Shen-Shuai-Ling Formulation Attenuates Renal Interstitial Fibrosis in Chronic Kidney Disease by Regulating SHH-Gli1 Signaling Pathway.

BACKGROUND: Shen-Shuai-Ling Formulation (SSLF) has apparent effects on improving renal function, delaying the progression of chronic kidney disease (CKD). METHODS: Fifty male SD rats were randomly divided into 5 groups: Sham group, Model group, SSLF group, CPN group, and C + S group. The morphological changes and the collagen fibers of the rat kidneys were observed by HE staining. The expression of α-SMA, Col I, SHH, Gli1, and snail1 was detected by Western blot and qPCR. Then, the cells were divided into the control group, SHH group, and SHH + SSLF serum group. RESULTS: Compared with the Model group, the fibrosis in SSLF, CPN, and C + S groups was significantly alleviated. And, compared with those in the Model group, the expression of α-SMA, Col I, SHH, Gli1, Snail in SSLF, CPN, and C + S groups decreased remarkably. CONCLUSIONS: SSLF remarkably improves renal function and alleviates renal interstitial fibrosis in UUO rats.

Ultra-small bimetallic phosphides for dual-modal MRI imaging guided photothermal ablation of tumors.

Metal phosphides have been proved to be potential theranostic agents of tumors. However, the limitations of single-modal imaging or the treatment effect of such materials need to be further improved. Here, we successfully prepared polyvinylpyrrolidone-modified bimetallic nickel cobalt phosphide (NiCoP/PVP) nanoparticles as a theranostic agent of tumors. Owing to the different types of magnetic properties of Ni and Co components, T1- and T2-weighted magnetic resonance imaging (MRI) could be simultaneously achieved to compensate the low accuracy brought about by single-modal MRI. In addition, NiCoP/PVP possesses excellent photothermal properties owing to its obvious absorption in the near-infrared (NIR) region, which endows NiCoP/PVP with high photothermal conversion efficiency (PCE) to serve as a photothermal agent for tumor ablation. Therefore, NiCoP/PVP is a promising theranostic agent for accurate diagnosis and effective treatment of tumors.

Progress of the use of alternatives to malt in the production of gluten-free beer.

Beer is the most widely consumed alcoholic drink in the world, but it is not suitable for patients who suffer from celiac disease (CD) because its main ingresdients, barley or wheat, contain gluten. Approximately 1% of the world's population is affected by CD, and the development of gluten-free beer is imperative. Gluten-free beers produced using alternative materials, such as rice, sorghum, maize, millet, oats, and pseudocereals (e.g., buckwheat, quinoa and Amaranth), are studied in this review that examines the effects of specific substitutions on the different characteristics of the final beer to ensure the appropriateness of their use. The use of alternatives to malt may affect the quality of gluten-free beer and result in some negative consequences. Accordingly, the influential factors are discussed in terms of the total substitution of malt with other grains in the production of beer. Research results have provided some new alternative solutions for the production of gluten-free beer, such as the use of malted grains to improve hydrolytic enzyme activity, the application of nonconventional mashing procedures involving the decoction method and extrusion cooking techniques to increase the extract yield, the use of exogenous enzymes and nitrogen supplements to improve the sugar and amino acid spectra necessary for yeast fermentation, and the application of combinations of alternative grains to improve the flavor, body and foam stability of gluten-free beers.

Engineering Cu2-xS-conjugated upconverting nanocomposites for NIR-II light-induced enhanced chemodynamic/photothermal therapy of cancer.

The integration of chemodynamic therapy (CDT) and photothermal therapy (PTT) has played a huge role in improved anticancer treatments. Here, a novel multifunctional nanoplatform based on Cu2-xS conjugated NaYF4:Yb/Er@NaYF4:Yb upconversion nanoparticles (UCNPs) was proposed and designed. In the UCNPs-Cu2-xS nanocomposites, UCNPs with excellent luminescent properties and a high X-ray attenuation coefficient can serve as an upconversion luminescence (UCL) and computer tomography (CT) imaging contrast agent; meanwhile, Cu(II) in the Cu2-xS nanodots enables the nanocomposites to have a magnetic resonance imaging (MRI) ability owing to the presence of unpaired electrons. Moreover, the Cu2-xS nanodots with a strong absorbance in the NIR II biowindow not only could be employed as a stable photothermal agent under NIR laser irradiation, but also could be used as a photothermal-enhanced Fenton nanocatalyst to respond to over-expressed H2O2 in the tumor microenvironment (TME) and generate toxic hydroxyl radicals (˙OH) to effectively kill cancer cells. Furthermore, the UCNPs-Cu2-xS nanocomposites possess negligible cytotoxicity and a high photothermal conversion efficiency (43.8%) in the NIR-II biowindow (1064 nm), indicating that they possess great potential for the UCL/CT/MR multi-modal imaging guided synergistic enhanced CDT/PTT of cancer.

Engineering Gadolinium-Integrated Tellurium Nanorods for Theory-Oriented Photonic Hyperthermia in the NIR-II Biowindow.

Near-infrared (NIR) light-triggered hyperthermia has exhibited promising prospects in oncology therapy due to the unique merits including minimal invasiveness, monitorable, excellent therapeutic effect, and negligible side effects. Especially, the second NIR biowindow (NIR-II, 1000-1700 nm) with less absorbance and scattering by skin tissue, and deep tissue penetration, has received extensive attention for photonic hyperthermia. Unfortunately, the dissatisfactory photothermal conversion efficiency (PCE) and cumbersome preparation process of photo-driven heat conversion nanomaterials seriously hamper the future clinical application. To combat the aforementioned challenges, high imaging performance and desired therapeutic outcome 1D nanorods are constructed based on gadolinium-integrated tellurium nanorods (Te-Gd). In this system, magnetic resonance (MR) imaging and X-ray computed tomography (CT) imaging-guided photonic hyperthermia can be easily implemented in cooperation with Te-Gd. Importantly, Te-Gd possesses high PCE (41%) in the NIR-II biowindow because the transition of the excited electron can easily occur from the valence band (VB) to the conduction band (CB) on (1 0 1) and (1 0 2) crystal planes. Furthermore, the distinctive photostability, high tumor accumulation, as well as low systemic adverse effects of Te-Gd guarantee the potential in the clinic.

Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer.

PURPOSE: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement. MATERIALS AND METHODS: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated. RESULTS: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00±0.1717 nm and an APS-loading efficiency of 54.89±2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo. CONCLUSION: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.

A highly active (102) surface-induced rapid degradation of a CuS nanotheranostic platform for in situ T1-weighted magnetic resonance imaging-guided synergistic therapy.

Polyvinylpyrrolidone-modified CuS nanocrystals (CuS NCs) with high photothermal conversion efficiency (46%) and pH and near-infrared (NIR) light-triggered degradation properties are a promising nanotheranostic platform for in situ magnetic resonance imaging (MRI)-guided synergistic photothermal and photodynamic therapy. On the one hand, the (102) surface of CuS NCs has a small bandgap based on density functional theory, which leads to high photothermal conversion efficiency. On the other hand, the S vacancy formation energy of the (102) surface is favourable. On entry into tumor cells through endocytosis, the S2- ions on the (102) surface of CuS NCs can be easily oxidized under the tumor microenvironment and 808 nm laser irradiation; then, a large amount of Cu+ ions can be released from CuS NCs and accelerate the degradation of nanocrystals. Cu+ ions can generate reactive oxygen species (ROS) under the tumor microenvironment and 808 nm laser irradiation. Meanwhile, the oxidation product Cu2+ ions can be generated from the oxidized Cu+ ions and applied for in situ T1-weighted magnetic resonance imaging. Moreover, the biodegradable CuS NCs possess a high tumor uptake and can be rapidly excreted with a low long-term retention/toxicity. Therefore, degradable and multifunctional CuS NCs are a safe and efficient candidate for the diagnosis and treatment of cancer.

[Mechanism of Gardenia jasminoides against cholestasis based on network pharmacology].

To screen the active ingredients of Gardenia jasminoides and potential targets,and investigate the mechanisms against cholestasis based on network pharmacology technology. Twenty-one active components of G. jasminoides were retrieved and the target sites were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP). Cytoscape3. 2. 1 was used to construct the component-target network. Two hundred and eight targets related to cholestasis were searched and screened through Dis Ge NET,KEGG and OMIM databases. The key targets of G. jasminoides components and cholestasis were integrated and screened,and the component-target-disease network was constructed with Cytoscape 3. 2. 1 software to screen out the core network whose freedom degree was greater than the average value. The Clue GO plug-in of Cytoscape 3. 2. 1 software was used to analyze the biological processes and pathway enrichment of G. jasminoides in regulation of cholestasis. GO biological process analysis revealed 17 biological processes,involving 3 signaling biological processes related to cholestasis,i.e. acute inflammatory response,positive regulation of reactive oxygen species metabolic process,and nitric oxide biosynthetic process. KEGG-KEEG-305 terms and REACTOME pathways analysis revealed 17 regulatory pathways,involving 4 signaling pathways related to cholestasis,i.e. metabolism of xenobiotics by cytochrome P450,nuclear receptor transcription pathway,GPVI-mediated activation cascade and platelet activation. It was found that aqueous extract of G. jasminoides could improve serum biochemical abnormalities in ANIT-induced cholestasis rats. Aqueous extract of G. jasminoides could decrease the protein and mRNA expression levels of ESR1 in liver tissues,and increase the protein and mRNA expression levels of PPARG,NOS2,F2 R,NOS3,and NR3 C1. To sum up,the possible mechanisms of G. jasminoides against cholestasis may be related with the above three processes and four pathways.

Ultrafast synthesis of ultrasmall polyethylenimine-protected AgBiS2 nanodots by "rookie method" for in vivo dual-modal CT/PA imaging and simultaneous photothermal therapy.

Developing a biocompatible nanotheranostic platform integrating diagnostic and therapeutic functions is a great prospect for cancer treatment. However, it is still a great challenge to synthesize nanotheranostic agents using an ultra-facile method. In the research reported here, ultrasmall polyethylenimine-protected silver bismuth sulfide (PEI-AgBiS2) nanodots were successfully synthesized using an ultra-facile and environmentally friendly strategy (1 min only at room temperature), which could be described as a "rookie method". PEI-AgBiS2 nanodots show good monodispersity and biocompatibility. For the first time, PEI-AgBiS2 nanodots were reported as a powerful and safe nanotheranostic agent for cancer treatment. PEI-AgBiS2 nanodots exhibit excellent computed tomography (CT) and photoacoustic (PA) dual-modal imaging ability, which could effectively guide photothermal cancer therapy. Furthermore, PEI-AgBiS2 nanodots exhibit a high photothermal conversion efficiency (η = 35.2%). The photothermal therapy (PTT) results demonstrated a highly efficient tumor ablation ability. More importantly, the blood biochemistry and histology analyses verify that the PEI-AgBiS2 nanodots have negligible long-term toxicity. This work highlights that PEI-AgBiS2 nanodots produced using this extremely effective method are a high-performance and safe PTT agent. These findings open a new gateway for synthesizing nanotheranostic agents by using this ultra-facile method in the future.

Nanoparticle based bio-bar code technology for trace analysis of aflatoxin B1 in Chinese herbs.

A novel and sensitive assay for aflatoxin B1 (AFB1) detection has been developed by using bio-bar code assay (BCA). The method that relies on polyclonal antibodies encoded with DNA modified gold nanoparticle (NP) and monoclonal antibodies modified magnetic microparticle (MMP), and subsequent detection of amplified target in the form of bio-bar code using a fluorescent quantitative polymerase chain reaction (FQ-PCR) detection method. First, NP probes encoded with DNA that was unique to AFB1, MMP probes with monoclonal antibodies that bind AFB1 specifically were prepared. Then, the MMP-AFB1-NP sandwich compounds were acquired, dehybridization of the oligonucleotides on the nanoparticle surface allows the determination of the presence of AFB1 by identifying the oligonucleotide sequence released from the NP through FQ-PCR detection. The bio-bar code techniques system for detecting AFB1 was established, and the sensitivity limit was about 10-8 ng/mL, comparable ELISA assays for detecting the same target, it showed that we can detect AFB1 at low attomolar levels with the bio-bar-code amplification approach. This is also the first demonstration of a bio-bar code type assay for the detection of AFB1 in Chinese herbs.

Comparison of the ameliorative effects of Qingfei Tongluo formula and azithromycin on Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae pneumonia (MPP) is a common disease in children. Qingfei Tongluo formula (QTF) has been used for the treatment of MPP clinically, but the therapeutic effect remains unclear compared to conventional treatments with Western medicines. Therefore, the aim of this study was to assess changes in the expression levels of relevant factors associated with microcirculation after MPP and to compare the therapeutic effect of QTF with that of azithromycin (AZM) on experimental mice with MPP. A total of 174 children admitted with clinical diagnoses of pneumonia (80 MPP and 94 non-MPP) were used to identify differences in the expression patterns of factors in the microcirculation using an enzyme-linked immunosorbent assay. A BALB/c mouse model of MPP infection was established to determine the therapeutic effect of QTF. The results showed that the expression level of thrombomodulin (TM), vascular endothelial growth factor (VEGF), d-dimer (D-D), interleukin (IL)-6, and IL-10 were upregulated after MPP both clinically in children and in the mouse model. After 3 days of therapy, the amount of total MPP DNA decreased, especially in the mid- and high-dose QTF treatment groups. The expression levels of VEGF, IL-6, and IL-10 also decreased in response to treatment with QTF or AZM. However, there was no influence on D-D levels. QTF treatment also decreased TM expression. In conclusion, QTF treatment inhibited the progression of MPP, reduced vascular permeability, and improved pulmonary microcirculation more effectively than conventional treatment with Western medicine.

Factors that contribute to the willingness to try "street hypnosis".

This study takes a context-specific approach to examine people's willingness to try hypnosis under various conditions and the factors that contribute to their willingness. It examined 378 participants, who completed a web-based hypnosis survey. The results showed that people's willingness to try hypnosis varies by context. Specifically, people are more willing to try hypnosis when it is framed as "peak focus" rather than "hypnosis" and when they perceive the environment as being safer. Moreover, factors including participants' demographics, hypnotists' demographics (relative to the subjects'), participants' control bias, and knowledge of hypnosis affect people's degrees of willingness to try hypnosis, depending on the specific context. The results suggest further analysis of hypnosis occurring in public contexts and the effects it may have on attitudes and therapeutic outcomes.

[Study on influence of glucoside Tripterygium total tablets on metabolism in rats by NMR metabonomic technique].

OBJECTIVE: To investigate the toxic effects of Glucoside Tripterygium total on rats with nuclear magnetic resonance (NMR)-based metabonomic method. METHOD: The influence of intragastric administration of Glucoside Tripterygium total suspension at two different doses on endogenetic metabolites in normal rat urine was determined with bio-NMR method then analyzed by pattern recognition technique and partial least-squares discriminant analysis (PLS-DA). Histopathological analysis was carried out. RESULT: Escalations of concentrations of urinary taurine, TMAO and glucose as well as reductions of concentrations of urinary citrate and 2-oxoglutarate were found by analysis of the 1H-NMR spectra, which was coincident with the result of histopathological analysis. The result of pathological examination indicated that pathologic change was not observed in nephridial tissue, but there were obvious changes in hepatic tissue. CONCLUSION: The urinary metabomic spectra were closely associated with the hepatic toxicity, which manifested the mitochondrial dysfunctions, the abnormal energy metabolism in TCA cycle as well as the abnormal glucose metabolism.

Frequency domain detection of biomolecules using silicon nanowire biosensors.

We demonstrate a new protein detection methodology based upon frequency domain electrical measurement using silicon nanowire field-effect transistor (SiNW FET) biosensors. The power spectral density of voltage from a current-biased SiNW FET shows 1/f-dependence in frequency domain for measurements of antibody functionalized SiNW devices in buffer solution or in the presence of protein not specific to the antibody receptor. In the presence of protein (antigen) recognized specifically by the antibody-functionalized SiNW FET, the frequency spectrum exhibits a Lorentzian shape with a characteristic frequency of several kilohertz. Frequency and conventional time domain measurements carried out with the same device as a function of antigen concentration show more than 10-fold increase in detection sensitivity in the frequency domain data. These concentration-dependent results together with studies of antibody receptor density effect further address possible origins of the Lorentzian frequency spectrum. Our results show that frequency domain measurements can be used as a complementary approach to conventional time domain measurements for ultrasensitive electrical detection of proteins and other biomolecules using nanoscale FETs.

[Blood lipid-regulation of stilbene glycoside from polygonum multiflorum].

OBJECTIVE: To study lipid-regulating action of 2, 3, 5, 4'-tetrahydroxy stilbene-2-O-beta-D-glucopyranoside (TSG) from Polygonum multiflorum on experimental model hyperlipidemic rats. METHOD: TSG 90 and 180 mg x kg(-10 x d(-1), atorvastatin mg kg(-1) x d(-1) and saline 2 mL x d(-1) were administered to hyperlipidemic rats. Groups of rats were determined and compared with those of saline group. The LDLR and HMGR mRNA expression were also detected. RESULT: TSG significantly reduced serum TC and LDL-C level and atherosclerosis index, increased the expression of LDLR in the liver cells. CONCLUSION: TSG, which shows effects and mechanism in part like atorcastatin, is a major constituent with blood-lipid regulating effect of P. multiflorum and can be explored as a potent medication for hyperlipidemia. Effects on LDL-C and AI, as well as on gene expression of TSG were first reported.