Apigenin Induces Apoptosis through a Mitochondria/Caspase-Pathway in Human Breast Cancer MDA-MB-453 Cells

In this study, we investigated the mechanistic role of the caspase cascade in extrinsic and intrinsic apoptosis induced by apigenin, which has been targeted as a candidate in the development of noncytotoxic anticancer medicines. Treatment with apigenin (1–100 µM) significantly inhibited the proliferation of MDA-MB-453 human breast cancer cells in a dose- and time-dependent manner with IC50 values of 59.44 and 35.15 µM at 24 and 72 h, respectively. This inhibition resulted in the induction of apoptosis and the release of cytochrome c in cells exposed to apigenin at its 72 h IC50. Subsequently, caspase-9, which acts in mitochondria-mediated apoptosis, was cleaved by apigenin. In addition, apigenin activated caspase-3, which functions downstream of caspase-9. The apigenin-induced activation of caspase-3 was accompanied by the cleavage of capases-6, -7, and -8. These results are supported by evidence showing that the activity patterns of caspases-3, -8, and -9 were similar. The present study supports the hypothesis that apigenin-induced apoptosis involves the activation of both the intrinsic and extrinsic apoptotic pathways

Mesenchymal Stem Cell-Extracellular Vesicle Therapy for Stroke: Scalable Production and Imaging Biomarker Studies

A major clinical hurdle to translate MSC-derived extracellular vesicles (EVs) is the lack of a method to scale-up the production of EVs with customized therapeutic properties. In this study, we tested whether EV production by a scalable 3D-bioprocessing method is feasible and improves neuroplasticity in animal models of stroke using MRI study. MSCs were cultured in a 3D-spheroid using a micro-patterned well. The EVs were isolated with filter and tangential flow filtration and characterized using electron microscopy, nanoparticle tracking analysis, and small RNA sequencing. Compared to conventional 2D culture, the production-reproduction of EVs (the number/size of particles and EV purity) obtained from 3D platform were more consistent among different lots from the same donor and among different donors. Several microRNAs with molecular functions associated with neurogenesis were upregulated in EVs obtained from 3D platform. EVs induced both neurogenesis and neuritogenesis via microRNAs (especially, miR-27a-3p and miR-132-3p)-mediated actions. EV therapy improved functional recovery on behavioral tests and reduced infarct volume on MRI in stroke models. The dose of MSC-EVs of 1/30 cell dose had similar therapeutic effects. In addition, the EV group had better anatomical and functional connectivity on diffusion tensor imaging and resting-state functional MRI in a mouse stroke model. This study shows that clinical-scale MSC-EV therapeutics are feasible, cost-effective, and improve functional recovery following experimental stroke, with a likely contribution from enhanced neurogenesis and neuroplasticity

Stability of wheat germ oil obtained by supercritical carbon dioxide associated with lipase ethanolysis

Wheat germ oil was extracted using an environmental friendly solvent, supercritical carbon dioxide (SCCO2) at a semi-batch flow extraction process. The supercritical carbon dioxide (SC-CO2) extraction was carried out to extract oil at temperature of 40°C and pressure of 25 MPa. Ethanolysis was performed with 1,3-regiospecific lipase at different temperatures (40 to 70°C) to produce diglycerides and monoglycerides containing fatty acid ethyl esters. For determination of stability, wheat germ oil obtained by ethanolysis reactants was characterized by measuring the acid value, peroxide value, free fatty acid contents, thiocyanate method, DPPH radical scavenging effect and rancimat test. The optimized condition of 40°C shows the highest oil stability among the various conditions.Keywords: Supercritical carbon dioxide, wheat germ oil, ethanolysis, immobilized lipases, oil stabilityAfrican Journal of Biotechnology Vol. 12(22), pp. 3570-357

Deficits of case marker processing in persons with mild cognitive impairment

The purpose of the current study was to investigate whether persons with mild cognitive impairment (MCI) showed deficits in processing case markers compared to normal elderly adults (NEA). Results revealed that individuals with MCI presented significantly lower accuracy than the NEA group on a case marker processing (CMP) task. Both groups showed greater difficulties in the passive sentences than sentences with the transitive verbs. The current results suggested that individuals with early stage of dementia started presenting deficits in case marker processing compared to the control group

17β-Estradiol strongly inhibits azoxymethane/dextran sulfate sodium-induced colorectal cancer development in Nrf2 knockout male mice

© 2020 The Author(s)Nuclear factor erythroid 2-related factor 2 (Nrf2) has dual effects on inflammation and cancer progression depending on the microenvironment. Estrogens have a protective effect on colorectal cancer (CRC) development. The aim of this study was to investigate CRC development in Nrf2 knockout (KO) mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO male mice were sacrificed at weeks 2 and 16 after AOM injection with/without 17β-estradiol (E2) treatment during week 1. Disease activity index and colon tissue damage at week 2 showed strong attenuation following E2 administration in WT mice but to a lesser extent in Nrf2 KO male mice. At week 16, E2 significantly diminished AOM/DSS-induced adenoma/cancer incidence at distal colon in the Nrf2 KO group, but not in the WT. Furthermore, mRNA or protein levels of NF-κB-related mediators (i.e., iNOS, TNF-α, and IL-1β) and Nrf2-related antioxidants (i.e., NQO1 and HO-1) were significantly lower in the Nrf2 KO group regardless of E2 treatment compared to the WT. The expression of estrogen receptor beta (ERβ) was higher in the Nrf2 KO group than in the WT. In conclusion, estrogen further inhibits CRC by upregulating ERβ-related alternate pathways in the absence of Nrf2.

Sequential whole cell conversion process for production of D-psicose and D- mannitol from D-fructose

Rare sugars, which exist only limited quantities naturally, have received considerable attention because of its various specific nutritional and biological functions. Likewise, D-psicose (D-ribo-2-hexulose or D-allulose), a C-3 epimer of D-fructose, has many uses which include reducing intra-abdominal fat accumulation, protecting pancreas beta-islets and improving insulin sensitivity. Especially, D-psicose has only 0.3% calories compared to sucrose, while it has 70% relative sweetness. Additionally, in 2012, D-psicose was approved as a food additive and designated as Generally Recognized As Safe (GRAS) by Food and Drug Administration (FDA). Despite such abundant advantages, there is no economical way of mass production of D-psicose. Recently, biological production of D-psicose from D-fructose using D-psicose 3-epimerase (DPE) has been developed. However, the conversion yield is below 30%, which causes an undesirable increase of purification cost because of the similar solubility of D-psicose and D-fructose. Thus, we addressed the problem by converting the residual fructose, after the reaction of D-psicose production, to D-mannitol, which has a low solubility. The sequential whole cell conversion reactions for D-psicose and D-mannitol allow a convenient and economic purification of both products. This work was supported by a grant from the Next-Generation BioGreen 21 Program (SSAC, grant#: PJ01106201), RDA, Korea. Reference 1) Carsten Bäumchen & Stephanie Bringer-Meyer (2007), Expression of glf Z.m. increases D-mannitol formation in whole cell biotransformation with resting cells of Corynebacterium glutamicum, Appl Microbiol Biotechnol 76(3):545–52. 2) Ortiz, M. E., Bleckwedel, J., Raya, R. R., & Mozzi, F. (2013). Biotechnological and in situ food production of polyols by lactic acid bacteria, Appl Microbiol Biotechnol 97:4713-4726 3) Park, Y., Oh, E. J., Jo, J., Jin, Y., & Seo, J. (2016). Recent advances in biological production of sugar alcohols. Curr Opin Biotechnol 37:105–113