Purification and Identification of a Novel Complex Which Is Involved in Androgen Receptor-Dependent Transcription

The androgen receptor (AR) binds to and activates transcription of target genes in response to androgens. In an attempt to isolate cofactors capable of influencing AR transcriptional activity, we used an immunoprecipitation method and identified a 44-kDa protein, designated p44, as a new AR-interacting protein. p44 interacts with AR in the nucleus and with an androgen-regulated homeobox protein (NKX3.1) in the cytoplasm of LNCaP cells. Transient-transfection assays revealed that p44 enhances AR-, glucocorticoid receptor-, and progesterone receptor-dependent transcription but not estrogen receptor- or thyroid hormone receptor-dependent transcription. p44 was recruited onto the promoter of the prostate-specific antigen gene in the presence of the androgen in LNCaP cells. p44 exists as a multiprotein complex in the nuclei of HeLa cells. This complex, but not p44 alone, enhances AR-driven transcription in vitro in a cell-free transcriptional system and contains the protein arginine methyltransferase 5, which acts synergistically with p44 to enhance AR-driven gene expression in a methyltransferase-independent manner. Our data suggest a novel mechanism by which the protein arginine methyltransferase is involved in the control of AR-driven transcription. p44 expression is dramatically enhanced in prostate cancer tissue compared with adjacent benign prostate tissue

Comparative Survival Outcomes of Hyperthermic Intraperitoneal Chemotherapy, Intraperitoneal Chemotherapy and Intravenous Chemotherapy for Primary Advanced Ovarian Cancer: A Network Meta-Analysis

Objective: We aimed to compare the survival outcomes and adverse events of hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP)and intravenous chemotherapy (IP)for primary advanced ovarian cancer. Methods: PubMed, CENTRAL (Cochrane Central Registry of Controlled Trials), Embase, Web of Science and Scopus were searched using multiple terms for primary advanced ovarian cancer, including randomized controlled trials and comparative studies in both Chinese and English (up to date 15 August 2022). Outcomes include overall survival, progression-free survival and adverse events. The data were pooled and reported as hazard ratio (HRs) with 95% confidence intervals. The Newcastle–Ottawa Scales were used to assess the risk of bias in the included comparative study. The Cochrane Collaboration’s Risk of Bias Tool was used for randomized controlled trials. Results: In total, 32 studies, including 6347 patients and 8 different platinum-based chemotherapy regimens, were included in this network meta-analysis. Our analysis results showed that HIPEC2 (carboplatin with area under the curve 10) exhibited a statistically significant OS benefit compared to IV, weekly dose-dense chemotherapy and HIPEC1 (cisplatin with 75/100 mg/m2). Intraperitoneal plus intravenous chemotherapy was associated with a statistically significantly better likelihood of overall survival compared to IV. For progression-free survival, our statistical results only suggest a better progression-free survival in ovarian cancer patients treated with HIPEC1 compared with weekly dose-dense chemotherapy. No evidence of difference was observed between the other comparison groups. Compared with the non-HIPEC group, HIPEC may had a higher incidence of electrolyte disturbances (≥grade 3). Conclusion: Our statistical analysis suggests that the groups receiving HIPEC2 had a better OS than the groups receiving IV, weekly dose-dense chemotherapy and HIPEC1. For PFS, our analysis only showed HIPEC1 is better than IV. Moreover, HIPEC may lead to a higher incidence of electrolyte disturbances (≥grade 3). HIPEC therapy for advanced ovarian cancer is currently controversial

Atmospheric deposition and air-soil exchange of polybrominated diphenyl ethers (PBDEs) in a background site in Central China

Jinsha (JSH) is one of the regional background sites in Central China. In this study, eight polybrominated diphenyl ethers (PBDEs) were measured in atmospheric deposition samples (dry particle, wet particle, and wet dissolved), air (gaseous and particle) samples, and soil samples that were collected from March 2012 to March 2013. Of all eight PBDEs, BDE-209 was the most abundant congener in both deposition samples and air/soil samples. Average dry particle, wet particle, and wet dissolved deposition fluxes of Sigma 8PBDEs were 270 +/- 310 pg m(-2) day(-1), 130 +/- 210 pg m(-2) day(-1), and 250 +/- 330 pg m(-2) day(-1), respectively, while those of BDE-209 were 210 +/- 290 pg m(-2) day(-1), 80 +/- 120 pg m(-2) day(-1), and 160 +/- 290 pg m(-2) day(-1), respectively. Dry deposition velocities of individual PBDE ranged from 0.11 +/- 0.15 cm s(-1) (BDE-183) to 0.24 +/- 0.38 cm s(-1) (BDE-209), and total washout ratios ranged from 5.0 x 10(3) (BDE-28) to 4.2 x 10(4) (BDE-209). The calculated net air-soil gas exchange flux of Sigma 8PBDEs was - 16 +/- 13 pg m(-2) day(-1), suggesting the deposition status of PBDEs. The gas exchange flux at the air-soil interface was significantly lower than the deposition flux, which only accounted for 2.5% of the total deposition flux, implying that atmospheric deposition was an important input pathway for PBDEs to soils. Overall, the pollution level of the soil was relatively low, and the soil serves as a sink for PBDEs from adjacent regions

Protocol to establish a lung adenocarcinoma immunotherapy allograft mouse model with FACS and immunofluorescence-based analysis of tumor response

Summary: Anti-PD-1/PD-L1 therapy shows long-term effects in many cancer types, but resistance and relapse remain the main limitations of this therapy. Here, we describe a protocol to evaluate the tumor response to immunotherapy in a mouse lung cancer model. The protocol includes the establishment of the lung cancer mouse model, anti-PD-1 treatment, tumor-infiltrating lymphocyte isolation, immunofluorescence, and flow cytometry analysis. This protocol can also be applied to other cancer types and immunotherapies.For complete details on the use and execution of this protocol, please refer to Yu et al. (2021

On the remarkable resistance to coke formation of nanometer-sized and hierarchical MFI zeolites during ethanol to hydrocarbons transformation

International audienceThe impact of the textural properties of H-ZSM-5 zeolites in the conversion of ethanol to hydrocarbons at 623 K and under 3.0 MPa pressure is investigated. We highlight that the lifetime of the catalysts is not correlated to the coking rate but to the number of pore mouths. The addition of macropores (fluoride leaching) or mesopores (alkaline leaching) to micron-sized zeolites is a simple approach to increase the number of pore mouths and reduce the diffusion path length of molecules in the micropores. However, the most efficient way is to reduce the zeolite crystal size to nanometers. The longest catalyst lifetime (>100 h) is obtained with a hierarchical nanometer-sized zeolite even though most of its acid sites are poisoned. The important impact of the nature of coke on the catalysts regeneration is also highlighted

Effects of postweaning cadmium exposure on socioemotional behaviors in adolescent male mice

Exposure to cadmium (Cd), a toxic heavy metal classified as an environmental endocrine disruptor, can exert significant toxicity in both animals and humans. However, the potential effects of Cd exposure on socioemotional behaviors are still poorly understood, as are the underlying mechanisms. In the present study, employing a series of behavioral tests as well as 16 S rRNA sequencing analysis, we investigated the long-term effects of Cd exposure on socioemotional behaviors and their associated mechanisms in mice based on the brain–gut interaction theory. The results showed that postweaning exposure to Cd reduced the ability to resist depression, decreased social interaction, subtly altered sexual preference, and changed the composition of the gut microbiota in male mice during adolescence. These findings provided direct evidence for the deleterious effects of exposure to Cd in the postweaning period on socioemotional behaviors later in adolescence, and suggested that these effects of Cd exposure may be linked to changes in the gut microbiota

⁶⁴Cu-Labeled Somatostatin Analogues Conjugated with Cross-Bridged Phosphonate-Based Chelators via Strain-Promoted Click Chemistry for PET Imaging: In silico through in Vivo Studies

Somatostatin receptor subtype 2 (sstr2) is a G-protein-coupled receptor (GPCR) that is overexpressed in neuroendocrine tumors. The homology model of sstr2 was built and was used to aid the design of new somatostatin analogues modified with phosphonate-containing cross-bridged chelators for evaluation of using them as PET imaging radiopharmaceuticals. The new generation chelators were conjugated to Tyr³-octreotate (Y3-TATE) through bioorthogonal, strain-promoted alkyne azide cycloaddition (SPAAC) to form CB-TE1A1P–DBCO–Y3-TATE (AP) and CB-TE1K1P–PEG4–DBCO–Y3-TATE (KP) in improved yields compared to standard direct conjugation methods of amide bond formation. Consistent with docking studies, the clicked bioconjugates showed high binding affinities to sstr2, with <i>K</i>_d values ranging from 0.6 to 2.3 nM. Selected isomers of the clicked products were used in biodistribution and PET/CT imaging. Introduction of the bulky dibenzocyclooctyne group in AP decreased clearance rates from circulation. However, the additional carboxylate group and PEG linker from the KP conjugate significantly improved labeling conditions and in vivo stability of the copper complex and ameliorated the slower pharmacokinetics of the clicked somatostatin analogues