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1.
Proc Natl Acad Sci U S A ; 119(32): e2208855119, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35914126

RESUMO

Wild-type (WT) mice maintain viable levels of blood glucose even when adipose stores are depleted by 6 d of 60% calorie restriction followed by a 23-h fast (hereafter designated as "starved" mice). Survival depends on ghrelin, an octanoylated peptide hormone. Mice that lack ghrelin suffer lethal hypoglycemia when subjected to the same starvation regimen. Ghrelin is known to stimulate secretion of growth hormone (GH), which in turn stimulates secretion of IGF-1 (insulin-like growth factor-1). In the current study, we found that starved ghrelin-deficient mice had a 90% reduction in plasma IGF-1 when compared with starved WT mice. Injection of IGF-1 in starved ghrelin-deficient mice caused a twofold increase in glucose production and raised blood glucose to levels seen in starved WT mice. Increased glucose production was accompanied by increases in plasma glycerol, fatty acids and ketone bodies, and hepatic triglycerides. All of these increases were abolished when the mice were treated with atglistatin, an inhibitor of adipose tissue triglyceride lipase. We conclude that IGF-1 stimulates adipose tissue lipolysis in starved mice and that this lipolysis supplies energy and substrates that restore hepatic gluconeogenesis. This action of IGF-1 in starved mice is in contrast to its known action in inhibiting adipose tissue lipase in fed mice. Surprisingly, the ghrelin-dependent maintenance of plasma IGF-1 in starved mice was not mediated by GH. Direct injection of GH into starved ghrelin-deficient mice failed to increase plasma IGF-1. These data call attention to an unsuspected role of IGF-1 in the adaptation to starvation.


Assuntos
Glicemia , Fator de Crescimento Insulin-Like I , Inanição , Adaptação Fisiológica , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/enzimologia , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Ácidos Graxos/sangue , Grelina/metabolismo , Gluconeogênese , Glicerol/sangue , Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Corpos Cetônicos/sangue , Lipase/antagonistas & inibidores , Lipase/metabolismo , Lipólise , Fígado/metabolismo , Camundongos , Compostos de Fenilureia/farmacologia , Inanição/sangue , Inanição/metabolismo , Triglicerídeos/metabolismo
2.
Int J Mol Sci ; 23(15)2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35955889

RESUMO

(1) Background: Depending on the type of hydrophilic polymer used, different types of hydrogels may be chemically stable or may degrade and eventually disintegrate, or dissolve upon exposure to sunlight. Many over-the-counter medications are now stored with a limited control of temperature, humidity and lighting. Therefore, in this study, the photostability of a gel made of cross-linked polyacrylic acid (PA), methylcellulose (MC) and aristoflex (AV) was assessed, and the interaction between the polymers used and ascorbic acid and its ethylated derivative was investigated. (2) Methods: The samples were continuously irradiated at constant temperature for six hours. The stability of the substance incorporated into the gels was assessed using a UV-Vis spectrophotometer. FTIR-ATR infrared spectroscopy was used to measure changes during the exposure. (3) Results: Ascorbic acid completely decomposed between the first and second hours of illumination in all samples. The exception is the preparation based on polyacrylic acid with glycerol, in which the decomposition of ascorbic acid slowed down significantly. After six hours of irradiation, the ethylated ascorbic acid derivative decomposed in about 5% for the polyacrylic acid-based gels and aristoflex, and in the methylcellulose gel it decomposed to about 2%. In the case of ascorbic acid, the most stable formulation was a gel based on polyacrylic acid and polyacrylic acid with glycerol, and in the case of the ethyl derivative, a gel based on methylcellulose. (4) Conclusions: The experiment showed significant differences in the decomposition rate of both compounds, resulting from their photostability and the polymer used in the hydrogel.


Assuntos
Ácido Ascórbico , Glicerol , Ácido Ascórbico/química , Hidrogéis/química , Luz , Metilcelulose/química , Polímeros/química
3.
Microbiology (Reading) ; 168(8)2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35925665

RESUMO

Hierarchical utilization of substrate by microbes (utilization of simple carbon sources prior to complex ones) poses a major limitation to the efficient remediation of aromatic pollutants. Aromatic compounds, being complex and reduced in nature, appear to be a deferred choice as the carbon source in the presence of a plethora of simple organic compounds in the environment. The soil bacterium Pseudomonas bharatica CSV86T displays a unique carbon source utilization hierarchy. It preferentially utilizes aromatics over glucose and co-metabolizes them with succinate or pyruvate (Basu et al., 2006, Applied and Environmental Microbiology, 72 : 22226-2230). In the present study, the substrate utilization hierarchy for strain CSV86T was tested for additional simple carbon sources such as glycerol, acetate, and tri-carboxylic acid (TCA) cycle intermediates like α-ketoglutarate and fumarate. When grown on a mixture of aromatics (benzoate or naphthalene) plus glycerol, the strain displayed a diauxic growth profile with significantly high activity of aromatic utilization enzymes (catechol 1,2- or 2,3-dioxygenase, respectively) in the first-log phase. This suggests utilization of aromatics in the first-log phase followed by glycerol in the second-log phase. On a mixture of an aromatic plus organic acid (acetate, α-ketoglutarate or fumarate), the strain displayed a monoauxic growth profile, indicating co-metabolism. Interestingly, the presence of glycerol, acetate, α-ketoglutarate or fumarate does not repress metabolism/utilization of the aromatic. Thus, the substrate utilization hierarchy of strain CSV86T is aromatics=organic acids>glucose/glycerol, which is unique as compared to other Pseudomonas species, where degradation of aromatics is repressed by glycerol, glucose, acetate or organic acids, including TCA cycle intermediates. This novel substrate utilization hierarchy appears to be a global metabolic phenomenon in strain CSV86T, thus implying it to be an ideal host for metabolic engineering as well as for its potential application in bioremediation.


Assuntos
Pseudomonas putida , Pseudomonas , Ácidos/metabolismo , Carbono/metabolismo , Fumaratos/metabolismo , Glucose/metabolismo , Glicerol/metabolismo , Ácidos Cetoglutáricos/metabolismo , Pseudomonas/metabolismo , Pseudomonas putida/metabolismo
4.
Int J Mol Sci ; 23(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35955611

RESUMO

Various different agri-food biomasses might be turned into renewable sources for producing biodegradable and edible plastics, potentially attractive for food, agricultural and cosmeceutical sectors. In this regard, different seeds utilized for edible and non-edible oil extraction give rise to high amounts of organic by-products, known as seed oil cakes (SOCs), potentially able to become protein-rich resources useful for the manufacturing of biodegradable films. This study reports the potential of SOC derived from Argania spinosa (argan), a well-known plant containing valuable non-refined oil suitable for food or cosmetic use, to be a promising valuable source for production of a protein-based matrix of biomaterials to be used in the pharmaco-cosmetic sector. Thus, glycerol-plasticized films were prepared by casting and drying using different amounts of argan seed protein concentrate, in the presence of increasing glycerol concentrations, and characterized for their morphological, mechanical, barrier, and hydrophilicity properties. In addition, their antioxidant activity and effects on cell viability and wound healing were investigated. The hydrophobic nature of the argan protein-based films, and their satisfying physicochemical and biological properties, suggest a biorefinery approach for the recycling of argan SOC as valuable raw material for manufacturing new products to be used in the cosmeceutical and food industries.


Assuntos
Cosmecêuticos , Sapotaceae , Glicerol , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Sapotaceae/química , Sementes
5.
Phys Chem Chem Phys ; 24(30): 18272-18280, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35880532

RESUMO

Using depolarized light scattering, we have recently shown that structural relaxation in a broad range of supercooled liquids follows, to good approximation, a generic line shape with high-frequency power law ω-1/2. We now continue this study by investigating a systematic series of polyalcohols (PAs), frequently used as model-systems in glass-science, i.a., because the width of their respective dielectric loss spectra varies strongly along the series. Our results reveal that the microscopic origin of the observed relaxation behavior varies significantly between different PAs: while short-chained PAs like glycerol rotate as more or less rigid entities and their light scattering spectra follow the generic shape, long-chained PAs like sorbitol display pronounced intramolecular dynamic contributions on the time scale of structural relaxation, leading to systematic deviations from the generic shape. Based on these findings we discuss an important limitation for observing the generic shape in a supercooled liquid: the dynamics that is probed needs to reflect the intermolecular dynamic heterogeneity, and must not be superimposed by effects of intramolecular dynamic heterogeneity.


Assuntos
Vidro , Sorbitol , Vidro/química , Glicerol/química , Sorbitol/química , Temperatura
6.
Biochem Biophys Res Commun ; 621: 1-7, 2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-35802941

RESUMO

Hepatic gluconeogenesis is crucial for maintaining blood glucose during starvation, and a major contributor for hyperglycemia. Cellular redox state is related to mitochondrial biology and regulates conversion of specific metabolites to glucose. General control of amino acid synthesis 5 (GCN5) like-1 (GCN5L1) is a mitochondria-enriched protein which modulates glucose and amino acid metabolism. Here we show a new regulatory mode of GCN5L1 on gluconeogenesis using lactate and glycerol. We observed GCN5L1 deletion dramatically inhibited glucose production derived from glycerol and lactate, due to increased cytosolic redox state. The underlying mechanism is that GCN5L1 directly binds to the key component of mitochondrial shuttle glycerol phosphate dehydrogenase 2 (GPD2) and modulates its activity. These results have significant implications for understanding the physiological role and regulatory mechanism of mitochondrial shuttle in diabetes development and provide a novel therapeutic potential for diabetes.


Assuntos
Gluconeogênese , Glicerolfosfato Desidrogenase , Aminoácidos/metabolismo , Glucose/metabolismo , Glicerol/metabolismo , Glicerolfosfato Desidrogenase/genética , Glicerolfosfato Desidrogenase/metabolismo , Ácido Láctico/metabolismo , Mitocôndrias/metabolismo , Oxirredução , Fosfatos/metabolismo
7.
Biomolecules ; 12(7)2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35883453

RESUMO

Aquaporins (AQPs) are transmembrane channels essential for water, energy, and redox homeostasis, with proven involvement in a variety of pathophysiological conditions such as edema, glaucoma, nephrogenic diabetes insipidus, oxidative stress, sepsis, cancer, and metabolic dysfunctions. The 13 AQPs present in humans are widely distributed in all body districts, drawing cell lineage-specific expression patterns closely related to cell native functions. Compelling evidence indicates that AQPs are proteins with great potential as biomarkers and targets for therapeutic intervention. Aquaporin-9 (AQP9) is the most expressed in the liver, with implications in general metabolic and redox balance due to its aquaglyceroporin and peroxiporin activities, facilitating glycerol and hydrogen peroxide (H2O2) diffusion across membranes. AQP9 is also expressed in other tissues, and their altered expression is described in several human diseases, such as liver injury, inflammation, cancer, infertility, and immune disorders. The present review compiles the current knowledge of AQP9 implication in diseases and highlights its potential as a new biomarker for diagnosis and prognosis in clinical medicine.


Assuntos
Aquaporinas , Peróxido de Hidrogênio , Aquaporinas/genética , Biomarcadores/metabolismo , Glicerol/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Fígado/metabolismo
8.
Am J Dent ; 35(2): 141-145, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35798709

RESUMO

PURPOSE: To evaluate the degree of stain absorption of resin composite following different finishing and polishing protocols and to evaluate the efficacy of prophylaxis paste with or without addition of carbamide peroxide to remove composite surface stain. METHODS: 50 resin composite blocks were prepared using nano-hybrid composite (Filtek Z250XT) and giomer (Beautifil II LS). Specimens were either polished with a disk or coated with 5th/7th generation bonding or glycerin gel. The color parameters (lightness, chroma and hue) of the specimens were measured prior to staining, and after 1 and 2 weeks of staining using a color chromometer. The composite surface stain removal capability of prophylaxis pastes with or without the addition of carbamide peroxide was evaluated before and after polishing. RESULTS: The repeated measures ANOVA showed that composite polished with a polishing disk or coated with glycerin gel have better color stability compared to composite without any polishing or coated with 5th or 7th generation bonding materials. The prophylaxis paste was able to remove composite surface stain; however, the addition of carbamide peroxide did not show any additional benefit. The results suggested that polishing with polishing disks or coating with glycerin gel is useful for the color stability of resin composite. CLINICAL SIGNIFICANCE: Selection of finishing and polishing protocols varies among individual practitioners. Each of these protocols has some pros and cons concerning the esthetic and color stability of composite. The present results suggested that the use of polishing disk or glycerin gel during polymerization would be a useful protocol to achieve and maintain esthetically stable composite restorations.


Assuntos
Corantes , Polimento Dentário , Peróxido de Carbamida , Cor , Resinas Compostas , Materiais Dentários , Polimento Dentário/métodos , Glicerol , Teste de Materiais , Propriedades de Superfície
9.
Sci Rep ; 12(1): 12460, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864283

RESUMO

Acid value (AV), is a widely used indicator of oil degradation that, by definition, measures the free fatty acids formed via the hydrolysis of triacyclglycerols. However, based on observations made in previous studies, we hypothesized that the oxidation of triacylglycerols leads to the formation of carboxylic acids with a glycerol backbone which are also calculated as AV. In this study, we aimed to identify such carboxylic acids and prove the above hypothesis. Heating a canola oil at 180 °C for 6 h without the addition of water resulted in an increase in AV from 0.054 to 0.241. However, the contribution of free fatty acids to this increase in AV was minimal; free fatty acid-derived AV before and after heating was 0.020 and 0.023, respectively. Then, via mass spectrometric analyses, we identified two 8-carboxy-octanoyl (azelaoyl) -triacylglycerols (i.e., dioleoyl-azelaoyl-glycerol and oleoyl-linoleoyl-azelaoyl-glycerol) in the heated oil. Azelaoyl-triacylglycerols-derived AV before and after heating the oil was 0.008 and 0.109, respectively, demonstrating that azelaoyl-triacylglycerols contribute to AV. Such an increase in AV by azelaoyl-triacylglycerols was also observed in an oil used to deep-fry potatoes (i.e., an oil with a relatively high water content). These results suggest that AV is also an indicator of the thermal oxidation of triacylglycerols.


Assuntos
Ácidos Graxos não Esterificados , Ácidos Graxos , Ácidos Carboxílicos , Ácidos Graxos/análise , Glicerol , Azeite de Oliva , Óleos Vegetais/química , Triglicerídeos/metabolismo , Água
10.
PLoS One ; 17(7): e0270699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35789217

RESUMO

BACKGROUND: A glycerol throat spray containing cold-adapted cod trypsin (GCTS) deactivates common cold virus in vitro and decreases pharyngeal rhinovirus load after inoculation in humans. We relied on early self-diagnosis and evaluated two different scales to detect a treatment effect in naturally occurring common colds. METHODS: Adults were enrolled in this randomised, prospective, parallel group, single-blind study to begin treatment six times daily at first sign of a common cold or were assigned to a non-treated group. Jackson's symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey (WURSS)-21 quality of life (QoL) domain were recorded daily by subjects and area under the curve over 12 days (AUC1-12) calculated. RESULTS: Treatment resulted in reduced symptoms with an AUC1-12 of 45.1 ± 32.5 for Jackson scores compared to 53.8 ± 35.7 in the controls (p = 0.023). AUC1-12 for the 9-item WURSS-21 QoL domain was likewise improved, 113.6 ± 107.7 and 152.7 ± 126.3 (p = 0.006), respectively. During the first four days fewer of the treated subjects (35.3%) used rescue medication than did the control group (50.4%, p = 0.014). CONCLUSIONS: Reduction in common cold symptoms was seen with treatment with a glycerol throat spray containing cold-adapted cod trypsin. This effect was best detected with the 9-item WURSS-21 QoL domain.


Assuntos
Resfriado Comum , Adulto , Resfriado Comum/diagnóstico , Resfriado Comum/tratamento farmacológico , Glicerol/uso terapêutico , Humanos , Faringe , Estudos Prospectivos , Qualidade de Vida , Rhinovirus , Índice de Gravidade de Doença , Método Simples-Cego , Tripsina
11.
Chem Commun (Camb) ; 58(63): 8850-8853, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35849079

RESUMO

A novel class of recyclable thermoset has been developed from cis-3,4-diphenylcyclobutane-1,2-dicarboxylic acid (CBDA-4) due to its thermocleavability at high temperature. This key CBDA-4 building block was synthesized from ß-trans-cinnamic acid using a [2+2] photocycloaddition reaction. CBDA-4 was subsequently linked with glycerol via esterification to give a thermoset with Tg of 68 °C. The thermoset was heated to 300 °C to analyze its degradation. A key intermediate was successfully obtained after purification of the degraded polymer. NMR, FT-IR, HRMS, and single crystal X-ray diffraction confirmed the intermediate was glycerol cinnamate, which was the result of splitting cyclobutane in the polymer backbone at high temperature. Glycerol cinnamate was readily hydrolyzed reforming the starting materials glycerol and trans-cinnamic acid to complete the recycling loop.


Assuntos
Ciclobutanos , Glicerol , Cinamatos/química , Ácidos Dicarboxílicos , Glicerol/química , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier
12.
Chem Commun (Camb) ; 58(63): 8766-8769, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35861259

RESUMO

In this study, novel functional polymers were obtained by using glycerol as a bio-based precursor, which is abundant and inexpensive renewable feedstock with a polyol skeleton. Cyclic vinyl ethers with acetal linkage were derived from glycerol to yield well-defined copolymers by reversible addition-fragmentation chain transfer (RAFT) radical copolymerization with common vinyl monomers. The resulting acetal-containing copolymers could be hydrolyzed under acidic conditions to afford water-soluble functional polymers with pendent diols.


Assuntos
Éteres Cíclicos , Glicerol , Acetais , Polimerização , Polímeros
13.
ACS Appl Mater Interfaces ; 14(30): 35114-35125, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35862578

RESUMO

The rapid development of flexible electronic devices has caused a boom in researching flexible sensors based on hydrogels, but most of the flexible sensors can only work at room temperature, and they are difficult to adapt to extremely cold or dry environments. Here, the flexible hydrogel fibers (PEDOT:PSS@PVA) with excellent resistance to extreme environments have been prepared by adding glycerin (GL) to the mixture of poly(vinyl alcohol) (PVA) and poly 3,4-dioxyethylene thiophene:polystyrene sulfonic acid (PEDOT:PSS) because GL molecules can form dynamic hydrogen bonds with an elastic matrix of PVA molecules. It is found that the prepared sensor exhibits very good flexibility and mechanical strength, and the ultimate tensile strength can reach up to 13.76 MPa when the elongation at break is 519.9%. Furthermore, the hydrogel fibers possess excellent water retention performance and low-temperature resistance. After being placed in the atmospheric environment for 1 year, the sensor still shows good flexibility. At a low temperature of -60 °C, the sensor can stably endure 1000 repeated stretches and shrinks (10% elongation). In addition to the response to a large strain, this fiber sensor can also detect extremely small strains as low as 0.01%. It is proved that complex human movements such as knuckle bending, vocalization, pulse, and others can be monitored perfectly by this fiber sensor. The above results mean that the PEDOT:PSS@PVA fiber sensor has great application prospects in physiological monitoring.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Hidrogéis , Compostos Bicíclicos Heterocíclicos com Pontes/química , Ambientes Extremos , Glicerol/química , Humanos , Hidrogéis/química , Monitorização Fisiológica , Polímeros
14.
Proc Natl Acad Sci U S A ; 119(31): e2119439119, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35895681

RESUMO

Archaeal viruses with a spindle-shaped virion are abundant and widespread in extremely diverse environments. However, efforts to obtain the high-resolution structure of a spindle-shaped virus have been unsuccessful. Here, we present the structure of SSV19, a spindle-shaped virus infecting the hyperthermophilic archaeon Sulfolobus sp. E11-6. Our near-atomic structure reveals an unusual sevenfold symmetrical virus tail consisting of the tailspike, nozzle, and adaptor proteins. The spindle-shaped capsid shell is formed by seven left-handed helical strands, constructed of the hydrophobic major capsid protein, emanating from the highly glycosylated tail assembly. Sliding between adjacent strands is responsible for the variation of a virion in size. Ultrathin sections of the SSV19-infected cells show that SSV19 virions adsorb to the host cell membrane through the tail after penetrating the S-layer. The tailspike harbors a putative endo-mannanase domain, which shares structural similarity to a Bacteroides thetaiotaomicro endo-mannanase. Molecules of glycerol dibiphytanyl glycerol tetraether lipid were observed in hydrophobic clefts between the tail and the capsid shell. The nozzle protein resembles the stem and clip domains of the portals of herpesviruses and bacteriophages, implying an evolutionary relationship among the archaeal, bacterial, and eukaryotic viruses.


Assuntos
Fuselloviridae , Sulfolobus , Proteínas do Capsídeo/química , Fuselloviridae/química , Fuselloviridae/genética , Fuselloviridae/isolamento & purificação , Genoma Viral , Glicerol , Sulfolobus/virologia , Vírion/química , Vírion/genética , Vírion/isolamento & purificação
15.
Proc Natl Acad Sci U S A ; 119(31): e2123193119, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35905325

RESUMO

Archaeal membrane lipids are widely used for paleotemperature reconstructions, yet these molecular fossils also bear rich information about ecology and evolution of marine ammonia-oxidizing archaea (AOA). Here we identified thermal and nonthermal behaviors of archaeal glycerol dialkyl glycerol tetraethers (GDGTs) by comparing the GDGT-based temperature index (TEX86) to the ratio of GDGTs with two and three cyclopentane rings (GDGT-2/GDGT-3). Thermal-dependent biosynthesis should increase TEX86 and decrease GDGT-2/GDGT-3 when the ambient temperature increases. This presumed temperature-dependent (PTD) trend is observed in GDGTs derived from cultures of thermophilic and mesophilic AOA. The distribution of GDGTs in suspended particulate matter (SPM) and sediments collected from above the pycnocline-shallow water samples-also follows the PTD trend. These similar GDGT distributions between AOA cultures and shallow water environmental samples reflect shallow ecotypes of marine AOA. While there are currently no cultures of deep AOA clades, GDGTs derived from deep water SPM and marine sediment samples exhibit nonthermal behavior deviating from the PTD trend. The presence of deep AOA increases the GDGT-2/GDGT-3 ratio and distorts the temperature-controlled correlation between GDGT-2/GDGT-3 and TEX86. We then used Gaussian mixture models to statistically characterize these diagnostic patterns of modern AOA ecology from paleo-GDGT records to infer the evolution of marine AOA from the Mid-Mesozoic to the present. Long-term GDGT-2/GDGT-3 trends suggest a suppression of today's deep water marine AOA during the Mesozoic-early Cenozoic greenhouse climates. Our analysis provides invaluable insights into the evolutionary timeline and the expansion of AOA niches associated with major oceanographic and climate changes.


Assuntos
Amônia , Archaea , Archaea/genética , Glicerol , Lipídeos de Membrana , Oxirredução , Filogenia , Água
16.
Eur J Pharm Biopharm ; 177: 147-156, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35779744

RESUMO

Insulin treatment is currently considered to be the main strategy for controlling diabetes. Although the recombinant insulin formulation is relatively mature, we found that a batch of insulin formulation exhibited an unusual degradation rate in the stability experiment. The main purposes of this article are to identify the root cause for this phenomenon and characterize of chemical and physical degradation products. We compared the chemical and physical stability of two batches of insulin formulations prepared separately with simulated repeated use and freshly opened glycerol. The chemical stability of insulin was identified by liquid chromatography coupled with tandem mass spectrometry (LC- MS/MS). Micro-flow imaging (MFI), far-ultraviolet circular dichroism (Far-UV CD) and Thioflavin T (ThT) fluorescent assays were used to reveal protein aggregation and fibrosis. The chemical and physical stability of the insulin formulation with newly opened glycerol was much better than that with degraded glycerol, and both groups of formulations were extremely sensitive to light. The results indicated that the original batch insulin formulation with abnormal stability was indeed caused by the excipient glycerol after long-term storage and repeated usage. More attention should be paid to the quality changes of excipients during repeated usage and storage of excipients for the practical purpose. Moreover, we have discovered a novel degradation pathway for insulin and peptides in general. In addition, LC-MS/MS results suggested that the N-terminus of insulin B-chain was prone to chemical degradation which enlightens that it could be potentially modified to improve the stability of insulin formulations.


Assuntos
Excipientes , Insulina , Cromatografia Líquida , Estabilidade de Medicamentos , Excipientes/química , Glicerol , Insulina/química , Espectrometria de Massas em Tandem
17.
Biomater Adv ; 139: 212996, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35891600

RESUMO

Although Amphotericin B (AMB) is considered the most effective anti-mycotic agent for treating Candida infections, its clinical use is limited due to its high toxicity. To address this issue, we developed cholesterol-based dendritic micelles of hyperbranched polyglycerol (HPG), including cholesterol-cored HPG (Chol-HPG) and cholesterol end-capped HPG (HPG@Chol), for AMB delivery. The findings suggested that the presence of cholesterol moieties could control AMB loading and release properties. Dendritic micelles inhibited AMB hemolysis and cytotoxicity in HEK 293 and RAW 264.7 cell lines while increasing antifungal activity against C. albicans biofilm formation. Furthermore, significantly lower levels of renal and liver toxicity biomarkers compared to Fungizone® ensured AMB-incorporated dendritic micelle biosafety, which was confirmed by histopathological evaluations. Overall, the Chol-HPG and HPG@Chol dendritic micelles may be a viable alternative to commercially available AMB formulations as well as an effective delivery system for other poorly soluble antifungal agents.


Assuntos
Anfotericina B , Candidíase , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida albicans , Candidíase/tratamento farmacológico , Glicerol , Células HEK293 , Humanos , Micelas , Polímeros
18.
J Org Chem ; 87(15): 10523-10530, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35895907

RESUMO

Recent years have witnessed significant achievements in the field of organic chemistry, which have led to new drugs and the discovery of new and biologically interesting molecules. Herein, we describe a practical and efficient approach to the synthesis of enantiomerically pure and diverse lysobisphosphatidic acid analogues. The key feature of the synthesis is a one-pot, sequential phosphorylation of a protected sn-2-O-oleoyl glycerol or sn-3-O-oleoyl glycerol with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, followed by oxidation.


Assuntos
Glicerol , Monoglicerídeos , Lisofosfolipídeos/química , Monoglicerídeos/química , Estereoisomerismo
19.
Sci Rep ; 12(1): 11946, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831366

RESUMO

In this study, effects of sesamol on improving the oxidative stability of sunflower oil and its oil-in-water emulsion was investigated. To investigate the kinetic parameters related to the initiation and propagation stages of oxidation, a sigmoidal-model was used. Sesamol exhibited higher antioxidant activity in sunflower oil-in-water emulsion than that of sunflower oil. In both sunflower oil and sunflower oil-in-water emulsion, the inhibitory effect of sesamol against lipid oxidation continued even after the induction period. To improve the efficiency of sesamol in sunflower oil, polyglycerol polyricinoleate (PGPR) was incorporated into the functional environment of the sesamol. Sesamol exhibited a synergistic effect with PGPR during both initiation (synergistic effect of 68.87%) and propagation (synergistic effect of 36.84%) stages. Comparison of the size of reverse micelles in samples containing PGPR with those without PGPR revealed that PGPR can enhance the efficiency of sesamol by increasing the acceptance capacity of lipid hydroperoxides in reveres micelles structures. This can result in enhancing the effective collisions between sesamol and lipid hydroperoxides in the presence of PGPR. The water produced as a major byproduct of oxidation played a key role on the antioxidant activity of sesamol alone or in combination with PGPR during oxidation process.


Assuntos
Antioxidantes , Micelas , Antioxidantes/farmacologia , Benzodioxóis , Emulsões/química , Glicerol/análogos & derivados , Fenóis , Ácidos Ricinoleicos/química , Óleo de Girassol , Água/química
20.
BMC Musculoskelet Disord ; 23(1): 670, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836166

RESUMO

INTRODUCTION: Chitosan and curcumin are natural products that have a wide range of beneficial effects including wound healing. However, their high molecular weight and poor water solubility limit their applications. AIMS: Therefore, the current study aims to evaluate the effects of chitosan (Cs) and curcumin (Cn) nanoparticles (NPs) on fibrosis and regeneration of glycerol-injured muscle. METHODS: Muscle injury was induced by intramuscular injection of glycerol into the tibialis anterior muscle of rats. Cs-NPs and Cn-NPs were administered at different doses intraperitoneally after injury. Injured muscles were collected at day 7 after injury, and muscle fibrosis and regeneration were assessed. RESULTS: The present results revealed that Cs-NPs and Cn-NPs treatment significantly decreased fibrosis index and increased the average myotube diameter with shifting of the distribution of myotube diameters towards larger diameters in a dose-dependent manner. Immunohistochemical analysis revealed that Cs-NPs and Cn-NPs treatment significantly decreased the number of CD-68+ cells and Col-1+ area. Results showed that Cn-NPs had a higher protective effect, in the form of attenuating muscle fibrosis and inflammation, and enhancing muscle regeneration, than that of Cs-NPs. CONCLUSIONS: To our knowledge, this is the first study to document the effects of Cs-NPs in injured muscles. The results of study might be a novel approach to attenuate muscle fibrosis in humans using curcumin and chitosan nanoparticles.


Assuntos
Quitosana , Curcumina , Doenças Musculares , Nanopartículas , Animais , Quitosana/efeitos adversos , Curcumina/efeitos adversos , Curcumina/química , Portadores de Fármacos/efeitos adversos , Fibrose , Glicerol/efeitos adversos , Humanos , Músculo Esquelético/patologia , Doenças Musculares/patologia , Nanopartículas/química , Ratos , Regeneração
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