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Burkitt lymphoma, an aggressive form of B-cell non-Hodgkin's lymphoma, is linked with a specific genetic alteration, i.e., t (8;14), a reciprocal translocation that involves the I c-MYC i oncogene on chromosome 8 and the I IGH i locus on chromosome 14, respectively. Hematology represents a dynamic specialty in clinical medicine that requires solid knowledge of normal and pathological hematopoiesis, cytomorphology, pathology, immunology, genetics and molecular biology. Consequently, Gonnella et al., evaluated the potential benefits of dimethyl fumarate administration in a cellular line of primary effusion lymphoma, as well as its impact on fresh lymphoma cells collected from murine models. [Extracted from the article]

Non-Hodgkin's malignant lymphomas are a heterogeneous group of hematological malignancies, characterized by a variety of clinical, morphological, histopathological, immuno-histochemical, molecular and evolutionary features. They represent a form of cancer that develops from the lymphatic tissue, as a result of the malignant transformation of B (85%) or T (15%) lymphocytes. Lymphomagenesis is described as a multi-stage process involving the mutation and proliferation of cell clones. Oxidative stress is defined as an imbalance of cellular redox status caused by the production of reactive oxygen species (ROS) and/or by decreasing antioxidant systems that allows their accumulation in the cell. Small quantities of ROS are involved in physiological mechanisms such as cell growth and differentiation, cell signaling, antimicrobial defense, phagocytosis. Normally, cells are capable of defending themselves against ROS damage through various scavenger systems. On the other hand, excessive ROS contribute to various diseases such as carcinogenesis, ischemia, atherosclerosis, neurodegenerative diseases. Oxidative stress exerts noxious effects on the cell structures by inducing structural changes in membranes, lipids, proteins or DNA. The present review summarizes the latest findings in understanding the ROS-linked signaling pathways in the initiation of lymphomagenesis, disease progression, metastasis, as well as in the pharmacodynamics of specific treatments for this malignancy. [ABSTRACT FROM AUTHOR]

Oxidative stress involves disruption of the cellular redox status through excessive production of reactive oxygen species or through deficiency in the cellular antioxidant capacity. It is involved in the pathogeny of multiple entities (hematological diseases, metabolic disorders, cardiovascular and renal pathology etc.), as well as in the pharmacokinetics of specific treatments for these pathologies. Chronic myeloid leukemia is a chronic myeloproliferative disease for which current standard treatment is BCR-ABL tyrosine kinase inhibitors. The innovation of this therapy has significantly improved life expectancy for patients with chronic myeloid leukemia, but in some cases, this treatment becomes ineffective, installing the resistance to tyrosine kinase inhibitors therapy. There were described two types of tyrosin kinase inhibitors resistance: primary and secondary resistance. In the present paper we proposed to evaluate the involvement of oxidative in the resistance to tyrosine kinase inhibitors therapy, in the clonal instability in chronic myeloid leukemia and in the progression of the disease to an advanced stage. We concluded that oxidative stress can play a dual role in the evolution of chronic myeloid leukemia: on the one hand it can promote genomic instability and accelerate the progression of the disease to advanced stages associated with tyrosin kinase inhibitors resistance and, on the other hand, it can contribute to leukemic cell apoptosis. It seems to be outlined a fragile balance between the pro- and anti-apoptotic effects of the reactive oxygen species, closely related to their level in the leukemic cells. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) implies an imbalance between the amount of tissue level of prooxidant and antioxidant compounds. It is involved in the pathophysiology of multiple pathological entities (neoplasms, disorders of carbohydrate and lipid metabolism, cardiovascular and renal pathology etc.), as well as in the pharmacokinetics of specific treatments for these pathologies. Chronic myeloid leukemia (CML) is a chronic myeloproliferative disease for which current standard treatment is BCR-ABL tyrosine kinase inhibitors (TKIs). It is known that OS is involved in CML pathogenesis and response to TKIs therapy, but in reality, there are a number of additional factors (associated comorbidities, specific therapies) that modulate oxidative status, possibly affecting the evolution and prognosis of CML. In the present paper we proposed the evaluation of OS in a group of patients with CML following treatment with TKIs, depending on the presence of comorbidities and associated treatments. There were considered associated comorbidities: diabetes mellitus, dyslipidemia, arterial hypertension, heart failure, chronic kidney disease. The variability of the oxidative status was found depending on the type of associated comorbidity, but also according to the associated treatment, with the possibility of producing drug interactions between the standard treatment of CML and the associated specific therapies. Their impact on the prognosis of CML patients in treatment with TKIs is not negligible and may represent a future research topic. [ABSTRACT FROM AUTHOR]

Hematological malignancies are severe diseases, fatal when untreated, which associate an acute stress response described as an usual response to diagnosis and treatment of the hematologic malignancy, occuring at each transitional point of illness : communication of diagnosis, beginning of treatment, relapse, treatment failure, disease progression. The emotional response is characterized by shock, denial, fear, hopelessness, anxiety, depression, disturbance in the development of personality, sleep and apetite disturbances. The factors which influence the psychosocial response are the emotional stability of the person before diagnosis and the existence of a social support. Hematological malignancies associate many social and emotional aspects which impose, beside specific treatment (chemotherapy, radiotherapy, bone marrow transplantation), a psychological treatment (psychopharmacological agents, individual or group psychotherapy) for psychosocial adaptation and a good quality of life for these patients. [ABSTRACT FROM AUTHOR]

Palbociclib and abemaciclib are two cyclin-dependent kinases 4 and 6 used for breast cancer treatment. Levels of these medicines present a significant interindividual variability, so monitoring those concentrations might be necessary in therapy. Most of the methods presented so far in the literature use simple protein precipitation of plasma proteins as sample preparation method followed by direct injection of the supernatant into the LC instrument, preceded or not by a simple filtration step. Within that approach, the probability of injecting proteins in the chromatographic system is increased. With the purpose of obtaining a cleaner extract of the drugs, we developed and validated a simple and accurate LC-MS method for determining palbociclib and abemaciclib in human plasma. Solid phase extraction (SPE) using Oasis PRiME HLB® cartridges was used for plasma sample preparation. The method provided clean extracts with a recovery extraction higher than 85% for both compounds. Separation was achieved by high-performance liquid chromatography (HPLC), using a C18 (4.6 × 50 mm) column, with a gradient elution of ammonium acetate/acetic acid-acetonitrile as the mobile phase. Detection was performed by mass spectrometry (MS) in single ion recording (SIR) mode. Intra-day and inter-day precision data for both analytes were 3.8–7.2% and 3.6–7.4%, respectively. Calibration curves were both linear between 2 and 400 ng/mL with a correlation coefficient higher than 0.998. The LC-MS method can be used to quantify the drugs in human plasma in routine analysis. The method proved to be useful in determining real plasma levels in patients involved in cancer therapy. Drug concentrations were determined in a 10 min run-time, including re-equilibration of the column. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPNs), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders defined by an excessive production of functionally mature and terminally differentiated myeloid cells. MPNs can transform into secondary acute myeloid leukemia (sAML/blast phase MPN) and are linked to alterations in the redox balance, i.e., elevated concentrations of reactive oxygen species and markers of oxidative stress (OS), and changes in antioxidant systems. We evaluated OS in 117 chronic phase MPNs and 21 sAML cases versus controls by measuring total antioxidant capacity (TAC) and 8-hydroxy-2′-deoxy-guanosine (8-OHdG) concentrations. TAC was higher in MPNs than controls (p = 0.03), particularly in ET (p = 0.04) and PMF (p = 0.01). MPL W515L-positive MPNs had higher TAC than controls (p = 0.002) and triple-negative MPNs (p = 0.01). PMF patients who had treatment expressed lower TAC than therapy-free subjects (p = 0.03). 8-OHdG concentrations were similar between controls and MPNs, controls and sAML, and MPNs and sAML. We noted associations between TAC and MPNs (OR = 1.82; p = 0.05), i.e., ET (OR = 2.36; p = 0.03) and PMF (OR = 2.11; p = 0.03), but not sAML. 8-OHdG concentrations were not associated with MPNs (OR = 1.73; p = 0.62) or sAML (OR = 1.89; p = 0.49). In conclusion, we detected redox imbalances in MPNs based on disease subtype, driver mutations, and treatment history. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory dermatosis with a complex pathogenesis, significantly impacting the quality of life of patients. The role of oxidative stress and gut microbiota in the pathogenesis of this disease is increasingly studied, appearing to underlie the comorbidities associated with this condition. We present the first prospective observational study conducted in Romania evaluating the interrelationship between gut microbiota and hematological, inflammatory, biochemical, and oxidative stress parameters in treatment-naïve psoriasis patients. Significant differences were observed in terms of microbiota composition, with lower levels of Firmicutes and Enterobacteriaceae in the psoriasis group compared to the control group. Moreover, a negative correlation was found between the serum triglyceride levels in patients with psoriasis and the Enterobacteriaceae family (p = 0.018, r = −0.722), and a positive correlation was found between the serum glucose levels and the Firmicutes/Bacteroides ratio (p = 0.03, r = 0.682). Regarding the oxidant–antioxidant status, a significant correlation was found between the FORT level and Lactobacillus (p = 0.034, r = 0.669). Lastly, the Firmicutes level negatively correlated with the DLQI level, independent of the clinical severity of the disease (p = 0.02, r = −0.685). In conclusion, even though the number of included patients is small, these results may serve as a starting point for future research into the involvement of the microbiota–inflammation–oxidative stress axis in psoriasis development. [ABSTRACT FROM AUTHOR]

Background: Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; MPN-10), was developed. We conducted the translation, cultural adaptation, and validation into Romanian of the MPN-10. Methods: We translated the MPN-10 and tested its psychometric properties. Results: We recruited 180 MPN patients: 66 polycythemia vera (36.67%), 61 essential thrombocythemia (33.89%), 51 primary and secondary myelofibrosis (SMF) (28.33%), and 2 MPN-unclassifiable (1.11%). The mean TSS was 19.51 ± 16.51 points. Fatigue, inactivity, and concentration problems were the most cumbersome symptoms. We detected scoring differences between MPN subtypes regarding weight loss (p < 0.001), fatigue (p = 0.006), early satiety (p = 0.007), night sweats (p = 0.047), pruritus (p = 0.05), and TSS (p = 0.021). There were strong positive associations between TSS and inactivity, fatigue, and concentration problems, and moderate negative correlations between QoL scores and all MPN-10 items. Cronbach's α internal consistency coefficient was 0.855. The Kaiser–Meyer–Olkin construct validity test result was 0.870 and the Bartlett Sphericity Test was significant (p < 0.001). Symptom scores were loaded into one single factor according to the exploratory factor analysis. Conclusions: The Romanian MPN-10 version displayed excellent psychometric properties and is a reliable instrument for assessing symptom burden and QoL in Romanian MPN patients. [ABSTRACT FROM AUTHOR]

Epilepsy is a neurological disease affecting people of all ages worldwide. Side effects of antiepileptic drugs and their association with oxidative stress stimulate the search for new drugs, which would be more affordable with fewer adverse effects. Accordingly, the aim of the present work is to evaluate the anticonvulsant effect of anacardic acid (AA), a natural compound extracted from cashew liquid ( Anacardium occidentalis ), in murine models, as well as its antioxidant actions in Saccharomyces cerevisiae . AA (>90% purity) was tested, in vivo , in male Swiss mice (25–30 g) with four convulsive models, (1) pentylenetetrazole, (2) pilocarpine, (3) electroshock, and (4) kainic acid, at doses of 25, 50, and 100 mg/kg, body weight (B.W.) Additionally, the effective dose, toxic dose, and protective index studies were also performed. Results revealed that AA exhibits anticonvulsive effects in models 1, 3, and 4, with a mean effective dose (ED 50 ) of 39.64 (model 1) >100 mg/kg, B.W. (model 2), and 38.36 (model 3); furthermore, AA displays a protection index of 1.49 (model 1), <0.6 (model 2, and 1.54 (model 3). In addition, AA showed antioxidant activities in S. cerevisiae mutated for superoxide dismutases (SOD). In conclusion, these results show that AA exhibits significant anticonvulsant and antioxidant activities and may be used as a promising natural product for the treatment of epilepsy. [ABSTRACT FROM AUTHOR]

The diterpene lactone andrographolide, isolated from Andrographis paniculata, has been proven to possess several important protective biological activities, including antioxidant, anti-inflammatory, immunomodulatory, antiseptic, antimicrobial, cytotoxic, hypolipidemic, cardioprotective, hepatoprotective, and neuroprotective effects. In addition, it has been reported to play a therapeutic role in the treatment of major human diseases, such as Parkinson's disease, rheumatoid arthritis, and colitis. This systematic review aims to highlight andrographolide as a promising agent in cancer treatment. To this purpose, a number of databases were used to search for the cytotoxic/anticancer effects of andrographolide in pre-clinical and clinical studies. Among 1703 identified literature articles, 139 were included in this review; 109 were investigated as non-clinical, whereas 24, 3, and 3 were pre-clinical, clinical, and non-pre-clinical trials, respectively. Among the model systems, cultured cell lines appeared as the most frequently (79.14%) used, followed by in vivo models using rodents, among others. Furthermore, andrographolide was found to exert cytotoxic/anticancer effects on almost all types of cell lines with the underlying mechanisms involving oxidative stress, cell cycle arrest, anti-inflammatory and immune system mediated effects, apoptosis, necrosis, autophagy, inhibition of cell adhesion, proliferation, migration, invasion, anti-angiogenic activity, and other miscellaneous actions. After careful consideration of the relevant evidence, we suggest that andrographolide can be one of the potential agents in the treatment of cancer in the near future. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates (n = 85), 113 records were screened. After the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis. [ABSTRACT FROM AUTHOR]

Introduction: CML is a chronic myeloproliferative neoplasm, following the oncoprotein bcr-abl; standard treatment in CML are TKIs; optimal response to the therapy involves BCR-ABL < 0.1% - major molecular response (MMR) one year after the start, while therapeutic resistance - the absence of MMR (primary resistance - PR) or its loss (secondary resistance - SR); there is evidence that OS is involved in the response to TKI therapy. The aim of the study is to determine the level of OS in patients with CML, in treatment with TKI I / II and to correlate the values with the response to the treatment - MMR, therapy failure (BCR-ABL decrease > 75% , without MMR), PR or SR. Materials and Methods: We analyzed 75 patients (35 M, 40 F, mean age 60.57 years) with CML (ELN criteria, informed consent), treated with TKI I / II / I + II, whom were obtained MMR / therapy failure / PR / SR; reactive oxigen species (ROS) were determined with a CyFlow- Space flow cytometer and total antioxidant capacity (TAC) with a FluoStar Omega microplate reader. Results and discussions: Statistically, we observed: male predominance among patients with therapy failure and TKI resistance; the minimum TAC value and the minimum ROS value were registered in the patients with therapy failure; the maximum ROS value was recorded in patients with TKI therapeutic resistance (subgroup PR) and the maximum TAC value was obtained in patients with MMR (subgroup ITK I). Conclusions: The PR predominance to TKI I therapy, as well as the unfavorable prognosis of the male were observed. A better correlation of TAC level with the response to TKI therapy was found. The minimum TAC value concomitantly with the maximum ROS value were registered in the subgroup with TKI II resistance. [ABSTRACT FROM AUTHOR]

Objectives: Essential thrombocythemia (ET) is a chronic BCR-ABL-negative myeloproliferative neoplasm associated with low-grade chronic inflammation, increased levels of oxidative stress and, in approximately 50-60% of cases, the JAK2V617F mutation. We aimed to evaluate serum ferritin and oxidative stress in ET patients based on the homozygous/heterozygous JAK2V617F genotype. Methods: We recruited 62 ET patients (informed consent obtained), diagnosed according to the 2016 revised WHO criteria, and a control group. ET patients were stratified based on age, sex, JAK2V617F status. The complete blood count was evaluated using a BM-800 analyzer, serum ferritin was evaluated by chemiluminescence, oxidative stress by determining reactive oxygen species (ROS) levels and the total antioxidant capacity (TAC), evaluated by flow-cytometry (CyFlow Space Sysmex, reagents from Abcam) and using a microplate reader (FLUOstar Omega, reagents from Sigma Aldrich), respectively. Results: The mean age of ET patients was at diagnosis 59.5 years and the sex distribution was women:men=4:3. The JAK2V617F mutation was positive in 36 ET patients (58.06%) patients (heterozygous genotype in 30 patients and homozygous genotype in 6 patients) and negative in 26 ET patients (41.94%). We registered increased ROS and serum ferritin levels and decreased TAC in ET patients vs. controls. We found positive weak correlations between ROS - serum ferritin rs = 0.16646, p (2-tailed) = 0.19598, and between TAC - serum ferritin rs = 0.05653, p (2-tailed) = 0.66253, without statistical significance between JAK2V617F-heterozygous and JAK2V617F- homozygous cases. Conclusions: ET patients depict increased oxidative stress and serum ferritin levels, with no significant differences between JAK2V617F-heterozygous and JAK2V617F-homozygous cases. Serum ferritin can be used as a marker of chronic inflammation in ET patients. [ABSTRACT FROM AUTHOR]

Objectives: Obesity is a pathological state characterized by increased numbers of structurally modified and functionally active macrophages in the adipose tissue which secrete pro-inflammatory cytokines (IL-6, IL-1β, TNF-α). Pro-inflammatory cytokines lead to chronic inflammation which is associated with increased reactive oxygen species (ROS) levels and stimulate the hepcidin synthesis by hepatocytes leading to reduced intestinal iron absorption by directly blocking ferroportin and causing iron sequestration in enterocytes, and also reducing erythropoiesis by blocking iron in macrophages. We aimed to evaluate serum ferritin, ROS levels and the total antioxidant capacity (TAC) in obese anemic versus obese non-anemic patients. Methods: We enrolled 85 patients diagnosed with obesity based on body mass index (BMI) according to the WHO criteria (informed consent obtained). Patients were stratified based on age, sex, area of residence, obesity class, presence/absence of anemia. Complete blood count, serum ferritin, ROS levels via the Free Oxygen Radical Testing (FORT) and TAC via the Free Oxigen Radical Defense (FORD) assays were evaluated. Results: The mean age of the patients was 61.85 ± 10.60 years, women/men ration 4/1; 54.12% resided in rural areas, 45.88% in urban areas. Distribution on obesity classes: I=44.70%, II=36.47%, III=18.33%. 47 patients had anemia (39 normochromic normocytic and 8 hypochromic microcytic anemia). Serum ferritin was high in patients with normochromic normocytic anemia versus low in patients with hypochromic microcytic anemia. FORT levels were high and FORD levels were low in obese anemic versus obese non-anemic patients (3.18 ± 0.33 mmol/L vs. 2.16 ± 0.38 mmol/L; 0.66 ± 0.13mmol/L vs. 1.41 ± 0.44 mmol/L). Conclusions: In obesity, chronic inflammation induces an increase in oxidative stress levels and contributes to the development of inflammatory anemia via reduced intestinal iron absorption and blocking iron in macrophages. [ABSTRACT FROM AUTHOR]