Cucurbitacin E is a pivotal member of the cucurbitacin family and has been shown to have anti-cancer effects. However, until now, the anti-cancer effect and mode of action of cucurbitacin E in human colon cancer cells remain unclear. In this study, we investigated whether cucurbitacin E inhibits the growth of HCT116 human colorectal cancer cells. Treatment of cucurbitacin E at 1 mM markedly reduced the survival of HCT116 cells. Moreover, treatment of cucurbitacin E at 1 mM caused nuclear DNA fragmentation in HCT116 cells, pointing out its apoptosis-inducing effect. Treatment of cucurbitacin E at 1 mM also led to the activation of caspase-9 and poly(ADP‑ribose) polymerase (PARP) cleavage without affecting expression of death receptor (DR)-4/5 in HCT116 cells. Furthermore, while treatment of cucurbitacin E at 1 mM had no effect on expression of Mcl-1, it largely increased expression and phosphorylation of eukaryotic translation initiation factor-2α (eIF-2α) and activating transcription factor-4 (ATF-4) in HCT116 cells. Treatment of cucurbitacin E at 1 mM further up-regulated phosphorylation of extracellular signal-regulated kinase-1/2 (ERK-1/2), but not c-Jun N-terminal kinase1/2 (JNK-1/2), in HCT116 cells. However, treatment with PD98059, an inhibitor of ERK-1/2, that strongly blocked activation of ERK-1/2 had no effect on reduction of survival of HCT116 cells treated with cucurbitacin E at 1 mM. Taken together, these findings demonstrate that cucurbitacin E at 1 mM has strong anti-survival and pro-apoptotic effects on HCT116 cells, which are mediated through control of the expression and phosphorylation levels of caspase-9, PARP, eIF-2α, and ATF-4.

BACKGROUND: Diabetic ketoacidosis (DKA) is characterized by a biochemical triad of hyperglycemia, acidosis, and ketonemia. This condition is life-threatening despite improvements in diabetic care. The purpose of this study was to evaluate the clinical and biochemical prognostic markers of DKA. We assessed correlations in prognostic markers with DKA-associated morbidity and mortality. METHODS: Two hundred and seventy patients that were hospitalized with DKA over a period of 2 years were evaluated clinically and by laboratory tests. Serial assays of serum electrolytes, glucose, and blood pH were performed, and clinical outcome was noted as either discharged to home or death. RESULTS: The analysis indicated that significant predictors included sex, history of type 1 diabetes mellitus or type 2 diabetes mellitus, systolic blood pressure, diastolic blood pressure, total leukocyte count, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, blood urea nitrogen, serum creatinine, serum magnesium, serum phosphate, serum osmolality, serum glutamic oxaloacetic transaminases, serum glutamic pyruvic transaminases, serum albumin, which were further regressed and subjected to multivariate logistic regression (MLR) analysis. The MLR analysis indicated that males were 7.93 times more likely to have favorable outcome compared with female patients (odds ratio, 7.93; 95% confidence interval, 3.99 to 13.51), while decreases in mean APACHE II score (14.83) and serum phosphate (4.38) at presentation may lead to 2.86- and 2.71-fold better outcomes, respectively, compared with higher levels (APACHE II score, 25.00; serum phosphate, 6.04). CONCLUSION: Sex, baseline biochemical parameters such as APACHE II score, and phosphate level were important predictors of the DKA-associated mortality.
Acidosis ; APACHE ; Blood Pressure ; Blood Urea Nitrogen ; Creatinine ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis* ; Electrolytes ; Female ; Glucose ; Humans ; Hydrogen-Ion Concentration ; Hyperglycemia ; Hyperglycemic Hyperosmolar Nonketotic Coma ; Ketosis ; Leukocyte Count ; Logistic Models ; Magnesium ; Male ; Mortality ; Osmolar Concentration ; Serum Albumin ; Transaminases

BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated disease caused by autoantibodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX. The etiology of ITP remains unclear. This study evaluated the association of polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP. METHODS: Genotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients and 100 controls by polymerase chain reaction restriction fragment length polymorphism and detection of variable number tandem repeats. RESULTS: Genotype differences in IL-1B-31 and IL-1Ra were significantly associated with ITP. Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52-fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence interval [CI]=1.04–2.22, P=0.034). The frequencies of both homozygous and heterozygous variant genotypes of IL-1B-31 were higher (OR=2.33, 95% CI=1.069–5.09, P=0.033 and OR=2.044, 95% CI=1.068–39, P=0.034) among patients and were significantly associated with ITP susceptibility. Both homozygous and heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95% CI=1.17–17.05, P=0.0230 and OR=1.80, 95% CI=1.03–3.14, P=0.0494) among patients and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant association with severe ITP. However, IL-1B-511 was not associated with ITP. CONCLUSION: IL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk, and they could be associated with disease severity, which may contribute to the pathogenesis of ITP.
Alleles ; Autoantibodies ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1* ; Interleukins ; Membrane Glycoproteins ; Minisatellite Repeats ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Purpura, Thrombocytopenic, Idiopathic*

BACKGROUND: Pain on injection is a limitation with propofol use. The effect of the Valsalva maneuver on pain during propofol injection has not been studied. This maneuver reduces pain through the sinoaortic baroreceptor reflex arc and by distraction. We aimed to assess the efficacy of the Valsalva maneuver in reducing pain during propofol injection. METHODS: Eighty American Society of Anesthesiologists class I adult patients undergoing general anesthesia were enrolled and divided into two groups of 40 each. Group I (Valsalva) patients blew into a sphygmomanometer tube raising the mercury column up to 30 mmHg for 20 seconds, while Group II (Control) patients did not. Anesthesia was induced with 1% propofol immediately afterwards. Pain was assessed on a 10-point visual analog scale (VAS), where 0 represented no pain, and 10, the worst imaginable pain, and a 4-point withdrawal response score, where 0 represented no pain, and 3, the worst imaginable pain. Scores were presented as median (interquartile range). RESULTS: We analyzed the data of 70 patients. The incidence of pain was significantly lower in the Valsalva than in the control group (53% vs 78%, P = 0.029). The withdrawal response score was significantly lower in the Valsalva group (1.00 [0.00-1.00] vs 2.00 [2.00-3.00], P < 0.001). The VAS score was significantly lower in the Valsalva group (1.00 [0.00-4.00] vs 7.00 [6.25-8.00], P < 0.001). CONCLUSIONS: A prior Valsalva maneuver is effective in attenuating injection pain due to propofol; it is advantageous in being a non-pharmacological, safe, easy, and time-effective technique.
Adult ; Anesthesia ; Anesthesia, General ; Baroreflex ; Humans ; Incidence ; Propofol* ; Prospective Studies* ; Sphygmomanometers ; Valsalva Maneuver* ; Visual Analog Scale