Parthenolide Attenuates Sepsis-Induced Acute Kidney Injury in Rats by Reducing Inflammation.

Background: Sepsis is a common complication of severe trauma, burns, infection, or major surgery. This disease-related end-organ dysfunction results from systemic inflammatory response syndrome (SIRS). Acute kidney damage (AKI), also known as acute renal failure, is one of the most frequent and serious sequelae of sepsis. Nuclear transcription factor-κB (NF-κB) regulates the transcription of inflammation-related genes and operates as a mediator in the immune system. While parthenolide (PTL) has been reported to prevent harmful inflammatory reactions, its effects on sepsis-associated AKI are unknown. The current study investigates the effects of PTL in sepsis-associated AKI using cell and cecal ligation and puncture (CLP) models. Methods: Lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells were treated with 10 µM PTL. Inflammatory mediators, including TNF-α, IL-6, and IL-1ß, in the culture supernatants were measured by ELISA, and NF-κB levels were assessed by qPCR. After the generation of the septic CLP model, rats were intraperitoneally injected with 500 g/kg PTL and were euthanized after 72 h. Serum and kidney samples were analyzed. Results: TNF-α, IL-1ß, and IL-6 levels were elevated after LPS treatment of rat glomerular mesangial cells (p=0.004, p=0.002, and p=0.004, respectively) but were significantly reduced in the PTL treatment group (p ≤ 0.001, p=0.01, and p ≤ 0.001). NF-κB p65 levels were also increased after LPS treatment in this group and were reduced in the PTL treatment group. PTL treatment also reduced kidney damage after CLP induction, as shown by histological analysis and reductions in the levels of BUN, Cre, KIM-1, and NAGL. CLP-induced kidney inflammation together with increased levels of proinflammatory cytokines and inflammatory-related proteins. The elevated levels of renal TNF-α, IL-6, and IL-1ß were downregulated after PTL treatment. The PTL treatment also reduced the CLP-induced activation of NF-κB p65 in the damaged kidneys. Conclusion: PTL reduced inflammation induced by CLP-induced AKI in rat models and LPS-induced damage to glomerular mesangial cells by suppressing NF-κB signaling.

Panax notoginseng Alleviates Sepsis-Induced Acute Kidney Injury by Reducing Inflammation in Rats.

Background: Sepsis is defined as a host inflammatory response to infection that can result in end-organ dysfunction. One of the most common consequences of sepsis is acute kidney injury (AKI). Panax notoginseng powder (PNP) has been previously reported to protect against overactive inflammation process. However, the potential effect of PNP on septic AKI is poorly described. The current study was conducted to investigate the protective effects of PNP in septic AKI rats. Methods: A model of septic AKI was established on male SD rats by using the cecal ligation and puncture procedure. PNP was administrated by gavage after the cecal ligation and puncture (CLP) procedure, and the mice were sacrificed at 6, 12, and 72 h after induction of sepsis. The serum and kidney samples were collected and assayed for biochemical tests, histopathological staining, inflammation, and apoptosis-related gene/protein expression. In addition, 15 rats in each group were used to calculate the 7-day survival rate. Results: CLP-induced kidney injury was observed by the histopathological score, which markedly was attenuated by PNP treatment. Consistently, PNP intervention significantly alleviated the elevated levels of serum creatinine and blood urea nitrogen in CLP-induced sepsis rats. The CLP procedure also triggered proinflammatory cytokine production and increased the expression of various inflammation-related proteins in the kidneys. However, PNP inhibited the renal expression of IL-18, IL-1ß, TNF-α, and IL-6 to substantially improve inflammatory response. Mechanistically, CLP induced the increase of the NF-κB p65 level in the injured kidneys, while PNP notably inhibited the corresponding protein expression. Conclusion: PNP attenuated kidney inflammation to protect against CLP-induced septic AKI in rats via inhibiting the NF-κB signaling pathway.

Application of Photoshop in Measurement of Microsphere Diameter and Microstructure Drawing of Medicinal Materials / 中国实验方剂学杂志

<b>Objective::To explore the feasibility of Photoshop image processing software in the micro-spherical diameter measurement and identification of medicinal materials, in order to provide a new method for the measurement and mapping of traditional Chinese medicine. <b>Method::Photoshop (CS3 version and above) software was used to measure the diameter of 200 Notoginseng Radix et Rhizoma albumin microspheres in the same batch, digital microscopy and Photoshop image processing software was used to draw schematic diagrams of microstructures of Notoginseng Radix et Rhizoma medicinal powders and its four common pseudo-products and powders, namely Bletillae Radix, Alpiniae Officinarum Rhizoma, Curcumae Longae Rhizoma and <italic>Manihot esculenta,</italic> and make the identification table for classification and identification. <b>Result::The average diameter of the microspheres was (30.62±4.21)μm, and the diameter was mainly distributed in 20-40 μm. The average diameter of the microspheres was verified by laser particle size analyzer (30.18±4.67)μm. The differences between the two methods were not statistically significant. There were many starch granules in Notoginseng Radix et Rhizoma powder, with no calcium oxalate needle, oil cell, brown pigment and stone cell. Microscopic identification could be made for Notoginseng Radix et Rhizoma powder and 4 common counterfeits. <b>Conclusion::Photoshop image processing software measures the diameter of the microspheres with a high speed, high accuracy, simplicity, and low requirements for measuring instruments. It provides a new way to quickly measure the diameter of microspheres. Photoshop image processing software draws a schematic diagram of the microstructure, which is convenient and faster. The original morphology of the ground-reactive microstructure provides a new method for the microstructural drawing.

Gold-caged copolymer nanoparticles as multimodal synergistic photodynamic/photothermal/chemotherapy platform against lethality androgen-resistant prostate cancer.

Given that there is no effective treatment method for lethality androgen-resistant prostate cancers (ARPC), herein we report a multifunctional gold-caged nanoparticle (PTX-PP@Au NPs) against ARPC through integrating functional organic/inorganic materials to exploit the superiors of gold particles such as photothermal effects (PTT), generating reactive oxygen species (photodynamic effects, PDT), carrying chemotherapeutic agents (chemotherapy effects, CT), and inhibiting ion channel. This synergistic PTT/PDT/CT platform consists of three components: i) the Pluronic-polyethylenimine assembling into micelles to encapsulate drugs and providing reduction sites for gold cage formation through a "green" method, ii) the gold cage with surface plasmon resonance peak at near-infrared (NIR) region in a broad window qualifying the PTT/PDT potentiality, iii) a chemotherapeutic agent paclitaxel (PTX) arresting the tumor cell cycle. As demonstrated, the system has remarkable performance on controlling drug release, blocking TRPV6 cation channel, enhancing cell cycle arrest, elevating temperature and generating ROS, thus improving cellular toxicity along with apoptosis, enhancing tumor targeting, and achieving the therapy to ARPC with low toxicity on liver function and minimal side effects to normal organs. Notably, both PTT and PDT effect are generated under single irradiation situation because of the broad absorbance window, along with limited skin damages. As a specific synergistic platform creatively integrating multiple treatment protocols with negative toxicity, PTX-PP@Au NPs provide a facile, effective, and broadly applicable strategy to deadly ARPC.

[Quantitative analysis of 16 components in Cyclocarya paliurus leaf by UPLC-QE-Orbitrap-MS].

Modern research showed that components in the dried leaf of Cyclocarya paliurus. had various biological activities. The current quality control research was focused on content determination of polysaccharides and flavonoids, while there were less research on quantitative analysis of terpenes and phenolic acids. In this paper, the contents of 16 components of 3 kinds in C. paliurus leaf were determined by UPLC-QE-Orbitrap-MS. The results were as following: good linear relationship of 16 analytes existed within the studied concentration rages (R²>0.996), and RSDs were of <3.0% in the precision test and replicate test, with the average recovery rates 95.20%-104.4%, respectively. The results indicatod that the method is simple and accurate, which can be used for the comprehensive quality evaluation of C. paliurus leaf. The established method was applied to determine the contents of 12 batches of C. paliurus leaf from different areas, and the 16 analvtes contents in the samples could be different from several times to dozens times, which indicated that there might be significant quality difference in C. paliurus leaf from different areas.

[Analysis of HPLC and NIRS fingerprints of Chrysanthemum indicum of different processing methods].

This paper studied the HPLC and NIRS fingerprints of Chrysanthemum with different processing methods, including directly drying, drying after steamed, and drying after fried. The method of discriminant analysis of TQ software was used to analysis the NIRS fingerprint of Chrysanthemum with three different processing methods, and the results were consistent with HPLC fingerprint similarity analysis. NIRS and HPLC fingerprints were of different characteristics, and the combination of the two methods can quickly and accurately identify Chrysanthemum with different processing methods.

Analysis of HPLC and NIRS fingerprints of Chrysanthemum indicum of different processing methods / 中国中药杂志

This paper studied the HPLC and NIRS fingerprints of Chrysanthemum with different processing methods, including directly drying, drying after steamed, and drying after fried. The method of discriminant analysis of TQ software was used to analysis the NIRS fingerprint of Chrysanthemum with three different processing methods, and the results were consistent with HPLC fingerprint similarity analysis. NIRS and HPLC fingerprints were of different characteristics, and the combination of the two methods can quickly and accurately identify Chrysanthemum with different processing methods.

Specific cell targeting with APRPG conjugated PEG-PLGA nanoparticles for treating ovarian cancer.

Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG-PLA and mPEG-PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative ζ-potential (-14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic.

Study on steroidal saponins from Dioscorea zingiberensis and their platelet aggregation activities / 中国中药杂志

Using the absorbent resin, silica gel and ODS column chromatography as well as semi-preparative HPLC, ten compounds were isolated from 70% ethanol extract of tubers of Dioscorea zingiberensis C. H. Wright, and their structures were elucidated as trigoneoside XIIIa (1), parvifloside (2), trigoneoside IVa (3), deltoside (4), protobioside (5), lilioglycoside k (6), zingiberensis newsaponin I (7), deltonin (8), prosapogenin A of dioscin (9), and trillin (10) on the basis of NMR and MS spectral data analysis. Among these compounds, 1, 3, 5 and 6 were isolated from this plant for the first time. In the screening test on platelet aggregation, compounds 7 and 8 exhibited induction effect on platelet aggregation, while compound 9 exhibited significant inhibitory effect on platelet aggregation in vitro.

Priming with EGFR tyrosine kinase inhibitor and EGF sensitizes ovarian cancer cells to respond to chemotherapeutical drugs.

Over-expression of EGFR, as in most cases of ovarian cancer, is associated with advanced-stage disease and poor prognosis. Activation of EGFR signaling pathway is involved in increased cell proliferation, angiogenesis, metastasis and decreased apoptosis. Tyrosine kinase activity is essential for signal transduction and receptor down-regulation. However, we found in this study that tyrosine kinase activity is not necessary in ligand-induced EGFR down-regulation in ovarian cancer cell line CaOV3 cells. EGFR tyrosine kinase inhibitors, such as PD153035, AG1478, as well as non-specific tyrosine kinase inhibitor PP2 cannot reverse EGF-induced down-regulation of EGFR. These findings thus permit us to develop the following exciting but unconventional strategy to sensitize cancer cells, namely, by priming ovarian cancer cells with EGF and EGFR inhibitor PD153035, before chemotherapy. This priming procedure down-regulates EGFR without induction of mitogenic signals such as ERK and PI3K/AKT. EGF plus EGFR inhibitor-primed ovarian cancer cells display increased sensitivity to taxol-induced cell death, resistant to EGF-induced cell migration and cell proliferation as well as ERK and PI3K/AKT activation. Further studies showed that PD153035, which does not reverse ligand-induced EGFR down-regulation, blocks EGF-induced EGFR activation as well as EGFR's binding to c-cbl and Grb2. Taken together, we contend that priming with EGFR inhibitors plus EGF inhibits cell signaling pathways leading to cell proliferation and survival, while down-regulating EGFR. This priming approach sensitizes ovarian cancer cells and would ultimately result in better chemotherapeutical outcome.