Circulating miRNAs as novel potential biomarkers for esophageal squamous cell carcinoma diagnosis: a meta-analysis update.

Early detection of esophageal squamous cell carcinoma (ESCC) is urgently needed to reduce the high morbidity and mortality of disease. Circulating microRNAs (miRNAs) are promising molecular biomarkers for ESCC prediction. We performed a comprehensive meta-analysis to systematically evaluate the diagnostic accuracy of circulating miRNAs in diagnosis of ESCC patients.

Regulation of Monocarboxylic Acid Transporter 1 Trafficking by the Canonical Wnt/β-Catenin Pathway in Rat Brain Endothelial Cells Requires Cross-talk with Notch Signaling.

The transport of monocarboxylate fuels such as lactate, pyruvate, and ketone bodies across brain endothelial cells is mediated by monocarboxylic acid transporter 1 (MCT1). Although the canonical Wnt/β-catenin pathway is required for rodent blood-brain barrier development and for the expression of associated nutrient transporters, the role of this pathway in the regulation of brain endothelial MCT1 is unknown. Here we report expression of nine members of the frizzled receptor family by the RBE4 rat brain endothelial cell line.

Beyond the Ribosome: Extra-translational Functions of tRNA Fragments.

High-throughput sequencing studies of small RNAs reveal a complex milieu of noncoding RNAs in biological samples. Early data analysis was often limited to microRNAs due to their regulatory nature and potential as biomarkers; however, many more classes of noncoding RNAs are now being recognized. A class of fragments initially excluded from analysis were those derived from transfer RNAs (tRNAs) because they were thought to be degradation products.

The interplay between genetic background and sexual dimorphism of doxorubicin-induced cardiotoxicity.

Background: Doxorubicin (DOX) is a very effective anticancer medication that is commonly used to treat hematological malignancies and solid tumors. Nevertheless, DOX is known to have cardiotoxic effects that may lead to cardiac dysfunction and failure. In experimental studies, female animals have been shown to be protected against DOX-induced cardiotoxicity; however, the evidence of this sexual dimorphism is inconclusive in clinical studies.

Establishment of a Developmental Compartment Requires Interactions between Three Synergistic Cis-regulatory Modules.

The subdivision of cell populations in compartments is a key event during animal development. In Drosophila, the gene apterous (ap) divides the wing imaginal disc in dorsal vs ventral cell lineages and is required for wing formation. ap function as a dorsal selector gene has been extensively studied.

Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat.

Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise.

Unconscious biases: racial microaggressions in American Indian health care.

Purpose: This article reports on the prevalence and correlates of microaggressive experiences in health care settings reported by American Indian (AI) adults with type 2 diabetes mellitus (T2DM).

Methods: This community-based participatory research project includes two AI reservation communities. Data were collected via in-person article-and-pencil survey interviews with 218 AI adults diagnosed with T2DM.

Khat use and appetite: an overview and comparison of amphetamine, khat and cathinone.

Ethnopharmacological Relevance: To understand the role of khat (Catha edulis) use on the aberrations in appetite and weight which are common comorbidities for khat and other amphetamine users.

Materials And Methods: We provide a comprehensive overview and conceptual summary of the historical cultural use of khat as a natural stimulant and describe the similarities and differences between cathinone (the main psychoactive constituent of khat) and amphetamine highlighting the limited literature on the neurophysiology of appetite and subsequent weight effects of khat.

Results: Animal and some human studies indicate that khat produces appetite suppression, although little is known about mechanisms of this effect.

Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats.

Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension.

The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations.

microRNAs (miRNAs) regulate expression by promoting degradation or repressing translation of target transcripts. miRNA target sites have been catalogued in databases based on experimental validation and computational prediction using various algorithms. Several online resources provide collections of multiple databases but need to be imported into other software, such as R, for processing, tabulation, graphing and computation.

Frizzled fissure to improve central nervous system drug delivery?

Delivery of therapeutics to the brain is challenging because of efflux pumps located in the vascular endothelium. A detailed analysis of Wnt signaling in a human brain endothelial cell line indicates that expression and function of P-glycoprotein, a major efflux transporter, is controlled by non-canonical Wnt signaling. Inhibition of this pathway leads to downregulation of P-glycoprotein and increased transcellular drug transport and reveals a potential strategy for improving drug delivery for treatment of neurologic diseases.

The Prevalence and Correlates of Mental and Emotional Health Among American Indian Adults With Type 2 Diabetes.

Aims: The purpose of this study was to examine the prevalence and correlates of mental and emotional health factors among a sample of American Indian (Indigenous) adults diagnosed with type 2 diabetes.

Methods: Data are from a community-based participatory research project involving 2 Indigenous reservation communities. Data were collected from 218 Indigenous adults diagnosed with type 2 diabetes via in-person paper-and-pencil survey interviews.

Fetal and neonatal iron deficiency exacerbates mild thyroid hormone insufficiency effects on male thyroid hormone levels and brain thyroid hormone-responsive gene expression.

Fetal/neonatal iron (Fe) and iodine/TH deficiencies lead to similar brain developmental abnormalities and often coexist in developing countries. We recently demonstrated that fetal/neonatal Fe deficiency results in a mild neonatal thyroidal impairment, suggesting that TH insufficiency contributes to the neurodevelopmental abnormalities associated with Fe deficiency. We hypothesized that combining Fe deficiency with an additional mild thyroidal perturbation (6-propyl-2-thiouracil [PTU]) during development would more severely impair neonatal thyroidal status and brain TH-responsive gene expression than either deficiency alone.

Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts.

Doxorubicin (DOX) is a widely prescribed treatment for a broad scope of cancers, but clinical utility is limited by the cumulative, dose-dependent cardiomyopathy that occurs with repeated administration. DOX-induced cardiotoxicity is associated with the production of reactive oxygen species (ROS) and oxidation of lipids, DNA and proteins. A major cellular defense mechanism against such oxidative stress is activation of the Keap1/Nrf2-antioxidant response element (ARE) signaling pathway, which transcriptionally regulates expression of antioxidant genes such as Nqo1 and Gstp1.

Complement activation is critical for placental ischemia-induced hypertension in the rat.

Preeclampsia is a major obstetric problem defined by new-onset hypertension and proteinuria associated with compromised placental perfusion. Although activation of the complement system is increased in preeclampsia compared to normal pregnancy, it remains unclear whether excess complement activation is a cause or consequence of placental ischemia. Therefore, we hypothesized that complement activation is critical for placental ischemia-induced hypertension.

Learning environment: the impact of clerkship location on instructional quality.

Background And Objectives: Students provide variable feedback on instructional quality at ambulatory training sites. We hypothesized several strengths and weaknesses of placing students at resident and non-resident training sites, including differences in faculty behaviors, patient characteristics, work environment, learning opportunities, and levels of student engagement. We systematically assessed for differences in learning quality between clerkship sites with and without residents.

North American Indigenous adolescent substance use.

Objectives: To investigate growth in problem drinking and monthly marijuana use among North American Indigenous adolescents from the upper Midwest and Canada.

Methods: Panel data from a community-based participatory research project includes responses from 619 adolescents residing on or near 7 different reservations/reserves. All respondents were members of the same Indigenous cultural group.

The Intergenerational Effects of Relocation Policies on Indigenous Families.

This research utilizes life-course perspective concepts of linked lives and historical time and place to examine the multigenerational effects of relocation experiences on Indigenous families. Data were collected from a longitudinal study currently underway on four American Indian reservations in the Northern Midwest and four Canadian First Nation reserves where residents share a common Indigenous cultural heritage. This paper includes information from 507 10 - 12 year old Indigenous youth and their biological mothers who participated in the study.

Advantages of stress process approaches for measuring historical trauma.

Despite growing attention to historical trauma (HT) as a key mechanism for documented Indigenous health disparities like alcohol abuse, the complexities of conceptualizing and measuring HT-related constructs have limited empirical tests of these relationships. In this article, we review the current evidence surrounding one HT measure: the Historical Loss Scale. In addition, we provide examples of the benefits of treating historical cultural losses as stressors within sociological and Indigenous stress process models of health.

Suppressed hepcidin expression correlates with hypotransferrinemia in copper-deficient rat pups but not dams.

Copper deficiency leads to anemia but the mechanism is unknown. Copper deficiency also leads to hypoferremia, which may limit erythropoiesis. The hypoferremia may be due to limited function of multicopper oxidases (MCO) hephaestin in enterocytes or GPI-ceruloplasmin in macrophages of liver and spleen whose function as a ferroxidase is thought essential for iron transfer out of cells.

HOPE clinic: a place to care.

The University of Minnesota Medical School and College of Pharmacy in Duluth worked with a local drop-in center in 2008 to start a free clinic. The HOPE (Health of People Everywhere) Clinic is a student-run, faculty-organized effort that offers students an opportunity to develop their clinical skills and learn how to work in interprofessional teams while providing needed care to people who are underserved or uninsured. This article describes how this initiative came about and the impact it is having on medical students.