Magnolol Induces the Extrinsic/Intrinsic Apoptosis Pathways and Inhibits STAT3 Signaling-Mediated Invasion of Glioblastoma Cells.

Glioblastoma multiforme (GBM) is the most common form of malignant brain tumor, with poor prognosis; the efficacy of current standard therapy for GBM remains unsatisfactory. Magnolol, an herbal medicine from Magnolia officinalis, exhibited anticancer properties against many types of cancers. However, whether magnolol suppresses GBM progression as well as its underlying mechanism awaits further investigation. In this study, we used the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay, apoptosis marker analysis, transwell invasion and wound-healing assays to identify the effects of magnolol on GBM cells. We also validated the potential targets of magnolol on GBM with the GEPIA (Gene Expression Profiling Interactive Analysis) and Western blotting assay. Magnolol was found to trigger cytotoxicity and activate extrinsic/intrinsic apoptosis pathways in GBM cells. Both caspase-8 and caspase-9 were activated by magnolol. In addition, GEPIA data indicated the PKCδ (Protein kinase C delta)/STAT3 (Signal transducer and activator of transcription 3) signaling pathway as a potential target of GBM. Magnolol effectively suppressed the phosphorylation and nuclear translocation of STAT3 in GBM cells. Meanwhile, tumor invasion and migration ability and the associated genes, including MMP-9 (Matrix metalloproteinase-9) and uPA (Urokinase-type plasminogen activator), were all diminished by treatment with magnolol. Taken together, our results suggest that magnolol-induced anti-GBM effect may be associated with the inactivation of PKCδ/STAT3 signaling transduction.

Multi-Omics Reveal the Immunological Role and the Theragnostic Value of miR-216a/GDF15 Axis in Human Colon Adenocarcinoma.

Colon adenocarcinoma (COAD) is the most common type of gastrointestinal cancer and is still the third leading cause of cancer-related mortality worldwide. Accurate screening tools for early diagnosis and prediction of prognosis and precision treatment strategies are urgently required to accommodate the unmet medical needs of COAD management. We herein aimed to explore the significance of the microRNA (miR)-216a/growth differentiation factor 15 (GDF15) axis in terms of clinical value, tumor immunity, and potential mechanisms in COAD by using multi-omic analysis. The gene expression levels of miR-216a and GDF15 showed an increase in the COAD group compared to those of the normal group. The expression of miR-216a presented a negative correlation with GDF15 in COAD tumor tissue. The use of an in vitro luciferase reporter assay and bioinformatic prediction revealed that miR-216a-3p acted toward translational inhibition on GDF15 by targeting its 3'untranslated region (UTR) site. High miR-216a expression was associated with decreased overall survival (OS), while the high expression of GDF15 was associated with increased OS. Enriched type 1 T-helper (Th1), enriched regulatory T (Treg), enriched eosinophils, and decreased nature killer T-cells (NKTs) in COAD tumor tissue may play counteracting factors on the tumor-regulatory effects of miR-216a and GDF15. In addition, high GDF15 expression had associations with suppressed immunoinhibitory genes and negative correlations with the infiltration of macrophages and endothelial cells. The enrichment analysis revealed that GDF15 and its co-expression network may be implicated in mitochondrial organization, apoptosis signaling, and endoplasmic reticulum (ER) stress response. The Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal (CTRP) analysis identified that Gemcitabine acted as a precision treatment for COAD when GDF15 expression was low. This study supports the miR-216a/GDF15 axis as a diagnostic/prognostic panel for COAD, identifies Th1, Treg, eosinophils, and NKTs as counteracting factors, indicates potential relationships underlying immunomodulation, mitochondrial organization, apoptotic signaling, and ER stress and unveil Gemcitabine as a potential drug for the development of treatment strategy when combined with targeting GDF15.

Does plain radiography still have a role in cases of fish bone ingestion in emergency rooms? A retrospective analysis.

BACKGROUND: Fish bones are the most common aerodigestive foreign bodies found in adults. Most cases of fish bone impaction improve after primary management by emergency physicians with a mirror laryngoscopy using a tongue depressor, before otolaryngologists perform a fiberoptic nasendoscopy. A computed tomography scan usually follows to determine the next step. Studies have recently been concerned about overdoses of radiation from computed tomography. However, clear algorithms remain unavailable for fish bone ingestion management to date. METHODS: A retrospective review was conducted on 180 patients who visited the emergency department with complaints of fish bone impaction between January 2017 and January 2019. RESULTS: A total of 81.6% of patients with fish bone impaction got symptomatic relief after primary management by emergency physicians and otolaryngologists. Out of 180 patients, 33 (18.3%) needed an endoscopic procedure due to persistent symptoms. Only one (0.56%) required an operation due to perforation. In the group failing primary management, the plain radiography of eight patients showed a positive finding and an esophagogastroscopy was done to remove the fish bones. CONCLUSION: Lateral neck radiography is still beneficial to patients with fish bone ingestion failure from primary management. Positive lateral soft tissue radiography in cases with persistent symptoms post primary management may directly suggest esophagogastroscopy without confirmation from a computed tomography, unless complications are suspected. For patients aged below 40, following up on their conditions after post management radiography shows negative results may increase their safety.

Infected aneurysm of the thoracic aorta probably caused by Bacillus cereus: a case report.

BACKGROUND: An infected aneurysm of the thoracic aorta is a rare clinical condition with significant morbidity and mortality. Patients with fast-growing aortic aneurysms show a high incidence of rupture. Gram-positive organisms, such as the Staphylococcus and Enterococcus species, are the most common cause of infection. CASE PRESENTATION: A 91-year-old man presented at our facility with high grade fever and tachypnea, which he had experienced for the previous two days. He had a history of end-stage renal disease and had been undergoing regular chest computed tomography (CT) follow-up for a left lower lung nodule. CT imaging with intravenous contrast media showed a thoracic aortic aneurysm with hemothorax. Rupture of the aneurysm was suspected. CT imaging performed a year ago showed a normal aorta. Blood samples showed a Bacillus cereus infection. The patient was successfully treated for a mycotic aortic aneurysm secondary to Bacillus cereus bacteremia. CONCLUSIONS: Here, we report a rare of an infected aneurysm of the thoracic aorta probably caused by Bacillus cereus. Although infected aneurysms have been described well before, an aneurysm infected with Bacillus cereus is rare. Bacillus cereus, a gram-positive spore-building bacterium, can produce biofilms, which attach to catheters. It has recently emerged as a new organism that can cause serious infection.

Extremely high levels of alkaline phosphatase in adult patients as a manifestation of bacteremia.

BACKGROUND/AIMS: Jaundice resulting from severe bacterial infection is well known, particularly in pediatric literature. Extremely high levels of alkaline phosphatase (ALP) have rarely been emphasized as a manifestation of bacteremia in adults. The aim of this study was to evaluate the characteristics of extremely high levels of ALP in adult patients as a manifestation of bacteremia. METHODOLOGY: Extremely high levels of ALP were defined as being more than 1000 U/L. From April 1998 to May 1999, we retrospectively reviewed those patients' charts who had ALP above 1000 U/L. Sixteen patients that had bacteremia among 96 patients with extremely high levels of ALP at the emergency department of Taichung Veterans General Hospital were included in this study. RESULTS: Sixteen patients had bacteremia with extremely high levels of ALP, including 9 patients with malignant biliary obstruction (MBO), and 7 patients without MBO. The ALP levels ranged from 1002 to 2061 (1430.13+/-353.84) U/L. Ten patients were male, and 6 were female. Their ages ranged from 19 to 83 (56.13+/-16.51) years. A variety of gram-negative, and gram-positive organisms were identified, and Escherichia coli was the most common pathogen. Among the seven patients of bacteremia without MBO, 5 patients had underlying diabetes mellitus as the predisposing factor for development of the bacteremia. The ages of the bacteremia patients with MBO were older than those of patients without MBO (66.3+/-10.1 us. 43.0+/-13.7 years, P=0.0025). CONCLUSIONS: Bacteremia from a variety of organisms is a common cause for extreme elevation of ALP. Escherichia coli is the most common pathogen and presented more often in patients with MBO than those without MBO. In the setting o f extremely high levels of ALP as a manifestation of bacteremia, the patients with MBO are as common as those without MBO. We have demonstrated clinically that hepatic dysfunction during bacteremia may be manifested predominantly by extreme elevation of alkaline phosphatase with little abnormality in serum bilirubin.