Telomerase reverse transcriptase activates transcription of miR500A to inhibit Hedgehog signalling and promote cell invasiveness.

Telomerase reverse transcriptase (TERT) maintains telomere homeostasis, thus ensuring chromosome stability and cell proliferation. In addition, several telomere-independent functions of human TERT have been described. In this study, we report that TERT binds directly to the TCF binding elements located upstream of the oncomiR miR500A, and induces its transcription.

Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats.

Medication-related osteonecrosis of the jaw (MRONJ) is defined as the exposed necrotic bone involving the maxillofacial structures in bisphosphonate treated patients, and the pathophysiology of this disease remains unclear. The aim of this study was to assess the effects of the allogeneic transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a model of Wistar mice with induced MRONJ disease. BM-MSCs from five male Wistar rats were characterized and cultured on β-tricalcium phosphate (β-TCP) granules.

High temperature CaSiO-Ca(PO) ceramic promotes osteogenic differentiation in adult human mesenchymal stem cells.

Silicophosphate calcium ceramics are widely used in orthopedic and oral surgery applications because of their properties for stimulating bone formation and bone bonding. These bioceramics, together with multipotent undifferentiated adult human mesenchymal stem cells, are serious candidates in the field of bone tissue engineering and regenerative medicine. For this reason, the influence of a novel 30 wt%CaSiO - 70 wt%Ca(PO) ceramic over a primary adult human mesenchymal stem cells culture has been investigated in this study, observing a total colonization of the biomaterial by cells at 21 days.

Tolerance Biomarkers in Liver Transplantation: Independent External Validation of the Predictive Strength of SENP6 and FEM1C Gene Expression.

Background: Numerous studies have emphasized the genetic and phenotypic profiles of tolerant transplant patients. Moreover, different groups have defined several biomarkers, trying to distinguish patients who are going to be tolerant from those who are going to reject. However, most of these biomarkers have not been validated by other groups or even established for clinical practice.

Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantation.

The artificial induction of tolerance in transplantation is gaining strength. In mice, a differential role of extracellular adenosine (eADO) for regulatory and effector T cells (Tregs and Teffs, respectively) has been proposed: inhibiting Teffs and inducing Tregs. The aim of this study was to analyze the action of extracellular nucleotides in human T cells and, moreover, to examine the influence of CD39 and CD73 ectonucleotidases and subsequent adenosine signaling through adenosine 2 receptor (A R) in the induction of clinical tolerance after liver transplant.

Role of Kupffer cells in the progression of CRC liver metastases after the first stage of ALPPS.

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been suggested as a potential therapy for extensive bilobar liver tumors, although in some circumstances this technique may induce tumor progression, a fact still not well studied. Our aim was to study tumor hepatic progression induced by the first step of ALPPS in a WAG/Rij rat syngenic model of metastatic colorectal carcinoma by subcapsular CC531 cell line inoculation. ALPPS induced: tumor progression on deportalized lobe and metastases; expression of hepatic vasculogenic factors (HIF1-α and VEGF); and a dramatic increase of Kupffer cells (KCs) and tumor-associated macrophages (TAMs).

Matrix Metalloproteinase 1 as a Novel Biomarker for Monitoring Hepatocellular Carcinoma in Liver Transplant Patients.

Introduction: Orthotopic liver transplantation (LT) is considered to be one of the few curative treatments available for early stages of hepatocellular carcinoma (HCC). Alfa-fetoprotein (AFP) is the most-used biomarker for HCC despite low sensitivity and specificity. Matrix metalloproteinase 1 (MMP-1) has been considered to be involved in the process of vascular invasion of the malignant cells.

Extracellular ATP Activates the NLRP3 Inflammasome and Is an Early Danger Signal of Skin Allograft Rejection.

Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18.

PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas.

The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4 and CD8 T-cells.

Intraarticular and intravenous administration of Tc-HMPAO-labeled human mesenchymal stem cells (TC-AH-MSC): In vivo imaging and biodistribution.

Introduction: Therapeutic application of intravenous administered (IV) human bone marrow-derived mesenchymal stem cells (ahMSCs) appears to have as main drawback the massive retention of cells in the lung parenchyma, questioning the suitability of this via of administration. Intraarticular administration (IAR) could be considered as an alternative route for therapy in degenerative and traumatic joint lesions. Our work is outlined as a comparative study of biodistribution of Tc-ahMSCs after IV and IAR administration, via scintigraphic study in an animal model.

Differential profile of activated regulatory T cell subsets and microRNAs in tolerant liver transplant recipients.

Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplantation (LT) patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on LT tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) LT recipients by cellular, genetic, and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the forkhead box P3 (FOXP3) regulatory T cell-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs.

Oncological Evaluation by Positron-emission Tomography, Circulating Tumor Cells and Alpha Fetoprotein in Patients With Hepatocellular Carcinoma on the Waiting List for Liver Transplantation.

Introduction: The objectives of this study are the determination of the number of circulating tumor cells (CTCs), by means of the IsoFlux enrichment system (Fluxion Biosciences Inc, San Francisco, California, United States) in patients with hepatocellular carcinoma (HCC) in compliance with the Milan criteria and on the waiting list for hepatic transplantation, as well as the study of its relation with the of α-fetoprotein levels (AFP) and positron-emission tomography-computed tomography (PET-CT) findings.

Patients And Methods: An oncologycal evaluation with PET-CT, CTCs, and AFP was conducted in 24 consecutive patients with HCC eligible for orthotopic liver transplantation according to the Milan criteria. The diagnosis of HCC was made according to clinical, biological, and radiological findings.

Tolerance in liver transplantation: Biomarkers and clinical relevance.

Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance.

Immunosuppressive potency of mechanistic target of rapamycin inhibitors in solid-organ transplantation.

Mammalian target of rapamycin, also known as mechanistic target of rapamycin (mTOR) is a protein kinase that belongs to the PI3K/AKT/mTOR signaling pathway, which is involved in several fundamental cellular functions such as cell growth, proliferation, and survival. This protein and its associated pathway have been implicated in cancer development and the regulation of immune responses, including the rejection response generated following allograft transplantation. Inhibitors of mTOR (mTORi) such as rapamycin and its derivative everolimus are potent immunosuppressive drugs that both maintain similar rates of efficacy and could optimize the renal function and diminish the side effects compared with calcineurin inhibitors.

Comparison of Two Types of Liquid Biopsies in Patients With Hepatocellular Carcinoma Awaiting Orthotopic Liver Transplantation.

Introduction: Orthotopic liver transplantation (OLT) is considered one of the few curative treatments available for early stages of hepatocellular carcinoma (HCC). It has been shown that more than 10% of transplanted individuals suffer relapse during the first year after surgery and most of them die because of the tumor. The circulating tumor cells (CTCs) are the main source of recurrences as they disseminate from a primary or metastatic tumor lesion through peripheral blood.

Associated Liver Partition and Portal Vein Ligation (ALPPS) vs Selective Portal Vein Ligation (PVL) for Staged Hepatectomy in a Rat Model. Similar Regenerative Response?

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage hepatectomy technique which can be associated with a hypertrophic stimulus on the future liver remnant (FLR) stronger than other techniques--such as portal vein ligation (PVL). However, the reason of such hypertrophy is still unclear, but it is suggested that liver transection combined with portal vein ligation (ALPPS) during the first stage of this technique may play a key role. The aim of this study is to compare the hypertrophic stimulus on the FLR and the clinical changes associated with both ALPPS and PVL in a rat surgical model.

Predictive value of MicroRNAs in the progression of barrett esophagus to adenocarcinoma in a long-term follow-up study.

Objective: The aim of this study is to identify a set of microRNAs (miRNAs) as prognostic molecular biomarkers for the progression of Barrett esophagus (BE) to esophageal adenocarcinoma (EAC) to rationalize the surveillance programs in patients with BE.

Background: Histological dysplasia is currently used as the main biomarker to identify the BE patients at high risk for developing EAC. Although miRNA expression profiles in BE and EAC have been reported, it has not been established which set of miRNAs could constitute a robust diagnostic test to predict the progression of BE to EAC.

What do we know about the clinical impact of complete withdrawal of immunosuppression in liver transplantation?

The liver is a privileged organ with a lower incidence of rejection than other organs. However, immunosuppressive regimens are still required to control the alloreactive T-lymphocyte response after transplantation. These treatments may lead to severe complications, such as infectious diseases, cancers, cardiovascular diseases, and chronic renal insufficiency.

[Development of immune tolerance in liver transplantation].

The liver is a privileged organ and has a lower incidence of rejection than other organs. However, immunosuppressive regimens are still required to control the alloreactive T-lymphocyte response after transplantation. These treatments may lead to severe complications, such as infectious diseases, cancers, cardiovascular diseases and chronic renal insufficiency.

Immunosuppression withdrawal improves long-term metabolic parameters, cardiovascular risk factors and renal function in liver transplant patients.

After liver transplantation, long-term immunosuppression (IS) administration is commonly complicated by renal dysfunction and cardiovascular complications. Twenty liver transplant patients on cyclosporine (CyA)-based IS were followed up prospectively after IS withdrawal. They consisted of 10 electively weaned patients and 10 either forcibly or incidentally weaned patients.

FoxP3 in peripheral blood is associated with operational tolerance in liver transplant patients during immunosuppression withdrawal.

Background: Human liver allografts do sometimes survive in a recipient after withdrawal of immunosuppression (IS), commonly referred to as "operational tolerance." Preliminary clinical data have suggested an increase in the frequency of regulatory T cells (Treg) CD4+CD25 high and FoxP3 expression in operationally tolerant liver transplant recipients (Gr-T). In the context of human liver transplantation, the dynamics of Treg have not been studied.

Preliminary protective capacity study of a Dicrocoelium dendriticum antigenic protein in hamsters.

The purpose of this study was to evaluate the protective capacity of 130 kDa Dicrocoelium dendriticum protein in hamsters experimentally infected with this parasite. Forty hamsters divided into four groups of ten animals each were used: G1 (control), G2 (infected), G3 (immunized with Freund's adjuvant and infected), G4 (130 kDa protein vaccinated + adjuvant and infected). Infection with 40 metacercariae/hamster was carried out 4 weeks after the last immunization.

Partial characterization and isolation of 130 kDa antigenic protein of Dicrocoelium dendriticum adults.

The study focused on characterizing and isolating Dicrocoelium dendriticum antigens or their fractions that could be used for the immunological diagnosis of dicrocoeliosis. Somatic (SoAg) and excretory-secretory antigens (ESAg) were analyzed by SDS-PAGE and their specificity was evaluated by Western blot with homologous and heterologous sera. The antigens were partially purified by chromatographic techniques of gel-filtration (Sephacryl S-300) and ion exchange (Hitrap-DEAE-Sepharose).

Transport of N-acetyl-D-galactosamine in Escherichia coli K92: effect on acetyl-amino sugar metabolism and polysialic acid production.

The N-acetyl-D-galactosamine (GalNAc) transport system of Escherichia coli K92 was studied when the bacterium was grown in a chemically defined medium containing GalNAc as a carbon source. Kinetic measurements were carried out in vivo at 37 degrees C in 25 mM phosphate buffer, pH 7.0.