Use of single-chain antibody derivatives for targeted drug delivery

Single-chain antibodies (scFvs), which contain only the variable domains of full-length antibodies, are relatively small molecules that can be used for selective drug delivery. In this review, we discuss how scFvs help improve the specificity and efficiency of drugs. Small interfering RNA (siRNA) delivery using scFv-drug fusion peptides, siRNA delivery using scFv-conjugated nanoparticles, targeted delivery using scFv-viral peptide-fusion proteins, use of scFv in fusion with cell-penetrating peptides for effective targeted drug delivery, scFv-mediated targeted delivery of inorganic nanoparticles, scFv-mediated increase of tumor killing activity of granulocytes, use of scFv for tumor imaging, site-directed conjugation of scFv molecules to drug carrier systems, use of scFv to relieve pain and use of scFv for increasing drug loading efficiency are among the topics that are discussed here. © 2016, University of Michigan. All rights reserved

A novel diblock copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells

Curcumin is a potent natural anticancer agent, but its effectiveness is limited by properties such as very low solubility, high rate of degradation, and low rate of absorption of its hydrophobic molecules in vivo. To date, various nanocarriers have been used to improve the bioavailability of this hydrophobic biomaterial. This study investigates the encapsulation of curcumin in a novel nanostructure of monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) and its anticancer effect. Tests were done to determine the critical micelle concentration (CMC), encapsulation efficiency, drug-loading efficiency, and cytotoxicity (against U87MG brain carcinoma cells and HFSF-PI3 cells as normal human fibroblasts) of some nanodevice preparations. The results of fluorescence microscopy and cell-cycle analyses indicated that the in vitro bioavailability of the encapsulated curcumin was significantly greater than that of free curcumin. Cytotoxicity evaluations showed that half maximal inhibitory concentrations of free curcumin and curcumin-loaded mPEG-OA for the U87MG cancer cell line were 48 μM and 24 μM, respectively. The Annexin-V-FLUOS assay was used to quantify the apoptotic effect of the prepared nanostructures. Apoptosis induction was observed in a dose-dependent manner after curcumin-loaded mPEG-OA treatments. Two common self-assembling structures, micelles and polymersomes, were observed by atomic force microscopy and dynamic light scat­tering, and the abundance of each structure was dependent on the concentration of the diblock copolymer. The mPEG-OA micelles had a very low CMC (13.24 μM or 0.03 g/L). Moreover, atomic force microscopy and dynamic light scattering showed that the curcumin-loaded mPEG-OA polymersomes had very stable structures, and at concentrations 1,000 times less than the CMC, at which the micelles disappear, polymersomes were the dominant structures in the dispersion with a reduced size distribution below 150 nm. Overall, the results from these tests revealed that this nanocarrier can be considered as an appropriate drug delivery system for delivering curcumin to cancer cells. © 2014 Erfani-Moghadam et al

Contributions of CH4-amine interactions by primary, secondary, and tertiary amines on CO2/CH4 separation efficiency

In designing amine-incorporated adsorbents for CO2/CH4 separation, it is essential to understand the individual effects amine moieties have on the separation of CO2/CH4 mixtures. In this work, primary, secondary, and tertiary amines are moderately grafted on SBA-15 to examine factors affecting adsorption of CO2 and CH4. Materials were characterised by thermogravimetric and elemental analysis, and their performance was measured by volumetric and gravimetric gas adsorption. An amine density of 1.6–1.7 mmol/g in secondary and tertiary amines showed an equivalent CH4 uptake of <0.04 mmol/g at 25 °C, while primary amines adsorbed 0.05 mmol/g, indicating stronger interaction forces with CH4. In terms of selectivity, primary and secondary amines grafted at 1.3–1.4 mmol/g had similar values, unaffected by amine type. Adsorption results cross analysed with DFT simulations indicate similar binding energies for CH4 by both amine moieties, concluding the facilitated access of gas molecules to primary amine moieties is the primary factor dictating degree of adsorption. At an amine density of ∼ 1.7 mmol/g for both primary and secondary amines, an increase in temperature from 25 to 40 °C at a CO2 partial pressure of 40 kPa showed a decrease in CO2/CH4 selectivity of only primary amines. Secondary amines are thus more selective amine moieties at these conditions. Furthermore, in isothermal adsorption–desorption conditions, moderately grafted secondary amines have an equal working capacity to primary amines. Both these qualities support secondary amines at moderate densities as candidates for adsorbent development in CO2/CH4 separations

Discovery of an Optimal Porous Crystalline Material for the Capture of Chemical Warfare Agents

Chemical warfare agents (CWAs) are regarded as a critical challenge in our society. Here, we use a high-throughput computational screening strategy backed up by experimental validation to identify and synthesize a promising porous material for CWA removal under humid conditions. Starting with a database of 2,932 existing metal-organic framework (MOF) structures, we selected those possessing cavities big enough to adsorb well-known CWAs such as sarin, soman, and mustard gas as well as their nontoxic simulants. We used Widom method to reduce significantly the simulation time of water adsorption, allowing us to shortlist 156 hydrophobic MOFs where water will not compete with the CWAs to get adsorbed. We then moved to grand canonical Monte Carlo (GCMC) simulations to assess the removal capacity of CWAs. We selected the best candidates in terms of performance but also in terms of chemical stability and moved to synthesis and experimental breakthrough adsorption to probe the predicted, excellent performance. This computational-experimental work represents a fast and efficient approach to screen porous materials in applications that involve the presence of moisture

Postactivation potentiation effect of two lower body resistance exercises on repeated jump performance measures

This study examined the postactivation potentiation effects of combining squat and deadlift exercises on subsequent repeated jump performance. Fifteen, resistance-trained youth wrestlers were randomly allocated to either undertake back squats (BSq), deadlift (DL) or BSq and DL as supersets (BSq+DL), with a repeated jump protocol performed 8-minutes post-exercise in each session. Thereafter, a control condition (CON) was completed involving a general warm-up, followed by the repeated jump protocols. Power outputs, flight time, contact time and reactive strength index were recorded from each repeated jump protocol. Measures were compared between the BSq, DL and BSq+DL sessions and between sessions that generated the best power output (BEST) with CON via inferential statistics and effect size (ES) calculations. The BSq condition exhibited significantly greater power output compared to the CON condition (p<0.05, ES = 1.07), although no differences were identified for the other conditioning activities. Furthermore, power output, flight time and reactive strength index were significantly greater for the BEST compared to the CON condition (p<0.05, ES = 0.97-1.47). Results indicated that BSq was the optimal conditioning activity to increase power output during a repeated jump protocol. However, greater improvement during the BEST condition suggests that the type of conditioning activity should also be considered on an individual-basis

Review paper: Introduction of pediatric balance therapy in children with vestibular dysfunction: Review of indications, mechanisms, and key exercises

The vestibular system is important for the development of normal movement reactions, motion tolerance, and motor control for postural alignment, balance, and vision. A vestibular system that is damaged by disease or injury in childhood can have a major impact on a child's development. In addition, the emergence of vestibular lesions may also lead to cognitive deficits, including attention deficit. Despite the advances in testing and documentation of vestibular deficits in children, the vestibular problems continue to be an overlooked entity. Many children do not receive treatment that could significantly improve function and address the developmental delays caused by vestibular disorders. Vestibular rehabilitation therapy (VRT) has been defined as an effective modality for most individuals with disorders of the vestibular or central balance system disorders. The basis for the success of VRT is the use of existing neural mechanisms in the human brain for adaptation, plasticity, and compensation. The vestibular system cannot be considered as a separate entity ignoring other balance subsystems. Hence, a modified VRT program, named pediatric balance therapy with special modifications in exercises, was developed for children with vestibular disorders, in accordance to the whole balance system

STAT4 deficiency reduces the development of atherosclerosis in mice

Atherosclerosis is a chronic inflammatory process that leads to plaque formation in large and medium sized vessels. T helper 1 (Th1) cells constitute the majority of plaque infiltrating pro-atherogenic T cells and are induced via IFNγ-dependent activation of T-box (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (STAT4). We thus aimed to define a role for STAT4 in atherosclerosis. STAT4-deficiency resulted in a ∼71% reduction (p < 0.001) in plaque burden in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice fed chow diet and significantly attenuated atherosclerosis (∼31%, p < 0.01) in western diet fed Stat4(-/-)Apoe(-/-) mice. Surprisingly, reduced atherogenesis in Stat4(-/-)Apoe(-/-) mice was not due to attenuated IFNγ production in vivo by Th1 cells, suggesting an at least partially IFNγ-independent pro-atherogenic role of STAT4. STAT4 is expressed in T cells, but also detected in macrophages (MΦs). Stat4(-/-)Apoe(-/-)in vitro differentiated M1 or M2 MΦs had reduced cytokine production compare to Apoe(-/-) M1 and M2 MΦs that was accompanied by reduced induction of CD69, I-A(b), and CD86 in response to LPS stimulation. Stat4(-/-)Apoe(-/-) MΦs expressed attenuated levels of CCR2 and demonstrated reduced migration toward CCL2 in a transwell assay. Importantly, the percentage of aortic CD11b(+)F4/80(+)Ly6C(hi) MΦs was reduced in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice. Thus, this study identifies for the first time a pro-atherogenic role of STAT4 that is at least partially independent of Th1 cell-derived IFNγ, and primarily involving the modulation of MΦ responses