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Alzheimer's disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aβ-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Aβ-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Aβ monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.

Salvia castanea (Family Labiatae), a perennial fragrant herb with castaneous flowers, is mainly distributed in areas with an altitude of 2500–3750 m. The roots of this plant were used as a tea drink by local residents to strengthen physical health. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the whole plant of S. castanea and to evaluate their potential anti-Alzheimer's disease. Six new sesquiterpene lactones, salcastanins A-F (1–6), together with three known guaiane-type sesquiterpenoids nubiol (7), nubdienolide (8), and nubenolide (9), were separated from the whole plant of S. castanea. The structures of these compounds were determined by HRESIMS and NMR experiments. The absolute configurations of 1–6 were ascertained by electronic circular dichroism (ECD) experiments. The humanized Caenorhabditis elegans AD pathological model was used to evaluate anti-Alzheimer's disease (AD) activities of 1–9. The results showed the compounds 1–3 and 7 significantly delayed AD-like symptoms of worm paralysis phenotype, which could be used as novel anti-AD candidates.

One new bisabolane-type sesquiterpenoid, together with four known bisabolane-type sesquiterpenoid derivatives and seven phenolics, was isolated from the rhizomes of Curcuma longa. Their structures were elucidated by extensive spectroscopic (IR, HR-ESI-MS, and NMR) data analysis. The possible anti-Alzheimer's disease (AD) activities of the isolated compounds were also evaluated using Caenorhabditis elegans AD pathological model, and 1β-hydroxybisabola-2,10-dien-4-one had the highest possible anti-AD activity.

Two new pregnane glycosides, 2α, 3β-dihydroxy-5α-pregn-16-en-20-one-3-O-{α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-galactopyranoside} (

Glioma is the most frequent primary central nervous system tumor. Although the current first-line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β-Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects. The molecular mechanisms were also investigated. We also optimized the delivery methods of bELE. We found that bELE selectively inhibits the proliferation and sphere formation of GSLCs, other than parental glioma cells, and TMZ exerts its effects on parental cells instead of GSLCs. The in vivo data confirmed that the combination of bELE and TMZ worked better in the xenografts of GSLCs, mimicking the situation of tumorigenesis of human cancer. Notch1 was downregulated with bELE treatment. Our data also demonstrated that the continuous administration of bELE produces an ideal effect to control tumor progression. Our findings have demonstrated, for the first time, that bELE could compensate for TMZ to kill both GSLCs and nonstem-like cancer cells, probably improving the prognosis of glioma patients tremendously. Notch1 might be a downstream target of bELE. Therefore, our data shed light on improving the outcomes of glioma patients by combining bELE and TMZ.

Two new pregnane glycosides, 2α, 3β-dihydroxy-5α-pregn-16-en-20-one-3-O-{α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-galactopyranoside} (1) and 2α, 3β-dihydroxy-5α-pregn-16-en-20-one-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside}(2), have been isolated along with two known spirostanol saponins from the underground parts of Hosta ventricosa. Their structures were elucidated on the basis of chemical and spectral evidence. The anti-inflammatory activities of these steroidal glycosides were evaluated using a xylene-induced ear edema model. Our results indicated that the compounds exhibited promising anti-inflammatory activities.

Commiphoins A-C (1-3), three new cadinane-type sesquiterpenes, together with two known cadinane-type sesquiterpenes (4 and 5) were isolated from the resinous exudates of Commiphora myrrha. Their structures and relative configurations were established on the basis of comprehensive spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses. Compounds 1 and 3-5 were screened for anti-Alzheimer's disease (AD) activities using the AD pathological model in Caenorhabditis elegans. The results showed that they all had significant anti-AD activities.

To study the role of JAK2 signaling pathway in prostate stromal cells and the effect of inhibitor WP1066 on its expression.The phosphorylation of JAK2 and STAT3 in prostate tissues of patients with benign prostatic hyperplasia (BHP) (JAK2 phosphorylation level (pJAK2) was significantly increased in the patients with severe HP plus BPH,and the expression of JAK2 or STAT3 was not decreased in WP1066 treatment cells. However,neither phosphorylation in JAK2 nor STAT3 was able to be detected in the cells treated with WP1066 or WP1066+IL-6,indicating that the signaling pathway of JAK2-STAT3 was inhibited.JAK/STAT signaling pathway is activated in patients with severe HP plus BPH , but could be inhibited by WP1066.

To investigate the clinical effect of 0.02% clobetasol propionate cream (CPC) on phimosis in prepubertal children.We retrospectively analyzed the clinical data about 237 prepubertal children with phimosis present at the Outpatient Department from June 2012 to December 2015. The patients were aged 2－14 (mean 8.6) years, all treated by topical application of 0.02% CPC to the narrowed opening and adhered part of the foreskin twice a day, in the morning and evening respectively. At the time of CPC application, the foreskin was slightly retracted. We evaluated the therapeutic effect every week from the end of the first week of treatment.Totally, 233 of the patients completed the 8-week treatment, of whom 181 (77.68%) showed full retraction of the foreskin, 28 (12.01%) experienced improvement (disappearance of the phimotic ring), and 24 (10.30%) failed to respond, with a total effectiveness rate of 89.70%. No significant local or systemic adverse reactions were observed during the treatment.Topical application of 0.02% Clobetasol Propionate Cream is a safe, effective, painless, and inexpensive option for the treatment of phimosis in prepubertal chilodren.目的: 探讨0.02%丙酸氯倍他索乳膏治疗小儿包茎的临床疗效。方法: 选取 2012年6月至2015年12月门诊包茎患儿237例，年龄2～14岁，平均8.6岁。按照包茎程度分为5组，分别给予0.02%丙酸氯倍他索乳膏，早晚各1次涂抹于包皮狭窄开口及粘连处，每次用药时轻微用力上翻包皮，每周门诊随访评价疗效，疗程最长8周。结果: 失访4例，共有233例患儿获得随访。181例患儿完全治愈，包皮外口狭窄环消失，包皮粘连处松解，可自由翻转以显露阴茎头，治愈率为77.68%；28例(12.01%)患儿有效，狭窄环部分松解可显露部分阴茎头，尚不足自由翻转显露阴茎头；无效患儿24例(10.30%)，包皮外口狭窄仍不能上翻显露阴茎头。总有效率为89.70%，治疗过程中无明显不良反应发生。结论： 0.02%丙酸氯倍他索乳膏治疗小儿包茎是一种安全、有效、无痛、经济的方法。.

This study reports the discovery of a novel sulfonated oxysterol found at high levels in the mitochondria and nuclei of primary rat hepatocytes after overexpression of the gene encoding steroidogenic acute regulatory protein (StarD1). Forty-eight hours after infection of primary rat hepatocytes with recombinant adenovirus encoding StarD1, rates of bile acid synthesis increased by 4-fold. Concurrently, [(14)C]cholesterol metabolites (oxysterols) were increased dramatically in both the mitochondria and nuclei of StarD1-overexpressing cells, but not in culture medium. A water-soluble [(14)C]oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Enzymatic digestion, HPLC, and tandem mass spectrometry analysis identified the water-soluble oxysterol as 5-cholesten-3beta,25-diol 3-sulfonate. Further experiments detected this cholesterol metabolite in the nuclei of normal human liver tissues. Based upon these observations, we hypothesized a new pathway by which cholesterol is metabolized in the mitochondrion.

A liquid chromatography method using volatile ion-pairing reagents and tandem mass spectrometry was developed to obviate observed matrix effect for ionizable polar compounds. The present study investigated the addition of volatile ion-pair reagents to the reconstitution solution instead of the mobile phase to enhance the efficiency of chromatographic separation and minimize the sensitivity loss due to the formation of ion-pairs. The volatile ion-pair reagents used were perfluorinated carboxylic acids with n-alkyl chains: heptafluorobutanoic acid (HFBA), nonafluoropentanoic acid (NFPA), tridecafluoroheptanoic acid (TDFHA) and pentadecafluorooctanoic acid (PDFOA). The model analytes evaluated were N-methylnicotinamide (MNA) chloride, N-methyl 2-pyridone 5-carboxamide (2PY) and phenylephrine. The effects of alkyl chain length and the concentrations of the ion-pair reagents on the retention of analytes were studied, as well as the effect of pH on the retention of phenylephrine. The volatile ion-pair reagents in the reconstitution solution showed significant effect on the retention of the ionizable polar compounds, and the sensitivity of detection was improved for plasma samples through decreasing the matrix effect. This methodology was successfully applied to establish a quantitative assay for the polar drug substance methadone in human plasma with a concentration range from 0.1 to 50 ng/mL. Ion-pair reagents not only shifted the retention time but also reduced the carry-over peak for methadone.

High performance liquid chromatography with atmospheric pressure ionization (API) mass spectrometry has been essential to a large number of quantitative analytical applications for a variety of compounds. Poor detection sensitivity however is a problem observed for a number of analytes because detection sensitivity can be affected by many factors. The two most critical factors are the chemical and physical properties of the analyte and the composition of the mobile phase. In order to address these critical factors which may lead to poor sensitivity, either the structure of the analyte must be modified or the mobile phase composition optimized. The introduction of permanently charged moieties or readily ionized species may dramatically improve the ionization efficiency for electrospray ionization (ESI), and thus the sensitivity of detection. Detection sensitivity may also be enhanced via introduction of moieties with high proton affinity or electron affinity. Mobile phase component modification is an alternative way to enhance sensitivity by changing the form of the analytes in solution thereby improving ionization efficiency. pH adjustment and adduct formation have been commonly used to optimize detection conditions. The sensitivity of detection for analytes in bio-matrices could also be enhanced by decreasing ion-suppression from the matrix through derivatization or mobile phase addition. In this review, we will discuss detection-oriented derivatization as well as the application of mobile phase additives to enhance the sensitivity of detection in liquid chromatograph/atmospheric ionization/mass spectrometry (LC/API/MS), focusing in particular on the applications involving small molecules in bio-matrices.

The objective of this study was to adopt a molecular modeling approach to understand changes in signal intensity due to adduct formation with short-chain alkylamines for two anticancer agents, paclitaxel and docetaxel, during electrospray mass spectrometric analysis. We describe a simple and intuitive modeling procedure using a comparison of hydropathic interaction (HINT) scores to explain differences in responses of amine adducts formed with the two analytes. The responses of paclitaxel and docetaxel were generally enhanced considerably (up to approximately 500% in some instances) on adding the amines. However, for the docetaxel adduct formed with added decylamine in the mobile phase, the response dropped by 32%. A mechanistic understanding for this behavior is proposed, and binding scores calculated from corresponding molecular models were found to be consistent with the trend obtained from mass spectrometric data.

We present a case of a patient with malignant melanoma of the glans penis and urethra, which was found in a 53-year-old man with nonhealing ulcerative penile lesion and bilateral, clinically palpable inguinal lymphadenopathies at diagnosis. A diagnostic biopsy showed the characteristics of a melanoma. We treated the patient with total penectomy and bilateral inguinal lymph node dissection. After surgery, chemotherapy with bleomycin, vincristine and cisplatin and immunotherapy with thymosin injection were started. No recurrence or metastasis occurred during the 3 years after the operation. Melanoma of the penis is very rare, and early diagnosis is important because the patient prognosis is very poor.

A new approach of adaptive Kalman filtering deconvolution (AKFD) via dyadic wavelet transform is proposed. Due to the computing complexity of the approach, a fast implementation technique is proposed. The AKFD via dyadic wavelet transform discards the assumption of stationarity for signals in predictive deconvolution, and solves the problem of improving resolution at the price of decreasing signal-to-noise rate (SNR) and therefore has a better ability of resistance noise. Suppressing false reflections and improving resolution in dyadic wavelet transform domain is better than that in time domain. The new approach also overcomes the drawback of increasing the low-frequency component of AKFD in time domain. The fast implementation technique makes use of the assumption of local stationary for 2D seismic data. The technique reduces the calculated amount of calculating the adaptive predictive operators by calculating an adaptive predictive operator in each segment, and then applying the algorithm of spline interpolation to interpolate in transverse and in portrait. The aim of fast implementation is thus achieved. A large number of experiments indicates that computing speed can be increased several hundred times. However, it retains the original calculation effect.

Jasmonic acid (JA) is strongly implicated in the long-distance signal transduction cascade increasing nicotine synthesis in the roots of plants after leaf wounding. In order to explore the structural requirements of the inducing signal, we examined jasmonates, mimics, and a biosynthetic precursor for nicotine-inducing activity (NIA). We examine the importance of the keto group on the five-membered ring and the double bond in then-pentenyl chain by comparing the NIA of methyl jasmonate (MJ) with that of cucurbic acid, 1,3-dithiolane-MJ, 1,3-dioxolane-MJ, methyl dihydrojasmonate (DHMJ), 1,3-dioxolane-DHMJ, 1-oxo-indan-4-carboxylic acid ILE-methyl ester, and 1-hydroxyl-indan-4-carboxylic acid ILE-methyl ester. We found that: 1,3-dioxolane MJ, cucurbic acid, and 1,3-dioxolane DHMJ were less active than MJ and that the isoleucine (ILE) conjugates of 1-oxo- and l-hydroxyindanon-4-carboxylic acid had the same NIA as MJ. The activities of these indanon amino acid conjugates may be due to the structural similarity of their keto or hydroxyl groups on the five-membered ring to MJ or to the keto-enolized MJ. These results support the hypothesis that the enolization of the keto group during or prior to its interaction with the putative JA receptor is required for activity. We explore the importance of the esterification of the carboxyl functional group by comparing the NIAs of cucurbic acid and cucurbic acid methyl ester, l-oxo-indan-4-carboxylic acid, 1-oxo-indan-4-carboxylic acid methyl ester, and l-oxo-indan-4-carboxylic acid ILE-methyl ester. In all cases, the esters were more active than the free acids. We compared the NIA of MJ of different epimeric composition (8% and 20% 3R,7S-MJ); 12-oxophytodienoic acid (12-oxo-PDA) methyl ester, an important precursor of JA; and coronatine (a well-known phytotoxin and putative structural mimic of 12-oxo-PDA).We found that: (1) the epimeric composition of MJ did not affect its NIA; (2) 12-oxo-PDA methyl ester had lower NIA than MJ; and (3) coronatine significantly inhibited plant growth but did not increase nicotine biosynthesis. In summary, JA, rather than its biosynthetic precursor, 12-oxo-PDA, is likely the endogenous signal inNicotiana sylvestris, and the keto functional group on the five-membered ring and the double bond in then-pentenyl side chain are crucial components of JA for NIA.

Jasmonic acid (JA) is part of a long-distance signal-transduction pathway that effects increases in de-novo nicotine synthesis in the roots of Nicotiana sylvestris Speg et Comes (Solanaceae) after leaf wounding. Elevated nicotine synthesis increases whole-plant nicotine pools and makes plants more resistant to herbivores. Leaf wounding rapidly increases JA pools in damaged leaves, and after a 90-min delay, root JA pools also increase. The systemic response in the roots could result from either: (i) the direct transport of JA from wounded leaves, or (ii) JA synthesis or its release from conjugates in roots in response to a second, systemic signal. We synthesized [2-14C]JA, and applied it to a single leaf in a quantity (189 μg) known to elicit both a whole-plant nicotine and root JA response equivalent to that found in plants subjected to leaf wounding. We quantified radioactive material in JA, and in metabolites both more and less polar than JA, from treated and untreated leaves and roots of plants in eight harvests after JA application. [2-14C]Jasmonic acid was transported from treated leaves to roots at rates and in quantities equivalent to the wound-induced changes in endogenous JA pools. The [2-14C]JA that had been transported to the roots declined at the same rate as endogenous JA pools in the roots of plants after leaf wounding. Most of the labeled material applied to leaves was metabolized or otherwise immobilized at the application site, and the levels of [2-14C]JA in untreated leaves did not increase over time. We measured the free JA pools before and after four different hydrolytic extractions of root and shoot tissues to estimate the size of the potential JA conjugate pools, and found them to be 10% or less of the free JA pool. We conclude that the direct transport of wound-induced JA from leaves to roots can account for the systemic increase in root JA pools after leaf wounding, and that metabolism into less polar structures determines the duration of this systemic increase. However, the conclusive falsification of this hypothesis will require the suppression of all other signalling pathways which could have shoot-to-root transport kinetics similar to that of endogenous JA.

Jasmonic acid (JA) is thought to be part of a signal-transduction pathway which dramatically increases de-novo nicotine synthesis in the roots and increases whole-plant (WP) nicotine pools in response to the wounding of the leaves in Nicotiana sylvestrisSpegazzini and Comes (Solanaceae). We report the synthesis of a doubly labeled JA ([1, 2-13C]JA) and use it as an internal standard to quantify by gas chromatography-mass spectrometry the changes in root and shoot JA pools in plants subjected to differing amounts of standardized leaf wounding. Wounding increased JA pools 10-fold locally in damaged leaves within 90 min and systemically in the roots (3.5-fold) 180 min after wounding. If JA functions as an intermediary between stimulus and response, quantitative relationships among the stimulus, JA, and the response should exist. To examine these relationships, we varied the number of punctures in four leaves and quantified both the resulting JA in damaged leaves after 90 min and the resulting WP nicotine concentration after 5 d. We found statistically significant, positive relationships among number of leaf punctures, endogenous JA, and WP nicotine accumulation. We used two inhibitors of wound-induced nicotine production, methyl salicylate and indole-3-acetic acid, to manipulate the relationships between wound-induced changes in JA and WP nicotine accumulation. Since wounding and the response to wounding occur in widely separated tissues, we applied inhibitors to different plant parts to examine their effects on the local and systemic components of this response. In all experiments, inhibition of the wound-induced increase in leaf JA 90 min after wounding was associated with the inhibition of the nicotine response 5 d after wounding. We conclude that wound-induced increases in leaf JA are an important component of this long-distance signal-transduction pathway.

To investigate the protective effect of retarded removal of the unilateral necrotic testis after long-time (24 h) spermatic cord torsion on the contralateral testis in rats.Thirty-three male SD rats aged 21 -42 days were divided into a sham-operation group (n = 11), a torsion-reservation group (n = 12) and a torsion-orchiectomy group (n = 10). The rats of the sham-operation group received dartos pouch orchidopexy on the left testis, while those of the latter two groups underwent 720 degrees unilateral spermatic cord torsion on the left side. Ninety-six hours later, the rats of the torsion-reservation group received detorsion with the ipsilateral testis preserved, while those of the torsion-orchiectomy group underwent orchiectomy. Three months after operation, blood samples were obtained from the rats for measurement of serum testosterone and antisperm antibodies by ELISA, and meanwhile testes and epididymides were harvested for determination of the volumes of various structures and the diameter of seminiferous tubules with stereological methods.There were no significant differences in the level of serum testosterone among the three groups. Anti-sperm antibody positive was found in only 1 animal in the torsion-reservation group. The Leydig cell nuclei in the contralateral testis appeared larger in the torsion groups than in the sham-operation group. Marked morphological changes were observed in 1, 3 and 0 of the animals in the sham-operation, torsion-reservation and torsion-orchiectomy group, respectively, mainly including atrophy of seminiferous tubules and reduced number of spermatogenic cells. The volume of the contralateral testis was increased by 19% and 21% in the torsion-reservation and torsion-orchiectomy group, respectively, in comparison with that in the sham-operation group (P0.05). No significant differences were observed in the volume of seminiferous tubules of the contralateral testis among the sham-operation, torsion-reservation and torsion-orchiectomy groups ([1.15 +/- 0.07], [1.30 +/- 0.04] and [1.35 +/- 0.05] cm3). The volume of the interstitial tissue was significantly increased in the latter two groups ([0.36 +/- 0.02 and 0.34 +/- 0.03] cm3) as compared with the former ([0.25 +/- 0.02] cm3) (P0.05). The diameters of the seminiferous tubules exhibited no significant differences among the three groups ([226.00 +/- 7.00], [223.00 +/- 6.00] and [221.00 +/- 3.0] microm).Long-time unilateral spermatic cord torsion may result in compensatory hypertrophy of the contralateral testis, and orchiectomy does not significantly affect the histology of the contralateral testis and epididymis.

Five new taxane diterpenes were isolated from the leaves and stems of Texus chinensis . Their structures were established as 2-deacetyl-5-decinnamatetaxagifine, taxagifine III, 4-deacetyltaxagifine III, 2α,13α-dihydroxy-9α,10β-diacetoxy-5α-cinnamatetaxa-4(20),11-diene and 10β-hydroxy-2α,9α,13α-triacetoxy-5α-cinnamatetaxa-4(20),11-diene.

To investigate polysomnographic determinants of excessive daytime sleepiness (EDS) and potential relationship in Chinese patients with obstructive sleep apnea-hypopnea syndrome (OSAS).A total of 410 patients with obstructive sleep apnea-hypopnea syndrome were analyzed retrospectively who were obtained in Sleep medicine center of West China hospital from January to April in 2010. All of the patients with an apnea-hypopnea index (AHI) greater than 5 h(-1) were evaluated using the Epworth Sleepiness Scale (ESS) and sleep disorders questionnaire. The patients who ESS score was more than 10 were defined as EDS; otherwise, the other was considered to without EDS.A total of 176 patients with EDS (ESS: 15 ± 3) and 234 without EDS (ESS: 6 ± 3) were studied. Patients with EDS were slightly higher BMI (28 ± 4 vs 26 ± 4) and shorter REM sleep latency (99 ± 65 vs 125 ± 81) than patients without EDS. Furthermore, there were significant difference in awake SaO2, AHI, minimum SaO2, oxygen desaturation index and arousal index between EDS group were No-EDS group (P0.001). There was a significant difference in waking SaO2 of severe OSAS between both groups.Long-term chronic hypoxia already exists in severe OSAS patients with prominent sleepiness. Waking SaO2 may play a role as a predictor in evaluation and diagnosis in patients with OSAS.

The formation of multiple molecular ions, especially due to sodium adduct ion formation, is commonly observed in electrospray mass spectrometry and may make reproducible and sensitive quantitation difficult. The objective of this work was to investigate the underlying mechanism involved in the suppression of multiple molecular ion formation and to improve the sensitivity of detection for the two anti-neoplastic agents paclitaxel and docetaxel. The results showed that alkylamine additives could significantly improve the detection of paclitaxel and docetaxel by suppression of multiple molecular ions through preferential formation of a predominant alkylamine adduct ion. Possible binding sites, binding interactions and binding competition were investigated for the sodium adduct and alkylamine adduct ions using various experimental techniques. The formation of a predominant amine adduct ion may be due to increased surface activity in the droplet. The optimal alkylamine for both analytes was octylamine, which increased peak heights of paclitaxel and docetaxel 4.8 and 3.7-fold (n = 3), respectively. The precision of the signals for the analytes was also improved 5.7-fold. A quantitative assay in plasma for paclitaxel was partially validated for the calibration range 1.0-1000 ng/mL (r = 0.9977) when using 0.05% octylamine as a reconstitution solution additive. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.5 and 0.9 ng/mL, respectively. Acceptable precision, accuracy, specificity and sample stability were demonstrated for this assay. This approach may prove useful for other analytes with similar binding sites.

The title compound, 2,3,4a,5,6,7,8,11,12,12a-decahydro-3,5-12-trihydroxy-9,12a,13,13-tetramethyl-6,12a,13,13-tetramenthyl-6,10-methano-[benzocyclodecene-4(1H)-spiro-2'-oxirane]-8,11-diyl diacetate, C 24 H 36 O 8 , is a structurally new taxane from Taxus chinensis. This X-ray diffraction study reveals the configurations at positions 2, 5, 9, 10 and 13 (IUPAC numbering: 5, 3, 12, 11 and 8, respectively), thus establishing that the investigated compound is the 2,9-desacetyl derivative of the already known taxane Baccatin I. Notably, the positions of the methyl groups of the dimethylmethano bridge of the cyclodecene ring (C16 and C17), which have been the subject of conflicting idscussions in some papers, are proven, as is the trans junction of the B/C rings. Furthermore, the trans positioning of the substituents at C atoms 9 and 10 is shown. The six-membered rings adopts chair conformations and the eight-membered B ring is severely puckered.

We examined the effects of inhibitors of the octadecanoid pathway (n-propyl gallate, acetosalicylic acid, salicylhydroxamic acid, methyl salicylate, and antipyrine) on wound- and jasmonate-induced nicotine accumulation and compared the nicotine-inducing ability of exogeneous additions of linolenic acid (18:3) and its methyl ester, linoleic acid (18:2), abscisic acid, traumatic acid, and methyl dihydrojasmonate to the nicotine-inducing ability of exogenous additions of methyl jasmonate (MJ). The first four of these inhibitors significantly reduced wound-induced nicotine accumulation when applied in a lanolin paste to wounded tissues immediately after wounding at concentrations of 89-90µg/plant. When methyl salicylate and propyl gallate were mixed individually with MJ, neither inhibited MJ-induced nicotine synthesis, which suggests that the inhibitors block jasmonate synthesis or release from stored pools and not its effects. Linolenic acid or its methyl ester applied to undamaged plants or damaged plants (to either damaged or undamaged leaves) or to the roots of hydroponically growing plants did not induce nicotine accumulation or increase nicotine accumulation above levels found in damaged plants. Similarly, traumatic acid, linoleic acid, and abscisic acid did not induce nicotine accumulations. Methyl dihydrojasmonate, which is biosynthetically derived from linoleic acid, had 12-56% of the nicotine-inducing acitivity of MJ when added to the roots of hydroponically grown plants. The signal transduction pathway mediating wound-induced nicotine production therefore shares many features of the pathway eliciting wound-induced proteinase inhibitor production but differs in not being regulated at the lipase step in jasmonic acid production and not being responsive to abscisic acid.

Background Although the incidence of glioma is relatively low, it is the most malignant tumor of the central nervous system. The prognosis of high-grade glioma patient is very poor due to the difficulties in complete resection and resistance to radio-/chemotherapy. Therefore, it is worth investigating the molecular mechanisms involved in glioma drug resistance. MicroRNAs have been found to play important roles in tumor progression and drug resistance. Our previous work showed that miR-181b is involved in the regulation of temozolomide resistance. In the current study, we investigated whether miR-181b also plays a role in antagonizing the effect of teniposide. Methods MiR-181b expression was measured in 90 glioma patient tissues and its relationship to prognosis of these patients was analyzed. Cell sensitivity to teniposide was tested in 48 primary cultured glioma samples. Then miR-181b stably overexpressed U87 cells were generated. The candidate genes of miR-181b from our previous study were reanalyzed, and the interaction between miR-181b and target gene MDM2 was confirmed by dual luciferase assay. Cell sensitivity to teniposide was detected on miR-181b over expressed and MDM2 down regulated cells. Results Our data confirmed the low expression levels of miR-181b in high-grade glioma tissues, which is related to teniposide resistance in primary cultured glioma cells. Overexpression of miR-181b increased glioma cell sensitivity to teniposide. Through target gene prediction, we found that MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3’-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b. Conclusions MiR-181b is an important positive regulator on glioma cell sensitivity to teniposide. It confers glioma cell sensitivity to teniposide through binding to the 3’-UTR region of MDM2 leading to its reduced expression. Our findings not only reveal the novel mechanism involved in teniposide resistance, but also shed light on the optimization of glioma treatment in the future.