design, 2 separate sessions, that are, the resting and TAES sessions, were conducted for each subject. The sedative effect was quantified by using the bispectral index (BIS). The difference in brain activities between resting and TAES sessions was investigated by analyzing the simultaneously recorded EEG signals. Our results showed that a statistically significant difference in BIS values existed between resting and TAES sessions, which suggested that TAES alone was capable of inducing observable sedation. Using power spectrum analysis, we showed that TAES-induced sedation was accompanied by a reduction in alpha band power and an increment in delta band power. Permutation entropy was lower during the TAES session, which suggested that TAES reduced the complexity of the EEG signal. Moreover, a significant reduction in the global strength of brain functional connections was observed during TAES. These findings suggest that TAES alone can induce observable sedative effects, and this sedation effect is accompanied by changes in brain activities that have shown to be correlated with consciousness.

Changes in metabolism modulate induced by viroid infection in the orchid Dendrobium officinale.

Dendrobium officinale is an important traditional Chinese medicinal herb, and the stem tissue is the main medicinal that is harvested from D. officinale. Recently, the first viroid was identified from D. officinale in China, and it has been named Dendrobium viroid (DVd). Whether DVd interferes with metabolic pathways in dendrobium plants and affects the medicinal value of the host is unknown. In this study, metabolomics data from stem tissues supported by transcriptome studies were used to investigate how metabolism modulate of D. officinale is altered by DVd infection. Our results show that metabolism of D. officinale is reprogrammed in many ways during DVd infection, and this is reflected by significant changes in the levels of flavonoids, alkaloids, and phenolic acids. Furthermore, we found that DVd infection significantly decreased the accumulation of flavonoids and alkaloid metabolites in infected stems, and the decreases in these metabolites appears to affect the medicinal components of the infected plants, weakening the host antiviral immune response as well. Conversely, phenolic acids occupy a larger proportion of the up-regulated metabolites from DVd infection in comparison with the mock-inoculated control, and the increase in the total phenolic acids may reflect the activation of the pathogen defense response in D. officinale. Taken together, our results provide an interesting overview and give a better understanding of the relationship between metabolism and DVd infection in the orchid D. officinale.

Berberine improves intralipid-induced insulin resistance in murine.

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 µM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.

HuoXue QianYang QuTan Recipe attenuates left ventricular hypertrophy in obese hypertensive rats by improving mitochondrial function through SIRT1/PGC-1α deacetylation pathway.

Mitochondrial dysfunction plays a vital role in the progression of left ventricular hypertrophy (LVH). Previous studies have confirmed that the disorder of SIRT1/PGC-1α deacetylation pathway aggravated mitochondrial dysfunction. HuoXue QianYang QuTan Recipe (HQQR) is a commonly used prescription that has shown therapeutic effects on obesity hypertension and its complications. However, the potential mechanisms are still unclear. In the present study, obesity hypertension (OBH) was established in rats and we investigated the efficacy and mechanisms of HQQR on LVH. Rats were divided into the five groups: (1) WKY-ND group, (2) SHR-ND group, (3) OBH-HF group, (4) OBH-HF/V group and (5) OBH-HF/H group. We evaluated body weight, Lee index and blood pressure (BP) before and every 2 weeks after treatment. After 10 weeks of treatment, we mainly detected glycolipid metabolic index, the severity of LVH, mitochondrial function along with SIRT1/PGC-1α deacetylation pathway. Our results showed that HQQR significantly lowered body weight, Lee index, BP and improved the disorder of glycolipid metabolism in OBH rats. Importantly, we uncovered HQQR could alleviate mitochondrial dysfunction in OBH rats by regulating SIRT1/PGC-1α deacetylation pathway. These changes could be associated with the inhibition of LVH.

[Systematic review of efficacy and safety of Lianhua Qingwen Capsules in treatment of viral influenza].

To evaluate the efficacy and safety of Lianhua Qingwen Capsules in the treatment of viral influenza in order to guide clinical medication. Randomized controlled trials(RCTs) regarding Lianhua Qingwen Capsules for treatment of viral influenza were searched in the CNKI, WanFang, VIP, SinoMed and PubMed. The quality of papers selected based on the inclusion criteria were assessed according to the Cochrane collaboration method and Meta-analysis was performed by using RevMan 5.3 software. A total of 8 articles were included, with a total sample size of 955 cases, including 478 cases in the treatment group, and 477 cases in the control group. In terms of the therapeutic effect, Lianhua Qingwen Capsules group was superior to the control group, with a total effective rate RR=1.20, 95%CI [1.09,1.32], P=0.70; recovery rate of body temperature RR=1.13, 95%CI [1.02,1.24], P=0.001; rate of symptom improvement RR=1.18, 95%CI [1.12,1.24], P=0.16. In terms of adverse reactions, the control group was superior to Lianhua Qingwen Capsules, with the incidence of adverse reactions RR=1.54, 95%CI [0.73,3.24], P=0.93. Lianhua Qingwen Capsules has a better therapeutic effect on viral influenza, but the incidence of adverse reactions is high, and its safety must be taken seriously. Given the small number of documents included and the low quality, the efficacy and safety of Lianhua Qingwen Capsules shall be confirmed by more high-quality clinical studies.

[Acupuncture combined with herbal-cake partitioned moxibustion is superior to routine acupuncture in the treatment of peripheral facial paralysis].

OBJECTIVE: To observe the clinical effect of acupuncture combined with herbal-cake (Qianzhengsan) partitioned moxibustion at Xiaguan (ST7), Qianzheng (EX-HN), etc. for patients with peripheral facial paralysis. METHODS: Seventy-eight patients with peripheral facial paralysis (within 7 days) were divided into acupuncture plus moxibustion (Acu-Moxi) group and routine acupuncture (control) group (n＝38 cases in each). Patients of the control group were treated by routine acupuncture of unilateral or bilateral Yangbai (GB14), Sibai (ST2), Taiyang (EX-HN5), Quanliao (SI18), Jiache (ST6), Dicang (ST4), Yifeng (SJ17), Hegu (LI4) and Zusanli (ST36), and those of the Acu-Moxi group were treated by routine acupuncture of the above-mentioned acupoints in combination with herbal-cake-partitioned moxibustion at ST7 and EX-HN. The treatment was conducted once daily for 20 days. The House-Brackmann facial grading scale (H-B FGS) was used to assess the degree of facial nerve palsy (Ⅰ－Ⅵ grades), the modified Portmann scale used to assess the severity of facial paralysis including the situations of movement of eyebrow raising, eye closing, cheek bulging, pouting, teeth showing and nostril widening, and symmetry during resting state (20 points in total) and the facial disability index (FDI) used to rate the physical function (FDIP) and social life function (FDIS) (5－30 points in total). The clinical efficacy of each group was evaluated after the treatment. RESULTS: After the treatment, the number of patients with H-B FGS grade IV and V and FDIS scores were significantly decreased, and patients' number of H-B FGS grade I and II , Portmann scale and FDIP scores were significantly increased in both control and Acu-Moxi groups in comparison with their own pre-treatment (P<0.01), suggesting an improvement of facial nerve function after treatment. The patients' number of H-B FGS grade I and II and Portmann scores of the Acu-Moxi group was significantly higher than those of the control group (P<0.05, P<0.01), but no significant differences were found between two groups in the FDIP and FDIS scores (P>0.05). Of the two 38 patients in the control group and Acu-Moxi group, 8 (21.05%) and 15 (39.47%) were cured, 7 (18.42%) and 8 (21.05%) experienced marked improvement, 14 (36.84%) and 13 (34.21%) were effective, and 9 (23.68%) and 2 (5.26%) invalid, with the effective rates being 76.32% and 94.74%, respectively. The therapeutic effect of the Acu-Moxi group was evidently superior to that of the control group (P<0.05). CONCLUSION: The acupuncture combined with Qianzhengsan-partitioned moxibustion is considerably superior to routine acupuncture in improving clinical symptoms and signs of peripheral facial paralysis patients.

Melanogenesis-Inhibitory and Cytotoxic Activities of Triterpene Glycoside Constituents from the Bark of Albizia procera.

Five oleanane-type triterpene glycosides including three new ones, proceraosides E-G (1-3), were isolated from a MeOH-soluble extract of Albizia procera bark. The structures of 1-3 were determined by use of NMR spectra, HRESIMS, and chemical methods. Compounds 1-5 exhibited inhibitory activities against the proliferation of the A549, SKBR3, AZ521, and HL60 human cancer cell lines (IC50 0.28-1.8 µM). Additionally, the apoptosis-inducing activity of compound 2 was evaluated by Hoechst 33342 staining and flow cytometry, while the effects of 2 on the activation of caspases-9, -8, and -3 in HL60 cells were revealed by Western blot analysis.

Identification and screening of cardiac glycosides in Streptocaulon griffithii using an integrated data mining strategy based on high resolution mass spectrometry.

The present study was designed to develop a practical strategy to tackle the problem of lacking standard compounds and limited references for identifying structure-related compounds in Streptocaulon griffithii Hook. f., especially those in trace concentrations, with a focus on antitumor activity. The cardiac glycosides (CGs)-enriched part was determined using in vitro bioactive assays in three cancer cell lines and then isolated using macroporous resins. The MS and MS/MS data were acquired using a high performance liquid chromatography coupled with hybrid quadrupole-time of flight (HPLC-Q-TOF-MS) system. To acquire data of trace compound in the extract, a multiple segment program was applied to modify the HPLC-Q-TOF-MS method. A mass defect filter (MDF) approach was employed to make a primary MS data filtration. Utilizing a MATLAB program, the redundant peaks obtained by imprecise MDF template calculated with limited references were excluded by fragment ion classification, which was based on the ion occurrence number in the MDF-filtered total ion chromatograms (TIC). Additionally, the complete cleavage pathways of CG aglycones were proposed to assist the structural identification of 29 common fragment ions (CFIs, ion occurrence number ≥ 5) and diagnostic fragment ions (DFIs, ion occurrence number < 5). As a result, 30 CGs were filtered out from the MDF results, among which 23 were identified. This newly developed strategy may provide a rapid and effective tool for identifying structure-related compounds in herbal medicines.

Monocarboxylate transporters MCT1 and MCT4 are independent prognostic biomarkers for the survival of patients with clear cell renal cell carcinoma and those receiving therapy targeting angiogenesis.

BACKGROUND: Prognostic biomarkers for patients with clear cell renal cell carcinoma (ccRCC), particularly those receiving therapy targeting angiogenesis, are not well established. In this study, we examined the correlations of monocarboxylate transporter 1 (MCT1) and MCT4, 2 critical transporters for glycolytic metabolism, with various clinicopathological parameters as well as survival of patients with ccRCC and those treated with vascular endothelial growth factor receptor (VEGFR) inhibitors. METHODS: A cohort of 150 ccRCC patients were recruited into this study. All patients underwent radical or partial nephrectomy as the first-line treatment, and 38 received targeted therapy (sorafenib or sunitinib) after the surgery. Expression levels of MCT1, MCT4, and CD34 were examined by immunohistochemistry. Correlations between MCT1 or MCT4 expression and different clinicopathological parameters or patient survival were analyzed among all as well as patients receiving targeted therapy. RESULTS: MCT1 or MCT4 expression did not significantly correlate with sex, age, tumor diameter, microvascular density, tumor staging, pathological Furmann grade, or MSKCC (P>0.05). High expression of either MCT1 or MCT4 significantly correlated with reduced overall survival (OS) and progression-free survival (PFS) among the total cohort of ccRCC patients. For patients receiving targeted therapy, high expression of either MCT1 or MCT4 significantly correlated with reduced PFS, but not OS. Both conditions were independent prognostic biomarkers for reduced PFS among all patients or those receiving targeted therapy. CONCLUSION: MCT1 and MCT4 are prognostic biomarkers for patients with ccRCC or those receiving targeted therapy. High expression of these 2 proteins predicts reduced PFS in these patients.

Naoxintong Retards Atherosclerosis by Inhibiting Foam Cell Formation Through Activating Pparα Pathway.

BACKGROUNDS: We recently reported that Naoxintong (NXT), a China Food and Drug Administration (FDA)-approved cardiac medicine, could reduce the plaque size, but the underlying mechanism remains elusive now. OBJECTIVE: In this study, we investigated the effects of NXT on foam cell accumulation both in vivo and in vitro and explored related mechanisms. METHOD: THP-1 cells and bone marrow-derived macrophages were incubated with oxidized low-density lipoprotein (ox-LDL) with/without Naoxintong. ApoE-/- mice fed an atherogenic diet were administered to receive NXT for eight weeks. Macrophage-derived foam cell formation in plaques was measured by immunohistochemical staining. Expression of proteins was evaluated by Western blot. Lentivirus was used to knockdown PPARα in THP-1 cells. RESULTS: After NXT treatment, foam cell accumulation was significantly reduced in atherosclerotic plaques. Further investigation revealed that oxidized low-density lipoprotein (ox-LDL) uptake was significantly decreased and expression of scavenger receptor class A (SR-A) and class B (SR-B and CD36) was significantly downregulated post-NXT treatment. On the other hand, NXT increased cholesterol efflux and upregulated ATP-binding cassette (ABC) transporters (ABCA-1 and ABCG-1) in macrophages. Above beneficial effects of NXT were partly abolished after lentiviral knockdown of PPARα. CONCLUSION: Our findings suggest that NXT could retard atherosclerosis by inhibiting foam cell formation through reducing ox-LDL uptake and enhancing cholesterol efflux and above beneficial effects are partly mediated through PPARα pathway.

New phenolic acids from Salvia yunnanensis C.H.Wright.

Two new phenolic acids, ethyl pro-lithospermate (1), n-butyl pro-lithospermate (2) were isolated from Salvia yunnanensis C.H.Wright, along with nineteen known compounds (3-21). The structures of the isolated compounds were elucidated on the basis of extensive spectrometry and by comparing their physical and spectroscopic data to the literature. Among them, compounds 11, 12 and 14-16 were firstly isolated from S. yunnanensis C.H.Wright. Some of the isolated compounds were evaluated for their neuroprotection. Compounds 10-12 showed significant neuroprotective effects in PC12 cells and compounds 1, 4-7 displayed moderate neuroprotective effects.

[Clinical Observation of Chaihu Guizhi Decoction in Treating SAPHO Syndrome].

Objective To evaluate the clinical efficacy and safety of Modified Chaihu Guizhi De- coction on SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Methods Totally 40 patients with SAPHO syndrome were randomized to the treatment group(20 cases) and control group(20 cases). The treatment group was treated with Modified Chaihu Guizhi Decoction, and the control group with alendronate sodium 70 mg each week. The therapeutic course for all was 12 weeks. The Visual Analogue Scale (VAS) pain scores, bath ankylosing spondylitis activity index (BASDAI) , bath ankylosing spondylitis functional index(BASFI) , erythrocyte sedimentation rate(ESR) and hypersensitivity C reactive protein (hs-CRP) were measured before and after treatment. Adverse events were observed. Results The VAS, BASDAI, and BASFI score significantly improved compared with baseline in the treatment group (P <0. 01 , P <0. 05). The VAS and BASDAI score of the treatment group improved compared with the control group after treatment (P <0. 05). Three patients in the control group reported adverse events with digestive tract symptoms, while there was no obvious adverse drug reactions in the treatment group. Conclusions Modified Chaihu Guizhi Decoction was superior to alendronate sodium in the treat- ment of SAPHO syndrome without obvious adverse drug reactions.