Isolation of Stilbenoids and Lignans from Dendrobium hongdie

Purpose: To isolate and characterize chemical compounds of biological importance from the whole plant of Dendrobium hongdie.Methods: The whole plants of Dendrobium hongdie was extracted with ethanol (EtOH) and separated using silica gel, Sephadex LH-20 and MCI gel to isolate the pure compounds. Characterization of the isolated compounds was achieved using 1H and 13C nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS).Results: Nine compounds including two phenanthrenes, three bibenzyls, a phenanthraquinone, two lignans and a sterol were isolated from the extract. The structures of the compounds were elucidated as nudol (1), gigantol (2), batatasin III (3), tristin (4), moscatin (5), ephemeranthoquinone (6), (-)- syringaresinol (7), liriodendrin (8) and β-sitosterol (9).Conclusion: Nine compounds have been successfully isolated from D. hongdie for the first time. This plant is a potential source of some useful phytochemicals.Keywords: Dendrobium hongdie, Isolation, Stilbenoids, Lignans, Phytochemical

Trends, correlates and patterns of concurrent substance use of prescription stimulants in the United States

Objective: The purpose of this study is to fill the knowledge gap regarding nonmedical prescription stimulant use. The study has three aims: 1) to explore the temporal trends of prescriptions, nonmedical use, and Emergency Department (ED) visits for specific prescription stimulants; 2) to investigate the source of the misused stimulants and whether different sources correspond to different risk profiles; and 3) to identify subgroups among nonmedical prescription stimulant users by their concurrent problematic substance use in different age groups. Method: National surveys across 2006 to 2011 were used in all three aims. Aim 1 used National Disease and Therapeutic Index (NDTI), National Survey on Drug Use and Health (NSDUH), and Drug Abuse Warning Network (DAWN) and ordinary linear square regression to assess the temporal trends in frequency of prescription, nonmedical use and ED visits involving Adderall and methylphenidate. Aim 2 used logistic regression models to compare the socio-demographic, mental health and behavioral problems and stimulant use-related problems according to source of nonmedically used stimulants using the NSDUH data. Aim 3 used latent class analysis to examine patterns of past-year problematic substance use in participants reporting past-year nonmedical prescription stimulant use in adult and adolescent participants in the NSDUH. Results: Analyses for Aim 1 revealed that temporal trends in treatment visits involving stimulants do not correspond to trends in nonmedical use and ED visits. Prescription visits for Adderall did not change over time, while nonmedical use and ED visits grew dramatically among adults. The major source of misused stimulants was a physician for both Adderall and methylphenidates. Aim 2 showed that sources of misused stimulants were associated with onset, recency and severity of stimulant use, with illegal and physician sources both associated with earlier onset, greater odds of recent use and meeting the diagnostic criteria for stimulant use disorder. Aim 3 identified a four-class model in both adults and adolescents including a Low substance class, a Prescription drug class, an Alcohol/Marijuana class, and a Multiple substance class. Individuals in the three classes other than the Low substance class were more likely to report psychological and social outcomes. Conclusions: The findings highlight the need to target drug diversion as a preventive strategy and a more nuanced preventive and treatment program that takes into account differences in risk profiles and needs of subgroups of nonmedical users of stimulants

CaSR Induces Osteoclast Differentiation and Promotes Bone Metastasis in Lung Adenocarcinoma

Objective: Explore the mechanism of CaSR's involvement in bone metastasis in lung adenocarcinoma. Methods: Immunohistochemistry (IHC) was used to detect the expression of calcium-sensing receptor (CaSR) in 120 cases of lung adenocarcinoma with bone metastasis. Stably transfected cell lines with CaSR overexpression and knockdown based on A549 cells were constructed. The expression of CaSR was verified by western blot and qPCR. The proliferation and migration abilities of A549 cells were tested using cholecystokinin-8 (CCK-8) and Transwell assays, respectively. Western blotting was used to detect the expression of matrix metalloproteinases MMP2, MMP9, CaSR, and NF-κB. The supernatant from each cell culture group was collected as a conditional co-culture solution to study the induction of osteoclast precursor cells and osteoblasts. Western blot and qPCR were used to validate the expression of bone matrix degradation-related enzymes cathepsin K and hormone calcitonin receptor (CTR) and osteoblast-induced osteoclast maturation and differentiation enzyme receptor activator of nuclear factor-κB ligand (RANKL), macrophage colony-stimulating factor (M-CSF), osteoprotegerin (OPG), and PTHrP. Immunofluorescent staining was used to detect F-actin ring formation and osteocalcin expression. Western blot results for NF-κB expression identified a regulatory relationship between NF-κB and CaSR. Results: CaSR expression in lung cancer tissues was significantly higher than that in adjacent and normal lung tissues. The expression of CaSR in lung cancer tissues with bone metastasis was higher than that in non-metastatic lung cancer tissues. The proliferation and migration ability of A549 cells increased significantly with overexpressed CaSR. The co-culture solution directly induced osteoclast precursor cells and the expression of bone matrix degradation-related enzymes significantly increased. Osteoblasts were significantly inhibited and osteoblast-induced osteoclast maturation and differentiation enzymes were significantly downregulated. It was found that the expression of NF-κB and PTHrP increased when CaSR was overexpressed. Osteoclast differentiation factor expression was also significantly increased, which directly induces osteoclast differentiation and maturation. These results were reversed when CaSR was knocked down. Conclusions: CaSR can positively regulate NF-κB and PTHrP expression in A549 cells with a high metastatic potential, thereby promoting osteoclast differentiation and maturation, and facilitating the occurrence and development of bone metastasis in lung adenocarcinoma

Menthyl 2-oxo-2H-chromene-3-carboxyl­ate

The title compound, C20H24O4, was synthesized from the reaction of 2-oxo-2H-chromene-3-acyl chloride and menthol. The mean plane of the ester group and that of the four essentially planar (maximum deviation 0.0112 Å) C atoms of the chair-form cyclo­hexyl ring form dihedral angles of 43.8 (3) ° and 81.8 (1)°, respectively, with the mean plane of the coumarin ring system. In the crystal structure, weak inter­molecular C—H⋯O hydrogen bonds connect the mol­ecules into a two-dimensional network

Tumor Microenvironment Varies under Different TCM ZHENG Models and Correlates with Treatment Response to Herbal Medicine

In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer