Epigenetic modifiers and minerals as tools to diversify secondary metabolite production in fungi

Secondary metabolite production of fungi can be modified by different approaches, including epigenetic modifiers, culture-dependent methods, and genomic-based methods. In this study, secondary metabolite production was explored in the presence of epigenetic modifiers and minerals using a microscale fermentation approach. Thirteen fungi originally isolated from mushrooms and soils were grown in 96-well microtiter plates (MTPs) using 70% of potato dextrose broth (PDB) with the addition of epigenetic modifiers and minerals in different combinations and concentrations. All cultures were fermented at 10 °C or 28 °C for 2, 3, or 5 weeks and extracted by solid phase extraction. The resulting extracts were subjected to high-performance liquid chromatography (HPLC) and the chromatograms were analyzed on a qualitative and quantitative basis. In addition, major secondary metabolites from four fungi were identified as penicillic acid, patulin, pseurotin A, and javanicin. Epigenetic modifiers and minerals induce significant changes in the profile of the secondary metabolites. Their usage combined with microscale fermentation provides a cost-efficient tool for exploring fungal secondary metabolism

Epigenetic modifiers and minerals as tools to diversify secondary metabolite production in fungi

Secondary metabolite production of fungi can be modified by different approaches, including epigenetic modifiers, culture-dependent methods, and genomic-based methods. In this study, secondary metabolite production was explored in the presence of epigenetic modifiers and minerals using a microscale fermentation approach. Thirteen fungi originally isolated from mushrooms and soils were grown in 96-well microtiter plates (MTPs) using 70% of potato dextrose broth (PDB) with the addition of epigenetic modifiers and minerals in different combinations and concentrations. All cultures were fermented at 10 °C or 28 °C for 2, 3, or 5 weeks and extracted by solid phase extraction. The resulting extracts were subjected to high-performance liquid chromatography (HPLC) and the chromatograms were analyzed on a qualitative and quantitative basis. In addition, major secondary metabolites from four fungi were identified as penicillic acid, patulin, pseurotin A, and javanicin. Epigenetic modifiers and minerals induce significant changes in the profile of the secondary metabolites. Their usage combined with microscale fermentation provides a cost-efficient tool for exploring fungal secondary metabolism

Stimulatory Effects of Lycium shawii on Human Melanocyte Proliferation, Migration, and Melanogenesis: In Vitro and In Silico Studies

There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In this study, traditional medicinal plant extracts were tested for cultured human melanocyte proliferation, migration, and melanogenesis using MTT, scratch wound-healing assays, transmission electron microscopy, immunofluorescence staining, and Western blot technology. Of the methanolic extracts, Lycium shawii L. (L. shawii) extract increased melanocyte proliferation at low concentrations and modulated melanocyte migration. At the lowest tested concentration (i.e., 7.8 μg/mL), the L. shawii methanolic extract promoted melanosome formation, maturation, and enhanced melanin production, which was associated with the upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2 melanogenesis-related proteins, and melanogenesis-related proteins. After the chemical analysis and L. shawii extract-derived metabolite identification, the in silico studies revealed the molecular interactions between Metabolite 5, identified as apigenin (4,5,6-trihydroxyflavone), and the copper active site of tyrosinase, predicting enhanced tyrosinase activity and subsequent melanin formation. In conclusion, L. shawii methanolic extract stimulates melanocyte functions, including melanin production, and its derivative Metabolite 5 enhances tyrosinase activity, suggesting further investigation of the L. shawii extract-derived Metabolite 5 as a potential natural drug for vitiligo treatment

Stimulatory effects of Lycium shawii on human melanocyte proliferation, migration, and melanogenesis: In vitro and in silico studies

There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In this study, traditional medicinal plant extracts were tested for cultured human melanocyte proliferation, migration, and melanogenesis using MTT, scratch wound-healing assays, transmission electron microscopy, immunofluorescence staining, and Western blot technology. Of the methanolic extracts, Lycium shawii L. (L. shawii) extract increased melanocyte proliferation at low concentrations and modulated melanocyte migration. At the lowest tested concentration (i.e., 7.8 μg/mL), the L. shawii methanolic extract promoted melanosome formation, maturation, and enhanced melanin production, which was associated with the upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2 melanogenesis-related proteins, and melanogenesis-related proteins. After the chemical analysis and L. shawii extract-derived metabolite identification, the in silico studies revealed the molecular interactions between Metabolite 5, identified as apigenin (4,5,6-trihydroxyflavone), and the copper active site of tyrosinase, predicting enhanced tyrosinase activity and subsequent melanin formation. In conclusion, L. shawii methanolic extract stimulates melanocyte functions, including melanin production, and its derivative Metabolite 5 enhances tyrosinase activity, suggesting further investigation of the L. shawii extract-derived Metabolite 5 as a potential natural drug for vitiligo treatment

Saudi female students learning English: Motivation, effort, and anxiety

Female students in Saudi Arabia who learn English as a foreign language (EFL) are increasing, and they may learn English for various purposes. These purposes may be broadly defined as integrative (focusing on understanding and affiliating with English-speakers) and instrumental (focusing on gaining pragmatic rewards, such as being accepted for university or getting a better job). Targeting 3rd year Intermediate (9th grade) and 3rd year Secondary (12th grade) female students, this study examined the relationship between these motivational constructs and effort, EFL anxiety, and differences between grades. Survey data from female students from two schools in Riyadh (N=200) were analysed using 2 (grade: 9th, 12th) x 2 (school) ANOVA. Results indicated that 12th graders were higher than 9th graders in instrumental motivation and effort, but lower in integrative motivation and anxiety. Differences between schools were small. Effort was positively correlated with integrative but not instrumental motivation for 9th graders, and was positively correlated with instrumental but negatively correlated with integrative motivation for 12th graders. Educators and curriculum designers should consider students' developmental needs to capitalize on their motivations in learning EFL

Association of genetic variations in Toll-Like receptor 3 with Acute Lymphoblastic leukemia

Objectives: This study investigates the association between specific SNPs in the Toll-like receptor 3 (TLR3) gene and susceptibility to Acute Lymphoblastic Leukemia (ALL) in the Saudi population, aiming to clarify genetic influences on ALL risk. Methods: We evaluated four SNPs of TLR3 (rs3775296 C/A, rs5743312 C/T, rs3775291 C/T, and rs3775290 C/T) for their association with ALL. The allelic and genotypic frequencies of these SNPs were compared between 150 patients and 115 control subjects in this case-control study. All participants were genotyped using TaqMan PCR techniques. Additionally, mRNA expression levels were assessed in patients with ALL and matched healthy individuals using Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Results: Significant differences in genotype frequencies were observed for the TLR3 SNPs rs5743312 C/T and rs3775290 C/T between the ALL patients and control subjects. No significant differences were detected for rs3775296 C/A and rs3775291 C/T. Notably, the rs5743312 SNP was associated with an increased risk of ALL, while rs3775290 was associated with a decreased risk in the Saudi population. Conclusions: Our study demonstrates significant associations of the TLR3 SNPs rs5743312 C/T and rs3775290 C/T with ALL in the Saudi population. These polymorphisms could be pivotal in developing genetic screening tools and enhancing risk prediction strategies for ALL

Saudi female students learning English : motivation, effort, and anxiety

Female students in Saudi Arabia who learn English as a foreign language (EFL) are increasing, and they may learn English for various purposes. These purposes may be broadly defined as integrative (focusing on understanding and affiliating with English-speakers) and instrumental (focusing on gaining pragmatic rewards, such as being accepted for university or getting a better job). Targeting 3rd year Intermediate (9th grade) and 3rd year Secondary (12th grade) female students, this study examined the relationship between these motivational constructs and effort, EFL anxiety, and differences between grades. Survey data from female students from two schools in Riyadh (N=200) were analysed using 2 (grade: 9th, 12th) x 2 (school) ANOVA. Results indicated that 12th graders were higher than 9th graders in instrumental motivation and effort, but lower in integrative motivation and anxiety. Differences between schools were small. Effort was positively correlated with integrative but not instrumental motivation for 9th graders, and was positively correlated with instrumental but negatively correlated with integrative motivation for 12th graders. Educators and curriculum designers should consider students' developmental needs to capitalize on their motivations in learning EFL

Natural Products as Novel Neuroprotective Agents; Computational Predictions of the Molecular Targets, ADME Properties, and Safety Profile

Neurodegenerative diseases (NDs) are one of the most challenging public health issues. Despite tremendous advances in our understanding of NDs, little progress has been made in establishing effective treatments. Natural products may have enormous potential in preventing and treating NDs by targeting microglia; yet, there have been several clinical concerns about their usage, primarily due to a lack of scientific evidence for their efficacy, molecular targets, physicochemical properties, and safety. To solve this problem, the secondary bioactive metabolites derived from neuroprotective medicinal plants were identified and selected for computational predictions for anti-inflammatory activity, possible molecular targets, physicochemical properties, and safety evaluation using PASS online, Molinspiration, SwissADME, and ProTox-II, respectively. Most of the phytochemicals were active as anti-inflammatory agents as predicted using the PASS online webserver. Moreover, the molecular target predictions for some phytochemicals were similar to the reported experimental targets. Moreover, the phytochemicals that did not violate important physicochemical properties, including blood-brain barrier penetration, GI absorption, molecular weight, and lipophilicity, were selected for further safety evaluation. After screening 54 neuroprotective phytochemicals, our findings suggest that Aromatic-turmerone, Apocynin, and Matrine are the most promising compounds that could be considered when designing novel neuroprotective agents to treat neurodegenerative diseases via modulating microglial polarization

<i>Limoniastrum monopetalum</i>–Mediated Nanoparticles and Biomedicines: In Silico Study and Molecular Prediction of Biomolecules

An in silico approach applying computer-simulated models helps enhance biomedicines by sightseeing the pharmacology of potential therapeutics. Currently, an in silico study combined with in vitro assays investigated the antimicrobial ability of Limoniastrum monopetalum and silver nanoparticles (AgNPs) fabricated by its aid. AgNPs mediated by L. monopetalum were characterized using FTIR, TEM, SEM, and DLS. L. monopetalum metabolites were detected by QTOF–LCMS and assessed using an in silico study for pharmacological properties. The antibacterial ability of an L. monopetalum extract and AgNPs was investigated. PASS Online predictions and the swissADME web server were used for antibacterial activity and potential molecular target metabolites, respectively. Spherical AgNPs with a 68.79 nm average size diameter were obtained. Twelve biomolecules (ferulic acid, trihydroxy-octadecenoic acid, catechin, pinoresinol, gallic acid, myricetin, 6-hydroxyluteolin, 6,7-dihydroxy-5-methoxy 7-O-β-d-glucopyranoside, methyl gallate, isorhamnetin, chlorogenic acid, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl 6-O-(6-deoxy-β-l-mannopyranosyl)-β-d-glucopyranoside) were identified. The L. monopetalum extract and AgNPs displayed antibacterial effects. The computational study suggested that L. Monopetalum metabolites could hold promising antibacterial activity with minimal toxicity and an acceptable pharmaceutical profile. The in silico approach indicated that metabolites 8 and 12 have the highest antibacterial activity, and swissADME web server results suggested the CA II enzyme as a potential molecular target for both metabolites. Novel therapeutic agents could be discovered using in silico molecular target prediction combined with in vitro studies. Among L. Monopetalum metabolites, metabolite 12 could serve as a starting point for potential antibacterial treatment for several human bacterial infections