Influx of T cells into corpus callosum increases axonal injury, but does not change the course of remyelination in toxic demyelination.

Multiple sclerosis (MS) is a focal inflammatory and demyelinating disease. The inflammatory infiltrates consist of macrophages/microglia, T and B cells. Remyelination (RM) is an endogenous repair process which frequently fails in MS patients. In earlier studies, T cells either promoted or impaired RM. Here, we used the combined cuprizone/MOG-EAE model to further dissect the functional role of T cells for RM. The combination of MOG immunization with cuprizone feeding targeted T cells to the corpus callosum and increased the extent of axonal injury. Global gene expression analyses demonstrated significant changes in the inflammatory environment; however, additional MOG immunization did not alter the course of RM. Our results suggest that the inflammatory environment in the combined model affects axons and oligodendrocytes differently and that oligodendroglial lineage cells might be less susceptible to T cell mediated injury.

Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model.

PURPOSE: Curcumin, a polyphenol isolated from the rhizomes of turmeric, holds great potential as a neuroprotective agent in addition to its anti-inflammatory and antioxidant characteristics. The poor bioavailability and low stability of curcumin are the greatest barriers to its clinical use. This study aims to investigate the neuroprotective effect of curcumin on axonal injury, by delivering the lipophilic polyphenol to a primary hippocampal neuron culture by means of a lipid-based drug delivery system, named emulsomes. METHODS: To study neuroregeneration ex vivo, an injury model was established through single-cell laser axotomy on hippocampal neurites. Upon treatment with curcumin-loaded emulsomes (CurcuEmulsomes), curcumin and CurcuEmulsome uptake into neurons was verified by three-dimensional Z-stack images acquired with confocal microscopy. Neuron survival after axonal injury was tracked by propidium iodide (PI) and Hoechst staining. Alterations in expression levels of physiological markers, such as anti-apoptotic marker Bcl2, apoptotic marker cleaved caspase 3, neuroprotective marker Wnt3a and the neuronal survival marker mTOR, were investigated by immunocytochemistry analyses. RESULTS: The results indicated significant improvement in the survival rate of injured neurons upon CurcuEmulsome treatment. Bcl2 expression was significantly higher for injured neurons treated with curcumin or CurcuEmulsome. Reduction in caspase 3 expression was seen in both curcumin and CurcuEmulsome treatment, whereas there were no significant changes in Wnt3a and mTOR expression. CONCLUSION: The established laser-axotomy model was proven as a reliable methodology to study neurodegenerative models ex vivo. CurcuEmulsomes delivered curcumin to primary hippocampal neurons successfully. Treated with CurcuEmulsomes, injured hippocampal neurons benefit from the neuroprotective effects of curcumin, exhibiting a higher survival rate and increased anti-apoptotic marker levels.

Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model.

Combination chemotherapy, administrating two chemotherapeutic agents concurrently, comes into prominence, as the heterogeneity or the level of the disease necessitates a collaborative action. Curcumin, isolated from turmeric, and piperine, isolated from black long pepper, are two dietary polyphenols studied for their intrinsic anti-cancer properties against various cancer types including colorectal cancer (CRC). Furthermore, piperine improves the therapeutic effect of curcumin. Addressing this mutual behavior, this study combines curcumin and piperine within emulsome nanoformulations. Curcumin- (CurcuEmulsomes) and piperine-loaded emulsomes (PiperineEmulsomes) have established a uniform, stable, spherical dispersion with average diameters of 184.21 and 248.76 nm, respectively. The solid tripalmitin inner core achieved encapsulation capacities of up to 0.10 mg/ml curcumin and 0.09 mg/ml piperine content. While piperine treatment alone - in its both free and emulsome forms - showed no inhibition in the proliferation of HCT116 cells in vitro, its presence as the second drug agent enhanced curcumin's effect. Combination of 7 µM PiperineEmulsome and 25 µM CurcuEmulsome concentrations was found to be most effective with an inhibition of cell proliferation of about 50% viability. Cell cycle arrest at G2/M phase and induced apoptosis verified the improved anti-cancer characteristics of the therapy. While CurcuEmulsomes achieved a fourfold increase in Caspase 3 level, combination of treatment with PiperineEulsomes achieved a sixfold increase in the level of this apoptotic marker. Combinational treatment of HCT116 cells with CurcuEmulsomes and PiperineEmulsomes improved the anticancer activity of the compounds and highlighted the potential of the approach for further in vivo studies.

Electrospun Polymers in Cartilage Engineering-State of Play.

Articular cartilage defects remain a clinical challenge. Articular cartilage defects progress to osteoarthritis, which negatively (e.g., remarkable pain, decreased mobility, distress) affects millions of people worldwide and is associated with excessive healthcare costs. Surgical procedures and cell-based therapies have failed to deliver a functional therapy. To this end, tissue engineering therapies provide a promise to deliver a functional cartilage substitute. Among the various scaffold fabrication technologies available, electrospinning is continuously gaining pace, as it can produce nano- to micro- fibrous scaffolds that imitate architectural features of native extracellular matrix supramolecular assemblies and can deliver variable cell populations and bioactive molecules. Herein, we comprehensively review advancements and shortfalls of various electrospun scaffolds in cartilage engineering.

The quality of ECG data acquisition, and diagnostic performance of a novel adhesive patch for ambulatory cardiac rhythm monitoring in arrhythmia detection.

BACKGROUND: Short and long ambulatory electrocardiographic monitoring with different systems is a widely used method to detect cardiac arrhythmias. In this study, we aimed to evaluate the effectiveness of a novel monitoring device on cardiac arrhythmia detection. METHODS: We used two different protocols to evaluate device performance. For the first one, 36 healthy subjects were enrolled. The standard 12­lead, 24-h Holter monitoring and the novel single lead electrocardiogram (ECG) Patch Monitor (EPM) device (BeyondCare®, Rooti Labs Ltd., Taipei, Taiwan) were simultaneously applied to all subjects for 24 h. The quality of ECG data acquisition of novel system was compared to that of standard Holter. The second phase included 73 patients that were referred from our outpatient arrhythmia clinic for evaluation of their symptoms relevant to the cardiac arrhythmias. Advanced algorithms, statistical methods (cross-correlation method, Pearson's correlation coefficient, Bland-Altman plots) were used to process and verify the acquired data. RESULTS: The overall average beat per minute correlation between BeyondCare® and standard 12­lead Holter was found 98% in 33 healthy subjects. The mean percentage of invalid measurements in BeyondCare® was 1.6% while the Holter's was 1.7%. In the second protocol of the study, prospective data from 67 patients who were referred for evaluation of their symptoms relevant to cardiac arrhythmias, showed that the mean BeyondCare® wear time was 4.7 ±â€¯0.5 days out of five total days per protocol. The mean analyzable wear time was 93.6%. The water-resistant design enabled 73.5% of the participants to take a shower. 7.3% of participants had minor skin irritations related to the electrodes. Among the patients with detected arrhythmia (40.2% of all patients), 29.6% had their first arrhythmia after the initial two days period. A clinically significant pause was detected in one patient, ventricular tachycardia was detected in four patients, and supraventricular tachycardia was detected in 15 patients. Paroxysmal atrial fibrillation was identified in seven patients. Three of them had their first episodes after the second day of monitoring. CONCLUSION: BeyondCare® Patch was well-tolerated and allowed prolonged time periods for continuous ECG monitoring, may result in an improvement in clinical accuracy and detection of arrhythmias by cloud-based artificial intelligence operating system.