A novel zein-selenium complex nanoparticle with controllable size: Quantitative design, physical properties and cytotoxicity in vitro.

In this study, after proposing a method for the preparation of selenium nanoparticles (Se NPs) with stable properties using zein, the physico-chemical properties of zein-Se NPs were tested. The complex structure of zein-Se NPs was deduced by SEM, and the binding mechanism was determined by FT-IR and XPS. The particle size of zein-Se NPs could be regulated from 11.4 ± 0.1 nm to 138.7 ± 0.9 nm under different preparation parameters, the reason for the change in particle size had been speculated. The pH responsiveness and 30-day storage stability of the zein-Se NPs were discussed. The zein-Se NPs still had strong DPPH radical scavenging activity after heat treatment. The zein-Se NPs were cell-friendly and was able to effectively protect cells from H2O2-induced cell-death. This study performed an extensive determination of the underlying physico-chemical properties of zein-Se NPs, we anticipate this approach will open up new possibilities in using natural material to stabilize Se NPs.

Effect and Mechanism of Baoshen Prescription in Alleviating Renal Fibrosis in UUO Mice by Regulating ERK/p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the protective effect of Baoshen prescription against renal fibrosis and explore its underlying mechanism through network pharmacology， molecular docking， and in vivo experiments. MethodAll mice were randomly divided into sham surgery group， model group， low-， medium-， and high-dose Baoshen prescription groups， and a benazepril hydrochloride group. Unilateral ureteral obstruction （UUO） was performed to establish a renal fibrosis model， and the administration of Baoshen prescription at low， medium， and high doses （0.455， 0.91， and 1.82 g·kg-1）， and benazepril hydrochloride （1.68 mg·kg-1） or distilled water began on the same day as model preparation. Mice in the model group and the sham surgery group were given an equal volume of distilled water. The intervention was carried out once daily for 14 days. Mouse serum levels of blood urea nitrogen （BUN） and creatinine （Cr） were measured. Hematoxylin-eosin （HE） staining and Masson staining were used to observe renal pathological changes. Western blot and immunohistochemistry were used to assess the expression of fibronectin （FN）， α-smooth muscle actin （α-SMA）， and E-cadherin， which are related to renal fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of transforming growth factor-β1 （TGF-β1）， tumor necrosis factor-α （TNF-α）， NOD-like receptor protein 3 （NLRP3）， and monocyte chemoattractant protein-1 （MCP-1） in renal tissues. The mechanism of Baoshen prescription in improving renal fibrosis was explored through network pharmacology， molecular docking， and Western blot experiments. ResultCompared with the sham surgery group， the model group showed significantly increased levels of BUN and Cr （P<0.01）. The model group exhibited abnormal renal glomerular morphology， loss of tubular brush borders， tubular dilation， and an enlarged area of blue collagen fibers. Mice in the model group showed significantly elevated levels of FN and α-SMA （P<0.01）， significantly decreased expression of E-cadherin （P<0.01）， and significantly increased expression of TGF-β1， TNF-α， NLRP3， and MCP-1 mRNA （P<0.05， P<0.01）. Compared with the model group， the Baoshen prescription groups showed significantly reduced BUN and Cr levels （P<0.01）， alleviated renal pathological damage， improved fibrosis， reduced expression of FN and α-SMA （P<0.01）， increased E-cadherin expression （P<0.01）， and downregulated mRNA expression of TGF-β1， TNF-α， NLRP3， and MCP-1 （P<0.05， P<0.01）. Network pharmacology and molecular docking predicted that Baoshen prescription could potentially improve renal fibrosis through the extracellular signal-regulated kinase （ERK）/p38 mitogen-activated protein kinase （MAPK） signaling pathway. Pharmacological research showed that compared with the sham surgery group， the model group exhibited significantly increased expression of phosphorylated （p）-ERK and p-p38 （P<0.05， P<0.01）. Compared with the model group， medium- and high-dose Baoshen prescription groups showed significantly downregulated expression of p-ERK and p-p38 proteins （P<0.05， P<0.01）. ConclusionBaoshen prescription can effectively improve renal fibrosis induced by UUO in mice， and its mechanism of action may be related to the ERK/p38 MAPK signaling pathway.

Fabrication of food grade zein-dispersed selenium dual-nanoparticles with controllable size, cell friendliness and oral bioavailability.

In this study, novel bioavailable selenium nanoparticles with controllable particle size and low toxicity were developed. With selenium modified zein nanoparticles (zein NPs) in-situ, dispersed nano-selenium particles with different structure were formed simultaneously. The particle size, zeta potential, morphology and binding mechanism of synthesized zein-selenium nanoparticles (zein-Se NPs) were systematically discussed. Selenium was considered to be combined with OH and -CO-NH- groups of zein. The selenium in the complex particles presented an amorphous structure with zero valence. The cytotoxicity of zein-Se NPs was significantly lower than that of sodium selenite, even exhibited a growth-promoting effect on normal liver cells (L-02), and were proven to be orally absorbed by organisms in vivo experiments. The difference in particle structure had certain effects on cytotoxicity and oral targeting. The complex particles obtained by this method were anticipated be further used as food fortifiers or medicines.

Visual, spectral, and microchemical quantification of crystalline anomalies in otoliths of wild and cultured delta smelt.

Developmental abnormalities in otoliths can impact growth and survival in teleost fishes. Here, we quantified the frequency and severity of developmental anomalies in otoliths of delta smelt (Hypomesus transpacificus), a critically endangered estuarine fish that is endemic to the San Francisco Estuary. Left-right asymmetry and anomalous crystalline polymorphs (i.e., vaterite) were quantified and compared between wild and cultured populations using digital image analysis. Visual estimates of vaterite were validated using X-ray diffraction, Raman spectroscopy, laser ablation ICPMS, and electron probe microanalysis. Results indicated that cultured delta smelt were 80 times more likely to contain a vateritic otolith and 18 times more likely to contain relatively large (≥ 15%) amounts of vaterite. Similarly, cultured fish exhibited 30% greater asymmetry than wild fish. These results indicate that cultured delta smelt exhibit a significantly higher frequency of vestibular abnormalities which are known to reduce fitness and survival. Such hatchery effects on otolith development could have important implications for captive culture practices and the supplementation of wild fish populations with cultured individuals.

Exploring the mechanism of hirudin in the treatment of diabetic kidney disease using network pharmacology combined with molecular docking verification.

OBJECTIVE: To explore the mechanism of hirudin in the treatment of diabetic kidney disease (DKD). METHOD: Cytoscape software was used to analyze the network between hirudin targets and active components in the treatment of DKD. The biological function and mechanism of effective targets of hirudin for DKD treatment were analyzed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Molecular docking technology was used to simulate the docking of key targets, and the DKD rat model was used to verify the first 4 key targets with high "Hydrogen number" among the top 10 targets verified by molecular docking. RESULTS: Total of 12334 DKD targets were screened in GeneCards, OMIM and other databases, Hirudin and DKD had 247 common target genes, and the protein interaction network got 2115 edges. The DAVID database was used for the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, confirming that hirudin in treatment of DKD involves multiple signaling pathways such as the forkhead box O signaling pathway, the phosphatidylinositol 3-kinase-protein kinase B signaling pathway, the vascular endothelial-derived growth factor signaling pathway and other signaling pathways. The top ten key targets of hirudin in treatment of DKD were verified by molecular docking. Animal experiments showed that hirudin could decrease the expression of caspase-3 in renal tissue of DKD rats, and increase the expression of RAC-alpha serine/threonine-protein kinase, Catalase, and Heat shock protein HSP 90-alpha in renal tissue of DKD rats. CONCLUSION: This study preliminarily reveals that hirudin treats DKD through multiple targets and pathways, and molecular docking and animal experiments indicates the feasibility of this study. Hirudin may be directly or indirectly involved in the regulation of cell metabolism, oxidative stress and other mechanisms in the treatment of DKD, which will lay the foundation for future molecular biological experiments of hirudin in the treatment of DKD.

Development, characterization and in vitro bile salts binding capacity of selenium nanoparticles stabilized by soybean polypeptides.

The paper presents the positive effect of soybean polypeptides (SP) on the stability and the potential hypolipidemic effect of selenium nanoparticles (SeNPs). After preparing SeNPs, SP with different molecular weight were introduced to stabilize SeNPs. We found that the SP with molecular weight >10 kDa (SP5) had the best stabilizing effect on SeNPs. We inferred that the steric resistance resulting from the long chains of SP5 protected SeNPs from collision-mediated aggregation, and the electrostatic repulsions between SP5 and SeNPs also played a positive role in stabilizing SeNPs. The as-prepared SP5-SeNPs were spherical, amorphous and zero valent. It was proved that SeNPs were bound with SP5 through O- and N- groups in SP5, and the main forces were hydrogen bonds and van der Waals forces. The bile salts binding assay showed that the SP5-SeNPs exhibited a high binding capacity to bile salts, which indicated their potential in hypolipidemic application.

Quality evaluation of Dalbergiae Odoriferae Lignum by HPLC fingerprint and multi-component quantitative analysis / 中国中药杂志

The present study detected the component content in Dalbergiae Odoriferae Lignum by HPLC fingerprint and the multi-component determination method. HPLC analysis was performed on the Agilent ZORBAX SB-C_(18) column(4.6 mm×250 mm, 5 μm). Acetonitrile-0.5% phosphoric acid aqueous solution with gradient elution was employed as the mobile phase. The flow rate was 1.0 mL·min~(-1) and the column temperature was maintained at 30 ℃. The detection wavelength was 210 nm and the sample volume was 10 μL. The similarity of 18 batches of Dalbergiae Odoriferae Lignum was 0.343-0.779, indicating that there were great differences between different batches of Dalbergiae Odoriferae Lignum. Eighteen common peaks were identified, including eight flavonoids such as liquiritigenin and latifolin. The mass fractions of liquiritigenin, luteolin, naringenin, isoliquiritigenin, formononetin, dalbergin, latifolin, and pinocembrin were in the ranges of 0.134 1%-0.495 2%, 0.028 2%-0.167 0%, 0.016 3%-0.591 3%, 0.053 5%-0.188 0%, 0.142 4%-0.640 1%, 0.068 0%-0.590 7%, 0.003 2%-1.980 7%, and 0.009 6%-0.740 2%, respectively. Eighteen batches of Dalbergiae Odoriferae Lignum were divided into three categories by cluster analysis and eight differential components in Dalbergiae Odoriferae Lignum were marked by partial least-squares discriminant analysis(PLS-DA). The cumulative variance contribution rate was 90.5%. The HPLC fingerprint combined with the multi-component determination method for Dalbergiae Odoriferae Lignum is easy in operation and accurate in results, with good repeatability and reliability. The quality of Dalbergiae Odoriferae Lignum can be evaluated and analyzed by the PLS-DA model. This study is expected to provide a reference for the quality control and clinical application of Dalbergiae Odoriferae Lignum.

Systematic characterization of the metabolites of defatted walnut powder extract in vivo and screening of the mechanisms against NAFLD by UPLC-Q-Exactive Orbitrap MS combined with network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Walnut kernel, a well-known TCM, is often used after being defatted in tradition. And defatted walnut powder extract (DWPE) has the actions of tonifying the liver and kidney, dissipating stagnation and removing blood stasis, which has the effect on non-alcoholic fatty liver disease (NAFLD). However, the effective components of DWPE in vivo were unclear and the multiple mechanisms of DWPE against NAFLD have not been explored. AIM OF THE STUDY: The studies were performed to screen the effective substances in vivo by identification of the metabolites of DWPE in rats and to seek the potential mechanisms of DWPE on NAFLD by construction of the network pharmacology based on metabolites and verification of the highly correlated pathway. MATERIALS AND METHODS: To explore the effective substances in vivo, the metabolites of DWPE were identified in SD rats' bio-samples through UPLC-Q-Exactive Orbitrap MS. To analyze the mechanisms of DWPE on NAFLD, a Metabolite-Target-Disease network was established and the potential mechanisms were predicted. Then, highly correlated pathway was verified in animal and cells studies. RESULTS: A total of 52 metabolites of DWPE were identified in vivo, which were derived from gallic acid, ellagic acid (EA) and glansreginin A (Gla A). The possible metabolic pathways were phase Ⅰ (hydroxylation, hydrolyzation, etc) and phase Ⅱ metabolic reactions (methylation, sulfation and glucuronidation). Furthermore, in the network pharmacology, 54 core targets were enriched into pathways in cancer, nitrogen metabolism and other 9 pathways, which were essential pathways of DWPE against NAFLD. And the mechanism of nitrogen metabolism was verified in both of animal and cells studies. The results showed that DWPE could decline the concentration of ammonia and increase the expressions of carbonic anhydrase 2 (CA2) and carbamoylphosphate synthetase (CPS1) in nitrogen metabolism. CONCLUSION: Taken together, the study revealed the absorption components and their metabolic pathways and demonstrated the mechanism of nitrogen metabolism of DWPE on anti-NAFLD.

Anti-NAFLD effect of defatted walnut powder extract in high fat diet-induced C57BL/6 mice by modulating the gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Walnut kernel has the actions of removing meteorism, dissipating stagnation and removing blood stasis and is used after being defatted in TCM. Defatted walnut powder extract (DWPE) has the abilities of anti-oxidation and lowering lipid levels in vivo. However, the effects and the potential mechanisms of DWPE on NAFLD have not been explored. AIM OF THE STUDY: The study were to investigate the anti-NAFLD effect of DWPE in high fat diet-induced C57BL/6 mice and demonstrate that whether DWPE developed the effect on anti-NAFLD by remodeling the compositions and abundances of gut microbiota. MATERIALS AND METHODS: The inhibitory effect of DWPE on the development of NAFLD was conducted on C57BL/6 mice with a high fat diet and the regulation effect of DWPE on gut microbiota was verified on pseudo-sterile mice with treatment of broad spectrum antibiotics. RESULTS: The results showed that the oral administration of DWPE remarkably alleviated hepatic lipid accumulation by decreasing the levels of TG, TC, LDL, MDA and increasing HDL. Meanwhile, the expressions of NF-κB and MAPKs family proteins were reduced by DWPE compared with HFD group. Otherwise, the efficacy of anti-NAFLD of DWPE was significantly decreased after treatment of antibiotics, which indicated the key role of gut microbiota in the therapeutic process. Furthermore, sequencing of 16S rRNA gene revealed that DWPE could revert the decreased relative abundance of gut microbiota caused by the long term of a high fat diet. And the disordered microflora was remodeled by DWPE including the reduction of Erysipelotrichia, Firmicutes and Actinobacteria as well as the increment of Bacteroidetes, Clostridiales, Bacteroidales S24-7, Prevotellaceae and Bacteroides. CONCLUSION: Taken together, DWPE had a preventing effect on NAFLD, which might be associated with the regulation of gut microbiota.

Evodiamine inhibits high-fat diet-induced colitis-associated cancer in mice through regulating the gut microbiota / 中西医结合学报

OBJECTIVE@#High-fat diet is one of the main risk factors that disrupt the balance of gut microbiota, which eventually will induce colorectal cancer (CRC). Evodiamine (EVO) is a wildly used multifunctional traditional Chinese medicine extract. In this study, we investigated the role of gut microbiota in high-fat diet-propelled CRC and the potential of EVO for CRC chemoprevention.@*METHODS@#Gut microbiota, serum d-lactic acid and endotoxin from 38 patients with colon cancer and 18 healthy subjects were detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). In addition, body mass index, phospho-signal transducer and activator of transcription 3 (p-STAT3) expression in cancer tissues and paracancerous tissues were detected by immunohistochemistry. A mouse intestinal inflammatory tumor model was established by azomethane/sodium dextran sulfate, followed by treatment with EVO and 5-aminosalicylic acid (ASA). Gut microbiota and inflammatory factors were detected by quantitative polymerase chain reaction, while serum d-lactic acid and endotoxin were detected by ELISA. Furthermore, cell proliferation, cell apoptosis, and interleukin (IL)-6/STAT3/P65 pathway were evaluated by 5-ethynyl-2'-deoxyuridine, terminal-deoxynucleotidyl transferase-mediated nick-end labeling, and Western blot assays.@*RESULTS@#In patients with colon cancer, the numbers of Enterococcus faecalis and Escherichia coli were increased, while those of Bifidobacterium, Campylobacter and Lactobacillus were decreased. Serum endotoxin and d-lactic acid levels and p-STAT3 levels were significantly increased. In the mouse model, both EVO and ASA inhibited tumor formation, decreased the proliferation of tumor cells, and induced apoptosis of tumor cells. Compared with the control group, the numbers of E. faecalis and E. coli were decreased, while Bifidobacterium, Campylobacter and Lactobacillus numbers were increased. In the EVO group, serum endotoxin and d-lactic acid levels and inflammatory factors were significantly decreased. Further, the IL6/STAT3/P65 signaling pathway was inhibited in the EVO group.@*CONCLUSION@#EVO may inhibit the occurrence of colon cancer by regulating gut microbiota and inhibiting intestinal inflammation. The potential mechanism involves inhibition of the IL6/STAT3/P65 signaling pathway, revealing its potential therapeutic significance in clinical applications.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Rapid Identification on Chemical Components in Dalbergiae Odoriferae Lignum by UPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

Objective::Dalbergiae Odoriferae Lignum is a rare traditional Chinese medicine material in China. However, there are many varieties of various sources and different qualities in the market at present. In order to further define the pharmacodynamic substance basis, electrospray time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was used to rapidly analyze chemical constituents of methanol extract of Dalbergiae Odoriferae Lignum. Method::Chromatographic separation was performed on an UPLC RRHD SB-C18(3.0 mm×100 mm, 1.8 μm)for gradient elution, with mixtures of acetonitrile and 0.1%formic acid-water as mobile phases at a flow rate of 0.3 mL·min-1. The column temperature was maintained at 40 ℃. The data was collected in a negative ion mode with electro-spray ionization source(ESI). Result::According to molecular ion peaks and MS2 mass spectrometry characteristic fragment ions, Mass Bank databases, as well as the mass spectrometry information of reference substances and relevant literatures, a total of 83 constituents were identified, including 18 flavones, 31 isoflavones, 10 neoflavonoids, 9 isoflavanones, 7 other flavonoids and 8 other components. Conclusion::UPLC-Q-TOF-MS/MS can quickly, accurately and comprehensively identify chemical constituents in methanol extract of Dalbergiae Odoriferae Lignum, and isoflavones, flavones, neoflavonoids and isoflavanones are the main chemical constituents, which laid a foundation for the basic research of medicinal substances of Dalbergiae Odoriferae Lignum, and provided theoretical basis and technical support for the improvement of quality standards of Dalbergiae Odoriferae Lignum.

Rapid Identification and Analysis of Chemical Components in Heartwood of Dalbergia cochinchinensis by UPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

Objective::To rapidly identify and analysis the chemical constituents in the methanol extract of heartwood of Dalbergia cochinchinensis by ultra high performance liquid chromatography-quadrupole-time-of-flight high resolution mass spectrometry (UPLC-Q-TOF-MS/MS). Method::UPLC RRHD SB-C18 column (3.0 mm×100 mm, 1.8 μm) was used for chromatographic separation with acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution (0-0.01 min, 5%B; 0.01-2 min, 5%-22%B; 2-28 min, 22%-35%B; 28-45 min, 35%-44%B; 45-55 min, 44%-100%B; 55-57 min, 100%B; 57-57.10 min, 100%~5%B) at a flow rate of 0.3 mL·min-1. The analytes were determined in negative ion mode with electrospray ionization (ESI) and data collection range of m/z 100-1 500. Result::A total of 101 chemical constituents were identified, including 22 flavonoids, 34 isoflavones, 15 neoflavonoids, 18 other flavonoids and 12 other components. Conclusion::UPLC-Q-TOF-MS/MS technique can quickly, accurately and comprehensively identify the chemical constituents in the heartwood of D. cochinchinensis. Isoflavones, flavonoids and neoflavonoids are the main chemical constituents in the heartwood of D. cochinchinensis, which is of great significance to reveal its internal material basis and provides experimental basis for this plant to be developed as a potential new resource of traditional Chinese medicine.

Identification of chemical constituents in Huangdi Anxiao Capsules by UPLC-Q-TOF-MS~E combined with UNIFI software / 中国中药杂志

In order to clarify the main chemical constituents of Huangdi Anxiao Capsules, an ultra-high performance liquid coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS~E) combined with Waters UNIFI software were successfully used to rapidly identify the chemical constituents in Huangdi Anxiao Capsules. The mass spectrometry data of chemical constituents from Huangdi Anxiao Capsules were collected by UPLC-Q-TOF-MS~E, and their structures were identified by the results of UNIFI software according to relative retention time of reference standards, MS feature fragments and literature data of each compound. A total of 100 compounds in Huangdi Anxiao Capsules were identified, including 25 compounds from Pueraria Lobate Radix, 22 compounds from Coptis Rhizoma, 6 compounds from Ophiopogonis Radix, 14 compounds from Eriobotryae Folium, 22 compounds from Rehmanniae Radix, and 15 compounds from Notoginseng Radix et Rhizoma. Among them, 3 compounds were common components. These 100 compounds included flavonoids, alkaloids, saponins and organic acids. This study systematically analyzed the chemical composition of Huangdi Anxiao Capsules, so as to provide evidences for defining the chemical material basis of Huangdi Anxiao Capsules.

Vitamin D3 Activates Phosphatidylinositol-3-Kinase/Protein Kinase B via Insulin-Like Growth Factor-1 to Improve Testicular Function in Diabetic Rats.

OBJECTIVE: In diabetes mellitus, vitamin D3 deficiency affects sex hormone levels and male fertility; however, the mechanism leading to the disorder is unclear. This research was designed to investigate the mechanism of vitamin D3 deficiency and hypogonadism in diabetic rats. Our aim was to assess serum vitamin D3 levels and the relationship among vitamin D3, insulin-like growth factor-1 (IGF-1), and testicular function. MATERIALS AND METHODS: Rats with streptozotocin-induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: no vitamin D3, low (0.025 µg/kg/day), high (0.1 µg/kg/day), and high (0.1 µg/kg/day) with JB-1 (the insulin-like growth factor-1 receptor inhibitor group, 100 µg/kg/day). The groups were compared with wild-type rats, which function as the control group. Various parameters such as vitamin D3 and IGF-1 were compared between the experimental and wild-type groups, and their correlations were determined. RESULTS: Twelve weeks of vitamin D3 supplementation improved the testosterone levels, as shown by the increase in the level of serum IGF-1 in diabetic rats. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), which was a downstream of the signaling pathway of IGF-1, was significantly increased after vitamin D3 treatment. CONCLUSIONS: The study shows that vitamin D3 may promote the expression of testosterone and improve testicular function in diabetic rats by activating PI3K/AKT via IGF-1.

Study on neoflavonoids from heartwood of Dalbergia latifolia / 中国中药杂志

Dalbergiae Odoriferae Lignum is derived from heartwood of Dalbergia odorifera,which is national Ⅱ level of rare and endangered protective plants in China. Its resources are scarce and its price is high. In order to find substitutes of D. odorifera,the chemical constituents of 70% ethanol extract of heartwood of D. catifolia were systematically studied by using silica gel,Sephadex LH-20 column chromatography,and semi-preparative HPLC. Sixteen neoflavanoids were isolated and identified as eight dalbergiphenols( 1-8),three dalbergiones( 9-11),two dalbergins( 12,13),two benzophenones( 14,15) and one other type neoflavanoids( 16) based on spectroscopic data analyses and/or comparing the spectroscopic data with those in literature. Among them,compounds 3,7 and 11 were isolated from the genus Dalbergia for the first time,and compounds 2,4-6,8,14 and 15 were isolated from the D. latifolia for the first time. Ten neoflavonoids were both discovered from D. latifolia and D. odorifera.

Development, physicochemical characterization and cytotoxicity of selenium nanoparticles stabilized by beta-lactoglobulin.

Novel Selenium nanoparticles (SeNPs) were developed using beta-lactoglobulin (Blg) as a stabilizer in redox systems of selenite and ascorbic acid in this study. Particle size, morphology, stability, and in vitro biological activity of synthesized Blg stabilized selenium nanoparticles (Blg-SeNPs) were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), ultraviolet-visible spectrophotometry (UV/Vis), and cell toxicity assays, respectively. Stabilizing mechanisms of Blg-SeNPs were investigated by Fourier-transform infrared spectroscopy (FTIR) and protein fluorescence probe. The results revealed that the Blg-SeNPs were spherical with mean particle size of 36.8±4.1nm. They were stable in acidic or neutral to basic solutions (pH 2.5-3.5 or 6.5-8.5) at 4°C for 30days as a result of electrostatic repulsions. FTIR results showed that functional groups of NH2 and OH on Blg molecules were responsible for binding with SeNPs. Furthermore, decreases in protein surface hydrophobicity indicated that possible binding happened between Se and the hydrophobic domains of Blg. The cell toxicity of Blg-SeNPs was significantly lower than that of sodium selenite on both cancerous and non-cancerous cells. This study provides a facile and green method for chemically synthesizing stable SeNPs which are suitable for further evaluation in medicinal applications.

System design and experimental research of lower esophageal sphincter stimulator for treatment of gastroesophageal reflux disease.

Electrical stimulation therapy (EST) of lower esophageal sphincters (LES) is a new technique for the treatment of gastroesophageal reflux disease (GERD). In this paper, an implantable LES stimulator with wireless power transmission is proposed for the treatment of GERD. The LES stimulator is composed of an implantable pulse generator (IPG), an external controller, and a wireless power transmission module. The IPG, whose area is 31×21 mm2, is designed to generate voltage-regulated constant-current stimulation pulses. The external controller allows for wireless programming of the IPG via a Bluetooth Low Energy (BLE) module. The wireless power transmission module provides power for the IPG. According to the measurement of output stimulus waveforms, the proposed LES stimulator is capable of delivering electrical stimulations with a current ranging between 0 and 8 mA. To evaluate the safety and efficacy of the proposed LES stimulator, experiments were performed on 12 male New Zealand white rabbits. Esophageal manometry was performed before and after the procedure and the LES pressure (LESP) has been recorded. The mean LESP is increased significantly in the stimulation group than the sham group (stimulation group: 9.25±1.24 mmHg vs 13.99 ±1.28 mmHg, p<;0.05; sham group: 9.00±1.22 mmHg vs 9.23±1.27 mmHg, p=0.267). The results show that the electrical stimulation delivered by the LES stimulator can safely and effectively increase resting LES pressure in acute animal models, suggesting that the implantable LES stimulator is a perspective approach for treating GERD in clinics.

[Treatment of Mixed Hemorrhoids by RPH with the Simplified Milligan-Morgan Surgery: a Multi-center, Randomized, Controlled Clinical Trial].

Objective To observe the safety and efficacy of RPH with the simplified. Milligan-Mor- gan(M-M) surgery on mixed hemorrhoids. Methods Totally 1 200 patients with mixed hemorrhoid were assigned to the control group(600 cases) and the treatment group(600 cases) according to randomized, parallel controlled,multi-center trial design. Patients in the control group received PPH with the simplified M-M surgery, and patients in the treatment group received RPH with the simplified M-M surgery. Postop- erative complications, operation time,the postoperative hospitalization days and the efficacy were ob- served. Results Compared with the control group, the numbers of postoperation hemorrhage, postop- erative uroschesis, anal fissure and anorectal stenosis in treatment group were decreased(P <0. 01 , P < 0. 05), operation time and the postoperative hospitalization days were decreased (P <0. 01 , P <0. 05 ), the cure rate for 3 and 12 months after operation were increased (P <0. 01, P <0. 05). Conclusions RPH with the simplified M-M surgery could reduce the incidence of postoperative complications,improve the clinical cure rate and the curative effect in treatment of mixed hemorrhoids.

Effects of Senegenin against hypoxia/reoxygenation-induced injury in PC12 cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect and the potential mechanism of Senegenin (Sen) against injury induced by hypoxia/reoxygenation (H/R) in highly differentiated PC12 cells.</p><p><b>METHODS</b>The cultured PC12 cells were treated with H/R in the presence or absence of Sen (60 μmol/L). Four groups were included in the experiment: control group, H/R group, H/R+Sen group and Sen group. Cell viability of each group and the level of lactate dehydrogenase (LDH) in culture medium were detected for the pharmacological effect of Sen. Hoechst 33258 staining and annexin V/propidium iodide double staining were used to analyze the apoptosis rate. Moreover, mitochondrial membrane potential (△Ψm), reactive oxygen species (ROS) and intracellular free calcium ([Ca(2+)]i) were measured by fluorescent staining and flow cytometry. Cleaved caspase-3 and activity of NADPH oxidase (NOX) were determined by colorimetric protease assay and enzyme linked immunosorbent assay, respectively.</p><p><b>RESULTS</b>Sen significantly elevated cell viability (P<0.05), decreased the leakage of LDH (P<0.05) and apoptosis rate (P<0.05) in H/R-injured PC12 cells. Sen maintained the value of △Ψm (P<0.05) and suppressed the activity of caspase-3 (P<0.05). Moreover, Sen reduced ROS accumulation P<0.05) and [Ca(2+)]i increment (P<0.05) by inhibiting the activity of NOX (P<0.05).</p><p><b>CONCLUSION</b>Sen may exert cytoprotection against H/R injury by decreasing the levels of intracellular ROS and [Ca(2+)]i, thereby suppressing the mitochondrial pathway of cellular apoptosis.</p>