Dimeric diarylheptanoids with anti-inflammatory activity from Zingiber officinale.

Two previously undescribed chain diarylheptanoid derivatives (2-3), five previously undescribed dimeric diarylheptanoids (4-8), together with one known cyclic diarylheptanoid (1) were isolated from Zingiber officinale. Their structures were elucidated by extensive spectroscopic analyses (HR-ESI-MS, IR, UV, 1D and 2D NMR) and ECD calculations. Biological evaluation of compounds 1-8 revealed that compounds 2, 3 and 4 could inhibit nitrite oxide and IL-6 production in lipopolysaccharide induced RAW264.

Correction: Non-peptide compounds from (Verhoeff) and their antitumor and iNOS inhibitory activities.

[This corrects the article DOI: 10.3762/bjoc.19.

Unusual acetylated flavonol glucuronides, oxyphyllvonides A-H with renoprotective activities from the fruits of Alpinae oxyphylla.

As a widely consumed spice and Traditional Chinese Medicine, Alpinae oxyphylla has been used to treat conditions such as diarrhea, ulcers, dementia, and enuresis. Fruits of A. oxyphylla were phytochemically studied and the bioactive constituents against renal fibrosis were identified.

Succipenoids A-C: A dimeric abietane and nor-abietane diterpenoids from fossil Chinese medicinal succinum and their anti-inflammatory potential.

An unprecedented dimeric abietane, succipenoid A (1), and two previously undescribed nor-abietane diterpenoids featuring a rarely occurring naphthalene ring or with a large conjugated system, succipenoids B and C (2 and 3), along with seven known diterpenoids (4-10) were isolated from the CHCl extract of succinum. The structures of these compounds, including their absolute configurations, were elucidated using spectroscopic and computational techniques. Notably, compounds 1-4 and 6-10 were isolated from succinum for the first time.

Nine pairs of undescribed enantiomers from the resin of Styrax tonkinensis (Pierre) Craib ex Hart with anti-inflammatory activity.

Nine pairs of undescribed enantiomers, (±)-styraxoids A-I (1-9), were isolated from the resin of Styrax tonkinensis, and their structures were assigned by spectroscopic and computational methods. Compounds (±)-1 are a pair of degraded lignans, and the remaining compounds (±)-(2-9) are phenylpropanoid skeletons. Compounds (±)-8 and (±)-9 feature a 1,3-dioxolane moiety.

Loss of ANCO1 Expression Regulates Chromatin Accessibility and Drives Progression of Early-Stage Triple-Negative Breast Cancer.

Mutations in the gene ankyrin repeat domain containing 11 (/) play a role in neurodegenerative disorders, and its loss of heterozygosity and low expression are seen in some cancers. Here, we show that low ANCO1 mRNA and protein expression levels are prognostic markers for poor clinical outcomes in breast cancer and that loss of nuclear ANCO1 protein expression predicts lower overall survival of patients with triple-negative breast cancer (TNBC). Knockdown of ANCO1 in early-stage TNBC cells led to aneuploidy, cellular senescence, and enhanced invasion in a 3D matrix.

Five new sesquiterpenoids from agarwood of .

Five new eudesmane-type sesquiterpenoids (aquisinenoids F-J (-)) and five known compounds (-) were isolated from the agarwood of . Their structures, including absolute configurations, were identified by comprehensive spectroscopic analyses and computational methods. Inspired by our previous study on the same kinds of skeletons, we speculated that the new compounds have anticancer and anti-inflammatory activities.

Non-peptide compounds from (Verhoeff) and their antitumor and iNOS inhibitory activities.

Six new compounds, including a tetralone , two xanthones and , a flavan derivative , and two nor-diterpenoids and , accompanied by two known flavan derivatives and and a known olefine acid () were isolated from whole bodies of (Verhoeff). The structures of the new compounds were determined by 1D and 2D nuclear magnetic resonance (NMR) and other spectroscopic methods, as well as computational methods. Selected compounds were evaluated for their biological properties against a mouse pancreatic cancer cell line and inhibitory effects on iNOS and COX-2 in RAW264.

Eight new 2-(2-phenylethyl)chromone derivatives from agarwood of Aquilaria sinensis with anti-inflammatory activity.

Eight previously unknown 2-(2-phenylethyl)chromone derivatives, called aquichromones A - E (1-3, 5 and 6) and 8-epi-aquichromone C (4), including two pairs of enantiomers [(±)-1 and (±)-2] were isolated from the agarwood of Aquilaria sinensis. The structures and absolute stereochemistry of these natural products were elucidated by using spectroscopic and computational methods. The result of biological assay showed that two members of this group, 4 and 5, have significant dose-dependent anti-inflammatory activity.

Six new diterpenoids from the resins of Populus euphratica and their anti-inflammatory activities.

Six new diterpenoids, identified as two abietane derivatives, euphraticanoids J and K (1 and 2), two pimarane derivatives, euphraticanoids L and M (3 and 4), and two 9,10-seco-abietane derivatives, euphraticanoids N and O (5 and 6) were isolated from Populus euphratica resins. Their structures including absolute configurations were characterized using spectroscopic, quantum chemical NMR, and ECD calculation methods. The anti-inflammatory activity of the compounds was tested and the results revealed that compounds 4 and 6 inhibited the production of iNOS and COX-2 in a dose-dependent manner in lipopolysaccharide (LPS)-induced RAW 264.

Does Chronic Use of High Dose Proton Pump Inhibitors Increase Risk for Pancreatic Cancer?

Objectives: To analyze whether use of proton pump inhibitors increase the risk for pancreatic cancer in a mouse model and human clinical cohorts.

Methods: p48-Cre/LSL-KrasG12D mice that develop precancerous pancreatic intraepithelial neoplasia (PanINs) were treated with low- or high-dose proton pump inhibitors (PPIs) orally for 1 and 4 months. The mechanism for the cholecystokinin receptor 2 (CCK-2R) activation was investigated in vitro.

Design and modeling for drug combination experiments with order effects.

Combinations of drugs are now ubiquitous in treating complex diseases such as cancer and HIV due to their potential for enhanced efficacy and reduced side effects. The traditional combination experiments of drugs focus primarily on the dose effects of the constituent drugs. However, with the doses of drugs remaining unchanged, different sequences of drug administration may also affect the efficacy endpoint.

Integrative analysis with a system of semiparametric projection non-linear regression models.

In integrative analysis parametric or nonparametric methods are often used. The former is easier for interpretation but not robust, while the latter is robust but not easy to interpret the relationships among the different types of variables. To combine the advantages of both methods and for flexibility, here a system of semiparametric projection non-linear regression models is proposed for the integrative analysis, to model the innate coordinate structure of these different types of data, and a diagnostic tool is constructed to classify new subjects to the case or control group.

External validation of a panel of plasma microRNA biomarkers for lung cancer.

We externally validate plasma miRNAs biomarkers for lung cancer in a large and retrospective sample set collected from a geographically distant population. Plasma samples are tested blindly to the clinical annotations by using PCR for quantitation of the four miRNAs in cohort 1 consisting of 232 lung cancer cases and 243 controls and cohort 2 comprising 239 cases and 246 controls. Combined use of the four plasma miRNAs has 91% sensitivity and 95% specificity for diagnosis of lung cancer, and 85% sensitivity for early-stage lung cancer, while maintaining a specificity of 95%.

Linear mixed models for association analysis of quantitative traits with next-generation sequencing data.

We develop linear mixed models (LMMs) and functional linear mixed models (FLMMs) for gene-based tests of association between a quantitative trait and genetic variants on pedigrees. The effects of a major gene are modeled as a fixed effect, the contributions of polygenes are modeled as a random effect, and the correlations of pedigree members are modeled via inbreeding/kinship coefficients. -statistics and χ likelihood ratio test (LRT) statistics based on the LMMs and FLMMs are constructed to test for association.

Prevention of Lipid Peroxidation-derived Cyclic DNA Adduct and Mutation in High-Fat Diet-induced Hepatocarcinogenesis by Theaphenon E.

Obesity is associated with cancer risk and its link with liver cancer is particularly strong. Obesity causes non-alcoholic fatty liver disease (NAFLD) that could progress to hepatocellular carcinoma (HCC). Chronic inflammation likely plays a key role.

An epigenetic classifier for early stage lung cancer.

Background: Methylated genes detected in sputum are promise biomarkers for lung cancer. Yet the current PCR technologies for quantification of DNA methylation and diagnostic value of the sputum biomarkers are not sufficient to be used for lung cancer early detection. The emerging droplet digital PCR (ddPCR) is a straightforward means for precise, direct, and absolute quantification of nucleic acids.

Integrating Circulating Immunological and Sputum Biomarkers for the Early Detection of Lung Cancer.

We have demonstrated that assessments of microRNA (miRNA) expressions in circulating peripheral blood mononucleated cell (PBMC) and sputum specimens, respectively, may help diagnose lung cancer. To assess the individual and combined analysis of the miRNAs across the different body fluids for lung cancer early detection, we analyse a panel of 3 sputum miRNAs (miRs-21, 31, and 210) and a panel of 2 PBMC miRNAs (miRs-19b-3p and 29b-3p) in a discovery cohort of 68 patients with lung cancer and 66 cancer-free smokers. We find that integrating 2 sputum miRNAs (miRs-31 and 210) and 1 PBMC miRNA (miR-19b-3p) has higher sensitivity (86.

A plasma miRNA signature for lung cancer early detection.

The early detection of lung cancer continues to be a major clinical challenge. Using whole-transcriptome next-generation sequencing to analyze lung tumor and the matched noncancerous tissues, we previously identified 54 lung cancer-associated microRNAs (miRNAs). The objective of this study was to investigate whether the miRNAs could be used as plasma biomarkers for lung cancer.

Experimental design for multi-drug combination studies using signaling networks.

Combinations of multiple drugs are an important approach to maximize the chance for therapeutic success by inhibiting multiple pathways/targets. Analytic methods for studying drug combinations have received increasing attention because major advances in biomedical research have made available large number of potential agents for testing. The preclinical experiment on multi-drug combinations plays a key role in (especially cancer) drug development because of the complex nature of the disease, the need to reduce development time and costs.

A prediction model for distinguishing lung squamous cell carcinoma from adenocarcinoma.

Accurate classification of squamous cell carcinoma (SCC) from adenocarcinoma (AC) of non-small cell lung cancer (NSCLC) can lead to personalized treatments of lung cancer. We aimed to develop a miRNA-based prediction model for differentiating SCC from AC in surgical resected tissues and bronchoalveolar lavage (BAL) samples. Expression levels of seven histological subtype-associated miRNAs were determined in 128 snap-frozen surgical lung tumor specimens by using reverse transcription-polymerase chain reaction (RT-PCR) to develop an optimal panel of miRNAs for acutely distinguishing SCC from AC.

A classifier integrating plasma biomarkers and radiological characteristics for distinguishing malignant from benign pulmonary nodules.

Lung cancer is primarily caused by cigarette smoking and the leading cancer killer in the USA and across the world. Early detection of lung cancer by low-dose CT (LDCT) can reduce the mortality. However, LDCT dramatically increases the number of indeterminate pulmonary nodules (PNs), leading to overdiagnosis.

The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory NRASQ61K melanoma.

Structure-based drug repositioning in addition to random chemical screening is now a viable route to rapid drug development. Proteochemometric computational methods coupled with kinase assays showed that mebendazole (MBZ) binds and inhibits kinases important in cancer, especially both BRAFWT and BRAFV600E. We find that MBZ synergizes with the MEK inhibitor trametinib to inhibit growth of BRAFWT-NRASQ61K melanoma cells in culture and in xenografts, and markedly decreased MEK and ERK phosphorylation.

A Prediction Model Based on Biomarkers and Clinical Characteristics for Detection of Lung Cancer in Pulmonary Nodules.

Lung cancer early detection by low-dose computed tomography (LDCT) can reduce the mortality. However, LDCT increases the number of indeterminate pulmonary nodules (PNs), whereas 95% of the PNs are ultimately false positives. Modalities for specifically distinguishing between malignant and benign PNs are urgently needed.