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1.
Int J Mol Sci ; 25(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38928161

RESUMO

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.


Assuntos
Cricetulus , Ovário , Extratos Vegetais , Insuficiência Ovariana Primária , Espécies Reativas de Oxigênio , Animais , Feminino , Camundongos , Células CHO , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/prevenção & controle , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Compostos de Vinila/farmacologia , Cicloexenos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos
2.
Biomolecules ; 14(6)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38927078

RESUMO

Risk of cardiovascular disease mortality rises in women after menopause. While increased cardiovascular risk is largely attributed to postmenopausal declines in estrogens, the molecular changes in the heart that contribute to risk are poorly understood. Disruptions in intracellular calcium handling develop in ovariectomized mice and have been implicated in cardiac dysfunction. Using a mouse model of menopause in which ovarian failure occurs over 120 days, we sought to determine if perimenopause impacted calcium removal mechanisms in the heart and identify the molecular mechanisms. Mice were injected with 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure over 120 days, mimicking perimenopause. Hearts were removed at 60 and 120 days after VCD injections, representing the middle and end of perimenopause. SERCA2a function was significantly diminished at the end of perimenopause. Neither SERCA2a nor phospholamban expression changed at either time point, but phospholamban phosphorylation at S16 and T17 was dynamically altered. Intrinsic SERCA inhibitors sarcolipin and myoregulin increased >4-fold at day 60, as did the native activator DWORF. At the end of perimenopause, sarcolipin and myoregulin returned to baseline levels while DWORF was significantly reduced below controls. Sodium-calcium exchanger expression was significantly increased at the end of perimenopause. These results show that the foundation for increased cardiovascular disease mortality develops in the heart during perimenopause and that regulators of calcium handling exhibit significant fluctuations over time. Understanding the temporal development of cardiovascular risk associated with menopause and the underlying mechanisms is critical to developing interventions that mitigate the rise in cardiovascular mortality that arises after menopause.


Assuntos
Modelos Animais de Doenças , Perimenopausa , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Animais , Feminino , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Camundongos , Perimenopausa/metabolismo , Compostos de Vinila/farmacologia , Miocárdio/metabolismo , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Insuficiência Ovariana Primária/metabolismo , Cicloexenos/farmacologia , Camundongos Endogâmicos C57BL , Fosforilação
3.
J Zoo Wildl Med ; 55(2): 412-423, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38875197

RESUMO

The nutria (Myocastor coypus) is a globally widespread invasive species. Attempts to eradicate nutria by shooting, poisoning, and trapping have been mostly unsuccessful, leading to calls for the development of new control methods. The compound 4-vinylcyclohexene diepoxide (VCD) is known to cause follicular atresia in mammals and may control conception when administered orally. It was hypothesized that VCD administered PO will cause follicular destruction in female nutria. VCD (250 mg/kg PO) was administered or coconut oil, as a control, to five nutria females each for 12 d. Sixty days following VCD exposure, males were introduced to the females. Over the following 7 mon, the effect of VCD on nutria fertility was assessed by conducting ultrasound monitoring to determine pregnancy status and measuring blood serum progesterone and estradiol levels. Finally, after performing ovariectomies, viable follicles were counted on histologic ovarian cortical sections. It was found that the female estrous cycles became synchronized, suggesting a Whitten effect in this species. Also, an increase in the females' serum progesterone levels following the introduction of males occurred, suggesting a male presence effect. Orally administered doses of 250 mg/kg VCD for 12 d had no significant effect on nutria pregnancy rates or on the number of follicles in the ovaries examined. Further studies, using a higher dose or longer administration period, are necessary to conclude whether orally administered VCD can be used as a contraceptive agent for nutria.


Assuntos
Cicloexenos , Compostos de Vinila , Animais , Feminino , Compostos de Vinila/farmacologia , Compostos de Vinila/administração & dosagem , Projetos Piloto , Cicloexenos/farmacologia , Cicloexenos/administração & dosagem , Fertilidade/efeitos dos fármacos , Masculino , Roedores , Animais de Zoológico , Gravidez
4.
Biomacromolecules ; 25(6): 3823-3830, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38773865

RESUMO

Sustainability and circularity are key issues facing the global polymer industry. The search for biodegradable and environmentally-friendly polymers that can replace conventional materials is a difficult challenge that has been met with limited success. Alternatives must be cost-effective, scalable, and provide equivalent performance. We report that latexes made by the conventional emulsion polymerization of vinyl acetate and functional vinyl ester monomers are efficient thickeners for consumer products and biodegrade in wastewater. This approach uses readily-available starting materials and polymerization is carried out in water at room temperature, in one pot, and generates negligible waste. Moreover, the knowledge that poly(vinyl ester)s are biodegradable will lead to the design of new green polymer materials.


Assuntos
Emulsões , Emulsões/química , Polimerização , Polímeros/química , Álcalis/química , Biodegradação Ambiental , Látex/química , Compostos de Vinila/química , Águas Residuárias/química
5.
J Pharm Biomed Anal ; 246: 116228, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38781726

RESUMO

Patiromer (Veltassa®) is a crosslinked, insoluble co-polymer drug used as a nonabsorbent potassium binder, approved for treatment of hyperkalemia. Quantitative solid-state 13C nuclear magnetic resonance (NMR) analysis with comprehensive peak assignment, component quantification, and calculation of mole and weight fractions of monomer units was performed on three doses of patiromer. The workflow is documented in detail. Spectrally edited solid-state 13C NMR spectra of patiromer show =CHn peaks of matching intensity at 116 and 141 ppm, characteristic of -CH=CH2 vinyl groups. Similar spectral features can be observed in earlier studies but were previously ignored. In this study, the vinyl signals are well-resolved in a 2-s direct polarization (DP) spectrum without and with dipolar dephasing, which confirms that these sp2-hybridized carbons are bonded to hydrogen and partially mobile, consistent with vinyl side groups from incompletely reacted divinyl crosslinkers. The vinyl groups account for 1.6% of all carbon, 3% of the monomer units, and nearly 1/3 of the crosslinkers. Furthermore, an unexpected OCH3 moiety accounting for ∼1.2% of all carbons was identified by spectral editing; its chemical shift of 54 ppm is more consistent with a methyl ester than with a methyl ether. It can originate from incomplete hydrolysis of ∼6% of methyl-2-fluoroacrylate, the main monomer of patiromer. Characteristic cross peaks in two-dimensional 1H-13C heteronuclear correlation NMR confirm the presence of the vinyl and OCH3 groups. Trace amounts of xanthan gum are also detected. The quantitative 13C NMR spectrum of patiromer has been matched in a simulation using a model with five monomer units.


Assuntos
Ésteres , Espectroscopia de Ressonância Magnética , Polímeros , Polímeros/química , Ésteres/química , Espectroscopia de Ressonância Magnética/métodos , Compostos de Vinila/química , Solubilidade , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13/métodos
6.
Mol Pharm ; 21(6): 3017-3026, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38758116

RESUMO

Sucrose and trehalose pharmaceutical excipients are employed to stabilize protein therapeutics in a dried state. The mechanism of therapeutic protein stabilization is dependent on the sugars being present in an amorphous solid-state. Colyophilization of sugars with high glass transition polymers, polyvinylpyrrolidone (PVP), and poly(vinylpyrrolidone vinyl acetate) (PVPVA), enhances amorphous sugar stability. This study investigates the stability of colyophilized sugar-polymer systems in the frozen solution state, dried state postlyophilization, and upon exposure to elevated humidity. Binary systems of sucrose or trehalose with PVP or PVPVA were lyophilized with sugar/polymer ratios ranging from 2:8 to 8:2. Frozen sugar-PVPVA solutions exhibited a higher glass transition temperature of the maximally freeze-concentrated amorphous phase (Tg') compared to sugar-PVP solutions, despite the glass transition temperature (Tg) of PVPVA being lower than PVP. Tg values of all colyophilized systems were in a similar temperature range irrespective of polymer type. Greater hydrogen bonding between sugars and PVP and the lower hygroscopicity of PVPVA influenced polymer antiplasticization effects and the plasticization effects of residual water. Plasticization due to water sorption was investigated in a dynamic vapor sorption humidity ramping experiment. Lyophilized sucrose systems exhibited increased amorphous stability compared to trehalose upon exposure to the humidity. Recrystallization of trehalose was observed and stabilized by polymer addition. Lower concentrations of PVP inhibited trehalose recrystallization compared to PVPVA. These stabilizing effects were attributed to the increased hydrogen bonding between trehalose and PVP compared to trehalose and PVPVA. Overall, the study demonstrated how differences in polymer hygroscopicity and hydrogen bonding with sugars influence the stability of colyophilized amorphous dispersions. These insights into excipient solid-state stability are relevant to the development of stabilized biopharmaceutical solid-state formulations.


Assuntos
Estabilidade de Medicamentos , Excipientes , Liofilização , Polímeros , Povidona , Temperatura de Transição , Trealose , Liofilização/métodos , Povidona/química , Trealose/química , Excipientes/química , Polímeros/química , Sacarose/química , Açúcares/química , Ligação de Hidrogênio , Armazenamento de Medicamentos , Química Farmacêutica/métodos , Varredura Diferencial de Calorimetria , Umidade , Pirrolidinas/química , Compostos de Vinila/química
7.
Pharm Res ; 41(6): 1233-1245, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744732

RESUMO

PURPOSE: This study was designed to develop ibuprofen (IBU) sustained-release amorphous solid dispersion (ASD) using polymer composites matrix with drug release plateaus for stable release and to further reveal intrinsic links between polymer' matrix ratios and drug release behaviors. METHODS: Hydrophilic polymers and hydrophobic polymers were combined to form different composite matrices in developing IBU ASD formulations by hot melt extrusion technique. The intrinsic links between the mixed polymer matrix ratio and drug dissolution behaviors was deeply clarified from the dissolution curves of hydrophilic polymers and swelling curves of composite matrices, and intermolecular forces among the components in ASDs. RESULTS: IBU + ammonio methacrylate copolymer type B (RSPO) + poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP VA64) physical mixtures presented unstable release behaviors with large error bars due to inhomogeneities at the micrometer level. However, IBU-RSPO-PVP VA64 ASDs showed a "dissolution plateau phenomenon", i.e., release behaviors of IBU in ASDs were unaffected by polymer ratios when PVP VA64 content was 35% ~ 50%, which could reduce risks of variations in release behaviors due to fluctuations in prescriptions/processes. The release of IBU in ASDs was simultaneously regulated by the PVP VA64-mediated "dissolution" and RSPO-PVP VA64 assembly-mediated "swelling". Radial distribution function suggested that similar intermolecular forces between RSPO and PVP VA64 were key mechanisms for the "dissolution plateau phenomenon" in ASDs at 35% ~ 50% of PVP VA64. CONCLUSIONS: This study provided ideas for developing ASD sustained-release formulations with stable release plateau modulated by polymer combinations, taking full advantages of simple process/prescription, ease of scale-up and favorable release behavior of ASD formulations.


Assuntos
Preparações de Ação Retardada , Composição de Medicamentos , Liberação Controlada de Fármacos , Ibuprofeno , Polímeros , Preparações de Ação Retardada/química , Ibuprofeno/química , Ibuprofeno/administração & dosagem , Polímeros/química , Composição de Medicamentos/métodos , Interações Hidrofóbicas e Hidrofílicas , Solubilidade , Tecnologia de Extrusão por Fusão a Quente/métodos , Compostos de Vinila/química , Pirrolidinas/química , Química Farmacêutica/métodos , Povidona/química
8.
Mol Pharm ; 21(6): 2908-2921, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38743928

RESUMO

The physical stability of amorphous solid dispersions (ASDs) is a major topic in the formulation research of oral dosage forms. To minimize the effort of investigating the long-term stability using cost- and time-consuming experiments, we developed a thermodynamic and kinetic modeling framework to predict and understand the crystallization kinetics of ASDs during long-term storage below the glass transition. Since crystallization of the active phrarmaceutical ingredients (APIs) in ASDs largely depends on the amount of water absorbed by the ASDs, water-sorption kinetics and API-crystallization kinetics were considered simultaneously. The developed modeling approach allows prediction of the time evolution of viscosity, supersaturation, and crystallinity as a function of drug load, relative humidity, and temperature. It was applied and evaluated against two-year-lasting crystallization experiments of ASDs containing nifedipine and copovidone or HPMCAS measured in part I of this work. We could show that the proposed modeling approach is able to describe the interplay between water sorption and API crystallization and to predict long-term stabilities of ASDs just based on short-term measurements. Most importantly, it enables explaining and understanding the reasons for different and sometimes even unexpected crystallization behaviors of ASDs.


Assuntos
Cristalização , Água , Cristalização/métodos , Água/química , Cinética , Estabilidade de Medicamentos , Nifedipino/química , Compostos de Vinila/química , Termodinâmica , Pirrolidinas/química , Viscosidade , Química Farmacêutica/métodos , Umidade , Temperatura , Solubilidade , Metilcelulose/química , Metilcelulose/análogos & derivados
9.
Dent Mater J ; 43(3): 367-374, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38583997

RESUMO

There is a growing need for a mouthguard sheet material with higher shock absorption and dispersion capacity than those obtained by conventional materials. A five-layer mouthguard sheet material was previously developed using laminated ethylene vinyl acetate and polyolefin copolymer resin. In this study, the shock absorption capacity and dispersion capability of the new sheet material were investigated and compared with those of other materials. Impact testing for the new sheet material showed that the force required to displace the sheet by 1 mm was significantly higher at all thicknesses (p<0.001), whereas the puncture energy and displacement were significantly lower than those for ethylene vinyl acetate (p<0.05). The five-layer mouthguard sheet material successfully absorbed and resisted shock. Therefore, the sheet material potentially increases resistance to applied deformation in teeth and alveolar bone and maintains structure. The five-layer sheet material could expand the range of mouthguard products and help prevent oral trauma.


Assuntos
Teste de Materiais , Protetores Bucais , Polienos/química , Compostos de Vinila/química , Desenho de Equipamento , Polivinil/química , Estresse Mecânico , Análise do Estresse Dentário
10.
Drug Discov Ther ; 18(2): 106-116, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38631868

RESUMO

Limited studies are associated with premature ovarian insufficiency (POI)-related osteoimmune disorder currently. Bu-Shen-Ning-Xin decoction (BSNXD) displayed a favorable role in treating postmenopausal osteoporosis. However, its impact on the POI-related osteoimmune disorder remains unclear. The study primarily utilized animal experiments and network pharmacology to investigate the effects and underlying mechanisms of BSNXD on the POI-related osteoimmune disorder. First, a 4-vinylcyclohexene dioxide (VCD)-induced POI murine model was conducted to explore the therapeutical action of BSNXD. Second, we analyzed the active compounds of BSNXD and predicted their potential mechanisms for POI-related osteoimmune disorder via network pharmacology, further confirmed by molecular biology experiments. The results demonstrated that VCD exposure led to elevated follicle-stimulating hormone (FSH) levels, a 50% reduction in the primordial follicles, bone microstructure changes, and macrophage activation, indicating an osteoimmune disorder. BSNXD inhibited macrophage activation and osteoclast differentiation but did not affect serum FSH and estradiol levels in the VCD-induced POI model. Network pharmacology predicted the potential mechanisms of BSNXD against the POI-related osteoimmune disorder involving tumor necrosis factor α and MAPK signaling pathways, highlighting BSNXD regulated inflammation, hormone, and osteoclast differentiation. Further experiments identified BSNXD treatment suppressed macrophage activation via downregulating FSH receptor (FSHR) expression and inhibiting the phosphorylation of ERK and CCAAT enhancer binding proteins ß. In conclusion, BSNXD regulated POI-related osteoimmune disorder by suppressing the FSH/FSHR pathway to reduce macrophage activation and further inhibiting osteoclastogenesis.


Assuntos
Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Hormônio Foliculoestimulante , Ativação de Macrófagos , Insuficiência Ovariana Primária , Receptores do FSH , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/induzido quimicamente , Animais , Feminino , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ativação de Macrófagos/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Receptores do FSH/metabolismo , Compostos de Vinila/farmacologia , Compostos de Vinila/uso terapêutico , Farmacologia em Rede , Cicloexenos/farmacologia , Cicloexenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Humanos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Diferenciação Celular/efeitos dos fármacos
11.
PeerJ ; 12: e17251, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646488

RESUMO

The occupational chemical 4-Vinylcyclohexene diepoxide (VCD) is a reproductively toxic environmental pollutant that causes follicular failure, leading to premature ovarian insufficiency (POI), which significantly impacts a woman's physical health and fertility. Investigating VCD's pathogenic mechanisms can offer insights for the prevention of ovarian impairment and the treatment of POI. This study established a mouse model of POI through intraperitoneal injection of VCD into female C57BL/6 mice for 15 days. The results were then compared with those of the control group, including a comparison of phenotypic characteristics and transcriptome differences, at two time points: day 15 and day 30. Through a comprehensive analysis of differentially expressed genes (DEGs), key genes were identified and validated some using RT-PCR. The results revealed significant impacts on sex hormone levels, follicle number, and the estrous cycle in VCD-induced POI mice on both day 15 and day 30. The DEGs and enrichment results obtained on day 15 were not as significant as those obtained on day 30. The results of this study provide a preliminary indication that steroid hormone synthesis, DNA damage repair, and impaired oocyte mitosis are pivotal in VCD-mediated ovarian dysfunction. This dysfunction may have been caused by VCD damage to the primordial follicular pool, impairing follicular development and aggravating ovarian damage over time, making it gradually difficult for the ovaries to perform their normal functions.


Assuntos
Cicloexenos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Camundongos Endogâmicos C57BL , Insuficiência Ovariana Primária , Compostos de Vinila , Animais , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia , Feminino , Compostos de Vinila/toxicidade , Camundongos , Transcriptoma/efeitos dos fármacos , Ciclo Estral/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Ovário/efeitos dos fármacos , Ovário/patologia , Ovário/metabolismo
12.
Org Biomol Chem ; 22(16): 3273-3278, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38572769

RESUMO

Arylsulfonyl group-bearing α,ß-unsaturated enol esters were readily assembled via the Cs2CO3-mediated union of 2-bromoallyl sulfones and cinnamic acids. The overall transformation is equivalent to an sp2 carbon-oxygen coupling reaction, and therefore constitutes a formal vinylic substitution. Several of the products display promising levels of antiproliferative activities higher than that of the anticancer drug carboplatin. Thiophenol reacted with 2-bromoallyl sulfones under identical conditions to afford α-thiophenyl-α'-tosyl acetone via an apparent aerial oxidation.


Assuntos
Antineoplásicos , Proliferação de Células , Ésteres , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Ésteres/química , Ésteres/farmacologia , Ésteres/síntese química , Humanos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Sulfonas/química , Sulfonas/farmacologia , Sulfonas/síntese química , Relação Estrutura-Atividade , Compostos de Vinila/química , Compostos de Vinila/farmacologia , Compostos de Vinila/síntese química
13.
Drug Dev Ind Pharm ; 50(4): 285-296, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38486377

RESUMO

The overactive bladder is a condition characterized by a sudden urge to urinate, even with small volumes of urine present in the bladder. The current treatments available for this pathology consist on conservative approaches and the continuous administration of drugs, which when made by conventional methods has limitations related to the first pass metabolism, bioavailability, severe side effects, and low patient adherence to treatments, ultimately leading to low effectiveness. Within this context, the present work proposes the design, manufacture, and characterization of an intravesical implant for the treatment of overactive bladder pathology, using EVA copolymer as a matrix and oxybutynin as a drug. The fabrication of devices through two manufacturing techniques (extrusion and additive manufacturing by fused filament fabrication, FFF) and the evaluation of the implants through characterization tests was proposed. The usability and functionality were evaluated through simulated insertion of the device/prototype in a bladder model through catheter insertion tests. The safety and effectiveness of the devices was investigated from mechanical testing as well as drug release assays. Drug release assays presented a burst release in the first 24 h, followed by a release of 1.8 and 2.8 mg/d, totalizing 32 d. Mechanical tests demonstrated an increase in the stiffness of the specimens due to the addition of the drug, showing a change in maximum stress and strain at break. The released dose was higher than that usually presented when considering the oral administration route, showing the optimization of the development of this implant has the potential to improve the quality of life of patients with overactive bladder.


Assuntos
Bexiga Urinária Hiperativa , Compostos de Vinila , Humanos , Bexiga Urinária Hiperativa/tratamento farmacológico , Preparações Farmacêuticas , Qualidade de Vida , Etilenos/uso terapêutico , Impressão Tridimensional
14.
Exp Physiol ; 109(5): 711-728, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38500268

RESUMO

The abrupt cessation of ovarian hormone release is associated with declines in muscle contractile function, yet the impact of gradual ovarian failure on muscle contractility across peri-, early- and late-stage menopause remains unclear. In this study, a 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure mouse model was used to examine time course changes in muscle mechanical function. Plantar flexors of female mice (VCD: n = 10; CON: n = 8) were assessed at 40 (early perimenopause), 80 (late perimenopause), 120 (menopause onset) and 176 (late menopause) days post-initial VCD injection. A torque-frequency relationship was established across a range of frequencies (10-200 Hz). Isotonic dynamic contractions were elicited against relative loads (10-80% maximal isometric torque) to determine the torque-velocity-power relationship. Mice then performed a fatigue task using intermittent 100 Hz isometric contractions until torque dropped by 60%. Recovery of twitch, 10 Hz and 100 Hz torque were tracked for 10 min post-task failure. Additionally, intact muscle fibres from the flexor digitorum brevis underwent a fatigue task (50 repetitions at 70 Hz), and 10 and 100 Hz tetanic [Ca2+] were monitored for 10 min afterward. VCD mice exhibited 16% lower twitch torque than controls across all time points. Apart from twitch torque, 10 Hz torque and 10 Hz tetanic [Ca2+], where VCD showed greater values relative to pre-fatigue during recovery, no significant differences were observed between control and VCD mice during recovery. These results indicate that gradual ovarian failure has minimal detriments to in vivo muscle mechanical function, with minor alterations observed primarily for low-frequency stimulation during recovery from fatigue.


Assuntos
Cálcio , Contração Muscular , Fadiga Muscular , Músculo Esquelético , Compostos de Vinila , Animais , Feminino , Camundongos , Compostos de Vinila/farmacologia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/metabolismo , Fadiga Muscular/fisiologia , Contração Muscular/fisiologia , Cálcio/metabolismo , Torque , Camundongos Endogâmicos C57BL , Cicloexenos/farmacologia , Contração Isométrica/fisiologia , Insuficiência Ovariana Primária/fisiopatologia , Insuficiência Ovariana Primária/metabolismo
15.
Mol Pharm ; 21(4): 1933-1941, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38502549

RESUMO

Islatravir, a highly potent nucleoside reverse transcriptase translocation inhibitor (NRTTI) for the treatment of HIV, has great potential to be formulated as ethylene-vinyl acetate (EVA) copolymer-based implants via hot melt extrusion. The crystallinity of EVA determines its physical and rheological properties and may impact the drug-eluting implant performance. Herein, we describe the systematic analysis of factors affecting the EVA crystallinity in islatravir implants. Differential scanning calorimetry (DSC) on EVA and solid-state NMR revealed drug loading promoted EVA crystallization, whereas BaSO4 loading had negligible impact on EVA crystallinity. The sterilization through γ-irradiation appeared to significantly impact the EVA crystallinity and surface characteristics of the implants. Furthermore, DSC analysis of thin implant slices prepared with an ultramicrotome indicated that the surface layer of the implant was more crystalline than the core. These findings provide critical insights into factors affecting the crystallinity, mechanical properties, and physicochemical properties of the EVA polymer matrix of extruded islatravir implants.


Assuntos
Desoxiadenosinas , Etilenos , Polivinil , Compostos de Vinila , Polivinil/química
16.
J Sep Sci ; 47(5): e2300746, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38471966

RESUMO

In this work, monodisperse and nano-porous poly(bismaleimide-co-divinylbenzene) microspheres with large specific surface area (427.6 m2 /g) and rich pore structure were prepared by one-pot self-stable precipitation polymerization of 2,2'-bis[4-(4-maleimidophenoxy) phenyl] propane and divinylbenzene. The prepared poly(bismaleimide-co-divinylbenzene) microspheres were employed as dispersive solid-phase extraction (DSPE) adsorbent for the extraction of triazine herbicides. Under optimized conditions, good linearities were obtained between the peak area and the concentration of triazine herbicides in the range of 1-400 µg/L (R2 ≥ 0.9987) with the limits of detection of 0.12-0.31 µg/L. Triazine herbicides were detected using the described approach in vegetable samples (i.e., cucumber, tomato, and maize) with recoveries of 93.6%-117.3% and relative standard deviations of 0.4%-3.5%. In addition, the recoveries of triazine herbicides remained above 80.7% after being used for nine DSPE cycles, showing excellent reusability of poly(bismaleimide-co-divinylbenzene) microspheres. The adsorption of poly(bismaleimide-co-divinylbenzene) microspheres toward triazine herbicides was a monolayer and chemical adsorption. The adsorption mechanism between triazine herbicides and adsorbents might be a combination of hydrogen bonding, electrostatic interaction, and π-π conjugation. The results confirmed the potential use of the poly(bismaleimide-co-divinylbenzene) microspheres-based DSPE coupled to the high-performance liquid chromatography method for the detection of triazine herbicide residues in vegetable samples.


Assuntos
Herbicidas , Verduras , Compostos de Vinila , Verduras/química , Cromatografia Líquida de Alta Pressão/métodos , Microesferas , Porosidade , Triazinas/análise , Extração em Fase Sólida/métodos , Herbicidas/análise , Limite de Detecção
17.
Food Chem ; 447: 139056, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38513495

RESUMO

Sinapic acid (SA), canolol (CAO) and canolol dimer (CAO dimer) are the main phenolic compounds in rapeseed oil. However, their possible efficacy against glycation remains unclear. This study aims to explore the impacts of these substances on the formation of advanced glycation end products (AGEs) based on chemical and cellular models in vitro. Based on fluorescence spectroscopy results, three chemical models of BSA-fructose, BSA-methylglyoxal (MGO), and arginine (Arg)-MGO showed that SA/CAO/CAO dimer could effectively reduce AGE formation but with different abilities. After SA/CAO/CAO dimer incubation, effective protection against BSA protein glycation was observed and three different MGO adducts were formed. In MGO-induced HUVEC cell models, only CAO and CAO dimer significantly inhibited oxidative stress and cell apoptosis, accompanied by the regulation of the Nrf2-HO-1 pathway. During the inhibition, 20 and 12 lipid mediators were reversed in the CAO and CAO dimer groups compared to the MGO group.


Assuntos
Produtos Finais de Glicação Avançada , Óxido de Magnésio , Compostos de Vinila , Produtos Finais de Glicação Avançada/química , Óleo de Brassica napus , Fenóis/química , Aldeído Pirúvico/química
18.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38396972

RESUMO

Due to growing concerns about environmental pollution from plastic waste, plastic recycling research is gaining momentum. Traditional methods, such as incorporating inorganic particles, increasing cross-linking density with peroxides, and blending with silicone monomers, often improve mechanical properties but reduce flexibility for specific performance requirements. This study focuses on synthesizing silica nanoparticles with vinyl functional groups and evaluating their mechanical performance when used in recycled plastics. Silica precursors, namely sodium silicate and vinyltrimethoxysilane (VTMS), combined with a surfactant, were employed to create pores, increasing silica's surface area. The early-stage introduction of vinyl functional groups prevented the typical post-synthesis reduction in surface area. Porous silica was produced in varying quantities of VTMS, and the synthesized porous silica nanomaterials were incorporated into recycled polyethylene to induce cross-linking. Despite a decrease in surface area with increasing VTMS content, a significant surface area of 883 m2/g was achieved. In conclusion, porous silica with the right amount of vinyl content exhibited improved mechanical performance, including increased tensile strength, compared to conventional porous silica. This study shows that synthesized porous silica with integrated vinyl functional groups effectively enhances the performance of recycled plastics.


Assuntos
Nanopartículas , Nanoestruturas , Silanos , Compostos de Vinila , Dióxido de Silício , Reciclagem , Poluição Ambiental
19.
Chirality ; 36(2): e23645, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38384154

RESUMO

We are looking into how well a copolymeric material made of poly (maleic acid-co-4-vinylpyridine) cross-linked with divinylbenzene can separate L-norepinephrine (L-NEP) from (±)-NEP. The initial step in this direction was the synthesis and subsequent analysis of L-NEP-maleimide chiral derivative. A 4-vinylpyridine/divinylbenzene combination was copolymerized with the resultant chiral maleimide. After heating the polymer materials in a high-alkaline environment to breakdown the connecting imide bonds, they were acidified in an HCl solution to eliminate the incorporated L-NEP species. Fourier transform infrared spectroscopy (FTIR) and a scanning electron microscope were used to examine the imprinted L-NEP-imprinted materials. The manufactured L-NEP-imprinted materials exhibited selectivity characteristics that were over 11 times greater for L-NEP than D-norepinephrine. The highest capacity observed in Langmuir adsorption studies was 170 mg/g at a pH of 7. After optical separation using a column technique, it was determined that the enantiomeric excess levels of D-norepinephrine and L-NEP in the first feeding and subsequent recovery solutions were 95% and 81%, respectively.


Assuntos
Impressão Molecular , Polímeros Molecularmente Impressos , Compostos de Vinila , Norepinefrina , Impressão Molecular/métodos , Estereoisomerismo , Polímeros/química , Adsorção , Maleimidas
20.
J Colloid Interface Sci ; 663: 73-81, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38394819

RESUMO

Electroactive materials are increasingly being used in strategies to regenerate cardiac tissue. These materials, particularly those with electrical conductivity, are used to actively recreate the electromechanical nature of the cardiac tissue. In the present work, we describe a novel combination of poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)), a highly electroactive polymer, with graphene (G), exhibiting high electrical conductivity. G/P(VDF-TrFE) films have been characterized in terms of topographical, physico-chemical, mechanical, electrical, and thermal properties, and studied the response of cardiomyocytes adhering to them. The results indicate that the crystallinity and the wettability of the composites remain almost unaffected after G incorporation. In turn, surface roughness, Young modulus, and electric properties are higher in G/P(VDF-TrFE). Finally, the composites are highly biocompatible and able to support cardiomyocyte adhesion and proliferation, particularly surface treated ones, demonstrating the suitability of these materials for cardiac tissue engineering applications.


Assuntos
Polímeros de Fluorcarboneto , Grafite , Hidrocarbonetos Fluorados , Polivinil , Compostos de Vinila , Engenharia Tecidual , Coração
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