Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia

The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 µM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML

Factors predicting functional outcome after rtPA for patients with acute ischemic stroke

Abstract Background Accurate outcome prediction for patients with acute ischemic stroke after intravenous recombinant tissue plasminogen activator (rtPA) treatment is essential for optimizing patients’ management. We aimed to identify factors associated with unfavorable outcomes following intravenous rtPA treatment. This study was carried out on 162 patients who presented with acute ischemic stroke within 4.5 h from onset of neurological symptoms and were eligible for intravenous rtPA. After exclusion of 48 patients, 114 patients were finally eligible for follow-up. After complete medical and neurological history, complete medical and neurological examination and brain image (CT and or MRI brain) were collected from the patients. patients eligible were included in the study. NIHS scale was assessed for all patients at time of admission, after 24 h, and follow-up for 3 months. Results After a 90-day follow-up period for 114 patients with acute ischemic stroke after rtPA, 35.8% had good outcome (MRS; 0–2), 18.5% had partial outcome (MRS; 3–4) and 12.5% had poor outcome (MRS; 5–6). Atrial fibrillation (AF), PH of stroke, stroke severity, and severity of symptom (NIHSS) score were significantly (P: 0.004, 0.001, 0.007 and 0.001) correlated with poor outcome after rtPA. Similarly, old age, high blood pressure at time of presentation, hypertension, and dyslipidemia were showed to carry poor outcome. Conclusions AF, high NIHSS score, PH of stroke, previous stroke, hypertension, dyslipidemia, and high blood pressure on presentation were significantly correlated with poor functional outcome