Oral squamous cell carcinoma (OSCC) is the fifth common cause of cancer mortality in Taiwan with high incidence and recurrence and needs new therapeutic strategies. In this study, ursolic acid (UA), ...a triterpenoid, was examined the antitumor potency in OSCC cells. Our results showed that UA inhibited the proliferation of OSCC cells in a dose‐ and time‐dependent manner in both Ca922 and SCC2095 oral cancer cells. UA induced caspase‐dependent apoptosis accompanied with the modulation of various biological biomarkers including downregulating Akt/mTOR/NF‐κB signaling, ERK, and p38. In addition, UA inhibited angiogenesis as evidenced by abrogation of migration/invasion and blocking MMP‐2 secretion in Ca922 cells. Interestingly, UA induced autophagy in OSCC cells, as manifested by LC3B‐II conversion and increased p62 expression and accumulation of autophagosomes. Inhibition by autophagy inhibitor enhanced UA‐mediated apoptosis in Ca922 cells. The experiment provides a rationale for using triterpenoid in the treatment of OSCC.
13‐Acetoxysarcocrassolide (13‐AC) is a marine cembranoid derived from the aquaculture soft coral of Lobophytum crassum. The cytotoxic effect of 13‐AC against leukemia cells was previously reported ...but its mechanism of action is still unexplored. In the current study, we showed that 13‐AC induced apoptosis of human acute lymphoblastic leukemia Molt4 cells, as evidenced by the cleavage of PARP and caspases, phosphatidylserine externalization, as well as the disruption of mitochondrial membrane potential. The use of N‐acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, attenuated the cytotoxic effect induced by 13‐AC. Molecular docking and thermal shift assay indicated that the cytotoxic mechanism of action of 13‐AC involved the inhibition of heat shock protein 90 (Hsp 90) activity by eliciting the level of Hsp 70 and topoisomerase IIα in Molt4 cells. 13‐AC also exhibited potent antitumor activity by reducing the tumor volume (48.3%) and weight (72.5%) in the in vivo Molt4 xenograft mice model. Our findings suggested that the marine cembranoid, 13‐AC, acted as a dual inhibitor of Hsp 90 and topoisomerase IIα, exerting more potent apoptotic activity via the enhancement of ROS generation.
Differentiation therapy is an alternative strategy used to induce the differentiation of blast cells toward mature cells and to inhibit tumor cell proliferation for cancer treatment. Nobiletin (NOB), ...a polymethoxyflavone phytochemical, is present abundantly in citrus peels and has been reported to possess anti-cancer activity. In this study, we investigated the anti-leukemic effects of NOB on cell differentiation and its underlying mechanisms in human chronic myeloid leukemia (CML) K562 cells. NOB (100 μM) treatment for 24 and 48 h significantly decreased viability of K562 cells to 54.4 ± 5.3% and 46.2 ± 9.9%, respectively. NOB (10-100 μM) significantly inhibited cell growth in K562 cells. Flow cytometry analysis and immunoblotting data showed that NOB (40 and 80 μM) could modulate the cell cycle regulators including p21, p27, and cyclin D2, and induce G1 phase arrest. NOB also increased the messenger RNA (mRNA) and protein expression of megakaryocytic differentiation markers, such as CD61, CD41, and CD42 as well as the formation of large cells with multi-lobulated nuclei in K562 cells. These results suggested that NOB facilitated K562 cells toward megakaryocytic differentiation. Furthermore, microarray analysis showed that expression of EGR1, a gene associated with promotion of megakaryocytic differentiation, was markedly elevated in NOB-treated K562 cells. The knockdown of EGR1 expression by small interference RNA (siRNA) could significantly attenuate NOB-mediated cell differentiation. We further elucidated that NOB induced EGR1 expression and CD61 expression through increases in MAPK/ERK phosphorylation in K562 cells. These results indicate that NOB promotes megakaryocytic differentiation through the MAPK/ERK pathway-dependent EGR1 expression in human CML cells. In addition, NOB when combined with imatinib could synergistically reduce the viability of K562 cells. Our findings suggest that NOB may serve as a beneficial anti-leukemic agent for differentiation therapy.
Leptospirosis is recognized as a zoonotic disease that is emerging worldwide. Severe manifestations are associated with high morbidity and mortality rates and may therefore pose an important risk to ...public health, especially in certain high prevalence areas like Taiwan. The severe pulmonary form of leptospirosis is a lesser known entity and is characterized by intra-alveolar hemorrhage and can lead to acute respiratory failure with resistant hypoxemia, which leads to high mortality rates despite maximally invasive mechanical ventilation and adequate treatment. We herein present a case of severe leptospirosis complicated by massive pulmonary hemorrhage, which was successfully managed by extra corporeal membrane oxygenation.
Refilling cholesteric liquid crystal (CLC) template gratings with circular polarization, wavelength selectivity, and dual operation mode are first demonstrated. The gratings with template and ...nontemplate regions are obtained through the two-beam interfering photo-polymerization, washing-out, and refilling procedure. The refilling CLC has different chiral handedness (left or right) and reflection band (at green and red regions). When the wavelength of a probe beam is within the refilled CLC reflection band of the nontemplate region, the device works as an amplitude grating since the sample in the template and nontemplate regions reflects distinct colour region. In addition, the diffraction intensity of the grating can be electrically controlled. Therefore, this CLC-based device can be potentially used in controllable diffraction elements in optics.
Viridians streptococcal shock syndrome is a subtype of toxic shock syndrome. Frequently, the diagnosis is missed initially because the clinical features are nonspecific. However, it is a rapidly ...progressive disease, manifested by hypotension, rash, palmar desquamation, and acute respiratory distress syndrome within a short period. The disease course is generally fulminant and rarely presents initially as a purpura over the plantar region. We present a case of a 54-year-old female hospital worker diagnosed with viridians streptococcal shock syndrome caused by Streptococcus gordonii. Despite aggressive antibiotic treatment, fluid hydration, and use of inotropes and extracorporeal membrane oxygenation, the patient succumbed to the disease. Early diagnosis of the potentially fatal disease followed by a prompt antibiotic regimen and appropriate use of steroids are cornerstones in the management of this disease to reduce the risk of high morbidity and mortality.
Dysphagia aortica: a fatal delay in diagnosis Liao, Chen-Yi, MD; Huang, Shih-Chung, MD; Wang, Yi-Chen, MD ...
The American journal of emergency medicine,
08/2015, Letnik:
33, Številka:
8
Journal Article
Recenzirano
Extrinsic esophageal compression leading to dysphagia is an uncommon and late presentation of large thoracic aortic aneurysm named dysphagia aortica. Herein, we report an 86-year-old man who ...presented with 1-week duration of chest pain, backache, and dysphagia and was eventually diagnosed as dysphagia aortica. Our patient developed progressive dyspnea due to tracheal compression and failed surgery. The case illustrates the importance of early identification of the rare entity of dysphagia especially in elderly cases with cardiovascular disease with complaint of undetermined dysphagia accompanied with chest pain and backache.
Hyperin, a flavonoid compound found in Ericaceae, Guttiferae, and Celastraceae, has been reported to have anti-inflammatory effects. In the present study, we investigated the effects of hyperin on ...cisplatin-induced acute kidney injury (AKI) in mice. The renal tissue damage induced by cisplatin was detected by H&E staining. Blood urea nitrogen (BUN), creatinine, reactive oxygen species (ROS), and malondialdehyde (MDA) were also detected. Further, the effects of hyperin on cisplatin-induced TNF-α, IL-1β and IL-6 were detected by ELISA. In addition, the phosphorylation of nuclear factor kappa B (NF-κB) and the expression of nuclear factor E2-related factor-2 (Nrf2) and HO-1 were detected by western blot analysis. The results showed that hyperin attenuated histological changes of kidney induced by cisplatin. The levels of BUN, creatinine, ROS, MDA, TNF-α, IL-1β and IL-6 induced by cisplatin were also inhibited by hyperin. Cisplatin-induced NF-κB activation was inhibited by hyperin. Additionally, hyperin was found to up regulate the expression of Nrf2 and HO-1. In conclusion, the results suggest that hyperin protects against cisplatin-induced AKI by inhibiting inflammatory and oxidant response.
•Hyperin attenuated histological changes of kidney induced by cisplatin.•The levels of blood urea nitrogen (BUN), creatinine, reactive oxygen species (ROS), malondialdehyde (MDA), TNF-α, IL-1β and IL-6 were inhibited by hyperin.•Cisplatin-induced NF-κB activation was inhibited by hyperin.•Additionally, hyperin was found to up-regulate the expression of Nrf2 and HO-1.
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