Evidence of linear and cubic Rashba effect in non-magnetic heterostructure.

TheLaAlO3/KTaO3system serves as a prototype to study the electronic properties that emerge as a result of spin-orbit coupling (SOC). In this article, we have used first-principles calculations to systematically study two types of defect-free (0 0 1) interfaces, which are termed as Type-I and Type-II. While the Type-I heterostructure produces a two dimensional (2D) electron gas, the Type-II heterostructure hosts an oxygen-rich 2D hole gas at the interface. Furthermore, in the presence of intrinsic SOC, we have found evidence of both cubic and linear Rashba interactions in the conduction bands of the Type-I heterostructure. On the contrary, there is spin-splitting of both the valence and the conduction bands in the Type-II interface, which are found to be only linear Rashba type. Interestingly, the Type-II interface also harbors a potential photocurrent transition path, making it an excellent platform to study the circularly polarized photogalvanic effect.

Pathophysiology Associated with Diabetes-induced Tauopathy and Development of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia that affects the elderly around the world. Chronic type 2 diabetes (T2DM) has been proven to be closely related to neurodegeneration, especially AD. T2DM is characterized by the cell's failure to take up insulin as well as chronic hyperglycemia. In the central nervous system, insulin plays vital regulatory roles, while in chronic hyperglycemia, it leads to the formation and accumulation of advanced glycation end products (AGEs). Inflammation plays a crucial role in development of insulin resistance in AD and T2DM. The microtubule-related protein tau is involved in the pathogenesis of several neurological diseases known as tauopathies, and is found to be abnormally hyperphosphorylated in AD and accumulated in neurons. Chronic neuroinflammation causes the breakdown of the blood-brain barrier (BBB) observed in tauopathies. The development of pro-inflammatory signaling molecules, such as cytokines, chemokines from glial cells, neurons and endothelial cells, decides the structural integrity of BBB and immune cell migration into the brain. This review highlights the use of antidiabetic compounds as promising therapeutics for AD, and also describes several new pathological molecular mechanisms associated with diabetes that increase AD pathogenesis.

Narrow-Bandgap LaMO3 (M = Ni, Co) nanomaterials for efficient interfacial solar steam generation.

Photothermal water evaporation provides a pathway towards a promising solution to global freshwater scarcity. Synergistic integration of functions in a material in diverse directions is a key strategy for designing multifunctional materials. Lanthanum-based perovskite complex oxides LaMO3 (M = Ni and Co) have narrow band gaps with a high absorption coefficient. These functionalities have not been appropriately explored for photothermal energy conversion. Here, we synthesized nanostructured metallic LaNiO3 and semiconducting LaCoO3 and used them to design interfacial solar steam generators. Effective light absorption capability over the entire solar spectrum of these materials leads to a photothermal efficiency of the order of 83% for both materials. Using a cone-shaped 3D interfacial steam generator with a LaNiO3 absorber, we achieved an evaporation rate of 2.3 kg m-2 h-1, corresponding to solar vapor generation efficiency of over 95%. To the best of our knowledge, this evaporation rate is higher than any oxide-based interfacial solar steam generator reported so far. Furthermore, we have also shown an effective way of using such evaporators for long-term seawater desalination.

Oncotherapeutic Application of Resveratrol-based Inorganic Nanoparticles.

BACKGROUND: Potential therapeutic benefits of natural phytoconstituents and the emergence of nano-structured drug delivery systems have expanded the scope of enhanced chemotherapy with minimal adverse effects. Various in vivo and in vitro studies have revealed Resveratrol to be a potent anti-carcinogenic agent. Researchers are currently applying the concept of nano-science for enhancing the delivery of phyto-drugs like resveratrol, in order to carry the drug to the affected tissues and organs of cancer patients with much ease and efficiency. METHODS: The current review emphasizes the use of inorganic nanoparticles for enhancing the delivery and efficacy of resveratrol into otherwise inaccessible tumorigenic tissues. CONCLUSION: The present review work summarizes a comprehensive update on the mechanism of actions of the resveratrol-based inorganic nanocomposite particles that are currently being studied against various cancer models. This work may be significant in laying the foundation for the future of metallic nanoparticles-based delivery and efficacy of phytochemicals in general and resveratrol in specific against non-invasive metastatic cancer.

CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice.

BACKGROUND AND OBJECTIVE: Targeted drug delivery of nanoparticles decorated with site-specific recognition ligands is of considerable interest to minimize cytotoxicity of chemotherapeutics in the normal cells. The study was designed to develop CD-340 antibody-conjugated polylactic-co-glycolic acid (PLGA) nanoparticles loaded with a highly water-soluble potent anticancer drug, doxorubicin (DOX), to specifically deliver entrapped DOX to breast cancer cells. METHODS: The study showed how to incorporate water-soluble drug in a hydrophobic PLGA (85:15) based matrix which otherwise shows poor drug loading due to leaching effect. The optimized formulation was covalently conjugated to anti-human epidermal growth factor receptor-2 (HER2) antibody (CD-340). Surface conjugation of the ligand was assessed by flow cytometry, confocal microscopy, and gel electrophoresis. Selectivity and cytotoxicity of the experimental nanoparticles were tested on human breast cancer cells SKBR-3, MCF-7, and MDA-MB-231. Both CD-340-conjugated and unconjugated nanoparticles were undergone in vitro and in vivo characterization. RESULT: Higher level of incorporation of DOX (8.5% W/W), which otherwise shows poor drug loading due to leaching effect of the highly water-soluble drug, was seen in this method. In HER2-overexpressing tumor xenograft model, radiolabeled antibody-conjugated nanoparticles showed preferentially more of the formulation accumulation in the tumor area when compared to the treatments with the unconjugated one or with the other control groups of mice. The ligand conjugated nanoparticles showed considerable potential in reduction of tumor growth and cardiac toxicity of DOX in mice, a prominent side-effect of the drug. CONCLUSION: In conclusion, CD-340-conjugated PLGA nanoparticles containing DOX preferentially delivered encapsulated drug to the breast cancer cells and in breast tumor and reduced the breast tumor cells by apoptosis. Site-specific delivery of the formulation to neoplastic cells did not affect normal cells and showed a drastic reduction of DOX-related cardiotoxicity.

Apigenin loaded nanoparticle delayed development of hepatocellular carcinoma in rats.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer related death globally. Apigenin, a dietary flavonoid, possesses anti-tumor activity against HCC cells in-vitro. Development, physicochemical characterization of apigenin loaded nanoparticles (ApNp), biodistribution pattern and pharmacokinetic parameters of apigenin upon intravenous administration of ApNp, and effect of ApNp treatment in rats with HCC were investigated. Apigenin loaded nanoparticles had a sustained drug release pattern and successfully reached the hepatic cancer cells in-vitro as well as in liver of carcinogenic animals. ApNp predominantly delayed the progress of HCC in chemical induced hepatocarcinogenesis in rats. Quantification of apigenin by liquid chromatography-mass spectroscopy (LC-MS/MS) showed that apigenin availability significantly increased in blood and liver upon ApNp treatment. Apigenin loaded nanoparticle delivery substantially controlled the severity of hepatocellular carcinoma and could be a future hope for lingering the survival in hepatic cancer patients.

Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood-brain barrier into brain.

Delivering highly water soluble drugs across blood-brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.

Variation of Pharmacokinetic Profiles of Some Antidiabetic Drugs from Nanostructured Formulations Administered Through Pulmonary Route.

BACKGROUND: Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. WHO projects that diabetes death will be doubled between 2005 and 2030, where 347 million people worldwide had diabetes as per the report of 2013. The increase in the prevalence of diabetes is due to three influences - lifestyle, ethnicity, and age. METHODS: The present review summarizes the pharmacokinetic parameters and challenges in the field of nanoparticles and nanoliposomes of insulin and other antidiabetic drugs given through pulmonary route to treat diabetes effectively. RESULTS: Current challenges in diabetes management include optimizing the use of the already available therapies to ensure adequate glycemic condition, blood pressure, lipid control and to reduce complications. At present, several pieces of research have been focusing on new management options for diabetes. Among these options, the use of nanomedicine is becoming an eye catching and most promising one. Currently, nanoparticles and nanoliposomes are thrust areas of research to treat any deadly disease like diabetes. These drug delivery systems ultimately result in longer circulation half-lives, improved drug pharmacokinetics, and reduced side effects of therapeutically active substances that may be insulin and non-insulin. CONCLUSIONS: Thus, the pulmonary route is the most promising alternative route of drug delivery since it is non-invasive and lungs have a large surface area, richly supplied by the capillary network, for absorption of drugs.

Size dependent variations of phospholipid based vesicular drug carriers in systemic drug activity.

Lipid based vesicular drug delivery system, one of the emerging technologies designed for addressing the delivery challenges of conventional drug delivery methods, has widespread applications in chemotherapeutics, immunotherapeutics, recombinant DNA technology, membrane biology and also as a diagnostic tool in different biological field. The enclosed phospholipid bilayer spherical structure, typically known as liposome, is a versatile vesicular delivery system to carry hydrophilic/hydrophobic drug generally efficiently to the site of action leading to reduced non-specific toxicity and improved bioavailability of the therapeutic moiety. Efficacy of drug encapsulated in liposome depends mainly on the circulation amount of liposome and its residence time, in vivo drug release, drug accumulation in the target site and uptake of the formulation in the reticuloendothelial system. Liposomal formulation factors that dictate those actions are liposomal size (hydrodynamic diameter), surface charge, lipid composition and steric stabilization. Variation in liposomal size shows around 100 fold alterations in pharmacokinetic parameters and systemic activity while the other factors such as surface charge, lipid composition and steric stabilization bring only about 10 fold changes in those properties. The findings indicate the critical role of vesicular size in liposomal efficacy. In the present review the effect of size-variation of liposome on systemic activity of drug as well as its pharmacokinetic profile will be discussed to understand the rational designing of liposomal preparation to maximize therapeutic activity of a drug at desired magnitude and to provide a wide range of product applications such as immunological vaccines, chemotherapy, antimicrobial therapy etc.

Is type 2 diabetes mellitus a predisposal cause for developing hepatocellular carcinoma?

Hepatic cancer stands as one of the frontier causes of cancer related mortality worldwide. Among the several risk factors already established, type 2 diabetes is now considered as one of the important risks in progression of liver cancer. Studies have shown that likelihood of occurrence of liver cancer is many folds higher in patients diagnosed with type II diabetes compared to patients without diabetes. Liver plays an important role in metabolism of glucose in our body, so may be type II diabetes as it is an important epiphenomenon of hepatic diseases such as liver cirrhosis, liver failure, fatty liver, chronic hepatitis and hepatocellular carcinoma. Some reports suggested that extensive change in enzyme structures in molecular level in diabetic patients may lead to liver function damage and hence accelerate hepatic cancer. Other strong links between these two diseases are "non alcoholic fatty liver diseases" and "nonalcoholic steatohepatitis" which are metabolic disorders caused by type II diabetes and eventually develops hepatocellular carcinoma. However, it still remains unanswered whether prevention of diabetes would effectively lower the chances of developing liver cancer or eliminating diabetes from the population would effectively reduce the liver cancer incidence. In this review, we will primarily focus on the molecular link between type2 diabetes and hepatic cancer and investigate underlying mechanism to establish type II diabetes as predisposed cause of hepatic cancer.

Peptides, proteins and peptide/protein-polymer conjugates as drug delivery system.

In the last few decades, novel drug delivery strategies have been a big priority to the formulation scientists. Peptides and proteins have drawn a special attention for their wide scope in the area. Serum albumin, transferrin, recom- binant proteins, virus capsids etc. are used as carrier for drug and biomolecules. Conjugates of polymers with proteins have also shown strong potency in the field of drug delivery. Polyethylene glycol is one of the most successful polymers that has been used extensively to develop protein conjugated formulations. Besides, polyvinyl pyrrolidone, polylactic-co- glycolic acid, N-(2-hydroxypropyl) methacrylamide copolymer, polyglutamic acid have also been investigated. In this re- view, we will highlight on the most recent overview of various advantages, limitations and marketed products of proteins, peptides and protein/peptide-polymer conjugates as drug carriers, such products in clinical trials and their various uses in the field of modern drug delivery. Understanding the key features of these materials and the vigorous research in this field will develop new drug formulations that will combat various types of life-threatening diseases.

Kidney cancer is characterized by aberrant methylation of tissue-specific enhancers that are prognostic for overall survival.

PURPOSE: Even though recent studies have shown that genetic changes at enhancers can influence carcinogenesis, most methylomic studies have focused on changes at promoters. We used renal cell carcinoma (RCC), an incurable malignancy associated with mutations in epigenetic regulators, as a model to study genome-wide patterns of DNA methylation at a high resolution. EXPERIMENTAL DESIGN: Analysis of cytosine methylation status of 1.3 million CpGs was determined by the HELP assay in RCC and healthy microdissected renal tubular controls. RESULTS: We observed that the RCC samples were characterized by widespread hypermethylation that preferentially affected gene bodies. Aberrant methylation was particularly enriched in kidney-specific enhancer regions associated with H3K4Me1 marks. Various important underexpressed genes, such as SMAD6, were associated with aberrantly methylated, intronic enhancers, and these changes were validated in an independent cohort. MOTIF analysis of aberrantly hypermethylated regions revealed enrichment for binding sites of AP2a, AHR, HAIRY, ARNT, and HIF1 transcription factors, reflecting contributions of dysregulated hypoxia signaling pathways in RCC. The functional importance of this aberrant hypermethylation was demonstrated by selective sensitivity of RCC cells to low levels of decitabine. Most importantly, methylation of enhancers was predictive of adverse prognosis in 405 cases of RCC in multivariate analysis. In addition, parallel copy-number analysis from MspI representations demonstrated novel copy-number variations that were validated in an independent cohort of patients. CONCLUSIONS: Our study is the first high-resolution methylome analysis of RCC, demonstrates that many kidney-specific enhancers are targeted by aberrant hypermethylation, and reveals the prognostic importance of these epigenetic changes in an independent cohort.

Selective trapping of single mammalian breast cancer cells by insulator-based dielectrophoresis.

The trapping or immobilization of individual cells at specific locations in microfluidic platforms is essential for single cell studies, especially those requiring cell stimulation and downstream analysis of cellular content. Selectivity for individual cell types is required when mixtures of cells are analyzed in heterogeneous and complex matrices, such as the selection of metastatic cells within blood samples. Here, we demonstrate a microfluidic device based on direct current (DC) insulator-based dielectrophoresis (iDEP) for selective trapping of single MCF-7 breast cancer cells from mixtures with both mammalian peripheral blood mononuclear cells (PBMC) as well MDA-MB-231 as a second breast cancer cell type. The microfluidic device has a teardrop iDEP design optimized for the selective capture of single cells based on their differential DEP behavior under DC conditions. Numerical simulations adapted to experimental device geometries and buffer conditions predicted the trapping condition in which the dielectrophoretic force overcomes electrokinetic forces for MCF-7 cells, whereas PBMCs were not trapped. Experimentally, selective trapping of viable MCF-7 cells in mixtures with PBMCs was demonstrated in good agreement with simulations. A similar approach was also executed to demonstrate the selective trapping of MCF-7 cells in a mixture with MDA-MB-231 cells, indicating the selectivity of the device for weakly invasive and highly invasive breast cancer cells. The DEP studies were complemented with cell viability tests indicating acceptable cell viability over the course of an iDEP trapping experiment.

Insulator-based dielectrophoretic single particle and single cancer cell trapping.

Trapping of individual cells at specific locations in a microfluidic lab-on-a-chip platform is essential for single cell studies, especially those requiring individual stimulation followed by downstream analysis. To this aim, we have designed microdevices based on direct current (DC) insulator-based dielectrophoresis (iDEP) acting as individual single cell traps. We present both the design of a negative iDEP trap and a positive iDEP trap using insulating posts integrated at microchannel intersections. We obtained electric field distributions via numerical simulations adapted to the intersection and trap geometry with which we predict single particle pathlines. With polystyrene particles of 10 µm diameter, we demonstrated an effective design for a single particle trap in the case of negative dielectrophoresis. The onset trapping voltage shows an inverse relation to the buffer conductivity, thus indicating the influence of electrokinetic effects on the trapping behavior. Additionally, we demonstrated the proof-of-principle of single MCF-7 breast cancer cell trapping in a positive iDEP trap. Our single particle trapping experiments were further in very good agreement with numerical simulations. To ensure that no significant damage occurred to the cells during the experiment, we further optimized medium conditions to ensure viability of the cells for at least 1 h, more than sufficient for microfluidic trapping experiments. Our results thus indicated the successful design of DC iDEP traps, which can easily be integrated into a variety of microchip operations for single cell analysis.