Otterbein Aegis May 1909

https://digitalcommons.otterbein.edu/aegis/1182/thumbnail.jp

The clinicopathological factors associated with disease progression in Luminal a breast cancer and characteristics of metastasis: A retrospective study from a single center in China

Background/Aim: This study investigated the clinicopathological factors associated with outcomes in patients with Luminal A breast cancer. Patients and Methods: Retrospective analysis of the association of clinicopathological factors and breast cancer outcome in 421 patients with newly diagnosed Luminal-A breast cancer that were enrolled from January 2008 to December 2014. Clinicopathological data were analyzed to validate the relationship with disease free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank tests were used to analyze the value of clinicopathological factors (tumor size, node status and lymphovascular invasion), and subsequent Cox regression analysis revealed significant prognostic factors. Results: With a median of 61 months follow up, the 5-year DFS and 5-year OS rate were 98.3% and 99.3%. Cox multivariate regression analysis showed that clinical anatomic stage, tumor size, status of lymph nodes, lymphovascular invasion and systemic treatment are strong prognostic factors for clinical outcome in patients with Luminal-A breast cancer. Of all 413 patients with stage I-III breast cancer, 14 presented with metastasis (3.4%) during the follow up. Bone (6/14, 42.9%) was the most common site of metastasis followed by liver (5/14, 35.7%) and lung (4/14, 28.6%). The median survival time after metastasis was 20.4 months. Of all the sites of distant metastasis, liver metastasis was the only factor that affected survival time after metastasis (χ2=6.263, p=0.012). Conclusion: Patients with Luminal A breast cancer have excellent outcomes. Liver metastasis is an important factor compressing the survival time after distant metastasis presents

Prognostic factors of the short-term outcomes of patients with hepatitis B virus-associated acute-on-chronic liver failure

OBJECTIVE: To investigate the impact of the baseline status of patients with hepatitis B virus-associated acute-on-chronic liver failure on short-term outcomes. METHODS: A retrospective study was conducted that included a total of 138 patients with hepatitis B virus-associated acute-on-chronic liver failure admitted to the Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, from November 2013 to October 2016. The patients were divided into a poor prognosis group (74 patients) and a good prognosis group (64 patients) based on the disease outcome. General information, clinical indicators and prognostic scores of the patients’ baseline status were analyzed, and a prediction model was established accordingly. RESULTS: Elder age, treatment with artificial liver support systems and the frequency of such treatments, high levels of white blood cells, neutrophils, neutrophil count/lymphocyte count ratio, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin, urea, and prognostic scores as well as low levels of albumin and sodium were all significantly associated with the short-term outcomes of hepatitis B virus-associated acute-on-chronic liver failure. The predictive model showed that logit (p) = 3.068 + 1.003 × neutrophil count/lymphocyte count ratio - 0.892 × gamma-glutamyl transferase - 1.138 × albumin - 1.364 × sodium + 1.651 × artificial liver support therapy. CONCLUSION: The neutrophil count/lymphocyte count ratio and serum levels of gamma-glutamyl transferase, albumin and sodium were independent risk factors predicting short-term outcomes of hepatitis B virus-associated acute-on-chronic liver failure, and the administration of multiple treatments with artificial liver support therapy during the early stage is conducive to improved short-term outcomes

Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling

Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced anxiety and decreased need for sleep, which suggests that the dysfunction of the striatum, a critical component of the brain motor and reward system, can be causally associated with mania. However, detailed molecular pathophysiology underlying the striatal dysfunction in mania remains largely unknown. In this study, we aimed to identify the molecular pathways showing alterations in the striatum of SH3 and multiple ankyrin repeat domains 3 (Shank3)-overexpressing transgenic (TG) mice that display manic-like behaviors. The results of transcriptome analysis suggested that mammalian target of rapamycin complex 1 (mTORC1) signaling may be the primary molecular signature altered in the Shank3 TG striatum. Indeed, we found that striatal mTORC1 activity, as measured by mTOR S2448 phosphorylation, was significantly decreased in the Shank3 TG mice compared to wild-type (WT) mice. To elucidate the potential underlying mechanism, we re-analyzed previously reported protein interactomes, and detected a high connectivity between Shank3 and several upstream regulators of mTORC1, such as tuberous sclerosis 1 (TSC1), TSC2 and Ras homolog enriched in striatum (Rhes), via 94 common interactors that we denominated “Shank3-mTORC1 interactome”. We noticed that, among the 94 common interactors, 11 proteins were related to actin filaments, the level of which was increased in the dorsal striatum of Shank3 TG mice. Furthermore, we could co-immunoprecipitate Shank3, Rhes and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) proteins from the striatal lysate of Shank3 TG mice. By comparing with the gene sets of psychiatric disorders, we also observed that the 94 proteins of Shank3-mTORC1 interactome were significantly associated with bipolar disorder (BD). Altogether, our results suggest a protein interaction-mediated connectivity between Shank3 and certain upstream regulators of mTORC1 that might contribute to the abnormal striatal mTORC1 activity and to the manic-like behaviors of Shank3 TG mice

Integrative Brain Transcriptome Analysis Reveals Region-Specific and Broad Molecular Changes in Shank3-Overexpressing Mice

Variants of the SH3 and multiple ankyrin repeat domain 3 (SHANK3) gene, encoding excitatory postsynaptic core scaffolding proteins, are causally associated with numerous neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), bipolar disorder, intellectual disability, and schizophrenia (SCZ). Although detailed synaptic changes of various Shank3 mutant mice have been well characterized, broader downstream molecular changes, including direct and indirect changes, remain largely unknown. To address this issue, we performed a transcriptome analysis of the medial prefrontal cortex (mPFC) of adult Shank3-overexpressing transgenic (TG) mice, using an RNA-sequencing approach. We also re-analyzed previously reported RNA-sequencing results of the striatum of adult Shank3 TG mice and of the prefrontal cortex of juvenile Shank3+/ΔC mice with a 50–70% reduction of Shank3 proteins. We found that several myelin-related genes were significantly downregulated specifically in the mPFC, but not in the striatum or hippocampus, of adult Shank3 TG mice by comparing the differentially expressed genes (DEGs) of the analyses side by side. Moreover, we also found nine common DEGs between the mPFC and striatum of Shank3 TG mice, among which we further characterized ASD- and SCZ-associated G protein-coupled receptor 85 (Gpr85), encoding an orphan Gpr interacting with PSD-95. Unlike the mPFC-specific decrease of myelin-related genes, we found that the mRNA levels of Gpr85 increased in multiple brain regions of adult Shank3 TG mice, whereas the mRNA levels of its family members, Gpr27 and Gpr173, decreased in the cortex and striatum. Intriguingly, in cultured neurons, the mRNA levels of Gpr27, Gpr85, and Gpr173 were modulated by the neuronal activity. Furthermore, exogenously expressed GPR85 was co-localized with PSD-95 and Shank3 in cultured neurons and negatively regulated the number of excitatory synapses, suggesting its potential role in homeostatic regulation of excitatory synapses in Shank3 TG neurons. Finally, we performed a gene set enrichment analysis of the RNA-sequencing results, which suggested that Shank3 could affect the directional expression pattern of numerous ribosome-related genes in a dosage-dependent manner. To sum up, these results reveal previously unidentified brain region-specific and broad molecular changes in Shank3-overexpressing mice, further elucidating the complexity of the molecular pathophysiology of SHANK3-associated brain disorders

Transcriptomic profiling suggests candidate molecular responses to waterlogging in cassava

Owing to climate change impacts, waterlogging is a serious abiotic stress that affects crops, resulting in stunted growth and loss of productivity. Cassava (Manihot esculenta Grantz) is usually grown in areas that experience high amounts of rainfall; however, little research has been done on the waterlogging tolerance mechanism of this species. Therefore, we investigated the physiological responses of cassava plants to waterlogging stress and analyzed global gene transcription responses in the leaves and roots of waterlogged cassava plants. The results showed that waterlogging stress significantly decreased the leaf chlorophyll content, caused premature senescence, and increased the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in the leaves and roots. In total, 2538 differentially expressed genes (DEGs) were detected in the leaves and 13364 in the roots, with 1523 genes shared between the two tissues. Comparative analysis revealed that the DEGs were related mainly to photosynthesis, amino metabolism, RNA transport and degradation. We also summarized the functions of the pathways that respond to waterlogging and are involved in photosynthesis, glycolysis and galactose metabolism. Additionally, many transcription factors (TFs), such as MYBs, AP2/ERFs, WRKYs and NACs, were identified, suggesting that they potentially function in the waterlogging response in cassava. The expression of 12 randomly selected genes evaluated via both quantitative real-time PCR (qRT-PCR) and RNA sequencing (RNA-seq) was highly correlated (R2 = 0.9077), validating the reliability of the RNA-seq results. The potential waterlogging stress-related transcripts identified in this study are representatives of candidate genes and molecular resources for further understanding the molecular mechanisms underlying the waterlogging response in cassava

Compound dietary fiber and high-grade protein diet improves glycemic control and ameliorates diabetes and its comorbidities through remodeling the gut microbiota in mice

Dietary intervention with a low glycemic index and full nutritional support is emerging as an effective strategy for diabetes management. Here, we found that the treatment of a novel compound dietary fiber and high-grade protein diet (CFP) improved glycemic control and insulin resistance in streptozotocin-induced diabetic mice, with a similar effect to liraglutide. In addition, CFP treatment ameliorated diabetes-related metabolic syndromes, such as hyperlipidemia, hepatic lipid accumulation and adipogenesis, systemic inflammation, and diabetes-related kidney damage. These results were greatly associated with enhanced gut barrier function and altered gut microbiota composition and function, especially those bacteria, microbial functions, and metabolites related to amino acid metabolism. Importantly, no adverse effect of CFP was found in our study, and CFP exerted a wider arrange of protection against diabetes than liraglutide. Thereby, fortification with balanced dietary fiber and high-grade protein, like CFP, might be an effective strategy for the management and treatment of diabetes