Interferon regulatory factors (IRFs) are a group of closely related proteins collectively referred to as the IRF family. Members of this family were originally recognized for their roles in inflammatory responses; however, recent research has suggested that they are also involved in tumor biology. This review focusses on current knowledge of the roles of IRF-1 and IRF-2 in human cancer, with particular attention paid to the impact of IRF-1 inactivation. The different mechanisms underlying IRF-1 inactivation and their implications for human cancers and the potential importance of IRF-1 in immunotherapy are also summarized.

Carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPAE) are globally a major medical issue, especially in intensive care units. The digestive tract is the main reservoir for these isolates; therefore, rectal swab surveillance is highly recommended. The purpose of this study was to detect the prevalence of gastrointestinal tract colonization of CRE and CRPAE in patients admitted to intensive care units in Saudi Arabia. This project also aimed to characterize carbapenem-hydrolyzing enzyme production in these isolates. From February to May 2015, 200 rectal swab specimens were screened by CHROMagar KPC. Organism identification and susceptibility testing were performed using the Vitek 2 system. One CRE and 13 CRPAE strains were identified, for a prevalence of 0.5% (1/200) and 6.5% (13/200) respectively. Strains showed high genetic diversity using enterobacterial repetitive intergenic consensus sequence-based PCR. NDM type and VIM type were detected by PCR in four and one CRPAE isolates respectively. ampC overexpression was detected in eight CRPAE isolates using Mueller-Hinton agar containing 1000 μg/mL cloxacillin. CTX-M-15 type was detected in 1 CRE by PCR. The prevalence of CRE strain colonization was lower than that of CRPAE isolates. The detection of NDM and VIM in the colonizing CRPAE strains is a major infection control concern. To our knowledge, this is the first study in Saudi Arabia and the gulf region focusing on digestive tract colonization of CRE and CRPAE organisms and characterizing the mechanisms of carbapenem resistance.

AGR2 forms an ER-resident signalling axis in cell development, limb regeneration, and in human diseases like asthma and cancer, yet molecular mechanisms underlying its effects remain largely undefined. A single integrated Flippase recombination target (FRT) site was engineered within the AGR2-non expressing A375 cell line to allow integration of a constitutively expressed AGR2 alleles. This allows an analysis of how AGR2 protein expression reprogrammes intracellular signalling. The engineered expression of AGR2 had marginal impact on global transcription signalling, compared to its paralogue AGR3. However, expression of AGR2 had a significant impact on remodelling the cellular proteome using a triple-labelled SILAC protocol. 29 045 peptides were detected for the identification and relative quantitation of 3003 proteins across the experimental conditions. Ingenuity Pathway annotation highlighted the dominant pathway suppressed by wt-AGR2 was the p53-signalling axis. DNA damage induced p53 stabilization and p21 induction by cisplatin treatment confirmed that wt-AGR2 expression suppressed the p53 pathway. The furthest outlying SILAC protein expression change induced by AGR2 was the anti-viral and cell cycle regulator tumour susceptibility gene 101 (TSG101), confirmed by immunoblotting. Transfection of TSG101 into MCF7 (AGR2+, oestrogen dependent), A549 (AGR2+, oestrogen independent) or A375 (AGR2-) cells confirmed that TSG101 attenuates p53 signalling. These systems wide screens suggest that the most dominant landscape reprogrammed by low levels of AGR2 protein is the cellular proteome, rather than the transcriptome, and provide focus for evaluating its role in proteostasis.

HighlightsChryseobacterium gleum is ubiquitously distributed in the environment.It can cause pneumonia in patients with underlying disease such as nephrotic syndrome especially with medical device use.The treatment of Chryseobacterium is challenging; the patient we presented was treated with levofloxacin.

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To our knowledge, this is the first report describing XDRKPN encoding at least seven resistance determinants and harbouring methyltransferases in Saudi Arabia.

Cancer is one of the leading causes of mortality worldwide. Platinum‑based chemotherapeutic agents such as cisplatin are the first line of treatment for many types of cancers. However, the development of cisplatin resistance after prolonged treatment is a common cause of cancer recurrence. In the present study, we investigated an approach designed to overcome resistance to cisplatin involving co‑treatment with a second chemotherapeutic agent, staurosporine, and examined the role of sequestosome 1 (SQSTM1/p62) in enhancing cellular sensitivity to cisplatin. We utilized experimental models of three different cancers comprising cell lines derived from colon, breast, and ovarian tumors and investigated cell proliferation, morphology and p62 levels after treatment with cisplatin, staurosporine, or a combination of the two. Western blot analysis showed that cisplatin treatment resulted in elevation of p62 levels when compared to the corresponding control cells. Conversely, treatment with staurosporine resulted in a marked reduction in p62 levels in all three cell types and abrogated the cisplatin‑induced upregulation of p62. These results suggest that staurosporine could sensitize cancer cells to cisplatin via a mechanism involving downregulation of p62.

Neonatal neuropsychiatric stress induces alterations in neurodevelopment that can lead to irreversible damage to neuronal physiology, and social, behavioral, and cognitive skills. In addition, this culminates to an elevated vulnerability to stress and anxiety later in life. Developmental deficits in hippocampal synaptic function and plasticity are among the primary contributors of detrimental alterations in brain function induced by early-life stress. However, the underlying molecular mechanisms are not completely understood. Localized protein translation, occurring at the synapse and triggered by neuronal activity, is critical for synapse function, maintenance, and plasticity. We used a rodent model of chronic maternal deprivation to characterize the effects of early-life neuropsychiatric stress on localized de novo protein translation at synaptic connections between neurons. Synaptoneurosomal preparations isolated biochemically from the hippocampi of rat pups that were subjected to maternal deprivation were deficient in depolarization-induced activity-dependent protein translation when compared with littermate controls. Conversely, basal unstimulated protein translation was not affected. Moreover, deficits in activity-driven synaptic protein translation were significantly correlated with a reduction in phosphorylated cell survival protein kinase protein B or Akt (p473 Ser and p308 Thr), but not phosphorylated extracellular signal-regulated kinase.