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Obesity is a major public health problem worldwide. Different approaches are known to face this problem, for example, dieting, surgery, or drug interventions. It has also been shown that placebos may help to reduce weight and hunger feelings, but the use of placebos is linked to problems with respect to the patient-healthcare-provider relationship. However, recent studies demonstrated that even placebos without deception (open-label placebos) affect symptoms such as pain, anxiety, or emotional distress. Here we aimed to examine whether an open-label placebo may help to lose weight in obesity. Our study included fifty-seven overweight and obese patients who aimed to lose weight using a combination of diet and sports. Patients were randomly divided into two groups. Participants in the open-label placebo group received two placebos each day. A treatment-as-usual group received no pills. Primary outcome included changes of body weight. Secondary outcomes were change of eating behavior and self-management abilities. After 4 weeks we found that participants in the open-label placebo condition lost more weight than the treatment-as-usual group. Furthermore, OLP treatment affected eating behavior. No effects for self-management abilities were found. Although further research is necessary, open-label placebos might help individuals to lose weight. [ABSTRACT FROM AUTHOR]

Snow, especially in mountainous regions, plays a major role acting as a quasi-reservoir, as it gradually releases fresh water during the melting season and thereby fills rivers, lakes, and groundwater aquifers. For vegetation and irrigation, the timing of the snowmelt is crucial. Therefore, it is necessary to understand how snowmelt varies under different local conditions. While differences in slope aspect and vegetation (individually) were linked to differences in snow accumulation and ablation, this study connects the two and describes their influence on the soil moisture response to snowmelt. This research focuses on the catchment of the "Brunnenkopfhütte" (BKH) in Bavaria, southern Germany, where an automatic weather station (AWS) has operated since 2016. In addition, soil temperature and moisture monitoring systems in the surrounding area on a south aspect slope on an open field (SO), on a south aspect slope in the forest (SF), and a north aspect slope in the forest (NF) have operated since 2020. On snow-free days in winter, the soil temperature at the SF site was on average 1 °C lower than on the open site. At the NF site, this soil temperature difference increased to 2.3 °C. At the same time, for a 1 °C increase in the air temperature, the soil temperature increases by 0.35 °C at the NF site. In addition, at this site, snow cover disappeared approximately one week later than on the south aspect slopes. Snow cover at the SF site disappeared even earlier than at the SO site. Finally, a significant difference in the soil moisture response was found between the sites. While the vegetation cover dampens the magnitude of the soil moisture increases, at the NF site, no sharp increases in soil moisture were observed. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with poor prognosis and limited therapeutic options. Alternating electrical fields with low intensity called "Tumor Treating Fields" (TTFields) are a new, non-invasive approach with almost no side effects and phase 3 trials are ongoing in advanced PDAC. We evaluated TTFields in combination with mild hyperthermia. Three established human PDAC cell lines and an immortalized pancreatic duct cell line were treated with TTFields and hyperthermia at 38.5°C, followed by microscopy, assays for MTT, migration, colony and sphere formation, RT-qPCR, FACS, Western blot, microarray and bioinformatics, and in silico analysis using the online databases GSEA, KEGG, Cytoscape-String, and Kaplan-Meier Plotter. Whereas TTFields and hyperthermia alone had weak effects, their combination strongly inhibited the viability of malignant, but not those of nonmalignant cells. Progression features and the cell cycle were impaired, and autophagy was induced. The identified target genes were key players in autophagy, the cell cycle and DNA repair. The expression profiles of part of these target genes were significantly involved in the survival of PDAC patients. In conclusion, the combination of TTFields with mild hyperthermia results in greater efficacy without increased toxicity and could be easily clinically approved as supporting therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: In macrophages, transient receptor potential vanilloid 2 (TRPV2) channel contributes to various cellular processes such as cytokine production, differentiation, phagocytosis and migration. Due to a lack of selective pharmacological tools, its function in immunological processes is not well understood and the identification of novel and selective TRPV2 modulators is highly desirable. Experimental Approach: Novel and selective TRPV2 modulators were identified by screening a compound library using Ca2+ influx assays with human embryonic kidney 293 (HEK293) cells heterologously expressing rat TRPV2. Hits were further characterized and validated with Ca2+ influx and electrophysiological assays. Phagocytosis and migration of macrophages were analysed and the contribution of TRPV2 to the generation of Ca2+ microdomains was studied by total internal reflection fluorescence microscopy (TIRFM). Key Results: The compound IV2‐1, a dithiolane derivative (1,3‐dithiolan‐2‐ylidene)‐4‐methyl‐5‐phenylpentan‐2‐one), is a potent inhibitor of heterologously expressed TRPV2 channels (IC50 = 6.3 ± 0.7 μM) but does not modify TRPV1, TRPV3 or TRPV4 channels. IV2‐1 also inhibits TRPV2‐mediated Ca2+ influx in macrophages. IV2‐1 inhibits macrophage phagocytosis along with valdecoxib and after siRNA‐mediated knockdown. Moreover, TRPV2 inhibition inhibits lipopolysaccharide‐induced migration of macrophages whereas TRPV2 activation promotes migration. After activation, TRPV2 shapes Ca2+ microdomains predominantly at the margin of macrophages, which are important cellular regions to promote phagocytosis and migration. Conclusions and Implications: IV2‐1 is a novel TRPV2‐selective blocker and underline the role of TRPV2 in macrophage‐mediated phagocytosis and migration. Furthermore, we provide evidence that TRPV2 activation generates Ca2+ microdomains, which may be involved in phagocytosis and migration of macrophages. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a worldwide pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various pathological conditions. The aim of this retrospective and observational pilot study was to investigate the range of cfDNA plasma concentrations in hospitalized COVID-19 patients during the first wave of SARS-CoV-2 infection, to relate them to established inflammatory parameters as a correlative biomarker for disease severity, and to compare them with plasma levels in a healthy control group. Methods: Lithium-Heparin plasma samples were obtained from COVID-19 patients (n = 21) during hospitalization in the University Medical Centre of Mainz, Germany between March and June 2020, and the cfDNA concentrations were determined by quantitative PCR yielding amplicons of long interspersed nuclear elements (LINE-1). The cfDNA levels were compared with those of an uninfected control group (n = 19). Results: Plasma cfDNA levels in COVID-19 patients ranged from 247.5 to 6,346.25 ng/ml and the mean concentration was 1,831 ± 1,388 ng/ml (± standard deviation), which was significantly different from the levels of the uninfected control group (p < 0.001). Regarding clinical complications, the highest correlation was found between cfDNA levels and the myositis (p = 0.049). In addition, cfDNA levels correlated with the "WHO clinical progression scale". D-Dimer and C-reactive protein (CRP) were the clinical laboratory parameters with the highest correlations with cfDNA levels. Conclusion: The results of this observational pilot study show a wide range in cfDNA plasma concentrations in patients with COVID-19 during the first wave of infection and confirm that cfDNA plasma concentrations serve as a predictive biomarker of disease severity in COVID-19. [ABSTRACT FROM AUTHOR]

Placebo effects are known for numerous clinical symptoms. Until recently, deception of placebos was thought to be essential for placebo effects, but intriguing new studies suggest that even placebos without concealment (open-label placebos) may help patients with various clinical disorders. Most of those studies compared open-label placebo treatments with no treatment conditions (or treatment "as usual"). Given that open-label placebo studies obviously cannot be blinded, additional control studies are important to assess the efficacy of open-label placebos. The current study aimed to fil this gap by comparing open-label with conventional double-blind placebos and treatment as usual. Patients with seasonal allergic rhinitis were randomly divided in different groups. The first group received open-label placebos, the second double-blind placebos, and the third was treated as usual. After 4 weeks, results demonstrated that open-label placebos improved allergic symptoms more than treatment-as-usual and even more as double-blind placebos. In addition, we observed that allergic symptoms in general (and also the open-label placebo effects) were reduced by the Covid-19 pandemic. The results suggest that seasonal allergic symptoms may be relieved by open-label placebos. We discuss these results by addressing possible different mechanisms of open-label and conventionally concealed placebo treatments. [ABSTRACT FROM AUTHOR]

Background and Purpose: Ca2+ signalling mediated by the thermosensitive, non‐selective, Ca2+‐permeable transient receptor potential channel TRPV3 is assumed to play a critical role in regulating several aspects of skin functions, such as keratinocyte proliferation, differentiation, skin barrier formation and wound healing. Studying the function of TRPV3 in skin homeostasis, however, is still constrained by a lack of potent and selective pharmacological modulators of TRPV3. Experimental Approach: By screening an in‐house compound library using fluorometric intracellular Ca2+ assays, we identified two chemically related hits. The more potent and efficient TRPV3 activator 2‐(2‐chloro‐3‐isopropylcyclopent‐2‐en‐1‐yl)‐4‐methylphenol (KS0365) was further evaluated in fluo‐4‐assisted Ca2+ assays, different Ca2+ imaging approaches, electrophysiological studies, cytotoxicity and migration assays. Key Results: KS0365 activated recombinant and native mouse TRPV3 more potently and with a higher efficacy compared with 2‐APB and did not activate TRPV2 or TRPV4 channels. The activation of TRPV3 by KS0365 super‐additively accelerated the EGF‐induced keratinocyte migration, which was inhibited by the TRP channel blocker ruthenium red or by siRNA‐mediated TRPV3 knockdown. Moreover, KS0365 induced strong Ca2+ responses in migrating front cells and in leading edges of keratinocytes. Conclusions and Implications: The selective TRPV3 activator KS0365 triggers increases in [Ca2+]i with most prominent signals in the leading edge and accelerates migration of keratinocytes. TRPV3 activators may promote re‐epithelialization upon skin wounding. [ABSTRACT FROM AUTHOR]

As coastal ecosystems become widely recognized for their capacity to sequester carbon (blue carbon), standard accounting methodologies for the generation of carbon credits are being developed. To ensure the applicability of these standards across blue carbon ecosystems, we investigated organic carbon provenance and burial in salt marshes and seagrass meadows of an arid, upwelling‐dominated Eastern Pacific lagoon. We found low carbon density in benthic sediments of Bahía de San Quintín (5.9 ± 0.5 mg C cm−3), only marginally higher in Zostera marina beds (6.9 ± 0.5 mg C cm−3), likely due to remineralization and hydrodynamically driven export of seagrass material, resulting in low carbon burial rates (4.5 ± 2.5 g C m−2 yr−1). Sediment organic carbon is mainly controlled by the fraction of fine sediment and its source is largely allochthonous, although sources differ spatially. Salt marshes at San Quintín derive 40% of their organic matter from autochthonous material and exhibit higher carbon burial rates (up to 414.7 ± 28.6 g C m−2 yr−1) and sediment carbon densities (32.0 ± 0.7 mg C cm−3) compared to benthic sediments. This study emphasizes the connectivity of blue carbon habitats with marsh plant detritus supplementing benthic carbon burial and incorporation of detrital eelgrass in marsh sediments. Our findings highlight the importance of allochthonous organic matter for carbon sequestration in blue carbon habitats, suggesting standard accounting practices that deduct allochthonous organic matter would miss the full potential for carbon burial. [ABSTRACT FROM AUTHOR]

Photoswitchable reagents can be powerful tools for high‐precision biological control. TRPC5 is a Ca2+‐permeable cation channel with distinct tissue‐specific roles, from synaptic function to hormone regulation. Reagents giving spatiotemporally‐resolved control over TRPC5 activity may be key to understanding and harnessing its biology. Here we develop the first photoswitchable TRPC5‐modulator, BTDAzo, to address this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5‐based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo‐benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with strong two‐colour photoswitching. BTDAzo′s ability to control TRPC5 across relevant channel biology settings makes it suitable for a range of dynamically reversible photoswitching studies in TRP channel biology, with the aim to decipher the various biological roles of this centrally important ion channel. [ABSTRACT FROM AUTHOR]

Photoswitchable reagents can be powerful tools for high‐precision biological control. TRPC5 is a Ca2+‐permeable cation channel with distinct tissue‐specific roles, from synaptic function to hormone regulation. Reagents giving spatiotemporally‐resolved control over TRPC5 activity may be key to understanding and harnessing its biology. Here we develop the first photoswitchable TRPC5‐modulator, BTDAzo, to address this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5‐based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo‐benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with strong two‐colour photoswitching. BTDAzo′s ability to control TRPC5 across relevant channel biology settings makes it suitable for a range of dynamically reversible photoswitching studies in TRP channel biology, with the aim to decipher the various biological roles of this centrally important ion channel. [ABSTRACT FROM AUTHOR]

Sensory processing sensitivity is described as a personality trait associated with a high sensitivity to environmental and social stimuli. It has been assumed that about 15–20% of the total population can be described as highly sensitive. The concept states that those individuals represent a higher sensitivity to subtle stimuli, thereby exhibiting a different somatic sensation. Here we aim to test the assumption that the brain's sensory perception is different in individuals with high sensory processing sensitivity. We used a German version of the Highly Sensitive Person scale to measure sensory processing sensitivity. Furthermore, we assessed the Big Five personality dimensions and trait empathy (using IRI). To test the hypothesis that the brain's handling of sensory information is different in individuals with high sensory-processing sensitivity, we scanned participant's brain activity with functional magnetic resonance imaging (fMRI) while they were touched by an experimenter's hand. Results showed positive correlations of sensory processing sensitivity with neuroticism, openness, and empathy. Introversion was not a significant predictor. Neuroimaging data demonstrated that sensory processing sensitivity (controlled for associated personality dimensions) was not related to primary or secondary somatosensory BOLD responses, but positively associated with BOLD activity in left posterior insular cortex. Based on these results we conclude that sensory processing sensitivity seems to represent insula-mediated affective touch. We discuss these results with previous studies reporting an engagement of the insula in individuals with high sensory processing sensitivity. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a significant worldwide public health challenge and is inextricably linked to adverse renal and cardiovascular outcomes. The inhibition of the transient receptor potential cation channel subfamily C member 6 (TRPC6) has been found to ameliorate renal outcomes in the unilateral ureteral obstruction (UUO) of accelerated renal fibrosis. Therefore, the pharmacological inhibition of TPRC6 could be a promising therapeutic intervention in the progressive tubulo-interstitial fibrosis in hypertension and metabolic syndrome. In the present study, we hypothesized that the novel selective TRPC6 inhibitor SH045 (larixyl N-methylcarbamate) ameliorates UUO-accelerated renal fibrosis in a New Zealand obese (NZO) mouse model, which is a polygenic model of metabolic syndrome. The in vivo inhibition of TRPC6 by SH045 markedly decreased the mRNA expression of pro-fibrotic markers (Col1α1, Col3α1, Col4α1, Acta2, Ccn2, Fn1) and chemokines (Cxcl1, Ccl5, Ccr2) in UUO kidneys of NZO mice compared to kidneys of vehicle-treated animals. Renal expressions of intercellular adhesion molecule 1 (ICAM-1) and α-smooth muscle actin (α-SMA) were diminished in SH045- versus vehicle-treated UUO mice. Furthermore, renal inflammatory cell infiltration (F4/80+ and CD4+) and tubulointerstitial fibrosis (Sirius red and fibronectin staining) were ameliorated in SH045-treated NZO mice. We conclude that the pharmacological inhibition of TRPC6 might be a promising antifibrotic therapeutic method to treat progressive tubulo-interstitial fibrosis in hypertension and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Giving and receiving touch are some of the most important social stimuli we exchange in daily life. By touching someone, we can communicate various types of information. Previous studies have also demonstrated that interpersonal touch may affect our altruistic behavior. A classic study showed that customers give bigger tips when they are lightly touched by a waitress, which has been called the Midas touch effect. Numerous studies reported similar effects of touch on different kinds of helping or prosocial behaviors. Here, we aim to examine the neural underpinnings of this effect by employing a functional magnetic resonance imaging approach. While lying in the scanner, participants played different rounds of the dictator game, a measure of prosocial behavior. Before each round, participants were touched (or not touched in the control condition) by an experimenter. We found that touching the hand increased the likeliness to behave prosocial (but not the general liking of control stimuli), thereby confirming the Midas touch effect. The effect was predicted by activity in the primary somatosensory cortex, indicating that the somatosensory cortex here plays a causal role in prosocial behavior. We conclude that the tactile modality in social life may be much more important than previously thought. [ABSTRACT FROM AUTHOR]

Zn2+, Mg2+ and Ca2+ are essential divalent cations implicated in many metabolic processes and signalling pathways. An emerging new paradigm is that the organismal balance of these cations predominantly depends on a common gatekeeper, the channel-kinase TRPM7. Despite extensive electrophysiological studies and recent cryo-EM analysis, an open question is how the channel activity of TRPM7 is activated. Here, we performed site-directed mutagenesis of mouse TRPM7 in conjunction with patch-clamp assessment of whole-cell and single-channel activity and molecular dynamics (MD) simulations to show that the side chains of conserved N1097 form an inter-subunit Mg2+ regulatory site located in the lower channel gate of TRPM7. Our results suggest that intracellular Mg2+ binds to this site and stabilizes the TRPM7 channel in the closed state, whereas the removal of Mg2+ favours the opening of TRPM7. Hence, our study identifies the structural underpinnings through which the TRPM7 channel is controlled by cytosolic Mg2+, representing a new structure–function relationship not yet explored among TRPM channels. [ABSTRACT FROM AUTHOR]

Many concepts of the human personality are based on assumptions about underlying physiological processes. The most prominent example is probably the concept of extraversion introduced by H.J. Eysenck decades ago. However, more recent approaches also propose that personality traits may be reflected by physiological processes. For example, empathic personality dimensions have been linked to tactile perception, suggesting that individuals with higher tactile sensitivity are also more empathetic to the sensations of others. Another recent example is the concept of sensory processing sensitivity, which has been linked to enhanced primary sensory processing. However, the exact relationship between tactile abilities and personality is still unclear, thus the current study aims to test whether different personality dimensions affect the performance in a tactile acuity task. Tactile abilities of healthy participants were tested with tactile 2-point-thresholds on the hands. Personality dimensions were examined with respect to empathy, sensory processing sensitivity, and the Big Five. Results revealed that empathy, but not sensory processing sensitivity, was associated with tactile performance. We conclude that the ability to feel with someone else seems to be linked to the perception of our own body. Thus, the sense of touch may play an important role for empathy. We discuss explanations of these results and highlight possible implications of our findings. [ABSTRACT FROM AUTHOR]

TRPC6, the sixth member of the family of canonical transient receptor potential (TRP) channels, contributes to a variety of physiological processes and human pathologies. This study extends the knowledge on the newly developed TRPC6 blocker SH045 with respect to its main target organs beyond the description of plasma kinetics. According to the plasma concentration-time course in mice, SH045 is measurable up to 24 h after administration of 20 mg/kg BW (i.v.) and up to 6 h orally. The short plasma half-life and rather low oral bioavailability are contrasted by its reported high potency. Dosage limits were not worked out, but absence of safety concerns for 20 mg/kg BW supports further dose exploration. The disposition of SH045 is described. In particular, a high extravascular distribution, most prominent in lung, and a considerable renal elimination of SH045 were observed. SH045 is a substrate of CYP3A4 and CYP2A6. Hydroxylated and glucuronidated metabolites were identified under optimized LC-MS/MS conditions. The results guide a reasonable selection of dose and application route of SH045 for target-directed preclinical studies in vivo with one of the rare high potent and subtype-selective TRPC6 inhibitors available. [ABSTRACT FROM AUTHOR]

Transient receptor potential channel subfamily C, member 6 (TRPC6), a non-selective cation channel that controls influx of Ca2+ and other monovalent cations into cells, is widely expressed in the kidney. TRPC6 gene variations have been linked to chronic kidney disease but its role in acute kidney injury (AKI) is unknown. Here we aimed to investigate the putative role of TRPC6 channels in AKI. We used Trpc6−/− mice and pharmacological blockade (SH045 and BI-749327), to evaluate short-term AKI outcomes. Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influences the short-term outcomes of AKI. Serum markers, renal expression of epithelial damage markers, tubular injury, and renal inflammatory response assessed by the histological analysis were similar in wild-type mice compared to Trpc6−/− mice as well as in vehicle-treated versus SH045- or BI-749327-treated mice. In addition, we also found no effect of TRPC6 modulation on renal arterial myogenic tone by using blockers to perfuse isolated kidneys. Therefore, we conclude that TRPC6 does not play a role in the acute phase of AKI. Our results may have clinical implications for safety and health of humans with TRPC6 gene variations, with respect to mutated TRPC6 channels in the response of the kidney to acute ischemic stimuli. [ABSTRACT FROM AUTHOR]

This paper discusses the investigation of the dipole formation at In2O3|TiO2 heterojunctions depending on preparation conditions, i.e., cleaning methods. In2O3 films were deposited using atomic layer deposition (ALD) onto solvent and in situ cleaned anatase and rutile film substrates. The interface dipole strength and film thickness were evaluated by photoemission spectroscopy. Our results indicate the formation of a large intrinsic and film thickness dependent interface dipole that reaches its maximum strength at monolayer thick ALD films. In addition, it was observed that UV photoelectron spectroscopy measurements introduced UV induced surface hydroxylation, which resulted in dipole potentials of -0.70 eV and -0.50 eV on solvent cleaned anatase and rutile, respectively. The overlayers also introduced small amounts of band bending (~0.10 eV) at the interfaces. Taking these effects into account, the total dipole strength at monolayer thick In2O3 films was determined to be -0.96 eV for solvent cleaned anatase and rutile and -0.81 eV for in situ cleaned rutile. The deposition of single ALD cycles on differently cleaned rutile substrates resulted in similar work function values, suggesting little influence of the sample preparation method prior to ALD deposition on the dipole formation. This was assigned to the fact that ALD oxides benefit from ambient water related contamination by integrating the molecules into the growing ALD layer. Highest initial growth was observed on solvent cleaned rutile, followed by in situ cleaned rutile and solvent cleaned anatase. The In2O3 growth converged at 0.3Å/c past the nucleation regime. [ABSTRACT FROM AUTHOR]

Coarse woody debris (CWD), or fallen logs, is known to be an essential habitat element for many organisms. CWD also supports ecosystem functioning through soil formation, nutrient cycling, and carbon storage. For these reasons, accurate assessments of CWD across landscapes are of interest to many ecologists and landscape managers, but traditional field-based measurements can be time-consuming and sampling strategies may not be representative of entire landscapes. Light detection and ranging (LiDAR) technologies may be able to provide a more rapid assessment of the number and volume of CWD across wide areas. However, most research using LiDAR for forest and woodland inventory assessment has focused on standing wood. Detection accuracy of CWD with LiDAR can be impacted by the point density of LiDAR data, ground layer vegetation, and sensor positioning relative to other vegetation or landscape structural features. We used a high-resolution terrestrial laser scanner (TLS), an unoccupied aerial vehicle (UAV) laser scanner (ULS), and a combination of data from both sensors (i.e. fused data, FLS) to estimate CWD in a grassy woodland ecosystem. The study area comprised plots with different types and amounts of vegetation cover and different types of CWD, both naturally occurring and introduced including dispersed, clumped, or a mixture of both types. This enabled a more detailed exploration of model performance across sensor types, vegetation types, and ground cover biomass. A random forest (RF) classification algorithm and noise removing operations on raster imagery were used to classify CWD. Completeness and correctness accuracy with the developed method were highly variable depending on the data and ground vegetation cover and ranged between 20% and 86%, and 12% and 96%, respectively, in comparison with field data. The LiDAR-derived digital surface model (DSM), surface roughness, and topographic position index were important variables for CWD detection. We found that the detection accuracy of CWD varied with the vegetation type, amount of ground vegetation cover, and LiDAR data. Ground cover density had a strong negative impact on accuracy, particularly for TLS and FLS data. [ABSTRACT FROM AUTHOR]

This review summarizes current studies on the psychological effects of sweet taste and its role in overweight and obesity. Recent psychological studies demonstrate intriguing relationships between the experience of sweet taste and social perceptions and behavior. For example, studies show that experiencing sweet taste affects "helping behavior" or interest in initiating a romantic relationship. Furthermore, given that the role of sweet taste in obesity has been suggested, we reviewed studies on the relationship between sweet taste preference and eating behavior, thereby examining the role of sweet taste (and the preference for it) in the global rise of overweight and obesity in adults and children. Finally, we provide an outlook on future research perspectives on the psychological effects of sweet taste, and suggest some fundamental issues that future research should address to help provide a comprehensive understanding of how sweet taste and sweet taste preference affect our thinking and eating behaviors. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with poor prognosis and limited therapeutic options. Alternating electrical fields with low intensity called "Tumor Treating Fields" (TTFields) are a new, non-invasive approach with almost no side effects and phase 3 trials are ongoing in advanced PDAC. We evaluated TTFields in combination with mild hyperthermia. Three established human PDAC cell lines and an immortalized pancreatic duct cell line were treated with TTFields and hyperthermia at 38.5°C, followed by microscopy, assays for MTT, migration, colony and sphere formation, RT-qPCR, FACS, Western blot, microarray and bioinformatics, and in silico analysis using the online databases GSEA, KEGG , Cytoscape-String, and Kaplan-Meier Plotter. Whereas TTFields and hyperthermia alone had weak effects, their combination strongly inhibited the viability of malignant, but not those of nonmalignant cells. Progression features and the cell cycle were impaired, and autophagy was induced. The identified target genes were key players in autophagy, the cell cycle and DNA repair. The expression profiles of part of these target genes were significantly involved in the survival of PDAC patients. In conclusion, the combination of TTFields with mild hyperthermia results in greater efficacy without increased toxicity and could be easily clinically approved as supporting therapy. [ABSTRACT FROM AUTHOR]

Taste-related terms such as bitter or sweet are often used to describe people's behavior. For example, sweetness metaphors are often used when giving nicknames for romantic partners or when characterizing a friendly person. Previous studies have suggested that sweet taste may be linked to prosocial behavior. Examining a total of 517 participants, we here demonstrate that experiencing sweet taste also seems to have an impact on subsequent attractiveness ratings of faces. Participants were asked to rate pictures of young people and of art. Before this task, they were primed either with sweet candies or with salty snacks. Results revealed that sweet taste increased subsequent attractiveness ratings of faces. In addition, results confirmed earlier findings that sweet taste affected prosocial behavior. Our results suggest that sweetness seems to be more than a mere linguistic metaphor; it influences prosocial behavior as well as attractiveness ratings of faces. We discuss the results with recent findings of physical-to-psychological links to certain figures in speech. [ABSTRACT FROM AUTHOR]

Previous research revealed an active network of brain areas such as insula and anterior cingulate cortex when witnessing somebody else in pain and feeling empathy. But numerous studies also suggested a role of the somatosensory cortices for state and trait empathy. While recent studies highlight the role of the observer's primary somatosensory cortex when seeing painful or nonpainful touch, the interaction of somatosensory cortex activity with empathy when receiving touch on the own body is unknown. The current study examines the relationship of touch related somatosensory cortex activity with dispositional empathy by employing an fMRI approach. Participants were touched on the palm of the hand either by the hand of an experimenter or by a rubber hand. We found that the BOLD responses in the primary somatosensory cortex were associated with empathy personality traits personal distress and perspective taking. This relationship was observed when participants were touched both with the experimenter's real hand or a rubber hand. What is the reason for this link between touch perception and trait empathy? We argue that more empathic individuals may express stronger attention both to other's human perceptions as well as to the own sensations. In this way, higher dispositional empathy levels might enhance tactile processing by top-down processes. We discuss possible implications of these findings. [ABSTRACT FROM AUTHOR]

Microplasma-assisted gas-phase nucleation has emerged as an important new approach to produce high-purity, nanometer-sized, and narrowly dispersed particles. This study aims to integrate this technique with vacuum conditions to enable synthesis and deposition in an ultrahigh vacuum compatible environment. The ultimate goal is to combine nanoparticle synthesis with photoemission spectroscopy-based electronic structure analysis. Such measurements require in vacuo deposition to prevent surface contamination from sample transfer, which can be deleterious for nanoscale materials. A homebuilt microplasma reactor was integrated into an existing atomic layer deposition system attached to a surface science multi-chamber system equipped with photoemission spectroscopy. As proof-of-concept, we studied the decomposition of ferrocene vapor in the microplasma to synthesize iron oxide nanoparticles. The injection parameters were optimized to achieve complete precursor decomposition under vacuum conditions, and nanoparticles were successfully deposited. The stoichiometry of the deposited samples was characterized in situ using X-ray photoelectron spectroscopy indicating that iron oxide was formed. Additional transmission electron spectroscopy characterization allowed the determination of the size, shape, and crystal lattice of the particles, confirming their structural properties. [ABSTRACT FROM AUTHOR]

The cation channel TRPML1 is an important regulator of lysosomal function and autophagy. Loss of TRPML1 is associated with neurodegeneration and lysosomal storage disease, while temporary inhibition of this ion channel has been proposed to be beneficial in cancer therapy. Currently available TRPML1 channel inhibitors are not TRPML isoform selective and block at least two of the three human isoforms. We have now identified the first highly potent and isoform-selective TRPML1 antagonist, the steroid 17β-estradiol methyl ether (EDME). Two analogs of EDME, PRU-10 and PRU-12, characterized by their reduced activity at the estrogen receptor, have been identified through systematic chemical modification of the lead structure. EDME and its analogs, besides being promising new small molecule tool compounds for the investigation of TRPML1, selectively affect key features of TRPML1 function: autophagy induction and transcription factor EB (TFEB) translocation. In addition, they act as inhibitors of triple-negative breast cancer cell migration and invasion. [ABSTRACT FROM AUTHOR]

The concept of empathy describes our capacity to understand the emotions and intentions of others and to relate to our conspecifics. Numerous studies investigated empathy as a state as well as a stable personality trait. For example, recent studies in neuroscience suggest, among other brain areas such as the insula or the ACC, a role of the somatosensory cortices for empathy (e.g., when observing someone else being touched). Since the classic understanding of the primary somatosensory cortex is to represent touch on the body surface, we here aimed to test whether tactile performance is linked to the personality trait empathy. To test this, we examined the tactile acuity of 95 healthy participants (mean age 31 years) by using a two-point discrimination threshold task at the index fingers. Trait empathy was assessed by employing the interpersonal reactivity index (IRI), which measures self-reported empathy with four scales (empathic concern, perspective taking, fantasy, and personal distress). Results of regression analyses suggested the subscale empathic concern to be positively associated with performance in the tactile acuity task. We discuss this finding in the light of recent studies on empathy and consider possible implications of tactile training to enhance empathy. [ABSTRACT FROM AUTHOR]

We and others have been aiming at modifications to maintain or to enhance solubility while enabling permeability for cyclic hexapeptides. Especially, the 2-pyridyl-Ala modification was investigated, since in this case, the pyridyl-nitrogen is able to form an H-bond to the NH of the same residue. The hypothesis of a backbone side-chain interaction was demonstrated by NMR experiments, and further results obtained on a variety of pyridyl-Ala derivatives, studied systematically in the context of permeability, are presented in this contribution. Thus, this study sheds some more light on the pyridyl-Ala modification, which had been reported earlier. In addition to the in vitro profiling, the extent of oral bioavailability was assessed in rats. In principle, the pyridyl-Ala residue can be considered as an amino acid supporting oral uptake. [ABSTRACT FROM AUTHOR]

Empathy influences how we perceive, understand, and interact with our social environment. Previous studies suggested a network of different brain regions as a neural substrate for empathy, including, in particular, insula and anterior cingulate cortex (ACC). In addition, a contribution of the somatosensory cortices for this empathy related network has been suggested. This is remarkable, given that other recent studies have revealed a role for the somatosensory cortex in various social tasks. For example, in experiments using tactile priming, incidental haptic sensations are found to influence judgment recommendations. Here, we aimed to test if this engagement of the somatosensory cortices during tactile priming can be predicted by the participant's empathy personality traits. We assessed participant's empathy and personality traits by means of the Interpersonal Reactivity Index (IRI) and NEO-FFI and tested whether trait empathy is associated with the tactile priming effect in social judgments. Results revealed that empathy predicted the tactile priming effect negatively. This was accompanied by a reduced engagement of the somatosensory cortex, which has been shown to be associated with the priming effect. We conclude that empathy seems to protect people from tactile priming effects. [ABSTRACT FROM AUTHOR]

Purpose: Increased ATP-binding-cassette (ABC) transporter activity is a major cause of chemotherapy resistance in cancer. The ABC transporter family member ABCB1 is often overexpressed in colorectal cancer (CRC). Phosphatidylinositol-4,5-bisphosphat (PI(4,5)P2)-dependent pathways are involved in the regulation of ABCB1 function. The protein Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) is a pivotal regulator of PI(4,5)P2 and inactivated in many CRC cancers via genetic deletion or hyperphosphorylation. Therefore, MARCKS may critically impact ABCB1. Methods: CRC samples as well as CRC cell lines were tested for a connection between MARCKS and ABCB1 via immunofluorescence and Western-blot analysis. ABCB1 function was studied via calcein influx assay under treatment with known ABCB1 inhibitors (verapamil, tariquidar) as well as the kinase inhibitor bosutinib. ABCB1 internalization and MARCKS translocation was analyzed via confocal microscopy exploiting the endocytosis inhibitors chlorpromazine and dynasore. Abundance of PI(4,5)P2 was monitored by intramolecular fluorescence resonance energy transfer (FRET). Reproductive cell survival was studied via colorimetric WST-1 and clonogenic assays in combination with exposure to the chemotherapeutics doxorubicin and 5-fuorouracil (5-FU). Results: We found increased ABCB1 expression in MARCKS negative CRC patient tumor samples and established CRC cell lines. Mechanistically, the reconstitution of MARCKS function via recombinant expression or the pharmacological inhibition of MARCKS phosphorylation led to a substantial decrease in ABCB1 activity. In CRC cells, bosutinib treatment resulted in a MARCKS translocation from the cytosol to the plasma membrane, while simultaneously, ABCB1 was relocated to intracellular compartments. Inhibition of MARCKS phosphorylation via bosutinib rendered cells more sensitive to the chemotherapeutics doxorubicin and 5-FU. Conclusions: Cells devoid of MARCKS function showed incomplete ABCB1 internalization, leading to higher ABCB1 activity enhancing chemoresistance. Vice versa our data suggest the prevention of MARCKS inhibition by reversing hyperphosphorylation or genomic restoration after deletion as two promising approaches to overcome tumor cell resistance towards chemotherapeutic ABCB1 substrates. [ABSTRACT FROM AUTHOR]

The selective microscopic imaging of the plasma membrane and adjacent structures by total internal reflection fluorescence (TIRF) microscopy is a versatile and frequently used technique in cell biology. A reduction of imaging artifacts in objective‐type TIRF microscopy can be achieved by circular or multi‐spot laser illumination or by using noncoherent light sources that are projected into the back focal plane as a light annulus. Light‐emitting diode (LED)‐based TIRF excitation is a recent advancement of the latter strategy. While some basic principles of LED‐TIRF remain the same as in laser‐based methods, the calculation of penetration depth, the flatness of illumination and the amount of available illumination power differ. This study provides the theoretical framework for the construction and adjustment of LED‐TIRF. Using state‐of‐the art high power LED emitters, LED‐TIRF achieves excitation efficiencies that are comparable to laser‐based systems and homogenously illuminate the entire field of view, thus, allowing variation of the penetration depth or quantitative photobleaching‐assisted imaging protocols. Using autofluorescent transmembrane, soluble and membrane‐attached fusion proteins, we provide examples for a photobleaching‐based assessment of the exchange kinetics of proteins within living human endothelial cells. [ABSTRACT FROM AUTHOR]

Discusses the use of the two-dimensional adaptive umbrella sampling with the first umbrella coordinate equal to the potential energy of the system and the second umbrella coordinate equal to a function that discriminates important folded conformations from unfolded conformations to determine the equilibrium properties of complex biomolecular systems.

Few human cell strains are suitable and readily available as in vitro adipocyte models. We used resected lipoma tissue from a patient with germline phosphatase and tensin homolog (PTEN) haploinsufficiency to establish a preadipocyte cell strain termed LipPD1 and aimed to characterize cellular functions and signalling pathway alterations in comparison to the established adipocyte model Simpson-Golabi-Behmel-Syndrome (SGBS) and to primary stromal-vascular fraction cells. We found that both cellular life span and the capacity for adipocyte differentiation as well as adipocyte-specific functions were preserved in LipPD1 and comparable to SGBS adipocytes. Basal and growth factor-stimulated activation of the PI3 K/AKT signalling pathway was increased in LipPD1 preadipocytes, corresponding to reduced PTEN levels in comparison to SGBS cells. Altogether, LipPD1 cells are a novel primary cell model with a defined genetic lesion suitable for the study of adipocyte biology. [ABSTRACT FROM AUTHOR]

(1) Background: Members of the TRPC3/TRPC6/TRPC7 subfamily of canonical transient receptor potential (TRP) channels share an amino acid similarity of more than 80% and can form heteromeric channel complexes. They are directly gated by diacylglycerols in a protein kinase C-independent manner. To assess TRPC3 channel functions without concomitant protein kinase C activation, direct activators are highly desirable. (2) Methods: By screening 2000 bioactive compounds in a Ca2+ influx assay, we identified artemisinin as a TRPC3 activator. Validation and characterization of the hit was performed by applying fluorometric Ca2+ influx assays and electrophysiological patch-clamp experiments in heterologously or endogenously TRPC3-expressing cells. (3) Results: Artemisinin elicited Ca2+ entry through TRPC3 or heteromeric TRPC3:TRPC6 channels, but did not or only weakly activated TRPC6 and TRPC7. Electrophysiological recordings confirmed the reversible and repeatable TRPC3 activation by artemisinin that was inhibited by established TRPC3 channel blockers. Rectification properties and reversal potentials were similar to those observed after stimulation with a diacylglycerol mimic, indicating that artemisinin induces a similar active state as the physiological activator. In rat pheochromocytoma PC12 cells that endogenously express TRPC3, artemisinin induced a Ca2+ influx and TRPC3-like currents. (4) Conclusions: Our findings identify artemisinin as a new biologically active entity to activate recombinant or native TRPC3-bearing channel complexes in a membrane-confined fashion. [ABSTRACT FROM AUTHOR]

Introduction Several studies suggest that gut microbiota may play an important role in allergic diseases. The present trial aims to examine effects of the probiotic Enterococcus faecalis on symptoms of allergic rhinitis in patients. Effects of this probiotic on the immune system have been reported by several studies, but the majority of the previous trials were animal studies. In addition, it is well known that symptoms in allergic rhinitis are prone to exhibit high placebo responses. Moreover, recent studies report that even placebos without deception (open-label placebos) are highly effective in reducing symptoms of allergic rhinitis. Our study design combines both new approaches to assess effects on allergic symptoms in patients. The objective of this study is to compare the effects of a probiotic treatment (E. faecalis) with effects seen by open-label placebo, concealed placebo treatment and no treatment control. Methods and analysis A total of 120 patients with allergic rhinitis will be randomly assigned to one of four different groups: a double-blind probiotic/placebo group (groups 1 and 2), an open-label placebo group (group 3) and a no-treatment group (group 4) to control for spontaneous variation of symptoms. The primary outcome is the evaluation of allergic symptoms using the Combined Symptoms Medication Score. Furthermore, health-related quality of life is examined (Rhinitis Quality of Life Questionnaire). Secondary outcomes include a visual analogue scale on allergic burden and a second quality of life questionnaire. This report describes the study design of the randomised controlled trial. Ethics and dissemination The study design was approved by the ethical committee of the UKT Department of Psychosomatic Medicine and Psychotherapy, Tübingen, Germany. The trial is registered at the German Clinical Trials Register ( www. drks. de, DRKS00015804). The trial results will be published in peer-reviewed journals and at conferences. [ABSTRACT FROM AUTHOR]

Several studies demonstrate that physical cleansing is actually efficacious to cope with threatened morality, thus demonstrating that physical and moral purity are psychologically interwoven. This so-called Macbeth effect has been explained, for example, by the conceptual metaphor theory that suggests an embodiment of the moral purity metaphor. Recent research draws attention to individual differences when using conceptual metaphors. The present study shows that the moral purity link interacts with different professions. Engineering and social science students were asked to hand copy a text in which the protagonist behaved in an immoral way (or in a moral way, control condition). Subsequently, they had to rate cleansing and other products. Both groups of participants showed higher ratings for cleansing products when hand copying the unethical story, but this Macbeth effect was significantly stronger for the group of engineering students. The results demonstrate that the Macbeth effect interacts with individual differences of the chosen profession. The outcome is discussed in terms of recent theories on individual differences in disgust sensitivity. [ABSTRACT FROM AUTHOR]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We report a new late‐stage functionalization of small peptides and cyclopeptides relying on the Negishi cross‐coupling of readily prepared iodotyrosine‐ or iodophenylalanine‐containing peptides with aryl‐, heteroaryl‐, and alkylzinc pivalates or halides. In silico and in vitro determinations of membrane permeability parameters of the modified cyclopeptides showed that in most cases, the solubility was improved by the introduction of polar pyridyl units while the cell‐membrane permeability was maintained. [ABSTRACT FROM AUTHOR]

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Brain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression, and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels are not available. Using controlled-cortical impact as an experimental model of brain trauma in adult mice, we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on the appearance of depressive-like behavior. We demonstrate that this alteration in behavior is associated with an impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in the expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission from hyperpolarizing to depolarizing after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma. [ABSTRACT FROM AUTHOR]

ABSTRACT: Like most public libraries in the United States during the First World War, the St. Louis (Missouri) Public Library (SLPL) removed literature from its collection that some considered "disloyal" or "pro-German propaganda." Library historians have drawn a broad, national picture of this practice, but this study examines at a local level what was censored at SLPL, when censorship occurred relative to other public libraries, and what forces might have influenced SLPL's librarian to temporarily remove items from public access. To answer the later question, the author examines the social sphere of SLPL's librarian, Arthur E. Bostwick: the SLPL's Board of Directors, his neighborhood, and the social organizations to which he belonged. This study reveals the extent to which the SLPL librarian and board were interwoven within a broader wealthy and powerful decision-making class financially invested in Allied success and responsible for insuring St. Louisans' loyalty to the war effort. It also reveals just how little is known about which titles were removed, when they were removed, and when they again became accessible to the public. [ABSTRACT FROM AUTHOR]

Background: Several studies demonstrated that placebo treatment may have a significant impact on many different symptoms. While in the traditional view concealment of the placebo is essential, recent studies report intriguing evidence that placebos may work even without deception. For example, it has been demonstrated that open-label placebos can improve symptoms in allergic rhinitis. However, the mechanisms of how placebos without concealment work remain unknown. Trial design: In order to examine expectancy effects we conducted a randomized controlled trial (N = 46), in which patients with allergic symptoms received either placebos without deception or no pills at all. In half of those patients we induced positive expectations about the placebo effect. After two weeks we tested whether symptoms and quality of life had changed. Results: Results revealed that open-label placebos improved allergic symptoms more than the control group. Inducing positive expectations had no effects on the improvement of allergic symptoms (the primary and more objective outcome), but on mental sum scores of the quality of life questionnaire. Conclusions: Placebos without deception can improve symptoms in allergic rhinitis. Positive expectations do not contribute to the efficacy of open-label placebos, but seem to have an effect on more global and subjective well-being (mental or emotional quality of life). Clinical trial registration number: German Clinical Trials Register, [ABSTRACT FROM AUTHOR]

Abstract: Recently, a variety of studies concerned with the permeability and oral bioavailability of cyclic peptides have been reported. In particular, strategies aiming at modifying peptides to maintain or to enhance solubility while enabling permeability constitute a significant challenge, but are of high interest to ensure a smooth drug discovery process. Current methodologies include N-methylation, matching of hydrogen bonding acceptors and donors across the macrocycle, and additional masking of polarity. In this study, we investigate further the pivotal effects of shielding on permeability and studied the metabolism of the corresponding peptides in more detail by comparing peptide concentrations in the portal versus the jugular vein in rats. Interestingly, minor changes in one particular side chain impacts both permeability and liver metabolism.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Biol. Sci. 1369; 1996: 377-386 5 Botvinick M., Cohen J. Rubber hands "feel" touch that eyes see. Although the other senses are certainly important as well, the sense of touch may still be particularly important today in establishing our identity and distinguishing it from the environment. The importance of touch in today's world was exemplified during the COVID-19 pandemic, where it became clear how difficult our social lives become when touch is no longer possible. [Extracted from the article]

Iron (Fe) and manganese (Mn) are the two most common redox-active elements in the Earth's crust and are well known to influence mineral formation and dissolution, trace metal sequestration, and contaminant transformations in soils and sediments. Here, we characterized the reaction of aqueous Fe(II) with pyrolusite (β-MnO) using electron microscopy, X-ray diffraction, aqueous Fe and Mn analyses, and Fe Mössbauer spectroscopy. We reacted pyrolusite solids repeatedly with 3 mM Fe(II) at pH 7.5 to evaluate whether electron transfer occurs and to track the evolving reactivity of the Mn/Fe solids. We used Fe isotopes (56 and 57) in conjunction with Fe Mössbauer spectroscopy to isolate oxidation of Fe(II) by Fe(III) precipitates or pyrolusite. Using these complementary techniques, we determined that Fe(II) is initially oxidized by pyrolusite and that lepidocrocite is the dominant Fe oxidation product. Additional Fe(II) exposures result in an increasing proportion of magnetite on the pyrolusite surface. Over a series of nine 3 mM Fe(II) additions, Fe(II) continued to be oxidized by the Mn/Fe particles suggesting that Mn/Fe phases are not fully passivated and remain redox active even after extensive surface coverage by Fe(III) oxides. Interestingly, the initial Fe(III) oxide precipitates became further reduced as Fe(II) was added and additional Mn was released into solution suggesting that both the Fe oxide coating and underlying Mn phase continue to participate in redox reactions when freshly exposed to Fe(II). Our findings indicate that Fe and Mn chemistry is influenced by sustained reactions of Fe(II) with Mn/Fe oxides. [ABSTRACT FROM AUTHOR]

Dimethyl fumarate ( DMF) is an immunomodulatory compound to treat multiple sclerosis and psoriasis with neuroprotective potential. Its mechanism of action involves activation of the antioxidant pathway regulator Nuclear factor erythroid 2-related factor 2 thereby increasing synthesis of the cellular antioxidant glutathione ( GSH). The objective of this study was to investigate whether post-traumatic DMF treatment is beneficial after experimental traumatic brain injury ( TBI). Adult C57Bl/6 mice were subjected to controlled cortical impact followed by oral administration of DMF (80 mg/kg body weight) or vehicle at 3, 24, 48, and 72 h after the inflicted TBI. At 4 days after lesion (dal), DMF-treated mice displayed less neurological deficits than vehicle-treated mice and reduced histopathological brain damage. At the same time, the TBI-evoked depletion of brain GSH was prevented by DMF treatment. However, nuclear factor erythroid 2-related factor 2 target gene mRNA expression involved in antioxidant and detoxifying pathways was increased in both treatment groups at 4 dal. Blood brain barrier leakage, as assessed by immunoglobulin G extravasation, inflammatory marker mRNA expression, and CD45+ leukocyte infiltration into the perilesional brain tissue was induced by TBI but not significantly altered by DMF treatment. Collectively, our data demonstrate that post-traumatic DMF treatment improves neurological outcome and reduces brain tissue loss in a clinically relevant model of TBI. Our findings suggest that DMF treatment confers neuroprotection after TBI via preservation of brain GSH levels rather than by modulating neuroinflammation. [ABSTRACT FROM AUTHOR]