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1.
Health Qual Life Outcomes ; 21(1): 87, 2023 Aug 11.
Article in English | MEDLINE | ID: mdl-37568236

ABSTRACT

BACKGROUND: In Brazil, cancer patients and caregivers of cancer patients seek judicial intervention for free access to medications from the public health system. Indeed, the COVID-19 pandemic potentially affected the health-related quality of life of cancer patients and caregivers of cancer patients. This study aimed to describe the sociodemographic profile and assess the health-related quality of life of patients and caregivers in the state of Goias, Brazil, in 2020. METHODS: A cross-sectional study was conducted using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and a sociodemographic questionnaire. RESULTS: A total of 88 (67,7%) patients and 42 (32,3%) caregivers participated in the study, mostly women (55,5%); aged from 18 to 60 (66%) years old; with up to nine years of education (73,1%) and monthly family income lower than the minimum wage (69,2%); married or in a stable union (92,3%); living with multiple people in the same household (73,8%). The quality of life domains with the best scores were mental health for patients and pain for caregivers. The most affected quality of life domain was physical limitation for patients and caregivers. Factors associated with better quality of life were female gender and age between 18 and 60 years in patients, more than 9 years of education, living with multiple people in the same house, and having a monthly family income higher than US$200 for caregivers. CONCLUSION: The study found evidence of physical and emotional vulnerability during the pandemic, highlighting the need to strengthen public policies of assistance support to this population.


Subject(s)
COVID-19 , Neoplasms , Humans , Female , Adolescent , Young Adult , Adult , Middle Aged , Male , Quality of Life/psychology , Pandemics , Caregivers/psychology , Cross-Sectional Studies , COVID-19/epidemiology
2.
Int J Equity Health ; 21(1): 112, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35978319

ABSTRACT

BACKGROUND: The significant increase in access to oncological medicines through court cases suggests that constitutional guarantees of integral and universal care in the Brazilian public health system are uncertain. METHODS: A retrospective observational study was conducted to analyze data from lawsuits requesting oncological medicines from 2014 to 2020 in the State of Goiás, Brazil, in state and federal courts. Sociodemographic, medical, and legal variables were statistically examined using descriptive, association, and correlation methods. RESULTS: Women brought more than half (54%) of the 301 processes analyzed. The most frequent age group was over 55 years, with income below 3 × the minimum wage (total about USD$600/month), and their cases were promoted through the public minister and public defender's offices. The most requested medications, not on official public health system lists, were indicated for multiple myeloma and brain cancer. CONCLUSIONS: Improved quality of life, frequently used as a justification, could be conceptually confused with increased survival. Finally, judicialization itself indicates that individual health needs arise even with properly defined and adequately implemented public policies. These needs should be considered for the adequate provisioning of services by the state to ensure the right to health.


Subject(s)
Drugs, Essential , Health Policy , Brazil , Female , Health Services Accessibility , Humans , Middle Aged , Quality of Life
3.
Sensors (Basel) ; 22(6)2022 Mar 11.
Article in English | MEDLINE | ID: mdl-35336353

ABSTRACT

Respiratory diseases are one of the most common causes of death in the world and this recent COVID-19 pandemic is a key example. Problems such as infections, in general, affect many people and depending on the form of transmission they can spread throughout the world and weaken thousands of people. Two examples are severe acute respiratory syndrome and the recent coronavirus disease. These diseases have mild and severe forms, in which patients gravely affected need ventilatory support. The equipment that serves as a basis for operation of the mechanical ventilator is the air-oxygen blender, responsible for carrying out the air-oxygen mixture in the proper proportions ensuring constant supply. New blender models are described in the literature together with applications of control techniques, such as Proportional, Integrative and Derivative (PID); Fuzzy; and Adaptive. The results obtained from the literature show a significant improvement in patient care when using automatic controls instead of manual adjustment, increasing the safety and accuracy of the treatment. This study presents a deep review of the state of the art in air-oxygen benders, identifies the most relevant characteristics, performs a comparison study considering the most relevant available solutions, and identifies open research directions in the topic.


Subject(s)
COVID-19 , Oxygen , COVID-19/therapy , Humans , Oxygen/therapeutic use , Pandemics , Ventilators, Mechanical
4.
Pharmacol Res ; 167: 105525, 2021 05.
Article in English | MEDLINE | ID: mdl-33667686

ABSTRACT

Natural biflavonoids, such as amentoflavone, bilobetin, ginkgetin, isoginkgetin, taiwaniaflavone, morelloflavone, delicaflavone, hinokiflavone, and other derivatives (~ 40 biflavonoids), are isolated from Selaginella sp., Ginkgo biloba, Garcinia sp., and several other species of plants. They are able to exert therapeutic benefits by regulating several proteins/enzymes (PPAR-γ, CCAAT/enhancer-binding protein α [C/EBPα], STAT5, pancreatic lipase, PTP1B, fatty acid synthase, α-glucosidase [AG]) and insulin signaling pathways (via PI3K-AKT), which are linked to metabolism, cell growth, and cell survival mechanisms. Deregulated insulin signaling can cause complications of obesity and diabetes, which can lead to cognitive disorders such as Alzheimer's, Parkinson's, and dementia; therefore, the therapeutic benefits of these biflavones in these areas are highlighted. Since biflavonoids have shown potential to regulate metabolism, growth- and survival-related protein/enzymes, their relation to tumor growth and metastasis of cancer associated with angiogenesis are highlighted. The translational role of biflavones in cancer with respect to the inhibition of metabolism-related processes/pathways, enzymes, or proteins, such as STAT3/SHP-1/PTEN, kinesins, tissue kallikreins, aromatase, estrogen, protein modifiers, antioxidant, autophagy, and apoptosis induction mechanisms, are discussed. Finally, considering their observed bioactivity potential, oral bioavailability studies of biflavones and related clinical trials are outlined.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Biflavonoids/therapeutic use , Metabolic Diseases/drug therapy , Neoplasms/drug therapy , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Biflavonoids/pharmacology , Humans , Metabolic Diseases/metabolism , Metabolic Networks and Pathways/drug effects , Neoplasms/metabolism
5.
Clin Oral Investig ; 25(3): 1513-1524, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32696210

ABSTRACT

OBJECTIVE: This randomized clinical trial evaluated the survival of direct restorations on first permanent molars (FPMs) with molar incisor hypomineralization (MIH) and its impact on self-reported dental pain and dental anxiety. MATERIAL AND METHOD: FPMs with MIH of 35 patients aged 7 to 16 years were included. The FPMs were randomized into the following two groups: total-etch (TE-37% phosphoric acid etching) and self-etch (SE-no prior etching). The FPMs were restored with universal adhesive and bulk-fill resin composites. The restoration survival was evaluated according to USPHS criteria modified by a blinded examiner. Dental anxiety (Venham picture test) and dental pain (Faces pain scale-revised) were evaluated before treatment and at 1, 6, and 12 months post-treatment. Survival rates were analyzed by the Kaplan-Meier method and the log-rank test. Nonparametric tests compared pain and anxiety in the follow-up periods. RESULTS: A total of 64 FPMs were restored (TE = 33; SE = 31). Survival rates were 96.9% (TE) and 96.7% (SE) after 1 month, 90.5% (TE) and 80.6% (SE) after 6 months, and 80.8% (TE) and 62.3% (SE) after 12 months (p > 0.05). Self-reported dental pain and anxiety level decreased after treatment in both groups (p < 0.05). Self-reported pain decreased after 1 month in SE, but it occurred at 6 months in TE. CONCLUSION: Both restorative protocols presented similar longevity, decreasing self-reported pain and anxiety levels. CLINICAL RELEVANCE: A universal adhesive could be appropriate for restoration of MIH-affected teeth, and the survival of restorations could be higher in the total-etch technique, reducing dental pain and anxiety.


Subject(s)
Dental Enamel Hypoplasia , Dental Restoration, Permanent , Adolescent , Child , Composite Resins , Dental Cements , Humans , Molar
6.
Dent Traumatol ; 37(4): 647-652, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33547850

ABSTRACT

This report describes the unexpected formation of root-like structures following the avulsion of immature permanent teeth without replantation. A 6-year-old female patient had avulsed the four permanent mandibular incisors and the two deciduous mandibular canines. The patient was seen in an emergency healthcare unit but did not receive specialized treatment for tooth replantation. As follow-up treatment, she received a removable prosthesis. After 4 years of follow-up, an image obtained by panoramic radiography showed formations similar to four root structures in the alveolus of the previously avulsed permanent teeth. This finding was confirmed by periapical radiography and computed tomography. This case report demonstrates that in teeth with incomplete root development, even after avulsion without replantation, cells from the pulp stump may have the capacity to form mineralized structures that appear radiographically comparable to root dentin.


Subject(s)
Tooth Avulsion , Child , Dental Pulp Necrosis , Dentition, Permanent , Female , Humans , Incisor/diagnostic imaging , Tooth Avulsion/diagnostic imaging , Tooth Replantation
7.
AAPS PharmSciTech ; 22(3): 128, 2021 Apr 09.
Article in English | MEDLINE | ID: mdl-33835304

ABSTRACT

The adoption of Quality by Design (QbD) and Analytical Method Lifecycle Management (AMLM) concepts to ensure the quality of pharmaceutical products has been applied and proposed over the last few years. These concepts are based on knowledge gained from the application of scientific and quality risk management approaches, throughout method lifecycle to assure continuous improvement and high reliability of analytical results. The overall AMLM starts with the definition of the method's intended use through the Analytical Target Profile definition, including three stages: (1) Method Design, taking advantage of the well-known concept of QbD; (2) Method Performance Qualification; (3) Continued Method Performance Verification. This is intended to holistically align method variability with product requirements, increasing confidence in the data generated, a regulatory requirement that the pharmaceutical industry must follow. This approach views all method-related activities, such as development, validation, transfer, and routine use as a continuum and interrelated process, where knowledge and risk management are the key enablers. An increase in method robustness, cost reduction, and decreased risk failures are some of the intrinsic benefits from this lifecycle management. This approach is clearly acknowledged both by regulators and industry. The roadmap of the regulatory and industry events that mark the evolution of these concepts helps to capture the current and future expectation of the pharmaceutical framework.


Subject(s)
Drug Industry/standards , Pharmaceutical Preparations/analysis , Chemistry, Pharmaceutical , Drug Design , Drug Industry/trends , Humans , Quality Control
8.
Int J Paediatr Dent ; 30(4): 436-444, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31900956

ABSTRACT

BACKGROUND: Pain is a major consequence of caries, which negatively impacts the quality of life of children and their families. AIM: To analyse the parental report of dental pain and discomfort in preschool children, and to identify clinical and sociodemographic factors associated. DESIGN: This cross-sectional study involved 375 four- and five-year-old preschoolers enrolled in the city of Campo Magro public school system, along with their parents and caregivers. Parents/caregivers answered the Brazilian version of the Dental Discomfort Questionnaire (DDQ-B) and a sociodemographic questionnaire. Two examiners (kappa > 0.79) performed clinical examinations using dmf-t and pufa index. The associations were statistically analysed by univariate and multiple Poisson regression with robust variance (α = 0.05). RESULTS: The prevalence of dental pain and discomfort was 70.3% (66%-75% 95% CI). Children from non-nuclear families (PRa 1.33; 95% CI: 1.01-1.76) and whose parents presented a lower level of education (PRa 2.43; 95% CI 1.66-3.55) presented a higher prevalence of dental pain or discomfort. Considering the clinical determinants, after adjusting, only the presence of clinical consequences of untreated dental caries (pufa ≥ 1) (PRa 1.37; 95% CI 1.02-1.84) was significantly associated with higher dental pain or discomfort. CONCLUSIONS: Dental pain and discomfort were associated with socioeconomic factors and with the presence of clinical consequences of untreated dental caries.


Subject(s)
Dental Caries , Brazil , Child, Preschool , Cross-Sectional Studies , Humans , Parents , Prevalence , Quality of Life , Surveys and Questionnaires
9.
Int J Paediatr Dent ; 29(4): 496-506, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30758096

ABSTRACT

BACKGROUND: Molar incisor hypomineralization (MIH) is associated with unfavourable dental conditions such as dental caries and may consequently impact oral health-related quality of life (OHRQoL). OBJECTIVE: To assess the impact of MIH on OHRQoL in children with early mixed dentition. METHOD: A population-based cross-sectional study of 728 8-year-old children from the public school system in Curitiba, Brazil, was conducted. The Child Perception Questionnaire for 8- to 10-year-olds (CPQ8-10 ) was used to evaluate OHRQoL. MIH was diagnosed according to the European Academy of Paediatric Dentistry (EAPD) criteria. The assessments of MIH, dental caries, and malocclusion were performed by four calibrated examiners (κ ≥ 0.80). Demographic and socioeconomic data (DSE) were obtained from the children's parents/caregivers using a structured questionnaire. The analysis of OHRQoL determinants was performed through a three-level hierarchical approach: mesial (DSE), intermediate (clinical conditions), and distal (child's oral self-perception), using Poisson regression with robust variance (α = 0.05). RESULTS: The prevalence of MIH was 12.1% (95% CI: 10-15). An association was found between MIH and OHRQoL in the "oral symptoms" domain of the CPQ8-10 (PR: 1.07, 95% CI: 1.03-1.11, P < 0.001) after adjusting for other clinical variables and DSE. CONCLUSION: Molar incisor hypomineralization was associated with a greater impact on OHRQoL in children's oral symptoms.


Subject(s)
Dental Caries , Dental Enamel Hypoplasia , Brazil , Child , Cross-Sectional Studies , Dentition, Mixed , Humans , Prevalence , Quality of Life
10.
Int J Paediatr Dent ; 29(5): 615-623, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31009135

ABSTRACT

BACKGROUND: Identifying patients with high levels of DA helps to define the most adequate oral healthcare strategy, especially for pediatric patients. AIM: To investigate the association between parental reports of dental anxiety (DA) and molar incisor hypomineralization (MIH) in schoolchildren. DESIGN: A cross-sectional study was conducted in a representative sample of 731 8-year-old schoolchildren from the city of Curitiba, Brazil, who were clinically examined (k ≥ 0.75) for the diagnosis of MIH and dental caries using the EAPD criteria and dmft/DMFT index, respectively. Parents/guardians reported children's DA using the Dental Anxiety Question (DAQ) and answered a self-administered structured questionnaire addressing socioeconomic and demographic characteristics. Associations were evaluated using Poisson regression analysis with robust variance (P < 0.05). RESULTS: A significant association was found between DA and MIH (PR = 1.20; 95%CI: 1.01-1.42; P = 0.038), but this association lost its significance when adjusted for the other characteristics (PR = 1.13; 95%CI: 0.93-1.38; P = 0.215). Caries experience in primary teeth was associated with lower levels of DA (PR = 0.83; 95%CI: 0.71-0.96; P = 0.0013). The most recent visit to the dentist due to pain increased the levels of DA (PR = 1.18; 95%CI: 1.07-1.30; P = 0.001). CONCLUSIONS: The presence of MIH in schoolchildren was not associated with parental reports of DA.


Subject(s)
Dental Caries , Dental Enamel Hypoplasia , Brazil , Child , Cross-Sectional Studies , Dental Anxiety , Humans , Incisor , Molar , Prevalence
11.
Crit Rev Food Sci Nutr ; 56 Suppl 1: S4-S28, 2016 Jul 29.
Article in English | MEDLINE | ID: mdl-26463658

ABSTRACT

Flavonoids and their derivatives are polyphenolic secondary metabolites with an extensive spectrum of pharmacological activities, including antioxidants, antitumor, anti-inflammatory, and antiviral activities. These flavonoids can also act as chemopreventive agents by their interaction with different proteins and can play a vital role in chemotherapy, suggesting a positive correlation between a lower risk of cancer and a flavonoid-rich diet. These agents interfere with the main hallmarks of cancer by various individual mechanisms, such as inhibition of cell growth and proliferation by arresting the cell cycle, induction of apoptosis and differentiation, or a combination of these mechanisms. This review is an effort to highlight the therapeutic potential of natural and synthetic flavonoids as anticancer agents in leukemia treatment with respect to the structure-activity relationship (SAR) and their molecular mechanisms. Induction of cell death mechanisms, production of reactive oxygen species, and drug resistance mechanisms, including p-glycoprotein efflux, are among the best-described effects triggered by the flavonoid polyphenol family.


Subject(s)
Antineoplastic Agents/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Leukemia/drug therapy , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Line, Tumor , Clinical Trials as Topic , Diet , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Promyelocytic, Acute/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Structure-Activity Relationship
12.
Photochem Photobiol Sci ; 14(4): 757-64, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25620620

ABSTRACT

A metal complex 1 derivative from a coumarin bearing a porphyrin unit was spectroscopically characterized and its sensing ability towards the alkaloids caffeine 2, nicotine 3 and cotinine 4 was evaluated in these studies. This probe shows to be sensitive to the alkaloids studied, where a detectable amount of 2.5 ± 0.3 µM of cotinine was determined in dam water from the Vigia Dam located in the Montoito village region, Alentejo district, Portugal. The interaction of 1 with cotinine was also verified by MALDI-TOF-MS, where it was found with peaks at 877.2 and 1053.3 m/z corresponding to the species [1H](+) and [1CotinineH](+), respectively.


Subject(s)
Caffeine/chemistry , Cotinine/chemistry , Coumarins/chemistry , Fresh Water/chemistry , Nicotine/chemistry , Porphyrins/chemistry , Zinc/chemistry , Ethanol/chemistry , Molecular Structure , Photochemical Processes , Portugal , Solutions , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Spectrum Analysis , Ultraviolet Rays
13.
Chemistry ; 20(42): 13644-55, 2014 Oct 13.
Article in English | MEDLINE | ID: mdl-25171181

ABSTRACT

In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorin e6 trimethyl ester and protoporphyrin IX dimethyl ester dyads as free bases and Zn(II) complexes. The synthesis of these molecules linked at the ß-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels-Alder reaction. The α-methylenechromanes, α-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn(II) complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn(II) complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn(II) complexes were also carried out to gain insights into their behavior for such applications.


Subject(s)
Coordination Complexes/chemical synthesis , Photosensitizing Agents/chemical synthesis , Porphyrins/chemical synthesis , Protoporphyrins/chemical synthesis , Zinc/chemistry , Chlorophyllides , Coordination Complexes/chemistry , Cycloaddition Reaction , Electrochemical Techniques , Methylation , Photosensitizing Agents/chemistry , Porphyrins/chemistry , Protoporphyrins/chemistry , Spectrum Analysis
14.
Bioorg Med Chem Lett ; 24(3): 808-12, 2014 Feb 01.
Article in English | MEDLINE | ID: mdl-24424133

ABSTRACT

Photodynamic inactivation of bioluminescent Escherichia coli in the presence of cationic chlorin and isobacteriochlorin photosensitizers (PSs) obtained from 5,10,15,20-tetrakis(pentafluorophenyl)-porphyrin is described. The spectroscopic data for the neutral and cationic derivatives and their photophysical characterizations, especially fluorescence and singlet oxygen generation capacity are also reported. The results show that there is a direct relation between the inactivation efficiency and the increasing number of charges on the molecules. The combined effect of higher wavelength absorption and number of positive charges on the PS shows a 6.1 log reduction during the inactivation process. Overall this study shows that the cationic isobacteriochlorin has high potential to be used as PS for the inactivation of Gram (-) bacteria.


Subject(s)
Escherichia coli/drug effects , Light , Microbial Viability/drug effects , Porphyrins/chemistry , Porphyrins/pharmacology , Cations , Limit of Detection , Luminescent Proteins , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Pyrrolidines/chemistry , Pyrrolidines/pharmacology
15.
J Appl Oral Sci ; 32: e20230229, 2024.
Article in English | MEDLINE | ID: mdl-38198369

ABSTRACT

AIM: Polymorphisms in the COMT gene can alter enzymatic functions, raising levels of endogenous catecholamines, which stimulates beta-adrenergic receptors related to pain. This study aimed to evaluate whether a polymorphism in the COMT gene (rs4818) is associated with dental pain in children. METHODOLOGY: A cross-sectional study was conducted with a representative sample of 731 pairs of children and parents randomly selected from a population-based sample of eight-year-old children. Reports of dental pain was evaluated using a question directed at the parents and self-reported pain using the Faces Pain Scale - Revised. Dental caries experience was determined using the Decayed, Missing, and Filled Teeth (DMFT) index. For genetic analysis, DNA was obtained from oral mucosa epithelial cells of 352 children randomly selected from the initial sample. RESULTS: Children with the CC genotype had higher odds of reporting moderate to intense pain than those with the GG genotype (OR=3.60; 95% CI=0.80-16.20; p=0.03). These same children had greater odds of parental reports of pain (OR=1.93; 95% CI=0.91-4.08; p=0.02). Moreover, lower schooling of parents/guardians and caries experience in the primary dentition were significantly associated with greater odds of a parental report of dental pain (OR=2.06; 95% CI=1.47-2.91; p<0.001; OR=6.26; 95% CI=4.46-8.78; p<0.001). CONCLUSIONS: The rs4818 polymorphism of the COMT gene is associated with dental pain. Children with the C allele are more likely to report higher levels of pain. Clinical Relevance: Even though the experience of pain is subjective and multifactorial, this study raises the hypothesis that there is a genetic predisposition to dental pain that should be considered in clinical practice.


Subject(s)
Catechol O-Methyltransferase , Dental Caries , Child , Humans , Catechol O-Methyltransferase/genetics , Cross-Sectional Studies , Dental Caries/genetics , Pain , Polymorphism, Genetic
16.
Membranes (Basel) ; 14(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38392670

ABSTRACT

Lysosomal degradation of tyrosinase, a pivotal enzyme in melanin synthesis, negatively impacts melanogenesis in melanocytes. Nevertheless, the precise molecular mechanisms by which lysosomes target tyrosinase have remained elusive. Here, we identify RING (Really Interesting New Gene) finger protein 152 (RNF152) as a membrane-associated ubiquitin ligase specifically targeting tyrosinase for the first time, utilizing AlphaScreen technology. We observed that modulating RNF152 levels in B16 cells, either via overexpression or siRNA knockdown, resulted in decreased or increased levels of both tyrosinase and melanin, respectively. Notably, RNF152 and tyrosinase co-localized at the trans-Golgi network (TGN). However, upon treatment with lysosomal inhibitors, both proteins appeared in the lysosomes, indicating that tyrosinase undergoes RNF152-mediated lysosomal degradation. Through ubiquitination assays, we found the indispensable roles of both the RING and transmembrane (TM) domains of RNF152 in facilitating tyrosinase ubiquitination. In summary, our findings underscore RNF152 as a tyrosinase-specific ubiquitin ligase essential for regulating melanogenesis in melanocytes.

17.
Braz Oral Res ; 38: e052, 2024.
Article in English | MEDLINE | ID: mdl-38922212

ABSTRACT

The aim of this study was to evaluate the impact of oral conditions and health-related quality of life (HRQoL) on oral health-related quality of life (OHRQoL) in children and adolescents with blood coagulation disorders and hemoglobinopathies (BCDH). The study was cross-sectional and included 61 individuals aged 2 to 18 years with BCDH. Exams for dental caries (dmft/DMFT index), oral hygiene (simplified oral hygiene index - OHI-S), and gingival health (modified gingival index - MGI) were performed. The pediatric quality of life inventory™ (PedsQL™) generic core scale and oral health scale were used to measure HRQoL and OHRQoL. Spearman's correlation coefficient (ρ) and the Mann-Whitney test (α = 0.05) were conducted to assess the relationship between covariates and the PedsQL™ oral health scale. The mean PedsQL™ oral health scale score was 76.66 (SD = 21.36). Worse OHRQoL was correlated with poor oral hygiene (ρ = -0.383; p: 0.004), poor gingival health (ρ = -0.327; p = 0.014), and better HRQoL (ρ = 0.488; p < 0.001). Greater untreated dental caries experience was associated with worse OHRQoL (p = 0.009). Worse oral health status in children and adolescents with BCDH negatively impacts OHRQoL, and OHRQoL and quality of life analyzed from a generic perspective are positively correlated constructs in this population.


Subject(s)
Blood Coagulation Disorders , Dental Caries , Hemoglobinopathies , Oral Health , Quality of Life , Humans , Child , Adolescent , Female , Male , Cross-Sectional Studies , Oral Health/statistics & numerical data , Child, Preschool , Dental Caries/psychology , Hemoglobinopathies/psychology , Hemoglobinopathies/physiopathology , Hemoglobinopathies/complications , Blood Coagulation Disorders/psychology , Statistics, Nonparametric , Oral Hygiene Index , Periodontal Index , DMF Index , Surveys and Questionnaires , Socioeconomic Factors , Oral Hygiene
18.
Rapid Commun Mass Spectrom ; 27(21): 2461-71, 2013 Nov 15.
Article in English | MEDLINE | ID: mdl-24097403

ABSTRACT

RATIONALE: 2-arylidene-4-methoxy (or hydroxy)-7-methyl-1-indanone derivatives inspired from donepezil, the current drug used for the treatment of Alzheimer's disease as inhibitor of acetylcholinesterase (AChE), were studied for the first time by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). Structurally, these arylidene-indanone compounds are considered as cyclic analogues of chalcones. METHODS: ESI-MS and tandem mass spectra were acquired using a Q-TOF 2 instrument. Fragmentation patterns were analyzed by CID-MS(2-3) spectra acquired in a Q-TOF and in LXQ linear ion trap mass spectrometers using standard isolation and excitation procedures. RESULTS: All the 2-arylidene indanones have shown a common fragmentation pathway leading to a (2(1), 1')A(+) product ion at m/z 187 and the retro-aldol product ion [(2, 2(1))B(+)] that allow to establish the substitution in the B ring. The effect of electron-donating and -withdrawing substituents on these fragmentation pathways was noticed. The presence of the OCH3, OH, NO2 and Br substituents gave typical fragmentation processes that allowed their unequivocal fingerprinting. The combined loss of the ortho substituent in the B-ring plus hydrogen (H, OCH3, Br and F) is proposed to form a stable cyclic ring product. CONCLUSIONS: Arylidene indanones with different substituents on the B ring are associated with a specific fragmentation pattern. In addition, differentiation between isomers with substituents in B ring at ortho and para positions were achieved using ESI-MS/MS. These fragmentation pathways can be used to further identify and determine the fate of these molecules in all stages of drug discovery.


Subject(s)
Cholinesterase Inhibitors/chemistry , Indans/chemistry , Piperidines/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Donepezil
19.
Rapid Commun Mass Spectrom ; 27(12): 1303-10, 2013 Jun 30.
Article in English | MEDLINE | ID: mdl-23681807

ABSTRACT

RATIONALE: Several methylenedioxy chalcones, flavanones and flavones substituted with mono-, di- and trimethoxy groups have been used in the treatment of proliferative conditions like cancer and inflammatory diseases. The application of these flavonoids in biology requires an analytical method to ensure a detailed knowledge of their structures after drug metabolism. METHODS: Electrospray ionization mass (ESI-MS) and tandem mass (ESI-MS/MS) spectra were acquired using a Q-TOF 2 instrument. Fragmentation patterns and their pathways were analyzed by CID-MS(2-3) spectra acquired in a LXQ linear ion trap mass spectrometer using standard isolation and excitation procedures (activation q value of 0.25, activation time of 30 ms). ESI-MS and ESI-MS(n) conditions: spray voltage 5 kV, nitrogen 8.00 sheath gas flow rate (arb), heated capillary temperature 275°C, capillary voltage 10.99 V; tube lens voltage 75.01 V. RESULTS: The ESI-MS/MS spectra of chalcones were nearly identical to their corresponding isomeric flavanones with (0,α)A(+)/(1,3)A(+) and (0,1')B(+)/(1,4)B(+) cleavages. Other common losses are of (•)CH3, H2O, HCHO and C2H2O. The characteristic loss of C2H2O and absence of a (0,α)B(+)/(1,3)B(+) product ion allows to distinguish between the 2- or 4-methoxy-substituted chalcones and flavanones. Common losses of (•)CH3, (•)CH3 and (•)H, and C2H2O2 characteristic for the presence of methylenedioxy groups were observed in flavones. CONCLUSIONS: The substitution pattern on the B-ring leads to distinct base peak formation in the flavones. In addition, differentiation of isomers with methoxy substituents in ortho and para positions of the B-ring was achieved using MS/MS in chalcones and flavanones. This method will be helpful for identification of these compounds in biological mixtures.


Subject(s)
Chalcones/analysis , Flavanones/analysis , Flavones/analysis , Tandem Mass Spectrometry/methods , Spectrometry, Mass, Electrospray Ionization/methods
20.
Sensors (Basel) ; 13(11): 15613-32, 2013 Nov 15.
Article in English | MEDLINE | ID: mdl-24248278

ABSTRACT

Measurement and diagnostic systems based on electronic sensors have been increasingly essential in the standardization of hospital equipment. The technical standard IEC (International Electrotechnical Commission) 60601-2-19 establishes requirements for neonatal incubators and specifies the calibration procedure and validation tests for such devices using sensors systems. This paper proposes a new procedure based on an inferential neural network to evaluate and calibrate a neonatal incubator. The proposal presents significant advantages over the standard calibration process, i.e., the number of sensors is drastically reduced, and it runs with the incubator under operation. Since the sensors used in the new calibration process are already installed in the commercial incubator, no additional hardware is necessary; and the calibration necessity can be diagnosed in real time without the presence of technical professionals in the neonatal intensive care unit (NICU). Experimental tests involving the aforementioned calibration system are carried out in a commercial incubator in order to validate the proposal.


Subject(s)
Biosensing Techniques/standards , Incubators, Infant , Neural Networks, Computer , Certification , Equipment Design , Humans , Infant, Newborn
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