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1.
Br J Haematol ; 204(4): 1507-1514, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38323352

RESUMO

The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.


Assuntos
Anemia Falciforme , Osteonecrose , Humanos , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Osteonecrose/genética , Anemia Falciforme/complicações , Anemia Falciforme/genética , Genótipo , Estudos de Casos e Controles , Proteína Morfogenética Óssea 6/genética , Receptores de Calcitriol/genética
2.
J Pharmacol Exp Ther ; 390(2): 203-212, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38262744

RESUMO

Patients with sickle cell disease (SCD) display priapism, a prolonged penile erection in the absence of sexual arousal. The current pharmacological treatments for SCD-associated priapism are limited and focused on acute interventions rather than prevention. Thus, there is an urgent need for new drug targets and preventive pharmacological therapies for this condition. This review focuses on the molecular mechanisms linked to the dysfunction of the NO-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) pathway implicated in SCD-associated priapism. In murine models of SCD, reduced nitric oxide (NO)-cGMP bioavailability in the corpus cavernosum is associated with elevated plasma hemoglobin levels, increased reactive oxygen species levels that inactive NO, and testosterone deficiency that leads to endothelial nitric oxide synthase downregulation. We discuss the consequences of the reduced cGMP-dependent PDE5 activity in response to these molecular changes, highlighting it as the primary pathophysiological mechanism leading to excessive corpus cavernosum relaxation, culminating in priapism. We also further discuss the impact of intravascular hemolysis on therapeutic approaches, present current pharmacological strategies targeting the NO-cGMP-PDE5 pathway in the penis, and identify potential pharmacological targets for future priapism therapies. In men with SCD and priapism, PDE5 inhibitor therapy and testosterone replacement have shown promising results. Recent preclinical research reported the beneficial effect of treatment with haptoglobin and NO donors. SIGNIFICANCE STATEMENT: This review discusses the molecular changes that reduce NO-cGMP bioavailability in the penis in SCD and highlights pharmacological targets and therapeutic strategies for the treatment of priapism, including PDE5 inhibitors, hormonal modulators, NO donors, hydroxyurea, soluble guanylate cyclase stimulators, haptoglobin, hemopexin, and antioxidants.


Assuntos
Anemia Falciforme , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Óxido Nítrico , Priapismo , Priapismo/etiologia , Priapismo/tratamento farmacológico , Priapismo/metabolismo , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/complicações , Anemia Falciforme/metabolismo , Humanos , Óxido Nítrico/metabolismo , Masculino , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , GMP Cíclico/metabolismo , Inibidores da Fosfodiesterase 5/uso terapêutico , Inibidores da Fosfodiesterase 5/farmacologia
3.
Ann Hematol ; 103(4): 1167-1179, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38386032

RESUMO

Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery.


Assuntos
Anemia Falciforme , Acidente Vascular Cerebral , Humanos , Células Endoteliais/metabolismo , Transcriptoma , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/complicações , Anemia Falciforme/complicações , Isquemia , Perfilação da Expressão Gênica , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Família de Proteínas EGF/genética , Família de Proteínas EGF/metabolismo
4.
Eur J Haematol ; 113(2): 172-182, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38634725

RESUMO

OBJECTIVES: Sickle cell disease (SCD) is an inherited disorder that causes lifelong complications, substantially impacting the physical and emotional well-being of patients and their caregivers. Studies investigating the effects of SCD on quality of life (QOL) are often limited to individual countries, lack SCD-specific QOL questionnaires, and exclude the caregiver experience. The SHAPE survey aimed to broaden the understanding of the global burden of SCD on patients and their caregivers and to capture the viewpoint of healthcare providers (HCPs). METHODS: A total of 919 patients, 207 caregivers, and 219 HCPs from 10, 9, and 8 countries, respectively, answered a series of closed-ended questions about their experiences with SCD. RESULTS: The symptoms most frequently reported by patients were fatigue/tiredness (84%) and pain/vaso-occlusive crises (71%). Patients' fatigue/tiredness had one of the greatest impacts on both patients' and caregivers' QOL. On average, patients and caregivers reported missing 7.5 days and 5.0 days per month, respectively, of school or work. HCPs reported a need for effective tools to treat fatigue/tiredness and a desire for more support to educate patients on long-term SCD-related health risks. CONCLUSIONS: The multifaceted challenges identified using the SHAPE survey highlight the global need to improve both patient and caregiver QOL.


Assuntos
Anemia Falciforme , Cuidadores , Pessoal de Saúde , Qualidade de Vida , Humanos , Anemia Falciforme/psicologia , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Cuidadores/psicologia , Adulto , Pessoal de Saúde/psicologia , Adolescente , Masculino , Feminino , Inquéritos e Questionários , Adulto Jovem , Efeitos Psicossociais da Doença , Conhecimentos, Atitudes e Prática em Saúde , Pessoa de Meia-Idade
5.
Support Care Cancer ; 32(9): 571, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105977

RESUMO

PURPOSE: To evaluate the oral health-related quality of life (OHRQoL) of individuals diagnosed with Fanconi anemia (FA). METHODS: A cross-sectional study was conducted with FA patients from two Brazilian referral centers. Participants underwent a complete dental, periodontal, and oral mucosa examination, as well as assessment of resting salivary flow. The short version of the Oral Health Impact Profile (OHIP-14) questionnaire was administered. Descriptive and bivariate analyses were performed, followed by multivariate analysis to examine the impact of independent variables on OHRQoL. RESULTS: The study included 20 (57.1%) males and 15 (42.9%) females, with a mean age of 18.9 years. Oral leukoplakia (OL) was found in 18 individuals. The overall OHIP-14 score was 9.9 ± 10.5. Individuals aged ≥ 16 years had higher OHIP-14 scores, indicating worse OHRQoL for physical pain (p = 0.007), psychological discomfort (p = 0.001), physical disability (p = 0.03), psychological disability (p = 0.001), handicap (p = 0.004), and overall score (p = 0.007). Females reported more negative OHRQoL than males for physical pain (p = 0.02), psychological discomfort (p = 0.03), psychological disability (p = 0.009), and overall score (p = 0.02). Individuals with OL had an overall OHIP-14 score 1.83 times higher than those without OL (95% CI: 1.02-3.28; p = 0.04). Lower salivary flow correlated with higher overall OHIP-14 scores (95% CI: 0.14-0.84; p = 0.01). CONCLUSION: This study represents the first attempt to evaluate OHRQoL in individuals with FA. The presence of OL and reduced salivary flow were identified as predictors of a negative impact on OHRQoL. It is imperative to integrate patients' quality of life in the clinical treatment protocols for the FA population.


Assuntos
Anemia de Fanconi , Saúde Bucal , Qualidade de Vida , Humanos , Masculino , Feminino , Estudos Transversais , Adolescente , Adulto Jovem , Anemia de Fanconi/psicologia , Inquéritos e Questionários , Brasil , Adulto , Leucoplasia Oral/psicologia , Criança , Análise Multivariada
6.
Odontology ; 112(1): 208-220, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37058199

RESUMO

PURPOSE: Periodontitis and coronavirus disease (COVID-19) share risk factors and activate similar immunopathological pathways, intensifying systemic inflammation. This study investigated the clinical, immunological and microbiological parameters in individuals with COVID-19 and controls, exploring whether periodontitis-driven inflammation contributes to worsening COVID-19 endpoints. METHODS: Case (positive RT-PCR for SARS-CoV-2) and control (negative RT-PCR) individuals underwent clinical and periodontal assessments. Salivary levels of TNF-α, IL-6, IL-1ß, IL-10, OPG, RANKL, neutrophil extracellular traps, and subgingival biofilm were analyzed at two timepoints. Data on COVID-19-related outcomes and comorbidity information were evaluated from medical records. RESULTS: Ninety-nine cases of COVID-19 and 182 controls were included for analysis. Periodontitis was associated with more hospitalization (p = 0.009), more days in the intensive care unit (ICU) (p = 0.042), admission to the semi-ICU (p = 0.047), and greater need for oxygen therapy (p = 0.042). After adjustment for confounders, periodontitis resulted in a 1.13-fold increase in the chance of hospitalization. Salivary IL-6 levels (p = 0.010) were increased in individuals with COVID-19 and periodontitis. Periodontitis was associated with increased RANKL and IL-1ß after COVID-19. No significant changes were observed in the bacterial loads of the periodontopathogens Porphyromona gingivalis, Aggregatibacter actinomycetemcomitans, Tanerella forsythia, and Treponema denticola. CONCLUSIONS: Periodontitis was associated with worse COVID-19 outcomes, suggesting the relevance of periodontal care to reduce the burden of overall inflammation. Understanding the crosstalk between SARS-CoV-2 infection and chronic conditions such as periodontitis that can influence disease outcome is important to potentially prevent complications of COVID-19.


Assuntos
COVID-19 , Periodontite Crônica , Periodontite , Humanos , Porphyromonas gingivalis , Interleucina-6 , Estudos de Casos e Controles , SARS-CoV-2 , Periodontite/epidemiologia , Periodontite/microbiologia , Inflamação , Treponema denticola , Periodontite Crônica/microbiologia
7.
J Stroke Cerebrovasc Dis ; 33(1): 107474, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38006767

RESUMO

OBJECTIVES: Stroke is a devastating clinical outcome that significantly contributes to the morbidity and mortality of sickle cell anemia (SCA) patients. Despite its advantages in predicting stroke risk, transcranial Doppler screening has limitations that restrict its applicability, highlighting the need for emerging prognostic tools. Thrombospondin-1 plays a crucial role in endothelial injury, platelet adhesion, and nitric oxide metabolism and may be implicated in stroke pathophysiology. Here, we aimed to evaluate the association of THBS1 genetic variations with the occurrence of stroke in SCA patients MATERIALS AND METHODS: By real-time PCR, 512 SCA patients were fully genotyped for THBS1 A-296G (rs1478605) polymorphism RESULTS: THBS1 GG genotype was associated with a lower risk for stroke occurrence [odds ratio (OR): 0.30; 95% confidence interval (CI): 0.11-0.78; P = 0.011], although these findings were not consistent with multivariate logistic regression analysis (OR: 0.73, 95% CI: 0.12 - 4.37; P = 0.736). In agreement, the cumulative incidence of stroke for patients with AG/AA genotypes was higher when compared to the GG genotype (P = 0.018). However, the association was not maintained in the multivariate proportional hazards model (hazard ratio: 0.67, 95% CI: 0.12-3.61; P = 0.643) CONCLUSIONS: In summary, the present study shows that the THBS1 A-296G (rs1478605) polymorphism may be a potential modifier for stroke in SCA.


Assuntos
Anemia Falciforme , Acidente Vascular Cerebral , Humanos , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Brasil/epidemiologia , Genótipo , Polimorfismo Genético , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética
8.
Br J Haematol ; 202(3): 657-668, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37011913

RESUMO

Haemoglobin S polymerization in the red blood cells (RBCs) of individuals with sickle cell anaemia (SCA) can cause RBC sickling and cellular alterations. Piezo1 is a mechanosensitive protein that modulates intracellular calcium (Ca2+ ) influx, and its activation has been associated with increased RBC surface membrane phosphatidylserine (PS) exposure. Hypothesizing that Piezo1 activation, and ensuing Gárdos channel activity, alter sickle RBC properties, RBCs from patients with SCA were incubated with the Piezo1 agonist, Yoda1 (0.1-10 µM). Oxygen-gradient ektacytometry and membrane potential measurement showed that Piezo1 activation significantly decreased sickle RBC deformability, augmented sickling propensity, and triggered pronounced membrane hyperpolarization, in association with Gárdos channel activation and Ca2+ influx. Yoda1 induced Ca2+ -dependent adhesion of sickle RBCs to laminin, in microfluidic assays, mediated by increased BCAM binding affinity. Furthermore, RBCs from SCA patients that were homo-/heterozygous for the rs59446030 gain-of-function Piezo1 variant demonstrated enhanced sickling under deoxygenation and increased PS exposure. Thus, Piezo1 stimulation decreases sickle RBC deformability, and increases the propensities of these cells to sickle upon deoxygenation and adhere to laminin. Results support a role of Piezo1 in some of the RBC properties that contribute to SCA vaso-occlusion, indicating that Piezo1 may represent a potential therapeutic target molecule for this disease.


Assuntos
Anemia Falciforme , Cálcio , Humanos , Cálcio/metabolismo , Laminina/metabolismo , Eritrócitos/metabolismo , Eritrócitos Anormais/metabolismo
9.
FASEB J ; 36(10): e22535, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36070139

RESUMO

Patients with sickle cell disease (SCD) display priapism. Clinical studies have shown a strong positive correlation between priapism and high levels of intravascular hemolysis in men with SCD. However, there are no experimental studies that show that intravascular hemolysis promotes alterations in erectile function. Therefore, we aimed to evaluate the corpus cavernosum smooth muscle relaxant function in a murine model that displays intravascular hemolysis induced by phenylhydrazine (PHZ), as well as the role of intravascular hemolysis in increasing the stress oxidative in the penis. Corpus cavernosum strips were dissected free and placed in organ baths. Acetylcholine and electrical field stimulation (EFS)-induced corpus cavernosum relaxations in vitro were obtained. Increased corpus cavernosum relaxant responses to acetylcholine and EFS were observed in the PHZ group. Protein expression of heme oxygenase-1 increased in the corpus cavernosum of the PHZ group, but PDE5 protein expression was not modified. Preincubation with the heme oxygenase inhibitor 1 J completely reversed the increased relaxant responses to acetylcholine and EFS in PHZ mice. Protein expression of NADPH oxidase subunit gp91phox, 3-nitrotyrosine, and 4-hydroxynonenal increased in the corpus cavernosum of the PHZ group, suggesting a state of oxidative stress. Basal cGMP production was lower in the PHZ group. Our results show that intravascular hemolysis promotes increased corpus cavernosum smooth muscle relaxation associated with increased HO-1 expression, as well as increased oxidative stress associated with upregulation of gp91phox expression. Moreover, our study supports clinical studies that point to a strong positive correlation between priapism and high levels of intravascular hemolysis in men with SCD.


Assuntos
Anemia Falciforme , Priapismo , Acetilcolina/farmacologia , Anemia Falciforme/complicações , Anemia Falciforme/metabolismo , Animais , Hemólise , Humanos , Masculino , Camundongos , Pênis , Priapismo/complicações
10.
J Nat Prod ; 86(4): 683-693, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36913505

RESUMO

Despite their relatively poorly investigated phytochemistry, species of the genus Chuquiraga are widely commercialized. The present study reports the use of a high-resolution liquid chromatography-mass spectrometry-based metabolomics approach coupled with exploratory and supervised multivariate statistical analyses for species classification and chemical marker identification of four species of Chuquiraga (C. jussieui, C. weberbaueri, C. spinosa, and Chuquiraga sp.) from Ecuador and Peru. Based on these analyses, a high percentage of correct classifications (87% to 100%) allowed the prediction of the taxonomic identity of Chuquiraga species. Through the metabolite selection process, several key constituents with the potential to be chemical markers were identified. Samples of C. jussieui displayed alkyl glycosides and triterpenoid glycosides as discriminating metabolites, while Chuquiraga sp. displayed high concentrations of p-hydroxyacetophenone, p-hydroxyacetophenone 4-O-glucoside, p-hydroxyacetophenone 4-O-(6-O-apiosyl)-glucoside, and quinic acid ester derivatives as the main metabolites. Caffeic acid was characteristic for C. weberbaueri samples, whereas C. spinosa displayed higher concentrations of the following new phenylpropanoid ester derivatives: 2-O-caffeoyl-4-hydroxypentanedioic acid (24), 2-O-p-coumaroyl-4-hydroxypentanedioic acid (34), 2-O-feruloyl-4-hydroxypentanedioic acid (46), 2,4-O-dicaffeoylpentanedioic acid (71), and 2-O-caffeoyl-4-O-feruloylpentanedioic acid (77).


Assuntos
Asteraceae , Flavonoides/análise , Glicosídeos/análise , Espectrometria de Massas , Glucosídeos , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão , Metabolômica
11.
Clin Oral Implants Res ; 34(11): 1299-1308, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37638406

RESUMO

BACKGROUND: There is insufficient evidence for pain control in preemptive analgesia (PA) after dental implant surgery, signaling the need for further studies. The objective of this study was to evaluate the efficacy of PA in single dental implant surgeries (SDIS), seeking to identify among the etoricoxib (ETOR), ibuprofen (IBU), nimesulide (NIME), and acetaminophen (ACETA)], which one has the higher efficacy effectiveness in relieving postoperative pain and reducing the use of rescue medication compared to placebo. METHODS: In this triple-blind, parallel, randomized controlled clinical trial, 135 individuals with a mean age of 57.6 years (±11.7), both genders, were randomly divided into five groups according to the test drug: I-PLACEBO; II-IBU (600 mg); III-NIME (100 mg); IV-ACETA (750 mg); and V-ETOR (90 mg). The occurrence, duration, and intensity of pain were analyzed using the Chi-square, Fisher's exact and ANOVA tests, and the generalized estimating equation models, when appropriate. RESULTS: Test drugs provided a reduction in postoperative pain scores and lower use of rescue medication when compared to placebo. The ETOR group presented significantly lower pain scores, when compared to other active treatments. The IBU group showed the highest mean number of rescue medication used. CONCLUSIONS: All test drugs provided a beneficial preemptive effect demonstrated by the reduced postoperative pain and reduced use of rescue medication. The ETOR group presented lower pain scores, and the IBU group showed the highest mean number of rescue medication used among the test groups.


Assuntos
Implantes Dentários , Ibuprofeno , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Ibuprofeno/uso terapêutico , Acetaminofen/uso terapêutico , Etoricoxib/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Método Duplo-Cego
12.
Lasers Med Sci ; 38(1): 116, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140820

RESUMO

The purpose of this study is to evaluate the scientific evidence on the impact of photobiomodulation adjunct to non-surgical periodontal treatment on individuals with type 2 diabetes mellitus (T2DM). The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was followed. A protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO #CRD42022310756). The research was carried out in seven databases, with no restrictions regarding the year of publication. Our work included studies that compared periodontal clinical parameters among individuals undergoing non-surgical periodontal therapy associated with photobiomodulation and a control group of individuals undergoing non-surgical periodontal treatment. Study selection, data extraction, and risk of bias assessment (RoB 2.0) were performed by two review authors. Meta-analysis was performed. Mean difference (MD) and a 95% confidence interval (CI) were provided. Three hundred forty-one studies were identified, of which eight studies were included. The meta-analysis demonstrated that photobiomodulation adjunctive to periodontal therapy in individuals with diabetes resulted in a greater reduction in probing depth and greater attachment gain in comparison to periodontal treatment alone (p < 0.05). The included studies exhibited a low risk of bias. Photobiomodulation adjunct to periodontal therapy contributes to the improvement of periodontal clinical parameters in individuals with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Terapia com Luz de Baixa Intensidade , Doenças Periodontais , Humanos , Diabetes Mellitus Tipo 2/complicações , Doenças Periodontais/terapia
13.
Int J Mol Sci ; 24(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37047304

RESUMO

Sickle cell disease (SCD) is an inherited blood disorder caused by a ß-globin gene point mutation that results in the production of sickle hemoglobin that polymerizes upon deoxygenation, causing the sickling of red blood cells (RBCs). RBC deformation initiates a sequence of events leading to multiple complications, such as hemolytic anemia, vaso-occlusion, chronic inflammation, and tissue damage. Macrophages participate in extravascular hemolysis by removing damaged RBCs, hence preventing the release of free hemoglobin and heme, and triggering inflammation. Upon erythrophagocytosis, macrophages metabolize RBC-derived hemoglobin, activating mechanisms responsible for recycling iron, which is then used for the generation of new RBCs to try to compensate for anemia. In the bone marrow, macrophages can create specialized niches, known as erythroblastic islands (EBIs), which regulate erythropoiesis. Anemia and inflammation present in SCD may trigger mechanisms of stress erythropoiesis, intensifying RBC generation by expanding the number of EBIs in the bone marrow and creating new ones in extramedullary sites. In the current review, we discuss the distinct mechanisms that could induce stress erythropoiesis in SCD, potentially shifting the macrophage phenotype to an inflammatory profile, and changing their supporting role necessary for the proliferation and differentiation of erythroid cells in the disease. The knowledge of the soluble factors, cell surface and intracellular molecules expressed by EBI macrophages that contribute to begin and end the RBC's lifespan, as well as the understanding of their signaling pathways in SCD, may reveal potential targets to control the pathophysiology of the disease.


Assuntos
Anemia Falciforme , Linfo-Histiocitose Hemofagocítica , Humanos , Eritropoese , Eritrócitos , Macrófagos/metabolismo , Inflamação/metabolismo
14.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36834745

RESUMO

Chikungunya virus (CHIKV) is an arthropod-borne virus that belongs to the genus Alphavirus (family Togaviridae). CHIKV causes chikungunya fever, which is mostly characterized by fever, arthralgia and, sometimes, a maculopapular rash. The bioactive constituents of hops (Humulus lupulus, Cannabaceae), mainly acylphloroglucinols, known as well as α- and ß-acids, exerted distinct activity against CHIKV, without showing cytotoxicity. For fast and efficient isolation and identification of such bioactive constituents, a silica-free countercurrent separation method was applied. The antiviral activity was determined by plaque reduction test and was visually confirmed by a cell-based immunofluorescence assay. All hops compounds demonstrated a promising post-treatment viral inhibition, except the fraction of acylphloroglucinols, in mixture. ß-acids fraction of 125 µg/mL expressed the strongest virucidal activity (EC50 = 15.21 µg/mL), in a drug-addition experiment on Vero cells. Hypothesis for mechanism of action were proposed for acylphloroglucinols based on their lipophilicity and chemical structure. Therefore, inhibition of some steps of the protein kinase C (PKC) transduction cascades was also discussed.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Humulus , Animais , Chlorocebus aethiops , Humanos , Antivirais/farmacologia , Células Vero , Replicação Viral
15.
Gen Dent ; 71(3): 40-45, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37083612

RESUMO

The aim of this study was to evaluate changes in periodontal bacterial species during the transition from hopeless teeth to denture-supporting immediate implants. Biofilm and saliva samples were collected from 13 women and 7 men before the extraction of hopeless teeth with severe periodontitis (baseline) and 90 days after the placement of immediate implants that supported immediately loaded complete dentures (day 90). The levels of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Streptococcus oralis were analyzed by real-time polymerase chain reaction. Differences in the levels of bacterial species in the subgingival biofilm and saliva and between baseline and day 90 were evaluated by a 2-way analysis of variance followed by the Tukey test. There was a significant reduction in the levels of T forsythia from baseline to day 90 in saliva and subgingival biofilms (P < 0.05) and a tendency toward a reduction of the other bacterial species. The total bacterial load was higher in saliva than in subgingival biofilm at baseline and day 90 (P < 0.05), while the individual levels of all species were higher in the biofilm than in saliva at both times (P < 0.05). The results showed an overall reduction in the levels of pathogenic bacterial species, particularly T forsythia, during the transition from hopeless dentition to implant-supported dentures. The subgingival biofilm harbored considerable levels of pathogenic species, suggesting that implant placement immediately after extraction of teeth with severe periodontitis may induce changes that favor colonization by pathogenic microorganisms.


Assuntos
Dentição , Periodontite , Masculino , Humanos , Feminino , Porphyromonas gingivalis , Carga Bacteriana
16.
Mol Vis ; 28: 1-10, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35400990

RESUMO

Purpose: Glaucoma is the world's leading cause of irreversible blindness, with primary open-angle glaucoma (POAG) being the most prevalent subtype. In recent years, there have been advances in knowledge about the genetics involved in POAG, but genetic studies in admixed populations, such as Brazilians, are still rare. This study aimed to evaluate the association of single nucleotide variants (SNV) of the ABCA1 (rs2472493) and GAS7 (rs9913911) genes with POAG in a sample of the Brazilian population. Furthermore, the study aimed to evaluate the relationship between these SNVs and the need for surgical intervention in glaucoma control. Methods: A cross-sectional association study with 1,009 subjects (505 patients with POAG and 504 controls) was performed. Participants underwent a comprehensive ocular examination, including the need for surgical procedures for intraocular pressure control. Genotyping of SNVs was performed using the TaqMan genotyping assay. Results: SNV rs9913911 of GAS7 was found to be associated with POAG in the presence of the risk allele A (p = 0.0004) and the AA genotype (p = 0.002). There was no association between SNV rs2472493 of ABCA1 for either the allele risk or genotypes. However, the combination of these variants showed an additive effect on the risk for POAG: ABCA1(GG) + GAS7(AA; p = 0.02), ABCA1(GG) + GAS7(AG; p = 0.003), and ABCA1(AG) + GAS7(AG; p = 0.004). Also, POAG patients carrying the AA genotype of the GAS7 gene required antiglaucomatous surgery more frequently than those without the AA genotype (p = 0.01). Conclusions: In a Brazilian population sample, there was an association identified between SNV rs9913911 (GAS7) and the risk of POAG, and an additive effect was found when GAS7 was combined with SNV rs2472493 (ABCA1). There was an association between SNV rs9913911 (GAS7) and the risk for antiglaucomatous surgery.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Transportador 1 de Cassete de Ligação de ATP/genética , Brasil , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Glaucoma/genética , Glaucoma de Ângulo Aberto/genética , Humanos , Pressão Intraocular , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único/genética
17.
J Clin Periodontol ; 49(3): 292-300, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34905803

RESUMO

AIM: To determine the impact of the degree of furcation involvement (FI) on the longevity of molar teeth and assess the risk variables (tooth- and patient-related factors) associated with the loss of molars (LM) in individuals treated for periodontitis and monitored in a private programme of supportive periodontal care (SPC). MATERIALS AND METHODS: The present retrospective cohort study included 222 individuals with 1329 molars under a 10-year monitoring period in SPC. Periodontal clinical parameters, FI, the type of molar, pulp vitality, and other variables of interest were collected at approximately 50 days after active periodontal therapy and after 10 years. The association of tooth- and patient-related factors with LM was assessed using a multilevel Cox regression analysis. RESULTS: Two-hundred and thirty-five molars were extracted during the SPC period of 12.4 ± 1.9 years. Age >50 years, male gender, diabetes, smoking, and non-compliance were identified as relevant patient-related factors for LM during SPC (p < .05). Significant tooth-related factors for LM were bleeding on probing (BoP) and probing depth (PD) ≥5 mm, tooth non-vitality, and class II and III FI (p < .05). CONCLUSIONS: Class III FI, tooth non-vitality, higher mean PD and BoP, age, male gender, diabetes, and smoking all strongly influenced the prognosis of molars during SPC.


Assuntos
Defeitos da Furca , Perda de Dente , Seguimentos , Defeitos da Furca/complicações , Defeitos da Furca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Dente Molar , Estudos Retrospectivos , Perda de Dente/complicações , Perda de Dente/prevenção & controle
18.
Oral Dis ; 28 Suppl 2: 2406-2416, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34245645

RESUMO

OBJECTIVES: To assess the self-perception of breath odour (SPBO) and oral hygiene habits (OHHs) while the wearing of face masks during the COVID-19 pandemic. SUBJECTS AND METHODS: This cross-sectional study included 4647 individuals who answered a structured questionnaire containing demographic, medical and dental variables and self-perceived breath odour. Variables associated with changes in self-perceived breath odour, self-perceived halitosis and changes in OHHs were assessed through multivariate logistic regression. RESULTS: Changes in self-perceived breath odour were reported by 1572 individuals and were associated with smoking, systemic conditions, dry mouth, tongue coating, the period of face mask use and its interaction with prior thinking of having bad breath. Likewise, 645 individuals started to consider having bad breath. This was associated with the interaction between prior family/friends saying they have bad breath and period of face mask use. Changes in OHHs were strongly associated with changes in SPBO and starting to consider having bad breath. CONCLUSION: Changes in one's SPBO was associated with the wearing of face masks and was significant for changes in OHHs. Findings may be important to guide comprehensive preventive and therapeutic strategies in relation to oral health care.


Assuntos
COVID-19 , Halitose , Humanos , Halitose/etiologia , Máscaras , COVID-19/prevenção & controle , Pandemias , Autorrelato , Estudos Transversais , Odorantes
19.
Orig Life Evol Biosph ; 52(4): 183-204, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36418513

RESUMO

We review the literature surrounding chiral symmetry-breaking in chemical systems, with a focus on understanding the mathematical models underlying these chemical processes. We comment in particular on the toy model of Sandars, Viedma's crystal grinding systems and the APED model. We include a few new results based on asymptotic analysis of the APED system.


Assuntos
Modelos Teóricos , Estereoisomerismo
20.
Clin Oral Investig ; 26(9): 5557-5574, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35716205

RESUMO

OBJECTIVES: To evaluate the role of metabolic syndrome (MetS) components in the association with periodontitis (PE) (#CRD42020218310). MATERIALS AND METHODS: A systematic electronic search was performed in PUBMED, Scielo and Lilacs databases up to April 2022. Cross-sectional, case-control, and cohort studies presenting data on the association between MetS and PE in the adult and elderly populations were included. A random effect meta-analysis was performed to determine association effect estimates. Results interpretation followed the assessment of methodological quality (Joana Briggs Institute tool) together with the certainty of evidence (GRADE approach). RESULTS: This review included 52 studies, totalling 140,434 participants, and 38 studies were meta-analyzed. Association between PE and MetS was observed (ORadj from 1.27 to 1.90; PRajd = 1.19; RRadj from 1.10 to 1.37) (low and very low certainty of evidence). Hyperglycaemia (OR = 1.18), HDL (OR = 1.16), obesity (OR = 1.08), and hypertension (OR = 1.11) were associated with PE, except triglycerides (low and very low certainty of evidence). There was a dose-response gradient between the number of MetS components and PE, with a gradual increase in the effect magnitude for 1 (OR = 1.14), 2 (OR = 1.52), 3 or more (OR = 1.79), and 4 or 5 components (OR = 2.02) (low to high certainty of evidence). CONCLUSIONS: MetS was associated with PE, with a dose-response gradient between the number of MetS components and the occurrence of PE, with an increasing effect magnitude according to an increasing number of components. CLINICAL RELEVANCE: Periodontal examination should be part of a comprehensive propaedeutic approach of MetS patients, particularly those presenting a great number of components.


Assuntos
Hipertensão , Síndrome Metabólica , Periodontite , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Periodontite/complicações , Periodontite/epidemiologia , Fatores de Risco
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