A study of the anti-inflammatory effects of the ethyl acetate fraction of the methanol extract of Forsythiae fructus

Background: The dried fruit of Forsythia suspensa (Thunb.) Vahl. (Oleaceae) are better known by their herbal name Forsythiae Fructus, and have a bitter taste, slightly pungent smell, and cold habit. FF has been widely used to treat symptoms associated with the lung, heart, and small intestine. Recently, bioactive compounds isolated from hydrophobic solvent fractions of FF have been reported to have anti-oxidant, anti-bacterial, and anti-cancer effects. Traditionally, almost all herbal medicines are water extracts, and thus, extraction methods should be developed to optimize the practical efficacies of herbal medicines.Materials and Methods: In this study, the anti-inflammatory effects of the ethyl acetate fraction of the methanol extract of FF (FFE) were assessed by measuring NO and PGE2 production by and intracellular ROS and protein levels of iNOS and COX-2 in RAW 264.7 cells.Results: FFE inhibited COX-2 expression in LPS-stimulated RAW 264.7 cells.Conclusion: In summary, FFE effectively reduced intracellular ROS and NO levels and inhibited PGE2 production by downregulating COX-2 levels.Keywords: Forsythiae Fructus, herb, inflammation, efficacy

A STUDY OF THE ANTI-INFLAMMATORY EFFECTS OF THE ETHYL ACETATE FRACTION OF THE METHANOL EXTRACT OF FORSYTHIAE FRUCTUS

Background: The dried fruit of Forsythia suspensa (Thunb.) Vahl. (Oleaceae) are better known by their herbal name Forsythiae Fructus, and have a bitter taste, slightly pungent smell, and cold habit. FF has been widely used to treat symptoms associated with the lung, heart, and small intestine. Recently, bioactive compounds isolated from hydrophobic solvent fractions of FF have been reported to have anti-oxidant, anti-bacterial, and anti-cancer effects. Traditionally, almost all herbal medicines are water extracts, and thus, extraction methods should be developed to optimize the practical efficacies of herbal medicines. Materials and Methods: In this study, the anti-inflammatory effects of the ethyl acetate fraction of the methanol extract of FF (FFE) were assessed by measuring NO and PGE2 production byand intracellular ROS and protein levels of iNOS and COX-2in RAW 264.7 cells. Results: FFE inhibited COX-2 expression in LPS-stimulated RAW 264.7 cells. Conclusion: In summary, FFE effectively reduced intracellular ROS and NO levels and inhibited PGE2 production by down- regulating COX-2 levels

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen’s efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE’s that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM

Nanoscale mapping of noise-source-controlled hopping and tunneling conduction in domains of reduced graphene oxide

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Urinary bisphenol A versus serum bisphenol A concentration and ovarian reproductive outcomes among IVF patients: Which is a better biomarker of BPA exposure?

© 2017, The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media B.V., part of Springer Nature. Bisphenol A (BPA) is an endocrine-disrupting compound (EDC) that is used widely in commercial products in the production of polycarbonate plastics for baby and water bottles, epoxy resins for lacquer lining of food and beverage cans and water pipes, dental sealants, dental composites and thermal receipts paper. There is inhibitory effect of BPA on nuclear estrogen (E2) production in granulosa cells of developing follicles that disrupt normal development to the antral follicles via suppression of E2 in granulosa cells of developing follicles during the menstrual cycle followed by reduction in the number of oocytes retrieved in in-vitro fertilization (IVF) patients. Several studies corroborate an inverse association between serum and/or urinary BPA concentration and the IVF outcome: Peak E2 levels and the number of oocytes retrieved. Upon oral ingestion, 99.5% of unconjugated parent BPA (free BPA) is metabolized to either BPA glucuronide (BPA-G) or BPA sulfate (BPA-S). The unconjugated BPA can bind to the estrogen receptors (ER) while conjugated BPA (biologically inactive BPA) do not bind the estrogen receptor (ER). The challenge is to assess the relationship between BPA exposure among infertile patients with respect to follicular response and health during IVF. The establishment of temporal sequence between BPA exposure and infertility would be the research question to answer: Which route is a better biomarker? The advantages of urine BPA collection would provide pragmatic advantages for clinicians in order to practice cost-effective medicine. However, unconjugated BPA measurement (compared to total BPA) introduces challenges in measurement accuracy since unconjugated BPA requires higher magnitude of limit of detection (LOD) with higher risk of contamination from the medical equipment. The difference in route of BPA assessment could introduce bias in the interpretation of results in terms of the association between BPA levels and the number of oocytes. Fujimoto et al. and Bloom et al. analyzed the relationship between serum BPA and IVF outcome in infertile women. It may sound hypothetically justified due to utilizing serum unconjugated BPA, this strategy is not successful in choosing a practical biomarker of BPA exposure due to toxicokinetic properties of BPA metabolism and excretion in humans

Nanoscale Mapping of Molecular Vibrational Modes via Vibrational Noise Spectroscopy

We have developed a “vibrational noise spectroscopy (VNS)” method to identify and map vibrational modes of molecular wires on a solid substrate. In the method, electrical-noises generated in molecules on a conducting substrate were measured using a conducting atomic force microscopy (AFM) with a nanoresolution. We found that the bias voltage applied to the conducting AFM probe can stimulate specific vibrational modes of measured molecules, resulting in enhanced electrical noises. Thus, by analyzing noise-voltage spectra, we could identify various vibrational modes of the molecular wires on the substrates. Further, we could image the distribution of vibrational modes on molecule patterns on the substrates. In addition, we found that VNS imaging data could be further analyzed to quantitatively estimate the density of a specific vibrational mode in the layers of different molecular species. The VNS method allows one to measure molecular vibrational modes under ambient conditions with a nanoresolution, and thus it can be a powerful tool for nanoscale electronics and materials researches in general

Prescription Drug Price Paradox: Cost Analysis of Canadian Online Pharmacies versus US Medicare Beneficiaries for the Top 100 Drugs

© 2017, Springer International Publishing AG. Background and objectives: Despite the introduction of Medicare Part D (MPD) and 2012 Affordable Care Act (ACA), patients have a cost burden due to increases in drug prices. To overcome cost barriers, some patients purchase their medications from Canadian online pharmacies as Canadian prescription drug prices are believed to be lower than US prescription drug prices. The objective of this study was to determine which top 100 Medicare drugs can be imported to the USA legally, and to determine which type of prescription drug would be more beneficial to be purchased from Canadian online pharmacies. Moreover, we also deemed it important to compare MPD beneficiary annual expenses with expenses patients would have when obtaining their prescriptions from Canadian online pharmacies. Methods: We conducted a cost analysis from a patient perspective. A list of the top 100 Medicare drugs was compiled and information on drug prices was collected from three Canadian online pharmacies and four MPD plans in Virginia. The annual cost of each Medicare drug and percent change between Canadian online pharmacies and MPD were compared. Results: A total of 78 drugs from the top 100 Medicare drugs were included in the final analysis. Seventy-six prescription drugs (97.4%) that could be purchased from Canadian online pharmacies showed a significantly lower average drug price percent change of −72.71% (P \u3c 0.0001). The heart health/blood pressure subgroup had the highest number of drugs that could be purchased from Canadian online pharmacies. Conclusion: The majority of prescription drugs can be purchased at lower prices from Canadian online pharmacies when compared to Medicare beneficiaries’ potential expenses. Purchasing medications from Canadian online pharmacies may be a viable option to address cost barriers

Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3

3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC50 value of 8a, (R)-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3

Discovery of a Potent and Selective JNK3 Inhibitor with Neuroprotective Effect Against Amyloid β-Induced Neurotoxicity in Primary Rat Neurons

As members of the MAPK family, c-Jun-N-terminal kinases (JNKs) regulate the biological processes of apoptosis. In particular, the isoform JNK3 is expressed explicitly in the brain at high levels and is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In this study, we prepared a series of five 6-dihydroxy-1H-benzo[d]imidazoles as JNK3 inhibitors and found them have potential as neuroprotective agents. Following a previous lead scaffold, benzimidazole moiety was modified with various aryl groups and hydroxylation, and the resulting compounds exhibited JNK3 inhibitory activity with improved potency and selectivity. Out of 37 analogues synthesized, (S)-cyclopropyl(3-((4-(2-(2,3-dihydrobenzo[b][1,4]dioxin -6-yl)-5,6-dihydroxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino) piperidin-1-yl)methanone (35b) demonstrated the highest JNK3 inhibition (IC50 = 9.7 nM), as well as neuroprotective effects against Aβ-induced neuronal cell death. As a protein kinase inhibitor, it also showed excellent selectivity over other protein kinases including isoforms JNK1 (>1000 fold) and JNK2 (−10 fold)