Lower levels of GATA6 expression were also found in cells harvested from younger mice or lower passage cultures. Our findings suggest that GATA6 is a critical regulator increased in aged MSCs that controls the downstream sonic hedgehog signaling and FOXP1 pathway to modulate cellular senescence and aging-related activities.In genetic diseases, the most prevalent mechanism of pathogenicity is an altered expression of dosage-sensitive genes. Drugs that restore physiological levels of these genes should be effective in treating the associated conditions. We developed a screening strategy, based on a bicistronic dual-reporter vector, for identifying compounds that modulate protein levels, and used it in a pharmacological screening approach. To provide a proof-of-principle, we chose autosomal dominant leukodystrophy (ADLD), an ultra-rare adult-onset neurodegenerative disorder caused by lamin B1 (LMNB1) overexpression. We used a stable Chinese hamster ovary (CHO) cell line that simultaneously expresses an AcGFP reporter fused to LMNB1 and a Ds-Red normalizer. Using high-content imaging analysis, we screened a library of 717 biologically active compounds and approved drugs, and identified alvespimycin, an HSP90 inhibitor, as a positive hit. We confirmed that alvespimycin can reduce LMNB1 levels by 30%-80% in five different cell lines (fibroblasts, NIH3T3, CHO, COS-7, and rat primary glial cells). In ADLD fibroblasts, alvespimycin reduced cytoplasmic LMNB1 by about 50%. We propose this approach for effectively identifying potential drugs for treating genetic diseases associated with deletions/duplications and paving the way toward Phase II clinical trials.The design of novel wound dressings for chronic wound treatment is still of great importance. One of the promising approaches is application of mesenchymal stem cells (MSCs), immobilized on a flexible polymer film, for healing. In this study, blended films based on polyvinyl alcohol (PVA) and pectin with different component ratio have been prepared by solution casting method and evaluated. Physicochemical properties of the formed PVA/pectin films, including their morphology, wettability, swelling, stability, mechanical characteristics, have been studied. We demonstrated that the surface of PVA/pectin films could be modified by ultraviolet or dielectric barrier discharge plasma exposure. After both ultraviolet and plasma treatment, the hydrophilicity of PVA/pectin films increased. It has been shown that additional crosslinking of PVA/pectin films with glutaraldehyde resulted in reinforcement of their structure. MSCs were cultured on neat and modified PVA/pectin samples to evaluate the effects of film characteristics and composition on cell behavior. It has been determined that MSCs effectively adhered to glutaraldehyde-crosslinked PVA/pectin films and formed on them the monolayer culture of fibroblast-like cells. The additional modification of PVA/pectin films with collagen resulted in enhancement of MSCs adhesion. Our results show that the obtained PVA/pectin films with adhered MSCs can be suggested for potential application as a part of novel complex wound dressings.The limited lymphocytes infiltration and immunosuppression in tumor are the major challenges of cancer immunotherapy. The use of immunogenic cell death (ICD)-inducing agents has potential to potentiate antitumor immune responses, but is tremendously hampered by the poor delivery efficiency.  https://www.selleckchem.com/products/tpen.html  Herein, a tumor-activated size-enlargeable bioinspired lipoprotein of oxaliplatin (TA-OBL) is designed to access cancer cells and boost the ICD-induced antitumor immunity for synergizing immune-checkpoint blockades (ICBs)-mediated immunotherapy. TA-OBL is constructed by integrating a legumain-sensitive melittin conjugate for improving intratumoral permeation and cancer cell accessibility, a pH-sensitive phospholipid for triggering size-enlargement and drug release in intracellular acidic environments, a nitroreductase-sensitive hydrophobic oxaliplatin prodrug (N-OXP) for eliciting antitumor immunity into the bioinspired nano-sized lipoprotein system. TA-OBL treatment produced robust antitumor immune responses and its combination with ICBs demonstrates strong therapeutic benefits with delayed tumor growth and extended survival rate, making it a promising delivery nanoplatform to elicit antitumor immunity for cancer immunotherapy.A facile route to PtII complexes doubly functionalized with bioactive molecules through a bipyridine-type ligand is described. Initially, ligands LEE (containing two ethacrynic acid units), LEF (ethacrynic acid+flurbiprofen) and LEB (ethacrynic acid+biotin) were obtained in moderate to good yields from 2,2'-bipyridine-4,4'-dicarboxylic acid. Subsequent reaction of the ligands with [PtCl2 (DMSO)2 ] afforded complexes [PtCl2 (LEE )] (2), [PtCl2 (LEF )] (3) and [PtCl2 (LEB )] (4) in high yields. All compounds were fully characterized by analytical and spectroscopic methods. Complexes 2-4 are highly stable in water/DMSO solution at 37 °C after 72 h, whereas progressive release of the bioactive fragments was detected in a cell culture medium. The compounds were assessed for their in vitro antiproliferative activity towards tumorigenic A2780, A2780cisR and Y79 cells and non-tumourigenic HEK293 cells. In particular, the combination of ethacrynic acid and flurbiprofen in 3 overcomes cisplatin-based resistance and provides strong cancer cell selectivity. Enzyme inhibition assays on human GST P1 and human COX-2 and cross-experiments with complex 1, analogous to 2-4 but lacking bio-groups, revealed a clear synergy between the PtII frame and the bioactive organic components.
  To compare the time duration of self-completion (SC) of the Edmonton Symptom Assessment Scale (ESAS) by patients with advanced cancer (ACPs) versus assisted completion (AC) with a health care professional.
 
  In this randomized comparison of ACPs seen in initial consultation at the outpatient Supportive Care Center at MD Anderson, ACPs who have never completed the ESAS at MD Anderson were allocated (11) to either SC of the ESAS form versus AC by a nurse. Time of completion was measured by the nurse using a stopwatch. Patients completed the Rapid Estimate of Adult Literacy in Medicine (REALM) test prior to administration of the ESAS. In the SC group, the nurse reviewed the responses to verify that the reported ESAS scores were correct.
 
  A total of 126 ACPs were enrolled (69 patients to AC and 57 to SC). Seventy-one patients were female, median age was 60 years, and median REALM score was 65. Median (interquartile range) time (in seconds) of SC was significantly less than AC (73 [42.9-89.1] vs. 109 [79.5-136.