Double diabetes-when type 1 diabetes meets type 2 diabetes: definition, pathogenesis and recognition.

Currently, the differentiation between type 1 diabetes (T1D) and type 2 diabetes (T2D) is not straightforward, and the features of both types of diabetes coexist in one subject. This situation triggered the need to discriminate so-called double diabetes (DD), hybrid diabetes or type 1.5 diabetes, which is generally described as the presence of the insulin resistance characteristic of metabolic syndrome in individuals diagnosed with T1D. DD not only raises the question of proper classification of diabetes but is also associated with a significantly greater risk of developing micro- and macroangiopathic complications, which was independent of glycaemic control. When considering the global obesity pandemic and increasing incidence of T1D, the prevalence of DD may also presumably increase. Therefore, it is of the highest priority to discover the mechanisms underlying the development of DD and to identify appropriate methods to prevent or treat DD. In this article, we describe how the definition of double diabetes has changed over the years and how it is currently defined. We discuss the accuracy of including metabolic syndrome in the DD definition. We also present possible hypotheses connecting insulin resistance with T1D and propose possible methods to identify individuals with double diabetes based on indirect insulin resistance markers, which are easily assessed in everyday clinical practice. Moreover, we discuss adjuvant therapy which may be considered in double diabetic patients.

VEGFR and DPP-IV as Markers of Severe COVID-19 and Predictors of ICU Admission.

The pathophysiology of the severe course of COVID-19 is multifactorial and not entirely elucidated. However, it is well known that the hyperinflammatory response and cytokine storm are paramount events leading to further complications. In this paper, we investigated the vascular response in the pathophysiology of severe COVID-19 and aimed to identify novel biomarkers predictive of ICU admission. The study group consisted of 210 patients diagnosed with COVID-19 (age range: 18-93; mean ± SD: 57.78 ± 14.16), while the control group consisted of 80 healthy individuals. We assessed the plasma concentrations of various vascular factors using the Luminex technique. Then, we isolated RNA from blood mononuclear cells and performed a bioinformatics analysis investigating various processes related to vascular response, inflammation and angiogenesis. Our results confirmed that severe COVID-19 is associated with vWF/ADAMTS 13 imbalance. High plasma concentrations of VEGFR and low DPP-IV may be potential predictors of ICU admission. SARS-CoV-2 infection impairs angiogenesis, hinders the generation of nitric oxide, and thus impedes vasodilation. The hypercoagulable state develops mainly in the early stages of the disease, which may contribute to the well-established complications of COVID-19.

Could Vaspin Be a Potential Diagnostic Marker in Endometrial Cancer?

Obesity and being overweight are risk factors for many types of cancer, including endometrial cancer. Adipose tissue is thought to be an endocrine organ that produces various hormones, including one known as vaspin. Insulin resistance, metabolic syndrome and type 2 diabetes are all associated with higher vaspin levels. A total of 127 patients divided into study (endometrial cancer) and control groups (non-cancerous) participated in this research. Serum vaspin levels were measured for all patients. The analysis was performed while taking into account grading and staging. In order to assess the usefulness of the tested protein as a new diagnostic marker, we used the plotting of a curve (ROC) and the calculation of the AUC curve to characterize the sensitivity and specificity of the parameters tested. We concluded that there were significantly lower vaspin levels in patients with endometrial cancer compared to patients with benign endometrial lesions. Vaspin may be a useful diagnostic marker in separating benign lesions from endometrial cancer.

The Diagnostic Role of FGF 21 in Endometrial Cancer and Other Pathologies of the Uterine Corpus.

Endometrial cancer is becoming an increasing problem. Taking into account its pathomechanisms, we aimed to investigate whether FGF 21, an important metabolism regulator, could be used as a biomarker for endometrial cancer. The study included 233 patients who were classified into five subgroups depending on the result of the histological examination: endometrial carcinomas, sarcomas, endometrial polyps, fibroids, and normal endometrium. Statistically significantly higher FGF 21 levels were found in patients diagnosed with malignant lesions (p < 0.001). FGF 21 concentration correlated with the degree of cellular differentiation (p = 0.020) and the presence of lymph node metastases (p = 0.009). The diagnostic performance characteristics of FGF 21 as an EC diagnostic marker demonstrated an AUC of 0.677. Of all of the assessed biomarkers, FGF 21 had the highest specificity (90%), yet limited sensitivity (41%). Additionally, HE4 and CA 125 were confirmed to have roles as EC biomarkers, with a higher accuracy for HE4 (79% vs. 72%).

Apoptosis Evaluation in Circulating CD34+-Enriched Hematopoietic Stem and Progenitor Cells in Patients with Abnormally Increased Production of Endogenous Glucocorticoids in Course of Cushing's Syndrome.

Abnormalities in hematological parameters of peripheral blood have been noted in patients with endogenous Cushing's Syndrome (CS) in the corticotropin (ACTH)-dependent and ACTH-independent forms. Nevertheless, the exact mechanism of glucocorticoids (GCs) action on human hematopoiesis is still not entirely clear. The aim of the study was to determine whether endogenous excessive production of GCs could affect apoptosis of CD34+ cells enriched in hematopoietic stem and progenitor cells (HSPCs) collected from the peripheral blood of newly diagnosed CS patients. Flow cytometry, Annexin-V enzyme-linked immunosorbent assay, TUNEL assay, real-time quantitative PCR, and microarray RNA/miRNA techniques were used to characterize CS patients' HSPCs. We found that the glucocorticoid receptor (GR) protein expression levels in CS were higher than in healthy controls. A complex analysis of apoptotic status of CS patients' HSPC cells showed that GCs significantly augmented apoptosis in peripheral blood-derived CD34+ cells and results obtained using different methods to detect early and late apoptosis in analyzed cell population were consistent. CS was also associated with significant upregulation in several members of the BCL-2 superfamily and other genes associated with apoptosis control. Furthermore, global gene expression analysis revealed significantly higher expression of genes associated with programmed cell death control in HSPCs from CS patients. These findings suggest that human endogenous GCs have a direct pro-apoptotic activity in hematopoietic CD34+ cells derived from CS subjects before treatment.

Evaluation of Paraoxonase-1 and Pentraxin-3 in the Diagnosis and Prognosis of Endometrial Cancer.

It is relevant to find new prognostic and diagnostic biomarkers for endometrial cancer. The study group consisted of 94 cases of endometrial cancer, the control group of 65 cases of normal endometrium. We evaluated PON1 and PTX3 serum levels. The ROC curve was plotted. The area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The Kaplan-Meier curve was used to assess survival. The cut-off level of PON1 was 142.6 ng/mL, with a sensitivity and specificity of 79 and 84% (p = 0.0321). The cut-off level of PTX3 was 4.2 ng/mL, with a sensitivity and specificity of 63 and 57% (p = 0.028). The favorable prognostic factor determined in serum was PON1 (for PFS: HR 0.93, 95% CI 0.86-1.03, p = 0.046; for OS: HR 0.96, 95% CI 0.89-1.08, p = 0.009). PON1 may be considered a potential biomarker in the diagnosis of endometrial cancer. Considering multivariate analysis, the PON1 serum level above the median is an independent favourable prognostic factor affecting PFS and OS. Considering Kaplan-Meier curves, longer recurrence-free survival and overall survival were found in patients with PON1 levels below the median. In view of the inconclusive results, we suggest that further studies should be conducted.

Molecular Changes in Chronic Myeloid Leukemia During Tyrosine Kinase Inhibitors Treatment. Focus on Immunological Pathways.

Introduction: The aim of our research was to investigate changes in the molecular background of the immune response in the chronic phase (CP) of chronic myeloid leukaemia (CML) during treatment with tyrosine kinase inhibitors (TKIs). Methods: Global gene and miRNA expression profiles were assessed using genome-wide RNA and miRNA microarray technology in bone marrow mononuclear cells. Fifty-one patients were recruited, and bone marrow samples were taken at diagnosis before treatment with TKIs and after 3, 6, and 12 months of treatment with TKIs. The largest number of upregulated genes was observed when the 0-month group (time of diagnosis) was compared to the 3-month group; 1774 genes were significantly upregulated, and 390 genes were significantly downregulated. Discussion: Upregulated biological processes according to gene ontology (GO) classification involved basic cellular processes such as cell division, cell cycle, cell-cell adhesion, protein transport, mitotic nuclear division, apoptosis, and DNA replication. Differentially expressed miRNAs were annotated using GO classification to several immunity-related processes, including the T cell receptor signalling pathway, T cell costimulation, immune response, and inflammatory response. TKI therapy exerts a significant impact on cellular cycle processes and T-cell activation, which was proven at the molecular level.

IgA-Based Secretory Response in Tears of COVID-19 Patients: A Potential Biomarker of Pro-Inflammatory State in Course of SARS-CoV-2 Infection.

Mucosal immunity, including secretory IgA (sIgA), plays an important role in the early defence against SARS-CoV-2 infection. However, a comprehensive evaluation of the local immune response in tears in relation to blood antibody reservoirs has not yet been conducted. A total of 179 symptomatic laboratory-confirmed COVID-19 patients were included in this single-centre study. Conjunctival swabs were analysed by a reverse transcription polymerase chain reaction for the detection of SARS-CoV-2 RNA. In parallel, tear samples collected by Schirmer test strips and plasma samples were analysed by ELISA to detect anti-S1 IgA levels. The concentrations of selected inflammatory cytokines in tears were determined by a magnetic bead assay. Anti-SARS-CoV-2 sIgA was present in the tears of 81 (45.25%) confirmed COVID-19 patients, and the tear IgA levels were correlated with the plasma IgA levels (Rs = +0.29, p = 0.0003). SARS-CoV-2 RNA in the conjunctival sac was identified in 18 COVID-19 patients (10%). Positive correlations between the tear IgA level and the concentrations of several cytokines TNF-α (Rs = +0.23, p = 0.002), IL-1ß (Rs = +0.25, p < 0.001), IL-2 (Rs = +0.20, p = 0.007), IL-4 (Rs = +0.16, p = 0.04), IL-5 (Rs = +0.36, p < 0.001), IL-6 (Rs = +0.32, p < 0.001), IL-8 (Rs = +0.31, p < 0.001), VEGF (Rs = +0.25, p < 0.001) and GM-CSF (Rs = +0.27, p < 0.001) were also found. Quantitative tear film-based sIgA could potentially serve as a rapid and easily accessible biomarker of external mucosal immunity to SARS-CoV-2. The concentration of sIgA is directly related to individual host immune responses to SARS-CoV-2 infection.

CXCL8, CCL2, and CMV Seropositivity as New Prognostic Factors for a Severe COVID-19 Course.

The exact pathophysiology of severe COVID-19 is not entirely elucidated, but it has been established that hyperinflammatory responses and cytokine storms play important roles. The aim of this study was to examine CMV status, select chemokines, and complement components in COVID-19, and how concentrations of given molecules differ over time at both molecular and proteomic levels. A total of 210 COVID-19 patients (50 ICU and 160 non-ICU patients) and 80 healthy controls were enrolled in this study. Concentrations of select chemokines (CXCL8, CXCL10, CCL2, CCL3, CCR1) and complement factors (C2, C9, CFD, C4BPA, C5AR1, CR1) were examined at mRNA and protein levels with regard to a COVID-19 course (ICU vs. non-ICU group) and CMV status at different time intervals. We detected several significant differences in chemokines and complement profiles between ICU and non-ICU groups. Pro-inflammatory chemokines and the complement system appeared to greatly contribute to the pathogenesis and development of severe COVID-19. Higher concentrations of CXCL8 and CCL2 in the plasma, with reduced mRNA expression presumably through negative feedback mechanisms, as well as CMV-positive status, correlated with more severe courses of COVID-19. Therefore, CXCL8, CCL2, and CMV seropositivity should be considered as new prognostic factors for severe COVID-19 courses. However, more in-depth research is needed.

Increased proinflammatory cytokines in tears correspond with conjunctival SARS-CoV-2 positivity in symptomatic COVID-19 patients.

Tear fluid cytokine levels may serve as biomarkers of innate immune system response against SARS-CoV-2 infection. Therefore, our aim was to analyze panel of selected inflammatory cytokines in tears of COVID-19 patients in relation to presence of SARS-CoV-2 viral load in conjunctival secretions. In this study concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay in tear film collected from 232 symptomatic COVID-19 patients. SARS-CoV-2 ocular infection was confirmed based on positive conjunctival swab-based RT-PCR testing. Viral RNA in conjunctival sac was detected in 21 patients (9%). No relation between presence and the duration of ophthalmic symptoms and SARS-CoV-2 infection detected in conjunctival secretions was found. The tear film concentrations of IFN-γ, TNF-α, IL-5, IL-8 and GM-CSF were found to be significantly greater among patients with positive conjunctival swab results as compared to the group negative for SARS-CoV-2 in conjunctival sac. Our current data depict a group of inflammatory mediators in human tears, which may play a significant role in ocular pathology of SARS-CoV-2 conjunctival infection.

Evaluating Ocular Symptoms and Tear Film Cytokine Profiles in Symptomatic COVID-19 Patients.

Background: This study investigated the presence and duration of ophthalmic symptoms in the early phase of COVID-19 to assess the corresponding local immune response on the ocular surface. Methods: The study included data from 180 COVID-19 patients and 160 age-matched healthy controls. The main finding was the occurrence of ophthalmological manifestations at the time of admission to the hospital and during the preceding 7 days. Tear film concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay. Results: Among the COVID-19 patients, 12.64% had at least one ocular symptom at the time of admission, and 24.14% had symptoms within the preceding 7 days (p < 0.001 vs. controls). We found that the COVID-19 patients complained more frequently about eye tearing (p = 0.04) and eye pain (p = 0.01) than controls. A multivariate analysis of the patients and controls adjusted for age and sex revealed that COVID-19 was an independent factor associated with higher VEGF and IL-10 tear film concentrations (ß = +0.13, p = 0.047 and ß = +0.34, p < 0.001, respectively) and lower IL-1ß, IL-8, and GM-CSF levels (ß = −0.25, p < 0.001; ß = −0.18, p = 0.004; and ß = −0.82, p = 0.0 respectively). Conclusions: SARS-CoV-2 does not attract a strong local response of the conjunctival immune system; therefore, ophthalmic symptoms may not constitute a substantial element in the clinical picture of novel COVID-19 infection.

Clinical Significance of BTLA, CD27, CD70, CD28 and CD80 as Diagnostic and Prognostic Markers in Ovarian Cancer.

It is very important to find new diagnostic and prognostic biomarkers. A total of 79 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 42 patients with benign ovarian lesions. Five proteins involved in the immune response were studied: BTLA, CD27, CD70, CD28, CD80. The study material was serum and peritoneal fluid. The ROC curve was plotted, and the area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The cut-off level of CD27 was 120.6 pg/mL, with the sensitivity and specificity of 66 and 84% (p = 0.014). Unfavorable prognostic factors determined in serum were: CD27 (for PFS: HR 1.26, 95% CI 1.21-1.29, p = 0.047; for OS: HR 1.20, 95% CI 1.15-1.22, p = 0.014). Unfavorable prognostic factors determined in peritoneal fluid were: BTLA (for OS: HR 1.26, 95% CI 1.25-1.31, p = 0.033). We conclude that CD27 should be considered as a potential biomarker in the diagnosis of ovarian cancer. BTLA and CD27 are unfavorable prognostic factors for ovarian cancer.

Renal and Inflammation Markers-Renalase, Cystatin C, and NGAL Levels in Asymptomatic and Symptomatic SARS-CoV-2 Infection in a One-Month Follow-Up Study.

The aim of our study was to evaluate the influence of asymptomatic infection and the occurrence of symptomatic COVID-19 on specific biochemical, renal, and immune parameters-renalase, neutrophil gelatinase-associated lipocalin (NGAL) cystatin C (CysC), and creatinine-and their weekly fluctuations during a one-month observation period in COVID-19 patients admitted to hospital. The study involved 86 individuals: 30 patients with diagnosed COVID-19, 28 people with asymptomatic infection confirmed with IgG antibodies-the IG(+) group-and 28 individuals without any (IgG, IgE) anti-SARS-CoV-2 antibodies-the IG(-) group. In the COVID-19 group, blood was drawn four times: (1) on day 0/1 after admission to hospital (C1 group), (2) 7 days later (C7 group), (3) 14 days later (C14 group), and (4) 28 days later (C28 group). In the IG(-) and IG(+) groups, blood was drawn once. There were no significant differences in creatinine, Cys C, and uric acid between any of the analyzed groups. NGAL levels were significantly higher in IG(+) and at all time-points in the COVID-19 groups than in controls. A similar observation was made for renalase at the C7, C14, and C28 time-points. Plasma renalase, NGAL, and CysC are unrelated to kidney function in non-critically ill COVID-19 patients and those with asymptomatic infection. Renalase and NGAL are most likely related to the activation of the immune system rather than kidney function. Asymptomatic SARS-CoV-2 infection causes a rise in plasma NGAL levels similar to those observed in symptomatic COVID-19 patients. Therefore, more attention should be paid to tracking and monitoring the health of these people.

Clinical Relevance of Soluble Forms of Immune Checkpoint Molecules sPD-1, sPD-L1, and sCTLA-4 in the Diagnosis and Prognosis of Ovarian Cancer.

It is crucial to find new diagnostic and prognostic biomarkers. A total of 80 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 43 patients with benign ovarian cystic lesions. Three proteins involved in the immune response were studied: PD-1, PD-L1, and CTLA-4. The study material was serum and peritoneal fluid. The ROC curve was plotted, and the area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The cut-off level of CTLA-4 was 0.595 pg/mL, with the sensitivity and specificity of 70.3% and 90.7% (p = 0.000004). Unfavorable prognostic factors determined in serum were: PD-L1 (for PFS: HR 1.18, 95% CI 1.11-1.21, p = 0.016; for OS: HR 1.17, 95% CI 1.14-1.19, p = 0.048) and PD-1 (for PFS: HR 1.01, 95% CI 0.91-1.06, p = 0.035). Unfavorable prognostic factors determined in peritoneal fluid were: PD-L1 (for PFS: HR 1.08, 95% CI 1.01-1.11, p = 0.049; for OS: HR 1.14, 95% CI 1.10-1.17, p = 0.045) and PD-1 (for PFS: HR 1.21, 95% CI 1.19-1.26, p = 0.044). We conclude that CTLA-4 should be considered as a potential biomarker in the diagnosis of ovarian cancer. PD-L1 and PD-1 concentrations are unfavorable prognostic factors for ovarian cancer.

Pleiotropic activity of nerve growth factor in regulating cardiac functions and counteracting pathogenesis.

Cardiac innervation density generally reflects the levels of nerve growth factor (NGF) produced by the heart-changes in NGF expression within the heart and vasculature contribute to neuronal remodelling (e.g. sympathetic hyperinnervation or denervation). Its synthesis and release are altered under different pathological conditions. Although NGF is well known for its survival effects on neurons, it is clear that these effects are more wide ranging. Recent studies reported both in vitro and in vivo evidence for beneficial actions of NGF on cardiomyocytes in normal and pathological hearts, including prosurvival and antiapoptotic effects. NGF also plays an important role in the crosstalk between the nervous and cardiovascular systems. It was the first neurotrophin to be implicated in postnatal angiogenesis and vasculogenesis by autocrine and paracrine mechanisms. In connection with these unique cardiovascular properties of NGF, we have provided comprehensive insight into its function and potential effect of NGF underlying heart sustainable/failure conditions. This review aims to summarize the recent data on the effects of NGF on various cardiovascular neuronal and non-neuronal functions. Understanding these mechanisms with respect to the diversity of NGF functions may be crucial for developing novel therapeutic strategies, including NGF action mechanism-guided therapies.

Articulation recovery in ALS patients after lineage-negative adjuvant cell therapy - preliminary report.

Background: Amyotrophic lateral sclerosis (ALS) is one of the most frequently occurring neurodegenerative diseases affecting speech and swallowing. This preliminary study aimed to investigate whether an autologous lineage-negative stem/progenitor cell therapy applied to ALS patients affects the level of selected trophic and proinflammatory factors, and subsequently improves the articulation. Methods: We enrolled 12 patients with sporadic ALS, who underwent autologous bone marrow-derived lineage negative (LIN-) cells administration into cerebrospinal fluid (CSF). We evaluated patients' articulation using the Frenchay Dysarthria Assessment on days 0 and 28 following the LIN- cells administration. Concentrations of various factors (BDNF, NGF, ANGP-2, VEGF, PDGF-AA, PEDF, COMP-FH, CRP, C3, C4) in CSF were quantified by multiplex fluorescent bead-based immunoassays in the samples collected on the day of LIN- cells administration and 28 days later. On top of this, we assessed levels of BDNF and NGF in the patients' plasma on the day of the injection, three, seven days and three months after the treatment. Results: Of the 12 patients who received the LIN- cell therapy 8 showed short-termed improvement in articulatory functions (group I), which was particularly noticeable in better phonation time, lips and soft palate performance, swallowing reflex and voice loudness. Four patients (group II) did not show substantial improvement. CSF concentrations of BDNF, ANGP-2 and PDGF-AA in group I decreased significantly 28 days after LIN- cells administration. The highest concentration levels of BDNF in group II and NGF in both groups in blood plasma were observed on day 3 following the injection. Conclusions: The outcomes of the LIN- cell application in ALS treatment of articulatory organs are promising. The procedure proved to be safe and feasible. A short-lasting trophic effect of autologous LIN- administration could encourage repeated cell's application in order to sustain their beneficial effects, however this approach needs further investigation.

Could Galectin 3 Be a Good Prognostic Factor in Endometrial Cancer?

Galectin 3 is a modulator of several basic biological functions. It may be involved in the development of obesity and type 2 diabetes-risk factors of endometrial cancer. The study involved 144 patients, after abrasion due to postmenopausal bleeding. Galectin 3 concentrations were quantified in serum by multiplex fluorescent bead-based immunoassays. Median serum galectin 3 concentrations revealed significant differences between FIGO III and IV vs. FIGO I and II patients. Statistically higher concentrations were reported for patients with lymph node metastases compared to patients without it (p = 0.001) as well as in patients with lymphovascular space invasion compared to patients without LVSI (p = 0.02). No statistically significant differences were observed for median of galectin 3 levels depending on the surgical procedure (laparoscopy vs. laparotomy, p = 0.0608). Patients with galectin 3 levels exceeding the median value were characterized by overall survival being shorter by 11.9 months. High levels of galectin 3 were correlated with shorter disease-free survival, the difference is up to 14.8 months. Galectin 3 can be an independent prognostic factor in patients with endometrial cancer. Among the recognized prognostic factors and the concentrations of the galectin 3 marker at the adopted time points, the univariate analysis showed a significant effect of staging, grading, and cutoff galectin 3 on the OS. For multivariate analysis, the galectin 3 cutoff point had the greatest significant impact on OS.

The Suitability of FGF21 and FGF23 as New Biomarkers in Endometrial Cancer Patients.

Endometrial cancer is one of the most common cancers of the reproductive organ in women. The incidence of it increases from year to year. In our study we assessed role of FGF21 and FGF23 in the diagnostics of patients with endometrial cancer. The study involved 182 patients, who were undergoing abrasion due to perimenopausal bleeding. FGF21, FGF23, and leptin concentration were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex Corporation). The median of FGF21 protein (181.8 pg/mL) as well as leptin (16.9 ng/mL) in patients with endometrial cancer was statistically significant higher compared to median of those proteins among patients from control group (152.1 pg/mL and 14.1 ng/mL, respectively). However, no significant differences were found in these groups at median FGF23 concentrations. For FGF21 and leptin, the AUC values were 0.81/0.79, while FGF23, the AUC values was 0.66 for all study patients. Leptin and FGF21 concentrations were statistically significantly higher in patients with poorly differentiated G3 tumors compared to patients with moderately differentiated G2 tumors and with moderately differentiated G2 with highly differentiated G1 respectively: p = 0.02/p = 0.03 and p = 0.02/p = 0.005. FGF21 appears to be useful as a diagnostic as well as prognostic factor in patients with endometrioid endometrial carcinoma.

The Effect of Intracoronary Infusion of Autologous Bone Marrow-Derived Lineage-Negative Stem/Progenitor Cells on Remodeling of Post-Infarcted Heart in Patient with Acute Myocardial Infarction.

Introduction: Regenerative capacity of the heart is limited, and the post-infarct left ventricle (LV) dysfunction is associated with poor prognosis. Administration of stem/progenitor cells (SPCs) is a promising approach for cardiac regeneration. Objectives: In the study, we assessed LV function and post-infarcted remodeling in patients with ST-elevated myocardial infarct (STEMI) who received autologous lineage-negative (LIN-) SPCs. Patients and methods: Patients with STEMI and one-vessel coronary artery disease treated with percutaneous revascularisation were divided into study group (LIN- group, 15 patients) that received standard therapy and autologous BM-derived LIN- SPCs and control group (standard therapy group, 19 patients). The cells were administered intracoronary 24 hours after STEMI. The follow-up was 12 months with subsequent non-invasive tests and laboratory parameter evaluation on days 1st, 3rd, and 7th as well as at 1st, 3rd, 6th and 12th month after STEMI. Results: All procedures related to SPCs administration were well tolerated by the patients. In 12-month follow-up, there were no major adverse cardiac events connected with LIN- SPCs administration. During 12-month follow-up, 9 patients from LIN- group (Responders) achieved an improvement in LV ejection fraction (>10% after 12 months) with no signs of unfavorable LV remodeling. Laboratory parameters analysis showed that Troponin T levels were significantly lower until day 7th in the Responders group, while brain natriuretic peptide (BNP) level remained significantly lower from day 3rd to 12th month respectively. Conclusions: Intracoronary infusion of autologous BM-derived LIN- stem/progenitor cells is feasible and safe for patient. Improvement in LV function and prevention of unfavorable remodeling in the 60% of study group seems relatively promising. Stem cell-based therapy for cardiac regeneration still needs more accurate and extensive investigations to estimate and improve their efficacy.

Novel Evidence of the Increase in Angiogenic Factor Plasma Levels after Lineage-Negative Stem/Progenitor Cell Intracoronary Infusion in Patients with Acute Myocardial Infarction.

Cell therapy raises hope to reduce the harmful effects of acute myocardial ischemia. Stem and progenitor cells (SPCs) may be a valuable source of trophic factors. In this study, we assessed the plasma levels of selected trophic factors in patients undergoing application of autologous bone marrow (BM)-derived, lineage-negative (Lin-) stem/progenitor cells into the coronary artery in the acute phase of myocardial infarction. The study group consisted of 15 patients with acute myocardial infarction (AMI) who underwent percutaneous revascularization and, afterwards, Lin- stem/progenitor cell administration into the infarct-related artery. The control group consisted of 19 patients. BM Lin- cells were isolated using immunomagnetic methods. Peripheral blood was collected on day 0, 2, 4, and 7 and after the first and third month to assess the concentration of selected trophic factors using multiplex fluorescent bead-based immunoassays. We found in the Lin- group that several angiogenic trophic factors (vascular endothelial growth factor, Angiopoietin-1, basic fibroblast growth factor, platelet-derived growth factor-aa) plasma level significantly increased to the 4th day after myocardial infarction. In parallel, we noticed a tendency where the plasma levels of the brain-derived neurotrophic factor were increased in the Lin- group. The obtained results suggest that the administered SPCs may be a valuable source of angiogenic trophic factors for damaged myocardium, although this observation requires further in-depth studies.