In vitro and in vivo studies of antiosteosarcoma activities of formononetin.

Osteogenic sarcoma (OGS) is a primary bone cancer, characterized by aggressive neoplasm from mesenchymal oncogenesis. However, the clinical therapeutic regimen against OGS is limited. Therefore, potential medication warrants to be further developed. Our previous study indicates that formononetin (FN) exerts effective pharmacological activity against OGS. This study aimed to further decipher the molecular mechanism behind this benefit. Patients with OGS were recruited for clinical data assay and immunoassay. Human OGS cell line (U2OS) and tumor-bearing nude mice were subjected to a battery of biochemical analyses and immunoassays for integrative evaluation of FN-exerted anti-OGS effects. In human data, OGS samples showed increased expressions of ERα, p-PI3KCATyr317 , and p-AKT Ser473 proteins, followed by notably upregulated miR-375 content in comparison with that in OGS-free. In addition, FN-treated U2OS cells showed inhibited cell proliferation, elevated lactic dehydrogenase production and lowered endogenous miR-375 level in cells. Further, reduced immunopositive cells of Ki-67, p-PI3KCA Tyr317 , and p-AKT Ser473 were observed by the treatments of FN, while the intracellular Bax- and Apaf-1-positive cells were increased dose-dependently. Beneficially, FN-treated tumor-bearing mice exhibited reduced tumor mass and intercellular miR-375 expression. Meanwhile, immuno-labeled cells and proteins of Bax, Caspase-3, and Apaf-1 in FN-treated mice were increased dose-dependently, whereas ERα, p-PI3KCA Tyr317 , and p-AKT Ser473 positive cells and proteins were downregulated, respectively. Collectively, our current results elucidate that FN exerts effective therapeutic benefits against OGS, and the pharmacological mechanism may be related to promoting cell apoptosis by inactivating intracellular miR-375/ERα-PI3K/AKT cascaded pathway.

Ligustilide suppresses RANKL-induced osteoclastogenesis and bone resorption via inhibition of RANK expression.

Osteoclast (OC) is the only cell involved in bone resorption. Dysfunction of OCs leads to a variety of bone diseases. Ligustilide (LIG) is the main component of the volatile oil isolated and purified from Angelica sinensis. LIG exerts many pharmacological activities, but its effects on osteoclastogenesis and bone resorption are still unclear. Our study showed that LIG inhibited receptor activator of nuclear factor-κB (NF-κB) ligand-induced OC formation and activation in a dose-dependent manner. Additionally, LIG downregulated the messenger RNA (mRNA) expression of OC-specific genes, such as V-ATPase d2, tartrate-resistant acid phosphatase, a dendritic cell-specific transmembrane protein, cathepsin K, and nuclear factor of activated T cells cl. Furthermore, LIG blocked the activation of NF-κB/extracellular signal-regulated kinase/p38/immunoreceptor tyrosine-based activation motif signaling pathways. Crucially, the expression of tumor necrosis factor receptor-associated factor 6 proteins and the expression of receptor activator of NF-κB mRNA were inhibited by LIG. However, LIG did not affect the formation and mineralization of osteoblasts. Collectively, this observation suggests that LIG may serve as a promising agent for the prevention and treatment of diseases caused by abnormal bone resorption.

Cutaneous paresthesia after internal plate fixation of clavicle fractures and underlying anatomical observations.

To assess the clinical and anatomical causes of cutaneous paresthesia after internal fixation of clavicle fractures.This study included 135 patients who underwent internal fixation of clavicle fractures from May 2013 to June 2016 at the First and Second Affiliated Hospital of Guangxi Medical University. The incidence of postoperative supraclavicular nerve injury, the duration of numbness, and improvements after plate removal were retrospectively analyzed. Seven human cadaver specimens were subsequently dissected to analyze the supraclavicular nerve and its relationship to numbness.Of the 135 patients who underwent internal fixation of clavicle fractures, 26 (19.3%) experienced postoperative cutaneous paresthesia, with 22 (16.3%) and 4 (2.8%) experiencing numbness and pain, respectively. The most intense numbness occurred during the first operative month. Of the 22 patients with numbness, 1 (4.5%), 1 (4.5%), and 20 (90.1%) patients reported mild, moderate, and severe numbness, respectively. Two patients described increased awareness of numbness when in contact with clothes, 2 were psychologically affected by numbness, and 20 (90.1%) reported reduced severity of numbness over time. At the last follow-up, numbness was found to persist in 2 (1.5%) patients. None of the patients was bothered by numbness. Cadaver dissection showed that the supraclavicular nerve emerged from the 1/2 posterior edge of the cervical sternocleidomastoid muscle and subsequently divided into 3 branches, with the lateral branch 2.26 ±â€Š1.17 cm from the lateral margin of the acromion, the middle branch near the mid-clavicle, and the medial branch 2.03 ±â€Š0.85 cm from the sternal lateral margin.Cutaneous paresthesia is common following internal fixation of the clavicle. Anatomic analysis showed that the nerve could be easily injured during clavicle operation. Numbness improved in most patients, but persisted for up to 2 years and was even permanent in a few. Most patients considered numbness as an insignificant factor in their daily lives.