Helicase-like transcription factor (HLTF)-deleted CDX/TME model of colorectal cancer increased transcription of oxidative phosphorylation genes and diverted glycolysis to boost S-glutathionylation in lymphatic intravascular metastatic niches.

Helicase-like transcription factor (HLTF) also known as SMARCA3, protects genome integrity. A tumor suppressor, HLTF is expressed in tumor cells but not in the tumor microenvironment (TME) in early-stage colorectal cancer (CRC). With disease progression, there is high concordance between epigenetic silencing of HLTF in CRC cells and negligible HLTF expression in the TME.

Helicase-like transcription factor (Hltf)-deletion activates Hmgb1-Rage axis and granzyme A-mediated killing of pancreatic β cells resulting in neonatal lethality.

Epigenetic mechanisms are integral to pancreatic β cell function. Promoter hypermethylation of the helicase like-transcription factor (HLTF) gene-a component of the cellular DNA damage response that contributes to genome stability-has been implicated in age-associated changes in β cells. To study HLTF, we generated global and β cell-specific (β) Hltf knockout (KO) immune competent (IC) and immune deficient (ID) Rag2-/IL2- mice.

Gene expression profiles of neonatal porcine Sertoli cells at baseline and after incubation in normal human serum as determined by RNA sequencing.

Sertoli cells are unique cells that contribute to the formation of the blood-testis barrier, which is important in sustaining the environment to promote spermatogenesis and to protect immunogenic germ cells from autoimmune destruction. This is achieved through tight junctions and production of regulatory immune factors. These Sertoli cell attributes make them a relevant model for various studies involving male reproduction, autoimmune protection, and even transplantation.

Regulation of complement by Sertoli cells may contribute to the immune protective environment within the blood-testis barrier.

Sertoli cells are a crucial component of the blood-testis barrier (BTB), which isolates the adluminal compartment of the seminiferous tubules from the rest of the testis thus forming an environment to immunely protect the developing germ cells. The mechanisms of regulating immune responses within this environment are currently under investigation. Here, we focused on Sertoli cell regulation of the complement system.

Sertoli Cells Express Accommodation, Survival, and Immunoregulatory Factors When Exposed to Normal Human Serum.

Transplantation is a clinical procedure that treats a variety of diseases yet is unattainable for many patients due to a nationwide organ shortage and the harsh side effects of chronic immune suppression. Xenografted pig organs are an attractive alternative to traditional allografts and would provide an endless supply of transplantable tissue, but transplants risk rejection by the recipient's immune system. An essential component of the rejection immune response is the complement system.

Complementing Testicular Immune Regulation: The Relationship between Sertoli Cells, Complement, and the Immune Response.

Sertoli cells within the testis are instrumental in providing an environment for spermatogenesis and protecting the developing germ cells from detrimental immune responses which could affect fertility. Though these immune responses consist of many immune processes, this review focuses on the understudied complement system. Complement consists of 50+ proteins including regulatory proteins, immune receptors, and a cascade of proteolytic cleavages resulting in target cell destruction.

The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival.

The complement system is an important component of transplant rejection. Sertoli cells, an immune regulatory testicular cell, survive long-term when transplanted across immunological barriers; thus, understanding the mechanisms behind this unique survival would be of great benefit to the transplantation field. This study focused on Sertoli cell inhibition of complement as relevant in xenotransplantation.

Immunoregulatory Sertoli Cell Allografts Engineered to Express Human Insulin Survive Humoral-Mediated Rejection.

An effective treatment and possible cure for type 1 diabetes is transplantation of pancreatic islets. Unfortunately, transplanted islets are rejected by the immune system with humoral-mediated responses being an important part of rejection. Sertoli cells (SC), an immune regulatory cell shown to survive as allografts long-term without immunosuppressants, have the potential to be used as a cell-based gene therapy vehicle to deliver endogenous insulin-a possible alternative to islets.

Mouse Sertoli Cells Inhibit Humoral-Based Immunity.

Transplantation is used to treat many different diseases; however, without the use of immunosuppressants, which can be toxic to the patient, grafted tissue is rejected by the immune system. Humoral immune responses, particularly antibodies and complement, are significant components in rejection. Remarkably, Sertoli cells (SCs), immunoregulatory testicular cells, survive long-term after transplantation without immunosuppression.

Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function.

Background Emerging research suggests hyperglycemia can increase intestinal permeability. Ginger and its bioactive compounds have been reported to benefit diabetic animals due to their anti-inflammatory and antioxidant properties. In this study, we revealed the beneficial effect of gingerol-enriched ginger (GEG) on intestinal health (i.

Sertoli Cell Immune Regulation: A Double-Edged Sword.

The testis must create and maintain an immune privileged environment to protect maturing germ cells from autoimmune destruction. The establishment of this protective environment is due, at least in part, to Sertoli cells. Sertoli cells line the seminiferous tubules and form the blood-testis barrier (BTB), a barrier between advanced germ cells and the immune system.

Mechanisms linking endoplasmic reticulum (ER) stress and microRNAs to adipose tissue dysfunction in obesity.

Over accumulation of lipids in adipose tissue disrupts metabolic homeostasis by affecting cellular processes. Endoplasmic reticulum (ER) stress is one such process affected by obesity. Biochemical and physiological alterations in adipose tissue due to obesity interfere with adipose ER functions causing ER stress.

Therapeutic application of Sertoli cells for treatment of various diseases.

Sertoli cells (SCs) are immune privileged cells found in the testis that function to immunologically protect maturing germ cells from immune destruction. This immune protection is due to the blood-testis-barrier, which prevents infiltration of cytotoxic immune cells and antibodies, and SC production of immunomodulatory factors, that favor a tolerogenic environment. The ability of SCs to create an immune privileged environment has led to the exploration of their potential use in the treatment of various diseases.

C-Peptide as a Therapy for Type 1 Diabetes Mellitus.

Diabetes mellitus (DM) is a complex metabolic disease affecting one-third of the United States population. It is characterized by hyperglycemia, where the hormone insulin is either not produced sufficiently or where there is a resistance to insulin. Patients with Type 1 DM (T1DM), in which the insulin-producing beta cells are destroyed by autoimmune mechanisms, have a significantly increased risk of developing life-threatening cardiovascular complications, even when exogenous insulin is administered.

Assessing Hand Hygiene and Low-Level Disinfection of Equipment Compliance in an Acute Care Setting: Mixed Methods Approach.

Background: Hand hygiene and low-level disinfection of equipment behaviors among hospital staff are some of the leading cost-effective methods to reduce hospital-acquired infections (HAI) among patients.

Objective: The aim of this study is to examine hand hygiene and low-level disinfection of equipment practices in a central Texas hospital and to explore pertaining gaps, perceptions, and challenges.

Methods: Data were collected using a multipronged mixed methods approach that included the following: (1) observation of hand hygiene and low-level disinfection practices (12 and 8 units during morning and evening shifts, respectively); (2) observation of usability/placement of hand sanitizer dispensers; (3) semistructured interviews; and (4) a follow-up email survey.

Conceptual Frameworks in Scientific Inquiry and the Centers for Disease Control and Prevention's Approach to Pesticide Toxicity (1948-1968).

This article examines the rise of the Centers for Disease Control and Prevention's (CDC's) small but influential program on the human toxicology of synthetic pesticides after World War II. For nearly 20 years, scientists working in the CDC's Toxicology Section conducted a range of laboratory, field, and clinical studies to assess whether pesticides, such as DDT), caused harm to humans. Applying an industrial hygiene approach to study pesticide toxicity, the team used the symptoms of poisoning as their criteria for harm and consistently found that, when used as intended, pesticides were generally safe for humans.

Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine -oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial.

Intermittent fasting (IF) has been connected with health benefits such as weight loss, lower risk of coronary artery disease (CAD) and diabetes, increased longevity, and improved quality of life. However, the mechanisms of these IF benefits in humans require further investigation. This study sought to elucidate some of these mechanisms through secondary analyses of the Fasting and ExprEssion of Longevity Genes during fOOD abstinence (FEELGOOD) trial, in which apparently healthy participants were randomized in a Latin square design to a 24-h water-only fast and a 24-h ad libitum fed day.

Measuring personal chemical exposures through biomonitoring: the experiences of research participants.

Using a technique called human biomonitoring, scientists can now measure hundreds of environmental chemicals and/or their metabolites in human body fluids and tissues. In this article, I examine the experiences of 28 women who participated in two different types of biomonitoring studies and received personal exposure results. I show that although the women's experiences of biomonitoring differed and were shaped by the contexts in which biomonitoring occurred, there were also remarkable similarities across contexts.

"I felt like a superhero": the experience of responding to drug overdose among individuals trained in overdose prevention.

Background: Overdose prevention programs (OPPs) train people who inject drugs and other community members to prevent, recognise and respond to opioid overdose. However, little is known about the experience of taking up the role of an "overdose responder" for the participants.

Methods: We present findings from qualitative interviews with 30 participants from two OPPs in Los Angeles, CA, USA from 2010 to 2011 who had responded to at least one overdose since being trained in overdose prevention and response.

Reconciling incongruous qualitative and quantitative findings in mixed methods research: exemplars from research with drug using populations.

Mixed methods research is increasingly being promoted in the health sciences as a way to gain more comprehensive understandings of how social processes and individual behaviours shape human health. Mixed methods research most commonly combines qualitative and quantitative data collection and analysis strategies. Often, integrating findings from multiple methods is assumed to confirm or validate the findings from one method with the findings from another, seeking convergence or agreement between methods.

Seeking help for attention deficit hyperactivity disorder in developing countries: a study of parental explanatory models in Goa, India.

This qualitative study analyzes the explanatory models employed by parents whose children have been diagnosed with attention deficit hyperactivity disorder (ADHD) and the ways in which these explanatory models change as they seek help for their child's problem. In-depth interviews were conducted with 24 parents recruited from a list of children who had been diagnosed with ADHD at a community-based child development center (CDC) in Goa, India. The most frequent reasons for consulting the CDC were educational difficulties.