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1.
J Obes Metab Syndr ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39098051

RESUMEN

Background: Peroxisome proliferator-activated receptor α (PPARα) is a nuclear transcription factor responsible for gene expression, particularly those associated with lipid metabolism. The lipoprotein lipase enzyme (LPL) is considered a key enzyme in lipid metabolism and transport. The link between dyslipidemia and obesity is well understood. Dyslipidemia is also an established risk feature for cardiovascular disease. Thus, it becomes progressively essential to identify the role of genetic factors as risk markers for the development of dyslipidemia among obese males. Methods: A case-control study was performed including 469 males. Anthropometric characteristics and serum lipid profiles such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were evaluated. Genomic DNA extraction and purification were performed using whole blood samples. Restriction enzyme fragment length polymorphism was used to genotype PPARα and LPL single nucleotide polymorphisms. The associations between these polymorphisms and dyslipidemia were examined. Results: The CC and CG genotypes of PPARα gene polymorphisms were significantly associated with higher TC and LDL-C levels (P<0.05). The TT genotype of the LPL gene polymorphism was significantly associated with higher TG levels and lower HDL-C levels (P<0.05). In contrast, the GG genotype may have a protective action against dyslipidemia. Conclusion: The study reaches the interesting conclusion that there was a significant association between PPARα as well as LPL gene polymorphisms and dyslipidemia among obese and non-obese males.

2.
Sci Rep ; 14(1): 19076, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154019

RESUMEN

The current investigation theoretically presents a one-dimensional phononic crystal (PnC) as a fluidic sensor. The sensor under consideration aims to distinguish the concentration of acetic acid. The primary configuration of the proposed sensor is constructed with lead, epoxy, and a defect layer in the middle of the structure, that is filled with acetic acid (vinegar). As a result of the rise in density and decline in the speed of sound at a 100% concentration of acetic acid in comparison to pure water, the peak frequency of the output has shifted towards lower frequencies. Given that the maximum permissible concentration of acetic acid in water for vinegar is above 30%, sensor simulations were conducted within the concentration range of 25-35% with a step size of 1%. Interestingly, the sensitivity of the sensor exhibits a polynomial change in response to the concentration of acetic acid. Consequently, the highest level of sensitivity, which corresponds to the lowest concentration of vinegar, is recorded as 48.44 × 106 (Hz). The proposed system exhibits a remarkable value of the quality factor of 2802.91. Furthermore, the optimal figure of merit (FOM) is achieved when the concentration is at its lowest, with a value of 94.00. Furthermore, the temperature effects are taken into account for a wide range between 10 and 60 °C. A pronouncing sensitivity is obtained for all temperatures changes and the highest one reached the value of 1.57 × 106 (Hz/°C) at a temperature of 25 °C. Considering the present circumstances, the suggested sensor configuration has the potential to cater to a diverse array of other fluids, specifically their concentration and temperature, thereby offering a broad scope of applications.

3.
Front Pharmacol ; 15: 1409210, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161899

RESUMEN

Acute myeloid leukemia (AML), an aggressive malignancy of hematopoietic stem cells, is characterized by the blockade of cell differentiation, uncontrolled proliferation, and cell expansion that impairs healthy hematopoiesis and results in pancytopenia and susceptibility to infections. Several genetic and chromosomal aberrations play a role in AML and influence patient outcomes. TP53 is a key tumor suppressor gene involved in a variety of cell features, such as cell-cycle regulation, genome stability, proliferation, differentiation, stem-cell homeostasis, apoptosis, metabolism, senescence, and the repair of DNA damage in response to cellular stress. In AML, TP53 alterations occur in 5%-12% of de novo AML cases. These mutations form an important molecular subgroup, and patients with these mutations have the worst prognosis and shortest overall survival among patients with AML, even when treated with aggressive chemotherapy and allogeneic stem cell transplant. The frequency of TP53-mutations increases in relapsed and recurrent AML and is associated with chemoresistance. Progress in AML genetics and biology has brought the novel therapies, however, the clinical benefit of these agents for patients whose disease is driven by TP53 mutations remains largely unexplored. This review focuses on the molecular characteristics of TP53-mutated disease; the impact of TP53 on selected hallmarks of leukemia, particularly metabolic rewiring and immune evasion, the clinical importance of TP53 mutations; and the current progress in the development of preclinical and clinical therapeutic strategies to treat TP53-mutated disease.

4.
Front Med (Lausanne) ; 11: 1402897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39149601

RESUMEN

Patients with leukemia experience profound immunosuppression both from their underlying disease as well as chemotherapeutic treatment. Little is known about the prevalence and clinical presentation of nontuberculous mycobacteria (NTM) in this patient population. We identified six cases of NTM infection from 29,743 leukemia patients who had acid-fast bacilli (AFB) cultures. Four cases had bloodstream infections and five had disseminated disease, including one who presented with an unusual case of diffuse cellulitis/myositis. All patients were lymphopenic at time of diagnosis, and two patients ultimately died from their NTM infection. NTM infections are a rare, but potentially life-threatening infection in patients with leukemia. Sending AFB cultures early is important to direct appropriate antimicrobial therapy and allow for future leukemia-directed therapy.

5.
Leukemia ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179671

RESUMEN

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell transplant physicians have united their expertise to explore the potential of menin inhibitors in pediatric leukemia treatment internationally. Our efforts aim to provide a comprehensive clinical overview of menin inhibitors, integrating preclinical evidence and insights from ongoing global clinical trials. Additionally, we propose future international, inclusive, and efficient clinical trial designs, integrating pediatric populations in adult trials, to ensure broad access to this promising therapy for all children and adolescents with menin-dependent leukemias.

6.
Sci Rep ; 14(1): 19733, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39183352

RESUMEN

This paper seeks to progress the field of topological photonic crystals (TPC) as a promising tool in face of construction flaws. In particular, the structure can be used as a novel temperature sensor. In this regard, the considered TPC structure comprising two different PC designs named PC1 and PC2. PC1 is designed from a stack of multilayers containing Silicon (Si) and Silicon dioxide (SiO2), while layers of SiO2 and composite layer named hyperbolic metamaterial (HMM) are considered in designing PC2. The HMM layer is engineered using subwavelength layers of Si and Bismuth Germinate, or BGO ( Bi 4 Ge 3 O 12 ). The mainstay of our suggested temperature sensor is mainly based on the emergence of some resonant modes inside the transmittance spectrum that provide the stability in the presence of the geometrical changes. Meanwhile, our theoretical framework has been introduced in the vicinity of transfer matrix method (TMM), effective medium theory (EMT) and the thermo-optic characteristics of the considered materials. The numerical findings have extensively introduced the role of some topological parameters such as layers' thicknesses, filling ratio through HMM layers and the periodicity of HMM on the stability or the topological features of the introduced sensor. Meanwhile, the numerical results reveal that the considered design provides some topological edge states (TESs) of a promising robustness and stability against certain disturbances or geometrical changes in the constituent materials. In addition, our sensing tool offers a relatively high sensitivity of 0.27 nm/°C.

7.
J Plant Res ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39147963

RESUMEN

Hibiscus is a charismatic genus of the Malvaceae family that is noted for its diversity, lacking identifiable characteristics for distinguishing its various species. Therefore, there is an urgent need to develop authentication methods for genus delimitation and species delineation. The present study aims to discern the taxonomic relationships between the well-known, globally familiar, and economically important five Hibiscus species, namely: H. × rosa-sinensis, H. sabdariffa, H. schizopetalus, H. syriacus and H. tiliaceus based on traditional morphological and anatomical characteristics compared to the contemporary chemotaxonomy. In this context, the leaf-based methanolic extracts of the studied species were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS) to estimate their secondary metabolites similarity. In addition, selected qualitative morphological and anatomical traits including leaf venation patterns, epidermal micromorphology, stomata types and trichomes diversity, petiole serial sectioning (outline, adaxial groove features, vasculature traces arrangement), and midrib characteristics of the studied species were investigated. The results of both chemotaxonomy and traditional taxonomy exhibited a remarkable agreement in the delineation of the five studied species. Specifically, the chemotaxonomy-based dendrogram separates the studied species into two main clusters with the H. sabdariffa as an outlier species in a single cluster and the remaining four species as another cluster with variant distances in its similarity indices. Similarly, the traditional morphological and anatomical characteristics revealed distinct traits for H. sabdariffa compared to the remaining four species. The findings of this study highlight the significance of integrating the structural features with phytochemicals profiling as a potential approach that could be harnessed for the delineation of the taxonomically challenging Hibiscus genus.

9.
Res Sq ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38947083

RESUMEN

Background and Purpose: Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus 12/15-LOX is an important target to prevent delayed cerebral ischemia. Methods: SAH was induced in C57BL/6 and 12/15-LOX-/- mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed in brain tissue slices and in vitro. C57BL/6 mice were administered either ML351 (12/15-LOX inhibitor) or vehicle. Mice were evaluated for daily neuroscore and euthanized on day five to assess cerebral 12/15-LOX expression, vessel constrictions, platelet activation, microthrombi, neurodegeneration, infarction, cortical perfusion, and for development of delayed deficits. Finally, the effect of 12/15-LOX inhibition on platelet activation was assessed in SAH patient samples using a platelet spreading assay. Results: In SAH mice, 12/15-LOX was upregulated in brain vascular cells and there was an increase in 12-S-HETE. Inhibition of 12/15-LOX improved brain perfusion on days 4-5 and attenuated delayed pathophysiological events, including microvessel constrictions, microthrombi, neuronal degeneration, and infarction. Additionally, 12/15-LOX inhibition reduced platelet activation in human and mouse blood samples. Conclusions: Cerebrovascular 12/15-LOX overexpression plays a major role in brain dysfunction after SAH by triggering microvessel constrictions and microthrombi formation, which reduces brain perfusion. Inhibiting 12/15-LOX may be a therapeutic target to improve outcomes after SAH.

11.
Saudi Dent J ; 36(7): 970-979, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39035557

RESUMEN

Background: The relationship between vitamin D deficiency with dental caries, periodontitis and oral cancer is controversial. Objectives: This review aimed to systematically evaluate the published literature and summarise the available evidence about the impact of vitamin D deficiency (VDD) on the oral diseases mentioned above. Methods: PubMed, Web of Science, Scopus and ScienceDirect databases were used. The search terms included were vitamin D, caries, periodontitis, and oral cancer. All papers published between January 2017 and November 2022 were included. The PRISMA process was used for the screening and selection studies. Results: Initially, 3001 studies were identified. However, after evaluating 46 full-text articles that explored the link between VDD and caries, periodontitis, and oral cancer, only 32 studies met the inclusion criteria for this systematic review. Among these, 15 studies focused on caries, 16 on periodontitis, and only one on oral cancer. Regarding study quality and risk of bias, 25 out of the 32 studies were deemed to have low risk. A total of 12 studies on periodontitis showed the impact of VDD. Conclusion: The review highlights that most evidence suggests an association between VDD and periodontitis. However, findings concerning the association between VDD and dental caries were controversial. Thus, further research is required to clarify the impacts of VDD on caries and oral cancer.

12.
JCO Oncol Pract ; : OP2400027, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013130

RESUMEN

PURPOSE: AML presenting with hyperleukocytosis is associated with poor outcomes. We aim to understand the factors associated with early mortality and overall survival (OS) to help guide management and improve early mortality. METHODS: We retrospectively reviewed data from 129 consecutive patients with newly diagnosed AML and a WBC count ≥100 × 109/L between January 2010 and April 2020. Logistic regression models estimated odds ratios for 4-week mortality. Cox proportional hazard models estimated hazard ratios for OS. RESULTS: The median age was 65 years (range, 23-86); the median WBC was 146 × 109/L (range, 100-687). Seventy-five (58%) patients had clinical leukostasis (CL). FLT3, NPM1, and RAS pathway mutations were detected in 63%, 45%, and 27% of patients, respectively. Cytoreduction consisted of hydroxyurea in 124 (96%) patients, cytarabine in 69 (54%), and leukapheresis in 31 (24%). The cumulative 4-week and 8-week mortality rates were 9% and 13%, respectively, all in patients age 65 years and older. By multivariate analysis, older age, CL, and thrombocytopenia <40 × 109/L were independently associated with a higher 4-week mortality rate. After a median follow-up of 49.4 months, the median OS was 14.3 months (95% CI, 7 to 21.6), with 4-year OS of 29%. Age 65 years and older, CL, tumor lysis syndrome, elevated LDH ≥2,000 U/L, elevated lactate ≥2.2 mmol/L, and poor-risk cytogenetics were independent factors associated with worse OS. CONCLUSION: Hyperleukocytosis is a life-threatening hematologic emergency. Early recognition and intervention including cytoreduction, blood product support, antibiotics, and renal replacement therapy may help mitigate the risk of morbidity and early mortality.

13.
Mol Biol Rep ; 51(1): 837, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39042337

RESUMEN

BACKGROUND: MiR-21-5p is a highly expressed microRNA that plays an important role in various cancer-promoting processes, including anchorage-independent growth, invasion, migration metastasis, and drug resistance in lung cancer. Studies indicate that miR-21-5p may contribute to these processes by promoting epithelial-mesenchymal transition (EMT). Ras homolog gene family member B (RhoB), a gene downregulated by miR-21-5p, has also been linked to EMT in lung cancer. However, the role of the miR-21-5p/RhoB axis in EMT regulation in lung adenocarcinoma remains unclear. In this study, we aimed to investigate the regulatory role of the miR-21-5p/RhoB axis in EMT and related in vitro functional characteristics such as migration, invasion, cisplatin resistance, and the formation of tumor spheroids. METHODS AND RESULTS: A549 cells were transfected with the miR-21-5p inhibitor, RhoB siRNA, and their corresponding negative controls. Wound healing, transwell invasion, Methyl thiazole tetrazolium (MTT), and sphere formation assays were also performed to evaluate the migration, invasion, cisplatin resistance, and anchorage-independent growth of A549 cells. RT-qPCR was used to determine the mRNA expression levels of EMT markers. MiR-21-5p knockdown inhibited migration, invasion, cisplatin resistance, and sphere formation while upregulating E-cadherin and downregulating Slug. Furthermore, RhoB silencing restored EMT and related in vitro functional characteristics in A549 cells. CONCLUSIONS: Knockdown of miR-21-5p inhibits EMT and related in vitro functional characteristics by upregulating RhoB, suggesting that miR-21-5p may promote EMT through downregulation of RhoB.


Asunto(s)
Adenocarcinoma del Pulmón , Movimiento Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , MicroARNs , Proteína de Unión al GTP rhoB , Humanos , Transición Epitelial-Mesenquimal/genética , MicroARNs/genética , MicroARNs/metabolismo , Proteína de Unión al GTP rhoB/genética , Proteína de Unión al GTP rhoB/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Movimiento Celular/genética , Células A549 , Resistencia a Antineoplásicos/genética , Cisplatino/farmacología , Regulación hacia Arriba/genética , Proliferación Celular/genética , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Invasividad Neoplásica/genética , Cadherinas/genética , Cadherinas/metabolismo
14.
Cureus ; 16(5): e59710, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38841008

RESUMEN

INTRODUCTION: Preoperative anxiety can negatively impact patient outcomes by influencing the intraoperative requirements for anesthetics and analgesics, increasing postoperative pain intensity, and augmenting the need for analgesia. Moreover, it may contribute to higher rates of postoperative morbidity and mortality following certain types of surgery. This study investigates the anxiolytic and sedative properties of sublingual melatonin as a premedication agent in young females undergoing cesarean section under spinal anesthesia. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in Nasiriyah, Iraq. Eighty females were included, 40 in each group, based on specific inclusion and exclusion criteria. Premedication was administered in the morning, 60 minutes before the procedure. In the melatonin group (M), patients received 10 mg of sublingual melatonin, while the placebo group (P) received placebo premedication. Anxiety and sedation levels were evaluated three times: before taking premedication, five minutes before the insertion of the spinal needle, and one hour postoperatively, using the visual analog scale and Richmond Sedation Scale. RESULTS: The results show a highly significant P-value regarding anxiety levels between the M Group and P Group (p-value < 0.001). There was a significant difference in the median sedation scores between the studied groups at pre-spinal insertion and postoperatively (p-value < 0.001). The mean heart rate in the M Group was significantly lower than in the P Group (p-value = 0.0019). Significant differences were noted in systolic and diastolic blood pressures between the two groups, measured five minutes before and after spinal needle insertion (p-value < 0.001). CONCLUSION: These findings contribute to understanding the impact of sublingual melatonin as an anxiolytic and sedative premedication agent on patients undergoing elective cesarean sections under spinal anesthesia. Further research is warranted to fully elucidate the benefits and implications of melatonin administration in such procedures.

15.
Poult Sci ; 103(8): 103732, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38925079

RESUMEN

The incidence of chronic respiratory disease (CRD) due to Mycoplasma gallisepticum (MG) contamination in hatching eggs poses a serious threat to poultry health and hatchability. Implementing effective sanitization methods while safeguarding the hatching potential of embryos is crucial. This study aimed to explore novel techniques for sanitizing hatching-fertile eggs to prevent and manage MG-associated CRD. The primary objective was to assess the efficacy of acidic electrochemically stimulated water (ECS), focusing on MG disinfection. Additionally, the study investigated 2 application methods, 1) electrostatic disinfection (ED) and 2) cold fog (CF) disinfection, to evaluate their bactericidal effects against MG-contaminated eggs. Deliberately infected MG strains were used for the experimental design, which compared the disinfection efficacy of ECS with its acidic properties. The comparison involved ED, which applies an electrostatic charge to water particles, and CF disinfection, a cold mist technique. Both methods aimed to target MG without compromising egg-hatching potential. The results indicated a significant (p < 0.05) reduction in colony-forming units per milliliter (CFU/mL). However, both application methods demonstrated distinct bactericidal effects. Eggs treated with electrostatic disinfection showed a significant (p < 0.001) reduction in embryonic mortality during incubation (10%) compared to control untreated eggs (18%). Similarly, the CF method exhibited a significant (p < 0.001) decrease in embryonic mortality (13%). The ECS potential in reducing embryonic mortality within the pH range of 2.5 to 6.5 was noted. Both the ED and CF methods show promise for preventing MG-induced hatchery infection while maintaining egg-hatching potential. This study presents innovative techniques to control MG in hatching eggs, contributing to improved poultry health and reduced CRD incidence.


Asunto(s)
Desinfección , Infecciones por Mycoplasma , Mycoplasma gallisepticum , Óvulo , Enfermedades de las Aves de Corral , Electricidad Estática , Animales , Desinfección/métodos , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/microbiología , Mycoplasma gallisepticum/efectos de los fármacos , Óvulo/efectos de los fármacos , Infecciones por Mycoplasma/veterinaria , Infecciones por Mycoplasma/prevención & control , Infecciones por Mycoplasma/microbiología , Pollos , Frío , Embrión de Pollo
16.
Phys Rev Lett ; 132(22): 225001, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38877942

RESUMEN

We report on an experimental observation of the streaking of betatron x rays in a curved laser wakefield accelerator. The streaking of the betatron x rays was realized by launching a laser pulse into a plasma with a transverse density gradient. By controlling the plasma density and the density gradient, we realized the steering of the laser driver, electron beam, and betatron x rays simultaneously. Moreover, we observed an energy-angle correlation of the streaked betatron x rays and utilized it in diagnosing the electron acceleration process in a single-shot mode. Our work could also find applications in advanced control of laser beam and particle propagation. More importantly, the angular streaked betatron x ray has an intrinsic spatiotemporal correlation, which makes it a promising tool for single-shot pump-probe applications.

17.
Blood ; 144(8): 888-903, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-38941612

RESUMEN

ABSTRACT: In acute myeloid leukemia (AML), leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) interact with various cell types in the bone marrow (BM) microenvironment, regulating their expansion and differentiation. To study the interaction of CD4+ and CD8+ T cells in the BM with LSCs and LPCs, we analyzed their transcriptome and predicted cell-cell interactions by unbiased high-throughput correlation network analysis. We found that CD4+ T cells in the BM of patients with AML were activated and skewed toward T-helper (Th)1 polarization, whereas interleukin-9 (IL-9)-producing (Th9) CD4+ T cells were absent. In contrast to normal hematopoietic stem cells, LSCs produced IL-9, and the correlation modeling predicted IL9 in LSCs as a main hub gene that activates CD4+ T cells in AML. Functional validation revealed that IL-9 receptor signaling in CD4+ T cells leads to activation of the JAK-STAT pathway that induces the upregulation of KMT2A and KMT2C genes, resulting in methylation on histone H3 at lysine 4 to promote genome accessibility and transcriptional activation. This induced Th1-skewing, proliferation, and effector cytokine secretion, including interferon gamma (IFN-γ) and tumor necrosis factor α (TNF-α). IFN-γ and, to a lesser extent, TNF-α produced by activated CD4+ T cells induced the expansion of LSCs. In accordance with our findings, high IL9 expression in LSCs and high IL9R, TNF, and IFNG expression in BM-infiltrating CD4+ T cells correlated with worse overall survival in AML. Thus, IL-9 secreted by AML LSCs shapes a Th1-skewed immune environment that promotes their expansion by secreting IFN-γ and TNF-α.


Asunto(s)
Linfocitos T CD4-Positivos , Interleucina-9 , Leucemia Mieloide Aguda , Células Madre Neoplásicas , Células TH1 , Interleucina-9/genética , Interleucina-9/metabolismo , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/inmunología , Células TH1/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Proliferación Celular , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Microambiente Tumoral/inmunología , Receptores de Interleucina-9/genética , Receptores de Interleucina-9/metabolismo , Interferón gamma/metabolismo , N-Metiltransferasa de Histona-Lisina/genética
18.
J Proteome Res ; 23(7): 2495-2504, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38829961

RESUMEN

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower than those of AML without deletion 7/7q, this observation was not significant. Low ASNS expression correlated with improved overall survival (46 versus 54 weeks, respectively, p = 0.011), whereas higher ASNS levels were associated with better response to venetoclax-based therapy. Protein correlation analysis demonstrated association between ASNS and proteins involved in methylation and DNA repair. In conclusion, while ASNS expression was not lower in patients with deletion 7/7q as initially predicted, ASNS levels were highly variable across AML patients. Further studies are needed to assess whether patients with low ASNS expression are susceptible to asparaginase-based therapy due to their inability to augment compensatory ASNS expression upon asparagine depletion.


Asunto(s)
Aspartatoamoníaco Ligasa , Leucemia Mieloide Aguda , Proteómica , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Aspartatoamoníaco Ligasa/genética , Aspartatoamoníaco Ligasa/metabolismo , Femenino , Proteómica/métodos , Masculino , Persona de Mediana Edad , Adulto , Anciano , Deleción Cromosómica , Análisis por Matrices de Proteínas/métodos , Asparaginasa/uso terapéutico , Asparaginasa/genética , Cromosomas Humanos Par 7/genética , Adulto Joven , Ligasas de Carbono-Nitrógeno con Glutamina como Donante de Amida-N
19.
Biology (Basel) ; 13(5)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38785810

RESUMEN

The rising demand for safe plant compounds and herbal products that contribute positively to human health is in line with current market trends. Plants belonging to the Satureja genus, particularly the aromatic medicinal S. montana L. from the Lamiaceae family, are well suited to these trends as they serve as pharmaceutical raw materials. This research aimed to assess the influence of sowing date and fertilization doses, as well as their interaction, on the fresh weight, essential oil content, and composition of S. montana. Experimental cultivation involved varying nitrogen and phosphorus levels. The second cut had the highest fresh weight and oil production compared to the first cut. The highest total plant biomass was achieved with autumn sowing and fertilization at 55 kg N/ha and 37 kg P/ha, whereas Spring sowing exhibited higher essential oil production, with the maximum oil % with 74 kg P/ha and oil yield after applying 55 kg N/ha and 74 kg P/ha. The GC-MS analysis revealed that carvacrol was the predominant compound, with it being recommended to grow S. montana in Spring at doses of 55 kg N/ha and 74 kg P/ha for the superior oil yield. Additionally, S. montana essential oil demonstrated notable biological and antimicrobial activity, positioning it as a potential alternative to chemical food preservatives.

20.
Foods ; 13(10)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38790803

RESUMEN

Illicium verum, commonly known as star anise, represents one of the notable botanical species and is recognized for its rich reservoir of diverse bioactive compounds. Beyond its culinary application as a spice, this plant has been extensively utilized in traditional medicine. Given the contemporary emphasis on incorporating natural resources into food production, particularly essential oils, to enhance sensory attributes and extend shelf life, our study seeks to elucidate the chemical composition and evaluate the antibacterial (in vitro, in situ) and insecticidal properties of Illicium verum essential oil (IVEO). Also, microbiological analyses of pumpkin sous vide treated with IVEO after inoculation of Salmonella enterica were evaluated after 1 and 7 days of study. GC/MS analysis revealed a significantly high amount of (E)-anethole (88.4%) in the investigated EO. The disc diffusion method shows that the antibacterial activity of the IVEO ranged from 5.33 (Streptococcus constellatus) to 10.33 mm (Citrobacter freundii). The lowest minimal inhibition concentration was found against E. coli and the minimum biofilm inhibition concertation was found against S. enterica. In the vapor phase, the best antimicrobial activity was found against E. coli in the pears model and against S. sonei in the beetroot model. The application of the sous vide method in combination with IVEO application decreased the number of microbial counts and eliminated the growth of S. enterica. The most isolated microbiota identified from the sous vide pumpkin were Bacillus amyloliquefaciens, B. cereus, B. licheniformis, and Ralstonia picketii. Modifications to the protein composition of biofilm-forming bacteria S. enterica were suggested by the MALDI TOF MS instigations. The IVEO showed insecticidal potential against Harmonia axyridis. Thanks to the properties of IVEO, our results suggest it can be used in the food industry as a natural supplement to extend the shelf life of foods and as a natural insecticide.

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