The microstructural evolution of highly ordered graphite during high temperature carbonization of cellulose nanocrystals (CNC) was traced in the temperature range of 1000–2500 °C. It was interesting ...to note that the direct carbonization of CNC under inert environment led to an irregular morphology due to molecular fusion whereas oxidative stabilization at 250 °C under air and subsequent carbonization preserved the pristine needle-like structure of the CNC during carbonization. Various characterizations such as high resolution transmission electron microscopy (HRTEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) exhibited that the carbonization of CNC undergoes three distinctive stages of structural changes depending on carbonization temperature: (1) formation of turbo-stratic graphitic structure below 1500 °C (1st stage), (2) phase conversion to polycrystalline graphite between 1500 and 2000 °C (2nd stage), and (3) in-plane homogenization to highly ordered graphite above 2000 °C (3rd stage).
Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance have been explored in both animal and human studies. However, our current ...understanding of obesity-associated insulin resistance relies on studies of artificial metabolic extremes. The purpose of this study was to explore the roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in human patients with modest obesity and early metabolic dysfunction. We obtained omental adipose tissue and fasting blood samples from 51 females undergoing gynecologic surgery. We investigated serum concentrations of proinflammatory cytokines and adipokines as well as the mRNA expression of proinflammatory and macrophage phenotype markers in visceral adipose tissue using ELISA and quantitative RT-PCR. We measured adipose tissue inflammation and macrophage infiltration using immunohistochemical analysis. Serum levels of adiponectin and leptin were significantly correlated with HOMA-IR and body mass index. The levels of expression of MCP-1 and TNF-α in visceral adipose tissue were also higher in the obese group (body mass index ≥ 25). The expression of mRNA MCP-1 in visceral adipose tissue was positively correlated with body mass index (r = 0.428, p = 0.037) but not with HOMA-IR, whereas TNF-α in visceral adipose tissue was correlated with HOMA-IR (r = 0.462, p = 0.035) but not with body mass index. There was no obvious change in macrophage phenotype or macrophage infiltration in patients with modest obesity or early metabolic dysfunction. Expression of mRNA CD163/CD68 was significantly related to mitochondrial-associated genes and serum inflammatory cytokine levels of resistin and leptin. These results suggest that changes in the production of inflammatory biomolecules precede increased immune cell infiltration and induction of a macrophage phenotype switch in visceral adipose tissue. Furthermore, serum resistin and leptin have specific roles in the regulation of adipose tissue macrophages in patients with modest obesity or early metabolic dysfunction.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles ...tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To investigate viruses in measles‐negative cases, 221 measles‐suspected samples collected in Gyeonggi Province, South Korea were tested using a real‐time PCR assay. Rubella virus was not detected. ...However, 11 cases of parvovirus B19 (5.0%), 47 cases of human herpesvirus 6 (21.3%), 25 cases of human herpesvirus 7 (11.3%), and one case of co‐infection with parvovirus B19 and human herpesvirus 7 were confirmed, as were eight cases of co‐infection with human herpesvirus 6 and human herpesvirus 7. This study showed that parvovirus B19, human herpesvirus 6, and human herpesvirus 7 should be considered by physicians for the diagnosis of measles‐suspected patients.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Food antioxidants have received prompt attention for controlling oxidative stress encountered in daily life. This study aimed to examine the protective effects of Aronia berry extract ...(ABE) supplementation on acute aerobic exercise (AAE)‐induced oxidative stress in healthy subjects.
Methods
We assessed a battery of antioxidant defence and oxidative stress parameters at pre‐exercise, immediately post‐exercise and 30 min post‐exercise in healthy middle‐aged adults with habitually low intakes of fruit and vegetables in an 8‐week, double‐blind, randomised, controlled clinical trial with two arms (n = 70). The AAE challenge model, characterised as a treadmill exercise for 30 min at 60% VO2 maximum, was applied to load oxidative stress at the end of the study. Pearson's correlation analysis assessed the association between the changes in antioxidant defence capacities and oxidative stress levels.
Results
The time–course‐dependent oxidative stress was well observed in the placebo group regarding the glutathione peroxidase (GPx) activity and the reduced glutathione (GSH) availability for antioxidant defence and erythrocyte malondialdehyde, interleukin‐6 and lactate levels for oxidative damage. Meanwhile, the ABE supplementation effectively strengthened the glutathione defence system by increasing GSH availability and GPx activity immediately post‐exercise and 30 min post‐exercise. In addition, the scatter plot and linear regression analysis revealed strong negative correlations of GSH availability with oxidised low‐density lipoprotein and plasma malonaldehyde levels.
Conclusion
These findings suggest that daily supplementation of 300 mg ABE might help boost GSH levels and an adaptive antioxidant enzyme defence system of erythrocytes in healthy adults with habitually low fruit and vegetable intakes.
Key points
Acute aerobic exercise (AAE)‐induced oxidative load was temporary and reversible, returning almost to baseline levels after 30 min post‐exercise.
Therefore, an AAE model can provide a unique opportunity to evaluate the antioxidant properties of food supplements.
Daily supplementation of 300 mg of Aronia berry extract (ABE) was beneficial to alleviate oxidative stress/damage and to enhance resting blood antioxidant capacity in healthy middle‐aged adults with habitually low intakes of fruits and vegetables.
We proposed that ABE supplementation boosts reduced glutathione (GSH) levels and adaptive antioxidant enzyme defence system of erythrocytes for explaining the underlying mechanisms.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Myogenic progenitors (MPs) generate myocytes that fuse to form myofibers during skeletal muscle development while maintaining the progenitor pool, which is crucial for generating sufficient muscle. ...Notch signaling has been known to reserve a population of embryonic MPs during primary myogenesis by promoting cell cycle exit and suppressing premature differentiation. However, the roles of individual Notch receptors (Notch1-4) during embryonic/fetal myogenesis are still elusive. In this study, we found that Notch1 and Notch2, which exhibit the highest structural similarity among Notch receptors, maintain the MP population by distinct mechanisms: Notch1 induces cell cycle exit and Notch2 suppresses premature differentiation. Moreover, genetic and cell culture studies showed that Notch1 and Notch2 signaling in MPs are distinctively activated by interacting with Notch ligand-expressing myofibers and MP-lineage cells, respectively. These results suggest that through different activation modes, Notch1 and Notch2 distinctively and cooperatively maintain MP population during fetal myogenesis for proper muscle development.
Zolgensma is a gene-replacement therapy that has led to a promising treatment for spinal muscular atrophy (SMA). However, clinical trials of Zolgensma have raised two major concerns: insufficient ...therapeutic effects and adverse events. In a recent clinical trial, 30% of patients failed to achieve motor milestones despite pre-symptomatic treatment. In addition, more than 20% of patients showed hepatotoxicity due to excessive virus dosage, even after the administration of an immunosuppressant. Here, we aimed to test whether a ubiquitination-resistant variant of survival motor neuron (SMN), SMN
, has improved therapeutic effects for SMA compared with wild-type SMN (SMN
).
A severe SMA mouse model, SMA type 1.5 (Smn
; SMN2
; SMN∆7
) mice, was used to compare the differences in therapeutic efficacy between AAV9-SMN
and AAV9-SMN
. All animals were injected within Postnatal Day (P) 1 through a facial vein or cerebral ventricle.
AAV9-SMN
-treated mice showed increased lifespan, body weight, motor neuron number, muscle weight and functional improvement in motor functions as compared with AAV9-SMN
-treated mice. Lifespan increased by more than 10-fold in AAV9-SMN
-treated mice (144.8 ± 26.11 days) as compared with AAV9-SMN
-treated mice (26.8 ± 1.41 days). AAV9-SMN
-treated mice showed an ascending weight pattern, unlike AAV9-SMN
-treated mice, which only gained weight until P20 up to 5 g on average. Several motor function tests showed the improved therapeutic efficacy of SMN
. In the negative geotaxis test, AAV9-SMN
-treated mice turned their bodies in an upward direction successfully, unlike AAV9-SMN
-treated mice, which failed to turn upwards from around P23. Hind limb clasping phenotype was rarely observed in AAV9-SMN
-treated mice, unlike AAV9-SMN
-treated mice that showed clasping phenotype for more than 20 out of 30 s. At this point, the number of motor neurons (1.5-fold) and the size of myofibers (2.1-fold) were significantly increased in AAV9-SMN
-treated mice compared with AAV9-SMN
-treated mice without prominent neurotoxicity. AAV9-SMN
had fewer liver defects compared with AAV9-SMN
, as judged by increased proliferation of hepatocytes (P < 0.0001) and insulin-like growth factor-1 production (P < 0.0001). Especially, low-dose AAV9-SMN
(nine-fold) also reduced clasping time compared with SMN
.
SMN
will provide improved therapeutic efficacy in patients with severe SMA with insufficient therapeutic efficacy. Low-dose treatment of SMA patients with AAV9-SMN
can reduce the adverse events of Zolgensma. Collectively, SMN
has value as a new treatment for SMA that improves treatment effectiveness and reduces adverse events simultaneously.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform ...metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.
Chronic inflammation is a driving force for the development of metabolic disease including diabetes and obesity. However, the functional characteristics of T-cell senescence in the abnormal glucose ...homeostasis are not fully understood. We studied the patients visiting a hospital for routine health check-ups, who were divided into two groups: normal controls and people with prediabetes. Gene expression profiling of peripheral blood mononuclear cells from normal controls and patients with type 2 diabetes was undertaken using microarray analysis. We also investigated the immunometabolic characteristics of peripheral and hepatic senescent T cells in the normal subjects and patients with prediabetes. Moreover, murine senescent T cells were tested functionally in the liver of normal or mice with metabolic deterioration caused by diet-induced obesity. Human senescent (CD28
CD57
) CD8
T cells are increased in the development of diabetes and proinflammatory cytokines and cytotoxic molecules are highly expressed in senescent T cells from patients with prediabetes. Moreover, we demonstrate that patients with prediabetes have higher concentrations of reactive oxygen species (ROS) in their senescent CD8
T cells via enhancing capacity to use glycolysis. These functional properties of senescent CD8
T cells contribute to the impairment of hepatic insulin sensitivity in humans. Furthermore, we found an increase of hepatic senescent T cells in mouse models of aging and diet-induced obesity. Adoptive transfer of senescent CD8
T cells also led to a significant deterioration in systemic abnormal glucose homeostasis, which is improved by ROS scavengers in mice. This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes.
The SUVmax is a measure of FDG uptake and is related with tumor aggressiveness in thyroid cancer, however, its association with molecular pathways is unclear. Here, we investigated the relationship ...between SUVmax and gene expression profiles in 80 papillary thyroid cancer (PTC) patients. We conducted an analysis of DEGs and enriched pathways in relation to SUVmax and tumor size. SUVmax showed a positive correlation with tumor size and correlated with glucose metabolic process. The genes that indicate thyroid differentiation, such as SLC5A5 and TPO, were negatively correlated with SUVmax. Unsupervised analysis revealed that SUVmax positively correlated with DNA replication(r = 0.29, p = 0.009), pyrimidine metabolism(r = 0.50, p < 0.0001) and purine metabolism (r = 0.42, p = 0.0001). Based on subgroups analysis, we identified that PSG5, TFF3, SOX2, SL5A5, SLC5A7, HOXD10, FER1L6, and IFNA1 genes were found to be significantly associated with tumor aggressiveness. Both high SUVmax PTMC and macro-PTC are enriched in pathways of DNA replication and cell cycle, however, gene sets for purine metabolic pathways are enriched only in high SUVmax macro-PTC but not in high SUVmax PTMC. Our findings demonstrate the molecular characteristics of high SUVmax tumor and metabolism involved in tumor growth in differentiated thyroid cancer.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
