-
Jornal de Pediatria 2024Malnutrition is characterized by situations of undernutrition and obesity resulting from the lack of micronutrients with the greatest impact on children. The objective... (Review)
Review
OBJECTIVE
Malnutrition is characterized by situations of undernutrition and obesity resulting from the lack of micronutrients with the greatest impact on children. The objective of this review was to highlight inadequate food consumption, food security, and nutritional inadequacy leading to hidden hunger and the prevention and treatment of the main micronutrient deficiencies in Brazil.
DATA SOURCE
Literature review carried out through a bibliographic survey in PubMed (National Library of Medicine, United States), Lilacs (Latin American and Caribbean Literature in Health Sciences), and SciELO (Scientific Electronic Library Online) databases. The search used the terms Occult hunger, (hidden hunger), and Child, in articles published between 2013 and 2023 in Portuguese, English and Spanish. The search was performed on 06/25/2023.
DATA SYNTHESIS
The lack of micronutrients can occur insidiously and without clinical manifestations, being called hidden hunger. The prevention of nutritional deficiencies is part of the recommended actions in childcare, with healthy eating. Studies were cited related to macro and micronutrient intake deficiencies, both national and international, and strategies to improve micronutrient intake, including routine supplementation of iron, and vitamins D and A. The diagnosis, prevention, and treatment of the main deficiencies in Brazil (iron, vitamin A, vitamin D, zinc), currently adopted, concluded the topic.
CONCLUSION
Zero hunger and zero obesity must be part of the same policy, together with a nutritional education program.
Topics: Child; Humans; Hunger; Malnutrition; Vitamin A; Micronutrients; Obesity; Iron
PubMed: 37918810
DOI: 10.1016/j.jped.2023.08.009 -
Journal of Advanced Research Jul 2023Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various...
INTRODUCTION
Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME).
METHODS
Ginsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, which were prepared by the thin-film hydration method. The stability of the Rg3-PTX-LPs was evaluated by particle size analysis through dynamic light scattering. The active targeting effect of Rg3-based liposomes was examined in an MCF-7/T xenograft model by an in a vivo imaging system. To evaluate the antitumor activity and mechanism of Rg3-PTX-LP, MTT, apoptosis assays, TAM regulation, and TME remodeling were performed in MCF-7/T cells in vitro and in vivo.
RESULTS
Rg3-PTX-LPs could specifically distribute to MCF7/T cancer cells and TME simultaneously, mainly through the recognition of GLUT-1. The drug resistance reversing capability and in vivo antitumor effect of Rg3-PTX-LPs were significantly improved compared with conventional cholesterol liposomes. The TME remodeling mechanisms of Rg3-PTX-LPs included inhibiting IL-6/STAT3/p-STAT3 pathway activation to repolarize protumor M2 macrophages to antitumor M1 phenotype, suppressing myeloid-derived suppressor cells (MDSCs), decreasing tumor-associated fibroblasts (TAFs) and collagen fibers in TME, and promoting apoptosis of tumor cells. Hence, through the dual effects of targeting tumor cells and TME remodeling, Rg3-PTX-LPs achieved a high tumor inhibition rate of 90.3%.
CONCLUSION
Our multifunctional Rg3-based liposome developed in the present study offered a promising strategy for rescuing the drug resistance tumor treatment.
Topics: Humans; Paclitaxel; Liposomes; Ginsenosides; Tumor Microenvironment; Lipopolysaccharides; Neoplasms
PubMed: 36167294
DOI: 10.1016/j.jare.2022.09.007 -
Advanced Science (Weinheim,... Apr 2024Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process...
Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3β (p-GSK-3β), thereby promoting β-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic β-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.
Topics: Animals; Mice; beta Catenin; Fibrosis; Glycogen Synthase Kinase 3 beta; Kidney; Kidney Diseases; Wikstroemia; Diterpenes; cdc42 GTP-Binding Protein
PubMed: 38240457
DOI: 10.1002/advs.202307850 -
Nature Communications Oct 2023High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA),...
High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tissues and 73 cell lines models, here we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and strongly associated with CIN and genome subclonality. Cell-based studies showed that high-prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel, the commonest treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.
Topics: Humans; Female; Ovarian Neoplasms; Paclitaxel; Centrosome; Cystadenocarcinoma, Serous
PubMed: 37845213
DOI: 10.1038/s41467-023-41840-3 -
Nutrients Jul 2023Recent research supports previous contentions that encapsulating vitamins and minerals with liposomes help improve overall bioavailability. This study examined whether... (Randomized Controlled Trial)
Randomized Controlled Trial
Recent research supports previous contentions that encapsulating vitamins and minerals with liposomes help improve overall bioavailability. This study examined whether ingesting a liposomal multivitamin and mineral supplement (MVM) differentially affects the appearance and/or clearance of vitamins and minerals in the blood compared to a non-liposomal MVM supplement. In a double-blind, randomized, and counterbalanced manner, 34 healthy men and women fasted for 12 h. Then, they ingested a non-liposomal (NL) or liposomal (L) MVM supplement and a standardized snack. Venous blood samples were obtained at 0, 2, 4, and 6 h after MVM ingestion and analyzed for a panel of vitamins and minerals. Plasma levels of vitamins and minerals and mean changes from baseline with 95% confidence intervals (CIs) were analyzed using general linear model statistics with repeated measures. The observed values were also entered into pharmacokinetic analysis software and analyzed through univariate analysis of variance with repeated measure contrasts. The results revealed an overall treatment x time interaction effect among the vitamins and minerals evaluated ( = 0.051, ηp2 = 0.054, moderate effect). Differences between treatments were also observed in volume distribution area (vitamin E, iron), median residence time (vitamin E, iron), volume distribution area (iron), volume of distribution steady state (vitamin A, E, iron), clearance rates (vitamin A, E), elimination phase half-life (vitamin E, iron), distribution/absorption phase intercept (vitamin A), and distribution/absorption phase slope and rate (vitamin C, calcium). Vitamin volume distribution was lower with liposomal MVM ingestion than non-liposomal MVM sources, suggesting greater clearance and absorption since similar amounts of vitamins and minerals were ingested. These findings indicate that coating a MVM with liposomes affects individual nutrient pharmacokinetic profiles. Additional research should evaluate how long-term supplementation of liposomal MVM supplements may affect vitamin and mineral status, nutrient function, and/or health outcomes.
Topics: Female; Humans; Male; Dietary Supplements; Iron; Liposomes; Minerals; Vitamin A; Vitamin E; Vitamin K; Vitamins; Double-Blind Method
PubMed: 37447400
DOI: 10.3390/nu15133073 -
Molecular Cancer Therapeutics Nov 2023Immune checkpoint inhibition combined with chemotherapy is currently approved as first-line treatment for patients with advanced PD-L1-positive triple-negative breast...
Immune checkpoint inhibition combined with chemotherapy is currently approved as first-line treatment for patients with advanced PD-L1-positive triple-negative breast cancer (TNBC). However, a significant proportion of metastatic TNBC is PD-L1-negative and, in this population, chemotherapy alone largely remains the standard-of-care and novel therapeutic strategies are needed to improve clinical outcomes. Here, we describe a triple combination of anti-PD-L1 immune checkpoint blockade, epigenetic modulation thorough bromodomain and extra-terminal (BET) bromodomain inhibition (BBDI), and chemotherapy with paclitaxel that effectively inhibits both primary and metastatic tumor growth in two different syngeneic murine models of TNBC. Detailed cellular and molecular profiling of tumors from single and combination treatment arms revealed increased T- and B-cell infiltration and macrophage reprogramming from MHCIIlow to a MHCIIhigh phenotype in mice treated with triple combination. Triple combination also had a major impact on gene expression and chromatin profiles shifting cells to a more immunogenic and senescent state. Our results provide strong preclinical evidence to justify clinical testing of BBDI, paclitaxel, and immune checkpoint blockade combination.
Topics: Humans; Animals; Mice; Triple Negative Breast Neoplasms; B7-H1 Antigen; Immune Checkpoint Inhibitors; Nuclear Proteins; Transcription Factors; Paclitaxel; Immunotherapy
PubMed: 37676980
DOI: 10.1158/1535-7163.MCT-23-0303 -
Notch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5.Nature Communications Sep 2023Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of...
Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of cardiac valves and septa. However, little is known about the molecular mechanism of endocardial-hematopoietic transition. In the current study, we identified the regulatory network of endocardial hematopoiesis. Signal network analysis from scRNA-seq datasets revealed that genes in Notch and retinoic acid (RA) signaling are significantly downregulated in Nkx2-5-null endocardial cells. In vivo and ex vivo analyses validate that the Nkx2-5-Notch axis is essential for the generation of both hemogenic and cushion endocardial cells, and the suppression of RA signaling via Dhrs3 expression plays important roles in further differentiation into macrophages. Genetic ablation study revealed that these macrophages are essential in cardiac valve remodeling. In summary, the study demonstrates that the Nkx2-5/Notch/RA signaling plays a pivotal role in macrophage differentiation from hematopoietic progenitors.
Topics: Endocardium; Macrophages; Histiocytes; Cell Differentiation; Tretinoin
PubMed: 37669937
DOI: 10.1038/s41467-023-41039-6 -
Marine Drugs Sep 2023Dictyotaceae algae have gained recognition as prolific producers of diterpenes, which are molecules with significant biotechnological potential. These diterpenes hold... (Review)
Review
Dictyotaceae algae have gained recognition as prolific producers of diterpenes, which are molecules with significant biotechnological potential. These diterpenes hold immense promise as potential active drug components, making the algae a compelling area of study. The present review aims to present the latest advancements in understanding the biopotential of Brazilian Dictyota and Canistrocarpus brown algae, shedding light on the remarkable diversity and the biological and pharmacological potential of the secondary metabolites they produce. A total of 78 articles featuring 26 distinct diterpenes are reported in this review, with their antiviral potential being the mosthighlighted biological activity. Despite considerable research on these algae and their diterpenes, significant knowledge gaps persist. Consequently, the present review is poised to serve as a pivotal resource for researchers who are actively engaged in the pursuit of active diterpenes beyond the immediate purview. Furthermore, it holds the potential to catalyze an increase in research endeavors centered around these algal species within the geographical confines of the Brazilian coastline. Also, it assumes a critical role in directing future scientific explorations toward a better comprehension of these compounds and their ecological implications.
Topics: Brazil; Phaeophyceae; Antiviral Agents; Biotechnology; Diterpenes
PubMed: 37755097
DOI: 10.3390/md21090484 -
International Journal of Molecular... Dec 2023species are important sources of polycyclic and macrocyclic diterpenes, which have been the focus of natural-product-based drug research due to their relevant... (Review)
Review
species are important sources of polycyclic and macrocyclic diterpenes, which have been the focus of natural-product-based drug research due to their relevant biological properties, including anticancer, multidrug resistance reversal, antiviral, and anti-inflammatory activities. Premyrsinane, cyclomyrsinane, and myrsinane diterpenes are generally and collectively designated as myrsinane-type diterpenes. These compounds are derived from the macrocyclic lathyrane structure and are characterized by having highly oxygenated rearranged polycyclic systems. This review aims to describe and summarize the distribution and diversity of 220 myrsinane-type diterpenes isolated in the last four decades from about 20 species. Some myrsinane diterpenes obtained from are also described. Discussion on their plausible biosynthetic pathways is presented, as well as isolation procedures and structural elucidation using nuclear magnetic resonance spectroscopy. Furthermore, the most important biological activities are highlighted, which include cytotoxic and immunomodulatory activities, the modulation of efflux pumps, the neuroprotective effects, and the inhibition of enzymes such as urease, HIV-1 reverse transcriptase, and prolyl endopeptidase, among other biological effects.
Topics: Diterpenes; Euphorbia; Immunomodulation; Jatropha; Prolyl Oligopeptidases
PubMed: 38203318
DOI: 10.3390/ijms25010147 -
Frontiers in Immunology 2023Vitamin A has long been associated with bladder cancer, and many exogenous vitamin A supplements, vitamin A derivatives, and synthetic drugs have been investigated over... (Review)
Review
Vitamin A has long been associated with bladder cancer, and many exogenous vitamin A supplements, vitamin A derivatives, and synthetic drugs have been investigated over the years. However, the effectiveness of these strategies in clinical practice has not met expectations, and they have not been widely adopted. Recent medical research on intestinal flora has revealed that bladder cancer patients exhibit reduced serum vitamin A levels and an imbalance of gut microbiota. In light of the close relationship between gut microbiota and vitamin A, one can speculate that a complex regulatory mechanism exists between the two in the development and occurrence of bladder cancer. As such, further exploration of their interaction in bladder cancer may help guide the use of vitamin A for preventive purposes. During the course of this review, attention is paid to the influence of intestinal microbiota on the vitamin A metabolism and the RA signaling pathway, as well as the mutual promotion relationships between them in the prevention of bladder cancer, In addition, it emphasizes the importance of intestinal microbiota for bladder cancer prevention and treatment.
Topics: Humans; Gastrointestinal Microbiome; Vitamin A; Urinary Bladder Neoplasms; Biomedical Research; Dietary Supplements
PubMed: 37711628
DOI: 10.3389/fimmu.2023.1252616