Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Golden Gate Cloning of Synthetic CRISPR RNA Spacer Sequences.

Prokaryotes use CRISPR-Cas systems to interfere with viruses and other mobile genetic elements. CRISPR arrays comprise repeated DNA elements and spacer sequences that can be engineered for custom target sites. These arrays are transcribed into precursor CRISPR RNAs (pre-crRNAs) that undergo maturation steps to form individual CRISPR RNAs (crRNAs). Each crRNA contains a single spacer that identifies the target cleavage site for a large variety of Cas protein effectors. Precise manipulation of spacer sequences within CRISPR arrays is crucial for advancing the functionality of CRISPR-based technologies. Here, we describe a protocol for the design and creation of a minimal, plasmid-based CRISPR array to enable the expression of specific, synthetic crRNAs. Plasmids contain entry spacer sequences with two type IIS restriction sites and Golden Gate cloning enables the efficient exchange of these spacer sequences. Factors that influence the compatibility of the CRISPR arrays with native or recombinant Cas proteins are discussed.

Impact of microbial-based biopreparations on soil quality, plant health, and fruit chemistry in raspberry cultivation.

Application of microbial-based biopreparations as a pre-harvest strategy offers a method to obtain sustainable agricultural practices and could be an important approach for advancing food science, promoting sustainability, and meeting global food market demands. The impact of a bacterial-fungal biopreparation mixture on soil-plant-microbe interactions, fruit chemical composition and yield of 7 raspberry clones was investigated by examining the structural and functional profiles of microbial communities within leaves, fruits, and soil. Biopreparation addition caused the enhancement of the microbiological utilization of specific compounds, such as d-mannitol, relevant in plant-pathogen interactions and overall plant health. The biopreparation treatment positively affected the nitrogen availability in soil (9-160%). The analysis of plant stress marker enzymes combined with the evaluation of fruit quality and chemical properties highlight changes inducted by the pre-harvest biopreparation application. Chemical analyses highlight biopreparations' role in soil and fruit quality improvement, promoting sustainable agriculture. This effect was dependent on tested clones, showing increase of soluble solid content in fruits, concentration of polyphenols or the sensory quality of the fruits. The results of the next-generation sequencing indicated increase in the effective number of bacterial species after biopreparation treatment. The network analysis showed stimulating effect of biopreparation on microbial communities by enhancing microbial interactions (increasing the number of network edges up to 260%) of and affecting the proportions of mutual relationships between both bacteria and fungi. These findings show the potential of microbial-based biopreparation in enhancing raspberry production whilst promoting sustainable practices and maintaining environmental homeostasis and giving inshght in holistic understanding of microbial-based approaches for advancing food science monitoring.

An integrative strategy used by the aphid Uroleucon formosanum to counter host sesquiterpene lactone defense: Insights from combined genomic and transcriptomic analysis.

Insect herbivores adapt and develop strategies to counteract plant chemical defenses. The aphid Uroleucon formosanum is a serious sap-sucking pest that infests lettuces containing toxic sesquiterpene lactones (STLs). Herein, we employed a combination of genome sequencing and RNA-seq transcriptome profiling to understand the mechanisms underlying phytotoxin tolerance in U. formosanum. We generated the first chromosome-level genome assembly for U. formosanum, with a total size of 453.26 Mb and a scaffold N50 of 33.22 Mb. Comparative genomic analyses revealed an enrichment of signals for positive selection and gene family expansion in immune-related pathways. Specifically, the expanded set of heat shock protein 70 (HSP70) genes showed upregulation after treatment with lactucin, suggesting that they may play a role in the immune response against STLs. The expression of takeout-like genes and cuticle-associated genes was also significantly increased in the lactucin-treated samples. Additionally, 53 cytochrome P450 monooxygenase, 30 carboxylesterase, 19 glutathione S-transferase, 32 uridine diphosphate glycosyltransferase and 63 ATP-binding cassette (ABC) transporter genes were identified in the U. formosanum genome. CYP4C1, CYP6A13 and 7 ABC genes were strongly upregulated in response to lactucin treatment, indicating the involvement of detoxifying enzymes in the tolerance of U. formosanum to STLs. Our findings suggest that the cuticle barrier, immune response and enzyme-mediated metabolic detoxification jointly enhance the tolerance of U. formosanum to phytotoxins and promote its adaptation to host plants. This study presents a valuable genomic resource and provides insights into insect adaptation to plant chemical challenges and future technological developments for pest management.

Investigating the antifungal potential of genetically modified hybrid chitinase enzymes derived from Bacillus subtilis and Serratia marcescens.

Chitinases are glycosyl hydrolase enzymes that break down chitin, an integral component of fungal cell walls. Bacteria such as Bacillus subtilis and Serratia marcescens produce chitinases with antifungal properties. In this study, we aimed to generate hybrid chitinase enzymes with enhanced antifungal activity by combining functional domains from native chitinases produced by B. subtilis and S. marcescens. Chitinase genes were cloned from both bacteria and fused together using overlap extension PCR. The hybrid constructs were expressed in E. coli and the recombinant enzymes purified. Gel electrophoresis and computational analysis confirmed the molecular weights and isoelectric points of the hybrid chitinases were intermediate between the parental enzymes. Antifungal assays demonstrated that the hybrid chitinases inhibited growth of the fungus Fusarium oxysporum significantly more than the native enzymes and also showed fungicidal activity against Candida albicans, Alternaria solani, and Rhizoctonia solani. The results indicate that hybrid bacterial chitinases are a promising approach to engineer novel antifungal proteins. This study provides insight into structure-function relationships of chitinases and strategies for generating biotherapeutics with enhanced bioactive properties. These hybrid chitinases result in a more potent and versatile antifungal agent.

Enhancement of cold-adapted heterotrophic nitrification and denitrification in Pseudomonas sp. NY1 by cupric ions: Performance and mechanism.

Cupric ions can restrain biological nitrogen removal processes, which comprise nitrite reductase and nitric oxide reductase. Here, Pseudomonas sp. NY1 can efficiently perform heterotrophic nitrification and aerobic denitrification with cupric ions at 15 °C. At optimal culturing conditions, low cupric ion levels accelerated nitrogen degradation, and ammonium and nitrite removal efficiencies increased by 2.33%-4.85% and 6.76%-12.30%, respectively. Moreover, the maximum elimination rates for ammonium and nitrite increased from 9.48 to 10.26 mg/L/h and 6.20 to 6.80 mg/L/h upon adding 0.05 mg/L cupric ions. Additionally, low cupric ion concentrations promoted electron transport system activity (ETSA), especially for nitrite reduction. However, high concentrations of cupric ions decreased the ETSA during nitrogen conversion processes. The crucial enzymes ammonia monooxygenase, nitrate reductase, and nitrite reductase possessed similarly trends as ETSA upon exposure to cupric ion. These findings deepen the understanding for the effect of cupric ions on nitrogen consumption and bioremediation in nitrogen-polluted waters.

Ecotoxicological effects of paracetamol on the biochemical and molecular responses of spinach (Spinacia oleracea L.).

The widespread use of pharmaceuticals, including paracetamol, has raised concerns about their impact on the environment and non-target species. The aim of this study was to investigate the biochemical and molecular responses of Spinacia oleracea (spinach) to high paracetamol concentrations in order to understand the plant's stress responses and underlying mechanisms. Under controlled conditions, spinach plants were exposed to different paracetamol concentrations (0, 50, 100, and 200 mg/L). The study evaluated the impact of paracetamol exposure on biochemical parameters such as oxidative stress markers (H2O2, MDA), activities of antioxidant enzymes (APX, CAT, GPOD, SOD), levels of non-enzymatic components (phenolics and flavonoids), and phytohormones (ABA, SA, and IAA). Furthermore, the study assessed molecular impacts by analyzing stress-related genetic variation and alterations in the gene expression of the antioxidant enzymes. Results showed that paracetamol exposure significantly increased oxidative stress in spinach, which was evident through the elevated H2O2 and MDA levels. However, the antioxidant defense mechanisms were activated to counteract this effect, as evidenced by increased activity of antioxidant enzymes and higher phenolics and flavonoid levels. Moreover, induction in the phytohormone levels indicated a stress response in paracetamol-treated plants compared to control plants. RAPD analysis revealed polymorphism indicating the DNA damage, and the Real-time qRT-PCR method showed significant upregulation of stress-responsive genes, highlighting the severe impact of paracetamol at the molecular level. The study concludes that high paracetamol concentrations pose a significant threat to spinach growth by affecting both biochemical and molecular processes. These findings underscore the need for strict environmental management practices to mitigate the possible impact of continuous release, accumulation, and long-term exposure of pharmaceutical contaminants to the environment and implement policies to reduce pharmaceutical pollutants to preserve ecological health and biodiversity.

Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.

AIMS: Interindividual variations in efavirenz (EFV) plasma concentrations are extensive, but paediatric data on its consequences for viral control are scarce. The aim of this study was to explore the role of genetic variation in achieving therapeutic efavirenz plasma concentrations in a cohort of Ugandan children and the linkage between genetic CYP2B6 variants, EFV plasma variability, viral resistance and viral outcome. METHODS: Ninety-nine treatment-naïve children, aged 3-12 years and living with HIV, were followed for 24 weeks after ART initiation assessing mid-dose efavirenz plasma concentrations, HIV RNA, HIV drug resistance and adherence. Polymorphisms in genes coding for drug-metabolizing enzymes were genotyped. Efavirenz concentrations were determined by liquid chromatography coupled with high-resolution tandem mass spectrometry. Metabolizer phenotype was predicted from composite genotypes of CYP2B6 (c.516G>T and c.983 T>C). A mixed effects restricted maximum likelihood regression model was used to identify important factors for efavirenz exposure. RESULTS: Efavirenz plasma concentrations were below the therapeutic interval (1000-4000 mg/mL) in 12-17% and above in 21-24% of measurements. Eight children had persisting subtherapeutic concentrations, five of which failed virologically and three acquired at least one new resistant mutation. Multivariate modelling explained 70% of interindividual variation in plasma concentration, with treatment duration, adherence, CYP2B6c.136A>G, and metabolizer phenotype as independent predictors of EFV concentration. In univariate analysis, metabolizer phenotype explained 50% of interindividual variation. CONCLUSIONS: Metabolizer phenotype explained 50% of interindividual variation in efavirenz plasma concentration. Autoinduction was not confirmed and >33% of the concentrations were outside the therapeutic interval. Subtherapeutic concentrations worsened virological resistance and outcomes. Genotype-based dosing may help avert both sub- and supratherapeutic efavirenz plasma concentrations in Ugandan children.

Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosis.

Enzyme replacement therapy (ERT) using velmanase alfa previously showed promising efficacy and safety outcomes for up to 4 years of therapy in patients with alpha-mannosidosis. This pooled analysis from two multicenter, open-label phase IIIb extension trials rhLAMAN-07 (N = 13; NCT01908712) and rhLAMAN-09 (N = 8; NCT01908725) evaluated the long-term effects of velmanase alfa. Sixteen patients who previously completed phase I-III rhLAMAN-02/-03/-04/-05/-08 trials and five ERT-naïve patients were enrolled. Patients received 1 mg/kg velmanase alfa once weekly. Endpoints included changes from treatment baseline (before initial dose of velmanase alfa in any trial) in serum oligosaccharides, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function (forced vital capacity [FVC], % predicted), serum immunoglobulin G (IgG) levels, and adverse events. The overall cohort comprised 21 patients, divided by age at treatment baseline into pediatric (n = 14) and adult subgroups (n = 7). Distance walked according to 6MWT increased or stabilized in pediatric patients, while in adults either stabilization or slight decline was observed. Similarly, pediatric patients performed better in the 3MSCT. Changes in FVC, % predicted, were comparable in both subgroups up to ~6 years of observation, diverging thereafter. Overall, sustained serum oligosaccharide clearance and serum IgG level increase was observed upon treatment initiation and persisted until last common observation. Velmanase alfa treatment was generally well tolerated, with the majority of reported adverse events being of mild-to-moderate intensity. With follow-up of up to 12 years, long-term efficacy and safety outcomes indicate continued benefits of velmanase alfa in patients with alpha-mannosidosis.

Absence of Survival Impact from Hepatitis During Immunotherapy in 193 Patients with Advanced Hepatocellular Carcinoma - An Observational Study from Taiwan.

Background: Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear. Methods: In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns. Results: One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses. Conclusion: Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.

Unveiling the Interplay: Antioxidant Enzyme Polymorphisms and Oxidative Stress in Preterm Neonatal Renal and Hepatic Functions.

AIMS: To explore the relationship between oxidative stress biomarkers and the occurrence of acute kidney injury (AKI) alongside notable liver function disturbances in preterm neonates. BACKGROUND: Given the immaturity of kidneys and incomplete liver development in preterm neonates, oxidative stress poses a considerable threat to their renal and hepatic health. OBJECTIVE: To find out the association between various oxidative stress biomarkers and polymorphisms of antioxidant enzymes with renal and live functions. METHODS: In this cross-sectional study, we gathered umbilical cord blood and peripheral blood samples for assessing oxidative stress biomarkers and identifying single nucleotide polymorphisms (SNPs) in antioxidant enzymes. Utilizing enzyme-linked immunosorbent assay kits, we quantified these oxidative stress biomarkers. Receiver-operating characteristics curve analysis was employed to ascertain the predictive capacity of these biomarkers, denoted by the area-under-the-curve (AUC). RESULTS: Our findings revealed that umbilical cord heat-shock proteins emerged as robust predictors of neonatal AKI (AUC: 0.92; 95% CI: 0.8-1) with a defined cut-off concentration of 1.8 ng/mL. Likewise, umbilical cord 8-hydroxy-2-deoxy guanosine demonstrated significant predictability for liver function alterations (AUC: 0.7; 95% CI: 0.6-0.9) at a cut-off concentration of 2487.6 pg/mL. CONCLUSIONS: We observed significant associations between SNPs in endothelial nitric oxide synthase and catalase with both AKI and impaired liver functions. Prospective studies are warranted to validate these findings, with a particular focus on exploring potential antioxidant interventions aimed at mitigating AKI and liver function abnormalities.

Bioactive compounds from food-grade Bacillus.

Bacillus species have attracted significant attention in recent years due to their potential for producing various bioactive compounds with diverse functional properties. This review highlights bioactive substances from food-grade Bacillus strains and their applications in functional foods and nutraceuticals. The metabolic capacities of Bacillus species have allowed them to generate a wide range of bioactive substances, including vitamins, enzymes, anti-microbial peptides, and other non-ribosomal peptides. These substances have a variety of positive effects, including potential cholesterol-lowering and immune-modulatory qualities in addition to anti-oxidant and anti-bacterial actions. The uses and mechanisms of action of these bioactive chemicals can be used to improve the functional qualities and nutritional profile of food products. Examples include the use of anti-microbial peptides to increase safety and shelf life, as well as the use of Bacillus-derived enzymes in food processing to improve digestibility and sensory qualities. The exploitation of bioactive compounds from food-grade Bacillus strains presents a promising frontier in the development of functional foods and nutraceuticals with enhanced health benefits. Due to their wide range of activity and applications, they are considered as important resources for the development of novel medications, agricultural biocontrol agents, and industrial enzymes. Ongoing research into the biosynthetic pathways, functional properties, and applications of these compounds is essential to fully realize their potential in the food industry. This review underscores the significance of various bioactive compounds generated from Bacillus in tackling global issues like environmental sustainability, sustainable agriculture, and antibiotic resistance. Future developments in microbiology and biotechnology will enable us to fully utilize the potential of these amazing microbes, resulting in novel approaches to industry, agriculture, and health. © 2024 Society of Chemical Industry.

Toxic Effects of 4-Bromodiphenyl Ether (BDE-3) on Antioxidant Enzymes, Cell Viability, Histology and Biomolecules in Zebrafish Embryo-Larvae.

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants that are being used widely in industrial and consumers products such as plastics, electronics, furniture, textiles and so forth. They can undergo debromination process to form less brominated diphenyl ethers, which are bioaccumulative, more volatile and more toxic in nature. The current study was conducted to reveal the biochemical, apoptotic, histopathological, ultrastructural and biomolecular (ATR-FTIR) toxicity of 4-bromodiphenyl ether (BDE-3) in zebrafish larvae. After the 96-h LC50 determination, the zebrafish embryos were exposed to sublethal concentrations of BDE-3, that is, 0.79 and 1.59 mg/L. The MDA content was found to be significantly increased in BDE-3 exposed larvae whereas the FRAP activity was found to be decreased. The catalase (CAT), glutathione-S-transferase (GST) and acetylcholinesterase (AChE) activity were observed to be significantly increased, and a decreased superoxide dismutase (SOD) activity was reported after the BDE-3 exposure in zebrafish larvae. The cell viability was reported to be decreased in zebrafish larvae after BDE-3 exposure. Histopathological and ultrastructural alterations were also observed in the BDE-3 exposed zebrafish larvae. The changes in the biomolecules such as DNA and protein were also revealed via ATR-FTIR analysis. The present investigation will help to understand the toxic nature of less brominated diphenyl ethers and could be utilised to assess environmental risk.

Assessing variability among culturable phylloplane basidiomycetous yeasts from Italian agroecosystems.

This study analysed basidiomycetous yeasts isolated from the phylloplane of crops and spontaneous plants in Italian agroecosystems. A total of 25 species belonging to 17 genera were recognized by analysing 83 isolates from vineyards and orchards, that are not treated with synthetic fungicides, and adjacent natural areas. Rhodotorula graminis and Filobasidium magnum were the most frequent species but 13 others were represented by a single isolate (e.g., Buckleyzyma salicina, Pseudozyma prolifica, and Moniliella megachiliensis). Preliminary analysis of (GTG)5-PCR fingerprinting revealed high genetic intraspecific heterogeneity. All isolates were characterized by their production of extracellular hydrolytic enzymes and their sensitivity to six commercial fungicides used in Italy. The isolates displayed great variability in these phenotypic traits, which play an important role in the survival of yeast populations in agroecosystems. Most of them exhibited lipolytic, proteolytic, ß-glucosidase and pectinolytic activities, but only three (F. magnum, Kwoniella mangroviensis and Ps. prolifica) also had cellulolytic and amylolytic activity. Most isolates were sensitive to four fungicides, and one R. graminis isolate was resistant to all six. This heterogeneity was not related to the geographical origin of the isolates. The lack of selective factors (i.e. pesticide treatments) in the sampling fields and the presence of adjacent natural areas may have favored the maintenance of an elevated level of strain diversity. This study provides new information on phylloplane basidiomycetous yeasts in agroecosystems and opens the way to further investigations into the impact of agricultural practices on the microbial diversity of these natural habitats.

Solubilization and enhanced degradation of benzene phenolic derivatives-Bisphenol A/Triclosan using a biosurfactant producing white rot fungus Hypocrea lixii S5 with plant growth promoting traits.

Introduction: Endocrine disrupting chemicals (EDCs) as benzene phenolic derivatives being hydrophobic partition to organic matter in sludge/soil sediments and show slow degradation rate owing to poor bioavailability to microbes. Methods: In the present study, the potential of a versatile white rot fungal isolate S5 identified as Hypocrea lixii was monitored to degrade bisphenol A (BPA)/triclosan (TCS) under shake flask conditions with concomitant production of lipopeptide biosurfactant (BS) and plant growth promotion. Results: Sufficient growth of WRF for 5 days before supplementation of 50 ppm EDC (BPA/TCS) in set B showed an increase in degradation rates by 23% and 29% with corresponding increase in secretion of lignin-modifying enzymes compared to set A wherein almost 84% and 97% inhibition in fungal growth was observed when BPA/TCS were added at time of fungal inoculation. Further in set B, EDC concentration stimulated expression of laccase and lignin peroxidase (Lip) with 24.44 U/L of laccase and 281.69 U/L of Lip in 100 ppm BPA and 344 U/L Lip in 50 ppm TCS supplemented medium compared to their respective controls (without EDC). Biodegradation was also found to be correlated with lowering of surface tension from 57.02 mN/m (uninoculated control) to 44.16 mN/m in case of BPA and 38.49 mN/m in TCS, indicative of biosurfactant (BS) production. FTIR, GC-MS, and LC-ESI/MSMS confirmed the presence of surfactin lipopeptide isoforms. The WRF also displayed positive plant growth promoting traits as production of ammonia, indole acetic acid, siderophores, Zn solubilization, and 1-1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, reflecting its soil restoration ability. Discussion: The combined traits of biosurfactant production, EDC degradation and plant growth promotion displayed by WRF will help in emulsifying the hydrophobic pollutants favoring their fast degradation along with restoration of contaminated soil in natural conditions.

Gamma Irradiation and Exogenous Proline Enhanced the Growth, 2AP Content, and Inhibitory Effects of Selected Bioactive Compounds against α-Glucosidase and α-Amylase in Thai Rice.

Exogenous proline can improve the growth, aroma intensities, and bioactive compounds of rice. This study evaluated the effects of gamma irradiation under proline conditions on the 2-acetyl-1-pyrroline (2AP), phenolic, and flavonoid contents of rice. Moreover, the bioactive compounds of gamma-irradiated rice under proline conditions that inhibited α-glucosidase and α-amylase were evaluated by in silico study. A low gamma dose (40 Gy) induced the highest rice growth under 5 mM proline concentration. The highest 2AP content was stimulated at a gamma dose of 5－100 Gy under 10 mM proline concentration. At 500 and 1,000 Gy gamma dose, the highest flavonoid and phenolic contents of rice were stimulated. 1-(2-Hydroxy-5-methylphenyl)-ethanone, which had the highest binding affinity (-7.9 kcal/mol) against α-glucosidase, was obtained at 500 and 1,000 Gy gamma dose under 5 and 10 mM proline concentrations. Meanwhile, 6-amino-1,3,5-triazine-2,4(1H,3H)-dione, which had the highest binding affinity (-6.3 kcal/mol) against α-amylase, was obtained under 10 mM proline concentration in non-gamma-irradiated rice. The results indicate that using a combination of gamma irradiation and exogenous proline is suitable for producing new rice varieties. Moreover, the bioactive compounds that were obtained in new rice varieties exhibited health benefits, especially for diabetes mellitus treatment (inhibition of α-glucosidase and α-amylase).

Acute Cyanide Toxicity and Emergency Management in a Goldsmith: A Case Report.

Acute cyanide toxicity is very rare but it is almost always associated with fatal outcomes. Here we describe the case of a 43-year-old healthy male who worked in a jewelry factory and presented with acute cyanide toxicity. He was successfully managed with all the supportive measures and an appropriate antidote kit containing amyl nitrite, sodium nitrite, and sodium thiosulfate. We also describe the relevant importance of knowing the history of easy access to cyanide as a part of the patient's profession, the critical nature of the patient at presentation, as well as the efforts needed to procure the antidote.

Inoculation with Jeotgalicoccus sp. improves nutritional quality and biological value of Eruca sativa by enhancing amino acid and phenolic metabolism and increasing mineral uptake, unsaturated fatty acids, vitamins, and antioxidants.

Plant growth-promoting bacteria (PGPB) are considered a promising tool for triggering the synthesis of bioactive compounds in plants and to produce healthy foods. This study aimed to demonstrate the impact of PGPB on the growth, accumulation of primary and secondary metabolites, biological activities, and nutritional qualities of Eruca sativa (arugula), a key leafy vegetable worldwide. To this end, Jeotgalicoccus sp. (JW0823), was isolated and identified by using partial 16S rDNA-based identification and phylogenetic analysis. The findings revealed that JW0823 significantly boosted plant biomass production by about 45% (P<0.05) and enhanced pigment contents by 47.5% to 83.8%. JW0823-treated plants showed remarkable improvements in their proximate composition and vitamin contents, with vitamin E levels increasing by 161.5%. JW0823 induced the accumulation of bioactive metabolites including antioxidants, vitamins, unsaturated fatty acids, and essential amino acids, thereby improving the nutritional qualities of treated plants. An increase in the amounts of amino acids was recorded, with isoleucine showing the highest increase of 270.2%. This was accompanied by increased activity of the key enzymes involved in amino acid biosynthesis, including glutamine synthase, dihydrodipicolinate synthase, cystathionine γ-synthase, and phenylalanine ammonia-lyase enzymes. Consequently, the total antioxidant and antidiabetic activities of the inoculated plants were enhanced. Additionally, JW0823 improved antimicrobial activity against several pathogenic microorganisms. Overall, the JW0823 treatment is a highly promising method for enhancing the health-promoting properties and biological characteristics of E. sativa, making it a valuable tool for improving the quality of this important leafy vegetable.

Inside out: Exploring edible biocatalytic biosensors for health monitoring.

Edible biosensors can measure a wide range of physiological and biochemical parameters, including temperature, pH, gases, gastrointestinal biomarkers, enzymes, hormones, glucose, and drug levels, providing real-time data. Edible biocatalytic biosensors represent a new frontier within healthcare technology available for remote medical diagnosis. The main challenges to develop edible biosensors are: i) finding edible materials (i.e. redox mediators, conductive materials, binders and biorecognition elements such as enzymes) complying with Food and Drug Administration (FDA), European Food Safety Authority (EFSA) and European Medicines Agency (EMEA) regulations; ii) developing bioelectronics able to operate in extreme working conditions such as low pH (∼pH 1.5 gastric fluids etc.), body temperature (between 37 °C and 40 °C) and highly viscous bodily fluids that may cause surface biofouling issues. Nowadays, advanced printing techniques can revolutionize the design and manufacturing of edible biocatalytic biosensors. This review outlines recent research on biomaterials suitable for creating edible biocatalytic biosensors, focusing on their electrochemical properties such as electrical conductivity and redox potential. It also examines biomaterials as substrates for printing and discusses various printing methods, highlighting challenges and perspectives for edible biocatalytic biosensors.

Addressing Drug-Drug Interaction Knowledge Gaps at the Time of Approval: An Analysis of FDA Postmarketing Requirements and Commitments from 2009 to 2023.

It has become increasingly common for patients to rely on the use of multiple prescription medications. The management of polypharmacy requires careful consideration for how drugs are metabolized and their potential for interaction with other drugs. Drug-drug interaction (DDI) assessments are typically performed in a stepwise manner during drug development, though knowledge gaps can exist at the time of approval. The US Food and Drug Administration can establish postmarketing requirements (PMRs) or postmarketing commitments (PMCs) to address these knowledge gaps. In this study, we systematically evaluated PMRs and PMCs established to new molecular entities (NMEs) at the time of initial approval between 2009 and 2023, for the assessment of pharmacokinetics-based DDIs (i.e., drug metabolizing enzyme- and transporter-related DDIs). We found that 22% of NMEs had at least one DDI-related PMR or PMC, with a total of 263 that were pharmacokinetic based. Of these, 67% were for the assessment of drug metabolizing enzymes, which were established most frequently for their evaluation as a substrate, and 28% for transporters, which were established most frequently for their evaluation as an inhibitor. The 89% of PMRs and PMCs that were considered fulfilled had a revision to the United States prescribing information, the majority of which resulted in updated new instructions for use. This study highlights the value in conducting PMRs and PMCs early in the drug development process allowing broad patient inclusion at the time of initial drug approval.