Impact of nanoparticles on amyloid β-induced Alzheimer’s disease, tuberculosis, leprosy and cancer: a systematic review

Nanotechnology is an interdisciplinary domain of science, technology and engineering that deals with nano-sized materials/particles. Usually, the size of nanoparticles lies between 1 and 100 nm. Due to their small size and large surface area-to-volume ratio, nanoparticles exhibit high reactivity, greater stability and adsorption capacity. These important physicochemical properties attract scientific community to utilize them in biomedical field. Various types of nanoparticles (inorganic and organic) have broad applications in medical field ranging from imaging to gene therapy. These are also effective drug carriers. In recent times, nanoparticles are utilized to circumvent different treatment limitations. For example, the ability of nanoparticles to cross the blood−brain barrier and having a certain degree of specificity towards amyloid deposits makes themselves important candidates for the treatment of Alzheimer’s disease. Furthermore, nanotechnology has been used extensively to overcome several pertinent issues like drug-resistance phenomenon, side effects of conventional drugs and targeted drug delivery issue in leprosy, tuberculosis and cancer. Thus, in this review, the application of different nanoparticles for the treatment of these four important diseases (Alzheimer’s disease, tuberculosis, leprosy and cancer) as well as for the effective delivery of drugs used in these diseases has been presented systematically. Although nanoformulations have many advantages over traditional therapeutics for treating these diseases, nanotoxicity is a major concern that has been discussed subsequently. Lastly, we have presented the promising future prospective of nanoparticles as alternative therapeutics. In that section, we have discussed about the futuristic approach(es) that could provide promising candidate(s) for the treatment of these four diseases

Complete solutions to the metric of spherically collapsing dust in an expanding spacetime with a cosmological constant

We present semi-analytical solutions to the background equations describing the Lema\^itre-Tolman-Bondi (LTB) metric as well as the homogeneous Friedmann equations, in the presence of dust, curvature and a cosmological constant Lambda. For none of the presented solutions any numerical integration has to be performed. All presented solutions are given for expanding and collapsing phases, preserving continuity in time and radius. Hence, these solutions describe the complete space time of a collapsing spherical object in an expanding universe. In the appendix we present for completeness a solution of the Friedmann equations in the additional presence of radiation, only valid for the Robertson-Walker metric.Comment: 23 pages, one figure. Numerical module for evaluation of the solutions released at http://web.physik.rwth-aachen.de/download/valkenburg/ColLambda/ Matches published version, published under Open Access. Note change of titl

On the covariant quantization of tensionless bosonic strings in AdS spacetime

The covariant quantization of the tensionless free bosonic (open and closed) strings in AdS spaces is obtained. This is done by representing the AdS space as an hyperboloid in a flat auxiliary space and by studying the resulting string constrained hamiltonian system in the tensionless limit. It turns out that the constraint algebra simplifies in the tensionless case in such a way that the closed BRST quantization can be formulated and the theory admits then an explicit covariant quantization scheme. This holds for any value of the dimension of the AdS space.Comment: 1+16 pages; v4 two clarifications adde

Absorbing-state phase transitions in fixed-energy sandpiles

We study sandpile models as closed systems, with conserved energy density $\zeta$ playing the role of an external parameter. The critical energy density, $\zeta_c$, marks a nonequilibrium phase transition between active and absorbing states. Several fixed-energy sandpiles are studied in extensive simulations of stationary and transient properties, as well as the dynamics of roughening in an interface-height representation. Our primary goal is to identify the universality classes of such models, in hopes of assessing the validity of two recently proposed approaches to sandpiles: a phenomenological continuum Langevin description with absorbing states, and a mapping to driven interface dynamics in random media. Our results strongly suggest that there are at least three distinct universality classes for sandpiles.Comment: 41 pages, 23 figure

B cell–activating factor modulates the factor VIII immune response in hemophilia A

Inhibitors of factor VIII (FVIII) remain the most challenging complication of FVIII protein replacement therapy in hemophilia A (HA). Understanding the mechanisms that guide FVIII-specific B cell development could help identify therapeutic targets. The B cell–activating factor (BAFF) cytokine family is a key regulator of B cell differentiation in normal homeostasis and immune disorders. Thus, we used patient samples and mouse models to investigate the potential role of BAFF in modulating FVIII inhibitors. BAFF levels were elevated in pediatric and adult HA inhibitor patients and decreased to levels similar to those of noninhibitor controls after successful immune tolerance induction (ITI). Moreover, elevations in BAFF levels were seen in patients who failed to achieve FVIII tolerance with anti-CD20 antibody–mediated B cell depletion. In naive HA mice, prophylactic anti-BAFF antibody therapy prior to FVIII immunization prevented inhibitor formation and this tolerance was maintained despite FVIII exposure after immune reconstitution. In preimmunized HA mice, combination therapy with anti-CD20 and anti-BAFF antibodies dramatically reduced FVIII inhibitors via inhibition of FVIII-specific plasma cells. Our data suggest that BAFF may regulate the generation and maintenance of FVIII inhibitors and/or anti-FVIII B cells. Finally, anti-CD20/anti-BAFF combination therapy may be clinically useful for ITI

Engineering and In Vitro Selection of a Novel AAV3B Variant with High Hepatocyte Tropism and Reduced Seroreactivity

Limitations to successful gene therapy with adeno-associated virus (AAV) can comprise pre-existing neutralizing antibodies to the vector capsid that can block cellular entry, or inefficient transduction of target cells that can lead to sub-optimal expression of the therapeutic transgene. Recombinant serotype 3 AAV (AAV3) is an emerging candidate for liver-directed gene therapy. In this study, we integrated rational design by using a combinatorial library derived from AAV3B capsids with directed evolution by in vitro selection for liver-targeted AAV variants. The AAV3B-DE5 variant described herein was undetectable in the original viral library but gained a selective advantage upon in vitro passaging in human hepatocarcinoma spheroid cultures. AAV3B-DE5 contains 24 capsid amino acid substitutions compared with AAV3B, distributed among all five variable regions, with strong selective pressure on VR-IV, VR-V, and VR-VII. In vivo, AAV3B-DE5 demonstrated improved human hepatocyte tropism in a liver chimeric mouse model. Importantly, this variant exhibited reduced seroreactivity to human intravenous immunoglobulin (i.v. Ig), as well as individual serum samples from 100 healthy human donors. Therefore, molecular evolution using a combinatorial library platform generated a viral capsid with high hepatocyte tropism and enhanced evasion of pre-existing AAV neutralizing antibodies

Linking Distributive and Procedural Justice to Employee Engagement Through Social Exchange: A Field Study in India

Research linking justice perceptions to employee outcomes has referred to social exchange as its central theoretical premise. We tested a conceptual model linking distributive and procedural justice to employee engagement through social exchange mediators, namely, perceived organizational support and psychological contract, among 238 managers and executives from manufacturing and service sector firms in India. Findings suggest that perceived organizational support mediated the relationship between distributive justice and employee engagement, and both perceived organizational support and psychological contract mediated the relationship between procedural justice and employee engagement. Theoretical and practical implications with respect to organizational functions are discussed