Anticancer and Anti-metastatic Effects of Supercritical Extracts of Hops (Humulus lupulus L.) and Mango ginger (Curcuma amada Roxb.) in Human Glioblastoma

Glioblastoma is one of the most aggressive, lethal and incurable primary brain tumors with a dismal prognosis in humans. Mango ginger (Curcuma amada) and hops (Humulus lupulus) are two botanicals containing phytochemicals with potential anticancer effects. We have investigated the anticancer and antimetastatic properties of supercritical CO2 extract of mango ginger (CA) and ethanol extract of hops (HL) in the U-87MG human glioblastoma cell line. Both CA and HL individually demonstrate strong cytotoxicity against glioblastoma cells. CompuSyn analysis of cytotoxicity data confirms that CA and HL are synergistic for cytotoxicity with combination index (CI) values of <1.0. Additionally, CA and HL individually as well as the combination significantly inhibit MMP-2 and MMP-9 activity, tumor cell migration (transendothelial cell migration assay) and AKT phosphorylation in U-87MG cells. CA and HL inhibit glycolysis in U-87MG cells as indicated by the inhibition of ATP and lactate synthesis with the CA+HL combination demonstrating strong inhibition of glycolysis via the reduction of ATP and lactate synthesis compared to cells treated by each extract alone. CA and HL treatment down regulates the expression of proteins associated with metastasis, MMP-2 and MMP-9 and up regulates the expression of TIMP1. Proteins associated with apoptosis, inflammation and energy metabolism were also modulated by CA and HL treatment of glioblastoma cells. These results suggest that CA and HL can be combined for the therapeutic management of glioblastomas

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Effect of a Proprietary Commiphora mukul Gum Resin Extract and Medium-Chain Triglyceride Preparation (GU-MCT810) on hypoxia-inducible factor-1 pathway in HepG2 cell line

The heterodimeric transcription factor HIF-1 is responsible for the regulation of genes that facilitate adaptation and survival of cells under hypoxic conditions. HIF-1 gene expression is also associated with angiogenesis, glucose transport, nitric oxide synthase activity and cell proliferation through the regulation of hundreds of genes associated with HIF-1 pathway. GU-MCT810 is a nutraceutical ingredient complex that includes a Commiphora mukul (guggul) extract prepared by a supercritical CO2-co-solvent extraction with ethanol and medium chain triglyceride (MCT) oil composed of C8 and C10 fatty acids. Since cancer cells use glycolytic pathway, 2-deoxyglucose (2-DG) has been reported to inhibit the glycolysis. We have investigated the anticancer potential of GU-MCT810 with and without 2-DG in HepG2 human hepatoma cell line. Even though GU-MCT810 and 2-DG are individually weakly cytotoxic, the combination is synergistic with combination index (CI) values of 0.21, 0.22 and 0.88 at IC50, IC75 and IC90 levels, respectively. The combination also showed a synergistic inhibitory effect on ATP-synthesis in HepG2 cells. GU-MCT810 inhibits CoCl2-induced HIF-1α expression significantly in a dose-dependent manner with complete inhibition at 50 µg/ml concentration. GU-MCT810 upregulates Bax and p21 genes and down regulates Bcl-2, BNIP3 and mutant p53 genes associated with apoptosis. It also down regulates proteins associated angiogenesis (VEGF, VEGF-R), cell proliferation (IGF-2), glucose transport (GLUT1) and adaptogenesis (HSP70 and HSP90). These results indicate that GU-MCT810 can be combined with 2-DG for inhibition of HIF-1 pathway genes which would be useful for elimination of refractory cancer cells present in the hypoxic region of human tumors

Hop Extract Acts as an Antioxidant with Antimicrobial Effects against Propionibacterium Acnes and Staphylococcus Aureus

Acne is associated with hyperkeratosis, elevated levels of skin sebum and growth of Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). Furthermore, P. acnes promotes inflammation by inducing IL-6 production and oxidative stress. The aim of this study was to assess the antioxidant, anti-inflammatory and antibacterial potential of a hop-CO2-extract with 50% humulone and lupulone. The susceptibility of P. acnes and S. aureus to the hop extract was tested by using the broth microdilution technique. The minimal inhibitory concentrations (MIC) for P. acnes and S. aureus were 3.1 and 9.4 µg/mL, respectively. In addition, the hop extract showed an antioxidative effect with a half maximal inhibitory concentration (IC50) of 29.43 µg/mL as well as additional anti-inflammatory effects by reducing the IL-6 expression (IC50: 0.8 µg/mL). In addition, a gel formulation with 0.3% hop extract (w/w) had antibacterial activity against P. acnes and S. aureus (inhibition zone value: 5.5 mm and 3 mm, respectively) which was significantly superior to the placebo gel. The positive control (a gel with the antibiotic clindamycin) showed an inhibition zone of 9 mm. Due to its antioxidant, anti-inflammatory and antibacterial effects hop extract might be a treatment option for acne-prone skin

Very high energy gamma-ray observation of the peculiar transient event Swift J1644+57 with the MAGIC telescopes and AGILE

Context. On March 28, 2011, the BAT instrument on board the Swift satellite detected a new transient event that in the very beginning was classified as a gamma ray burst (GRB). However, the unusual X-ray flaring activity observed from a few hours up to days after the onset of the event made a different nature seem to be more likely. The long-lasting activity in the X-ray band, followed by a delayed brightening of the source in infrared and radio activity, suggested that it is better interpreted as a tidal disruption event that triggered a dormant black hole in the nucleus of the host galaxy and generated an outflowing jet of relativistic matter. Aims. Detecting a very high energy emission component from such a peculiar object would be enable us to constrain the dynamic of the emission processes and the jet model by providing information on the Doppler factor of the relativistic ejecta. Methods. The MAGIC telescopes observed the peculiar source Swift J1644+57 during the flaring phase, searching for gamma-ray emission at very-high energy (VHE, E > 100 GeV), starting observations nearly 2.5 days after the trigger time. MAGIC collected a total of 28 h of data during 12 nights. The source was observed in wobble mode during dark time at a mean zenith angle of 35 degrees. Data were reduced using a new image-cleaning algorithm, the so-called sum-cleaning, which guarantees a better noise suppression and a lower energy threshold than the standard analysis procedure. Results. No clear evidence for emission above the energy threshold of 100 GeV was found. MAGIC observations permit one to constrain the emission from the source down to 100 GeV, which favors models that explain the observed lower energy variable emission. Data analysis of simultaneous observations from AGILE, Fermi and VERITAS also provide negative detection, which additionally constrain the self-Compton emission component

Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells

Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic “universal” cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products. In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing