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Amino Acids Jul 2024Carnosine's protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with...
Carnosine's protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with diabetic kidney disease. In contrast to rodents however, carnosine is rapidly degraded by the carnosinase-1 enzyme. To overcome this hurdle, we sought to protect hydrolysis of carnosine by conjugation to Methoxypolyethylene glycol amine (mPEG-NH). PEGylated carnosine (PEG-car) was used to study the hydrolysis of carnosine by human serum as well as to compare the pharmacokinetics of PEG-car and L-carnosine in mice after intravenous (IV) injection. While L-carnosine was rapidly hydrolyzed in human serum, PEG-car was highly resistant to hydrolysis. Addition of unconjugated PEG to carnosine or PEG-car did not influence hydrolysis of carnosine in serum. In mice PEG-car and L-carnosine exhibited similar pharmacokinetics in serum but differed in half-life time (t) in kidney, with PEG-car showing a significantly higher t compared to L-carnosine. Hence, PEGylation of carnosine is an effective approach to prevent carnosine degradations and to achieve higher renal carnosine levels. However, further studies are warranted to test if the protective properties of carnosine are preserved after PEGylation.
Topics: Carnosine; Animals; Polyethylene Glycols; Hydrolysis; Dipeptidases; Mice; Humans; Kidney; Male
PubMed: 38960916
DOI: 10.1007/s00726-024-03405-6 -
Life Science Alliance Sep 2024In many animal species, the oocyte meiotic spindle, which is required for chromosome segregation, forms without centrosomes. In some systems, Ran-GEF on chromatin...
In many animal species, the oocyte meiotic spindle, which is required for chromosome segregation, forms without centrosomes. In some systems, Ran-GEF on chromatin initiates spindle assembly. We found that in oocytes, endogenously-tagged Ran-GEF dissociates from chromatin during spindle assembly but re-associates during meiotic anaphase. Meiotic spindle assembly occurred after auxin-induced degradation of Ran-GEF, but anaphase I was faster than controls and extrusion of the first polar body frequently failed. In search of a possible alternative pathway for spindle assembly, we found that soluble tubulin concentrates in the nuclear volume during germinal vesicle breakdown. We found that the concentration of soluble tubulin in the metaphase spindle region is enclosed by ER sheets which exclude cytoplasmic organelles including mitochondria and yolk granules. Measurement of the volume occupied by yolk granules and mitochondria indicated that volume exclusion would be sufficient to explain the concentration of tubulin in the spindle volume. We suggest that this concentration of soluble tubulin may be a redundant mechanism promoting spindle assembly near chromosomes.
Topics: Animals; Caenorhabditis elegans; Tubulin; Spindle Apparatus; Anaphase; Caenorhabditis elegans Proteins; Oocytes; Prometaphase; Meiosis; ran GTP-Binding Protein; Guanosine Triphosphate; Chromatin; Chromosome Segregation
PubMed: 38960623
DOI: 10.26508/lsa.202402884 -
Annals of Allergy, Asthma & Immunology... Jul 2024
Topics: Humans; Polyethylene Glycols; Drug Hypersensitivity; Female; Allergens; Male
PubMed: 38960568
DOI: 10.1016/j.anai.2024.04.003 -
Advances in Protein Chemistry and... 2024We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent... (Review)
Review
Long-term culture of patient-derived mammary organoids in non-biogenic electrospun scaffolds for identifying metalloprotein and motor protein activities in aging and senescence.
We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent intracellular trafficking of metalloproteins for cellular energy production in mitochondria. TMEM230 is also required for transport and secretion of metalloproteinases for autophagy and phagosome dependent clearance of misfolded proteins, defective RNAs and damaged cells, activities that decline with aging. This suggests that aberrant levels of TMEM230 may contribute to aging and regain of proper levels may have therapeutic applications. The components of the endomembrane system include the Golgi complex, other membrane bound organelles, and secreted vesicles and factors. Secreted cellular components modulate immune response and tissue regeneration in aging. Upregulation of intracellular packaging, trafficking and secretion of endosome components while necessary for tissue homeostasis and normal wound healing, also promote secretion of pro-inflammatory and pro-senescence factors. We recently determined that TMEM230 is co-regulated with trafficked cargo of the endomembrane system, including lysosome factors such as RNASET2. Normal tissue regeneration (in aging), repair (following injury) and aberrant destructive tissue remodeling (in cancer or autoimmunity) likely are regulated by TMEM230 activities of the endomembrane system, mitochondria and autophagosomes. The role of TMEM230 in aging is supported by its ability to regulate the pro-inflammatory secretome and senescence-associated secretory phenotype in tissue cells of patients with advanced age and chronic disease. Identifying secreted factors regulated by TMEM230 in young patients and patients of advanced age will facilitate identification of aging associated targets that aberrantly promote, inhibit or reverse aging. Ex situ culture of patient derived cells for identifying secreted factors in tissue regeneration and aging provides opportunities in developing therapeutic and personalized medicine strategies. Identification and validation of human secreted factors in tissue regeneration requires long-term stabile scaffold culture conditions that are different from those previously reported for cell lines used as cell models for aging. We describe a 3 dimensional (3D) platform utilizing non-biogenic and non-labile poly ε-caprolactone scaffolds that supports maintenance of long-term continuous cultures of human stem cells, in vitro generated 3D organoids and patient derived tissue. Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.
Topics: Humans; Organoids; Aging; Membrane Proteins; Cellular Senescence; Female; Tissue Scaffolds; Mammary Glands, Human
PubMed: 38960479
DOI: 10.1016/bs.apcsb.2024.03.008 -
International Journal of Pharmaceutics Jul 2024Solasonine (SS) and solamargine (SM) are alkaloids known for their antioxidant and anticancer properties, which can be further enhanced by encapsulating them in...
Solasonine (SS) and solamargine (SM) are alkaloids known for their antioxidant and anticancer properties, which can be further enhanced by encapsulating them in nanoparticles. This led to a study on the potential therapeutic benefits of SS and SM against bladder cancer when encapsulated in lipid-polymer hybrid nanoparticles (LPHNP). The LPHNP loaded with SS/SM were prepared using the emulsion and sonication method and their physical-chemical properties characterized. The biological effects of these nanoparticles were then tested in both 2D and 3D bladder cancer cell culture models, as well as in a syngeneic orthotopic mouse model based on the MB49 cell line and ethanol epithelial injury. The LPHNP-SS/SM had an average size of 130 nm, a polydispersity index of 0.22 and a positive zeta potential, indicating the presence of chitosan coating on the nanoparticle surface. The dispersion of LPHNP-SS/SM was found to be monodispersed with a span index of 0.539, as measured by nanoparticle tracking analysis (NTA). The recrystallization index, calculated from DSC data, was higher for the LPHNP-SS/SM compared to LPHNPs alone, confirming the presence of alkaloids within the lipid matrix. The encapsulation efficiency (EE%) was also high, with 91.08 % for SS and 88.35 % for SM. Morphological analysis by AFM and Cryo-TEM revealed that the nanoparticles had a spherical shape and core-shell structure. The study showed that the LPHNP-SS/SM exhibited mucoadhesive properties by physically interacting with mucin, suggesting a potential improvement in interaction with mucous membrane. Both the free and nanoencapsulated SS/SM demonstrated dose-dependent cytotoxicity against bladder cancer cell lines after 24 and 72 h of treatment. In 3D bladder cell culture, the nanoencapsulated SS/SM showed an IC two-fold lower than free SS/SM. In vivo studies, the LPHNP-SS/SM displayed an antitumoral effect at high doses, leading to a significant reduction in bladder volume compared to the positive control. However, there were observed instances of systemic toxicity and liver damage, indicated by elevated levels of transaminases (TGO and TGP). Overall, these results indicate that the LPHNPs effectively encapsulated SS/SM, showing high encapsulation efficiency and stability, along with promising in vitro and in vivo antitumoral effects against bladder cancer. Further evaluation of its systemic toxicity effects is necessary to ensure its safety and efficacy for potential clinical application.
PubMed: 38960341
DOI: 10.1016/j.ijpharm.2024.124411 -
International Journal of Biological... Jul 2024Flame resistance is required for the deployment of bio-based materials, especially those forming cellular structures that endow thermal insulation. This study proposes a...
Flame resistance is required for the deployment of bio-based materials, especially those forming cellular structures that endow thermal insulation. This study proposes a one-pot strategy to prepare cellular lignocellulosic composites with excellent flame resistance. Lignocellulosic microfibers were used as the substrate onto which a flame-retardant complex consisting of P-containing phytic acid (PA) and N-containing polyethyleneimine (PEI) was formed. Following the prediction of ab initio molecular dynamics simulation, PA and PEI are integrated onto MF-CTMP following a single-step complexation assembly triggered by pH effects. The PA-PEI modified MF-CTMP can be readily transformed into a composite solid foam by dewatering a wet foam followed by oven drying. At the expense of a slightly reduced thermal insulation (thermal conductivity increase from 33.6 ± 0.6 to 40.0 ± 0.6 mW/(m·K)) the presence of PA-PEI complexes significantly improved the mechanical performance of the foam and uniquely endows it with flame resistance. Compared to unmodified MF-CTMP foams, the composite foams showed significant improvement in the Young's, specific compression, and flexural moduli (increased by 13.5, 5.5, and 7.3 folds, respectively), a high oxygen index (up to 40.8 %) and self-extinguishing effects. The results suggest the suitability of the introduced lignocellulosic foam as an alternative to traditional synthetic polymer-based counterparts as well as inorganic matter for insulation, particularly relevant to the building sector.
PubMed: 38960267
DOI: 10.1016/j.ijbiomac.2024.133521 -
International Journal of Biological... Jul 2024The ongoing challenge of water scarcity persists alongside a concerning rise in water pollution driven by population expansion and industrial development. As a result,...
The ongoing challenge of water scarcity persists alongside a concerning rise in water pollution driven by population expansion and industrial development. As a result, urgent measures are imperative to address the pressing need for a clean and sustainable water supply. In this study, a sustainable and green approach was utilized to prepare four chitosan-based sponges from a chemically modified chitosan with different alkyl chains in aqueous medium and at room temperature. The resulting sponges displayed excellent stability in water with outstanding dye removal efficiency. The adsorption capacity was associated with the alkyl chain length incorporated to the polymer backbone. All sponges displayed a high adsorption capacity of methyl orange (MO) ranges between 238 and 380 mg g, while a low capacity were obtained for methylene blue (MB) and rhodium B (RB). Competitive adsorption experiments were conducted on binary and ternary mixtures to assess the selective removal of MO from a mixture of dyes in which the separation factor was found to be ranging between 1.6 and 32. The adsorption kinetics isotherms of all sponges followed the pseudo-second-order, and Langmuir model was found to be more suitable than the Freundlich for the adsorption of MO on the sponges. The chitosan-based sponges showed stable performance, robustness and reusability over 5 adsorption-desorption cycles, indicating their great potential for water treatment applications.
PubMed: 38960254
DOI: 10.1016/j.ijbiomac.2024.133577 -
International Journal of Biological... Jul 2024Traditional plastics reshaped the society thanks to their brilliant properties and cut-price manufacturing costs. However, their protracted durability and limited... (Review)
Review
Traditional plastics reshaped the society thanks to their brilliant properties and cut-price manufacturing costs. However, their protracted durability and limited recycling threaten the environment. Worthy alternatives seem to be polyhydroxyalkanoates, compostable biopolymers produced by several microbes. The most common 3-hydroxybutyrate homopolymer has limited applications calling for copolymers biosynthesis to enhance material properties. As a growing number of researches assess the discovery of novel comonomers, great endeavors are dedicated as well to copolymers production scale-up, where the choice of the microbial carbon source significantly affects the overall economic feasibility. Diving into novel metabolic pathways, engineered strains, and cutting-edge bioprocess strategies, this review aims to survey up-to-date publications about copolymers production, focusing primarily on precursors origins. Specifically, in the core of the review, copolymers precursors have been divided into three categories based on their economic value: the costliest structurally related ones, the structurally unrelated ones, and finally various low-cost waste streams. The combination of cheap biomasses, efficient pretreatment strategies, and robust microorganisms paths the way towards the development of versatile and circular polymers. Conceived to researchers and industries interested in tackling polyhydroxyalkanoates production, this review explores an angle often underestimated yet of prime importance: if PHAs copolymers offer advanced properties and sustainable end-of-life, the feedstock choice for their upstream becomes a major factor in the development of plastic substitutes.
PubMed: 38960239
DOI: 10.1016/j.ijbiomac.2024.133575 -
International Journal of Biological... Jul 2024In situ forming poly(dimethylaminoethyl methacrylate-co-glycidylmethacrylate)/Chitosan, P(DMAEMA-co-GMA)/Chitosan, (PDG/CS) cryobeads based on "dropwise freezing into...
In situ forming poly(dimethylaminoethyl methacrylate-co-glycidylmethacrylate)/Chitosan, P(DMAEMA-co-GMA)/Chitosan, (PDG/CS) cryobeads based on "dropwise freezing into cryogenic liquid method" combined with "blending with polymer method" are promising for applications due to their pH-responsiveness and stability under physiological conditions. Based on classical contact mechanics, Hertzian elasticity of semi-interpenetrated network (semi-IPN) cryobeads was analyzed to examine whether there is a direct correlation between elastic properties of single particle and its macroscopic behavior. A one-step procedure has been proposed to design chitosan-interpenetrated cryobeads with a cationic nature via combination of structural properties as well as functionality of chitosan containing primary and secondary hydroxyl and amino groups. The study is focused on characterization of network formation kinetics in different shapes and how different production variables affect the elasticity/swelling performance of cross-linked system. The elastic properties of semi-IPN cryobeads were improved by both adding chitosan to copolymer PDG structure and lowering the gelation temperature to cryogelation conditions. The results obtained highlighted the importance of composition to modulate elasticity, the influence of preparation temperature and shape of cryobeads on their elasticity. Findings regarding the topography-dependent local elastic properties of chitosan-incorporated semi-IPN gels offer possibilities for modulating the behavior of chitosan-based soft materials.
PubMed: 38960237
DOI: 10.1016/j.ijbiomac.2024.133600 -
International Journal of Biological... Jul 2024Stimuli-responsive optical hydrogels are widely used in various fields including environmental sensing, optical encryption, and intelligent display manufacturing....
Stimuli-responsive optical hydrogels are widely used in various fields including environmental sensing, optical encryption, and intelligent display manufacturing. However, these hydrogels are susceptible to water losses when exposed to air, leading to structural damage, significantly shortened service lives, and compromised durability. This study presents mechanically robust, environmentally stable, and multi-stimuli responsive optical organohydrogel fibers with customizable iridescent colors. These fibers are fabricated by incorporating tunicate cellulose nanocrystals, alginate, and acrylamide in a glycerol-water binary system. The synthesized fibers exhibit high strength (1.38 MPa), moisture retention capabilities, and elastic properties. Furthermore, a sensor based on these fibers demonstrates high- and low-temperature resistance along with stimuli-responsive characteristics, effectively detecting changes in environmental humidity and strains. Moreover, the fiber sensor demonstrates continuous, repeatable, and quantitatively predictable moisture discoloration responses across a humidity range of 11 % and 98 %. During strain sensing, the optical-organohydrogel-based sensor demonstrates a large working strain (50 %) and excellent cycling stability, underscoring its potential for effectively monitoring a wide range of intricate human motions. Overall, the synthesized fibers and their simple fabrication method can elicit new avenues for numerous related applications including the large-scale implementation of advanced wearable technology.
PubMed: 38960229
DOI: 10.1016/j.ijbiomac.2024.133501