BRCA1-associated protein 1 (
) is emerging as an intensively studied cancer-associated gene. Germline mutations in
lead to a cancer syndrome, and somatic loss is found in several cancer types. BAP1 ...encodes a deubiquitinase enzyme, which plays key roles in cell-cycle regulation, cell death, and differentiation. Recent studies have demonstrated that BAP1 is also involved in several aspects of cellular metabolism, including metabolic homeostasis, glucose utilization, control of ferroptosis, and stress response. A better knowledge of the metabolic roles of cancer-associated genes is important to understanding tumor initiation and progression, as well as highlighting potential therapeutic avenues. With this review, we summarize the current knowledge regarding BAP1-mediated regulation of metabolic activities that may support new strategies to treat BAP1-mutated cancers.
Antioxidant intake has been suggested to be associated with a reduced osteoporosis risk, but the effect of dietary total antioxidant capacity (TAC) on bone health and the risk of osteoporosis remains ...unclear. We aimed to assess the hypothesis that dietary TAC is positively associated with bone mass and negatively related to the risk of osteoporosis in Korean women. This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey. Dietary TAC was estimated using task automation and an algorithm with 24-h recall data. In total, 8230 pre- and postmenopausal women were divided into four groups according to quartiles of dietary TAC. Dietary TAC was negatively associated with the risk of osteoporosis (odds ratio, 0.73; 95% confidence interval, 0.54-0.99;
-value = 0.045) in postmenopausal women, but not in premenopausal women. Dietary TAC was positively associated with bone mineral content (BMC) and bone mineral density of the femoral neck and lumbar spine in postmenopausal women and BMC of the total femur and lumbar spine in premenopausal women. Our study suggests that dietary TAC is inversely associated with the risk of osteoporosis in postmenopausal women and positively associated with bone mass in both pre- and postmenopausal women.
The increased life expectancy and the occurrence of premature menopause prolong the mean postmenopausal phase in women's lifespans. Although the roles of poor socioeconomic status (SES), ...anthropometric characteristics, and nutritional status in premature menopause and the health of postmenopausal women are well understood, the differences in nutritional status and metabolic syndrome (MetS) prevalence in postmenopausal women depending on their menopause age are less explored. Furthermore, the association between SES and MetS risk in postmenopausal women is not studied. Thus, this study aimed to compare distinct nutritional status and MetS risk between women with premature menopause and natural menopause. Additionally, the association among SES, health-related lifestyle behaviors (HLBs), and MetS risk in postmenopausal women was studied. This study included 31,799 postmenopausal women from the 8th National Health and Nutrition Examination Survey (KNHANES). The relationship between disease prevalence and nutrient intake of the subjects was analyzed using analysis of variance (GLM), and Scheffé test was performed. Multiple logistic regression analysis was used to evaluate the association among SES, HLBs, and MetS as well as premature menopause. Women with premature menopause showed poor SES, anthropometric characteristics, and HLBs compared with women with natural menopause. Additionally, premature menopausal women had markedly lower intakes of protein, polyunsaturated fatty acid,
-3 fatty acid, and β-carotene, but higher intakes of energy, carbohydrate, saturated fatty acid, and sugar than women with natural menopause (
< 0.0001). Premature menopausal women showed significantly higher MetS prevalence by having hypertriglyceridemia (
< 0.0001), hypertension (
= 0.0145), and reduced HDL cholesterol levels (
< 0.0001) relative to natural menopausal women. Furthermore, our findings indicate a substantial link among SES, HLBs, and the risk of premature menopause. In postmenopausal women, deteriorating SES and HLBs appear to influence the prevalence of MetS. Notably, our study reveals that higher intakes of protein, calcium, phosphate, and iron are correlated with a lower risk of developing MetS. These observations suggest that proactive nutritional education for premature menopausal women is necessary to improve MetS risk and their nutritional status. Also, SES-dependent interventions regarding nutrition and HLBs in postmenopausal women will be significant to lower MetS risk, MetS-derived chronic disease, and mortality in postmenopausal women.
The health-beneficial outcomes of doenjang, a Korean fermented food have been questioned due to its high salt content; moreover, the detailed underlying mechanisms of its health beneficial effects ...are not fully investigated. Thus, this study aimed to investigate doenjang's anti-obesity effects, anti-hypertensive effects, and its underlying mechanisms in high-fat diet -induced obesity. Sprague-Dawley rats fed with normal diet (ND), high-fat diet (HD), HD with 8% additive salt (HDS), or HD with doenjang containing 8% salt (HDJ) for 13 weeks. Compared to HD and HDS groups, the HDJ group had lower body and epididymal fat tissue weight gain and showed hypotrophy and hypoplasia. The RAS-related mRNA levels in the adipose tissue, including Renin and Ace were downregulated in the HDJ group compared to HD and HDS groups. Additionally, HDJ groups had significant improvements in systolic blood pressure, serum RAS-associated parameters (e.g., angiotensin II and aldosterone), renal mRNA levels related to RAS (e.g., angiotensin II receptor type 1 and 2), and aldosterone-associated mRNA expressions (e.g., mineralocorticoid receptor) in the kidney of HD-induced obese rats. Most importantly, HDS and HDJ groups showed distinct outcomes regarding adipogenesis and electrolytes metabolism, even though both diets contain a high level of salt. HDS group showed a higher epididymal fat tissue weight, mass, and adipocyte size than HDJ group. In addition, compared with HDJ group, HDS group significantly decreased the release of Na+ and K+ throughout the urine and feces. The present study addresses that doenjang has anti-obesity effects and anti-hypertensive effects by activating RAS in the adipose tissue and kidney, respectively. Additionally, this study also demonstrates that salt in doenjang and the additive salt differently influences adipogenesis and electrolytes metabolism, supporting doenjang has health advantageous effects regardless of its high salt contents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ezrin, one of the ezrin‐radixin‐moesin (ERM) proteins, is involved in the formation of cell membrane processes and has been implicated in the promotion of cancer proliferation and metastasis. ...However, the possible role of ezrin in hepatocellular carcinoma (HCC) metastasis and glycolysis reprogramming has remained unclear. In this study, we found that ezrin was upregulated in HCC tissues, and its overexpression was linked with HCC patients’ aggressive tumor characteristics and poor prognosis. Functional experiments further revealed that ezrin overexpression promoted HCC cell proliferation, epithelial‐to‐mesenchymal transition (EMT) progression and angiogenesis. In addition, by measuring glucose consumption, lactate production, ATP levels and the expression of glucose metabolism‐related markers in HCC cells, we investigated whether ezrin regulated glucose metabolism. Moreover, 2‐deoxy‐D‐glucose (2‐DG) affected ezrin‐mediated proliferation, migration and EMT of HCC cells, which suggested that ezrin may, at least in part, promote HCC progression by regulating glycolysis reprogramming. Based on our results, we proposed that ezrin was involved in HCC progression and may be a valid prognostic marker.
Ezrin regulated glycolysis in HCC cells and linked the molecular mechanisms of reprogrammed metabolism to proliferation and metastasis. Our study linked ezrin to HCC progression and established ezrin as a promising biomarker for clinical prognosis and a novel therapeutic target for HCC.
Cancer cells have an imbalance in oxidation-reduction (redox) homeostasis. Understanding the precise mechanisms and the impact of the altered redox microenvironment on the immunologic reaction to ...tumors is limited.
We isolated exosomes from ovarian cancer cells through ultracentrifuge and characterized by Western-blots and Nanoparticle Tracking Analysis. 2D, 3D-coculture tumor model, and 3D live cell imaging were used to study the interactions between tumor cells, macrophages and CD3 T cells in vitro. The role of exosomal miR-155-5p in tumor growth was evaluated in xenograft nude mice models and immune-competent mice models. Flow cytometry and flow sorting were used to determine the expression levels of miR-155-5p and PD-L1 in ascites and splenic macrophages, and the percentages of CD3 T cells subpopulations.
The elevation of reactive oxygen species (ROS) greatly downregulated exosomal miR-155-5p expression in tumor cells. Neutralization of ROS with N-acetyl-L-cysteine (NAC) increased the levels of miR-155-5p in tumor exosomes that were taken up by macrophages, leading to reduction of macrophage migration and tumor spheroid infiltration. We further found that programmed death ligand 1 (PD-L1) is a functional target of miR-155-5p. Co-culture of macrophages pre-treated with NAC-derived tumor exosomes or exosomal miR-155-5p with T-lymphocytes leading to an increased percentage of CD8
T-lymphocyte and a decreased CD3
T cell apoptosis through PD-L1 downregulation. Tumor growth in nude mice was delayed by treatment with NAC-derived tumor exosomes. Delivery of tumor exo-miR-155-5p in immune-intact mice suppressed ovarian cancer progression and macrophage infiltration, and activated CD8
T cell function. It is of note that exo-miR-155-5p inhibited tumor growth more potently than the PD-L1 antibody, suggesting that in addition to PD-L1, other pathways may also be targeted by this approach.
Our findings demonstrate a novel mechanism, ROS-induced down-regulation of miR-155-5p, by which tumors modulate the microenvironment that favors tumor growth. Understanding of the negative impact of ROS on the tumor immune response will improve current therapeutic strategies. Targeting miR-155-5p can be an alternative approach to prevent formation of an immunosuppressive TME through downregulation of PD-L1 and other immunosuppressive factors.
It is unknown whether Gochujang, a traditional Korean fermented food triggers thermogenic energy expenditure. This study aims to investigate the impact of Gochujang on brown adipose tissue (BAT) ...activation and white adipose tissue (WAT) browning. The groups were: normal diet (ND), high-fat diet (HD, 60% of fat calories), HD with 10% of Gochujang (HG), HD with equivalent capsaicin dose found in Gochujang (HCL; 0.00003%), HD with high-dose of capsaicin (HCH; 0.01%). Compared to HD group, HG group had a lower tendency in body weight gain, while HCH group showed a significant reduction. After acute cold exposure, HG group showed higher rectal temperature than HD group. HG group had upregulated BAT activation-related protein levels in both basal and cold conditions. After cold treatment, HG group showed increased levels of WAT browning associated protein. This study demonstrated Gochujang’s thermogenic capacity, also its roles in BAT activation and WAT browning independent of capsaicin.
In utero environment is known to affect fetal development. Especially, the distinct fetal programming of carcinogenesis was reported in offspring exposed to maternal diets containing soy protein ...isolate (SPI) or genistein. Therefore, we investigated whether maternal consumption of low-isoflavone SPI or genistein alters hepatic gene expression and liver development in rat offspring. Female Sprague–Dawley rats were fed a casein diet, a low-isoflavone SPI diet or a casein diet supplemented with genistein (250 mg/kg diet) for 2 weeks before mating and throughout pregnancy and lactation. Male offspring were studied on postnatal day 21 (CAS, SPI and GEN groups). Among 965 differentially expressed hepatic genes related to maternal diet (P<.05), the expression of 590 was significantly different between CAS and SPI groups. Conversely, the expression of 88 genes was significantly different between CAS and GEN groups. Especially, genes involved in drug metabolism were significantly affected by the maternal diet. SPI group showed increased cell proliferation, reduced apoptosis and activation of the mTOR pathway, which may contribute to a higher relative liver weight compared to other groups. We observed higher serum homocysteine levels and lower global and CpG site-specific DNA methylation of Gadd45b, a gene involved in cell proliferation and apoptosis, in SPI group compared to CAS group. Maternal SPI diet also reduced histone H3-Lysine 9 (H3K9) trimethylation and increased H3K9 acetylation in offspring. These results demonstrate that maternal consumption of a low-isoflavone SPI diet alters the hepatic gene expression profile and liver development in offspring possibly by epigenetic processes.
Many prominent models propose that selfcontrol requires deliberative control of impulses. We propose that people s subjective mental construals of events can alter temptation impulses without ...requiring conscious deliberation. Research has indicated that high-level construals (subjective mental representations that capture the core, essential, and abstract features of events) lead to greater self-control than low-level construals (representations that capture secondary, incidental, and concrete features). We demonstrate that higher-level construals make it easier for people to associate temptations with negativity, as measured by the Implicit Association Test, and that, in turn, these construal-dependent changes in evaluative associations promote self-control. These findings indicate that subjective construals can influence selfcontrol without conscious deliberation.
The current study aimed to investigate the distinct outcomes of table salt and salt in Gochujang on blood pressure (BP). Animals were divided into 3 groups, including normal diet (NS, 0.5 % NaCl), ...high-salt diet (HS, normal diet with 8 % NaCl), or high-salt Gochujang diet (HSG, normal diet with Gochujang containing 8 % NaCl). Compared to the NS groups, the HS group showed significantly increased systolic blood pressure (SBP), while the HSG group did not elevate SBP. The HS group had lower serum angiotensin II and aldosterone levels than the NS group, while the HSG group showed higher levels of those parameters than the HS group. The renal mRNA expression related to the renin-angiotensin-aldosterone system (RAAS) was significantly higher in the HS group than the NS group, while the HSG group had markedly lower expression of those markers. The urinary and fecal Na+/K+ proportion was higher in both HS and HSG groups relative to the NS group, but the HSG group showed a decreased Na+/K+ ratio in urine and feces compared to the HS group. Moreover, the HS group had a significantly upregulated mRNA level of Na+/HCO3− co-transporter (Slc4a4) in the kidney than the NS group, whereas the HSG group showed downregulated mRNA expression of Slc4a4 compared to the HS group. This study demonstrates that Gochujang has anti-hypertensive effects regardless of its high salt content and provide the evidence regarding the distinct impacts between salt in Gochujang and the table salt.
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