Bifidobacterium bifidum PRL2010 Modulates the Host Innate Immune Response

Here, we describe data obtained from transcriptome profiling of human cell lines and intestinal cells of a murine model upon exposure and colonization, respectively, with Bifidobacterium bifidum PRL2010. Significant changes were detected in the transcription of genes that are known to be involved in innate immunity. Furthermore, results from enzyme-linked immunosorbent assays (ELISAs) showed that exposure to B. bifidum PRL2010 causes enhanced production of interleukin 6 (IL-6) and IL-8 cytokines, presumably through NFκB activation. The obtained global transcription profiles strongly suggest that Bifidobacterium bifidum PRL2010 modulates the innate immune response of the host. © 2014, american Society for Microbiology. All Rights Reserved.We thank GenProbio srl for financial support of the Laboratory of Probiogenomics. This work was financially supported by Fondazione Cariplo (grant 2010-0678 to S.G. and V.T.) and by a FEMS Jensen Award to F.T. This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) under grant SFI/12/RC/2273. The grant ILINK2010-0122, funded by CSIC, is also acknowledged.Peer Reviewe

AA-amyloidosis in cats (Felis catus) housed in shelters.

Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis

Bifidobacterium bifidum PRL2010 Modulates the Host Innate Immune Response

Here, we describe data obtained from transcriptome profiling of human cell lines and intestinal cells of a murine model upon exposure and colonization, respectively, with Bifidobacterium bifidum PRL2010. Significant changes were detected in the transcription of genes that are known to be involved in innate immunity. Furthermore, results from enzyme-linked immunosorbent assays (ELISAs) showed that exposure to B. bifidum PRL2010 causes enhanced production of interleukin 6 (IL-6) and IL-8 cytokines, presumably through NF\u3baB activation. The obtained global transcription profiles strongly suggest that Bifidobacterium bifidum PRL2010 modulates the innate immune response of the host

Development of a clinical program aimed to improve the safety of living donor kidney transplantation: the role of renal functional reserve, radioisotope glomerular filtration rate and urinary biomarkers

Background. I donatori di rene (KD) presentano un aumentato rischio di insufficienza renale cronica: ènecessaria un’accurata valutazione statica e dinamica della funzione renale pre e post-donazione, il cuirecupero è dovuto alla riserva funzionale renale (RFR) ossia la capacità di aumentare la velocità difiltrazione glomerulare in risposta a stimoli fisiologici o condizioni patologiche. E’ stato studiato il ruolo delGFR radioisotopico (mGFR), della misurazione della RFR e di biomarkers urinari di danno (NGAL,Nephrocheck) e di staminalità (CD133 su microvescicole urinarie) pre e post donazione. E’ stato inoltreverificato se esiste una soglia di RFR di sicurezza per la donazione.Pazienti e metodi. La funzione renale di 112 KD è stata studiata pre tramite mGFR + scintigrafia sequenziale99mTc-MAG, ripetuta a 1 anno dalla donazione. E’ stata misurata la RFR mediante stress test glomerularedue settimane prima della donazione e dopo 1 anno. I biomarkers urinari sono stati analizzati predonazione e post. E’ stata eseguita curva ROC per stabilire soglia di sicurezza della RFR.Risultati. Ad 1 anno dalla donazione i KD presentano mGFR mediano di 63 ml/min (+37% rispetto al basale).mGFR basale e età predicono mGFR a 1 anno. NGAL e Nephrocheck risultano negativi in VII giornata postdonazione ed a 1 anno con netto incremento di micorvescicole urinarie CD133+ post donazione. Per unincremento compensatorio mGFR ≥ 10 mL/min a 1 anno, il livello soglia di RFR pre è 18 mL/min.Conclusioni. La valutazione dinamica della funzione renale pre e post donazione di rene contribuisce adaumentare la sicurezza del KD. L’mGFR è accurato nel valutare la funzione renale, predicendone il valorepost donazione. La misurazione RFR rappresenta un elemento utile come selezione dei donatori. Lanegatività dei biomarkers di danno e la positività del marker di staminalità dimostrano l’adattamentofisiologico del monorene post donazione

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors, and functional microRNAs (miRNAs) that may modulate expression of recipient cell genes. As paracrine factors, neutrophil- and macrophage-derived EVs exert immunosuppressive and immune-stimulating effects on dendritic cells, respectively. Dendritic cell-derived EVs mediate alloantigen spreading and modulate antigen presentation to T lymphocytes. At systemic level, EVs exert pleiotropic effects on complement and coagulation. Depending on their biogenesis, they can amplify complement activation or shed complement inhibitors and prevent cell lysis. Likewise, endothelial- and platelet-derived EVs can exert procoagulant/prothrombotic effects and also promote endothelial survival and angiogenesis after ischemic injury. Kidney endothelial- and tubular-derived EVs play a key role in ischemia-reperfusion injury (IRI) and during the healing process; additionally, they can trigger rejection by inducing both alloimmune and autoimmune responses. Endothelial EVs have procoagulant/pro-inflammatory effects and can release sequestered self-antigens, generating a tissue-specific autoimmunity. Renal tubule-derived EVs shuttle pro-fibrotic mediators (TGF-\u3b2 and miR-21) to interstitial fibroblasts and modulate neutrophil and T-lymphocyte influx. These processes can lead to peritubular capillary rarefaction and interstitial fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells (MSCs), have been employed as a therapeutic tool in experimental models of rejection and IRI. These particles protect tubular and endothelial cells (by inhibition of apoptosis and inflammation-fibrogenesis or by inducing autophagy) and stimulate tissue regeneration (by triggering angiogenesis, cell proliferation, and migration). Finally, urinary and serum EVs represent potential biomarkers for delayed graft function (DGF) and acute rejection. In conclusion, EVs sustain an intricate crosstalk between graft tissue and innate/adaptive immune systems. EVs play a major role in allorecognition, IRI, autoimmunity, and alloimmunity and are promising as biomarkers and therapeutic tools in KT

[What if it is not an acute pyelonephritis? A monocentric experience of renal infarcts]

BACKGROUND: Often the reduced contrast enhancement on CT renal imaging is radiologically interpreted as acute pyelonephritis (PNA), but it is the task of the clinician to assess a possible differential diagnosis such as a renal infarct and look for a cause. METHODS: In our experience (2010-2013), we hospitalized 51 patients with radiological imaging consistent with acute pyelonephritis in native kidneys. However, three of these cases result, after a second look, to be ischemic lesions, only sometimes complicated by over-infections RESULTS: First case: a woman hospitalized for fever and flank pain with blood culture positive for Klebsiella Pneumoniae. Antibiotic therapy allowed a clinical-laboratory improvement, but after 45 days persisted a focal wedge to the CT scan. The labs showed a anemia due to a sickle cell disease (SLC). The overview was finally interpreted as a renal infarct secondary to a sickle cell anemia, initially complicated by over-infection. Second Case: a men hospitalized for a acute flank pain. The CT scan showed a left renal infarct and a partial renal artery thrombosis, resulting in abuse of cannabinoids and LAC positivity. Third case: a woman hospitalized for flank pain and slight movement of inflammatory markers. CT showed a cuneiform area in the right kidney not vascularized, that did not resolved after prolonged antibiotic therapy. The labs evidence a heterozygous mutation of prothrombin and MTHFR causing the renal infarction. CONCLUSIONS: 6% of radiographic imaging consistent with acute pyelonephritis concealed an underlying infarct, due to a unknown state of thrombophilia. The presence of hypovascular imaging to the TC scan, therefore, requires a differential diagnosis between PNA and infarct, especially in the case of atypical development