Reactive oxygen species and mitochondrial sensitivity to oxidative stress determine induction of cancer cell death by p21.

p21(Waf1/Cip1/Sdi1) is a cyclin-dependent kinase inhibitor that mediates cell cycle arrest. Prolonged p21 up-regulation induces a senescent phenotype in normal and cancer cells, accompanied by an increase in intracellular reactive oxygen species (ROS). However, it has been shown recently that p21 expression can also lead to cell death in certain models. The mechanisms involved in this process are not fully understood. Here, we describe an induction of apoptosis by p21 in sarcoma cell lines that is p53-independent and can be ameliorated with antioxidants. Similar levels of p21 and ROS caused senescence in the absence of significant death in other cancer cell lines, suggesting a cell-specific response. We also found that cells undergoing p21-dependent cell death had higher sensitivity to oxidants and a specific pattern of mitochondrial polarization changes. Consistent with this, apoptosis could be blocked with targeted expression of catalase in the mitochondria of these cells. We propose that the balance between cancer cell death and arrest after p21 up-regulation depends on the specific effects of p21-induced ROS on the mitochondria. This suggests that selective up-regulation of p21 in cancer cells could be a successful therapeutic intervention for sarcomas and tumors with lower resistance to mitochondrial oxidative damage, regardless of p53 status.

The Impact of Abdominoplasty vs Non-abdominoplasty on Weight Loss in Bariatric and Non-bariatric Malaysian Patients: A Multicentre Retrospective Study.

Background and aims Weight loss associated with abdominoplasty remains controversial as to whether it is contributed by the procedure alone, or if there are other patient factors. Therefore, we evaluated the relationship between weight loss in pre- and post-abdominoplasty and compared the weight loss of those who do not undergo abdominoplasty in bariatric and non-bariatric patients. Methods This study measured weight changes at designated time points in four different groups comprising 98 patients. The groups were abdominoplasty after bariatric surgery (group A), patients with abdominoplasty alone (B), bariatric surgery alone (group C), and diet alone (group D). Results are compared within and between the groups. Results Patients in groups A and B (patients who had abdominoplasty regardless with or without bariatric surgery) had a significant weight loss after six months (mean difference=10.70kg, 95% CI=4.05, 17.34, p<0.001) compared to pre abdominoplasty weight. Patients in group B were statistically significant (mean difference=4.01kg, 95% CI=0.92, 7.10, p=0.007) with 3.60kg weight reduction (4.59%). Patients in group A had clinically significant weight reduction (4.45kg, 5.14%) but it was not statistically significant (p>0.05) and had no significant additional weight reduction as compared to non-abdominoplasty (group C) patients (p=0.650). Patients in group C had a statistically significant difference from those in group D (F [1.00, 48.00] = 8.56, p=0.005) with an average weight loss of 3.60kg (4.59%) vs 2.56kg (2.8%) respectively. Conclusions All patients with abdominoplasty had significant weight loss after six months. Bariatric patients did not experience significant additional weight loss with abdominoplasty. Weight reduction after abdominoplasty alone was greater than diet alone.

Whole Genome Sequencing Analysis of Salmonella enterica Serovar Typhi: History and Current Approaches.

In recent years, the advance in whole-genome sequencing technology has changed the study of infectious diseases. The emergence of genome sequencing has improved the understanding of infectious diseases, which has revamped many fields, such as molecular microbiology, epidemiology, infection control, and vaccine production. In this review we discuss the findings of Salmonella enterica serovar Typhi genomes, publicly accessible from the initial complete genome to the recent update of Salmonella enterica serovar Typhi genomes, which has greatly improved Salmonella enterica serovar Typhi and other pathogen genomic research. Significant information on genetic changes, evolution, antimicrobial resistance, virulence, pathogenesis, and investigation from the genome sequencing of S. Typhi is also addressed. This review will gather information on the variation of the Salmonella enterica serovar Typhi genomes and hopefully facilitate our understanding of their genome evolution, dynamics of adaptation, and pathogenesis for the development of the typhoid point-of-care diagnostics, medications, and vaccines.

Draft Genome Sequence of the Extended-Spectrum ß-Lactamase-Producing Escherichia coli Isolate INF13/18/A, Recovered from Kelantan, Malaysia.

We describe here the draft genome sequence and basic characteristics of Escherichia coli isolate INF13/18/A, which was isolated from Universiti Sains Malaysia (USM) Hospital. This isolate was identified as an extended-spectrum ß-lactamase-producing Escherichia coli strain harboring the antimicrobial resistance genes TEM, CTX-M-1, and CTX-M-9.