Intramammary calcitriol treatment of mastitis alters profile of milk somatic cells and indicators of redox activity in milk.

The objective of this experiment was to determine the effect of intramammary calcitriol treatment on indicators of inflammation during an intramammary bacterial infection. Lactating Holstein cows were challenged with intramammary Streptococcus uberis. At the onset of mild or moderate mastitis, cows were randomly assigned to receive 10 µg of intramammary calcitriol (CAL, n = 7) or placebo control (CON; n = 6) after every milking for 5 days.

Evaluation of exosome derivatives as bio-informational reprogramming therapy for cancer.

Exosomes are nanoparticle sized (100 ± 50 nm) extracellular vesicles (ECVs) that play important roles in cell-to-cell communication. They do this by utilizing their natural ability to shuttle signaling molecules across the cellular microenvironment and promote paracrine signaling. Currently, exosomes are being explored for their potential as therapeutic agents for various degenerative diseases including cancer.

Vitamin D signaling increases nitric oxide and antioxidant defenses of bovine monocytes.

Vitamin D contributes to multiple aspects of bovine immunity and is reported to decrease the effects of mastitis and metritis in dairy cows. We hypothesized that vitamin D signaling in bovine monocytes increases antioxidant responses as part of its immunomodulatory actions. Our objectives were to assess the effects of vitamin D on oxidant and antioxidant responses of bovine monocytes.

The mechanism of cancer drug addiction in ALK-positive T-Cell lymphoma.

Rational new strategies are needed to treat tumors resistant to kinase inhibitors. Mechanistic studies of resistance provide fertile ground for development of new approaches. Cancer drug addiction is a paradoxical resistance phenomenon, well-described in MEK-ERK-driven solid tumors, in which drug-target overexpression promotes resistance but a toxic overdose of signaling if the inhibitor is withdrawn.

Feeding supplemental 25-hydroxyvitamin D increases serum mineral concentrations and alters mammary immunity of lactating dairy cows.

Objectives were to determine the effects of feeding supplemental 25-hydroxyvitamin D [25(OH)D] on concentrations of vitamin D metabolites and minerals in serum, mammary immune status, and responses to intramammary bacterial infection in dairy cows. Sixty multiparous, pregnant lactating Holstein cows with somatic cell count <200,000/mL were blocked by days in milk and milk yield and randomly assigned to receive a daily top-dressed dietary supplement containing 1 or 3 mg of vitamin D (1mgD or 3mgD), or 1 or 3 mg 25(OH)D (1mg25D or 3mg25D) for 28 d (n = 15/treatment). Cows were kept in a freestall barn and fed a total mixed ration in individual feeding gates.

CRISPR genome editing of murine hematopoietic stem cells to create causes ALK lymphoma after transplantation.

CRISPR/Cas9 genomic editing of wild-type hematopoietic stem cells generates , leading to ALK large-cell lymphomas in recipients. CD30 postthymic T-cell lymphomas are polyclonal but transplantable to secondary recipients with long latency.

Short communication: Inhibition of DNA methyltransferase and histone deacetylase increases β-defensin expression but not the effects of lipopolysaccharide or 1,25-dihydroxyvitamin D in bovine mammary epithelial cells.

Antimicrobial peptides are a common defense against bacterial infections in many species and a significant part of the innate immune response of the bovine mammary gland. The objective of this study was to investigate the influence of epigenetic factors on vitamin D and toll-like receptor-mediated induction of β-defensins in mammary epithelial cells. Primary bovine mammary epithelial cells were treated with lipopolysaccharide (LPS, 0 or 100 ng/mL), 1,25-dihydroxyvitamin D [1,25(OH)D, 0 or 10 nM], and 5-aza-2'-deoxycytidine (5-Aza, inhibitor of DNA methyltransferase, 0 or 5 μM) or trichostatin A (TSA, inhibitor of histone deacetylase, 0 or 80 nM) in a factorial arrangement.

Symposium review: Targeting antimicrobial defenses of the udder through an intrinsic cellular pathway.

The bovine innate immune system has a strong repertoire of antimicrobial defenses to rapidly attack infectious pathogens that evade physical barriers of the udder. Exploration of the intracrine vitamin D pathway of bovine macrophages has improved understanding of the signals that initiate antimicrobial defenses that protect the udder. In the intracrine vitamin D pathway, pathogen recognition receptors upregulate CYP27B1 mRNA that encodes for the enzyme that converts 25-hydroxyvitamin D [25(OH)D] to the active vitamin D hormone, 1,25-dihydroxyvitamin D [1,25(OH)D].

Intramammary 1,25-dihydroxyvitamin D treatment increases expression of host-defense genes in mammary immune cells of lactating dairy cattle.

Bacterial infection of the mammary gland activates an intracrine vitamin D pathway in macrophages of dairy cows. The active hormone of the vitamin D pathway, 1,25-dihydroxyvitamin D (1,25D), stimulates nitric oxide and β-defensin responses in bovine monocyte cultures, but the effect of 1,25D on innate immune genes in the mammary gland remained unknown. Therefore, the objective of this study was to determine the effects intramammary 1,25D treatment on expression of vitamin D associated host-defenses of the bovine mammary gland.

Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin).

Multiple β-defensin genes are upregulated by the vitamin D pathway in cattle.

Experimental models of bacterial and viral infections in cattle have suggested vitamin D has a role in innate immunity of cattle. The intracrine vitamin D pathway of bovine macrophages, however, has only been shown to activate a nitric oxide-mediated defense mechanism, as opposed to cathelicidin and β-defensin antimicrobial peptides in human macrophages. In this study we have investigated the actions of 1,25-dihydroxyvitamin D3 (1,25D) on a cluster of eleven bovine β-defensin genes on the basis of RNAseq data indicating they were targets of 1,25D in cattle.