1,3,6-Trigalloylglucose: A Novel Potent Anti-Helicobacter pylori Adhesion Agent Derived from Aqueous Extracts of Terminalia chebula Retz.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.

Effect of Traditional Chinese Non-Pharmacological Therapies on Knee Osteoarthritis: A Narrative Review of Clinical Application and Mechanism.

Knee osteoarthritis (KOA) stands as a degenerative ailment with a substantial and escalating prevalence. The practice of traditional Chinese non-pharmacological therapy has become a prevalent complementary and adjunctive approach. A mounting body of evidence suggests its efficacy in addressing KOA. Recent investigations have delved into its underlying mechanism, yielding some headway. Consequently, this comprehensive analysis seeks to encapsulate the clinical application and molecular mechanism of traditional Chinese non-pharmacological therapy in KOA treatment. The review reveals that various therapies, such as acupuncture, electroacupuncture, warm needle acupuncture, tuina, and acupotomy, primarily target localized knee components like cartilage, subchondral bone, and synovium. Moreover, their impact extends to the central nervous system and intestinal flora. More perfect experimental design and more comprehensive research remain a promising avenue in the future.

Study on the mechanism of Wumei San in treating piglet diarrhea using network pharmacology and molecular docking.

Wumei San (WMS) is a traditional Chinese medicine that has been widely applied in the treatment of piglet diarrhea (PD). However, the mechanism of WMS in PD has not been investigated. In this study, the main active compounds of WMS and the target proteins were obtained from the Traditional Chinese Medicine Systematic Pharmacology, PubChem, and SwissTargetPrediction databases. The molecular targets of PD were identified using GeneCards, OMIM, and NCBI databases. The common targets of WMS and PD were screened out and converted into UniProt gene symbols. PD-related target genes were constructed into a protein-protein interaction network, which was further analyzed by the STRING online database. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to construct the component-target gene-disease network. Molecular docking was then used to examine the relationship between the core compounds and proteins. As a result, a total of 32 active compounds and 638 target genes of WMS were identified, and a WMS-compound-target network was successfully constructed. Through network pharmacology analysis, 14 core compounds in WMS that showed an effect on PD were identified. The targets revealed by GO and KEGG enrichment analysis were associated with the AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, IL-17 signaling pathway, and other pathways and physiological processes. Molecular docking analysis revealed that the active compounds in WMS spontaneously bind to their targets. The results indicated that WMS may regulate the local immune response and inflammatory factors mainly through the TNF signaling pathway, IL-17 signaling pathway, and other pathways. WMS is a promising treatment strategy for PD. This study provides new insights into the potential mechanism of WMS in PD.

Ultrasound Combined With Single-Use Cervical Dilation Sticks And Lidocaine Achieved Good Clinical Outcomes In Hysteroscopic Removal Of The Intrauterine Device: A Pilot Study.

Objective: Our purpose of this study was to investigate the value of ultrasound combined with disposable cervical dilating stick and lidocaine in hysteroscopic intrauterine device (IUD) removal in postmenopausal women. Methods: Ninety-six postmenopausal women who requested IUD removal in our hospital from March 2020 to March 2022 were selected and randomly divided into a control group (48 cases) and a study group (48 cases) according to random number table method, with the control group undergoing conventional hysteroscopic IUD removal and the study group undergoing hysteroscopic IUD removal with ultrasound combined with a single-use cervical dilator rod and lidocaine. The time of IUD removal, subjective comfort evaluation scale (SECS) scores, treatment compliance, quality of life scale (SF-36) scores, IUD removal results, hospital anxiety and depression scale (HAD) scores and complications were compared between the two groups. Results: The ring removal time of the study group was shorter than that of the control group, the postoperative SECS and SF-36 scores were higher than those of the control group, the compliance rate and the excellent and good rate of ring removal efficacy were higher than those of the control group, the postoperative HAD score was lower than that of the control group, and the incidence rate of complications was lower than that of the control group (P < .05). Conclusions: In hysteroscopic IUD removal, ultrasound combined with single-use cervical dilation sticks and lidocaine can gently soften and dilate the cervix in a short time, shortening the procedure time and reducing pain. The procedure is simplified, rapid, safe and has a high success rate.

Vertical distribution, environmental occurrence, and risk assessment of organic pollutants in lacustrine sediments in southeast China.

To clarify the impact of human activities on the natural environment, as well as the current ecological risks to the environment surrounding Zhushan Bay in Taihu Lake, the characteristics of deposited organic materials, including elements and 16 polycyclic aromatic hydrocarbons (∑16PAHs), in a sediment core from Taihu Lake were determined. The nitrogen (N), carbon (C), hydrogen (H), and sulfur (S) contents ranged from 0.08 to 0.3%, 0.83 to 3.6%, 0.63 to 1.12%, and 0.02 to 0.24%, respectively. The most abundant element in the core was C followed by H, S, and N, while elemental C and the C/H ratio displayed a decreasing trend with depth. The ∑16PAH concentration was in the range of 1807.48-4674.83 ng g-1, showing a downward trend with depth, with some fluctuations. Three-ring PAHs dominated in surface sediment, while 5-ring PAHs dominated at a depth of 55-93 cm. Six-ring PAHs appeared in the 1830s and gradually increased over time before slowly decreasing from 2005 onward due to the establishment of environmental protection measures. The ratio of PAH monomers indicated that PAHs in samples from a depth of 0 to 55 cm were mainly derived from the combustion of liquid fossil fuels, while the PAHs in the deeper samples mainly originated from petroleum. The results of a principal component analysis (PCA) showed that the PAHs in the sediment core of Taihu Lake were mainly derived from the combustion of fossil fuels, such as diesel, petroleum, gasoline, and coal. The contributions of biomass combustion, liquid fossil fuel combustion, coal combustion, and unknown source were 8.99%, 52.68%, 1.65%, and 36.68%, respectively. The results of a toxicity analysis indicated that most of the PAH monomers had little impact on the ecology, and the annual increase of a small number of monomers might have toxic effects on the biological community, resulting in a serious ecological risks, that requires the imposition of control measures.

Discovery of a DFR gene that controls anthocyanin accumulation in the spiny Solanum group: roles of a natural promoter variant and alternative splicing.

Anthocyanins are important pigments that impart color in plants. In Solanum, different species display various fruit or flower colors due to varying degrees of anthocyanin accumulation. Here we identified two anthocyanin-free mutants from an ethylmethane sulfonate-induced mutant library and naturally occurring mutants in Solanum melongena, with mutations in the 5' splicing site of the second intron of dihydroflavonol-4-reductase (DFR) - leading to altered splicing. Further study revealed that alternative splicing of the second intron was closely related to anthocyanin accumulation in 17 accessions from three cultivated species: S. melongena, Solanum macrocarpon and Solanum aethiopicum, and their wild related species. Analysis of natural variations of DFR, using an expanded population including 282 accessions belonging to the spiny Solanum group, identified a single-nucleotide polymorphism in the MYB recognition site in the promoter region, which causes differential expression of DFR and affects anthocyanin accumulation in fruits of the detected accessions. Our study suggests that, owing to years of domestication, the natural variation in the DFR promoter region and the alternative splicing of the DFR gene account for altered anthocyanin accumulation during spiny Solanum domestication.

[Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of insomnia].

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of insomnia by frequency network Meta-analysis. Randomized controlled trials of Chinese patent medicines for insomnia were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library databases from the time of database establishment to October 2020. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 11 kinds of Chinese patent medicines in 27 RCTs were included. According to Meta-analysis, in term of the effective rate, Tianmeng Liquid, Zaoren Anshen Capsules, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Anshen Bunao Liquid and Qiye Anshen Tablets combined with nonbenzodiazepine drugs(NBZDs) were superior to NBZDs alone. In term of the improvement of Pittsburg sleeping quality index(PSQI) score, Tianmeng Liquid, Shumian Capsules, Shensong Yangxin Capsules, Bailemian Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Yangxue Qingnao Granules and Yindan Xinnaotong Capsules combined with NBZDs were superior to NBZDs alone. In terms of the safety, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets and Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. In terms of the avoidance of dizziness and headache, Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. The results of Network Meta-analysis indicated that in term of the effective rate, top three optimal medication regimens were NBZDs combined with Shugan Jieyu Capsules, combined with Zaoren Anshen Capsules and combined with Shensong Yangxin Capsules in the order from high to low. With the respect of improvement of PSQI score, top three optimal medication regimens were NBZDs combined with Yangxue Qingnao Granules, combined with Tianmeng Liquid and combined with Yindan Xinnaotong Capsules in the order from high to low. In terms of the safety, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Shensong Yangxin Capsules and combined with Shenqi Wuweizi Tablets in the order from high to low. In terms of the avoidance of dizziness and headache, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Zaoren Anshen Capsules and combined with Shumian Capsules in the order from high to low. In terms of the avoidance of fatigue, top three optimal medication regimens were NBZDs combined with Shensong Yangxin Capsules, combined with Shumian Capsules and combined with Qiye Anshen Tablets in the order from high to low. In conclusion, Chinese patent medicines combined with NBZDs can effectively alleviate the symptoms of insomnia with a high safety. However, the conclusion of this study needs to be verified by more high-quality studies because of the low methodological quality of the included studies.

Downregulation of let-7 by Electrical Acupuncture Increases Protein Synthesis in Mice.

BACKGROUND: Our previous study found that acupuncture with low frequency electrical stimulation (Acu/LFES) prevents muscle atrophy by attenuation of protein degradation in mice. The current study examines the impact of Acu/LFES on protein synthesis. METHOD: C57/BL6 mice received Acu/LFES treatment on hindlimb for 30 min once. Acu/LFES points were selected by WHO Standard Acupuncture Nomenclature and electric stimulation applied using an SDZ-II Electronic acupuncture instrument. Muscle protein synthesis was measured by the surface-sensing of translation (SUnSET) assay. Exosomes were isolated using serial centrifugation and concentration and size of the collected exosomes were measured using a NanoSight instrument. The mature microRNA library in serum exosomes was validated using a High Sensitivity DNA chip. RESULTS: Protein synthesis was enhanced in the both hindlimb and forelimb muscles. Blocking exosome secretion with GW4869 decreased the Acu/LFES-induced increases in protein synthesis. MicroRNA-deep sequencing demonstrated that four members of the Let-7 miRNA family were significantly decreased in serum exosomes. Real time qPCR further verified Acu/LFES-mediated decreases of let-7c-5p in serum exosomes and skeletal muscles. In cultured C2C12 myotubes, inhibition of let-7c not only increased protein synthesis, but also enhanced protein abundance of Igf1 and Igf1 receptors. Using a luciferase reporter assay, we demonstrated that let-7 directly inhibits Igf1. CONCLUSION: Acu/LFES on hindlimb decreases let-7-5p leading to upregulation of the Igf1 signaling and increasing protein synthesis in both hindlimb and forelimb skeletal muscles. This provides a new understanding of how the electrical acupuncture treatment can positively influence muscle health.

Bergenin attenuates bleomycin-induced pulmonary fibrosis in mice via inhibiting TGF-ß1 signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by epithelial cell damage, fibroblast activation, and collagen deposition. IPF has high mortality and limited therapies, which urgently needs to develop safe and effective therapeutic drugs. Bergenin, a compound derived from a variety of medicinal plants, has demonstrated multiple pharmacological activities including anti-inflammatory and anti-tumor, also acts as a traditional Chinese medicine to treat chronic bronchitis, but its effect on the pulmonary fibrosis is unknown. In this study, we demonstrated that bergenin could attenuate bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro studies indicated that bergenin inhibited the transforming growth factor-ß1 (TGF-ß1)-induced fibroblast activation and the extracellular matrix accumulation by inhibiting the TGF-ß1/Smad signaling pathway. Further studies showed that bergenin could induce the autophagy formation of myofibroblasts by suppressing the mammalian target of rapamycin signaling and that bergenin could promote the myofibroblast apoptosis. In vivo experiments revealed that bergenin substantially inhibited the myofibroblast activation and the collagen deposition and promoted the autophagy formation. Overall, our results showed that bergenin attenuated the BLM-induced pulmonary fibrosis in mice by suppressing the myofibroblast activation and promoting the autophagy and the apoptosis of myofibroblasts.

Graphene Oxide Nanoparticle-Loaded Ginsenoside Rg3 Improves Photodynamic Therapy in Inhibiting Malignant Progression and Stemness of Osteosarcoma.

Osteosarcoma serves as a prevalent bone cancer with a high metastasis and common drug resistance, resulting in poor prognosis and high mortality. Photodynamic therapy (PDT) is a patient-specific and non-invasive tumor therapy. Nanoparticles, like graphene oxide have been widely used in drug delivery and PDT. Ginsenoside Rg3 is a principal ginseng component and has presented significant anti-cancer activities. Here, we constructed the nanoparticles using GO linked with photosensitizer (PS) indocyanine green (ICG), folic acid, and polyethylene glycol (PEG), and loaded with Rg3 (PEG-GO-FA/ICG-Rg3). We aimed to explore the effect of PEG-GO-FA/ICG-Rg3 combined with PDT for the treatment of osteosarcoma. Significantly, we found that Rg3 repressed proliferation, invasion, and migration, and enhanced apoptosis and autophagy of osteosarcoma cells, while the PEG-GO-FA/ICG-Rg3 presented a higher activity, in which NIR laser co-treatment could remarkably increase the effect of PEG-GO-FA/ICG-Rg3. Meanwhile, stemness of osteosarcoma cell-derived cancer stem cells was inhibited by Rg3 and PEG-GO-FA/ICG-Rg3, and the combination of PEG-GO-FA/ICG-Rg3 with NIR laser further significantly attenuated this phenotype in the system. Moreover, NIR laser notably improved the inhibitor effect of PEG-GO-FA/ICG-Rg3 on the tumor growth of osteosarcoma cells in vivo. Consequently, we concluded that PEG-GO-FA/ICG-Rg3 improved PDT in inhibiting malignant progression and stemness of osteosarcoma cell. Our finding provides a promising and practical therapeutic strategy for the combined treatment of osteosarcoma.

[Study on oral absorption mechanisms of puerarin in nanocrystals self-stabilized pickering emulsion].

Nanocrystals self-stabilized Pickering emulsion(NSSPE) is a new kind of emulsion where only nanocrystals of poorly soluble drugs are used as stabilizers. Our previous study showed that NSSPE with Ligusticum chuanxiong oil as the main oil phase can significantly promote oral absorption of puerarin. The present study aimed to explore its absorption mechanism in oral administration. The in vitro dissolution test was carried out to study the effect of NSSPE on release of puerarin. The effects and mechanism of NSSPE on uptake and transport of puerarin across Caco-2 cell were investigated. The results showed that the drug release rate of NSSPE was similar to that of nanocrystals, with their cumulative dissolution of puerarin not affected by pH of releasing mediums, both significantly higher than that of crude material. The uptake of puerarin in NSSPE was concentration-dependent and significantly higher than that of solution or surfactant stabilized emulsion. Genistein and indomethacin, inhibitors of lipid rafts/caveolin, could significantly reduce the uptake of puerarin in NSSPE. Compared with solution, NSSPE and surfactants stabilized emulsion obviously increased transport rate K_a and apparent permeability coefficient P_(app) of puerarin in AP → BL direction, but there was no significant difference in BL → AP direction. It could be inferred that there were both passive and active transport mechanisms, as well as lipid raft/caveolin mediated endocytosis for absorption of NSSPE. The promoted oral absorption of puerarin in NSSPE was mainly related to the existing nanocrystal form which could promote dissolution, puerarin as well as Ligusticum chuanxiong oil which could promote drug transmembrane transport and inhibit drug efflux. It is the unique structure and composition of the compound NSSPE that promoted the oral absorption of puerarin.

Transcriptome analysis reveals underlying immune response mechanism of fungal (Penicillium oxalicum) disease in Gastrodia elata Bl. f. glauca S. chow (Orchidaceae).

BACKGROUND: Gastrodia elata Bl. f. glauca S. Chow is a medicinal plant. G. elata f. glauca is unavoidably infected by pathogens in their growth process. In previous work, we have successfully isolated and identified Penicillium oxalicum from fungal diseased tubers of G. elata f. glauca. As a widespread epidemic, this fungal disease seriously affected the yield and quality of G. elata f. glauca. We speculate that the healthy G. elata F. glauca might carry resistance genes, which can resist against fungal disease. In this study, healthy and fungal diseased mature tubers of G. elata f. glauca from Changbai Mountain area were used as experimental materials to help us find potential resistance genes against the fungal disease. RESULTS: A total of 7540 differentially expressed Unigenes (DEGs) were identified (FDR < 0.01, log2FC > 2). The current study screened 10 potential resistance genes. They were attached to transcription factors (TFs) in plant hormone signal transduction pathway and plant pathogen interaction pathway, including WRKY22, GH3, TIFY/JAZ, ERF1, WRKY33, TGA. In addition, four of these genes were closely related to jasmonic acid signaling pathway. CONCLUSIONS: The immune response mechanism of fungal disease in G. elata f. glauca is a complex biological process, involving plant hormones such as ethylene, jasmonic acid, salicylic acid and disease-resistant transcription factors such as WRKY, TGA.

Stepwise elution by high-speed counter-current chromatography combined with a modified macroporous resin to isolate and purify antioxidant phenolics from discarded jackfruit (Artocarpusheterophyllus Lam.) peels.

Combined with modified macroporous resin (MR), high-speed counter-current chromatography (HSCCC) was developed to separate and purify the antioxidant phenolics from waste jackfruit peels. First, the 4,4'-bis(chloromethyl)-1,1'-biphenyl was used to modify the commercially available adsorbent resin XAD-4 in order to enrich the antioxidant phenolics. Second, the resultant phenolics-rich fractions were further purified by HSCCC. In the separation process, the petroleum ether-ethyl acetate-methanol-0.1% acetic acid (5 : 5 : 3 : 7, v/v) upper phase was employed as an immobile phase. Afterwards, stepwise elution using petroleum the ether-ethyl acetate-methanol-0.1% acetic acid (5 : 5 : 3 : 7, v/v) lower phase was carried out during the initial 3.5 h, whereas the petroleum ether-ethyl acetate-methanol-0.1% acetic acid (5 : 5 : 6 : 4, v/v) lower phase was adopted for stepwise elution during the later 2.0 h. Four phenolics were obtained from 179 mg of the phenolics-rich fraction in a single run, including 41 mg chlorogenic, 27 mg gallic acid, 33 mg quercetin, and 29 mg catechin. 13C NMR, 1H NMR, and ESI-MS were employed to identify their structures.

Response of the nitrogen load and its driving forces in estuarine water to dam construction in Taihu Lake, China.

To regulate the water level and minimize the occurrence of water eutrophication in shallow lakes, dams and gates are often constructed in rivers. However, this practice may result in a deterioration of water quality in some estuaries. In the present study, using the correction of Nemerow pollution index (CNPI) and a redundancy analysis (RDA), water samples from different dammed rivers around Taihu Lake were compared to assess the pollution risk and identify the factors responsible for water eutrophication. The average total nitrogen (TN), total phosphorus (TP), total organic carbon (TOC) concentrations, and chemical oxygen demand (CODMn) were 2.45 ± 2.28, 0.08 ± 0.06, 43.01 ± 18.75, and 10.78 ± 4.86 mg L-1, respectively. The CNPI values indicated that approximately 76.47% of the estuarine water was moderately polluted (1 < CNPI < 7.28). A positive correlation was observed between dam construction and nutrient concentrations (e.g., rTN = 0.38, p < 0.05; rTP = 0.89, p < 0.01). Under the effects of dam construction, land use change, estuary shape, and meteorological conditions, there was a clear spatial variation of the TN concentrations. Dams that were closed all year round accelerated the TN accumulation in the water around them. The pollution risk in a trumpet-shaped estuary was higher than that in other regions (t = 2.92, p = 0.02). Endogenous release of pollutants was an important factor that may have a priming effect on algal blooms and should be given more attention. In Wuli Lake, exogenous pollution was the dominant pollutant source. A total of 74.49% of the nitrogen losses with the runoff into the estuarine water in 2018 were derived from urban domestic sewage and constructed land, with the load being 4.40 times higher than in 2000. The RDA results revealed that dam construction was the main factor (43.70%) affecting water quality, while meteorological conditions, land use types, estuary shape, and other factors contributed 56.30%. Scientific regulation and control of dam operation is important to protect the water environment of Taihu Lake.

Aldosterone Decreases Vasopressin-Stimulated Water Reabsorption in Rat Inner Medullary Collecting Ducts.

Aldosterone indirectly regulates water reabsorption in the distal tubule by regulating sodium reabsorption. However, the direct effect of aldosterone on vasopressin-regulated water and urea permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether aldosterone regulates osmotic water permeability in isolated perfused rat IMCDs. Adding aldosterone (500 nM) to the bath significantly decreased osmotic water permeability in the presence of vasopressin (50 pM) in both male and female rat IMCDs. Aldosterone significantly decreased aquaporin-2 (AQP2) phosphorylation at S256 but did not change it at S261. Previous studies show that aldosterone can act both genomically and non-genomically. We tested the mechanism by which aldosterone attenuates osmotic water permeability. Blockade of gene transcription with actinomycin D did not reverse aldosterone-attenuated osmotic water permeability. In addition to AQP2, the urea transporter UT-A1 contributes to vasopressin-regulated urine concentrating ability. We tested aldosterone-regulated urea permeability in vasopressin-treated IMCDs. Blockade of gene transcription did not reverse aldosterone-attenuated urea permeability. In conclusion, aldosterone directly regulates water reabsorption through a non-genomic mechanism. Aldosterone-attenuated water reabsorption may be related to decreased trafficking of AQP2 to the plasma membrane. There may be a sex difference apparent in the inhibitory effect of aldosterone on water reabsorption in the inner medullary collecting duct. This study is the first to show a direct effect of aldosterone to inhibit vasopressin-stimulated osmotic water permeability and urea permeability in perfused rat IMCDs.

The correlation between the methylation of PTEN gene and the apoptosis of osteosarcoma cells mediated by SeHA nanoparticles.

The invasive spreading of residual osteosarcoma cells becomes a serious threat to human health, urgently needing new bone regenerative biomaterials for orthopedic therapy. Thus, in this work, selenite-substituted hydroxyapatite (SeHA) nanoparticles were prepared for both inhibiting the recurrence of the tumor and accelerating the regenerative repair of bone defect. Physicochemical characterization showed these synthetic nanoparticles were spherical poly-crystals with the shape of snowflakes. Such structure benefited them to inhibit the cellular viability of osteosarcoma cells by about (58.90 ± 14.37)% during 24 h co-culturing. The expression level of cell growth-related genes such as PTEN, MMP-9, Cyclin D1, Cyclin A2, Annexin A2 and CDC2 decreased. Bisulfite Sequence PCR of PTEN gene exhibited about (22.40 ± 5.39)%, (45.91 ± 6.36)% and (25.90 ± 5.36)% promoter methylation in control, HA and SeHA group. Animal experiment also proved the similar effects. Almost no recurrence were observed in SeHA group. Oppositely, the slowly recurrent growth of the remnant tumor appeared in purely surgical group. The overall survival and toxicity analysis showed that, in the usage dose of 0-0.1 g, the SeHA-0.01 exhibited higher inhibitory recurrence and metastasis potentials, lower renal toxicity and better anti-inflammation function. Immunohistochemistry stain showed the reduced expression of PTEN, MMP-9, Ki-67 and Annexin A2, but slightly increased expression of DNMT1 and BMP-2. Compared the methylation status of PTEN gene in each group, it was confirming that SeHA nanoparticles hardly possessed the de-methylation effect, but the pure HA strikingly increased the methylation level of such gene. It seemed the dopant selenite ions possessed de-methylation effect onto PTEN gene. Therefore, from the viewpoint of inhibiting metastatic potentials, the SeHA-0.01 might be a feasible biomaterial to inhibit the relapse of the tumor post-surgery.

Revisiting Mechanisms Underlying Digestion of Starches.

The factors that determine the digestion rate of starches were revealed using different forms of starches and a mixture of α-amylase and amyloglucosidase. Gelatinized starch samples with a degree of gelatinization (DG) from 12.2 to 100% for potato starch and from 7.1 to 100% for lotus seed starch were obtained. With an increasing DG, the short- and long-range molecular orders of both starches were disrupted progressively. The first-order digestion rate constant (k) of both starches increased with an increasing DG, although the positive linear relationships between DG and k differed (R2 = 0.87 for potato starch, and R2 = 0.74 for lotus seed starch). The mean fluorescence intensity showed a positive linear correlation with DG, which was strong for potato starch (R2 = 0.99) and relatively weaker for lotus seed starch (R2 = 0.54). These results indicated that DG is a major determinant for the digestion rate of potato starch and lotus seed starch and that the access/binding of enzymes to starch was the main rate-limiting factor for digestion of starches.

[Effect of modified Buyang Huanwu Decoction on hemorrhagic transformation after rt-PA intravenous thrombolysis in patients with super early cerebral infarction].

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.

Scutellaria barbata D. Don (SBD) protects oxygen glucose deprivation/reperfusion-induced injuries of PC12 cells by up-regulating Nrf2.

This study aimed to investigate the potential effect of Scutellaria barbata D. Don (SBD) on oxygen glucose deprivation/reperfusion (OGD/R)-injured PC12 cells. PC12 cells were pretreated with various concentrations of 0.1-0.8 mg/ml SBD for indicated times (12-48 h) and then subjected to OGD/R injury. Cell viability, apoptosis and proliferation were detected using MTT assay, flow cytometry, Ki67 staining and western blot. Oxidative damage was assessed by detecting MDA content, SOD activity and GSH levels. The mitochondrial membrane potential (Δψm) was measured by Rh123 staining. Western blot was performed to assess the expression levels of Nrf2 and PI3K/AKT pathway-related proteins. We found that SBD pretreatment promoted cell viability and proliferation but inhibited apoptosis of OGD/R-injured PC12 cells in dosage- and time-dependent manner. Meanwhile, SBD attenuated oxidative damage and restored mitochondria dysfunction, as evidenced by the reduced MDA content, the increased SOD and GSH levels, and the increased Δψm. Furthermore, SBD induced the expression of Nrf2 in a PI3K/AKT-dependent signalling. Knockdown of Nrf2 blocked the protective effects of SBD on PC12 cells. In conclusion, this study demonstrates that SBD pretreatment protects PC12 cells against OGD/R-induced injury. The potential mechanism may be through up-regulating the expression of Nrf2 in a PI3K/AKT-dependent pathway.

Effect of CaCl2 pre-treatment on the succinylation of potato starch.

Potato starch was pre-treated with CaCl2 solutions prior to modification with octenyl succinic anhydride (OSA). Starch pre-treated with 1.0 M CaCl2 showed higher degree of substitution (DS) and reaction efficiency (RE) on OSA modification, whereas pre-treatment with CaCl2 solutions at 0.05 M, 0.1 M and 0.5 M had no effect on DS and RE. CaCl2 pre-treatment decreased the swelling power, paste clarity, peak viscosity (PV), breakdown (BD) and some textural parameters of potato starch, with the effects being greater at higher concentrations of CaCl2. Pre-treatment with 1.0 M CaCl2 caused a small disruption to starch crystallinity and granule morphology. OSA modification significantly decreased the textural parameters, PV, BD, relative crystallinity, swelling power, gelatinization temperatures and enthalpy of potato starch, but it increased the paste clarity and emulsifying activity. OSA-1.0 M-starch showed improved functional properties over OSA-starch, indicating that CaCl2 pre-treatment provides advantages for improving the functional characters of succinylated starch.