Association between anti-Ro 60kDa (SS-A) autoantibodies and hypocomplementemia in systemic lupus erythematosus patients from Algiers prefectures

AbstractBackgroundSystemic lupus erythematosus (SLE) is characterized by a vicious cycle maintaining systemic inflammation. It starts by autoantibody production, immune complex formation and complement activation that contribute to inflammation, tissue damage and further autoantibody production.Aim of the workTo evaluate the association between the auto-antibodies (abs), circulating immune complexes (CIC), and complement activity in SLE patients.Patients and methodsThis study involved 30 female SLE patients analyzed for autoantibodies, complement profile including complement hemolytic 50 (CH50), alternative pathway 50, factor B, C1q, C2, C3 and C4 as well as C1q-CIC. SLE disease activity was assessed by the SLE Disease Activity Index (SLEDAI).ResultsThe age of patients was 34±12.8years, disease duration was 5.2±3.2years and their mean SLEDAI was 9.96±4.2. Anti-SSA, anti-dsDNA, anti-C1q abs, and CIC were detected in 36.7%, 50%, 50% and 30% of patients, respectively. Anti-SSA were higher in patients with lower compared to normal CH50 activity and C3 level (24.7 vs 88.6U/ml; p=0.002 and 118.6±25.18U/ml vs 15.9±7.3; p<0.0001 respectively) than the other autoantibodies. Increased CIC were higher in patients with lupus nephritis and were associated with anti-SSA, anti-SSB, anti-C1q, anti-Sm and in patients with low CH50 activity. The CIC significantly correlated with anti-C1q (r=0.69, p<0.0001), anti-SSA (r=0.5, p=0.005) and negatively with CH50 (r=−0.4, p=0.046).ConclusionsThe current study confirms that the etiopathogenic anti-SSA autoantibodies are the most associated with hypocomplementemia in SLE. This would stimulate future researches for validation of predictive biomarkers earlier than hypocomplementemia which is still the major unmet need in lupus research and patient care

Steady Flow of Purely Viscous Shear-Thinning Fluids in a 1:3 Planar Gradual Expansion

Laminar flow of non-Newtonian fluid (shear-thinning) through a 1:3 planar gradual expansion is numerically investigated, for various Power-Law index (0.6, 0.8 and 1.0) and expansion angles (15, 30, 45, 60 and 90°) at different generalized Reynolds number (1 ≤ Reg ≤ 400). The study of these parameters effect on the flow pattern allowed the determination of the two critical generalized Reynolds numbers (Regcr1 and Regcr2), which correspond to the transition from the symmetric to the asymmetric flow and the appearance of the third recirculation zone respectively. The results showed that decreasing the Power-Law index or the expansion angle stabilizes the flow by increasing significantly the two critical generalized Reynolds numbers. In order to predict the two critical generalized Reynolds numbers, two correlations have been proposed

Reprogramming of pancreatic adenocarcinoma immunosurveillance by a microbial probiotic siderophore

There is increasing evidence suggesting the role of microbiome alterations in relation to pancreatic adenocarcinoma and tumor immune functionality. However, molecular mechanisms of the interplay between microbiome signatures and/or their metabolites in pancreatic tumor immunosurveillance are not well understood. We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms tumor-associated macrophages (TAMs) and increases CD8 + T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer. Interestingly, this altered immune response improved anti-PD-L1 therapy that suggests promise of a novel combination (ferrichrome and immune checkpoint inhibitors) therapy for pancreatic cancer treatment. Mechanistically, ferrichrome induced TAMs polarization via activation of the TLR4 pathway that represses the expression of iron export protein ferroportin (FPN1) in macrophages. This study describes a novel probiotic based molecular mechanism that can effectively induce anti-tumor immunosurveillance and improve immune checkpoint inhibitors therapy response in pancreatic cancer

Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition

Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background HTLV-I is associated with the development of an aggressive form of lymphocytic leukemia known as adult T-cell leukemia/lymphoma (ATLL). A major obstacle for effective treatment of ATLL resides in the genetic diversity of tumor cells and their ability to acquire resistance to chemotherapy regimens. As a result, most patients relapse and current therapeutic approaches still have limited long-term survival benefits. Hence, the development of novel approaches is greatly needed. Methods In this study, we found that a small molecule inhibitor of poly (ADP-ribose) polymerase (PARP), PJ-34, is very effective in activating S/G2M cell cycle checkpoints, resulting in permanent cell cycle arrest and reactivation of p53 transcription functions and caspase-3-dependent apoptosis of HTLV-I-transformed and patient-derived ATLL tumor cells. We also found that HTLV-I-transformed MT-2 cells are resistant to PJ-34 therapy associated with reduced cleaved caspase-3 activation and increased expression of RelA/p65. Conclusion Since PJ-34 has been tested in clinical trials for the treatment of solid tumors, our results suggest that some ATLL patients may be good candidates to benefit from PJ-34 therapy

Lobar and segmental liver atrophy associated with hilar cholangiocarcinoma and the impact of hilar biliary anatomical variants: a pictorial essay

The radiological features of lobar and segmental liver atrophy and compensatory hypertrophy associated with biliary obstruction are important to recognise for diagnostic and therapeutic reasons. Atrophied lobes/segments reduce in volume and usually contain crowded dilated bile ducts extending close to the liver surface. There is often a “step” in the liver contour between the atrophied and non-atrophied parts. Hypertrophied right lobe or segments enlarge and show a prominently convex or “bulbous” visceral surface. The atrophied liver parenchyma may show lower attenuation on pre-contrast computed tomography (CT) and CT intravenous cholangiography (CT-IVC) and lower signal intensity on T1-weighted magnetic resonance imaging (MRI). Hilar biliary anatomical variants can have an impact on the patterns of lobar/segmental atrophy, as the cause of obstruction (e.g. cholangiocarcinoma) often commences in one branch, leading to atrophy in that drainage region before progressing to complete biliary obstruction and jaundice. Such variants are common and can result in unusual but explainable patterns of atrophy and hypertrophy. Examples of changes seen with and without hilar variants are presented that illustrate the radiological features of atrophy/hypertrophy

(B)ordering South of Lebanon: Hizbullah’s identity building strategy

International audienceThis paper examines the importance of the Lebanese southern borderland area in the political strategy of Hizbullah's identity building. It highlights how Hizbullah succeeded in its quest to become a major political player in Lebanon by using South Lebanon. The main hypothesis is that this borderland area has been ordered and bordered by Hizbullah to create a common identity among the Lebanese Shi'i population based on a Shi'i religious involvement and the " duty " of armed resistance against Israel. To support this idea, I will rely on a theoretical framework articulating space and identity building and will refer to concepts provided by Middle Eastern studies. In the first part of the paper, I will discuss the conditions of the emergence of the group of solidarity and how it articulates to the religious Shi'i ideology. Then, I will highlight the " lebanonization " process Hizbullah undertaken at the end of the civil war and how during the 1990s it transformed the South into a sanctuary. Finally, I will show how Hizbullah enforced the national legitimacy of its social, political and military actions before targeting the state apparatus