Intergenerational Impact of Parental Zinc Deficiency on Metabolic and Redox Outcomes in Drosophila melanogaster.

Zinc deficiency is a common nutritional disorder with detrimental health consequences. Whether parental zinc deficiency induces intergenerational effects remains largely unknown. We investigated the effects of a combined maternal and paternal zinc deficiency on offspring's metabolic outcomes and gene expression changes in Drosophila melanogaster. The parent flies were raised on zinc-deficient diets throughout development, and their progeny were assessed. Offspring from zinc-deprived parents exhibited a significant (p < 0.05) increase in body weight and whole-body zinc levels. They also displayed disrupted glucose metabolism, altered lipid homeostasis, and diminished activity of antioxidant enzymes. Gene expression analysis revealed significant (p < 0.05) alterations in zinc transport genes, with increases in mRNA levels of dZIP1 and dZnT1 for female and male offspring, respectively. Both sexes exhibited reduced dZnT35C mRNA levels and significant (p < 0.05) increases in the mRNA levels of DILP2 and proinflammatory markers, Eiger and UPD2. Overall, female offspring showed higher sensitivity to parental zinc deficiency. Our findings underscore zinc's crucial role in maintaining health and the gender-specific responses to zinc deficiency. There is the need for further exploration of the underlying mechanisms behind these intergenerational effects.

Neurotoxic Snakebites in Africa: Clinical Implications, Therapeutic Strategies, and Antivenom Efficacy.

Snakebite is a significant health concern in Africa, particularly due to neurotoxic envenomation which can lead to neuromuscular paralysis and respiratory failure. In Nigeria, snakes from the Elapidae family are a notable cause of envenomation cases, though these incidents are underreported. This review examined case reports of neurotoxic envenomation in Africa, highlighting the clinical impacts and the efficacy of available antivenoms. Preclinical studies showed that the polyvalent antivenom from the South African Institute for Medical Research (SAIMR) was highly effective against neurotoxicity with a protective efficacy (R) of 1346.80 mg/mL, while clinical assessment emphasized the need for high-dose antivenom therapy along with supportive measures like mechanical ventilation. Unlike hemorrhagic envenomation, where antivenom promptly resolves bleeding, neurotoxic cases often require additional interventions. The review underscores the necessity for tailored approaches in antivenom therapy to address the complexities of neurotoxic snakebites and reduce their public health burden in Africa.

Transgenerational impact of maternal zinc deficiency on offspring metabolic outcomes in Drosophila melanogaster.

Maternal zinc deficiency significantly influences fetal development and long-term health outcomes, yet its transgenerational effects remain poorly understood. This study aims to investigate the transgenerational effects of maternal zinc deficiency on metabolic outcomes in Drosophila melanogaster. Zinc deficiency was induced in Drosophila by incorporating TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine) into their diet. Offspring (F1 to F3) were maintained on a standard diet for subsequent analyses. Various metabolic markers, including glucose, trehalose, glycogen, and triglyceride levels, were assessed, and gene expression analyses were conducted to examine the molecular responses across generations. Significant reductions in locomotor performance in female F1 flies and increased body weight in the F2 generation were observed. Maternal zinc deficiency exhibited gender- and generation-specific impacts on metabolic markers. Notably, an adaptive response in the F3 generation included increased catalase activity and total antioxidant capacity, along with decreased malondialdehyde levels. Gene expression analyses revealed upregulation of DILP2 mRNA across generations and significant variations in PEPCK, SOD1, CAT, EGR, and UPD2 mRNA levels, demonstrating intricate responses to maternal zinc deficiency. This study provides a holistic understanding of the consequences of maternal zinc deficiency, emphasizing the complex interplay between zinc status and metabolic outcomes across generations in Drosophila. These findings lay the foundation for future research elucidating the underlying molecular mechanisms, with potential implications for humans. The insights gained contribute to informing targeted interventions aimed at optimizing offspring health in the context of maternal zinc deficiency.

Revolutionizing snakebite care with novel antivenoms: Breakthroughs and barriers.

Snakebite envenoming (SBE) is a global public health concern, primarily due to the lack of effective antivenom for treating snakebites inflicted by medically significant venomous snakes prevalent across various geographic locations. The rising demand for safe, cost-effective, and potent snakebite treatments highlights the urgent need to develop alternative therapeutics targeting relevant toxins. This development could provide promising discoveries to create novel recombinant solutions, leveraging human monoclonal antibodies, synthetic peptides and nanobodies. Such technologies as recombinant DNA, peptide and epitope mapping phage display etc) have the potential to exceed the traditional use of equine polyclonal antibodies, which have long been used in antivenom production. Recombinant antivenom can be engineered to target certain toxins that play a critical role in snakebite pathology. This approach has the potential to produce antivenom with improved efficacy and safety profiles. However, there are limitations and challenges associated with these emerging technologies. Therefore, identifying the limitations is critical for overcoming the associated challenges and optimizing the development of recombinant antivenoms. This review is aimed at presenting a thorough overview of diverse technologies used in the development of recombinant antivenom, emphasizing their limitations and offering insights into prospects for advancing recombinant antivenoms.

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.

Transgenerational Effects of Maternal Zinc Deficiency on Zinc Transporters in Drosophila melanogaster.

Maternal nutrition, including the availability of micronutrients such as zinc, influences the health of the offspring. Using Drosophila melanogaster, we studied the impact of zinc deficiency on development and reproduction, as well as the effects of maternal zinc status on the offspring's expression of zinc transporters across F1 to F3 generations. Zinc deficiency was induced by adding N,N,N',N'-Tetrakis (2-pyridylmethyl)-ethylenediamine (TPEN) to the diet on which the eggs representing the F0 generation flies were laid. Then, virgin F0 females were mated with control males to produce F1, and subsequently thereafter to generate F2 and F3. Offspring from F1 to F3 were analyzed for body zinc status and zinc transporter mRNA levels. We found that zinc deficiency significantly (p < 0.05) impaired the development of flies, as evidenced by a reduced eclosion rate of zinc-deficient flies. Similarly, zinc deficiency significantly (p < 0.05) reduced the egg-laying rate in F0 flies, highlighting its impact on reproductive functions. Also, zinc levels were consistently lower in the F0 and persisted in subsequent generations for both male and female offspring, indicating transgenerational alterations in zinc status. Furthermore, gene expression analysis revealed significant (p < 0.05) variations in the mRNA levels of dZip42C.1, dZnT63C, dZip71B, and dZnT35C genes across different generations and between male and female offspring. These findings indicate gender-specific dynamics of gene expression in response to zinc deficiency, suggesting potential regulatory mechanisms involved in maintaining zinc homeostasis. Our study emphasizes the detrimental effects of zinc deficiency on development and reproduction in Drosophila and highlights potential implications for offspring and human health.

Iron chelation and supplementation: A comparison in the management of inflammatory bowel disease using drosophila.

AIMS: Inflammatory Bowel Disease (IBD) is associated with systemic iron deficiency and has been managed with iron supplements which cause adverse side effects. Conversely, some reports highlight iron depletion to ameliorate IBD. The underlying intestinal response and comparative benefit of iron depletion and supplementation in IBD is unknown. The aims of this work were to characterize and compare the effects of iron supplementation and iron depletion in IBD. MAIN METHODS: IBD was induced in Drosophila melanogaster using 3 % dextran sodium sulfate (DSS) in diet for 7 days. Using this model, we investigated the impacts of acute iron depletion (using bathophenanthroline disulfonate, BPS) and supplementation (using ferrous sulphate, FS), before and after IBD induction, on gut iron homeostasis, cell death, gut permeability, inflammation, antioxidant defence, antimicrobial response and several fly phenotypes. KEY FINDINGS: DSS decreased fly mass (p < 0.001), increased gut permeability (p < 0.001) and shortened lifespan (p = 0.035) compared to control. The DSS-fed flies also showed significantly elevated lipid peroxidation (p < 0.001), and the upregulated expression of apoptotic marker- drice (p < 0.001), tight junction protein - bbg (p < 0.001), antimicrobial peptide - dpta (p = 0.002) and proinflammatory cytokine - upd2 (p < 0.001). BPS significantly (p < 0.05) increased fly mass and lifespan, decreased gut permeability, decreased lipid peroxidation and decreased levels of drice, bbg, dpta and upd2 in IBD flies. This iron chelation (using BPS) showed better protection from DSS-induced IBD than iron supplementation (using FS). Preventive and curative interventions, by BPS or FS, also differed in outcomes. SIGNIFICANCE: This may inform precise management strategies aimed at tackling IBD and its recurrence.

Neonatal administration of fenofibrate had no developmental programming effect on the lipid profile and relative leucocyte telomere lengths of adolescent rats fed a high-fructose diet postnatally.

Telomere length, a marker of ageing, is susceptible to developmental programming that may cause its accelerated attrition. Metabolic syndrome triggers telomere attrition. Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, is protective against telomere attrition. We investigated the impact of fenofibrate administered during suckling on the lipid profile and leucocyte telomere lengths of rats fed a high-fructose diet post-weaning. Suckling Sprague-Dawley pups (n = 119) were allocated to four groups and gavaged with either 10 mL·kg-1 body mass 0.5% dimethyl sulfoxide, 100 mg·kg-1 body mass fenofibrate, fructose (20%, w / v), or a combination of fenofibrate and fructose for 15 days. Upon weaning, each of the initial groups was split into two subgroups: one had plain water while the other had fructose solution (20%, w / v) to drink for 6 weeks. Blood was collected for DNA extraction and relative leucocyte telomere length determination by real-time PCR. Plasma triglycerides and cholesterol were also quantified. The treatments had no effect (p > 0.05) on body mass, cholesterol concentration, and relative leucocyte telomere lengths in both sexes. Post-weaning fructose increased triglyceride concentrations (p < 0.05) in female rats. Fenofibrate administered during suckling did not affect ageing nor did it prevent high fructose-induced hypertriglyceridaemia in female rats.

Nutrigenomic Effects of White Rice and Brown Rice on the Pathogenesis of Metabolic Disorders in a Fruit Fly Model.

Consumption of white rice (WR) has been shown to predispose individuals to metabolic disorders. However, brown rice (BR), which is relatively richer in bioactive compounds, possesses anti-glycaemic and antioxidant effects. In this study, fifteen cultivars of paddy rice that are predominantly consumed in North West Nigeria were analysed for their nutritional composition, bioactive contents and effects on metabolic outcomes in a fruit fly model. Gene expression analyses were conducted on the whole fly, targeting dPEPCK, dIRS, and dACC. The protein, carbohydrate, and fibre contents and bioactives of all BR cultivars were significantly different (p < 0.05) from the WR cultivars. Moreover, it was demonstrated that the glucose and trehalose levels were significantly higher (p < 0.05), while glycogen was significantly lower (p < 0.05) in the WR groups compared to the BR groups. Similarly, the expression of dACC and dPEPCK was upregulated, while that of dIRS was downregulated in the WR groups compared to the BR groups. Sex differences (p < 0.05) were observed in the WR groups in relation to the nutrigenomic effects. Our findings confirm metabolic perturbations in fruit flies following consumption of WR via distortion of insulin signalling and activation of glycogenolysis and gluconeogenesis. BR prevented these metabolic changes possibly due to its richer nutritional composition.

The potential of Artemisia species for use as broad-spectrum agents in the management of metabolic syndrome: a review.

Although the prevalence of metabolic syndrome (MetS), a cluster of cardiometabolic risk factors that predispose to the development of type 2 diabetes mellitus and cardiovascular diseases, is increasing globally, there is no broad-spectrum agent for its holistic treatment. Natural plant-derived products with a wide spectrum of biological activities are currently being explored as alternatives in the management of diseases. Artemisia species are a heterozygous group of plants of the Compositae family that possess several health benefits. Here we highlight their antidiabetic, anti-obesity, anti-hyperlipidaemic, hepatoprotective and cardioprotective properties among others. These activities have been linked to the presence of phytochemicals that act on several molecular targets to exert their effects and the species of Artemisia are considered to be relatively safe. Artemisia species offer significant anti-MetS activity and thus are strong therapeutic candidates for the effective management of MetS.

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.

Hepatitis B Therapeutic Vaccine: A Patent Review.

Viral hepatitis has long been underrated as a danger to global health. The UN only recently called for worldwide action to tackle viral hepatitis and lessen the disease burden in its "2030 Agenda for Sustainable Development". Hepatitis B virus (HBV), which causes liver cirrhosis and malignancy, is a main cause of death globally. This review analyses innovative HBV therapeutic vaccine candidates for which a patent was filed between January 2010 and March 2022 and presents future improvement techniques for vaccine efficacy. Although there is a preventative vaccine for HBV infection, over 3% of people worldwide have the disease on a long-term basis and can no longer benefit from it. Most people will have chronic HBV infection for the rest of their lives once it has been diagnosed. Moreover, only a small percentage of treated patients experience a functional cure with persistent hepatitis B surface antigen reduction. A significant proportion of deaths are caused by liver cirrhosis and hepatocellular cancer, which are both caused by chronic hepatitis B infection. Hence, there is an urgent need for novel medications due to the inadequacies of the current therapies.

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.

Medicinal Plants, Phytochemicals, and Their Impacts on the Maturation of the Gastrointestinal Tract.

The gastrointestinal tract (GIT) is the first point of contact for ingested substances and thus represents a direct interface with the external environment. Apart from food processing, this interface plays a significant role in immunity and contributes to the wellbeing of individuals through the brain-gut-microbiota axis. The transition of life from the in utero environment, to suckling and subsequent weaning has to be matched by phased development and maturation of the GIT; from an amniotic fluid occupancy during gestation, to the milk in the suckling state and ultimately solid food ingestion at weaning. This phased maturation of the GIT can be affected by intrinsic and extrinsic factors, including diet. Despite the increasing dietary inclusion of medicinal plants and phytochemicals for health benefits, a dearth of studies addresses their impact on gut maturation. In this review we focus on some recent findings mainly on the positive impact of medicinal plants and phytochemicals in inducing precocious maturation of the GIT, not only in humans but in pertinent animals. We also discuss Paneth cells as mediators and potential markers of GIT maturation.

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.