Immunomodulatory Properties of Polysaccharides from Lentinula edodes.

Lentinula edodes (Berk.) Pegler, also known as shiitake mushroom, is a popular edible macrofungus and a source of numerous bioactive substances with multiple beneficial health effects. L. edodes-derived polysaccharides are the most valuable compounds, with anticancer, antioxidant, antimicrobial, and immunomodulatory properties. It has been demonstrated that their biological activity depends on the extraction method, which affects monosaccharide composition, molecular weight, branching degrees, and helical conformation. In this review, we discuss the immunomodulatory properties of various polysaccharides from L. edodes in animal models and in humans.

Selenium-Containing Exopolysaccharides Isolated from the Culture Medium of Lentinula edodes: Structure and Biological Activity.

In continuation of our research on the influence of selenium incorporation on the biosynthesis, structure, and immunomodulatory and antioxidant activities of polysaccharides of fungal origin, we have isolated from a post-culture medium of Lentinula edodes a selenium (Se)-containing exopolysaccharide fraction composed mainly of a highly branched 1-6-α-mannoprotein of molecular weight 4.5 × 106 Da, with 15% protein component. The structure of this fraction resembled mannoproteins isolated from yeast and other mushroom cultures, but it was characterized by a significantly higher molecular weight. X-ray absorption fine structure spectral analysis in the near edge region (XANES) suggested that selenium in the Se-exopolysaccharide structure was present mainly at the IV oxidation state. The simulation analysis in the EXAFS region suggested the presence of two oxygen atoms in the region surrounding the selenium. On the grounds of our previous studies, we hypothesized that selenium-enriched exopolysaccharides would possess higher biological activity than the non-Se-enriched reference fraction. To perform structure-activity studies, we conducted the same tests of biological activity as for previously obtained mycelial Se-polyglucans. The Se-enriched exopolysaccharide fraction significantly enhanced cell viability when incubated with normal (human umbilical vein endothelial cells (HUVEC)) cells (but this effect was absent for malignant human cervical HeLa cells) and this fraction also protected the cells from oxidative stress conditions. The results of tests on the proliferation of human peripheral blood mononuclear cells suggested a selective immunosuppressive activity, like previously tested Se-polyglucans isolated from L. edodes mycelium. The Se-exopolysaccharide fraction, in concentrations of 10-100 µg/mL, inhibited human T lymphocyte proliferation induced by mitogens, without significant effects on B lymphocytes. As with previously obtained Se-polyglucans, in the currently tested Se-polymannans, the selenium content increased the biological activity. However, the activity of selenium exopolysaccharides in all tests was significantly lower than that of previously tested mycelial isolates, most likely due to a different mode of selenium binding and its higher degree of oxidation.

Identification of the Primary Structure of Selenium-Containing Polysaccharides Selectively Inhibiting T-Cell Proliferation.

We previously described the biosynthesis, isolation, and immunosuppressive activity of the selenium-containing polysaccharide fraction isolated from the mycelial culture of Lentinula edodes. Structural studies have shown that the fraction was a protein-containing mixture of high molar mass polysaccharides α- and ß-glucans. However, which of the components of the complex fraction is responsible for the immunosuppressive activity non-typical for polysaccharides of fungal origin has not been explained. In the current study, we defined four-polysaccharide components of the Se-containing polysaccharide fraction determined their primary structure and examined the effect on T- and B-cell proliferation. The isolated Se-polysaccharides, α-1,4-glucan (Mw 2.25 × 106 g/mol), unbranched ß-1,6-d-glucan, unbranched ß-1,3-d-glucan and ß-1,3-branched ß-1,6-d-glucan (Mw 1.10 × 105 g/mol), are not typical as components of the cell wall of L. edodes. All are biologically active, but the inhibitory effect of the isolated polysaccharides on lymphocyte proliferation was weaker, though more selective than that of the crude fraction.

The preliminary association study of osteopontin 707 C/T polymorphism with systemic lupus erythematosus in a Polish population.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by genetic, environmental, and still unknown factors which lead to deregulation of the immune system. Osteopontin (OPN) is a multifunctional glycoprotein, expressed in various cell types, and found to play key roles in immunity. OPN and variants of the OPN gene are involved in inflammatory conditions, however, their role in SLE are controversial. AIM: To investigate the frequency of single nucleotide polymorphism (SNP) rs1126616 (707 C/T) variants in the OPN gene and its associations with SLE manifestations in Polish patients. MATERIAL AND METHODS: The study population consisted of 83 SLE patients and 100 gender-, age- and ethnically matched healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotyping was performed by real-time polymerase chain reaction (RT-PCR). The association between clinical features of SLE and 707 C/T genotypes was determined. RESULTS: The mutant (CT, TT) genotypes were observed more frequently than the wild-type (CC) genotype in SLE patients compared to controls (p = 0.037). However, no association between 707 C/T variants and SLE clinical manifestations or laboratory parameters was found. CONCLUSIONS: The present data suggest that CT and TT genotypes of OPN 707 C/T SNP are associated with a higher SLE risk, but do not affect the clinical course of the disease in the Polish population.

The role of osteopontin in kidney diseases.

BACKGROUND: Osteopontin (OPN) is a pleiotropic glycoprotein expressed in various cell types in animals and in humans, including bone, immune, smooth muscle, epithelial and endothelial cells. Moreover, OPN is found in kidneys (in the thick ascending limbs of the loop of Henle and in distal nephrons) and urine. The protein plays an important role in mineralization and bone resorption. In addition, OPN is involved in the regulation of immunity and inflammation, angiogenesis and apoptosis. It was demonstrated that OPN and some OPN gene polymorphic variants are associated with the pathogenesis and progression of multiple disorders, such as cancer, autoimmune, neurodegenerative and cardiovascular diseases. Moreover, recent studies suggested that OPN is associated with the pathogenesis of renal failure. METHODS: In this review, I briefly discussed the role of OPN and its gene polymorphisms in kidney physiology, as well as in various kidney diseases. FINDINGS AND CONCLUSION: Most studies reported that OPN expression is elevated in urolithiasis, and also in acute and chronic kidney diseases, and in renal allograft dysfunction. Moreover, it was demonstrated that polymorphic variants of the OPN gene may be associated with renal failure. However, some reports suggested that OPN is essential for tubulogenesis, and that it inhibits calcium oxalate crystal formation and retention, nitric oxide synthesis, cell apoptosis and promotes cell regeneration. Thus, further studies are required to fully understand the role of OPN in kidney physiology and pathology. Eventually, these studies may result in the identification of OPN as a valuable marker for renal dysfunction prognosis and treatment.

Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy.

Haemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of haemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. This study was aimed at investigating the potential role of PGRN in the mechanisms underlying the pathogenesis of HA. The serum levels of PGRN were measured by enzyme-linked immunosorbent assay (ELISA) in patients with end-stage knee joint HA (n = 20) and end-stage primary knee joint OA (n = 20) who met the inclusion and exclusion criteria. The clinical and radiological assessment of disease severity was evaluated by the Knee Society Score (KSS) and Kellgren-Lawrence scale. Median PGRN levels in HA patients was 349.1 ng/mL (232.8-415.6 ng/mL) and in OA patients 148.3 ng/mL (112.1-275.3 ng/mL) with statistically significant differences between both groups (P < 0.015). Further analysis revealed no correlation between PGRN levels and any of the patient demographics and clinical parameters. This study demonstrates increased PGRN serum levels in patients with HA and provides new insights into the mechanisms underlying the pathogenesis of HA indicating a new potential target for therapeutic intervention.

Anti-Müllerian hormone level is associated with vitamin D receptor polymorphisms in women with polycystic ovary syndrome.

OBJECTIVE: Our study aimed to investigate the relationship between polymorphisms (Apa1, Bsm1, Fok1, and Cdx2) in the VDR gene as well as AMH and AMHR2 genes and their influence on AMH and 25(OH)D levels in PCOS women. STUDY DESIGN: Seventy-five patients with PCOS and 23 control women were included. Serum AMH and 25(OH)D levels in patients and controls were measured by enzyme-linked immunosorbent assay (ELISA). Polymorphisms in VDR gene Fok1 C/T (rs2228587), Bsm1 A/G (rs1544410), Apa1 A/C (rs7975232), and Cdx2 A/G (rs11568820) polymorphisms as well as AMH G/T (rs10407022) and AMHR2 A/G (rs2002555) were analyzed using real-time PCR. RESULTS: Analysis of the VDR Cdx2 polymorphism showed a significantly higher frequency of the homozygous GG (mutant) genotype in the PCOS group as compared with the control group (p < 0.05). The analysis revealed a statistically significant correlation between the presence of FokI and ApaI polymorphisms and AMH levels in PCOS women (p < 0.05). The presence of mutant genotypes (CT, TT) in the Fok1 and (CA, CC) in the Apa1 polymorphisms were associated with higher AMH level in PCOS women (p < 0.05). No statistically significant correlations between AMH and AMHR2 polymorphisms and AMH level were found. Moreover, there was no correlation between AMH and 25(OH)D levels in the PCOS or in the control group. CONCLUSION: It seems that the elevated AMH level is associated with VDR Fokl and Apal polymorphisms, but not with 25(OH)D levels in PCOS women. Further research is needed to determine the role of VDR polymorphism in AMH level in PCOS.

Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties.

BACKGROUND: Cell-based therapy is a treatment method in tendon injuries. Bone morphogenic protein 12 (BMP-12) possesses tenogenic activity and was proposed as a differentiating factor for stem cells directed to transplantation. However, BMPs belong to pleiotropic TGF-ß superfamily and have diverse effect on cells. Therefore, the aim of this study was to determine if BMP-12 induces tenogenic differentiation of human adipose stem cells (hASCs) and how it affects other features of this population. RESULTS: Human ASCs from 6 healthy donors were treated or not with BMP-12 (50 or 100 ng/ml, 7 days) and tested for gene expression (COLL1, SCX, MKH, DCN, TNC, RUNX2), protein expression (COLL1, COLL3, MKH), proliferation, migration, secretory activity, immunomodulatory properties and susceptibility to oxidative stress. RT-PCR revealed up-regulation of SCX, MKH and RUNX2 genes in BMP-12 treated cells (2.05, 2.65 and 1.87 fold in comparison to control, respectively, p < 0.05) and Western Blot revealed significant increase of COLL1 and MHK expression after BMP-12 treatment. Addition of BMP-12 significantly enhanced secretion of VEGF, IL-6, MMP-1 and MPP-8 by hASCs while had no effect on TGF-ß, IL-10, EGF and MMP-13. Moreover, BMP-12 presence in medium attenuated inhibitory effect of hASCs on allo-activated lymphocytes proliferation. At the same time BMP-12 displayed no influence on hASCs proliferation, migration and susceptibility to oxidative stress. CONCLUSION: BMP-12 activates tenogenic pathway in hASCs but also affects secretory activity and impairs immunomodulatory potential of this population that can influence the clinical outcome after cell transplantation.

Mesenchymal Stem Cells from Human Amniotic Membrane and Umbilical Cord Can Diminish Immunological Response in an in vitro Allograft Model.

BACKGROUND/AIM: Mesenchymal stem cells (MSCs) are gaining rising interest in gynecology and obstetrics. MSCs immunomodulatory properties are suitable enough to reduce perinatal morbidity caused by inflammation in premature neonates. The aim of this study was to evaluate and compare the ability to inhibit allo-activated lymphocytes proliferation by MSCs derived from different sources: amniotic membrane (AM), umbilical cord (UC) and adipose tissue (AT). METHODS: MSCs were isolated from AM (n = 7) and UC (n = 6) and AT (n = 6) of healthy women. Cells were characterized by flow cytometry and differentiation assay. To evaluate the potential of fetal and adult MSCs to diminish immunological response, mixed lymphocytes reaction (MLR) was performed. RESULTS: Amnion and UC-derived cells displayed typical MSCs characteristics. Addition of MSCs to MLR significantly inhibited the proliferation of stimulated lymphocytes. The effect was observed regardless of the MSCs type used (p < 0.01 in all groups). Comparative analysis revealed no significant differences in this action between tested MSCs types. Additionally, no type of MSCs significantly stimulated allogeneic lymphocytes. CONCLUSION: The results prove the immunosuppressive capacities of fetal-derived MSCs in vitro. In the future, they may be potentially used to treat premature newborn as well as in immunomodulation in post-transplant therapy.

Premature fetal tissues are possible source of valuable mesenchymal stem cells.

OBJECTIVES: Comparison of the ability to inhibit alloactivated lymphocytes proliferation of human Wharton Jelly (WJ) and amniotic membrane (AM) mesenchymal stem cells (MSCs) from preterm and term pregnancies. MATERIAL AND METHODS: Term-WJ-MSCs (n = 5) and Preterm-WJ-MSCs (n = 1) were obtained from tissue explants by adherent method. Term-AM-MSCs (n = 5) and Preterm-AM-MSCs (n = 1) were obtained by tripsin and collagenase digestion method. Term and Preterm MSCs phenotype was confirmed in vitro by flow cytometry. To evaluate the potential of fetal and adult MSCs to diminish immunological response mixed lymphocytes reaction (MLR) has been performed. RESULTS: Term and Preterm cells were positively identified as MSCs by the expression of CD73 and CD90 and CD105 with simultaneous absence of CD11b, CD14, CD19, CD34, CD45 and HLA-DR. The mean inhibition of allostimulated lymphocytes after addition of fetal derived MSCs amounted 64.8% for term AM-MSCs and 42.1% for term WJ-MSCs (for both populations the effect was statistically significant, p < 0.01). The addition of preterm-MSCs to MLR resulted in reduction of stimulated lymphocytes proliferation by 64.9% for AM-MSCs and 86.1% for WJ-MSCs. CONCLUSIONS: Presented results suggest that preterm fetal tissues contain MSCs which posses similar immunosuppressive capacity as those from term pregnancies. In the future MSCs from the umbilical cord and amnion can be potentially used to prevent immuno-dependent injuries in premature newborns.

Association between Fok I vitamin D receptor gene (VDR) polymorphism and impulsivity in alcohol-dependent patients.

Vitamin D appears to have an important role in the modulation of the central nervous system. Vitamin D exerts its biological effects through its interaction with the vitamin D receptor (VDR). Located on chromosome 12 (12q13.1), the VDR gene has many different polymorphisms. Some of them are known to affect the VDR function, such as FokI (rs2228570, T/C) single nucleotide polymorphism. We aimed to explore a potential relationship between FokI VDR polymorphism and impulsiveness in alcohol-dependent (AD) patients. The study population consisted of 148 patients diagnosed with alcohol dependence (DSM-IV criteria) and 212 healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotypes were analyzed using a real-time PCR method. We found that FokI VDR gene polymorphism was associated with impulsivity [Barratt Impulsiveness Scale (BIS)-11 total score; P = 0.014], and with attentional impulsivity (BIS-11 subscale; P = 0.002) in the male AD patients. Our results suggest that CC FokI genotype of the VDR gene is associated with a higher level of impulsivity in these patients. This finding supports the hypothesis that impulsiveness, which significantly contributes to development of alcohol dependence, has a genetic background.

The effect of incretin-based drugs on the riks of acute pancreatitis: a review.

Objectives: In recent years, new hypoglycaemic drugs that affect the incretin system have become increasingly popular in the treatment of type 2 diabetes mellitus (T2DM): glucagon-like receptor 1 agonists (GLP1RAs), dipeptidyl peptidase 4 inhibitors (DPP4is) and the recently developed dual glucagon-like receptor 1 agonist and glucose-dependent insulinotropic polypeptide (tirzepatide). Their main role of these drugs is to normalise blood glucose levels. In addition, GLP1RAs are approved for the treatment of excessive body weight. The efficacy of drugs affecting the incretin system is well described in the literature, however, there are still only few reports about their safety. This review aims to summarize the results of current research and meta-analyses on risk of acute pancreatitis (AP) during incretin-affecting drugs treatment. Methods: A narrative review was performed using present literature in an attempt to identify the relationship between AP and incretin-affecting drugs. The following keywords were used: acute pancreatitis, glucagon-like receptor 1 agonists, dipeptidyl peptidase 4 inhibitors and tirzepatide. Results: It was demonstrated that the use of DPP4is is safe for the majority of patients with T2DM, whereas a risk of AP should be noted in case of GLP1RAs therapy. To date, most studies found no significant association between tirzepatide therapy and the increased risk of AP. Conclusion: The majority of studies have shown that DPP4is, GLP1RAs and tirzepatide are effective and safe in most T2DM patients. However, the follow-up time for patients treated with tirzepatide is short, therefore more studies are required to confirm the safety of this drug.

Chimeric Antigen Receptor T Cell Therapy for Pancreatic Cancer: A Review of Current Evidence.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of malignant and non-malignant disorders. CARs are synthetic transmembrane receptors expressed on genetically modified immune effector cells, including T cells, natural killer (NK) cells, or macrophages, which are able to recognize specific surface antigens on target cells and eliminate them. CAR-modified immune cells mediate cytotoxic antitumor effects via numerous mechanisms, including the perforin and granzyme pathway, Fas and Fas Ligand (FasL) pathway, and cytokine secretion. High hopes are associated with the prospective use of the CAR-T strategy against solid cancers, especially the ones resistant to standard oncological therapies, such as pancreatic cancer (PC). Herein, we summarize the current pre-clinical and clinical studies evaluating potential tumor-associated antigens (TAA), CAR-T cell toxicities, and their efficacy in PC.

[Multiple primary malignancies in BRCA1 mutation carriers--two clinical cases]. / Mnogie nowotwory pierwotne u kobiet nosicielek mutacji genu BRCA1--dwa przypadki kliniczne.

Mutations of BRCA1 and BRCA2 genes account for the majority of hereditary breast and ovarian cancers. So far; risk-reducing salpingo-oophorectomy has been the most effective strategy for gynecological cancer prevention in susceptibility gene mutation carriers. It does not prevent, however from the occurrence of primary peritoneal cancer We present two clinical cases of patients with the BRCA1 gene mutation. Both patients had a family history of cancer and both were presenting with metachronic malignances. The first patient, whose mother suffered from breast and ovarian cancer, was diagnosed with left breast cancer in 2004. The patient was 44 years old at diagnosis. Genetic testing revealed the BRCA1 gene mutation. A breast conserving therapy (BCT) was conducted, followed by chemotherapy, radiotherapy and immunotherapy with trastuzumab due to HER2 overexpression. Due to BRCA1 mutation, in November 2005, prophylactic hysterectomy with appendages was performed. Histological examination revealed bilateral ovarian cancer (adenocarcinoma G3) with metastasis to the paraaortal lymph node. The patient received six cycles of chemotherapy: paclitaxel and carboplatin. Ovarian cancer relapsed 3 years later After that the patient received 5 lines of chemotherapy and finally died due to disease progression in September 2011. The second patient, a 49-year-old woman, was diagnosed with breast cancer in July 2003 and subsequently treated with neoadjuvant chemotherapy breast conserving surgery and radiotherapy Genetic testing was also performed and revealed the BRCA1 gene mutation. A year earlier the patient had undergone hysterectomy with appendages due to uterine myomas. Three of her five sisters suffered from breast and ovarian cancer The patients father died of colorectal cancer The patient remained under surveillance. Because of the increasing level of Ca-125 (since October 2004), PET-CT was performed and revealed a tumor lesion of the peritoneum. Histological examination from the biopsy confirmed primary peritoneal cancer (papillary serous adenocarcinoma--primary peritoneal carcinoma). Reexamination of the tissues from hysterectomy with appendages was also performed and revealed an adenocarcinoma in the right ovary Pathologic examination excluded metastasis of a breast cancer Pathomorphology of the ovarian lesion was also different than in the lesions of the peritoneum. Thus, three different tumor types (breast, ovarian and peritoneal cancer) coexisted independently The patient received chemotherapy: paclitaxel and cisplatin. Later on, due to disease progression she was treated with five consecutive chemotherapy regimens and hormonal therapy The patient died in January 2008. These case illustrate that genetic diagnosis may be critical for the overall treatment plan.

In Situ Programming of CAR-T Cells: A Pressing Need in Modern Immunotherapy.

Chimeric antigen receptor-T (CAR-T) cell-based therapy has become a successful option for treatment of numerous hematological malignancies, but also raises hope in a range of non-malignant diseases. However, in a traditional approach, generation of CAR-T cells is associated with the separation of patient's lymphocytes, their in vitro modification, and expansion and infusion back into patient's bloodstream. This classical protocol is complex, time-consuming, and expensive. Those problems could be solved by successful protocols to produce CAR-T cells, but also CAR-natural killer cells or CAR macrophages, in situ, using viral platforms or non-viral delivery systems. Moreover, it was demonstrated that in situ CAR-T induction may be associated with reduced risk of the most common toxicities associated with CAR-T therapy, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and "on-target, off-tumor" toxicity. This review aims to summarize the current state-of-the-art and future perspectives for the in situ-produced CAR-T cells. Indeed, preclinical work in this area, including animal studies, raises hope for prospective translational development and validation in practical medicine of strategies for in situ generation of CAR-bearing immune effector cells.

Optimization of Se- and Zn-Enriched Mycelium of Lentinula edodes (Berk.) Pegler as a Dietary Supplement with Immunostimulatory Activity.

Mycelial cultures of Lentinula edodes, an edible and medicinal mushroom, have been used in our previous research to obtain selenium-containing immunomodulatory preparations. Our current attempts to obtain a new preparation containing both selenium and zinc, two micronutrients necessary for the functioning of the immune system, extended our interest in the simultaneous accumulation of these elements by mycelia growing in media enriched with selenite and zinc(II) ions. Subsequently, we have studied the effects of new L. edodes mycelium water extracts with different concentrations of selenium and zinc on the activation of T cell fraction in human peripheral blood mononuclear cells (PBMCs). Flow cytometry analysis was used to measure the expression of activation markers on human CD4+ and CD8+ T cells stimulated by anti-CD3 and anti-CD3/CD28 antibodies (Abs). It was demonstrated that statistically significant changes were observed for PD-1 and CD25 antigens on CD8+ T cells. The selenium and zinc content in the examined preparations modified the immunomodulatory activity of mycelial polysaccharides; however, the mechanisms of action of various active ingredients in the mycelial extracts seem to be different.

Osteopontin-A Potential Biomarker for IgA Nephropathy: Machine Learning Application.

Many potential biomarkers in nephrology have been studied, but few are currently used in clinical practice. One is osteopontin (OPN). We compared urinary OPN concentrations in 80 participants: 67 patients with various biopsy-proven glomerulopathies (GNs)-immunoglobulin A nephropathy (IgAN, 29), membranous nephropathy (MN, 20) and lupus nephritis (LN, 18) and 13 with no GN. Follow-up included 48 participants. Machine learning was used to correlate OPN with other factors to classify patients by GN type. The resulting algorithm had an accuracy of 87% in differentiating IgAN from other GNs using urinary OPN levels only. A lesser effect for discriminating MN and LN was observed. However, the lower number of patients and the phenotypic heterogeneity of MN and LN might have affected those results. OPN was significantly higher in IgAN at baseline than in other GNs and therefore might be useful for identifying patients with IgAN. That observation did not apply to either patients with IgAN at follow-up or to patients with other GNs. OPN seems to be a valuable biomarker and should be validated in future studies. Machine learning is a powerful tool that, compared with traditional statistical methods, can be also applied to smaller datasets.

The Effect of Novel Selenopolysaccharide Isolated from Lentinula edodes Mycelium on Human T Lymphocytes Activation, Proliferation, and Cytokines Synthesis.

Polysaccharides isolated from Lentinula edodes are bioactive compounds with immunomodulatory properties. In our previous studies from L. edodes mycelium, we have isolated a selenium(Se)-enriched fraction (named Se-Le-30), a mixture of linear 1,4-α-glucan and linear 1,3-ß- and 1,6-ß-glucans. In this study, we analyzed the effects of Se-Le-30 on the activation and proliferation of human T lymphocytes stimulated by anti-CD3 and anti-CD3/CD28 antibodies (Abs) and on the production of cytokines by peripheral blood mononuclear cells (PBMCs). Se-Le-30 had effects on T cell proliferation induced by Abs against CD3 and CD28. It significantly inhibited the proliferation of CD3-stimulated CD4+ and CD8+ T cells and enhanced the proliferation of CD4+ T cells stimulated with anti-CD3/CD28 Ab. Moreover, Se-Le-30 downregulated the number of CD3-stimulated CD4+CD69+ cells, CD4+CD25+ cells, as well as CD8+CD25+ cells, and upregulated the expression of CD25 marker on CD4+ and CD8+ T cells activated with anti-CD3/CD28 Abs. Furthermore, Se-Le-30 enhanced the synthesis of IFN-γ by the unstimulated and anti-CD3/CD28-stimulated PBMCs, inhibited synthesis of IL-2 and IL-4 by CD3-stimulated cells, and augmented the synthesis of IL-6 and IL-10 by unstimulated, CD3-stimulated, and CD3/CD28-stimulated PBMCs. Together, we demonstrated that Se-Le-30 exerts immunomodulatory effects on human T lymphocytes. These observations are of importance for the prospective use of Se-Le-30 in research or as a therapeutic compound.

[Usefulness of osteopontin (OPN) determinations in ovarian cancer patients who underwent first-line chemotherapy]. / Przydatnosc oznaczen stzenia osteopontyny (OPN) u chorych na raka jajnika poddanych chemioterapii I rzutu.

INTRODUCTION: Currently CA 125 is a marker of choice for monitoring ovarian cancer Nonetheless, scientists are still searching for new markers, which could provide additional information for the evaluation of treatment, especially in patients with normal CA 125 levels, despite the progression of the disease. According to the latest reports, OPN can be a potential new marker: AIM: Estimation of usefulness of OPN determinations in the monitoring of ovarian cancer patients. MATERIAL AND METHODS: The study included 54 ovarian cancer patients, undergoing chemotherapy Markers were measured before, during and after treatment. The dynamics of the change of OPN levels was shown on line graphs, using Microsoft Excel programme. Statistical analysis was performed by Kaplan-Meier method and log-rank test. RESULTS: 44% of patients from the study group were found to have low CA 125 levels. In these cases only the increase of OPN concentration indicated recurrence of the disease. In 43% of patients the high initial CA 125 and OPN levels decreased during chemotherapy and complete regression was stated in these patients. Nevertheless, in 13/17 patients a repeated increase of OPN concentration signalling the recurrence, earlier than CA 125 and clinical recurrence manifestation, was observed. In 13% of patients high initial levels of markers did not decrease during chemotherapy which correlated with the progression of the disease. Our study showed that only the CA 125 levels had a significant influence (p=0.00063) on the disease-free survival time. CONCLUSIONS: Our data suggest a potential usefulness of the OPN determinations in estimating ovarian cancer recurrence. Nonetheless, there was no correlation between the initial OPN concentration and the disease-free survival time.

Osteopontin and Transplantation: Where Are We Now?

Organ transplantation represents the optimal therapeutic tool for patients with end-stage organ failure. Hematopoietic stem cell transplantation (HSCT) is likewise an effective therapy for a wide range of malignant and non-malignant diseases. Better understanding of transplantation immunology and the use of multi-modal immunosuppression protocols, can decrease the risk of graft failure and graft-versus-host disease (GVHD) after HSCT. Nevertheless, a major challenge of modern transplantology still seems to be finding non-invasive biomarkers for recipients selection, monitoring of allograft function, and diagnosis of rejection. Since proinflammatory cytokine osteopontin (OPN) is closely involved in regulating both adaptive and innate immune responses, as well as the pathogenesis of inflammatory and autoimmune diseases, it is likely to play an important role in organ and HSC transplantation. This review is to summarize recent advances in our knowledge about OPN function in the kidney, heart, liver, lung, and HSC transplantation. Most studies found that elevated OPN is associated with poorer graft function in kidney, heart, liver and lung recipients. Moreover, some reports suggested that this protein can play role in GVHD pathogenesis. However, due to relatively small number of similar studies, as well as some inconclusive results, future investigation in this field is needed to verify if OPN can serve as a biomarker of organ and HSC transplantation. The knowledge about such markers will promote our understanding of the mechanisms underlying graft dysfunction and posttransplant mortality. In addition, such knowledge may be helpful in the development of new treatment strategies and identification of recipients with increased risk of allograft failure.