Apolipoprotein E4 and Alzheimer's disease causality under adverse environments and potential intervention by senolytic nutrients.

Apolipoprotein E (apoE) has a pivotal role in Alzheimer's Disease (AD) pathophysiology. APOE4 has been recognized as a risk factor for developing late-onset AD. Recently, APOE4 homozygosity was regarded as a new familial genetic trait of AD.

Pros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.

Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity.

The Costly Vicious Cycle of Infections and Malnutrition.

Malnutrition, which continues to affect hundreds of millions of people worldwide, is both a cause and consequence of a range of infectious diseases. In this perspective piece, we provide an overview of the bidirectional relationship between malnutrition and infectious diseases. In addition to enteric infections, we use tuberculosis as a case study of this relationship between malnutrition and infectious diseases, and to demonstrate the potential of nutritional interventions to mitigate mortality and morbidity from infectious diseases.

Early-Life Enteric Pathogen Exposure, Socioeconomic Status, and School-Age Cognitive Outcomes.

Early-life experiences of enteric infections and diarrheal illness are common in low-resource settings and are hypothesized to affect child development. However, longer-term associations of enteric infections with school-age cognitive outcomes are difficult to estimate due to lack of long-term studies. The objective of this study was to examine the relationship between enteropathogen exposure in the first 2 years of life with school-age cognitive skills in a cohort of children followed from birth until 6 to 8 years in low-resource settings in Brazil, Tanzania, and South Africa.

Giardia hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy.

Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and middle-income countries (LMICs). Although Giardia associates with early-life linear growth restriction, mechanistic explanations for Giardia-associated growth impairments remain elusive. Unlike other intestinal pathogens associated with constrained linear growth that cause intestinal or systemic inflammation or both, Giardia seldom associates with chronic inflammation in these children.

Myeloperoxidase as a biomarker for intestinal-brain axis dysfunction induced by malnutrition and Cryptosporidium infection in weanling mice.

Cryptosporidiosis is a waterborne protozoal infection that may cause life-threatening diarrhea in undernourished children living in unsanitary environments. The aim of this study is to identify new biomarkers that may be related to gut-brain axis dysfunction in children suffering from the malnutrition/infection vicious cycle, necessary for better intervention strategies. Myeloperoxidase (MPO) is a well-known neutrophil-related tissue factor released during enteropathy that could drive gut-derived brain inflammation.

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers.

Apolipoprotein E (apoE) mimetic peptides are engineered fragments of the native apoE protein's LDL-receptor binding site that improve the outcomes following a brain injury and intestinal inflammation in a variety of models. The vicious cycle of enteric infections and malnutrition is closely related to environmental-driven enteric dysfunction early in life, and such chronic inflammatory conditions may blunt the developmental trajectories of children with worrisome and often irreversible physical and cognitive faltering. This window of time for microbiota maturation and brain plasticity is key to protecting cognitive domains, brain health, and achieving optimal/full developmental potential.

Impact of Shigella infections and inflammation early in life on child growth and school-aged cognitive outcomes: Findings from three birth cohorts over eight years.

Background: Shigella infections cause inflammation, which has been hypothesized to mediate the associations between Shigella and child development outcomes among children in low-resource settings. We aimed to assess whether early life inflammation and Shigella infections affect school-aged growth and cognitive outcomes from 6-8 years of age.

Methodology/principal Findings: We conducted follow-up assessments of anthropometry, reasoning skills, and verbal fluency in 451 children at 6-8 years of age in the Brazil, Tanzania, and South Africa sites of MAL-ED, a longitudinal birth cohort study.

The Epidemiology of Sapovirus in the Etiology, Risk Factors, and Interactions of Enteric Infection and Malnutrition and the Consequences for Child Health and Development Study: Evidence of Protection Following Natural Infection.

Background: Sapovirus is one of the principal agents of acute viral enteritis in children. Because it has not been routinely included in diagnostic evaluations, the epidemiology and natural history remain poorly described.

Methods: A birth cohort of 1715 children from 8 countries contributed surveillance samples (n = 35 620) and diarrheal specimens (n = 6868) from 0 to 24 months of age.

Enteropathogenic Escherichia coli (EPEC) expressing a non-functional bundle-forming pili (BFP) also leads to increased growth failure and intestinal inflammation in C57BL/6 mice.

Bundle-forming pili (BFP) are implicated in the virulence of typical enteropathogenic E. coli (EPEC), resulting in enhanced colonization and mild to severe disease outcomes; hence, non-functional BFP may have a major influence on disease outcomes in vivo. Weaned antibiotic pre-treated C57BL/6 mice were orally infected with EPEC strain UMD901 (E2348/69 bfpA C129S); mice were monitored daily for body weight; stool specimens were collected daily; and intestinal tissues were collected at the termination of the experiment on day 3 post-infection.

Clostridioides difficile colonization among very young children in resource-limited settings.

Objectives: To describe the epidemiology and risk factors for Clostridioides difficile (C. difficile) colonization among young children in eight low-resource settings.

Methods: We tested 41 354 monthly non-diarrhoeal and diarrhoeal stools for C.

The CHO Cell Clustering Response to Pertussis Toxin: History of Its Discovery and Recent Developments in Its Use.

Chinese hamster ovary (CHO) cells respond to pertussis toxin (PT) with a novel clustering pattern, which is dependent on biologically active PT. Since its description in 1983, this cellular response has been refined and used extensively for detection and quantification of PT activity, as well as anti-PT antibodies. There are limitations, however, in the use of this phenomenon as originally described.

Detecting Glucose Fluctuations in the N-Glycan Structure.

is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins. We characterized 98 isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac. Mass spectrometric analyses indicated these isolates express a hexasaccharide lacking the glucose branch.

S100B Inhibition Attenuates Intestinal Damage and Diarrhea Severity During Infection by Modulating Inflammatory Response.

The involvement of the enteric nervous system, which is a source of S100B, in () infection (CDI) is poorly understood although intestinal motility dysfunctions are known to occur following infection. Here, we investigated the role of S100B in CDI and examined the S100B signaling pathways activated in toxin A (TcdA)- and B (TcdB)-induced enteric glial cell (EGC) inflammatory response. The expression of S100B was measured in colon tissues and fecal samples of patients with and without CDI, as well as in colon tissues from -infected mice.

Immunoinflammatory role of apolipoprotein E4 in malnutrition and enteric infections and the increased risk for chronic diseases under adverse environments.

Apolipoprotein E plays a crucial role in cholesterol metabolism. The immunomodulatory functions of the human polymorphic APOE gene have gained particular interest because APOE4, a well-recognized risk factor for late-onset Alzheimer's disease, has also been recently linked to increased risk of COVID-19 infection severity in a large UK biobank study. Although much is known about apoE functions in the nervous system, much less is known about APOE polymorphism effects on malnutrition and enteric infections and the consequences for later development in underprivileged environments.

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes.

Developing effective therapeutics or preventive interventions for important health threats is greatly enhanced whenever accessible models can enable the assessment of clinically important outcomes. While no non-human model is ever perfect, inexpensive small animal models in such as mice are often of great help in assessing the relevant efficacy of potential interventions. In addition to acute diarrhea, the long-term growth and developmental effects of enteric infections, with or without overt diarrhea, are increasingly recognized.

Investigation of a monoclonal antibody against enterotoxigenic , expressed as secretory IgA1 and IgA2 in plants.

Passive immunization with antibodies is a promising approach against enterotoxigenic diarrhea, a prevalent disease in LMICs. The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in plants, with a view to facilitating access to ETEC passive immunotherapy. SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in .

Enteropathogenic Infection Induces Diarrhea, Intestinal Damage, Metabolic Alterations, and Increased Intestinal Permeability in a Murine Model.

Enteropathogenic  (EPEC) are recognized as one of the leading bacterial causes of infantile diarrhea worldwide. Weaned C57BL/6 mice pretreated with antibiotics were challenged orally with wild-type EPEC or mutant (lacking type 3 secretion system) to determine colonization, inflammatory responses and clinical outcomes during infection. Antibiotic disruption of intestinal microbiota enabled efficient colonization by wild-type EPEC resulting in growth impairment and diarrhea.

Seasonality of drinking water sources and the impact of drinking water source on enteric infections among children in Limpopo, South Africa.

Enteric infections and water-related illnesses are more frequent during times of relative water abundance, especially in regions that experience bimodal rainfall patterns. However, it is unclear how seasonal changes in water availability and drinking water source types affect enteric infections in young children. This study investigated seasonal shifts in primary drinking water source type and the effect of water source type on enteric pathogen prevalence in stool samples from 404 children below age 5 in rural communities in Limpopo Province, South Africa.

Higher Energy and Zinc Intakes from Complementary Feeding Are Associated with Decreased Risk of Undernutrition in Children from South America, Africa, and Asia.

Background: Few studies have focused on quantitatively analyzing nutrients from infant diets, compromising complementary feeding evaluation and health promotion worldwide.

Objectives: This study aimed to describe dietary intake in infants from 9 to 24 mo of age, determining nutrient intakes associated with the risk of underweight, wasting, and stunting.

Methods: Usual nutrient intakes from complementary feeding were determined by 24-h recalls collected when infants were 9-24 mo of age in communities from 7 low- and middle-income countries: Brazil (n = 169), Peru (n = 199), South Africa (n = 221), Tanzania (n = 210), Bangladesh (n = 208), India (n = 227), and Nepal (n = 229), totaling 1463 children and 22,282 food recalls.

Impact of Low-Cost Point-of-Use Water Treatment Technologies on Enteric Infections and Growth among Children in Limpopo, South Africa.

Enteric infections early in life have been associated with poor linear growth among children in low-resource settings. Point-of-use water treatment technologies provide effective and low-cost solutions to reduce exposure to enteropathogens from drinking water, but it is unknown whether the use of these technologies translates to improvements in child growth. We conducted a community-based randomized controlled trial of two water treatment technologies to estimate their effects on child growth in Limpopo, South Africa.

Intervention and Mechanisms of Alanyl-glutamine for Inflammation, Nutrition, and Enteropathy: A Randomized Controlled Trial.

Objective: Determine the minimum dosage of alanyl-glutamine (Ala-Gln) required to improve gut integrity and growth in children at risk of environmental enteropathy (EE).

Methods: This was a double-blinded randomized placebo-controlled dose-response trial. We enrolled 140 children residing in a low-income community in Fortaleza, Brazil.

Apolipoprotein E Effects on Mammalian Ovarian Steroidogenesis and Human Fertility.

Apolipoprotein E (ApoE) is a glycoprotein consisting of 299 amino acids, highly produced in the mammalian ovaries. The main function of the ApoE is to transport cholesterol from the peripheral tissues to be metabolized in the liver. In humans, the ApoE gene is polymorphic, with three alleles in a single chromosome-19 locus: APOE2, APOE3, and APOE4.