Cyclodextrin-erythromycin complexes as a drug delivery device for orthopedic application

Wei Song1, Xiaowei Yu2, Sunxi Wang5, Ralph Blasier4, David C Markel3, Guangzhao Mao5, Tong Shi1, Weiping Ren1,31Department of Biomedical Engineering, Wayne State University, Detroit, MI, USA; 2Department of Orthopedic Surgery, Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3Detroit Medical Center and Providence Hospital Orthopedic Residency, Detroit, 4Orthopedic Section, St Francis Hospital, Escanaba, 5Department of Chemical Engineering, Wayne State University, Detroit, MI, USABackground: Erythromycin, a hydrophobic antibiotic used to treat infectious diseases, is now gaining attention because of its anti-inflammatory effects and ability to inhibit osteoclasts formation. The aim of this study was to explore a cyclodextrin-erythromycin (CD-EM) complex for sustained treatment of orthopedic inflammation.Methods and results: Erythromycin was reacted with ß-cyclodextrin to form a nonhost-guest CD-EM complex using both kneading and stirring approaches. Physiochemical measurement data indicated that erythromycin and cyclodextrin formed a packing complex driven by intermolecular forces instead of a host-guest structure due to the limited space in the inner cavity of ß-cyclodextrin. The CD-EM complex improved the stability of erythromycin in aqueous solution and had a longer duration of bactericidal activity than free erythromycin. Cytotoxicity and cell differentiation were evaluated in both murine MC3T3 preosteoblast cells and RAW 264.7 murine macrophage cells. The CD-EM complex was noncytotoxic and showed significant inhibition of osteoclast formation but had little effect on osteoblast viability and differentiation.Conclusion: These attributes are especially important for the delivery of an adequate amount of erythromycin to the site of periprosthetic inflammation and reducing local inflammation in a sustained manner.Keywords: erythromycin, cyclodextrin, drug stability, bactericidal activity, osteoclastogenesi

Chinese expert consensus on minimally invasive interventional treatment of trigeminal neuralgia

Background and purposeTrigeminal neuralgia is a common condition that is associated with severe pain, which seriously affects the quality of life of patients. When the efficacy of drugs is not satisfactory or adverse drug reactions cannot be tolerated, minimally invasive interventional therapy has become an important treatment because of its simple operation, low risk, high repeatability and low cost. In recent years, minimally invasive interventional treatments, such as radiofrequency thermocoagulation (RF) of the trigeminal nerve and percutaneous microcompression (PMC), have been widely used in the clinic to relieve severe pain in many patients, however, some related problems remain to be addressed. The Pain Association of the Chinese Medical Association organizes and compiles the consensus of Chinese experts to standardize the development of minimally invasive interventional treatment of trigeminal neuralgia to provide a basis for its clinical promotion and application.Materials and methodsThe Pain Association of the Chinese Medical Association organizes the Chinese experts to compile a consensus. With reference to the evidence-based medicine (OCEBM) system and the actual situation of the profession, the Consensus Development Committee adopts the nominal group method to adjust the recommended level.ResultsPrecise imaging positioning and guidance are the keys to ensuring the efficacy and safety of the procedures. RF and PMC are the most widely performed and effective treatments among minimally invasive interventional treatments for trigeminal neuralgia.ConclusionsThe pain degree of trigeminal neuralgia is severe, and a variety of minimally invasive intervention methods can effectively improve symptoms. Radiofrequency and percutaneous microcompression may be the first choice for minimally invasive interventional therapy

Model Passengers’ Travel Time for Conventional Bus Stop

Limited number of berths can result in a subsequent bus stopping at the upstream of a bus stop when all berths are occupied. When this traffic phenomenon occurs, passengers waiting on the platform usually prefer walking to the stopped bus, which leads to additional walking time before boarding the bus. Therefore, passengers’ travel time consumed at a bus stop is divided into waiting time, additional walking time, and boarding time. This paper proposed a mathematical model for analyzing passengers’ travel time at conventional bus stop based on theory of stochastic service system. Field-measured and simulated data were designated to demonstrate the effectiveness of the proposed model. By analyzing the results, conclusion was conducted that short headway can reduce passengers’ waiting time at bus stop. Meanwhile, the theoretical analysis explained the inefficiency of bus stops with more than three berths from the perspective of passengers’ additional walking time. Additional walking time will increase in a large scale when the number of berths at a bus stop exceedsthe threshold of three

Construction and expression identification of human secreted apoptosis-related protein 1 gene yeast two-hybrid bait vector

Objective: To construct human secreted apoptosis-related protein 1 (SARP1) gene yeast two-hybrid bait vector so as to study the biological functions of the SARP1 gene in the scar tissue. Methods: The target gene from SARP1 gene full-length DNA segment was amplified by PCR, the upstream and downstream primers of the SARP1 gene with restriction enzymes Nde I and Sal I were designed. pGBKT7-SARP1 recombination plasmid was constructed by ligating the vector and the PCR production and identified by PCR and sequencing. Furthermore, pGBKT7-SARP1 was transformed into competent AH109 which contained kanamycin for selecting positive clones and screened the positive clony on the plate of SD/-Trp. The toxicity and transcriptional activation were tested by the phenotype assay. Results SARP1 was amplified and cloned into pGBKT7 successfully, SARP1 gene sequence in recombinant plasmid pGBKT7-SARP1 was verified by gel electrophoresis and DNA sequencing analysis. The sequence of inserted SARP1 gene was the same as the corresponding sequence found in GenBank database. The recombinant pGBKT7-SARP1 plasmids and empty pGBKT7 vector could form white colonies on SD/-Trp plates and none could survive on SD/-Leu plates. Conclusion The recombinant pGBKT7-SARP1 gene yeast two-hybrid bait vector is successfully constructed

The mechanisms of MicroRNA 21 in premature ovarian insufficiency mice with mesenchymal stem cells transplantation

Abstract Umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation has been deeply explored for premature ovarian insufficiency (POI) disease. However, the associated mechanism remains to be researched. To explore whether and how the microRNA 21 (miR-21) functions in POI mice with UCMSCs transplantation, the autoimmune-induced POI mice model was built up, transplanted with or without UCMSCs transfect with the LV-hsa-miR-21-5p/LV-hsa-miR-21-5p-inhibition, with the transfection efficiency analyzed by QRT-PCR. Mice hormone secretion and the anti-Zona pellucida antibody (AZPAb) levels were analyzed, the ovarian morphological changes and folliculogenesis were observed, and the ovarian apoptosis cells were detected to evaluate ovarian function. The expression and localization of the PTEN/Akt/FOXO3a signal pathway-related cytokines were analyzed in mice ovaries. Additionally, the spleen levels of CD8 + CD28-T cells were tested and qualified with its significant secretory factor, interleukin 10 (IL-10). We found that with the LV-hsa-miR-21-5p-inhibition-UCMSCs transplantation, the mice ovarian function can be hardly recovered than mice with LV-NC-UCMSCs transplantation, and the PTEN/Akt/FOXO3a signal pathway was activated. The expression levels of the CD8 + CD28-T cells were decreased, with the decreased levels of the IL-10 expression. In contrast, in mice with the LV-hsa-miR-21-5p-UCMSCs transplantation, the injured ovarian function can be reversed, and the PTEN/AKT/FOXO3a signal pathway was detected activated, with the increased levels of the CD8 + CD28-T cells, and the increased serum levels of IL-10. In conclusion, miR-21 improves the ovarian function recovery of POI mice with UCMSCs transplantation, and the mechanisms may be through suppressing the PTEN/AKT/FOXO3a signal pathway and up-regulating the circulating of the CD8 + CD28-T cells

Oxygen surface groups of activated carbon steer the chemoselective hydrogenation of substituted nitroarenes over nickel nanoparticles

Oxygen surface groups of activated carbon, produced by nitric acid treatment, are not only able to prevent Ni particles from sintering but are also able to preferentially interact with the nitro group of substituted nitroarenes. The resulting Ni/AC(OX) catalyst is highly active and chemoselective for hydrogenation of nitroarenes to produce functionalized anilines and oximes

Human Grasp Mechanism Understanding, Human-Inspired Grasp Control and Robotic Grasping Planning for Agricultural Robots

As the end execution tool of agricultural robots, the manipulator directly determines whether the grasping task can be successfully completed. The human hand can adapt to various objects and achieve stable grasping, which is the highest goal for manipulator design and development. Thus, this study combines a multi-sensor fusion tactile glove to simulate manual grasping, explores the mechanism and characteristics of the human hand, and formulates rational grasping plans. According to the shape and size of fruits and vegetables, the grasping gesture library is summarized to facilitate the matching of optimal grasping gestures. By analyzing inter-finger curvature correlations and inter-joint pressure correlations, we investigated the synergistic motion characteristics of the human hand. In addition, the force data were processed by the wavelet transform algorithms and then the thresholds for sliding detection were set to ensure robust grasping. The acceleration law under the interaction with the external environment during grasping was also discussed, including stable movement, accidental collision, and placement of the target position. Finally, according to the analysis and summary of the manual gripping mechanism, the corresponding pre-gripping planning was designed to provide theoretical guidance and ideas for the gripping of robots

Oxygen surface groups of activated carbon steer the chemoselective hydrogenation of substituted nitroarenes over nickel nanoparticles

Oxygen surface groups of activated carbon, produced by nitric acid treatment, are not only able to prevent Ni particles from sintering but are also able to preferentially interact with the nitro group of substituted nitroarenes. The resulting Ni/AC(OX) catalyst is highly active and chemoselective for hydrogenation of nitroarenes to produce functionalized anilines and oximes

Genome-Wide Analysis and Functional Characterization of the UDP-Glycosyltransferase Family in Grapes

Grape (Vitis vinifera) produces a variety of secondary metabolites, which can enhance nutrients and flavor in fruit and wine. Uridine diphosphate-glycosyltransferases (UGTs) are primarily responsible for the availability of secondary metabolites by glycosylation modification. Here, a total of 228 putative UGTs were identified in V. vinifera, and VvUGTs were clustered into 15 groups (A to O) and unevenly distributed on 18 chromosomes. Diverse VvUGT members from 12 groups were transcribed, and they responded to different external stresses. More than 72% of VvUGT members were expressed at one or more stages of grape fruit development, and the expression levels of 34 VvUGT members increased gradually with fruit ripening. The VvUGT members of different groups may be involved in the synthesis and accumulation of flavonoid glycosides, glycosidically bound volatiles, and stilbenes. These results will provide guidance for further research on the functions and regulating mechanisms of UGT genes