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Biofilms are emerging platforms for the production of valuable compounds. The present study is the first to assess the capacity of Escherichia coli biofilms to produce curcumin through the expression of a biosynthetic pathway involving three genes: 4-coumarate-CoA ligase (4CL), diketide-CoA synthase (DCS), and curcumin synthase (CURS). The effects of chemical induction with isopropyl β-d-1-thiogalactopyranoside (IPTG) and ferulic acid (FA), and the incubation temperature on biofilm formation and curcumin production were evaluated. Biofilms were formed in 12-well microtiter plates over three days and then induced with 1 mM IPTG and FA at 2 or 8 mM. After induction, the samples were incubated for two days at 26 or 30 °C. Total and culturable planktonic and biofilm cells, as well as biofilm thickness and volumetric and specific curcumin production, were assessed on days 3, 4, and 5. The results demonstrated that biofilms produced up to 10-fold higher curcumin levels (0.9–2.2 fg·cell−1) than their planktonic counterparts (0.1–0.3 fg·cell−1). The highest specific curcumin production (2.2 fg·cell−1) was achieved using 8 mM FA. However, no significant differences in curcumin production were observed between the induced samples incubated at the tested temperatures. These results validated the potential of biofilm systems for expressing a complete exogenous biosynthetic pathway using metabolic engineering, particularly for curcumin production.

Oils and lipids help make water-insoluble drugs soluble by dispersing them in an aqueous medium with the help of a surfactant and enabling their absorption across the gut barrier. The emergence of microemulsions (thermodynamically stable), nanoemulsions (kinetically stable), and self-emulsifying drug delivery systems added unique characteristics that make them suitable for prolonged storage and controlled release. In the 1990s, solid-phase lipids were introduced to reduce drug leakage from nanoparticles and prolong drug release. Manipulating the structure of emulsions and solid lipid nanoparticles has enabled multifunctional nanoparticles and the loading of therapeutic macromolecules such as proteins, nucleic acid, vaccines, etc. Phospholipids and surfactants with a well-defined polar head and carbon chain have been used to prepare bilayer vesicles known as liposomes and niosomes, respectively. The increasing knowledge of targeting ligands and external factors to gain control over pharmacokinetics and the ever-increasing number of synthetic lipids are expected to make lipid nanoparticles and vesicular systems a preferred choice for the encapsulation and targeted delivery of therapeutic agents. This review discusses different lipids and oil-based nanoparticulate systems for the delivery of water-insoluble drugs. The salient features of each system are highlighted, and special emphasis is given to studies that compare them.

Pancreatic cancer represents one of the most lethal cancer types worldwide, with a 5-year survival rate of less than 5%. Due to the inability to diagnose it promptly and the lack of efficacy of existing treatments, research and development of innovative therapies and new diagnostics are crucial to increase the survival rate and decrease mortality. Nanomedicine has been gaining importance as an innovative approach for drug delivery and diagnosis, opening new horizons through the implementation of smart nanocarrier systems, which can deliver drugs to the specific tissue or organ at an optimal concentration, enhancing treatment efficacy and reducing systemic toxicity. Varied materials such as lipids, polymers, and inorganic materials have been used to obtain nanoparticles and develop innovative drug delivery systems for pancreatic cancer treatment. In this review, it is discussed the main scientific advances in pancreatic cancer treatment by nano-based drug delivery systems. The advantages and disadvantages of such delivery systems in pancreatic cancer treatment are also addressed. More importantly, the different types of nanocarriers and therapeutic strategies developed so far are scrutinized.

The Lactococcus lactis bacterium found in different natural environments is traditionally associated with the fermented food industry. But recently, its applications have been spreading to the pharmaceutical industry, which has exploited its probiotic characteristics and is moving towards its use as cell factories for the production of added-value recombinant proteins and plasmid DNA (pDNA) for DNA vaccination, as a safer and industrially profitable alternative to the traditional Escherichia coli host. Additionally, due to its food-grade and generally recognized safe status, there have been an increasing number of studies about its use in live mucosal vaccination. In this review, we critically systematize the plasmid replicons available for the production of pharmaceutical-grade pDNA and recombinant proteins by L. lactis. A plasmid vector is an easily customized component when the goal is to engineer bacteria in order to produce a heterologous compound in industrially significant amounts, as an alternative to genomic DNA modifications. The additional burden to the cell depends on plasmid copy number and on the expression level, targeting location and type of protein expressed. For live mucosal vaccination applications, besides the presence of the necessary regulatory sequences, it is imperative that cells produce the antigen of interest in sufficient yields. The cell wall anchored antigens had shown more promising results in live mucosal vaccination studies, when compared with intracellular or secreted antigens. On the other side, engineering L. lactis to express membrane proteins, especially if they have a eukaryotic background, increases the overall cellular burden. The different alternative replicons for live mucosal vaccination, using L. lactis as the DNA vaccine carrier or the antigen producer, are critically reviewed, as a starting platform to choose or engineer the best vector for each application.

Glyphosate is a systemic, broad-spectrum and post-emergent herbicide. The use of glyphosate has grown in the last decades, and it is currently the most used herbicide worldwide. The rise of glyphosate consumption over the years also brought an increased concern about its possible toxicity and consequences for human health. However, a scientific community consensus does not exist at the present time, and glyphosate’s safety and health consequences are controversial. Since glyphosate is mainly applied in fields and can persist several months in the soil, concerns have been raised about the impact that its presence in food can cause in humans. Therefore, this work aims to review the glyphosate use, toxicity and occurrence in diverse food samples, which, in certain cases, occurs at violative levels. The incidence of glyphosate at levels above those legally allowed and the suspected toxic effects of this compound raise awareness regarding public health.

The vimentin network displays remarkable plasticity to support basic cellular functions and reorganizes during cell division. Here, we show that in several cell types vimentin filaments redistribute to the cell cortex during mitosis, forming a robust framework interwoven with cortical actin and affecting its organization. Importantly, the intrinsically disordered tail domain of vimentin is essential for this redistribution, which allows normal mitotic progression. A tailless vimentin mutant forms curly bundles, which remain entangled with dividing chromosomes leading to mitotic catastrophes or asymmetric partitions. Serial deletions of vimentin tail domain gradually impair cortical association and mitosis progression. Disruption of f-actin, but not of microtubules, causes vimentin bundling near the chromosomes. Pathophysiological stimuli, including HIV-protease and lipoxidation, induce similar alterations. Interestingly, full filament formation is dispensable for cortical association, which also occurs in vimentin particles. These results unveil implications of vimentin dynamics in cell division through its interplay with the actin cortex. The intermediate filament vimentin reorganizes during mitosis, but its molecular regulation and impact on the cell during cell division is unclear. Here, the authors show that vimentin filaments redistribute to the cell cortex during mitosis intertwining with and affecting actin organization.

Background/Objectives: The development of innovative materials for disease diagnostics and therapeutics is a fast-growing area of scientific research. In this work, we report the development of innovative hydrogels incorporating carbon dots (Cdots) for bioimaging purposes. Methods: The Cdots were prepared using a sustainable and low-cost process, starting with an underused fiber from the Brazilian semiarid region. Spectroscopy analysis (Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, UV-visible spectroscopy), X-ray diffraction, photoluminescence, zeta potential, scanning electron microscopy, and transmission electron microscopy were used to characterize these hydrogels. In addition, biocompatibility using the resazurin assay and cellular uptake by confocal microscopy were evaluated. Results: Our results showed that the Cdots changed the structure and crystallinity of hydrogels, mainly due to heat treatment. In addition, hydrogels’ chemical groups suffer red and blue shifts following the Cdots incorporation. Moreover, the Cdots were homogeneously incorporated into the hydrogel matrix. Importantly, the cytotoxicity levels were maintained above 90% (p < 0.01), and cellular uptake studies using HeLa cells demonstrated intracellular fluorescence of both the Cdots and hydrogels after incubation. Additionally, the concentration of Cdots within hydrogels significantly affected fluorescence intensity, even compared with pure Cdots. Conclusions: These results showcase the potential for these hydrogels to be further developed as biomarkers and therapeutic biomaterials for women’s health.

Rett Syndrome is a progressive neurodevelopmental disorder caused mainly by mutations in the gene encoding methyl-CpG-binding protein 2. The relevance of MeCP2 for GABAergic function was previously documented in animal models. In these models, animals show deficits in brain-derived neurotrophic factor, which is thought to contribute to the pathogenesis of this disease. Neuronal Cation Chloride Cotransporters (CCCs) play a key role in GABAergic neuronal maturation, and brain-derived neurotrophic factor is implicated in the regulation of CCCs expression during development. Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group. The presence of bumetanide sensitive NKCC1 and KCC2 was analysed in cerebrospinal fluid samples from a control pediatric population (1 day to 14 years of life) and from Rett syndrome patients (2 to 19 years of life), by immunoblot analysis. Both proteins were detected in the cerebrospinal fluid and their levels are higher in the early postnatal period. However, Rett syndrome patients showed significantly reduced levels of KCC2 and KCC2/NKCC1 ratio when compared to the control group. Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective.

The World Health Organization identifies tuberculosis (TB), caused by Mycobacterium tuberculosis, as a leading infectious killer. Although conventional treatments for TB exist, they come with challenges such as a heavy pill regimen, prolonged treatment duration, and a strict schedule, leading to multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The rise of MDR strains endangers future TB control. Despite these concerns, the hunt for an efficient treatment continues. One breakthrough has been the use of nanotechnology in medicines, presenting a novel approach for TB treatment. Nanocarriers, such as lipid nanoparticles, nanosuspensions, liposomes, and polymeric micelles, facilitate targeted delivery of anti-TB drugs. The benefits of nanocarriers include reduced drug doses, fewer side effects, improved drug solubility, better bioavailability, and improved patient compliance, speeding up recovery. Additionally, nanocarriers can be made even more targeted by linking them with ligands such as mannose or hyaluronic acid. This review explores these innovative TB treatments, including studies on nanocarriers containing anti-TB drugs and related patents.

One of the fundamental patterns in macroecology is the increase in the number of observed taxa with size of sampled area. For microbes, the shape of this relationship remains less clear. The current study assessed the diversity of aquatic fungi, by the traditional approach based on conidial morphology (captures reproducing aquatic hyphomycetes) and next generation sequencing (NGS; captures other fungi as well), on graded sizes of alder leaves (0.6 to 13.6 cm2). Leaves were submerged in two streams in geographically distant locations: the Oliveira Stream in Portugal and the Boss Brook in Canada. Decay rates of alder leaves and fungal sporulation rates did not differ between streams. Fungal biomass was higher in Boss Brook than in Oliveira Stream, and in both streams almost 100% of the reads belonged to active fungal taxa. In general, larger leaf areas tended to harbour more fungi, but these findings were not consistent between techniques. Morphospecies-based diversity increased with leaf area in Boss Brook, but not in Oliveira Stream; metabarcoding data showed an opposite trend. The higher resolution of metabarcoding resulted in steeper taxa-accumulation curves than morphospecies-based assessments (fungal conidia morphology). Fungal communities assessed by metabarcoding were spatially structured by leaf area in both streams. Metabarcoding promises greater resolution to assess biodiversity patterns in aquatic fungi and may be more accurate for assessing taxa-area relationships and local to global diversity ratios.