SPION based magnetic PLGA nanofibers for neural differentiation of mesenchymal stem cells.

Recently, magnetic platforms have been widely investigated in diagnostic, therapeutic and research applications due to certain properties, such as cell and tissue tracking and imaging, thermal therapy and being dirigible. In this study, the incorporation of magnetic nanoparticles (MNPs) in nanofibers has been proposed to combine the advantages of both nanofibers and MNPs to induce neural differentiation of mesenchymal stem cells. Magnetic poly (lactic-co-glycolic acid) nanofibers (containing 0%, 5% and 10% SPION) were fabricated and utilized as the matrix for the differentiation of mesenchymal stem cells (MSCs). Morphological, magnetic and mechanical properties were analyzed using FESEM, VSM and tensile test, respectively. The expression of neural markers (TUJ-1, NSE, MAP-2) was assessed quantitative and qualitatively utilizing RT-PCR and immunocytochemistry. Results confirmed the incorporation of MNPs in nanofibrous scaffold, presenting a saturation magnetization of 9.73 emu g-1. Also, with increase in magnetic particle concentration (0%-10%), tensile strength increased from 4.08 to 5.85 MPa, whereas the percentage of elongation decreased. TUJ-1 expression was 3.8 and 1.8 fold for 10% and 5% magnetic scaffold (versus non-magnetic scaffold) respectively, and the expression of NSE was 6.3 and 1.2-fold for 10% and 5%, respectively. Consequently, it seems that incorporation of magnetic biomaterial can promote the neural differentiation of MSCs, during which the augmentation of super paramagnetic iron oxide concentration from 0% to 10% accelerates the neural differentiation process.

Adsorption, and controlled release of doxorubicin from cellulose acetate/polyurethane/multi-walled carbon nanotubes composite nanofibers.

The cellulose acetate (CA)/poly (ε-caprolactone diol)/poly (tetramethylene ether) glycol-polyurethane (PCL-Diol/PTMG-PU)/multi-walled carbon nanotubes (MWCNTs) composite nanofibers were prepared via two-nozzle electrospinning on both counter sides of the collector. The performance of synthesized composite nanofibers was investigated as an environmental application and anticancer delivery system for the adsorption/release of doxorubicin (DOX). The synergic effect of MWCNTs and DOX incorporated into the nanofibers was investigated against LNCaP prostate cancer cells. The status of MWCNTs and DOX in composite nanofibers was demonstrated by SEM, FTIR and UV-vis determinations. The adsorption tests using nanofibrous adsorbent toward DOX sorption was evaluated under various DOX initial concentrations (100-2000 mg l-1), adsorption times (5-120 min), and pH values (pH:2-9). Due to the fitting of isotherm and kinetic data with Redlich-Peterson and pseudo-second order models, both chemisorption and surface adsorption of DOX molecules mechanisms have been predicted. The drug release from both nanofibers and MWCNTs-loaded nanofibers was compared. The better drug sustained release profiles verified in the presence of composite nanofibers. LNCaP prostate cancer and L929 normal cells were treated to investigate the cytotoxicity and compatibility of synthesized composite nanofibers. The apoptosis/necrosis of hybrid nanofibers and MWCNTs loaded-nanofibers was investigated. The obtained results demonstrated the synergic effects of MWCNTs and DOX loaded-nanofibers on the LNCaP prostate cancer cells death.

Comparing the use of conventional and three-dimensional printing (3DP) in mandibular reconstruction.

BACKGROUND: There are a number of clinical disorders that require mandibular reconstruction (MR). Novel three-dimensional (3D) printing technology enables reconstructions to be more accurate and beneficial to the patient. However, there is currently no evidence identifying which techniques are better suited for MR, based on the type of clinical disorder the patient has. In this study, we aim to compare 3D techniques with conventional techniques to identify how best to reconstruct the mandible based on the clinical cause that necessitates the reconstructive procedure: cancerous or benign tumours, clinical disorders, infection or disease and trauma or injury. METHODS: PubMed, Scopus, Embase and Medline were searched to identify relevant papers that outline the clinical differences between 3D and conventional techniques in MR. Data were evaluated to provide a clear outline of suitable techniques for surgery. RESULTS: 20 of 2749 papers met inclusion criteria. These papers were grouped based on the clinical causes that required MR into four categories: malignant or benign tumour resection; mandibular trauma/injury and other clinical disorders. CONCLUSIONS: The majority of researchers favoured 3D techniques in MR. However, due to a lack of standardised reporting in these studies it was not possible to determine which specific techniques were better for which clinical presentations.

The application of 3D printing in preoperative planning for transcatheter aortic valve replacement: a systematic review.

BACKGROUND: Recently, transcatheter aortic valve replacement (TAVR) has been suggested as a less invasive treatment compared to surgical aortic valve replacement, for patients with severe aortic stenosis. Despite the attention, persisting evidence suggests that several procedural complications are more prevalent with the transcatheter approach. Consequently, a systematic review was undertaken to evaluate the application of three-dimensional (3D) printing in preoperative planning for TAVR, as a means of predicting and subsequently, reducing the incidence of adverse events. METHODS: MEDLINE, Web of Science and Embase were searched to identify studies that utilised patient-specific 3D printed models to predict or mitigate the risk of procedural complications. RESULTS: 13 of 219 papers met the inclusion criteria of this review. The eligible studies have shown that 3D printing has most commonly been used to predict the occurrence and severity of paravalvular regurgitation, with relatively high accuracy. Studies have also explored the usefulness of 3D printed anatomical models in reducing the incidence of coronary artery obstruction, new-onset conduction disturbance and aortic annular rapture. CONCLUSION: Patient-specific 3D models can be used in pre-procedural planning for challenging cases, to help deliver personalised treatment. However, the application of 3D printing is not recommended for routine clinical practice, due to practicality issues.

Impact of heterotopic ossification following lumbar total disk replacement: a systematic review.

BACKGROUND CONTEXT: Lumbar total disc replacement (TDR) is an alternative to lumbar fusion in the treatment of lower back pain and reduces the risk of adjacent segment degeneration. Heterotopic ossification (HO) has been identified as a common complication following lumbar TDR. PURPOSE: This systematic review aims to determine the prevalence, risk factors and clinical and radiological impact of HO following lumbar TDR. STUDY DESIGN: Systematic Review. METHODS: MEDLINE, Scopus, PubMed and Cochrane Central were searched for articles that referred to lumbar TDR and HO. The hits were assessed against inclusion and exclusion criteria. Data from each included study was extracted and analysed with respect to the study aims. RESULTS: Twenty-six studies were included in this review and the pooled prevalence of HO was estimated to be between 13.2% (participants) and 15.3% (vertebral levels). TDR clinical outcomes were not found to be reduced by HO and there was insufficient data to identify a given impact upon radiological outcomes. Age and follow up time were identified as potential risk factors for HO. CONCLUSIONS: This review was hampered by inconsistencies in the reporting of HO across the studies. We therefore recommend that a set of guidelines should be produced to aid future researchers and reduce the risk of bias.

Microclimatic Evaluation of Five Types of Colombian Greenhouses Using Geostatistical Techniques.

In Colombia, the second-largest exporter of cut flowers worldwide and one of the South American countries with the largest area of crops under cover, passive or naturally ventilated greenhouses predominate. Locally, there are several types of greenhouses that differ in architecture, size, height, shape of roof and ventilation surfaces, of which many characteristics of the microclimate generated in their interior environment are unknown. This generates productive limitations that in some way may be limiting the yield, quality and health of the final products harvested; in addition, Colombian producers do not have the ability to monitor the microclimate of their farms, much less to correlate microclimate data with data on crop production and yield. Therefore, there is a need for the Colombian grower to know the most relevant microclimate characteristics generated in the main greenhouses used locally. The objective of this work was to carry out a microclimatic characterization of the five most used types of greenhouses in Colombia. The main results allowed determining that in these structures, there are conditions of high humidity and low vapor pressure for several hours of the day, which affects the physiological processes of growth and development of the plants. It was also identified that for each type of greenhouse, depending on the level of radiation, there is a significant microclimatic heterogeneity that may be the cause of the heterogeneity in plant growth, which is a common characteristic observed by the technical cultivation personnel. Therefore, it can be concluded that it is urgent to propose microclimatic optimization strategies to help ensure the sustainability of the most important production systems in the country.

Potential anticancer activity of a new pro-apoptotic peptide-thioctic acid gold nanoparticle platform.

Targeted nanoparticle platforms designed to induce cell death by apoptosis can bypass the resistance mechanisms of cancer cells. With this in mind we have constructed a new cancer-targeting peptide-functionalized nanoparticle using gold nanoparticles (AuNPs) and a thioctic acid-DMPGTVLP peptide (TA-peptide) conjugate. Morphological analysis of the nanoparticles by transmission electron microscopy showed average diameters of about 3.52 nm and 26.2 nm for the AuNP core and shell, respectively. Strong affinity toward the nucleolin receptors of breast cancer cell lines MCF-7 and T47D was observed for the TA-peptide gold nanoparticles (TAP@AuNPs) based on IC50 values. Furthermore, the nanoparticles showed excellent hemocompatibility. Quantitative results of atomic absorption showed improved uptake of TAP@AuNPs. Treatment of the cells with TAP@AuNPS resulted in greater release of cytochrome c following caspase-3/7 activation compared with free TA-peptide. The cytosolic level of adenosine triphosphate for TAP@AuNPs was higher than in controls. Higher anti-tumor efficiency was observed for TAP@AuNPs than TA-peptide compared with phosphate-buffered saline after intratumoral injection in tumor-bearing mice. It can be concluded that the design and development of a receptor-specific peptide-AuNP platform will be valuable for theranostic applications in cancer nanomedicine.

Assessing demographic access to hip replacement surgery in the United Kingdom: a systematic review.

Persisting evidence suggests significant socioeconomic and sociodemographic inequalities in access to medical treatment in the UK. Consequently, a systematic review was undertaken to examine these access inequalities in relation to hip replacement surgery. Database searches were performed using MEDLINE, PubMed and Web of Science. Studies with a focus on surgical need, access, provision and outcome were of interest. Inequalities were explored in the context of sociodemographic characteristics, socioeconomic status (SES), geographical location and hospital-related variables. Only studies in the context of the UK were included. Screening of search and extraction of data were performed and 482 articles were identified in the database search, of which 16 were eligible. Eligible studies consisted of eight cross-sectional studies, seven ecological studies and one longitudinal study. Although socioeconomic inequality has somewhat decreased, lower SES patients and ethnic minority patients demonstrate increased surgical needs, reduced access and poor outcomes. Lower SES and Black minority patients were younger and had more comorbidities. Surgical need increased with age. Women had greater surgical need and provision than men. Geographical inequality had reduced in Scotland, but a north-south divide persists in England. Rural areas received greater provision relative to need, despite increased travel for care. In all, access inequalities remain widespread and policy change driven by research is needed.

Long-term training on sand changes lower limb muscle activities during running in runners with over-pronated feet.

BACKGROUND: Running on sand could be a promising exercise intervention for the treatment of over-pronated feet. However, there is a lack of knowledge about the effects of running on sand on muscle activities. Therefore, this study aims to evaluate the long-term effects of running on sand on the activities of selected lower limb muscles in individuals with OPF compared with healthy controls. METHODS: Sixty recreational adult male runners with over-pronated feet (foot posture index > 10) were divided into two equal groups (intervention and control). Participants ran barefoot at a pre-defined speed (⁓3.3 m/s) over level stable ground both before and after long-term training on the sand. Muscle activities were recorded using a surface bipolar electromyography system. RESULTS: For the intervention group, we found a reduced foot posture index (p < 0.001; d = 2.00) and significant group-by-time interactions for gluteus medius activity during the mid-stance phase (p < 0.028; d = 0.59). Significantly higher gluteus medius activity (p = 0.028, d = 0.569) was found during the post-test. We also observed significant group-by-time interactions for medial gastrocnemius activity during the push-off phase (p < 0.041; d = 0.54). Significantly larger medial gastrocnemius activity (p = 0.041; d = 0.636) was found during the post-test compared to the pre-test. CONCLUSIONS: Long-term running on sand resulted in reduced pronation, increased medial gastrocnemius activity, and improved frontal plane pelvic stability due to higher gluteus medius activity. TRIAL REGISTRATION: IRCT20191211045704N1. Registered 25 February 2020. Retrospectively registered.

Critical evaluation of stents in coronary angioplasty: a systematic review.

BACKGROUND: Coronary stents are routinely placed in the treatment and prophylaxis of coronary artery disease (CAD). Current coronary stent designs are prone to developing blockages: in-stent thrombosis (IST) and in-stent re-stenosis (ISR). This is a systematic review of the design of current coronary stent models, their structural properties and their modes of application, with a focus on their associated risks of IST and ISR. The primary aim of this review is to identify the best stent design features for reducing the risk of IST and ISR. To review the three major types of stents used in clinical settings today, determining best and relevant clinical practice by exploring which types and features of offer improved patient outcomes regarding coronary angioplasty. This information can potentially be used to increase the success rate of coronary angioplasty and stent technology in the future taking into account costs and benefits. METHODS: Scientific databases were searched to find studies concerning stents. After the exclusion criteria were applied, 19 of the 3192 searched literature were included in this review. Studies investigating three major types of stent design were found: bare-metal stents (BMS), drug-eluting stents (DES) and bioresorbable stents (BRS). The number of participants varied between 14 and 1264. On average 77.4% were male, with a mean age of 64 years. RESULTS: From the findings of these studies, it is clear that DES are superior in reducing the risk of ISR when compared to BMS. Conflicting results do not clarify whether BRS are superior to DES at reducing IST occurrence, although studies into newer BRS technologies show reducing events of IST to 0, creating a promising future for BRS showing them to be non-inferior. Thinner stents were shown to reduce IST rates, due to better re-endothelialisation. Scaffold material has also been shown to play a role with cobalt alloy stents reducing the risk of IST. This study found that thinner stents that release drugs were better at preventing re-blockages. Some dissolvable stents might be better at stopping blood clots blocking the arteries when compared to metal stents. The method and procedure of implanting the stent during coronary angioplasty influences success rate of these stents, meaning stent design is not the only significant factor to consider. CONCLUSIONS: Positive developments in coronary angioplasty could be made by designing new stents that encompass all the most desirable properties of existing stent technology. Further work is needed to investigate the benefits of BRS in reducing the risk of IST compared to DES, as well as to investigate the effects of different scaffold materials on IST and ISR outcomes.

Impact of Aceria alhagi (Acari: Eriophyidae) as a potential biological control agent on the invasive weed Alhagi maurorum (Fabaceae) in its native range.

Camelthorn, Alhagi maurorum Medik. (Fabaceae, Leguminosae), a native component of the Asian flora, is invasive in Australia, South Africa and the USA where it is considered a noxious weed in several states. To date there is no biological control program against this weed; however, initial investigations into potential biocontrol agents revealed an eriophyid mite, Aceria alhagi Vidovic & Kamali, causing considerable damage in the native range. The mite attacks the growing tips as well as the flowers of the plants, not only reducing height and plant vigor but also reducing seed set. To assess the host range and impact of this potential biological control agent, on the target weed, no-choice tests as well as an open-field impact experiment were conducted at the research farm of the School of Agriculture, Shiraz University, Shiraz, Iran, over 2 years (2018 and 2019). Results from the no-choice tests suggest that A. alhagi poses negligible risk to the non-target plants tested in this study. In the first year of the open field impact test, plants did not flower; however, plant height was significantly reduced by mite attack. In the second year, significant reductions in plant biomass (26%), seed production (95%) and photosynthesis (53%) were observed in response to mite attack that would potentially limit the competitiveness of camelthorn as well as long-distance dispersal through seed in the invaded range. These results suggest that A. alhagi is a promising candidate for the biological control of camelthorn and should be prioritized for any future studies, expanding on the host range testing and safety.

Sustainable waste management of medical waste in African developing countries: A narrative review.

Africa is the second populous continent, and its population has the fastest growing rate. Some African countries are still plagued by poverty, poor sanitary conditions and limited resources, such as clean drinking water, food supply, electricity, and effective waste management systems. Underfunded healthcare systems, poor training and lack of awareness of policies and legislations on handling medical waste have led to increased improper handling of waste within hospitals, healthcare facilities and transportation and storage of medical waste. Some countries, including Ethiopia, Botswana, Nigeria and Algeria, do not have national guidelines in place to adhere to the correct disposal of such wastage. Incineration is often the favoured disposal method due to the rapid diminishment of up to 90% of waste, as well as production of heat for boilers or for energy production. This type of method - if not applying the right technologies - potentially creates hazardous risks of its own, such as harmful emissions and residuals. In this study, the sustainability aspects of medical waste management in Africa were reviewed to present resilient solutions for health and environment protection for the next generation in Africa. The findings of this research introduce policies, possible advices and solutions associated with sustainability and medical waste management that can support decision-makers in developing strategies for the sustainability by using the eco-friendly technologies for efficient medical waste treatment and disposal methods and also can serve as a link between the healthcare system, decision-makers, and stakeholders in developing health policies and programmes.

Fabrication of a Controlled-Release Core-Shell Floating Tablet of Ketamine Hydrochloride Using a 3D Printing Technique for Management of Refractory Depressions and Chronic Pain.

In this study, a novel floating, controlled-release and core-shell oral tablet of ketamine hydrochloride (HCl) was produced using a dual extrusion by 3D printing method. A mixture of Soluplus® and Eudragit® RS-PO was extruded by a hot-melt extrusion (HME) nozzle at 150-160 °C to fabricate the tablet shell, while a second nozzle known as a pressure-assisted syringe (PAS) extruded the etamine HCl in carboxymethyl cellulose gel at room temperature (25 °C) inside the shell. The resulting tablets were optimized based on the United States pharmacopeia standards (USP) for solid dosage forms. Moreover, the tablet was characterized using Fourier-transform infrared (FTIR) spectrum, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and buoyancy techniques. The results showed a desired dissolution profile for a 100% infill optimized tablet with total drug release (100%) during 12 h. Weight variation and content uniformity of the tablets achieved the USP requirements. SEM micrographs showed a smooth surface with acceptable layer diameters. According to the FTIR analysis, no interference was detected among peaks. Based on DSC analysis, the crystallinity of ketamine HCl did not change during melt extrusion. In conclusion, the floating controlled-release 3D-printed tablet of ketamine HCl can be a promising candidate for management of refractory depressions and chronic pain. Additionally, the additive manufacturing method enables the production of patient-tailored dosage with tunable-release kinetics for personalized medicine in point-of care setting.

Evaluating the therapeutic effects of isotretinoin on patients with coronavirus disease 2019 (COVID-19): A controlled open-label clinical trial.

Coronavirus disease 2019 (COVID-19) is still a global health issue with no certain treatment option. So far, various treatments have been suggested among which one can mention isotretinoin. The aim of the present study was to investigate the potential of this medication as a side treatment for COVID-19. This open-label controlled clinical trial with the approval ID of IRCT20190624043993N3 was conducted in Farabi Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. Considering the inclusion and exclusion criteria, 52 patients diagnosed with COVID-19 were enrolled. The control group only received standard of care (SOC) treatment while the intervention arm received 40 mg per day of isotretinoin along with the SOC. The patients were followed until discharge. The results showed no death among the groups. The hospitalization duration in the intervention and SOC groups were 5.1 ± 2.29 and 5.1 ± 3.44 days, respectively with no statistical difference (P = 0.98). Moreover, the SpO2, pulse rate, respiratory rate, and blood pressure also showed no statistical difference neither at admission nor upon discharge (P > 0.05). The laboratory investigations showed that white blood cells, absolute lymphocyte count, hemoglobin value, and platelet count did not differ between the groups at admission or upon discharge (P > 0.05). According to the results, it seems that isotretinoin didn't act as a potent side therapy in patients with COVID-19. However, due to the small sample size, we suggest further investigations.

A doxycycline-loaded microfiber of poly-metformin/PCL for eradicating melanoma stem cells.

Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for treating melanoma cancer after surgery was made using polycaprolactone and polymetformin microfibers that were loaded with doxycycline (PolyMet/PCL@DOX), an anti-cancer stem cell agent. The morphology, structure, mechanical characteristics, swelling, and porosity of the electrospun microfibers were examined. Drug release andanticancereffectiveness of PolyMet/PCL@DOXwas evaluated against A375 melanoma cancer stem cells using the MTS, Flow cytometry, colony formation and CD44 expression assays. Scanning electron microscopy (SEM) verified the micro fibrous structure with a diameter of about 2.31 µm. The porosity and swelling percentages for microfibers was 73.5 % and 2.9 %, respectively. The tensile strength at the breaking point was equal to 3.84 MPa. The IC50 of PolyMet/PCL@DOX was 7.4 µg/mL. The survival rate of A375 cells after 72 h of PolyMet/PCL@DOX treatment was 43.9 %. The colony formation capacity of A375 cells decreased after PolyMet/PCL@DOX treatment. The level of CD44 expression in the PolyMet/PCL@DOX group decreased compared to the control group. Generally, PolyMet/PCL@DOX microfibers can be a promising candidate as a patch after surgery to eradicate cancer stem cells, effectively.

Levofloxacin loaded poly (ethylene oxide)-chitosan/quercetin loaded poly (D,L-lactide-co-glycolide) core-shell electrospun nanofibers for burn wound healing.

This study developed a new burn wound dressing based on core-shell nanofibers that co-deliver antibiotic and antioxidant drugs. For this purpose, poly(ethylene oxide) (PEO)-chitosan (CS)/poly(D,L-lactide-co-glycolide) (PLGA) core-shell nanofibers were fabricated through co-axial electrospinning technique. Antibiotic levofloxacin (LEV) and antioxidant quercetin (QS) were incorporated into the core and shell parts of PEO-CS/PLGA nanofibers, respectively. The drugs could bond to the polymer chains through hydrogen bonding, leading to their steady release for 168 h. An in vitro drug release study showed a burst effect followed by sustained release of LEV and QS from the nanofibers due to the Fickian diffusion. The NIH 3T3 fibroblast cell viability of the drug loaded core-shell nanofibers was comparable to that in the control (tissue culture polystyrene) implying biocompatibility of the nanofibers and their cell supportive role. However, there was no significant difference in cell viability between the drug loaded and drug free core-shell nanofibers. According to in vivo experiments, PEO-CS-LEV/PLGA-QS core-shell nanofibers could accelerate the healing process of a burn wound compared to a sterile gauze. Thanks to the synergistic therapeutic effect of LEV and QS, a significantly higher wound closure rate was recorded for the drug loaded core-shell nanofibrous dressing than the drug free nanofibers and control. Conclusively, PEO-CS-LEV/PLGA-QS core-shell nanofibers were shown to be a promising wound healing material that could drive the healing cascade through local co-delivery of LEV and QS to burn wounds.

Incorporation of montmorillonite into microfluidics-generated chitosan microfibers enhances neuron-like PC12 cells for application in neural tissue engineering.

The complexity in structure and function of the nervous system, as well as its slow rate of regeneration, makes it more difficult to treat it compared to other tissues. Neural tissue engineering aims to create an appropriate environment for nerve cell proliferation and differentiation. Fibrous scaffolds with suitable morphology and topography and better mimicry of the extracellular matrix have been promising for the alignment and migration of neural cells. On this premise, to improve the properties of the scaffold, we combined montmorillonite (MMT) with chitosan (CS) polymer and created microfibers with variable diameters and varied concentrations of MMT using microfluidic technology and tested its suitability for the rat pheochromocytoma cell line (PC12). According to the findings, CS/MMT 0.1 % compared to CS/MMT 0 % microfibers showed a 201 MPa increase in Young's modulus, a 68 mS/m increase in conductivity, and a 1.4-fold increase in output voltage. Analysis of cell mitochondrial activity verified the non-toxicity, resulting in good cell morphology with orientation along the microfiber. Overall, the results of this project showed that with a low concentration of MMT, the properties of microfibers can be significantly improved and a suitable scaffold can be designed for neural tissue engineering.

Nanoarchitectonics of doxycycline-loaded vitamin E-D-α-tocopheryl polyethylene glycol 1000 succinate micelles for ovarian cancer stem cell treatment.

Aim: This study aim to develop doxycycline within the D-α-tocopheryl polyethylene glycol 1000 succinate micelle platform as an anticancer stem cell agent. Materials & methods: The optimized nanomicelle formulation was prepared using the solvent casting method and evaluated through physicochemical and biological characterization. Results: Nanomicelles exhibited mean particle sizes of 14.48 nm (polydispersity index: 0.22) using dynamic light scattering and 18.22 nm using transmission electron micrography. Drug loading and encapsulation efficiency were 2% and 66.73%, respectively. Doxycycline-loaded micelles exhibited sustained release, with 98.5% released in 24 h. IC50 values were 20 µg/ml for free drug and 5 µg/ml for micelles after 48 h of cell exposure. A significant 74% reduction in CD44 biomarker and 100% colony formation inhibition were observed. Conclusion: Doxycycline in hemo/biocompatible nanomicelles holds potential for ovarian cancer stem cell therapy.

Cancer, a global leading cause of death, has a significant impact on human health. Among the various types of cancer, ovarian cancer ranks as the seventh most prevalent, posing a significant threat to women and contributing significantly to deaths in this population. Recent studies have highlighted the importance of targeting cancer stem cells to enhance the effectiveness of cancer treatments and prevent tumor relapse. Cancer stem cells are cells that can differentiate into different cell types in a tumor, driving the growth and spread of cancer. Over the past few decades, certain antibiotics, including doxycycline, have emerged as potent and selective anticancer stem cell agents by specifically targeting mitochondrial biogenesis. In line with this, the authors developed a doxycycline-loaded micelle delivery system. Micelles are spheres made of a single layer of a type of fat called phospholipids; they have been combined with drugs to increase the successful delivery and effectiveness of that drug. This research revealed that this micelle formulation demonstrated a fourfold increase in efficacy against ovarian cancer stem cells compared with free antibiotics. Moreover, it efficiently reduced colony formation and CD44 biomarker levels among the stem cells, indicating damage to cancer stem cells. These findings underscore the potential of this doxycycline-loaded micelle system as a promising approach for eradicating ovarian cancer stem cells and improving therapeutic outcomes.

Anti-inflammation-based treatment of atherosclerosis using Gliclazide-loaded biomimetic nanoghosts.

In the study, a biomimetic platform for anti-inflammatory-based treatment of atherosclerotic plaque was developed. Gliclazide (GL) as an anti-inflammasome agent was encapsulated in PLGA nanoparticles (NP), which were coated by monocyte membrane using an extrusion procedure. The size and zeta potential of the nanoghost (NG) changed to 292 and - 10 nm from 189.5 to -34.1 in the core NP. In addition, the actual size of 62.5 nm with a coating layer of 5 nm was measured using TEM. The NG was also showed a sustained release profile with the drug loading content of about 4.7%. Beside to attenuated TNFα, decrease in gene expression levels of NLRP3, MyD88, NOS, IL-1ß, IL-18 and caspases 1/3/8/9 in LPS-primed monocytes exposed to NG strongly indicated remarkable inflammation control. After systemic toxicity evaluation and pharmacokinetic analysis of NP and NG, intravenous NG treatment of rabbits with experimentally induced atherosclerosis revealed remarkably less plaque lesions, foam cells, lipid-laden macrophages, and pathological issues in tunica media of aorta sections. Higher expression of CD163 than CD68 in aorta of NG-treated rabbits strongly reveals higher M2/M1 macrophage polarization. The bio/hemocompatible, biomimetic and anti-inflammatory NG can be considered as a potential platform for immunotherapy of particularly atherosclerosis in the field of personalized medicine.

Design and Fabrication of a High Performance Microfluidic Chip for Blood Plasma Separation: Modelling and Prediction of System Behaviour via CFD Method.

This paper presents a single-step microfluidic system designed for passive separation of human fresh blood plasma using direct capillary forces. Our microfluidic system is composed of a cylindrical well between upper and lower channel pairs produced by soft photolithography. The microchip was fabricated based on hydrophobicity differences upon suitable cylindrical surfaces using gravitational and capillary forces and lateral migration of plasma and red blood cells. The plasma radiation was applied to attach the polymeric segment (polydimethylsiloxane (PDMS)) to the glass. Meanwhile, Tween 80 was used as a surfactant to increase the hydrophobicity of the lateral channel surfaces. This led to the higher movement of whole blood, including plasma. Fick's law of diffusion was validated for this diffusion transfer, the Navier-Stokes equation was used for the momentum balance, and the Laplace equation was utilized for the dynamics of the mesh. A model with high accuracy using the COMSOL Multiphysics software was created to predict the capillary forces and chip model validation. RBCs (red blood cells) were measured by the H3 cell counter instrument, by which 99% plasma purity was achieved. Practically, 58.3% of the plasma was separated from the blood within 12 min. Correlation between plasma separation results obtained from software and experimental data showed a coefficient of determination equal to 0.9732. This simple, rapid, stable, and reliable microchip can be considered as a promising candidate for providing plasma in point-of-care diagnostics.