ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Antivenins , Snake Bites , Snake Bites/drug therapy , Snake Bites/therapy , Antivenins/therapeutic use , Humans , Animals , Africa/epidemiology , Neurotoxicity Syndromes/etiologyABSTRACT
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.
Subject(s)
Drosophila melanogaster , Zinc , Animals , Female , Zinc/deficiency , Zinc/metabolism , Male , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Maternal Nutritional Physiological PhenomenaABSTRACT
Bovine babesiosis has substantial economic implications in the cattle industry, emphasizing the need for a thorough understanding of the genetic diversity of the causative apicomplexan pathogen. Although babesiosis has been extensively studied globally, the genetic diversity of Babesia species in Malaysian and Nigerian cattle remains unreported. This study aims to bridge this gap by detecting and characterizing Babesia species in selected cattle herds. Our investigation explores the genetic diversity of Babesia species in cattle from Selangor, Malaysia, and Ribah, Nigeria. Blood samples revealed a 32.9% infection rate via PCR analysis. Further genetic analysis detected variations in Malaysian Babesia bigemina isolates but genetic similarity among Nigerian isolates. Conversely, all Babesia bovis isolates displayed genetic homogeneity. In summary, this research identifies genetic diversity in Babesia species affecting Malaysian and Nigerian cattle, highlighting regional disparities.
ABSTRACT
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.
Subject(s)
Anemia, Iron-Deficiency , Cognition , Iron Deficiencies , Animals , Child , Female , Humans , Male , Pregnancy , Age Factors , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/blood , Cognitive Dysfunction/etiology , Cognitive Dysfunction/epidemiology , Iron/blood , Maternal Nutritional Physiological Phenomena , Pregnancy Complications , Prenatal Exposure Delayed Effects , Sex FactorsABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Quail egg yolk oil (QEYO) has a rich history of medicinal use, showcasing heightened antioxidant and bioactive properties in our prior studies. This positions QEYO as a promising candidate for therapeutic and cosmetic applications. In this investigation, QEYO was extracted using ethanol/chloroform and 2-propanol/hexane solvents. GC-MS and FTIR analyses quantified 14 major bioactive compounds in the ethanol/chloroform fraction and 12 in the 2-propanol/hexane fraction. Toxicity evaluations in fruit flies, spanning acute, sub chronic, and chronic exposures, revealed no adverse effects. Negative geotaxis assays assessed locomotor activity, while biochemical assays using fly hemolymph gauged antioxidant responses. Real-time PCR revealed the relative expression levels of the antioxidant and anti-inflammatory genes. FTIR spectra indicated diverse functional groups, and the GC-MS results associated bioactive compounds with the regulation of the anti-inflammatory genes EIGER and UPD2. While no significant change in SOD activities was noted, male flies treated with specific QEYO doses exhibited increased catalase activity and total antioxidant capacity, coupled with a significant decrease in their malondialdehyde levels. This study offers valuable insights into the bioactive compounds of QEYO and their potential regulatory roles in gene expression.
ABSTRACT
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.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Animals , Mice , Colitis/chemically induced , Drosophila , Drosophila melanogaster , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/metabolism , Iron/metabolism , Dietary Supplements , Iron Chelating Agents/pharmacology , Dextran Sulfate , Disease Models, Animal , Mice, Inbred C57BL , Colon/metabolismABSTRACT
Background: Although tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previously showed, qualitatively, that erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit SARS-COV-2-induced cytopathic effect (CPE) in Vero cells. Aim: This study aimed to quantitatively explore the inhibition of SARS-CoV-2-induced CPE by erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin and to determine the effect of these drugs on SARS-CoV-2 papain-like protease and 3CL protease (MPRO) enzymes. Methods: Neutral red (3-amino-7-dimethylamino-2-methyl-phenazine hydrochloride) cell viability assay was used to quantify CPE after infecting pre-treated Vero cells with clinical SARS-Cov-2 isolates. Furthermore, SensoLyte® 520 SARS-CoV-2 papain-like protease and SensoLyte® 520 SARS-CoV-2 MPRO activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes. Results: Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC50) values of 3.27 µM, 4.23 µM, 9.29 µM, 3.19 µM, and 84.31 µM, respectively. Furthermore, erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibited SARS-CoV-2 papain-like protease with IC50 values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (MPRO) with IC50 values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively. Conclusion: The IC50 for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Chlorocebus aethiops , Humans , Papain , Ivermectin/pharmacology , Pyridoxine , Peptide Hydrolases , Vero Cells , COVID-19 Vaccines , Erythromycin/pharmacology , Folic Acid/pharmacology , Antiviral Agents/pharmacology , Protease Inhibitors/pharmacologyABSTRACT
To overcome the COVID-19 pandemic, the development of safe and effective vaccines is crucial. With the enormous information available on vaccine development for COVID-19, there are still grey areas to be considered when designing a potential vaccine. The rapid regulatory approval of nucleic acid-based vaccines was unique to the COVID-19; these vaccines were rapidly produced cost-effectively and with lesser risk of infectivity. Additionally, they demonstrated relative stability at room temperature (DNA). However, a comparative understanding of the immunogenic impact and efficacy of these vaccines is lacking. Immunogenicity is essential for developing and maintaining effective and long-lasting post-vaccination immunity to pathogenic microorganisms. This systematic review aims to assess and summarize the immunogenicity and protective efficacy of the nucleic acid-based vaccines against COVID-19. The Preferred Reporting Items for Systematic Reviews (PRISMA) recommendations were followed in this review. CASP tool was used for quality assessment of randomized controlled trials. All included studies employed a randomized control method, and the results demonstrated promising immune responses and effectiveness that provided high-level protection against COVID-19 infection. This study offers vital insights for advancing vaccine technology. Furthermore, it guides formulation, informs personalized vaccination strategies, and enhances global health preparedness, particularly in regions with limited vaccine access.
ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is associated with a high mortality rate due to early recurrence and its metastasis features. To this day, effective treatment options for metastatic HCC remain a major challenge to patient treatment. Flavokawain B (FKB) is a naturally occurring chalcone molecule capable of providing effective therapy against this life-threatening disease. OBJECTIVE: This study investigated the anti-metastatic effects of FKB on the growth and development of metastatic HCC. METHODS: HepG2 cells were used in this study and a neutral red assay was performed to determine the IC50 value of FKB. Cell scratch and exclusion zone assays were performed to assess the rate of cell migration and invasion. Relative mRNA levels of UCK2, STAT3, VEGF and HIF-1α genes were quantified using RT-qPCR. RESULTS: FKB inhibited the proliferation of HepG2 cells at an IC50 value of 28 µM after 72 h of incubation. Its cytotoxic effect was confirmed to induce apoptosis through the phase-contrast inverted microscope. Cell migration and invasion were significantly inhibited at 7, 14, and 28 µM of FKB as compared to untreated cells. The inhibition in the cell migration significantly increased with the increasing concentrations of the bioactive compound. The relative expression levels of the UCK2 gene and its downstream genes, STAT3, VEGF and HIF-1α, were significantly downregulated after 72 h exposure to FKB treatment. CONCLUSION: Our data suggest that FKB inhibited HepG2 proliferation and further suppressed its metastasis partly by regulating the STAT3/Hif-1α/VEGF signalling pathway. FKB could be a potential alternative and viable strategy against HCC.
Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Vascular Endothelial Growth Factor A/genetics , Liver Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Proliferation , Cell Line, Tumor , Uridine Kinase , STAT3 Transcription Factor/pharmacologyABSTRACT
Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and implementation considerations, to identify potential drugs for COVID-19 using iterative computational and wet laboratory methods. The drugs were screened at doses that are known to be achievable in humans. Furthermore, inhibition of viral induced cytopathic effect (CPE) was used as the laboratory surrogate to predict efficacy. Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms.
ABSTRACT
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.
Subject(s)
Metabolic Diseases , Oryza , Blood Glucose/metabolism , Insulin/metabolism , Nutrigenomics , Oryza/chemistry , Drosophila , AnimalsABSTRACT
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.
Subject(s)
Colorectal Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Proliferation/genetics , Cell Line, Tumor , MicroRNAs/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Gene Expression Regulation, NeoplasticABSTRACT
The oxidative stress resulting from the production of reactive oxygen species plays a vital role in inflammatory processes and is associated with neurodegenerative changes. In view of the ability of germinated brown rice (GBR) to improve learning and memory, this present study aimed to investigate the mechanistic basis of GBR's neuroprotection in a high-fat diet (HFD)-induced oxidative changes in adult Sprague-Dawley rats. Ferulate-rich GBR ethyl acetate extract (GBR-EA; 100 mg/kg and 200 mg/kg body weight) was supplemented orally for the last 3 months of 6 months HFD feeding during the study. GBR-EA supplementation was found to improve lipid profile and serum antioxidant status, when compared to the HFD group. Elevated mRNA expressions of SOD1, SOD2, SOD3, Catalase, and GPX were demonstrated in the frontal cortex and hippocampus of GBR-EA treated animals. The pro-inflammatory changes induced by HFD in the hippocampus were attenuated by GBR-EA through the downregulation of CRP and TNF- α and upregulation of PPAR-γ. GBR also reduced the hippocampal mRNA expression and enzyme level of acetylcholinesterase. In conclusion, this study proposed the possible transcriptomic regulation of antioxidant and inflammation in neurodegenerative processes resulting from high cholesterol consumption, with an emphasis on GBR's potential to ameliorate such changes.
Subject(s)
Diet, High-Fat , Oryza , Acetates , Acetylcholinesterase , Animals , Antioxidants/pharmacology , Brain , Diet, High-Fat/adverse effects , Oxidative Stress , RNA, Messenger , Rats , Rats, Sprague-DawleyABSTRACT
Objective: Hypercholesterolemia is a strong risk factor for cardiovascular diseases. Side effects associated with the use of pharmaceutical agents can cancel out their benefits. Dietary management of hypercholesterolemia is, therefore, receiving much attention due to fewer side effects. In this study, we explored the effectiveness of edible bird's nest (EBN) in the prevention of hypercholesterolemia in rats. Methods: High-cholesterol diet (HCD) (4.5% cholesterol and 0.5% cholic acid) with or without EBN (low (2.5%) or high dose (20%)) was given to rats for 12 weeks, and their weights were observed. Simvastatin (10 mg/kg/day) was administered for the same period as a control drug. Serum and tissue samples were collected at the end of the study, from which biochemical parameters (lipid profiles, oxLDL, liver enzymes, urea, creatinine, uric acid, and lipase activity) and hepatic mRNA levels were measured. Results: The HCD group had higher levels of serum lipids, liver enzymes, uric acid, urea, and lipase activity compared with those of the other groups. The hepatic mRNA levels of cholesterol metabolism genes (APOB, PCSK9, HMGCR, LDLR, and CYP7A1) in the HCD group also tended toward increased cholesterol production and reduced cholesterol clearance. EBN, especially the highest dose, attenuated the HCD-induced changes, partly through improving the transcriptional regulation of hepatic cholesterol metabolism genes with fold changes of 0.7, 0.6, 0.5, 1.7, and 2.7, respectively, in comparison to the HCD group. In fact, EBN produced better results than simvastatin. Conclusion: Thus, the results suggest that EBN can regulate cholesterol metabolism and, therefore, be a source of functional ingredients for the management of hypercholesterolemia.
ABSTRACT
Traumatic brain injury (TBI) remains a public health challenge and represents one of the major contributors to disability and mortality worldwide among all trauma-related injuries. This study aimed to determine a precise effect size of secretome intervention in TBI. We performed a systematic literature search through Cochrane, MEDLINE Complete, PubMed and Scopus databases for articles published until June 2021. The search terms used include cells OR stem cells OR mesenchymal stem cells AND secretome OR conditioned medium OR extracellular vesicles OR exosomes OR microvesicles AND traumatic brain injury OR head injury. Neurological deficits and neuroinflammation were the outcome measures assessed after the intervention. Thirty-one (31) studies involving mouse, rat and swine were enrolled for the meta-analysis. Secretome significantly improved structural and functional recovery when compared with control. The mean effect sizes were as follows: modified neurological severity score (mNSS) (-2.65, 95% CI: -3.42, -1.87, p < 0.00001), impact size (-3.02 mm3, 95% CI: -4.97, -1.08, p = 0.002) and latency to platform (-17.20 s, 95% CI: -23.91, -10.50, p < 0.00001). Similarly, intervention with secretome reduced neuroinflammation after TBI. The results of meta-regression showed that the source of secretome, TBI models and duration of follow-up did not influence the mNSS. Furthermore, the methodological quality of the studies was moderate as shown by the risk of bias assessment. Publication bias was observed for the mNSS. This meta-analysis provides preclinical evidence of secretome intervention in TBI, suggesting that it can be explored as a therapeutic agent for TBI and other neurological disorders in humans.
Subject(s)
Brain Injuries, Traumatic , Mesenchymal Stem Cells , Animals , Brain Injuries, Traumatic/therapy , Culture Media, Conditioned/pharmacology , Mice , Rats , Secretome , Stem Cells , SwineABSTRACT
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.
ABSTRACT
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.