Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Although measurements of GABA levels in vivo in the human brain using edited proton magnetic resonance spectroscopy (1H-MRS) have been established for some time, it is has not been established how regional GABA levels vary with age in the normal human brain. In this study, 49 healthy men and 51 healthy women aged between 20 and 76 years were recruited and J-difference edited spectra were recorded at 3 Tesla to determine the effect of age on GABA levels, and to investigate whether there are regional and gender differences in GABA in mesial frontal and parietal regions. Because the signal detected at 3.02 ppm using these experimental parameters is also expected to contain contributions from both macromolecules (MM) and homocarnosine, in this study the signal is labeled GABA+ rather than GABA. Significant negative correlations were observed between age and GABA+ in both regions studied (GABA+/Cr: frontal region, r = -0.68, p< 0.001, parietal region, r = -0.54, p< 0.001; GABA+/NAA: frontal region, r = -0.58, p< 0.001, parietal region, r = -0.49, p< 0.001). The decrease in GABA+ with age in the frontal region was more rapid in women than men. Evidence of a measureable decline in GABA is important in considering the neurochemical basis of the cognitive decline that is associated with normal aging.

Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study’s protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.

In the past decade, iron oxide nanoparticles (IONPs) have attracted more and more attention for their excellent physicochemical properties and promising biomedical applications. In this review, we summarize and highlight recent progress in the design, synthesis, biocompatibility evaluation and magnetic theranostic applications of IONPs, with a special focus on cancer treatment. Firstly, we provide an overview of the controlling synthesis strategies for fabricating zero-, one- and three-dimensional IONPs with different shapes, sizes and structures. Then, the in vitro and in vivo biocompatibility evaluation and biotranslocation of IONPs are discussed in relation to their chemo-physical properties including particle size, surface properties, shape and structure. Finally, we also highlight significant achievements in magnetic theranostic applications including magnetic resonance imaging (MRI), magnetic hyperthermia and targeted drug delivery. This review provides a background on the controlled synthesis, biocompatibility evaluation and applications of IONPs as cancer theranostic agents and an overview of the most up-to-date developments in this area.

Considerable evidence supports that the CD4+ T cell-mediated immune response contributes to the development of atherosclerotic plaque. However, the effects of Th17 cells on atherosclerosis are not thoroughly understood. In this study, we evaluated the production and function of Th17 and Th1 cells in atherosclerotic-susceptible ApoE−/− mice. We observed that the proportion of Th17 cells, as well as Th1, increased in atherosclerotic ApoE−/− mice compared with nonatherosclerotic wild-type littermates. In ApoE−/− mice with atherosclerosis, the expression of IL-17 and retinoic acid-related orphan receptor γt was substantially higher in the arterial wall with plaque than in the arterial wall without plaque. Increased Th17 cells were associated with the magnitude of atherosclerotic plaque in ApoE−/− mice. Importantly, treatment of ApoE−/− mice with neutralizing anti–IL-17 Ab dramatically inhibited the development of atherosclerotic plaque, whereas rIL-17 application significantly promoted the formation of atherosclerotic plaque. These data demonstrate that Th17 cells play a critical role in atherosclerotic plaque formation in mice, which may have implications in patients with atherosclerosis.

Integration of two or more drugs into a multiagent delivery system has been considered to have profound impact on both in vitro and in vivo cancer treatment due to their efficient synergistic effect. This study presents a cheap and simple chitosan hydrogel cross-linked with telechelic difunctional poly(ethylene glycol) (DF-PEG-DF) for synthesis of an injectable and self-healing thermosensitive dual-drug-loaded magnetic hydrogel (DDMH), which contains both doxorubicin (DOX) and docetaxel (DTX) for chemotherapy and iron oxide for magnetic hyperthermia induced stimuli responsive drug release. The as-prepared DDMH not only have good biocompatibility but also exhibit unique self-healing, injectable, asynchronous control release properties. Meanwhile, it shows an excellent magnetic field responsive heat-inducing property, which means that DDMH will produce a large amount of heat to control the surrounding temperature under the alternative magnetic field (AMF). A remarkably improved synergistic effect to triple negative breast cancer cell line is obtained by comparing the therapeutic effect of codelivery of DOX and DTX/PLGA nanoparticles (DTX/PLGA NPs) with DOX or DTX/PLGA NPs alone. In vivo results showed that DDMH exhibited significant higher antitumor efficacy of reducing tumor size compared to single drug-loaded hydrogel. Meanwhile, the AMF-trigger control release of drugs in codelivery system has a more efficient antitumor effect of cancer chemotherapy, indicating that DDMH was a promising multiagent codelivery system for synergistic chemotherapy in the cancer treatment field.