Author
Shweta Sharma
Bio: Shweta Sharma is an academic researcher from University of Puerto Rico, Río Piedras. The author has contributed to research in topics: Apoptosis & Conjugate. The author has an hindex of 4, co-authored 4 publications receiving 102 citations.
Topics: Apoptosis, Conjugate, Transferrin, Endocytosis, Cytochrome c
Papers
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TL;DR: The first X-ray crystal structure of a Ti(IV)-bound sTf is solved, which provides the first glimpse into the citrate-transferrin synergism in the regulation of Ti( IV) bioactivity and offers insight into the future design of Ti-based anticancer drugs.
Abstract: Human serum transferrin (sTf) is a protein that mediates the transport of iron from blood to cells. Assisted by the synergistic anion carbonate, sTf transports Fe(III) by binding the metal ion in a closed conformation. Previous studies suggest sTf’s role as a potential transporter of other metals such as titanium. Ti is a widely used metal in colorants, foods, and implants. A substantial amount of Ti is leached into blood from these implants. However, the fate of the leached Ti and its transport into the cells is not known. Understanding Ti interaction with sTf assumes a greater significance with our ever increasing exposure to Ti in the form of implants. On the basis of in vitro studies, it was speculated that transferrin can bind Ti(IV) assisted by a synergistic anion. However, the role and identity of the synergistic anion(s) and the conformational state in which sTf binds Ti(IV) are not known. Here we have solved the first X-ray crystal structure of a Ti(IV)-bound sTf. We find that sTf binds Ti(IV) in...
50 citations
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TL;DR: By closely examining the biological use of TiO2 and the influence of biomolecules on its stability and solubility, the reactivity of the material is reassessed in the presence and absence of UV energy.
Abstract: Titanium is one of the most abundant elements in the earth’s crust and while there are many examples of its bioactive properties and use by living organisms, there are few studies that have probed its biochemical reactivity in physiological environments. In the cosmetic industry, TiO2 nanoparticles are widely used. They are often incorporated in sunscreens as inorganic physical sun blockers, taking advantage of their semiconducting property, which facilitates absorbing ultraviolet (UV) radiation. Sunscreens are formulated to protect human skin from the redox activity of the TiO2 nanoparticles (NPs) and are mass-marketed as safe for people and the environment. By closely examining the biological use of TiO2 and the influence of biomolecules on its stability and solubility, we reassess the reactivity of the material in the presence and absence of UV energy. We also consider the alarming impact that TiO2 NP seepage into bodies of water can cause to the environment and aquatic life, and the effect that it can have on human skin and health, in general, especially if it penetrates into the human body and the bloodstream.
38 citations
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TL;DR: Based on its chemical similarities with Fe, the biological coordination chemistry of Fe(III) and Ti(IV) is compared and it is hypothesized that Ti( IV) can bind to similar intracellular biomolecules and inhibit Fe bioavailability.
32 citations
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TL;DR: The neo-conjugate developed has promise for future development to target cancers with enhanced transferrin receptor expression and maintained an IC50 value similar to the well known drug cisplatin in A549 cancer cells but also was nontoxic to the normal lung (MRC5) cells.
Abstract: One of the major drawbacks of many of the currently used cancer drugs are off-target effects. Targeted delivery is one method to minimize such unwanted and detrimental events. To actively target lung cancer cells, we have developed a conjugate of the apoptosis inducing protein cytochrome c with transferrin because the transferrin receptor is overexpressed by many rapidly dividing cancer cells. Cytochrome c and transferrin were cross-linked with a redox sensitive disulfide bond for the intra-cellular release of the protein upon endocytosis by the transferrin receptor. Confocal results demonstrated the cellular uptake of the cytochrome c-transferrin conjugate by transferrin receptor overexpressing A549 lung cancer cells. Localization studies further validated that this conjugate escaped the endosome. Additionally, an in vitro assay showed that the conjugate could induce apoptosis by activating caspase-3. The neo-conjugate not only maintained an IC50 value similar to the well known drug cisplatin (50 μM) in A549 cancer cells but also was nontoxic to the normal lung (MRC5) cells. Our neo-conjugate holds promise for future development to target cancers with enhanced transferrin receptor expression.
31 citations
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TL;DR: The main cellular uptake pathways of metal compounds, including passive diffusion, active uptake through transport channels and endocytosis-mediated uptake, provide a link between chemical forms of the metal species in the medium and their biological activities, leading to conflicting evidence of activities.
171 citations
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TL;DR: Most of the binary Ti alloys with alloying <20% elements of Zr, In, Ag, Cu, Au, Pd, Nb, Mn, Cr, Mo, Sn and Co have high potential as implant materials, due to good mechanical performance without compromising the biocompatibility and biological behaviour compare to cp-Ti.
Abstract: Titanium (Ti) has been used for long in dentistry and medicine for implant purpose During the years, not only the commercially pure Ti but also some alloys such as binary and tertiary Ti alloys were used The aim of this review is to describe and compare the current literature on binary Ti alloys, including Ti-Zr, Ti-In, Ti-Ag, Ti-Cu, Ti-Au, Ti-Pd, Ti-Nb, Ti-Mn, Ti-Mo, Ti-Cr, Ti-Co, Ti-Sn, Ti-Ge and Ti-Ga, in particular to mechanical, chemical and biological parameters related to implant application Literature was searched using the PubMed and Web of Science databases, as well as google without limiting the year, but with principle key terms such as ' Ti alloy', 'binary Ti ', 'Ti-X' (with X is the alloy element), 'dental implant' and 'medical implant' Only laboratory studies that intentionally for implant or biomedical applications were included According to available literatures, we might conclude that most of the binary Ti alloys with alloying <20% elements of Zr, In, Ag, Cu, Au, Pd, Nb, Mn, Cr, Mo, Sn and Co have high potential as implant materials, due to good mechanical performance without compromising the biocompatibility and biological behaviour compare to cp-Ti
164 citations
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TL;DR: Progress in engineering the architecture and biological functions of peptide-based biomaterials —naturally derived, chemically synthesized and recombinant— with a focus on the molecular features that modulate their structure-function relationships for drug delivery are discussed.
132 citations
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TL;DR: An overview of the key role played by the cytochrome c-cardiolipin interaction in apoptosis is provided, which provides interesting perspectives for applications in clinical diagnostics that use the protein as a biomarker.
107 citations