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Cell Reports Jun 2024The intestinal environment facilitates HIV-1 infection via mechanisms involving the gut-homing vitamin A-derived retinoic acid (RA), which transcriptionally reprograms...
The intestinal environment facilitates HIV-1 infection via mechanisms involving the gut-homing vitamin A-derived retinoic acid (RA), which transcriptionally reprograms CD4 T cells for increased HIV-1 replication/outgrowth. Consistently, colon-infiltrating CD4 T cells carry replication-competent viral reservoirs in people with HIV-1 (PWH) receiving antiretroviral therapy (ART). Intriguingly, integrative infection in colon macrophages, a pool replenished by monocytes, represents a rare event in ART-treated PWH, thus questioning the effect of RA on macrophages. Here, we demonstrate that RA enhances R5 but not X4 HIV-1 replication in monocyte-derived macrophages (MDMs). RNA sequencing, gene set variation analysis, and HIV interactor NCBI database interrogation reveal RA-mediated transcriptional reprogramming associated with metabolic/inflammatory processes and HIV-1 resistance/dependency factors. Functional validations uncover post-entry mechanisms of RA action including SAMHD1-modulated reverse transcription and CDK9/RNA polymerase II (RNAPII)-dependent transcription under the control of mammalian target of rapamycin (mTOR). These results support a model in which macrophages residing in the intestine of ART-untreated PWH contribute to viral replication/dissemination in an mTOR-sensitive manner.
PubMed: 38943643
DOI: 10.1016/j.celrep.2024.114414 -
Health Care Science Feb 2024Early childhood development (ECD) centres are important community hubs in South Africa and act as sites for community detection of childhood nutrition problems. This...
INTRODUCTION
Early childhood development (ECD) centres are important community hubs in South Africa and act as sites for community detection of childhood nutrition problems. This study aimed to assess the ability of trained ECD practitioners with optimal support to correctly classify the nutritional status of infants and young children at ECD centres in the Nelson Mandela Bay.
METHODS
A descriptive, cross-sectional study was used to collect data from 1645 infants and children at 88 ECD centres. Anthropometric measurements were taken by trained fieldworkers and growth monitoring and promotion infrastructure was audited at ECD centres.
RESULTS
Of the sample, 4.4% ( = 72) were underweight by weight for age Z-score (WAZ < -2) and 0.8% ( = 13) were severely underweight (WAZ < -3). Results showed that 13.1% ( = 214) were stunted by height for age Z-score (HAZ < -2) and 4.5% ( = 74) were severely stunted (HAZ < -3). The prevalence of moderate acute malnutrition was 1.2% and severe acute malnutrition was 0.5%, while the prevalence of overweight was 9.2% and the prevalence of obesity was 4%. A significant level of agreement between the correct interpretation and the ECD practitioners' interpretation was observed across all the anthropometric indicators investigated. The true positive wasting cases had a mean mid-upper arm circumference (MUAC) of 14.6 cm, which may explain the high false negative rate found in terms of children identified with wasting, where ECD practitioners fail to use the weight for height Z-score (WHZ) interpretation for screening.
CONCLUSION
By using ECD centres as hub to screen for malnutrition, it may contribute to the early identification of failure to thrive among young children. Although it was concerning that trained ECD practitioners are missing some children with an unacceptably high false negative rate, it may have been due to the fact that wasting in older children cannot be identified with MUAC alone and that accurate WFH plotting is needed. Onsite mentorship by governmental health workers may provide ECD practitioners with more confidence to screen children for growth failure based on regular WFH measurements. Moreover, ECD practitioners will be more confident to monitor the Road to Health booklets for missed vaccinations, vitamin A and deworming opportunities.
PubMed: 38939170
DOI: 10.1002/hcs2.83 -
Nutrients Jun 2024The relationship between vitamin A supplementation and myopia has been a topic of debate, with conflicting and inconclusive findings. We aimed to determine whether there... (Meta-Analysis)
Meta-Analysis
The relationship between vitamin A supplementation and myopia has been a topic of debate, with conflicting and inconclusive findings. We aimed to determine whether there is a causal relationship between vitamin A supplementation and the risk of myopia using Mendelian randomization (MR) and meta-analytical methods. Genetic variants from the UK Biobank and FinnGen studies associated with the response to vitamin A supplementation were employed as instrumental variables to evaluate the causal relationship between vitamin A supplementation and myopia. Fixed-effects meta-analysis was then used to combine MR estimates from multiple sources for each outcome. The meta-analysis of MR results found no convincing evidence to support a direct causal relationship between vitamin A supplementation and myopia risk (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.82-1.20, = 0%, = 0.40). The analysis of three out of the four sets of MR analyses indicated no direction of causal effect, whereas the other set of results suggested that higher vitamin A supplementation was associated with a lower risk of myopia (OR = 0.002, 95% CI 1.17 × 10-3.099, = 0.096). This comprehensive MR study and meta-analysis did not find valid evidence of a direct association between vitamin A supplementation and myopia. Vitamin A supplementation may not have an independent effect on myopia, but intraocular processes associated with vitamin A may indirectly contribute to its development.
Topics: Humans; Myopia; Mendelian Randomization Analysis; Vitamin A; Dietary Supplements; Polymorphism, Single Nucleotide; Risk Factors; Odds Ratio
PubMed: 38931287
DOI: 10.3390/nu16121933 -
Nutrients Jun 2024Cardiovascular diseases (CVD) are the leading cause of death worldwide, influenced by the interaction of factors, including age, sex, genetic conditions,...
Cardiovascular diseases (CVD) are the leading cause of death worldwide, influenced by the interaction of factors, including age, sex, genetic conditions, overweight/obesity, hypertension, an abnormal lipid profile, vitamin deficiencies, diabetes, and psychological factors. This study aimed to assess the relationships between psychosocial and nutritional factors in a group of 61 patients with CVD (i.e., atherosclerosis, hypertension, ischemic heart disease, and myocardial infarction) and their possible impact on the course of the disease. The plasma concentrations of vitamins A, E, D, and β-carotene were determined using validated HPLC-MS/MS, while the lipid profile was analyzed enzymatically. Psychosocial factors and nutritional behaviors were assessed using author-designed questionnaires. Over 50% of patients had 25-OH-D3 and retinol deficiencies, while >85% of patients exhibited significant deficiencies in α-tocopherol and β-carotene. The lipid profile showed no specific relationship with any particular CVD. Dietary behavior minimally impacted biochemical parameters except for higher β-carotene concentrations in the group with higher fruit and vegetable intake. The negative impact of the CVD on selected parameters of quality of life was noticed. To increase the effectiveness of the prevention and treatment of CVD, the need for interdisciplinary cooperation observed between doctors, psychologists, and specialists in human nutrition seems to be justified.
Topics: Humans; Female; Male; Middle Aged; Cardiovascular Diseases; Aged; Vitamins; Nutritional Status; beta Carotene; Quality of Life; Adult; Vitamin A; Feeding Behavior; Diet; Lipids; Vitamin E
PubMed: 38931221
DOI: 10.3390/nu16121866 -
Plants (Basel, Switzerland) Jun 2024Unraveling the intricate physiological and biochemical intricacies associated with female dominance in grape berries across diverse developmental stages is imperative...
Unraveling the intricate physiological and biochemical intricacies associated with female dominance in grape berries across diverse developmental stages is imperative for optimizing grape production and ensuring the attainment of high-quality yields. This study conducted a thorough analysis of grape berries across phenological stages (BBCH-79, BBCH-81, BBCH-89) and cultivars. At BBCH-89, Bozcaada Çavuşu*Vasilâki demonstrated the highest berry weight and total soluble solids (TSS) levels, emphasizing its enological potential. Acidity peaked at BBCH-79 (28.16) and declined at BBCH-89 (6.11), signaling a shift towards lower acidity in later stages. Bozcaada Çavuşu*Vasilâki consistently showed the highest maturity index (MI). Mineral content variations were observed across nitrogen (N), calcium (Ca), potassium (K), phosphorus (P), magnesium (Mg), sulfur (S), iron (Fe), manganese (Mn), boron (B), zinc (Zn), and copper (Cu), with Bozcaada Çavuşu*Vasilâki often having the highest concentrations, particularly in potassium, calcium, and boron. Hormonal analysis revealed a significant surge in concentrations at BBCH-89, with Bozcaada Çavuşu*Vasilâki standing out. Notably, Indole-3-acetic acid (IAA) concentrations increased by 106%, and abscisic acid (ABA) levels peaked at BBCH-79 with a 38% increase in Bozcaada Çavuşu*Kuntra. Sugar content analysis showed variations in fructose, glucose, sucrose, rhamnose, xylose, galactose, and arabinose levels across sampling times and cultivars. Bozcaada Çavuşu*Vasilâki consistently exhibited higher sugar levels, especially at BBCH-81 and BBCH-89. Vitamin concentrations varied temporally and among cultivars, with BBCH-89 displaying the highest vitamin A concentration (6.24 mg/100 g FW), and Bozcaada Çavuşu*Vasilâki often exhibiting maximum values for vitamin B1, B2, B6, and C. Further research and targeted cultivation practices focusing on the unique attributes of Bozcaada Çavuşu*Vasilâki could enhance grape production efficiency, emphasizing its potential contribution to achieving consistently high-quality yields across various phenological stages.
PubMed: 38931044
DOI: 10.3390/plants13121612 -
Children (Basel, Switzerland) May 2024Food insecurity is a public health concern that affects children worldwide, yet it represents a particular burden for low- and middle-income countries. This study aims...
Food insecurity is a public health concern that affects children worldwide, yet it represents a particular burden for low- and middle-income countries. This study aims to utilize machine learning to identify the associations between food insecurity and nutrient intake among children aged 5 to 18 years. The study's sample encompassed 1040 participants selected from a 2022 food insecurity household conducted in the West Bank, Palestine. The results indicated that food insecurity was significantly associated with dietary nutrient intake and sociodemographic factors, such as age, gender, income, and location. Indeed, 18.2% of the children were found to be food-insecure. A significant correlation was evidenced between inadequate consumption of various nutrients below the recommended dietary allowance and food insecurity. Specifically, insufficient protein, vitamin C, fiber, vitamin B12, vitamin B5, vitamin A, vitamin B1, manganese, and copper intake were found to have the highest rates of food insecurity. In addition, children residing in refugee camps experienced significantly higher rates of food insecurity. The findings emphasize the multilayered nature of food insecurity and its impact on children, emphasizing the need for personalized interventions addressing nutrient deficiencies and socioeconomic factors to improve children's health and well-being.
PubMed: 38929205
DOI: 10.3390/children11060625 -
Foods (Basel, Switzerland) Jun 2024The present study explored the nutritional composition, phytochemicals analysis, and antioxidant capacity of two indigenous varieties of red and green water chestnut...
The present study explored the nutritional composition, phytochemicals analysis, and antioxidant capacity of two indigenous varieties of red and green water chestnut (WCN) fruit grown in Pakistan. Accordingly, this study was designed to investigate the proximate composition (moisture, ash, fiber, proteins, fat, and energy), physicochemical properties (pH, °Brix, and glycemic index), minerals, and vitamins. The methanolic extracts of WCN fruits were explored for phytochemicals (total phenolic and flavonoid content), and antioxidant potential was examined in vitro by 1,1-diphenyl-2-picrylhydrazyl radical scavenging capacity (DPPH) and Ferric reducing antioxidant power (FRAP). Quantitative determination of mineral (sodium, potassium, calcium, phosphorus, iron, manganese, copper, and zinc) and vitamin (vitamin C, vitamin B6, vitamin B2, vitamin B3, vitamin A, and -Carotene) composition was also assessed. Based on the findings, the proximate compositions of WCN green and red varieties varied greatly as WCN green contained significantly higher protein (1.72%), fat (0.65%), dietary fiber (2.21%), moisture (70.23%), ash (1.16%), and energy content (112.8 Kcal) than WCN red. In WCN green, the macro-micromineral concentrations were significantly higher than WCN red. Among the minerals analyzed, potassium was the most abundant mineral found in both varieties. Levels of vitamin C, B, A, and -Carotene were significantly higher in WCN green. In this study, methanolic extract showed higher extraction efficiency than acetone, ethanol, and distilled water. WCN green had a significantly higher quantum of total phenolic (91.13 mg GAE/g) and total flavonoid (36.6 mg QE/g) and presented significantly higher antioxidant activity than the WCN red. This study showed that, among both varieties, WCN green extract has therapeutic potential against free radical mediated health conditions and suggested the potential use of this fruit as a source of natural antioxidants in nutraceuticals.
PubMed: 38928824
DOI: 10.3390/foods13121883 -
International Journal of Molecular... Jun 2024All- retinoic acid (ATRA), the major active metabolite of all- retinol (vitamin A), is a key hormonal signaling molecule. In the adult organism, ATRA has a widespread... (Review)
Review
All- retinoic acid (ATRA), the major active metabolite of all- retinol (vitamin A), is a key hormonal signaling molecule. In the adult organism, ATRA has a widespread influence on processes that are crucial to the growth and differentiation of cells and, in turn, the acquisition of mature cell functions. Therefore, there is considerable potential in the use of retinoids to treat diseases. ATRA binds to the retinoic acid receptors (RAR) which, as activated by ATRA, selectively regulate gene expression. There are three main RAR isoforms, RARα, RARβ, and RARγ. They each have a distinct role, for example, RARα and RARγ regulate myeloid progenitor cell differentiation and hematopoietic stem cell maintenance, respectively. Hence, targeting an isoform is crucial to developing retinoid-based therapeutics. In principle, this is exemplified when ATRA is used to treat acute promyelocytic leukemia (PML) and target RARα within PML-RARα oncogenic fusion protein. ATRA with arsenic trioxide has provided a cure for the once highly fatal leukemia. Recent in vitro and in vivo studies of RARγ have revealed the potential use of agonists and antagonists to treat diseases as diverse as cancer, heterotopic ossification, psoriasis, and acne. During the final drug development there may be a need to design newer compounds with added modifications to improve solubility, pharmacokinetics, or potency. At the same time, it is important to retain isotype specificity and activity. Examination of the molecular interactions between RARγ agonists and the ligand binding domain of RARγ has revealed aspects to ligand binding that are crucial to RARγ selectivity and compound activity and key to designing newer compounds.
Topics: Humans; Retinoic Acid Receptor gamma; Receptors, Retinoic Acid; Animals; Tretinoin; Protein Binding; Leukemia, Promyelocytic, Acute; Antineoplastic Agents
PubMed: 38928275
DOI: 10.3390/ijms25126568 -
Reproductive Biology and Endocrinology... Jun 2024Testis is an immune privileged organ, which prevents the immune response against sperm antigens and inflammation. Testicular cells responsible for immune tolerance are...
BACKGROUND
Testis is an immune privileged organ, which prevents the immune response against sperm antigens and inflammation. Testicular cells responsible for immune tolerance are mainly Sertoli cells, which form the blood-testis barrier and produce immunosuppressive factors. Sertoli cells prevent inflammation in the testis and maintain immune tolerance by inhibiting proliferation and inducing lymphocyte apoptosis. It has been shown that 9-cis-retinoic acid (9cRA) blocks ex vivo apoptosis of peripheral blood lymphocytes and promotes the differentiation of Treg cells in the gut. However, the role of retinoid signaling in regulating the immune privilege of the testes remains unknown.
OBJECTIVE
The aim of this study was to determine whether 9cRA, acting via the retinoic acid receptors (RAR) and the retinoic X receptors (RXR), controls the immunomodulatory functions of Sertoli cells by influencing the secretion of anti-inflammatory/pro-inflammatory factors, lymphocyte physiology and Treg cell differentiation.
METHODS
Experiments were performed using in vitro model of co-cultures of murine Sertoli cells and T lymphocytes. Agonists and antagonists of retinoic acid receptors were used to inhibit/stimulate retinoid signaling in Sertoli cells.
RESULTS
Our results have demonstrated that 9cRA inhibits the expression of immunosuppressive genes and enhances the expression of pro-inflammatory factors in Sertoli cells and lymphocytes, increases lymphocyte viability and decreases apoptosis rate. Moreover, we have found that 9cRA blocks lymphocyte apoptosis acting through both RAR and RXR and inhibiting FasL/Fas/Caspase 8 and Bax/Bcl-2/Caspase 9 pathways. Finally, we have shown that 9cRA signaling in Sertoli cells inhibits Treg differentiation.
CONCLUSION
Collectively, our results indicate that retinoid signaling negatively regulates immunologically privileged functions of Sertoli cells, crucial for ensuring male fertility. 9cRA inhibits lymphocyte apoptosis, which can be related to the development of autoimmunity, inflammation, and, in consequence, infertility.
Topics: Male; Animals; Sertoli Cells; T-Lymphocytes, Regulatory; Signal Transduction; Mice; Tretinoin; Cell Differentiation; Alitretinoin; Receptors, Retinoic Acid; Apoptosis; Coculture Techniques; Mice, Inbred C57BL; Cells, Cultured; Immunomodulation
PubMed: 38926848
DOI: 10.1186/s12958-024-01246-2 -
Scientific Reports Jun 2024Dietary diversity among children is a crucial factor influencing their nutritional status; therefore, this paper uses data from four rounds of the Cambodia Demographic...
Dietary diversity among children is a crucial factor influencing their nutritional status; therefore, this paper uses data from four rounds of the Cambodia Demographic and Health Survey (CDHS) to examine the minimum dietary diversity among children aged 6-23 months. Multilevel binary regression is used to evaluate the variation in minimum dietary diversity at the cluster and province levels. The results show that nearly half of Cambodian children consistently lacked access to vitamin A-rich fruits and vegetables. Although the prevalence of inadequate minimum dietary diversity (MDD) among children significantly dropped from 76% in 2005 to 51% in 2021-2022, it is still high and needs attention. A decomposition analysis (Blinder-Oaxaca decomposition) was further used to understand the drivers of this temporal change in dietary diversity. The empirical results show that clusters represented the most significant source of geographic variation with respect to all eight food groups and MDD. Nutritional policy should improve education and awareness, reduce socio-economic disparities, leverage media, and promote full antenatal care to improve dietary diversity in Cambodia. Initiatives targeting the enhancement of insufficient minimum dietary diversity intake should encompass individual aspects and be customized to suit geographic and community settings.
Topics: Humans; Cambodia; Infant; Female; Diet; Male; Health Surveys; Nutritional Status; Fruit; Vegetables; Socioeconomic Factors
PubMed: 38926408
DOI: 10.1038/s41598-024-64714-0