Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD / 生理学报

The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1β (IL-1β), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1β, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.

Computer simulation of molecular docking between methylene blue and some proteins of Porphyromonas gingivalis / 北京大学学报(医学版)

OBJECTIVE@#To study the binding target of photosensitizer and bacteria in antimicrobial photodynamic therapy with computer-simulated target prediction and molecular docking research methods and to calculate the binding energy.@*METHODS@#The protein names of Porphyromonas gingivalis (Pg) were obtained and summarized in Uniprot database and RCSB PDB database; the structure diagrams of methy-lene blue were screened in SciFinder database, PubChem database, ChemSpider database, and Chemical Book, and ChemBioDraw software was used to draw and confirm the three-dimensional structure for target prediction and Cytoscape software was used to build a visual network diagram; a protein interaction network was searched and built between the methylene blue target and the common target of Pg in the String database; then we selected FimA, Mfa4, RgpB, and Kgp K1 proteins, used AutoDock software to calculate the docking energy of methylene blue and the above-mentioned proteins and performed molecular docking.@*RESULTS@#The target prediction results showed that there were 19 common targets between the 268 potential targets of methylene blue and 1 865 Pg proteins. The 19 targets were: groS, radA, rplA, dps, fabH, pyrG, thyA, panC, RHO, frdA, ileS, bioA, def, ddl, TPR, murA, lepB, cobT, and gyrB. The results of the molecular docking showed that methylene blue could bind to 9 sites of FimA protein, with a binding energy of -6.26 kcal/mol; with 4 sites of Mfa4 protein and hydrogen bond formation site GLU47, and the binding energy of -5.91 kcal/mol, the binding energy of LYS80, the hydrogen bond forming site of RgpB protein, was -5.14 kcal/mol, and the binding energy of 6 sites of Kgp K1 protein and the hydrogen bond forming site GLY1114 of -5.07 kcal/mol.@*CONCLUSION@#Computer simulation of target prediction and molecular docking technology can initially reveal the binding, degree of binding and binding sites of methylene blue and Pg proteins. This method provides a reference for future research on the screening of binding sites of photosensitizers to cells and bacteria.

Evaluation of Literature Quality of Randomized Controlled Trials on Wrist-ankle Acupuncture for Low-back Pain / 中国中医药信息杂志

Objective To evaluate the literature quality of randomized controlled trials (RCTs) on wrist-ankle acupuncture (WAA) for low-back pain in recent ten years; To analyze the existing problems in the clinical research;To provide corresponding improvement suggestions. Methods A computer-based retrieval was performed to search out the reports of RCTs on WAA for low-back pain from CNKI, Wanfang Data, CBM, Chongqing VIP, PubMed, and Cochrane Library was retrieved by computers. The search scope was January 1, 2007 - December 31, 2016. The 25 items in the Consolidated Standards of Reporting Trials (CONSORT) Statement and 6 items of the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were consulted for assessing the literature quality of RCTs on WAA for low-back pain. Results 18 articles were included. There were many problems about literature of RCTs on WAA for low-back pain, mainly including that the type of test design was not clear, outcome indicators were incomplete, random method reports were not specific, accepted diagnostic criteria and efficacy criteria were not used, reporting interventions were incomplete. Conclusion Recently, literature quality of RCTs on WAA for low-back pain is low. It is suggested that CONSORT Statement and STRICTA should be taken into consideration in the conducting and reporting of RCTs on WAA for low-back pain, and the report quality of clinical research in this field should be improved.

A dynamic finite element analysis of stress distribution in bone tissue surrounding solely or splinted implant-borne fixed partial denture / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study the distribution patterns of stresses induced in bone tissue surrounding solely and splinted implants under dynamic loads.</p><p><b>METHODS</b>Three dimensional finite-element models were created of two 765 sections of the mandible with solely or splinted implants embedded in. Vertical and oblique dynamic loads were applied in a circle of mastication (0.875 s). The stress distribution was analyzed to study the biomechanical behavior of bone tissue surrounding solely or splinted implants.</p><p><b>RESULTS</b>As loading on the solely implant 5, the maximum von Mises value in the surrounding bone tissue under oblique loads at 0.300 s was 4.2 times as much as that under vertical loads at 0.150 s. Meanwhile, as coincidently loading on the splinted implants, the maximum von Mises value at 0.300 s was 1.2 times as much as that at 0.150 s. As loading on the solely implant 5, the maximum stress value was 48.393 MPa at 0.300 s. As separately loading on the splinted implant 5, the maximum stress value of the whole model was 9.541 MPa in the same loading course, and the maximum stress was located at the distal cervical of the indirectly loaded implant 7. When loading on the pontic, the stress in bone tissue surrounding implant 7 was more than that of implant 5.</p><p><b>CONCLUSIONS</b>Stress in the bone-interface of the splinted implants is evenly distributed at the cervical level, which may also reduce disadvantages from oblique loads.</p>