Hair analysis receives a large amount of academic and commercial interest for wide-ranging applications. However, in many instances, especially for elemental or 'mineral' analysis, the degree of ...success of analytical interpretation has been quite minimal with respect to the extent of such endeavors. In this
critical review
we address the questions surrounding hair analysis with specific intent of discovering what hair concentrations can actually relate to in a biogenic sense. This is done from a chemistry perspective to explain why and how elements are incorporated into hair and their meaning. This includes an overview of variables attributed to altering hair concentrations, such as age, gender, melanin content, and other less reported factors. Hair elemental concentrations are reviewed with regard to morbidity, with specific examples of disease related effects summarized. The application of hair analysis for epidemiology and etiology studies is enforced. A section is dedicated specifically to the area of population studies with regards to mercury, which highlights how endogenous and exogenous incorporation relies on species dependant metabolism and metabolic products. Many of the considerations are relevant to other areas of interest in hair analysis, such as for drug and isotopic analysis. Inclusion of a table of elemental concentrations in hair should act as a valuable reference (298 references).
Exploring hair elemental analysis. How is it useful, what does it mean and how can it be applied?
Light‐emitting semiconductor quantum dots (QDs) combined with magnetic resonance imaging contrast agents within a single nanoparticle platform are considered to perform as multimodal imaging probes ...in biomedical research and related clinical applications. The principles of their rational design are outlined and contemporary synthetic strategies are reviewed (heterocrystalline growth; co‐encapsulation or assembly of preformed QDs and magnetic nanoparticles; conjugation of magnetic chelates onto QDs; and doping of QDs with transition metal ions), identifying the strengths and weaknesses of different approaches. Some of the opportunities and benefits that arise through in vivo imaging using these dual‐mode probes are highlighted where tumor location and delineation is demonstrated in both MRI and fluorescence modality. Work on the toxicological assessments of QD/magnetic nanoparticles is also reviewed, along with progress in reducing their toxicological side effects for eventual clinical use. The review concludes with an outlook for future biomedical imaging and the identification of key challenges in reaching clinical applications.
Light‐emitting semiconductor quantum dots (QDs) combined with magnetic components offer appealing potential for biomedical applications. This review summarizes recent achievements in contemporary synthesis strategies identifying the strengths and weaknesses of different approaches, describes multimodal imaging of tumors in vivo, examines current understanding of the toxicity of QDs/magnetic nanoparticles, and discusses key challenges in reaching clinical applications with these materials and the perspectives for their future use in biomedical imaging.
Lead (Pb) bioaccessibility was assessed using 2 in vitro methods in 12 Pb-contaminated soils and compared to relative Pb bioavailability using an in vivo mouse model. In vitro Pb bioaccessibility, ...determined using the intestinal phase of the Solubility Bioaccessibility Research Consortium (SBRC) assay, strongly correlated with in vivo relative Pb bioavailability (R 2 = 0.88) following adjustment of Pb dissolution in the intestinal phase with the solubility of Pb acetate at pH 6.5 (i.e., relative Pb bioaccessibility). A strong correlation (R 2 = 0.78) was also observed for the relative bioaccessibility leaching procedure (RBALP), although the method overpredicted in vivo relative Pb bioavailability for soils where values were <40%. Statistical analysis of fit results from X-ray absorption near-edge structure (XANES) data for selected soils (n = 3) showed that Pb was strongly associated with Fe oxyhydroxide minerals or the soil organic fraction prior to in vitro analysis. XANES analysis of Pb speciation during the in vitro procedure demonstrated that Pb associated with Fe minerals and the organic fraction was predominantly solubilized in the gastric phase. However, during the intestinal phase of the in vitro procedure, Pb was strongly associated with formation of ferrihydrite which precipitated due to the pH (6.5) of the SBRC intestinal phase. Soils where Fe dissolution was limited had markedly higher concentrations of Pb in solution and hence exhibited greater relative bioavailability in the mouse model. This data suggests that coexistence of Fe in the intestinal phase plays an important role in reducing Pb bioaccessibility and relative bioavailability.
Metals and metalloids play important roles in plant function and metabolism. Likewise, plants subsequently introduce vital dietary nutrition to people and animals. Understanding the transport, ...localisation and speciation of these elements is critical for understanding availability and metabolic pathways. Subsequently this knowledge can be applied to plant physiology and agricultural research, food science and genetic engineering.
This review focuses on the most recent status of
in situ techniques to visualise spatial distributions and assess the speciation of metals and metalloids. The techniques addressed include: histochemical analysis, autoradiography, LA-ICP-MS, SIMS, SEM including EDX, PIXE; and synchrotron methods: XRF, differential and fluorescence tomography, and X-ray absorption techniques.
This review has been written with the intent of plant researchers to gain familiarity with techniques to which they are not accustom but wish to extend their research with alternative, but complementary, capabilities. Importantly, the disadvantages as well as advantages, have been highlighted for each technique and potential artefacts induced by the analysis or sample preparation are reviewed. These often overlooked aspects are the points critical for novice use of unfamiliar techniques and are offered for advancing research approaches commensurate with the accelerating interest regarding metal(loid)s in botanical specimens.
•Non-small cell lung cancer (NSCLC) frequently presents genetic mutuations.•NSCLC upregulates glucose metabolism and subsequent accumulates lactate.•Lactate as key molecule leads various phenomena in ...tumor microenvironment.•Lactate oxidase (LOX) can directly oxidize tumor-secreted lactate.•Consuming or oxidizing tumor-secreted lactate provides a potential route.
Targeted-therapy failure in treating nonsmall cell lung cancer (NSCLC) frequently occurs because of the emergence of drug resistance and genetic mutations. The same mutations also result in aerobic glycolysis, which further antagonizes outcomes by localized increases in lactate, an immune suppressor. Recent evidence indicates that enzymatic lowering of lactate can promote an oncolytic immune microenvironment within the tumour. Here, we review factors relating to lactate expression in NSCLC and the utility of lactate oxidase (LOX) for governing therapeutic delivery, its role in lactate oxidation and turnover, and relationships between lactate depletion and immune cell populations. The lactate-rich characteristic of NSCLC provides an exploitable property to potentially improve NSCLC outcomes and design new therapeutic strategies to integrate with conventional therapies.
Nanoparticle radiosensitization has been demonstrated well to enhance the effects of radiotherapy, motivate the improvement of therapeutic ratios, and decrease morbidity in cancer treatment. A ...significant challenge exists in optimizing formulations and translation due to insufficient knowledge of the associated mechanisms, which have historically been limited to physical concepts. Here, we investigated a concept for the role of biological mechanisms. The mere presence of gold nanoparticles led to a down-regulation of thymidylate synthase, important for DNA damage repair in the radioresistant S-phase cells. By developing a cross-correlative methodology to reveal probabilistic gold nanoparticle uptake by cell sub-populations and the associated sensitization as a function of the uptake, a number of revealing observations have been achieved. Surprisingly, for low numbers of nanoparticles, a desensitization action was observed. Sensitization was discovered to preferentially impact S-phase cells, in which impairment of the DNA damage response by the homologous recombination pathway dominates. This small but radioresistant cell population correlates with much greater proliferative ability. Thus, a paradigm is presented whereby enhanced DNA damage is not necessarily due to an increase in the number of DNA double-strand breaks (DSBs) created but can be from a nanoparticle-induced impairment of the damage response by down-regulating repair proteins such as thymidylate synthase.
As of 2020, hepatocellular carcinoma (HCC), a form of liver cancer, stood as the third most prominent contributor to global cancer-related mortality. Combining immune checkpoint inhibitors (ICI) with ...other therapies has shown promising results for treating unresectable HCC, offering new opportunities. Recombinant adeno-associated viral type 2 (AAV2) virotherapy has been approved for clinical use but it efficacy is stifled through systemic administration. On the other hand, iron oxide nanoparticles (ION) can be cleared via the liver and enhance macrophage polarization, promoting infiltration of CD8
T cells and creating a more favorable tumor microenvironment for immunotherapy.
To enhance the efficacy of virotherapy and promote macrophage polarization towards the M1-type in the liver, ION-AAV2 were prepared through the coupling of ION-carboxyl and AAV2-amine using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC)/N-hydroxysulfosuccinimide (Sulfo-NHS). Efficacy after systemic delivery of ION-AAV2 in an orthotopic HCC model was evaluated.
After 28 days, the tumor weight in mice treated with ION-AAV2 was significantly reduced by 0.56-fold compared to the control group. The ION-AAV2 treatment led to an approximate 1.80-fold increase in the level of tumor associated M1-type macrophages, while the number of M2-type macrophages was reduced by 0.88-fold. Moreover, a proinflammatory response increased the population of tumor-infiltrating CD8
T cells in the ION-AAV2 group. This transformation converted cold tumors into hot tumors.
Our findings suggest that the conjugation of ION with AAV2 could be utilized in virotherapy while simultaneously exploiting macrophage-modulating cancer immunotherapies to effectively suppress HCC growth.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Many tumors develop resistance to most of the apoptosis-based cancer therapies. In this sense targeting non-apoptotic forms of cell death including necroptosis, autophagy and ferroptosis may have ...therapeutic benefits in apoptosis-defective cancer cells. Nanomaterials have shown great advantages in cancer treatment owing to their unique characteristics. Besides, the capability of nanomaterials to induce different forms of cell death has gained widespread attention in cancer treatment. Reports in this field reflect the therapeutic potential of necroptotic cell death induced by nanomaterials in cancer. Also, autophagic cell death induced by nanomaterials alone and as a part of chemo-, radio- and photothermal therapy holds great promise as anticancer therapeutic option. Besides, ferroptosis induction by iron-based nanomaterials in drug delivery, immunotherapy, hyperthermia and imaging systems shows promising results in malignancies. Hence, this review is devoted to the latest efforts and the challenges in this field of research and its clinical merits.
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Solid tumors characteristically display higher levels of lactate production due to anaerobic metabolism of glucose. Meanwhile, the U.S. Food and Drug Administration (FDA) has approved virotherapy for ...use in cancer treatment; however systemic administration remains as a particular challenge. Here we report exploitation of tumor lactate production in designing a hypoxia-responsive carrier, self-assembled from hyaluronic acid (HA) conjugated with 6-(2-nitroimidazole)hexylamine, for localized release of recombinant adeno-associated virus serotype 2 (AAV2). The carrier is loaded with lactate oxidase (LOX) and is permeable to small molecules such as the lactate that accumulates in the tumor. Subsequently, LOX oxidizes the lactate to pyruvate inside the carrier, accompanied by internal lowering of oxygen partial pressure. Bioreduction of the 2-nitroimidazole of the HA conjugated with 6-(2-nitroimidazole)hexylamine converts it into a hydrophilic moiety and electrostatically dissociates the carrier and virus. Efficacious and specific delivery was proven by transduction of a photosensitive protein (KillerRed), enabling significant limitation in tumor growth in vivo with photodynamic therapy. An approximate 2.44-fold reduction in tumor weight was achieved after a 2-week course, compared with control groups. Furthermore, conjugation of the AAV2 with iron oxide nanoparticles (“magnetized” AAV2) facilitated magnetic resonance imaging tracking of the virus in vivo. Taken together, the solid tumor microenvironment promotes bioreduction of the lactate-responsive carrier, providing rapid and specific delivery of AAV2 for light-triggered virotherapy via systemic administration.
Deregulated proliferation of tumors is generally associated with altered energy metabolism. A high rate of anaerobic glycolysis in solid tumors contributes to an acidification of pH to ∼6.7–7.2 in ...the tumor microenvironment and lactate accumulation. Macrophages in the tumor microenvironment can be educated by tumor cells. Tumor-derived lactate induces the polarization of M2 macrophages and promotes tumor invasion and metastasis. However, a particular challenge is to sustain lactate depletion. We propose that the repolarization of the tumor-supportive M2 macrophage to the tumor-suppressive M1 macrophage after the depletion of lactate by lactate oxidase (LOX) released from the hydrogels in the tumor microenvironment may enhance the antitumor treatment efficacy.
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