Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα) and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6), a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells.</p> <p>Results</p> <p>Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at <it>IL-6 </it>proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the <it>CD133 </it>promoter region 1 and of <it>CD44 </it>proximal promoter, enhancing <it>CD133 </it>and <it>CD44 </it>gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα) promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of <it>IL-6 </it>distal promoter and of <it>CD133 </it>promoter region 2, which harbour putative repressor regions.</p> <p>Conclusion</p> <p>We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.</p

Intraoperative Monitoring of the Obese Patient Undergoing Surgery: A Narrative Review

With the increasing prevalence of obesity in the population, anaesthetists must confidently manage both the pathophysiological and technical challenges presented in bariatric and non-bariatric surgery. The intraoperative period represents an important opportunity to optimise and mitigate risk. However, there is little formal guidance on what intraoperative monitoring techniques should be used in this population. This narrative review collates the existing evidence for intraoperative monitoring devices in the obese patients. Although a number of non-invasive blood pressure monitors have been tested, an invasive arterial line remains the most reliable monitor if accurate, continuous monitoring is required. Goal-directed fluid therapy is recommended by clinical practice guidelines, but the methods tested to assess this had guarded applicability to the obese population. Transcutaneous carbon dioxide (CO2) monitoring may offer additional benefit to standard capnography in this population. Individually titrated positive end expiratory pressure (PEEP) and recruitment manoeuvres improved intraoperative mechanics but yielded no benefit in the immediate postoperative period. Depth of anaesthesia monitoring appears to be beneficial in the perioperative period regarding recovery times and complications. Objective confirmation of reversal of neuromuscular blockade continues to be a central tenet of anaesthesia practice, particularly relevant to this group who have been characterised as an "at risk" extubation group. Where deep neuromuscular blockade is used, continuous neuromuscular blockade is suggested. Both obesity and the intraoperative context represent somewhat unstable search terms, as the clinical implications of the obesity phenotype are not uniform, and the type and urgency of surgery have significant impact on the intraoperative setting. This renders the generation of summary conclusions around what intraoperative monitoring techniques are suitable in this population highly challenging

What is the role of locoregional anesthesia in breast surgery? A systematic literature review focused on pain intensity, opioid consumption, adverse events, and patient satisfaction

Breast surgery in the United States is common. Pain affects up to 50% of women undergoing breast surgery and can interfere with postoperative outcomes. General anesthesia is the conventional, most frequently used anaesthetic technique. Various locoregional anesthetic techniques are also used for breast surgeries. A systematic review of the use of locoregional anesthesia for postoperative pain in breast surgery is needed to clarify its role in pain management

Hazelnut (Corylus avellana l.) shells extract: Phenolic composition, antioxidant effect and cytotoxic activity on human cancer cell lines

Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract). Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%-2.93%, w/w). The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (EC50 = 31.7 µg/mL with respect to α-tocopherol EC50 = 10.1 µg/mL), and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 µg/mL, respectively). The expression of cleaved forms of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28) and human cervical cancer (HeLa) cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin), and phenol derivatives (gallic acid), showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells

COVID-19 in Low- and Middle-Income Countries (LMICs): A Narrative Review from Prevention to Vaccination Strategy

The management of the COVID-19 pandemic represents a challenging process, especially for low- and middle-income countries (LMICs) due to the serious economic and health resource problems it generates. In this article, we assess COVID-19 situation in LMICs and outline emerging problems and possible solutions. The prevention and control of COVID-19 would be based on focused tests exploiting those systems (e.g., GeneXpert®) already used in other scenarios. This would be less stressful for the healthcare system in LMICs. Avoiding close contact with people suffering from acute respiratory infections, frequent handwashing, and avoiding unprotected contact with farm or wild animals are recommended infection control interventions. The appropriate use of personal protective equipment (PPE) is required, despite its procurement being especially difficult in LMICs. Patients’ triage should be based on a simple and rapid logarithm to decide who requires isolation and targeted testing for SARS-CoV-2. Being able to estimate which patients will develop severe disease would allow hospitals to better utilize the already limited resources more effectively. In LMICs, laboratories are often in the capital cities; therefore, early diagnosis and isolation become difficult. The number of ICU beds is often insufficient, and the equipment is often old and poorly serviced. LMICs will need access to COVID-19 treatments at minimal prices to ensure that all who need them can be treated. Year-to-date, different vaccines have been approved and are currently available. The main obstacle to accessing them is the limited ability of LMICs to purchase significant quantities of the vaccine

Cefiderocol for Carbapenem-Resistant Bacteria: Handle with Care! A Review of the Real-World Evidence

(1) Background: healthcare-associated infections are one of the most frequent adverse events in healthcare delivery worldwide. Several antibiotic resistance mechanisms have been developed, including those to carbapenemase. Cefiderocol (CFD) is a novel siderophore cephalosporin designed to treat carbapenem-resistant bacteria. (2) Methods: we performed a systematic review of all cases reported in the literature to outline the existing evidence. We evaluated real-world evidence studies of CFD in the treatment of carbapenem-resistant (CR) bacteria. (3) Results: a total of 19 publications treating cases of infection by CR bacteria were included. The three most frequent CR pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. A regimen of 2 g every 8 h was most frequently adopted for CFD with a mean treatment duration of 25.6 days. CFD was generally well tolerated, with fewer side effects. The success rate of CFD therapy was satisfactory and almost 70% of patients showed clinical recovery; of these, nearly half showed negative blood cultures and infection-free status. (4) Conclusions: This review indicates that CFD is active against important GN organisms including Enterobacteriaceae, P. aeruginosa, and A. baumannii. CFD seems to have a safe profile