Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who ...underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), APC (60%), and KRAS (49%). TP53 mutations were significantly linked to higher overall stage (p = 0.038) and lower disease-free survival (DFS) (p = 0.039). ATM mutation was significantly associated with higher tumor stage (p = 0.012) and shorter overall survival (OS) (p = 0.041). Stage 3 and 4 patients with ATM mutations (p = 0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p = 0.002). However, the OS of patients with or without TP53, RAS, APC, PIK3CA, and SMAD4 mutations did not differ significantly (p = 0.59, 0.72, 0.059, 0.25, and 0.12, respectively). Similarly, the DFS between patients with RAS, APC, PIK3CA, and SMAD4 mutations and those with wild-type were not statistically different (p = 0.3, 0.79, 0.13, and 0.59, respectively). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p = 0.043). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.
Isocitrate dehydrogenase 2 (IDH2) is an NADP
-dependent enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate in the mitochondrial matrix, and is critical for the ...production of NADPH to limit the accumulation of mitochondrial reactive oxygen species (ROS). Here, we showed that high-fat diet (HFD) feeding resulted in accelerated weight gain in the IDH2KO mice due to a reduction in whole-body energy expenditure. Moreover, the levels of NADP
, NADPH, NAD
, and NADH were significantly decreased in the brown adipose tissue (BAT) of the HFD-fed IDH2KO animals, accompanied by decreased mitochondrial function and reduced expression of key genes involved in mitochondrial biogenesis, energy expenditure, and ROS resolution. Interestingly, these changes were partially reversed when the antioxidant butylated hydroxyanisole was added to the HFD. These observations reveal a crucial role for IDH2 in limiting ROS-dependent mitochondrial damage when BAT metabolism is normally enhanced to limit weight gain in response to dietary caloric overload.
Astrocytes, which are homeostatic cells of the central nervous system (CNS), display remarkable heterogeneity in their morphology and function. Besides their physical and metabolic support to ...neurons, astrocytes modulate the blood-brain barrier, regulate CNS synaptogenesis, guide axon pathfinding, maintain brain homeostasis, affect neuronal development and plasticity, and contribute to diverse neuropathologies via secreted proteins. The identification of astrocytic proteome and secretome profiles has provided new insights into the maintenance of neuronal health and survival, the pathogenesis of brain injury, and neurodegeneration. Recent advances in proteomics research have provided an excellent catalog of astrocyte-secreted proteins. This review categorizes astrocyte-secreted proteins and discusses evidence that astrocytes play a crucial role in neuronal activity and brain function. An in-depth understanding of astrocyte-secreted proteins and their pathways is pivotal for the development of novel strategies for restoring brain homeostasis, limiting brain injury/inflammation, counteracting neurodegeneration, and obtaining functional recovery.
Bimetallic Pd-Fe catalyst supported on ordered mesoporous carbon (Pd-Fe/OMC) was prepared by a surfactant-templating method and a subsequent incipient wetness impregnation method. The catalyst was ...applied to the catalytic cleavage of C-O bond in benzyl phenyl ether to aromatics. For comparison, monometallic Pd/OMC and Fe/OMC catalysts were also investigated. Benzyl phenyl ether was used as a lignin model compound for representing alpha-O-4 linkage in lignin. The combined effect of palladium and iron on the physicochemical properties and catalytic activities of Pd-Fe/OMC was investigated. Although Pd/OMC catalyst showed the highest conversion of benzyl phenyl ether, selectivity for aromatics was low due to saturation of aromatic ring. On the other hand, Fe/OMC catalyst showed lower conversion of benzyl phenyl ether than Pd/OMC, but Fe/OMC catalyst showed higher C-O bond cleavage selectivity than Pd/OMC catalyst without saturation of aromatics. Bimetallic Pd-Fe/OMC catalyst showed the highest yield for aromatics. The introduction of Fe into Pd/OMC catalyst resulted in the modification of electronic properties of Pd by electron transfer from Fe to Pd, which led to the enhanced yield for aromatics.
Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT ...regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.
Hypothalamic inflammation plays an important role in disrupting feeding behavior and energy homeostasis as well as in the pathogenesis of obesity and diabetes. Here, we show that pyruvate ...dehydrogenase kinase (PDK)-2 plays a role in hypothalamic inflammation and its sequelae in mouse models of diabetes. Cell type-specific genetic ablation and pharmacological inhibition of PDK2 in hypothalamic astrocytes suggest that hypothalamic astrocytes are involved in the diabetic phenotype. We also show that the PDK2-lactic acid axis plays a regulatory role in the observed metabolic imbalance and hypothalamic inflammation in mouse primary astrocyte and organotypic cultures, through the AMPK signaling pathway and neuropeptidergic circuitry governing feeding behavior. Our findings reveal that PDK2 ablation or inhibition in mouse astrocytes attenuates diabetes-induced hypothalamic inflammation and subsequent alterations in feeding behavior.
Betulinic acid (BA) is a naturally arising pentacyclic triterpenoid that has anti-malarial, anti-retroviral, anti-inflammatory, and anti-cancer biological effects. More recently, it has been reported ...to possess anti-obesity activity mediated by the activation of AMP-activated protein kinase (AMPK). We further investigated antidiabetic activity of BA in mouse tissues at the cellular and systemic levels. We found that BA stimulated AMPK in a similar fashion to the known AMPK activators, such as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside and metformin. Notably, the level of glucose uptake by BA was not altered by wortmannin, suggesting that this activation did not depend on phosphoinositide 3-kinase. Furthermore, BA diminished blood glucose levels in alloxane-treated ICR mice and in untreated mice during the glucose tolerance test. BA also stimulated mRNA expression of glucose transporter 4, which could partly explain increased glucose uptake. BA also increased AS160 phosphorylation by insulin-independent mechanisms in the extensor digitorum longus muscle. These results indicate that BA may serve as a promising therapeutic agent for diabetes by activating AMPK, like metformin. Notably, BA also enhanced mouse endurance capacity, indicating that it also affects metabolic regulation in addition to its antidiabetic activity.
A series of butyric acid (BA)-assisted nickel/alumina catalysts (denoted as XBAN/A) with different butyric acid/Ni molar ratio (X) were prepared by an impregnation method, and they were applied to ...the hydrogen production by steam reforming of natural gas. All the XBAN/A catalysts exhibited X-ray diffraction patterns indicative of highly stable nickel aluminate phase. However, a XBAN/A catalyst with an appropriate amount of butyric acid showed the enhanced nickel dispersion because of steric hindrance of butyric acid shell surrounding nickel particle. Addition of butyric acid also increased methane adsorption capacity of the catalysts, which was directly related to the catalytic performance. In the steam reforming of natural gas, both natural gas conversion and hydrogen yield showed volcano-shaped trends with respect to butyric acid/Ni molar ratio (X). Nickel dispersion of XBAN/A catalysts was well correlated with natural gas conversion and hydrogen yield over the catalysts. Natural gas conversion and hydrogen yield increased with increasing nickel dispersion. Among the catalysts tested, 0.25BAN/A catalyst with the highest nickel dispersion exhibited the best catalytic performance in the steam reforming of natural gas.
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•A series of butyric acid-assisted Ni/Al2O3 (XBAN/A) catalysts were prepared.•Hydrogen was produced by steam reforming of natural gas.•Hydrogen yield increased with increasing methane adsorption capacity.•Hydrogen yield increased with increasing nickel dispersion.
•(0.6−x)Re–xRu/MC catalysts with different Ru content (x, mol%) were prepared.•Liquid-phase hydrogenation of succinic acid to 1,4-butanediol (BDO) was conducted.•Yield for BDO showed a volcano-shaped ...trend with respect to Ru content.•TOFBDO increased with increasing the amount of weak hydrogen-binding sites.
A series of Re–Ru bimetallic catalysts supported on mesoporous carbon (denoted as (0.6−x)Re–xRu/MC) were prepared by a single-step surfactant-templating method and a subsequent incipient wetness impregnation method with a variation of ruthenium loading (x, mol%), and they were applied to the liquid-phase hydrogenation of succinic acid to 1,4-butanediol (BDO). The effect of metal content on the catalytic activities and physicochemical properties of (0.6−x)Re–xRu/MC catalysts was investigated. It was found that a Re–Ru miscible phase was formed in the catalysts during the reduction process, and it was responsible for strong interaction between rhenium and ruthenium. It was also revealed that reducibility, metal dispersion, and oxidation state of (0.6−x)Re–xRu/MC catalysts were affected by Re:Ru molar ratio. In particular, the oxidation state was closely related to the hydrogen adsorption behavior of the catalysts. The amount of weak hydrogen-binding sites increased with increasing the ratios of metallic rhenium (Re0) and ruthenium (Ru0) with respect to total metallic species in the reduced (0.6−x)Re–xRu/MC catalysts. Catalytic performance in the hydrogenation of succinic acid to BDO over (0.6−x)Re–xRu/MC showed a volcano-shaped trend with respect to Re:Ru molar ratio. This result was well correlated with the amount of weak hydrogen-binding sites of the catalysts. Among the catalysts tested, 0.3Re–0.3Ru/MC with the largest amount of weak hydrogen-binding sites showed the best catalytic performance in the BDO production by hydrogenation of succinic acid.
Diabetes mellitus (DM) is strongly associated with depression, especially in women. This study was designed to investigate the gender-specific association between DM and depressive mood by family ...history of diabetes. Data from the Korea National Health and Nutrition Examination Survey, a population-based cross-sectional survey in 2020, were used. Of 6,133 participants aged 19 years or older, 4,259 participants were included after excluding participants without data of laboratory or physical examination, medical or family history of diseases, or depression scores of Patient Health Questionnaire–9. We examined associations of glucose and insulin metabolism, and DM with depressed mood by sex and family history of diabetes using logistic regression analyses with three stepwise models. In men, fasting glucose and HbA1c (odds ratio OR: 1.25, 95% confidence interval CI: 1.10, 1.42) levels were significantly associated with depressed mood. Men with DM and a family history of diabetes were also significantly associated with depressed mood (OR: 1.84, 95% CI: 1.12, 3.05), whereas DM without a family history showed no association. In women, glucose and insulin metabolism had no associations with depressed mood, and DM was also not associated with depressed mood regardless of a family history of diabetes. In Korean adults, DM with a family history of diabetes and glucose metabolism showed significant associations with depressed mood in men, but not in women. Our results suggest that men with both DM and a family history of diabetes should be paid more attention to depressed moods, considering ethnic characteristics.
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