Interest and uptake of science and medicine peer-reviewed literature by readers outside of a paper's topical subject, field or even discipline is ever-expanding. While the application of knowledge from one field or discipline to others can stimulate innovative solutions to problems facing modern society, it is also fraught with danger for misuse. In the practice of law in the United States, academic papers are submitted to the courts as evidence in personal injury litigation from both the plaintiff (complainant) and defendant.
View Article and Find Full Text PDFThe blood glycoprotein von Willebrand factor (vWF) is involved in coagulopathy and inflammation; however, its role in the pathogenesis of acute liver failure, as suggested by its higher expression levels in such patients, remains unknown. In this study, vWF-knockout (KO) mice showed more severe carbon tetrachloride (CCl)-induced liver injury than wild-type mice. Patients with acute liver injury also showed elevated vWF protein activity and expression in liver tissues, as compared to healthy individuals.
View Article and Find Full Text PDFCastration-resistant prostate cancer (CRPC) has greater intratumoral testosterone concentrations than similar tumors from eugonadal men; simple diffusion does not account for this observation. This study was undertaken to ascertain the androgen uptake kinetics, functional, and clinical relevance of expression of the steroid hormone transporter OATP1B3 (). Experiments testing the cellular uptake of androgens suggest that testosterone is an excellent substrate of OATP1B3 ( = 23.
View Article and Find Full Text PDFWorld J Gastrointest Pharmacol Ther
November 2016
Despite little evidence for the therapeutic benefits of a high-fiber diet for diverticulitis, it is commonly recommended as part of the clinical management. The ongoing uncertainty of the cause(s) of diverticulitis confounds attempts to determine the validity of this therapy. However, the features of a high-fiber diet represent a logical contradiction for colon diverticulitis.
View Article and Find Full Text PDFBackground: Auditory and vestibular disorders are prevalent sensory disabilities caused by genetic and environmental (noise, trauma, chemicals) factors that often damage mechanosensory hair cells of the inner ear. Development of treatments for inner ear disorders of hearing and balance relies on the use of animal models such as fish, amphibians, reptiles, birds, and non-human mammals. Here, we aimed to augment the utility of the genus Xenopus for uncovering genetic mechanisms essential for the maintenance of inner ear structure and function.
View Article and Find Full Text PDFThrough positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, that play distinctive roles in the immune system. Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors, ranging from cytokine signaling modules to transcription factors and epigenetic modifiers. Members of the E26 transformation specific (Ets) family of transcription factors, in particular, are potent regulators of these CD4(+) or CD8(+) T-cell processes.
View Article and Find Full Text PDFInt Rev Immunol
September 2016
Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity.
View Article and Find Full Text PDFA systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD.
View Article and Find Full Text PDFInnate lymphoid cells (ILCs) are involved in the development of mucosal-associated lymphoid tissues and serve as a rapid and early source of the effector cytokines that are typically associated with the T helper cell subsets in response to pathogen-induced changes in the microenvironment. Recent research has implicated ILCs as potential contributing factors to the spectrum of inflammation-related hepatic diseases, particularly hepatitis, fibrosis and carcinoma. In this review, we summarize the current knowledge on the roles of ILCs in these hepatic pathogeneses, providing insights into the underlying cellular and signaling mechanisms to help guide the future research to elucidate the ILCs' characters under normal and diseased conditions and provide interventional targets with therapeutic potential.
View Article and Find Full Text PDFInnate lymphoid cells (ILCs) promptly initiate cytokine responses to pathogen exposure in the mucosa and mucosal-associated lymphoid tissues. ILCs were recently categorized as being of the lymphoid lineage and have been classified into three groups. ILCs play important roles in immunity against pathogens, and an anti-tumor immune-related function was recently demonstrated.
View Article and Find Full Text PDFBrucellosis is a global bacterial zoonosis responsible for high morbidity in humans and significant livestock economic losses. While brucellosis remains a public health concern worldwide, its global geographic distribution is variable, largely due to different management schemes; however, paucity of information renders the status of brucellosis unclear and incomplete in many countries, especially those with low income and under-developed infrastructure. This short article summarizes and discusses recent important updates on brucellosis from the North African countries, with a particular brief emphasis on the current status and recent updates in Libya.
View Article and Find Full Text PDFBackground: Sepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical characterizations fail to identify those at greatest risk of progression and mortality.
Methods: The Community Acquired Pneumonia and Sepsis Outcome Diagnostic study enrolled 1,152 subjects with suspected sepsis.
The functional interaction of progesterone receptor (PR) isoforms PRA and PRB regulates myometrial transition from the resting state to excitation-contraction to initiate parturition. However, the regulatory mechanisms responsible for maintenance and functional alteration of the PRA and PRB expression levels during human pregnancy and term labor, respectively, remain unknown. Therefore, this study was designed to investigate whether and how epigenetic DNA modifications, specifically methylations, at the PRs' promoter regions contribute to the differential expression of PRA and PRB in laboring term myometrium of humans.
View Article and Find Full Text PDFUnlabelled: Hepatitis B virus (HBV) alters the expression of host cellular genes to support its replication and survival and to promote the liver cell injury. However, the underlying mechanism remained incompletely understood. In this study, we investigated HBV-induced epigenetic changes in HepG2 cells by profiling the landscapes of the active histone modification mark H3K4me3 and repressive mark H3K27me3 using chromatin immunoprecipitation-sequencing.
View Article and Find Full Text PDFSepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later.
View Article and Find Full Text PDFIL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV) causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated.
View Article and Find Full Text PDFStaphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics.
View Article and Find Full Text PDFThe lymphocyte-derived helper T (Th) cells are critical regulators of the adaptive immune response and are associated with inflammatory disease. The most recently recognized Th-cell lineage, Th17, plays an important role in host defense against extracellular pathogens by secreting the proinflammatory cytokine, interleukin 17, and recruiting reactive oxygen species (ROS)-producing monocytes to the site of infection. However, accumulating evidence has implicated Th17-cell dysregulation as an underlying cause for some immune-related pathogenic conditions, including allograft rejection.
View Article and Find Full Text PDFBackground: It is well known that both heat shock protein (HSP) and Toll-like receptor (TLR)3 agonist polyinosinic:polycytidylic acid (poly(I:C)) are capable of promoting the antigen-specific immune responses. In the current study, we assessed whether the anti-tumor effects of the HPV16E7(49-57)-based vaccine can be elevated by combined applications of poly(I:C) and oxygen-regulated protein 150 (ORP150) in a mouse cervical cancer model.
Methods: Recombinant mouse ORP150 and HPV E7(49-57) peptide were combined to passively form the ORP150-E7(49-57) complex under heat shock conditions.
T helper 17 (Th17) cells are a newly identified subset of T helper cells that play important roles in host defense against extracellular bacteria, as well as in the pathogenesis of autoimmune disease. Research interest in these cells was piqued when hepatitis B virus (HBV)-infected patients were found to have significantly elevated Th17 cell frequency, and it was proposed that these proinflammatory effectors may promote the HBV disease process. Subsequent studies have revealed that Th17 cells drive immune-mediated pathology of HBV infection, and that IL-23 amplifies the Th17 cell responses and liver inflammation.
View Article and Find Full Text PDFAntimicrobial-resistant bacteria represent a major threat to human and animal health. We compared equine fecal samples (n=264) from 138 horses from hospital and nonhospital (livery stable and riding school) premises in North West England to determine the prevalence of Escherichia coli, Salmonella, and Campylobacter and rates of antimicrobial-resistant E. coli strains.
View Article and Find Full Text PDFRegulatory T cells (Treg) contribute to the crucial immunological processes of self-tolerance and immune homeostasis. Genomic mechanisms that regulate cell fate decisions leading to Treg or conventional T cells (Tconv) lineages and those underlying Treg function remain to be fully elucidated, especially at the histone modification level. We generated high-resolution genome-wide distribution maps of monomethylated histone H3 lysine 4 (H3K4me1) and trimethylated H3K4 (H3K4me3) in human CD4(+)CD25(+)FOXP3(+) Tregs and CD4(+)CD25(+)FOXP3(-) activated (a)Tconv cells by DNA sequencing-by-synthesis.
View Article and Find Full Text PDFBackground: Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.
Study Objectives: To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis.