Tension pneumopericardium after removal of pericardiocentesis drainage catheter

This image showed tension pneumopericardium caused by removing the pericardiocentesis catheter, which was inserted to drain malignant pericardial effusion. Tension pneumopericardium is a rare and potentially fatal event. Mortality from tension pneumopericardium can be as high as 50%. Therefore, it is important to suspect and detect early, if the patient complained of dyspnea after removing the pericardiocentesis drainage cathete

HRT, Herbal Formula, Induces G 2

We have demonstrated the anticancer effect of HRT in HCT116, human colon carcinoma cells. HRT inhibited cancer cell growth by causing cell cycle arrest at G2/M and inducing apoptosis as evidenced by DNA fragmentation assay. We found that HRT induces the activation of caspase-3, -8, and -9, whereas it reduces the level of Bcl-2 protein and results in the cleavage of PARP. Further, HRT decreased the level of phosphorylation of Akt and its downstream signals such as mTOR and GSK-3β. These results indicate that HRT stimulates the apoptotic signaling pathway and represses the survival and proliferation of colon cancer cells via inhibiting Akt activity. Hence, our results suggest that HRT has a potential to be developed as a therapeutic agent against colon cancer cells

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug's reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Glucose repression of the Escherichia coli sdhCDAB operon, revisited: regulation by the CRP·cAMP complex

Expression of the Escherichia coli sdhCDAB operon encoding the succinate dehydrogenase complex is regulated in response to growth conditions, such as anaerobiosis and carbon sources. An anaerobic repression of sdhCDAB is known to be mediated by the ArcB/A two-component system and the global Fnr anaerobic regulator. While the cAMP receptor protein (CRP) and Cra (formerly FruR) are known as key mediators of catabolite repression, they have been excluded from the glucose repression of the sdhCDAB operon. Although the glucose repression of sdhCDAB was reported to involve a mechanism dependent on the ptsG expression, the molecular mechanism underlying the glucose repression has never been clarified. In this study, we re-examined the mechanism of the sdhCDAB repression by glucose and found that CRP directly regulates expression of the sdhCDAB operon and that the glucose repression of this operon occurs in a cAMP-dependent manner. The levels of phosphorylated enzyme IIA(Glc) and intracellular cAMP on various carbon sources were proportional to the expression levels of sdhC-lacZ. Disruption of crp or cya completely abolished the glucose repression of sdhC-lacZ expression. Together with data showing correlation between the intracellular cAMP concentrations and the sdhC-lacZ expression levels in several mutants and wild type, in vitro transcription assays suggest that the decrease in the CRP·cAMP level in the presence of glucose is the major determinant of the glucose repression of the sdhCDAB operon

Nutritional compositions in roots, twigs, leaves, fruit pulp, and seeds from pawpaw (Asimina triloba [L.] Dunal) grown in Korea

Pawpaw (Asimina triloba L.) roots, twigs, leaves, fruit, and seeds were analyzed for their nutritional compositions. Seeds exhibited significantly higher levels of crude protein, lipid, fiber, and dietary fiber than those of the other parts. Sucrose in fruit was 9321.24 mg%, which was the highest among the samples. The total essential amino acid to total amino acid ratio was highest in the leaves, and the leaves contained the highest amount of potassium. The calcium content ranged between 8.15-153.41 mg%. Oleic and linoleic acids in seeds were 5905.11 and 8045.56 mg%, respectively, which were the highest among the pawpaw parts. The highest amount of linolenic acid was measured in the leaves, and β-carotene, vitamin C, and vitamin E were also the most abundant in the leaves. These results suggest that every part of pawpaw is a good source of an important food item. Additionally, this study provides basic data for improving the sitological value of pawpaw

Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes.

Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing AKT phosphorylation against oxidative stress. These results strongly indicate that activation of cAMP/PKA pathway has an important role in astrocyte dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic potential for glaucomatous ONH degeneration

17-Oxo-docosahexaenoic acid induces Nrf2-mediated expression of heme oxygenase-1 in mouse skin in vivo and in cultured murine epidermal cells

Recently, growing attention has been given to new classes of bioactive lipid mediators derived from omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), especially in the context of their role as endogenous signal modulators. One such molecule is 17-oxo-DHA, generated from DHA by the action of COX2 and a dehydrogenase. The redox-sensitive transcription factor, Nrf2 plays a key role in cellular stress responses. In the present study, the effects of 17-oxo-DHA on Nrf2-mediated expression of cytoprotective enzymes were examined in mouse skin in vivo and cultured murine epidermal JB6 cells. Topical application of 17-oxo-DHA markedly elevated the nuclear localization of Nrf2 and expression of heme oxygenase-1 (HO-1) and NAD(P) H:quinone oxidoreductase-1 in hairless mouse skin. In contrast to 17-oxo-DHA, the non-electrophilic metabolic precursor 17-hydroxy-DHA was a much weaker inducer of Nrf2 activation and its target protein expression. Likewise, 17-oxo-DHA significantly enhanced nuclear translocation and transcriptional activity of Nrf2 with concomitant upregulation of HO-1 expression in cultured JB6 cells. 17-Oxo-DHA was a much stronger inducer of Nrf2-mediated antioxidant response than its parent molecule, DHA. HO-1 expression was abolished in Nrf2 knockdown JB6 cells or embryo fibroblasts from Nrf2 knock out mice. 17-Oxo-DHA also markedly reduced the level of Keap1 protein by inducing ubiquitination. Mutation of Cys151 and Cys273 in Keap1 abrogated 17-oxo-DHA-induced ubiquitination and proteasome-mediated degradation of Keap1 as well as HO-1 expression, suggesting that these cysteine residues are putative sites for 17-oxo-DHA binding. Further, Keap1 degradation stimulated by 17-oxo-DHA coincided with accumulation of the autophagy substrate, p62/SQSTM1.