Short-term therapy with R568 ameliorated secondary hyperparathyroidism but does not prevent aortic valve calcification in uremic rats.

Introduction: Renal failure associated aortic valve calcification (AVC) is the result of hyperphosphatemia and hyperparathyroidism. Calcimimetics is an effective tool for management of secondary hyperparathyroidism. Our goal was to evaluate the effect of the medical intervention with calcimimetic R568 on the AVC process.

Cardiac Left Ventricular miRNA-26a Is Downregulated in Ovariectomized Mice, Upregulated upon 17-Beta Estradiol Replacement, and Inversely Correlated with Collagen Type 1 Gene Expression.

Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood. Data in humans is confounded by age and co-morbidities.

RNA Sequencing Reveals Unique Transcriptomic Signatures of the Thyroid in a Murine Lung Cancer Model Treated with PD-1 and PD-L1 Antibodies.

Immune checkpoint inhibitors (ICI) are commonly associated with thyroid immune-related adverse events, yet the mechanism has not been fully elucidated. We aimed to further explore the mechanism of ICI-induced thyroid dysfunction by assessing changes induced in the thyroid transcriptome by ICI treatment (αPD-1/αPD-L1) in a lung cancer murine model. RNA-sequencing of thyroid tissues revealed 952 differentially expressed genes (DEGs) with αPD-1 treatment (|fold-change| ≥1.

Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice.

Objective: Menopause is associated with visceral adiposity, hepatic steatosis and increased risk for cardiovascular disease. As estrogen replacement therapy is not suitable for all postmenopausal women, a need for alternative therapeutics and biomarkers has emerged.

Methods: 9-week-old C57BL/6 J female mice were subjected to ovariectomy (OVX) or SHAM surgery (n = 10 per group), fed a standard diet and sacrificed 6- & 12 weeks post-surgery.

Sirt1 Promotes a Thermogenic Gene Program in Bone Marrow Adipocytes: From Mice to (Wo)Men.

Bone marrow adipose tissue (MAT) is influenced by nutritional cues, and participates in whole body energy metabolism. To investigate the role of Sirtuin1 (Sirt1), a key player in metabolism, in MAT, marrow adiposity was evaluated in inbred 5-month-old 129/Sv haplo-insufficient ( ) and wild type (WT) mice. Decreased expression of the thermogenic genes: α, and β was detected in whole tibiae derived from compared to WT female mice.

Reduced Sirtuin1 expression at the femoral neck in women who sustained an osteoporotic hip fracture.

Unlabelled: To investigate the role of Sirtuin1 in osteoporosis, Sirtuin1 was determined at the femoral neck in female patients undergoing hip operation for fractured hip or osteoarthritis. Reduced Sirtuin1 was found in osteoporotic patients. Pharmacologic activation of Sirtuin1 reduced sclerostin, an inhibitor of bone formation.

The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells.

Increased osteoclast-mediated bone resorption is characteristic of osteoporosis, malignant bone disease and inflammatory arthritis. Targeted deletion of Sirtuin1 (Sirt1), a key player in aging and metabolism, in osteoclasts results in increased osteoclast-mediated bone resorption in vivo, making it a potential novel therapeutic target to block bone resorption. Sirt1 activating compounds (STACs) were generated and were investigated in animal disease models and in humans however their mechanism of action was a source of controversy.

The Sirtuin1 activator SRT3025 down-regulates sclerostin and rescues ovariectomy-induced bone loss and biomechanical deterioration in female mice.

Estrogen deficiency leads to rapid bone loss and skeletal fragility. Sclerostin, encoded by the sost gene, and a product of the osteocyte, is a negative regulator of bone formation. Blocking sclerostin increases bone mass and strength in animals and humans.

Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor.

Sirt1, the mammalian ortholog of the yeast Sir2 (silent information regulator 2), was shown to play an important role in metabolism and in age-associated diseases, but its role in skeletal homeostasis and osteoporosis has yet not been studied. Using 129/Sv mice with a germline mutation in the Sirt1 gene, we demonstrate that Sirt1 haplo-insufficient (Sirt1(+/-)) female mice exhibit a significant reduction in bone mass characterized by decreased bone formation and increased marrow adipogenesis. Importantly, we identify Sost, encoding for sclerostin, a critical inhibitor of bone formation, as a novel target of Sirt1.

Mutation of SYNE-1, encoding an essential component of the nuclear lamina, is responsible for autosomal recessive arthrogryposis.

Arthrogryposis multiplex congenita (AMC) is a group of disorders characterized by congenital joint contractures caused by reduced fetal movements. AMC has an incidence of 1 in 3000 newborns and is genetically heterogeneous. We describe an autosomal recessive form of myogenic AMC in a large consanguineous family.

Spinal muscular atrophy.

Spinal muscular atrophies (SMA) are frequent autosomal recessive disorders characterized by degeneration of lower motor neurons. SMA are caused by mutations of the survival of motor neuron gene (SMN1) leading to a reduction of the SMN protein amount. The identification of SMN interacting proteins involved in the formation of the spliceosome and splicing changes in SMN-deficient tissues of mutant mice strongly support the view that SMN is involved in the splicing reaction.

Protection induced in mice against a lethal orthopox virus by the Lister strain of vaccinia virus and modified vaccinia virus Ankara (MVA).

The Lister (Elstree) strain of vaccinia virus, used in Israel for vaccination against smallpox, was studied in tissue cultures and in a mouse model. The virus failed to reach the brain of the mice when inoculated intranasally at a dose of 500,000 plaque forming units, but was lethal for 50% of them, when injected intracranially. Lower doses of virus injected intracranially caused some weight loss initially, but later the mice completely recovered.

Pathogenicity and immunogenicity in mice of vaccinia viruses mutated in the viral envelope proteins A33R and B5R.

The pathogenicity and immunogenicity in mice of WR.cl and WR.c3, two mutants of the Western Reserve (WR) strain of vaccinia virus, mutated in the A33R and B5R proteins of the outer envelope of the virus, respectively, were studied.