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1.
Transpl Int ; 37: 13218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100754

RESUMO

Delayed graft function (DGF) after kidney transplantation heralds a worse prognosis. In patients with hyperoxaluria, the incidence of DGF is high. Oxalic acid is a waste product that accumulates when kidney function decreases. We hypothesize that residual diuresis and accumulated waste products influence the DGF incidence. Patients transplanted between 2018-2022 participated in the prospective cohort study. Pre-transplant concentrations of oxalic acid and its precursors were determined. Data on residual diuresis and other recipient, donor or transplant related variables were collected. 496 patients were included, 154 were not on dialysis. Oxalic acid, and glyoxylic acid, were above upper normal concentrations in 98.8%, and 100% of patients. Residual diuresis was ≤150 mL/min in 24% of patients. DGF occurred in 157 patients. Multivariable binary logistic regression analysis demonstrated a significant influence of dialysis type, recipient BMI, donor type, age, and serum creatinine on the DGF risk. Residual diuresis and glycolic acid concentration were inversely proportionally related to this risk, glyoxylic acid directly proportionally. Results in the dialysis population showed the same results, but glyoxylic acid lacked significance. In conclusion, low residual diuresis is associated with increased DGF incidence. Possibly accumulated waste products also play a role. Pre-emptive transplantation may decrease the incidence of DGF.


Assuntos
Função Retardada do Enxerto , Diurese , Glioxilatos , Transplante de Rim , Ácido Oxálico , Humanos , Transplante de Rim/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/epidemiologia , Adulto , Estudos Prospectivos , Idoso , Diálise Renal , Glicolatos , Hiperoxalúria/etiologia , Fatores de Risco , Incidência
2.
Appl Environ Microbiol ; 90(7): e0041624, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38837369

RESUMO

Ethylene glycol (EG) is a widely used industrial chemical with manifold applications and also generated in the degradation of plastics such as polyethylene terephthalate. Rhodococcus jostii RHA1 (RHA1), a potential biocatalytic chassis, grows on EG. Transcriptomic analyses revealed four clusters of genes potentially involved in EG catabolism: the mad locus, predicted to encode mycofactocin-dependent alcohol degradation, including the catabolism of EG to glycolate; two GCL clusters, predicted to encode glycolate and glyoxylate catabolism; and the mft genes, predicted to specify mycofactocin biosynthesis. Bioinformatic analyses further revealed that the mad and mft genes are widely distributed in mycolic acid-producing bacteria such as RHA1. Neither ΔmadA nor ΔmftC RHA1 mutant strains grew on EG but grew on acetate. In resting cell assays, the ΔmadA mutant depleted glycolaldehyde but not EG from culture media. These results indicate that madA encodes a mycofactocin-dependent alcohol dehydrogenase that initiates EG catabolism. In contrast to some mycobacterial strains, the mad genes did not appear to enable RHA1 to grow on methanol as sole substrate. Finally, a strain of RHA1 adapted to grow ~3× faster on EG contained an overexpressed gene, aldA2, predicted to encode an aldehyde dehydrogenase. When incubated with EG, this strain accumulated lower concentrations of glycolaldehyde than RHA1. Moreover, ecotopically expressed aldA2 increased RHA1's tolerance for EG further suggesting that glycolaldehyde accumulation limits growth of RHA1 on EG. Overall, this study provides insights into the bacterial catabolism of small alcohols and aldehydes and facilitates the engineering of Rhodococcus for the upgrading of plastic waste streams.IMPORTANCEEthylene glycol (EG), a two-carbon (C2) alcohol, is produced in high volumes for use in a wide variety of applications. There is burgeoning interest in understanding and engineering the bacterial catabolism of EG, in part to establish circular economic routes for its use. This study identifies an EG catabolic pathway in Rhodococcus, a genus of bacteria well suited for biocatalysis. This pathway is responsible for the catabolism of methanol, a C1 feedstock, in related bacteria. Finally, we describe strategies to increase the rate of degradation of EG by increasing the transformation of glycolaldehyde, a toxic metabolic intermediate. This work advances the development of biocatalytic strategies to transform C2 feedstocks.


Assuntos
Proteínas de Bactérias , Etilenoglicol , Rhodococcus , Rhodococcus/metabolismo , Rhodococcus/genética , Etilenoglicol/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Glicolatos/metabolismo , Glioxilatos/metabolismo , Álcool Desidrogenase/metabolismo , Álcool Desidrogenase/genética , Peptídeos
3.
Life Sci Alliance ; 7(8)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38760174

RESUMO

Amyotrophic lateral sclerosis (ALS) leads to death within 2-5 yr. Currently, available drugs only slightly prolong survival. We present novel insights into the pathophysiology of Superoxide Dismutase 1 (SOD1)- and in particular Fused In Sarcoma (FUS)-ALS by revealing a supposedly central role of glycolic acid (GA) and D-lactic acid (DL)-both putative products of the Parkinson's disease associated glyoxylase DJ-1. Combined, not single, treatment with GA/DL restored axonal organelle phenotypes of mitochondria and lysosomes in FUS- and SOD1-ALS patient-derived motoneurons (MNs). This was not only accompanied by restoration of mitochondrial membrane potential but even dependent on it. Despite presenting an axonal transport deficiency as well, TDP43 patient-derived MNs did not share mitochondrial depolarization and did not respond to GA/DL treatment. GA and DL also restored cytoplasmic mislocalization of FUS and FUS recruitment to DNA damage sites, recently reported being upstream of the mitochondrial phenotypes in FUS-ALS. Whereas these data point towards the necessity of individualized (gene-) specific therapy stratification, it also suggests common therapeutic targets across different neurodegenerative diseases characterized by mitochondrial depolarization.


Assuntos
Esclerose Lateral Amiotrófica , Glicolatos , Ácido Láctico , Mitocôndrias , Proteína Desglicase DJ-1 , Proteína FUS de Ligação a RNA , Superóxido Dismutase-1 , Humanos , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/genética , Proteína FUS de Ligação a RNA/metabolismo , Proteína FUS de Ligação a RNA/genética , Glicolatos/metabolismo , Glicolatos/farmacologia , Mitocôndrias/metabolismo , Proteína Desglicase DJ-1/metabolismo , Proteína Desglicase DJ-1/genética , Ácido Láctico/metabolismo , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética , Potencial da Membrana Mitocondrial , Neurônios Motores/metabolismo , Lisossomos/metabolismo
4.
Dermatol Surg ; 50(5): 467-470, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38460193

RESUMO

BACKGROUND: Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines. METHODS: A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale. RESULTS: Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51-71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands ( p < .01). No adverse events were noted. CONCLUSION: A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines.


Assuntos
Abrasão Química , Glicolatos , Ácido Tricloroacético , Humanos , Ácido Tricloroacético/administração & dosagem , Ácido Tricloroacético/efeitos adversos , Glicolatos/administração & dosagem , Pessoa de Meia-Idade , Abrasão Química/métodos , Estudos Prospectivos , Idoso , Feminino , Masculino , Lentigo/tratamento farmacológico , Método Simples-Cego , Mãos , Ceratolíticos/administração & dosagem , Resultado do Tratamento
5.
Odontology ; 112(3): 739-750, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38507151

RESUMO

This study aims to investigate glycolic acid (GA) as a final irrigant on push-out bond strength of fiber post and smear removal. Ninety mandibular premolars were stabilized with a silicone key and photographed, and canal cross-section was calculated by image processing software. Round canal morphology was selected. The specimens were divided into five groups (n = 18); 10%GA, 17%EDTA, NaOCl + 10%GA, NaOCl + 17%EDTA, and the control. Fifteen specimens were used for the push-out. Three specimens were evaluated using a scanning electron microscope after post space preparation. Two-way ANOVA and Chi-square were used for statistics. GA presented higher strength than EDTA (p < 0.05). The NaOCl + GA showed higher strength than the NaOCl + EDTA (p < 0.05). The highest values were observed in cervical and lowest in apical thirds (p < 0.05). The most failure type was between dentin and resin (p < 0.05). GA removed the smear in the post space including the apical third. The NaOCl + GA has superiority to NaOCl + EDTA on push-out strength. Glycolic acid improved the bond strength of fiber post when used as a final post space irrigant. The combination of NaOCl and glycolic acid did not negatively affect the bond strength and was more effective compared to the combination with EDTA. Glycolic acid improved the bond strength of fiber post when used as a final post space irrigant. The combination of NaOCl and glycolic acid did not negatively affect the bond strength and was more effective compared to the combination with EDTA.


Assuntos
Ácido Edético , Glicolatos , Microscopia Eletrônica de Varredura , Técnica para Retentor Intrarradicular , Irrigantes do Canal Radicular , Camada de Esfregaço , Humanos , Irrigantes do Canal Radicular/química , Técnicas In Vitro , Hipoclorito de Sódio/química , Colagem Dentária , Análise do Estresse Dentário , Dente Pré-Molar , Teste de Materiais
6.
Dermatol Surg ; 50(7): 656-661, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38530985

RESUMO

BACKGROUND: Melasma is a common chronic, relapsing pigmentary disorder that causes psychological impact. Chemical peels are a well-known therapeutic modality used for accelerating the treatment of melasma. OBJECTIVE: To review the published evidence on the efficacy and safety of chemical peels in the treatment of melasma. METHODS: A systematic review was done. A meta-analysis could not be done due to the heterogeneity of data. RESULT: The authors conducted a PubMed search and included prospective case series of more than 10 cases and randomized controlled trials (RCTs) that have studied the safety and/or efficacy of chemical peel in melasma. Out of 24 studies, 9 were clinical/comparative trials and 15 were RCTs. The total sample size was 1,075. The duration of the study varied from 8 to 36 weeks. Only 8 studies were split face. All studies used self-assessment, physician global assessment, and Melasma Area and Severity Index (MASI) for quantifying the results. Glycolic acid was found to be the most safe and effective in melasma. CONCLUSION: Chemical peels were found to be safe and effective in the management of melasma.


Assuntos
Abrasão Química , Melanose , Melanose/terapia , Humanos , Abrasão Química/métodos , Glicolatos/uso terapêutico , Glicolatos/administração & dosagem , Resultado do Tratamento , Ceratolíticos/uso terapêutico , Ceratolíticos/administração & dosagem
7.
Obes Surg ; 34(4): 1102-1112, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38363496

RESUMO

INTRODUCTION: Bariatric surgery is an effective intervention to reduce obesity and improve associated comorbidities. However, its effects on cognitive function are still the subject of debate. Given that the bioavailability of circulating metabolites can influence brain metabolism and cognitive performance, we aimed to assess the effects of bariatric surgery on plasma metabolic profiles and cognitive performance. METHODS: We recruited 26 women undergoing gastric bypass surgery. We conducted anthropometric assessments and collected plasma samples for metabolomic analysis. A set of 4 cognitive tests were used to evaluate cognitive performance. Participants were reevaluated 1 year post-surgery. RESULTS: After surgery, attention capacity and executive function were improved, while immediate memory had deteriorated. Regarding metabolic profile, reduction of beta-tocopherol and increase of serine, glutamic acid, butanoic acid, and glycolic acid were observed. To better understand the relationship between cognitive function and metabolites, a cluster analysis was conducted to identify more homogeneous subgroups based on the cognitive performance. We identified cluster 1, which did not show changes in cognitive performance after surgery, and cluster 2, which showed improved attention and executive function, but reduced performance in the immediate memory test. Thus, cluster 2 was more homogeneous group that replicated the results of non-clustered subjects. Analysis of the metabolic profile of cluster 2 confirmed serine, glutamic acid, and glycolic acid as potential metabolites associated with cognitive performance. CONCLUSIONS: Metabolites identified in this study have potential for biomarkers and alternative therapeutic target to prevent obesity-related cognitive decline. KEY POINTS: • Attention capacity and executive function were improved 12 months post bariatric surgery. • Immediate memory was worsened 12 months post bariatric surgery. • Serine, glutamic acid, and glycolic acid are potential metabolites linked to the alteration of cognitive performance.


Assuntos
Cirurgia Bariátrica , Glicolatos , Obesidade Mórbida , Humanos , Feminino , Obesidade Mórbida/cirurgia , Ácido Glutâmico , Resultado do Tratamento , Cirurgia Bariátrica/métodos , Obesidade/cirurgia , Cognição , Serina
8.
Appl Microbiol Biotechnol ; 108(1): 58, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38175243

RESUMO

Ethylene glycol is an industrially important diol in many manufacturing processes and a building block of polymers, such as poly(ethylene terephthalate). In this study, we found that a mycolic acid-containing bacterium Rhodococcus jostii RHA1 can grow with ethylene glycol as a sole source of carbon and energy. Deletion of a putative glycolate dehydrogenase gene (RHA1_ro03227) abolished growth with ethylene glycol, indicating that ethylene glycol is assimilated via glycolate in R. jostii RHA1. Transcriptome sequencing and gene deletion analyses revealed that a gene homologous to mycofactocin (MFT)-associated dehydrogenase (RHA1_ro06057), hereafter referred to as EgaA, is essential for ethylene glycol assimilation. Furthermore, egaA deletion also negatively affected the utilization of ethanol, 1-propanol, propylene glycol, and 1-butanol, suggesting that EgaA is involved in the utilization of various alcohols in R. jostii RHA1. Deletion of MFT biosynthetic genes abolished growth with ethylene glycol, indicating that MFT is the physiological electron acceptor of EgaA. Further genetic studies revealed that a putative aldehyde dehydrogenase (RHA1_ro06081) is a major aldehyde dehydrogenase in ethylene glycol metabolism by R. jostii RHA1. KEY POINTS: • Rhodococcus jostii RHA1 can assimilate ethylene glycol via glycolate • A mycofactocin-associated dehydrogenase is involved in the oxidation of ethylene glycol • An aldehyde dehydrogenase gene is important for the ethylene glycol assimilation.


Assuntos
Etilenoglicol , Glicóis , Glicolatos , Etilenos , Aldeído Desidrogenase
9.
Toxicol Sci ; 198(1): 31-39, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38175793

RESUMO

In order to evaluate the role of the placenta in the etiology of ethylene glycol (EG) developmental toxicity, the distribution of EG and its main metabolites, glycolic acid (GA) and oxalic acid (OX), into the conceptus was determined at the beginning and completion of placentation in the rat and rabbit. Two groups (n = 28) of timed-pregnant Wistar rats were administered EG (1000 mg/kg bw/day, oral gavage) from gestation day (GD) 6 to either GD 11 or GD 16; similarly, two groups (n = 28) of timed-pregnant New Zealand White rabbits were administered EG from GD 6 to either GD 10 or GD 19. Four animals from each group were sacrificed at 1, 3, 6, 9, 12, 18, or 24 h after the final administration, and maternal blood, extraembryonic fluid, and embryonic tissue were removed for analysis of EG, GA, and OX. The three analytes were predominantly cleared from all compartments in both species within 24 h. Neither EG nor OX preferentially accumulated into the conceptus compartments, compared with the maternal blood, in either species. Critically, GA was preferentially accumulated from the maternal blood only into the rat embryo at GD 11, but not at GD 16 and not into the rabbit embryo at either GD 10 or GD 19. The accumulation of GA into the rat embryo, and its decline over the course of placentation, is discussed in relation to the expression of monocarboxylate transporter isoforms across the syncytiotrophoblast.


Assuntos
Etilenoglicol , Glicolatos , Placentação , Gravidez , Feminino , Ratos , Coelhos , Animais , Etilenoglicol/toxicidade , Ratos Wistar , Administração Oral
10.
Hernia ; 28(2): 527-535, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38212505

RESUMO

PURPOSE: Using small instead of large bites for laparotomy closure results in lower incidence of incisional hernia, but no consensus exists on which suture material to use. This study aimed to compare five different closure strategies in a standardized experimental setting. METHODS: Fifty porcine abdominal walls were arranged into 5 groups: (A) running 2/0 polydioxanone; (B) interlocking 2/0 polydioxanone; (C) running size 0 barbed polydioxanone; (D) running size 0 barbed glycolic acid and trimethylene carbonate; (E) running size 0 suturable polypropylene mesh. The small-bites technique was used for linea alba closure in all. The abdominal walls were divided into a supra- and infra-umbilical half, resulting in 20 specimens per group that were pulled apart in a tensile testing machine. Maximum tensile force and types of suture failure were registered. RESULTS: The highest tensile force was measured when using barbed polydioxanone (334.8 N ± 157.0), but differences did not reach statistical significance. Infra-umbilical abdominal walls endured a significantly higher maximum tensile force compared to supra-umbilical (397 N vs 271 N, p < 0.001). Barbed glycolic acid and trimethylene carbonate failed significantly more often (25% vs 0%, p = 0.008). CONCLUSION: Based on tensile force, both interlocking and running suture techniques using polydioxanone, and running sutures using barbed polydioxanone or suturable mesh, seem to be suitable for abdominal wall closure. Tensile strength was significantly higher in infra-umbilical abdominal walls compared to supra-umbilical. Barbed glycolic acid and trimethylene carbonate should probably be discouraged for fascial closure, because of increased risk of suture failure.


Assuntos
Parede Abdominal , Técnicas de Fechamento de Ferimentos Abdominais , Glicolatos , Suínos , Animais , Parede Abdominal/cirurgia , Polidioxanona , Herniorrafia , Técnicas de Sutura/efeitos adversos , Modelos Animais , Resistência à Tração , Laparotomia , Suturas , Técnicas de Fechamento de Ferimentos Abdominais/efeitos adversos
11.
J Inorg Biochem ; 252: 112475, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38199050

RESUMO

Utilizing isoquinoline as a carrier ligand, we have evaluated the reactivity of selected trans­platinum planar amine (TPA) carboxylate compounds by varying the leaving carboxylate group (acetate, hydroxyacetate, and lactate) in an effort to optimize the cytotoxic and metabolic efficiency. To measure the pharmacological properties of these compounds, a combination of systematic biophysical and biological studies were carried out mainly involving substitution reaction with NAM (N-acetyl-methionine), effects on DNA structural perturbation, cytotoxicity, cellular accumulation, metabolic stability, and cell cycle effects. TPA compounds showed minimal losses in cytotoxic efficacy and outperformed cisplatin after pre-incubation with serum, while displaying a distinct micromolar cytotoxic activity with minimal DNA binding and unaltered cell cycle. Monitoring the TPA compounds with NAM suggests the following trend for the reactivity: hydroxyacetate > lactate > acetate. The same trend was seen for the cytotoxicity in tumor cells and DNA binding, while the rate of drug inactivation/protein binding in cells was not significantly different among these leaving groups. Thus, our results show superior cellular efficacy of TPA compounds and distinct micromolar cytotoxic activities different than cisplatin. Moreover, we found the TPA compounds had prolonged survival and decreased tumor burden compared to the control mice in a relevant human ovarian cancer mouse model with A2780 cells expressing luciferase. Therefore, we propose that further optimization of the basic TPA structure can give further enhanced in vivo activity and may eventually be translated into the development of clinically relevant non-traditional platinum drugs.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Humanos , Animais , Feminino , Camundongos , Platina/farmacologia , Platina/química , Cisplatino/farmacologia , Cisplatino/química , Linhagem Celular Tumoral , Compostos Organoplatínicos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , DNA/química , Acetatos , Lactatos , Glicolatos , Ensaios de Seleção de Medicamentos Antitumorais
12.
Adv Healthc Mater ; 13(6): e2301848, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37870153

RESUMO

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, an injectable thermoresponsive gel-based controlled release formulation is developed for the FDA-approved Toll-like-receptor 7 (TLR7) agonist imiquimod ("Imigel") that forms a tumor-resident depot upon injection and contains a contrast agent for visualization under computed tomography (CT). The poly-lactic-co-glycolic acid-polyethylene glycol-poly-lactic-co-glycolic acid (PLGA-PEG-PLGA)-based amphiphilic copolymer gel's underlying micellar nature enables high drug concentration and a logarithmic release profile that is additive with the neo-antigen release from cryoablation, requiring only a single injection. Rheological testing demonstrated the thermoresponsive increase in viscosity at body temperature and radio-opacity via microCT. Its ability to significantly augment the abscopal rate of cryoablation is demonstrated in otherwise immunotherapy resistant metastatic tumors in two aggressive colorectal and breast cancer dual tumor models with an all or nothing response, responders generally demonstrating complete regression of bilateral tumors in 90-day survival studies.


Assuntos
Criocirurgia , Glicolatos , Neoplasias , Humanos , Adjuvantes Imunológicos , Meios de Contraste
13.
J Biomed Mater Res A ; 112(3): 402-420, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37941485

RESUMO

Triple negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and it is difficult to progress through traditional chemotherapy. Therefore, the treatment of TNBC urgently requires agents with effective diagnostic and therapeutic capabilities. In this study, we obtained programmed death-ligand 1 (PD-L1) antibody conjugated gold nanoshelled poly(lactic-co-glycolic acid) (PLGA) nanocapsules (NCs) encapsulating doxorubicin (DOX) (DOX@PLGA@Au-PD-L1 NCs). PLGA NCs encapsulating DOX were prepared by a modified single-emulsion oil-in-water (O/W) solvent evaporation method, and gold nanoshells were formed on the surface by gold seed growth method, which were coupled with PD-L1 antibodies by carbodiimide method. The fabricated DOX@PLGA@Au-PD-L1 NCs exhibited promising contrast enhancement in vitro ultrasound imaging. Furthermore, DOX encapsulated in NCs displayed good pH-responsive and photo-triggered drug release properties. After irradiating 200 µg/mL NCs solution with a laser for 10 min, the solution temperature increased by nearly 23°C, indicating that the NCs had good photothermal conversion ability. The targeting experiments confirmed that the NCs had specific target binding ability to TNBC cells overexpressing PD-L1 molecules. Cell experiments exhibited that the agent significantly reduced the survival rate of TNBC cells through photochemotherapy combination therapy. As a multifunctional diagnostic agent, DOX@PLGA@Au-PD-L1 NCs could be used for ultrasound targeted contrast imaging and photochemotherapy combination therapy of TNBC cells, providing a promising idea for early diagnosis and treatment of TNBC.


Assuntos
Glicolatos , Nanocápsulas , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Nanocápsulas/química , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Glicóis , Medicina de Precisão , Ouro/química , Antígeno B7-H1 , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Ultrassonografia/métodos , Linhagem Celular Tumoral , Nanopartículas/química
14.
Int J Biol Macromol ; 256(Pt 1): 128059, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37989428

RESUMO

This study aimed to functionalize a novel porous PLGA (Poly lactic-co-glycolic acid) composite scaffold in combination with nano­calcium sulphate (nCS) and/or fucoidan (FU) to induce osteogenic differentiation of human bone marrow stromal cells. The composite scaffolds (PLGA-nCS-FU, PLGA-nCS or PLGA-FU) were fabricated and subjected to characterization using Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), Scanning electron microscopy (SEM) and Energy Dispersive X-Ray (EDX). The biocompatibility and osteogenic induction potential of scaffolds on seeded human bone marrow derived mesenchymal stromal cells (hBMSCs) were studied using cell attachment and alamar blue cell viability and alkaline phosphatase (ALP), osteocalcin and osteogenic gene expression, respectively. The composition of different groups was reflected in FTIR, XRD and EDX. The SEM micrographs revealed a difference in the surface of the scaffold before and after FU addition. The confocal imaging and SEM micrographs confirmed the attachment of cells onto all three composite scaffolds. However, the AB assay indicated a significant increase (p < 0.05) in cell viability/proliferation seeded on PLGA-nCS-FU on day 21 and 28 as compared with other combinations. A 2-fold significant increase (p < 0.05) in ALP and OC secretion of seeded hBMSCs onto PLGA-nCS-FU was observed when compared with other combinations. A significant increase in RUNX2, OPN, COL-I and ALP genes were observed in the cells seeded on PLGA-nCS-FU on day 14 and 28 as compared with day 0. In conclusion, the incorporation of both Fucoidan and Nano­calcium sulphate with PLGA showed a promising improvement in the osteogenic potential of hBMSCs. Therefore, PLGA-nCS-FU could be the ideal candidate for subsequent pre-clinical studies to develop a successful bone substitute to repair critical bone defects.


Assuntos
Glicolatos , Células-Tronco Mesenquimais , Polissacarídeos , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Osteogênese , Alicerces Teciduais/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Glicóis , Medula Óssea , Diferenciação Celular , Sulfatos , Células da Medula Óssea
15.
Biomater Sci ; 11(18): 6280-6286, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37548917

RESUMO

Stimuli-responsive transformable biomaterials development can be manipulated practically by fine-tuning the built-in molecular design of their structural segments. Here, we demonstrate a peptide assembly by the bola-type amphiphilic polypeptide, glycolic acid-polysarcosine (PSar)13-b-(L-Leu-Aib)6-b-PSar13-glycolic acid (S13L12S13), which shows morphological transformations between hydrophilic chain-driven and hydrophobic unit-driven morphologies. The hydrophobic α-helical unit (L-Leu-Aib)6 precisely controls packing in the hydrophobic layer of the assembly and induces tubule formation. The densified, hydrophilic PSar chain on the assembly surface becomes slightly more hydrophobic as the temperature increases above 70 °C, starting to disturb the helix-helix interaction-driven formation of tubules. As a result, the S13L12S13 peptide assembly undergoes a reversible vesicle-nanotube transformation following a time course at room temperature and a heat treatment above 80 °C. Using membrane fluidity analysis with DPH and TMA-DPH and evaluating the environment surrounding the PSar side chain with NMR, we clarify that the vesicle was in a kinetically stable state driven by the dehydrated PSar chain, while the nanotube was in a thermodynamically stable state.


Assuntos
Glicolatos , Peptídeos , Peptídeos/química , Sarcosina/química
16.
Crit Care ; 27(1): 56, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36765419

RESUMO

Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.


Assuntos
Antídotos , Intoxicação , Humanos , Antídotos/uso terapêutico , Fomepizol , Etanol , Diálise Renal/métodos , Glicolatos , Etilenoglicol , Intoxicação/terapia
17.
Am J Kidney Dis ; 82(1): 43-52.e1, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36610611

RESUMO

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.


Assuntos
Injúria Renal Aguda , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Injúria Renal Aguda/etiologia , Glicolatos , Oxalato de Cálcio , Rim/patologia
18.
J Chromatogr A ; 1685: 463601, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36323101

RESUMO

The radiation stability of two extraction chromatography resins containing diglycolamide ligands viz. TPDGA (N,N,N',N'-tetra-n-pentyl diglycolamide) and TODGA (N,N,N',N'-tetra-n-octyl diglycolamide) in a room temperature ionic liquid (C4mim.NTf2) was studied by exposing to gamma rays from a 60Co source. The resins were irradiated to varying gamma ray dose up to 1000 kGy where both the dry resins and wet resins (containing a fixed amount nitric acid in contact) were used. The performance assessment of the resins was done by physicochemical characterization as well as uptake studies; both by batch as well as column methods. The physicochemical characterization of the resins was done using FTIR analysis while the surface morphology of the resins was carried out by scanning electron microscopy. The uptake of the metal ions, typically that of Am(III) and Eu(III), representing the trivalent actinides and lanthanides was studied by batch method. The dry resins and those in contact with nitric acid yielded nearly identical results suggesting minimal effect of the radiolytic products of nitric acid on the resin performance. There was negligible change in the Kd values up to an absorbed dose of 300 kGy beyond which there was sharp decrease. However, the Kd values were still quite large even after an absorbed dose of 1000 kGy. The column performance of the irradiated resins was also assessed by the uptake and elution of Eu(III) ion and though loading was affected, the elution behavior was found to have insignificant effect.


Assuntos
Líquidos Iônicos , Líquidos Iônicos/química , Ácido Nítrico/química , Ligantes , Glicolatos/química , Cromatografia , Íons
19.
BMC Surg ; 22(1): 349, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138405

RESUMO

BACKGROUND: In accordance with previous reports on the utility of polyethylene glycolic acid (PGA) felt and fibrin glue for postoperative pancreatic fistula (POPF), we usually perform distal pancreatectomy (DP) with a PGA felt reinforcement stapler when dissecting the pancreas and cover the stump with PGA felt and fibrin glue (the PPF method). In this study, we retrospectively analyzed our DP cases to compare the risk factors for POPF and the postoperative course of patients receiving the PPF method of treatment versus that of those receiving conventional treatment. METHODS: A total of 127 DP procedures performed in our department between January 2008 and June 2021 were retrospectively analysed. RESULTS: In the PPF method, grade B/C POPF rate tended to decrease, and POPF rate showed a significant decrease. The duration of drainage and the length of postoperative hospitalisation were also significantly shorter with the PPF method. The risk of grade B/C POPF significantly decreased with the PPF method if the pancreas was thick (> 13.5 mm) or the patients were obese. CONCLUSIONS: The PPF method is useful for POPF in DP and is particularly effective when a thick pancreas or obese patient is involved. Removing the drainage tube early in the PPF method may lead to early discharge.


Assuntos
Adesivo Tecidual de Fibrina , Fístula Pancreática , Humanos , Adesivo Tecidual de Fibrina/uso terapêutico , Glicolatos , Obesidade/cirurgia , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Fístula Pancreática/cirurgia , Polietileno , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
20.
Chem Commun (Camb) ; 58(83): 11657-11660, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36164825

RESUMO

A Ru/NH2-MCM-41 catalyst was prepared via a coordination-assisted strategy for chemoselective hydrogenation of dimethyl oxalate with a high selectivity of methyl glycolate (ca. 100%) and ethylene glycol (>90%) at reaction temperatures of 343 K and 433 K, respectively. The amino groups help to anchor and form stable electron-rich Ru active sites, which accounts for the excellent CO bond activation and hydrogenation selectivity.


Assuntos
Etilenoglicol , Oxalatos , Catálise , Etilenoglicol/química , Glicolatos , Hidrogenação , Oxalatos/química
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