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1.
Sci Rep ; 14(1): 15032, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951590

RESUMO

In agriculture, hydrogels can be addressed for effective operation of water and controlled-release fertilizers. Hydrogels have a significant ability for retaining water and improving nutrient availability in soil, enhancing plant growth while reducing water and fertilizer usage. This work aimed to prepare a hydrogel composite based on microalgae and biopolymers including chitosan and starch for use as a soil conditioner. The hydrogel composite was characterized by FTIR, XRD, and SEM. All hydrogel properties were studied including swelling degree, biodegradability, water-holding capacity, water retention, and re-swelling capacity in soil and water. The urea fertilizer loading and releasing behavior of the prepared hydrogels were investigated. The results revealed that the range of the maximal urea loading was between 99 and 440%, and the kinetics of loading was fitted with Freundlich model. The urea release % exhibited 78-95%, after 30 days, and the kinetics of release was fitted with zero-order, Higuchi, and Korsmeyer-Peppas models. Furthermore, the prepared hydrogels obtained a significant water-holding capacity, after blending soil (50 g) with small amount of hydrogels (1 g), the capacity increased in the range of 99.4-101.5%. In sum, the prepared hydrogels have the potential to be applied as a soil conditioner.


Assuntos
Fertilizantes , Hidrogéis , Microalgas , Ureia , Fertilizantes/análise , Hidrogéis/química , Ureia/química , Microalgas/química , Preparações de Ação Retardada/química , Cinética , Água/química , Solo/química , Quitosana/química , Amido/química
2.
Front Cell Infect Microbiol ; 14: 1414188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979511

RESUMO

In Escherichia coli, the disaccharide trehalose can be metabolized as a carbon source or be accumulated as an osmoprotectant under osmotic stress. In hypertonic environments, E. coli accumulates trehalose in the cell by synthesis from glucose mediated by the cytosolic enzymes OtsA and OtsB. Trehalose in the periplasm can be hydrolyzed into glucose by the periplasmic trehalase TreA. We have previously shown that a treA mutant of extraintestinal E. coli strain BEN2908 displayed increased resistance to osmotic stress by 0.6 M urea, and reduced production of type 1 fimbriae, reduced invasion of avian fibroblasts, and decreased bladder colonization in a murine model of urinary tract infection. Since loss of TreA likely results in higher periplasmic trehalose concentrations, we wondered if deletion of otsA and otsB genes, which would lead to decreased internal trehalose concentrations, would reduce resistance to stress by 0.6 M urea and promote type 1 fimbriae production. The BEN2908ΔotsBA mutant was sensitive to osmotic stress by urea, but displayed an even more pronounced reduction in production of type 1 fimbriae, with the consequent reduction in adhesion/invasion of avian fibroblasts and reduced bladder colonization in the murine urinary tract. The BEN2908ΔtreAotsBA mutant also showed a reduction in production of type 1 fimbriae, but in contrast to the ΔotsBA mutant, resisted better than the wild type in the presence of urea. We hypothesize that, in BEN2908, resistance to stress by urea would depend on the levels of periplasmic trehalose, but type 1 fimbriae production would be influenced by the levels of cytosolic trehalose.


Assuntos
Fímbrias Bacterianas , Osmorregulação , Trealose , Bexiga Urinária , Infecções Urinárias , Animais , Trealose/metabolismo , Camundongos , Bexiga Urinária/microbiologia , Fímbrias Bacterianas/metabolismo , Fímbrias Bacterianas/genética , Infecções Urinárias/microbiologia , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Modelos Animais de Doenças , Feminino , Pressão Osmótica , Escherichia coli Extraintestinal Patogênica/metabolismo , Escherichia coli Extraintestinal Patogênica/genética , Ureia/metabolismo , Trealase/metabolismo , Trealase/genética , Deleção de Genes , Glucose/metabolismo
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(6): 643-648, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38991965

RESUMO

OBJECTIVE: To investigate the dynamic changes of diaphragm and limb skeletal muscle in patients with sepsis by bedside ultrasound and their correlation with the ratio of blood urea/creatinine ratio (UCR) in 7 days after intensive care unit (ICU) admission. METHODS: A prospective observational study was conducted. A total of 55 patients with sepsis admitted to ICU of General Hospital of Ningxia Medical University from June 2022 to February 2023 were selected as the research objects. General information, laboratory indicators [urea, serum creatinine (SCr), and UCR] on days 1, 4, and 7 of ICU admission, and prognostic indicators were observed. Bedside ultrasound was used to assess the dynamic changes of diaphragm morphology [including diaphragmatic excursion (DE), end-inspiratory diaphragm thickness (DTei), and end-expiratory diaphragm thickness (DTee)] on days 1, 4, and 7 of ICU admission, as well as limb skeletal muscle (quadriceps femoris) morphology [including rectus femoris-muscle layer thickness (RF-MLT), vastus intermedius-muscle layer thickness (VI-MLT), and rectus femoris-cross sectional area (RF-CSA)]. Diaphragm thickening fraction (DTF) and RF-CSA atrophy rate were calculated, and the incidence of diaphragm and limb skeletal muscle dysfunction was recorded. The correlation between ultrasound morphological parameters of diaphragm and quadriceps and UCR at each time points in 7 days after ICU admission was analyzed by Pearson correlation. RESULTS: A total of 55 patients with sepsis were included, of which 29 were in septic shock. As the duration of ICU admission increased, the incidence of diaphragm dysfunction in patients with sepsis increased first and then decreased (63.6%, 69.6%, and 58.6% on days 1, 4, and 7 of ICU admission, respectively), while the incidence of limb skeletal muscle dysfunction showed an increasing trend (54.3% and 62.1% on days 4 and 7 of ICU admission, respectively), with a probability of simultaneous occurrence on days 4 and 7 of ICU admission were 32.6% and 34.5%, respectively. The UCR on day 7 of ICU admission was significantly higher than that on day 1 [121.77 (95.46, 164.55) vs. 97.00 (70.26, 130.50)], and RF-CSA atrophy rate on day 7 was significantly higher than that on day 4 [%: -39.7 (-52.4, -22.1) vs. -26.5 (-40.2, -16.4)]. RF-CSA was significantly lower on day 7 compared to day 1 [cm2: 1.3 (1.0, 2.5) vs. 2.1 (1.7, 2.9)], with all differences being statistically significant (all P < 0.05). Pearson correlation analysis showed that RF-CSA on day 7 of ICU admission was negatively associated with the UCR on the same day (r = -0.407, P = 0.029). CONCLUSIONS: Diaphragmatic dysfunction in patients with sepsis occurred early and can be improved. Limb skeletal muscle dysfunction occurred relatively later and progresses progressively. The RF-CSA on day 7 of ICU admission may be a reliable measure of limb skeletal muscle dysfunction in patients with sepsis, can be an indicator of early identification and diagnosis of ICU-acquired weakness (ICU-AW). Continuous loss of muscle mass occurring in septic patients is mainly associated with persistent organismal catabolism, and undergoes significant changes around a week in ICU.


Assuntos
Creatinina , Diafragma , Unidades de Terapia Intensiva , Músculo Esquelético , Sepse , Ultrassonografia , Ureia , Humanos , Diafragma/diagnóstico por imagem , Diafragma/fisiopatologia , Estudos Prospectivos , Ultrassonografia/métodos , Músculo Esquelético/diagnóstico por imagem , Creatinina/sangue , Ureia/sangue , Extremidades , Masculino , Feminino , Sistemas Automatizados de Assistência Junto ao Leito , Pessoa de Meia-Idade
4.
J Pak Med Assoc ; 74(6): 1153-1155, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38948988

RESUMO

To assess the effect of haemodialysis practice guidelines on dialysis indicators and haemodynamic complications, the comparative study was conducted at the dialysis unit of Sheikh Zayed Hospital, Lahore, Pakistan, and comprised patients undergoing haemodialysis who were divided into intervention group A in which updated haemodialysis practice guidelines were used, and control group B in which routine base dialysis was given. Data was collected using a self-structured tool. Data was analysed using McNemar test and Mann-Whitney U-test with p<0.05. Compared to baseline, there was a significant improvement in post-intervention ratio of effective removal of clearance (K) resulting from the treatment characterised by time (t) in the patient with a specific volume of distribution (V), or Kt/V, median & IQR 0.83(0.355) vs 1.21(0.11) and percentage of urea reduction ratio with median & IQR 49(12) vs. 66.5(18.65) (p<0.05). Intradialytic hypotension was found in 17(56.6%) subjects in group B and in 4(13.4%) in group A (p=0.002). Intradialytic hypertension was found in 8(25.6%) patients in group B and 1(3.4%) in group A (p=0.039). It is recommended that dialysis be performed in accordance with the most recent clinical guidelines in order to improve practices and to increase haemodialysis effectiveness.


Assuntos
Hipotensão , Guias de Prática Clínica como Assunto , Diálise Renal , Humanos , Diálise Renal/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Hipotensão/etiologia , Paquistão , Adulto , Falência Renal Crônica/terapia , Hemodinâmica/fisiologia , Hipertensão/terapia , Idoso , Ureia
5.
Sci Rep ; 14(1): 15525, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969741

RESUMO

For patients presenting with prostate imaging reporting and data system (PI-RADS) 3/4 findings on magnetic resonance imaging (MRI) examinations, the standard recommendation typically involves undergoing a biopsy for pathological assessment to ascertain the nature of the lesion. This course of action, though essential for accurate diagnosis, invariably amplifies the psychological distress experienced by patients and introduces a host of potential complications associated with the biopsy procedure. However, [18F]DCFPyL PET/CT imaging emerges as a promising alternative, demonstrating considerable diagnostic efficacy in discerning benign prostate lesions from malignant ones. This study aims to explore the diagnostic value of [18F]DCFPyL PET/CT imaging for prostate cancer in patients with PI-RADS 3/4 lesions, assisting in clinical decision-making to avoid unnecessary biopsies. 30 patients diagnosed with PI-RADS 3/4 lesions through mpMRI underwent [18F]DCFPyL PET/CT imaging, with final biopsy pathology results as the "reference standard". Diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, evaluating the diagnostic efficacy of molecular imaging PSMA (miPSMA) visual analysis and semi-quantitative analysis in [18F]DCFPyL PET/CT imaging. Lesions were assigned miPSMA scores according to the prostate cancer molecular imaging standardized evaluation criteria. Among the 30 patients, 13 were pathologically confirmed to have prostate cancer. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis in [18F]DCFPyL PET/CT imaging for diagnosing PI-RADS 3/4 lesions were 61.5%, 88.2%, 80.0%, 75.0%, and 76.5%, respectively. Using SUVmax 4.17 as the optimal threshold, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis were 92.3%, 88.2%, 85.7%, 93.8%, and 90.0%, respectively. The area under the ROC curve (AUC) for semi-quantitative analysis was 0.94, significantly higher than visual analysis at 0.80. [18F]DCFPyL PET/CT imaging accurately diagnosed benign lesions in 15 (50%) of the PI-RADS 3/4 patients. For patients with PI-RADS 4 lesions, the positive predictive value of [18F]DCFPyL PET/CT imaging reached 100%. [18F]DCFPyL PET/CT imaging provides potential preoperative prediction of lesion nature in mpMRI PI-RADS 3/4 patients, which may aid in treatment decision-making and reducing unnecessary biopsies.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Pessoa de Meia-Idade , Biópsia , Ureia/análogos & derivados , Lisina/análogos & derivados , Próstata/patologia , Próstata/diagnóstico por imagem , Radioisótopos de Flúor , Curva ROC
6.
Clin Exp Dent Res ; 10(4): e916, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38970227

RESUMO

OBJECTIVES: This study assessed the effects of 15% and 20% carbamide peroxide (CP) on color, surface roughness, and hardness of computer-aided design/computer-aided manufacturing (CAD/CAM) dental ceramics. MATERIALS AND METHODS: This in vitro study was conducted on 120 Vita Mark II, Celtra Duo, and Suprinity CAD/CAM ceramic specimens. The ceramic specimens in each group (n = 40) were randomly assigned to two subgroups (n = 20) for polishing and glazing, and their baseline color, surface roughness (Ra), and hardness were assessed. In each subgroup, half of the specimens were exposed to 15% CP, while the other half were exposed to 20% CP. Their color change (ΔE), surface roughness, and hardness were then measured again. Surface roughness, hardness, and color were analyzed sequentially by profilometer, Vickers hardness tester, and spectrophotometer, respectively. Data were analyzed by repeated measures ANOVA, one-way ANOVA, and post hoc Bonferroni test (α = 0.05). RESULTS: The surface roughness of all groups significantly increased after bleaching treatment (p < 0.05). Surface hardness of all groups decreased after bleaching treatment, but this reduction was only significant in Vita Mark II subgroups (glazed, polished, 15%, and 20% CP). The ΔE was not clinically and visually perceivable in any group. CONCLUSION: The present results revealed that concentration of CP and type of surface treatment affected the surface properties of CAD/CAM ceramics. Type of surface treatment only affected the surface hardness of Vita Mark II ceramics (p < 0.05). Concentration of CP had a significant effect only on polished Vita Mark II.


Assuntos
Peróxido de Carbamida , Cerâmica , Cor , Desenho Assistido por Computador , Dureza , Teste de Materiais , Peróxidos , Propriedades de Superfície , Peróxido de Carbamida/química , Propriedades de Superfície/efeitos dos fármacos , Dureza/efeitos dos fármacos , Cerâmica/química , Peróxidos/química , Porcelana Dentária/química , Ureia/química , Ureia/análogos & derivados , Ureia/farmacologia , Clareadores Dentários/química , Humanos , Técnicas In Vitro , Materiais Dentários/química , Espectrofotometria
7.
Molecules ; 29(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38998913

RESUMO

This study explored the potential of a series of PZM21 analogues for pain treatment. Specifically, the hydroxyphenyl ring of PZM21 was replaced with a naphthyl ring, the thienyl ring was substituted with either a phenyl ring or furan rings, and the essential dimethylamine and urea groups were retained. These compounds aimed to enhance safety and minimize the adverse effects associated with opioid drugs. The research findings suggest that compound 6a does not induce ß-arrestin recruitment at low-nanomolar concentrations but exhibits significant analgesic effects in established mouse models. Compared to morphine, 6a shows advantages in alleviating respiratory depression and minimizing physical dependence. Molecular docking studies underscore the pivotal role of the D147 amino acid residue in the analgesic mechanism of 6a. Consequently, 6a is a compelling candidate for the development of safer opioid analgesics and warrants further attention.


Assuntos
Analgésicos Opioides , Simulação de Acoplamento Molecular , Receptores Opioides mu , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Animais , Camundongos , Analgésicos Opioides/farmacologia , Analgésicos Opioides/química , Analgésicos Opioides/síntese química , Humanos , Relação Estrutura-Atividade , Dor/tratamento farmacológico , Masculino , Estrutura Molecular , Tiofenos , Ureia/análogos & derivados
8.
Molecules ; 29(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38998987

RESUMO

The inhibition of soluble epoxide hydrolase (sEH) can reduce the level of dihydroxyeicosatrienoic acids (DHETs) effectively maintaining endogenous epoxyeicosatrienoic acids (EETs) levels, resulting in the amelioration of inflammation and pain. Consequently, the development of sEH inhibitors has been a prominent research area for over two decades. In the present study, we synthesized and evaluated sulfonyl urea derivatives for their potential to inhibit sEH. These compounds underwent extensive in vitro investigation, revealing their potency against human and mouse sEH, with 4f showing the most promising sEH inhibitory potential. When subjected to lipopolysaccharide (LPS)-induced acute lung injury (ALI) in studies in mice, compound 4f manifested promising anti-inflammatory efficacy. We investigated the analgesic efficacy of sEH inhibitor 4f in a murine pain model of tail-flick reflex. These results validate the role of sEH inhibition in inflammatory diseases and pave the way for the rational design and optimization of sEH inhibitors based on a sulfonyl urea template.


Assuntos
Inibidores Enzimáticos , Epóxido Hidrolases , Ureia , Epóxido Hidrolases/antagonistas & inibidores , Epóxido Hidrolases/metabolismo , Animais , Camundongos , Humanos , Ureia/farmacologia , Ureia/análogos & derivados , Ureia/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/uso terapêutico , Lipopolissacarídeos , Relação Estrutura-Atividade , Solubilidade , Modelos Animais de Doenças , Dor/tratamento farmacológico
9.
Med ; 5(7): 655-659, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39002536

RESUMO

A key area of therapeutic progress in obstructive hypertrophic cardiomyopathy revolves around the emergence of cardiac myosin inhibitors, of which mavacamten and aficamten represent the first and second molecules. We summarize the key research evidence, including many similarities and potential differences between various clinical trials studying these molecules.


Assuntos
Miosinas Cardíacas , Cardiomiopatia Hipertrófica , Humanos , Cardiomiopatia Hipertrófica/tratamento farmacológico , Miosinas Cardíacas/metabolismo , Barbitúricos/uso terapêutico , Ureia/análogos & derivados , Ureia/uso terapêutico , Ureia/farmacologia , Uracila/análogos & derivados , Uracila/uso terapêutico , Uracila/farmacologia , Benzilaminas/uso terapêutico , Ensaios Clínicos como Assunto
10.
Sci Rep ; 14(1): 14658, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918518

RESUMO

Previous published data have confirmed that the addition of a citric acid meal improves the accuracy of the 13C-urea breath test (13C-UBT). However, some studies have suggested that a citric acid test meal may not be necessary. Thus, the aim of this study was to evaluate the combination of a 13C-UBT with a citric acid meal for the diagnosis of Helicobacter pylori (Hp) infection in a Chinese population, particularly for patients with results in the gray zone. In this paired self-controlled study, all subjects had previously undergone 13C-UBTs without citric acid meals and were randomly divided into two groups based on different doses of citric acid (a low-dose citric acid group and a high-dose citric acid group, comprising meals with 0.68 g and 3.84 g citric acid powder, respectively). Positive rapid urease test (CLO) test and histology results were considered the 'gold standard'. The mean delta over baseline (DOB) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were compared between the two groups, particularly for patients with results in the gray zone. In total, 285 patients were tested. Of these patients, 189 were included in the low-dose citric acid group, and 96 were included in the high-dose citric acid group. Among patients with a positive 13C-UBT result without citric acid [delta over baseline (DOB) value ≥ 4‰, n = 174] and a negative 13C-UBT result without citric acid (DOB value < 4‰, n = 111), 8.0% (14/174) were false positive, and 0.9% (1/111) was false negative as determined by gold standard. Of 14 patients with false positive, 78.6% (11/14) false positive were in the gray zone of 4-10‰. However, there were no false positive 13C-UBT results with citric acid in the the gray zone of 4-10‰. In the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, NPV and accuracy at 15 min were as follows: 99.1% vs. 99.1%, 97.5% vs. 88.9%, 98.2% vs. 92.2%, 98.8% vs. 98.6% and 98.4% vs. 94.7%, respectively. In the the gray zone of 4.0-10.0‰, the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, and accuracy at 15 min were as follows: 94.4% vs. 100.0%, 100.0% vs. 0%, 100.0% vs. 75.0% and 95.8% vs. 75.0%, respectively. No significant difference was observed between the 15-min and 30-min measurement intervals in the low- and high-dose citric acid groups, including patients with results in the gray zone. The low-dose citric acid test, with an optimal measurement interval of 15 min, was highly accurate in the diagnosis of Hp infection in the Chinese population, especially for individuals with results in the gray zone.


Assuntos
Testes Respiratórios , Isótopos de Carbono , Ácido Cítrico , Infecções por Helicobacter , Helicobacter pylori , Ureia , Humanos , Testes Respiratórios/métodos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Masculino , Feminino , Ureia/análise , Pessoa de Meia-Idade , Adulto , China , Idoso , Sensibilidade e Especificidade , População do Leste Asiático
11.
Cells ; 13(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38920664

RESUMO

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce the risk of end-stage liver diseases to the level observed in patients who have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here, we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to the accumulation of arginine, and up-regulates proline oxidase with a concomitant decrease in proline concentrations. The addition of exogenous proline moderately suppressed viral replication. HCV up-regulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity, pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV's imprint on cell metabolism.


Assuntos
Hepacivirus , Poliaminas , Prolina , Ureia , Replicação Viral , Prolina/metabolismo , Humanos , Hepacivirus/fisiologia , Hepacivirus/efeitos dos fármacos , Poliaminas/metabolismo , Ureia/metabolismo , Ureia/farmacologia , Replicação Viral/efeitos dos fármacos , Arginase/metabolismo , Antivirais/farmacologia , Antivirais/metabolismo , Hepatite C/metabolismo , Hepatite C/virologia , Linhagem Celular Tumoral , Prolina Oxidase/metabolismo
12.
J Drugs Dermatol ; 23(6): 466-471, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38834224

RESUMO

Xerosis is experienced by almost everyone at some time in their lives and the foundation of management of dry skin (both consumer- and healthcare professional--directed) rests on the use of moisturizers. Given the wide range of available moisturizers, counseling patients about selecting the optimum moisturizer for their individual situation relies on knowledge of ingredients and formulations. Traditionally, the main focus for many moisturizers centered on the core functional and structural role of ceramides within the epidermal barrier.  However, while a key aspect of transepidermal water loss and other skin barrier functions, components other than ceramides are equally essential in increasing moisturization. The skin's natural moisturizing factors (NMFs) are a complex mixture of water-attracting compounds such as amino acids, urea, lactate, pyrrolidone carboxylic acid (PCA), and electrolytes which play a fundamental role in preserving physiologic function by regulating the water content of the stratum corneum. By facilitating water retention, NMFs contribute significantly to the suppleness, elasticity, normal desquamation, and overall integrity of the skin barrier. Incorporation of NMFs into moisturizers addresses critical deficiencies in the skin's moisture balance that exist in xerotic and atopic skin, and in many skin disorders, mitigating signs and symptoms associated with xerosis and promoting optimal skin health. The biochemical composition of NMFs and the intricate interplay with epidermal homeostasis translate to a central role in moisturizers used for prophylactic and therapeutic management of various dry skin conditions, beyond ceramides alone. J Drugs Dermatol. 2024;23(6):466-471.     doi:10.36849/JDD.8358.


Assuntos
Ceramidas , Emolientes , Perda Insensível de Água , Humanos , Ceramidas/administração & dosagem , Perda Insensível de Água/efeitos dos fármacos , Emolientes/administração & dosagem , Creme para a Pele/administração & dosagem , Administração Cutânea , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Epiderme/fisiologia , Ureia/administração & dosagem
14.
Asian Pac J Cancer Prev ; 25(6): 2203-2210, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38918684

RESUMO

INTRODUCTION: Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively co-prescribed, even though its efficacy is doubtful. Aloe vera gel with urea cream might potentiate each other. This trial was intended to prove the efficacy of this combination. MATERIALS AND METHODS: The investigators conducted a randomized single-blinded phase II study. The participants were randomized 1:1 to receive the combination of aloe vera gel and 10% urea cream (n = 30), the experimental A+U arm and 10% urea cream alone (n = 31), the U arm. The sample size was calculated to have 90% power to show the significant 20% reduction in the incidence of HFS grade 2-3 of the combination therapy with alpha level = 0.05. Both the CTCAE criteria version 5 and the dermatology life quality index (DLQI) were assessed to determine the severity of HFS and quality of life, respectively. RESULTS: Most of the participants had rectal cancer (A+U: 43.3%; U: 41.9%). In the A+U group, 86.7% had grade 0-1 HFS and 13.3% had grade 2-3 HFS. In the U group, 64.5% had grade 0-1 HFS and 35.5% had grade 2-3 HFS (Mann-Whitney U test, p = 0.045). Grade 2-3 HFS was significantly lower in the combination group. CONCLUSION: Combination of aloe vera gel and 10% urea cream ameliorated the severity of HFS in participants taking capecitabine; however, no significant difference in DLQI between the groups was demonstrated.


Assuntos
Antimetabólitos Antineoplásicos , Capecitabina , Síndrome Mão-Pé , Qualidade de Vida , Ureia , Humanos , Capecitabina/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/prevenção & controle , Ureia/análogos & derivados , Ureia/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Método Simples-Cego , Preparações de Plantas/uso terapêutico , Preparações de Plantas/administração & dosagem , Prognóstico , Seguimentos , Adulto , Administração Tópica , Idoso , Neoplasias/tratamento farmacológico , Creme para a Pele , Aloe
15.
Biochem Med (Zagreb) ; 34(2): 020707, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882581

RESUMO

Introduction: We compared the quality control efficiency of artificial intelligence-patient-based real-time quality control (AI-PBRTQC) and traditional PBRTQC in laboratories to create favorable conditions for the broader application of PBRTQC in clinical laboratories. Materials and methods: In the present study, the data of patients with total thyroxine (TT4), anti-Müllerian hormone (AMH), alanine aminotransferase (ALT), total cholesterol (TC), urea, and albumin (ALB) over five months were categorized into two groups: AI-PBRTQC group and traditional PBRTQC group. The Box-Cox transformation method estimated truncation ranges in the conventional PBRTQC group. In contrast, in the AI-PBRTQC group, the PBRTQC software platform intelligently selected the truncation ranges. We developed various validation models by incorporating different weighting factors, denoted as λ. Error detection, false positive rate, false negative rate, average number of the patient sample until error detection, and area under the curve were employed to evaluate the optimal PBRTQC model in this study. This study provides evidence of the effectiveness of AI-PBRTQC in identifying quality risks by analyzing quality risk cases. Results: The optimal parameter setting scheme for PBRTQC is TT4 (78-186), λ = 0.03; AMH (0.02-2.96), λ = 0.02; ALT (10-25), λ = 0.02; TC (2.84-5.87), λ = 0.02; urea (3.5-6.6), λ = 0.02; ALB (43-52), λ = 0.05. Conclusions: The AI-PBRTQC group was more efficient in identifying quality risks than the conventional PBRTQC. AI-PBRTQC can also effectively identify quality risks in a small number of samples. AI-PBRTQC can be used to determine quality risks in both biochemistry and immunology analytes. AI-PBRTQC identifies quality risks such as reagent calibration, onboard time, and brand changes.


Assuntos
Controle de Qualidade , Humanos , Inteligência Artificial , Tiroxina/sangue , Hormônio Antimülleriano/sangue , Alanina Transaminase/sangue , Colesterol/sangue , Ureia/sangue , Laboratórios Clínicos
16.
Chem Biol Drug Des ; 103(6): e14569, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38877369

RESUMO

Staphylococcus aureus has the ability to invade cortical bone osteocyte lacuno-canalicular networks (OLCNs) and cause osteomyelitis. It was recently established that the cell wall transpeptidase, penicillin-binding protein 4 (PBP4), is crucial for this function, with pbp4 deletion strains unable to invade OLCNs and cause bone pathogenesis in a murine model of S. aureus osteomyelitis. Moreover, PBP4 has recently been found to modulate S. aureus resistance to ß-lactam antibiotics. As such, small molecule inhibitors of S. aureus PBP4 may represent dual functional antimicrobial agents that limit osteomyelitis and/or reverse antibiotic resistance. A high throughput screen recently revealed that the phenyl-urea 1 targets PBP4. Herein, we describe a structure-activity relationship (SAR) study on 1. Leveraging in silico docking and modeling, a set of analogs was synthesized and assessed for PBP4 inhibitory activities. Results revealed a preliminary SAR and identified lead compounds with enhanced binding to PBP4, more potent antibiotic resistance reversal, and diminished PBP4 cell wall transpeptidase activity in comparison to 1.


Assuntos
Antibacterianos , Simulação de Acoplamento Molecular , Proteínas de Ligação às Penicilinas , Staphylococcus aureus , Proteínas de Ligação às Penicilinas/metabolismo , Proteínas de Ligação às Penicilinas/antagonistas & inibidores , Antibacterianos/farmacologia , Antibacterianos/química , Relação Estrutura-Atividade , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Ureia/química , Ureia/farmacologia , Ureia/análogos & derivados , Animais , Camundongos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores
18.
Nat Commun ; 15(1): 4885, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849353

RESUMO

Inherited cardiomyopathies are common cardiac diseases worldwide, leading in the late stage to heart failure and death. The most promising treatments against these diseases are small molecules directly modulating the force produced by ß-cardiac myosin, the molecular motor driving heart contraction. Omecamtiv mecarbil and Mavacamten are two such molecules that completed phase 3 clinical trials, and the inhibitor Mavacamten is now approved by the FDA. In contrast to Mavacamten, Omecamtiv mecarbil acts as an activator of cardiac contractility. Here, we reveal by X-ray crystallography that both drugs target the same pocket and stabilize a pre-stroke structural state, with only few local differences. All-atom molecular dynamics simulations reveal how these molecules produce distinct effects in motor allostery thus impacting force production in opposite way. Altogether, our results provide the framework for rational drug development for the purpose of personalized medicine.


Assuntos
Simulação de Dinâmica Molecular , Contração Miocárdica , Ureia , Contração Miocárdica/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Ureia/análogos & derivados , Ureia/farmacologia , Ureia/química , Miosinas Cardíacas/metabolismo , Miosinas Cardíacas/química , Miosinas Cardíacas/genética , Miosinas Ventriculares/metabolismo , Miosinas Ventriculares/química , Miosinas Ventriculares/genética , Animais , Benzilaminas , Uracila/análogos & derivados
19.
Clin Genitourin Cancer ; 22(4): 102108, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38843766

RESUMO

PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.


Assuntos
Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prostatectomia , Neoplasias da Próstata , Terapia de Salvação , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Estudos Retrospectivos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Fatores de Risco , Metástase Linfática , Pelve/diagnóstico por imagem , Pelve/efeitos da radiação , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/efeitos da radiação , Lisina/análogos & derivados , Ureia/análogos & derivados
20.
Phytomedicine ; 131: 155751, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38852476

RESUMO

BACKGROUND: Moringa oleifera leaves are rich in bioactive substances. PURPOSE: The purpose of this study was to evaluate the effects of Moringa oleifera leaf aqueous extract supplements on energy metabolism and antioxidant function in young male adults. METHODS: Forty-four young male adults (26.3 ± 3.5 years) were randomly assigned to two groups: a supplement group (n = 23) receiving aqueous extract of Moringa oleifera leaves and a placebo group (n = 21). The supplementation period lasted for 30 days. Baseline measurements were taken at the beginning of the study, and further measurements were taken at the end of the supplementation period. Changes in upper- and lower-body strength, treadmill endurance, and certain blood biochemical parameters were evaluated. RESULTS: After 30 days of supplementation, participants in the supplement group exhibited enhanced performance in push-ups and treadmill exhaustion tests compared to the placebo group. Levels of glucose, urea, malondialdehyde, and glutathione peroxidase activity in serum were also improved in the supplement group. CONCLUSION: The findings suggest that Moringa oleifera leaf aqueous extracts have the potential to improve post-exercise energy metabolism and antioxidant function in young male adults.


Assuntos
Antioxidantes , Metabolismo Energético , Moringa oleifera , Extratos Vegetais , Folhas de Planta , Humanos , Moringa oleifera/química , Masculino , Extratos Vegetais/farmacologia , Adulto , Folhas de Planta/química , Antioxidantes/farmacologia , Projetos Piloto , Adulto Jovem , Metabolismo Energético/efeitos dos fármacos , Suplementos Nutricionais , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Malondialdeído/sangue , Exercício Físico , Glicemia/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Ureia/sangue , Teste de Esforço , Método Duplo-Cego
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