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Introduction: Brucellosis is a zoonotic endemic disease in Lebanon. It is caused by direct transmission of Brucella from contaminated animal products to humans. If left untreated brucellosis might lead to several complications and a chronic disease state. The prompt diagnosis of brucellosis has the ability to limit the progression of the disease, especially if the correct treatment is administered for the adequate amount of time. The aim of this study is to determine the optimal diagnostic tool and to assess Brucella burden in Lebanon. Methodology: This retrospective study was performed by reviewing the medical charts of 46 brucellosis patients from three Lebanese hospitals. Brucellosis diagnostic tests were compared and sensitivity of each test was calculated, as well as, the level of agreement with other standard diagnostic tools. Data retrieved were analyzed for relevance and statistical significance using the statistical package for social sciences version 23. Results: Sensitivity results of the diagnostic tests were: Rose Bengal test (RBT) 94.7%, blood culture 65.6%, standard agglutination test (SAT) melitensis 95.1% and SAT abortus 97.6%. The level of agreement between RBT and SAT melitensis as well as abortus is 98% and 90.18%, respectively. While the level of agreement between Blood culture and SAT melitensis as well as abortus is 66.88% and 64.5%, respectively. Discussion: Culture techniques require further optimization in order to find the best diagnostic tool for brucellosis. Meanwhile, Blood Rose Bengal test held a significant potential for identifying Brucella infection in a highly sensitive, cost effective and time saving manner.

Aims Coronary artery disease (CAD) is a common cause of heart failure (HF). It remains unclear who, when and why to direct towards coronary revascularization. The outcomes of coronary revascularization in HF patients are still a matter of debate nowadays. This study aims to evaluate the effect of revascularization strategy on all‐cause of death in the context of ischaemic HF. Methods and results An observational cohort was conducted on 692 consecutive patients who underwent coronary angiography at the University Hospital of Toulouse between January 2018 and December 2021 for either a recent diagnosis of HF or a decompensated chronic HF, and in whom coronary angiograms showed at least 50% obstructive coronary lesion. The study population was divided into two groups according to the performance or not of a coronary revascularization procedure. The living status (alive or dead) of each of the study's participants was observed by April 2022. Seventy‐three per cent of the study population underwent coronary revascularization either by percutaneous coronary intervention (66.6%) or coronary artery bypass grafting (6.2%). Baseline characteristics including age, sex and cardiovascular risk factors did not differ between the invasive and conservative groups, respectively. Death occurred in 162 study participants resulting in an all‐cause mortality rate of 23.5%; 26.7% of observed deaths have occurred in the conservative group versus 22.2% in the invasive group (P = 0.208). No difference in survival outcomes has been observed over a mean follow‐up period of 2.5 years (P = 0.140) even after stratification by HF categories (P = 0.132) or revascularization modalities (P = 0.366). Conclusions Findings from the present study showed comparable all‐cause mortality rates between groups. Coronary revascularization does not modify short‐term survival outcomes in HF patients compared with optimal medical therapy alone outside the setting of acute coronary syndrome.

To clarify the function of cyclin A2 in colon homeostasis and colorectal cancer (CRC), we generated mice deficient for cyclin A2 in colonic epithelial cells (CECs). Colons of these mice displayed architectural changes in the mucosa and signs of inflammation, as well as increased proliferation of CECs associated with the appearance of low- and high-grade dysplasias. The main initial events triggering those alterations in cyclin A2-deficient CECs appeared to be abnormal mitoses and DNA damage. Cyclin A2 deletion in CECs promoted the development of dysplasia and adenocarcinomas in a murine colitis-associated cancer model. We next explored the status of cyclin A2 expression in clinical CRC samples at the mRNA and protein levels and found higher expression in tumors of patients with stage 1 or 2 CRC compared with those of patients with stage 3 or 4 CRC. A meta-analysis of 11 transcriptome data sets comprising 2239 primary CRC tumors revealed different expression levels of CCNA2 (the mRNA coding for cyclin A2) among the CRC tumor subtypes, with the highest expression detected in consensus molecular subtype 1 (CMS1) and the lowest in CMS4 tumors. Moreover, we found high expression of CCNA2 to be a new, independent prognosis factor for CRC tumors.

Assembly of the multi‐subunit eukaryotic translation initiation factor‐4F (eIF4F) is critical for protein synthesis and cell growth and proliferation. eIF4F formation is regulated by the translation‐inhibitory protein 4E‐BP1. While proliferation factors and intracellular pathways that impinge upon 4E‐BP1 phosphorylation have been extensively studied, how they control 4E‐BP1 expression remains unknown. Here, we show that Smad4, a transcription factor normally required for TGFβ‐mediated inhibition of normal cell proliferation, enhances 4E‐BP1 gene‐promoter activity through binding to a conserved element. 4E‐BP1 expression is specifically modulated by treatment with TGFβ and by manipulations of the natural Smad4 regulators (co‐Smads) in cells isolated from Smad4 +/+ human tumours, whereas no response is observed in cells isolated from Smad4 −/− human tumours or in cells where Smad4 has been knocked down by specific siRNAs. In addition, cells where 4E‐BP1 has been knocked down (inducible shRNAs in human pancreatic cancer cells or siRNAs in non‐malignant human keratinocytes) or has been knocked out (mouse embryonic fibroblasts isolated from 4E‐BP1 −/− mice) proliferate faster and are resistant to the antiproliferative effect of TGFβ. Thus, 4E‐BP1 gene appears critical for TGFβ/Smad4‐mediated inhibition of cell proliferation.

The aim of this study was to describe and understand the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis rate in erythroleukemia cells after apoptosis induction by Berberis libanotica (Bl) extract. To achieve this goal we used erythroleukemia cell lines expressing COX-2 (HEL cell line) or not (K562 cell line). Moreover, we made use of COX-2 cDNA to overexpress COX-2 in K562 cells. In light of the reported chemopreventive and chemosensitive effects of natural products on various tumor cells and animal models, we postulated that our Bl extract may mediate their effects through apoptosis induction with suppression of cell survival pathways. Our study is the first report on the specific examination of intrinsic apoptosis and Akt/NF-κB/COX-2 pathways in human erythroleukemia cells upon Bl extract exposure. Even if Bl extract induced apoptosis of three human erythroleukemia cell lines, a dominant effect of Bl extract treatment on K562 cells was observed resulting in activation of the late markers of apoptosis with caspase-3 activation, PARP cleavage and DNA fragmentation. Whereas, we showed that Bl extract reduced significantly expression of COX-2 by a dose-dependent manner in HEL and K562 (COX-2+) cells. Furthermore, in regard to our results, it is clear that the simultaneous inhibition of Akt and NF-κB signalling can significantly contribute to the anticancer effects of Bl extract in human erythroleukemia cells. We observed that the Bl extract is clearly more active than the berberine alone on the induction of DNA fragmentation in human erythroleukemia cells.

Assembly of the multi-subunit eukaryotic translation initiation factor-4F (eIF4F) is critical for protein synthesis and cell growth and proliferation. eIF4F formation is regulated by the translation-inhibitory protein 4E-BP1. While proliferation factors and intracellular pathways that impinge upon 4E-BP1 phosphorylation have been extensively studied, how they control 4E-BP1 expression remains unknown. Here, we show that Smad4, a transcription factor normally required for TGFbeta-mediated inhibition of normal cell proliferation, enhances 4E-BP1 gene-promoter activity through binding to a conserved element. 4E-BP1 expression is specifically modulated by treatment with TGFbeta and by manipulations of the natural Smad4 regulators (co-Smads) in cells isolated from Smad4(+/+) human tumours, whereas no response is observed in cells isolated from Smad4(-/-) human tumours or in cells where Smad4 has been knocked down by specific siRNAs. In addition, cells where 4E-BP1 has been knocked down (inducible shRNAs in human pancreatic cancer cells or siRNAs in non-malignant human keratinocytes) or has been knocked out (mouse embryonic fibroblasts isolated from 4E-BP1(-/-) mice) proliferate faster and are resistant to the antiproliferative effect of TGFbeta. Thus, 4E-BP1 gene appears critical for TGFbeta/Smad4-mediated inhibition of cell proliferation.

Assembly of the multi-subunit eukaryotic translation initiation factor-4F (eIF4F) is critical for protein synthesis and cell growth and proliferation. eIF4F formation is regulated by the translation-inhibitory protein 4E-BP1. While proliferation factors and intracellular pathways that impinge upon 4E-BP1 phosphorylation have been extensively studied, how they control 4E-BP1 expression remains unknown. Here, we show that Smad4, a transcription factor normally required for TGFbeta-mediated inhibition of normal cell proliferation, enhances 4E-BP1 gene-promoter activity through binding to a conserved element. 4E-BP1 expression is specifically modulated by treatment with TGFbeta and by manipulations of the natural Smad4 regulators (co-Smads) in cells isolated from Smad4+/+ human tumours, whereas no response is observed in cells isolated from Smad4-/- human tumours or in cells where Smad4 has been knocked down by specific siRNAs. In addition, cells where 4E-BP1 has been knocked down (inducible shRNAs in human pancreatic cancer cells or siRNAs in non-malignant human keratinocytes) or has been knocked out (mouse embryonic fibroblasts isolated from 4E-BP1-/- mice) proliferate faster and are resistant to the antiproliferative effect of TGFbeta. Thus, 4E-BP1 gene appears critical for TGFbeta/Smad4-mediated inhibition of cell proliferation. [PUBLICATION ABSTRACT]

Assembly of the multi-subunit eukaryotic translation initiation factor-4F (eIF4F) is critical for protein synthesis and cell growth and proliferation. eIF4F formation is regulated by the translation-inhibitory protein 4E-BP1. While proliferation factors and intracellular pathways that impinge upon 4E-BP1 phosphorylation have been extensively studied, how they control 4E-BP1 expression remains unknown. Here, we show that Smad4, a transcription factor normally required for TGFb-mediated inhibition of normal cell proliferation, enhances 4E-BP1 gene-promoter activity through binding to a conserved element. 4E-BP1 expression is specifically modulated by treatment with TGFb and by manipulations of the natural Smad4 regulators (co-Smads) in cells isolated from Smad4 super(+/+) human tumours, whereas no response is observed in cells isolated from Smad4 super(-/-) human tumours or in cells where Smad4 has been knocked down by specific siRNAs. In addition, cells where 4E-BP1 has been knocked down (inducible shRNAs in human pancreatic cancer cells or siRNAs in non-malignant human keratinocytes) or has been knocked out (mouse embryonic fibroblasts isolated from 4E-BP1 super(-/-) mice) proliferate faster and are resistant to the antiproliferative effect of TGFb. Thus, 4E-BP1 gene appears critical for TGFb/Smad4-mediated inhibition of cell proliferation.

Background: Adult T-cell Leukemia (ATL) is a disease with no known cure. The disease manifests itself as an aggressive proliferation of CD4 super(+) cells with the human T-cell Lymphotropic virus type 1 (HTLV-1). The leukemogenesis of the virus is mainly attributed to the viral oncoprotein. Tax activates the Nuclear Factor kappa B (NF-[kappa]B) which stimulates the activity and expression of the matrix metalloproteinase-9 (MMP-9). The objective of this study was to investigate the efficacy of a specific nutrient synergy (SNS) on proliferation, Tax expression, NF-[kappa]B levels as well as on MMP-9 activity and expression both at the transcriptional and translational levels in two HTLV-1 positive cell lines, HuT-102 and C91-PL at 48h and 96h of incubation. Cytotoxicity of Epigallocatechin-3-gallate (EGCG) was assayed using CytoTox 96 Non-radioactive and proliferation was measured using Cell Titer96 super(TM) Nonradioactive Cell Proliferation kit (MTT- based assay). Enzyme linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA) were used to assess the effect of SNS on NF-[kappa]B mobility. Zymography was used to determine the effects of SNS on the activity and secretion of MMP-9. The expression of MMP-9 was done using RT-PCR at the translational level and Immunoblotting at the transcriptional level. Results: A significant inhibition of proliferation was seen in both cell lines starting at a concentration of 200[mu]g/ml and in a dose dependent manner. SNS induced a dose dependent decrease in Tax expression, which was paralleled by a down-regulation of the nuclearization of NF-[kappa]B. This culminated in the inhibition of the activity of MMP-9 and their expression both at the transcriptional and translational levels. Conclusions: The results of this study indicate that a specific nutrient synergy targeted multiple levels pertinent to the progression of ATL. Its activity was mediated through the NF-[kappa]B pathway, and hence has the potential to be integrated in the treatment of this disease as a natural potent anticancer agent.