Nanoparticles represent highly promising platforms for the development of imaging and therapeutic agents, including those that can either be detected via more than one imaging technique (multi‐modal ...imaging agents) or used for both diagnosis and therapy (theranostics). A major obstacle to their medical application and translation to the clinic, however, is the fact that many accumulate in the liver and spleen as a result of opsonization and scavenging by the mononuclear phagocyte system. This focused review summarizes recent efforts to develop zwitterionic‐coatings to counter this issue and render nanoparticles more biocompatible. Such coatings have been found to greatly reduce the rate and/or extent of non‐specific adsorption of proteins and lipids to the nanoparticle surface, thereby inhibiting production of the “biomolecular corona” that is proposed to be a universal feature of nanoparticles within a biological environment. Additionally, in vivo studies have demonstrated that larger‐sized nanoparticles with a zwitterionic coating have extended circulatory lifetimes, while those with hydrodynamic diameters of ≤5 nm exhibit small‐molecule‐like pharmacokinetics, remaining sufficiently small to pass through the fenestrae and slit pores during glomerular filtration within the kidneys, and enabling efficient excretion via the urine. The larger particles represent ideal candidates for use as blood pool imaging agents, whilst the small ones provide a highly promising platform for the future development of theranostics with reduced side effect profiles and superior dose delivery and image contrast capabilities.
Cloak of invisibility. The coating of nanoparticles with zwitterionic species limits the non‐specific adsorption of biomolecules to their surface and enables them to evade phagocytosis, opening up a promising route for the development of clinically‐approved nanoparticle‐based theranostic agents with fewer off‐target effects.
Epithelial junctions are transmembrane protein complexes that regulate cell adhesion, cell polarity, tissue permeability, and tissue mechanics. Most junctional complexes contain membrane attached ...cytoplasmic plaques that regulate junction assembly and are composed of multivalent scaffold proteins. In this review, we discuss phase separation of multivalent proteins as a general process that drives assembly of many membrane-less cellular compartments. And we summarise recent evidence that phase separation of junctional scaffold proteins is involved in the assembly of tight junctions and focal adhesions.
Lung cancer is the leading cause of cancer-related death. Unfortunately, targeted-therapies have been unsuccessful for most patients with lung adenocarcinoma (LUAD). Thus, new early biomarkers and ...treatment options are a pressing need. Fatty acid binding protein 5 (FABP5) has been associated with various types of cancers. Its contribution to LUAD onset, progression and metabolic reprogramming is, however, not fully understood. In this study we assessed the importance of FABP5 in LUAD and its role in cancer lipid metabolism.
By radioactive labeling and metabolite quantification, we studied the function of FABP5 in fatty acid metabolism using genetic/pharmacologic inhibition and overexpression models in LUAD cell lines. Flow cytometry, heterologous transplantation and bioinformatic analysis were used, in combination with other methodologies, to assess the importance of FABP5 for cellular proliferation in vitro and in vivo and in patient survival.
We show that high expression of FABP5 is associated with poor prognosis in patients with LUAD. FABP5 regulates lipid metabolism, diverting fatty acids towards complex lipid synthesis, whereas it does not affect their catabolism in vitro. Moreover, FABP5 is required for de novo fatty acid synthesis and regulates the expression of enzymes involved in the pathway (including FASN and SCD1). Consistently with the changes in lipid metabolism, FABP5 is required for cell cycle progression, migration and in vivo tumor growth.
Our results suggest that FABP5 is a regulatory hub of lipid metabolism and tumor progression in LUAD, placing it as a new putative therapeutic target for this disease.
•High expression of FABP5 is associated with poor prognosis in patients with LUAD.•FABP5 regulates de novo fatty acid synthesis and the expression of lipogenic enzymes.•The synthesis of complex glycerolipids requires FABP5.•Unlike anabolic routes, oxidative metabolism is not affected by FABP5 alteration.•FABP5 is required for cell cycle progression and promotes xenograft tumor growth.
Alzheimer's disease (AD) is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits, such as alterations in social interactions. The major ...pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. The double transgenic mouse model of AD (2xTg-AD) with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs), when transplanted into the brain, produce positive effects by reducing amyloid-beta (Aβ) deposition in transgenic amyloid precursor protein (APP)/presenilins1 (PS1) mice. Vascular endothelial growth factor (VEGF), exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration. The present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with vascular endothelial growth factor cloned in uP vector under control of modified CMV promoter (uP-VEGF) vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. The animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by immunohistochemistry (IHC) for vascularization and Aβ plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by AD.
Mitosis has been traditionally considered a metabolically inactive phase. We have previously shown, however, that extensive alterations in lipids occur as the cells traverse mitosis, including ...increased de novo fatty acid (FA) and phosphatidylcholine (PtdCho) synthesis and decreased lysophospholipid content. Given the diverse structural and functional properties of these lipids, we sought to study their metabolic fate and their importance for cell cycle completion. Here we show that FA and PtdCho synthesized at the mitotic exit are destined to the nuclear envelope. Importantly, FA and PtdCho synthesis, but not the decrease in lysophospholipid content, are necessary for cell cycle completion beyond G
2
/M. Moreover, the presence of alternative pathways for PtdCho synthesis renders the cells less sensitive to its inhibition than to the impairment of FA synthesis. FA synthesis, thus, represents a cell cycle-related metabolic vulnerability that could be exploited for combined chemotherapy. We explored the combination of fatty acid synthase (FASN) inhibition with agents that act at different phases of the cell cycle. Our results show that the effect of FASN inhibition may be enhanced under some drug combinations.
Bottle-fed infants are at greater risk for overfeeding and rapid weight gain (RWG); evidence-based strategies for promoting healthy bottle-feeding practices are needed.
Our aim was to assess whether ...policy, systems, and environmental (PSE) strategies for promoting responsive bottle-feeding practices within the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) were associated with lower risk for RWG.
We conducted a matched-pair cluster randomized trial. PSE strategies were implemented at 3 WIC clinics in Los Angeles County. PSE clinics were compared with 3 matched control clinics. Mothers and infants were assessed when infants were newborn and 3 months and 6 months of age.
Participants were mothers (n = 246) who enrolled their newborn infants (younger than 60 days) into WIC between May and August 2019.
Infant weight was assessed and standardized to sex- and age-specific z scores. RWG was defined as weight-for-age z score change > 0.67. Mothers completed questionnaires assessing responsive and pressuring feeding styles, breast- and bottle-feeding patterns, and perceptions of WIC experiences.
Logistic regression with estimation via generalized estimating equations and linear mixed models with repeated measures assessed effects of PSE strategies on categorical and continuous outcomes, respectively.
Infants in PSE clinics had significantly lower likelihood of exhibiting RWG (P = .014) than infants in control clinics. Mothers in PSE and control clinics reported similar levels of responsive and pressuring feeding style and similar prevalence of breastfeeding and bottle-feeding. Mothers in PSE clinics trended toward feeling better supported with respect to their decision to bottle-feed (P = .098) and had more stable intentions to stay in the WIC program (P = .002) compared with mothers in control clinics.
PSE strategies focused on promoting more inclusive assessment of infant feeding, tailored bottle-feeding counseling, and increased education and support for responsive bottle-feeding were associated with lower risk for RWG among WIC infants.
This study investigates the thermotolerant fungal biodiversity in caves and hot springs, focusing on their potential for extracellular enzyme production, specifically proteases. Samples were ...collected from the Cardonal region in Hidalgo, Mexico, using three different isolation methods. The study characterizes the morphological diversity of the isolated fungi and identifies various genera, including Aspergillus, Penicillium, Trichoderma, Cladosporium, and Fusarium, based on morphology. The isolated fungi were screened for their ability to produce extracellular enzymes on solid media, with a particular emphasis on proteases due to their industrial significance. Among the 35 isolated fungi, 20 exhibited proteolytic activity, and 12 strains were identified as good protease producers based on enzymatic index values. The study also evaluated the formation of fungal pellets by proteolytic fungi and found certain strains to display significant pellet formation. Additionally, protease production was examined by fungal pellets in submerged cultures, with isolate 6 demonstrating the highest protease activity. The findings highlight the diverse thermotolerant fungal biodiversity in extreme environments, and emphasize their potential for enzymatic production. This research contributes to our understanding of fungal ecology and provides insights into the biotechnological applications of these enzymes. The study recommends further molecular investigations to enhance biodiversity studies in such extreme environments.
The degradation of poly(ethylene terephthalate) by ethylene carbonate with potassium hydroxide was studied. Model reactions were carried out to determine the chemical species produced. Ethylene ...carbonate reacted with potassium hydroxide to yield oligomers with a limited content of carbonate groups. Bis(2-hydroxyethyl) terephthalate condensed to PET oligomers without significant incorporation of ethylene carbonate in the chains when potassium hydroxide was not present and produced difunctional oligomers with hydroxyl terminal groups containing aromatic rings esterified with polyether short chains and some residual carbonate groups when potassium hydroxide was added. Poly(ethylene terephthalate) was converted into difunctional oligomers of approximately 1000–2000 g·mol−1 molecular weight with short polyether chains connecting the terephthalate rings and a significant content of carbonate groups. The resulting oligomers could find application as polyols for the synthesis of polyurethanes.
The antioxidant phenotype caused by resveratrol has been recognized as a key piece in the health benefits exerted by this phytochemical in diseases related to aging. It has recently been proposed ...that a mitochondrial pro‐oxidant mechanism could be the cause of resveratrol antioxidant properties. In this regard, the hypothesis that resveratrol impedes electron transport to complex III of the electron transport chain as its main target suggests that resveratrol could increase reactive oxygen species (ROS) generation through reverse electron transport or by the semiquinones formation. This idea also explains that cells respond to resveratrol oxidative damage, inducing their antioxidant systems. Moreover, resveratrol pro‐oxidant properties could accelerate the aging process, according to the free radical theory of aging, which postulates that organism's age due to the accumulation of the harmful effects of ROS in cells. Nonetheless, there is no evidence linking the chronological lifespan (CLS) shorten occasioned by resveratrol with a pro‐oxidant mechanism. Hence, this study aimed to evaluate whether resveratrol shortens the CLS of Saccharomyces cerevisiae due to a pro‐oxidant activity. Herein, we provide evidence that supplementation with 100 μM of resveratrol at 5% glucose: (1) shortened the CLS of ctt1Δ and yap1Δ strains; (2) decreased ROS levels and increased the catalase activity in WT strain; (3) maintained unaffected the ROS levels and did not change the catalase activity in ctt1Δ strain; and (4) lessened the exponential growth of ctt1Δ strain, which was restored with the adding of reduced glutathione. These results indicate that resveratrol decreases CLS by a pro‐oxidant mechanism.
In this article, the authors present evidence of how resveratrol decreases the chronological aging of Saccharomyces cerevisiae through a pro‐oxidant mechanism. Also, they provide insights into the essential role of the cytosolic catalase T to counteract the resveratrol pro‐oxidant phenotype.
Take Away
High‐glucose supplementation promotes pro‐oxidant resveratrol phenotype.
Resveratrol augments chronological aging by a pro‐oxidant mechanism.
Catalase T is essential to counteract resveratrol pro‐oxidative properties.
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