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1.
Int J Mol Sci ; 25(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396657

RESUMO

The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has been investigated and shown successful results in clinical trials. Various hypoglycemia-inducing drugs such as Metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, amylin analogs, and Sodium-Glucose Cotransporters 2 (SGLT-2) inhibitors, developed good outcomes in patients with T1DM. Currently, SGLT-2 inhibitors have remarkably improved the treatment of patients with diabetes by preventing cardiovascular events, heart failure hospitalization, and progression of renal disease. However, their pharmacological potential has not been explored enough. Thus, the substantial interest in SGLT-2 inhibitors (SGLT-2is) underlines the present review. It begins with an overview of carrier-mediated cellular glucose uptake, evidencing the insulin-independent transport system contribution to glucose homeostasis and the essential roles of Sodium-Glucose Cotransporters 1 and 2. Then, the pharmacological properties of SGLT-2is are detailed, leading to potential applications in treating T1DM patients with automated insulin delivery (AID) systems. Results from several studies demonstrated improvements in glycemic control, an increase in Time in Range (TIR), a decrease in glycemic variability, reduced daily insulin requirements without increasing hyperglycemic events, and benefits in weight management. However, these advantages are counterbalanced by increased risks, particularly concerning Diabetic Ketoacidosis (DKA). Several clinical trials reported a higher incidence of DKA when patients with T1DM received SGLT-2 inhibitors such as Sotagliflozin and Empagliflozin. On the other hand, patients with T1DM and a body mass index (BMI) of ≥27 kg/m2 treated with Dapagliflozin showed similar reduction in hyperglycemia and body weight and insignificantly increased DKA incidence compared to the overall trial population. Additional multicenter and randomized studies are required to establish safer and more effective long-term strategies based on patient selection, education, and continuous ketone body monitoring for optimal integration of SGLT-2 inhibitors into T1DM therapeutic protocol.


Assuntos
Diabetes Mellitus Tipo 1 , Insulina , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glucose/uso terapêutico , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Estudos Multicêntricos como Assunto , Medição de Risco , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
2.
Int J Mol Sci ; 24(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37511185

RESUMO

The excess of free radicals causes numerous imbalances in the body that lead to premature aging, the degradation of internal structures, and the appearance of numerous pathologies responsible for the increased risk of premature death. The present work aims to evaluate the physical, chemical, pharmacotechnical, and antioxidant activity of newly achieved capsule formulations. These two formulations were F1a.i., which contains melatonin:biotin:coenzyme Q10 (weight ratio of 1:2:60), and F2a.i., which contains quercetin:resveratrol:biotin:coenzyme Q10 (weight ratio of 10:10:1:10). The adequate selection of the excipient types and amounts for final capsule formulations (F1c.c., F2c.c.) was based on preformulation studies performed on the powders containing active ingredients. The antioxidant activity assessed using three methods (ABTS, DPPH, and FRAP) compared with acid ascorbic as a positive control demonstrated that the F2c.c. formulation possesses the strongest antioxidant capacity. The results confirmed the suitable formulation and the accurate selection of the types and amounts of active ingredients, as well as the auxiliary excipients used in newly developed capsule formulations as supplements with an excellent antioxidant effect on the human body.


Assuntos
Antioxidantes , Biotina , Humanos , Antioxidantes/metabolismo , Resveratrol , Suplementos Nutricionais , Quercetina , Excipientes/química
3.
Artigo em Inglês | MEDLINE | ID: mdl-36981958

RESUMO

The treatment and interdisciplinary management of patients with chronic kidney disease (CKD) continue to improve long-term outcomes. The medical nutrition intervention's role is to establish a healthy diet plan for kidney protection, reach blood pressure and blood glucose goals, and prevent or delay health problems caused by kidney disease. Our study aims to report the effects of medical nutrition therapy-substituting foods rich in phosphorus-containing additives with ones low in phosphates content on phosphatemia and phosphate binders drug prescription in stage 5 CKD patients with hemodialysis. Thus, 18 adults with high phosphatemia levels (over 5.5 mg/dL) were monitored at a single center. Everyone received standard personalized diets to replace processed foods with phosphorus additives according to their comorbidities and treatment with prosphate binder drugs. Clinical laboratory data, including dialysis protocol, calcemia, and phosphatemia, were evaluated at the beginning of the study, after 30 and 60 days. A food survey was assessed at baseline and after 60 days. The results did not show significant differences between serum phosphate levels between the first and second measurements; thus, the phosphate binders' initial doses did not change. After 2 months, phosphate levels decreased considerably (from 7.322 mg/dL to 5.368 mg/dL); therefore, phosphate binder doses were diminished. In conclusion, medical nutrition intervention in patients with hemodialysis significantly reduced serum phosphate concentrations after 60 days. Restricting the intake of processed foods containing phosphorus additives-in particularized diets adapted to each patient's comorbidities-and receiving phosphate binders represented substantial steps to decrease phosphatemia levels. The best results were significantly associated with life expectancy; at the same time, they showed a negative correlation with the dialysis period and participants' age.


Assuntos
Hiperfosfatemia , Falência Renal Crônica , Insuficiência Renal Crônica , Adulto , Humanos , Hiperfosfatemia/etiologia , Hiperfosfatemia/prevenção & controle , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Fosfatos/uso terapêutico , Fósforo , Insuficiência Renal Crônica/complicações
4.
Int J Mol Sci ; 23(23)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36499160

RESUMO

Oxidative stress is associated with aging, cancers, and numerous metabolic and chronic disorders, and phenolic compounds are well known for their health-promoting role due to their free-radical scavenging activity. These phytochemicals could also exhibit pro-oxidant effects. Due to its bioactive phenolic secondary metabolites, Usnea barbata (L.) Weber ex. F.H. Wigg (U. barbata) displays anticancer and antioxidant activities and has been used as a phytomedicine for thousands of years. The present work aims to analyze the properties of U. barbata extract in canola oil (UBO). The UBO cytotoxicity on oral squamous cell carcinoma (OSCC) CLS-354 cell line and blood cell cultures was explored through complex flow cytometry analyses regarding apoptosis, reactive oxygen species (ROS) levels, the enzymatic activity of caspase 3/7, cell cycle, nuclear shrinkage (NS), autophagy (A), and synthesis of deoxyribonucleic acid (DNA). All these studies were concomitantly performed on canola oil (CNO) to evidence the interaction of lichen metabolites with the constituents of this green solvent used for extraction. The obtained data evidenced that UBO inhibited CLS-354 oral cancer cell proliferation through ROS generation (316.67 × 104), determining higher levels of nuclear shrinkage (40.12%), cell cycle arrest in G0/G1 (92.51%; G0 is the differentiation phase, while during G1 phase occurs preparation for cell division), DNA fragmentation (2.97%), and autophagy (62.98%) than in blood cells. At a substantially higher ROS level in blood cells (5250.00 × 104), the processes that lead to cell death-NS (30.05%), cell cycle arrest in G0/G1 (86.30%), DNA fragmentation (0.72%), and autophagy (39.37%)-are considerably lower than in CLS-354 oral cancer cells. Our work reveals the ROS-mediated anticancer potential of UBO through DNA damage and autophagy. Moreover, the present study suggests that UBO pharmacological potential could result from the synergism between lichen secondary metabolites and canola oil phytoconstituents.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Usnea , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Usnea/química , Usnea/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Óleo de Brassica napus/farmacologia , Autofagia , Dano ao DNA , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Extratos Vegetais/farmacologia , Fenóis/farmacologia , DNA/farmacologia , Linhagem Celular Tumoral
5.
Artigo em Inglês | MEDLINE | ID: mdl-36078830

RESUMO

Cereals whole grains contain vitamins, phytochemicals, antioxidants, resistant starch, and minerals with potential benefits to human health. The consumption of whole grains is correlated with a lowered risk of the most important chronic diseases, including type II diabetes, cardiovascular diseases, and some cancers. This study aimed to characterize and evaluate the content of five cultivars of wheat (Triticum aestivum L.) and five cultivars of barley (Hordeum vulgare L.) obtained by conventional plant breeding using crossing and selection methods. The novelty and the purpose of this research was to quantitatively and qualitatively analyze these ten cultivars from Romania and to show the importance of, and the changes produced by, crossing and selection methods when these are aimed at the physiological or morphological development of the cultivars. Studies based on gluten dosing; spectrophotometry using Bradford, fructan and protein dosing; Kjeldahl protein dosing; GC-MS/MS-protein and amino acid dosing; and identification of protein fractions using polyacrylamide gel electrophoretic method were conducted. This study demonstrates the possibility of developing future cultivars using conventional methods of improvement to modify the content and composition of nutrients to increase their health benefits.


Assuntos
Diabetes Mellitus Tipo 2 , Hordeum , Pão , Hordeum/química , Humanos , Melhoramento Vegetal , Romênia , Espectrometria de Massas em Tandem , Triticum/química
6.
Antioxidants (Basel) ; 11(8)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36009320

RESUMO

Usnea lichens are known for their beneficial pharmacological effects with potential applications in oral medicine. This study aims to investigate the extract of Usnea barbata (L.) Weber ex F.H. Wigg from the Calimani Mountains in canola oil as an oral pharmaceutical formulation. In the present work, bioadhesive oral films (F-UBO) with U. barbata extract in canola oil (UBO) were formulated, characterized, and evaluated, evidencing their pharmacological potential. The UBO-loaded films were analyzed using standard methods regarding physicochemical and pharmacotechnical characteristics to verify their suitability for topical administration on the oral mucosa. F-UBO suitability confirmation allowed for the investigation of antimicrobial and anticancer potential. The antimicrobial properties against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27353, Candida albicans ATCC 10231, and Candida parapsilosis ATCC 22019 were evaluated by a resazurin-based 96-well plate microdilution method. The brine shrimp lethality assay (BSL assay) was the animal model cytotoxicity prescreen, followed by flow cytometry analyses on normal blood cells and oral epithelial squamous cell carcinoma CLS-354 cell line, determining cellular apoptosis, caspase-3/7 activity, nuclear condensation and lysosomal activity, oxidative stress, cell cycle, and cell proliferation. The results indicate that a UBO-loaded bioadhesive film's weight is 63 ± 1.79 mg. It contains 315 µg UBO, has a pH = 6.97 ± 0.01, a disintegration time of 124 ± 3.67 s, and a bioadhesion time of 86 ± 4.12 min, being suitable for topical administration on the oral mucosa. F-UBO showed moderate dose-dependent inhibitory effects on the growth of both bacterial and fungal strains. Moreover, in CLS-354 tumor cells, F-UBO increased oxidative stress, diminished DNA synthesis, and induced cell cycle arrest in G0/G1. All these properties led to considering UBO-loaded bioadhesive oral films as a suitable phytotherapeutic formulation with potential application in oral infections and neoplasia.

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