Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

Background  

Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.     

Adult Hemolytic-Uremic Syndrome Associated with Urosepsis Due to Shigatoxin-Producing Escherichia Coli O138:H-

We report the case of a 62-year-old man without prodromal symptoms who developed a hemolytic-uremic syndrome (HUS) one week after the diagnosis of an acute bacteremic urinary infection (UTI). In this patient, the E. coli isolated in blood cultures was a non-O157:H7 Shigatoxin-producing strain that could subsequently be identified as O138:H-. This is a strain that is normally found in pigs and that has never been isolated in humans previously. UTI-related HUS is a rare event, as until now, only 14 pediatric and 3 adult cases have been reported. Indeed, this new case, besides its interesting microbiological aspects, should heighten our awareness of UTI-related HUS as a rare but real condition, not only in young children but also in adult patients. This should emphasize the necessity to search actively for other sources of Shigatoxin-producing E. coli in patients presenting with HUS without gastrointestinal symptoms.     

NADPH oxidases and cardiac remodelling

A heart under chronic stress undergoes cardiac remodelling, a process that comprises structural and functional changes including cardiomyocyte hypertrophy, interstitial fibrosis, contractile dysfunction, cell death and ventricular dilatation. Reactive oxygen species (ROS)-dependent modulation of intracellular signalling is implicated in the development of cardiac remodelling. Among the different ROS sources that are present in the heart, NADPH oxidases (NOXs) are particularly important in redox signalling. NOX isoforms are expressed in multiple cell types including cardiomyocytes, fibroblasts, endothelial cells and inflammatory cells—with the two main isoforms expressed in the heart being NOX2 and NOX4. Recent studies indicate that NOX-dependent signalling is involved in the development of cardiomyocyte hypertrophy, interstitial fibrosis and post-MI remodelling. NOXs may also be involved in the genesis of contractile dysfunction and myocyte apoptosis. Here, we review the main effects of NOXs in the pathogenesis of cardiac remodelling and the redox-sensitive signalling pathways that underlie these effects. The elucidation of mechanisms involved in NOX-dependent regulation of cardiac remodelling may lead to new therapeutic targets for heart failure.     

Probiotic E.faecalis — adjuvant therapy in children with recurrent rhinosinusitis

Sinusitis is a frequent complication of respiratory tract infections. Probiotics are perceived to be useful in infections, allergies, and inflammations. Our prospective trial stratified 204 children with recurrent rhinosinusitis by age (2–11 years, 54m:64f; 12–18 years, 39m:47f) and assigned them to standard treatment (antibiotics, anticongestants) or additional 60 days Symbioflor-1 (SF1; Enterococcus faecalis 1.5–4.5x10⁷ CFU). The number of sinusitis episodes was lower in SF1-treated patients (2.52±0.91) than among controls (3.27±1.36; p=0.01). Mean duration of the first sinusitis episode was 11.9±8.6 days with SF1, whereas it was 16.1±12.9 days in the younger controls (p=0.023) and 9.86±5.05 days in the elder controls (n.s.). Duration of subsequent sinusitis episodes was also shorter in SF1 patients (15.2±13.6 days) compared with controls (22.7±14.8 days; p=0.030). No adverse events were observed. Probiotic Enterococcus faecalis adjuvant to conventional therapy can reduce the number and duration of rhinosinusitis episodes in children and adolescents.     

Who Benefits from Oncoplastic Surgical Techniques?

Breast-conserving therapy, which includes wide local excision of the tumor followed by irradiation, has become a standard treatment option for women with early-stage invasive breast cancer. The potential advantages of conservative breast surgery include the minor outpatient nature of the procedures, lower incidence of post-operative pain and complications, preservation of the breast and nipple areolar complex, and shorter delay to adjuvant therapy. However, not all patients are optimal candidates for breast-conserving procedures. Oncoplastic techniques combine the removal of breast cancer tumors in combination with either local volume replacement techniques to correct small defects, or by immediate reconstruction of larger defects using techniques of plastic surgery with or without contralateral breast procedures for symmetry. Therefore, oncoplastic techniques offer the potential to perform a wider excision of the tumor with an improved cosmetic result, thus potentially increasing the eligible pool for breast conservation.