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Nanoparticles for multivalent display and delivery of vaccine antigens have emerged as a promising avenue for enhancing B cell responses to protein subunit vaccines. Here, we evaluated B cell responses in rhesus macaques immunized with prefusion-stabilized respiratory syncytial virus (RSV) F glycoprotein trimer compared with nanoparticles displaying 10 or 20 copies of the same antigen. We show that multivalent display skews antibody specificities and drives epitope-focusing of responding B cells. Antibody cloning and repertoire sequencing revealed that focusing was driven by the expansion of clonally distinct B cells through recruitment of diverse precursors. We identified two antibody lineages that developed either ultrapotent neutralization or pneumovirus cross-neutralization from precursor B cells with low initial affinity for the RSV-F immunogen. This suggests that increased avidity by multivalent display facilitates the activation and recruitment of these cells. Diversification of the B cell response by multivalent nanoparticle immunogens has broad implications for vaccine design.
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Mpv17 (mitochondrial inner membrane protein MPV17) deficiency causes severe mitochondrial DNA depletion syndrome in mammals and loss of pigmentation of iridophores and a significant decrease of melanophores in zebrafish. The reasons for this are still unclear. In this study, we established an mpv17 homozygous mutant line in Nile tilapia. The developing mutants are transparent due to loss of iridophores and aggregation of pigment granules in the melanophores and disappearance of the vertical pigment bars on the side of the fish. Transcriptome analysis using skin of fish at 30 dpf (days post fertilization) revealed that the genes related to purine (especially pnp4a) and melanin synthesis were significantly downregulated. However, administration of guanine diets failed to rescue the phenotype of the mutants. In addition, no obvious apoptosis signals were observed in the iris of the mutants by TUNEL staining. Significant downregulation of genes related to iridophore differentiation was detected by qPCR. Insufficient ATP, as revealed by ATP assay, α-MSH treatment and adcy5 mutational analysis, might account for the defects of melanophores in mpv17 mutants. Several tissues displayed less mtDNA and decreased ATP levels. Taken together, these results indicated that mutation of mpv17 led to mitochondrial dTMP deficiency, followed by impaired mtDNA content and mitochondrial function, which in turn, led to loss of iridophores and a transparent body color in tilapia.
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Monkeypox (Mpox) is a zoonotic disease caused by a virus (monkeypox virus-MPV) belonging to the Poxviridae family. In humans, the disease has an incubation period of 5-21 days and then progresses in two phases, the prodromal phase and the rash phase. The prodromal phase is characterized by non-specific symptoms such as fever, muscle pain, malaise, lymphadenopathy, headache, and chills. Skin lesions appear in the rash phase of the disease. These lesions progress through different stages (macules, papules, vesicles, and pustules). In May 2022, WHO reported an outbreak of human Mpox in several countries which were previously Mpox-free. As per the CDC report of March 01, 2023, a total of 86,231 confirmed cases of Mpox and 105 deaths have been reported from 110 countries and territories across the globe. Notably, more than 90% of these countries were reporting Mpox for the first time. The phylogenetic analysis revealed that this outbreak was associated with the virus from the West African clade. However, most of the cases in this outbreak had no evidence of travel histories to MPV-endemic countries in Central or West Africa. This outbreak was primarily driven by the transmission of the virus via intimate contact in men who have sex with men (MSM). The changing epidemiology of Mpox raised concerns about the increasing spread of the disease in non-endemic countries and the urgent need to control and prevent it. In this chapter, we present all the documented cases of Mpox from 1970 to 2023 and discuss the past, present, and future of MPV.
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Surtos de Doenças , Monkeypox virus , Mpox , Animais , Humanos , Monkeypox virus/genética , Monkeypox virus/patogenicidade , Mpox/epidemiologia , Mpox/transmissão , Mpox/virologia , Filogenia , Zoonoses/epidemiologia , Zoonoses/virologia , Zoonoses/transmissãoRESUMO
During the pandemic, Favipiravir (FVP) and Molnupiravir (MPV) have been widely used for COVID-19 treatment, leading to their presence in the environment. A green synchronous spectrofluorimetric method was developed to simultaneously detect them in environmental water, human plasma, and binary mixtures. Maximum fluorescence intensity was achieved at pH 8, with MPV exhibiting two peaks at 300 and 430 nm, and FVP showing one peak at 430 nm. A fluorescence subtraction method effectively removed interference, enabling direct determination of MPV at 300 nm and FVP at 430 nm. The method showed linearity within 2-13 ng/mL for FVP and 50-600 ng/mL for MPV, with recoveries of 100.35% and 100.12%, respectively. Limits of detection and quantification were 0.19 and 0.57 ng/mL for FVP and 10.52 and 31.88 ng/mL for MPV. Validation according to ICH and FDA guidelines yielded acceptable results. The method demonstrated good recoveries of FVP and MPV in pharmaceuticals, tap water and Nile water (99.62% ± 0.96% and 99.69% ± 0.64%) as per ICH guidelines and spiked human plasma (94.87% ± 2.111% and 94.79% ± 1.605%) following FDA guidelines, respectively. Its environmental friendliness was assessed using Green Analytical Procedure Index (GAPI) and the Analytical Greenness Metric (AGREE) tools.
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Amidas , Antivirais , Pirazinas , Espectrometria de Fluorescência , Pirazinas/análise , Pirazinas/sangue , Pirazinas/química , Amidas/análise , Amidas/química , Amidas/sangue , Espectrometria de Fluorescência/métodos , Humanos , Antivirais/análise , Antivirais/sangue , Uridina/análise , Uridina/sangue , Limite de Detecção , Citidina/análise , Citidina/sangue , Citidina/análogos & derivados , Tratamento Farmacológico da COVID-19 , Mercaptopurina/sangue , Mercaptopurina/análise , SARS-CoV-2 , HidroxilaminasRESUMO
BACKGROUND: Platelet count (PLT) is associated positively with lung cancer risk but has a more complex association with body mass index (BMI), positive only in women (mainly never smokers) and inverse in men (mainly ever smokers), raising the question whether platelets interact with obesity in relation to lung cancer risk. Prospective associations of platelet size (an index of platelet maturity and activity) with lung cancer risk are unclear. METHODS: We examined the associations of PLT, mean platelet volume (MPV), and platelet distribution width (PDW) (each individually, per one standard deviation increase) with lung cancer risk in UK Biobank men and women using multivariable Cox proportional hazards models adjusted for BMI and covariates. We calculated Relative Excess Risk from Interaction (RERI) with obese (BMI ≥ 30 kg/m2), dichotomising platelet parameters at ≥ median (sex-specific), and multiplicative interactions with BMI (continuous scale). We examined heterogeneity according to smoking status (never, former, current smoker) and antiaggregant/anticoagulant use (no/yes). RESULTS: During a mean follow-up of 10.4 years, 1620 lung cancers were ascertained in 192,355 men and 1495 lung cancers in 218,761 women. PLT was associated positively with lung cancer risk in men (hazard ratio HR = 1.14; 95% confidence interval (CI): 1.09-1.20) and women (HR = 1.09; 95%CI: 1.03-1.15) but interacted inversely with BMI only in men (RERI = - 0.53; 95%CI: - 0.80 to - 0.26 for high-PLT-obese; HR = 0.92; 95%CI = 0.88-0.96 for PLT*BMI). Only in men, MPV was associated inversely with lung cancer risk (HR = 0.95; 95%CI: 0.90-0.99) and interacted positively with BMI (RERI = 0.27; 95%CI = 0.09-0.45 for high-MPV-obese; HR = 1.08; 95%CI = 1.04-1.13 for MPV*BMI), while PDW was associated positively (HR = 1.05; 95%CI: 1.00-1.10), with no evidence for interactions. The associations with PLT were consistent by smoking status, but MPV was associated inversely only in current smokers and PDW positively only in never/former smokers. The interactions with BMI were retained for at least eight years of follow-up and were consistent by smoking status but were attenuated in antiaggregant/anticoagulant users. CONCLUSIONS: In men, PLT was associated positively and MPV inversely with lung cancer risk and these associations appeared hindered by obesity. In women, only PLT was associated positively, with little evidence for interaction with obesity.
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Bancos de Espécimes Biológicos , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Obesidade/diagnóstico , Obesidade/epidemiologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Anticoagulantes , Reino Unido/epidemiologiaRESUMO
MPV17 is a mitochondrial inner membrane protein, and its deficiency can cause mitochondrial DNA (mtDNA) depletion, increase reactive oxygen species (ROS), and promote apoptosis in several cell types, suggesting that MPV17 plays a protective role in cells although the underlying mechanism remains unknown. To test whether MPV17 is also protective in diabetic kidney disease, we treated Mpv17-deficient mice with streptozotocin (STZ) and surprisingly found that they were resistant to diabetes. Mpv17 deficiency was also found to confer resistance to the diabetes induced by an insulin mutation (Ins2Akita), which represents a mouse model of monogenic diabetes characterized by proinsulin misfolding and ß-cell failure. In both STZ and Ins2Akita models, Mpv17 mutants had significantly less severe ß-cell loss and apoptosis compared with the wild-type mice. We next showed that MPV17 is expressed in ß-cells of mice normally, suggesting that MPV17 acts ß-cells autonomously to facilitate apoptosis. Consistently, Mpv17 knockdown improved the viability and ameliorated the apoptosis of cultured MIN6 cells treated with STZ and palmitic acid (PA), respectively, accompanied by prevention of caspase 3 activation. The proapoptotic effect of MPV17 in ß-cells is in contrast with its known anti-apoptotic effect in other cell types. Thus, we have identified a novel regulator of ß-cell death in diabetes development.
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Células Secretoras de Insulina , Proteínas Mitocondriais , Animais , Camundongos , Apoptose , DNA Mitocondrial/genética , Células Secretoras de Insulina/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , MutaçãoRESUMO
M-LP/Mpv17L (Mpv17-like protein) is an atypical cyclic nucleotide phosphodiesterase (PDE) without the molecular structure characteristic of the PDE family. Deficiency of M-LP/Mpv17L in mice has been found to result in development of ß-cell hyperplasia and improved glucose tolerance. Here, we report another phenotype observed in M-LP/Mpv17L-knockout (KO) mice: afferent cardiac hypertrophy. Although the hearts of M-LP/Mpv17L-KO mice did not differ in size from those of wild-type mice, there was marked narrowing of the left ventricular lumen and thickening of the ventricular wall. The diameter and cross-sectional area of cardiomyocytes in 8-month-old M-LP/Mpv17L-KO mice were increased 1.16-fold and 1.35-fold, respectively, relative to control mice, but showed no obvious abnormalities of cell structure, fibrosis or impaired cardiac function. In 80-day-old KO mice, the expression of hypertrophic marker genes, brain natriuretic peptide (BNF), actin alpha cardiac muscle 1 (ACTC1) and actin alpha 1 skeletal muscle (ACTA1), as well as the Wnt/ß-catenin pathway target genes, lymphoid enhancer-binding factor-1 (LEF1), axis inhibition protein 2 (AXIN2) and transcription factor 7 (TCF7), was significantly up-regulated relative to control mice, whereas fibrosis-related genes such as fibronectin 1 (FN1) and connective tissue growth factor (CTGF) were down-regulated. Western blot analysis revealed increased phosphorylation of molecules downstream of the cAMP/PKA signaling pathway, such as ß-catenin, ryanodine receptor 2 (RyR2), phospholamban (PLN) and troponin I (cTnI), as well as members of the MEK1-ERK1/2 signaling pathway, which is strongly involved in afferent cardiac hypertrophy. Taken together, these findings indicate that M-LP/Mpv17L is one of the PDEs actively functioning in the heart and that deficiency of M-LP/Mpv17L in mice promotes physiological cardiac hypertrophy.
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3',5'-AMP Cíclico Fosfodiesterases , Cardiomegalia , Animais , Camundongos , Actinas/metabolismo , beta Catenina/metabolismo , Cardiomegalia/genética , Cardiomegalia/metabolismo , Fibrose , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , 3',5'-AMP Cíclico Fosfodiesterases/genética , 3',5'-AMP Cíclico Fosfodiesterases/metabolismoRESUMO
BACKGROUND: Acute appendicitis (AA) is among the most common nontraumatic indications for emergent abdominal surgical procedures. However, accurately diagnosing all cases can be challenging, physical examination, biochemical markers, and imaging techniques can sometimes be insufficient. This study aimed to (a) compare the mean platelet volume (MPV) and total white blood cell count (TWBCs) in patients with or without histological evidence of an inflamed appendix and (b) determine the positive predictive value, negative predictive value, sensitivity, and specificity of both MPV and TWBCs as diagnostic biomarkers in the diagnosis of AA. We conducted this research at Omdurman Military Hospital, focusing on patients who presented with symptoms suggestive of AA. MATERIALS AND METHODS: An analytical cross-sectional study conducted at Omdurman Military Hospital from December 2020 - December 2021. The study population was patients who presented to our emergency department with symptoms and signs suggestive of AA. Participants were patients operated on as cases of AA. Data variables included sociodemographic characteristics, clinical presentations, intraoperative appendix macroscopic findings, preoperative MPV and total white blood cell count (TWBCs), and postoperative histopathological findings. RESULTS: A total of 106 patients were included in this study, with 75 (68.2%) males; half were 10-19 years old. Sixty-three patients (57.3%) had low (< 7.5 fL) MPV, whereas 47 (42.7%) had normal values. Comparing MPV to total white blood cells (TWBCs) revealed that MPV was more sensitive (84.6%) and specific (90%) than TWBCs during the first 24 h of inflammation. However, the TWBCs were more sensitive (97.2%) but less specific (94.7% vs. 100%) after 24 h of onset. CONCLUSION: In this study, MPV was lower in patients with AA, while there was an increase in TWBCs. The high sensitivity and specificity of TWBCs and MPV indicated that they form a promising diagnostic marker for AA.
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Apendicite , Volume Plaquetário Médio , Masculino , Estados Unidos , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Feminino , Apendicite/diagnóstico , Apendicite/cirurgia , Estudos Transversais , Hospitais Militares , Contagem de Leucócitos , Biomarcadores , Doença Aguda , Leucócitos , Estudos RetrospectivosRESUMO
BACKGROUND: The course of monkeypox can be severe. Our aim was to retrospectively compare the risk of hospital admission, the need for ventilation, sepsis, pneumonitis and death between the recent outbreak and historical outbreaks. MATERIALS AND METHODS: Cases of monkeypox were retrieved from the TriNetX database and assigned to either cohort I (recent outbreak between May 1st and September 16th, 2022) and cohort II (historical outbreaks before May 1st, 2022). After matching for age distribution, statistical analysis was performed. RESULTS: Of 640 patients with monkeypox 81 subjects per cohort remained after matching (mean age±standard deviation = 36.1±18.3 years). Within 56 days after diagnosis 10 patients per cohort were hospitalized (12.4%) and/or developed sepsis (12.4%). The risk of ventilation and pneumonitis were significantly lower among cohort I compared with cohort II (0 vs. 10 cases; risk difference = 12.4%; p = 0.001; Log-Rank test). No cases of death were recorded. CONCLUSION: Even though monkeypox provides a risk of severe courses, the infection is self-limiting in most cases. Unlike past outbreaks, the risk of ventilation and pneumonitis may be relatively low among recent outbreaks.
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Mpox , Pneumonia , Sepse , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Pneumonia/epidemiologia , Sepse/epidemiologia , Surtos de Doenças , HospitaisRESUMO
Currently, there is a great interest in the development of sustainable and green technologies for production of biofuels and chemicals. In this sense, much attention is being paid to lignocellulosic biomass as feedstock, as alternative to fossil-based resources, inasmuch as its fractions can be transformed into value-added chemicals. Two important platform molecules derived from lignocellulosic sugars are furfural and levulinic acid, which can be transformed into a large spectrum of chemicals, by hydrogenation, oxidation, or condensation, with applications as solvents, agrochemicals, fragrances, pharmaceuticals, among others. However, in many cases, noble metal-based catalysts, scarce and expensive, are used. Therefore, an important effort is performed to search the most abundant, readily available, and cheap transition-metal-based catalysts. Among these, copper-based catalysts have been proposed, and the present review deals with the hydrogenation of furfural and levulinic acid, with Cu-based catalysts, into several relevant chemicals: furfuryl alcohol, 2-methylfuran, and cyclopentanone from FUR, and γ-valerolactone and 2-methyltetrahydrofuran from LA. Special emphasis has been placed on catalytic processes used (gas- and liquid-phase, catalytic transfer hydrogenation), under heterogeneous catalysis. Moreover, the effect of addition of other metal to Cu-based catalysts has been considered, as well as the issue related to catalyst stability in reusing studies.
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Cobre , Furaldeído , Furaldeído/química , Hidrogenação , Cobre/química , Ácidos Levulínicos/química , CatáliseRESUMO
Objective: The neutrophil-lymphocyte ratio (NLR) can be helpful both in demonstrating acute and chronic liver injury and predicting malignant potential. The mean platelet volume (MPV) is also a marker that can be used as a risk indicator in atherosclerosis-associated diseases, reflecting inflammation. Within the scope of this research, we aimed to elucidate the relationship between the mean platelet volume and neutrophil-lymphocyte ratio in liver fibrosis in chronic hepatitis B patients. Materials and Methods: A total of 84 patients who were followed up with the diagnosis of chronic hepatitis B and who underwent liver biopsy were included in this prospective study. Complete blood count parameters (neutrophil, lymphocyte, neutrophil-lymphocyte ratio, hemoglobin, thrombocyte, MCV, and MPV values), demographic data, biochemistry panel (AST, ALT), HBV DNA, and liver biopsy fibrosis scores obtained from hospital database were analyzed. Since the follow-up period of chronic hepatitis B patients is six months, patients were screened in order to include a full 3-year screening pool. Results: A total of 84 patients were enrolled within the scope of this study. The chronicity index was '0' in 7.1% (n = 6), '1' in 23.8% (n = 20), '2' in 56% (n = 47), and '3' in 13.1% (n = 11)of the patients. According to the chronicity index groups, there was a statistically significant difference between the medians of the hepatitis activity index (HAI) values at the 5% significance level (p < 0.001). The correlation analysis revealed a statistically significant relationship between the chronicity index and the mean platelet volume to lymphocyte ratio (MPVL). However, considering the degree of the relationship, it can be said that it was a positive and weak relationship (p = 0.046, r = 0.218). Conclusions: Regarding the outcomes of this research, a significant relationship was found between the neutrophil-lymphocyte ratio, mean platelet volume, and fibrosis.
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Hepatite B Crônica , Volume Plaquetário Médio , Humanos , Hepatite B Crônica/complicações , Neutrófilos , Estudos Prospectivos , Cirrose Hepática , Linfócitos/patologia , Biomarcadores , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim: This study aims to assess the role of platelets and platelet indices as a cost-effective predictive marker of the cervical cancer patient's response before, 15th, and 25th external radiation. PATIENTS AND METHODS: Materials and methods: A total of 54 cervical cancer patients at Dr. Kariadi Hospital were divided into good and poor therapeutic response groups. Measurements of platelet count and indices including PDW, P-LCR, and PCT were carried out before, 15th, and 25th external radiation. RESULTS: Results: There was no difference in platelet counts, MPV, PDW, P-LCR, and PCT in both groups, but patients with decreased MPV and P-LCR values on 15th-25th external radiation had a better therapeutic response (p= 0.005 and 0.007). CONCLUSION: Conclusions: MPV and P-LCR values at 15th to 25th external radiation appeared to decrease further in the group that responded better to therapy.
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Volume Plaquetário Médio , Neoplasias do Colo do Útero , Feminino , Humanos , Contagem de Plaquetas , Neoplasias do Colo do Útero/radioterapia , Plaquetas , HospitaisRESUMO
Background: Inflammation biomarkers known as acute phase reactants (APRs) show significant variations in serum concentrations during inflammation brought on by both viral and noninfectious diseases. The erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP), the lactate dehydrogenase (LDH), the ferritin, the fibrinogen, the procalcitonin, the D-dimer, and the troponin I are all significant APRs. During inflammation, the serum levels of each of these positive APRs rise. The sensitivity and specificity of hematologic parameters and indices are as high as the inflammatory biomarkers mentioned above for monitoring disease severity and treatment response. Aim: We aimed to evaluate the differences in hematological parameters and indices, and to reveal their treatment and prognostic values, especially in deceased patients with COVID-19. Materials and Methods: The hemogram parameters of 169 critical patients with COVID-19 (125 males and 44 females) who received inpatient treatment at .between 1 March 2020 and 31 December 2021 were analyzed retrospectively. The patients were divided into two groups-deceased (77) and surviving (92)-noting demographic data such as age and gender. All analyses were performed using SPSS 25.0. Results: Analyses of the hematological parameters used during the treatment processes revealed statistically significant differences between the two patient groups. White blood cell (WBC), neutrophil, and neutrophil-to-lymphocyte ratio (NLR) values were significantly higher (P = 0.019, P = 0.000 and P = 0.000, respectively) for deceased subjects, while lymphocyte, platelet and plateletcrit (PCT) values were significantly lower (for all values, P = 0.000). Platelet volume (MPV) and platelet distribution width (PDW), as well as MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT, levels were significantly higher in deceased subjects (P = 0.000). Particularly in our deceased cases, receiver operating characteristic analyses were performed to reveal the importance of such analyses in prognostic status evaluation in COVID-19 since the hematological parameters are quite different. Cut-off values were determined for each parameter, and sensitivity and specificity ratios were calculated. While the sensitivities of MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT indices are over 80%, neutrophil and white blood cell sensitivities were found to be lower (74%, 68.8%, respectively). Conclusion: In addition to NLR, which is an important biomarker, the hematological indices MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT can be used to determine the risk of death in patients with severe COVID-19.
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COVID-19 , Masculino , Feminino , Humanos , Estudos Retrospectivos , Contagem de Plaquetas , Plaquetas , Prognóstico , Biomarcadores , InflamaçãoRESUMO
Reactive oxygen species (ROS) contribute to cellular damage in several different contexts, but their role during chilling damage is poorly defined. Chilling sensitivity both limits the distribution of plant species and causes devastating crop losses worldwide. Our screen of chilling-tolerant Arabidopsis (Arabidopsis thaliana) for mutants that suffer chilling damage identified a gene (At4g03410) encoding a chloroplast Mpv17_PMP22 protein, MPD1, with no previous connection to chilling. The chilling-sensitive mpd1-1 mutant is an overexpression allele that we successfully phenocopied by creating transgenic lines with a similar level of MPD1 overexpression. In mammals and yeast, MPD1 homologs are associated with ROS management. In chilling conditions, Arabidopsis overexpressing MPD1 accumulated H2O2 to higher levels than wild-type controls and exhibited stronger induction of ROS response genes. Paraquat application exacerbated chilling damage, confirming that the phenotype occurs due to ROS dysregulation. We conclude that at low temperature increased MPD1 expression results in increased ROS production, causing chilling damage. Our discovery of the effect of MPD1 overexpression on ROS production under chilling stress implies that investigation of the nine other members of the Mpv17_PMP22 family in Arabidopsis may lead to new discoveries regarding ROS signaling and management in plants.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cloroplastos/metabolismo , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: MPV17-related mitochondrial DNA maintenance defect (MPV17 deficiency) is a rare, autosomal recessive mitochondrial DNA depletion syndrome with a high mortality rate in infancy and early childhood due to progression to liver failure. Liver transplantation for children with MPV17 deficiency has been considered controversial due to uncertainty about the potential progression of extrahepatic manifestations following liver transplantation. METHODS: We describe our institution's experience for two infants diagnosed with infantile MPV17 deficiency who presented in acute on chronic liver failure, but with normal development and normal neurological status who successfully underwent liver transplantation. RESULTS: Both patients underwent successful liver transplantation with normal development and neurological status at 3 years and 16 months post-transplant, respectively. CONCLUSIONS: In this rare disease population, we describe two infants with MPV17 deficiency who underwent liver transplantation for acute on chronic liver failure who continue to have normal development, without progression of neurological disease. MPV17 deficiency should not be considered a contraindication to liver transplantation.
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Insuficiência Hepática Crônica Agudizada , Transplante de Fígado , Criança , Pré-Escolar , DNA Mitocondrial/genética , Transtornos Heredodegenerativos do Sistema Nervoso , Humanos , Lactente , Hepatopatias , Proteínas de Membrana/genética , Doenças Mitocondriais , Proteínas Mitocondriais/genética , Doenças do Sistema Nervoso PeriféricoRESUMO
Stratifying patients according to disease severity has been a major hurdle during the COVID-19 pandemic. This usually requires evaluating the levels of several biomarkers, which may be cumbersome when rapid decisions are required. In this manuscript we show that a single nanoparticle aggregation test can be used to distinguish patients that require intensive care from those that have already been discharged from the intensive care unit (ICU). It consists of diluting a platelet-free plasma sample and then adding gold nanoparticles. The nanoparticles aggregate to a larger extent when the samples are obtained from a patient in the ICU. This changes the color of the colloidal suspension, which can be evaluated by measuring the pixel intensity of a photograph. Although the exact factor or combination of factors behind the different aggregation behavior is unknown, control experiments demonstrate that the presence of proteins in the samples is crucial for the test to work. Principal component analysis demonstrates that the test result is highly correlated to biomarkers of prognosis and inflammation that are commonly used to evaluate the severity of COVID-19 patients. The results shown here pave the way to develop nanoparticle aggregation assays that classify COVID-19 patients according to disease severity, which could be useful to de-escalate care safely and make a better use of hospital resources.
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Our objective was to analyze if there was a significant relationship between platelet parameters (PLT, MPV, PDW, P-LCR, PCT) among dengue, its serological subgroups and controls. Serologically proven adult patients with dengue {(n = 238) (NS1 positive = 218, IgM positive = 14, NS1 & IgM positive = 6)} and age- and gender-matched controls (n = 254) were included. The MPV, PDW and P-LCR were significantly higher, and PLT and PCT were significantly lower in cases compared with controls. Cases as well as controls showed a positive correlation between PLT and PCT, both parameters individually showed negative correlation with MPV, PDW, P-LCR. MPV, PDW and P-LCR showed positive correlation with each other. The results were similar in the serological subgroups. Comparison of our results with other studies points toward an overall hyperdestructive etiology for thrombocytopenia in dengue. There were two subgroups of cases based on the severity of thrombocytopenia. The mean/median value of all the platelet parameters was lesser in the ≤20k group than the >20k group, except for PDW, which was high although not statistically significant. Suppression of megakaryopoiesis with concomitant immune destruction of platelets in severe dengue could explain low MPV and P-LCR with a high PDW in view of the presence of microthrombocytes as a result of immune destruction. Although an overall hyperdestructive mechanism contributes to thrombocytopenia in dengue, regular monitoring of the platelet indices could reflect the status of megakaryopoiesis and thrombokinetic axis, thus aiding easy determination of pathophysiology and treatment.
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Plaquetas/metabolismo , Dengue/sangue , Estudos de Casos e Controles , Estudos Transversais , Dengue/patologia , Hospitalização , Humanos , Estudos RetrospectivosRESUMO
The present study investigated the sperm quality parameters and platelet indices in adolescent and adult varicocele rats. Twenty male Wistar rats were distributed into four groups (n = 5): I-sham adolescent group, II-sham adult group, III-varicocele adolescent group, and IV-varicocele adult group. Rats were sacrificed on the 61st day of the experiment. Sperm count (×106 ml-1 ), sperm motility and viability (%) were significantly (p < 0.05) different between varicocele and sham groups in adolescent and adult rats. Varicocele adults had significant (p < 0.05) lower platelet count (PLT) than sham adolescents and adults. The mean platelet volume (MPV), the MPV/PLT ratio, plateletcrit (PCT) and platelet distribution width (PDW) differ significantly (p < 0.05) between varicocele and sham groups of adolescent and adult rats. It is the first time the ratio MPV/PLT was evaluated in association with other platelet indices in adolescent and adult varicocele rats. Based on the results, it would appear these indicators can become a promising tool in varicocele diagnosis.
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Volume Plaquetário Médio , Varicocele , Adolescente , Animais , Plaquetas , Humanos , Masculino , Contagem de Plaquetas , Ratos , Ratos Wistar , Motilidade dos Espermatozoides , Varicocele/complicaçõesRESUMO
Background: Platelets are crucial players in thrombus formation during ischemic stroke. Platelet (PLT) count and Mean platelet volume (MPV) are important parameters that affect platelet functions. The current study has been carried out with an aim to evaluate the association of MPV and PLT count with ischemic stroke in a population from the Malwa region of Punjab.Material and Methods: The study included one hundred and fifty ischemic stroke patients. The extent of disability occurs by stroke was measured by mRS. MPV and PLT was evaluated using cell counter. Further, PLT count was confirmed in 50% of patients using flow cytometer. Clot formation rate was evaluated using Sonoclot Coagulation and Platelet Function Analyzer. All the statistical analysis was carried out using SPSS.Results: A significant association of increased MPV (p < 0.02) was found with the ischemic stroke. However, PLT count did not show a significant association with the disease (p < 0.07). Further, a stepwise multiple logistic regression (MLR) analysis controlling the other confounding risk factors evaluated the association of hypertension and MPV with the disease. Patients with higher mRS were found to have high MPV values confirming that higher MPV is correlated with disability occurs by ischemic stroke. MPV was also found to be significantly associated with large artery atherosclerosis (p < 0.001). Clot formation analysis revealed that ischemic stroke patients bear higher clot rate (CR) and Platelet function (PF) values.Conclusions: Elevated MPV is an independent risk factor for Ischemic stroke along with hypertension. In addition, higher MPV associated significantly with stroke disability as well.
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The early detection of sepsis can be highly beneficial for the treatment and prognosis of critically ill children. Bacterial culture is the gold standard of bacterial infection, but it takes considerable time to get the result. Some biomarkers had been used as infection markers in children, such as C-reactive protein (CRP), full blood count with differential count and procalcitonin level. Platelet profile had been linked to infection in many studies. Platelet profile consists of mean platelet volume, platelet volume distribution width and plateletcrit. Platelet profiles are relatively inexpensive and widely available examination. It is routinely measured by automated hematology analysers in routine full blood examination, but its clinical importance and application is still limited, especially in children. The aim of this study is to analyse the correlations between platelet profiles with procalcitonin and CRP in critically ill children. A cross sectional study was conducted at Haji Adam Malik Hospital Medan, Indonesia. Patients admitted to paediatric intensive care unit, aged 1 month to 18 years were recruited. Platelet profile, procalcitonin and CRP were measured within 24 hours after admission at PICU. The most common indication of PICU admissions were central nervous system (27.9%) and respiratory (25.3%) disorders. Both MPV (r=0.217; p=0.045) and PDW (r=0.23; p=0.033) had statistically significant correlation with procalcitonin, while none of platelet indicators had significant correlation with CRP. PDW and MPV had statistically significant correlation with procalcitonin as a marker of bacterial infection, their roles as an initial marker of bacterial infection needs further research.