A Multivalent DNA Nanoparticle/Peptide Hybrid Molecular Modality for the Modulation of Protein-Protein Interactions in the Tumor Microenvironment.

Despite success in the treatment of some blood cancers and melanoma, positive response to immunotherapies remains disappointingly low in the treatment of solid tumors. The context of the molecular crosstalk within the tumor microenvironment can result in dysfunctional immune cell activation, leading to tumor tolerance and progression. Although modulating these protein-protein interactions (PPIs) is vital for appropriate immune cell activation and recognition, targeting nonenzymatic PPIs has proven to be fraught with challenges.

Wheat-Based Glues in Conservation and Cultural Heritage: (Dis)solving the Proteome of Flour and Starch Pastes and Their Adhering Properties.

Plant-based adhesives, such as those made from wheat, have been prominently used for books and paper-based objects and are also used as conservation adhesives. Starch paste originates from starch granules, whereas flour paste encompasses the entire wheat endosperm proteome, offering strong adhesive properties due to gluten proteins. From a conservation perspective, understanding the precise nature of the adhesive is vital as the longevity, resilience, and reaction to environmental changes can differ substantially between starch- and flour-based pastes.

Diabetes and the Microvasculature of the Bone and Marrow.

Purpose Of Review: The purpose of this review is to highlight the evidence of microvascular dysfunction in bone and marrow and its relation to poor skeletal outcomes in diabetes mellitus.

Recent Findings: Diabetes mellitus is characterized by chronic hyperglycemia, which may lead to microangiopathy and macroangiopathy. Micro- and macroangiopathy have been diagnosed in Type 1 and Type 2 diabetes, coinciding with osteopenia, osteoporosis, enhanced fracture risk and delayed fracture healing.

Myogenic autoregulation in bone marrow arterioles and in vivo intramedullary pressure in femora of conscious, female Long Evans rats.

Objectives: The ability to regulate skeletal blood flow is critical for the maintenance of bone. The myogenic response is essential for regulating tissue blood flow. Myogenic responsiveness in bone marrow arterioles has not yet been determined.

Old and new biomarkers for volumetric muscle loss.

Volumetric muscle loss (VML) impacts skeletal muscles and causes damage to associated tissues such as blood vessels and other structural tissues. Despite progress in the VML field, current preclinical approaches are often ineffective at restoring muscle volume. Additional research is paramount to develop strategies that improve muscle mass and function, while restoring supporting tissues.

Bone Marrow Microvasculature.

The skeleton is highly vascularized due to the various roles blood vessels play in the homeostasis of bone and marrow. For example, blood vessels provide nutrients, remove metabolic by-products, deliver systemic hormones, and circulate precursor cells to bone and marrow. In addition to these roles, bone blood vessels participate in a variety of other functions.

The cardiovascular disease burden of non-traumatic fractures for adults with and without cerebral palsy.

Background: Individuals with cerebral palsy (CP) are vulnerable to non-trauma fracture (NTFx) and have an elevated burden of cardiovascular disease (CVD) related morbidity and mortality. However, very little is known about the contribution of NTFx to CVD risk among adults with CP. The purpose of this study was to determine if NTFx is a risk factor for CVD among adults with CP and if NTFx exacerbates CVD risk compared to adults without CP.

Short-term intermittent parathyroid hormone (1-34) administration increased angiogenesis and matrix metalloproteinase 9 in femora of mature and middle-aged C57BL/6 mice.

New Findings: What is the central question of this study? We sought to assess the effects of intermittent parathyroid hormone (1-34) administration on bone angiogenesis, the redistribution of bone marrow blood vessels, and matrix metalloproteinase 9 as a function of advancing age in mice. What is the main finding and its importance? Short-term (i.e.

An Implanted Magnetic Microfluidic Pump for In Vivo Bone Remodeling Applications.

Modulations of fluid flow inside the bone intramedullary cavity has been found to stimulate bone cellular activities and augment bone growth. However, study on the efficacy of the fluid modulation has been limited to external syringe pumps connected to the bone intramedullary cavity through the skin tubing. We report an implantable magnetic microfluidic pump which is suitable for in vivo studies in rodents.

Low-Trauma Fracture Increases 12-Month Incidence of Cardiovascular Disease for Adults With Cerebral Palsy.

Individuals with cerebral palsy (CP) have poor skeletal and cardiovascular health. However, no studies have examined if skeletal fragility enhances cardiovascular disease (CVD) risk for this population. The purpose of this study was to determine whether adults with CP have higher 12-month CVD incidence following a low-trauma fracture compared with adults without CP.

Discovery of a bone-like blood particle in the peripheral circulation of humans and rodents.

Objective: To characterize ossified bone marrow blood vessels and confirm the presence of ossified particles (OSP) in humans and rodents.

Methods: Human bone marrow blood vessels were processed for scanning and transmission electron microscopy. Whole blood samples were collected from younger (26-39 years; n = 6) and older (55-63 years; n = 6) volunteers and male Fischer-344 rats (1 month, n = 7; 6 months, n = 7; 12 months, n = 7; 18-months, n = 6; 24 months, n = 8).

Progressive ossification of the bone marrow vasculature with advancing age corresponds with reduced red blood cell count and percentage of circulating lymphocytes in male Fischer-344 rats.

Objective: Assess the link between bone marrow blood vessel ossification, Tb. and cortical bone, and hematological parameters across the lifespan in rats.

Methods: Right femora and whole blood samples were taken from male Fischer-344 rats at 1, 6, 12, 18 and 24 months.

Short-term intermittent PTH 1-34 administration and bone marrow blood vessel ossification in Mature and Middle-Aged C57BL/6 mice.

Intermittent parathyroid hormone (PTH) administration augments bone and progressive bone marrow blood vessel (BMBV) ossification occurs with advancing age. Since intermittent PTH administration augments bone, it may also serve to increase BMBV ossification. We assessed the influence of 5- and 10-days of intermittent PTH 1-34 administration on trabecular and cortical bone and BMBV ossification in mature (6-8 mon; n = 30) and middle-aged (10-12 mon; n = 30) male and female C57BL/6 mice.

Intermittent PTH 1-34 administration improves the marrow microenvironment and endothelium-dependent vasodilation in bone arteries of aged rats.

Inflammation coincides with diminished marrow function, vasodilation of blood vessels, and bone mass. Intermittent parathyroid hormone (PTH) administration independently improves marrow and vascular function, potentially impacting bone accrual. Currently, the influence of marrow and intermittent PTH administration on aged bone blood vessels has not been examined.

Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone.

Bone tissue is highly vascularized due to the various roles bone blood vessels play in bone and bone marrow function. For example, the vascular system is critical for bone development, maintenance and repair and provides O, nutrients, waste elimination, systemic hormones and precursor cells for bone remodeling. Further, bone blood vessels serve as egress and ingress routes for blood and immune cells to and from the bone marrow.

Intermittent parathyroid hormone administration attenuates endothelial dysfunction in old rats.

Unlabelled: Aging is an independent risk factor for cardiovascular disease and is characterized by a decline in endothelial function. Parathyroid hormone (PTH) administration has been shown to increase endothelial nitric oxide synthase (eNOS) expression. The purpose of this investigation was to determine the effect of intermittent PTH administration on aortic endothelial function in old rodents.

Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries.

Unlabelled: Parathyroid hormone (PTH) augments bone metabolism and bone mass when given intermittently. Enhanced blood flow is requisite to support high tissue metabolism. The bone arteries are responsive to all three PTH analogs, which may serve to augment skeletal blood flow during intermittent PTH administration.

Effects of hindlimb unloading and ionizing radiation on skeletal muscle resistance artery vasodilation and its relation to cancellous bone in mice.

Spaceflight has profound effects on vascular function as a result of weightlessness that may be further compounded by radiation exposure. The purpose of the present study was to assess the individual and combined effects of hindlimb unloading (HU) and radiation (Rad) on vasodilator responses in the skeletal muscle vasculature. Adult male C57BL/6J mice were randomized to one of four groups: control (Con), HU (tail suspension for 15 days), Rad (200 cGy of (137)Cs), and HU-Rad (15-day tail suspension and 200 cGy of (137)Cs).

Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat.

Bone health and cardiovascular function are compromised in individuals with type 2 diabetes mellitus (T2DM). The purpose of this study was to determine whether skeletal vascular control mechanisms are altered during the progression of T2DM in Zucker diabetic fatty (ZDF) rats. Responses of the principal nutrient artery (PNA) of the femur from obese ZDF rats with prediabetes, short-term diabetes, and long-term diabetes to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilation and potassium chloride, norepinephrine (NE), and a myogenic vasoconstrictor were determined in vitro.

Effects of skeletal unloading on the vasomotor properties of the rat femur principal nutrient artery.

Spaceflight and prolonged bed rest induce deconditioning of the cardiovascular system and bone loss. Previous research has shown declines in femoral bone and marrow perfusion during unloading and with subsequent reloading in hindlimb-unloaded (HU) rats, an animal model of chronic disuse. We hypothesized that the attenuated bone and marrow perfusion may result from altered vasomotor properties of the bone resistance vasculature.

Kinetic examination of femoral bone modeling in broilers.

Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent.

Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis.

Chronic skeletal unloading of the rat femur: mechanisms and functional consequences of vascular remodeling.

Chronic skeletal unloading diminishes hindlimb bone blood flow. The purpose of the present investigation was to determine 1) whether 7 and 14days of skeletal unloading alter femoral bone and marrow blood flow and vascular resistance during reloading, and 2) whether putative changes in bone perfusion are associated with a gross structural remodeling of the principal nutrient artery (PNA) of the femur. Six-month old male Sprague-Dawley rats were assigned to 7-d or 14-d hindlimb unloading (HU) or weight-bearing control groups.

Vasodilation to PTH (1-84) in bone arteries is dependent upon the vascular endothelium and is mediated partially via VEGF signaling.

Background: Intermittent PTH administration directly stimulates osteoblasts; however, mechanisms of bone accrual that are independent of the direct actions on osteoblasts may be under-appreciated. Our aims were to decipher (1) whether PTH 1-84 augments vasodilation of the femoral principal nutrient artery (PNA), (2) whether 15 days of intermittent PTH 1-84 augments endothelium-dependent and/or -independent vasodilation of the femoral PNA, and (3) the signaling mechanisms involved.

Methods: Experiment 1: Femoral PNAs from male Wistar rats were exposed to cumulative doses of PTH 1-84 with and without an anti-vascular endothelial growth factor antibody and/or the endothelial NO synthase inhibitor l-NAME.

Bone circulatory disturbances in the development of spontaneous bacterial chondronecrosis with osteomyelitis: a translational model for the pathogenesis of femoral head necrosis.

This review provides a comprehensive overview of the vascularization of the avian growth plate and its subsequent role in the pathogenesis of bacterial chondronecrosis with osteomyelitis (BCO, femoral head necrosis). BCO sporadically causes high incidences of lameness in rapidly growing broiler (meat-type) chickens. BCO is believed to be initiated by micro-trauma to poorly mineralized columns of cartilage cells in the proximal growth plates of the leg bones, followed by colonization by hematogenously distributed opportunistic bacteria.