Evaluating the effect of lactic acid bacterial fermentation on salted soy whey for development of a potential novel soy sauce-like condiment.

There were two main objectives of this study: (1) to understand the effect of salt concentration on the growth of four lactic acid bacteria (LAB) in soy whey and determine the non-volatile and volatile profiles generated after fermentation; (2) to evaluate the potential of using salted soy whey to develop a sauce-like condiment through LAB fermentation. The four LAB included non-halophilic Lactiplantibacillus plantarum ML Prime, Limosilactobacillus fermentum PCC, Oenococcus oeni Enoferm Beta and halophilic Tetragenococcus halophilus DSM20337. At 2% salt, all LAB grew remarkably from day 0 to day 1, except for T. halophilus, while at 6% salt, the growth of L. plantarum, L. fermentum and O. oeni was suppressed. Conversely, the higher salt concentration enhanced the growth of T. halophilus in soy whey as the cell count only increased from 6.36 to 6.60 log CFU/mL at 2% salt but it elevated from 6.61 to 7.55 log CFU/mL at 6% salt. Similarly, the higher salt content negatively affected the sugar and amino acids metabolism and organic acids production by non-halophilic LAB. L. plantarum and O. oeni generated significantly (p < 0.05) more lactic acid (3.83 g/L and 4.17 g/L, respectively) than L. fermentum and T. halophilus (2.02 g/L and 0 g/L, respectively) at 2% salt. In contrast, a higher amount of acetic acid was generated by L. fermentum (0.72 g/L at 2% salt) and T. halophilus (0.51 g/L at 6% salt). LAB could remove the green and beany off-flavours in soy whey by metabolizing C6 and C7 aldehydes. However, to develop a novel soy sauce-like condiment, yeast fermentation and Maillard reaction may be required to generate more characteristic soy sauce-associated aroma compounds.

Exploring the feasibility of biotransforming salted soy whey into a soy sauce-like condiment using wine yeast Torulaspora delbrueckii and soy sauce yeasts Zygosaccharomyces rouxii and Candida versatilis as single starter cultures.

Salted soy whey, a liquid by-product from salted tofu processing, is a source of valuable nutrients. However, it is often under-utilized due to its high salt content. The objective of this study was to investigate the feasibility of using different species of yeast to transform salted soy whey into a soy sauce-like condiment. Three yeasts were used for salted soy whey biotransformation: Zygosaccharomyces rouxii NCYC 1682, Candida versatilis NCYC 1433, and Torulaspora delbrueckii Biodiva. This study focused on the growth of the yeasts in soy whey added with different levels of NaCl and the physicochemical changes of salted soy whey after fermentation. The soy sauce yeasts (Z. rouxii and C. versatilis) grew by approximately 2 log CFU/mL in soy whey with 2% and 10% salt while the cell count of wine yeast T. delbrueckii increased by around 1.5 log CFU/mL at 10% salt and 1.78 log CFU/mL at 2% salt after 14 days of fermentation. Candida versatilis grew better at 10% salt with less glucose consumption (consumed 68.49% at 10% versus 94.05% at 2% salt) than at 2% salt. It was also found that all three yeasts converted isoflavone glycosides (bound isoflavones) into aglycones (free isoflavones), the latter having better bioavailability. C. versatilis showed the greatest ability to transform isoflavone glycosides in salted soy whey into higher amounts of aglycones (conversion efficiency of 23.04% at 2% salt and 15.05% at 10% salt). Salted soy whey fermented with different yeasts had different volatile profiles. Soy sauce yeasts produced more isobutyl alcohol, isoamyl alcohol and volatile phenols while T. delbrueckii generated a substantial amount of ethanol and esters. This study revealed the growth and flavour modulating potential of yeasts in salted soy whey fermentation, which provides a possible avenue to develop a soy sauce-like condiment using salted soy whey as a substrate.

Imaging of vitreous cortex hyalocyte dynamics using non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy in human subjects.

Vitreous cortex hyalocytes are resident macrophage cells that help maintain the transparency of the media, provide immunosurveillance, and respond to tissue injury and inflammation. In this study, we demonstrate the use of non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy (AOSLO) to non-invasively visualize the movement and morphological changes of the hyalocyte cell bodies and processes over 1-2 hour periods in the living human eye. The average velocity of the cells 0.52 ± 0.76 µm/min when sampled every 5 minutes and 0.23 ± 0.29 µm/min when sampled every 30 minutes, suggesting that the hyalocytes move in quick bursts. Understanding the behavior of these cells under normal physiological conditions may lead to their use as biomarkers or suitable targets for therapy in eye diseases such as diabetic retinopathy, preretinal fibrosis and glaucoma.

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine.

Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and Drug Administration (FDA) after multiple studies showed that it was well-tolerated, safe, and effective in the treatment of migraines. Further research is needed to elucidate the long-term effects of fremanezumab and CGRP-antagonists in general, and additional data is required in less healthy patients to estimate its effects in these populations and potentially increase the eligible group of recipients. This is a comprehensive review of the current literature on the efficacy and safety of fremanezumab for the treatment of chronic migraine. In this review we provide an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarize the evidence for fremanezumab as a treatment for migraine.

Development of a minimal physiologically-based pharmacokinetic/pharmacodynamic model to characterize target cell depletion and cytokine release for T cell-redirecting bispecific agents in humans.

T cell-redirecting bispecific antibodies (bsAbs) are highly potent tumor-killing molecules. Following bsAb mediated engagement with target cells, T cells get activated and kill target cells while inducing cytokine release, which at higher levels may lead to life-threatening cytokine release syndrome (CRS). Clinical evidence suggests that CRS can be mitigated by implementing a stepwise dosing strategy. Here, we developed a mechanism-based minimal physiologically-based pharmacokinetic/pharmacodynamic (mPBPK/PD) model using reported preclinical and clinical data from blinatumomab. The mPBPK/PD model reasonably captured blinatumomab PK and B cell depletion profiles in blood and in various tissue sites of action (i.e., red marrow perivascular niche, spleen, and lymph nodes) in patients with non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL). Using interleukin 6 (IL-6) as an example, our model quantitatively characterized the mitigation of cytokine release by a blinatumomab 5-15-60 µg/m2/day stepwise dosing regimen comparing to a 60 µg/m2/day flat dose in NHL patients. Furthermore, by only modifying the system parameters specific for ALL patients, the mPBPK/PD model successfully predicted the mitigation of IL-6 release by a blinatumomab 5-15 µg/m2/day stepwise dosing regimen comparing to a 15 µg/m2/day flat dose. Our work provided a case example to show how mPBPK/PD model can be used to support the discovery and clinical development of T cell-redirecting bsAbs.

Development of a Target cell-Biologics-Effector cell (TBE) complex-based cell killing model to characterize target cell depletion by T cell redirecting bispecific agents.

T-cell redirecting bispecific antibodies (bsAbs) or antibody-derived agents that combine tumor antigen recognition with CD3-mediated T cell recruitment are highly potent tumor-killing molecules. Despite the tremendous progress achieved in the last decade, development of such bsAbs still faces many challenges. This work aimed to develop a mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) modeling framework that can be used to assist the development of T-cell redirecting bsAbs. A Target cell-Biologics-Effector cell (TBE) complex-based cell killing model was developed using in vitro and in vivo data, which incorporates information on binding affinities of bsAbs to CD3 and target receptors, expression levels of CD3 and target receptors, concentrations of effector and target cells, as well as respective physiological parameters. This TBE model can simultaneously evaluate the effect of multiple system-specific and drug-specific factors on the T-cell redirecting bsAb exposure-response relationship on a physiological basis; it reasonably captured multiple reported in vitro cytotoxicity data, and successfully predicted the effect of some key factors on in vitro cytotoxicity assays and the efficacious dose of blinatumomab in humans. The mechanistic nature of this model uniquely positions it as a knowledge-based platform that can be readily expanded to guide target selection, drug design, candidate selection and clinical dosing regimen projection, and thus support the overall discovery and development of T-cell redirecting bsAbs.