Garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit ofGarcinia indica, a plant found extensively in tropical regions. Although the fruit has been consumed traditionally over centuries, its biological activities, specifically its anticancer potential is a result of recent scientific investigations. The anticarcinogenic properties of garcinol appear to be moderated via its antioxidative, anti-inflammatory, antiangiogenic, and proapoptotic activities. In addition, garcinol displays effective epigenetic influence by inhibiting histone acetyltransferases (HAT 300) and by possible posttranscriptional modulation by mi RNA profiles involved in carcinogenesis.In vitroas well as somein vivostudies have shown the potential of this compound against several cancers types including breast, colon, pancreatic, and leukemia. Although this is a promising molecule in terms of its anticancer properties, investigations in relevant animal models, and subsequent human trials are warranted in order to fully appreciate and confirm its chemopreventative and/or therapeutic potential.
24 March 2022 in Brain, Behavior, & Immunity - Health
African American women are reported to have greater inflammation compared with women from other racial groups. Higher inflammation during pregnancy has been associated with increased risk of adverse perinatal outcomes. We hypothesized that maternal inflammation is related to depressive symptoms and social and behavioral risk factors among pregnant African American women. Pregnant African American women (n = 187) were recruited at prenatal clinics in the Midwest. Women completed questionnaires and had blood drawn at a prenatal visit. Plasma levels of cytokines (interferon gamma [IFN]-γ, interleukin [IL]-6, IL-8, IL-10, tumor necrosis factor [TNF]-α) and C-reactive protein (CRP) were measured by multiplex assays. Women had a mean age of 26.58±5.42 years and a mean gestational age at data collection of 16.35±5.95 weeks. Twenty-six percent of women had Center for Epidemiological Studies-Depression (CES-D) scores ≥23 (scores that have been correlated with clinical diagnosis of depression), 15.5% smoked cigarettes, 16.6% used marijuana, and 5.3% reported experiencing intimate partner violence (IPV). Higher CES-D scores were correlated with higher plasma CRP levels (r = 0.16, p = 0.046). Women who reported any experiences of IPV during pregnancy had higher levels of IL-8 (p = 0.018) and lower levels of IFN-γ (p = 0.012) compared with women who did not report IPV. Cigarette smoking during pregnancy was associated with lower levels of the anti-inflammatory cytokine IL-10 (p = 0.003). These findings suggest that depressive symptoms, IPV, and cigarette smoking during pregnancy relate to select inflammatory markers in pregnant African American women. The relationships of inflammation with these factors should be further investigated to better understand the mechanisms which influence maternal and fetal health outcomes.
Prenatal testosterone (T)-treated female sheep manifest peripheral insulin resistance, ectopic lipid accumulation, and insulin signaling disruption in liver and muscle. This study investigated transcriptional changes and transcriptome signature of prenatal T excess–induced hepatic and muscle-specific metabolic disruptions. Genome-wide coding and noncoding (nc) RNA expression in liver and muscle from 21-month-old prenatal T-treated (T propionate 100 mg intramuscular twice weekly from days 30-90 of gestation; term: 147 days) and control females were compared. Prenatal T (1) induced differential expression of messenger RNAs (mRNAs) in liver (15 down, 17 up) and muscle (66 down, 176 up) (false discovery rate < 0.05, absolute log2 fold change > 0.5); (2) downregulated mitochondrial pathway genes in liver and muscle; (3) downregulated hepatic lipid catabolism and peroxisome proliferator-activated receptor (PPAR) signaling gene pathways; (4) modulated noncoding RNA (ncRNA) metabolic processes gene pathway in muscle; and (5) downregulated 5 uncharacterized long noncoding RNA (lncRNA) in the muscle but no ncRNA changes in the liver. Correlation analysis showed downregulation of lncRNAs LOC114112974 and LOC105607806 was associated with decreased TPK1, and LOC114113790 with increased ZNF470 expression. Orthogonal projections to latent structures discriminant analysis identified mRNAs HADHA and SLC25A45, and microRNAs MIR154A, MIR25, and MIR487B in the liver and ARIH1 and ITCH and miRNAs MIR369, MIR10A, and MIR10B in muscle as potential biomarkers of prenatal T excess. These findings suggest downregulation of mitochondria, lipid catabolism, and PPAR signaling genes in the liver and dysregulation of mitochondrial and ncRNA gene pathways in muscle are contributors of lipotoxic and insulin-resistant hepatic and muscle phenotype. Gestational T excess programming of metabolic dysfunctions involve tissue-specific ncRNA–modulated transcriptional changes.
6 April 2024 in Molecular and Cellular Endocrinology
African American women have the highest rate of preterm birth (PTB; <37 completed weeks’ gestation) of any racial and ethnic group in the United States (14.1%). Depressive symptoms (DS) have been linked to PTB risk of African American women. We hypothesized that maternal lipidomic profiles are related to prenatal DS and gestational age at birth among African American women. Women were enrolled at 9–25 weeks’ gestation, completed questionnaires, and provided plasma samples. Lipidomic profiles were determined by “shotgun” Orbitrap high-resolution/accurate mass spectrometry. Data were analyzed using SIMCA P+ software. There was a clear separation in the orthogonal projections to latent structures discriminant analysis score plot between women with Center for Epidemiologic Studies Depression Scale (CES-D) scores ≥23 and women with CES-D scores ≤22. Similarly, a clear separation was observed in the model between PTB and full-term birth. Corresponding S-plot, loading plot, and variable importance in projection plot/list were used to identify the lipids responsible for the groupings. Higher levels of specific triglyceride (TG) species and lower levels of specific phosphatidylcholines (PCs) PC(37:1), PC(41:6), and PC(39:3) were associated with PTB. PC PC(37:1) levels were also lower among women with CES-D scores ≥23, pointing toward a possible connection between DS and PTB. Although overweight pregnant women showed higher levels of TGs, the PTB model showed specific TGs unique to PTB. Lipidomic profiles in pregnant African American women are related to DS, and our data suggest a role for specific TGs and PCs in PTB.
Preterm birth (PTB; <37 weeks gestation) rates have increased for 5 of the last 6 consecutive years in the United States. These rates are particularly alarming for U.S. non-Hispanic Black women who give birth prematurely at 1.5 times the rate of non-Hispanic White women. Previous research suggests that psychological stress is associated with PTB in Black women. However, the biological pathways by which stress alters birth timing are not clear. We examined DNA methylation (DNAm) in peripheral blood leukocytes in 6 glucocorticoid, stress-related genes in 44 (22 PTB; 22 term birth) pregnant Black women. Four cytosine-phosphate-guanine (CpG) sites were identified as differentially methylated ( p < 0.05) between women with PTB and women with term births. The ability to identify stress-related biological markers that are associated with PTB among Black women would provide a critical step toward decreasing the PTB disparity among these women. Future studies should include larger sample sizes and gene expression analyses of the stress-related biological pathways to PTB.