RESUMO

Many Omani patients with sickle cell disease (SCD) undergo red blood cell (RBC) transfusions that are only matched for ABO and D, making RBC alloimmunization a significant concern in this population. Currently, the integration of molecular assays and hemagglutination testing helps to determine RBC phenotypes and genotypes, facilitating the provision of compatible blood and minimizing additional alloimmunization risks in patients with SCD. Based on this finding, our objective was to use molecular methods to predict the extended antigen profile of Omani patients with SCD across various blood group systems including Rh, Kell, Duffy, Kidd, Colton, Lutheran, Dombrock, Diego, Cartwright, and Scianna. This approach aims to implement RBC matching strategies and enhance daily transfusion practices for these patients. Molecular methods encompassed multiplex polymerase chain reaction for RHD, BeadChip arrays for variants of RHD and RHCE, and ID CORE XT for the primary allelic variants of RBCs. This study enrolled 38 patients with SCD, comprising 34 patients with homozygous HbSS, 1 patient with HbSC, and 3 patients with HbS Oman. The predominant ABO blood group was group O, observed in 44.7 percent of patients, followed by group A in 21.1 percent and group B in 13.2 percent. The most prevalent Rh phenotype predicted from the genotype was D+C+E-c+e+, identified in 34.2 percent of patients. All patient samples were K-, exhibiting the k+ Kp(b+) Js(b+) phenotype, with 81.6 percent demonstrating Fy(a-b-) due to the homozygous FY*02N.01 genotype and 28.9 percent displaying Jk(a+b-). RH variant alleles were detected in five patients (13.2 %), with only one type of RHD variant (RHD*DIIIa) and one type of RHCE variant (RHCE*ceVS.02.01) identified. Alloantibodies were present in 26 patients (68.4%). This study presents the initial comprehensive report of extended RBC antigen profiling in Omani patients with SCD, revealing disparities in the prevalence of RBC phenotypes compared with SCD patients from other regions and countries. Furthermore, our findings underscore a high rate of alloimmunization in these patients, emphasizing the need to implement antigen-matching programs to improve daily transfusion practices.

Assuntos

Anemia Falciforme , Antígenos de Grupos Sanguíneos , Tipagem e Reações Cruzadas Sanguíneas , Humanos , Anemia Falciforme/terapia , Anemia Falciforme/sangue , Anemia Falciforme/imunologia , Anemia Falciforme/genética , Omã , Masculino , Feminino , Tipagem e Reações Cruzadas Sanguíneas/métodos , Adolescente , Adulto , Criança , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/imunologia , Eritrócitos/imunologia , Pré-Escolar , Transfusão de Eritrócitos , Adulto Jovem , Sistema do Grupo Sanguíneo Rh-Hr/genética , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Genótipo , Pessoa de Meia-Idade

RESUMO

INTRODUCTION: The incidence of feto-maternal complications is high in women with sickle cell disease. The paucity of high-quality evidence has led to conditional recommendations for transfusional support in pregnant patients. This study aimed to assess if scheduled partial red cell exchanges impact pregnancy outcomes in sickle cell disease patients. METHODS: Forty-seven pregnancies were divided into two groups based on whether patients received scheduled partial red cell exchanges. Collected data included demographics, laboratory values, number of hospital visits, and prenatal/perinatal/postnatal outcomes. Data were analyzed using descriptive statistics, t-test, Chi-square and Fisher's exact tests, and binary regression. RESULTS: The mean age was 25.09 ± 4.39 years. Of 47 patients, 14 (29.8%) received scheduled red cell exchanges with 78.6% compliance with no evidence of alloimmunization. This procedure during pregnancy was associated with fewer admissions for pain crises (p=0.032), higher gestational age at delivery (p=0.007), and a lower incidence of neonatal intensive care admissions (p=0.011; odds ratio: 0.071; 95% confidence interval: 0.008-0.632). Logistic regression did not show any significant associations. CONCLUSIONS: Sickle cell disease patients with complications in previous pregnancies, including high hospitalization/admission rates and preterm deliveries, could benefit from scheduled partial red cell exchanges or simple transfusions. Further research is needed to guide clinical practice pertaining to transfusional support in pregnant patients with sickle cell disease.

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OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

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The early detection of sickle cell disease (SCD) is vital to reduce mortality among affected children. Suriname currently lacks a newborn screening programme (NSP) for SCD. We performed a pilot programme to evaluate the scalability of such an initiative. Dried blood spots were collected from five birth centres and subjected to electrophoresis analysis. The programme scalability was evaluated using the non-adoption, abandonment, scale-up, spread, and sustainability framework. Challenges across six domains (illness, technology, value proposition, adopter system, organisation, and societal system), were categorised hierarchically as simple 😊, complicated 😐, or complex 😢. It has been proven that implementing programmes with mainly complicated challenges is difficult and those in mainly complex areas may be unachievable. SCD was detected in 33 of 5185 (0.64%) successfully screened newborns. Most of the domains were classified as simple or complicated. Disease detection and technology suitability for screening in Suriname were confirmed, with favourable parental acceptance. Only minor routine adjustment was required from the medical staff for programme implementation. Complex challenges included a reliance on external suppliers for technical maintenance, ensuring timely access to specialised paediatric care for affected newborns, and securing sustainable financial funding. Scaling up is challenging but feasible, particularly with a targeted focus on identified complex challenges.

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Background: A subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to a transvenous implantable cardio defibrillator (TV-ICD). An S-ICD reduces the risk of transvenous lead placement. However, further research is required to determine how S-ICDs affect patients with hypertrophic cardiomyopathy (HCM). In this study, we investigated the comparative efficacy and safety of S-ICDs versus TV-ICDs in HCM. Methods: On December 6th, 2023, we performed a comprehensive search of the PubMed, Embase, Scopus, and Cochrane databases to identify randomized clinical trials (RCTs) and observational studies comparing S-ICDs with TV-ICDs in HCM patients published from 2004 until 2023. No language restrictions were applied. The primary outcome was appropriate shocks (AS), with inappropriate shocks (IAS), and device-related complications considered as secondary outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random effects model. The ROBINS-I tool was used to assess the risk of bias of the studies. Results: The search yielded 1,114 records. Seven studies comprising 4,347 HCM patients were included, of whom 3,325 (76.0%) had TV-ICDs, and 1,022 (22.6%) had S-ICDs. There were 2,564 males (58.9%). The age range was from 39.1 to 49.4 years. Compared with the TV-ICD group, the S-ICD cohort had a significantly lower incidence of device-related complications (OR 0.52; 95% CI: 0.30-0.89; P=0.02; I2=4%). Contrastingly, there were no statistically significant differences in the occurrences of AS (OR 0.49; 95% CI: 0.22-1.08; P=0.08; I2=75%) and IAS (OR 1.03; 95% CI: 0.57-1.84; P=0.93; I2=65%) between the two device modalities. In the analysis of the overall risk of bias in the studies, we found 42% of them with several, 28% with moderate, and 14% with low risk of bias. Conclusions: In HCM patients, S-ICDs were associated with a lower incidence of device-associated problems than TV-ICDs. AS and IAS incidence rates were similar between groups. These findings may assist clinicians in determining the most suitable device for treating patients with HCM.

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Our group generated two induced pluripotent stem cell (iPSC) lines for in vitro red blood cell (RBC) production from blood donors with extensively known erythrocyte antigen profiles. One line was intended to give rise to RBCs for transfusions in patients with sickle cell disease (SCD), while the other was developed to create RBC panel reagents. Two blood donors were selected based on their RBC phenotypes, further complemented by high-throughput DNA array analysis to obtain a more comprehensive erythrocyte antigen profile. Enriched erythroblast populations from the donors' peripheral blood mononuclear cells were reprogrammed into iPSCs using nonintegrative plasmid vectors. The iPSC lines were characterized and subsequently subjected to hematopoietic differentiation. iPSC PB02 and iPSC PB12 demonstrated in vitro and in vivo iPSC features and retained the genotype of each blood donor's RBC antigen profile. Colony-forming cell assays confirmed that iPSC PB02 and iPSC PB12 generated hematopoietic progenitors. These two iPSC lines were generated with defined erythrocyte antigen profiles, self-renewal capacity, and hematopoietic differentiation potential. With improvements in hematopoietic differentiation, these cells could potentially be more efficiently differentiated into RBCs in the future. They could serve as a complementary approach for obtaining donor-independent RBCs and addressing specific demands for blood transfusions.

Assuntos

Doadores de Sangue , Diferenciação Celular , Eritrócitos , Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Humanos , Eritrócitos/metabolismo , Eritrócitos/citologia , Linhagem Celular , Animais , Antígenos de Grupos Sanguíneos , Camundongos , Anemia Falciforme/terapia , Anemia Falciforme/sangue

RESUMO

AIM: The soluble scavenger receptor differentiation antigen 163 (sCD163), a monocyte/macrophage activation marker, is related to cardiovascular mortality in the general population. This study aimed to evaluate their relationship between serum levels of sCD163 with cardiovascular risk indicators in rheumatoid arthritis (RA). METHODS: A cross-sectional study was performed on 80 women diagnosed with RA. The cardiovascular risks were determined using the lipid profile, metabolic syndrome, and QRISK3 calculator. For the assessment of RA activity, we evaluated the DAS28 with erythrocyte sedimentation rate (DAS28-ESR). The serum levels of sCD163 were determined by the ELISA method. Logistic regression models and receiver operating characteristics (ROC) curve were used to assess the association and predictive value of sCD163 with cardiovascular risk in RA patients. RESULTS: Levels of sCD163 were significantly higher in RA patients with high sensitivity protein C-reactive to HDL-c ratio (CHR)≥0.121 (p=0.003), total cholesterol/HDL-c ratio>7% (p=0.004), LDL-c/HDL-c ratio>3% (p=0.035), atherogenic index of plasma>0.21 (p=0.004), cardiometabolic index (CMI)≥1.70 (p=0.005), and high DAS28-ESR (p=0.004). In multivariate analysis, levels of sCD163≥1107.3ng/mL were associated with CHR≥0.121 (OR=3.43, p=0.020), CMI≥1.70 (OR=4.25, p=0.005), total cholesterol/HDL-c ratio>7% (OR=6.63, p=0.044), as well as with DAS28-ESR>3.2 (OR=8.10, p=0.008). Moreover, levels of sCD163 predicted CHR≥0.121 (AUC=0.701), cholesterol total/HDL ratio>7% (AUC=0.764), and DAS28-ESR>3.2 (AUC=0.720). CONCLUSION: Serum levels of sCD163 could be considered a surrogate of cardiovascular risk and clinical activity in RA.

RESUMO

BACKGROUND: We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed. RESULTS: We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts. CONCLUSIONS: For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.

Assuntos

Distrofia Miotônica , Ácido Oleico , Ácido Oleico/farmacologia , Distrofia Miotônica/tratamento farmacológico , Distrofia Miotônica/metabolismo , Humanos , Diferenciação Celular/efeitos dos fármacos , MicroRNAs/metabolismo , Autofagia/efeitos dos fármacos , Linhagem Celular , Proteínas de Ligação a RNA/metabolismo

RESUMO

Sudden cardiac death (SCD) is an unpredictable and common mode of death in patients with heart failure (HF). Alterations in calcium handling may lead to malignant arrhythmias, resulting in SCD, and variants in calcium signaling-related genes have a significant association with SCD. Therefore, the aim of the present retrospective cohort study was to investigate the association of Ser96Ala [histidine-rich calcium-binding protein (HRC)], Ser49Gly [ß1-adrenergic receptor (ADRB1)], Arg389Gly (ADRB1) and Gly1886Ser [ryanodine receptor 2 (RYR2)] polymorphisms with serious arrhythmic events and overall mortality in patients with HF with reduced left ventricular ejection fraction of non-ischemic etiology. In total, 136 patients with HF underwent physical examination, routine laboratory tests, non-invasive assessment of cardiac function and an invasive electrophysiological study. The primary outcome was the occurrence of serious arrhythmic events, set as either SCD or appropriate implantable cardioverter-defibrillator (ICD) therapy, and the secondary outcome was all-cause death. During a median follow-up of 37 months, arrhythmic events occurred in 26 patients (19%) and 41 patients (30%) died. Patients carrying the Ser allele of the Ser96Ala polymorphism in HRC had worse survival than those with the Ala/Ala genotype (log-rank P=0.043). Despite the difference in survival time, the Ala/Ala genotype was not associated with all-cause death in the regression analysis [unadjusted hazard ratio (HR)=0.17; 95% CI, 0.02-1.21]. Regarding the Ser49Gly and Arg389Gly polymorphisms in ADRB1, homozygosity for the major alleles at both sites (Ser49Ser and Arg389Arg) was associated with a two-fold increased risk of all-cause death compared with the other genotype combinations (unadjusted HR=1.98; 95% CI, 1.02-3.82). However, this association was lost after controlling for clinical covariates. No association was observed for the Gly1886Ser polymorphism in RYR2. Overall, the present findings are concurrent with the hypothesis that the Ser96Ala (HRC), Ser49Gly (ADRB1) and Arg389Gly (ADRB1) polymorphisms may be associated with HF prognosis. In particular, the Ser96Ala polymorphism might aid in risk stratification and patient selection for ICD implantation.

RESUMO

Background We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed. Results We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts. Conclusions For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.

RESUMO

BACKGROUND: RBC alloimmunization remains a significant problem for many patients with SCD. To reduce alloimmunization some strategies have been implemented to provide limited or extended antigen matched RBC transfusions to patients with SCD who need chronic transfusion support. The aim of this study was to evaluate the effects of prophylactic RBC transfusion with extended antigen matching on alloimmunization in patients with SCD. METHODS: This is a 20-year retrospective study of patients with SCD transfused with RBCS that were prospectively matched for D, C, c, E, e, K, Fya/Fyb, Jka/Jkb and S antigens. Our study included 95 patients, and none had antibodies documented before their first transfusion. Patients and donors were phenotyped and molecular typing was performed in all patients who had recent transfusions or a positive direct antiglobulin test to predict their antigen profile. Unexpected antibodies to the Rh system, meaning anti-Rh antibodies in patients whose serologic phenotype was Rh positive, were investigated by molecular genotyping for RH variant alleles. RESULTS: During this study-period, 12 (12.6%) were alloimmunized and 83 (87.4%) were not. Among the 12 patients who alloimmunized, 7 (58.3%) developed antibodies to Rh antigens and 5 (41.7%) produced antibodies to low prevalence antigens. All patients who developed Rh antibodies had RH variant alleles. Autoantibodies were found in 16 (16.8%) transfused patients. CONCLUSION: SCD patients benefit from receiving prophylactic RBC transfusions with extended antigen matching, as demonstrated by the reduction on the rates of alloimmunization and the lack of antibodies to K, FY, JK and S antigens, however, this strategy does not avoid alloimmunization to Rh and low-prevalence antigens.

Assuntos

Anemia Hemolítica Autoimune , Anemia Falciforme , Antígenos de Grupos Sanguíneos , Humanos , Estudos Retrospectivos , Eritrócitos , Transfusão de Eritrócitos , Transfusão de Sangue , Isoanticorpos

RESUMO

Introduction: Proteolytic processing of amyloid protein precursor by ß-site secretase enzyme (BACE1) is dependent on the cellular lipid composition and is affected by endomembrane trafficking in dementia and Alzheimer's disease (AD). Stearoyl-CoA desaturase 1 (SCD1) is responsible for the synthesis of fatty acid monounsaturation (MUFAs), whose accumulation is strongly associated with cognitive dysfunction. Methods: In this study, we analyzed the relationship between BACE1 and SCD1 in vivo and in vitro neurodegenerative models and their association in familial AD (FAD), sporadic AD (SAD), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) using microscopy, biochemical, and mass SPECT approach. Results: Our findings showed that BACE1 and SCD1 immunoreactivities were increased and colocalized in astrocytes of the hippocampus in a rat model of global cerebral ischemia (2-VO). A synergistic effect of double BACE1/SCD1 silencing on the recovery of motor and cognitive functions was obtained. This neuroprotective regulation involved the segregation of phospholipids (PLs) associated with polyunsaturated fatty acids in the hippocampus, cerebrospinal fluid, and serum. The double silencing in the sham and ischemic groups was stronger in the serum, inducing an inverse ratio between total phosphatydilcholine (PC) and lysophosphatidylcholine (LPC), represented mainly by the reduction of PC 38:4 and PC 36:4 and an increase in LPC 16:0 and LPC 18:0. Furthermore, PC 38:4 and PC:36:4 levels augmented in pathological conditions in in vitro AD models. BACE1 and SCD1 increases were confirmed in the hippocampus of FAD, SAD, and CADASIL. Conclusion: Therefore, the findings suggest a novel convergence of BACE-1 and SCD1 in neurodegeneration, related to pro-inflammatory phospholipids.

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The aim of this study was to evaluate the effectiveness of the original sperm chromatin dispersion (SCD) assay and the toluidine blue (TB) stain to assess DNA fragmentation and chromatin condensation, respectively, in cat sperm obtained by urethral catheterization (CT) and epididymis slicing (EP). CT and EP samples were collected from the same cat, and sperm motility, concentration, morphology, DNA integrity and chromatin condensation were evaluated. As controls, aliquots of the samples were incubated with 0.3 M NaOH and with 1% of dithiothreitol (DTT) to promote DNA fragmentation and chromatin decondensation, respectively. With SCD, four DNA dispersion halo patterns were observed: large, medium, small and no halo. TB staining patterns were as follows: light blue (condensed chromatin), light violet (moderate chromatin decondensation) and dark blue-violet (high chromatin decondensation). Sperm incubations with NaOH and with DTT were effective in inducing DNA fragmentation and chromatin decondensation, respectively. No significant differences were observed in the percentages of the SCD and TB patterns between samples (CT and EP) and no correlation was observed between sperm head abnormalities and the different SCD and TB patterns. The original SCD technique and the TB stain were adapted to evaluate DNA integrity and chromatin condensation in cat sperm obtained by CT and EP.

Assuntos

Cromatina , Cateterismo Urinário , Masculino , Animais , Cateterismo Urinário/veterinária , Epididimo , Hidróxido de Sódio , Sêmen , Motilidade dos Espermatozoides , Espermatozoides , DNA , Corantes , Cloreto de Tolônio , Fragmentação do DNA

RESUMO

The aim of this study was to analyze molecules associated with regulatory immune response in unvaccinated, recovered COVID-19 patients with and without diabetes mellitus (DM) and hypertension (HTN). We determined anti-SARS-CoV-2 nucleocapsid IgG in plasma by electrochemiluminescence immunoassay. The levels of sCD40, TGF-ß, IL-10, and sCTLA-4 were assessed by ELISA in the serum of the subjects, as well as in healthy donors. We observed that only half of the subjects in the non-comorbid group produced antibodies, whereas all subjects in comorbid groups were IgG-positive for the anti-SARS-CoV-2 nucleocapsid. High levels of sCTL-4 were observed in the non-comorbid group, and the level of IL-10 was observed to increase in seropositive subjects without comorbidities. TGF-ß concentration was similar in all groups studied. Finally, sCD40 decreased in the comorbid group. In conclusion, our results suggest that comorbidities such as DM and HTN alter the production of co-stimulatory inhibitory molecules sCTLA-4 and sCD40 in subjects recovering from mild COVID-19. The alterations observed here were independent of seropositivity, suggesting an effective humoral immune response against COVID-19 separate from the levels of co-stimulatory inhibitory molecules.

RESUMO

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease that affects the central nervous system (CNS), varying from relatively benign to severely disabling. Although the roles of several cytokines and chemokines in MS are well established, their roles in MS lesions and evolution remain a matter of debate. Soluble CD40L (sCD40L) is a ligand that induces lymphocyte proinflammatory activity by stimulating the activation and maturation of B cells, promoting isotype switching and affinity hypermutation. Circulating sCD40L levels reflect activation of the CD40-CD40L complex. The interaction between CD40 and CD40L is of fundamental importance, suggesting their role in MS pathogenesis. Interleukin-31 (IL-31) is a proinflammatory cytokine that plays a role in allergies, autoimmune diseases, and is a major factor in several chronic inflammatory diseases. IL-31 triggers the JAK-STAT pathway in several different cell types, to induce proliferation and tissue remodeling in fibroblasts, epithelial cells, and endothelial cells. Some studies have described a correlation between these two cytokines and decreased serum levels of sCD40L and IL-31 after MS treatment, accompanied by a lower inflammatory response. In this review, we emphasize the possible correlation and positive feedback between IL31 and sCD40L in the MS proinflammatory response. We also describe the justification for this hypothesis and whether it is possible to investigate these cytokines as biomarkers of MS.

Assuntos

Ligante de CD40 , Esclerose Múltipla , Humanos , Ligante de CD40/metabolismo , Células Endoteliais/metabolismo , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Biomarcadores , Interleucinas , Citocinas

RESUMO

The study's objective was to adapt the Sperm Chromatin Dispersion (SCD) protocol to evaluate sperm DNA fragmentation and implement a fragmentation control in dogs. Correlation between DNA status and routine sperm parameters was also analysed. To adapt the SCD, two different mercaptoethanol (ME) concentrations were assayed (2.5% and 5%) in fourteen ejaculates from seven dogs and semen incubation with 0.3 M NaOH for 15 min at room temperature was assayed as a control for sperm DNA fragmentation. Data were analysed using a Mann-Whitney test and either Pearson's or Spearman's correlation. The selected ME concentration to use in the SCD test was 5%, as it produced the largest DNA dispersion halo while preserving the core nucleus structure. Four DNA halo patterns were identified as follows: large dispersion halos, medium halos, small halos and nuclei without halos. Semen incubated with NaOH showed 100% sperm without halos (damaged DNA). A significant positive correlation was observed between sperm with fragmented DNA and sperm with coiled tails. Thus, it was possible to adapt the SCD protocol to evaluate dog sperm DNA fragmentation in raw semen without using a commercial kit and establish incubation with NaOH as a DNA fragmentation control. Only coiled tails showed correlation with DNA fragmentation.

Assuntos

Sêmen , Espermatozoides , Animais , Cromatina , DNA/análise , Fragmentação do DNA , Cães , Masculino , Mercaptoetanol , Hidróxido de Sódio , Espermatozoides/química

RESUMO

PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in the world. Stearoyl-CoA desaturase-1 (SCD-1) is one of major enzymes in the de novo synthesis of fatty acids and is related to cancer aggressiveness and poor patient prognosis. The study aimed to construct exosomes loaded SCD-1 interference, investigate its effects and mechanisms on the cell proliferation and apoptosis of ATC cells. METHODS: The expressions of SCD-1 in normal thyroid cell line and ATC cell lines were determined by qRT-PCR and western blotting, respectively. Exosomes were prepared and purification then loaded with SCD-1 siRNA by electroporation and observed by transmission electron microscopy. Higher SCD-1 mRNA and protein levels were found in ATC cell lines compared than normal thyroid cell line (P < 0.05), and both Hth-7 and FRO cells could uptake PKH67-labeled exosomes. The effects of exosomes loaded SCD-1 siRNA on ATC cells were measured by CCK8 assay and apoptosis detection kit. RESULTS: When compared with control group, the cell viability significantly decreased in both two ATC cell lines taken up exosomes loaded SCD-1 siRNA (P < 0.001), and apoptotic and necrotic cells obviously increased (P < 0.05). In order to explore the mechanism of exosomes loaded SCD-1 on ATC, the ROS level was detected by fluorescence reagent. It was found that exosomes loaded SCD-1 siRNA significantly increased intracellular ROS level of ATC cells (P < 0.05). CONCLUSIONS: Exosomes loaded SCD-1 siRNA inhibited ATC cellular proliferation and promoted cellular apoptosis, and the mechanisms involved maybe the regulation of fatty acids metabolism and ROS level. Our study provides a promising therapeutic strategy for ATC.

Assuntos

Exossomos/fisiologia , RNA Interferente Pequeno/fisiologia , Estearoil-CoA Dessaturase/metabolismo , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Apoptose , Proliferação de Células , Humanos , Células Tumorais Cultivadas

RESUMO

Objective: Dental caries is one of the most common microbial diseases. Because of the infectious nature of the disease, the immunologic response by the host plays an essential role in its development. Therefore, the aim of this study was to evaluate the sCD14 levels in patients exhibiting two to three teeth with caries involving pulp along with apical periodontitis requiring root canal treatment. Material and Methods: This study was carried out on 20 participants, of whom 10 were caries-free (Control) and 10 had two to three teeth with symptomatic irreversible pulpitis along with apical periodontitis requiring root canal treatment, within the ages of 20- 30 years. Unstimulated saliva of the participants was collected with disposable needle-less syringe from buccal and labial vestibules. The sCD14 levels in salivary samples were assessed before and following endodontic treatment. The results were analyzed by ELISA. Results: The obtained levels of sCD14 were analyzed statistically. Paired T test was performed to assess the significance. The results revealed that there was a significant difference in sCD14 levels with a P=0.0005, as it had drastically reduced once the inflammation has subsided. Conclusion: Higher values of sCD14 levels were seen in patients with symptomatic irreversible pulpitis along with apical periodontitis than in caries free group. The study also showed that sCD levels were significantly reduced following post endodontic treatment. Therefore, increased levels of sCD14 can be considered as a marker of inflammation. (AU)

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Objetivo: A cárie dentária é uma das doenças microbianas mais comuns. Devido à natureza infecciosa da doença, a resposta imunológica do hospedeiro desempenha um papel essencial no seu desenvolvimento. Portanto, o objetivo deste estudo foi avaliar os níveis de sCD14 em pacientes que possuiam dois a três dentes com necessidade de tratamento endodôntico por apresentarem lesão de cárie envolvendo polpa e periodontite periapical. Material e Métodos: Este estudo foi realizado em 20 participantes, dos quais 10 estavam livres de cárie (controle) e 10 tinham dois a três dentes com pulpite irreversível sintomática e periodontite periapical com necessidade de tratamento endodôntico, nas idades de 20 a 30 anos. A saliva não estimulada das crianças foi coletada com seringa descartável sem agulha dos vestíbulos bucal e labial. Os níveis de sCD14 em amostras salivares foram avaliados antes e após o tratamento endodôntico. Os resultados foram analisados por ELISA. Resultados: Os níveis de sCD14 obtidos foram analisados estatisticamente. O teste T pareado foi realizado para avaliar a significância. Os resultados revelaram que houve uma diferença significativa nos níveis de sCD14 com um P = 0,0005, uma vez que reduziu drasticamente uma vez que a inflamação diminuiu. Resultados: Os níveis de sCD14 obtidos foram analisados estatisticamente. O teste T pareado foi realizado para avaliar a significância. Os resultados revelaram que houve uma diferença significativa nos níveis de sCD14 com um P = 0,0005, uma vez que reduziu drasticamente uma vez que a inflamação diminuiu. Conclusão: Valores mais elevados de níveis de sCD14 foram observados em pacientes com pulpite irreversível sintomática junto com periodontite periapical do que no grupo livre de cárie. O estudo também mostrou que os níveis de sCD foram significativamente reduzidos após o tratamento endodôntico. Portanto, níveis aumentados de sCD14 podem ser considerados um marcador de inflamação. (AU)

Assuntos

Humanos , Adulto , Periodontite Periapical , Ensaio de Imunoadsorção Enzimática , Receptores de Lipopolissacarídeos , Cárie Dentária

RESUMO

Design of Experiments (DoE) is a statistical tool used to plan and optimize experiments and is seen as a quality technology to achieve products excellence. Among the experimental designs (EDs), the mixture designs (MDs) stand out, being widely applied to improve conditions for processing, developing, or formulating novel products. This review aims to provide useful updated information on the capacity and diversity of MDs applications for the industry and scientific community in the areas of food, beverage, and pharmaceutical health. Recent works were selected following the Preferred Reporting Items for Systematic Review and Meta-Analyses statement (PRISMA) flow diagram. Data analysis was performed by self-organizing map (SOM) to check and understand which fields of application/countries/continents are using MDs. Overall, the SOM indicated that Brazil presented the largest number of works using MDs. Among the continents, America and Asia showed a predominance in applications with the same amount of work. Comparing the MDs application areas, the analysis indicated that works are prevalent in food and beverage science in the American continent, while in Asia, health science prevails. MDs were more used to develop functional/nutraceutical products and the formulation of drugs for several diseases. However, we briefly describe some promising research fields in that MDs can still be employed.