LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome

Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to depend on the glucocorticoid receptor (GR), maps to the distal region of the X-chromosome. The GR-inducible gene Tsc22d3, encoding the protein Gilz and located in the critical region on the X-chromosome, showed a higher expressed SPRET/Ei allele, regulated in cis. Higher Gilz levels were causally related to reduced inflammation, as shown with knockdown and overexpression studies in macrophages. Transient overexpression of Gilz by hydrodynamic plasmid injection confirmed that Gilz protects mice against endotoxemia Our data strongly suggest that Gilz is responsible for the LPS resistance of SPRET/Ei mice and that it could become a treatment option for sepsis

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Distribution of Meloidogyne chitwoodi in potato tubers and comparison of extraction methods

Meloidogyne chitwoodi and M. fallax are quarantine organisms in Europe. One measure to restrict the spread of these nematodes is careful inspection of potato tubers. The distribution of M. chitwoodi in heavily infected tubers was studied and several methods for extraction of these nematodes from tubers were compared. The majority of the nematodes (96%) were found in the first 5.25 mm of the tuber, corresponding to the depth of the vascular ring. About half of them were found between 1.75 and 3.50 mm deep. Incubation of small pieces of tuber on Baermann funnels in the misting chamber during 36 days yielded about 12 times fewer juveniles than mixing potato tissues and extracting them using zonal centrifugation, a process that took about 1 h. Enzymatic maceration of potato tissues for 24 or 48 h did not liberate more nematodes than 2 min of blending the tissues at high speed. More nematodes, with 95% consisting of eggs, were extracted by zonal centrifuging than by pouring the macerated suspension over a set of 500 mu m 250 mu m and 20 mu m sieves

HSP70 protects against TNF-induced lethal inflammatory shock.

AbstractThe heat shock (HS) response is a universal response activated after exposure to various stimuli. The major HS protein (HSP) is the 72 kDa HSP70 with strong homology in different eukaryotic species. We demonstrate that HS treatment of mice leads to a strong induction of HSP70 in several organs and confers significant protection against lethality induced by tumor necrosis factor (TNF). HS prevents high production of interleukin-6 and nitric oxide and reduces severe damage and apoptosis of the enterocytes in the bowel. Mice deficient in the inducible hsp70.1 gene were no longer protected by HS treatment. We show that HS can be applied successfully in an antitumor protocol based on TNF and interferon-γ, leading to a significant inhibition of lethality but not to a reduction of antitumoral capacity

2,2,2-Trichloro-N-((2-(2-(dimethylamino)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo(de)isoquinolin-5-yl)carbamoyl)acetamide (UNBS3157), a novel non-hematotoxic naphthalimide derivative with potent anti-tumor activity.

Abstract A261info:eu-repo/semantics/nonPublishe

UNBS5162 is a novel naphthalimide derivative that induces autophagy and senescence in human prostate cancer cells.

Abstract A119info:eu-repo/semantics/nonPublishe

Targeting pro-angiogenic CXCL chemokines as a new encouraging way to combat prostate cancer.

Abstract 4752info:eu-repo/semantics/nonPublishe