BackgroundFor several decades, Black patients have carried a higher burden of laryngeal cancer among all races. Even when accounting for sociodemographics, a disparity remains. Differentially expressed microRNAs have been linked to racially disparate clinical outcomes in breast and prostate cancers, yet an association in laryngeal cancer has not been addressed. In this study, we present our computational analysis of differentially expressed miRNAs in Black compared with White laryngeal cancer and further validate microRNA-9-5p (miR-9-5p) as a potential mediator of cancer phenotype and chemoresistance.MethodsBioinformatic analysis of 111 (92 Whites, 19 Black) laryngeal squamous cell carcinoma (LSCC) specimens from the TCGA revealed miRNAs were significantly differentially expressed in Black compared with White LSCC. We focused on miR-9-5 p which had a significant 4-fold lower expression in Black compared with White LSCC (p<0.05). After transient transfection with either miR-9 mimic or inhibitor in cell lines derived from Black (UM-SCC-12) or White LSCC patients (UM-SCC-10A), cellular migration and cell proliferation was assessed. Alterations in cisplatin sensitivity was evaluated in transient transfected cells via IC50 analysis. qPCR was performed on transfected cells to evaluate miR-9 targets and chemoresistance predictors, ABCC1 and MAP1B.ResultsNorthern blot analysis revealed mature miR-9-5p was inherently lower in cell line UM-SCC-12 compared with UM-SCC-10A. UM -SCC-12 had baseline increase in cellular migration (p < 0.01), proliferation (p < 0.0001) and chemosensitivity (p < 0.01) compared to UM-SCC-10A. Increasing miR-9 in UM-SCC-12 cells resulted in decreased cellular migration (p < 0.05), decreased proliferation (p < 0.0001) and increased sensitivity to cisplatin (p < 0.001). Reducing miR-9 in UM-SCC-10A cells resulted in increased cellular migration (p < 0.05), increased proliferation (p < 0.05) and decreased sensitivity to cisplatin (p < 0.01). A significant inverse relationship in ABCC1 and MAP1B gene expression was observed when miR-9 levels were transiently elevated or reduced in either UM-SCC-12 or UM-SCC-10A cell lines, respectively, suggesting modulation by miR-9.ConclusionCollectively, these studies introduce differential miRNA expression in LSCC cancer health disparities and propose a role for low miR-9-5p as a mediator in LSCC tumorigenesis and chemoresistance.

Background: Advanced stage laryngeal squamous cell carcinoma (LSCC) has sustained one of the lowest five-year survival rates across all other head and neck squamous cancers. For several decades, Black patients have maintained a greater likelihood of presenting with advanced LSCC and a higher overall mortality rate compared with White patients. Even when accounting for sociodemographics, a disparity remains, underscoring the importance of investigating the biologic basis of this disparity. Differential microRNA (miRNA) expression has been linked to racially disparate clinical outcomes in other cancers including breast and prostate, but remains underdetermined in LSCC. We present our findings where we investigated miR-9 levels and their influence on LSCC tumorigenesis and chemoresistance using in vitro cell lines derived from Black and White patients. Methods: We previously identified miR-9-5p as significantly lower (5X) in Black compared with White advanced stage LSCC in vivo samples. For functional studies, we obtained two LSCC cell lines derived from a Black patient (UM-SCC-12) and from a White patient (UM-SCC-10A) (provided by Tom Carey, University of Michigan). After transfection with either miR-9 mimic or inhibitor, we used the scratch wound assay to assess cell migration and the cell titer blue assay to assess cell proliferation and chemoresistance. Results: Prior to transfection, we found that UM-SCC-12 had baseline increases in cellular migration, proliferation and chemoresistance compared to UM-SCC-10A. By Northern blot analysis, we further determined that mature miR-9-5p was inherently 5X lower in UM-SCC-12 compared with UM-SCC-10A. After transient transfection, we noted that overexpressing miR-9 in UM-SCC-12 resulted in decreased cellular migration, decreased proliferation and increased chemosensitivity compared to a mock oligo control, whereas inhibiting miR-9 in UM-SCC-10A resulted in increased cellular migration, increased proliferation and decreased chemosensitivity compared to a mock oligo control. Conclusion: Collectively, these studies support that low miR-9 may play a role in LSCC tumorigenesis and chemoresistance. In this manner, it may contribute to cancer health disparate outcomes observed in advanced stage LSCC. Future studies will involve characterizing significant downstream mediators of low miR-9-5p gene regulation. Citation Format: Christina Gobin, Samuel Inkabi, Chayil Lattimore, James Menefee, Tengfei Bian, Christopher Fields, Mingyi Xie, Chengguo Xing, Kristianna Fredenburg. Low miR-9 impacts tumorigenesis and chemoresistance in Black compared with White laryngeal squamous cell carcinoma [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C042.

Identifying the molecular mechanisms of animal behaviour is an enduring goal for researchers. Gaining insight into these mechanisms enables us to gain a greater understanding of behaviour and their genetic control. In this paper, we perform Quantitative Trait Loci (QTL) mapping of tonic immobility behaviour in an advanced intercross line between wild and domestic chickens. Genes located within the QTL interval were further investigated using global expression QTL (eQTL) mapping from hypothalamus tissue, as well as causality analysis. This identified five candidate genes, with the genes PRDX4 and ACOT9 emerging as the best supported candidates. In addition, we also investigated the connection between tonic immobility, meat pH and struggling behaviour, as the two candidate genes PRDX4 and ACOT9 have previously been implicated in controlling muscle pH at slaughter. We did not find any phenotypic correlations between tonic immobility, struggling behaviour and muscle pH in a smaller additional cohort, despite these behaviours being repeatable within-test.

Significant evidence from various sources suggests that structural alterations in mitochondrial function may play a role in both the pathogenesis of mood disorders and the therapeutic effects of available treatments. PGC-1α is a distinct transcriptional regulator designed to mediate the synchronous release of neurotransmitter in the brain and thereby to coordinate a number of gene expression pathways to promote mitochondrial biogenesis and oxidative phosphorylation. The role of PGC-1α in the context of affective disorder phenotypes and treatments has been suggested but not studied in depth. To further investigate the possible involvement of PGC-1α in affective disorders, we generated conditional PGC-1α null mice through transgenic expression of cre recombinase under the control of a Dlx5/6 promoter; cre-mediated excision events were limited to γ-amino-butyric-acid (GABA)-ergic specific neurons. We tested these mice in a battery of behavioral tests related to affective change including spontaneous activity, elevated plus maze, forced swim test, and tail suspension test. Results demonstrated that mice lacking PGC-1α in GABAergic neurons exhibited increased activity across tests that might be related to a mania-like phenotype. These results suggest possible relevance of PGC-1α to affective change, which corresponds with data connecting mitochondrial function and affective disorders and their treatment.

Physical exercise induces modifications in the immune system influencing either positively or negatively on health depending on its frequency, duration, and intensity. Acute or moderate physical exercise increases appreciably the immune cells, including cytokine levels while decreasing other components like NK cells, leading to a stronger response to pathogens as well as decreasing liability to allergic reactions. The expression of Toll-like receptors (TLR) is elevated as well, augmenting the positive effect. Exhaustive physical exercise, by contrast, modifies the immune system adversely. This review explores the links between physical exercise, immune cells and cytokines, and the immunological effects that have been studied by the performance of different kinds of physical exercise.

Background: Cancer is one of the many diseases of global concern due to its high mortality rate with drug resistance becoming a major challenge to chemotherapy and this have propelled many cancer patients to seek alternative and complementary methods of treatment. The objective for this study was, therefore, to determine the antiproliferative activity as well as phytochemical, total phenolic content (TPC), and antioxidant activity of the stem and leaf extracts (FPS and FPL) of Ficus pumila (L.) using standard methods.Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate anti-proliferative effect and spectrophotometric-based assays for antioxidant and TPC. Phytochemical constituents were accessed by standard methods.Results: The hydroethanolic extracts of the leaves and stems were rich in tannins, general glycosides, saponins, terpenoids, alkaloids, flavonoids (leaves only), and sterols (stem only). Strong total antioxidant activities were observed with FPL and FPS with EC50 values of 0.07 mg/ml and 0.089 mg/ml, respectively. All the crude extracts showed anti-proliferative effect towards the three human leukemic cell lines used (Jurkat, CEM, and HL-60). However, FPL gave the strongest inhibition concentration at 50% values of 130.97 µg/ml (Jurkat) and 56.31 µg/ml (HL-60).Conclusion: These findings suggest that crude extracts of FPS and FPL have anti-proliferative effect on the leukemia cells. The antioxidant properties of the plant including phenolics may be partly responsible for the anti-proliferative activity. Further studies are required to isolate chemical components of the plant and establish their anti-proliferative activities and mechanism of action.