Multiple Infections, Nutrient Deficiencies, and Inflammation as Determinants of Anemia and Iron Status during Pregnancy: The MINDI Cohort.

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.

Multiple Indicators of Undernutrition, Infection, and Inflammation in Lactating Women Are Associated with Maternal Iron Status and Infant Anthropometry in Panama: The MINDI Cohort.

Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations of MINDI variables with maternal anemia, elevated serum transferrin receptor (sTfR), low serum iron, hepcidin, ferritin, and infant weight-for-age (WAZ), length-for-age (LAZ), and head-circumference-for-age (HCAZ) Z-scores in 99 mother-infant dyads. A bootstrapping resampling procedure preselected covariates for inclusion in multivariable regressions models from chronic maternal infections and nutritional status [folate, vitamins A, D, retinol-binding protein (RBP), insulin-growth factor-1 (IGF-1)] and inflammation [C-reactive protein (CRP), cytokines, platelet indices] indicators. Anemia was prevalent (53.5%) but underestimated due to widespread low plasma volume (<2.2 L, 79.9%) and was associated with indicators of malnutrition [lower IGF-1, body mass index (BMI), vitamin D, and intake of green/leafy vegetables], but not inflammation. Higher CRP was associated with lower serum iron, and higher hepcidin and ferritin, whereas maternal platelets were associated with lower HCAZ (ß = −0.22), WAZ (ß = −0.17), and LAZ (ß = −0.17). Higher LAZ was also associated with maternal serum vitamin D (ß = 0.23), whereas maternal iron supplementation lowered LAZ (ß = −0.22). Assessment of iron status in this MINDI cohort is complex and supplementation strategies must consider consequences for both the mother and the infant.

Pouteria sapota (Red Mamey Fruit): Chemistry and Biological Activity of Carotenoids.

BACKGROUND: Red mamey is the fruit of P. sapota, a tree found in Mesoamerica and Asia. This fruit is considered a nutraceutical due to its multiple beneficial health including antiamyloidogenic activity and potential anti-tumorigenic property. Red mamey contain a variety of carotenoids including novel ketocarotenoids such as sapotexanthin and cryptocapsin. A ketocarotenoid is a chemical compound with a carbonyl group present in the ß-ring or in the double bond chain of a carotenoid. In red mamey, the 3'-deoxy-k-end group in sapotexanthin has proven to be an important pro-vitamin A source, which is essential for maintaining a healthy vision and cognitive processes. OBJECTIVE: This work reviews the current knowledge about the chemistry and biological activities of carotenoids in red mamey. METHOD: An exhaustive extraction is the most usual methodology to isolate and thoroughly characterize the carotenoids present in this fruit. High performance liquid chromatography is used to determine the profile of total carotenoids and its purity, while atmospheric pressure chemical ionization was used to determine their molecular weight and nuclear magnetic resonance determined their structure. RESULT: For each 100 g of fresh weight, 0.12 mg of total carotenoid from this fruit can be obtained. Out of the more than 47 reported carotenoids in red mamey, only 34 have a detailed characterization. CONCLUSION: It is important to continue studying the chemical composition and biological activity of this unique tropical fruit with commercial and nutritional value.

Maternal and cord blood parameters are associated with placental and newborn outcomes in indigenous mothers: A case study in the MINDI cohort / Parámetros maternos y de sangre de cordón asociados con medidas placentarias y del recién nacido: Un estudio de casos en madres indígenas de la cohorte MINDI

Abstract Background: Multiple infections, nutrient deficiencies and inflammation (MINDI) occur in indigenous communities, but their associations with perinatal outcomes have not been described. Objective: To assess maternal and cord blood micronutrient and inflammation status in peripartum mothers from the Ngäbe-Buglé comarca in Panama, and their associations with placental and infant outcomes. Methods: In 34 mother-newborn dyads, placental weight and diameter were measured, and maternal and cord blood were processed for complete cell counts, serum C-reactive protein, ferritin, serum transferrin receptor (sTfR), vitamins A and D. Blood volumes were calculated using Nadler's formula. Results: Mothers had low plasma volume (<2.8 L, 96%), vitamin A (52.9%), vitamin D (29.4%), iron (58.8%) and hemoglobin (23.5%), but high hematocrit (>40%, 17.6%) and inflammation (C-reactive protein >8.1 mg/L, 85.3%). Birthweights were normal, but low placental weight (35.3%), low head circumference Z-scores (17.6%), and low cord hemoglobin (5.9%), iron (79.4%), vitamin A (14.7%) and vitamin D (82.3%) were identified. Maternal and cord vitamin D were highly correlated. Higher maternal plasma volume was associated with heavier placentae (β= 0.57), and higher cord D (β= 0.43) and eosinophils (β= 0.43) with larger placentae. Hemoconcentration (higher cord hematocrit) was associated with lower newborn weight (β= -0.48) and head circumference (β= -0.56). Inflammation [higher maternal neutrophils (β= -0.50), and cord platelets (β= -0.32)] was associated with lower newborn length and head circumference. Conclusion: Maternal-newborn hemoconcentration, subclinical inflammation and multiple nutrient deficiencies, particularly neonatal vitamin D deficiency, were identified as potential targets for interventions to improve pregnancy outcomes in vulnerable communities.

Resumen Antecedentes: Las Múltiples Infecciones, Nutrición Deficiente e Inflamación (MINDI), son frecuentes en comunidades indígenas, sin embargo, sus asociaciones con resultados de salud perinatales no han sido descritos. Objetivo: Evaluar la inflamación y los micronutrientes en sangre materna y de cordón de madres en trabajo de parto en la comarca Ngäbe-Buglé en Panamá, así como sus asociaciones con medidas placentarias y del recién nacido. Métodos: En 34 pares madre-recién nacido, se midieron peso y diámetro placentario, y se analizaron muestras de sangre materna y de cordón umbilical para hemograma completo, proteína-C reactiva (PCR), ferritina, receptor sérico de transferrina (RsTf), vitaminas A y D. Se usó la fórmula de Nadler para calcular volúmenes sanguíneos. Resultados: Las madres presentaron volumen plasmático (<2.8 L, 96%), vitamina A (52.9%), vitamina D (29.4%), hierro (58.8%) y hemoglobina (23.5%) bajos, pero el 17.6% presentaron hematocrito >40% y 85.3% presentaron inflamación (PCR >8.1 mg/L). Los pesos al nacer fueron normales, pero se identificó bajo peso placentario (35.3%), bajo puntaje-z de circunferencia cefálica neonatal, y en sangre de cordón, bajos hemoglobina (5.9%), hierro (79.4%), vitamina A (14.7%) y vitamina D (82.3%). Se encontró una fuerte correlación positiva entre la vitamina D materna y de sangre de cordón. Un mayor volumen plasmático materno se asoció con placentas de mayor peso (β= 0.57), en tanto que concentraciones más altas de vitamina D (β= 0.43) y mayor número de eosinófilos (β= 0.43) se asociaron con mayor diámetro placentario. Una mayor hemoconcentración (hematocrito en cordón más alto) se asoció con menores peso al nacer (β= -0.48) y circunferencia cefálica (β= -0.56). La inflamación [mayor número de neutrófilos maternos (β= -0.50) y plaquetas en sangre de cordón (β= -0.32)] se asoció con menor talla y circunferencia cefálica neonatales. Conclusión: La hemoconcentración materna y del recién nacido, la inflamación subclínica y las múltiples deficiencias en micronutrientes, particularmente la deficiencia de vitamina D neonatal, se identificaron como potenciales áreas de intervención para mejorar los resultados de salud del embarazo en comunidades vulnerables.

NLRP3 Regulates IL-4 Expression in TOX+ CD4+ T Cells of Cutaneous T Cell Lymphoma to Potentially Promote Disease Progression.

In cutaneous T cell lymphoma (CTCL), a dominant Th2 profile associated with disease progression has been proposed. Moreover, although the production and regulation of IL-4 expression during the early stages of the disease may have important implications in later stages, these processes are poorly understood. Here, we demonstrate the presence of TOX+ CD4+ T cells that produce IL-4+ in early-stage skin lesions of CTCL patients and reveal a complex mechanism by which the NLRP3 receptor promotes a Th2 response by controlling IL-4 production. Unassembled NLRP3 is able to translocate to the nucleus of malignant CD4+ T cells, where it binds to the human il-4 promoter. Accordingly, IL-4 expression is decreased by knocking down and increased by promoting the nuclear localization of NLRP3. We describe a positive feedback loop in which IL-4 inhibits NLRP3 inflammasome assembly, thereby further increasing its production. IL-4 induced a potentially malignant phenotype measured based on TOX expression and proliferation. This mechanism of IL-4 regulation mediated by NLRP3 is amplified in late-stage CTCL associated with disease progression. These results indicate that NLRP3 might be a key regulator of IL-4 expression in TOX+ CD4+ T cells of CTCL patients and that this mechanism might have important implications in the progression of the disease.

Induction of Progenitor Exhausted Tissue-Resident Memory CD8+ T Cells Upon Salmonella Typhi Porins Adjuvant Immunization Correlates With Melanoma Control and Anti-PD-1 Immunotherapy Cooperation.

Immunotherapy has improved the clinical response in melanoma patients, although a relevant percentage of patients still cannot be salvaged. The search for the immune populations that provide the best tumor control and that can be coaxed by immunotherapy strategies is a hot topic in cancer research nowadays. Tumor-infiltrating TCF-1+ progenitor exhausted CD8+ T cells seem to grant the best melanoma prognosis and also efficiently respond to anti-PD-1 immunotherapy, giving rise to a TIM-3+ terminally exhausted population with heightened effector activity. We tested Porins from Salmonella Typhi as a pathogen associated molecular pattern adjuvant of natural or model antigen in prophylactic and therapeutic immunization approaches against murine melanoma. Porins induced protection against melanomas, even upon re-challenging of tumor-free mice. Porins efficiently expanded IFN-γ-producing CD8+ T cells and induced central and effector memory in lymph nodes and tissue-resident (Trm) T cells in the skin and tumors. Porins induced TCF-1+ PD-1+ CD8+ Trm T cells in the tumor stroma and the presence of this population correlated with melanoma growth protection in mice. Porins immunization also cooperated with anti-PD-1 immunotherapy to hamper melanoma growth. Importantly, the potentially protective Trm populations induced by Porins in the murine model were also observed in melanoma patients in which their presence also correlated with disease control. Our data support the use of cancer vaccination to sculpt the tumor stroma with efficient and lasting Trm T cells with effector activities, highlighting the use of Porins as an adjuvant. Furthermore, our data place CD8+ Trm T cells with a progenitor exhausted phenotype as an important population for melanoma control, either independently or in cooperation with anti-PD-1 immunotherapy.

Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-ß Aggregation in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Brain inflammation plays a key role in the progression of AD. Deposition of senile plaques in the brain stimulates an inflammatory response with the overexpression of pro-inflammatory mediators, such as the neuroinflammatory cytokine. interleukin-6. Curcumin has been revealed to be a potential agent for treating AD following different neuroprotective mechanisms, such as inhibition of aggregation and decrease in brain inflammation. We synthesized new curcumin derivatives with the aim of providing good anti-aggregation capacity but also improved anti-inflammatory activity. Nine curcumin derivatives were synthesized by etherification and esterification of the aromatic region. From these derivatives, compound 8 exhibited an anti-inflammatory effect similar to curcumin, while compounds 3, 4, and 10 were more potent. Moreover, when the anti-aggregation activity is considered, compounds 3, 4, 5, 6, and 10 showed biological activity in vitro. Compound 4 exhibited a strong anti-aggregation effect higher than curcumin. Monofunctionalized curcumin derivatives showed better bioactivity than difunctionalized compounds. Moreover, the presence of bulky groups in the chemical structure of curcumin derivatives decreased bioactivity.

Interactions among urogenital, intestinal, skin, and oral infections in pregnant and lactating Panamanian Ngäbe women: a neglected public health challenge.

Interrelationships among bacteria, protozoa, helminths, and ectoparasites were explored in a cross-sectional survey of 213 pregnant and 99 lactating indigenous women. Prevalences in pregnancy and lactation, respectively, were: vaginitis (89.2%; 46.8%), vaginal trichomoniasis (75.3%; 91.1%), bacterial vaginosis (BV; 60.6%; 63.3%), hookworm (56.6%; 47.8%), asymptomatic bacteriuria/urinary tract infection (AB/UTI; 56.2%; 36.2%), cervicitis (33.3%; 6.3%), vaginal yeast (24.9%; 11.4%), Ascaris (32.5%; 17.4%), vaginal diplococci (20.4%; 31.6%), caries (19.7%; 18.2%), scabies (17.4%; 8.1%), and Trichuris (12.5%; 8.7%). Multiple regressions revealed positive associations during pregnancy (trichomoniasis and AB/UTI; diplococci and Ascaris) and lactation (yeast and scabies). Negative associations were detected in pregnancy (BV and trichomoniasis; hookworm and diplococci) and lactation (BV and yeast). Vaginal Lactobacillus reduced odds of diplococci in pregnancy and lactation, but increased Ascaris eggs per gram (epg) and odds of trichomoniasis in pregnancy and yeast in lactation. These associations raised a concern that treatment of one condition may increase the risk of another.

Antioxidant activity and polyphenol content in cultivated and wild edible fruits grown in Panama.

OBJECTIVES: The present research was undertaken to determine the antioxidant activity and total polyphenol content of cultivated and wild edible fruits consumed in Panama. MATERIALS AND METHODS: 39 cultivated and wild edible fruits antioxidant activity and total polyphenol content was assessed by using the DPPH and the Folin-Ciocalteu assays, respectively. RESULTS AND DISCUSSION: The antioxidant composition of the fruits varied between 1083.33 and 16.22 mg TEAC/100 g fresh weight. On the other hand, the total phenolic content of the 39 fruits tested ranged from 604.80 to 35.10 mg GAE/100 g FW. Ziziphus mauritania presented the highest antioxidant activity and the largest phenolic content, whereas most fruits had a moderate TEAC value. CONCLUSION: Fruits polyphenol content was strongly correlated with antioxidant properties, which pointed out the important role of these compounds in the prevention of many types of cancer, neurological ailments, and cardiovascular diseases through diverse antioxidant mechanisms.

Carotenoid composition and antioxidant activity of the raw and boiled fruit mesocarp of six varieties of Bactris gasipaes.

Total carotenoid content and composition of carotenoids of six varieties of Bactris gasipaes were determined by spectrophotometry and HPLC, with photodiode array detector. Significant differences in total carotenoid content (1.1 to 22.3 mg/100g) were detected among these varieties. Boiling the fruits for 30 minutes did not affect total carotenoid content, but did change the amount of some specific carotenoids, mainly by the production of Z-isomers. Peach palm varieties had the same carotenoids, but in different proportions, presenting mainly, all E-beta-carotene (26.2% to 47.9%), Z-gamma-carotene (18.2% to 34.3%) and Z-lycopene (10.2% to 26.8%). When antioxidant activity was evaluated using DPPH, it was observed that the variety with higher percentages of beta-carotene (54.1%) presented the higher activity. This is one of the first reports in carotenoid content and antioxidant activity in well typified varieties of Bactris gasipaes, whose results could have a positive impact in the consumption of certain peach palm varieties.

Carotenoid composition and antioxidant activity of the raw and boiled fruit mesocarp of six varieties of Bactris gasipaes / Composición de carotenoides y actividad antioxidante del mesocarpo crudo y hervido del fruto de seis variedades de Bactris gasipaes

Se determinó la concentración y composición de carotenoides a seis variedades de Bactris gasipaes, mediante espectrofotometría y HPLC con un detector de arreglo de diodos. Las diferencias en el contenido de carotenoides totales fueron significativas entre las variedades estudiadas (1.1 a 22.3 mg/100g). El hervir los frutos por 30 minutos no afectó de forma significativa el contenido de carotenoides totales, pero sí la concentración de algunos carotenoides, principalmente de los isómeros Z. Las distintas variedades presentaron los mismos carotenoides pero en diferente proporción, principalmente: todo E-ß-caroteno (26.2 por ciento - 47.9 por ciento), Z-y-caroteno (18.2 por ciento a 34.3 percent) y Z-licopeno (10.2 por ciento a 26.8 por ciento). Al evaluarse la actividad antioxidante con DPPH, se observó que la variedad con el mayor porcentaje de ß-caroteno presentó la mayor actividad. Este es uno de los primeros reportes de composición de carotenoides de Bactris gasipaes bien tipificados, cuyo resultado puede incidir directamente en el consumo de ciertas poblaciones de Bactris.

Total carotenoid content and composition of carotenoids of six varieties of Bactris gasipaes were determined by spectrophotometry and HPLC, with photodiode array detector. Significant differences in total carotenoid content (1.1 to 22.3 mg/100g) were detected among these varieties. Boiling the fruits for 30 minutes did not affect total carotenoid content, but did change the amount of some specific carotenoids, mainly by the production of Z-isomers. Peach palm varieties had the same carotenoids, but in different proportions, presenting mainly, all E-ß-carotene (26.2 percent to 47.9 percent), Z-y-carotene (18.2 percent to 34.3 percent) and Z-lycopene (10.2 percent to 26.8 percent). When antioxidant activity was evaluated using DPPH, it was observed that the variety with higher percentages of ß-carotene (54.1 percent) presented the higher activity. This is one of the first reports in carotenoid content and antioxidant activity in well typified varieties of Bactris gasipaes, whose results could have a positive impact in the consumption of certain peach palm varieties.