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BACKGROUND: Ballota acetabulosa native to the Mediterranean region, belonging to the Lamiaceae family, holds significance in folk medicine. Externally, it is applied for treating cuts and burns, while internally, it is utilized to alleviate inflammation, suppress cough, and address gastrointestinal issues. METHODS: This study aimed to investigate the chemical composition of the essential oil of Ballota acetabulosa and to evaluate the antioxidant capacity of the essential oil, as well as the aqueous and ethanolic extracts of the plant. Essential oil analysis was performed using Gas Chromatography- Mass Spectrometry (GC-MS), while 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and inhibition of lipid peroxidation assays were applied to the essential oil, water, and ethanol extracts of the plant. RESULTS: Spathulenol was found to be the predominant constituent of the essential oil, comprising 25.03% of the oil. Compared to the control group (Propyl gallate for DPPH, IC50 0.109; BHT for inhibition of lipid peroxidation, IC50 0.133), the essential oil was found to have insignificant antioxidant activity (IC50 value 10.395 mg/mL for DPPH, 1.051 mg/mL for inhibition of lipid peroxidation). Moreover, ethanolic extract (IC50 value 1.583 mg/mL for DPPH, 0.029 mg/mL for inhibition of lipid peroxidation) exerted more antioxidant activity than aqueous extract (IC50 value 1.9017 mg/mL for DPPH, 0.161 mg/mL for inhibition of lipid peroxidation). CONCLUSION: Hitherto, this is the earliest report on the composition and activity of the essential oil Ballota acetabulosa. However, further investigation of different antioxidant capacity assays is suggested to highlight potential variations in mechanisms of action and subsequent results. Everything considered, this study advances the comprehension of the chemical composition and possible therapeutic uses of Ballota acetabulosa, highlighting the need for more research into its uses.
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BACKGROUND: Infertility caused by drugs that inhibit serotonin reuptake has been attributed to serotonin toxicity. Serotonin has been linked to cause a rise in prolactin and cortisol. This study examined the effects of meperidine, sertraline, tianeptine and combinations on female rat reproductive function. METHODS: Female rats were split into 8 groups (n=7): healthy control (HG), meperidine (MG), sertraline (SG), tianeptine (TG), meperidine+sertraline (MSG), meperidine+tianeptine (MTG), sertraline+tianeptine (STG), meperidine+sertraline+tianeptine (MSTG). Meperidine (20â¯mg/kg, 2×1) was injected intramuscularly. Sertraline (30â¯mg/kg, 1×1) and tianeptine (5â¯mg/kg, 1×1) were given orally. The HG received distilled water as solvent. Treatments continued for 20 days. Then, adult males were added to the rat groups and drug treatment continued for another five days. Blood samples were collected on day 26 for biochemical tests. RESULTS: Total oxidant status (TOS) and total antioxidant status (TAS) were not statistically significant between groups (p>0.05). Meperidine (p<0.001) and sertraline (p<0.001) alone increased prolactin levels in comparison to HG and tianeptine inhibited the increase (p<0.001). While meperidine increased corticosterone levels versus HG (p<0.001), sertraline and tianeptine were close to HG (p>0.05). Number of infertile animals was 6 for meperidine, 3 for sertraline, and none for tianeptine. While the duration of pregnancy in MG (15 days) and SG (15 days) was longer compared to HG (2.86 days), no change was observed in TG (2.5 days). CONCLUSION: Tianeptine and other serotonin re-uptake stimulants may be useful in the treatment of reproductive dysfunction and infertility due to serotonin re-uptake inhibitor treatment.
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Background/aim: LUNGBANK was established as part of Project LUNGMARK, pioneering a biorepository dedicated exclusively to lung cancer research. It employs cutting-edge technologies to streamline the handling of biospecimens, ensuring the acquisition of high-quality samples. This infrastructure is fortified with robust data management capabilities, enabling seamless integration of diverse datasets. LUNGBANK functions not merely as a repository but as a sophisticated platform crucial for advancing lung cancer research, poised to facilitate significant discoveries. Materials and methods: LUNGBANK was meticulously designed to optimize every stage of biospecimen handling, from collection and storage to processing. Rigorous standard operating procedures and stringent quality control measures guarantee the integrity of collected biospecimens. Advanced data management protocols facilitate the efficient integration and analysis of various datasets, enhancing the depth and breadth of research possibilities in lung cancer. Results: LUNGBANK has amassed a comprehensive collection of biospecimens essential for unraveling the intricate molecular mechanisms of lung cancer. The integration of state-of-the-art technologies ensures the acquisition of top-tier data, fostering breakthroughs in translational and histological research. Moreover, the establishment of patient-derived systems by LUNGBANK underscores its pivotal role in personalized medicine approaches. Conclusion: The establishment of LUNGBANK marks a significant milestone in addressing the critical challenges of lung cancer research. By providing researchers with high-quality biospecimens and advanced research tools, LUNGBANK not only supports Project LUNGMARK's objectives but also contributes extensively to the broader landscape of personalized medicine. It promises to enhance our understanding of lung cancer initiation, progression, and therapeutic interventions tailored to individual patient needs, thereby advancing the field towards more effective diagnostic and therapeutic strategies.
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Introduction: Today's labor market is comprised of different generations and in the near future, the majority of it will consist of Generation Z. In this respect, it is of great importance to know the perspective of Generation Z, which will take its place in leadership positions in organizations, on leadership and what kind of leader they will be. The present study probes to investigate how Generation Z will become a leader and their perspective on leadership. In this regard, the study aims to offer suggestions and guidance to the literature and organizations by providing information on what kind of leaders they will be as well as knowing the characteristics of Generation Z leaders. Methods: In the study conducted Generation Z, employed in the IT sector, semi-structured interviews were held with 13 participants. While analyzing the data obtained from the interviews, the MAXQDA 2020 program was utilized and the thematic analysis method was applied. Results: In our findings about how Generation Z will be leaders in the future, two themes were identified, which include intra-organizational communication and working conditions. In the light of findings on the leadership of Generation Z, the sub-themes of being supportive, empathetic, egoless, managing people well and managing with love and respect were reached on the theme of intra-organizational communication. On the other hand, on the theme of working conditions, sub-themes such as providing training, offering payment according to output, preferring flexible working hours, being friendly, assigning appropriate work to the employee, being fun and not giving importance to gender were identified. Discussion: The results revealed that Generation Z prefers managing their team with a people-oriented approach when they take leadership positions. From their perspective, the leader should understand and value his employees. Leaders who know the expectations of Generation Z will contribute to their organizations. In addition, organizations should improve their leadership skills by providing leadership training for Generation Z, who will be leaders in the future. In this way, they will make investment both in their leaders and their organizations.
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Seborrheic dermatitis (SD) and osteoarthritis involve similar factors in their pathogenesis. Both of these diseases are associated with an increased frequency of metabolic syndrome and underlying systemic inflammation. This study evaluated the thickness of the distal femoral cartilage using ultrasonography in patients with SD. The study enrolled 60 patients with SD (19 females and 41 males, mean age: 34.07â ±â 12.56 years) and 60 controls matched for age and sex (20 females and 40 males, mean age: 35.08â ±â 12.78 years). Ultrasonography was used to measure the distal femoral cartilage thickness (FCT) of the right medial condyle, right lateral condyle, right intercondylar area, left medial condyle, left lateral condyle, and left intercondylar area. FCT values at all points were significantly higher in patients with SD than in the controls (Pâ <â .05). Further, all FCT values were significantly higher in patients with moderate SD than in those with mild SD (Pâ <â .001). A strong positive correlation was observed between disease severity and FCT measured at right medial condyle (râ =â .7, Pâ <â .001), right lateral condyle (râ =â .749, Pâ <â .001), right intercondylar area (râ =â .79, Pâ <â .001), left medial condyle (râ =â .624, Pâ <â .001), and left intercondylar area (râ =â .703, Pâ <â .001). Further, a moderately positive correlation was observed between disease severity and FCT measured at left lateral condyle (râ =â .581, Pâ <â .001). Increased FCT in patients with SD might be an early indicator of osteoarthritis. However, further studies, especially those evaluating older patients with SD, are required to support our findings.
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Cartílago Articular , Dermatitis Seborreica , Osteoartritis , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Articulación de la Rodilla/patología , Cartílago Articular/patología , Fémur/patología , Osteoartritis/complicaciones , Osteoartritis/diagnóstico por imagen , Osteoartritis/patologíaRESUMEN
BACKGROUND: Pathogenic variants in the nicotinamide nucleotide transhydrogenase gene (NNT) are a rare cause of primary adrenal insufficiency (PAI), as well as functional impairment of the gonads. OBJECTIVE: Despite the description of different homozygous and compound heterozygous NNT variants in PAI patients, the extent to which the function and expression of the mature protein are compromised remains to be clarified. DESIGN: The activity and expression of mitochondrial NAD(P)+ transhydrogenase (NNT) were analyzed in blood samples obtained from patients diagnosed with PAI due to genetically confirmed variants of the NNT gene (n = 5), heterozygous carriers as their parents (n = 8), and healthy controls (n = 26). METHODS: NNT activity was assessed by a reverse reaction assay standardized for digitonin-permeabilized peripheral blood mononuclear cells (PBMCs). The enzymatic assay was validated in PBMC samples from a mouse model of NNT absence. Additionally, the PBMC samples were evaluated for NNT expression by western blotting and reverse transcription quantitative polymerase chain reaction and for mitochondrial oxygen consumption. RESULTS: NNT activity was undetectable (<4% of that of healthy controls) in PBMC samples from patients, independent of the pathogenic genetic variant. In patients' parents, NNT activity was approximately half that of the healthy controls. Mature NNT protein expression was lower in patients than in the control groups, while mRNA levels varied widely among genotypes. Moreover, pathogenic NNT variants did not impair mitochondrial bioenergetic function in PBMCs. CONCLUSIONS: The manifestation of PAI in NNT-mutated patients is associated with a complete lack of NNT activity. Evaluation of NNT activity can be useful to characterize disease-causing NNT variants.
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Enfermedad de Addison , NADP Transhidrogenasas , Animales , Humanos , Ratones , Leucocitos Mononucleares/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , NAD , NADP Transhidrogenasa AB-Específica/genética , NADP Transhidrogenasa AB-Específica/metabolismo , NADP Transhidrogenasas/genética , NADP Transhidrogenasas/metabolismoRESUMEN
Acute myeloid leukemia (AML) is a heterogeneous disease and the most common form of acute leukemia with a poor prognosis. Due to its complexity, the disease requires the identification of biomarkers for reliable prognosis. To identify potential disease genes that regulate patient prognosis, we used differential co-expression network analysis and transcriptomics data from relapsed, refractory, and previously untreated AML patients based on their response to treatment in the present study. In addition, we combined functional genomics and transcriptomics data to identify novel and therapeutically potential systems biomarkers for patients who do or do not respond to treatment. As a result, we constructed co-expression networks for response and non-response cases and identified a highly interconnected group of genes consisting of SECISBP2L, MAN1A2, PRPF31, VASP, and SNAPC1 in the response network and a group consisting of PHTF2, SLC11A2, PDLIM5, OTUB1, and KLRD1 in the non-response network, both of which showed high prognostic performance with hazard ratios of 4.12 and 3.66, respectively. Remarkably, ETS1, GATA2, AR, YBX1, and FOXP3 were found to be important transcription factors in both networks. The prognostic indicators reported here could be considered as a resource for identifying tumorigenesis and chemoresistance to farnesyltransferase inhibitor. They could help identify important research directions for the development of new prognostic and therapeutic techniques for AML.
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Leucemia Mieloide Aguda , Humanos , Farnesiltransferasa/genética , Farnesiltransferasa/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Pronóstico , Perfilación de la Expresión Génica/métodos , Inhibidores Enzimáticos/uso terapéutico , Factores de Transcripción/genética , Biomarcadores de Tumor/genéticaRESUMEN
Bolanthus aziz-sancarii identified in 2019 for the first time is an endemic species of Bolanthus genus belonging to Caryophyllaceae family. Ten compounds were isolated from aerial parts of the plant. The potential antioxidant and anti-inflammatory effects of all four phases (hexane, chloroform, ethyl acetate, and water) from the methanol extract of the plant were investigated. After considering the findings regarding both antioxidant and anti-inflammatory capacities, it was decided to investigate the phytochemical profile of the EtOAc layer of B. aziz-sancarii. An abscisic acid-type sesquiterpene glucoside and nine flavonoid derivatives were isolated from the ethyl acetate fraction of the B. aziz-sancarii methanol extract through the use of column chromatography with silica gel.
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Introduction: Co-normalization of RNA profiles obtained using different experimental platforms and protocols opens avenue for comprehensive comparison of relevant features like differentially expressed genes associated with disease. Currently, most of bioinformatic tools enable normalization in a flexible format that depends on the individual datasets under analysis. Thus, the output data of such normalizations will be poorly compatible with each other. Recently we proposed a new approach to gene expression data normalization termed Shambhala which returns harmonized data in a uniform shape, where every expression profile is transformed into a pre-defined universal format. We previously showed that following shambhalization of human RNA profiles, overall tissue-specific clustering features are strongly retained while platform-specific clustering is dramatically reduced. Methods: Here, we tested Shambhala performance in retention of fold-change gene expression features and other functional characteristics of gene clusters such as pathway activation levels and predicted cancer drug activity scores. Results: Using 6,793 cancer and 11,135 normal tissue gene expression profiles from the literature and experimental datasets, we applied twelve performance criteria for different versions of Shambhala and other methods of transcriptomic harmonization with flexible output data format. Such criteria dealt with the biological type classifiers, hierarchical clustering, correlation/regression properties, stability of drug efficiency scores, and data quality for using machine learning classifiers. Discussion: Shambhala-2 harmonizer demonstrated the best results with the close to 1 correlation and linear regression coefficients for the comparison of training vs validation datasets and more than two times lesser instability for calculation of drug efficiency scores compared to other methods.
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Objectives: The underlying mechanisms for the development of chronic thromboembolic pulmonary hypertension and prognostic biomarkers are not clear yet. Thus, our aim is to assess and identify new biomarkers for the expression of 84 key genes linked to angiogenesis. Methods: Patients who had levels more than 1000 dynes·sec·cm-5 were included in the test group, and the other patients were included in the control group. Twelve specimens were taken from the patients. RT2 Profiler PCR Array (Qiagen) was used to quantify the expression of the 84 key genes. Results: Eight patients (6 male, 2 female, median age 54.4 ± 13.1 years) who underwent pulmonary endarterectomy were included. Pulmonary vascular resistance improved significantly from 811 ± 390 dyn/s/cm-5 to 413.3 ± 144.9 dyn/s/cm-5 (P < .005). A difference was also detected in median mean pulmonary arterial pressure, which decreased from 49.8 ± 9 mm Hg to 32.62 ± 2.50 mm Hg (P > .005) after surgery. Median length of hospital stay was 11.62 ± 2.97 days. The test group had a distinct pattern of impaired angiogenic and antiangiogenic genes. The expression levels of TGFA, TGFB1, THBS2, THBS1, TGFBR1, SERPINE1, SERPINF1, TGFB2, TIMP2, VEGFC, IFNA1, TNF, CXCL10, NOS3, IGF1, and MMP14 were downregulated in the specimens from the patients who had higher pulmonary vascular resistance values, whereas some genes, including PDGFA, showed upregulation that was statistically nonsignificant in the same group. Conclusions: These results can lead to the development of new markers that could predict adverse outcomes of patients with CTEPH. Identification of new markers that are related to worse outcomes would enable screening patients for early diagnosis and treatment.
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With the development and approval of new proteasome inhibitors, proteasome inhibition is increasingly recognized in cancer therapy. Besides successful anti-cancer effects in hematological cancers, side effects such as cardiotoxicity are limiting effective treatment. In this study, we used a cardiomyocyte model to investigate the molecular cardiotoxic mechanisms of carfilzomib (CFZ) and ixazomib (IXZ) alone or in combination with the immunomodulatory drug dexamethasone (DEX) which is frequently used in combination therapies in the clinic. According to our findings, CFZ showed a higher cytotoxic effect at lower concentrations than IXZ. DEX combination attenuated the cytotoxicity for both proteasome inhibitors. All drug treatments caused a marked increase in K48 ubiquitination. Both CFZ and IXZ caused an upregulation in cellular and endoplasmic reticulum stress protein (HSP90, HSP70, GRP94, and GRP78) levels and DEX combination attenuated the increased stress protein levels. Importantly, IXZ and IXZ-DEX treatments caused upregulation of mitochondria fission and fusion gene expression levels higher than caused by CFZ and CFZ-DEX combination. The IXZ-DEX combination reduced the levels of OXPHOS proteins (Complex II-V) more than the CFZ-DEX combination. Reduced mitochondrial membrane potential and ATP production were detected with all drug treatments in cardiomyocytes. Our findings suggest that the cardiotoxic effect of proteasome inhibitors may be due to their class effect and stress response and mitochondrial dysfunction may be involved in the cardiotoxicity process.
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Antineoplásicos , Inhibidores de Proteasoma , Humanos , Inhibidores de Proteasoma/toxicidad , Cardiotoxicidad , Antineoplásicos/farmacología , Dexametasona/toxicidad , Mitocondrias , Línea Celular TumoralRESUMEN
Almost half of the trials failed to recruit their targeted sample size of which 89% could be preventable. Successful implementation of mental health trials in a context of forcibly displaced individuals can be even more challenging. Mental health difficulties have the potential to impact parenting skills, which are linked to poor development in children, while parenting interventions can improve parents' mental health and parenting behaviors. However, the evidence on parenting interventions for refugees is limited. A parenting intervention, Learning Through Play Plus Eye Movement Desensitization and Reprocessing Group Treatment Protocol, has been designed to address parental mental health. This pretrial qualitative study, conducted with refugees, asylum seekers and professionals, aimed to explore their perceptions of the intervention and to identify barriers and recommendations for better engagement, recruitment, and delivery. Three themes were generated from thematic analysis: the content of the intervention, suggestions for improvement and implementation, and understanding the role of the facilitator. These themes provided insights into the issues that might predict the barriers for delivery of the intervention and offered several changes, including destigmatization strategies to improve engagement.
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Ludoterapia , Refugiados , Niño , Humanos , Investigación CualitativaRESUMEN
Background: Biallelic QRSL1 mutations cause mitochondrial 'combined oxidative phosphorylation deficiency-40' (COXPD40). COXPD40 has been reported to be invariably lethal in infancy. Adrenal insufficiency was weakly reported and investigated among seven previously reported patients with COXPD40. Objective: We report the clinical, biochemical, molecular, and functional characteristics of a patient with adrenal insufficiency due to COXPD40. Methods: The medical history and adrenal function tests were examined. Genetic analysis was performed using whole-exome sequencing. Mitochondrial function was tested using mitochondrial membrane potential (MMP) and superoxide dismutase (SOD) enzyme assays. Results: An 8-year-old boy was investigated for adrenal insufficiency. He also had mild developmental delay, sensorineural hearing loss, hypertrophic cardiomyopathy, nephrocalcinosis, elevated parathyroid hormone and creatine kinase, and lactic acidosis. Biallelic novel QRSL1 variants (c.300T>A;Y100* and c.610G>A;G204R) were identified. Oxidative damage in mitochondria was shown by reduced MMP and SOD assays in the patient compared to controls (P < 0.0001). Adrenal function tests revealed a 'primary adrenal insufficiency other than congenital adrenal hyperplasia' (non-CAH PAI) with an isolated glucocorticoid deficiency. In the 8-year follow-up, having the longest survival of reported COXPD40 patients, he had preserved mineralocorticoid functions and gonadal steroidogenesis. Conclusion: Biallelic QRSL1 mutations can cause non-CAH PAI. Adrenal functions should be monitored in mitochondrial disorders to improve clinical outcomes.
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Enfermedad de Addison , Hiperplasia Suprarrenal Congénita , Insuficiencia Suprarrenal , Hiperplasia Suprarrenal Congénita/genética , Insuficiencia Suprarrenal/genética , Niño , Humanos , Masculino , Mutación/genética , Superóxido Dismutasa/genéticaRESUMEN
Plastoquinone analogs are privileged structures among the known antiproliferative natural product-based compound families. Exploiting one of these analogs as a lead structure, we report the investigation of the brominated PQ analogs (BrPQ) in collaboration with the National Cancer Institute of Bethesda within the Developmental Therapeutics Program (DTP). These analogs exhibited growth inhibition in the micromolar range across leukemia, non-small cell lung cancer (EKVX, HOP-92, and NCI-H522), colon cancer (HCT-116, HOP-92), melanoma (LOX IMVI), and ovarian cancer (OVCAR-4) cell lines. One brominated PQ analog (BrPQ5) was selected for a full panel five-dose in vitro assay by the NCI's Development Therapeutic Program (DTP) division to determine GI50, TGI, and LC50 parameters. The brominated PQ analog (BrPQ5) displayed remarkable activity against most tested cell lines, with GI50 values ranging from 1.55 to 4.41 µM. The designed molecules (BrPQ analogs) obeyed drug-likeness rules, displayed a favorable predictive Absorption, Distribution, Metabolism, and Excretion (ADME) profile, and an in silico simulation predicted a possible BrPQ5 interaction with proteasome catalytic subunits. Furthermore, the in vitro cytotoxic activity of BrPQ5 was assessed, and IC50 values for U-251 glioma, MCF-7 and MDA-MB-231 breast cancers, DU145 prostate cancer, HCT-116 colon cancer, and VHF93 fibroblast cell lines were evaluated using an MTT assay. MCF-7 was the most affected cell line, and the effects of BrPQ5 on cell proliferation, cell cycle, oxidative stress, apoptosis/necrosis induction, and proteasome activity were further investigated in MCF-7 cells. The in vitro assay results showed that BrPQ5 caused cytotoxicity in MCF-7 breast cancer cells via cell cycle arrest and oxidative stress induction. However, BrPQ5 did not inhibit the catalytic activity of the proteasome. These results provide valuable insights for further discovery of novel antiproliferative agents.
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In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Humanos , Isocitrato Deshidrogenasa/genética , MutaciónRESUMEN
Acute myeloid leukemia (AML) is a common, complex, and multifactorial malignancy of the hematopoietic system. AML diagnosis and treatment outcomes display marked heterogeneity and patient-to-patient variations. To date, AML-related biomarker discovery research has employed single omics inquiries. Multiomics analyses that reconcile and integrate the data streams from multiple levels of the cellular hierarchy, from genes to proteins to metabolites, offer much promise for innovation in AML diagnostics and therapeutics. We report, in this study, a systems medicine and multiomics approach to integrate the AML transcriptome data and reporter biomolecules at the RNA, protein, and metabolite levels using genome-scale biological networks. We utilized two independent transcriptome datasets (GSE5122, GSE8970) in the Gene Expression Omnibus database. We identified new multiomics molecular signatures of relevance to AML: miRNAs (e.g., mir-484 and miR-519d-3p), receptors (ACVR1 and PTPRG), transcription factors (PRDM14 and GATA3), and metabolites (in particular, amino acid derivatives). The differential expression profiles of all reporter biomolecules were crossvalidated in independent RNA-Seq and miRNA-Seq datasets. Notably, we found that PTPRG holds important prognostication potential as evaluated by Kaplan-Meier survival analyses. The multiomics relationships unraveled in this analysis point toward the genomic pathogenesis of AML. These multiomics molecular leads warrant further research and development as potential diagnostic and therapeutic targets.
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Leucemia Mieloide Aguda , MicroARNs , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , MicroARNs/genética , Análisis de Sistemas , Transcriptoma/genéticaRESUMEN
Aim of this study is to investigate whether the risk of miscarriage increases in pregnant women who had COVID-19 in first trimester. Our study included 52 patients with SARS-CoV-2 infection detected by RT-PCR and 53 patients with negative RT-PCR test in samples taken with nasopharyngeal swab in the first trimester between March 1 and December 31, 2020. Complete abortion, incomplete abortion, blighted ovum, intrauterine exitus, biochemical pregnancies were accepted as in the miscarriage group (MG). Pregnant women with COVID-19 and control group were compared in terms of demographic data, miscarriage rate and laboratory results. Patients were divided into MG and ongoing pregnancy groups (OPG) and compared in terms of the diagnosed weeks, clinical findings, laboratory results, treatments, and hospitalization. While miscarriage was observed in 15 (28.8%) of pregnant women infected with SARS-CoV-2 in the first trimester, this number was 7 (13.2%) in the control group. While the common symptoms in the MG were cough (60%), fever (53.3%), shortness of breath (53.3%), and fatigue (46.7%) (p<0.05); asymptomatic patients (51.4%) were higher in the OPG (p<0.001). Hospitalized patients were 33.3% in the MG and 8.1% in the OPG (p=0.02). According to the results of our study, the risk of miscarriage increases in pregnant women infected with SARS-CoV-2 (especially in severe infection) in the first trimester.
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Aborto Espontáneo , COVID-19 , Complicaciones Infecciosas del Embarazo , Aborto Espontáneo/etiología , COVID-19/complicaciones , Femenino , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Primer Trimestre del Embarazo , SARS-CoV-2RESUMEN
BACKGROUND: Proteasome inhibitors target different pathways in cells and therefore are promising drugs in cancer therapy. The use of these inhibitors is approved mainly in hematological cancers, and recently many clinical trials and preclinical studies have been conducted on efficacy in solid tumors. Carfilzomib is a second-generation inhibitor and was developed to decrease the side effects of bortezomib. Although there are many valid therapies for breast cancer, resistance and recurrence are inevitable in many cases and the proteasomal system plays an important role in related pathways. OBJECTIVE: This study is a preliminary work to evaluate the combined effects of bortezomib and carfilzomib in four different breast cancer cells. METHODS: MDA-MB-231, MCF-7, UACC-2087, and SKBR-3 cell lines were used. Cell viability was determined using bortezomib and carfilzomib alone and in combination. Combination effect values were determined using the Chou- Talalay method. Apoptosis, proteasome activity, cleaved PARP, and HSP70 expressions were analyzed in the determined doses. RESULTS: The response to the combination of the two inhibitors was different in four cell lines. Apoptosis was significantly higher in combination groups compared to carfilzomib in three cell lines except for SKBR-3, and higher in the combination group compared to bortezomib only in UACC-2087. Combination decreased cleaved PARP levels in MDA-MB-231 and MCF-7 and increased SKBR-3 compared to bortezomib. HSP70 levels decreased in combination with UACC-2087 and SKBR-3 compared to carfilzomib. CONCLUSION: Taken together, the combination of the two inhibitors was more apoptotic compared to carfilzomib and apoptosis was higher only in UACC-2087 compared to bortezomib. This apoptosis data can not be directly correlated to the degree of proteasome inhibition, PARP cleavage, and HSP70 response.