Knockdown of Stromal Interaction Molecule 1 (STIM1) Suppresses Acute Myeloblastic Leukemia-M5 Cell Line Survival Through Inhibition of Reactive Oxygen Species Activities

Objective: This study aimed to investigate the role of the stromal interaction molecule 1 (STIM1) gene in the survival of the acute myeloblastic leukemia (AML)-M5 cell line (THP-1). Materials and Methods: The STIM1 effect was assessed via dicersubstrate siRNA-mediated STIM1 knockdown. The effect of STIM1 knockdown on the expression of AKT and MAPK pathway-related genes and reactive oxygen species (ROS) generation-related genes was tested using real-time polymerase chain reaction. Cellular functions, including ROS generation, cell proliferation, and colony formation, were also evaluated following STIM1 knockdown. Results: The findings revealed that STIM1 knockdown reduced intracellular ROS levels via downregulation of NOX2 and PKC. These findings were associated with the downregulation of AKT, KRAS, MAPK, and CMYC. BCL2 was also downregulated, while BAX was upregulated following STIM1 knockdown. Furthermore, STIM1 knockdown reduced THP-1 cell proliferation and colony formation. Conclusion: This study has demonstrated the role of STIM1 in promoting AML cell proliferation and survival through enhanced ROS generation and regulation of AKT/MAPK-related pathways. These findings may help establish STIM1 as a potential therapeutic target for AML treatment.

Poisoning among children in Malaysia: A 10-years retrospective study.

BACKGROUND: Poisoning commonly occurs among children due to their curiosity, where they tend to explore and investigate their surroundings. They frequently put what they find into their mouths as they do not understand the danger and probably cannot read the warning label. As this issue has not been extensively studied in Malaysia; hence, a retrospective analysis of records was carried out to determine the profile of phone call enquiries regarding poisoning among children at the National Poison Centre (NPC). METHODOLOGY: The records of all cases of poisoning among children below the age of 18 years were retrospectively reviewed over a period of 10 years from 2006 to 2015. The data on the cases were analysed according to age group and gender, the circumstances and the toxic agent implicated in the poisoning. RESULTS: During the 10-year study period, 13,583 calls that met the criteria for this study were referred to the NPC. Of these calls, 62.2% involved children between the age of 0 to 5 years, 9% were children aged between 6 to 12 years, and 28.8% were children between 13 to 18 years. Unintentional poisoning accounted for 96.7% of the incidents involving children between the age of 0 to 5 years, although among the children who were between the age of 13 to 18 years, 76% of the cases were intentional. In all the cases involving children, pharmaceutical agents were the most frequent source of the poisoning. More than 95% of the cases were exposed to poisoning through the oral route. CONCLUSION: Poisoning in children between the age of 0 to 5 years was mainly unintentional, while poisoning in children between the age of 13 to 18 years was mainly intentional, where pharmaceutical and household agents were responsible for more than two-thirds of the poisoning cases. Most of these incidents could have been prevented if protective measures, such as child-resistant enclosures, had been implemented and if the parents and guardians had been educated about preventive measures, such as keeping poisoning agents out of the reach of children.

Knowledge and Perceptions of Blood Safety among Blood Donors in Kelantan, Malaysia.

BACKGROUND: Unsafe blood products may cause transfusion-transmissible infections. This study aimed to evaluate the knowledge and perceptions of blood donors regarding blood safety. METHODS: This was a cross-sectional study conducted in the Kelantan state of Malaysia. The questionnaire comprised 39 questions that covered areas such as donors' social demographic information, knowledge of transfusion-transmitted diseases, blood screening and donor eligibility and perceptions towards blood safety. The knowledge score was categorised as good or poor. RESULTS: Of the 450 distributed questionnaires, 389 were suitable for analysis. Only 18.5% of the donors had good knowledge, with 81.5% having poor knowledge. Less than 30% were aware that people with multiple sexual partners, bisexual people and male homosexual people are permanently deferred from blood donation. Only 29.4% agreed that donors are responsible if their blood causes infection. Furthermore, 39.3% assumed that they could check their HIV status through blood donation, and 10.3% and 5.4% of the respondents believed that donors are free from infection if they wear a condom during sex or only have oral sex when involved in prostitution, respectively. CONCLUSION: Poor knowledge and notable misperceptions concerning safe blood donation were found among blood donors. The Ministry of Health should incorporate safe blood education in future public awareness programmes.

Recombinant activated factor VII (rFVIIa) in refractory haemorrhage for non-haemophiliacs: an eleven-year single-centre experience.

BACKGROUND: Massive bleeding is one of the commonest salvageable causes of death. The search for an ideal haemostatic agent during massive bleeding is still ongoing. One of the novel haemostatic medications is recombinant activated factor VII (rFVIIa). To date, the usage of rFVIIa during massive haemorrhage among non-haemophiliac patients remains off-label. The aim of this study is to report our experience in using rFVIIa to treat refractory bleeding. METHODS: Medical records of all patients treated with rFVIIa for massive bleeding over an eleven-year period in a single institution were recorded. Treatment indications, 24-h and 30-day mortality, changes in transfusion needs and coagulation profiles after rFVIIa administration were analysed. RESULTS: rFVIIa were administered in 76 patients. Of these, 41 (53.9%) were non-surgical bleeding, followed by 22 patients (28.9%) with trauma, other surgery bleedings in 9 patients (11.8%) and 4 patients (5.4%) with peripartum haemorrhage. Total survival rate was 78.9% within 24 h and 44.7% over 30 days. Among all these patients who had received rFVIIa due to life-threatening haemorrhage, blood and blood product requirements were significantly reduced (P < 0.001), and the coagulation profiles improved significantly (P < 0.05). Two patients with preexisting thromboembolism were given rFVIIa due to intractable bleeding, both survived. No thromboembolic events were reported after the administration of rFVIIa. CONCLUSIONS: rFVIIa significantly improved coagulation parameters and reduced blood product requirements during refractory haemorrhage. Additionally, usage of rFVIIa in trauma and peripartum haemorrhage patients yield better outcomes than other groups of patients. However, the overall mortality rate remained high.