Tribological behavior of shape-specific microplate-enriched synovial fluids on a linear two-axis tribometer

Nano- and micro-particles are being increasingly used to tune interfacial frictional properties in diverse applications, from friction modifiers in industrial lubrication to enhanced biological fluids in human osteoarthritic joints. Here, we assessed the tribological properties of a simulated synovial fluid enriched with non-spherical, poly lactic-co-glycolic acid (PLGA) microparticles (μPL) that have been previously demonstrated for the pharmacological management of osteoarthritis (OA). Three different μPL configurations were fabricated presenting a 20 μm 20 μm square base and a thickness of 5 μm (thin, 5H μPL), 10 μm (10H μPL), and 20 μm (cubical, 20H μPL). After extensive morphological and physicochemical characterizations, the apparent Young’s modulus of the μPL was quantified under compressive loading returning an average value of 6 kPa, independently of the particle morphology. Then, using a linear two-axis tribometer, the static (μs) and dynamic (μd) friction coefficients of the μPL-enriched simulated synovial fluid were determined in terms of particle configuration and concentration, varying from 0 (fluid only) to 6105 μPL/mL. The particle morphology had a modest influence on friction, possibly because the μPL were fully squeezed between two mating surfaces by a 5.8 N normal load realizing boundary-like lubrication conditions. Differently, friction was observed to depend on the dimensionless parameter , defined as the ratio between the total volume of the μPL enriching the simulated synovial fluid and the volume of the fluid itself. Both coefficients of friction were documented to grow with reaching a plateau of μs 0.4 and μd 0.15, already at  210-3. Future investigations will have to systematically analyze the effect of sliding velocity, normal load, and rigidity of the mating surfaces to elucidate in full the tribological behavior of μPL in the context of osteoarthritis

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination

Simple SummaryEmerging evidence has suggested that cancer-derived extracellular vesicles (EVs) have a crucial role in mediating directional metastasis to the peritoneal surface in colorectal cancer (CRC). We investigated the EV-mediated crosstalk between tumor and mesothelial cells which may drive remodeling of the premetastatic niche to allow tumor spread to the peritoneal surface. Our findings demonstrated that cancer-derived EVs triggered apoptosis and reduced mesothelial cell invasiveness and mesothelial-to-mesenchymal transition. On the other hand, mesothelial cells actively supported tumor invasion by releasing EVs, which induced upregulation of the major pro-invasive system in tumor cells. For the first time, we provide evidence of EV-driven mechanisms of CRC progression in patient-derived models, highlighting the crucial role of EVs in the reprogramming of mesothelial and tumor cells to establish the metastatic process.Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-beta 1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients

Performance Evaluation of a Commercial Real-Time PCR Method for the Detection of Lupin Traces in Food

In accordance with U.S. FDA Foods Program Regulatory Science Steering Committee guidelines, with this study, we optimized and validated a commercial real-time PCR method for the detection of low amounts of lupin in four classes of food matrices: chocolate cookies, ragù, Olivier salad, and barley and rice flour. DNA extracted from blank (true negative) samples artificially contaminated with lupin (Lupinus albus) flour at 1000 ppm underwent dilutions with the DNA extracted from the true negative samples up to 0.5 ppm. The limit of detection for real-time PCR was 0.5 ppm in the complex matrices (range, Ct 26–34), making this a specific, robust, and rapid method for lupin allergen detection and labeling. Our validation data support the suitability of this commercially available real-time PCR method for this purpose

Nonobstructive versus obstructive coronary artery disease in acute coronary syndrome: A meta-analysis

Background--Differences in prognosis and baseline clinical presentation have been documented among patient with acute coronary syndrome and coronary artery disease with obstructive (ObCAD) or nonobstructive arteries (NObCAD), but the rates of events largely varied across single studies. We carried out a meta-analysis to compare the clinical presentation and prognosis of NObCAD versus ObCAD acute coronary syndrome patients, as well as of the subjects with zero versus mild occlusion. Methods and Results--Searches were made in MedLine, EMBASE, Cochrane databases, and proceedings of international meetings up to June 30, 2015. We compared the risk of events of NObCAD versus ObCAD patients using random-effect metaanalyses. We also performed meta-analyses to estimate the yearly or monthly outcome rates in each single group. In NObCAD and ObCAD patients, respectively, the combined yearly rates were as follows: 2.4% versus 10.1% (all-cause mortality); 1.2% versus 6.0% (myocardial infarction), 4.0% versus 12.8% (all-cause mortality plus myocardial infarction), 1.4% versus 5.9% (cardiac death), and 9.2% versus 16.8% (major cardiovascular events). In the studies directly comparing NObCAD versus ObCAD, all of the above outcomes were significantly less frequent in NObCAD subjects (with risk ratios ranging from 0.33 to 0.66). No differences in any outcome rate were observed between mild occlusion (1-49% stenosis) and zero occlusion patients. Conclusions--NObCAD in patients with acute coronary syndrome has a significantly lower cardiovascular risk at baseline and a subsequent lower likelihood of death or main cardiovascular events. However, these subjects are still at high risk for cardiovascular mortality and morbidity, suggesting potential undertreatment and calling for specific management

Tribological behavior of shape-specific microplate-enriched synovial fluids on a linear two-axis tribometer

Abstract Nano- and micro-particles are being increasingly used to tune interfacial frictional properties in diverse applications, from friction modifiers in industrial lubrication to enhanced biological fluids in human osteoarthritic joints. Here, we assessed the tribological properties of a simulated synovial fluid enriched with non-spherical, poly lactic-co-glycolic acid (PLGA) microparticles (µPL) that have been previously demonstrated for the pharmacological management of osteoarthritis (OA). Three different µPL configurations were fabricated presenting a 20 µm × 20 µm square base and a thickness of 5 µm (thin, 5H µPL), 10 µm (10H µPL), and 20 µm (cubical, 20H µPL). After extensive morphological and physicochemical characterizations, the apparent Young’s modulus of the µPL was quantified under compressive loading returning an average value of ∼ 6 kPa, independently of the particle morphology. Then, using a linear two-axis tribometer, the static (µ s) and dynamic (µ d) friction coefficients of the µPL-enriched simulated synovial fluid were determined in terms of particle configuration and concentration, varying from 0 (fluid only) to 6µ105 µPL/mL. The particle morphology had a modest influence on friction, possibly because the µPL were fully squeezed between two mating surfaces by a 5.8 N normal load realizing boundary-like lubrication conditions. Differently, friction was observed to depend on the dimensionless parameter Ω, defined as the ratio between the total volume of the µPL enriching the simulated synovial fluid and the volume of the fluid itself. Both coefficients of friction were documented to grow with Ω reaching a plateau of µ s ∼ 0.4 and µ d ∼ 0.15, already at Ω ∼ 2×10−3. Future investigations will have to systematically analyze the effect of sliding velocity, normal load, and rigidity of the mating surfaces to elucidate in full the tribological behavior of µPL in the context of osteoarthritis

Augmented efficacy of nano-formulated docetaxel plus curcumin in orthotopic models of neuroblastoma

Neuroblastoma is a biologically heterogeneous extracranial tumor, derived from the sympathetic nervous system, that affects most often the pediatric population. Therapeutic strategies relying on aggressive chemotherapy, surgery, radiotherapy, and immunotherapy have a negative outcome in advanced or recurrent disease. Here, spherical polymeric nanomedicines (SPN) are engineered to co-deliver a potent combination therapy, including the cytotoxic docetaxel (DTXL) and the natural wide-spectrum anti-inflammatory curcumin (CURC). Using an oil-in-water emulsion/solvent evaporation technique, four SPN configurations were engineered depending on the therapeutic payload and characterized for their physico-chemical and pharmacological properties. All SPN configurations presented a hydrodynamic diameter of similar to 185 nm with a narrow size distribution. A biphasic release profile was observed for all the configurations, with almost 90 % of the total drug mass released within the first 24 h. SPN cytotoxic potential was assessed on a panel of human neuroblastoma cells, returning IC50 values in the order of 1 nM at 72 h and documenting a strong synergism between CURC and DTXL. Therapeutic efficacy was tested in a clinically relevant orthotopic model of neuroblastoma, following the injection of SH-SY5Y-Luc(+) cells in the left adrenal gland of athymic mice. Although -2 % of the injected SPN per mass tissue reached the tumor, the overall survival of mice treated with CURC/DTXL-SPN was extended by 50 % and 25 % as compared to the untreated control and the monotherapies, respectively. In conclusion, these results demonstrate that the therapeutic potential of the DTXL/CURC combination can be fully exploited only by reformulating these two compounds into systemically injectable nanoparticles

A Novel Technique of Digestive Anastomosis Reinforcement Using Bovine Pericardium Patch

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