An RNA Helicase DHX33 Inhibitor Shows Broad Anticancer Activity via Inducing Ferroptosis in Cancer Cells.

RNA helicase DHX33 has been identified as a critical factor promoting cancer development. In the present study, a previously developed small molecule inhibitor for DHX33, KY386, was found to robustly kill cancer cells via a new path, the ferroptosis pathway. Mechanistically, DHX33 promotes the expression of critical players in lipid metabolism including FADS1, FADS2, and SCD1 genes, thereby sensitizing cancer cells to ferroptosis mediated cell death. Our study reveals a novel mechanism of DHX33 in promoting tumorigenesis and highlights that pharmacological targeting DHX33 can be a feasible option in human cancers. Normally differentiated cells are insensitive to DHX33 inhibition, and DHX33 inhibitors have little cellular toxicity in vitro and in vivo. Our studies demonstrated that DHX33 inhibitors can be promising anticancer agents with great potential for cancer treatment.

RNA helicase DHX33 regulates HMGB family genes in human cancer cells.

RNA helicase DHX33 has been shown to be aberrantly expressed in various human cancers, however, its role in tumorigenesis remains incompletely understood. In this report, we uncovered that a family of DNA architecture proteins, HMGBs, can be regulated by DHX33 in cancer cells but not in normal cells. Specifically, DHX33 knockdown caused the downregulation of HMGBs at the levels of both gene transcription and protein expression. Notably, in RAS driven lung tumorigenesis, nuclear HMGBs proteins can be induced via DHX33. When DHX33 was knocked out, HMGBs overexpression was debilitated. Mechanistically, DHX33 was found to bind to the promoters of HMGB family genes and regulated their transcription through demethylation on gene promoters. Our study reveals a novel mechanism for DHX33 to promote tumorigenesis and highlights its therapeutic value in human cancers.

Safety and efficacy of administering reduced doses of pegylated recombinant human granulocyte-colony stimulating factors in patients treated with cisplatin and etoposide for small cell carcinoma: A retrospective study.

BACKGROUND: The aim of this study was to discuss the safety and efficacy of administering reduced doses (3 mg) of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) at approximately 24 h or up to three days following treatment with etoposide and cisplatin (EP). METHODS: A total of 104 cycles from 31 patients were divided into a PEG-rhG-CSF prophylaxis group (PP-Group) and a control group (No-PP-Group). The PP-Group received a reduced dose of 3 mg of PEG-rhG-CSF within a minimum of 15 h and a maximum of 72 h following EP chemotherapy, while the rest did not receive any G-CSF prophylaxis (No-PP-Group). For both groups, complete blood counts, incidence of febrile neutropenia (FN), grade III or IV neutropenia, and the use of antibiotics to treat neutropenia were recorded. RESULTS: There was statistically no significant difference in the incidence of FN (0% vs. 1.4%, p = 1), antibiotic use due to neutropenia (0% vs. 2.7%, p = 0.881), estimated lowest mean marginal (EM) platelet (106.56 × 109 /L vs. 127.70 × 109 /L, p = 0.056) and hemoglobin (110.48 g/L vs. 110.14 g/L, p = 0.906) levels between the two groups. However, when compared with the No-PP-group, the white blood cell count in the PP-group was significantly higher (EM means: 4.95 × 109 /L vs. 2.80 × 109 /L, p < 0.01), while the incidence of grade III or IV neutropenia was significantly lower (9.1% vs. 68.1%, p < 0.01). CONCLUSIONS: The administration of a low dose (3 mg) of PEG-rhG-CSF within approximately 24 h or up to three days following EP treatment is safe and effective at reducing the risk of neutropenia. These findings bring a more flexible administration interval between PEG-rhG-CSF and EP treatment.

Design, synthesis, and in vitro antitumor activity of a transferrin receptor-targeted peptide-doxorubicin conjugate.

In this study, a peptide-drug conjugate was designed and synthesized by connecting a transferrin receptor (TfR)-targeted binding peptide analog BP9a (CAHLHNRS) with doxorubicin (DOX) through N-succinimidyl-3-maleimidopropionate (SMP) as the cross-linker. Confocal laser scanning microscopy results indicated that free DOX mainly accumulated in the nuclei of both TfR overexpressed HepG2 hepatoma cells and L-O2 normal liver cells expressing low level of TfR; most of the BP9a-DOX conjugate displayed cytoplasmic location, and its cellular uptake by HepG2 cells was obviously reduced by TfR blockage test. Nevertheless, the cellular uptake of this conjugate by L-O2 cells was much less than that of free DOX. Meanwhile, the BP9a-DOX conjugate exhibited lower in vitro antiproliferative activity against HepG2 cells than free DOX, but its cytotoxic effect on L-O2 cells was decreased compared with that of free DOX. These results suggest that BP9a could be applied as a potential TfR-targeted peptide vector for selective drug delivery.

Synergetic effect of dual co-catalysts on the activity of BiVO4 for photocatalytic carbamazepine degradation.

An efficient visible-light driven three components photocatalyst for carbamazepine (CBZ) degradation has been assembled by co-loading reduction cocatalyst Pt and oxidation cocatalyst Co3O4 (MnO x ) on BiVO4. The apparent rate constant of the three components photocatalyst Pt/BiVO4/Co3O4 for degradation of CBZ is 54 times that of Co3O4/BiVO4 and 2.5 times that of Pt/BiVO4, which shows a synergetic effect in the photocatalytic activity. The same synergetic effect is also observed for Pt/BiVO4/MnO x . The spatial separation of the reduction and oxidation cocatalysts could reduce the recombination of the photogenerated charges, which mainly accounts for the high photocatalytic activity of the three components photocatalyst. The photocatalytic intermediates of CBZ were detected by HPLC-ESI-MS, and a deductive degradation pathway of CBZ was proposed.

Roles of cocatalysts in semiconductor-based photocatalytic hydrogen production.

A photocatalyst is defined as a functional composite material with three components: photo-harvester (e.g. semiconductor), reduction cocatalyst (e.g. for hydrogen evolution) and oxidation cocatalyst (e.g. for oxidation evolution from water). Loading cocatalysts on semiconductors is proved to be an effective approach to promote the charge separation and transfer, suppress the charge recombination and enhance the photocatalytic activity. Furthermore, the photocatalytic performance can be significantly improved by loading dual cocatalysts for reduction and oxidation, which could lower the activation energy barriers, respectively, for the two half reactions. A quantum efficiency (QE) as high as 93 per cent at 420 nm for H2 production has been achieved for Pt-PdS/CdS, where Pt and PdS, respectively, act as reduction and oxidation cocatalysts and CdS as a photo-harvester. The dual cocatalysts work synergistically and enhance the photocatalytic reaction rate, which is determined by the slower one (either reduction or oxidation). This work demonstrates that the cocatalysts, especially the dual cocatalysts for reduction and oxidation, are crucial and even absolutely necessary for achieving high QEs in photocatalytic hydrogen production, as well as in photocatalytic water splitting.

Hybrid artificial photosynthetic systems comprising semiconductors as light harvesters and biomimetic complexes as molecular cocatalysts.

Solar fuel production through artificial photosynthesis may be a key to generating abundant and clean energy, thus addressing the high energy needs of the world's expanding population. As the crucial components of photosynthesis, the artificial photosynthetic system should be composed of a light harvester (e.g., semiconductor or molecular dye), a reduction cocatalyst (e.g., hydrogenase mimic, noble metal), and an oxidation cocatalyst (e.g., photosystem II mimic for oxygen evolution from water oxidation). Solar fuel production catalyzed by an artificial photosynthetic system starts from the absorption of sunlight by the light harvester, where charge separation takes place, followed by a charge transfer to the reduction and oxidation cocatalysts, where redox reaction processes occur. One of the most challenging problems is to develop an artificial photosynthetic solar fuel production system that is both highly efficient and stable. The assembly of cocatalysts on the semiconductor (light harvester) not only can facilitate the charge separation, but also can lower the activation energy or overpotential for the reactions. An efficient light harvester loaded with suitable reduction and oxidation cocatalysts is the key for high efficiency of artificial photosynthetic systems. In this Account, we describe our strategy of hybrid photocatalysts using semiconductors as light harvesters with biomimetic complexes as molecular cocatalysts to construct efficient and stable artificial photosynthetic systems. We chose semiconductor nanoparticles as light harvesters because of their broad spectral absorption and relatively robust properties compared with a natural photosynthesis system. Using biomimetic complexes as cocatalysts can significantly facilitate charge separation via fast charge transfer from the semiconductor to the molecular cocatalysts and also catalyze the chemical reactions of solar fuel production. The hybrid photocatalysts supply us with a platform to study the photocatalytic mechanisms of H2/O2 evolution and CO2 reduction at the molecular level and to bridge natural and artificial photosynthesis. We demonstrate the feasibility of the hybrid photocatalyst, biomimetic molecular cocatalysts, and semiconductor light harvester for artificial photosynthesis and therefore provide a promising approach for rational design and construction of highly efficient and stable artificial photosynthetic systems.

A hybrid photocatalytic system comprising ZnS as light harvester and an [Fe(2)S(2)] hydrogenase mimic as hydrogen evolution catalyst.

Photo opportunity: A highly efficient and stable hybrid artificial photosynthetic H(2) evolution system is assembled by using a semiconductor (ZnS) as light-harvester and an [Fe(2)S(2)] hydrogenase mimic ([(µ-SPh-4-NH(2) )(2) Fe(2) (CO)(6)]) as catalyst for H(2) evolution. Photocatalytic H(2) production is achieved with more than 2607 turnovers (based on [Fe(2)S(2)]) and an initial turnover frequency of 100 h(-1) through the efficient transfer of photogenerated electrons from ZnS to the [Fe(2)S(2)] complex.

Visible light driven hydrogen production from a photo-active cathode based on a molecular catalyst and organic dye-sensitized p-type nanostructured NiO.

A molecular device with a photocathode for hydrogen generation has been successfully demonstrated, based on an earth abundant and inexpensive p-type semiconductor NiO, an organic dye P1 and a cobalt catalyst Co1.

A visible-light-driven transfer hydrogenation on CdS nanoparticles combined with iridium complexes.

A visible-light-driven transfer hydrogenation of carbonyl and C=C compounds has been developed by coupling CdS nanoparticles with iridium complexes, exhibiting high activities, excellent selectivities and a unique pH-dependent catalytic activity.

Visible light driven H(2) production in molecular systems employing colloidal MoS(2) nanoparticles as catalyst.

Colloidal MoS(2) nanoparticles with diameters of less than 10 nm were prepared with a simple solvothermal method and demonstrated high efficiency in catalyzing H(2) evolution in Ru(bpy)(3)(2+)-based molecular systems under visible light.

Enhancement of photocatalytic H2 evolution on CdS by loading MoS2 as Cocatalyst under visible light irradiation.

This communication presents our recent results that the activity of photocatalytic H2 production can be significantly enhanced when a small amount of MoS2 is loaded on CdS as cocatalyst. The MoS2/CdS catalysts show high rate of H2 evolution from photocatalytic re-forming of lactic acid under visible light irradiation. The rate of H2 evolution on CdS is increased by up to 36 times when loaded with only 0.2 wt % of MoS2, and the activity of MoS2/CdS is even higher than those of the CdS photocatalysts loaded with different noble metals, such as Pt, Ru, Rh, Pd, and Au. The junction formed between MoS2 and CdS and the excellent H2 activation property of MoS2 are supposed to be responsible for the enhanced photocatalytic activity of MoS2/CdS.

[Preparation of nanometer TiO2 doped with upconversion luminescence agent and investigation on degradation of ethyl violet using visible light].

A novel upconversion luminescence agent 40CdF2 x 60BaF2 x 1.6Er2O3 was synthesized and the fluorescent spectrum was determined. This upconversion luminescence agent can emit five upconversion fluorescent peaks whose wavelengths are all below 387nm under the excitation of 488 nm visible light. This upconversion luminescence agent was mixed into nanometer TiO2 powder by ultrasonic dispersion and the doped nanometer TiO2 photocatalyst utilizing visible light was prepared. The doped TiO2 powder was charactered by XRD and TEM and its photocatalytic activity was checked through the photocatalytic degradation of ethyl violet dye as a model compound under the visible light irradiation emitted by three basic color lamp. Otherwise, in order to compare the photocatalytic activities the same experiment was carried out for undoped photocatalytic TiO2 powder. The degradation ratio of ethyl violet dye in the presence of doped nanometer TiO2 powder reached 99.68% under visible light irradiation at 12.0 h which was obviously higher than the corresponding degradation ratio in the presence of undoped nanometer TiO2 powder, which indicate that the upconversion luminescence agent prepared as dopant can effectively turn visible lights to ultraviolet lights which are absorbed by nanometer TiO2 particles and produce the electron-cavity pairs.

Investigation on photocatalytic degradation of ethyl violet dyestuff using visible light in the presence of ordinary rutile TiO2 catalyst doped with upconversion luminescence agent.

To use solar irradiation or interior lighting efficiently, a new photocatalyst with high catalytic activity in visible light was sought. In this work, an upconversion luminescence agent, 40 CdF(2).60 BaF(2).1.0 Er(2)O(3), was synthesized and its fluorescent spectrum was determined. It is found that this upconversion luminescence agent can emit five upconversion fluorescent peaks below 387nm under the excitation of 488nm visible light. The upconversion luminescence agent has revealed an improvement over ordinary titanium dioxide (TiO(2)) in photocatalytic activity under visible light irradiation for the photocatalytic degradation of ethyl violet in aqueous solution as a model compound. The TiO(2) photocatalyst doped with upconversion luminescence agent was characterized by X-ray diffraction (XRD) and transmission electron microscope (TEM). The photocatalytic degradation of ethyl violet was tracked by UV-vis and (1)H-NMR spectra, and the influences of irradiation time, initial concentration of ethyl violet, addition amount of TiO(2) catalyst and initial pH value were also investigated. To affirm the complete mineralization, the total organic carbon (TOC) was also tested. The degradation rate of ethyl violet in the presence of doped rutile TiO(2) photocatalyst reached 87.08% at 4.0h visible light irradiation, which was obviously higher than the corresponding degradation rate (35.42%) in the presence of undoped rutile TiO(2) powder. The research results show that the upconversion luminescence agent is necessary to transform visible lights into ultraviolet lights and thus make the best use of visible lights. By calculation, the upconversion efficiency of the emission peak at 380nm was estimated to be about 0.78%. The TiO(2) powder doped upconversion luminescence agent under visible light irradiation is able to decompose the ethyl violet in aqueous solution efficiently, therefore, this method may be envisaged as a technology for treating dyes wastewaters using solar energy, especially at textile industries in developing countries.

Sonocatalytic degradation of methyl parathion in the presence of nanometer and ordinary anatase titanium dioxide catalysts and comparison of their sonocatalytic abilities.

The degradation of methyl parathion (O,O-dimethyl-O-(4-nitrophenyl)-phosphorothioate) using anatase titanium dioxide (TiO(2)) powder as heterogeneous sonocatalysts is reported. The influences of reaction parameters such as the species of TiO(2) sonocatalysts, methyl parathion concentrations, TiO(2) adding amount, pH, ultrasonic intensity, ultrasonic frequency and temperature have been investigated and the optimal conditions for eliminating methyl parathion have been identified. The efficiencies of sonocatalytic degradation in both nanometer and ordinary anatase systems are compared and the results indicate that the sonocatalytic activity of nanometer anatase TiO(2) powder is better than that of ordinary anatase TiO(2) powder. The primary degradation and the total mineralization of methyl parathion have been monitored by high performance liquid chromatography (HPLC) and UV-vis spectra, respectively. Methyl parathion got destroyed to some extent in both nanometer and ordinary anatase systems under ultrasonic irradiation. The kinetics for the degradation process of methyl parathion follows the first-order reaction. The degradation ratio of methyl parathion surpassed 90% within 50min in the optimal experiment conditions.

Degradation of dyestuff wastewater using visible light in the presence of a novel nano TiO2 catalyst doped with upconversion luminescence agent.

A new upconversion luminescence agent, 40CdF2 x 60BaF2 x 0.8Er2O3, was synthesized and its fluorescent spectra were determined. This upconversion luminescence agent can emit five upconversion fluorescent peaks shown in the fluorescent spectra whose wavelengths are all below 387 nm under the excitation of 488 nm visible light. This upconversion luminescence agent was mixed into nano rutile TiO2 powder by ultrasonic and boiling dispersion and the novel doped nano TiO2 photocatalyst utilizing visible light was firstly prepared. The doped TiO2 powder was charactered by XRD and TEM and its photocatalytic activity was tested through the photocatalytic degradation of methyl orange as a model compound under the visible light irradiation emitted by six three basic color lamps. In order to compare the photocatalytic activities, the same experiment was carried out for undoped TiO2 powder. The degradation ratio of methyl orange in the presence of doped nano TiO2 powder reached 32.5% under visible light irradiation at 20 h which was obviously higher than the corresponding 1.64% in the presence of undoped nano TiO2 powder, which indicate the upconversion luminescence agent prepared as dopant can effectively turn visible lights to ultraviolet lights that are absorbed by nano TiO2 particles to produce the electron-cavity pairs. All the results show that the nano rutile TiO2 powder doped with upconversion luminescence agent is a promising photocatalyst using sunlight for treating the industry dye wastewater in great force.