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1.
Carbohydr Polym ; 346: 122653, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39245511

RESUMO

A combination of maleic acid and sodium hypophosphite as a durable press finishing agent has been reported as a safer but equally effective alternative to conventional formaldehyde-based cross-linking agents for applications in cellulose-based fiber and textile finishing. However, the mechanistic details of this system have not yet been fully elucidated to allow optimization of the conditions. Effective cross-linking treatment requires high curing temperatures of ≥160 °C, which enhances oxidative and thermal degradation of cellulose. In this work, the sequential steps of the cross-linking mechanism were investigated both with model compounds and cellulosic substrates. Extensive NMR studies on model compounds revealed several side reactions alongside the synthesis of the targeted cross-linkable moiety. As an alternative, to circumvent side reactions, a two-step procedure was used by synthesizing the cross-linker sodium 2-[(1,2-dicarboxyethyl)phosphinate]succinic acid in a well-defined pre-condensation reaction before application onto the cellulosic substrate. Further, the effect of the cross-linking treatment on the molecular weight distribution of cellulose was studied by gel permeation chromatography, which showed degradation due to maleic acid/sodium hypophosphite treatment. By using sodium 2-[(1,2-dicarboxyethyl)phosphinate]succinic acid and sodium hypophosphite, this degradation could be significantly limited.

2.
J Virol ; : e0063124, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248459

RESUMO

Upon binding to the host cell receptor, CD4, the pretriggered (State-1) conformation of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer undergoes transitions to downstream conformations important for virus entry. State 1 is targeted by most broadly neutralizing antibodies (bNAbs), whereas downstream conformations elicit immunodominant, poorly neutralizing antibody (pNAb) responses. Extraction of Env from the membranes of viruses or Env-expressing cells disrupts the metastable State-1 Env conformation, even when detergent-free approaches like styrene-maleic acid lipid nanoparticles (SMALPs) are used. Here, we combine three strategies to solubilize and purify mature membrane Envs that are antigenically native (i.e., recognized by bNAbs and not pNAbs): (1) solubilization of Env with a novel amphipathic copolymer, Amphipol A18; (2) use of stabilized pretriggered Env mutants; and (3) addition of the State-1-stabilizing entry inhibitor, BMS-806. Amphipol A18 was superior to the other amphipathic copolymers tested (SMA and AASTY 11-50) for preserving a native Env conformation. A native antigenic profile of A18 Env-lipid-nanodiscs was maintained for at least 7 days at 4°C and 2 days at 37°C in the presence of BMS-806 and was also maintained for at least 1 h at 37°C in a variety of adjuvants. The damaging effects of a single cycle of freeze-thawing on the antigenic profile of the A18 Env-lipid-nanodiscs could be prevented by the addition of 10% sucrose or 10% glycerol. These results underscore the importance of the membrane environment to the maintenance of a pretriggered (State-1) Env conformation and provide strategies for the preparation of lipid-nanodiscs containing native membrane Envs.IMPORTANCEThe human immunodeficiency virus (HIV-1) envelope glycoproteins (Envs) mediate virus entry into the host cell and are targeted by neutralizing antibodies elicited by natural infection or vaccines. Detailed studies of membrane proteins like Env rely on purification procedures that maintain their natural conformation. In this study, we show that an amphipathic copolymer A18 can directly extract HIV-1 Env from a membrane without the use of detergents. A18 promotes the formation of nanodiscs that contain Env and membrane lipids. Env in A18-lipid nanodiscs largely preserves features recognized by broadly neutralizing antibodies (bNAbs) and conceals features potentially recognized by poorly neutralizing antibodies (pNAbs). Our results underscore the importance of the membrane environment to the native conformation of HIV-1 Env. Purification methods that bypass the need for detergents could be useful for future studies of HIV-1 Env structure, interaction with receptors and antibodies, and immunogenicity.

3.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39273206

RESUMO

Lignin is endowed with antioxidant activity due to its diverse chemical structure. It is necessary to explore the relationship between antioxidant activity and the chemical structure of the lignin to develop its high-value utilization. Herein, we employed maleic acid (MA) as a hydrotropic agent to preferably isolate the lignin from distinct herbaceous sources (wheat straw and switchgrass) under atmospheric pressure conditions. The resultant acid hydrotropic lignin (AHL) isolated from wheat straw exhibited high radical scavenging rates, up to 98% toward DPPH and 94% toward ABTS. Further investigations indicated that during the MA hydrotropic fractionation (MAHF) process, lignin was carboxylated by MA at γ-OH of the side-chain, providing additional antioxidant activity from the carboxy group. It was also found that the radical scavenging rate of AHL has a positive correlation with carboxyl, phenolic hydroxyl contents, and the S-G (syringyl-guaiacyl) ratio, which could be realized by increasing the MAHF severity. Overall, this work underlies the enhancement origin of the antioxidant property of lignin, which will facilitate its application in biological fields as an efficient, cheap, and renewable antioxidant additive.


Assuntos
Antioxidantes , Biomassa , Fracionamento Químico , Lignina , Maleatos , Triticum , Lignina/química , Lignina/isolamento & purificação , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Triticum/química , Fracionamento Químico/métodos , Maleatos/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/isolamento & purificação , Panicum/química
4.
Gels ; 10(8)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39195029

RESUMO

Covalent cross-linked hydrogels based on chitosan and poly(maleic acid-alt-vinyl acetate) were prepared as spherical beads. The structural modifications of the beads during the preparation steps (dropping in liquid nitrogen and lyophilization, thermal treatment, washing with water, and treatment with NaOH) were monitored by FT-IR spectroscopy. The hydrogel beads have a porous inner structure, as shown by SEM microscopy; moreover, they are stable in acidic and basic pH due to the covalent crosslinking. The swelling degree is strongly influenced by the pH since the beads possess ionizable amine and carboxylic groups. The binding capacity for Cu2+ ions was examined in batch mode as a function of sorbent composition, pH, contact time, and the initial concentration of Cu2+. The kinetic data were well-fitted with the pseudo-second-order kinetic, while the sorption equilibrium data were better fitted with Langmuir and Sips isotherms. The maximum equilibrium sorption capacity was higher for the beads obtained with a 3:1 molar ratio between the maleic copolymer and chitosan (142.4 mg Cu2+ g-1), compared with the beads obtained using a 1:1 molar ratio (103.7 mg Cu2+ g-1). The beads show a high degree of reusability since no notable decrease in the sorption capacity was observed after five consecutive sorption/desorption cycles.

5.
J Chromatogr A ; 1732: 465227, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39116685

RESUMO

Styrene-maleic acid (SMA) copolymer has received much attention for its excellent solubilization characteristics. In this work, SMA copolymer brush-based chromatographic stationary phases were exploited and developed for the first time. First, SMA copolymer brush was in situ grown on the surface of spherical silica via living/controlled reversible addition-fragmentation chain transfer (RAFT) polymerization method. Subsequently, as a proof-of-concept demonstration, the copolymer was esterified by diethylene glycol mono-2-ethylhexyl ether (DGME) and 2-(2-ethylhexyloxy) ethanol (EHOE), respectively. The obtained Sil-SMA-DGME and Sil-SMA-EHOE copolymer-brush chromatographic stationary phases were characterized by transmission electron microscopy, Fourier transform infrared spectrometer, X-ray photoelectron spectroscopy, and thermogravimetric analysis, respectively. The chromatographic retention mechanism indicated that both the two packed columns exhibited hydrophilic/reverse mixed-mode retention modes. The maximum column efficiency was up to 71,000 N/m. The chromatographic separation performance evaluation indicated that the novel kind of stationary phases had excellent separation capabilities for hydrophilic, hydrophobic compounds and phospholipid standards. In addition, by combination with mass spectrometry identification, the Sil-SMA-DGME column was further exploited for separation and identification of phospholipids in human lung cancer cells. Totally, 9 classes including 186 phospholipid species were successfully identified. The results demonstrated the promising application prospects of the novel kind of SMA copolymer-brush chromatographic stationary phases.


Assuntos
Maleatos , Dióxido de Silício , Maleatos/química , Dióxido de Silício/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Poliestirenos/química , Esterificação , Cromatografia Líquida de Alta Pressão/métodos , Polímeros/química
6.
Acta Crystallogr E Crystallogr Commun ; 80(Pt 7): 777-782, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38974158

RESUMO

In the title compound, C19H18BrFN2O, the pyrrolidine ring adopts an envelope conformation. In the crystal, mol-ecules are linked by inter-molecular N-H⋯O, C-H⋯O, C-H⋯F and C-H⋯Br hydrogen bonds, forming a three-dimensional network. In addition, C-H⋯π inter-actions connect mol-ecules into ribbons along the b-axis direction, consolidating the mol-ecular packing. The inter-molecular inter-actions in the crystal structure were qu-anti-fied and analysed using Hirshfeld surface analysis.

7.
Polymers (Basel) ; 16(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38932086

RESUMO

In this study, we report an easy approach for the production of aqueous dispersions of C60 fullerene with good stability. Maleic acid copolymers, poly(styrene-alt-maleic acid) (SM), poly(N-vinyl-2-pyrrolidone-alt-maleic acid) (VM) and poly(ethylene-alt-maleic acid) (EM) were used to stabilize C60 fullerene molecules in an aqueous environment by forming non-covalent complexes. Polymer conjugates were prepared by mixing a solution of fullerene in N-methylpyrrolidone (NMP) with an aqueous solution of the copolymer, followed by exhaustive dialysis against water. The molar ratios of maleic acid residues in the copolymer and C60 were 5/1 for SM and VM and 10/1 for EM. The volume ratio of NMP and water used was 1:1.2-1.6. Water-soluble complexes (composites) dried lyophilically retained solubility in NMP and water but were practically insoluble in non-polar solvents. The optical and physical properties of the preparations were characterized by UV-Vis spectroscopy, FTIR, DLS, TGA and XPS. The average diameter of the composites in water was 120-200 nm, and the ξ-potential ranged from -16 to -20 mV. The bactericidal properties of the obtained nanostructures were studied. Toxic reagents and time-consuming procedures were not used in the preparation of water-soluble C60 nanocomposites stabilized by the proposed copolymers.

8.
J Chromatogr A ; 1729: 465057, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38857565

RESUMO

The histamine H1 receptor (H1R) plays a pivotal role in allergy initiation and undergoes the necessity of devising a high-throughput screening approach centered on H1R to screen novel ligands effectively. This study suggests a method employing styrene maleic acid (SMA) extraction and His-tag covalent bonding to immobilize H1R membrane proteins, minimizing the interference of nonspecific proteins interference while preserving native protein structure and maximizing target exposure. This approach was utilized to develop a novel material for high-throughput ligand screening and implemented in cell membrane chromatography (CMC). An H1R-His-SMALPs/CMC model was established and its chromatographic performance (selectivity, specificity and lifespan) validated, demonstrating a significant enhancement in lifespan compared to previous CMC models. Subsequently, this model facilitated high-throughput screening of H1R ligands in the compound library and preliminary activity verification of potential H1R antagonists. Identification of a novel H1R antagonist laid the foundation for further development in this area.


Assuntos
Ensaios de Triagem em Larga Escala , Maleatos , Receptores Histamínicos H1 , Ligantes , Maleatos/química , Ensaios de Triagem em Larga Escala/métodos , Receptores Histamínicos H1/química , Receptores Histamínicos H1/metabolismo , Humanos , Histidina/química , Animais , Proteínas Imobilizadas/química , Proteínas Imobilizadas/metabolismo , Células CHO , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Antagonistas dos Receptores Histamínicos H1/química , Poliestirenos/química , Cricetulus , Oligopeptídeos/química
9.
Eur J Pharm Biopharm ; 201: 114378, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38917949

RESUMO

Carrier materials always account for the majority particularly in nanosized formulations, which are administrated along with the active ingredient part might result in metabolism related toxicity. The usage of bioactive excipients could not only reduce the sided effect but also provide additional therapeutic effects. In the present study, a triterpene based micellar drug delivery system was developed using a bioactive solanesol derivative. Solanesylamine was prepared firstly followed by conjugating with poly (ethylene glycol) using maleic acid amide linkage. The amphiphilic drug carrier PEGylated (2-propyl-3-methylmaleic acid)-block-solanesol amine (mPEG-CDM-NH-SOL) could be formed into micelles and loaded with doxorubicin (DOX) inside. The micelles were about 112 nm in size and the drug loading content was about 5.97 wt%. An acid triggered drug release behavior was obviously observed for the DOX loaded pH-sensitive micelle mPEG-CDM-NH-SOL-DOX. While not for DOX-loaded micelles without pH-sensitivity (mPEG-NHS-NH-SOL). CCK8 assay showed that the micelles of PEGylated solanesylamines exhibited certain inhibitory effect on tumor cells at high concentration and the pH sensitive ones seemed more toxic. In vivo studies showed that the pH sensitive mPEG-CDM-NH-SOL-DOX had a superior anti-tumor effect, indicating its great potential in cancer treatment.


Assuntos
Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Neoplasias Hepáticas , Micelas , Polietilenoglicóis , Triterpenos , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Animais , Humanos , Triterpenos/administração & dosagem , Triterpenos/química , Triterpenos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Portadores de Fármacos/química , Camundongos , Sistemas de Liberação de Medicamentos/métodos , Polietilenoglicóis/química , Liberação Controlada de Fármacos , Células Hep G2 , Masculino , Camundongos Nus , Camundongos Endogâmicos BALB C , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Terpenos
10.
Heliyon ; 10(10): e31313, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38831811

RESUMO

Approaches aiming to recover proteins without denaturation represent attractive strategies. To accomplish this, a membrane lysis agent based on poly(styrene-alt-maleic acid) or PSMA was synthesized by photopolymerization using Irgacure® 2959 and carbon tetrabromide (CBr4) as a radical initiator and a reversible chain transfer agent, respectively. Structural elucidation of our in-house synthesized PSMA, so-called photo-PSMA, was performed by using NMR spectroscopy. The use of this photo-PSMA in soybean enzyme extraction was also demonstrated for the first time in this study. Without a severe cell rupture, energy input or any organic solvent, recovery of lipolytic enzymes directly into nanometric-sized particles was accomplished in one-step process. Due to the improved structural regularity along the photo-PSMA backbone, the most effective protective reservoir for enzyme immobilization was generated through the PSMA aggregation. Formation of such reservoir enabled soybean enzymes to be shielded from the surroundings and resolved in their full functioning state. This was convinced by the increased specific lipolytic activity to 1,950 mU/mg, significantly higher than those of sodium dodecyl sulfate (SDS) and the two commercially-available PSMA sources (1000P and 2000P). Our photo-PSMA had thus demonstrated its great potential for cell lyse application, especially for soybean hydrolase extraction.

11.
Int J Biol Macromol ; 271(Pt 2): 132495, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38763256

RESUMO

Incorporating starch, which is a potential biodegradable substitute for petroleum-based polymers, into conventional polymers is challenging owing to limitations in processability and weak-performing resulting materials. Herein, corn starch/polyvinyl alcohol (PVA) blend films (starch: PVA ratio of 50:50) were prepared via the solvent casting method using glycerol as a plasticizer and with varying concentrations of maleic acid as the crosslinking agent. Fourier transform infrared spectroscopy revealed the molecular interactions of the maleic acid crosslinker with the polymeric network of starch and PVA through an ester linkage. The properties of the films were strongly dependent on the maleic acid concentration. An increasing maleic acid concentration imparted hydrophobicity to the film; therefore, water swelling was significantly reduced, and water resistance was enhanced. The film containing 20 wt% maleic acid exhibited excellent barrier properties, with the lowest oxygen and water vapor transmission rates of 0.5 ± 0.2 cc/m2⋅day and 232.3 ± 5.4 g/m2⋅day, respectively. Moreover, the mechanical properties of the film improved with increasing crosslinking. This study demonstrates that the addition of maleic acid leads to an improvement in the overall performance of starch/PVA blend films. Therefore, maleic acid-crosslinked films can be used as barrier materials in food packaging applications.


Assuntos
Embalagem de Alimentos , Maleatos , Álcool de Polivinil , Amido , Álcool de Polivinil/química , Amido/química , Maleatos/química , Embalagem de Alimentos/métodos , Reagentes de Ligações Cruzadas/química , Interações Hidrofóbicas e Hidrofílicas , Água/química , Espectroscopia de Infravermelho com Transformada de Fourier , Permeabilidade , Plastificantes/química , Vapor
12.
Acta Crystallogr E Crystallogr Commun ; 80(Pt 5): 537-542, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38721417

RESUMO

In the title compound, C24H21NO3S, the cyclopentene ring adopts an envelope conformation. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming ribbons along the a axis. Inter-molecular C-H⋯O hydrogen bonds connect these ribbons to each other, forming layers parallel to the (01) plane. The mol-ecular packing is strengthened by van der Waals inter-actions between the layers. The inter-molecular contacts were qu-anti-fied using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing the relative contributions of the contacts to the crystal packing to be H⋯H 46.0%, C⋯H/H⋯C 21.1%, O⋯H/H⋯O 20.6% and S⋯H/H⋯S 9.0%.

13.
Chemosphere ; 360: 142437, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797208

RESUMO

The construction and modification of a Graphene Oxide (GO) membrane, incorporating polyvinyl alcohol (PVA) cross-linked with maleic acid (MA) and supported by a nylon membrane, have been successfully completed. Systematic variations in PVA and MA concentrations were conducted to achieve membranes with favorable characteristics, stability, and excellent desalination performance. Optimization studies utilizing the Central Composite Design (CCD) revealed that the most optimal desalination results were obtained with 10 mL of PVA (0.1 mg mL-1) and 0.9 M of MA (GO-MA0.9-PVA10/Nylon membrane). Experimental findings demonstrated that the inclusion of PVA and MA resulted in an increased interlayer distance of GO and enhanced membrane stability. The addition of PVA increases GO membrane hydrophilicity, while the addition of MA reduces membrane hydrophilicity. The GO-MA0.9-PVA10/Nylon membrane exhibited the highest desalination performance, boasting a rejection value exceeding >99.9% and a permeance of 18.76 kg m-2.h-1 under 1% NaCl feed at a temperature of 50 °C. This membrane demonstrated consistent desalination performance stability over an extended period of up to 70 h. Moreover, it exhibited durability through 8 cycles of 24-h usage with washing treatment. In conclusion, the GO-MA0.9-PVA10/Nylon membrane is strongly recommended for practical applications, outperforming other membrane options based on the comprehensive evaluation of its stability and desalination efficiency.


Assuntos
Grafite , Membranas Artificiais , Álcool de Polivinil , Cloreto de Sódio , Purificação da Água , Grafite/química , Álcool de Polivinil/química , Purificação da Água/métodos , Cloreto de Sódio/química , Filtração/métodos , Maleatos/química , Salinidade , Interações Hidrofóbicas e Hidrofílicas , Nylons/química
14.
Talanta ; 274: 125987, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38552478

RESUMO

Multidrug resistance (MDR) is a dominant challenge in cancer chemotherapy failure. The over-expression of breast cancer resistance protein (BCRP) in tumorous cells, along with its extensive substrate profile, is a leading cause of tumor MDR. Herein, on the basis of styrene maleic acid (SMA) polymer membrane protein stabilization strategy and surface plasmon resonance (SPR) biosensor, a novel high-throughput screening (HTS) system for BCRP inhibitors has been established. Firstly, LLC-PK1 and LLC-PK1/BCRP cell membranes were co-incubated with SMA polymers to construct SMA lipid particles (SMALPs). PK1-SMALPs were thus immobilized in channel 1 of the L1 chip as the reference channel, and BCRP-SMALPs were immobilized in channel 2 as the detection channel to establish the BCRP-SMALPs-SPR screening system. The methodological investigation demonstrated that the screening system was highly specific and stable. Three active compounds were screened out from 26 natural products and their affinity constants with BCRP were determined. The KD of xanthotoxin, bergapten, and naringenin were 5.14 µM, 4.57 µM, and 3.72 µM, respectively. The in vitro cell verification experiments demonstrated that xanthotoxin, bergapten, and naringenin all significantly increased the sensitivity of LLC-PK1/BCRP cells to mitoxantrone with possessing reversal BCRP-mediated MDR activity. Collectively, the developed BCRP-SMALPs-SPR screening system in this study has the advantages of rapidity, efficiency, and specificity, providing a novel strategy for the in-depth screening of BCRP inhibitors with less side effects and higher efficacy.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Maleatos , Proteínas de Neoplasias , Ressonância de Plasmônio de Superfície , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/análise , Humanos , Maleatos/química , Maleatos/farmacologia , Animais , Ensaios de Triagem em Larga Escala/métodos , Suínos , Poliestirenos/química , Técnicas Biossensoriais/métodos
15.
J Drug Target ; 32(4): 433-443, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38385752

RESUMO

Traditional treatments for head and neck squamous cell carcinoma (HNSCC) such as surgery, radiation therapy, and chemotherapy, often have severe side effects. Local delivery of chemotherapeutic agents can be a promising approach to minimise systemic toxicity and improve efficacy. Lauric acid (LA), was explored as a novel injectable thermosensitive drug reservoir as a depot for sustained release of anticancer drugs to treat HNSCC. LA was characterised in terms of melting temperature and gelation time. The efficacy of LA-based drug formulations was tested in vitro in a HNSCC cell line and in vivo in a mouse model of HNSCC. LA was modified to have a melting point of 38.5 °C and a gelation time of 40 s at 37.5 °C, rendering it suitable for injection at body temperature. LA- based doxorubicin (DOXO) formulation showed slow release with a maximum of 18% release after 3 days. The in vitro study showed that LA enhanced the cytotoxic effect of DOXO. LA combined with DOXO prevented tumour progression and LA alone significantly reduced the original tumour volume compared to the untreated control group. These findings confirmed that LA can function as practical carrier for the local delivery of chemotherapeutics and provides a safe and simple strategy for the delivery of hydrophobic anticancer drugs and warrant further testing in clinical trials.


Assuntos
Antineoplásicos , Neoplasias de Cabeça e Pescoço , Animais , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Ácidos Láuricos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico
16.
Elife ; 122024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38358918

RESUMO

Bacterial cell surface glycoconjugates are critical for cell survival and for interactions between bacteria and their hosts. Consequently, the pathways responsible for their biosynthesis have untapped potential as therapeutic targets. The localization of many glycoconjugate biosynthesis enzymes to the membrane represents a significant challenge for expressing, purifying, and characterizing these enzymes. Here, we leverage cutting-edge detergent-free methods to stabilize, purify, and structurally characterize WbaP, a phosphoglycosyl transferase (PGT) from the Salmonella enterica (LT2) O-antigen biosynthesis. From a functional perspective, these studies establish WbaP as a homodimer, reveal the structural elements responsible for dimerization, shed light on the regulatory role of a domain of unknown function embedded within WbaP, and identify conserved structural motifs between PGTs and functionally unrelated UDP-sugar dehydratases. From a technological perspective, the strategy developed here is generalizable and provides a toolkit for studying other classes of small membrane proteins embedded in liponanoparticles beyond PGTs.


Assuntos
Salmonella enterica , Transferases , Transferases/genética , Transferases/química , Antígenos O , Metabolismo dos Carboidratos , Membrana Celular , Salmonella enterica/genética
17.
Apoptosis ; 29(5-6): 620-634, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38281282

RESUMO

Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel target to develop new strategies for better prevention and treatment of MA-induced AKI.


Assuntos
Injúria Renal Aguda , Apoptose , Maleatos , Camundongos Endogâmicos C57BL , Mitocôndrias , ATPases Mitocondriais Próton-Translocadoras , Animais , Humanos , Masculino , Camundongos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , ATPases Mitocondriais Próton-Translocadoras/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Espécies Reativas de Oxigênio/metabolismo
18.
Med Chem ; 20(5): 537-545, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38279756

RESUMO

BACKGROUND: Hydroxyapatite and its derivatives have been used for a lot of applications. One of them is drug release studies. Due to its low adhesion strength and lack of the strength and durability required for load-carrying applications, there is a need to improve the properties of hydroxyapatite. For this aim, the most important factors are increasing pH sensitivity and preventing coagulation. Mixing it with multifunctional polymers is the best solution. OBJECTIVES: The main objectives are: 1- preparing poly(acrylamide-co-acrylic acid/maleic acid)- hydroxyapatite (PAm-co-PAA/PMA-HApt), 2- assessment of (PAm-co-PAA/PMA-HApt) and dox-loaded poly(acrylamide-co-acrylic acid/maleic acid) (Dox-(PAm-co-PAA/PMA-HApt)) composite hydrogels, and 3- elucidating the difference in behavior of drug release studies between hydroxyapatite (HApt) and poly(acrylamide-co-acrylic acid/maleic acid) composite hydrogels. METHODS: A composite of PAm-co-PAA/PMA-HApt was prepared by direct polymerization of acrylamide-co-acrylic acid/maleic acid in a suspension of HApt. The drug loading and release features of PAm-co-PAA/PMA-HApt and HApt were then investigated for doxorubicin (dox) release. Using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TG/DTA), this unique composite hydrogel has been physicochemically investigated. Also, a colorimetric assay was used to assess the in vitro biocompatible support and anticancer activity of HApt and the newly developed composite hydrogel XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay. RESULTS: According to the results of drug release studies of this new material, it is pH sensitive, and PAm-co-PAA/PMA-HApt demonstrated a faster release than HApt at 37°C in the acidic solution of pH 4.5 than in the neutral solution of pH 7.4. The XTT assay outcomes also demonstrated the biocompatibility of PAm-co-PAA/PMA-HApt and HApt and the cytotoxic effect of dox-loaded PAm-co-PAA/PMA-HApt. CONCLUSION: It should be inferred that the drug release profile was improved at pH 4.5 by the newly produced pH-sensitive composite hydrogel.


Assuntos
Doxorrubicina , Liberação Controlada de Fármacos , Durapatita , Hidrogéis , Maleatos , Doxorrubicina/química , Doxorrubicina/farmacologia , Durapatita/química , Maleatos/química , Hidrogéis/química , Hidrogéis/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Humanos , Resinas Acrílicas/química , Resinas Acrílicas/síntese química , Acrilamidas/química , Concentração de Íons de Hidrogênio
19.
J Pharm Sci ; 113(4): 1047-1053, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37844758

RESUMO

The purpose of this study was to elucidate and compare styrene maleic acid copolymer (SMA)-coated lipid emulsions (SMA emulsions) uptake pathway in vascular endothelial cells and surrounding cancer cells under not only neutral but also acidic pH, which is often observed in tumor microenvironment. DiI-labeled SMA emulsions were prepared using 1-palmitoyl-2-oleoyl-sn­glycero-3-phosphocholine and triolein. In murine melanoma B16-BL6 (B16) cells and human umbilical vein endothelial cells (HUVEC), DiI-labeled SMA emulsions uptake under near-neutral (pH 7.4) and acidic (pH 6.0) conditions was determined by fluorescent analysis. SMA emulsions were taken up more efficiently into HUVEC than B16 cells under acidic condition in a temperature-dependent manner. Uptake study using endocytosis inhibitors showed that SMA emulsions were taken up by macropinocytosis and clathrin-mediated endocytosis in B16 cells. In HUVEC, however, they were taken up by clathrin- and caveolae-independent, but dynamin-dependent pathway. SMA emulsions would be internalized efficiently into vascular endothelial cells as well as cancer cells under acidic microenvironment via different endocytosis pathways. SMA emulsions could be a promising drug delivery carrier for anti-angiogenic drugs.


Assuntos
Células Endoteliais , Microambiente Tumoral , Camundongos , Humanos , Animais , Emulsões , Poliestirenos , Maleatos , Portadores de Fármacos , Clatrina
20.
Food Chem X ; 20: 100934, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38144752

RESUMO

This present study investigated the effect of cold atmospheric plasma (CAP) pre-treatment on the quality of ready-to-eat drunken red shrimp (Solenocera crassicornis) during chilled storage. The shrimp were pre-treated with the CAP at 40 kV and 36 kH for 100 s in a plasma generating equipment before the drunken treatment and compared with an untreated control sample. The results showed that the CAP pre-treatment significantly inhibited the total viable count (TVC) values, total volatile basic nitrogen (TVB-N) content, and polyphenol oxidase (PPO) activity of the drunken shrimp compared to the control treatment. Furthermore, the CAP pre-treatment also significantly maintained the myofibrillar protein (MP) content, texture properties, and a more stable histological structure of muscle fibers compared to the control. High-throughput sequencing results confirmed that the CAP pre-treatment significantly reduced the diversity and abundance of several bacteria in the shrimp. Gas chromatography-ion mobility spectrometry (GC-IMS) analysis detected that the CAP pre-treatment effectively maintained the stability of volatile organic compounds (VOCs). These findings provide valuable theoretical support for the processing and storage of drunken shrimp.

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