Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION: FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Two new alkaloids from a strain of endophytic fungus Aspergillus sp.

19-Hydroxybrevianamide M (1) and 6 R-methoxybrevianamide V (2), two new alkaloids, were isolated from an extract of the endophytic fungus Aspergillus sp. JNU18HC0517J, together with six known analogues (3- 8). Their structures were elucidated by extensive spectroscopic analyses, NMR calculations, and ECD calculations. 6 R-methoxybrevianamide V (2) was the first L-proline indole DKP alkaloid with substitution at C-6 on the proline ring. Furthermore, the cytotoxities and antimicrobial activities of these isolated compounds were also evaluated. Compound 8 exhibited moderate antibacterial activity against Staphylococcus aureus 209 P with a minimal inhibitory concentration (MIC) value of 16 µg/ml.[Figure: see text].

Recent Advances and Perspective of Nanotechnology-Based Implants for Orthopedic Applications.

Bioimplant engineering strives to provide biological replacements for regenerating, retaining, or modifying injured tissues and/or organ function. Modern advanced material technology breakthroughs have aided in diversifying ingredients used in orthopaedic implant applications. As such, nanoparticles may mimic the surface features of real tissues, particularly in terms of wettability, topography, chemistry, and energy. Additionally, the new features of nanoparticles support their usage in enhancing the development of various tissues. The current study establishes the groundwork for nanotechnology-driven biomaterials by elucidating key design issues that affect the success or failure of an orthopaedic implant, its antibacterial/antimicrobial activity, response to cell attachment propagation, and differentiation. The possible use of nanoparticles (in the form of nanosized surface or a usable nanocoating applied to the implant's surface) can solve a number of problems (i.e., bacterial adhesion and corrosion resilience) associated with conventional metallic or non-metallic implants, particularly when implant techniques are optimised. Orthopaedic biomaterials' prospects (i.e., pores architectures, 3D implants, and smart biomaterials) are intriguing in achieving desired implant characteristics and structure exhibiting stimuli-responsive attitude. The primary barriers to commercialization of nanotechnology-based composites are ultimately discussed, therefore assisting in overcoming the constraints in relation to certain pre-existing orthopaedic biomaterials, critical factors such as quality, implant life, treatment cost, and pain alleviation.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants for venous thromboembolism: a meta-analysis.

OBJECTIVE: Several trials had compared the efficacy and safety between non-vitamin K antagonist oral anticoagulants and warfarin for acute venous thromboembolism, but the results were incomplete. This updated review comprehensively assessed the efficacy and safety of non-vitamin K antagonist oral anticoagulants for venous thromboembolism. DESIGN: Meta-analysis of randomised control trials. Six databases were searched from January 2000 to December 2018. SETTING: Adult patients had got non-vitamin K antagonist oral anticoagulants or warfarin for venous thromboembolism. PARTICIPANTS: Randomised control trials that compared the efficacy and safety between non-vitamin K antagonist oral anticoagulants and warfarin. MAIN OUTCOME MEASURES: The efficacy and safety of non-vitamin K antagonist oral anticoagulants . RESULTS: Seven studies involving 29,879 cases were included, among which 14,943 cases were assigned to non-vitamin K antagonist oral anticoagulants group and 14,936 cases to warfarin group. Meta-analysis showed that compared with warfarin, recurrent venous thromboembolism (odds ratio 0.94 [95% confidence interval 0.81 to 1.11]), death related to venous thromboembolism or fatal pulmonary embolism (odds ratio 1.00 [95% confidence interval 0.63 to 1.60]), symptomatic deep-vein thrombosis (odds ratio 0.88 [95% confidence interval 0.72 to 1.09]), symptomatic nonfatal pulmonary embolism (odds ratio 1.03 [(95% confidence interval 0.82 to 1.30]) and all deaths (odds ratio 0.92 [95% confidence interval 0.76 to 1.12]) are similar in non-vitamin K antagonist oral anticoagulants group, but major bleeding event (odds ratio 0.61 [95% confidence interval 0.50 to 0.75]) and clinically relevant non-major bleeding event (odds ratio [95% confidence interval 0.53 to 0.85]) are less in non-vitamin K antagonist oral anticoagulants group. . CONCLUSIONS: For the treatment of venous thromboembolism, non-vitamin K antagonist oral anticoagulants is as effective as warfarin, and has a better safety profile than warfarin.

HMGB1 promotes bone fracture healing through activation of ERK signaling pathway in a rat tibial fracture model.

This work was to investigate potential roles of HMGB1-mediated ERK pathway in the healing process of bone fracture. Rat tibial fracture models were established and divided into control (rats with normal saline), HMGB1 (rats with HMGB1), and HMGB1+ PD98059 groups (rats with HMGB1 and 1 mg/kg of ERK1/2 inhibitor PD98059) with 30 rats per each. The healing of rats' fracture was observed by X-ray films, the morphological changes of bone fractures by HE staining, the callus formation by micro-CT and biomechanical test, and the expression of osteogenesis-related genes, HMGB1 and ERK-related proteins by qRT-PCR and Western blot. Rats in the HMGB1 group was increased in X-ray scores, peak torque, torsional stiffness, and the bone volume fraction (bone volume/total volume, BV/TV); meanwhile, those rats presented elevations in osteogenesis-related genes and HMGB1 expressions, as well as p-ERK/ERK ratio. However, rats in the HMGB1+ PD98059 group was significantly reduced in X-ray score, peak torque, torsional stiffness, and BV/TV, as well as the expression of osteogenesis-related genes and the ratio of p-ERK/ERK, as compared to those from HMGB1 group. HMGB1 could promote the expressions of osteogenesis-related genes and accelerate the healing process of fracture via activation of the ERK signaling pathway.

[Effect of qi benefiting stasis removing method on systemic inflammatory response and coagulation function in MODS patients].

OBJECTIVE: To observe the effect of qi benefiting stasis removing method (QBSRM) on systemic inflammatory response and coagulation function in multiple organ dysfunction syndrome (MODS) patients. METHODS: Totally 40 MODS patients who were admitted to Affiliated Hospital of Nanjing University of Traditional Chinese Medicine between May 2010 to December 2011 were randomly assigned to two groups, the experimental group (21 cases) and the control group (19 cases). Patients in the control group were treated with routine Western therapy, while those in the experimental group additionally took decoction for benefiting qi removing stasis. Inflammatory factors (including interleukin-1, interleukin-6, tumor necrosis factor-alpha) and coagulation parameters [including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (DD)] were observed before treatment, and 3, 7, and 14 days after treatment in the two groups. RESULTS: At day 7 after treatment,levels of interleukin-1, interleukin-6, and PT were significantly lower in the experimental group than in the control group (P < 0.05). At day 14 after treatment, tumor necrosis factor-x and DD were significantly lower in the experimental group than in the control group (P < 0. 05). There was no statistical difference in APTT or FIB at day 3, 7 and 14 after treatment (P > 0.05). CONCLUSION: QBSRM could relieve systemic inflammatory response and improve coagulation functions.