Phytoconsitutents As Bioenhancers: A Review

Bio-enhancers are the compounds that enhance the bioavailability of active pharmaceutical ingredients without itself having any pharmacological action. Most of them are of natural origin and do not have any side effects. They enhance the bioavailability by influencing variety of mechanisms involved in the drug action like penetration enhancement, improving metabolism, enzyme inhibition, drug targeting etc. Use of these compounds help to reduce the dose frequency which in turn reduces drug retention in turn causing the toxicity and it also helps in developing cost-effective products. Present days these are widely used to enhance the bioavailability of anti-bacterial, anti-viral, antibiotic, anticancer, anti-inflammatory, cardiovascular drugs etc and effective drug targeting. The present review is designed to emphasize the importance of certain phytoconstituents working as bio-enhancers, their classification and different mechanisms of their activity.

Phenylpropanoid metabolism enzyme activities and gene expression in postharvest melons inoculated with Alternaria alternata

This study explored the mechanism of melon resistance to Alternaria alternata (A. alternata) infection in Jiashi and 86-1 melons. Melons were inoculated with A.alternata and the change in lesion diameter was measured. The changes in cinnamic acid-4-hydroxylase (C4H), phenylalanine ammonia lyase (PAL), and 4-coumaric acid coenzyme A ligase (4CL) activity and gene expression were studied in the pericarp tissues of Jiashi and 86-1 melons. The lesion diameter was smaller in Jiashi melon than in 86-1 melon, and the pericarp lesions were smaller than pulp lesions, indicating that Jiashi melon can resist A. alternata infection better than 86-1 melon. After inoculation with A. alternata, the C4H, PAL, and 4CL activities of Jiashi and 86-1 melons peaked in the middle and late storage period, and the peak was higher in Jiashi melons. The gene expression changes were consistent with the enzyme activity. The C4H, PAL, and 4CL gene expression was significantly higher in Jiashi melon pericarp than in 86-1 melon, and the C4H, PAL, and 4CL activities in Jiashi melon were positively correlated with their gene expression, confirming the role of phenylpropanoid metabolism enzymes in resistance to A. alternata.

The Quality of Superior Seedless Bunches during Shelf Life as Determined by Growth on Different Rootstocks

Vineyard rootstocks are an important tool in the local and international market for growing the Superior Seedless grape cultivar, which is highly favored by customers. As a result, it is vital to pay close attention to the quality of clusters during handling. The current study aimed to determine whether Superior Seedless vines can be grown on specific rootstocks, resulting in higher quality during shelf life. Vines of the Superior Seedless vine cultivar that were used were 13 years old and had been grown on sandy soil. These vines were grafted onto four different rootstocks (genotypes), namely Freedom, 1103 Paulsen, SO4, and Own Root. The soluble solids content (SSC%) was selected as 16%. Bunches were subsequently stored in the lab at 27 ± 1 °C with 57 ± 3% air relative humidity for three days. Rootstock 1103 Paulsen’s quality was found to be superior to that of the other rootstocks, according to the results of the study. Rootstock 1103 Paulsen maintained its ascorbic acid (AA) content, which is reflected in its antioxidant capacity, according to the results. In addition, lipid peroxidation accumulation and ion leakage percentages indicated that oxidative reactions were at their lowest levels. The results show that 1103 Paulsen decreases cellular metabolism enzyme activities at the shelf life level and improves the bunch quality of Superior Seedless (scion) grapes within 4 days of application. As a whole, the results show that the 1103 Paulsen rootstock produces Superior Seedless bunches of a high quality that is preserved throughout the shelf life period.

Metformin sensitises hepatocarcinoma cells to methotrexate by targeting dihydrofolate reductase

Metformin, the first-line drug for type II diabetes, has recently been considered an anticancer agent. However, the molecular target and underlying mechanism of metformin’s anti-cancer effects remain largely unclear. Herein, we report that metformin treatment increases the sensitivity of hepatocarcinoma cells to methotrexate (MTX) by suppressing the expression of the one-carbon metabolism enzyme DHFR. We show that the combination of metformin and MTX blocks nucleotide metabolism and thus effectively inhibits cell cycle progression and tumorigenesis. Mechanistically, metformin not only transcriptionally represses DHFR via E2F4 but also promotes lysosomal degradation of the DHFR protein. Notably, metformin dramatically increases the response of patient-derived hepatocarcinoma organoids to MTX without obvious toxicity to organoids derived from normal liver tissue. Taken together, our findings identify an important role for DHFR in the suppressive effects of metformin on therapeutic resistance, thus revealing a therapeutically targetable potential vulnerability in hepatocarcinoma.

Significance of TPMT and NUDT15 variants in 6-mercaptopurine metabolism in acute lymphoblastic leukaemia/lymphoma patients

Introduction. Among main curative substances in acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is 6-mercaptopurine (6-MP). However, the severity of adverse reactions (ADRs) to this drug varies considerably among patients, which is sometimes conditioned by individual single nucleotide polymorphisms in key 6-MP metabolism enzyme genes.Aim — a literature review on the role of TPMT and NUDT15 gene variants in 6-MP metabolism in ALL/LBL.Main findings. The TPMT and NUDT15 genes encode enzymes mediating key steps of the 6-MP metabolism. The metabolites determine the 6-MP therapeutic and toxic properties, with ADRs emerging when their concentrations alter. A number of TPMT and NUDT15 single nucleotide polymorphisms are associated with varied activities of the encoded enzymes, and their allelic combinations condition functional and non-functional phenotypes. Non-functional variant carriers more likely develop toxicity on 6-MP treatment compared to functional phenotypes. Non-functional TPMT/NUDT15 carriers should have the 6-MP dosage reduced to minimise emerging ADRs.

LFR Physically and Genetically Interacts With SWI/SNF Component SWI3B to Regulate Leaf Blade Development in Arabidopsis

Leaves start to develop at the peripheral zone of the shoot apical meristem. Thereafter, symmetric and flattened leaf laminae are formed. These events are simultaneously regulated by auxin, transcription factors, and epigenetic regulatory factors. However, the relationships among these factors are not well known. In this study, we conducted protein-protein interaction assays to show that our previously reported Leaf and Flower Related (LFR) physically interacted with SWI3B, a component of the ATP-dependent chromatin remodeling SWI/SNF complex in Arabidopsis. The results of truncated analysis and transgenic complementation showed that the N-terminal domain (25–60 amino acids) of LFR was necessary for its interaction with SWI3B and was crucial for LFR functions in Arabidopsis leaf development. Genetic results showed that the artificial microRNA knockdown lines of SWI3B (SWI3B-amic) had a similar upward-curling leaf phenotype with that of LFR loss-of-function mutants. ChIP-qPCR assay was conducted to show that LFR and SWI3B co-targeted the promoters of YABBY1/FILAMENTOUS FLOWER (YAB1/FIL) and IAA carboxyl methyltransferase 1 (IAMT1), which were misexpressed in lfr and SWI3B-amic mutants. In addition, the association between LFR and the FIL and IAMT1 loci was partly hampered by the knockdown of SWI3B. These data suggest that LFR interacts with the chromatin-remodeling complex component, SWI3B, and influences the transcriptional expression of the important transcription factor, FIL, and the auxin metabolism enzyme, IAMT1, in flattened leaf lamina development.

Identification of Essential Genes Associated With Prodigiosin Production in Serratia marcescens FZSF02

Prodigiosin is a promising secondary metabolite produced mainly by Serratia strains. To study the global regulatory mechanism of prodigiosin biosynthesis, a mutagenesis library containing 23,000 mutant clones was constructed with the EZ-Tn5 transposon, and 114 clones in the library showed altered prodigiosin production ability. For 37 of the 114 clones, transposon insertion occurred on the prodigiosin biosynthetic cluster genes; transposon inserted genes of the 77 clones belonged to 33 different outside prodigiosin biosynthetic cluster genes. These 33 genes can be divided into transcription-regulating genes, membrane protein-encoding genes, and metabolism enzyme-encoding genes. Most of the genes were newly reported to be involved in prodigiosin production. Transcriptional levels of the pigA gene were significantly downregulated in 22 mutants with different inserted genes, which was in accordance with the phenotype of decreased prodigiosin production. Functional confirmation of the mutant genes involved in the pyrimidine nucleotide biosynthesis pathway was carried out by adding orotate and uridylate (UMP) into the medium. Gene complementation confirmed the regulatory function of the EnvZ/OmpR two-component regulatory system genes envZ and ompR in prodigiosin production.

Effects of Microplastics Exposure on the Acropora sp. Antioxidant, Immunization and Energy Metabolism Enzyme Activities

Graphical AbstractThe experiment flow chart of anti-inflammatory and analgesic effects of P. orientale extracts.

A Comparative Assessment of the Chronic Effects of Micro- and Nano-Plastics on the Physiology of the Mediterranean Mussel Mytilus galloprovincialis

The ocean contamination caused by micro- and nano-sized plastics is a matter of increasing concern regarding their potential effects on marine organisms. This study compared the effects of a 21-day exposure to 1.5, 15, and 150 ng/L of polystyrene microplastics (PS-MP, 3-µm) and nanoplastics (PS-NP, 50-nm) on a suite of biomarkers measured in the Mediterranean mussel Mytilus galloprovincialis. Endpoints encompassed immunological/lysosomal responses, oxidative stress/detoxification parameters, and neurotoxicological markers. Compared to PS-MP, PS-NP induced higher effects on lysosomal parameters of general stress. Exposures to both particle sizes increased lipid peroxidation and catalase activity in gills; PS-NP elicited greater effects on the phase-II metabolism enzyme glutathione S-transferase and on lysozyme activity, while only PS-MP inhibited the hemocyte phagocytosis, suggesting a major role of PS particle size in modulating immunological/detoxification pathways. A decreased acetylcholinesterase activity was induced by PS-NP, indicating their potential to impair neurological functions in mussels. Biomarker data integration in the Mussel Expert System identified an overall greater health status alteration in mussels exposed to PS-NP compared to PS-MP. This study shows that increasing concentrations of nanoplastics may induce higher effects than microplastics on the mussel’s lysosomal, metabolic, and neurological functions, eventually resulting in a greater impact on their overall fitness.