Vincristine is an anti-cancer compound and one of the most crucial vinca alkaloids produced by the medicinal plant Catharanthus roseus (L.) G. Don. (Apocynaceae). This plant is home to hundreds of endophytic microbes, which produce a variety of bioactive secondary metabolites that are known for their medicinal properties. In this study, we focused on isolating an endophytic fungus that could increase the yield of vincristine under laboratory conditions as an alternative to plant-mediated extraction of vincristine. The endophytic fungus Nigrospora zimmermanii (Apiosporaceae) was isolated from Catharanthus roseus and it was found to be producing the anticancer compound vincristine. It was identified using high-performance thin-layer chromatography by matching the Rf value and spectral data with the vincristine standard and mass spectrometry data and the reference molecule from the PubChem database. The generation study of this microbe showed that the production of vincristine in the parent fungus was at its maximum, i.e., 5.344 µg/mL, while it was slightly reduced in subsequent generations. A colonization study was also performed and it showed that the fungus N. zimmermanii was able to re-infect the plant Catharanthus roseus after 20 days of inoculation. The colonization study showed that N. zimmernanii could infect the plant after isolation. This method is an efficient and easy way to obtain a high yield of vincristine, as compared to plant-mediated production. Full article

The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica showed 99.5% and 92% inhibition, respectively, with virucidal as the main mode of action. Furthermore, the anti-MERS-CoV and anti-SARS-CoV-2 activities of S. tomentosa were measured. Notably, the anti-SARS-CoV-2 activity of S. tomentosa was very high (100%) and anti-MERS-CoV inhibition was slightly lower (96%). Therefore, the phytochemical investigation of the very promising S. tomentosa L. led to the isolation and structural identification of nine compounds (1–9). Then, both the CC₅₀ and IC₅₀ values for the isolated compounds against SARS-CoV-2 were measured. Compound 4 (genistein 4’-methyl ether) achieved superior anti-SARS-CoV-2 activity with an IC₅₀ value of 2.13 µm. Interestingly, the mode of action of S. tomentosa against SARS-CoV-2 showed that both virucidal and adsorption mechanisms were very effective. Additionally, the IC₅₀ values of S. tomentosa against SARS-CoV-2 and MERS-CoV were found to be 1.01 and 3.11 µg/mL, respectively. In addition, all the isolated compounds were subjected to two separate molecular docking studies against the spike (S) and main protease (M^pr°) receptors of SARS-CoV-2. Full article

Clostridium autoethanogenum protein (CAP) is a new single-cell protein explored in aquatic feeds in recent years. This study investigated the dietary effects of CAP replacing fishmeal (FM) on the growth, intestinal histology and flesh metabolism of largemouth bass (Micropterus salmoides). In a basal diet containing 700 g/kg of FM, CAP was used to substitute 0%, 15%, 30%, 45%, 70% and 100% of dietary FM to form six isonitrogenous diets (Con, CAP-15, CAP-30, CAP-45, CAP-70, CAP-100) to feed largemouth bass (80.0 g) for 12 weeks. Only the CAP-100 group showed significantly lower weight gain (WG) and a higher feed conversion ratio (FCR) than the control (p < 0.05). A broken-line analysis based on WG and FCR showed that the suitable replacement of FM with CAP was 67.1–68.0%. The flesh n-3/n-6 polyunsaturated fatty acid, intestinal protease activity, villi width and height in the CAP-100 group were significantly lower than those in the control group (p < 0.05). The Kyoto Encyclopedia of Genes and Genomes analysis showed that the metabolic pathway in flesh was mainly enriched in the “lipid metabolic pathway”, “amino acid metabolism”, “endocrine system” and “carbohydrate metabolism”. In conclusion, CAP could successfully replace 67.1–68.0% of dietary FM, while the complete substitution decreased the growth, damaged the intestinal morphology and down-regulated the lipid metabolites. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with a continuously growing prevalence. The pathophysiology of the disease is complex and includes several mechanisms, with metabolic syndrome and insulin resistance playing a major role. It is crucial to diagnose NAFLD before it advances to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis, presented by its complications which include ascites, portal hypertension, bleeding varices and encephalopathy. Another important complication of NAFLD and cirrhosis is hepatocellular carcinoma (HCC), a cancer with increasing incidence and poor prognosis. Even with the growing prevalence of NAFLD, diagnosis via liver biopsies is unrealistic, considering the costs and complications. Noninvasive tests, including serum biomarkers and elastography, are cost-effective and convenient, thereby replacing liver biopsies in diagnosing and excluding liver fibrosis. However, currently, these noninvasive tests have several limitations, such as variability, inadequate accuracy and risk factors for error. The limitations and variability of these tests comet the investigator to propose combining them in diagnostic algorithms to produce more accurate tools. Identifying patients with significant fibrosis is important for targeted therapies to prevent disease progression. Effective screening using noninvasive tests can be crucial for patient risk stratification and early diagnosis. Full article

Carbohydrate intake is one of the main determinants of glycemic control. In pregnancy, achievement of tight glycemic control is of utmost importance; however, data on the role of hybrid closed-loop systems (HCLs) in pregnancy are scarce. Therefore, we aimed to assess glycemic control achieved through the use of HCLs, and its association with carbohydrate intake in type 1 diabetes pregnancy. We included data from women with a sensor-augmented pump (SAP) during their first pregnancy and HCL use during the subsequent pregnancy. Student’s paired t-test was used to compare data between both pregnancies. Six women were identified, with age 30.2 ± 3.6 vs. 33.0 ± 3.6 years, diabetes duration 23 ± 5 vs. 26 ± 5 years, and baseline HbA_1c 6.7 ± 0.7% (50.1 ± 7.7 mmol/mol) vs. 6.3 ± 0.6% (45.2 ± 6.5 mmol/moll) in the first and second pregnancies, respectively. Time with glucose in the range 3.5–7.8 mmol/L was 69.1 ± 6.7 vs. 78.6 ± 7.4%, p = 0.045, with the HCLs compared to SAP. Higher meal frequency, but not the amount of carbohydrate consumption, was associated with more time spent in the target range and lower glycemic variability. HCLs and meal frequency were associated with better glycemic control in a small series of pregnant women with type 1 diabetes. Whether this translates to better perinatal outcomes remains to be seen. Full article

The complex microbiota and sialylated oligosaccharides in breastmilk are important bioactive components that affect the gut microbiota. However, the effect of breastmilk microbiota and sialylated oligosaccharides on the gut microbiota during the neonatal period has been largely overlooked. Here, 16S rRNA gene sequencing and metabolomics analysis were applied to the breastmilk and feces of 69 newborns to clarify the link between breastmilk components and the newborn gut. Results showed that Staphylococcus, Enterococcus, and Bacteroides were commonly shared and positively correlated between breastmilk and the neonatal intestine and they were the main bacteria of breastmilk that interacted with the newborn fecal metabolome. Breastmilk Staphylococcus mainly interacted with amino acids, whereas Bacteroides was involved in the tryptophan, nucleotide, and vitamin metabolism. Breastmilk sialylated oligosaccharides were related to Bacteroides and amino acids of the newborn fecal metabolites. Moreover, Bacteroides was related to the interaction between breastmilk 3′-sialyllactose and newborn fecal metabolites in the mediation effect models. Finally, we pointed out that breastmilk Bacteroides was important in the milk–gut interaction, and it was negatively associated with waist circumference in infants aged 1 year. Our study provides a scientific basis for understanding the role of breastmilk in the development of newborn gut microbiota and metabolome. Full article

The aim of the current study was to assess the cadmium (Cd) phytoremediation potential of Helianthus annuus L. that was exposed to 50, 100, and 150 mg/kg of cadmium for 15, 30, and 60 days with application of EDTA (Ethylenediaminetetraacetic acid) in the soil and IAA (indole acetic acid) as a foliar spray. The results indicated that the concentration, duration of exposure, and amount of Cd affect the phytoremediation potential. The maximum Cd was observed at 60 days (32.05, 16.86, and 10.63%) of Cd application, compared to 15 (2.04, 0.60, and 1.17%) or 30 days (8.41, 3.93, and 4.20%, respectively), in a dose-dependent manner. The application of EDTA in the soil and foliar IAA enhanced the Cd accumulation in the plants at 15, 30, and 60 days of exposure, with maximum accumulation at 60 days. Exposed plants with foliar IAA application showed 64.82%, 33.77%, and 25.84% absorption at 50, 100, and 150 mg/kg, respectively. Apart from higher absorption, the cadmium translocation to the edible part of the plants ceased, i.e., the seeds had 0% accumulation. The interesting fact was recorded that efficient phytoremediation was recorded at 15 days of exposure, whereas maximum phytoremediation was recorded at 60 days of exposure. To minimize the stress, the host also produced stress-related metabolites (i.e., flavonoids, phenolics, proline, and sugar) and antioxidants (i.e., catalases and ascorbate peroxidases). From the current evidence, it could be assumed that the use of EDTA and IAA, along with hyperaccumulating plants, could be a possible green method to remediate Cd-contaminated soil efficiently in a short period of time. Full article

Euclea divinorum Hiern is a medicinal plant widely distributed in the northeast parts of South Africa. This plant has been used to treat miscarriage and to alleviate gastrointestinal problems. It can also be used externally for the treatment of ulcers and gonorrhea. In this study, we investigated the phytochemical composition of E. divinorum leaf extract using LC-MS and explored its antioxidant properties in vitro and in vivo. The total polyphenolic content of the extract was determined by the Folin–Ciocalteu method. DPPH and FRAP assays were employed to confirm the plant’s antioxidant potential in vitro. A survival assay in the Caenorhabditis elegans model was used to evaluate the extract’s ability to counteract juglone-induced oxidative stress. Moreover, a docking study was performed for the extract’s metabolites, in order to predict possible molecular targets that could explain the antioxidant effect of the plant on a molecular level. This in silico approach was accomplished on three different proteins; xanthine oxidase enzyme, heat shock protein 90 (Hsp90), and induced nitric oxide synthase (iNOS). Docking scores of the resulting poses and their interactions with binding sites’ residues were explored for each protein and were compared to those of simultaneously docked respective co-crystallized and reference substrates. The extract furnished promising antioxidant activities in vitro and in vivo in the C. elegans model that might be attributed to the presence of 46 compounds, which showed several interactions and low binding scores with the tested enzymes. In conclusion, E. divinorum is a promising, safe, and effective antioxidant candidate that could be used to ameliorate oxidative stress-related disorders. Full article

Candida albicans is a human pathogen that is part of the healthy microbiome. However, it is often associated with opportunistic fungal infections. The treatment of these infections is challenging because prolonged exposure to antifungal drugs can culminate in fungal resistance during therapy, and there is a limited number of available drugs. Therefore, this study investigated the antifungal activity of ononin by in silico and in vitro assays, and in Tenebrio molitor as an alternative in vivo model of infection caused by C. albicans. Ononin is an isoflavone glycoside derived from formononetin that has various biological activities. According in silico evaluation, ononin showed the best electron affinity in molecular docking with CaCYP51, with a binding free energy of −10.89 kcal/mol, superior to that of the antifungal drugs fluconazole and posaconazole. The ononin + CaCYP51 complex formed hydrogen bonds with Tyr132, Ser378, Phe380, and Met508, as well as hydrophobic connections with Tyr118, Leu121, Phe126, Leu131, Ile304, and Leu309, and interactions with the heme group. Ononin exerted anti-Candida albicans activity, with MIC between 3.9 and 7.8 µg/mL, and inhibited young and mature biofilms, with a reduction in cell density and metabolic activity of 50 to 80%. The compound was not cytotoxic to sheep red blood cells at concentrations up to 1000 µg/mL. Larvae of the mealworm T. molitor were used as an alternative in vivo model of C. albicans infection. Ononin was able to prolong larval survival at concentrations of 0.5, 1, and 5 mg/kg, and was not toxic up to a concentration of 20 mg/kg. Moreover, ononin reduced the fungal charge in treated animals. In conclusion, our results suggest that ononin has anti-Candida albicans activity and is a potential candidate for the development of new therapeutic alternatives. Full article

Lake Mariout is Egypt’s degraded coastal marine habitat that encompasses a variety of wastes. The biodiversity and hard environmental conditions allow the co-existence of organisms with high resistance and rich metabolism, making them potential candidates for screening and isolating novel microbial strains. A bacterial isolate (BF202) cultured from the marine sediments of Alexandria’s Mariout Lake (Egypt) was tested for its antimicrobial and anticancer potential. The phylogenetic analysis of the isolated strain’s 16S rDNA and gyrB revealed that BF202 belongs to Brevibacillus laterosporus (B. laterosporus). Antibiosis of B. laterosporus was confirmed against microbial pathogens including Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, and Staphylococcus aureus. The highest antibacterial activity was detected on glucose peptone medium after 18 h of incubation at 35 °C, and at pH of 7.0 in the presence of mannose and ammonium carbonate as carbon and nitrogen sources, respectively. The cytotoxicity of the methanolic extract against breast cancer (MCF-7) and normal Vero cell lines, using the MTT test, revealed IC₅₀ values of 7.93 and 23.79 µg/mL, respectively. To identify apoptotic and necrotic cells, a flow cytometric analysis using annexin V-FITC/PI dual-labeling was utilized and recorded a higher number of necrotic cells compared to apoptotic ones. Similarly, the cell cycle S-phase arrest was reported. The LC-MS-MS investigation of B. laterosporus extract and the molecular networking database analysis demonstrated five strategic diketopiperazine compounds with antimicrobial and anticancer activities. Taken together, this research shows that the crude extract of B. laterosporus might be an effective agent against drug-resistant bacteria and malignant disorders due to its richness in diketopiperazines. Full article

Cardamine violifolia, a species belonging to the Brassicaceae family, is a selenium hyperaccumulator and a nutritious leafy vegetable. Our previous study showed that C. violifolia leaves are rich in total phenolic acids, but the composition and corresponding genes remain unknown. In this study, we investigated the phenolic acid compounds and potential gene regulation network in the outer leaves (OL) and central leaves (CL) of C. violifolia using transcriptome and metabolome analyses. Results showed that the OL contained a higher total phenolic acid content than the CL. Metabolome analysis revealed a total of 115 phenolic acids, 62 of which (e.g., arbutin, rosmarinic acid, hydroxytyrosol acetate, and sinapic acid) were differentially accumulated between the CL and OL of C. violifolia. Transcriptome analysis showed that the differentially expressed genes were significantly enriched in the pathways of secondary metabolite biosynthesis and phenylpropanoid biosynthesis. Conjoint analysis of the transcriptome and metabolome indicated that seven genes (CYP84A1, CYP84A4, CADH9, SGT1, UGT72E1, OMT1, and CCR2) and eight phenolic acids (sinapic acid, sinapyl alcohol, 5-O-caffeoylshikimic acid, sinapoyl malate, coniferin, coniferyl alcohol, L-phenylalanine, and ferulic acid) constituted a possible regulatory network. This study revealed the phenolic acid compounds and possible regulatory network of C. violifolia leaves and deepened our understanding of its nutrient value. Full article

Glucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins in American ginseng (Panaxquinquefolius L.) showed potential activity to promote glucose uptake, which can be used for stabilizing levels of postprandial blood glucose. The aim of this study was to identify key components of American ginseng with glucose uptake-promoting activity and to elucidate their metabolic regulatory mechanisms. Bio-guided isolation using zebrafish larvae and 2-NBDG indicator identified ginsenoside Rb1 (GRb1) as the most potential promotor of glucose uptake. Using UPLC-QTOF-MS/MS combined with RT-qPCR and phenotypic verification, we found that riboflavin metabolism is the hinge for GRb1-mediated facilitation of glucose transport. GRb1-induced restoration of redox homeostasis was mediated by targeting riboflavin transporters (SLC52A1 and SLC52A3) and riboflavin kinase (RFK). Full article

Four compounds, hippacine, 4,2′-dihydroxy-4′-methoxychalcone, 2′,5′-dihydroxy-4-methoxychalcone, and wighteone, were selected from 4924 African natural metabolites as potential inhibitors against SARS-CoV-2 papain-like protease (PLpro, PDB ID: 3E9S). A multi-phased in silico approach was employed to select the most similar metabolites to the co-crystallized ligand (TTT) of the PLpro through molecular fingerprints and structural similarity studies. Followingly, to examine the binding of the selected metabolites with the PLpro (molecular docking. Further, to confirm this binding through molecular dynamics simulations. Finally, in silico ADMET and toxicity studies were carried out to prefer the most convenient compounds and their drug-likeness. The obtained results could be a weapon in the battle against COVID-19 via more in vitro and in vivo studies. Full article

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. This work aims to investigate the translational potential of a multi-omics study (comprising metabolomics, lipidomics, glycomics, and metallomics) in revealing biomechanistic insights into AMI. Following the N-glycomics and metallomics studies performed by our group previously, untargeted metabolomic and lipidomic profiles were generated and analysed in this work via the use of a simultaneous metabolite/lipid extraction and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis workflow. The workflow was applied to blood plasma samples from AMI cases (n = 101) and age-matched healthy controls (n = 66). The annotated metabolomic (number of features, n = 27) and lipidomic (n = 48) profiles, along with the glycomic (n = 37) and metallomic (n = 30) profiles of the same set of AMI and healthy samples were integrated and analysed. The integration method used here works by identifying a linear combination of maximally correlated features across the four omics datasets, via utilising both block-partial least squares-discriminant analysis (block-PLS-DA) based on sparse generalised canonical correlation analysis. Based on the multi-omics mapping of biomolecular interconnections, several postulations were derived. These include the potential roles of glycerophospholipids in N-glycan-modulated immunoregulatory effects, as well as the augmentation of the importance of Ca–ATPases in cardiovascular conditions, while also suggesting contributions of phosphatidylethanolamine in their functions. Moreover, it was shown that combining the four omics datasets synergistically enhanced the classifier performance in discriminating between AMI and healthy subjects. Fresh and intriguing insights into AMI, otherwise undetected via single-omics analysis, were revealed in this multi-omics study. Taken together, we provide evidence that a multi-omics strategy may synergistically reinforce and enhance our understanding of diseases. Full article

Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000–400,000 for the homozygous and ~1:200–300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important cardiovascular risk factor with prevalence rate of ~20% in the general population. Novel Lp(a)-lowering therapies have been recently developed and their cardiovascular efficacy is currently investigated. Although a considerable proportion of FH patients is also diagnosed with high Lp(a) levels, there is a debate whether these two entities are associated. Nevertheless, Lp(a), particularly among patients with FH, has been established as a significant cardiovascular risk factor. In this narrative review, we present up-to-date evidence on the pathophysiology, diagnosis, and treatment of both FH and elevated Lp(a) with a special focus on their association and joint effect on ASCVD risk. Full article