Change in body temperature, not acute-phase reaction, predict anti-Osteoporosis efficacy after the first administration of Zoledronic acid: a prospective observational cohort study.

BACKGROUND: Acute-phase reactions (APRs) are common among people treated for the first time with zoledronate (ZOL). The current view is that both the APRs caused by ZOL and its efficacy are related to the mevalonic acid pathway. However, the relationship between APRs and ZOL efficacy remains unclear. METHODS: This was a prospective observational cohort study involving postmenopausal women with osteoporosis in Shanghai, China, for 1 year. A total of 108 patients with an average age of 67.4 ± 5.8 years were treated with 5 mg intravenous ZOL for the first time. Data on demographic characteristics, APRs, blood counts, bone turnover markers, including C-telopeptide collagen crosslinks (CTX) and N-terminal propeptide of type 1 collagen (PINP), and bone mineral density (BMD) were collected. RESULTS: (1) The results did not reveal a relationship between APRs and changes in bone turnover markers and BMD but showed that changes in body temperature (T) within 3 days after administration were positively correlated with changes in the BMD of the LS at Month 12 (ß = 0.279 P = 0.034). (2) This effect was mediated mainly by changes in serum CTX (b = 0.046, 95% CI [0.0010-0.0091]). (3) The ROC curve revealed that when T increased by 1.95 °C, the sensitivity and specificity of identifying clinically important changes in LS BMD after 1 year were optimized. CONCLUSIONS: In this study, we tested the hypothesis that people with elevated body T after initial ZOL treatment had greater improvements in BMD and better outcomes. TRIAL REGISTRATION: NCT, NCT03158246. Registered 18/05/2017.

Therapeutic Effect of Vinorine on Sciatic Nerve Injured Rat.

Vinorine is a monoterpenoid indole alkaloid, a type of natural alkaloids. Growing reports exhibited the numerous pharmacology activities of vinorine such as anti-inflammation, anti-bacterial and anti-tumor. In this study, the effect of vinorine injection (7.5, 15 and 30 mg/kg) on motor function, sensation and nerve regeneration in sciatic nerve crush injury rat was investigated. The results of behavioral analysis, electrophysiological analysis and muscle histological analysis suggested that vinorine promoted the motor function recovery after sciatic nerve injury. The results of mechanical withdrawal thresholds assay and hot plate test demonstrated that vinorine improved the sensation recovery after sciatic nerve injury. The results of Fluoro-gold retrograde labeling, transmission electron microscope assay, toluidine blue and HE staining showed that vinorine attenuated the nerve damage caused by sciatic nerve injury and promoted the nerve regeneration. Furthermore, nerve growth factor (NGF) and its downstream extracellular signal-regulated kinase (ERK) signaling pathway participated in the neuro-recovery effect of vinorine after crush. In conclusion, vinorine treatment accelerated the sciatic nerve regeneration, motor function recovery and sensation recovery after crush injury via regulation of NGF and ERK activity. These results suggested that vinorine is a promising agent for never injury therapy.

Diagnostic values of NLR and miR-141 in patients with osteoarthritis and their association with severity of knee osteoarthritis.

The present study aimed to explore the diagnostic values of neutrophil-lymphocyte ratio (NLR) and microRNA (miR)-141 in patients with osteoarthritis and their association with the severity of knee osteoarthritis. In total 142 patients with osteoarthritis (the study group) admitted to Shanghai TCM-Integrated Hospital, Shanghai University of TCM from January 2017 to January 2019 and 150 healthy controls (the control group) were enrolled in the present study. NLR and miR-141 in peripheral blood and their diagnostic values for osteoarthritis were compared between the two groups. The two indicators in the study group were significantly increased (P<0.001), and their combined detection had a better diagnostic value for the disease (P<0.001). Moreover, they were closely associated to the progression of the disease and were independent risk factors (P<0.001). To sum up, NLR and miR-141 were significantly increased in the peripheral blood of patients with osteoarthritis. Their combined detection exhibited a good diagnostic value for the disease and may become a potential therapeutic target osteoarthritis in the future.

Heliangin inhibited lipopolysaccharide-induced inflammation through signaling NF-κB pathway on LPS-induced RAW 264.7 cells.

The heliangin is a natural agent mainly isolated from Helianthus tuberosus L. (Asteraceae). In order to investigate the anti-inflammatory effect of heliangin, several typical models in vivo and in vitro were performed. The RAW264.7 mouse macrophages cells were employed in vitro and dexamethasone were conducted as positive. The cytotoxicity results of heliangin on RAW 264.7 cells provided the safety in vitro for further study. The mRNA of TNF-α, IL-6, iNOS and COX-2 were degraded under heliangin exposure in LPS-stimulated RAW 264.7 cells. The protein expression of iNOS, COX-2 were decreased via heliangin exposure in a dose-dependent manner. Heliangin inhibited TNF-α, NO, IL-6 and PGE2 expression levels in macrophage cells lysate. The immunocytochemistry assay showed the fluorescence image of heliangin treatment intercepted the p65 translocation process from outside to inside of nuclei triggered by LPS. Moreover, we founded that MAPK and NF-κB signaling pathway play important roles in heliangin's activity on RAW264.7 cells. Secondly, the acute toxic study results of heliangin manifested the safety in vivo. Heliangin exerted anti-inflammation effect in a xylene-induced ear swelling in BALB/C mice and carrageenan-induced paw edema model in SD rats. The cytokines levels (TNF-α, IL-6 and PGE2) were decreased. The paw tissue immunochemistry assay demonstrated the IL-6 protein level changes in carrageenan-induced paw edema model under heliangin administration.

Antidesmone, a unique tetrahydroquinoline alkaloid, prevents acute lung injury via regulating MAPK and NF-κB activities.

Acute lung injury, characterized by inflammation, is a main cause of respiratory failure that affects patients worldwide. Antidesmone is one compound mainly isolated from Ajugade cumbens Thunb (Labiatae), an herb agent of Labiatae family. In this research, we investigated the anti-inflammation effect of antidesmone in vitro and in vivo. Antidesmone exerted none apparently cytotoxicity in vitro and toxic in vivo. In vitro results demonstrated that antidesmone suppressed the excess inflammatory cytokines production, including tumor necrosis factor-α, interleukin-6 and interleukin-1ß in lipopolysaccharide (LPS)-exposed RAW264.7 cells. In vivo results suggested that antidesmone inhibited inflammatory cytokines in the bronchoalveolar lavage fluid and lung tissue after LPS stimulation. Moreover, antidesmone attenuated the nuclear translocation of p65. Mechanism study revealed that mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways play important roles in antidesmone's action. Taken together, our data uncover a relative toxic anti-inflammatory drug, antidesmone, can inhibit inflammation on stimulated macrophages and thereby prevents acute lung injury by regulating MAPK and NF-κB signaling pathways.

13-Methyl-palmatrubine induces apoptosis and cell cycle arrest in A549 cells in vitro and in vivo.

Corydalis yanhusuo, a well-known herbaceous plant, is commonly used in the treatment of inflammation, injury and pain. One natural agent isolated from Corydalis yanhusuo, 13-methyl-palmatrubine, was found to have a cytotoxic effect on cancer cells as reported in published studies. In the present study, we synthesized a potential anti-lung tumor agent, 13-methyl-palmatrubine and analyzed its activity. 13-Methyl-palmatrubine exhibited a cytotoxic effect on a panel of cancer cell lines in a time- and concentration-dependent manner. Among all the tested cancer cell lines, lung cancer A549 cells were most sensitive to 13-methyl-palmatrubine treatment. Meanwhile 13-methyl-palmatrubine showed less cytotoxicity in human normal cells. Our investigation revealed that 13-methyl­palmatrubine induced apoptosis and cell cycle arrest in A549 cells in a dose-dependent manner. Furthermore, 13-methyl-palmatrubine treatment caused activation of P38 and JNK pathways and blocked the EGFR pathway. In conclusion, our findings demonstrated that 13-methyl-palmatrubine inhibited the growth of A549 cells mediated by blocking of the EGFR signaling pathway and activation of the MAPK signaling pathway and provides a better understanding of the molecular mechanisms of 13-methyl-palmatrubine.