Thai pigmented rice bran extracts inhibit production of superoxide, nitric oxide radicals and inducible nitric oxide synthase in cellular models

Objective:To study the inhibitory effect of rice bran extracts of Thai black Kam Muang and red Hawm Dawk Mali Deang on oxidative stress factors including superoxide(O2·-),nitric oxide(NO·),and inducible nitric oxide synthase(iNOS).Methods:Bran extracts(40%ethanol)of Kam Muang and Hawm Dawk Mali Deang were obtained and evaluated for in vitro 2-2′-azino-di-(3-ethylbenzthiazoline sulfonate)(ABTS)and NO·scavenging activity.Their inhibitory effects on cellular O2·-and NO·were measured in phorbol 12-myristate 13-acetate-stimulated neutrophil-like HL-60 cells and lipopolysaccharidestimulated RAW264.7 macrophages,respectively,and their viability was monitored using the MTT assay.The effect on iNOS expression was also assessed by the Western blotting assay.Total contents of phenolics,flavonoids,and subtypes were also determined.Results:Hawm Dawk Mali Deang exhibited about 3.5-fold greater cellular O2·-inhibitory activity than Kam Muang[EC50 values of(23.57±4.54)and(81.98±1.45)μg/mL,respectively]in phorbol 12-myristate 13-acetate-stimulated HL-60 cells.Hawm Dawk Mali Deang exhibited about 2-fold higher in vitro ABTS·+and NO·scavenging activity than Kam Muang,but it exerted cellular NO·inhibitory activity of only about 26%(undetermined EC50 value)in lipopolysaccharide-stimulated RAW264.7 cells.Conversely,Kam Muang exerted potent cellular NO·inhibitory activity[EC50 value:(281.13±59.18)μg/mL]and dose-dependently decreased iNOS levels.No cytotoxicity of both extracts was detected in both cell types.As for corresponding contents,Hawm Dawk Mali Deang contained higher contents of phenolics and flavonoids than Kam Muang.Moreover,Kam Muang and Hawm Dawk Mali Deang had a high content of total anthocyanins[(14.73±0.52)mg C3GE/g of extract]and total proanthocyanidins[(115.13±1.47)mg CE/g of extract],respectively.Conclusions:Based on these data,bran extracts of Thai black Kam Muang and red rice Hawm Dawk Mali Deang can help lower oxidative stress and inflammation attributed partly to O2·-and NO·.

Addition of Protease Enzyme to Dog and Cat Feed and Its Influence on the Digestibility Coefficient, Immune Response, and Metabolic Biomarkers

Promoting better protein digestibility through exogenous enzymes in the diet is essential in the nutrition of companion animals, mainly for better performance and maintenance of the animals’ physiological and metabolic systems, promoting health and adequate growth. In addition, it reduces the cost of the diet by possibly reducing protein in the diet, which is the main and most expensive ingredient for dogs and cats. The objective of this study was to verify whether the addition of protease to dog and cat food can improve the protein digestibility of the food, thus facilitating greater absorption of amino acids and influencing metabolic biomarkers and immune response. To this end, two experiments were carried out to evaluate the protease from the fermentation of Aspergillus niger and Bacillus subtilis. Experiment 1 was carried out with ten male, non-castrated beagles divided into two groups of five animals: the control group (without enzyme) and the test group (with 250 g of protease/ton). The animals underwent two 45-day experimental periods, and in the second period, after a 15-day interval, the dogs in the control group became part of the treatment group (crossover model). Adding this enzyme to the dogs’ diet had no adverse effects on the animals’ health besides improving the digestibility of dry matter and crude protein consumed by the dogs. Experiment 2 was carried out with sixteen female cats of no defined breed, non-castrated, divided into four groups with four animals per group, namely: Treatment A (without enzyme), Treatment B (with protease at a dose of 100 g/ton), Treatment C (with protease at a dose of 200 g/ton) and Treatment D (with protease at a dose of 400 g/ton). The cats underwent two 30-day experimental periods, and in the second period, after a 15-day interval, the animals switched between treatments (crossover model) to increase the power of the statistical test. The enzyme consumption did not affect the felines’ metabolism and health but improved the digestibility of crude protein at doses of 200 and 400 g/ton. The results allow us to conclude that the protease used in this study can improve the digestibility of crude protein for dogs and cats.

Arabidopsis FtsZ2-1 and FtsZ2-2 Are Functionally Redundant, But FtsZ-Based Plastid Division Is Not Essential for Chloroplast Partitioning or Plant Growth and Development

FtsZ1 and FtsZ2 are phylogenetically distinct families of FtsZ in plants that co-localize to mid-plastid rings and facilitate division of chloroplasts. In plants, altered levels of either FtsZ1 or FtsZ2 cause dose-dependent defects in chloroplast division; thus, studies on the functional relationship between FtsZgenes require careful manipulation of FtsZ levels in vivo. To define the functional relationship between the two FtsZ2 genes in Arabidopsis thaliana, FtsZ2-1 and FtsZ2-2, we expressed FtsZ2-1 in an ftsZ2-2 null mutant, and vice versa, and determined whether the chloroplast division defects were rescued in plants expressing different total levels of FtsZ2. Full rescue was observed when either the FtsZ2-1 or FtsZ2-2 level approximated total FtsZ2 levels in wild-type （WT）. Additionally, FtsZ2-2 interacts with ARC6, as shown previously for FtsZ2- 1. These data indicate that FtsZ2-1 and FtsZ2-2 are functionally redundant for chloroplast division in Arabidopsis. To rigorously validate the requirement of each FtsZ family for chloroplast division, we replaced FtsZ1 with FtsZ2 in vivo, and vice versa, while maintaining the FtsZ level in the transgenic plants equal to that of the total level in WT. Chloroplast division defects were not rescued, demonstrating conclusively that FtsZ1 and FtsZ2 are non-redundant for maintenance of WT chloroplast numbers. Finally, we generated ftsZtriple null mutants and show that plants completely devoid of FtsZ protein are viable and fertile. As plastids are presumably essential organelles, these findings suggest that an FtsZ-independent mode of plastid partitioning may occur in higher plants.

Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

Toll-like receptors （TLRs）, which are found in innate immune cells, are essential mediators of rapid inflammatory responses and appropriate T-cell activation in response to infection and tissue damage. Accumulating evidence suggests that TLR signaling is involved in normal hematopoiesis and specific hematologic pathologies. Particular TLRs and their downstream signaling mediators are expressed not only in terminally differentiated innate immune cells but also in early hematopoietic progenitors. Sterile activation of TLR signaling is required to generate early embryonic hematopoietic progenitor cells. In adult animals, TLR signaling directly or indirectly promotes differentiation of myeloid cells at the expense of that of lymphoid cells and the self renewal of hematopoietic stem cells during infection and tissue damage. Activating mutations of the MyD88 gene, which codes for a key adaptor involved in TLR signaling, are commonly detected in B-cell lymphomas and other B-cell hematopathologies. Dysregulated TLR signaling contributes to the pathogenesis of many hematopoietic disorders, including bone marrow failure, myelodysplastic syndrome, and acute myeloid leukemia. Complete elucidation of the molecular mechanisms by which TLR signaling mediates the regulation of both normal and pathogenic hematopoiesis will prove valuable to the development of targeted therapies and strategies for improved treatment of hematopoietic disorders.

Lineage plasticity-mediated therapy resistance in prostate cancer

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.