MiR-126 Modulates Angiogenesis in Breast Cancer by Targeting VEGF-A -mRNA

Background: Breast cancer is most serious reasons of women death around worldwide result in increasing itsmorbidity and mortality. MicroRNAs are considered as significant regulators of cancer biological processes. The mainaim of this study is restoration of miR-126 could lead to modulate breast cell line and impairs their proliferation bytargeting vascular endothelial growth factor gene (VEGF-A). Methods: Breast cancer cell line (MCF7) was transfectedby miR-126 lipofectamine and negative miR control for 24 hr. Cytotoxic effects of miR-126 lipofectamine weredetermined by cell viability assay. Cell proliferation and cell cycle were quantitatively measured using PicoGreenassay and DAPI stain-flow cytometer analysis. For further investigation, Taq-Man real time PCR assay was performedto detect relative VEGF-A and miRNA-126 level. Results: MiR-126 was overexpressed in treated breast cancer cell(MCF7) compared with control cells. miR-126 expression has been associated –with a decrease in cell proliferationand arrested MCF7 cells at G1 phase. The study found that vascular endothelial growth factor is regulated by miR-126. Hence, VEGF-A is considered as functional vital and direct target to miR-126 in breast cancer cell line (MCF7).Conclusions: This study provided that manipulated miR-126 level may suggest a novel therapeutic approach in breastcancer treatment. However, an animal models study is needed to address and prove predictive ability of miR-126 onbreast cancer controlling.     

Adverse events experienced with intrahospital transfer of critically ill patients: A national survey

Research that focuses on transfers to and from the intensive care unit (ICU) could highlight important patients’ safety issues. This study aims to describe healthcare workers’ (HCWs) practices involved in patient transfers to or from the ICU.This cross-sectional study was conducted among HCWs during the Saudi Critical Care Society''s annual International Conference, April 2017. Responses were assessed using Likert scales and frequencies. Bivariate analysis was used to evaluate the significance of different indicators.Overall, 312 HCWs participated in this study. Regarding transfer to ICUs, the most frequently reported complications were deterioration in respiratory status (51.4%), followed by deterioration in hemodynamic status (46.5%), and missing clinical information (35.5%). Regarding transfers from ICUs to the general ward, the most commonly reported complications were changes in respiratory status (55.6%), followed by incomplete clinical information (37.9%), and change in hemodynamic conditions (29%). The most-used models for communicating transfers were written documents in electronic health records (69.3%) and verbal communication (62.8%). One-fourth of the respondents were not aware of the Situation, Background, Assessment, Recommendation (SBAR) method of patients’ handover. Pearson''s test of correlation showed that the HCW''s perceived satisfaction with their hospital transfer guidelines showed significant negative correlation with their reported transfer-related complications (r = −0.27, P < .010).Hemodynamic and respiratory status deterioration is representing significant adverse events among patients transferred to or from the ICU. Factors controlling the perceived satisfaction of HCWs involved in patients, transfer to and from the ICU need to be addressed, focusing on their compliance to the hospital-wide transfer and handover policies. Quality improvement initiatives could improve patient safety to transfer patients to and from the ICU and minimize the associated adverse events.     

Changes in healthcare workers’ knowledge,attitudes, practices,and stress during the COVID-19 pandemic

Coronavirus disease 2019 (COVID-19) has caused an unprecedented health crisis around the world, not least because of its heterogeneous clinical presentation and course. The new information on the pandemic emerging daily has made it challenging for healthcare workers (HCWs) to stay current with the latest knowledge, which could influence their attitudes and practices during patient care.This study is a follow-up evaluation of changes in HCWs’ knowledge, attitudes, and practices as well as anxiety levels regarding COVID-19 since the beginning of the pandemic. Data were collected through an anonymous, predesigned, self-administered questionnaire that was sent online to HCWs in Saudi Arabia.The questionnaire was sent to 1500 HCWs, with a 63.8% response rate (N = 957). The majority of respondents were female (83%), and the most common age group was 31 to 40 years (52.2%). Nurses constituted 86.3% of the respondents. HCWs reported higher anxiety during the COVID-19 pandemic which increased from 4.91 ± 2.84 to 8.6 ± 2.27 on an 11-point Likert scale compared to other viral outbreaks. HCWs believed that their own preparedness as well as that of their hospital''s intensive care unit or emergency room was higher during the COVID-19 pandemic than during the Middle East respiratory syndrome coronavirus pandemic (2012–2015). About 58% of HCWs attended one or more simulations concerning the management of COVID-19 patients in their intensive care unit/emergency room, and nearly all had undergone N95 mask fit testing. The mean score of HCWs’ knowledge of COVID-19 was 9.89/12. For most respondents (94.6%), the perception of being at increased risk of infection was the main cause of anxiety related to COVID-19; the mean score of anxiety over COVID-19 increased from 4.91 ± 2.84 before to 8.6 ± 2.27 during the pandemic in Saudi Arabia.HCWs’ anxiety levels regarding COVID-19 have increased since a pandemic was declared. It is vital that healthcare facilities provide more emotional and psychological support for all HCWs.     

Role of mitochondria in ciprofloxacin induced apoptosis in bladder cancer cells

PURPOSE: In our earlier series we showed that ciprofloxacin inhibits bladder tumor cell growth with concomitant S/G2M cell cycle arrest and reported an increased Bax-to-Bcl-2 ratio in cells undergoing cell death. In the current series we elucidated the molecular mechanisms by which ciprofloxacin induces apoptotic processes. MATERIALS AND METHODS: Ciprofloxacin mediated mitochondrial depolarization was detected by flow cytometry in HTB9 cells. Mitochondrial permeability transition was measured by spectrophotometry in isolated mitochondria treated with ciprofloxacin in the presence and absence of cyclosporin. The consequential decrease in mitochondrial calcium, cytochrome c release and Bax translocation to mitochondria, which resulted in the activation of caspase 3 leading to apoptotic cell death, was measured by biochemical and confocal microscopy. RESULTS: Mitochondrial depolarization was observed during ciprofloxacin induced apoptotic processes. Cyclosporin A, a known inhibitor of the mitochondrial permeability transition pore, protected cells against decreased mitochondrial potential. Also, ciprofloxacin induced an alteration of mitochondrial calcium as early as 5 minutes and this disruption of intracellular calcium homeostasis was prevented by cyclosporin. Ciprofloxacin also had a direct effect on swelling of isolated mitochondria, which was absent in the presence of cyclosporin. Mitochondrial changes were accompanied by cytochrome c release and caspase 3 activation. Our findings also showed Bcl-2 dependent subcellular redistribution of Bax to the mitochondrial membrane in ciprofloxacin treated bladder tumor cells. CONCLUSIONS: The disruption of calcium homeostasis, mitochondrial swelling and redistribution of Bax to the mitochondrial membrane are key events in the initiation of apoptotic processes in ciprofloxacin treated bladder cancer cells.     

Pleotropic effects of genistein on MCF-7 breast cancer cells

Soy isoflavone, genistein has been shown to induce growth inhibition, cell cycle arrest and apoptosis in cultured cancer cell lines derived from head and neck, breast, lung, and prostate cancers and showed antitumor activity against tumors in multiple animal models. In the present study we show that genistein inhibits the growth of MCF-7 breast cancer cell line in a dose dependent manner. The genistein induced growth inhibition is accompanied by the reduction in the number of mitotic cells and overexpression of cyclin dependent kinase inhibitor p21WAF1 leading to cell cycle arrest. In addition, the telomeric area was significantly reduced in genistein treated MCF-7 cells. Analysis of multiple genes involving the apoptotic pathway reveals inhibition of Akt activity without affecting the steady state levels of Akt protein expression and the down regulation of proapoptotic gene BAD expression. From these results, we conclude that genistein-induced inhibition of cell division is partly mediated by decreased telomere length, reduced mitosis and inhibition of Akt activation, leading to induction of apoptosis.     

Childhood nephrolithiasis and nephrocalcinosis caused by metabolic diseases and renal tubulopathy: A retrospective study from 2 tertiary centers

Objectives:To study childhood nephrolithiasis and nephrocalcinosis caused by metabolic disorders, distal renal tubular acidosis (dRTA), and familial hypomagnesemia, hypercalciuria, and nephrocalcinosis (FHHNC).Methods:We retrospectively evaluated 86 children presented over 10 years (2011-2021), with nephrolithiasis (89%) and nephrocalcinosis (11%) caused by metabolic disorders (62%), FHHNC (21%), and dRTA (17%).Results:The mean age at discovery was 72.7 months. The underlying metabolic etiologies included hyperoxaluria (38%), cystinuria (32%), hypercalciuria (24%), and hyperuricosuria (6%). Genetic testing was carried out for 23 patients. Hyperoxaluria was typically treated medically (75%). However, the majority progressed to end-stage kidney disease (ESKD). Most children with cystinuria, hypercalciuria, and hyperuricosuria required medical and surgical intervention. Patients with FHHNC typically presented with nephrocalcinosis. Genetic testing revealed Claudin-16 mutations in 7 children. Patients often progressed to stage II-IV chronic kidney disease (61%) and ESKD (6%). Patients with dRTA typically presented with nephrocalcinosis (80%), as well as poor weight gain and failure to thrive (86%), and medical treatment included sodium bicarbonate and potassium replacement. Despite nephrocalcinosis progression, most patients had normal renal function (53%), although the remaining 47% progressed to chronic kidney disease (none reached ESKD).Conclusion:Childhood nephrolithiasis is mainly related to metabolic disorders and is associated with poor renal outcomes. Nephrocalcinosis and nephrolithiasis have poor outcomes when associated with FHHNC, while nephrocalcinosis associated with dRTA has relatively good renal outcomes.     

Induction of apoptosis and inhibition of c-erbB-2 in breast cancer cells by flavopiridol.

Flavopiridol is a flavone that inhibits several cyclin-dependent kinases and exhibits potent growth-inhibitory activity against a number of human tumor cell lines, both in vitro and when grown as xenografts in mice. It is presently being investigated as a novel antineoplastic agent in the primary screen conducted by the Developmental Therapeutics Program, National Cancer Institute. Because breast cancer is the most common cancer and second leading cause of cancer-related deaths in women in the United States, we investigated whether flavopiridol could be an effective agent against a series of isogenic breast- cancer cell lines having different levels of erbB-2 expression and differential invasion and metastatic characteristics. Flavopiridol was found to inhibit the growth of MDA-MB-435 (parental) and 435.eB (stable transfectants) cells that were established by transfecting c-erbB-2 cDNA into MDA-MB-435. Induction of apoptosis was also observed in these cell lines when treated with flavopiridol, as measured by DNA laddering, PARP, and CPP32 cleavages. We also found modest up-regulation of Bax and down-regulation of Bcl-2, but there was a significant down-regulation of c-erbB-2 in flavopiridol-treated cells. Gelatin zymography showed that flavopiridol inhibits the secretion of matrix metalloproteinase (MMP; MMPs 2 and 9) in the breast cancer cells and that the inhibition of c-erbB-2 and MMPs may be responsible for the inhibition of cell invasion observed in flavopiridol-treated cells. Collectively, these molecular effects of flavopiridol, however, were found to be independent of c-erbB-2 overexpression, suggesting that flavopiridol may be effective in all breast cancer. From these results, we conclude that flavopiridol inhibits the growth of MDA-MB-435 breast cancer cells, induces apoptosis, regulates the expression of genes, and inhibits invasion and, thus, may inhibit metastasis of breast cancer cells. These findings suggest that flavopiridol may be an effective chemotherapeutic or preventive agent against breast cancer.     

Molecular mechanism(s) of actinomycin-D induced sensitization of pancreatic cancer cells to CD95 mediated apoptosis.

The death receptor CD95 transduces apoptotic death signaling in many cell types. However, in pancreatic tumor cells CD95 mediated apoptotic machinery is blocked by unknown protein(s). We and others have recently demonstrated that actinomycin-D (ActD) treatment induces sensitization of pancreatic cancer cells as well as other cell types to CD95 mediated apoptosis. In addition, NF-kappaB/Akt system has been implicated in the processes of CD95 mediated apoptosis, however the precise mechanism by which ActD sensitizes pancreatic tumor cells to CD95 mediated apoptosis is still unknown. In the present study, we demonstrated that HPAC and PANC1 pancreatic cancer cells constitutively express high levels of NF-kappaB and phosphorylated form of Akt. ActD at a dose that is known to sensitize pancreatic cancer cells to CD95 mediated apoptosis abrogated the DNA binding activity of NF-kappaB but did not affect expression of phosphorylated Akt. Co-treatment of pancreatic cancer cells with ActD and agonist anti-CD95 antibodies showed no effect on the abrogation on the DNA binding activity of NF-kappaB, but decreased the expression of phosphorylated Akt. Moreover, treatment with PI3-kinase inhibitor LY294002 did not show any sensitization of pancreatic cancer cells to CD95 mediated apoptosis. Our data suggest that ActD sensitizes pancreatic cancer cells to CD95 mediated apoptosis through the abrogation of DNA binding activity of NF-kappaB, rather than PI3-kinase/Akt system. Over-expression of phosphorylated Akt in pancreatic cancer cells is controlled by effective apoptotic signaling from CD95 receptors, but do not protect tumor cells from CD95 induced apoptosis. Thus, our results indicate that modulation of NF-kappaB activity rather then Akt may provide a useful tool to sensitize pancreatic cancer cells to CD95 mediated apoptosis.     

Retained gastric band port and tube 5 years after gastric band removal and laparoscopic Roux-en-Y gastric bypass: a case report

Background

While LAGB has become uncommon in the bariatric surgery practice, band removal with or without revision surgery is still common. Retained postoperative foreign body, of which surgical sponges are the most common, is a rare condition. We report a rare case of retained gastric band port and the attached tube.

Case presentation

A 31-year-old Caucasian female presented to the outpatient clinic, 5?years after her last surgery, complaining of a left upper quadrant abdominal mass over the last 2?years. She had a history of 2 weight loss operations. She had no significant family history nor smoking. CT of the abdomen and pelvis revealed a retained foreign body. On exploration, the port with 10?cm of the connected tube was found and removed through a small incision without laparotomy. The patient made an uneventful recovery.

Conclusion

A bariatric surgeon should be involved in the evaluation of any patient who complains of abdominal pain and/or palpable mass if she/he has a previous weight loss procedure because the bariatric surgeon is fully aware of the possible complications of the bariatric surgeries.