Numerical simulation of burn injuries with temperature-dependent thermal conductivity and metabolism under different surface heat sources.

In the present paper, the phenomena of heat transport inside human forearm tissue are studied through a one-dimensional nonlinear bioheat transfer model under the influence of various boundary and interface conditions. In this study, we considered temperature-dependent thermal conductivity and metabolic heat to predict temperature distribution inside the forearm tissue. We have studied the temperature distribution inside inner tissue and bone because it has been found that burn injuries are mostly affected by layer thickness. The temperature distribution inside human forearm tissue is analyzed using the finite difference and bvp4c numerical techniques. To examine the accuracy of present numerical code, we compare the obtained numerical result with the exact analytical result in a specific case and find an excellent agreement with the exact results. We also validated our present numerical code with a hybrid scheme based on Runge-Kutta (4,5) and finite difference technique and found it in good compliance. From the obtained results, we observed that the homogeneous heat flux has a greater impact on the temperature at the outer surface of the skin, but the sinusoidal heat flux has a greater impact on the temperature of the subcutaneous layer and inner tissue. It is found that there is no burn injury in the first type of heat source (Tw=44°C), but it may occur in the second and third types of heat sources. It has been observed that by raising the blood perfusion rate and reducing the values of reference metabolic heat, coefficient of thermal conductivity, and heat fluxes, we can manage and reduce burn injuries and achieve hyperthermia temperature.

Numerical estimation of temperature response with step heating of a multi-layer skin under the generalized boundary condition.

In this article, we discussed a one-dimensional bioheat transfer mathematical model that describes the process of temperature distribution in tissue for the multi-layer skin under the step heating generalized boundary condition. The finite difference scheme is used to estimate the temperature profile along with time and distance. We discussed the stability of the numerical scheme and also validated the accuracy of the numerical code by comparing the present results with the previous reference results. To remove heat from the skin is considered by the surface temperature, heat flux, and ambient temperature to be zero with the help of the unit step like function. Then, we observed that the skin temperature in the second kind boundary condition was slowly decreasing over time as compared to the first and third kind boundary conditions. The temperature or heat flux at the skin surface is assumed to be high then there is negligible effect of the blood perfusion rate on the temperature response over a short time period and the effect of blood perfusion rate is visible when the time duration is long. Effect of blood perfusion rate, heating and after removal of heating, water diffusion, and generalized boundary condition for the analysis of the behavior of temperature response in multi-layer skin are discussed in detail and the results obtained are presented graphically.

Correction to: Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents.

After publication of the original article [1], the authors found that Figure 2e (Hsp70-Ch-Lf-ZF in Jurkat cells, 2 h), Figure 5b (HSP70-Lf-ZF) and Figure 5c (control) contained incorrect images. This does not affect the figure legends, results and conclusions of the article.

Psammomys obesus: a Natural Diet-Controlled Model for Diabetes and Cardiovascular Diseases.

PURPOSE OF REVIEW: This review specifically summarises and reports terrestrial mammals of the gerbil subfamily, known as Israeli sand rats or Psammomys obesus (P. obesus) as a diet-controlled, unique, polygenic rodent model for research in the areas of obesity, type 2 diabetes, and cardiovascular diseases. The animal model closely mimics phenotypic and pathophysiological resemblance with human populations. RECENT FINDINGS: The physiological status and biochemical composition in P. obesus can be manipulated effectively by controlling its nutritional intake, making it a natural model for cardiovascular and diabetic research. Humans exhibit remarkable disparity in physiology and pathology, which are inter-dependent factors. However, variations in these factors in most animal models currently being used for cardiovascular/diabetes research are insignificant. Consequently, it is a necessity to identify and develop animal models exhibiting physiological variations mimicking human pathological conditions. We have compiled research developments conducted with this rodent model manifesting pathophysiology, closely mimicking that in human beings, thereby enabling better translation of novel therapeutic and diagnostic discoveries.

Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers.

The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe3O4)-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1(+)/CIMP2(-)/chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER(-)/PR(-)/HER2(-); MDA-MB-231) breast cancer model. Mice fed orally on the Zn-Fe-bLf NC diet showed downregulation in tumor volume and complete regression in tumor volume after 45 days of feeding. In human xenograft colon cancer, vehicle-control NC diet-group (n=5) mice showed a tumor volume of 52.28±11.55 mm(3), and Zn-Fe-bLf NC diet (n=5)-treated mice had a tumor-volume of 0.10±0.073 mm(3). In the human xenograft breast cancer model, Zn-Fe-bLf NC diet (n=5)-treated mice showed a tumor volume of 0.051±0.062 mm(3) within 40 days of feeding. Live mouse imaging conducted by near-infrared fluorescence imaging of Zn-Fe-bLf NCs showed tumor site-specific localization and regression of colon and breast tumor volume. Ex vivo fluorescence-imaging analysis of the vital organs of mice exhibited sparse localization patterns of Zn-Fe-bLf NCs and also confirmed tumor-specific selective localization patterns of Zn-Fe-bLf NCs. Dual imaging using magnetic resonance imaging and computerized tomography scans revealed an unprecedented theranostic ability of the Zn-Fe-bLf NCs. These observations warrant consideration of multimodular Zn-Fe-bLf NCs for real-time cancer imaging and simultaneous cancer-targeted therapy.

Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents.

BACKGROUND: Cardiovascular diseases are the most prevalent cause of morbidity and mortality affecting millions of people globally. The most effective way to counter cardiovascular complications is early diagnosis and the safest non-invasive diagnostic approach is magnetic resonance imaging (MRI). In this study, superparamagnetic ferrite nanoparticles doped with zinc, exhibiting highly enhanced saturation magnetization and T2 and computed tomography (CT) contrast were synthesized. These nanoparticles have been strategically engineered using bovine lactoferrin (Lf), polyethylene glycol (PEG), and heat shock protein (Hsp)-70 antibody specifically targeting atherosclerosis with potential therapeutic value. The nanocomplexes were further validated in vitro to assess their cytotoxicity, internalization efficiency, effects on cellular proliferation and were assessed for MRI as well as X-ray CT in ex vivo Psammomys obesus rat model. RESULTS: Optimized zinc doped ferrite nanoparticles (Zn0.4Fe2.6O4) with enhanced value of maximum saturation magnetization value on 108.4 emu/g and an average diameter of 24 ± 2 nm were successfully synthesized. Successfully incorporation with bovine lactoferrin, PEG and Hsp-70 (70 kDa) antibody led to synthesis of spherical nanocomplexes (size 224.8 nm, PDI 0.398). A significantly higher enhancement in T2 (p < 0.05, 1.22-fold) and slightly higher T1 (1.09-fold) and CT (1.08-fold) contrast compared to commercial ferrite nanoparticles was observed. The nanocomplexes exhibited effective cellular internalization within 2 h in both THP-1 and Jurkat cells. MRI scans of contrast agent injected animal revealed significant arterial narrowing and a significantly higher T2 (p < 0.05, 1.71-fold) contrast in adult animals when compared to juvenile and control animals. The excised heart and aorta agar phantoms exhibited weak MRI contrast enhancement in juvenile animal but significant contrast enhancement in adult animal specifically at the aortic arch, descending thoracic aorta and iliac bifurcation region with X-ray CT scan. Histological investigation of the contrast agent injected aorta and heart confirmed site target-specific accumulation at the atherosclerotic aortic arch and descending thoracic aorta of the adult animal with severely damaged intima full of ruptured microatheromas. CONCLUSION: Overall, the study demonstrates the strategic development of nanocomplex based bimodal MRI and CT contrast agents and its validation on Psammomys obesus for atherosclerosis diagnostics.

Immobilization of ß-glucosidase on a magnetic nanoparticle improves thermostability: application in cellobiose hydrolysis.

The objective of the present work was to develop a thermostable ß-glucosidase through immobilization on a nanoscale carrier for potential application in biofuel production. ß-Glucosidase (BGL) from Aspergillus niger was immobilized to functionalized magnetic nanoparticles by covalent binding. Immobilized nanoparticles showed 93% immobilization binding. Immobilized and free BGL were characterized using Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) techniques. Free and immobilized enzyme exhibited different pH-optima at pH 4.0 and 6.0, respectively, but had the same temperature optima at 60 °C. Michaelis constant (KM) was 3.5 and 4.3mM for free and immobilized BGL. Thermal stability of the immobilized enzyme was enhanced at 70 °C. The immobilized nanoparticle-enzyme conjugate retained more than 50% enzyme activity up to the 16th cycle. Maximum glucose synthesis from cellobiose hydrolysis by immobilized BGL was achieved at 16 h.

Emerging engineered magnetic nanoparticulate probes for molecular MRI of atherosclerosis: how far have we come?

Atherosclerosis is a chronic, progressive, immunoinflammatory disease of the large and medium-sized arteries, and a major cause of cardiovascular diseases. Atherosclerosis often progresses silently for decades until the occurrence of a major catastrophic clinical event such as myocardial infarction, cardiac arrest and stroke. The main challenge in the diagnosis and management of atherosclerosis is to develop a safe, noninvasive technique that is accurate and reproducible, which can detect the biologically active high-risk vulnerable plaques (with ongoing active inflammation, angiogenesis and apoptosis) before the occurrence of an acute clinical event. This article reviews the events involved in the pathogenesis of atherosclerosis in light of recently advanced understanding of the molecular pathogenesis of the disease. Next, we elaborate on the interesting developments in molecular MRI, by describing the recently engineered magnetic nanoparticulate probes targeting clinically promising molecular and cellular players/processes, involved in early atherosclerotic lesion formation to plaque rupture and erosion.

Emerging engineered magnetic nanoparticulate probes for targeted MRI of atherosclerotic plaque macrophages.

Inflammation is known to present at all stages of atherosclerotic lesion/plaque development, which often progresses silently for decades, before the occurrence of acute clinical events. Rupture of mature complex plaques with ongoing inflammation can lead to thrombosis, and many adverse acute clinical events such as stroke, myocardial infarction and/or sudden coronary death. Among new-generation noninvasive imaging modalities, molecular MRI with target-specific novel nanoparticulate contrast agents has shown great promise for the visualization of atherosclerosis at the molecular and cellular level in both animals and humans. Considering the key role macrophages play in atherosclerotic inflammation from lesion initiation to plaque rupture, this article reviews the recently engineered magnetic nanoparticulate probes targeting macrophages, their phagocytic activities, surface receptors and molecular products such as neutrophil gelatinase-associated lipocalin. The usefulness of some of these probes as multimodal and drug monitoring agents is also reviewed along with the challenges and future perspectives of the present developments for clinical benefit.