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2.
Pain Physician ; 25(6): 459-470, 2022 09.
Article in English | MEDLINE | ID: mdl-36122255

ABSTRACT

BACKGROUND: Cervicogenic headache (CGH) can often be difficult to treat, given the overlapping clinical features of other headaches and the varying sources of pain that patients report. While imaging is not useful in diagnosing CGH, anesthetic blockade of the atlanto-occipital joint, lateral atlantoaxial joint, or specific cervical zygapophyseal joints can be used to confirm the diagnosis. When conservative treatment measures, such as physical therapy, fail, interventional techniques, such as intraarticular steroid injections, have been shown in observational studies to provide relief in some patients. OBJECTIVES: To determine the efficacy of intraarticular cervical facet steroid injections in the treatment of CGH. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We conducted a comprehensive search of Ovid Medline, Embase, Cochrane Central Register of Controlled Trials , Cumulative Index to Nursing and Allied Health Literature Plus with Full Text, Scopus, and the Web of Science platform, from inception to April 2021, for studies using intraarticular cervical facet injections to treat CGH in adults aged 18 or older. Primary outcomes included mean postinjection pain scores. Outcomes were pooled using a random effects model and reported as mean differences (MD) with 95% confidence intervals (CI). RESULTS: Three studies with a total of 64 patients met the inclusion criteria. According to data from each of the included studies, intraarticular cervical facet injections were shown to demonstrate improvement in the mean pain score from baseline to postintervention. The overall effect size-pooled MD in the Visual Analog Scale score-was 3.299 (95% CI: 2.045 to 4.552, P < 0.001). Heterogeneity (I2) was 36.11%. LIMITATIONS: Small sample size, lack of control group, and varying pain generators and interventional technique between studies contribute to the limitations of the analysis. CONCLUSIONS: Our findings suggest that therapeutic intraarticular cervical facet injections may be effective in the treatment of CGH. Because of the heterogeneity among the studies, these results should be interpreted with caution.


Subject(s)
Post-Traumatic Headache , Zygapophyseal Joint , Adult , Headache , Humans , Injections, Intra-Articular/methods , Post-Traumatic Headache/drug therapy , Steroids/therapeutic use
3.
Metabolites ; 12(5)2022 Apr 23.
Article in English | MEDLINE | ID: mdl-35629889

ABSTRACT

While the roles of a few specific lipids in plant freezing tolerance are understood, the effect of many plant lipids remains to be determined. Acclimation of plants to non-freezing cold before exposure to freezing temperatures improves the outcome of plants, compared to plants exposed to freezing without acclimation. Arabidopsis thaliana plants were subjected to one of three treatments: (1) "control", i.e., growth at 21 °C, (2) "non-acclimated", i.e., 3 days at 21 °C, 2 h at -8 °C, and 24 h recovery at 21 °C, and (3) "acclimated", i.e., 3 days at 4 °C, 2 h at -8 °C, and 24 h recovery at 21 °C. Plants were harvested at seven time points during the treatments, and lipid levels were measured by direct-infusion electrospray ionization tandem mass spectrometry. Ion leakage was measured at the same time points. To examine the function of lipid species in relation to freezing tolerance, the lipid levels in plants immediately following the freezing treatment were correlated with the outcome, i.e., ion leakage 24-h post-freezing. Based on the correlations, hypotheses about the functions of specific lipids were generated. Additionally, analysis of the lipid levels in plants with mutations in genes encoding patatin-like phospholipases, lipoxygenases, and 12-oxophytodienoic acid reductase 3 (opr3), under the same treatments as the wild-type plants, identified only the opr3-2 mutant as having major lipid compositional differences compared to wild-type plants.

4.
Plants (Basel) ; 9(7)2020 Jul 04.
Article in English | MEDLINE | ID: mdl-32635518

ABSTRACT

In response to elevated temperatures, plants alter the activities of enzymes that affect lipid composition. While it has long been known that plant leaf membrane lipids become less unsaturated in response to heat, other changes, including polygalactosylation of galactolipids, head group acylation of galactolipids, increases in phosphatidic acid and triacylglycerols, and formation of sterol glucosides and acyl sterol glucosides, have been observed more recently. In this work, by measuring lipid levels with mass spectrometry, we confirm the previously observed changes in Arabidopsis thaliana leaf lipids under three heat stress regimens. Additionally, in response to heat, increased oxidation of the fatty acyl chains of leaf galactolipids, sulfoquinovosyldiacylglycerols, and phosphatidylglycerols, and incorporation of oxidized acyl chains into acylated monogalactosyldiacylglycerols are shown. We also observed increased levels of digalactosylmonoacylglycerols and monogalactosylmonoacylglycerols. The hypothesis that a defect in sterol glycosylation would adversely affect regrowth of plants after a severe heat stress regimen was tested, but differences between wild-type and sterol glycosylation-defective plants were not detected.

5.
Nanomedicine ; 13(2): 383-390, 2017 02.
Article in English | MEDLINE | ID: mdl-27558349

ABSTRACT

A nanobiosensor for arginase detection was designed and synthesized. It features a central dopamine-coated iron/iron oxide nanoparticle to which sulfonated cyanine 7.0 is tethered via a stable amide bond. Cyanine 5.5 is linked to the N-terminal of the peptide sequence GRRRRRRRG. Arginine (R) reacts to ornithine (O) in the presence of arginase. Based on calibration with commercially obtained arginase II, the limit of detection (LOD) is picomolar. It is noteworthy that the nanobiosensor for arginase detection does not show a fluorescence increase when incubated with the enzyme NO-reductase, which also uses arginase as substrate, but is indicative of an inflammatory response by the host to cancer and infections. Arginase activity was determined in a syngeneic mouse model for aggressive breast cancer (4T1 tumors in BALB/c mice). It was found that the arginase activity is systemically enhanced, but especially pronounced in the active tumor regions.


Subject(s)
Arginase/metabolism , Biosensing Techniques , Metal Nanoparticles , Animals , Arginine , Breast Neoplasms/diagnosis , Breast Neoplasms/enzymology , Mice, Inbred BALB C , Nitric Oxide , Ornithine
6.
Beilstein J Nanotechnol ; 7: 364-373, 2016.
Article in English | MEDLINE | ID: mdl-27335730

ABSTRACT

Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.

7.
Chembiochem ; 16(4): 611-7, 2015 Mar 02.
Article in English | MEDLINE | ID: mdl-25663046

ABSTRACT

Cholesterol is a fundamental lipid component of eukaryotic membranes and a precursor of potent signaling molecules, such as oxysterols and steroid hormones. Cholesterol and oxysterols are also essential for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Despite their importance, the use of imaging sterols in cells is currently very limited. We introduce a robust and versatile method for sterol microscopy based on C19 alkyne cholesterol and oxysterol analogues. These sterol analogues are fully functional; they rescue growth of cholesterol auxotrophic cells and faithfully recapitulate the multiple roles that sterols play in Hedgehog signal transduction. Alkyne sterol analogues incorporate efficiently into cellular membranes and can be imaged with high resolution after copper(I)-catalyzed azide-alkyne cycloaddition reaction with fluorescent azides. We demonstrate the use of alkyne sterol probes for visualizing the subcellular distribution of cholesterol and for two-color imaging of sterols and choline phospholipids. Our imaging strategy should be broadly applicable to studying the role of sterols in normal physiology and disease.


Subject(s)
Hedgehog Proteins/metabolism , Optical Imaging , Signal Transduction , Sterols/analysis , Alkynes/chemistry , Animals , Azides/chemistry , Cholesterol/analogs & derivatives , Click Chemistry , Copper/chemistry , Cycloaddition Reaction , Humans , Mice , Microscopy/methods , Molecular Probes/chemistry , NIH 3T3 Cells , Optical Imaging/methods , Sterols/metabolism
8.
Photochem Photobiol Sci ; 13(2): 231-40, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24096539

ABSTRACT

Numerous proteases are known to be necessary for cancer development and progression including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins. The goal of this research is to develop an Fe/Fe3O4 nanoparticle-based system for clinical diagnostics, which has the potential to measure the activity of cancer-associated proteases in biospecimens. Nanoparticle-based "light switches" for measuring protease activity consist of fluorescent cyanine dyes and porphyrins that are attached to Fe/Fe3O4 nanoparticles via consensus sequences. These consensus sequences can be cleaved in the presence of the correct protease, thus releasing a fluorescent dye from the Fe/Fe3O4 nanoparticle, resulting in highly sensitive (down to 1 × 10(-16) mol l(-1) for 12 proteases), selective, and fast nanoplatforms (required time: 60 min).


Subject(s)
Enzyme Assays/methods , Magnetite Nanoparticles/chemistry , Nanotechnology/methods , Neoplasms/enzymology , Peptide Hydrolases/metabolism , Spectrometry, Fluorescence/methods , Calibration , Carbocyanines/chemistry , Consensus Sequence , Fluorescence Resonance Energy Transfer , Matrix Metalloproteinase 13/chemistry , Matrix Metalloproteinase 13/metabolism , Peptide Hydrolases/chemistry , Porphyrins/chemistry , Reproducibility of Results , Surface Properties
9.
Physiol Plant ; 150(4): 517-28, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24286212

ABSTRACT

Formation of galactose-acylated monogalactosyldiacylglycerols has been shown to be induced by leaf homogenization, mechanical wounding, avirulent bacterial infection and thawing after snap-freezing. Here, lipidomic analysis using mass spectrometry showed that galactose-acylated monogalactosyldiacylglycerols, formed in wheat (Triticum aestivum) and tomato (Solanum lycopersicum) leaves upon wounding, have acyl-galactose profiles that differ from those of wounded Arabidopsis thaliana, indicating that different plant species accumulate different acyl-galactose components in response to the same stress. Additionally, the composition of the acyl-galactose component of Arabidopsis acMGDG (galactose-acylated monogalactosyldiacylglycerol) depends on the stress treatment. After sub-lethal freezing treatment, acMGDG contained mainly non-oxidized fatty acids esterified to galactose, whereas mostly oxidized fatty acids accumulated on galactose after wounding or bacterial infection. Compositional data are consistent with acMGDG being formed in vivo by transacylation with fatty acids from digalactosyldiacylglycerols. Oxophytodienoic acid, an oxidized fatty acid, was more concentrated on the galactosyl ring of acylated monogalactosyldiacylglycerols than in galactolipids in general. Also, oxidized fatty acid-containing acylated monogalactosyldiacylglycerols increased cumulatively when wounded Arabidopsis leaves were wounded again. These findings suggest that, in Arabidopsis, the pool of galactose-acylated monogalactosyldiacylglycerols may serve to sequester oxidized fatty acids during stress responses.


Subject(s)
Arabidopsis/chemistry , Galactolipids/chemistry , Galactose/chemistry , Plant Leaves/chemistry , Solanum lycopersicum/chemistry , Triticum/chemistry , Acylation , Arabidopsis/microbiology , Esterification , Fatty Acids/chemistry , Freezing , Host-Pathogen Interactions , Mass Spectrometry , Molecular Structure , Oxidation-Reduction , Plant Leaves/microbiology , Pseudomonas syringae/physiology , Species Specificity , Stress, Mechanical
10.
J Am Chem Soc ; 135(18): 6842-5, 2013 May 08.
Article in English | MEDLINE | ID: mdl-23611424

ABSTRACT

A prototype of a nano solar cell containing the mycobacterial channel protein MspA has been successfully designed. MspA, an octameric transmembrane channel protein from Mycobacterium smegmatis, is one of the most stable proteins known to date. Eight Ruthenium(II) aminophenanthroline-viologen maleimide Diads (Ru-Diads) have been successfully bound to the MspA mutant MspAA96C via cysteine-maleimide bonds. MspA is known to form double layers in which it acts as nanoscopic surfactant. The nanostructured layer that is formed by (Ru-Diad)8MspA at the TiO2 electrode is photochemically active. The resulting "protein nano solar cell" features an incident photon conversion efficiency of 1% at 400 nm. This can be regarded as a proof-of-principle that stable proteins can be successfully integrated into the design of solar cells.


Subject(s)
Electric Power Supplies , Porins/chemistry , Solar Energy , Viologens/chemistry , Electrodes , Nanostructures/chemistry , Organometallic Compounds/chemistry , Phenanthrolines/chemistry , Ruthenium/chemistry , Surface Properties , Titanium/chemistry
11.
Methods Mol Biol ; 918: 179-268, 2012.
Article in English | MEDLINE | ID: mdl-22893293

ABSTRACT

Herein, current approaches to electrospray ionization mass spectrometry-based analyses of membrane lipid molecular species found in Arabidopsis thaliana are summarized. Additionally, the identities of over 500 reported membrane lipid molecular species are assembled.


Subject(s)
Arabidopsis/chemistry , Membrane Lipids/analysis , Membrane Lipids/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Oxidation-Reduction
12.
ACS Nano ; 4(12): 7093-104, 2010 Dec 28.
Article in English | MEDLINE | ID: mdl-21058696

ABSTRACT

Localized magnetic hyperthermia as a treatment modality for cancer has generated renewed interest, particularly if it can be targeted to the tumor site. We examined whether tumor-tropic neural progenitor cells (NPCs) could be utilized as cell delivery vehicles for achieving preferential accumulation of core/shell iron/iron oxide magnetic nanoparticles (MNPs) within a mouse model of melanoma. We developed aminosiloxane-porphyrin functionalized MNPs, evaluated cell viability and loading efficiency, and transplanted neural progenitor cells loaded with this cargo into mice with melanoma. NPCs were efficiently loaded with core/shell Fe/Fe(3)O(4) MNPs with minimal cytotoxicity; the MNPs accumulated as aggregates in the cytosol. The NPCs loaded with MNPs could travel to subcutaneous melanomas, and after A/C (alternating current) magnetic field (AMF) exposure, the targeted delivery of MNPs by the cells resulted in a measurable regression of the tumors. The tumor attenuation was significant (p < 0.05) a short time (24 h) after the last of three AMF exposures.


Subject(s)
Electric Conductivity , Magnetic Field Therapy/methods , Melanoma/metabolism , Melanoma/therapy , Nanoparticles , Nervous System/cytology , Stem Cells/metabolism , Animals , Biological Transport , Cell Line, Tumor , Female , Ferric Compounds/chemistry , Ferric Compounds/metabolism , Humans , Iron/chemistry , Iron/metabolism , Melanoma/pathology , Mice , Proteomics , Stem Cell Transplantation , Temperature
13.
BMC Cancer ; 10: 119, 2010 Mar 30.
Article in English | MEDLINE | ID: mdl-20350328

ABSTRACT

BACKGROUND: There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. METHODS: The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands. RESULTS: The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection. CONCLUSIONS: These results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art.


Subject(s)
Ferrosoferric Oxide/administration & dosage , Hyperthermia, Induced/methods , Iron/administration & dosage , Magnetic Field Therapy/methods , Melanoma, Experimental/therapy , Metal Nanoparticles/administration & dosage , Animals , Apoptosis/physiology , Female , Ferrosoferric Oxide/chemistry , Iron/analysis , Melanoma, Experimental/pathology , Metal Nanoparticles/chemistry , Mice , Mice, Inbred C57BL , Porphyrins/administration & dosage , Porphyrins/chemistry
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