Preparation, characterization, and bioavailability evaluation of antioxidant phosvitin peptide-ferrous complex.

BACKGROUND: Iron deficiency anemia (IDA) is one of the commonest global nutritional deficiency diseases, and the low bioavailability of iron is a key contributing factor. The peptide-iron complex could be used as a novel iron supplement to improve iron bioavailability. RESULTS: In this study, antioxidant low molecular weight (<3 kDa) phosvitin peptide (named PP-4) was separated to prepare a phosvitin peptide-ferrous complex (named PP-4-Fe); then the structural conformation of PP-4-Fe was characterized and its bioavailability by in vitro digestion was evaluated. The results showed that PP-4 had good ferrous-binding activity with 96.14 ± 2.86 µg Fe2+ mg-1 , and had a strong antioxidant effect with 995.61 ± 79.75 µmol TE mg-1 in 2,2'-azinobis'3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 62.3 ± 3.95 µmol FeSO4 mg-1 in ferric ion reducing antioxidant power (FRAP). After ferrous binding, the FRAP activity of PP-4-Fe, enhanced by 1.8 times, formed a more ordered structure with an increase in α-helix and decrease in γ-random coil. The ferrous binding sites of PP-4 involved were the amino, carboxyl, imidazole, and phosphate groups. The PP-4-Fe complex displayed excellent gastrointestinal stability and antioxidant effects during digestion. The iron dialysis percentage of PP-4-Fe was 74.59% ± 0.68%, and increased to 81.10% ± 0.89% with the addition of 0.25 times vitamin C (VC). This indicated that PP-4-Fe displayed excellent bioavailability and VC in sufficient quantities had a synergistic effect on improving bioavailability. CONCLUSIONS: This study demonstrated that antioxidant phosvitin peptide was an efficient delivery system to protect ferrous ions and suggested that the phosvitin peptide-ferrous complex has strong potential as a ferrous supplement. © 2023 Society of Chemical Industry.

Uncovering the pharmacological mechanism of Shou Tai Wan on recurrent spontaneous abortion: A integrated pharmacology strategy-based research.

ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.

Binding mechanism and bioavailability of a novel phosvitin phosphopeptide (Glu-Asp-Asp-pSer-pSer) calcium complex.

Phosvitin has excellent calcium binding capacity, related to its phosphopeptides. The phosphopeptides may be used as functional ingredients for improving calcium bioavailability, but the calcium-binding mechanism is unclear. In this study, a novel phosvitin phosphorylated pentapeptide (Glu-Asp-Asp-pSer-pSer, EDDpSpS) was selected to prepare an EDDpSpS calcium complex (EDDpSpS-Ca), and the calcium-binding mechanism and bioavailability investigated. The calcium-binding capacity of EDDpSpS was up to 468 ± 152.80 mg/g. Calcium ions prompted the folding of the EDDpSpS structure to form spherical nanoparticles. The calcium binding sites of EDDpSpS involved peptide bonds, carboxyl, amino, and phosphate groups. Molecular forces involved in these interactions were electrostatic in nature. Moreover, EDDpSpS-Ca had excellent bioavailability when compared to CaCO3, calcium lactate, and d-calcium gluconate. This study revealed the calcium-binding mechanism of phosvitin phosphopeptide, and suggested that EDDpSpS-Ca has the potential to be a novel, efficient, and promising calcium supplement.

Safety and efficacy of probiotic supplementation in 8 types of inflammatory arthritis: A systematic review and meta-analysis of 34 randomized controlled trials.

Objective: To evaluate Safety and efficacy of probiotic supplementation in inflammatory arthritis. Methods: The literature on the treatment of inflammatory arthritis with probiotics has been collected in databases such as CNKI, Pubmed, Cochrane library, Embase, etc. The search time is for them to build the database until May 2022. The included literatures are randomized controlled trials (RCTs) of probiotics in the treatment of hyperuricemia and gout. The Cochrane risk assessment tool was used for quality evaluation, and the Rev Man5.3 software was used for meta-analysis. Results: A total of 37 records were finally included, involving 34 RCTs and 8 types of autoimmune disease (Hyperuricemia and gout, Inflammatory bowel disease arthritis, juvenile idiopathic arthritis [JIA], Osteoarthritis [OA], Osteoporosis and Osteopenia, Psoriasis, rheumatoid arthritis (RA), Spondyloarthritis). RA involved 10 RCTs (632 participants) whose results showed that probiotic intervention reduced CRP. Psoriasis involved 4 RCTs (214 participants) whose results showed that probiotic intervention could reduce PASI scores. Spondyloarthritis involved 2 RCTs (197 participants) whose results showed that probiotic intervention improved symptoms in patients. Osteoporosis and Ostepenia involving 10 RCTs (1156 participants) showed that probiotic intervention improved bone mineral density in patients. Hyperuricemia and gout involving 4 RCTs (294 participants) showed that probiotic intervention improved serum uric acid in patients. OA involving 1 RCTs (433 participants) showed that probiotic intervention improved symptoms in patients. JIA involving 2 RCTs (72 participants) showed that probiotic intervention improved symptoms in patients. Inflammatory bowel disease arthritis involving 1 RCTs (120 participants) showed that probiotic intervention improved symptoms in patients. All of the above RCTs showed that probiotics did not increase the incidence of adverse events. Conclusion: Probiotic supplements may improve Hyperuricemia and gout, Inflammatory bowel disease arthritis, JIA, OA, Osteoporosis and Osteopenia, Psoriasis, RA, Spondyloarthritis. However, more randomized controlled trials are needed in the future to determine the efficacy and optimal dosing design of probiotics. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021286425, identifier CRD42021286425.

The Hydrolytic Peptides of Soybean Protein Induce Cell Cycle Arrest and Apoptosis on Human Oral Cancer Cell Line HSC-3.

Protein hydrolysates from various sources, including tuna cooking juice, soy protein isolate, sodium caseinate, wheat gluten and skin gelatin from porcine, tilapia, halibut and milkfish were analyzed to screen their antiproliferative activities against the human oral squamous carcinoma cell line, HSC-3. The soy protein isolate was selected for further investigations based on its hydrolysates with bromelain (SB) and thermolysin (ST), showing the greatest inhibition of cell growth. The SB and ST hydrolysates showed antiproliferative activities up to 35.45-76.39% against HSC-3 cells at 72 h, and their IC50 values were 0.74 and 0.60 mg/mL, respectively. SB and ST induced cell cycle arrest in the S phase through a pathway independent of p21 and p27 protein expression. Further, ST induced the apoptosis of HSC-3 cells by downregulating expression of Bcl-2, PARP, caspase 3 and caspase 9, but an upregulating expression of p53 and cleaved caspase 3. Unlike ST, SB may induce necrosis on HSC-3 cells. Thus, soybean hydrolysates may be a good source for providing antiproliferative peptides against HSC-3, while SB and ST may have the potential to be developed as functional foods.

Systematic Pharmacology-Based Strategy to Explore the Molecular Network Mechanism of Modified Taohong Siwu Decoction in the Treatment of Premature Ovarian Failure.

OBJECTIVE: To explore the molecular network mechanism of modified Taohong Siwu Decoction (MTHSWD) to interfere with premature ovarian failure based on systematic pharmacological strategy. METHODS: The network pharmacology strategy was used to explore the potential mechanism of MTHSWD intervention in POF, and then it was verified through animal experiments. Mouse zona pellucida 3 was used as an antigen to subcutaneously immunize BALB/c female mice to establish an immune POF model. Mice were divided into MTHSWD low-, medium-, and high-dose groups, positive control group, model group, and normal group. After 30 days of drug intervention, ovarian tissue was taken for pathological hematoxylin-eosin (HE) staining, and immunohistochemical methods were used to detect the expression of TGF-ß1 and TGF-ßRII and Smad2/3 protein expression in follicular wall granular cells and ovarian tissue, respectively. RESULTS: Network pharmacology studies have shown that MTHSWD may interfere with the TGF-ß signaling pathway. Animal experimental research shows that, compared with the model group, the number of ovarian mature follicles in the MTHSWD groups and the positive group was significantly increased, and the number of atresia follicles decreased. Immunohistochemistry showed that, compared with the control group, the expression of TGF-ß1, TGF-ßRII, and Smad2/3 in the follicular wall granulosa cells and ovarian tissues of MTHSWD groups was significantly higher than that of the model group (P < 0.05). CONCLUSION: MTHSWD may improve the ovarian function of POF mice by upregulating the protein expression of granulosa cells TGF-ß1, TGF-ßRII, and Smad2/3.

Structural Characteristic and In-Vitro Anticancer Activities of Dandelion Leaf Polysaccharides from Pressurized Hot Water Extraction.

Dandelion (Taraxacum mongolicum Hand.-Mazz.) is a medicinal and edible plant. Dandelion has great development value for its health promoting benefits; additionally, Dandelion grows almost anywhere in the world. In this study, we report the structural characteristics and anti-cancer activity of novel dandelion leaf polysaccharides extracted by pressurized hot water extraction at 120 °C (DLP120) with Mw relative to dextran of 1.64 × 106 Da. Structural analysis indicated that DLP120 is a complex polysaccharide composed of pectin and arabinogalactan. It was mainly composed of arabinose (32.35 mol%) and galactose (44.91 mol%). The main glycosidic linkages of DLP120 were 4-ß-D-Galp, 4-α-D-GalpA, T-ß-D-Galp, 5-α-L-Araf, 3,5-α-L-Araf, and T-α-L-Araf. In vitro, DLP120 inhibited HepG2 cell proliferation in a dose-dependent manner by inducing cell apoptosis. Cell cycle detection results revealed that DLP120 mainly arrests the cell cycle in S phase. Cells treated with DLP120 displayed obvious apoptotic morphology, including cell volume shrinks and cytoskeleton breaks down. In short, DLP120 has potential as an anti-cancer agent.

Exploring the Effect of Jiawei Buguzhi Pills on TGF-ß-Smad Pathway in Postmenopausal Osteoporosis Based on Integrated Pharmacological Strategy.

OBJECTIVE: To explore the effect of Jiawei Buguzhi Pills (JWBGZP) on the TGF-ß-Smad pathway in postmenopausal osteoporosis (PMO) based on integrated pharmacological strategy. METHOD: The ETCM database was used to collect JWBGZP. GeneCards and OMIM databases were utilized to obtain PMO-related genes. Cytoscape was used for network construction and analysis, and DAVID was used for GO and KEGG enrichment analysis of key targets. Animal experiments and cell experiments were conducted to further explore the mechanism. The bone mass density was detected by dual-energy X-ray bone densitometer. The TGF-ß1 and Smad4 mRNA in bone tissue were detected by RT-qPCR. The TGF-ß1 and Smad4 protein in bone tissue were detected by the western blot. The TGF-ß1 and Smad4 protein in osteoblasts were determined by immunohistochemistry. RESULT: A total of 721 JWBGZP potential targets and 385 PMO-related genes were obtained. The enrichment analysis showed that JWBGZP may regulate the TGF-beta signaling pathway, oxidation-reduction process, aging, response to hypoxia, response to ethanol, negative regulation of cell proliferation, PI3K-Akt, HIF-1, and other signaling pathways. The animal experiments showed that compared with the model group, the femoral bone mineral density and lumbar bone mineral density of the JWBGZP group increased (P < 0.05); the expression levels of TGF-ß1 and Smad mRNA and proteins in the JWBGZP group were significantly higher (P < 0.05). The cell experiment results showed a large number of osteoblast stained blue-purple and orange-red calcified nodules. The expression levels of TGF-ß1 and Smad proteins in the JWBGZP group were significantly higher than those in the blank control group and the sham operation group, and the protein expression levels in the model group were the lowest (P < 0.05). CONCLUSION: JWBGZP may be involved in PI3K-Akt, HIF-1, estrogen, prolactin, and other signaling pathways and regulate MAPK1, AKT1, PIK3CA, JAK2, and other gene targets, regulate bone metabolism, and thereby treat PMO.

Apoptosis of hepatocellular carcinoma HepG2 cells induced by seleno-ovalbumin (Se-OVA) via mitochondrial pathway.

Seleno-ovalbumin (Se-OVA) was a selenium conjugating protein synthesized by the combination of ovalbumin (OVA) and inorganic selenium. In this paper, the structure of Se-OVA was characterized, and the anticancer effect of Se-OVA on hepatocellular carcinoma HepG2 cells was investigated. Through FT-IR, UV, endogenous fluorescence and XRD assays, it was found that the structural characterization of Se-OVA changed after seleno-modification. In addition, the cell assays showed that Se-OVA could induce apoptosis of HepG2 cells by arresting cell cycle in S phase, generating intracellular reactive oxygen species, reducing the mitochondrial transmembrane potential, and triggering the Bax- and Bcl-2-mediated mitochondria apoptosis pathway. These findings revealed that Se-OVA might serve as a novel anticancer drug for cancer adjuvant therapy.

Isolation of a novel calcium-binding peptide from phosvitin hydrolysates and the study of its calcium chelation mechanism.

A new peptide with strong calcium binding capacity was isolated from phosvitin hydrolysates. Taking calcium chelating rate as an indicator, phosvitin hydrolysates were separated gradually by anion-exchange chromatography, gel filtration chromatography and reversed-phase high performance liquid chromatography. A peptide with a molecular weight of 1106.44402 Da was identified by liquid chromatography-electrospray/mass spectrometry (LC-ESI/MS), and its amino acid sequence was DEEENDQVK, the calcium binding capacity reached 151.10 ± 3.57 mg/g. Its chelating mechanism was investigated. Results showed that, the ß-sheet structure of peptide increased after adding calcium ion, and the main binding sites were carboxyl oxygen atom and amino nitrogen atom. In vitro simulated digestion experiments showed that, the solubility and dialysis rate of calcium in peptide-calcium chelate were higher than those in CaCO3 and D-calcium gluconate. This finding would promote the development of calcium supplements from food resources.

Systematic biological and proteomics strategies to explore the regulation mechanism of Shoutai Wan on recurrent spontaneous Abortion's biological network.

ETHNOPHARMACOLOGICAL RELEVANCE: Shoutai Wan (STW) is a classic herbal formula for the treatment of recurrent spontaneous abortion (RSA), and clinical studies have shown the effectiveness of STW on RSA. However, the molecular mechanism of STW treatment of RSA is still unclear. METHODS: (1) Animal experiments: The normal pregnancy model was established with CBA/J*BALB/C, and the RSA model was established by CBA/J*DBA/2. The RSA model CBA/J*DBA/2 pregnant mice were randomly divided into four groups (RSA model group, STW low, medium and high dose groups) according to the order of pregnancy, respectively. The drug administration starts from the first day of pregnancy to the 14th day of pregnancy. The embryo loss rate (ELR) of each group was calculated. (2) Proteomic analysis of decidual tissue: The total protein of decidual tissue of each group was isolated by solid phase pH gradient 2-DE technique. The differentially expressed protein spots were analyzed and identified by PDQuest images; the peptide quality fingerprinting (PMF) was obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Then, the proteins were identified by Mascot software searching, their functions were identified by bioinformatics strategy. (3) The expression of HSP27, α-enolase and Transferrin was detected by Western blotting and the expression of Annexin A2 and Transferrin was detected by immunohistochemistry. (4) The differential proteins and potential targets were analyzed by systematic biological strategy. RESULTS: (1) Compared with the normal group, the ELR in the RSA model group was significantly higher (P < 0.01). Compared with the model group, the ELR in the STW high, medium dose groups was lower (P < 0.01). (2) A 2-DE map of the decidual tissue of the RSA model group, normal pregnancy group, STW low, medium and high dose groups was established. Thirty proteins were identified. (3) The results of western blot showed that the expression of HSP27 and a-enolase in the RSA model group was higher than that in the normal group, and the expression of transferrin was lower (P < 0.01). Compared with the model group, the expression of HSP27 and a-enolase in STW high, medium dose groups was decreased (P < 0.01); Compared with the model group, the expression of Transferrin in the STW high dose group was increased (P < 0.01). (5) A lot of RSA treatment-related targets, biological processes and pathways were found after the systematic biological analysis. CONCLUSION: (1) STW may reduce the ELR of the RSA mice. (2) The results of proteomics suggest that RSA is a complex process involving multiple proteins. STW can regulate the expression of various proteins in the decidual tissue of RSA mice, suggesting that it can act on multiple targets. (3) The results of western blotting of HSP27, a-enolase, transferrin were consistent with the results of proteomic analysis. (4) STW may achieve therapeutic effects by interfering with the targets, biological processes and signaling pathways discovered in this study.

The oxytocin receptor signalling system and breast cancer: a critical review.

Breast cancer is making up one-quarter of all new female cancer cases diagnosed worldwide. Breast cancer surgeries, radiation therapies, cytotoxic chemotherapies and targeted therapies have made significant progress and play a dominant role in breast cancer patient management. However, many challenges remain, including resistance to systemic therapies, tumour recurrence and metastasis. The cyclic neuropeptide oxytocin (OT) elicits a plethora of biological responses via the oxytocin receptor (OTR) in both the central and peripheral nervous system, including social bonding, stress, maternal behaviour, sexual activity, uterus contraction, milk ejection and cancer. As a typical member of the G protein-coupled receptor family, OTR represents also an intriguing target for cancer therapy. There is emerging evidence that OTR plays a role in breast cancer development and progression, and several breast cancer cell lines express OTR. However, despite supporting evidence that OT lowers breast cancer risks, its mechanistic role in breast cancer development and the related signalling pathways are not fully understood. Here, we review the current knowledge of the OT/OTR signalling system in healthy breast tissue as well as in breast cancer, and discuss OTR as a potential therapeutic target for breast cancer management.

[Analysis on regularity of traditional Chinese patent medicine in treating hyperlipidemia].

To explore the regularity of traditional Chinese patent medicines for the treatment of hyperlipidemia recorded in Newly Edited National Chinese Traditional Patent Medicines,the Composition Principles of Chinese Patent Drugs,New Drug Conversion Standard,the Compilation of National Standard for Traditional Chinese Medicines and Chinese Pharmacopoeia. Researchers extracted the information of prescriptions from these cases according to the inclusion and exclusion criteria. Then microsoft excel 2010 was used to conduct frequency statistics and count the frequency of traditional Chinese medicine. SPSS Clementine( ver.12. 0) and SPSS( ver. 18. 0)were adopted respectively for frequency analysis,association rules analysis,cluster analysis and factor analysis. Besides,KMO test and Bartlett spherical test were performed for factor adaptation test. Finally,a total of 173 traditional Chinese medicines were included,involving 94 Chinese patent medicine prescriptions. The frequency results of traditional Chinese medicine showed that there were 33 kinds of high-frequency traditional Chinese medicine,mainly including those for tonifying medicine,activating blood and resolving stasis and blood-stasis,and clearing damp. The association rules analysis found out 12 association rules of drug pairs,3-herb pairs of 25 and4-herb pairs of 6. Totally 11 medicine groups with relevance were respectively extracted by cluster analysis. KMO test and Bartlett spherical test indicated that the method was suitable for factor analysis and 11 common factors were respectively extracted by factor analysis. The association rules reflected the therapeutic method for tonify the liver and kidney,activating blood and resolving stasis. Cluster analysis and factor analysis showed the therapeutic method of Qi-enriching and Yin-nourishing,and the factor analysis focused more on removing blood stasis and dampness. The decision tree with hawthorn as the dependent variable reflects the importance of alisma orientalis and fructus schisandrae in the drug matching. In conclusion,data mining technique can comprehensively analyze the regularity of prescriptions of traditional Chinese patent medicine for hyperlipidemia,and is helpful for guiding the development of Chinese patent medicines and the clinical practice of traditional Chinese medicine.

Genetic dissection of root morphological traits as related to potassium use efficiency in rapeseed under two contrasting potassium levels by hydroponics.

To reveal the genetic basis of potassium use efficiency (KUE) in rapeseed, root morphology (RM), biomass and KUE-related traits were measured in a recombinant inbred line population with 175 F7 lines that were subjected to high-potassium (HK) and low-potassium (LK) treatments by hydroponics. A total of 109 significant QTLs were identified to be associated with the examined traits. Sixty-one of these QTLs were integrated into nine stable QTLs. The higher heritability for RM and biomass traits and lower heritability for KUE-related traits, as well as nine stable QTLs for RM traits and only two for KUE-related traits, suggested that regulating RM traits would be more effective than selecting KUE traits directly to improve KUE by marker-assisted selection. Furthermore, the integration of stable QTLs identified in the HK, LK, high-nitrogen (HN) and low-nitrogen (LN) conditions gave 10 QTL clusters. Seven of these clusters were classified into major QTLs that explained 7.4%-23.7% of the total phenotypic variation. Five of the major QTL clusters were detected under all of the treated conditions, and four clusters were specifically detected under the LK and LN conditions. These common and specific QTL clusters may be useful for the simultaneous improvement of multiple traits by marker-assisted selection.

Mitochondrial Pyruvate Carriers Prevent Cadmium Toxicity by Sustaining the TCA Cycle and Glutathione Synthesis.

Cadmium (Cd) is a major heavy metal pollutant, and Cd toxicity is a serious cause of abiotic stress in the environment. Plants protect themselves against Cd stress through a variety of pathways. In a recent study, we found that mitochondrial pyruvate carriers (MPCs) are involved in Cd tolerance in Arabidopsis (Arabidopsis thaliana). Following the identification of MPCs in yeast (Saccharomyces cerevisiae) in 2012, most studies have focused on the function of MPCs in animals, as a possible approach to reduce the risk of cancer developing. The results of this study show that AtMPC protein complexes are required for Cd tolerance and prevention of Cd accumulation in Arabidopsis. AtMPC complexes are composed of two elements, AtMPC1 and AtMPC2 (AtNRGA1 or AtMPC3). When the formation of AtMPCs was interrupted by the loss of AtMPC1, glutamate could supplement the synthesis of acetyl-coenzyme A and sustain the TCA cycle. With the up-regulation of glutathione synthesis following exposure to Cd stress, the supplementary pathway could not efficiently drive the tricarboxylic acid cycle without AtMPC. The ATP content decreased concomitantly with the deletion of tricarboxylic acid activity, which led to Cd accumulation in Arabidopsis. More importantly, ScMPCs were also required for Cd tolerance in yeast. Our results suggest that the mechanism of Cd tolerance may be similar in other species.

Suppression of the NF­κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute.

Colorectal cancer (CRC) is a major cause of mortality and morbidity. Chronic inflammation is closely associated with the development, progression and prognosis of the majority of intestinal malignancies. In recent years, targeting the nuclear factor (NF)­κB signaling pathway for CRC therapy has become an attractive strategy. Riccardin D, a novel macrocyclicbis (bibenzyl) compound, was isolated from the Chinese liverwort plant. Previous studies have suggested that Riccardin D exerted chemo­preventative effects against the intestinal malignancy formation. In the present study, cell counting kit­8, Hochest 33258 staining, mitochondria membrane permeability assay, western blotting analysis, reverse transcription­polymerase chain reaction, luciferase reporter gene assay and molecular modeling analysis were performed to detect the effect and mechanisms of Riccardin D on human colon cancer cells. The results demonstrated that Riccardin D significantly inhibited the growth of HT­29 cells. In addition, the cDNA expression of cyclooxygenase­2, and the protein expression and activity of NF­κB and tumor necrosis factor­α were downregulated; however, the protein expression of cleaved caspase­3 and ­9, and cleaved poly (adenosine diphosphate­ribose) polymerase, and the B­cell lymphoma (Bcl)­2: Bcl­2­associated X protein ratio were upregulated. Furthermore, Auto Dock analysis identified binding sites between Riccardin D and NF­κB. These results indicated that Riccardin D may inhibit cell proliferation and induce apoptosis in HT­29 cells, which may be associated with the blocking of the NF­κB signaling pathway. Thus, Riccardin D should be investigated as an NF­κB inhibitor in cancer therapy.

Extraction of a Novel Cold-Water-Soluble Polysaccharide from Astragalus membranaceus and Its Antitumor and Immunological Activities.

The polysaccharides of Astragalus membranaceus have received extensive study and attention, but there have been few reports on the extraction of these polysaccharides using cold water (4 °C). In this study, we fractionated a novel cold-water-soluble polysaccharide (cAMPs-1A) from Astragalus membranaceus with a 92.00% carbohydrate content using a DEAE-cellulose 52 anion exchange column and a Sephadex G-100 column. Our UV, Fourier-transform infrared spectroscopy (FTIR), high-performance gel permeation chromatography, and ion chromatography analysis results indicated the monosaccharide composition of cAMPs-1A with 1.23 × 104 Da molecular weight to be fucose, arabinose, galactose, glucose, and xylose, with molar ratios of 0.01:0.06:0.20:1.00:0.06, respectively. The UV spectroscopy detected no protein and nucleic acid in cAMPs-1A. We used FTIR analysis to characterize the α-d-pyranoid configuration in cAMPs-1A. In addition, we performed animal experiments in vivo to evaluate the antitumor and immunomodulatory effects of cAMPs-1A. The results suggested that cAMPs-1A oral administration could significantly inhibit tumor growth with the inhibitory rate of 20.53%, 36.50% and 44.49%, respectively, at the dosage of 75,150, and 300 mg/kg. Moreover, cAMPs-1A treatment could also effectively protect the immune organs, promote macrophage pinocytosis, and improve the percentages of lymphocyte subsets in the peripheral blood of tumor-bearing mice. These findings demonstrate that the polysaccharide cAMPs-1A has an underlying application as natural antitumor agents.

A network pharmacology approach to investigate the pharmacological effects of Guizhi Fuling Wan on uterine fibroids.

To investigate the pharmacological mechanism of Guizhi Fuling Wan (GFW) in the treatment of uterine fibroids, a network pharmacology approach was used. Information on GFW compounds was collected from traditional Chinese medicine (TCM) databases, and input into PharmMapper to identify the compound targets. Genes associated with uterine fibroids genes were then obtained from the GeneCards and Online Mendelian Inheritance in Man databases. The interaction data of the targets and other human proteins was also collected from the STRING and IntAct databases. The target data were input into the Database for Annotation, Visualization and Integrated Discovery for gene ontology (GO) and pathway enrichment analyses. Networks of the above information were constructed and analyzed using Cytoscape. The following networks were compiled: A compound-compound target network of GFW; a herb-compound target-uterine fibroids target network of GWF; and a compound target-uterine fibroids target-other human proteins protein-protein interaction network, which were subjected to GO and pathway enrichment analyses. According to this approach, a number of novel signaling pathways and biological processes underlying the effects of GFW on uterine fibroids were identified, including the negative regulation of smooth muscle cell proliferation, apoptosis, and the Ras, wingless-type, epidermal growth factor and insulin-like growth factor-1 signaling pathways. This network pharmacology approach may aid the systematical study of herbal formulae and make TCM drug discovery more predictable.

Efficacy of Aidi Injection () on overexpression of P-glycoprotein induced by vinorelbine and cisplatin regimen in patients with non-small cell lung cancer.

OBJECTIVE: To investigate the efficacy of Aidi Injection () on overexpression of P-glycoprotein (P-gp) induced by vinorelbine and cisplatin (NP) regimen in patients with non-small cell lung cancer (NSCLC), and study the difference between intravenous administration and targeting intratumor administration of Aidi Injection with thoracoscope. METHODS: Totally 150 patients with NSCLC were randomly assigned to the control group, the intravenous group and the intratumor group by the random envelope method, 50 cases in each group. The patients were treated with NP regimen (2 cycles), NP regimen (2 cycles) plus Aidi intravenous injection, or NP regimen (2 cycles) plus Aidi intratumor injection with thoracoscope, respectively for 6 weeks. The clinical effificacy was observed based on Response Evaluation Criteria in Solid Tumors (RECIST) rules, the expression of P-gp in the tumor tissue was tested before, 3 and 6 weeks after treatment, the safety was evaluated by monitoring the toxicity in the process of treatment, and the progression-free survival (PFS) was measured. RESULTS: Fifteen cases dropped out because of the irreconcilable conditions which had no relationship with the treatment, 4 in the control group, 5 in the intravenous group, and 6 in the intratumor group, respectively. Compared with the control group, the response rates (complete remission + partial response) and the disease control rates (complete remission + partial response + stable disease) were significantly higher, the P-gp expressions were significantly decreased after 3 and 6 weeks of treatment, and the Kaplan-Meier survival curves of PFS were significantly longer in the intravenous and intratumor groups (P<0.05 or P<0.01), and the intratumor group showed better effects than the intravenous group (P<0.05 or P<0.01). Compared with the control group, the occurrences of rash, nausea and leukocytopenia were signifificantly decreased in the intravenous and intratumor groups (P<0.05), but without signifificant difference between the intravenous and intratumor groups (P>0.05). CONCLUSION: Aidi Injection not only improves the effificacy of NP regime, but also has the function of reducing adverse events and preventing against overexpression of P-gp induced by chemotherapy of NP regimen.

Iodide and iodate effects on the growth and fruit quality of strawberry.

BACKGROUND: Iodine deficiency is an environmental health problem affecting one-third of the global population. An iodine biofortification hydroponic experiment was conducted to explore the iodide and iodate uptake characteristics of strawberry plants, to measure the dosage effects of iodine on plant growth and to evaluate the influence of I- or IO3- application on fruit quality. RESULTS: After biofortification, the iodine contents of the fresh strawberry fruits were 600-4000 µg kg-1 , covering the WHO dietary iodine allowance of 150 µg · day-1 for adults. The iodine uptake of the strawberry plants increased with increasing I- or IO3- concentration of the culture solution. At the same iodine concentration, the iodate uptakes of various plant organs under I- treatments were apparently more than those under IO3- treatments. Low-level exogenous iodine (I- ≤ 0.25 mg L-1 or IO3- ≤ 0.50 mg L-1 ) not only promoted plant growth and increased biomass per plant, but also improved fruit quality by enhancing the vitamin C and soluble sugar contents of the strawberry fruits. Nevertheless, excessive exogenous iodine inhibited plant growth and reduced biomass per plant. IO3- uptake apparently increased the total acidity and nitrate content of the fruits, reducing the quality of the strawberry fruits. Conversely, I- uptake obviously decreased the total acidity and nitrate content of the strawberry fruits, improving the fruit quality. CONCLUSION: The strawberry can be used as a target crop for iodine biofortification. Furthermore, applying an appropriate dose of KI can improve the fruit quality of the strawberry plants. © 2016 Society of Chemical Industry.