Flower-Shaped Hollow VOOH Spheres Wrapped by Carbon Nanotubes as the Cathode Electrocatalyst Enable Ultrafast and Long-Lasting Li-S Batteries.

Lithium-sulfur batteries (LSBs) have been considered promising candidates for next-generation energy storage devices owing to their high energy density, low price, and environment-friendly characteristics. However, their commercialization has been hindered by the "shuttle effect", which occurs during the charge/discharge cycles and leads to poor cycling performance and low coulombic efficiency. Here, we synthesized flower-shaped hollow VOOH spheres on the carbon nanotube (CNT) network, which were used as the multifunctional sulfur host materials for the first time in LSBs. These VOOH spheres can chemically and physically confine polysulfides as well as catalyze their redox conversion; additionally, their hollow structure can effectively accommodate the volume change during cycling. Moreover, the CNTs among spheres can improve the conductivity of the host material and increase the number of active sites for interfacial reactions. Accordingly, when used as a cathode material, VOOH@CNTs/S composites exhibited a large specific discharge capacity of 1414.63 mAh/g at 0.1 C and excellent cycling stability. At a low current density of 0.5 C, VOOH@CNTs/S exhibited a capacity decay of 0.044% per cycle after 100 cycles. Importantly, at an ultrahigh current density of 5 C, a specific capacity as high as 455.09 mAh/g could be still be delivered after 1000 cycles, corresponding to a superior capacity retention of 90.46% and an ultralow capacity decay of 0.009% per cycle. These findings open up a new material for the practical application of LSBs with ultrafast charge/discharge property and long-lasting cyclic stability.

Sorafenib overcomes the chemoresistance in HBx-expressing hepatocellular carcinoma cells through down-regulation of HBx protein stability and suppresses HBV gene expression.

Previous studies have revealed that HBx expression has anti-apoptotic effects, resulting in increased drug resistance in HCC cells. Thus, we examined if sorafenib efficiently induces apoptosis in HBx-overexpressing HCC cells. Noticeably, sorafenib efficiently induced apoptosis, even in HBx-expressing HepG2 cells, indicating that the HBx protein does not attenuate sorafenib-induced apoptosis. We next investigated if sorafenib modulates autophagy, allowing HCC cells to overcome the chemoresistance conferred by the HBx protein. Although autophagy plays a cytoprotective role against sorafenib-induced lethality, sorafenib was effective irrespective of HBx protein overexpression. We next examined if sorafenib exerts its cytotoxic effect via direct effects on the HBx protein. Importantly, sorafenib decreased HBx protein stability through a proteasome-dependent degradation pathway. Moreover, sorafenib decreased HBV gene expression and viral promoter activity. Taken together, sorafenib efficiently induces apoptotic cell death in HBx-expressing HCC cells via the downregulation of the HBx protein, a key factor in the anti-cancer drug resistance observed in HBV-induced HCC.

Measurement of Critical Structures around Paraclinoidal Area : A Cadaveric Morphometric Study.

OBJECTIVE: Although removal of the anterior clinoid process (ACP) is essential surgical technique, studies about quantitative measurements of the space broadening by the anterior clinoidectomy are rare. The purposes of this study are to investigate the dimension of the ACP, to quantify the improved exposure of the parasellar space after extradural anterior clinoidectomy and to measure the correlation of each structure around the paraclinoidal area. METHODS: Eleven formalin-fixed Korean adult cadaveric heads were used and frontotemporal craniotomies were done bilaterally. The length of C6 segment of the internal carotid artery on its lateral and medial side and optic nerve length were checked before and after anterior clinoidectomy. The basal width and height of the ACP were measured. The relationships among the paraclinoidal structures were assessed. The origin and projection of the ophthalmic artery (OA) were investigated. RESULTS: The mean values of intradural basal width and height of the ACP were 10.82 mm and 7.61 mm respectively. The mean length of the C6 lateral and medial side increased 49%. The mean length of optic nerve increased 97%. At the parasellar area, the lengths from the optic strut to the falciform liament, distal dural ring, origin of OA were 6.69 mm, 9.36 mm and 5.99 mm, respectively. The distance between CN III and IV was 11.06 mm. CONCLUSION: With the removal of ACP, exposure of the C6 segments and optic nerve can expand 49% and 97%, respectively. This technique should be among a surgeon's essential skills for treating lesions around the parasellar area.

Bisphenol A exposure during adulthood causes augmentation of follicular atresia and luteal regression by decreasing 17ß-estradiol synthesis via downregulation of aromatase in rat ovary.

BACKGROUND: Bisphenol A (BPA) has been detected in human body fluids, such as serum and ovarian follicular fluids. Several reports indicated that BPA exposure is associated with the occurrence of several female reproductive diseases resulting from the disruption of steroid hormone biosynthesis in the adult ovary. OBJECTIVE: We hypothesized that long-term exposure to low concentrations of BPA disrupts 17ß-estradiol (E2) production in granulosa cells via an alteration of steroidogenic proteins in ovarian cells. METHODS: Adult female rats received BPA for 90 days by daily gavage at doses of 0, 0.001, or 0.1 mg/kg body weight. We determined serum levels of E2, testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). We also analyzed the expressions of steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), 3ß-hydroxysteroid dehydrogenase isomerase (3ß-HSD), and aromatase cytochrome P450 (P450arom) in the ovary. RESULTS: Exposure to BPA significantly decreased E2 serum concentration, which was accompanied by augmented follicular atresia and luteal regression via increase of caspase-3-associated apoptosis in ovarian cells. After BPA exposure, P450arom and StAR protein levels were significantly decreased in granulosa cells and theca-interstitial (T-I) cells, respectively. However, P450scc and 3ß-HSD protein levels remained unchanged. The increase in LH levels appeared to be associated with the decreased synthesis of T in T-I cells after BPA exposure via homeostatic positive feedback regulation. CONCLUSIONS: BPA exposure during adulthood can disturb the maintenance of normal ovarian functions by reducing E2. The steroidogenic proteins StAR and P450arom appear to be targeted by BPA.

Fatty acid synthase inhibitor cerulenin inhibits topoisomerase I catalytic activity and augments SN-38-induced apoptosis.

Fatty acid synthase (FASN) is overexpressed in a wide variety of human cancers, making it an attractive target for anticancer therapy. One of the most widely used inhibitors of FASN, cerulenin, is a natural product of Cephalosporium caerulens. Cerulenin is selectively toxic to human cancer cells in vitro. However, the mechanism by which FASN inhibition causes apoptosis in tumor cells remains unclear. Because of the widespread clinical interest in combining cerulenin with other chemotherapeutic agents, we performed this study to gain insight into the downstream effects of FASN inhibition that lead to apoptosis. Here, we observed the increased antitumor effect of cerulenin when combined with the topoisomerase inhibitor SN-38. We identified topoisomerase I as a potential mediator of cerulenin-induced apoptosis, possibly by upregulating intracellular polyunsaturation. Finally, we show that suppressing topoisomerase I catalytic activity results in synergistic effects between cerulenin and LY294002. Our results suggest that topoisomerase I could participate in cerulenin-induced apoptosis by upregulating intracellular polyunsaturation. These results will help determine the molecular basis of the cerulenin and SN-38 drug combination. Further investigation of this pathway will provide new insight into cancer cell metabolism and may aid in the design of additional cancer chemotherapeutic agents.

Benzo[a]pyrene reduces testosterone production in rat Leydig cells via a direct disturbance of testicular steroidogenic machinery.

BACKGROUND: Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells. OBJECTIVE: We hypothesized that long-term exposure to low concentrations of B[a]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins. RESULTS: Oral exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[a]P in vivo produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[a]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3ß-HSD may occur because B[a]P can negatively target 3ß-HSD, which is required for testosterone production. CONCLUSIONS: B[a]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[a]P or other PAHs.

Arsenic trioxide-induced apoptosis in TM4 Sertoli cells: the potential involvement of p21 expression and p53 phosphorylation.

Arsenic is a toxic metalloid that exists ubiquitously in the environment, and exhibits carcinogenicity. Conversely, arsenic trioxide (AsTO) has successfully been employed in the treatment of acute promyelocytic leukemia (APL). It has been shown that AsTO efficiently induces apoptosis in the malignant cells of APL in vitro. Although the mechanisms underlying AsTO-induced apoptosis in certain types of cancer cells, such as APL cells, have been delineated, the mechanism underlying AsTO-induced cell death in non-cancer cells remains unknown. In the present study, we examined AsTO-provoked cytotoxicity and cell death mechanism(s) in TM4 Sertoli cells. Exposure of these cells to AsTO generates reactive oxygen species and alters mitochondrial apoptosis, inducing cell death via both caspase-dependent and caspase-independent pathways. AsTO-induced apoptosis was concomitant with the downregulation of p53, phosphorylation of p53 at serine residues, and G2/M cell cycle arrest. Particularly, the interaction of p21 with caspase-3 proteins during AsTO treatment suggested an antiapoptotic role of p21 against genotoxic stresses in TM4 Sertoli cells. However, clinically relevant concentrations of AsTO failed to induce cell death in TM4 Sertoli cells, indicating that these cells could be resistant to cancer treatment. The results presented herein may not represent the actual effect of AsTO on Sertoli cells in vivo. Thus, further studies on the exposure effects of AsTO on the morphology and function of Sertoli cells in animal experiments will provide a more precise knowledge of AsTO cytotoxicity on male reproduction.

The novel resveratrol analog HS-1793-induced polyploid LNCaP prostate cancer cells are vulnerable to downregulation of Bcl-xL.

Since resveratrol is not a potent cytotoxic compound when compared with other chemotherapeutic agents, several previous studies have been performed to obtain synthetic analogs of resveratrol with potent activity. Our previous study demonstrated that the resveratrol analog HS-1793 showed stronger antitumor activity than resveratrol in various cancer cells. We examined the antitumor activity exerted by HS-1793 in prostate cancer cells, and we observed that HS-1793 acts as a polyploidy inducer. Noticeably, multinucleation and polyploidization were induced in most LNCaP cells treated with HS-1793 at the dose causing a slight decline in cell viability. However, the induction of multinucleation and polyploidization was much lower in PC-3 prostate cancer cells treated with the same dose of HS-1793. Western blot and RT-PCR analyses showed that the expression of Aurora B was almost undetectable in LNCaP cells, but it was highly expressed in PC-3 cells. Further, silencing of Aurora B sensitized PC-3 cells to HS-1793-induced multi-nucleation. These results indicate that expression of Aurora B determines multinucleation in prostate cancer cells treated with HS-1793. Additional assays using multiple cancer cell lines show that the population of multinucleated cells induced by HS-1793 treatment is inversely proportional to Aurora B expression. We further elicited that the HS-1793-induced polyploid LNCaP cells are vulnerable to downregulation of Bcl-xL. Since the polyploidization in LNCaP induced by HS-1793 does not appear to cause definite commitment to apoptosis, the termination of polyploid cells by inhibition of Bcl-xL could provide an advantageous means to improve chemotherapeutic efficacy of HS-1793.

A novel resveratrol analogue HS-1793 treatment overcomes the resistance conferred by Bcl-2 and is associated with the formation of mature PML nuclear bodies in renal clear cell carcinoma Caki-1 cells.

Bcl-2 protects cancer cells from the apoptotic effects of various chemotherapeutic agents. Inhibition or downregulation of Bcl-2 represents a new therapeutic approach to bypass chemoresistance in cancer cells. Previously we designed and synthesized the resveratrol analogue HS-1793 displaying stronger antitumor efficacy than resveratrol and further demonstrated the HS-1793 resistance conferred by Bcl-2 in human leukemic U937 cells. We undertook this study to determine if HS-1793 treatment can bypass the anti-apoptotic effects of Bcl-2 in human renal cancer cells, with a specific focus on the involvement of promyelocytic leukemia nuclear bodies (PML-NBs). Experiments were conducted with Bcl-2-overexpressing human renal clear cell carcinoma Caki-1 cells. Various apoptosis assessment assays demonstrated that HS-1793 overcomes the resistance conferred by Bcl-2 in Caki-1 cells by inducing apoptosis. We elucidated that HS-1793-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with overcoming the anti-apoptotic effects of Bcl-2 in Caki-1 cells. Our findings show that the resveratrol analogue HS-1793 might provide a novel promising strategy for overcoming the resistance conferred by Bcl-2 via PML protein and the formation of mature PML-NBs.

Abundance of aryl hydrocarbon receptor potentiates benzo[a]pyrene-induced apoptosis in Hepa1c1c7 cells via CYP1A1 activation.

Although B[a]P-induced apoptosis has been demonstrated in Hepa1c1c7 cells, the cellular signaling pathway(s) by which benzo[a]pyrene (B[a]P) elicits a cytotoxicity-mediated apoptogenic role remains to be elucidated. In this study, we showed that B[a]P induces apoptosis in a p53-mediated and caspase-3-dependent manner, which relates to the accumulation of the S phase of the cell cycle. Importantly, we have shown for the first time that Hepa1c1c7 cells retain a considerably high content of aryl hydrocarbon receptor (AhR) protein before B[a]P exposure, assuming that this status enables the cells to respond to B[a]P more readily as well as more efficiently. B[a]P treatment resulted in the downregulation of AhR and induced cytochrome P450 1A1 (CYP1A1) (but not cytochrome P450 1B1 (CYP1B1)) expression and activity. While alpha-naphtoflavone (alpha-NF) and ellipticine suppressed B[a]P-induced CYP1A1 activation as well as apoptosis, the 2,3',4,5'-tetramethoxystilbene (TMS) and pyrene, known CYP1B1 inhibitors, failed to inhibit apoptosis. However, alpha-NF alone significantly increased CYP1A1 protein expression but not its activity, suggesting that alpha-NF more likely works as an AhR agonist in Hepa1c1c7 cells after B[a]P, rather than a direct inhibitor of CYP1A1 activity. In conclusion, it is suggested that the abundance of endogenous AhR level is an indispensable condition for an efficient cellular signaling of B[a]P and that control of AhR activity in Hepa1c1c7 cells might be important to cell fate resulting from CYP1A1 activation after B[a]P.

Nuclear interaction of Smac/DIABLO with Survivin at G2/M arrest prompts docetaxel-induced apoptosis in DU145 prostate cancer cells.

Smac/DIABLO is released by mitochondria in response to apoptotic stimuli and is thought to antagonize the function of inhibitors of apoptosis proteins. Recently, it has been shown that, like XIAP, Survivin can potentially interact with Smac/DIABLO. However, the precise mechanisms and cellular location of their action have not been determined. We report for the first time that Smac/DIABLO translocates to the nucleus and is colocalized with Survivin at mitotic spindles during apoptosis resulting from G2/M arrest due to docetaxel treatment of DU145 prostate cancer cells. Our data demonstrate that the nuclear interaction of Smac/DIABLO with Survivin is an important step for suppressing the anti-apoptotic function of Survivin in Doc-induced apoptosis. This suggests that the balance between cellular Smac/DIABLO and Survivin levels could be critical for cellular destiny in taxane-treated cancer cells.

Trichostatin A induces apoptosis of p815 mastocytoma cells in histone acetylation- and mitochondria-dependent fashion.

Although inhibition of histone deacetylase has been demonstrated to induce apoptosis of various cancer cells, there is no report on its effect on mast cell demise to date. Here we studied whether a histone deacetylase inhibitor Trichostatin A (TSA) produces apoptosis in p815 mastocytoma cells. TSA prominently increased the amount of acetylated histones, H3, H4, H2A and H2B, in p815 mastocytoma cells. TSA reduced the viability of p815 mastocytoma cells, and many apoptotic manifestations such as generation of DNA fragmentation, activation of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and increase of DNA hypoploidy proved that the reduction of viability resulted from apoptosis. Whereas TSA treatment increased the expression level of Bad, it decreased the level of Bcl-2, Bcl-xL, and X-linked inhibitor of apoptosis protein. The reduction of mitochondrial membrane potential, the release of cytochrome c and Smac/DIABLO to cytosol, and mitochondrial localization of Bad were also shown. Taken together, TSA induces apoptosis on p815 mastocytoma cells in histone acetylation- and mitochondria-dependent fashion. Our data therefore provide the possibility that TSA could be considered as a novel therapeutic strategy for mastocytoma from its apoptosis-inducing activity.