A novel step towards the heterologous biosynthesis of paclitaxel: Characterization of T1βOH taxane hydroxylase.

In the quest for innovative cancer therapeutics, paclitaxel remains a cornerstone in clinical oncology. However, its complex biosynthetic pathway, particularly the intricate oxygenation steps, has remained a puzzle in the decades following the characterization of the last taxane hydroxylase. The high divergence and promiscuity of enzymes involved have posed significant challenges.

Tobacco is a Leading Risk Factor for Liver and Extrahepatic Cancers in Patients With Liver Cirrhosis: A Prospective Cohort Study.

Background & Aims: This study aims to assess the incidence and characteristics of all cancers, hepatocellular carcinoma (HCC), and extrahepatic cancers in patients with cirrhosis of various etiologies.

Methods: Prospective cohort study in patients with cirrhosis but no cancer, followed every 6-9 months through the HCC early detection program. Cancer incidence was compared with Spanish population data to calculate standardized incidence ratios (SIR), and cumulative incidence was calculated separately for cancer and competing events.

Insights into enhancing organ cell biofactories via hairy root protein profiling.

Recent advancements in plant biotechnology have highlighted the potential of hairy roots as a biotechnological platform, primarily due to their rapid growth and ability to produce specialized metabolites. This study aimed to delve deeper into hairy root development in and explore the optimization of genetic transformation for enhanced bioactive compound production. Previously established hairy root lines of were categorized based on their centelloside production capacity into HIGH, MID, or LOW groups.

Overexpression of BAPT and DBTNBT genes in Taxus baccata in vitro cultures to enhance the biotechnological production of paclitaxel.

Paclitaxel is one of the most effective anticancer drugs ever developed. Although the most sustainable approach to its production is provided by plant cell cultures, the yield is limited by bottleneck enzymes in the taxane biosynthetic pathway: baccatin-aminophenylpropanoyl-13-O-transferase (BAPT) and 3'-N-debenzoyltaxol N-benzoyltransferase (DBTNBT). With the aim of enhancing paclitaxel production by overcoming this bottleneck, we obtained distinct lines of Taxus baccata in vitro roots, each independently overexpressing either of the two flux-limiting genes, BAPT or DBTNBT, through a Rhizobium rhizogenes A4-mediated transformation.

Exploring the Interplay between Metabolic Pathways and Taxane Production in Elicited Cell Suspensions.

cell cultures are a reliable biotechnological source of the anticancer drug paclitaxel. However, the interplay between taxane production and other metabolic pathways during elicitation remains poorly understood. In this study, we combined untargeted metabolomics and elicited cell cultures to investigate variations in taxane-associated metabolism under the influence of 1 µM coronatine (COR) and 150 µM salicylic acid (SA).

Polyploidy as a strategy to increase taxane production in yew cell cultures: Obtaining and characterizing a Taxus baccata tetraploid cell line.

Novel approaches to optimize the production of plant specialized metabolites are crucial to reach maximum productivity of plant biofactories. Plant polyploidization frequently enhances protein synthesis and thereby increases the biosynthesis of specialized metabolites. Paclitaxel is a valuable anticancer agent scarcely produced in nature.

Immune changes over time and survival in patients with cirrhosis treated with non-selective beta-blockers: A prospective longitudinal study.

Background: Treatment with non-selective beta-blockers (NSBB) has been associated with anti-inflammatory and anti-cancer effects in patients with cirrhosis. This study aims to analyze the impact of chronic NSBB treatment on immune activation and disease progression in stable outpatients with cirrhosis.

Methods: In this prospective follow-up of 150 patients with cirrhosis, 39 received treatment with NSBB.

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

Background & Aims: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis.

Impact of Elicitation on Plant Antioxidants Production in Cell Cultures.

Elicited cell cultures of spp. are successfully used as sustainable biotechnological production systems of the anticancer drug paclitaxel, but the effect of the induced metabolomic changes on the synthesis of other bioactive compounds by elicitation has been scarcely studied. In this work, a powerful combinatorial approach based on elicitation and untargeted metabolomics was applied to unravel and characterize the effects of the elicitors 1 µM of coronatine (COR) or 150 µM of salicylic acid (SA) on phenolic biosynthesis in cell suspensions.

Genetic approaches in improving biotechnological production of taxanes: An update.

Paclitaxel (PTX) and its derivatives are diterpene alkaloids widely used as chemotherapeutic agents in the treatment of various types of cancer. Due to the scarcity of PTX in nature, its production in cell cultures and plant organs is a major challenge for plant biotechnology. Although significant advances have been made in this field through the development of metabolic engineering and synthetic biology techniques, production levels remain insufficient to meet the current market demand for these powerful anticancer drugs.

Biodiversity, Biochemical Profiling, and Pharmaco-Commercial Applications of : A Review.

L. Dunal (Ashwagandha), a key medicinal plant native to India, is used globally to manage various ailments. This review focuses on the traditional uses, botany, phytochemistry, and pharmacological advances of its plant-derived constituents.

Iron Trichloride-Mediated Cascade Reaction of Aminosugar Derivatives for the Synthesis of Fused Tetrahydroisoquinoline-Tetrahydrofuran Systems.

A method to obtain tetrahydroisoquinolines (THIQs) fused to tetrahydrofuran rings from aminosugar derivatives has been developed. The procedure relies on a key deprotection of benzyl ethers followed by a double-cyclization sequence, using FeCl as the sole reagent. This tandem reaction affords the construction of novel fused polycyclic heterocycles with total stereochemical control.

Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding.

Background: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown.

Using machine learning to link the influence of transferred genes to the hormone profile and morphological traits in hairy roots.

Hairy roots are made after the integration of a small set of genes from in the plant genome. Little is known about how this small set is linked to their hormone profile, which determines development, morphology, and levels of secondary metabolite production. We used hairy root line cultures to determine the putative links between the and gene expressions with morphological traits, a hormone profile, and centelloside production.

Biotic Elicitors in Adventitious and Hairy Root Cultures: A Review from 2010 to 2022.

One of the aims of plant in vitro culture is to produce secondary plant metabolites using plant cells and organ cultures, such as cell suspensions, adventitious, and hairy roots (among others). In cases where the biosynthesis of a compound in the plant is restricted to a specific organ, unorganized systems, such as plant cell cultures, are sometimes unsuitable for biosynthesis. Then, its production is based on the establishment of organ cultures such as roots or aerial shoots.

Insights into the control of taxane metabolism: Molecular, cellular, and metabolic changes induced by elicitation in cell suspensions.

More knowledge is needed about the molecular/cellular control of paclitaxel (PTX) production in spp. cell cultures. In this study, the yield of this anticancer agent in cell suspensions was improved 11-fold after elicitation with coronatine (COR) compared to the untreated cells, and 18-fold when co-supplemented with methyl-β-cyclodextrins (β-CDs).

Gene expression pattern and taxane biosynthesis in a cell suspension culture of Taxus baccata L. subjected to light and a phenylalanine ammonia lyase (PAL) inhibitor.

Taxus baccata L. cell culture is a promising commercial method for the production of taxanes with anti-cancer activities. In the present study, a T.

The Epigenetic Regulation in Plant Specialized Metabolism: DNA Methylation Limits Paclitaxel Biotechnological Production.

Environmental conditions are key factors in the modulation of the epigenetic mechanisms regulating gene expression in plants. Specifically, the maintenance of cell cultures in optimal conditions alters methylation patterns and, consequently, their genetic transcription and metabolism. Paclitaxel production in cell cultures is reduced during its maintenance in conditions, compromising the biotechnological production of this valuable anticancer agent.

Ethnoveterinary Medicine and Ethnopharmacology in the Main Transhumance Areas of Castilla-La Mancha (Spain).

In this study, we document the practices of ethnoveterinary medicine and ethnopharmacology in the context of traditional transhumance routes that cross Castilla La Mancha from north to south. Transhumance is a type of grazing system that allows advantage to be taken of winter pastures (wintering places) and summer pastures by seasonal movement, twice a year, of cattle and their shepherds. Our study is based on over 200 interviews (from 1994 to 2021) conducted in 86 localities along eight major transhumance routes "cañadas reales" and 25 other minor transhumance routes, and involved 210 informants, 89 single and 121 groups, and 562 individuals, of which the majority were men.

Phenylpropanoids in Silybum marianum cultures treated with cyclodextrins coated with magnetic nanoparticles.

The glucose oligosaccharide-derived cyclodextrins (CDs) are used for improving bioactive compound production in plant cell cultures because, in addition to their elicitation activity, CDs promote product removal from cells. However, despite these advantages, the industrial application of CDs is hampered by their high market price. A strategy to overcome this constraint was recently tested, in which reusable CD polymers coated with magnetic FeO nanoparticles were harnessed in Vitis vinifera cell cultures to produce t-resveratrol (t-R).

Cutaneous Metastases of Solid Tumors: Demographic, Clinical, and Survival Characteristics.

Background: Cutaneous metastasis (CM), while uncommon, is usually an indicator of poor prognosis. With cancer patients living longer, the incidence of CM has increased, which justifies its analysis.

Objectives: The objective of this study was to carry out a descriptive study of CM diagnosed for 18 years in a dermatology department of a tertiary care hospital and to assess the epidemiological, clinical, and histological variables that condition them, as well as data on their survival and prognosis.

Effect of Polyploidy Induction on Natural Metabolite Production in Medicinal Plants.

Polyploidy plays an important role in plant diversification and speciation. The ploidy level of plants is associated with morphological and biochemical characteristics, and its modification has been used as a strategy to alter the quantitative and qualitative patterns of secondary metabolite production in different medicinal plants. Polyploidization can be induced by many anti-mitotic agents, among which colchicine, oryzalin, and trifluralin are the most common.

Methyl-β-cyclodextrin and coronatine as new elicitors of tropane alkaloid biosynthesis in Atropa acuminata and Atropa belladonna hairy root cultures.

Hyoscyamine (HYO) and scopolamine (SCO) are tropane alkaloids acting as anticholinergic factors on the parasympathetic nervous system in humans and are produced by Solanaceous plants. Two strains of Agrobacterium rhizogenes, A4 and LBA9402, were used to infect Atropa acuminata Royle ex Miers and Atropa belladonna L. leaf explants.