Quinine-Based Semisynthetic Ion Transporters with Potential Antiproliferative Activities.

Synthetic ion transporters have attracted tremendous attention for their therapeutic potential against various ion-transport-related diseases, including cancer. Inspired by the structure and biological activities of natural products, we synthesized a small series of squaramide and thiourea derivatives of quinine and investigated their ion transport activities. The involvement of a quinuclidine moiety for the cooperative interactions of Cl- and H+ ions with the thiourea or squaramide moiety resulted in an effectual transport of these ions across membranes. The interference of ionic equilibrium by the potent Cl- ion carrier selectively induced cancer cell death by endorsing caspase-arbitrated apoptosis. In vivo assessment of the potent ionophore showed an efficient reduction in tumor growth with negligible immunotoxicity to other organs.

Nontoxic, double-deletion-mutant rabies viral vectors for retrograde targeting of projection neurons.

Recombinant rabies viral vectors have proven useful for applications including retrograde targeting of projection neurons and monosynaptic tracing, but their cytotoxicity has limited their use to short-term experiments. Here we introduce a new class of double-deletion-mutant rabies viral vectors that left transduced cells alive and healthy indefinitely. Deletion of the viral polymerase gene abolished cytotoxicity and reduced transgene expression to trace levels but left vectors still able to retrogradely infect projection neurons and express recombinases, allowing downstream expression of other transgene products such as fluorophores and calcium indicators. The morphology of retrogradely targeted cells appeared unperturbed at 1 year postinjection. Whole-cell patch-clamp recordings showed no physiological abnormalities at 8 weeks. Longitudinal two-photon structural and functional imaging in vivo, tracking thousands of individual neurons for up to 4 months, showed that transduced neurons did not die but retained stable visual response properties even at the longest time points imaged.

Thioaptamer targeted discoidal microparticles increase self immunity and reduce Mycobacterium tuberculosis burden in mice.

Worldwide, tuberculosis (TB) remains one of the most prevalent infectious diseases causing morbidity and death in >1.5 million patients annually. Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, usually resides in the alveolar macrophages. Current tuberculosis treatment methods require more than six months, and low compliance often leads to therapeutic failure and multidrug resistant strain development. Critical to improving TB-therapy is shortening treatment duration and increasing therapeutic efficacy. In this study, we sought to determine if lung hemodynamics and pathological changes in Mtb infected cells can be used for the selective targeting of microparticles to infected tissue(s). Thioaptamers (TA) with CD44 (CD44TA) targeting moiety were conjugated to discoidal silicon mesoporous microparticles (SMP) to enhance accumulation of these agents/carriers in the infected macrophages in the lungs. In vitro, CD44TA-SMP accumulated in macrophages infected with mycobacteria efficiently killing the infected cells and decreasing survival of mycobacteria. In vivo, increased accumulations of CD44TA-SMP were recorded in the lung of M. tuberculosis infected mice as compared to controls. TA-targeted carriers significantly diminished bacterial load in the lungs and caused recruitment of T lymphocytes. Proposed mechanism of action of the designed vector accounts for a combination of increased uptake of particles that leads to infected macrophage death, as well as, activation of cellular immunity by the TA, causing increased T-cell accumulation in the treated lungs. Based on our data with CD44TA-SMP, we anticipate that this drug carrier can open new avenues in TB management.

A study on the phytoaccumulation of waste elements in wetland plants of a Ramsar site in India.

Some wetland plant species are adapted to growing in the areas of higher metal concentrations. Use of such vegetation in remediation of soil and water contaminated with heavy metals is a promising cost-effective alternative to the more established treatment methods. Throughout the year, composite industrial effluents bringing various kinds of heavy metals contaminate our study site, the East Calcutta Wetlands, a Ramsar site at the eastern fringe of Kolkata city (formerly Calcutta), India. In the present study, possible measures for remediation of contaminated soil and water (with elements namely, Ca, Cr, Cu, Pb, Zn, Mn, and Fe) of the ecosystem had been investigated. Ten common regional wetland plant species were selected to study their efficiency and diversity in metal uptake and accumulation. Results showed that Bermuda grass (Cynodon dactylon) had the highest total Cr concentration (6,601 ± 33 mg kg( -1) dw). The extent of accumulation of various elements in ten common wetland plants of the study sites was: Pb (4.4-57 mg kg( -1) dw), Cu (6.2-39 mg kg( -1) dw), Zn (59-364 mg kg( -1) dw), Mn (87-376 mg kg( -1) dw), Fe (188-8,625 mg kg( -1) dw), Ca (969-3,756 mg kg( -1) dw), and Cr (27-660 mg kg( -1) dw) indicating an uptake gradient of elements by plants as Ca>Fe>Mn>Cr>Zn>Cu>Pb. The present study indicates the importance of identification and efficiency of metal uptake and accumulation capabilities by plants in relation to their applications in remediation of a contaminated East Calcutta Wetland ecosystem.