Widely targeted metabolomics reveals differences in metabolites of Paeonia lactiflora cultivars.

INTRODUCTION: Paeonia lactiflora contains diverse active constituents and exhibits various pharmacological activities. However, only partial identification of biologically active substances from P. lactiflora has been achieved using low-throughput techniques. Here, the roots of P. lactiflora, namely, Fenyunu (CK), Dafugui (DFG), and Red Charm (HSML), were studied. The primary and secondary metabolites were investigated using ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESIMS/MS). METHODS: The chemical compounds and categories were detected using broadly targeted UPLC-MS/MS. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and hierarchical clustering analysis (HCA) were carried out for metabolites of different varieties of P. lactiflora. RESULTS: A total of 1237 compounds were detected and classified into 11 categories. HCA, PCA, and OPLS-DA of these metabolites indicated that each variety of P. lactiflora was clearly separated from the other groups. Differential accumulated metabolite analysis revealed that the three P. lactiflora varieties contained 116 differentially activated metabolites (DAMs) involved in flavonoid, flavone, and flavonol metabolism. KEGG pathway analysis revealed that, in 65 pathways, 336 differentially abundant metabolites (DMs) were enriched in the CK and DFG groups; moreover, the type and content of terpenoids were greater in the CK group than in the DFG group. The CK and HSML groups contained 457 DMs enriched in 61 pathways; the type and amount of flavonoids, terpenoids, and tannins were greater in the CK group than in the HSML group. The DFG and HSML groups contained 497 DMs enriched in 65 pathways; terpenoids and alkaloids were more abundant in the HSML variety than in the DFG variety. CONCLUSIONS: A total of 1237 compounds were detected, and the results revealed significant differences among the three P. lactiflora varieties. Among the three P. lactiflora varieties, phenolic acids and flavonoids composed the largest and most diverse category of metabolites, and their contents varied greatly. Therefore, CK is suitable for medicinal plant varieties, and DFG and HSML are suitable for ornamental plant varieties. Twelve proanthocyanidin metabolites likely determined the differences in color among the three varieties.

Study on the mechanism of naringin in promoting bone differentiation: In vitro and in vivo study.

Objective: Osteoporosis is a common clinical bone disease that occurs most frequently in middle-aged and elderly people. Various traditional herbal medicine formulations have shown significant benefits in models of osteoporosis. In this study, we aim to investigate the osteogenic efficacy of naringin (NRG) in the osteoporotic state. Design: We treated Bone marrow stromal cells (BMSCs) with various concentrations of NRG for 3 and 7 days. BMSC proliferation was measured by the MTT assay. The effect of NRG on the osteogenic differentiation of BMSCs was detected by ALP and alizarin red staining. The effect of NRG on the BMP2/Runx2/Osterix signaling pathway was analyzed by using real-time PCR. The effect of NRG on the oestrogen receptor was measured by Enzyme-linked immunosorbent assay. In vivo animal experiments were performed by micro-computed tomography and ALP immunohistochemistry to determine the ectopic osteogenic effect of NRG sustained-release nanoparticles in a mouse model of osteoporosis. Results: NRG promoted the proliferation and osteogenic differentiation of BMSCs. Moreover, it also activated the BMP2/Runx2/Osterix signaling pathway. When NRG sustained-release nanoparticles were added in vivo in animal experiments, we found that NRG sustained-release nanoparticles had better ectopic osteogenic effects in a mouse model of osteoporosis. Conclusions: NRG induced osteoblastic differentiation of BMSCs by activating the BMP2/Runx2/Osterix signaling pathway and promoted the regulation of oestrogen receptor pathway protein expression, and NRG sustained-release nanoparticles exerted a more significant in vivo ectopic osteogenic effect in an osteoporosis mouse model. Therefore, naringin is expected to be developed as a novel treatment for inducing osteogenesis, because of its ubiquitous, cost-efficient, and biologically active characteristics. However, further research is needed on how to improve the pharmacokinetic properties of naringin and its specific mechanism.

Genome-wide identification of Apetala2 gene family in Hypericum perforatum L and expression profiles in response to different abiotic and hormonal treatments.

The Apetala2 (AP2) gene family of transcription factors (TFs) play important functions in plant development, hormonal response, and abiotic stress. To reveal the biological functions and the expression profiles of AP2 genes in Hypericum perforatum, genome-wide identification of HpAP2 family members was conducted. Methods: We identified 21 AP2 TFs in H. perforatum using bioinformatic methods; their physical and chemical properties, gene structures, conserved motifs, evolutionary relationships, cis-acting elements, and expression patterns were investigated. Results: We found that based on the structural characteristics and evolutionary relationships, the HpAP2 gene family can be divided into three subclasses: euANT, baselANT, and euAP2. A canonical HpAP2 TF shared a conserved protein structure, while a unique motif 6 was found in HpAP2_1, HpAP2_4, and HpAP2_5 from the euANT subgroup, indicating potential biological and regulatory functions of these genes. Furthermore, a total of 59 cis-acting elements were identified, most of which were associated with growth, development, and resistance to stress in plants. Transcriptomics data showed that 57.14% of the genes in the AP2 family were differentially expressed in four organs. For example, HpAP2_18 was specifically expressed in roots and stems, whereas HpAP2_17 and HpAP2_11 were specifically expressed in leaves and flowers, respectively. HpAP2_5, HpAP2_11, and HpAP2_18 showed tissue-specific expression patterns and responded positively to hormones and abiotic stresses. Conclusion: These results demonstrated that the HpAP2 family genes are involved in diverse developmental processes and generate responses to abiotic stress conditions in H. perforatum. This article, for the first time, reports the identification and expression profiles of the AP2 family genes in H. perforatum, laying the foundation for future functional studies with these genes.

The chromosome-scale genome assembly, annotation and evolution of Rhododendron henanense subsp. lingbaoense.

Rhododendron henanense subsp. lingbaoense (hereafter referred to as R. henanense) is an endemic species naturally distributed in the Henan province, China, with high horticultural, ornamental and medicinal value. Herein, we report a de novo genome assembly for R. henanense using a combination of PacBio long read and Illumina short read sequencing technologies. In total, we assembled 634.07 Mb with a contig N50 of 2.5 Mb, representing ~96.93% of the estimated genome size. By applying Hi-C data, 13 pseudochromosomes of R. henanense genome were assembled, covering ~98.21% of the genome assembly. The genome was composed of ~65.76% repetitive sequences and 31,098 protein-coding genes, 88.77% of which could be functionally annotated. Rhododendron henanense displayed a high level of synteny with other Rhododendron species from the Hymenanthes subgenus. Our data also suggests that R. henanense genes related to stress responses have undergone expansion, which may underly the unique abiotic and biotic stress resistance of the species. This alpine Rhododendron chromosome-scale genome assembly provides fundamental molecular resources for germplasm conservation, breeding efforts, evolutionary studies, and elucidating the unique biological characteristics of R. henanense.

One-step synthesis of multifunctional nanoparticles for CT/PA imaging guided breast cancer photothermal therapy.

Advances in nanotheranostics have promoted the development of precision medicine, which has great potential as a weapon for clinical diagnosis and therapy of tumors. However, the combination of three functional principle components (imaging probes, therapeutic agents and surface coating) in traditional theranostic system is difficult to be achieved in only one step, while undergoing multiple synthesis procedures, time-consuming process and unknown toxicity. Herein, we fabricated iodinated polyaniline (LC@I-PANi) nanoparticles via a facile one-step synthesis approach integrating chemical oxidative polymerization and iodine-doping process for computed tomography (CT) imaging and photoacoustic (PA) imaging-guided photothermal therapy (PTT). Iodic acid (HIO3) as an oxidant induces chemical oxidation polymerization of aniline monomers. Meanwhile, iodine is incorporated into the polyaniline structural units in the process of polymerization to obtain LC@I-PANi nanoparticles. Moreover, thel-cysteine (LC) has an effect on diameter of LC@I-PANi nanoparticles, which enables nanoparticles have size-controlled spherical morphology and good colloidal stability. The hemolysis assay and cytotoxicity assessment verified the good biocompatibility of LC@I-PANi. Moreover, our LC@I-PANi nanoparticles could not only exhibit appealing PTT efficiency, but also achieve excellent CT/PA dual-mode imaging effect. The histological evaluations suggested the negligible toxicity of LC@I-PANi in vivo. This is the first time to our knowledge that multifunctional LC@I-PANi nanoparticles were prepared by an ingenious one-step method. This work not only highlights a one-step strategy that simplified the complex synthesis of LC@I-PANi nanoparticles, but also provides insight for further biomedical application of "all-in-one" theranostic agent.

Coupling metal organic frameworks with molybdenum disulfide nanoflakes for targeted cancer theranostics.

The superior properties of metal organic frameworks (MOF) can provide great opportunities for merging functional nanoparticles to construct smart and versatile cancer theranostic agents. In this study, on the basis of non-mesoporous nanoparticles (molybdenum disulfide, MoS2), the structure of the MOF shell layer with an adjustable structure can be constructed through the natural coordination interaction between polydopamine (PDA) and iron ion, and the tumor cell target ligand was modified on the surface of the nanocomposite after loading the anticancer drug doxorubicin hydrochloride (DOX) to form a multifunctional cancer theranostics nanoplatform (DOX@MoS2-PMA). Benefiting from the excellent properties of MoS2 and MOF, the favorable photothermal properties and pH/near-infrared (NIR) laser-triggered DOX release behavior of composite nanoparticles were demonstrated. Its well-defined nanostructure, adequate colloidal stability, and satisfactory biocompatibility were further evidenced. Furthermore, the selective tumor cell targeting ability of DOX@MoS2-PMA can improve the cellular uptake efficacy and the photothermal-chemotherapy combination therapy can significantly enhance the killing effect on cancer cells both in vitro and in vivo. In addition, fluorescence imaging results show that nanoparticles can efficiently accumulate inside tumors. The photoacoustic (PA) and magnetic resonance (MR) imaging capabilities derived from different components of nanoparticles can perform better imaging effects. To the best of our knowledge, this is the first attempt to merge the performance of MoS2 with MOF for PA/MR dual-modality imaging-guided photothermal-chemotherapy combination therapy. Our work presented herein proves that MOF can be combined with non-mesoporous nanoparticles and exhibits excellent performance, thus opening a new avenue for endowing non-mesoporous nanoparticles with an efficient drug loading capacity and practical applications of MOFs in nanomedicine.

Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials.

A potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

Merging metal organic framework with hollow organosilica nanoparticles as a versatile nanoplatform for cancer theranostics.

With great potential in nanomedicine, the integration of a metal organic framework (MOF) with a nanocarrier for smart and versatile cancer theranostics still seeks to expand. In this study, MOF was successfully merged with hollow mesoporous organosilica nanoparticles (HMONs) with a polydopamine (PDA) interlayer to form molecularly organic/inorganic hybridized nanocomposites (HMONs-PMOF). The well-defined nanostructure and favorable biocompatibility of HMONs-PMOF were demonstrated first. Doxorubicin hydrochloride (DOX) and indocyanine green (ICG) were separately loaded into the interior cavity of HMONs and the outer porous shell of MOF with high loading efficacy, respectively. The obtained dual drug-loaded nanocomposites (DI@HMONs-PMOF) displayed favorable photothermal properties and pH/NIR-triggered DOX release manner. Furthermore, in vitro cell experiments validated that HMONs-PMOF can efficiently deliver DOX into cancer cells. Upon entry into cancer cells, the photothermal effect of DI@HMONs-PMOF can induce the lysosome rupture, thereby facilitating the "lysosome escape" process and accelerating the DOX diffusion in the cytoplasm. Benefiting from the iron ion coordinated on PDA and ICG confined in MOF, magnetic resonance (MR) and photoacoustic (PA) dual-modality imaging were performed to verify the effective accumulation of DI@HMONs-PMOF at the tumor site. Interestingly, the results also suggested that the existence of ICG can cooperatively enhance the MR imaging capability of prepared nanocomposites. In addition, the significantly improved synergistic therapeutic efficacy was confirmed both in vitro and in vivo. Thus, our results indicated that the merged nanostructure of HMONs and MOF is promising for versatile cancer theranostics. STATEMENT OF SIGNIFICANCE: Metal organic framework (MOF) has recently emerged as a class of fascinating nanocarriers. The integration of MOF with other nanostructures can endow the new nanoformulation with collective functionality and synergistic performance that are not accessed from single-component nanostructure. Herein, we reported the successful merging of MOF and hollow mesoporous organosilica nanoparticles (HMONs) to form a hollow nanocontainer with a well-defined nanostructure. The large cavity of HMONs and highly porous network of MOF enable high drug loading efficacy. Moreover, the dual-modality magnetic resonance and photoacoustic imaging can be realized, which is also benefited from the merged nanostructure. Overall, we expected this paradigm could pave way for integrating MOF with other nanocarriers to achieve more diverse applications.

Characterization and transferability of microsatellites for Gentiana lawrencei var. farreri (Gentianaceae).

PREMISE OF THE STUDY: Microsatellite markers were developed for a medicinal herb, Gentiana lawrencei var. farreri (Gentianaceae), for the future assessment of population genetic structure and potential hybridization events with related taxa. METHODS AND RESULTS: Using the 454 FLX+ sequencing platform, we obtained 81,717 clean reads with an average length of 291 bp. A total of 3031 primer pairs were designed, and 96 were selected for validation. A set of 20 fluorescently labeled primer pairs was further selected and screened for polymorphisms in three G. lawrencei var. farreri populations and one G. veitchiorum population. Among the four populations, the average number of alleles per locus was 15.2. Finally, a set of 17 unlinked loci were determined to be in Hardy-Weinberg equilibrium after two linked loci were removed. CONCLUSIONS: The identified simple sequence repeat markers will be useful for genetic diversity and evolution studies in G. lawrencei var. farreri and related taxa.

Integrated Treatment of Prostaglandin E1 and Angiotensin-Converting Enzyme Inhibitor in Diabetic Kidney Disease Rats: Possible Role of Antiapoptosis in Renal Tubular Epithelial Cells.

To investigate the therapeutic mechanisms underlying prostaglandin E1 (PGE1) and angiotensin-converting enzyme inhibitor (ACEI) on reducing urinary protein in diabetic kidney disease (DKD). DKD rats were established and randomly divided into four groups: PGE1 (10 µg/kg/day) (P group), ACEI (10 mg/kg/day) (A group), combination of PGE1 with ACEI treatment (P + A group), and saline treatment group (DKD group). Untreated rats were used as normal control (N group). Urinary albumin, endothelin-1 (ET-1), angiotensin II (AngII), TUNEL assay, Masson's trichrome staining, and immunohistochemistry staining for CD68 were evaluated in all groups. Ten days after treatment, urinary albumin was significantly decreased in the P and P + A groups (p < 0.01 vs. the DKD group). At the end of 8 weeks, the albumin was still significantly reduced in the P + A group (p < 0.05 vs. the A group). ET-1 and AngII were also significantly decreased in three treatment groups (p < 0.01 vs. the DKD group), especially in the P + A group. Few cells underwent apoptosis in glomerular regions in DKD rats, while amounts of apoptotic cells were seen in tubules regions. Further, apoptosis and the areas of fibrosis in tubulointerstitial were both decreased most in the P + A group compared with the DKD group. Apoptosis of renal tubular epithelial cells may participate in the development and progression of DKD in rats. Combination of PGE1 with AGEI remarkably protects renal function compared with PGE1 or ACEI monotherapy. The potential therapeutic mechanisms of PGE1 and AGEI might be via multiple targets and, at least in part, through inhibiting the apoptosis of renal tubular epithelial cells.

One-Pot Synthesis of MoS2 Nanoflakes with Desirable Degradability for Photothermal Cancer Therapy.

Developing biodegradable photothermal agent holds great significance for potential clinical translation of photothermal therapy. In the current study, one-pot hydrothermal synthesis of MoS2 nanoflakes with desirable degradation capability was presented. The participation of poly(acrylic acid) (PAA) in hydrothermal process could not only facilitate the modification of polyethylene glycol (PEG), but also bestow degradability to the prepared MoS2 nanoflakes. Moreover, the PEGylated hybrid nanoflakes (MoS2-PPEG) also exhibited excellent stability in various medium and outstanding photothermal properties. Interestingly, MoS2-PPEG behaved distinctly different degradation rate in diverse condition. The rapid degradation of MoS2-PPEG was observed in neutral pH solution, whereas much slower degradation occurred in an acidic tumor microenvironment. Furthermore, data indicated that the major degradation product of MoS2-PPEG was water-soluble Mo-based ion. Meanwhile, the good in vitro biocompatibility of MoS2-PPEG was also confirmed in terms of cytotoxicity and hemolysis. With favorable photothermal performance, MoS2-PPEG can efficiently killing cancer cells in vitro and suppress the tumor growth in vivo. More importantly, the gradual decreasing content of MoS2-PPEG in organs and detectable Mo element in urine of mice suggested that the degradability of MoS2-PPEG might facilitate its excretion to some degree. Hence, the degradable MoS2 nanoflakes prepared by one-pot hydrothermal routine may provide insight for further biomedical applications of inorganic photothermal agent.

Precise Diagnosis and Treatment of Thymic Epithelial Tumors Based on Molecular Biomarkers.

Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare malignant tumors. The mainstay of treatment patients with TET is surgical resection, and chemotherapy is necessary for patients with tumor invasion or metastasis who are unable to undergo complete radical excision. However, for those patients who are resistant to chemotherapy, targeted therapy has become the most popular tumor treatment program, as well as for thymic tumors. Many genes implicated in tumorigenesis and metastasis have also been reported to be therapeutic targets in thymic malignancies. A significant advance in TET treatment may derive from the identification of novel molecular biomarkers that can improve the diagnosis, prognosis, and treatment of tumors. We review a number of case reports and small clinical trials reporting that a few inhibitors, such as sorafenib and sunitinib, are effective in the treatment of thymoma. In this review, we describe the current potential drug targets and their roles in the development of thymic malignancy.

Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy.

Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS2) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS2-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation, and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS2-PEG nanoflakes under the irradiation. These results thus suggest that the MoS2-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.

Au/polypyrrole@Fe3O4 nanocomposites for MR/CT dual-modal imaging guided-photothermal therapy: an in vitro study.

Construction of multifunctional nanocomposites as theranostic platforms has received considerable biomedical attention. In this study, a triple-functional theranostic agent based on the cointegration of gold nanorods (Au NRs) and superparamagnetic iron oxide (Fe3O4) into polypyrrole was developed. Such a theranostic agent (referred to as Au/PPY@Fe3O4) not only exhibits strong magnetic property and high near-infrared (NIR) optical absorbance but also produces high contrast for magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Importantly, under the irradiation of the NIR 808 nm laser at the power density of 2 W/cm(2) for 10 min, the temperature of the solution containing Au/PPY@Fe3O4 (1.4 mg/mL) increased by about 35 °C. Cell viability assay showed that these nanocomposites had low cytotoxicity. Furthermore, an in vitro photothermal treatment test demonstrates that the cancer cells can be efficiently killed by the photothermal effects of the Au/PPY@Fe3O4 nanocomposites. In summary, this study demonstrates that the highly versatile multifunctional Au/PPY@Fe3O4 nanocomposites have great potential in simultaneous multimodal imaging-guided cancer theranostic applications.

In vitro and in vivo toxicity studies of copper sulfide nanoplates for potential photothermal applications.

Copper sulfide (CuS) has emerged as a promising photothermal agent. However, its potential toxic effects still remained poorly understood. Herein, CuS nanoplates were synthesized for toxicity assessment. The in vitro study indicated that the cell viability decreased when CuS nanoplate concentration was higher than 100 µg/mL. CuS nanoplates caused apparent toxicity to HUVEC and RAW 264.7 cells. For acute toxicity, maximum tolerated dose and lethal dose 50 were 8.66 and 54.5 mg/kg, respectively. Furthermore, the sub-chronic toxicity test results indicated that there was no obvious effect at tested doses during the test period. The biodistribution study showed that intravenously administrated CuS nanoplates were mainly present in the spleen, liver and lung. Taken together, our results shed light on the rational design of CuS nanomaterials to minimize toxicity, thus providing a useful guideline in selecting CuS as the photothermal agent for cancer therapy. FROM THE CLINICAL EDITOR: Photothermal ablation therapy is a promising new treatment modality for cancer. One of the potential photothermal agents is copper sulfide (CuS). In this article, the potential toxic effects of CuS nanoplates were studied. The authors showed that further modification on the design of CuS nanomaterials was needed to minimize toxicity.

Osthole induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.

CONTEXT: Osthole [7-methoxy-8-(3-methyl-2-butenyl) coumarin] isolated from the fruit of Cnidium monnieri (L.) Cuss, one of the commonly used Chinese medicines listed in the Shennong's Classic of Materia Medica in the Han Dynasty, had remarkable antiproliferative activity against human hepatocellular carcinoma HepG2 cells in culture. OBJECTIVES: This study evaluated the effects of osthole on cell growth, nuclear morphology, cell cycle distribution, and expression of apoptosis-related proteins in HepG2 cells. MATERIALS AND METHODS: Cytotoxic activity of osthole was determined by the MTT assay at various concentrations ranging from 0.004 to 1.0 µmol/ml in HepG2 cells. Cell morphology was assessed by Hoechst staining and fluorescence microscopy. Apoptosis and cell-cycle distribution was determined by annexin V staining and flow cytometry. Apoptotic protein levels were assessed by Western blot. RESULTS: Osthole exhibited significant inhibition of the survival of HepG2 cells and the half inhibitory concentration (IC50) values were 0.186, 0.158 and 0.123 µmol/ml at 24, 48 and 72 h, respectively. Cells treated with osthole at concentrations of 0, 0.004, 0.02, 0.1 and 0.5 µmol/ml showed a statistically significant increase in the G2/M fraction accompanied by a decrease in the G0/G1 fraction. The increase of apoptosis induced by osthole was correlated with down-regulation expression of anti-apoptotic Bcl-2 protein and up-regulation expression of pro-apoptotic Bax and p53 proteins. CONCLUSION: Osthole had significant growth inhibitory activity and the pro-apoptotic effect of osthole is mediated through the activation of caspases and mitochondria in HepG2 cells. Results suggest that osthole has promising therapeutic potential against hepatocellular carcinoma.

Perioperative pain in patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation of the Gasserian ganglion.

Trigeminal neuralgia is the worst pain that human beings have ever experienced. Few researches have illustrated perioperative pain in patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation (RFT) of the gasserian ganglion under local anesthesia. Because there are some undeniable drawbacks of using intravenous short-term anesthesia during the intervention repeatedly, some physicians keep patients awake throughout the puncture procedure, using local anesthesia. The purpose of this investigation was to examine perioperative pain in patients with trigeminal neuralgia undergoing RFT of the gasserian ganglion. Participants were 104 patients with classic trigeminal neuralgia. Worst pain intensity, mean pain intensity, quality of sleep, and analgesia satisfaction were evaluated for 24 hours before admission, 24 hours before operation, and 24 hours after operation. Intraoperative worst pain intensity was determined. Preoperative pain was serious, and preoperative sleep quality significantly and positively correlated with preoperative mean pain (r = 0.52; P = 0.00) and worst pain (r = 0.49; P = 0.00). Few patients (1.9%) responded to preoperative treatment, and the preoperative treatment obtained low analgesia satisfaction scores (3.9 [1.3]). Most patients experienced severe pain during cannulation under local anesthesia. No patients complained of pain during radiofrequency lesioning. The RFT of the gasserian ganglion alleviated pain obviously. Most patients (94.2%) responded to the operation, and the operation got high analgesia satisfaction scores (8.9 [0.7]). The results demonstrate that preoperative pain in patients with trigeminal neuralgia undergoing RFT of the gasserian ganglion is prevalent and undertreated and that intraoperative pain is severe under local anesthesia during cannulation.

[Research on the features of DNA damage in nasopharyngeal carcinoma patients of normal constitution and abnormal constitution and in high-risk population of nasopharyngeal carcinoma].

OBJECTIVE: To explore the features of DNA damage in nasopharyngeal carcinoma (NPC) patients of normal constitution and abnormal constitution and in high-risk population of NPC. METHODS: Using single cell gel electrophoresis technique, the DNA damage of peripheral blood lymphocytes was detected in 28 healthy subjects, 27 in high-risk population of NPC, and 13 NPC patients at their first visits. The DNA damage was detected in the populations of normal constitution and of abnormal constitution. The tail length, the tail moment, and the tail DNA% were taken as the indices of DNA damage. RESULTS: The tail length was (35.77 +/- 4.22) microm, the tail moment was (8.10 +/- 1.63) microm, and the tail DNA% was 57.48% +/- 4.63% in NPC patients. They were (15.25 +/- 4.15) microm, (5.01 +/- 1.92) microm, and 31.99% +/- 4. 11% in high-risk population of NPC. They were (14.31 +/- 3.64) microm, (4. 37 +/- 1.80) microm, and 29. 89% +/- 3. 15% in healthy subjects. There was statistical difference in the three indices among the three populations (P <0.05). In all the three populations, more DNA damage existed in those of abnormal constitution than in those of normal constitution (P <0.05). CONCLUSIONS: Obvious instability of genetic materials exists in NPC patients, manifested as severe DNA damage of lymphocytes. In all the three populations, more DNA damage existed in those of abnormal constitution than in those of normal constitution.

Paris chinensis dioscin induces G2/M cell cycle arrest and apoptosis in human gastric cancer SGC-7901 cells.

AIM: To investigate the anti-tumor effects of Paris chinensis dioscin (PCD) and mechanisms regarding cell cycle regulation and apoptosis in human gastric cancer SGC-7901 cells. METHODS: Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Cell apoptosis was evaluated by flow cytometry and laser scanning confocal microscope (LSCM) using Annexin-V/propidium iodide (PI) staining, and the cell cycle was evaluated using PI staining with flow cytometry. Intracellular calcium ions were detected under fluorescence microscope. The expression of cell cycle and apoptosis-related proteins cyclin B1, CDK1, cytochrome C and caspase-3 was measured by immunohistochemical staining. RESULTS: PCD had an anti-proliferation effect on human gastric cancer SGC-7901 cells in a dose- and time-dependent manner. After treatment of SGC-7901 cells with PCD, apoptosis appeared in SGC-7901 cells. Morphological changes typical of apoptosis were also observed with LSCM by Annexin V/PI staining, and the cell number of the G0/G1 phase was decreased, while the number of cells in the G2/M phase was increased. Cell cycle-related proteins, such as cyclin B1 and CDK1, were all down-regulated, but caspase-3 and cytochrome C were up-regulated. Moreover, intracellular calcium accumulation occurred in PCD-treated cells. CONCLUSION: G2/M phase arrest and apoptosis induced by PCD are associated with the inhibition of CDK-activating kinase activity and the activation of Ca(2+)-related mitochondrion pathway in SGC-7901 cells.

[Research on therapeutic effect and hemorrheology change of berberine in new diagnosed patients with type 2 diabetes combining nonalcoholic fatty liver disease].

OBJECTIVE: To explore the therapeutic effect and the hemorrheology change of berberine in new diagnosed patients with type 2 diabetes combining nonalcoholic fatty liver disease. METHOD: Sixty patients, in our department from March 2009 to March 2010, with type 2 diabetes and nonalcoholic fatty liver disease were randomly divided into two groups. One group was given berberine, another group was given Xuezhikang, both for 12 weeks. The indicators, include B-ultrasound of liver, triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspertate aminotransferase (AST), hemorrheology, were detected before and after treatment. RESULT: After treatment by berberine, B-ultrasound of liver were better than before, the effective rate was 70%, vs 73.3% after treatment by Xuezhikang. ALT, AST, TC, TG, LDL-L, hemorrheology (including the whole blood viscosity, whole blood viscosity, high cutting reduction of whole blood viscosity, plasma cutting reductive low viscosity, blood sedimentation, RBC deposited, fibrinogen) were significantly lower than before, however, HDL-L significantly increased (P<0.05). The therapeutic effect of xuezhikang was the same as berberine. The distance between the indicators of the two groups was no different. CONCLUSION: Berberine can obviously improve the conditions of new diagnostic T2DM patients with nonalcoholic liver lesions, effectively reduce hemorrheology indicators, and has good application prospect.