Magnetically-assisted viral transduction (magnetofection) medical applications: An update.

Gene therapy involves replacing a faulty gene or adding a new gene inside the body's cells to cure disease or improve the body's ability to fight disease. Its popularity is evident from emerging concepts such as CRISPR-based genome editing and epigenetic studies and has been moved to a clinical setting. The strategy for therapeutic gene design includes; suppressing the expression of pathogenic genes, enhancing necessary protein production, and stimulating the immune system, which can be incorporated into both viral and non-viral gene vectors. Although non-viral gene delivery provides a safer platform, it suffers from an inefficient rate of gene transfection, which means a few genes could be successfully transfected and expressed within the cells. Incorporating nucleic acids into the viruses and using these viral vectors to infect cells increases gene transfection efficiency. Consequently, more cells will respond, more genes will be expressed, and sustained and successful gene therapy can be achieved. Combining nanoparticles (NPs) and nucleic acids protects genetic materials from enzymatic degradation. Furthermore, the vectors can be transferred faster, facilitating cell attachment and cellular uptake. Magnetically assisted viral transduction (magnetofection) enhances gene therapy efficiency by mixing magnetic nanoparticles (MNPs) with gene vectors and exerting a magnetic field to guide a significant number of vectors directly onto the cells. This research critically reviews the MNPs and the physiochemical properties needed to assemble an appropriate magnetic viral vector, discussing cellular hurdles and attitudes toward overcoming these barriers to reach clinical gene therapy perspectives. We focus on the studies conducted on the various applications of magnetic viral vectors in cancer therapies, regenerative medicine, tissue engineering, cell sorting, and virus isolation.

The risk of pancreatic adenocarcinoma following SARS-CoV family infection.

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.

Graphene-Based Materials Prove to Be a Promising Candidate for Nerve Regeneration Following Peripheral Nerve Injury.

Peripheral nerve injury is a common medical condition that has a great impact on patient quality of life. Currently, surgical management is considered to be a gold standard first-line treatment; however, is often not successful and requires further surgical procedures. Commercially available FDA- and CE-approved decellularized nerve conduits offer considerable benefits to patients suffering from a completely transected nerve but they fail to support neural regeneration in gaps > 30 mm. To address this unmet clinical need, current research is focused on biomaterial-based therapies to regenerate dysfunctional neural tissues, specifically damaged peripheral nerve, and spinal cord. Recently, attention has been paid to the capability of graphene-based materials (GBMs) to develop bifunctional scaffolds for promoting nerve regeneration, often via supporting enhanced neural differentiation. The unique features of GBMs have been applied to fabricate an electroactive conductive surface in order to direct stem cells and improve neural proliferation and differentiation. The use of GBMs for nerve tissue engineering (NTE) is considered an emerging technology bringing hope to peripheral nerve injury repair, with some products already in preclinical stages. This review assesses the last six years of research in the field of GBMs application in NTE, focusing on the fabrication and effects of GBMs for neurogenesis in various scaffold forms, including electrospun fibres, films, hydrogels, foams, 3D printing, and bioprinting.

Platelet-rich plasma fibrin glue for treatment of chylothorax following cavopulmonary connections.

OBJECTIVES: The postoperative persistence of chylothorax is a fatal complication of paediatric cardiac surgery. There is an urgent need for an effective treatment of chylothorax. This study reports the application of allogenic platelet-rich plasma fibrin glue (PRP-FG) as a conservative therapy before reoperation. METHODS: Over a 9-year period, from 2010 to 2019, 27 patients with persistent chylothorax following a cavopulmonary connection, with a mean latency period of 11 days (range 10-15 days), were treated with PRP-FG. These patients were selected because they had not responded positively to initial conservative management plans. The patients were followed up for 9 years. RESULTS: Twenty-five patients (92%) responded positively to treatment with PRP-FG; 2 patients did not respond to the treatment and died after reoperation. All of the successfully treated patients in follow-up continued to live a healthy life without further complications. CONCLUSIONS: Recalcitrant chylothorax that persists after paediatric cardiac surgery responded positively to treatment with PRP-FG. This technique precluded the need for another operation and significantly decreased the morbidity and mortality rates.

A New Nanocomposite Copolymer Based On Functionalised Graphene Oxide for Development of Heart Valves.

Polymeric heart valves seem to be an attractive alternative to mechanical and biological prostheses as they are more durable, due to the superior properties of novel polymers, and have the biocompatibility and hemodynamics comparable to tissue substitutes. This study reports a comprehensive assessment of a nanocomposite based on the functionalised graphene oxide and poly(carbonate-urea)urethane with the trade name "Hastalex" in comparison with GORE-TEX, a commercial polymer routinely used for cardiovascular medical devices. Experimental data have proved that GORE-TEX has a 2.5-fold (longitudinal direction) and 3.5-fold (transverse direction) lower ultimate tensile strength in comparison with Hastalex (p < 0.05). The contact angles of Hastalex surfaces (85.2 ± 1.1°) significantly (p < 0.05) are lower than those of GORE-TEX (127.1 ± 6.8°). The highest number of viable cells Ea.hy 926 is on the Hastalex surface exceeding 7.5-fold when compared with the GORE-TEX surface (p < 0.001). The platelet deformation index for GORE-TEX is 2-fold higher than that of Hastalex polymer (p < 0.05). Calcium content is greater for GORE-TEX (8.4 mg/g) in comparison with Hastalex (0.55 mg/g). The results of this study have proven that Hastalex meets the main standards required for manufacturing artificial heart valves and has superior mechanical, hemocompatibility and calcific resistance properties in comparison with GORE-TEX.

Emerging roles of exosomal miRNAs in breast cancer drug resistance.

Breast cancer (BC), as a heterogeneous disease, is considered as one of the most common malignancies in women worldwide. The resistance of BC cells to therapeutic agents has remained a big challenge in the treatment of BC patients. Some factors such as cytokines, exosomes, and soluble receptors were recognized as crucial agents involved in the development of drug resistance. However, the exact mechanisms underlying the drug resistance is still unknown. There is growing evidence to support the emerging roles of exosomes, especially exosomal miRNAs, in tumor initiation, angiogenesis, proliferation, migration, invasion, metastasis, and drug resistance. Therefore, identification of BC-specific exosomal miRNAs and their underlying mechanisms would be helpful to define sensitivity to therapeutic drugs and establish an appropriate therapeutic strategy. This review focuses mainly on the roles of exosomal miRNAs and their associated mechanisms in the resistance of BC cells to therapeutic agents, as well as critically examines the potential of these macromolecules as a treatment biomarker in BC patients.

Human Adipose-Derived Stem Cells with Great Therapeutic Potential.

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in regenerative medicine. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. While clinically, adipose-derived stem cells (ADSCs) are one of the most widely used types of stem cells used more than five years in clinically setting. It has many advantages including; yields a high number of ADSCs per volume of tissue, high rate of proliferation, anti-fibrotic, anti-apoptotic, anti-inflammation, immunomodulation, and paracrine mechanisms have been demonstrated in various preclinical studies. It is much easier to harvest compared with bone marrow stem cells. Results of clinical studies have demonstrated the potentials of ADSCs for stem cells therapy for a number of clinical disorders. The aim of this paper was to provide an update on the most recent developments of ADSCs, by highlighting the properties and features of ADSCs, critically discussing its clinical benefit and its clinical trials in treatment and regeneration. This is a multi-billion dollars industry with huge interest to clinician, academia and industries.

In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application.

BACKGROUND: Graphene is considered as a wonder material; it is the strongest material on the planet, super-elastic, and conductive. Its application in biomedicine is huge, with a multibillion-dollar industry, and will revolutionize the diagnostic and treatment of diseases. However, its safety and potential toxicity is the main challenge. METHODS: This study assessed the potential toxicity of graphene oxide nanoplatelets (GONs) in an in vivo animal model using systemic, hematological, biochemical, and histopathological examinations. Normal saline (control group) or GONs (3-6 layers, lateral dimension=5-10 µm, and thickness=0.8-2 nm) at dose rate of 50, 150, or 500 mg/kg were intraperitoneally injected into adult male Wistar rats (n=5) every 48 hours during 1 week to receive each animal a total of four doses. The animals were allowed 2 weeks to recover after the last dosing. Then, animals were killed and the blood was collected for hematological and biochemical analysis. The organs including the liver, kidney, spleen, lung, intestine, brain, and heart were harvested for histopathological evaluations. RESULTS: The results showed GONs prevented body weight gain in animals after 21 days, treated at 500 mg/kg, but not in the animals treated at 150 or 50 mg/kg GONs. The biochemical analysis showed a significant increase in total bilirubin, with a significant decrease in triglycerides and high-density lipoprotein in animals treated at 500 mg/kg. Nonetheless, other hematological and biochemical parameters remained statistically insignificant in all GONs treated animals. The most common histopathological findings in the visceral organs were granulomatous reaction with giant cell formation and accumulation of GONs in capsular regions. Also, small foci of neuronal degeneration and necrosis were the most outstanding findings in the brain, including the cerebellum. CONCLUSION: In conclusion, this study shows that GONs without functionalization are toxic. The future study is a comparison of the functionalized with non-functionalized GONs.

3D Protein-Based Bilayer Artificial Skin for the Guided Scarless Healing of Third-Degree Burn Wounds in Vivo.

Severe burn injuries can lead to delays in healing and devastating scar formation. Attempts have been made to develop a suitable skin substitute for the scarless healing of such skin wounds. Currently, there is no effective strategy for completely scarless healing after the thermal injuries. In our recent work, we fabricated and evaluated a 3D protein-based artificial skin made from decellularized human amniotic membrane (AM) and electrospun nanofibrous silk fibroin (ESF) in vitro. We also characterized both biophysical and cell culture investigation to establish in vitro performance of the developed bilayer scaffolds. In this report, we evaluate the appropriate utility of this fabricated bilayered artificial skin in vivo with particular emphasis on healing and scar formation due to the biochemical and biomechanical complexity of the skin. For this work, AM and AM/ESF membranes alone or seeded with adipose-tissue-derived mesenchymal stem cells (AT-MSCs) are implanted on full-thickness burn wounds in mice. The healing efficacy and scar formation are evaluated at 7, 14, and 28 days post-implantation in vivo. Our data reveal that ESF accelerates the wound-healing process through the early recruitment of inflammatory cells such as macrophages into the defective site as well as the up-regulation of angiogenic factors from the AT-MSCs and the facilitation of the remodeling phase. In vivo application of the prepared AM/ESF membrane seeded with the AT-MSCs reduces significantly the post-burn scars. The in vivo data suggest that the potential applications of the AM/ESF bilayered artificial skin may be considered a clinical translational product with stem cells to guide the scarless healing of severe burn injuries.

Emerging In Vitro 3D Tumour Models in Nanoparticle-Based Gene and Drug Therapy.

3D models are emerging as valuable tools for personalised nanoparticle-based cancer treatments. 3D models represent in vivo cancers more realistically than 2D patterns that are grown in Petri dishes. However, creating a 3D cancer model that mimics the complexity and heterogeneity of cancers in vivo remains difficult.

Effect of Laser Irradiation on Cell Cycle and Mitosis.

Introduction: In this research, low-level helium-neon (He-Ne) laser irradiation effects on monkey kidney cells (Vero cell line) mitosis were studied. Methods: The experiment was carried out on a monkey kidney cell line "Vero (CCL-81)". This is a lineage of cells used in cell cultures and can be used for efficacy and media testing. The monolayer cells were formed on coating glass in a spectral cuvette (20×20×30 mm). The samples divided into two groups. The first groups as irradiated monolayer cells were exposed by a He-Ne laser (PolyaronNPO, L'vov, Ukraine) with λ=632.8 nm, max power density (P) = 10 mW/cm2 , generating linearly polarized and the second groups as the control monolayer cells were located in a cuvette protected by a lightproof screen from the first cuvette and also from the laser exposure. Then, changing functional activity of the monolayer cells, due to the radiation influence on some physical factors were measured. Results: The results showed that low-intensity laser irradiation in the range of visible red could make meaningful changes in the cell division process (the mitosis activity). These changes depend on the power density, exposure time, the presence of a magnetic field, and the duration of time after exposure termination. The stimulatory effects on the cell division within the power density of 1-6 mW/(cm2 ) and exposure time in the range of 1-10 minutes was studied. It is demonstrated that the increase in these parameters (power density and exposure time) leads to destructing the cell division process. Conclusion: The results are useful to identify the molecular mechanisms caused by low-intensity laser effects on the biological activities of the cells. Thus, this study helps to optimize medical laser technology as well as achieving information on the therapeutic effects of low-intensity lasers.

Osteogenic potential of stem cells-seeded bioactive nanocomposite scaffolds: A comparative study between human mesenchymal stem cells derived from bone, umbilical cord Wharton's jelly, and adipose tissue.

Bone regeneration is considered as an unmet clinical need, the aim of this study is to investigate the osteogenic potential of three different mesenchymal stem cells (MSCs) derived from human bone marrow (BM-MSCs), umbilical cord Wharton's jelly (UC-MSCs), and adipose (AD-MSCs) seeded on a recently developed nanocomposite scaffold (bioactive glass/gelatin) implanted in rat animal models with critical size calvarial defects. In this study, after isolation, culture, and characterization, the MSCs were expanded and seeded on the scaffolds for in vitro and in vivo studies. The adhesion, proliferation, and viability of the cells on the scaffolds evaluated in vitro, showed that the scaffolds were biocompatible for further examinations. In order to evaluate the scaffolds in vivo, rat animal models with critical size calvarial defects were randomly categorized in four groups and treated with the scaffolds. The animals were sacrificed at the time points of 4 and 12 weeks of post-implantation, bone healing process were investigated. The histological and immunohistological observations showed (p < 0.01) higher osteogenesis capacity in the group treated with BM-MSCs/scaffolds compared to the other groups. However, the formation of new angiogenesis was evidently higher in the defects filled with UC-MSCs/scaffolds. This preliminary study provides promising data for further clinical trials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 61-72, 2018.

Silk fibroin/amniotic membrane 3D bi-layered artificial skin.

Burn injuries have been reported to be an important cause of morbidity and mortality and they are still considered as unmet clinical need. Although there is a myriad of effective stem cells that have been suggested for skin regeneration, there is no one ideal scaffold. The aim of this study was to develop a three-dimensional (3D) bi-layer scaffold made of biological decellularized human amniotic membrane (AM) with viscoelastic electrospun nanofibrous silk fibroin (ESF) spun on top. The fabricated 3D bi-layer AM/ESF scaffold was submerged in ethanol to induce ß-sheet transformation as well as to get a tightly coated and inseparable bi-layer. The biomechanical and biological properties of the 3D bi-layer AM/ESF scaffold were investigated. The results indicate significantly improved mechanical properties of the AM/ESF compared with the AM alone. Both the AM and AM/ESF possess a variety of suitable adhesion cells without detectable cytotoxicity against adipose tissue-derived mesenchymal stem cells (AT-MSCs). The AT-MSCs show increased expression of two main pro-angiogenesis factors, vascular endothelial growth factor and basic fibroblast growth factor, when cultured on the AM/ESF for 7 days, when comparing with AM alone. The results suggest that the AM/ESF scaffold with autologous AT-MSCs has excellent cell adhesion and proliferation along with production of growth factors which serves as a possible application in a clinical setting for skin regeneration.

Limitations in Clinical Translation of Nanoparticle-Based Gene Therapy.

Organic nanoparticle-based (ONP) gene therapy is a potential strategy to cure human cancer. However, there are still many practical barriers before the promising results from in vitro and preclinical studies can be translated to clinical success. We discuss the reasons behind the hesitant uptake by the clinic.

Will Nanotechnology Bring New Hope for Gene Delivery?

The high mortality rates of cancer patients receiving standard treatments emphasize the crucial need for alternative treatments. One promising strategy is to use organic nanoparticles (NPs) for gene delivery. Although multifunctional NPs theoretically have many desirable properties as gene vectors, there are several practical barriers to successful gene delivery. In this review we discuss the properties of NPs and overview in vitro and preclinical studies of organic NPs over the past 5 years. The results of recent clinical trials suggest that the NP field holds significant promise. The annual market value for successful gene delivery could exceed US$30 billion, and this will encourage researchers to study the application of NPs to therapeutic gene delivery.

The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery.

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose-derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery.

Towards reconstruction of epithelialized cartilages from autologous adipose tissue-derived stem cells.

Deformities of the upper airways, including those of the nose and throat, are typically corrected by reconstructive surgery. The use of autologous somatic stem cells for repair of defects could improve quality and outcomes of such operations. The present study explored the ability of paediatric adipose-derived stem cells (pADSCs), a readily available source of autologous stem cells, to generate a cartilage construct with a functional epithelium. Paediatric ADSCs seeded on the biodegradable nanocomposite polymer, polyhedral oligomeric silsesquioxane poly(ϵ-caprolactone-urea) urethane (POSS-PCL), proliferated and differentiated towards mesenchymal lineages. The ADSCs infiltrated three-dimensional POSS-PCL nanoscaffold and chondroid matrix was observed throughout chondrogenically induced samples. In ovo chorioallantoic membrane-grafted ADSC-nanoscaffold composites were enwrapped by host vessels indicating good compatibility in an in vivo system. Furthermore, pADSCs could be induced to transdifferentiate towards barrier-forming epithelial-like cells. By combining differentiation protocols, it was possible to generate epithelial cell lined chondrogenic micromasses from the same pADSC line. This proof-of-concept study appears to be the first to demonstrate that individual pADSC lines can differentiate towards two different germ lines and be successfully co-cultured. This has important implications for bioengineering of paediatric airways and further confirms the plastic nature of ADSCs. Copyright © 2016 John Wiley & Sons, Ltd.

Conjugation with RGD Peptides and Incorporation of Vascular Endothelial Growth Factor Are Equally Efficient for Biofunctionalization of Tissue-Engineered Vascular Grafts.

The blend of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) has recently been considered promising for vascular tissue engineering. However, it was shown that PHBV/PCL grafts require biofunctionalization to achieve high primary patency rate. Here we compared immobilization of arginine-glycine-aspartic acid (RGD)-containing peptides and the incorporation of vascular endothelial growth factor (VEGF) as two widely established biofunctionalization approaches. Electrospun PHBV/PCL small-diameter grafts with either RGD peptides or VEGF, as well as unmodified grafts were implanted into rat abdominal aortas for 1, 3, 6, and 12 months following histological and immunofluorescence assessment. We detected CD31⁺/CD34⁺/vWF⁺ cells 1 and 3 months postimplantation at the luminal surface of PHBV/PCL/RGD and PHBV/PCL/VEGF, but not in unmodified grafts, with the further observation of CD31⁺CD34-vWF⁺ phenotype. These cells were considered as endothelial and produced a collagen-positive layer resembling a basement membrane. Detection of CD31⁺/CD34⁺ cells at the early stages with subsequent loss of CD34 indicated cell adhesion from the bloodstream. Therefore, either conjugation with RGD peptides or the incorporation of VEGF promoted the formation of a functional endothelial cell layer. Furthermore, both modifications increased primary patency rate three-fold. In conclusion, both of these biofunctionalization approaches can be considered as equally efficient for the modification of tissue-engineered vascular grafts.

Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury.

AIM: To investigate the hepatic microcirculatory changes due to Haemoxygenase (HO), effect of HO inhibition on remote ischemic preconditioning (RIPC) and modulation of CINC. METHODS: Eight groups of animals were studied - Sham, ischemia reperfusion injury (IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion, RIPC (remote ischemic preconditioning) + IRI group, remote ischemic preconditioning in sham (RIPC + Sham), PDTC + IR (Pyridodithiocarbamate, HO donor), ZnPP + RIPC + IRI (Zinc protoporphyrin prior to preconditioning), IR-24 (45 min of ischemia followed by 24 h of reperfusion), RIPC + IR-24 (preconditioning prior to IR). After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS: Velocity of flow (160.83 ± 12.24 µm/s), sinusoidal flow (8.42 ± 1.19) and sinusoidal perfusion index (42.12 ± 7.28) in hepatic IR were lower (P < 0.05) in comparison to RIPC and PDTC (HO inducer). RIPC increased velocity of flow (328.04 ± 19.13 µm/s), sinusoidal flow (17.75 ± 2.59) and the sinusoidal perfusion index (67.28 ± 1.82) (P < 0.05). PDTC (HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity (300.88 ± 22.109 µm/s), sinusoidal flow (17.66 ± 3.71) and sinusoidal perfusion (82.33 ± 3.5) to near sham levels. ZnPP (HO inhibition) reduced velocity of flow of RBC in the RIPC group (170.74 ± 13.43 µm/s and sinusoidal flow in the RIPC group (9.46 ± 1.34). ZnPP in RIPC (60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules (769.05 ± 87.48) and sinusoids (97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules (219.66 ± 93.79) and sinusoids (25.69 ± 9.08) (P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules (89.58 ± 58.32) and sinusoids (17.98 ± 11.01) (P < 0.05) reproducing the effects of RIPC. ZnPP (HO inhibition) increased venular (589.04 ± 144.36) and sinusoidal neutrophil adhesion in preconditioned animals (121.39 ± 30.65) (P < 0.05). IR after 24 h of reperfusion increased venular and sinusoidal neutrophil adhesion in comparison to the early phase and was significantly reduced by RIPC. Hepatocellular cell death in IRI (80.83 ± 13.03), RIPC + IR (17.35 ± 2.47), and PTDC + IR (11.66 ± 1.17) reduced hepatocellular death. ZnPP + RIPC + IR (41.33 ± 3.07) significantly increased hepatocellular death (P < 0.05 PTDC/RIPC vs ZnPP and IR). The CINC cytokine levels in sham (101.32 ± 6.42). RIPC + sham (412.18 ± 65.24) as compared to sham (P < 0.05). CINC levels in hepatic IR were (644.08 ± 181.24). PDTC and RIPC CINC levels were significantly lower than hepatic IR (P < 0.05). HO inhibition in preconditioned animals with Zinc protoporphyrin increased serum CINC levels (521.81 ± 74.9) (P < 0.05). The serum CINC levels were high in the late phase of hepatic IR (15306 ± 1222.04). RIPC reduced CINC levels in the late phase of IR (467.46 ± 26.06), P < 0.05. CONCLUSION: RIPC protects hepatic microcirculation by induction of HO and modulation of CINC in hepatic IR.

Quantum dot nanoparticle for optimization of breast cancer diagnostics and therapy in a clinical setting.

Breast cancer is the most common cancer in the world. Sentinel lymph node (SLN) biopsy is used for staging of axillary lymph nodes. Organic dyes and radiocolloid are currently used for SLN mapping, but expose patients to ionizing radiation, are unstable during surgery and cause local tissue damage. Quantum dots (QD) could be used for SLN mapping without the need for biopsy. Surgical resection of the primary tumor is the optimal treatment for early-diagnosed breast cancer, but due to difficulties in defining tumor margins, cancer cells often remain leading to reoccurrences. Functionalized QD could be used for image-guided tumor resection to allow visualization of cancer cells. Near Infrared QD are photostable and have improved deep tissue penetration. Slow elimination of QD raises concerns of potential accumulation. Nevertheless, promising findings with cadmium-free QD in recent in vivo studies and first in-human trial suggest huge potential for cancer diagnostic and therapy.