Search

A new naphthalene derivative and three known compounds were isolated from the petroleum ether extract of the bulbs of Eleutherine americana by using various chromatographic techniques, such as column chromatography over silica gel and semi-preparative HPLC. Their structures were elucidated by spectroscopic date (MS, UV, IR, NMR), which were identified as eleutherol B (1), 4,8-dihydroxy-3-methoxy-1-methylanthraquinone-2-carboxylic acid methyl ester (2), 8-hydroxy-3,4-dimethoxy-1-methylanthraquinone-2-carboxylic acid methyl ester (3), and isoeleutherine (4). Compound 1 is a new compound. The diastolic blood vessels activity of compound 1 and 2 were potent, reaching 82.5% and 85.3% at the concentration of 10 μmol·L⁻¹, which were basically the same as that of the positive drug tanshinone ⅡA., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Five new naphthalene derivatives, named Eleutherols A⁻C ( 1 ⁻ 3 ) and Eleuthinones B⁻C ( 4 , 5 ), together with three known compounds were isolated from the bulbs of Eleutherine americana . Their structures were elucidated on the basis of spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR techniques. These compounds exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro.

Background: Pelvic incidence (PI) is an important variable in assessing spinopelvic balance that is associated with hip pathology. A lateral radiograph of the pelvis can be used to measure PI, but this view is not routinely performed in the clinical setting during evaluation of hip pain. The false-profile (FP) radiographic view of the hip is commonly obtained to measure acetabular coverage., Purpose: To evaluate the tolerance of PI measurements to pelvic rotation and assess the feasibility of using an FP radiograph to obtain an accurate measurement of PI., Study Design: Cohort study (diagnosis); Level of evidence, 2., Methods: A mathematical model was developed to predict the change in PI with rotation. Fluoroscopic images were obtained of 6 reconstructed cadaveric adult pelvis and femur specimens at varying degrees of rotation, including a perfect lateral and FP image. PI was measured with the midpoint between the centers of the femoral heads as a reference point. The findings were confirmed clinically by retrospectively reviewing FP radiographs and computed tomography (CT) scans of 40 clinical patients. PI was measured on FP radiographs and CT scans by 2 independent reviewers., Results: With dry cadaveric pelvis specimens, the discrepancy in PI measured between fluoroscopic FP and lateral views was 1.6° (95% CI, 0.7°-2.4°). There was excellent agreement between CT and FP radiographs with regard to measurement of PI (intraclass correlation coefficient = 0.92; 95% CI, 0.78-0.98). Mean discrepancy in PI measured between the 40 clinical FP radiographs and CT scans was 2.8° (range, 0.1°-9.1°)., Conclusion: Increased rotation from a lateral view results in greater error in measuring PI, although relatively nominally with a 2.8° error with the 25° of rotation in clinical true FP views. These data demonstrate that FP radiographs can be used to measure PI with reasonable accuracy.

Three new compounds (1 - 3), including two euphane type triterpenes, 24,24-dimethoxy-25,26,27-trinoreuphan-3β-ol (1) and (24S)-24-hydroperoxyeupha-8,25-dien-3β-ol (2), and an ent-atisine diterpene, ent-atisane-3α,16α,17-triol (3), were isolated from an acetone extract of the stems of Euphorbia antiquorum, together with eight known diterpenes (4 - 11). The structures of compounds (1 - 11) were elucidated using NMR and MS spectroscopic methods. Compound 7 showed moderate activity against HIV-1 replication in vitro (EC 50 = 1.38 μm)., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Inspired by the enormous importance attributed to the biological function of miRNA, we pour our attention into the design and synthesis of four ruthenium(II) complexes and evaluate their applications as miR-185 detection agents by spectroscopic measurements. It was found that all complexes can form sensing platform for the detection of the complementary target miR-185 through the introduction of carboxyfluorescein (FAM) labeled single stranded DNA (P-DNA), giving the detection limits of 0.42nM for Ru 1, 0.28nM for Ru 2, 0.32nM for Ru 3, 0.85nM for Ru 4, all with instantaneous detection time in 1min. The results of the binding constant, fluorescence anisotropy (FA) and polyacrylamide gel electrophoresis experiments (PAGE) revealed that the ruthenium(II) complexes prefer to bind P-DNA other than hybrid duplexes DNA@RNA upon recognition, resulting in the detection of miR-185. These results provide useful suggestions in the new type of metal-based miRNA detection agents., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Postoperative pain control can be challenging in reduction mammaplasty patients. This study compares perioperative liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, Inc, San Diego, Calif) with standard local anesthetics to determine if liposomal bupivacaine decreases opioid and antiemetic use, impacting length of stay and complication rates, thus improving patient outcomes., Methods: A retrospective review of 170 reduction mammaplasty patients was performed. Patients were divided into groups based on local anesthetic used (bupivacaine only and liposomal bupivacaine) and into subgroups based on obesity classification. Length of hospital stay; pain scores immediately postoperatively, at discharge, and at follow-up; and postoperative analgesics and antiemetics were compared. Further analysis was performed after weight stratification within pre- and postmenopausal categories., Results: Liposomal bupivacaine resulted in less pain than bupivacaine immediately postoperatively and at discharge in obesity class I (P = 0.021 and P = 0.018). In obesity class II, antiemetic use was lower in the liposomal bupivacaine group (P = 0.012). Length of stay was persistently lower with liposomal bupivacaine for premenopausal women, and this difference was significant in obesity class I (P = 0.038). In premenopausal women, discharge pain scores were lower in the overweight liposomal bupivacaine group (P = 0.034) and analgesic use was lower in obesity class III (P = 0.004)., Conclusions: Liposomal bupivacaine decreases postoperative pain, opioid, and antiemetic use in select patients. Liposomal bupivacaine might not be equally efficacious in pain reduction in obese or postmenopausal women given the theoretical increased absorption by adipose tissue. In addition, liposomal bupivacaine may have a dose-dependent effect, and weight-based dosing should be investigated.

In this study, we aim to determine the function of miR-124 on gastric cancer (GC) cells and the underlying mechanism that involves jaddeg1 (JAG1) and the Notch signaling pathway. GC tissues and adjacent tissues from 100 patients suffering from GC were selected. GC SGC-7901 and AGS cells were selected and grouped into control, mimic-NC, miR-124 mimic, inhibitor-NC, miR-124 inhibitor, and miR-124 inhibitor + si-JAG1 groups. RT-qPCR and a Western blotting assay were conducted to detect the expression of miR-124, JAG1, and Notch signaling pathway-related proteins (NICD, HES1, and HES5). MTS, wound-healing, transwell assay and flow cytometry were performed to detect cell proliferation, migration, invasion, cell cycle distribution, and apoptosis, respectively. Compared with adjacent tissues, a lower miR-124 expression and higher JAG1 expression were found in GC tissues. JAG1 is a direct target gene of miR-124. Compared with the control group, the expression of JAG1, NICD, HES1, and HES5, cell invasion, migration, and proliferation in the miR-124 mimic group were decreased, while the apoptosis rate was increased and cells were arrested at the G0/G1 phase. Compared with the miR-124 inhibitor group, the expression of JAG1, NICD, HES1, and HES5, cell invasion, migration, and proliferation in the miR-124 inhibitor + si-JAG1 group were decreased, while the apoptosis rate and cell ratio at the G0/G1 phase were increased. The demonstration that miR-124 inhibits GC cell growth supports the concept that miR-124 functions as a tumor suppressor by a mechanism that involves translational repression of the JAG1 and the inhibition of Notch signaling pathway., (© 2017 Wiley Periodicals, Inc.)

Cam morphology of the proximal femur is an abnormal contour of the femoral head-neck junction present in approximately 15% to 25% of the asymptomatic population, predominantly in males. Alpha angle and femoral head-neck offset ratio are 2 objective measurement tools that define cam morphology. Both primary (idiopathic) and secondary cam deformity develops through distinct mechanisms. The cause of primary (idiopathic) cam morphology remains incompletely understood. Mounting evidence suggests that idiopathic cam morphology develops during adolescence through alterations in the capital femoral epiphysis in response to participation in vigorous sporting activity. While the exact cause of epiphyseal extension has not yet been determined, preliminary evidence suggests that epiphyseal extension may reflect a short-term adaptive response to provide stability to the physis at the long-term cost of the development of cam morphology. Commonly recognized causes of secondary cam deformity include frank slipped capital femoral epiphysis, Legg-Calve-Perthes disease, and deformity after fracture of the proximal femur. Recent studies also support subtle slipped capital femoral epiphysis as a unique and silent cause of a small percentage of subjects previously thought to have idiopathic cam deformity.

Six previously undescribed diterpenoids, named euphorantins S-T and euphorneroids A-D, including ingol and ent-atisane types, along with eleven known diterpenoids, were isolated from Euphorbia neriifolia. Their structures were elucidated on the basis of extensive NMR analysis and high resolution mass spectrometry. Euphorneroid D and ent-3-oxoatisan-16α,17-acetonide exhibited moderate anti-HIV-1 activities, with EC 50 values of 34 μM (SI = 2.3) and 24 μM (SI = 1.9), respectively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Twenty-eight protostane triterpenoids, including a new degraded one (1), nine new ones (2 - 10), and two new natural ones (11 and 12), have been isolated from the dried rhizomes of Alisma orientale. Alisol R (1) was the first 20,21,22,23,24,25,26,27-octanorprotostane triterpenoid. The absolute configurations of 25-methoxyalisol F (2) and 16β-hydroperoxyalisol B 23-acetate (3) were determined by X-ray diffraction analysis. In addition, alismaketone-B 23-acetate (28) showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl., (© 2017 Wiley-VHCA AG, Zurich, Switzerland.)

Lung transplantation is a definitive treatment for select patients with end-stage pulmonary disease. Following transplantation, the reported rate of lung cancer is between 1-9% and is associated with a variety of risk factors, including smoking history and chronic immunosuppression. The majority of post-transplant lung cancer reported in the literature is histologically classified as non-small cell lung carcinoma (NSCLC). We report a unique case of early stage small cell lung carcinoma (SCLC) identified in the native lung following single lung transplantation., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

The sympatric closely related species Helicoverpa armigera and Helicoverpa assulta use 97:3 and 7:93 of (Z)-11-hexadecenal and (Z)-9-hexadecenal, respectively, as their sex pheromone to find/locate correct sex mates. Moreover, (Z)-11-hexadecenyl alcohol and (Z)-9-hexadecenyl alcohol are more abundant in the pheromone gland of H. assulta than in that of H. armigera. To clarify the molecular basis of these differences, we sequenced the pheromone gland transcriptomes of the two species and compared the expression patterns of the candidate enzyme genes involved in the pheromone biosynthetic pathways by FPKM values and quantitative RT-PCR analysis. We found that the desaturase gene LPAQ expressed about 70 times higher in H. armigera than in H. assulta, whereas another desaturase gene NPVE expressed about 60 times higher in H. assulta than in H. armigera. We also observed significantly higher expression of the fatty acyl reductase (FAR) gene FAR1 and the aldehyde reductase (AR) gene AR3 in H. assulta than in H. armigera. Examination of the pheromone glands of the backcross offspring of their hybrids to H. assulta showed a positive linear correlation between the expression level of LPAQ and the amount of Z11-16:Ald and between the expression level of NPVE and the amount of Z9-16:Ald in the pheromone glands. Taken together, these data demonstrate that the expressional divergences of LPAQ and NPVE determine the opposite sex pheromone component ratios in the two species and the divergent expression of FAR1 and AR3 may account for the greater accumulation of alcohols in the pheromone gland of H. assulta., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Three new compounds ( 1  -  3 ), including a sesterterpenoid, aspterpenacid C ( 1 ), with an unusual 5/3/7/6/5 pentacyclic skeleton, together with seven known ones ( 4  -  10 ), were isolated from the ethanol extract of the traditional Chinese medicinal plant Swertia bimaculata. Their structures were elucidated on the basis of the methods of spectroscopic NMR, MS, and computational chemistry. The structure of 1 was further confirmed by single-crystal X-ray diffraction analysis. Compounds 1  -  10 were tested for activities on the inhibition of nitric oxide production and HIV-1 replication in vitro . Compound 1 exhibited moderate activity in inhibiting nitric oxide production (IC 50  = 16.1 µM) and HIV-1 replication (EC 50  = 1.35 µM)., Competing Interests: Conflict of Interest: We declare that all authors have read the manuscript conscientiously, and all agreed with the treatment of this manuscript, including content, the sequence of authors, and submission. All authors state no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Hypermethylation of the transcription factor AP-2 epsilon (TFAP2E) gene affects 5-fluorouridine (5-FU) resistance in gastric cancer (GC) patients. The epigenetic inhibitor 5-Aza-2'-deoxycytidine (DAC), which reverses DNA methylation by targeting DNA methyltransferases (DNMTs), has potential to sensitize GC to 5-FU. Nevertheless, DNA demethylation only DAC transiently occurs since DAC is unstable in aqueous solutions, which limits its potential. Here we developed intelligent nanoparticles (NPs) comprising gelatinase with polyethylene glycol (PEG) and poly-ε-caprolactone) (PCL) to specifically deliver DAC (DAC-TNPs) to tumors. DAC-carrying PEG-PCL NPs (DAC-NPs) lacking gelatinase features served as controls. 72 hours after administration of DAC-TNPs or DAC-NPs, 5-FU was sequentially applied to GC cells and human GC xenografts in nude mice. Both in vitro and in vivo evaluations demonstrated that the combination treatment of DAC-TNPs and 5-FU greatly improved tumor suppression in GC cells and mouse xenograft models with hypermethylation TFAP2E (MKN45 cells). We thus propose that the sequential administration of DAC-TNPs and 5-FU could be significant in the development of novel targeted therapies., Competing Interests: CONFLICTS OF INTEREST The authors have no competing interests to declare.

Realgar nanoparticles (NPs) are increasingly used as therapeutic agents for their enhanced anti-proliferation effect and cytotoxicity on cancer cells. However, the alteration of particle size may enhance biological reactivity as well as toxicity. A LC/MS and GC/MS based metabolomics approach was employed to explore the mechanism of realgar NPs-induced hepatotoxicity and identify potential biomarkers. Male Sprague-Dawley rats were administrated intragastrically with realgar or realgar NPs at a dose of 1.0 g·kg -1 ·d -1 for 28 days and toxic effects of realgar NPs on liver tissues were examined by biochemical indicator analysis and histopathologic examination. Increased levels of serum enzymes and high hepatic steatosis were discovered in the realgar NPs treated group. Multivariate data analysis revealed that rats with realgar NPs-induced hepatotoxicity could be distinctively differentiated from the animals in the control and realgar treated groups. In addition, 21 and 32 endogenous metabolites were apparently changed in the serum and live extracts, respectively. Realgar NPs might induce free fatty acid and triglyceride accumulation, resulting in hepatotoxicity. In conclusion, the present study represents the first comprehensive LC/MS- and GC/MS-based metabolomics analysis of realgar NPs-induced hepatotoxicity, which may help further research of nanotoxicity., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Aim: To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma (HCC)., Methods: A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases (the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL., Results: Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response (PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade II bone marrow suppression and the remaining patients had no significant hematological side effects., Conclusion: Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective., Competing Interests: Conflict-of-interest statement: None declared.

To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells.

Six new highly oxygenated grayanane diterpenoids, neopierisoids G-L, 1-6, together with 10 known related compounds, 7-16, were identified from the flowers of the poisonous plant Pieris japonica. The structures were elucidated on the basis of comprehensive NMR spectroscopy and mass analysis. The relative configurations of 1-6 were elucidated by analysis of ROESY spectra and comparison of NMR data with the analogues. The absolute configurations of 1-6 were established by the X-ray diffraction analysis of 1 and comparison of the CD spectra of 1-6. Compared with the skeleton of the normal grayanane diterpenoids, compounds 1-6 shared an unusual seco A ring moiety. The antifeedant activities of compounds 1-16 against Pieris brassicae were evaluated by using a dual-choice bioassay, and compounds 1-10 with a normal grayanane skeleton showed potent antifeedant activity against P. brassicae. The structure-activity relationships of antifeedant activities of 1-16 against P. brassicae are discussed.

MiR-21 is an oncogenic miR frequently elevated in gastric cancer. Overexpression of miR-21 decreases the sensitivity of gastric cancer cells to trastuzumab, which is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2. However, optimization of miRNA or its anti-miRNA oligonucleotides (AMOs) for delivery is a challenge. Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including AMOs. This study is a continuation of our earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target gastric cancer cells with HER2 receptor over-expression using anti-miRNA-21 antisense oligonucleotides (AMO-21). The antibody conjugates (HER-PEG-PCL NPs) act against target cells via antibody-dependent mechanisms and also based on encapsutalated AMO-21. X-ray photoelectron spectroscopy validated the presence of trastuzumab on NP surface. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a stable antibody expression. The cell line specificity, cellular uptake, AMO-21 delivery, and cytotoxicity of the HER-PEG-PCL NPs were investigated. We found that the antibody conjugates significantly enhanced the cellular uptake of NPs. The HER-PEG-PCL NPs effectively suppressed the target miRNA expression in gastric cancer cells, which further up-regulated phosphatase and tensin homolog (PTEN). As a result, the sensitivity of HER2-expressing gastric cancer cells to trastuzumab was enhanced. The approach enhances the targeting by trastuzumab as well as antibody-dependent cellular cytotoxicity of immune effector cells. The antitumor effects of AMO-21-HER-PEG-PCL NPs were compared with trastuzumab in xenograft gastric cancer mice. The results provide insight into the biological and clinical potential of targeted AMO-21 delivery using modified trastuzumab for gastric cancer treatment., Competing Interests: CONFLICTS OF INTEREST The authors have no competing interests to declare.

Four new naphthoquinones ( 1 - 4 ), including a dimeric one, shikometabolin G ( 1 ), together with six known ones ( 6 - 10 ), were isolated from the methanol extract of Onosma paniculatum . Their structures were established based on the analysis of NMR and MS spectroscopic data. All of the compounds were evaluated for inhibitory effects on NO production in murine macrophage RAW 264.7 cells. Compounds 2, 3, 5, 6, 7, 8 , and 10 displayed good activity on the inhibition of NO production (IC 50 = 0.4-16.5 µM), suggesting the potential property of anti-inflammation., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: This study aimed to explore the effects of diet-induced hypercholesterolemia (HC) on the production of G protein-coupled receptor autoantibodies and to elucidate the potential mechanisms involved., Materials and Methods: Male Wistar rats were fed a normal or high-cholesterol diet for 8 weeks. Cardiac function, autoantibodies against G protein-coupled receptors, the beat frequency of neonatal cardiomyocytes, the CD4+/CD8+ T-lymphocyte ratio and lymph leukocyte counts in the spleen were determined., Results: Diet-induced hypercholesterolemia significantly increased the levels of autoantibodies against α1- and β1-adrenergic receptors and the angiotensin II type 1 receptor in sera, as well as the CD4+/CD8+ T-lymphocyte ratio and lymph leukocyte count in the spleen, and decreased cardiac function. There were strong negative correlations between the levels of autoantibodies and cardiac injury., Conclusions: The present study demonstrates, for the first time, that G protein-coupled receptor autoantibodies exist in the sera of hypercholesterolemic rats and that the levels of these autoantibodies are related to cardiac function, which implies that these cardiac receptor autoantibodies may play a role in cardiac dysfunction in hypercholesterolemic rats.

Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.

A novel class of urea-containing peptide boronic acids as proteasome inhibitors was designed by introducing a urea scaffold to replace an amido bond. Compounds were synthesized and their antitumor activities were evaluated. After two rounds of optimizations, the compound I-14 was found to be a potent proteasome inhibitor. Compared with Bortezomib, I-14 showed higher potency against the chymotrypsin-like activity of human 20S proteasome (IC 50  < 1 pM), similar potency against four different cancer cell lines (IC 50  < 10 nM), and better pharmacokinetic profile. Furthermore, I-14 significantly inhibited tumor growth in Bel7404 mouse xenograft model. The excellent proteasome inhibition by I-14 was rationalized through docking and molecular dynamics studies., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma cochlear. The chemical structures of new compounds were elucidated on the basis of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were assigned by ECD calculations. Biological activities of these isolates against renal fibrosis were accessed in rat normal or diseased renal interstitial fibroblast cells. Importantly, the plausible biosynthetic pathway for this class of alkaloids was originally proposed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Twelve guaiane-type sesquiterpenoids, including four new ones, 10-O-methyl-orientalol A (1), 10-O-ethyl-alismoxide (2), 3β,4β-expoxy-chrysothol (3), orientalol G (4), and a new norsesquiterpenoid, orientalol H (5), were isolated from Chinese Alismatis Rhizoma, the dried rhizome of Alisma orientale. The structures of new compounds were elucidated on the basis of spectroscopic data. Moreover, the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells of all compounds was tested.

(±)-Evodiakine (1a and 1b), a pair of rearranged rutaecarpine-type alkaloids with an unprecedented 6/5/5/7/6 ring system, were isolated from the nearly ripe fruits of Evodia rutaecarpa. Separation of the enantiomers have been achieved by chiral HPLC column. The structures of (±)-evodiakine were unambiguously elucidated by 1D and 2D NMR spectra, mass spectrometry, and single-crystal X-ray diffraction. Their absolute configurations were determined by comparison of experimental and calculated electronic circular dichroism spectra. A hypothetical biogenetic pathway for (±)-evodiakine was also proposed. Compounds 1a, 1b, and the racemate (1) were tested for their cytotoxic and anti-inflammatory activities., Competing Interests: The authors declare no conflict of interest.

A new flavonoid glycoside, eriodictyol 7-O-(6″-caffeoyl)-β-D-glucopyranoside (1), along with 14 known compounds, were isolated from the whole plants of Elsholtzia bodinieri. All of the structures were determined by spectroscopic methods and chemical transformation. Compound 1 and luteolin (9) exhibited potent anti-HCV activities with a selective index of 135.85 and 20.84, respectively.

Background: Pressure ulcers (PUs) challenge many in the healthcare field requiring costly and complex care. PUs result from prolonged ischemia and subsequent soft-tissue injury caused by unrelieved pressure over a bony prominence. Proper risk assessment and implementation of prevention strategies for PUs are crucial to providing comprehensive care while reducing healthcare costs. The emphasis has led to the expansion of research in PU prevention technologies in the recent years. The aim of this review is to present an evidence-based summary of some of the new innovations in PU prevention., Methods: A literature search was performed. Articles were included if the article discussed the cost, prevalence, assessment, diagnosis, and/or prevention of PUs. The literature search was limited to 2013 to 2016., Results: A total of 1393 potential studies were identified using the search criteria. Three hundred fifty-three articles were reviewed and when possible, preference for inclusion was given to those studies with a higher level of evidence or those discussing novel ideas/innovations., Conclusion: The summary of topics explored includes the following: the use of risk assessment scales as an adjunct in risk identification, the benefit of alternative support surfaces to aid in prevention as compared with standard hospital mattresses, effective repositioning strategies, silicone prophylactic dressing for shear reduction, microclimate control, nutritional considerations, use of electrical stimulation for spinal cord injury patients, and the importance of patient participation.

Cisplatin is one of the most common drugs used for treatment of solid tumors such as ovarian cancer. Unfortunately, the development of resistance against this cytotoxic agent limits its clinical use. Here we report that YSY01A, a novel proteasome inhibitor, is capable of suppressing survival of cisplatin-resistant ovarian cancer cells by inducing apoptosis. And YSY01A treatment enhances the cytotoxicity of cisplatin in drug-resistant ovarian cancer cells. Specifically, YSY01A abrogates regulatory proteins important for cell proliferation and anti-apoptosis including NF-κB p65 and STAT3, resulting in down-regulation of Bcl-2. A dramatic increase in cisplatin uptake was also observed by inductively coupled plasma-mass spectrometry following exposure to YSY01A. Taken together, YSY01A serves as a potential candidate for further development as anticancer therapeutics targeting the proteasome.

Purpose: The triradiate cartilage transiently projects medially within the pelvic brim around the time of triradiate closure, mimicking the ischial spine sign. The purpose of this study was to characterize this newly identified radiographic sign using a longitudinal radiographic study., Methods: We identified 72 subjects from a longitudinal radiographic study of healthy adolescents, each with at least four consecutive, annual anterior-posterior radiographs of the left hip, including physeal closure. Images were reviewed to identify the presence of the triradiate bump, the year it was most prominent, and the number of years relative to triradiate closure after which it had completely remodeled., Results: The transient medial projection of the triradiate cartilage (triradiate bump) was identified in 26/40 (65 %) females and 22/32 (69 %) males (p = 0.74). The medial projection of the triradiate cartilage was most prominent at 10.8 ± 0.8 years of age in females and 12.6 ± 0.7 years of age in males (p < 0.001). The triradiate cartilage projected medially a mean of 4.7 ± 0.8 or 5.1 ± 1.4 mm for females and males, respectively (p = 0.29), but remodeled completely in all cases around triradiate closure., Conclusions: The transient medial projection of the triradiate cartilage within the pelvic brim, the 'triradiate bump sign', is a common radiographic finding in healthy adolescents around the time of closure of the triradiate cartilage that may mimic the ischial spine sign. These two signs can be distinguished as the projection of the ischial spine is located more inferiorly within the pelvic brim and the triradiate bump has a horizontal limb of radiolucency extending to its medial border.

Aim: The novel anticancer compound TM208 is an EGFR tyrosine kinase inhibitor (EGFR-TKI). Since the development of resistance to EGFR-TKIs is a major challenge in their clinical usage, we investigated the profiles of resistance following continuous treatment with TM208 in human breast cancer xenograft mice, and identified the relationship between the tumor pEGFR levels and tumor growth inhibition., Methods: Female BALB/c nude mice were implanted with human breast cancer MCF-7 cells, and the xenograft mice received TM208 (50 or 150 mg·kg(-1)·d(-1), ig) or vehicle for 18 d. The pharmacokinetics (PK) and pharmacodynamics (PD) of TM208 were evaluated., Results: The PK properties of TM208 were described by a one-compartment model with first-order absorption kinetics. Our study showed the inhibitory effects of TM208 on tumor pEGFR levels gradually reached a maximum effect, after which it became weaker over time, which was characterized by a combined tolerance/indirect response PD model with an estimated EC50 (55.9 μg/L), as well as three parameters ('a' of 27.2%, 'b' of 2730%, 'c' of 0.58 h(-1)) denoting the maximum, extent and rate of resistance, respectively. The relationship between the tumor pEGFR levels and tumor growth inhibition was characterized by a combined logistic tumor growth/transit compartment model with estimated parameters associated with tumor growth characteristics kng (0.282 day(-1)), drug potency kTM208 (0.0499 cm(3)/day) and the kinetics of tumor cell death k1 (0.141 day(-1)), which provided insight into drug mechanisms and behaviors., Conclusion: The proposed PK/PD model provides a better understanding of the pharmacological properties of TM208 in the treatment of breast cancer. Furthermore, simulation based on a tolerance model allows prediction of the occurrence of resistance.

Two new ursane-type triterpenoid saponins, bodiniosides M (1) and N (2), along with three known saponins, oblonganosides I (3), pseudobuxussaponin B (4) and bodinioside A (5), were isolated from the aerial parts of Elsholtzia bodinieri. The structures of compounds 1 and 2 were characterized by spectroscopic data as well as acid hydrolysis and GC analysis as 3-O-β-D-xylopyranosyl-19α-hydroxy-23-acetoxy-urs-12(13)-en-28-oic acid 28-O-α-L-rhamnopyranosyl-(1-2)-β-D-glucopyranoside and 3-O-β-D-glucopyranosyl-2α,19α-dihydroxy-urs-12(13)-en-28,20β-lactone. Compounds 1 and 5 exhibited potent anti-HCV activities in vitro with a selective index of 6.53 and 4.41, respectively.

Objective: To study the relationship between clinicopathological characteristics, prognosis and gastrointestinal bleeding in primary gastrointestinal stromal tumors (GIST)., Methods: The clinicopathological and follow-up data of 200 patients with gastrointestinal stromal tumors treated in our hospital from April 2008 to December 2014 were retrospectively reviewed. The correlation of gastrointestinal bleeding with gastrointestinal stromal tumor clinicopathological characteristics and prognosis were analyzed., Results: The 200 GIST patients were divided into two groups according to the bleeding in the digestive tract, including 57 gastrointestinal bleeding patients and 143 non-bleeding patients. The mean tumor diameter was 6.5 cm (range 1.8-22 cm) in the bleeding group and 2.5 cm (range 0.4-18 cm) in the non-bleeding group (P<0.05). Of the 57 bleeding patients, 31 located in the stomach, 25 in the small intestine, and one had colorectal bleeding. Fifty patients had mitotic index (MI) ≤ 5/50 HPF, other 6 patients ranged between 5 and 10/50 HPF and one patient had MI >10/50 HPF. Six GIST patients were complicated with tumor rapture. But in the non-bleeding group, 125 patients had gastric GIST, 8 in the small intestine, one colorectum, and 9 had esophageal or other GIST. 141 patients had MI ≤5/50 HPF, 1 patients ranged between 5 and 10/50 HPF and one patient had MI >10/50 HPF. Only 1 GIST patients was complicated with tumor rapture. The gastrointestinal bleeding was closely associated with tumor size, mitotic index, tumor location, risk classifications, tumor rapture and tumor recurrence (P<0.05 for all). The 3-year and 5-year survival rates of the 200 patients were 96.5% and 86.8%, respectively. 16 patients developed recurrence or metastasis, and 11 died of GIST. The 5-year survival rate of patients with gastrointestinal bleeding was 76.2%, significantly lower than that of patients without gastrointestinal bleeding (91.6%, P<0.05)., Conclusions: GIST patients complicated with gastrointestinal bleeding have poor prognosis, and attention should be paid to stratifying patients for therapy.

A series of new analogs based on the structure of lead compound 10 were designed, synthesized and evaluated for their in vitro anti-cancer activities against four selected human cancer cell lines (HL-60, Bel-7402, SK-BR-3 and MDA-MB-468). Several synthesized compounds exhibited improved anti-cancer activities comparing with lead compound 10. Among them, 1,3,4-oxadiazole analogs 17o showed highest bioactivity with IC50 values of 1.23, 0.58 and 4.29 μM against Bel-7402, SK-BR-3 and MDA-MB-468 cells, respectively. It is noteworthy that 17o has potent anti-proliferation activity toward a panel of cancer cells with relatively less cytotoxicity to nonmalignant cells. The further mechanistic study showed that it induced apoptosis and cell cycle arrest through disrupting spindle assembly in mitotic progression, indicating these synthesized dithiocarbamates represented a novel series of anti-cancer compounds targeting mitosis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Three new monoterpenoid indole alkaloids, 19-hydroxyl-10-methoxy-19, 20-dihydrovinorine (1), 19-O-acetyl-10-methoxy-19, 20-dihydrovinorine (2), and 19, 21α-dihydroxyl-10-methoxy-19, 20-dihydrovinorine (3), along with five known analogues (4-8), were isolated from the whole plants of Vinca major. The new structures were elucidated by extensive NMR and MS analysis and comparison with known compounds. In addition, compounds 1-3 were evaluated for their cytotoxicities against five human cancer cell lines.

Two new [neougonins A (1) and B (2)] and nine known prenylated flavonoids were isolated from the whole plants of Helminthostachys zeylanica. The structures of the new isolates were elucidated by extensive NMR techniques, including one and two dimensional (1D)- and (2D)-NMR experiments, as well as comparison with spectroscopic data of known analogous compounds. Moreover, compound 1 inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells with an IC50 value of 3.32 µM.

Context: Wearable performance devices and sensors are becoming more readily available to the general population and athletic teams. Advances in technology have allowed individual endurance athletes, sports teams, and physicians to monitor functional movements, workloads, and biometric markers to maximize performance and minimize injury. Movement sensors include pedometers, accelerometers/gyroscopes, and global positioning satellite (GPS) devices. Physiologic sensors include heart rate monitors, sleep monitors, temperature sensors, and integrated sensors. The purpose of this review is to familiarize health care professionals and team physicians with the various available types of wearable sensors, discuss their current utilization, and present future applications in sports medicine., Evidence Acquisition: Data were obtained from peer-reviewed literature through a search of the PubMed database. Included studies searched development, outcomes, and validation of wearable performance devices such as GPS, accelerometers, and physiologic monitors in sports., Study Design: Clinical review., Level of Evidence: Level 4., Results: Wearable sensors provide a method of monitoring real-time physiologic and movement parameters during training and competitive sports. These parameters can be used to detect position-specific patterns in movement, design more efficient sports-specific training programs for performance optimization, and screen for potential causes of injury. More recent advances in movement sensors have improved accuracy in detecting high-acceleration movements during competitive sports., Conclusion: Wearable devices are valuable instruments for the improvement of sports performance. Evidence for use of these devices in professional sports is still limited. Future developments are needed to establish training protocols using data from wearable devices., (© 2015 The Author(s).)

The fungal species of the genus Ganoderma attracted great interest in the last decades. Our recent investigation on Ganoderma petchii afforded five new compounds, (-)-petchioics A and B (1 and 2), petchiates A and B (3 and 4), petchine (5), and a known compound. The structures of the new compounds were elucidated on the basis of spectroscopic data. The absolute configurations of 1 and 2 were assigned by computational methods. Biological activities of these isolates towards human cancer cells, COX-1/2, and influenza virus were evaluated., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Solitary fibrous tumor (SFT) which is an extremely rare clinical entity has been reported infrequently. Most commonly it is distinguished into pleural and extrapleural forms, with same morphological resemblance. There has been many literatures reported regarding extrapleural form of SFT but few cases of SFT originating from small bowel mesentery have been reported till now. We here report one case of SFT of small bowel mesentery with some eventful postoperative bowel obstruction and literature review.

Aberrant methylation of the transcription factor AP-2 epsilon (TFAP2E) has been attributed to 5-fluorouridine (5-FU) sensitivity. 5-Aza-2'-deoxycytidine (DAC), an epigenetic drug that inhibits DNA methylation, is able to cause reactive expression of TFAP2E by demethylating activity. This property might be useful in enhancing the sensitivity of cancer cells to 5-FU. However, the effect of DAC is transient because of its instability. Here, we report the use of intelligent gelatinases-stimuli nanoparticles (NPs) to coencapsulate and deliver DAC and 5-FU to gastric cancer (GC) cells. The results showed that NPs encapsulating DAC, 5-FU, or both could be effectively internalized by GC cells. Furthermore, we found that the NPs enhanced the stability of DAC, resulting in improved re-expression of TFAP2E. Thus, the incorporation of DAC into NPs significantly enhanced the sensitivity of GC cells to 5-FU by inhibiting cell growth rate and inducing cell apoptosis. In conclusion, the results of this study clearly demonstrated that the gelatinases-stimuli NPs are an efficient means to simultaneously deliver epigenetic and chemotherapeutic drugs that may effectively inhibit cancer cell proliferation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

YSY01A is a new tripeptideboronic acid and an analog of PS341. However, YSY01A's antitumor effects and mechanism have not yet been elucidated. This study demonstrates that YSY01A inhibited proteasome activity by combining with the chymotrypsin-like (CT-L) site (β5i/β5), the post-glutamyl peptide hydrolase (PGPH) site (β1i/β1) and the trypsin-like (T-L) site (β2i/β2) in special fluorgonic substrates and proteasome probe tests. We explored the anticancer effect using methyl thiazolyltetrazolium (MTT) or sulforhodamine B (SRB), and PC-3M cells were sensitive to YSY01A among the four cancer cell types tested. The YSY01A antiproliferative effect was stronger than that of PS341. In vivo, YSY01A (1.25, 2.25, and 3.25 mg/kg) inhibited PC-3M cell xenograft tumor growth, and the tumor volume inhibition rate was approximately 40% to 60%. YSY01A arrested PC-3M cells in the G2/M phase of the cell cycle by flow cytometry (FCM). Many proteins related to the cell cycle were analyzed using western blot, and YSY01A was shown to increase p21, p27, cyclinB1, P-cdc2 (tyr15) and wee1 protein expression in both cells and tumor tissue in a concentration-dependent manner. YSY01A, a proteasome inhibitor, exerts anticancer effects on PC-3M cells in vitro and in vivo. The mechanism of the YSY01A-mediated antitumor effect is that the cell cycle is arrested at the G2/M stage. This study suggests that YSY01A may be a novel therapeutic agent for prostate cancer.

A series of dual dithiocarbamates were synthesized and evaluated for their in-vitro anticancer activities on human non-small cell lung cancer cell line H460. Nine compounds exhibited significant antiproliferative activities with IC50 less than 1 μM. Among them, compound 14m showed the highest inhibitory activity against H460 cell and inhibited the growth of nine types of tumor cells with IC50 values less than 1 μM. It also achieved IC50 of 54 nM and 23 nM against HepG2 and MCF-7 cell lines, respectively. Preliminary structure-activity relationship study indicated that: a) when the methyl group (region A) is substituted with benzene rings, ortho substitution on the benzene ring is favored for activity; b) substitution with heterocyclic structures at region A exhibited greater impact on the anti-tumor activity of compounds, in which pyridine ring, thiazole ring, coumarin and benzo[b]thiophene are favored and quinoline ring is the most favored; c) substitution with different amines (region B) also showed marked effect on the activity of compounds and dimethylamine and morpholine are preferred to other tested amines., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Applanatumin A (1), a novel meroterpenoid dimer, was isolated from the fungus Ganoderma applanatum. Its structure and absolute configuration were assigned on the basis of spectroscopic and computational data. Notably, 1 possesses a new hexacyclic skeleton containing a spiro[benzofuran-2,1'-cyclopentane] motif. A plausible pathway, involving a key Diels-Alder reaction, is proposed for the biosynthesis of 1. Applanatumin A exhibits potent antifibrotic activity in TGF-β1-induced human renal proximal tubular cells.

Two new abietane diterpene glycosides, wilfordosides A (1) and B (2), were isolated from the roots of Tripterygium wilfordii. The structures of compounds 1 and 2 were established using spectroscopic methods including extensive 1D and 2D NMR analysis, in combination with chemical reactions.

Six Diels-Alder adducts (1-6) and nine prenylated flavanones (7-15) were isolated from the root bark of Morus alba L. Among them, soroceal B (1) and sanggenol Q (7) were new compounds. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques. Compounds 1-3, 9, 10, 12, 13 and 15 exhibited cytotoxic activity against five human tumour lines and compound 2 inhibited significantly selective cytotoxic activities towards HL-60 and AGS cells with IC50 of 3.4 and 3.6 μM. Compounds 3, 5, 9 and 12 exhibited moderate inhibitory activity against nitric oxide production in LPS-activated RAW264.7.

(+)- and (-)-cochlearols A (1) and B (2), two meroterpenoids with novel polycyclic skeletons, were isolated from the fruiting bodies of the fungus Ganoderma cochlear. Their structures and stereochemistry were determined by using spectroscopic, computational and single-crystal X-ray diffraction methods. Cochlearol A is a new normeroterpenoid containing a naturally unusual dioxaspiro[4.5]decane motif. Biological studies showed that (-)-2 is a strong inhibitor of p-Smads, exhibiting renoprotective activities in TGF-β1 induced rat renal proximal tubular cells.

A novel four-component one-pot approach for the synthesis of 2-amino-1,3,4-thiadiazoles from primary amines, carbon disulfide, hydrazine, and acyl chlorides has been developed. A series of 5-substituted-2-amino-1,3,4-thiadiazoles were synthesized in medium-to-good yields utilizing this newly developed method.

Forty-six abietane type diterpenoids possessing nine different fused ring systems were characterized from the roots of Salvia yunnanensis, six of which (salyunnanins A-F, 1-6) had different nor-abietane, homo-abietane, seco-abietane, and normal abietane architectures. Their structures were elucidated by comprehensive NMR and MS spectroscopic analyses. The inhibitory activities of these isolates against six human tumor lines were tested in vitro. Several of the compounds exhibited substantial cytotoxicity with IC50 values of 0.86-10.1μM., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Natural products especially flavonoids are being explored for their therapeutic potentials in reducing bone loss and maintaining bone health. The present study is to investigate the effects of isoquercitrin from Craibiodendron yunnanense with different concentrations at 1 x 10(-4), 1 x 10(-5), 1 x 10(-6), 1 x 10(-7) mol x L(-1) on proliferation, differentiation and mineralization of MC3T3-E1. Cell proliferation was assessed by CCK-8 kit at 1, 3, 5 and 7 days of culture. Alkaline phosphatase (ALP) activity were performed qualitatively and quantitatively on day 7, and alizarin red S staining was employed to access the mineralization of cells on day 21. The osteogenic markers ALP, collagen type I (COL 1A1), runt-related transcription factor 2 (Runx-2) and Osterix were detected to analysis early osteogenic differentiation of cells on day 3 by RT-PCR. The results showed that isoquercitrin had a dose-dependent effect on the proliferation, osteogenic differentiation, mineralization and gene expression of MC3T3-E1 in the range from 1 x 10(-7) to 1 x 10(-5) mol x L(-1). At concentrations above 1 x 10(-4) mol x L(-1) isoquercitrin showed cytotoxicity, while 1 x 10(-6) mol x L(-1) is the optimal concentration of isoquercitrin to improve the osteoblastic activity. All these results implied that isoquercitrin might be the major composition of traditional Chinese medicine C. yunnanense to treat bone fractures.