Assessment of Total Antioxidant Capacity, 8-Hydroxy-2'-deoxy-guanosine, the Genetic Landscape, and Their Associations in BCR::ABL-1-Negative Chronic and Blast Phase Myeloproliferative Neoplasms.

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.

Schizophrenia polygenic risk scores, clinical variables and genetic pathways as predictors of phenotypic traits of bipolar I disorder.

AIM: We investigated the predictive value of polygenic risk scores (PRS) derived from the schizophrenia GWAS (Trubetskoy et al., 2022) (SCZ3) for phenotypic traits of bipolar disorder type-I (BP-I) in 1878 BP-I cases and 2751 controls from Romania and UK. METHODS: We used PRSice-v2.3.3 and PRS-CS for computing SCZ3-PRS for testing the predictive power of SCZ3-PRS alone and in combination with clinical variables for several BP-I subphenotypes and for pathway analysis. Non-linear predictive models were also used. RESULTS: SCZ3-PRS significantly predicted psychosis, incongruent and congruent psychosis, general age-of-onset (AO) of BP-I, AO-depression, AO-Mania, rapid cycling in univariate regressions. A negative correlation between the number of depressive episodes and psychosis, mainly incongruent and an inverse relationship between increased SCZ3-SNP loading and BP-I-rapid cycling were observed. In random forest models comparing the predictive power of SCZ3-PRS alone and in combination with nine clinical variables, the best predictions were provided by combinations of SCZ3-PRS-CS and clinical variables closely followed by models containing only clinical variables. SCZ3-PRS performed worst. Twenty-two significant pathways underlying psychosis were identified. LIMITATIONS: The combined RO-UK sample had a certain degree of heterogeneity of the BP-I severity: only the RO sample and partially the UK sample included hospitalized BP-I cases. The hospitalization is an indicator of illness severity. Not all UK subjects had complete subphenotype information. CONCLUSION: Our study shows that the SCZ3-PRS have a modest clinical value for predicting phenotypic traits of BP-I. For clinical use their best performance is in combination with clinical variables.

Retention of Ciprofloxacin and Carbamazepine from Aqueous Solutions Using Chitosan-Based Cryostructured Composites.

Water pollution is becoming a great concern at the global level due to highly polluted effluents, which are charged year by year with increasing amounts of organic residues, dyes, pharmaceuticals and heavy metals. For some of these pollutants, the industrial treatment of wastewater is still relevant. Yet, in some cases, such as pharmaceuticals, specific treatment schemes are urgently required. Therefore, the present study describes the synthesis and evaluation of promising cryostructured composite adsorbents based on chitosan containing native minerals and two types of reinforcement materials (functionalized kaolin and synthetic silicate microparticles). The targeted pharmaceuticals refer to the ciprofloxacin (CIP) antibiotic and the carbamazepine (CBZ) drug, for which the current water treatment process seem to be less efficient, making them appear in exceedingly high concentrations, even in tap water. The study reveals first the progress made for improving the mechanical stability and resilience to water disintegration, as a function of pH, of chitosan-based cryostructures. Further on, a retention study shows that both pharmaceuticals are retained with high efficiency (up to 85.94% CIP and 86.38% CBZ) from diluted aqueous solutions.

LncRNAs expression profile in a family household cluster of COVID-19 patients.

More than 3 years after the start of SARS-CoV-2 pandemic, the molecular mechanisms behind the viral pathogenesis are still not completely understood. Long non-coding RNAs (lncRNAs), well-known players in viral infections, can represent prime candidates for patients' risk stratification. The purpose of the current study was to investigate the lncRNA profile in a family cluster of COVID-19 cases with different disease progression, during the initial wave of the pandemic and to evaluate their potential as biomarkers for COVID-19 evolution. LncRNA expression was investigated in nasopharyngeal swabs routinely collected for diagnosis. Distinct expression patterns of five lncRNAs (HOTAIR, HOTAIRM1, TMEVPG1, NDM29 and snaR) were identified in all the investigated cases, and they were associated with disease severity. Additionally, a significant increase in the expression of GAS5-family and ZFAS1 lncRNAs, which target factors involved in the inflammatory response, was observed in the sample collected from the patient with the most severe disease progression. An lncRNA prognostic signature was defined, opening up novel research avenues in understanding the interactions between lncRNAs and SARS-CoV-2.

Leukemic conversion involving RAS mutations of type 1 CALR-mutated primary myelofibrosis in a patient treated for HCV cirrhosis: a case report.

Somatic frameshift mutations in exon 9 of calreticulin (CALR) gene are recognized as disease drivers in primary myelofibrosis (PMF), one of the three classical Philadelphia-negative myeloproliferative neoplasms (MPNs). Type 1/type 1-like CALR mutations particularly confer a favorable prognostic and survival advantage in PMF patients. We report an unusual case of PMF incidentally diagnosed in a 68-year-old woman known with hepatitis C virus (HCV) cirrhosis who developed a progressive painful splenomegaly, without anomalies in blood cell counts. While harboring a type 1 CALR mutation, the patient underwent a leukemic transformation in less than 1 year from diagnosis, with a lethal outcome. Analysis of paired DNA samples from chronic and leukemic phases by a targeted next-generation sequencing (NGS) panel and single-nucleotide polymorphism (SNP) microarray revealed that the leukemic clone developed from the CALR-mutated clone through the acquisition of genetic events in the RAS signaling pathway: an increased variant allele frequency of the germline NRAS Y64D mutation present in the chronic phase (via an acquired uniparental disomy of chromosome 1) and gaining NRAS G12D in the blast phase. SNP microarray analysis showed five clinically significant copy number losses at regions 7q22.1, 8q11.1-q11.21, 10p12.1-p11.22, 11p14.1-p11.2, and Xp11.4, revealing a complex karyotype already in the chronic phase. We discuss how additional mutations, detected by NGS, as well as HCV infection and antiviral therapy, might have negatively impacted this type 1 CALR-mutated PMF. We suggest that larger studies are required to determine if more careful monitoring would be needed in MPN patients also carrying HCV and receiving anti-HCV treatment.

Soluble PD-L1 as a diagnostic and prognostic biomarker in resectable gastric cancer patients.

BACKGROUND: In this study, we compared programmed death-ligand 1 (PD-L1) expression in primary tissue samples and its soluble form (sPD-L1) concentration in matched preoperative plasma samples from gastric cancer patients to understand the relationship between tissue and plasma PD-L1 expression and to determine its diagnostic and prognostic value. METHODS: PD-L1 expression in tissue was assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), and sPD-L1 concentration in plasma was quantified by ELISA. The levels of the CD274 gene, which encodes for PD-L1 protein, were examined as part of bulk tissue RNA-sequencing analyses. Additionally, we evaluated the association between sPD-L1 levels and various laboratory parameters, disease characteristics, and patient outcomes. RESULTS: GC patients had significantly higher levels of sPD-L1 in their plasma (71.69 pg/mL) compared to healthy controls (35.34 pg/mL) (p < 0.0001). Moreover, sPD-L1 levels were significantly correlated with tissue PD-L1 protein, CD274 mRNA expression, larger tumor size, advanced tumor stage, and lymph node metastasis. Elevated sPD-L1 levels (> 103.5 ng/mL) were associated with poor overall survival (HR = 2.16, 95%CI 1.15-4.08, p = 0.017). Furthermore, intratumoral neutrophil and dendritic cell levels were directly correlated with plasma sPD-L1 concentration in the GC patients. CONCLUSIONS: sPD-L1 was readily measurable in GC patients, and its level was associated with GC tissue PD-L1 expression, greater inflammatory cell infiltration, disease progression, and survival. Thus, sPD-L1 may be a useful minimally invasive diagnostic and prognostic biomarker in GC patients.

Synergistic Sustained Drug-Release System Based on Immobilized Rhamnus frangula L. Phytoextract into Layered Double Hydroxide Covered by Biocompatible Hydrogel.

This work focuses on the synergetic effect obtained by immobilization of Rhamnus frangula L. (RfL) phytoextract in layered double hydroxides (LDHs) matrixes and their subsequent encapsulation into biocompatible hydrogels (HG). In this respect, the LDHs were used as hosts for the immobilization of the phytoextract by a reconstruction method, after which the LDHsRfL were embedded into biocompatible hydrogel (HG) matrixes, based on polyethylene glycol diacrylate (PEGDA), by a radical polymerization reaction. The resulted biocompatible hydrogel composites were characterized by modern methods, while the swelling and rheology measurements revealed that the HG composites steadily improved as the content of RfL phytoextract immobilized on LDHs (LDHsRfL) increased. The following in vitro sustained release of the RfL phytoextract was highlighted by measurements at pH 6.8, in which case the composite HGs with LDHsRfL presented an improved release behavior over the LDHsRfL, thus, underlining the synergistic effect of PEGDA network and LDH particles on the slow-release behavior. The kinetic models used in the RfL release from composite HGs clearly indicate that the release is diffusion controlled in all the cases. The final composite HGs described here may find applications in the pharmaceutical field as devices for the controlled release of drugs.

Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells.

Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatment of long-term ethanol-exposed cells, inducing fluctuations in its target metabolic enzymes proportionally with treatment intensity. The wound healing assay demonstrated that the cells recovered after stress conditions, showing that the ethanol-exposed cells that passed the acute step had the same proliferation profile as the cells unexposed to ethanol. Deferoxamine-treated cells displayed higher proliferative activity than the control cells in the proliferation-migration assay, emphasizing the neuroprotective effect. Cells have overcome the critical point of the alcohol-induced traumatic impact and adapted to ethanol (a chronic phenomenon), sustaining the regeneration process. However, further experiments are needed to ensure recovery efficiency is more effective in chronic ethanol exposure.

A Top-Down Procedure for Synthesizing Calcium Carbonate-Enriched Chitosan from Shrimp Shell Wastes.

Chitosan is used in medicine, pharmaceuticals, cosmetics, agriculture, water treatment, and food due to its superior biocompatibility and biodegradability. Nevertheless, the complex and relatively expensive extraction costs hamper its exploitation and, implicitly, the recycling of marine waste, the most abundant source of chitosan. In the spirit of developing environmental-friendly and cost-effective procedures, the present study describes one method worth consideration to deliver calcium-carbonate-enriched chitosan from shrimp shell waste, which proposes to maintain the native minerals in the structure of chitin in order to improve the thermal stability and processability of chitosan. Therefore, a synthesis protocol was developed starting from an optimized deacetylation procedure using commercial chitin. The ultimate chitosan product from shrimp shells, containing native calcium carbonate, was further compared to commercial chitosan and chitosan synthesized from commercial chitin. Finally, the collected data during the study pointed out that the prospected method succeeded in delivering calcium-carbonate-enriched chitosan with high deacetylation degree (approximately 75%), low molecular weight (Mn ≈ 10.000 g/ mol), a crystallinity above 59 calculated in the (020) plane, high thermal stability (maximum decomposition temperature over 300 °C), and constant viscosity on a wide range of share rates (quasi-Newtonian behavior), becoming a viable candidate for future chitosan-based materials that can expand the application horizon.

Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer.

Despite advances in cancer detection and therapy, it has been estimated that the incidence of cancers will increase, while the mortality rate will continue to remain high, a fact explained by the large number of patients diagnosed in advanced stages when therapy is often useless. Therefore, it is necessary to invest knowledge and resources in the development of new non-invasive biomarkers for the early detection of cancer and new therapeutic targets for better health management. In this review, we provided an overview on the collagen family as promising biomarkers and on how they may be exploited as therapeutic targets in cancer. The collagen family tridimensional structure, organization, and functions are very complex, being in a tight relationship with the extracellular matrix, tumor, and immune microenvironment. Moreover, accumulating evidence underlines the role of collagens in promoting tumor growth and creating a permissive tumor microenvironment for metastatic dissemination. Knowledge of the molecular basis of these interactions may help in cancer diagnosis and prognosis, in overcoming chemoresistance, and in providing new targets for cancer therapies.

Kinetics and persistence of cellular and humoral immune responses to SARS-CoV-2 vaccine in healthcare workers with or without prior COVID-19.

SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses.

Modified Plasma Cytokine Profile in Occupational Dermatitis.

BACKGROUND: Despite significant progress in the diagnosis of contact dermatitis, the identification by specific tests or biomarkers remains an unsolved issue, particularly when needed for the confirmation of the occupational origin of the disease. OBJECTIVE: To characterize the plasma proteome profile in occupational dermatitis in workers of paint industry. METHODS: The study has a case-control design, comparing exposed workers with and without occupational contact dermatitis, matched for age, gender, occupational history, and comorbidities. An immunological assay (Human XL Cytokine Array Kit - ARY022B, R&D Systems) was used to measure the plasma levels of 105 cytokines and chemokines in a pooled sample of the cases and a pooled sample of the controls. RESULTS: A 1.5-fold increase was noticed for interleukin 3, interleukin 10, and leptin in cases, as compared to controls. Fibroblast growth factor-7 and growth/differentiation factor-15 showed a 1.4-fold increase, while interleukin 19, interleukin 31, and macrophage inflammatory protein 3a.had only a 1.3- fold increase. The leukemia inhibitory factor was the only plasma cytokine that showed a 1.3-fold decrease. All other cytokines had a variation of less than 1.2-fold between cases and controls. CONCLUSION: The recognition of the molecular signatures is very important for an accurate and indisputable diagnosis of occupational contact dermatitis. In workers from the paint industry, plasma levels of interleukins 3, 10, 13 and 19, fibroblast growth factor-7, and growth/differentiation factor-15, together with leukemia inducible factor, may differentiate subjects with contact dermatitis from those without skin lesions.

High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients.

BACKGROUND: Gastric cancer (GC) remains an aggressive malignancy with a high rate of mortality, being the third leading cause of cancer-related death. More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018. GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients. The discovery of new biomarkers useful in the early diagnosis of GC is mandatory. AIM: To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients. METHODS: Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1. Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue. The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients. Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients. RESULTS: Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue (P < 0.05). COL10A1 seems to show an elevated expression from the beginning of carcinogenesis, in the early stages, and its increased level remains elevated during cancer progression. A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified. Moreover, increased COL10A1 plasma level was associated with poor survival of the patients. Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve (AUC) of 0.9171 (P = 0.0002), sensitivity of 87.76%, and specificity of 100.0%. Furthermore, this study demonstrated the potential role of plasma COL10A1 in the early detection of GC, as in the early stage, we obtained an AUC of 0.8789 (P = 0.0030), sensitivity of 81.25%, and specificity of 100.0%. CONCLUSION: Circulating expression level of COL10A1 is significantly increased in gastric adenocarcinoma patients being associated with poor survival and is a potential biomarker for early detection of GC.

Gastrointestinal cancer stem cells as targets for innovative immunotherapy.

The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized. Gastrointestinal cancer stem cells (GCSCs) are considered to be responsible for tumor initiation, growth, resistance to cytotoxic therapies, recurrence and metastasis due to their unique properties. These properties make the current therapeutic trials against GCSCs ineffective. Moreover, recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have an additional off-target effect on the immune system. Recent advances in oncology and precision medicine have opened alternative therapeutic strategies in the form of cancer immunotherapy. This approach differs from classical anti-cancer therapy through its mechanism of action involving the activation and use of a functional immune system against tumor cells, instead of aiming physically destruction of cancer cells through radio- or chemotherapy. New immunological approaches for GCSCs targeting involve the use of different immune cells and various immune mechanisms like targeting specific surface antigens, using innate immune cells like the natural killer and T cells, T-cell chimeric antigen receptor technology, dendritic cell vaccine, or immune checkpoint inhibitors. In this respect, better understandings of immune regulatory mechanisms that govern anti-tumor response bring new hope in obtaining long-term remission for cancer therapy.

Predictive power of the ADHD GWAS 2019 polygenic risk scores in independent samples of bipolar patients with childhood ADHD.

BACKGROUND: Although there is evidence of genetic correlation between bipolar disorder (BP) and ADHD, the extent of the shared genetic risk and whether childhood ADHD (cADHD) influences the characteristics of the adult BP remain unclear. Our objectives were: (i) to test the ability of polygenic risk scores (PRS) derived from the latest PGC ADHD-GWAS (Demontis et al., 2019) to predict the presence of cADHD in BP patients; (ii) to examine the hypothesis that BP preceded by cADHD is a BP subtype with particular clinical traits and (iii) partially shares its molecular basis with ADHD. METHOD: PRS derived from the ADHD-GWAS-2019 were tested in BP patients (N = 942) assessed for cADHD with the Wender Utah Rating Scale and in controls from Romania and UK (N = 1616). RESULTS: The ADHD-PRS differentiated BP cases with cADHD from controls. Proband sex and BP age-of-onset significantly influenced the discriminative power of the ADHD-PRS. The ADHD-PRS predicted the cADHD score only in males and in BP cases with early age-of-onset (≤21 years). Bipolar patients with cADHD had a younger age-of-onset of mania/depression than patients without cADHD. The ADHD-PRS predicted the BP-affection status in the comparison of early-onset BP cases with controls suggesting a partial molecular overlap between early-onset BP and ADHD. LIMITATIONS: Retrospective diagnosis of cADHD, small sample size. CONCLUSIONS: The PRS-analysis indicated an acceptable predictive ability of the ADHD-SNP-set 2019 in independent BP samples. The best prediction of both cADHD and BP-affection status was found in the early-onset BP cases. The results may have impact on the individual disease monitoring.

Recent advances in gastric cancer early diagnosis.

Gastric cancer (GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva, stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

Association of age-of-onset groups with GWAS significant schizophrenia and bipolar disorder loci in Romanian bipolar I patients.

We investigated the influence of the age-of-onset (AO) on the association of 45 loci conferring risk for bipolar disorder (BP) and schizophrenia with BP-type-I in a Romanian sample (461 patients, 436 controls). The AO-analysis implicated the EGFR gene, as well as loci in other genes, in the AO variation of BP-type-I and revealed for the first time the link between BP-type-I and risk variants considered specific to schizophrenia (polymorphisms in MMP16/RIPK2 and CNNM2 genes).

Circulating biomarker panels for targeted therapy in brain tumors.

An important goal of oncology is the development of cancer risk-identifier biomarkers that aid early detection and target therapy. High-throughput profiling represents a major concern for cancer research, including brain tumors. A promising approach for efficacious monitoring of disease progression and therapy could be circulating biomarker panels using molecular proteomic patterns. Tailoring treatment by targeting specific protein-protein interactions and signaling networks, microRNA and cancer stem cell signaling in accordance with tumor phenotype or patient clustering based on biomarker panels represents the future of personalized medicine for brain tumors. Gathering current data regarding biomarker candidates, we address the major challenges surrounding the biomarker field of this devastating tumor type, exploring potential perspectives for the development of more effective predictive biomarker panels.

Cancer stem cells: involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics.

Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells (CSCs). In pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. Involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs.

MECHANISMS OF THROMBOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS.

Thrombotic events are highly prevalent in systemic lupus erythematosus (SLE). Antiphospholipid antibodies play an essential role in promoting thrombosis by activating several intracellular signaling pathways (TLR4, p38MAPK, NFkB) in platelets, monocytes and endothelial cells. New therapeutic opportunities might be offered by addressing these molecular targets. Chronic inflammatory status, the degree of disease activity and accelerated atherosclerosis are also responsible for the thrombotic phenotype in patients with SLE. The aim of this review is to highlight thrombosis mechanisms and to look for possible connection between SLE, antiphospholipid antibodies and cancer, especially myeloproliferative neoplasms.