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Capsaicin (CAP) is a well-known anti-cancer agent. Recently, we reported capsaicin-induced apoptosis in anaplastic thyroid cancer (ATC) cells. It is well accepted that the generation of cancer stem cells (CSCs) is responsible for the dedifferentiation of ATC, the most lethal subtype of thyroid cancer with highly dedifferentiation status. Whether CAP inhibited the ATC growth through targeting CSCs needed further investigation. In the present study, CAP was found to induce autophagy in ATC cells through TRPV1 activation and subsequent calcium influx. Meanwhile, CAP dose-dependently decreased the sphere formation capacity of ATC cells. The stemness-inhibitory effect of CAP was further by extreme limiting dilution analysis (ELDA). CAP significantly decreased the protein level of OCT4A in both 8505C and FRO cells. Furthermore, CAP-induced OCT4A degradation was reversed by autophagy inhibitors 3-MA and chloroquine, BAPTA-AM and capsazepine, but not proteasome inhibitor MG132. Collectively, our study firstly showed CAP suppressed the stemness of ATC cells partially via calcium-dependent autophagic degradation of OCT4A. Our study lent credence to the feasible application of capsaicin in limiting ATC stemness.

It is widely accepted that anaplastic thyroid carcinoma (ATC), a rare, extremely aggressive malignant, is enriched by cancer stem cells (CSCs), which are closely related to the pathogenesis of ATC. In the present study, we demonstrated that diallyl trisulphide (DATS), a well-known hydrogen sulphide (H2 S) donor, suppressed sphere formation and restored the expression of iodide-metabolizing genes in human ATC cells, which were associated with H2 S generation. Two other H2 S donors, NaHS and GYY4137, could also suppress the self-renewal properties of ATC cells in vitro. Compared with normal thyroid tissues and papillary thyroid carcinomas (PTCs), the elevated expressions of SOX2 and MYC, two cancer stem cell markers, in ATCs were validated in the combined Gene Expression Omnibus (GEO) cohort. DATS decreased the expression of SOX2, which was mediated by H2 S generation. Furthermore, knockdown of AKT or inhibition of AKT by DATS led to a decrease of SOX2 expression in ATC cells. AKT knockdown phenocopied restoration of thyroid-specific gene expression in ATC cells. Our data suggest that H2 S donors treatment can compromise the stem cell phenotype and restore thyroid-specific gene expression of ATC cells by targeting AKT-SOX2 pathway, which may serve as a therapeutic strategy to intervene the CSC progression of ATC.

BACKGROUND Repeated radiotherapy brings limited benefits and significant side effects for differentiated thyroid cancer patients (DTC) with radioiodine refractory (RAIR). However, the prognostic role of preoperative thyroglobulin (pre-Tg) in predicting RAIR is unclear. METHODS In the present study, data was retrospectively reviewed from 5,173 patients who underwent radiotherapy in Jiangyuan Hospital from January 2006 to December 2020. RESULTS A total of 1,102 patients with or without repeated radiotherapy was compared (repeated vs. single radiotherapy; n = 199 vs. n = 903). Pre-Tg was significantly elevated in patients with repeated radiotherapy. After the classification of RAIR (non-RAIR, n = 786 vs. RAIR, n = 90), elevated pre-Tg was also correlated with RAIR after uni- and multi-analysis. According to the receiver operating curve analysis, elevated pre-Tg well predicted RAIR (AUC = 0.76, CI: 0.71-0.82, P < 0.0001). To control the selection bias, the propensity scoring match was used. Pre-Tg level was found to be an independent predictor of RAIR (P < 0.001, HR = 7.25, CI: 2.55-20.62). CONCLUSION Our results indicates that markedly elevated pre-Tg level can be served as an independent predictor of RAIR-DTC, which can guide a more precise treatment strategy and/or an active surveillance during surgery and follow-ups.

Duchenne muscular dystrophy (DMD) is a lethal genetic muscle disorder caused by recessive mutations in dystrophin gene, affecting 1/3000 males. Gene therapy has been proven to ameliorate dystrophic pathology. To investigate therapeutic benefits from long-term effect of human mini-dystrophin and functional outcomes, transgenic mdx mice (Tg-mdx) containing a single copy of human mini-dystrophin (∆hDys3849) gene, five rods (Rods1-2, Rods22-24), and two hinges (H1 and H4) driven by a truncated creatine-kinase promoter (dMCK) in a recombinant adeno-associated viral vector (rAAV) backbone, were generated and used to determine gene expression and improvement of muscle function. Human mini-dystrophin gene expression was found in a majority of the skeletal muscles, but no expression in cardiac muscle. Dystrophin-associated glycoproteins (DAGs) such as sarcoglycans and nNOS were restored at the sarcolemma and coincided with human mini-dystrophin gene expression at the ages of 6, 10, and 20 months; Morphology of dystrophic muscle expressing the human mini-dystrophin gene was improved and central nuclei were reduced. Myofiber membrane integrity was improved by Evans blue dye test. Improvement in treadmill running and grip force was observed in transgenic mice at 6 months. Tetanic force and specific force of tibialis anterior (TA) muscle were significantly increased at the ages of 6, 10, and 20 months. Pseudohypertrophy was not found in TA muscle at 10 and 20 months when compared with wild-type C57 (WT) group. This study demonstrated that the long-term effects of human mini-dystrophin effectively ameliorated pathology and improved the functions of the dystrophic muscles in the transgenic DMD mouse model.

Sphingosine-1-phosphate (S1P) plays important roles in cardiovascular development and immunity. S1P is abundant in plasma because erythrocytes-the major source of S1P-lack any S1P-degrading activity; however, much remains unclear about the source of the plasma S1P precursor, sphingosine (SPH), derived mainly from the hydrolysis of ceramides by the action of ceramidases that are encoded by 5 distinct genes, acid ceramidase 1 ( ASAH1)/ Asah1, ASAH2/ Asah2, alkaline ceramidase 1 ( ACER1)/ Acer1, ACER2/ Acer2, and ACER3/ Acer3, in humans/mice. Previous studies have reported that knocking out Asah1 or Asah2 failed to reduce plasma SPH and S1P levels in mice. In this study, we show that knocking out Acer1 or Acer3 also failed to reduce the blood levels of SPH or S1P in mice. In contrast, knocking out Acer2 from either whole-body or the hematopoietic lineage markedly decreased the blood levels of SPH and S1P in mice. Of interest, knocking out Acer2 from whole-body or the hematopoietic lineage also markedly decreased the levels of dihydrosphingosine (dhSPH) and dihydrosphingosine-1-phosphate (dhS1P) in blood. Taken together, these results suggest that ACER2 plays a key role in the maintenance of high plasma levels of sphingoid base-1-phosphates-S1P and dhS1P-by controlling the generation of sphingoid bases-SPH and dhSPH-in hematopoietic cells.-Li, F., Xu, R., Low, B. E., Lin, C.-L., Garcia-Barros, M., Schrandt, J., Mileva, I., Snider, A., Luo, C. K., Jiang, X.-C., Li, M.-S., Hannun, Y. A., Obeid, L. M., Wiles, M. V., Mao, C. Alkaline ceramidase 2 is essential for the homeostasis of plasma sphingoid bases and their phosphates.

The frequent disease of Panax notoginseng caused by the pathogenic fungi in field cultivation has become the major threaten to the sustainable development of it. The present study was conducted to find natural agent with potential inhibition against pathogen. Therefore, the inhibitory effects of Cinnamomum cassia (L.) J.Presl essential oils (EOs) against P. notoginseng associated pathogenic fungi were conducted both in vitro and in vivo experiments. The results of the Oxford cup test revealed that C. cassia dry bark EO (50 mg/mL) had significant inhibitory activity on the growth of all tested fungi, and the growth of various pathogens was completely inhibited, except for that of Fusarium solani. Therefore, the constituents of C. cassia EOs were analyzed by GC/MS, and the research demonstrated that the main constituents of C. cassia dry bark EO were trans-cinnamaldehyde (75.65 %), (E)-2-methoxycinnamaldehyde (6.08 %), cinnamaldehyde (3.47 %) and cinnamyl acetate (1.02 %). The MIC results showed that C. cassia dry bark EO and the main compounds had good antifungal effect on the tested strains, and the inhibitory effect was similar to that of hymexazol (chemical pesticide). By analyzing the value of the fraction inhibitory concentration index (FICI), additive effects, irrelevant effects and synergistic effects were observed after the mixture of hymexazol against various pathogens. Moreover, in vivo model showed that C. cassia dry bark EO could reduce the occurrence of anthrax in P. notoginseng. To widen the resources of C. cassia available, the compositions of both C. cassia fresh bark and leaf EOs were also tested and many common compositions existed among them. Taken together, it was concluded that C. cassia EO had the potential use in the field to reduce the pathogenic disease.

Panax notoginseng root is a traditional Chinese herb, of which the yield and quality have been seriously affected by microorganisms, and is commonly used to treat various kinds of bleeding. In this experiment, the effects of the antifungal properties of essential oils (EOs) from five kinds of Rutaceae plants on the growth of three kinds of pathogens were studied to develop natural, environmentally friendly antifungal agents. Citrus medica EO was found to have stronger inhibitory effects on the growth of pathogenic fungi in vitro than other EOs with the Oxford cup method, of which the chemical composition was further investigated by GC/MS. The major components were d-limonene (22.79 %) and γ-terpinene (9.71 %). The antifungal activities were evaluated by MIC and FIC assays. In these assays, C. medica EO, d-limonene and γ-terpinene were effective against three pathogens of P. notoginseng with MIC values ranging from 0.12 to 12.05 mg/mL. The association between hymexazol and C. medica EO showed a high synergistic effect with lower FIC index values (FICi=0.31-2.00). Furthermore, C. medica EO was further assessed in P. notoginseng planted in a continuous cropping soil (CCS) and was found to reduce the disease incidence and disease severity compared with P. notoginseng planted in CCS only without EO addition. This finding suggested that C. medica EO has potential as a natural environmentally antifungal agent against pathogens of P. notoginseng, ensuring its safety.

KEY POINTS Channelopathies of autoimmune origin are novel and are associated with corrected QT (QTc) prolongation and complex ventricular arrhythmias. We have recently demonstrated that anti-SSA/Ro antibodies from patients with autoimmune diseases and with QTc prolongation on the ECG target the human ether-a-go-go-related gene (HERG) K+ channel by inhibiting the corresponding current, IKr , at the pore region. Immunization of guinea-pigs with a peptide (E-pore peptide) corresponding to the extracellular loop region connecting the S5 and S6 segments of the HERG channel induces high titres of antibodies that inhibit IKr , lengthen the action potential and cause QTc prolongation on the surface ECG. In addition, anti-SSA/Ro-positive sera from patients with connective tissue diseases showed high reactivity to the E-pore peptide. The translational impact is the development of a peptide-based approach for the diagnosis and treatment of autoimmune-associated long QT syndrome. ABSTRACT We recently demonstrated that anti-SSA/52 kDa Ro antibodies (Abs) from patients with autoimmune diseases and corrected QT (QTc) prolongation directly target and inhibit the human ether-a-go-go-related gene (HERG) K+ channel at the extracellular pore (E-pore) region, where homology with SSA/52 kDa Ro antigen was demonstrated. We tested the hypothesis that immunization of guinea-pigs with a peptide corresponding to the E-pore region (E-pore peptide) will generate pathogenic inhibitory Abs and cause QTc prolongation. Guinea-pigs were immunized with a 31-amino-acid peptide corresponding to the E-pore region of HERG. On days 10-62 after immunization, ECGs were recorded and blood was sampled for the detection of E-pore peptide Abs. Serum samples from patients with autoimmune diseases were evaluated for reactivity to E-pore peptide by enzyme-linked immunosorbent assay (ELISA), and histology was performed on hearts using Masson's Trichrome. Inhibition of the HERG channel was assessed by electrophysiology and by computational modelling of the human ventricular action potential. The ELISA results revealed the presence of high titres of E-pore peptide Abs and significant QTc prolongation after immunization. High reactivity to E-pore peptide was found using anti-SSA/Ro Ab-positive sera from patients with QTc prolongation. Histological data showed no evidence of fibrosis in immunized hearts. Simulations of simultaneous inhibition of repolarizing currents by anti-SSA/Ro Ab-positive sera showed the predominance of the HERG channel in controlling action potential duration and the QT interval. These results are the first to demonstrate that inhibitory Abs to the HERG E-pore region induce QTc prolongation in immunized guinea-pigs by targeting the HERG channel independently from fibrosis. The reactivity of anti-SSA/Ro Ab-positive sera from patients with connective tissue diseases with the E-pore peptide opens novel pharmacotherapeutic avenues in the diagnosis and management of autoimmune-associated QTc prolongation.

A simple dispersive solid-phase extraction (DSPE) used to extract and preconcentrate ultra-trace MeHg, EtHg and Hg(2+) from water sample, and a sensitive method for the simultaneous analysis of MeHg, EtHg and Hg(2+) by using capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICP-MS) with field-amplified sample stacking injection (FASI) were first reported in this study. The DSPE used thiol cotton particles as adsorbent, and is simple and effective. It can be used to extract and preconcentrate ultra-trace mercury compounds in water samples within 30 min with a satisfied recovery and no mercury species alteration during the process. The FASI enhanced the sensitivity of CE-ICP-MS with 25-fold, 29-fold and 27-fold for MeHg, EtHg and Hg(2+) , respectively. Using FASI-CE-ICP-MS together with DSPE, we have successfully determined ultra-trace MeHg, EtHg and Hg(2+) in tap water with a limits of quantification (LOQs) of 0.26-0.45 pg/mL, an RSD (n = 3) < 6% and a recovery of 92-108%. Ultra-high sensitivity, as well as much less sample and reagent consumption and low operating cost, make our method a valuable technique to the speciation analysis of ultra-trace mercury.

A phytochemical investigation of the resin of Toxicodendron vernicifluum resulted in the isolation of two new sesquiterpenoids, toxicodenanes D (1), endowed with a new carbon skeleton, and E (2), along with six known sesquiterpenoids (Fig.1). Their structures were determined by spectroscopic analysis, including 1D- and 2D-NMR and mass spectrometry.

A reproducible, highly efficient, and racemization-free protocol for the triphosgene-mediated solid-phase coupling of proteinogenic amino acids was developed. The efficiency of the reaction was demonstrated by the first total synthesis of the bioactive natural octacyclopeptide brachystemin A. This protocol will broaden the application of triphosgene in the synthesis of a wide range of peptides, including aromatic amino acids, N-alkylated amino acids, as well as proteinogenic amino acids.

Lingzhifuran A (1) and lingzhilactones D–F (2–4), four new phenolic meroterpenoids were isolated from the fruiting bodies of Ganoderma lucidum. Their structures were identified by spectroscopic data. Chiral HPLC analysis indicates the racemic nature of 2–4. Chiral separation followed by X-ray diffraction analysis discloses the absolute configuration of (−)-2. Compounds 1 and 2 could selectively inhibit TGF-β1-induced Smad3 phosphorylation in rat renal tubular epithelial cells, representing novel scaffolds of selective Smad3 activation inhibitors. Total synthesis accompanied by in vivo rodent experiments reveals antifibrotic activities of 1 against kidney fibrosis. Finally, a plausible biosynthetic pathway for 1 was proposed.

Sphingosine-1-phosphate (S1P) is an amphiphilic signaling molecule, which is enriched in functional high density lipoprotein (HDL) and shows arterial protection. The distribution of S1P is changed with increased plasma phospholipid transfer protein (PLTP) activity and impaired HDL function in patients with coronary heart diseases. Therefore, we hypothesized that PLTP might transfer S1P among cells or lipoproteins. We found that plasma S1P contents were decreased by 60.1 % in PLTP knockout mice (PLTP−/−, N = 5) compared with their wild type littermates (WT, N = 5) (151.70 ± 38.59 vs. 379.32 ± 59.90 nmol/l, P

A new low-dimensional benzyl viologen/iodoargentate hybrid, [(BV)2(Ag5I9)]n (1) (BV2+ = benzyl viologen) was prepared. In 1, (Ag6I9)n2– chain exhibits a new type of one-dimensional chain constructed from vertex-sharing of Ag5I10 units, and its two-dimensional layer structure was constructed from C–H···I hydrogen bonds. Strong luminescence at 404 nm can be detected in 1. DFT calculation suggests that 1 displays a reduced bandgap, which is led by a more dispersed LUMO band of BV2+ compared with MV2+ in [MV(Ag2I4)]n.

Total synthesis of (±)-Lingzhilactone B has been achieved for the first time in 13 steps. The key step features a semipinacol rearrangement to construct 5/5 bicyclic ring with adjacent quaternary carbon.

Applanatumols A (1) and B [(±)-2], two unique meroterpenoids with a novel spiro[benzofuran-2,2′-bicyclo[3.2.2]nonane] ring system and a naturally unusual dioxacyclopenta[cd]inden motif, respectively, were isolated from Ganoderma applanatum. Their structures were determined using spectroscopic data. In particular, the absolute configurations of 1 and 2 were assigned by X-ray diffraction analysis using the Flack parameter and ECD calculations, respectively. A plausible biosynthetic pathway for 1 and 2 is proposed. The biological activities of 1 and 2 against renal fibrosis were accessed in rat proximal tubular epithelial cells.

Two coriamyrtin-type sesquiterpenes, fengfangin A (1) and tutin (2), and six diarylheptanoids, namely alnusone (3), centrolobol (4), muricarpone B (5), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptan-3-one (6), (3S)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptan-3-ol (7), and (3S)-1-(4-hydroxyphenyl)-7-(3,4-dihydroxyphenyl)heptan-3-ol (8), were isolated from the 95% EtOH extract of nidus vespae, the nest of Polistes species. Their structures were identified by spectroscopic methods. Compounds 1 and 8 are new products. The absolute configuration of 1 was determined by single-crystal X-ray diffraction analysis using Flack parameter. The biological tests showed that compounds 5, 6, and 8 could inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with IC50 values in the range of 1317 mu M, whereas the sesquiterpenes were inactive in this assay (>25 mu M). In addition, the ecological significance of the presence of neurotoxic sesquiterpene lactones in nidus vespae is briefly discussed.

The rolling contact fatigue (RCF) behaviour of the plasma-sprayed CrC-NiCr cermet coatings under different tribological conditions of contact stress was investigated. Four sets of fatigue life data of coatings were characterized by Weibull distributions. The failure modes of the coatings were classified on the basis of worn surface observations of the failed coatings. Results showed that the failure mode of the coating was related to the magnitude of contact stress. The RCF life data of the coatings tested at high contact stresses exhibited high scattering, because the bimodal distribution of the fatigue life data was seen in the Weibull plot. Generally, when the contact stress was relatively low, the coatings were prone to fail in spalling and cohesive delamination. However, at high contact stress, the coatings often failed due to interfacial delamination. At different contact stress levels, the maximum shear stress amplitude was the main reason for the generation of spall and delamination.

Investigation on the extracts of Hydnocarpus anthelminthica seeds led to the isolation of three new compounds, anthelminthicins A-C (1-3, resp.), and two known ones, namely chaulmoogric acid (4) and ethyl chaulmoograte (5). Their structures were determined mainly by using spectroscopic techniques. The absolute configuration at the cyclopentenyl moiety of compound 2 was rationalized by quantum calculations. Base hydrolysis, followed by optical-rotation comparison, allowed assignment of the configuration of chaulmoogric-acid moiety of compounds 3 and 5. Biological assays revealed that compounds 1-5 significantly inhibit Mycobacterium tuberculosis (MTB) growth with MIC values of 5.54, 16.70, 4.38, 9.82, and 16.80 microM, respectively. Compound 3 was found to inhibit the pathway between chorismate and para-aminobenzoic acid (pAba) with a MIC value of 11.3 microM, representing a new example of pAba inhibitor isolated from a natural source. All compounds were not toxic to Candida albicans SC5314 at a concentration up to 100 microM.

Many studies have suggested that VSMC (vascular smooth muscle cell) apoptosis plays a key role in destabilization and rupture of atherosclerotic plaques. Therefore protection for VSMCs from apoptosis is a promising approach to stabilize 'vulnerable' lesions. However, the mechanisms as to why VSMCs in the fibrous cap often appear as profilerated in early stages, but turn apoptotic in advanced stages, are still unknown. In the present study, using RNAi (RNA interference) technology and a CaN (calcineurin) antagonist, the correlation between CaN and RANTES (regulated upon activation, normal T-cell expressed and secreted) in cultured rat apoptotic VSMCs stimulated by IFNgamma (interferon gamma; 20 ng/ml) and CD40L (CD40 ligand; 100 ng/ml) was investigated. RANTES released from VSMCs in each group was measured by ELISA and its mRNA in VSMCs was determined by RT (reverse transcription)-PCR. The total activity and expression of CaN in VSMCs were detected by the zymochemistry method and Western blot analysis respectively. From the results of the present study it can be hypothesized that an elevated CaN concentration in endochylema, by the CD40-CD40L signal pathway, induces VSMC apoptosis accomplished by the overexpression of RANTES. Therefore RANTES is a potential target for treating vulnerable atherosclerotic plaques owing to its crucial downstream regulating role in CaN-dependent VSMC apoptosis.

Objectives: To investigate the complete process of cell injuries in the blood-air barrier after perfluoroisobutylene (PFIB) exposure. Methods: Rats were exposed to PFIB (140 mg/m3) for 5 min. The pathological changes were evaluated by lung wet-to-dry weight ratio, total protein concentration of bronchoalveolar lavage fluid and HE stain. Ultrastructural changes were observed by transmission electron microscope. Apoptosis was detected by in situ apoptosis detection. Changes of actin in the lung tissue were evaluated by western blot assay. Results: No significant pulmonary edema or increased permeability was observed within the first 4 h, post PFIB exposure. However, inflammatory cell infiltration and alveolar wall thickening were observed from 2 h. Destruction of the alveoli constitution integrity, edema and protein leakage were observed at 8 h. The injuries culminated at 24 h and then recovered gradually. The ultrastructural injuries of alveolar type I epithelial cells, alveolar type II epithelial cells and pulmonary microvascular endothelial cells were observed at 30 min post PFIB exposure. Some injuries were similar to apoptosis. Compared with control, more serious injuries were observed in PFIB-exposed rats after 30 min. At 8 h, some signs of cell necrosis were observed. The injuries culminated at 24 h and then ameliorated. The number of apoptotic cells abnormally increased at 30 min post PFIB exposure, the maximum appeared at 24 h, and then ameliorated gradually. Western blot analysis revealed that the level of actin in the lung showed no significant changes within the first 4 h post PFIB exposure. However, it decreased at 8 h, reached a nadir at 24 h, and then recovered gradually. Conclusions: The pathological processes were in progress persistently post PFIB exposure. The early injuries probably were the result of the direct attack of PFIB and the advanced injuries probably arose from the inflammatory reaction induced by PFIB.

The 12 May 2008 Wenchuan MS8.0 (Mw7.9) earthquake occurred on the Longmen Shan (Mountains) thrust-nappe structure zone in the eastern margin of the Tibetan plateau. It has produced 240 km long and 72 km long rupture zones on the surface along the Yingxiu–Beichuan fault and Guanxian–Jiangyou fault, respectively, which are branches of the Longmen Shan fault system. Besides, our field investigation found that this shock has also caused a weak rupture zone on the ground nearby the Shigu town, Shifang city that lies in the western Chengdu plain east to the epicenter. This rupture zone and the other two ruptures in the Longmen Shan mountainous area aforementioned constitute a northwest-dipping imbricate structure. It is about 7.5 km long, trends in 30-, and is manifested by a series of deformation phenomena such as damages of buildings, channel dislocations, ground folds, erupted sand and earth fissures on the surface. Observations in the exploratory trenches indicate that there is a fold uplift of 0.2 m in the youngest strata (including the surface) produced by the Wenchuan MS8.0 event, and a fold uplift of 0.4 m in the clay bottom in the trench, presumably resulted from a paleoearthquake of similar size to the Wenchuan shock in 2008. Seismic exploration of shallow subsurface demonstrates that in the place of seismic rupture zone in the Chengdu plain exist active faults of the late Pleistocene as well as active folds of the Quaternary.

Three new cyclic diarylheptanoids myricananins F-H (1-3, resp.), along with five known ones, 4-8. were isolated from the roots of Myrica nana. Compound 3 has been obtained by Nagai et al. by reduction of porson with NaBH(4). In this work, compound 3 was isolated from natural origin for the first time. The structures of 1-8 were elucidated using spectroscopic methods.

Two new compounds hastatusides A and B (1 and 2, resp.), together with five known compounds, resveratrol, rumeroside, torachrysone-8-yl beta-D-glucopyranoside, rutin, nepodin, and orientaloside were isolated form the roots of Rumex hastatus. Their structures were determined by spectroscopic methods including 1D- and 2D-NMR spectroscopy.

The matrix (M) protein of vesicular stomatitis virus (VSV) plays a key role in inducing cell apoptosis during infection. To investigate whether M protein-mediated apoptosis could be used in cancer therapy, its cDNA was amplified and cloned into eukaryotic expression vector pcDNA3.1(+). The recombinant plasmid or the control empty plasmid pcDNA3.1(+) was mixed with cationic liposome and introduced into various tumor cell lines in vitro, including lung cancer cell LLC, A549, colon cancer cell CT26 and fibrosarcoma cell MethA. Our data showed that the M protein induced remarkable apoptosis of cancer cells in vitro compared with controls. Fifty micrograms of plasmid in a complex with 250 microg cationic liposome was injected intratumorally into mice bearing LLC or MethA tumor model every 3 days for 6 times. It was found that the tumors treated with M protein plasmid grew much more slowly, and the survival of the mice was significantly prolonged compared with the mice treated with the control plasmid. In MethA fibrosarcoma, the tumors treated with M protein plasmid were even completely regressed, and the mice acquired longtime protection against the same tumor cell in rechallenge experiments. Both apoptotic cells and CD8(+) T cells were widely distributed in M protein plasmid-treated tumor tissue. Activated cytotoxic T lymphocytes (CTLs) were further detected by means of (51)Cr release assay in the spleen of the treated mice. These results showed that M protein of VSV can act as both apoptosis inducer and immune response initiator, which may account for its extraordinary antitumor effect and warrant its further development in cancer gene therapy.

Five new triterpenoids, serrulatins A-E (1-5), including two new artifacts, together with ten known serrulatins, were isolated from the edible leaves of Photinia serrulata after extraction and purification. Their structures were identified on the basis of spectroscopic methods including 2D NMR experiments. Compounds I and 3 are unusual ursolic triterpenoids characterized by the occurrence of a C(13)=C(18) bond.