Age and sex-based impacts of maternal iron deficiency on offspring's cognitive function and anemia: A systematic review.

Iron deficiency is a recognized global health concern, particularly impactful during pregnancy where the mother serves as the primary source of iron for the developing fetus. Adequate maternal iron levels are crucial for fetal growth and cognitive development. This review investigates the correlation between maternal iron deficiency and cognitive impairment and anemia in offspring, considering age and gender differentials. PubMed, ScienceDirect, and Google Scholar databases were queried using keywords "maternal," "iron," "gender/sex," and "cognition." The review included studies on human and animal subjects where maternal iron deficiency was the exposure and offspring cognitive function and anemia were outcomes. Out of 1139 articles screened, fourteen met inclusion criteria. Twelve studies highlighted cognitive deficits in offspring of iron-deficient mothers, with females generally exhibiting milder impairment compared to males. Additionally, two studies noted increased anemia prevalence in offspring of iron-deficient mothers, particularly affecting males and younger individuals. The findings suggest that male offspring are at higher risk of both anemia and cognitive dysfunction during youth, while females face increased risks in adulthood. Thus, maternal iron deficiency elevates the likelihood of anemia and cognitive impairments in offspring, underscoring the importance of addressing maternal iron status for optimal child health.

Iron deficiency and its epigenetic effects on iron homeostasis.

Iron deficiency is a common micronutrient deficiency associated with metabolic changes in the levels of iron regulatory proteins, hepcidin and ferroportin. Studies have associated dysregulation of iron homeostasis to other secondary and life-threatening diseases including anaemia, neurodegeneration and metabolic diseases. Iron deficiency plays a critical role in epigenetic regulation by affecting the Fe2+/α-ketoglutarate-dependent demethylating enzymes, Ten Eleven Translocase 1-3 (TET 1-3) and Jumonji-C (JmjC) histone demethylase, which are involved in epigenetic erasure of the methylation marks on both DNA and histone tails, respectively. In this review, studies involving epigenetic effects of iron deficiency associated with dysregulation of TET 1-3 and JmjC histone demethylase enzyme activities on hepcidin/ferroportin axis are discussed.

LncRNA SNHG15: A potential therapeutic target in the treatment of colorectal cancer.

The global burden of colorectal cancer (CRC) is increasing annually. CRC could develop from genetic and phenotypic factors involving changes in gene expression. Incredibly, the human genome transcribes into non-coding RNAs, among which long non-coding RNAs (lncRNAs) signify the most crucial part of the transcriptome in multicellular organisms. lncRNAs affect gene expression at multiple levels, from transcription to protein localization and stability. Recent studies have implicated lncRNA small nucleolar RNA host gene 15 (SNHG15) in cancers occurrence and progression. Previously, an indication suggests SNHG15 overexpression triggers proliferation, metastasis, and impedes apoptosis in CRC. Further, through its activity of binding micro-RNAs, lncRNA SNHG15 modulates genes associated with CRC progression and promotes CRC resistance to chemotherapeutic drugs. Here, we reviewed recent findings on the various mechanisms and roles of lncRNA SNHG15 implicated in CRC tumorigenesis. We further highlight how SNHG15 plays a vital role in regulating critical pathways linked to the development and progression of CRC. Finally, we highlight how SNHG15 can be modulated for CRC treatments and the various therapeutic strategies to be implored when targeting SNHG15 in the context of CRC treatments. Findings from these studies present SNHG15 as a potential therapeutic target for preventing and treating CRC.

Evaluation of acute and sub-acute toxicity profile of 5-methylcoumarin-4ß-glucoside in mice.

Vernonia glaberrima leaves are traditionally used to alleviate bodily pain, skin cancer, and other skin-related disorders. The purpose of the study was to investigate the acute and sub-acute toxicity of 5-methylcoumarin-4ß-glucoside, a promising chemotherapeutic agent against colon cancer isolated from the leaves of Vernonia glaberrima. 5-methylcoumarin-4ß-glucoside was isolated from the methanol leaf extract of Vernonia glaberrima following a previously described method. The acute toxicity study involved a two-phase 24 h observation for signs of mortality and toxicity following single oral dose administration of the isolated compound. For the sub-acute study, four groups of mice, averagely aged eight weeks, were administered graded doses of the compound (250, 500 and 1000 mg/kg) or vehicle for 28 days. On the 29th day, the mice were fasted, anesthetized, euthanized, then their blood and tissues were harvested for hematological, biochemical and histopathological evaluations. There were no signs of mortality or moribund status with an increasing dose of up to 5000 mg/kg over a 24 h period in the acute study. Also, there was no evidence of toxicity on the biochemical or hematopoietic systems in the sub-acute study (p < 0.05). At the dose of 1000 mg/kg, the mice showed some distorted histology with no corresponding alterations in serum biochemicals. Overall, the results showed that 5-methylcoumarin-4ß-glucoside at dosages up to 500 mg/kg is tolerable in mice.

Prophylactic Use of Natural Products against Developmentally Programmed Metabolic Syndrome.

Parental dietary choices and/or nutritional interventions in the offspring are critical to early life development, especially during the periods of active developmental plasticity in the offspring. Exposure to a high-fructose, high-fat diet during the fetal or neonatal period predisposes the affected individuals to the development of one or more features of metabolic syndrome, such as dyslipidemia, insulin resistance, diabetes, and associated cardiovascular diseases, later in their life. Owing to the increasing global prevalence of metabolic syndrome and multiple side effects that accompany conventional medicines, much attention is directed towards medicinal plants and phytochemicals as alternative interventions. Several studies have investigated the potential of natural agents to prevent programmed metabolic syndrome. This present review, therefore, highlights an inextricable relationship between the administration of medicinal plants or phytochemicals during the intrauterine or neonatal period, and the prevention of metabolic dysfunction in adulthood, while exploring the mechanisms by which they exert such an effect. The review also identifies plant products as a novel approach to the prevention and management of metabolic syndrome.

Rodent models of metabolic disorders: considerations for use in studies of neonatal programming.

Epidemiologically, metabolic disorders have garnered much attention, perhaps due to the predominance of obesity. The early postnatal life represents a critical period for programming multifactorial metabolic disorders of adult life. Though altricial rodents are prime subjects for investigating neonatal programming, there is still no sufficiently generalised literature on their usage and methodology. This review focuses on establishing five approach-based models of neonatal rodents adopted for studying metabolic phenotypes. Here, some modelled interventions that currently exist to avoid or prevent metabolic disorders are also highlighted. We also bring forth recommendations, guidelines and considerations to aid research on neonatal programming. It is hoped that this provides a background to researchers focused on the aetiology, mechanisms, prevention and treatment of metabolic disorders.

MALAT1: A Promising Therapeutic Target for the Treatment of Metastatic Colorectal Cancer.

Cancer metastasis research has emerged in recent years as one of the most important topics of debate in the discovery and development of novel anticancer therapies. Colorectal cancer (CRC), the third most common cancer worldwide, has a high mortality rate due to recurrence and distant metastasis to the liver. Several non-coding RNAs (ncRNAs) have been linked to metastatic CRC (mCRC), including the long non-coding RNA (lncRNA) Metastasis-Associated Lung-Adenocarcinoma Transcript 1 (MALAT1). MALAT1 is an RNA that has been linked to tumor cell proliferation, progression, epithelial-mesenchymal transition (EMT), cell migration and invasion, metastasis, and survival in mammalian species. Previously, there was no convincing evidence linking MALAT1 to mCRC. Studies have shown that MALAT1 functions as a competitive endogenous RNA (ceRNA) with microRNAs (miRNAs) and interacts directly with oncogenes and proteins. This RNA also activates several signaling pathways, including Wnt/ß-catenin, PI3K/Akt/mTOR, and EMT. Meanwhile, standard chemotherapy and immunotherapy are the current treatment options for mCRC patients. However, evidence-based studies have recently demonstrated that inhibiting the MALAT1 RNA transcript can be considered as a treatment option for mCRC, highlighting the need to investigate its roles as a therapeutic target in mCRC. Thus, in this review, we looked at studies that linked MALAT1 to multiple signaling pathways implicated in mCRC, as well as its potential as a therapeutic target for the treatment of mCRC.

Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies.

The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.

Zinc Metalloproteins in Epigenetics and Their Crosstalk.

More than half a century ago, zinc was established as an essential micronutrient for normal human physiology. In silico data suggest that about 10% of the human proteome potentially binds zinc. Many proteins with zinc-binding domains (ZBDs) are involved in epigenetic modifications such as DNA methylation and histone modifications, which regulate transcription in physiological and pathological conditions. Zinc metalloproteins in epigenetics are mainly zinc metalloenzymes and zinc finger proteins (ZFPs), which are classified into writers, erasers, readers, editors, and feeders. Altogether, these classes of proteins engage in crosstalk that fundamentally maintains the epigenome's modus operandi. Changes in the expression or function of these proteins induced by zinc deficiency or loss of function mutations in their ZBDs may lead to aberrant epigenetic reprogramming, which may worsen the risk of non-communicable chronic diseases. This review attempts to address zinc's role and its proteins in natural epigenetic programming and artificial reprogramming and briefly discusses how the ZBDs in these proteins interact with the chromatin.

Effect of maternal zinc deficiency on offspring health: The epigenetic impact.

BACKGROUND: Zinc deficiency is associated with adverse effects on maternal health and pregnancy outcomes. These consequences have been reported over the years from zinc supplementation trials and observational studies whereby outcomes of maternal, foetal and infant health were measured. Owing to the importance of zinc in the functions of epigenetic enzymes, pre-clinical studies have shown that its deficiency could disrupt biological activities that involve epigenetic mechanisms in offspring. Thus, this review assessed the link between epigenetics and the effects of maternal zinc deficiency on the offspring's health in animal studies. METHODS: Research articles were retrieved without date restriction from PubMed, Web of Science, ScienceDirect, and Google Scholar databases, as well as reference lists of relevant articles. The search terms used were "zinc deficiency", "maternal zinc deficiency", "epigenetics", and "offspring." Six studies met the eligibility criteria and were reviewed. RESULTS: All the eligible studies reported maternal zinc deficiency and observed changes in epigenetic markers on the progeny during prenatal and postnatal stages of development. The main epigenetic markers reported were global and gene specific methylation and/ or acetylation. The epigenetic changes led to mortality, disruption in development, and risk of later life diseases. CONCLUSION: Maternal zinc deficiency is associated with epigenetic modifications in offspring, which induce pathologies and increase the risk of later life diseases. More research and insight into the epigenetic mechanisms could spring up new approaches to combat the associated disease conditions.

Compositional analyses of white, brown and germinated forms of popular Malaysian rice to offer insight into the growing diet-related diseases.

Diet-related metabolic diseases, and especially obesity, are metabolic disorders with multifactorial aetiologies. Diet has been a cornerstone in both the aetiology and management of this metabolic disorders. Rice, a staple food for over half of the world's population, could be exploited as part of the solution to check this menace which has been skyrocketing in the last decade. The present study investigated nine forms of rice from three widely grown Malaysian rice cultivars for in vitro and in vivo (glycaemic index and load) properties that could translate clinically into a lower predisposition to diet-related diseases. The germinated brown forms of MRQ 74 and MR 84 rice cultivars had high amylose content percentages (25.7% and 25.0%), high relative percentage antioxidant scavenging abilities of 85.0% and 91.7%, relatively low glycaemic indices (67.6 and 64.3) and glycaemic load (32.3 and 30.1) values, and modest glucose uptake capabilities of 33.69% and 31.25%, respectively. The results show that all things being equal, rice cultivars that are germinated and high in amylose content when compared to their white and low amylose counterparts could translate into a lower predisposition to diet-related diseases from the dietary point of view in individuals who consume this cereal as a staple food.

Predisposition to insulin resistance and obesity due to staple consumption of rice: Amylose content versus germination status.

Type 2 diabetes is a metabolic disorder with established, well-defined precursors. Obesity and insulin resistance are amongst most important factors in predisposition to diabetes. Rice is a staple for about half the global population and its consumption has been strongly linked with diabetogenesis. We assert that tackling the prevalence of predisposing factors by modifying certain rice cultivars could reduce the global burden of obesity and insulin resistance, and by extension type 2 diabetes. Several rice cultivars with various properties were fed to nulliparous rats (five weeks old at the start of the experiment) for 90 days. They were then returned to a diet of standard pellets and mated with males raised on a standard diet. The resulting pups and dams were investigated for obesity and insulin resistance markers. We found that germination did more to reduce predisposition to obesity and insulin resistance than high amylose content. The combined reducing effect of germination and high amylose content on predisposition to obesity and insulin resistance was greater than the sum of their independent effects. Polished (white) rice with a low amylose content predisposed dams on a high-fat diet to markers of insulin resistance and obesity and this predisposition was inherited (in biochemical terms) by their F1 offspring. Overall, the results suggest that harnessing the beneficial properties of germination and amylose in rice would reduce the burden of obesity and insulin resistance, which are known to be key risk factors for development of type 2 diabetes.