Generating Cytokines and Growth Factors for Functional Activity: Feasibility of Method Using MIF Protein.

Cytokines and growth factors are signaling molecules that regulate a variety of biological processes. Understanding their role is essential for basic research and clinical utilization. Thus, cytokines and growth factors are widely used throughout research labs in a significant number of applications.

Prosurvival Pathway Protects From Clostridioides difficile Toxin-Mediated Cell Death.

There is an urgent need for new nonantibiotic-based treatment strategies for Clostridioides difficile infection. C. difficile toxin B (TcdB) is a virulent factor that is essential for causing disease.

Infection and inflammation stimulate expansion of a CD74 Paneth cell subset to regulate disease progression.

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level.

Clostridioides difficile Infection in Children: Recent Updates on Epidemiology, Diagnosis, Therapy.

Clostridioides (formerly Clostridium) difficile is the most important infectious cause of antibiotic-associated diarrhea worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of C. difficile infection (CDI) in children has increased, with 20 000 cases now reported annually, also posing indirect educational and economic consequences.

Alcohol Abuse Drug Disulfiram Is Effective against Cyst Stages of Entamoeba histolytica Parasite.

New anti-Entamoeba histolytica multistage drugs are needed because only one drug class, nitroimidazoles, is available for treating invasive disease, and it does not effectively eradicate the infective cyst stage. Zinc ditiocarb (ZnDTC), a main metabolite of the FDA-approved drug disulfiram, was recently shown to be highly effective against the invasive trophozoite stage. In this brief report, we show that ZnDTC is active against cysts, with similar potency to first-line cysticidal drug paromomycin.

Drug Repurposing of the Alcohol Abuse Medication Disulfiram as an Anti-Parasitic Agent.

Parasitic infections contribute significantly to worldwide morbidity and mortality. Antibiotic treatment is essential for managing patients infected with these parasites since control is otherwise challenging and there are no vaccines available for prevention. However, new antimicrobial therapies are urgently needed as significant problems exist with current treatments such as drug resistance, limited options, poor efficacy, as well as toxicity.

COVID-19 and Corticosteroids: Unfamiliar but Potentially Fatal Infections That Can Arise following Short-Course Steroid Treatment.

Corticosteroid use is increasing worldwide as recent studies confer survival benefit of corticosteroids in the management of patients with severe COVID-19. Strongyloides and amebic infections are neglected diseases that can progress to catastrophic complications in patients exposed to corticosteroids, even with short treatment courses. To prevent lethal outcomes, clinicians should be aware of the threat these two parasitic infections pose to at-risk patients receiving corticosteroids, especially in the era of COVID-19.

Acute appendicitis in four children with SARS-CoV-2 infection.

We describe 4 children (11-17 years in age) at our institution with acute appendicitis in the setting of SARS-CoV-2 infection, suggesting a possible association. Providers should consider testing for this infection in patients with severe gastrointestinal symptoms, in order to take appropriate transmission based precautions, until more is understood.

COP9 signalosome is an essential and druggable parasite target that regulates protein degradation.

Understanding how the protozoan protein degradation pathway is regulated could uncover new parasite biology for drug discovery. We found the COP9 signalosome (CSN) conserved in multiple pathogens such as Leishmania, Trypanosoma, Toxoplasma, and used the severe diarrhea-causing Entamoeba histolytica to study its function in medically significant protozoa. We show that CSN is an essential upstream regulator of parasite protein degradation.

Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair.

Wound healing after an injury is essential for life. An in-depth understanding of the healing process is necessary to ultimately improve the currently limited treatment options for patients suffering as a result of damage to various organs and tissues. Injuries, even the most minor, trigger an inflammatory response that protects the host and activates repair pathways.

The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function.

Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival.

CD74 Signaling Links Inflammation to Intestinal Epithelial Cell Regeneration and Promotes Mucosal Healing.

Background & Aims: The inflammatory response to intestinal damage promotes healing through mechanisms that are incompletely understood. Gene expression of cluster of differentiation 74 (CD74), the receptor for cytokine macrophage migration inhibitory factor, is increased in patients with inflammatory bowel disease (IBD), however, the role of CD74 signaling in intestinal inflammation remains poorly understood. The aim of this study was to determine the functional role of CD74 signaling in intestinal inflammation.

Purification of Antibodies Against Entamoeba histolytica MIF and Their Use in Analyzing Human and Mouse Samples.

Macrophage migration inhibitory factor (MIF) is a proinflammatory and proproliferative cytokine expressed in humans. MIF homologs also exist in many pathogenic protozoans, including Entamoeba, Plasmodium, Toxoplasma, and Leishmania. Production of antibodies against parasite proteins allows for the generation of assays to measure and visualize parasite infection within hosts.

Targeting Parasite-Produced Macrophage Migration Inhibitory Factor as an Antivirulence Strategy With Antibiotic-Antibody Combination to Reduce Tissue Damage.

Targeting virulence factors represents a promising alternative approach to antimicrobial therapy, through the inhibition of pathogenic pathways that result in host tissue damage. Yet, virulence inhibition remains an understudied area in parasitology. Several medically important protozoan parasites such as Plasmodium, Entamoeba, Toxoplasma, and Leishmania secrete an inflammatory macrophage migration inhibitory factor (MIF) cytokine homolog, a virulence factor linked to severe disease.

Case Report: Lower Gastrointestinal Bleeding due to Detected Early by Multiplex PCR: Case Report and Review of the Laboratory Diagnosis of Amebiasis.

We report a case of infection in a young man who presented with cerebral infarction and shortly after admission developed bloody diarrhea with fever. A rapid diagnosis of severe colitis was established through the use of a multiplex polymerase chain reaction enteropathogen stool panel. This result was unexpected in a patient native to the United States without known risk factors for amebiasis and negative stool microscopy examination for ova and parasites.

Parasite-Produced MIF Cytokine: Role in Immune Evasion, Invasion, and Pathogenesis.

Protozoan parasites represent a major threat to health and contribute significantly to morbidity and mortality worldwide, especially in developing countries. This is further compounded by lack of effective vaccines, drug resistance and toxicity associated with current therapies. Multiple protozoans, including , and produce homologs of the cytokine MIF.

Tissue Destruction Caused by Parasite Cell Death, Inflammation, Invasion, and the Gut Microbiome.

Purpose Of Review: is a protozoan parasite that causes amebiasis, which remains a significant cause of morbidity and mortality worldwide. causes tissue destruction which leads to clinical disease. This review outlines some of the recent advances that have furthered our understanding of the processes that lead to the tissue damage caused by

Recent Findings: Recent studies have identified new mechanisms involved in -induced tissue damage.

A Review of the Global Burden, New Diagnostics, and Current Therapeutics for Amebiasis.

Amebiasis, due to the pathogenic parasite is a leading cause of diarrhea globally. Largely an infection of impoverished communities in developing countries, amebiasis has emerged as an important infection among returning travelers, immigrants, and men who have sex with men residing in developed countries. Severe cases can be associated with high case fatality.

The Impact of Systemic Inflammation on Neurodevelopment.

Inflammatory mediators affect the brain during development. Neurodevelopmental disorders such as autism spectrum disorders, cognitive impairment, cerebral palsy, epilepsy, and schizophrenia have been linked to early life inflammation. Recent advances have shown the effects of systemic inflammation on children's neurodevelopment.

Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function.

Multiple protozoans produce homologs of the cytokine MIF which play a role in immune evasion, invasion and pathogenesis. However, how parasite-encoded MIF activity is controlled remains poorly understood. Cytokine activity can be inhibited by intracellular binding partners that are released in the extracellular space during cell death.

Entamoeba Species in South Africa: Correlations With the Host Microbiome, Parasite Burdens, and First Description of Entamoeba bangladeshi Outside of Asia.

Background: Diarrhea is frequent in communities without clean water, which include low-income South African populations in Giyani and Pretoria. In these populations, the amount of diarrhea caused by Entamoeba histolytica, inclusive of all ages, sexes, and human immunodeficiency virus status, is uncertain. Infection with E.

Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis.

The disease severity of Entamoeba histolytica infection ranges from asymptomatic to life-threatening. Recent human and animal data implicate the gut microbiome as a modifier of E. histolytica virulence.

Entamoeba histolytica-Encoded Homolog of Macrophage Migration Inhibitory Factor Contributes to Mucosal Inflammation during Amebic Colitis.

Understanding the mechanisms by which Entamoeba histolytica drives gut inflammation is critical for the development of improved preventive and therapeutic strategies. E. histolytica encodes a homolog of the human cytokine macrophage migration inhibitory factor (MIF).

Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic Review.

Background: Amebic colitis, caused by intestinal infection with the parasite, Entamoeba histolytica, is a common cause of diarrhea worldwide. Fulminant amebic colitis is the most devastating complication of this infection, associated with both high mortality and morbidity. We conducted a review of the English literature to describe cases of fulminant amebic colitis associated with exposure to corticosteroid medications in order to identify the risk factors for poor outcome and determine difficulties in diagnosis and treatment.