Human studies suggest that a meal elevates glucose uptake in brown adipose tissue (BAT). However, in postprandial state the thermogenic activity and the metabolism of non-esterified fatty acids (NEFAs) in BAT remain unclear. Using indirect calorimetry combined with positron emission tomography and computed tomography (PET/CT), we showed that whole-body and BAT thermogenesis (oxygen consumption) increases after the ingestion of a mixed carbohydrate-rich meal, to the same extent as in cold stress. Postprandial NEFA uptake into BAT is minimal, possibly due to elevated plasma insulin inhibiting lipolysis. However, the variation in postprandial NEFA uptake is linked to BAT thermogenesis. We identified several genes participating in lipid metabolism to be expressed at higher levels in BAT compared with white fat in postprandial state, and to be positively correlated with BAT UCP1 expression. These findings suggest that substrates preferred by BAT in postprandial state are glucose or LPL-released NEFAs due to insulin stimulation.

To examine whether early β-amyloid (Aβ) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia.

Many malignant tumours have increased TSPO expression, which has been related to a poor prognosis. TSPO-PET tracers have not comprehensively been evaluated in peripherally located tumours. This study aimed to evaluate whether N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ([18F]F-DPA) can reflect radiotherapy (RT)-induced changes in TSPO activity in head and neck squamous cell carcinoma (HNSCC).

Fabry disease (FD) is caused by a defect in α-galactosidase A gene (GLA) which leads to a progressive accumulation of neutral shingolipids, mainly globotriaosylceramide and its metabolites in several organs. Pulmonary manifestations of FD mimic chronic obstructive pulmonary disease and are disproportionate to smoking status. The effect of enzyme replacement therapy (ERT) on pulmonary function is inconclusive. We studied the effect of ERT on pulmonary function in FD with a mutation p. Arg227Ter (p.R227*) which is one of the most common mutations causing classical FD in Finland and worldwide.

In this retrospective cohort study, we explored the correlation of blood human myxovirus resistance protein A (MxA) level with severity of disease in hospitalized COVID-19 patients.

Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate-intensity continuous training (MICT) on intestinal metabolism and microbiota in subjects with insulin resistance.

Bisphosphonates are used for prevention of osteoporosis and metastatic bone diseases. Anti-invasive effects on various cancer cells have also been reported, but the mechanisms involved are not well-understood. We investigated the effects of the nitrogen-containing bisphosphonate alendronate (ALN) on the regulation of actin cytoskeleton in PC-3 cells. We analyzed the ALN effect on the organization and the dynamics of actin, and on the cytoskeleton-related regulatory proteins cofilin, p21-associated kinase 2 (PAK2), paxillin and focal adhesion kinase. Immunostainings of cofilin in ALN-treated PC-3 cells and xenografts were performed, and the role of cofilin in ALN-regulated F-actin organization and migration/invasion in PC-3 cells was analyzed using cofilin knockdown and transfection. We demonstrate that disrupted F-actin organization and decreased cell motility in ALN-treated PC-3 cells were associated with decreased levels of total and phosphorylated cofilin. PAK2 levels were also lowered but adhesion-related proteins were not altered. The knockdown of cofilin similarly impaired F-actin organization and decreased invasion of PC-3 cells, whereas in the cells transfected with a cofilin expressing vector, ALN treatment did not decrease cellular cofilin levels and migration as in mock transfected cells. ALN also reduced immunohistochemical staining of cofilin in PC-3 xenografts. Our results suggest that reduction of cofilin has an important role in ALN-induced disruption of the actin cytoskeleton and inhibition of the PC-3 cell motility and invasion. These data also support the idea that the nitrogen-containing bisphosphonates could be efficacious in inhibition of prostate cancer invasion and metastasis, if delivered in a pharmacological formulation accessible to the tumors.

Type 2 diabetes mellitus (T2DM) is associated with reduced myocardial glucose uptake (GU) and increased free fatty acid uptake (FFAU). Sprint interval training (SIT) improves physical exercise capacity and metabolic biomarkers, but effects of SIT on cardiac function and energy substrate metabolism in diabetic subjects are unknown. We tested the hypothesis that SIT is more effective than moderate-intensity continuous training (MICT) on adaptations in left and right ventricle (LV and RV) glucose and fatty acid metabolism in diabetic subjects. Twenty-six untrained men and women with T2DM or prediabetes were randomized into two-week-long SIT (n = 13) and MICT (n = 13) interventions. Insulin-stimulated myocardial GU and fasted state FFAU were measured by positron emission tomography and changes in LV and RV structure and function by cardiac magnetic resonance. In contrast to our hypothesis, SIT significantly decreased GU compared to MICT in LV. FFAU of both ventricles remained unchanged by training. RV end-diastolic volume (EDV) and RV mass increased only after MICT, whereas LV EDV, LV mass, and RV and LV end-systolic volumes increased similarly after both training modes. As SIT decreases myocardial insulin-stimulated GU compared to MICT which may already be reduced in T2DM, SIT may be metabolically less beneficial than MICT for a diabetic heart.

There may be some differences in the in vivo behavior of 68Ga-chloride and 68Ga-citrate leading to different accumulation profiles. This study compared 68Ga-citrate and 68Ga-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n = 32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using 68Ga-citrate or 68Ga-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUVmax of 68Ga-chloride and 68Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp.) were significantly higher (P = 0.0019 and P = 0.0020, resp.) than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.). In osteomyelitic tibias, the SUVmax of 68Ga-citrate was significantly higher than the uptake of 68Ga-chloride (P = 0.0017). In animals with uncomplicated bone healing, no difference in the SUVmax of 68Ga-chloride or 68Ga-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of 68Ga-citrate for PET imaging of osteomyelitis.

Recent studies have linked activated spinal glia to neuropathic pain. Here, using a positron emission tomography (PET) scanner with high spatial resolution and sensitivity, we evaluated the feasibility and sensitivity of N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl)acetamide ([18F]F-DPA) imaging for detecting spinal cord microglial activation after partial sciatic nerve ligation (PSNL) in rats.

Severe COVID-19 is associated with an imbalanced immune response. We hypothesized that patients with enhanced inflammation, as demonstrated by increased levels of certain inflammatory biomarkers, would benefit from interleukin-6 blockage.

In the development of new 18F-labelled tracers, it is important to assess the amount of released [18F]fluoride taken up in the bones of experimental animals because all 18F-labelled PET-tracers are prone, to lesser or higher degree, to undergo defluorination, with subsequent release of [18F]fluoride during scanning. However, the pharmacokinetics of [18F]fluoride in bones and other organs of healthy rats have not been well documented in a comprehensive manner. We aimed to study pharmacokinetics of [18F]NaF in rats in order to increase our understanding of the biodistribution of [18F]fluoride originating from defluorination of 18F-labelled tracers. We studied [18F]fluoride uptake in Sprague Dawley rat bones, including the epiphyseal parts of the tibia and radius, the mandible, ilium, lumbar vertebrae, costochondral joints, tibia, radius, and ribs, with 60-min in vivo PET/CT imaging. Kinetic parameters, K1, Ki, Ki/K1, and k3 were calculated with a three-compartment model. In addition, separate groups of male and female rats were studied with ex vivo bone and soft tissue harvesting and gamma counting over a 6-h period.

The diagnosis of inflammatory bowel diseases (IBD) may be challenging and their clinical course, characterized by relapses and spontaneous or drug-induced remissions, is difficult to predict. Novel prognostic biomarkers are needed. Keratin 7 (K7) is a cytoskeletal intermediate filament protein which is not normally expressed in the colonic epithelium. It was recently shown that K7 expression in the colonic epithelium is associated with ulcerative colitis and Crohn's disease, the two main subtypes of IBD. Here we investigated IBD associated K7 neo-expression in different regions of colon and terminal ileum. The correlation of the K7 expression with the inflammatory activity of the epithelium was analyzed in each region. The prognostic value of K7 was estimated by comparing the clinical disease activity after 3 years with the K7 expression at the time of enrollment. Our data shows that the level of K7 expression in inflamed epithelium varies depending on the anatomical region and it is the most pronounced in ascending and descending colon, but it did not predict the severity of IBD for the following 3 years. These results warrant future studies focusing on the biological role of K7 in colon and its utilization as potential IBD biomarker.

This study aimed to investigate whether a reduction in daily sedentary behavior (SB) improves insulin sensitivity in adults with metabolic syndrome in 6 months, without adding intentional exercise training.

α2-adrenoceptors are important regulators of vascular tone and blood pressure. Regulation of cell proliferation is a less well investigated consequence of α2-adrenoceptor activation. We have previously shown that α2B-adrenoceptor activation stimulates proliferation of vascular smooth muscle cells (VSMCs). This may be important for blood vessel development and plasticity and for the pathology and therapeutics of cardiovascular disorders. The underlying cellular mechanisms have remained mostly unknown. This study explored pathways of regulation of gene expression and intracellular signaling related to α2B-adrenoceptor-evoked VSMC proliferation.

In this study, we evaluated the anti-amyloid effect of functionalized nanoliposomes (mApoE-PA-LIP) in a mouse model of Alzheimer's disease with use of positron emission tomography and β-amyloid (Aβ)-targeted tracer [11C]Pittsburgh compound B ([11C]PIB). APP23 mice were injected with mApoE-PA-LIP or saline (3 times per week for 3 weeks) and [11C]PIB imaging was performed at baseline, after the treatment and after 3 months follow-up period, accompanied by Aβ immunohistochemistry and ELISA. After the treatment, [11C]PIB binding ratios between mApoE-PA-LIP and saline groups were equivalent in all analyzed brain regions; however, in the saline group, binding ratios increased from the baseline, whereas no increase was detected in the mApoE-PA-LIP group. During the additional follow-up, [11C]PIB binding increased significantly from baseline in both groups, and binding ratios correlated with the immunohistochemically defined Aβ load. This study further supports the use of [11C]PIB positron emission tomography imaging as a biomarker of Aβ deposition in APP23 mice and highlights the benefits of noninvasive follow-up, that is, using baseline data for animal stratification and normalization of treatment effects to baseline values, for future anti-amyloid treatment studies.

Parent-infant closeness during hospital care of newborns has many benefits for both infants and parents. We developed an educational intervention for neonatal staff, Close Collaboration with Parents, to increase parent-infant closeness during hospital care. The aim of this study was to evaluate the effectiveness of the intervention on parent-infant closeness in nine hospitals in Finland.

We investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex.

The aim of this study was to examine the associations of cardiometabolic health markers with device-measured sedentary behavior (SB) duration and different intensities of physical activity (PA) among overweight working-aged adults with low self-reported PA levels. This cross-sectional analysis included 144 subjects (42 men) with mean age of 57 (SD 6.5) years and mean BMI of 31.7 (SD 4) kg/m2. SB and standing time, breaks in sedentary time, light PA (LPA) and moderate-to-vigorous PA (MVPA) were measured for 4 consecutive weeks (mean 25 days, SD 4) with hip-worn accelerometers. Fasting plasma glucose, insulin, HbA1c, triglycerides and total cholesterol, HDL and LDL were measured from venous blood samples. HOMA-IR index was calculated as a surrogate of insulin resistance. The associations were examined using linear models. LPA, MVPA, and daily steps associated with better insulin sensitivity and favorable plasma lipid profile, when adjusted for age, sex and BMI, whereas greater proportion of SB associated with insulin resistance and unfavorable lipid profile. As all PA intensities associated with better cardiometabolic health, the total daily duration of PA may be more relevant than intensity in maintaining metabolic health in overweight adults, if the current guidelines for PA are not met.Trial Registration: ClinicalTrials.gov NCT03101228, registered 05/04/2017, https://clinicaltrials.gov/show/NCT03101228 .

Contradictory findings on the role of the type 1 cannabinoid receptor (CB1R) during the pathogenesis of Alzheimer's disease (AD) have been reported. Here, we evaluated the CB1R brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CB1R, [18F]FMPEP-d2. APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CB1R immunohistochemistry with additional mice. [18F]FMPEP-d2 positron emission tomography demonstrated lower (p < 0.05) binding ratios in the parietotemporal cortex and hippocampus of APP/PS1-21 mice compared with age-matched wild-type mice. Western blot demonstrated no differences between APP/PS1-21 and wild-type mice in the CB1R abundance, whereas significantly lower (p < 0.05) receptor expression was observed in male than female mice. The results provide the first demonstration that [18F]FMPEP-d2 is a promising imaging tool for AD research in terms of CB1R availability, but not expression. This finding may further facilitate the development of novel therapeutic approaches based on endocannabinoid regulation.