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Communications Biology Jul 2023Proper organization of intracellular assemblies is fundamental for efficient promotion of biochemical processes and optimal assembly functionality. Although advances in...
Proper organization of intracellular assemblies is fundamental for efficient promotion of biochemical processes and optimal assembly functionality. Although advances in imaging technologies have shed light on how the centrosome is organized, how its constituent proteins are coherently architected to elicit downstream events remains poorly understood. Using multidisciplinary approaches, we showed that two long coiled-coil proteins, Cep63 and Cep152, form a heterotetrameric building block that undergoes a stepwise formation into higher molecular weight complexes, ultimately generating a cylindrical architecture around a centriole. Mutants defective in Cep63•Cep152 heterotetramer formation displayed crippled pericentriolar Cep152 organization, polo-like kinase 4 (Plk4) relocalization to the procentriole assembly site, and Plk4-mediated centriole duplication. Given that the organization of pericentriolar materials (PCM) is evolutionarily conserved, this work could serve as a model for investigating the structure and function of PCM in other species, while offering a new direction in probing the organizational defects of PCM-related human diseases.
Topics: Humans; Cell Cycle; Centrioles; Centrosome; Molecular Weight; Protein Domains; Protein Serine-Threonine Kinases
PubMed: 37433832
DOI: 10.1038/s42003-023-05067-8 -
Advanced Biology May 2024Yeast is an excellent model organism for research for regulating aging and lifespan, and the studies have made many contributions to date, including identifying various... (Review)
Review
Yeast is an excellent model organism for research for regulating aging and lifespan, and the studies have made many contributions to date, including identifying various factors and signaling pathways related to aging and lifespan. More than 20 years have passed since molecular biological perspectives are adopted in this research field, and intracellular factors and signal pathways that control aging and lifespan have evolutionarily conserved from yeast to mammals. Furthermore, these findings have been applied to control the aging and lifespan of various model organisms by adjustment of the nutritional environment, genetic manipulation, and drug treatment using low-molecular weight compounds. Among these, drug treatment is easier than the other methods, and research into drugs that regulate aging and lifespan is consequently expected to become more active. Chronological lifespan, a definition of yeast lifespan, refers to the survival period of a cell population under nondividing conditions. Herein, low-molecular weight compounds are summarized that extend the chronological lifespan of Saccharomyces cerevisiae and Schizosaccharomyces pombe, along with their intracellular functions. The low-molecular weight compounds are also discussed that extend the lifespan of other model organisms. Compounds that have so far only been studied in yeast may soon extend lifespan in other organisms.
Topics: Schizosaccharomyces; Saccharomyces cerevisiae; Longevity; Molecular Weight; Signal Transduction; Aging
PubMed: 38616173
DOI: 10.1002/adbi.202400138 -
Food Chemistry Mar 2024Fructan, a widespread functional polysaccharide, has been used in the food, pharmaceutical, cosmetic, and material production fields because of its versatile... (Review)
Review
Fructan, a widespread functional polysaccharide, has been used in the food, pharmaceutical, cosmetic, and material production fields because of its versatile physicochemical properties and biological activities. Inulin from plants and levan from microorganisms are two of the most extensively studied fructans. Fructans from different plants or microorganisms have inconsistent molecular weights, and the molecular weight of fructan affects its properties, functions, and applications. Recently, increasing attention has been paid to the production and application of fructans having various molecular weights, and biotechnological processes have been explored to produce tailor-made fructans from sucrose. This review encompasses the introduction of extraction, enzymatic transformation, and fermentation production processes for fructans with diverse molecular weights. Notably, it highlights the enzymes involved in fructan biosynthesis and underscores their physiological effects, with a special emphasis on their prebiotic properties. Moreover, the applications of fructans with varying molecular weights are also emphasized.
Topics: Molecular Weight; Fructans; Inulin; Prebiotics; Sucrose
PubMed: 37924765
DOI: 10.1016/j.foodchem.2023.137895 -
Critical Reviews in Food Science and... 2024Food industry is actively looking for alternative ingredients to replace saturated and trans fats in foods while preserving their original organoleptic attributes to... (Review)
Review
Food industry is actively looking for alternative ingredients to replace saturated and trans fats in foods while preserving their original organoleptic attributes to ensure consumers' acceptance. A plausible approach is the replacement of solid fats with oleogels. Oleogels can be engineered to mimic properties that are commonly played by regular solid fats but using hydrophobic liquid vegetable oil with an optimum fatty acid profile and, they can also act as carriers for lipophilic bioactive substance. Low molecular weight oleogelators (LMOGs) are well studied and reviewed. In contrast, high molecular weight oleogelators (HMOGs) e.g., polysaccharides and proteins, are not fully researched yet. This review focusses on development of HMOG oleogels produced by means of emulsion templated, direct dispersion, foam templated and solvent exchange methods that can influence the stability, physicochemical properties and their potential application in food industry. Multi-component oleogels can solve the inefficiencies in a single component oleogel and, thus, combinations of HMOGs and HMOGs & LMOGs can produce oleogels with desired properties. These new oleogels can find application as fat substitutes in food products, providing better nutritional and sensory acceptance. A comprehensive overview of recent developments in the field of HMOG and multicomponent oleogels with HMOG is deeply reviewed.
Topics: Organic Chemicals; Fat Substitutes; Molecular Weight; Humans; Emulsions; Food Industry; Polysaccharides
PubMed: 36369891
DOI: 10.1080/10408398.2022.2142195 -
Journal of the Mechanical Behavior of... Jul 2023Hyaluronic acid (HA) is frequently formulated in eye drops to improve the stability of the tear film by hydration and lubrication. Mucoadhesion is related to the ocular...
Hyaluronic acid (HA) is frequently formulated in eye drops to improve the stability of the tear film by hydration and lubrication. Mucoadhesion is related to the ocular residence time and therefore to the effectiveness of the eye drops. The ocular residence time of the HA formulation is correlated with the ability of HA to create specific strong interactions in the ocular surface with the mucus layer, mainly composed of a mixture of secreted mucins (MUC; gel forming MUC5AC and MUC2) and shed membrane-bound soluble mucins (MUC1, MUC4, and MUC16). Dry eye disease (DED) is a multifactorial pathology of the preocular tear film with possible damage to the ocular surface classified in two types: (1) aqueous-deficient dry eye and (2) evaporative dry eye, caused by a decrease in goblet cell density that reduces MUC expression and/or by meibomian gland dysfunction, that results in a drop in the lipidic fraction of the tear film. In this work, the binding affinity between HA and MUC2 has been evaluated with three complementary approaches because the secreted MUCs play a pivotal role in the viscoelastic properties of the tear film: 1. Rheological analysis, measuring the mucoadhesive index and the complex viscosity in relation to MM (Molecular Mass) and concentration; 2. Fluorescence analysis, using a fluorescent hydrophobic probe, to investigate the conformational change of MUC2 during the interaction with the HA polymer; 3. Surface plasmon resonance analysis, used to measure the affinity between MUC2 (immobilized on the surface of a sensor chip) and the HA polymers that flowed on it at the molecular level. For all these tests, the mucoadhesive performance of the natural HA linearly increases with the MM, whereas cross-linked HA and other emollient and gelling agents (formulated in artificial tears) do not show the same mucoadhesive properties (with the exception of xanthan gum). The mucoadhesive performance of high MM HA has also been confirmed in conditions that simulate the pathological condition of the tear film during DED by decreasing the MUC2 or oleic acid concentration. Physico-chemical analysis of a series of marketed artificial tears confirms the linear correlation between the MM of the HA used in the products and the mucoadhesive index measured on the ocular surface model.
Topics: Humans; Hyaluronic Acid; Lubricant Eye Drops; Molecular Weight; Eye; Dry Eye Syndromes; Mucins
PubMed: 37209594
DOI: 10.1016/j.jmbbm.2023.105908 -
International Journal of Pharmaceutics Nov 2023For oral delivery, the physicochemical properties of nanocarriers are decisive factors for permeation through the intestinal epithelium. These properties are determined...
For oral delivery, the physicochemical properties of nanocarriers are decisive factors for permeation through the intestinal epithelium. These properties are determined by the composition of the nanocarriers as well as by the process parameters during their self-assembly. For macromolecular drugs, there is still little understanding of the drug-polymer interactions during nanocarrier self-assembly and the effects on carrier properties. In this study, the effect of drug molecular weight on nanocarrier self-assembly, physicochemical properties of nanocarriers as well as their permeation across the intestinal epithelium was investigated. Our results show that the drug molecular weight impacts the physicochemical properties of nanocarriers. Further, the physicochemical properties of the nanocarriers, governed by the molecular weight of the drug, determine their permeation properties across the intestinal epithelium. Comparative in vitro and ex vivo studies revealed that intestinal absorption is dependent on both, the properties of the tissue as well as properties of the carrier system. In conclusion, the molecular weight of drug payload is a key factor determining the physiochemical properties of polymeric nanocarriers and is closely linked to their oral absorption. Using different preclinical models to evaluate intestinal permeation of nanocarriers allows for novel insights into key formulation properties governing oral bioavailability.
Topics: Drug Carriers; Polymers; Molecular Weight; Nanoparticles; Biological Availability; Intestinal Absorption; Drug Delivery Systems; Administration, Oral
PubMed: 37802258
DOI: 10.1016/j.ijpharm.2023.123483 -
The Science of the Total Environment Jul 2023Algal organic matter (AOM) is considered to be threatening for the consumption of disinfectants and the formation of disinfection by-products (DBPs) during the...
Algal organic matter (AOM) is considered to be threatening for the consumption of disinfectants and the formation of disinfection by-products (DBPs) during the disinfection process. Incompatible parameters in the conventional pretreatment of algal-laden water will lead to counterproductive results, such as AOM release. Therefore, the generation of AOM and its conversion to DBPs during pretreatment should be observed. The characteristics of DBPs from extracellular organic matter (EOM) and intracellular organic matter (IOM) were epitomized and simulation experiments were conducted in deionized (DI) water and source water under pretreatment conditions. Differences in DBP formation between the different backgrounds during chlorination and powdered activated carbon (PAC) treatment were investigated. Instead of monotonous excitation-emission matrix (EEM) spectra, molecular weight (MW) fractionation was simultaneously applied to elucidate the mechanisms of chlorination and PAC adsorption on AOM-based DBPs. The fluorescence regional integration (FRI) EEM results showed a clear correlation between the fluorescent properties and MW distribution of AOM. A decreasing trend was observed after a rapid increase in fluorescence intensity during the chlorination and PAC treatment of water samples in the simulation experiments in deionized (DI) water and source water. The DBP formation potential (FP) in the source water was consistent with the change in AOM during chlorination and PAC adsorption. In addition, EEM showed decent predictability of AOM-based trihalomethanes (THM) FPs (R = 0.77-0.99) invoking a combination with MW fractionation. Macromolecular protein compounds were highly correlated with the formation of dichloroacetonitrile (DCAN) (R = 0.89-0.98). These post-mortems results imply that EEM spectra are a useful tool for identifying AOM-based precursors to reveal the accurate environmental fate and risk assessments of AOM.
Topics: Disinfection; Fluorescence; Molecular Weight; Water Purification; Water Pollutants, Chemical; Disinfectants; Organic Chemicals; Water; Charcoal; Halogenation
PubMed: 37087012
DOI: 10.1016/j.scitotenv.2023.163589 -
Biopolymers Jul 2023The regulation of the biodegradation rate of 3D-regenerated silk fibroin scaffolds and the avoidance of premature collapse are important concerns for their effective...
The regulation of the biodegradation rate of 3D-regenerated silk fibroin scaffolds and the avoidance of premature collapse are important concerns for their effective applications in tissue engineering. In this study, bromelain, which is specific to sericin, was used to remove sericin from silk, and high molecular weight silk fibroin was obtained after the fibroin fibers were dissolved. Afterwards, a 3D scaffold was prepared via freeze-drying. The Sodium dodecyl sulfate-polyacrylamide gel electrophoresis results showed that the average molecular weight of the regenerated silk fibroin prepared by using the bromelain-degumming method was approximately 142.2 kDa, which was significantly higher than that of the control groups prepared by using the urea- and Na CO -degumming methods. The results of enzyme degradation in vitro showed that the biodegradation rate and internal three-dimensional structure collapse of the bromelain-degumming fibroin scaffolds were significantly slower than those of the two control scaffolds. The proliferation activity of human umbilical vein vascular endothelial cells inoculated in bromelain-degumming fibroin scaffolds was significantly higher than that of the control scaffolds. This study provides a novel preparation method for 3D-regenerated silk fibroin scaffolds that can effectively resist biodegradation, continuously guide cell growth, have good biocompatibility, and have the potential to be used for the regeneration of various connective tissues.
Topics: Humans; Fibroins; Tissue Scaffolds; Bromelains; Biocompatible Materials; Sericins; Molecular Weight; Endothelial Cells; Tissue Engineering; Silk; Cell Proliferation
PubMed: 37232459
DOI: 10.1002/bip.23554 -
Expert Opinion on Drug Discovery Jul 2023Protein-protein interactions (PPIs) have been often considered undruggable targets although they are attractive for the discovery of new therapeutics. The spread of... (Review)
Review
INTRODUCTION
Protein-protein interactions (PPIs) have been often considered undruggable targets although they are attractive for the discovery of new therapeutics. The spread of artificial intelligence and machine learning complemented with experimental methods is likely to change the perspectives of protein-protein modulator research. Noteworthy, some novel low molecular weight (LMW) and short peptide modulators of PPIs are already in clinical trials for the treatment of relevant diseases.
AREAS COVERED
This review focuses on the main molecular properties of protein-protein interfaces and on key concepts pertaining to the modulation of PPIs. The authors survey recently reported state-of-the-art methods dealing with the rational design of PPI modulators and highlight the role of several computer-based approaches.
EXPERT OPINION
Interfering specifically with large protein interfaces is still an open challenge. The initial concerns about the unfavorable physicochemical properties of many of these modulators are nowadays less acute with several molecules lying beyond the rule of 5, orally available and successful in clinical trials. As the cost of biologics interfering with PPIs is very high, it would seem reasonable to put more effort, both in academia and the private sectors, on actively developing novel low molecular weight compounds and short peptides to perform this task.
Topics: Humans; Molecular Weight; Artificial Intelligence; Protein Binding; Peptides; Drug Discovery; Proteins
PubMed: 37246811
DOI: 10.1080/17460441.2023.2218641 -
Water Research Sep 2023Iron coagulants have been used extensively in drinking water treatment. This typically produces substantial quantities of insoluble iron hydrolysis products which...
Iron coagulants have been used extensively in drinking water treatment. This typically produces substantial quantities of insoluble iron hydrolysis products which interact with natural and anthropogenic organic substances during the coagulation process. Previous studies have shown that the removal of low molecular weight (MW) organics is relatively poor by coagulation, which leads to their presence during disinfection, with the formation of halogenated byproducts, and in treated water supplies as potentially biodegradable material. Currently, there is little knowledge about the changes that occur in the nature of coagulant flocs as they age with time and how such changes affect interactions with organic matter, especially low MW organics. To improve this deficiency, this study has investigated the variation of aged flocs obtained from two commonly used iron salts and their impact on representative organic contaminants, natural organic matter (NOM) and tetracycline antibiotic (TC), in a real surface water. It was found that aging resulted in increasing crystallization of the flocs, which can play a beneficial role in activating persulfate oxidant to remove the representative organics. Furthermore, acidification was also found to further improve the removal of low MW natural organics and tetracycline. In addition, the results showed that the low MW fractions of NOM (<1 K Dalton) were substantially removed by the aging flocs. These results are in marked contrast to the poor removal of low MW organic substances by conventional coagulation, with or without added oxidants, and show that aged flocs have a high potential of reuse for re-coagulation and activation of oxidants to reduce low MW organics, and enhance drinking water quality.
Topics: Molecular Weight; Crystallization; Drinking Water; Flocculation; Water Purification; Iron; Tetracyclines
PubMed: 37459797
DOI: 10.1016/j.watres.2023.120328