Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer

Cancer was recently annexed to diabetic complications. Furthermore, recent studies suggest that cancer can increase the risk of diabetes. Consequently, diabetes and cancer share many risk factors, but the cellular and molecular pathways correlating diabetes and colon and rectal cancer (CRC) remain far from understood. In this study, we assess the effect of hyperglycemia on cancer cell aggressiveness in human colon epithelial adenocarcinoma cells in vitro and in an experimental animal model of CRC. Our results show that Nox (NADPH oxidase enzyme) 4-induced reactive oxygen species (ROS) production is deregulated in both diabetes and CRC. This is paralleled by inactivation of the AMPK and activation of the mammalian target of rapamycin (mTOR) C1 signaling pathways, resulting in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulation, induction of DNA damage, and exacerbation of cancer cell aggressiveness, thus contributing to the genomic instability and predisposition to increased tumorigenesis in the diabetic milieu. Pharmacologic activation of AMPK, inhibition of mTORC1, or blockade of Nox4 reduce ROS production, restore the homeostatic signaling of 8-oxoguanine DNA glycosylase/8-oxodG, and lessen the progression of CRC malignancy in a diabetic milieu. Taken together, our results identify the AMPK/mTORC1/Nox4 signaling axis as a molecular switch correlating diabetes and CRC. Modulating this pathway may be a strategic target of therapeutic potential aimed at reversing or slowing the progression of CRC in patients with or without diabetes.-Mroueh, F. M., Noureldein, M., Zeidan, Y. H., Boutary, S., Irani, S. A. M., Eid, S., Haddad, M., Barakat, R., Harb, F., Costantine, J., Kanj, R., Sauleau, E.-A., Ouhtit, A., Azar, S. T., Eid, A. H., Eid, A. A. Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer.Scopu

Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats

Introduction: Oxidative stress is a major instigator of various cardiovascular diseases, including myocardial infarction (MI). Despite available drugs, there is still an increased need to look for alternative therapies or identify new bioactive compounds. Sanguisorba minor (S. minor) is a native herb characterized by its potent antioxidant activity. This study was designed to evaluate the effect of S. minor against isoprenaline-induced MI.Methods: Rats were treated with the hydro-ethanolic extract of the aerial parts of S. minor at doses of 100 or 300 mg/kg orally for 9 days. Isoprenaline was injected subcutaneously at the dose of 85 mg/kg on days 8 and 9. Then, the activities of various cardiac injury markers including cardiac troponin (cTnT), lactate dehydrogenase (LDH), creatinine kinase muscle brain (CK-MB), creatinine phosphokinase (CPK), and antioxidant enzymes in serum were determined. Malondialdehyde (MDA) and thiol content were measured in cardiac tissue, and histopathological analysis was conducted.Results: Our results show that isoprenaline increased the serum levels of cTnT, LDH, CK-MB, and CPK (p < 0.001) and elevated MDA levels (p < 0.001) in cardiac tissue. Isoprenaline also reduced superoxide dismutase (SOD), catalase, and thiol content (p < 0.001). Importantly, the extract abolished isoprenaline-induced MI by elevating SOD and catalase (p < 0.001), reducing levels of MDA, and diminishing levels of cTnT, LDH, CK-MB, and CPK cardiac markers (p < 0.001). Histopathological studies of the cardiac tissue showed isoprenaline-induced injury that was significantly attenuated by the extract.Conclusion: Our results suggest that S. minor could abrogate isoprenaline-induced cardiac toxicity due to its ability to mitigate oxidative stress

Immune Checkpoint Inhibitor-Induced Diabetes Mellitus: Potential Role of T Cells in the Underlying Mechanism

Immunotherapy is now a recognized treatment option for several types of cancer. However, some cancer patients treated with immune checkpoint inhibitors (ICIs) are subject to immune-related adverse events, including induced diabetes mellitus. The exact role and molecular/genetic action of ICIs in diabetes are still not well understood. Elucidating the underlying mechanisms in a proper fashion would allow better refining of biomarkers that would help diagnose patients at risk of altered immune system homeostasis, but would also hold the potential of new therapeutic options for diabetes. In the present narrative review, we propose to discuss the case of autoimmune diabetes following treatment with ICIs and the role of ICIs in the pathophysiology of diabetes. We also present some scarce available data on interesting potential immune therapies for diabetes

Carriage of beta-lactamase-producing Enterobacteriaceae among nursing home residents in north Lebanon

Background: Multidrug-resistant (MDR) Enterobacteriaceae can cause severe infections with high morbidity, mortality, and health care costs. Individuals can be fecal carriers of these resistant organisms. Data on the extent of MDR Enterobacteriaceae fecal carriage in the community setting in Lebanon are very scarce. The aim of this study was to investigate the fecal carriage of MDR Enterobacteriaceae among the elderly residents of two nursing homes located in north Lebanon. Methods: Over a period of 4 months, five fecal swab samples were collected from each of 68 elderly persons at regular intervals of 3–4 weeks. Fecal swabs were subcultured on selective media for the screening of resistant organisms. The phenotypic detection of extended-spectrum beta-lactamase (ESBL), AmpC, metallo-beta-lactamase (MBL), and Klebsiella pneumoniae carbapenemase (KPC) production was performed using the beta-lactamase inhibitors ethylenediaminetetraacetic acid, phenylboronic acid, and cloxacillin. A temocillin disk was used for OXA-48. Multiplex PCRs were used for the genotypic detection of ESBL and carbapenemase genes, and sequencing was performed to identify CTX-M-15. The medical records of each subject were reviewed on a regular basis in order to assess the risk factors associated with MDR Enterobacteriaceae fecal carriage. Results: Over the study period, 76.5% of the recruited elderly persons were at least one-time carriers. A total of 178 isolates were obtained. Phenotypic testing revealed that 91.5% of them were ESBL producers, 4% were AmpC producers, 2.8% were co-producers of ESBL and AmpC, and 1.7% were co-producers of OXA-48 and ESBL. Recent antibiotic intake was found to be the only independent risk factor associated with the fecal carriage of MDR Enterobacteriaceae. Conclusions: The high prevalence of MDR Enterobacteriaceae detected in this study and the emergence of carbapenem resistance is alarming. Efficient infection control measures and antibiotic stewardship programs are urgently needed in these settings in order to limit the spread of resistant strains

Draft Genome Sequences of Two Multidrug-Resistant Sequence Type 405 Escherichia coli Isolates without Clinical Infection

International audienceWe present the genome sequences of two carbapenemase-producing sequence type 405 Escherichia coli clinical isolates, strains Marseille-Q1950 and Marseille-Q1951. The isolates were obtained 1 month apart during the patient’s hospitalization in Lebanon, in May (Marseille-Q1950) and June (Marseille-Q1951) 2019. The genome sizes of strains Marseille-Q1950 and Marseille-Q1951 were 5,181,515 bp and 5,213,451 bp, respectively

Draft Genome Sequence of an NDM-1-Producing Sequence Type 101 (ST101) Klebsiella pneumoniae Strain, Marseille-Q1949

International audienceA pan-drug-resistant Klebsiella pneumoniae strain was isolated from the blood of a 70-year-old critically ill patient in April 2019. Interestingly, the patient recovered and was discharged home a month later. The genome of strain Marseille-Q1949 is 5,607,584-bp long and has a 57.1% G+C content and 5,467 protein-coding genes

First Detection of Colistin-Resistant Klebsiella pneumoniae in Association with NDM-5 Carbapenemase Isolated from Clinical Lebanese Patients

International audienc