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1.
Cells ; 10(10)2021 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-34685755

RESUMO

Mitochondria are ubiquitous organelles of eukaryotic organisms with a number of essential functions, including synthesis of iron-sulfur clusters, amino acids, lipids, and adenosine triphosphate (ATP). During aging of the fungal aging model Podospora anserina, the inner mitochondrial membrane (IMM) undergoes prominent morphological alterations, ultimately resulting in functional impairments. Since phospholipids (PLs) are key components of biological membranes, maintenance of membrane plasticity and integrity via regulation of PL biosynthesis is indispensable. Here, we report results from a lipidomic analysis of isolated mitochondria from P. anserina that revealed an age-related reorganization of the mitochondrial PL profile and the involvement of the i-AAA protease PaIAP in proteolytic regulation of PL metabolism. The absence of PaIAP enhances biosynthesis of characteristic mitochondrial PLs, leads to significant alterations in the acyl composition of the mitochondrial signature PL cardiolipin (CL), and induces mitophagy. These alterations presumably cause the lifespan increase of the PaIap deletion mutant under standard growth conditions. However, PaIAP is required at elevated temperatures and for degradation of superfluous CL synthase PaCRD1 during glycolytic growth. Overall, our study uncovers a prominent role of PaIAP in the regulation of PL homeostasis in order to adapt membrane plasticity to fluctuating environmental conditions as they occur in nature.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Homeostase , Mitocôndrias/metabolismo , Fosfolipídeos/metabolismo , Podospora/crescimento & desenvolvimento , Podospora/metabolismo , Cardiolipinas/metabolismo , Fermentação/efeitos dos fármacos , Proteínas Fúngicas/metabolismo , Deleção de Genes , Glicerol/farmacologia , Homeostase/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Podospora/efeitos dos fármacos , Podospora/genética , Proteólise/efeitos dos fármacos
2.
Int J Mol Sci ; 22(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34445455

RESUMO

Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol's effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments.


Assuntos
Glicerol/farmacologia , Imiquimode/efeitos adversos , Psoríase/tratamento farmacológico , Pele/metabolismo , Animais , Aquaporina 3/genética , Aquaporina 3/metabolismo , Modelos Animais de Doenças , Humanos , Imiquimode/farmacologia , Camundongos , Camundongos Knockout , Fosfolipase D/deficiência , Fosfolipase D/metabolismo , Psoríase/induzido quimicamente , Psoríase/genética , Psoríase/metabolismo
3.
Sci Rep ; 11(1): 15428, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326357

RESUMO

Cryopreservation is the only reliable method for long-term storage of biological material that guarantees genetic stability. This technique can be extremely useful for the conservation of endangered species and restock natural populations for declining species. Many factors have negatively affected the populations of high economical value shellfish in Spain and, as a result, many are declining or threatened nowadays. This study was focused on early-life stages of Venerupis corrugata, Ruditapes decussatus and Ruditapes philippinarum to develop successful protocols to enhance the conservation effort and sustainable shellfishery resources. Firstly, common cryoprotecting agents (CPAs) were tested to select the suitable permeable CPA attending to toxicity. Cryopreservation success using different combinations of CPA solutions, increasing equilibrium times and larval stages was evaluated attending to survival and shell growth at 2 days post-thawing. Older clam development stages were more tolerant to CPA toxicity, being ethylene-glycol (EG) and Propylene-glycol (PG) the least toxic CPAs. CPA solution containing EG yielded the highest post-thawing survival rate and the increase of equilibration time was not beneficial for clam larvae. Cryopreservation of trochophores yielded around 50% survivorship, whereas over 80% of cryopreserved D-larvae were able to recover after thawing.


Assuntos
Bivalves , Conservação dos Recursos Naturais/métodos , Criopreservação/métodos , Espécies em Perigo de Extinção , Pesqueiros , Larva , Frutos do Mar , Animais , Bivalves/efeitos dos fármacos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia , Etilenoglicol/farmacologia , Glicerol/farmacologia , Larva/efeitos dos fármacos , Propilenoglicol/farmacologia , Espanha
4.
Mar Biotechnol (NY) ; 23(4): 590-601, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34272626

RESUMO

Germ cell cryopreservation has been used to preserve many fish species. However, this method has not been established for crustaceans; thus, we attempted to do this herein. The efficiency of slow freezing was compared to vitrification methods for germ cell cryopreservation in two types of marine shrimp, Fenneropenaeus merguiensis and Penaeus monodon. In situ hybridization with a vasa probe was used to identify germ cells. The effects of three cryoprotectants, dimethyl sulfoxide (DMSO), glycerol (GLY), and magnesium chloride (MgCl2), on germ cell viability and recovery rate were compared at three concentrations (5%, 10%, and 15%). The effects of thawing temperature, including 10 and 27 °C, were also investigated. We discovered that 10% DMSO with the vitrification is suitable for preserving the germ cells of F. merguiensis for a long time, whereas 10% GLY with vitrification is suitable for P. monodon. Moreover, the most suitable thawing temperature was 10 °C for both species. This is the first report of germ cell cryopreservation in crustaceans. Thus, we provide evidence that crustacean germ cells can be preserved long-term in liquid nitrogen; this is the first step in the sustainable preservation of crustaceans, especially shrimp.


Assuntos
Criopreservação/métodos , Crioprotetores/farmacologia , Penaeidae , Testículo , Animais , Dimetil Sulfóxido/farmacologia , Congelamento , Glicerol/farmacologia , Cloreto de Magnésio/farmacologia , Masculino , Espermatogônias/citologia , Vitrificação
5.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201004

RESUMO

Cadmium is a carcinogen that can induce ER stress, DNA damage, oxidative stress and cell death. The yeast mitogen-activated protein kinase (MAPK) signalling pathways paly crucial roles in response to various stresses. Here, we demonstrate that the unfolded protein response (UPR) pathway, the high osmolarity glycerol (HOG) pathway and the cell wall integrity (CWI) pathway are all essential for yeast cells to defend against the cadmium-induced toxicity, including the elevated ROS and cell death levels induced by cadmium. We show that the UPR pathway is required for the cadmium-induced phosphorylation of HOG_MAPK Hog1 but not for CWI_MAPK Slt2, while Slt2 but not Hog1 is required for the activation of the UPR pathway through the transcription factors of Swi6 and Rlm1. Moreover, deletion of HAC1 and IRE1 could promote the nuclear accumulation of Hog1, and increase the cytosolic and bud neck localisation of Slt2, indicating crucial roles of Hog1 and Slt2 in regulating the cellular process in the absence of UPR pathway. Altogether, our findings highlight the significance of these two MAPK pathways of HOG and CWI and their interrelationship with the UPR pathway in responding to cadmium-induced toxicity in budding yeast.


Assuntos
Cádmio/toxicidade , Parede Celular/química , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Glicerol/farmacologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Parede Celular/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Concentração Osmolar , Fosforilação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Transdução de Sinais
6.
Cryobiology ; 101: 61-66, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102184

RESUMO

Wider implementation of AI in sheep in the field condition has not been possible till date due to very poor conception rate after cervical insemination with cryopreserved semen. Poor cervical penetrability in ewe and diminished sperm functions in cryopreserved semen are considered responsible for it. In the present study, effect of carboxymethyl cellulose (CMC) on post-thaw qualities of ram semen was investigated. Ejaculates from eight adult Malpura rams were pooled and diluted (800 × 106 sperm mL-1) with TES-Tris-fructose-egg yolk extender having either 5 or 6% glycerol and supplemented with 0, 0.25, 0.5, 0.75 and 1.0% (w/v) CMC and packaged into 0.25 mL French mini straws. The straws were progressively cooled to 5 °C inside a cold cabinet (5 °C) and then equilibrated for 22 h inside a refrigerator (2-5 °C). Straws were frozen at -25 °C min-1 up to -125 °C using a programmable cell freezer (Planer Biomed R-204, UK) and finally plunged into liquid nitrogen. The post-thaw progressive motility was higher (P < 0.05) in 0.75% CMC-treated group compared to control. Overall, both pre-freeze and post-thaw sperm kinetics was comparable between CMC-treated and control groups. The post-thaw sperm viability, acrosomal integrity and sperm with high mitochondrial membrane potential (hMMP) were relatively higher while sperm with high membrane cholesterol was significantly (P < 0.05) higher in presence of 0.25% CMC compared to the control. Both sperm having hMMP and non-capacitated sperm were significantly (P < 0.05) higher in presence of 5% glycerol than 6% glycerol. Similarly, functional membrane integrity (FMI) was higher in presence of 5% glycerol than 6% glycerol when CMC was added at 0.5% to extender. In conclusion, both 0.25% CMC and 5% glycerol resulted in improvement in several post-thaw sperm functions in cryopreserved ram semen. Thus CMC demonstrated cryoprotective effect on ram sperm in a synergistic manner with glycerol.


Assuntos
Crioprotetores , Preservação do Sêmen , Animais , Carboximetilcelulose Sódica , Criopreservação/métodos , Crioprotetores/farmacologia , Feminino , Glicerol/farmacologia , Masculino , Sêmen , Preservação do Sêmen/veterinária , Ovinos , Motilidade Espermática , Espermatozoides
7.
Reprod Domest Anim ; 56(7): 958-964, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33829560

RESUMO

Semen cryopreservation is not available for massive use in South American Camelids (SACs) due to the lack of an efficient protocol and the low pregnancy rates obtained with artificial insemination (AI). The use of a single cryoprotectant (CP) is commonly used in SACs frozen semen. The objective of the study was to evaluate the combined cryoprotective capacity of two permeable CPs at different stages of the cryopreservation protocol in llama semen. Sixteen ejaculates from 4 llama males were analysed, and sperm quality was assayed in raw semen, at 5°C, after equilibration of samples with the CPs and when samples were thawed. The following CPs and combination were used: 6% glycerol (GL), 6% dimethylformamide (DMF) and the combination of both CPs: 3% GL and 3% DMF. A Kruskal-Wallis test and an experimental factorial design, considering one factor with four levels (raw semen, 6% GL, 6% DMF and GL/DMF), were used. Total sperm motility and live sperm with intact acrosomes remained unchanged after equilibration of samples (p > .05). A significant decrease in the percentage of functional membrane, motile and live sperm with intact acrosomes was observed when samples were thawed (GL, DMF and GL/DMF). Nevertheless, the cryopreservation protocols used preserved sperm DNA quality; thus, sperm chromatin condensation and DNA fragmentation were unaffected (p > .05) when GL, DMF and GL/DMF were used. To conclude, no superiority was found between the use of a single or a combination of permeable cryoprotectants to freeze llama semen.


Assuntos
Camelídeos Americanos , Criopreservação/veterinária , Crioprotetores/farmacologia , Espermatozoides/efeitos dos fármacos , Acrossomo , Animais , Criopreservação/métodos , Fragmentação do DNA , Dimetilformamida/farmacologia , Glicerol/farmacologia , Masculino , Análise do Sêmen/veterinária , Motilidade Espermática/efeitos dos fármacos
8.
Am J Physiol Lung Cell Mol Physiol ; 320(6): L1064-L1073, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33825493

RESUMO

In the United States, millions of adults use electronic cigarettes (e-cigs), and a majority of these users are former or current cigarette smokers. It is unclear, whether prior smoking status affects biological responses induced by e-cigs. In this study, differentiated human nasal epithelial cells (hNECs) from nonsmokers and smokers at air-liquid interface were acutely exposed to the e-cig generated aerosols of humectants, propylene glycol (PG), and glycerol (GLY). Mucin levels were examined in the apical washes, and cytokine levels were assessed in the basolateral supernatants 24 h postexposure. The aerosol from the GLY exposure increased mucin 5, subtype AC (MUC5AC) levels in the apical wash of hNECs from nonsmokers, but not smokers. However, the aerosol from GLY induced pro-inflammatory responses in hNECs from smokers. We also exposed hNECs from nonsmokers and smokers to e-cig generated aerosol from PG:GLY with freebase nicotine or nicotine salt. The PG:GLY with freebase nicotine exposure increased MUC5AC and mucin 5, subtype B (MUC5B) levels in hNECs from nonsmokers, but the nicotine salt exposure did not. The PG:GLY with nicotine salt exposure increased pro-inflammatory cytokines in hNECs from smokers, which was not seen with the freebase nicotine exposure. Taken together, these data indicate that the e-cig generated aerosols from the humectants, mostly GLY, and the type of nicotine used cause differential effects in airway epithelial cells from nonsmokers and smokers. As e-cig use is increasing, it is important to understand that the biological effects of e-cig use are likely dependent on prior cigarette smoke exposure.


Assuntos
Células Epiteliais/efeitos dos fármacos , Nicotina/farmacologia , não Fumantes , Fumantes , Vaping/efeitos adversos , Sistemas Eletrônicos de Liberação de Nicotina , Glicerol/farmacologia , Humanos , Higroscópicos/farmacologia , Pulmão/efeitos dos fármacos , Propilenoglicol/farmacologia
9.
Nutrients ; 13(5)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922631

RESUMO

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg-1) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1ß) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.


Assuntos
Ácidos Graxos Voláteis/biossíntese , Microbioma Gastrointestinal/efeitos dos fármacos , Glicerol/farmacologia , Inflamação/microbiologia , Metabolismo/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Citocinas/sangue , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Hormônios/sangue , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL
10.
Int J Mol Sci ; 22(8)2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33920155

RESUMO

Pacific abalone (Haliotis discus hannai) is a highly commercial seafood in Southeast Asia. The aim of the present study was to improve the sperm cryopreservation technique for this valuable species using an antifreeze protein III (AFPIII). Post-thaw sperm quality parameters including motility, acrosome integrity (AI), plasma membrane integrity (PMI), mitochondrial membrane potential (MMP), DNA integrity, fertility, hatchability, and mRNA abundance level of heat shock protein 90 (HSP90) were determined to ensure improvement of the cryopreservation technique. Post-thaw motility of sperm cryopreserved with AFPIII at 10 µg/mL combined with 8% dimethyl sulfoxide (DMSO) (61.3 ± 2.7%), 8% ethylene glycol (EG) (54.3 ± 3.3%), 6% propylene glycol (PG) (36.6 ± 2.6%), or 2% glycerol (GLY) (51.7 ± 3.0%) was significantly improved than that of sperm cryopreserved without AFPIII. Post-thaw motility of sperm cryopreserved with 2% MeOH and 1 µg/mL of AFPIII was also improved than that of sperm cryopreserved without AFPIII. A combination of 10 µg/mL AFPIII with 8% DMSO resulted in the highest post-thaw motility, showing AI of 60.1 ± 3.9%, PMI of 67.2 ± 4.0%, and MMP of 59.1 ± 4.3%. DNA integrity of sperm cryopreserved using 10 µg/mL AFPIII combined with 8% DMSO was not significantly (p > 0.05) different from that of fresh sperm. Cryopreservation using a combination of AFPIII with 8% DMSO improved fertilization and hatching rates of sperm compared to that of cryopreservation without supplementation of 10 µg/mL AFPIII. Sperm cryopreserved using AFPIII showed higher mRNA abundance levels of HSP90 than those cryopreserved without AFPIII. Results of the present study suggest that 10 µg/mL AFPIII combined with 8% DMSO can be used for large scale cryopreservation of Pacific abalone sperm and for hatchery production.


Assuntos
Proteínas Anticongelantes/farmacologia , Criopreservação , Preservação do Sêmen , Espermatozoides/efeitos dos fármacos , Acrossomo/efeitos dos fármacos , Animais , Proteínas Anticongelantes/genética , Sobrevivência Celular/efeitos dos fármacos , Crioprotetores/farmacologia , Gastrópodes/crescimento & desenvolvimento , Glicerol/farmacologia , Humanos , Masculino , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/crescimento & desenvolvimento
11.
Ann R Coll Surg Engl ; 103(6): 452-458, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33851890

RESUMO

INTRODUCTION: Several treatment modalities have been postulated to improve the efficacy of varicose vein treatment. Addition of glycerine to the sclerosing material has been documented to increase its viscosity and subsequently prolong the duration of stability, in addition to the direct sclerosing effect of glycerine. This histological and immunohistochemical study investigated the efficacy of addition of glycerine 72% to sclerotherapy on the human varicose vein. METHODS: After surgical stripping of great saphenous veins, three equal segments were resected between two clamps. Specimen 1 was injected with saline only, specimen 2 was exposed to foam sclerosant 2%, and specimen 3 was exposed to a mixture of foam sclerosant 2% and glycerine 72%. All segments were left for 5min. Vein segments were then processed for histological and immunohistochemical study. RESULTS: Microscopically, haematoxylin and eosin-stained specimen 1 showed endothelial swelling, cytoplasmic eosinophilia and pyknotic nuclei. The media showed sarcoplasm vacuolisation and necrosis. Specimen 3 showed hypereosinophilic sarcoplasm of the smooth muscle fibres. Oedema was less evident, with a relative decrease in the thickness of the wall compared with specimen 2. Immunohistochemically, the expression of smooth muscle actin was weak in specimen 3 compared with specimens 1 and 2. Expression of CD31 antibody was much reduced in specimen 2 which showed conserved islands of endothelial cells. By contrast, there was a complete loss of endothelial cells in specimen 3. CONCLUSION: Addition of glycerine 72% to foam sclerosant has a more damaging effect on human vein wall.


Assuntos
Edema/patologia , Glicerol/farmacologia , Polidocanol/farmacologia , Veia Safena/patologia , Soluções Esclerosantes/farmacologia , Actinas/metabolismo , Combinação de Medicamentos , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Endotélio/patologia , Glicerol/uso terapêutico , Humanos , Imuno-Histoquímica , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Polidocanol/uso terapêutico , Veia Safena/efeitos dos fármacos , Veia Safena/metabolismo , Soluções Esclerosantes/uso terapêutico , Varizes/terapia , Viscosidade
12.
J Oleo Sci ; 70(4): 571-580, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33692238

RESUMO

Polyglycerol monolaurates are generally recognized as safe food additives and are commonly used as food emulsifiers. In this study, the antimicrobial effect of four polyglycerol monolaurates on two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Escherichia. coli and Pseudomonas aeruginosa) were investigated. The minimum inhibitory concentration (MIC) of diglycerol monolaurate (PG2ML), triglycerol monolaurate (PG3ML), hexaglycerol monolaurate (PG6ML), and decaglycerol monolaurate (PG10ML) against S. aureus was 0.16, 0.32, 0.63, and 1.25 mg/mL, respectively. The MIC of PG2ML, PG3ML, PG6ML, and PG10ML against B. subtilis was 0.32, 0.63, 1.25, and 3.75 mg/mL, respectively. No apparent antimicrobial effect of these four polyglycerol monolaurates on E. coli and P. aeruginosa was observed even up to 10.00 mg/mL. The underlying mechanism was investigated by assessing cell membrane permeability, the integrity of cell membrane, and morphology. We concluded that polyglycerol monolaurates might eliminate Gram-positive bacteria by disrupting the cell membrane, thereby increasing cell membrane permeability, releasing the cellular contents, and altering the cell morphology.


Assuntos
Antibacterianos , Emulsificantes , Aditivos Alimentares , Glicerol/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Lauratos/farmacologia , Polímeros/farmacologia , Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Microbiologia de Alimentos , Glicerol/química , Bactérias Gram-Negativas/citologia , Bactérias Gram-Positivas/citologia , Lauratos/química , Testes de Sensibilidade Microbiana , Polímeros/química , Relação Estrutura-Atividade
13.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670858

RESUMO

Interleukin-6 (IL-6) is involved in physiological and pathological processes. Different pharmacological agents have been developed to block IL-6 deleterious effects and to recover homeostatic IL-6 signaling. One of the proposed nanostructures in pre-clinical investigations which reduced IL-6 concentrations is polyglycerol dendrimer, a nano-structure with multiple sulfate groups. The aim of the present study was to uncover the type of binding between critical positions in the human IL-6 structure available for binding dPGS and compare it with heparin sulfate binding. We studied these interactions by performing docking simulations of dPGS and heparins with human IL-6 using AutoDock Vina. These molecular docking analyses indicate that the two ligands have comparable affinities for the positively charged positions on the surface of IL-6. All-atom molecular dynamics simulations (MD) employing Gromacs were used to explore the binding sites and binding strengths. Results suggest two major binding sites and show that the strengths of binding are similar for heparin and dPGS (-5.5-6.4 kcal/ mol). dPGS or its analogs could be used in the therapeutic intervention in sepsis and inflammatory disorders to reduce unbound IL-6 in the plasma or tissues and its binding to the receptors. We propose that analogs of dPGS could specifically block IL-6 binding in the desired signaling mode and would be valuable new probes to establish optimized therapeutic intervention in inflammation.


Assuntos
Dendrímeros/química , Glicerol/farmacologia , Interleucina-6/antagonistas & inibidores , Modelos Moleculares , Polímeros/farmacologia , Anti-Inflamatórios/farmacologia , Heparina , Humanos , Inflamação , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica
14.
Trop Anim Health Prod ; 53(1): 173, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599873

RESUMO

The search for healthy food leads to demand for functional foods that do not harm the health of the consumers. The objective was to evaluate the impact of the supply of cottonseed and crude glycerin as modulators of the lipid profile of the beef produced on pasture. The concentrated supplement was formulated with two levels of cottonseed (0 and 25%) and/or two levels of crude glycerin (0 and 15%), totaling four experimental groups. Two experiments were conducted; the first experiment was outlined in a 5 × 5 Latin square design, contrasting the protein-energy supplementation with the mineral supplementation. The concentrate supplementation allowed the increase in intake and digestibility of the dry matter (P = 0.03), ether extract, crude protein, and non-fibrous carbohydrate (P < 0.01). However, the results showed no effect of crude glycerin or cottonseed inclusion on intake or nutrients digestibility. The second experiment evaluated the protein-energy supplementation and its impact on the lipid profile of meat produced, carcass characteristics, and animal performance. There was no influence of cottonseed or crude glycerin in performance or carcass characteristics. However, the use of the cottonseed reduced the content of short-chain fatty acids, omega 3 linolenic acid, conjugated linoleic acid (CLA) C18: 2 cis 9 trans 11 (P < 0.01), and the inclusion of crude glycerin led to increased conjugated linoleic acid (CLA) C18: 2 cis 9 trans 11 (P = 0.04). An important result is given by illustrating the impact of these fatty acids in the nutritional quality of the meat. Thus, it is possible to manipulate the lipid profile of meat produced by cottonseed or crude glycerin supplementation, without affecting the animal performance.


Assuntos
Óleo de Sementes de Algodão/farmacologia , Glicerol/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Carne Vermelha/análise , Ração Animal/análise , Animais , Bovinos , Dieta , Suplementos Nutricionais , Ácidos Graxos/química , Ácidos Graxos/metabolismo
15.
Pharm Biol ; 59(1): 157-166, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33556300

RESUMO

CONTEXT: Epigallocatechin-3-gallate (EGCG) is unstable and easily oxidized, which limits its applications. Ascorbic acid (Vc) is a natural antioxidant. OBJECTIVE: The effects of EGCG combined with Vc and glycerol on stability and uric acid-lowering activity of EGCG were examined. MATERIALS AND METHODS: EGCG (aqueous solution), EGCG + Vc (aqueous solution), EGCG (glycerol solution) and EGCG + Vc (glycerol solution) were prepared and incubated under different conditions in vitro. The recovery rate of EGCG was calculated by HPLC. Kunming mice were randomly divided into normal control group, model group, allopurinol (5 mg/kg), EGCG (10 mg/kg), EGCG + Vc (both 10 mg/kg), EGCG (10 mg/kg) + glycerol (60%), and EGCG (10 mg/kg) + Vc (10 mg/kg) + glycerol (60%) (n = 6). Allopurinol was injected intraperitoneally to mice, others were administered intragastrically to (2 cases) mice. All mice were continuously administrated for 7 days, once a day. RESULTS: EGCG recovery rates of EGCG group and EGCG + Vc + glycerol group respectively reached to 32.34 ± 1.86% and 98.90 ± 0.64% when they were incubated for 4 h at 80 °C. EGCG recovery rates reached to 91.82 ± 5.13% (incubated for 6 h at pH 8) and 88.85 ± 2.63% (incubated for 4 h in simulated intestinal fluid) when EGCG incubated with Vc and glycerol. Compared with the model group, UA values of EGCG + Vc + glycerol group reduced by 43.49% while EGCG group reduced by 25.63%. The activities of xanthine oxidase (XOD, 31.41 U/gprot) and adenosine deaminase (ADA, 10.05 U/mgprot), and the mRNA expression levels of glucose transporter 9 (GLUT9, 1.03) and urate transporter 1 (URAT1, 0.44) in EGCG + Vc + glycerol group were notably lower than those of EGCG group (38.12 U/gprot, 13.16 U/mgprot, 1.54, and 0.55). The mRNA expression levels of ATP-binding cassette superfamily G member 2 (ABCG2, 1.39) and organic anion transport 1/2 (OAT1/2, 2.34, 2.53) in EGCG + Vc + glycerol group were notably higher than those of EGCG group (0.57, 1.13, and 1.16). DISCUSSION AND CONCLUSIONS: Our findings suggest that when EGCG used in combination with Vc and glycerol could effectively increase its biology activities and can be generalized to the broader pharmacological studies. This sheds light on the development and application of EGCG in the fields of food and medicine.


Assuntos
Ácido Ascórbico/farmacologia , Catequina/análogos & derivados , Glicerol/farmacologia , Ácido Úrico/metabolismo , Alopurinol/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/química , Catequina/administração & dosagem , Catequina/química , Catequina/farmacologia , Estabilidade de Medicamentos , Glicerol/administração & dosagem , Hiperuricemia/tratamento farmacológico , Masculino , Camundongos , Oxirredução
16.
Sci Rep ; 11(1): 329, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431907

RESUMO

Imaging depth and quality of optical microscopy can be enhanced by optical clearing. Here we investigate the optical clearing of the ex vivo human skin by 50% glycerol topical application, which is allowed for cosmetic usage. Harmonic generation microscopy, by combining second and third harmonic generation (THG) modalities, was utilized to examine the clearing effect. The THG image intensity is sensitive to the improved optical homogeneity after optical clearing, and the second harmonic generation (SHG) image intensity in the dermis could serve as a beacon to confirm the reduction of the scattering in the epidermis layer. As a result, our study supports the OC effect through 50% glycerol topical application. Our study further indicates the critical role of stratum corneum shrinkage for the observed SHG and THG signal recovery.


Assuntos
Glicerol/farmacologia , Microscopia , Fenômenos Ópticos , Pele/efeitos dos fármacos , Pele/diagnóstico por imagem , Relação Dose-Resposta a Droga , Humanos
17.
PLoS Genet ; 17(1): e1009314, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33493203

RESUMO

The environmental conditions of microorganisms' habitats may fluctuate in unpredictable ways, such as changes in temperature, carbon source, pH, and salinity to name a few. Environmental heterogeneity presents a challenge to microorganisms, as they have to adapt not only to be fit under a specific condition, but they must also be robust across many conditions and be able to deal with the switch between conditions itself. While experimental evolution has been used to gain insight into the adaptive process, this has largely been in either unvarying or consistently varying conditions. In cases where changing environments have been investigated, relatively little is known about how such environments influence the dynamics of the adaptive process itself, as well as the genetic and phenotypic outcomes. We designed a systematic series of evolution experiments where we used two growth conditions that have differing timescales of adaptation and varied the rate of switching between them. We used lineage tracking to follow adaptation, and whole genome sequenced adaptive clones from each of the experiments. We find that both the switch rate and the order of the conditions influences adaptation. We also find different adaptive outcomes, at both the genetic and phenotypic levels, even when populations spent the same amount of total time in the two different conditions, but the order and/or switch rate differed. Thus, in a variable environment adaptation depends not only on the nature of the conditions and phenotypes under selection, but also on the complexity of the manner in which those conditions are combined to result in a given dynamic environment.


Assuntos
Adaptação Fisiológica/genética , Evolução Biológica , Código de Barras de DNA Taxonômico , Seleção Genética/genética , Aclimatação/genética , Análise por Conglomerados , Variação Genética/genética , Genoma Fúngico/genética , Glicerol/metabolismo , Glicerol/farmacologia , Fenótipo , Análise de Componente Principal , Saccharomyces cerevisiae/genética
18.
Pharm Res ; 38(2): 289-299, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33515137

RESUMO

PURPOSE: Penetration enhancers are necessary to overcome a formidable barrier function of the stratum corneum in the development of topical formulations. Recently, non-lamella liquid crystal (NLLC)-forming lipids such as glycerol monooleate and phytantriol (PHY) are gaining increasing attention as a novel skin permeation enhancer. In the present study, fluorescein sodium (FL-Na) was used as a model hydrophilic drug, and acryl-base pressure-sensitive adhesive (PSA) tape containing NLLC forming lipids, mono-O-(5,9,13-trimethyl-4-tetradecenyl) glycerol ester (MGE) or PHY, was prepared to enhance drug permeation through the skin. METHODS: A PSA patch containing FL-Na was prepared by mixing FL-Na entrapped in NLLC and acrylic polymer. FL permeation through excised hairless rat skin, and also human skin, was investigated. Changes in lipid structure, folding/unfolding state of keratin in the stratum corneum, and penetration of MGE into the stratum corneum were investigated using confocal Raman microscopy. RESULTS: Enhanced FL permeation was observed by the application of a PSA patch containing MGE and PHY. Especially, dramatically enhancement effect was confirmed by 15% of MGE contained formulation. Penetration of MGE provided diminished orthorhombic crystal structure and a peak shift of the aliphatic CH3 vibration of keratin chains toward lower wavenumbers. CONCLUSION: The present results suggested that the formulation development by adding MGE may be useful for improving the skin permeation of mal-permeable drugs such as hydrophilic drugs.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Epiderme/metabolismo , Glicerol/farmacologia , Absorção Cutânea/efeitos dos fármacos , Adesivo Transdérmico , Adesivos/química , Administração Cutânea , Animais , Epiderme/efeitos dos fármacos , Fluoresceína/administração & dosagem , Fluoresceína/farmacocinética , Glicerol/análogos & derivados , Glicerol/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cristais Líquidos/química , Permeabilidade/efeitos dos fármacos , Ratos
19.
Protein Expr Purif ; 177: 105753, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32950627

RESUMO

Staphylococcus aureus (S. aureus), which has developed multidrug resistance, leads to many healthcare-associated infections resulting in significant medical and economic losses. Therefore, the development of new efficient strategies to deal with these bacteria has been gaining importance. Lysostaphin is a peptidoglycan hydrolase that has considerable potential as a bacteriocin. However, there have been few reported optimization and scale-up studies of the lysostaphin bioproduction process. Our preliminary results have revealed that the composition of auto-induction media at 30 °C increases the produced lysostaphin around 10-fold in shake flasks. In this study, achieving higher yields for recombinant lysostaphin in E. coli at a laboratory scale has been the aim, through the use of auto-induction media. Optimized medium composition and fermentation parameters were transferred to a laboratory-scale bioreactor. The tested conditions improved protein yields up to 184 mg/L in a 3 L stirred bioreactor and the productivity was improved 2-fold in comparison to previously published reports. Furthermore, this study also showed that lysostaphin is an effective bacteriocin on both commercially available and isolated S. aureus strains. These results will contribute to future larger-scale production of lysostaphin via the proposed fermentation conditions.


Assuntos
Antibacterianos/biossíntese , Lisostafina/biossíntese , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus/metabolismo , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Reatores Biológicos , Clonagem Molecular , Meios de Cultura/química , Meios de Cultura/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Fermentação , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Glucose/metabolismo , Glucose/farmacologia , Glicerol/metabolismo , Glicerol/farmacologia , Lisostafina/genética , Lisostafina/isolamento & purificação , Lisostafina/farmacologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Staphylococcus/genética , Staphylococcus aureus/crescimento & desenvolvimento
20.
Methods Mol Biol ; 2180: 523-538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32797432

RESUMO

Frozen blood reserves are an important component in meeting blood needs. The idea behind a frozen blood reserve is twofold: to freeze units of rare blood types for later use by patients with special transfusion needs and for managing special transfusion circumstances. The permeating additive glycerol is used as a cryoprotectant to protect red blood cells (RBCs) from freezing damage. The use of thawed RBCs has been hampered by a 24-h outdating period due to the potential bacterial contamination when a functionally open system is used for addition and removal of the glycerol. The introduction of an automated, functionally closed system for glycerolization and deglycerolization of RBCs improved the operational practice. More importantly, the closed process allowed for extended shelf life of the thawed RBCs. In the current chapter, a cryopreservation procedure for RBCs using a functionally closed processing system is described.


Assuntos
Preservação de Sangue/métodos , Criopreservação/métodos , Crioprotetores/farmacologia , Eritrócitos/citologia , Congelamento , Glicerol/farmacologia , Transfusão de Sangue , Eritrócitos/efeitos dos fármacos , Humanos
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