The effect of charge density on the velocity and attenuation of ultrasound waves in human cancellous bone

Cancellous bone is a highly porous material, and two types of waves, fast and slow, are observed when ultrasound is used for detecting bone diseases. There are several possible stimuli for bone remodelling processes, including bone fluid flow, streaming potential, and piezoelectricity. Poroelasticity has been widely used for elucidating the bone fluid flow phenomenon, but the combination of poroelasticity with charge density has not been introduced. Theoretically, general poroelasticity with a varying charge density is employed for determining the relationship between wave velocity and attenuation with charge density. Fast wave velocity and attenuation are affected by porosity as well as charge density; however, for a slow wave, both slow wave velocity and attenuation are not as sensitive to the effect of charge density as they are for a fast wave. Thus, employing human femoral data, we conclude that charged ions gather on trabecular struts, and the fast wave, which moves along the trabecular struts, is significantly affected by charge density.     

Artesunate inhibits RANKL‐induced osteoclastogenesis and bone resorption in vitro and prevents LPS‐induced bone loss in vivo

Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side‐effects caused by the currently available drugs, a continuous search for novel bone‐protective therapies is essential. Artesunate (Art), the water‐soluble derivative of artemisinin has been investigated owing to its anti‐malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis, the mRNA expression of osteoclastic‐specific genes, and resorption pit formation in a dose‐dependent manner in primary bone marrow‐derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL‐induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF‐κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)‐induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL‐induced osteoclastogenesis by suppressing the NF‐κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases.     

Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide

The past two decades have seen a proliferation in bioarchaeological literature on the identification of scurvy, a disease caused by chronic vitamin C deficiency, in ancient human remains. This condition is one of the few nutritional deficiencies that can result in diagnostic osseous lesions. Scurvy is associated with low dietary diversity and its identification in human skeletal remains can provide important contextual information on subsistence strategy, resource allocation, and human-environmental interactions in past populations. A large and robust methodological body of work on the paleopathology of scurvy exists. However, the diagnostic criteria for this disease employed by bioarchaeologists have not always been uniform. Here we draw from previous research on the skeletal manifestations of scurvy in adult and juvenile human skeletal remains and propose a weighted diagnostic system for its identification that takes into account the pathophysiology of the disease, soft tissue anatomy, and clinical research. Using a sample of individuals from the prehistoric Atacama Desert in Northern Chile, we also provide a practical example of how diagnostic value might be assigned to skeletal lesions of the disease that have not been previously described in the literature.     

PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p

MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl₄ and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.