Cedrol restricts the growth of colorectal cancer in vitro and in vivo by inducing cell cycle arrest and caspase-dependent apoptotic cell death.

Background: Cedrol is a natural sesquiterpene alcohol found in Cedrus atlantica, which has been proven to have a broad spectrum of biological activities, such as antimicrobial, anti-inflammatory, analgesic, anxiolytic, and anti-cancer effects. However, the underlying anticancer mechanisms and in vivo inhibitory effects of cedrol on colorectal cancer (CRC) have not been elucidated. In the present study, we investigated the anti-CRC potential of cedrol using in vitro and in vivo models. Methods: The effects of cedrol on cell viability, cell cycle progression, and apoptosis of HT-29 and CT-26 cells were detected by MTT, flow cytometry, and TUNEL assays. Western blotting was used to measure protein expression for molecular signaling analyses. Results: Cedrol inhibited HT-29 and CT-26 cell proliferation in a time- and dose-dependent manner, with IC50 values of 138.91 and 92.46 µM, respectively. Furthermore, cedrol induced cell cycle arrest at the G0/G1 phase by regulating the expression of cell cycle regulators, such as CDK4 and cyclin D1, and triggered apoptosis through extrinsic (FasL/caspase-8) and intrinsic (Bax/caspase-9) pathways. In addition, cedrol in combination with the clinical drug 5-fluorouracil exhibited synergistic inhibitory effects on CRC cell growth. Importantly, cedrol treatment suppressed the progression of CRC and improved the survival rate of animals at a well-tolerated dose. Conclusion: These results suggest that cedrol has an anti-cancer potential via induction of cell cycle arrest and apoptosis, and it could be considered as an effective agent for CRC therapy.

Association between Anemia Severity and Ischemic Stroke Incidence: A Retrospective Cohort Study.

Stroke patients presenting with anemia at the time of stroke onset had a higher risk of mortality and development of other cardiovascular diseases and comorbidities. The association between the severity of anemia and the risk of developing a stroke is still uncertain. This retrospective study aimed to evaluate the association between stroke incidence and anemia severity (by WHO criteria). A total of 71,787 patients were included, of whom 16,708 (23.27%) were identified as anemic and 55,079 patients were anemia-free. Female patients (62.98%) were more likely to have anemia than males (37.02%). The likelihood of having a stroke within eight years after anemia diagnosis was calculated using Cox proportional hazard regression. Patients with moderate anemia had a significant increase in stroke risk compared to the non-anemia group in univariate analyses (hazard ratios [HR] = 2.31, 95% confidence interval [CI], 1.97-2.71, p < 0.001) and in adjusted HRs (adj-HR = 1.20, 95% CI, 1.02-1.43, p = 0.032). The data reveal that patients with severe anemia received more anemia treatment, such as blood transfusion and nutritional supplementation, and maintaining blood homeostasis may be important to preventing stroke. Anemia is an important risk factor, but other risk factors, including diabetes and hyperlipidemia, also affect stroke development. There is a heightened awareness of anemia's severity and the increasing risk of stroke development.

Applying Healthcare Failure Mode and Effect Analysis and the Development of a Real-Time Mobile Application for Modified Early Warning Score Notification to Improve Patient Safety During Hemodialysis.

OBJECTIVE: Patients undergoing hemodialysis are a high-risk population. This study identified possible errors by using a healthcare failure mode and effect analysis system to improve patient safety during hemodialysis. METHODS: A multidisciplinary collaborative team, including physicians, nurses, information technicians, and medical staff members, was assembled. A flow diagram was used to indicate each process of the hemodialysis procedure from evaluating patient condition to transporting the patient back to the ward from the hemodialysis center. We scored all possible failure modes using the hazard scoring method as a combination of the occurrence frequency and severity. These potential failure modes were used to identify and evaluate possible risks by using a risk scoring matrix. RESULTS: Thirty failure modes were identified across 6 processes, and their potential causes were explored. Four major strategies for addressing most of the failure modes were implemented: establishment of a mobile application that sends real-time automated alerts to the medical team based on the Modified Early Warning Score, design of a modified dialysis Identify-Situation-Background-Assessment-Recommendation checklist for dialysis, technician education and training, and internal auditing and monitoring of the implementation of the entire process. After the implementation of the strategies, the hazard scores of patients during dialysis dropped by 71.2% from 170 points to 49 points. CONCLUSIONS: The healthcare failure mode and effect analysis system was useful for evaluating potential risk during dialysis. Using the mobile application reduced the occurrence of emergency resuscitation during hemodialysis and significantly improved the communication between medical personnel.

Cedrus atlantica extract exerts antiproliferative effect on colorectal cancer through the induction of cell cycle arrest and apoptosis.

Cedrus atlantica is a tree species found in Morocco with many clinical benefits in genitourinary, musculoskeletal, and skin systems. Previous studies have reported that extracts of Cedrus atlantica have antioxidant, antimicrobial, and anticancer properties. However, its role in colorectal cancer (CRC) remains unclear. The present study investigated the effects and underlying mechanisms of Cedrus atlantica extract (CAt) using HT-29 (human colorectal adenocarcinoma) and CT-26 CRC cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to measure cell viability. Flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were used to study the cell cycle and cell apoptosis, respectively. The expression of cell cycle and apoptosis-associated proteins was detected by western blotting or immunohistochemical (IHC) staining. CAt showed significant inhibitory effects on the proliferation of HT-29 and CT-26 cells, and combined with the clinical drug, 5-fluorouracil (5-FU), exhibited synergistic effects. CAt induced cell cycle arrest at the G0/G1 phase through the upregulation of p53/p21 and the downregulation of cyclin-dependent kinases (CDKs)/cyclins. In addition, CAt-treated cells exhibited chromatin condensation, DNA fragmentation, and apoptotic bodies, which are typical characteristics of apoptosis activated via both the extrinsic (Fas ligand (FasL)/Fas/caspase-8) and intrinsic (Bax/caspase-9) pathways. Importantly, CAt suppressed tumor progression and prolonged the life span of mice within a well-tolerated dose. Therefore, our findings provide novel insights into the use of CAt for the treatment of CRC.

Pogostemon cablin extract as an anticancer agent on human acute myeloid leukemia.

Pogostemon cablin has been indicated to treat many kinds of diseases and the progression of cancers, such as colorectal cancer. However, the effects of P. cablin extract (PPa extract) against acute myeloid leukemia have not been investigated. Thus, this study explored the anticancer potential of PPa extract and its mechanism in HL-60 cells. The MTT assay results showed that PPa extract significantly inhibited the proliferation of HL-60 cells in a dose-dependent manner and affected cell morphology, causing cell shrinkage and the formation of debris. PPa extract blocked cell cycle progression at the G0/G1 phase in a dose- and time-dependent manner and induced cell apoptosis, as shown by the observation of DNA fragments and apoptotic bodies. Furthermore, PPa extract caused the accumulation of a population of cells at G0/G1 phase via a reduction in p-Rb, increasing p21 expression, and downregulating cell cycle regulator protein expression. Then, PPa extract was found to activate the extrinsic and intrinsic apoptosis pathways, leading to cell death. These data demonstrated that PPa extract exerted inhibitory activity and triggered cell apoptosis in HL-60 cells and that PPa extract might be a chemopreventive agent for cancer therapy.

Associated Factors With Acute Transfusion Reaction From Hospital Online Reporting Events: A Retrospective Cohort Study.

OBJECTIVES: In our hospital's hemovigilance system, a Wi-Fi-based vital signs monitor that automatically transmits data to ensure patient safety has been implemented. We derived the potential clinical characteristics for subsequent association of acute transfusion reactions (ATRs) using the hospital information system database. METHODS: We retrospectively analyzed multiple factors to identify the possible associations between clinical factors and developing ATRs. The following data were collected: recipient's pretransfusion and posttransfusion vital signs, clinical and laboratory characteristics, and presence of ATRs. RESULTS: In all, 44,691 events were analyzed. Of these, ATR events occurred in 1586 (3.5%). Logistic regression analysis revealed that leukopenia (<5×10/µL) before transfusion was shown a statistically associated with developing mild ATRs (odds ratio [OR] = 2.38, 95% confidence interval [CI] = 1.68-3.35, P < 0.001). The association between elevated body temperature (forehead temperature > 37.5°C) and moderate ATRs was significant (OR = 1.55, 95% CI = 1.22-1.98, P < 0.001). In addition, the association between high diastolic pressure (>90 mm Hg) and severe ATRs was significant (OR = 1.78, 95% CI = 1.06-2.99, P = 0.03). Therefore, evaluated patient's status such as vital signs before transfusion is very important. In addition, every hospital should established a complete hemovigilance program focus on effectively reporting and real-time monitoring ATRs to improve transfusion patient safety. CONCLUSIONS: Vital signs monitoring and leukocyte counts before transfusion were significantly associated with the subsequent risk of ATRs. When patients with elevated body temperature, leukopenia, and high diastolic pressure who are scheduled to receive transfusion, clinicians should be aware of increasing the risk of ATRs in these patients.

Extract of Pogostemon cablin Possesses Potent Anticancer Activity against Colorectal Cancer Cells In Vitro and In Vivo.

Pogostemon cablin (PCa), an herb used in traditional Chinese medicine, is routinely used in the amelioration of different types of gastrointestinal discomfort. However, the mechanisms underlying the cancer suppression activity of PCa in colorectal cancer (CRC) cells have yet to be clarified. The aim of this study was to investigate the anticancer effects of PCa, specifically the induction of apoptosis in CRC cells. The growth inhibition curve of CRC cells following exposure to PCa was detected by an MTT assay. Moreover, PCa combined with 5-FU revealed a synergic effect of decreased cell viability. PCa inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase and cell apoptosis through regulation of associated protein expression. An in vivo study showed that PCa suppressed the growth of CRC via induction of cell apoptosis with no significant change in body weight or organ histology. Our results demonstrated that PCa inhibits the growth of CRC cells and induces apoptosis in vitro and in vivo, which suggests the potential applicability of PCa as an anticancer agent.

Detection of BCR-ABL gene mutations in Philadelphia chromosome positive leukemia patients resistant to STI-571 cancer therapy.

The ABL-BCR fusion protein is a constitutively activated tyrosine kinase thought to play a central role in chronic myeloid leukemia (CML) and Philadelphia (Ph) chromosome acute lymphoid leukemia (ALL). Targeting the tyrosine kinase activity of ABL-BCR has been shown to be a promising therapeutic strategy in treating this disorder. Among the tyrosine kinase inhibitors, STI571 is a very effective therapeutic agent when administered to CML patients in the stable chronic phase. However, it has been reported that many CML patients with blast cell crisis treated with STI571 relapsed and became resistant to STI571. In order to understand the possible molecular mechanisms underlying STI571 resistance caused by ABL gene mutations, we investigated 19 patients (18 CML patients and 1 Ph (+) ALL patient) who either relapsed after initial response or had no response to STI571 treatment. We used polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis, dHPLC, and direct DNA sequencing to analyze any possible mutations in exons 5 to 9 of the ABL gene. Our results showed that 5 out of 19 patients had various mutations between exons 5 and 7 of the ABL gene. The Ph (+) ALL patient had a Glu255Lys mutation in exon 5 and a Thr315Ile mutation in exon 7. The Glu255Lys substitution has a G to A change, and the Thr315Ile substitution has a C to T change in the ABL gene. The other unique mutations found in this study include: Tyr253His, Met351Thr, GAA tri-nucleotides insertion, and Leu213Pro.

Serum Procalcitonin and Procalcitonin Clearance as a Prognostic Biomarker in Patients with Severe Sepsis and Septic Shock.

We evaluated the tendency of the plasma concentration and procalcitonin (PCT) clearance (PCTc) to act as biomarkers of prognosis in patients with severe sepsis and septic shock. From 2011 to 2013, we prospectively analyzed patients with sepsis admitted to the intensive care unit (ICU). The serum PCT was evaluated at the time of sepsis diagnosis and again after 48 h (day 3) and 96 h (day 5). PCTc after 48 h (PCTc-day 3) and 96 h (PCTc-day 5) was also calculated to evaluate the prognostic value for survival in patients with sepsis. A total of 48 patients were included. Overall mortality was 16.7% (8 patients). PCTc was higher in survivors than in nonsurvivors, with significant differences on day 3 and day 5 (p = 0.033; p = 0.002, resp.); however, serum PCT levels on day 1, day 3, and day 5 were not significant prognostic factors for survival. The prognosis of patients with severe sepsis and septic shock may be associated with PCTc. Dynamic changes of PCT reflected as PCTc at 48 h (day 3) and 96 h (day 5) after admission to the ICU may serve as a predictor of survival in critically ill patients with severe sepsis.