G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion

G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.open

Factors affecting bone mineral density in children and adolescents with systemic lupus erythematosus

Purpose Patients with juvenile-onset systemic lupus erythematosus (JSLE) are at a high risk of entering adulthood with disease-related morbidities like reduced bone mass and osteoporosis. This study aimed to evaluate the clinical characteristics of JSLE and to analyze the factors associated with low bone mineral density (BMD) in these patients. Methods Children and adolescents diagnosed with JSLE at a single institution in Korea were included. Demographic, clinical, and laboratory data as well as details about the use of glucocorticoids (GCs) and disease-modifying antirheumatic drugs were collected. The lumbar spine (LS) BMD z-score was measured using dual energy x-ray absorptiometry, and lateral thoracolumbar spine radiographs were collected. Results A total of 29 patients with JSLE were included in this study. Of these patients, 7 had a BMD z-score of -2.0 or lower and were designated as the low BMD group. The differences in the clinical parameters and treatment variables between the low BMD and non-low BMD groups were compared. Higher cumulative GC dose, longer GC exposure, and higher cumulative hydroxychloroquine (HCQ) dose were all associated with low BMD; among them, the main factor was the duration of GC exposure. There was no significant correlation between BMD and clinical profile, disease activity, or bone-metabolism markers. Conclusions The duration of GC exposure, cumulative GC dose, and cumulative HCQ dose were risk factors for low BMD in patients with JSLE, with the main factor being the duration of GC exposure. Thus, patients with JSLE should be routinely monitored for low BMD and potential fracture risks, and GC-sparing treatment regimens should be considered

The Cyclosporine-A Treatment does not have Harmful Effect on the Linear Growth of Pediatric Patients with Steroid-dependent and Steroid-resistant Nephrotic Syndrome

Purpose This study was performed to evaluate the effects of cyclosporine-A (CsA) on linear growth in pediatric patients with steroid-dependent (SDNS) or resistant nephrotic syndrome (SRNS). Methods Thirty-five pediatric patients with SDNS or SRNS undergoing glucocorticoid (GC) and/or CsA treatment were retrospectively reviewed. Seventeen patients were treated with GC alone and 18 were treated with GC and CsA. The cumulative doses of GC and CsA were quantified (mg/kg/day). Linear growth during the follow-up period was defined as the difference in Z-score between the initial and final height according to the follow-up period (Δ height Z score/year). The associations between linear growth and clinical parameters were analyzed. Results The linear growth of patients in the two groups was not significantly different (P =0.262). The Δ height Z score/year did not show a significant correlation with the cumulative doses of CsA, but was negatively correlated with the cumulative dose of GC and positively correlated with the Z score for height at the time of diagnosis. Conclusion In children with SDNS or SRNS undergoing GC therapy, added CsA treatment may not have harmful effects on linear growth

Macrolide-refractory Mycoplasma pneumoniae pneumonia and hemophagocytic lymphohistiocytosis: case report and literature review

Mycoplasma pneumoniae causes various extra-pulmonary complications. As a rare but fatal hematological complication, hemophagocytic lymphohistiocytosis (HLH) can be observed in children with M. pneumoniae infection. We report a case of a 6-year-old girl with HLH who was initially presumed to have macrolide-refractory M. pneumoniae pneumonia. Despite the combination treatment of antimicrobial and anti-inflammatory agents, she showed persistent fever, hepatosplenomegaly, and thrombocytopenia. Secondary HLH associated with M. pneumoniae should be considered if unexplained clinical deterioration is noted in children with macrolide-refractory M. pneumoniae pneumonia

Effect of Agrimonia pilosa Ledeb Extract on the Antinociception and Mechanisms in Mouse

In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 µg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (α2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by α2-adrenergic receptor, but not opioidergic and serotonergic receptors