ABSTRACT
We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human remains from North America are not always generalizable worldwide. Here we propose the following globally applicable guidelines, taking into consideration diverse contexts. These hold that: (1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives. We commit to adhering to these guidelines and expect they will promote a high ethical standard in DNA research on human remains going forward.
Subject(s)
Cadaver , DNA, Ancient/analysis , Guidelines as Topic , Human Genetics/ethics , Internationality , Molecular Biology/ethics , American Indian or Alaska Native , Anthropology/ethics , Archaeology/ethics , Community-Institutional Relations , Humans , Indigenous Peoples , Stakeholder Participation , TranslationsABSTRACT
A rhodamine appended Fe(iii)-catecholate complex Fe(RhoCat)3 is reported as a smart dual-modal T1 MRI-optical imaging probe. The high spin Fe(iii) coordination sphere and rhodamine unit act as MRI and optical reporters, respectively. The probe showed a r1-relaxivity of 4.37 mM-1 s-1 at 1.41 T via the interaction of second sphere water molecules to coordinated oxygen atoms. It produced an enhanced signal intensity of phantom images on the 7.0 T animal research MRI/MRS scanner at 25 °C and pH 7.3. The interaction of the probe with bovine serum albumin (BSA) significantly improved r1 relaxivity (7.09 mM-1 s-1). Moreover, the optical imaging reporter rhodamine moiety exhibited sensitivity towards biomolecule nitric oxide (NO) and acidic pH via the formation of a ring-opened tautomer of rhodamine, wherein the r1 relaxivity of the probe was enhanced to 5.19 mM-1 s-1 for NO and slightly decreased for acidic pH. Further, the probe visualized NO in adenocarcinoma gastric (AGS) cells via a turn-on fluorescence mechanism with 80% cell viability. Thus, Fe(RhoCat)3 is demonstrated as a potential dual "MRI-ON and Fluorescence-ON" molecular imaging probe to visualize the NO molecule and acidic pH in the tumour microenvironment.
Subject(s)
Coordination Complexes/chemistry , Iron/chemistry , Magnetic Resonance Imaging/methods , Optical Imaging/methods , Rhodamines/chemistry , Catechols/chemistry , Cell Line, Tumor , Coordination Complexes/metabolism , Humans , Hydrogen-Ion Concentration , Nitric Oxide/chemistry , Serum Albumin, Bovine/metabolism , Tomography, Optical CoherenceABSTRACT
Vanadyl compounds of clinical significance are recommended as drugs against diseases such as tuberculosis, diabetes, cancer, etc. In order to check the potential of the salphen ligands and oxovanadium(IV)-salphen complexes as drugs their binding with bovine serum albumin (BSA) is investigated. The binding constants measured at pH 7.4 using UV-vis absorption and fluorescence techniques are in the range of 10(3)-10(5) M(-1). The quenching of the fluorescence of BSA and appearance of enhanced luminescence of the salphen ligand/vanadium(IV) complex at the increased [quencher] show efficient FRET from the protein to the quencher and the distance of energy transfer estimated using Forster's theory is in the range of 1.4-3.5 nm. Molecular docking studies (DFT) utilizing oxovanadium(IV)-salphen derivatives show strong binding with BSA and give insight into the binding modes, interaction pattern and stability of synthesized complexes in the target site. The cytotoxicity study shows the ability of these V(IV) complexes to inhibit the growth of AGS gastric cell lines.
Subject(s)
Coordination Complexes/metabolism , Phenylenediamines/chemistry , Serum Albumin, Bovine/metabolism , Vanadates/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Binding Sites , Cattle , Cell Line, Tumor , Cell Survival/drug effects , Coordination Complexes/chemistry , Coordination Complexes/toxicity , Fluorescence Resonance Energy Transfer , Humans , Molecular Docking Simulation , Protein Binding , Protein Structure, Tertiary , Serum Albumin, Bovine/chemistry , ThermodynamicsABSTRACT
The present study focused on the development of a novel biodegradable nanoparticle system based on polyethyleneglycol-modified gelatin (PEG-GEL) and polylactic acid (PLA) biopolymers for improving the photodynamic efficacy of cyclohexane-1,2-diamino hypocrellin B (CHA2HB), a potent photodynamic therapeutic (PDT) agent. The CHA2HB-loaded PEG-GEL/PLA nanoparticles showed near-spherical morphology with an average size of 190 nm at a PLA to PEG-GEL ratio of 1:3. The drug loading was sufficient enough to produce potentially toxic reactive oxygen species (ROS) needed for photodynamic therapy (PDT). Slow and controlled drug release was observed in normal conditions, whereas enzyme assistance resulted in a relatively fast release due to partial disintegration of CHA2HB-loaded PEG-GEL/PLA nanoparticles. In vitro experiments indicated that CHA2HB-loaded PEG-GEL-PLA nanoparticles are efficiently taken up by cancer cells such as human breast adenocarcinoma (MCF-7), human gastric sarcoma (AGS) and mice specific Dalton's lymphoma (DLA) in a time dependent manner. Further, CHA2HB-loaded PEG-GEL/PLA nanoparticles evoked superior phototoxicity compared to free-CHA2HB towards all the three cell lines investigated. Interestingly, PDT effectiveness was different for the different cell type studied. CHA2HB-loaded PEG-GEL/PLA nanoparticles induced both apoptotic and necrotic cell death as a result of photoirradiation. Thus, our data suggest that PEG-GEL/PLA nanoparticles are highly effective in delivery and phototoxic enhancement of CHA2HB against model cancer cells in vitro.