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Background & Aims More than 50% of liver tumours occur in patients aged 65 years or more. Assessment of functional liver regeneration capacity is crucial to minimize postoperative liver failure. We aimed to study functional hepatocellular regeneration, through scintigraphic quantification of Mebrofenin hepatic extraction fraction ( HEF), after partial hepatectomy, comparing elderly patients with younger ones. Methods One hundred and two patients undergoing partial hepatectomy for primary or secondary hepatic lesions were prospectively included and divided in two groups: Group A - 58 patients aged <65 years (33 men, 53.9 ± 8.7 years), Group B - 44 patients aged ≥65 years (32 men, 71 ± 5 years). Groups were comparable in several aspects except for the presence of cirrhosis (more common in Group B, all patients Child-Pugh score A) and the initial diagnosis (Group B - primary lesions, Group A - metastases). The scintigraphic evaluation of Mebrofenin- HEF was performed before surgery, on the 5th and 30th day post-hepatectomy. Results Mortality and morbidity were 3.4 and 12.1%, respectively, in Group A and 2.3 and 11.4% in Group B (n.s.). HEF values (%), T1/2 (min) and Tmax (min) showed no significant differences between the two groups: Group A (preoperative: HEF = 99.2 ± 1.5%, T1/2 = 36.7 ± 21.3, Tmax = 15 ± 6. Day 5: HEF = 96.3 ± 10.8%, T1/2 = 76.4 ± 75.9; Tmax = 13.3 ± 4.9. Day 30: HEF = 98.4 ± 5.5%, T1/2 = 38.6 ± 7.7, Tmax = 12.8 ± 3.6) and Group B (preoperative: HEF = 95.3 ± 13%, T1/2 = 38.1 ± 24.1; Tmax = 15.9 ± 9.4. Day 5: HEF = 98.4 ± 2.6%, T1/2 = 106.6 ± 131.7; Tmax = 15.1 ± 6.2. Day 30: HEF = 99 ± 2.1%, T1/2 = 40.5 ± 27; Tmax = 15.5 ± 6.7). Conclusion Our results suggest that functional hepatocellular regeneration is early, fast and similar between elderly and younger patients. Thus, age alone, does not appear to represent an absolute contraindication to hepatectomy. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is a rare malignant proliferative hematopoietic disease due to overexpression of a tyrosine kinase (TK) derived from the breakpoint cluster region (BCR)‐abelson tyrosine‐protein kinase 1 (ABL1) gene fusion. Imatinib (IM), blocks this tyrosine kinase, and is the first line TK inhibitor (TKI) used in CML treatment. In a high percentage of CML patients, a poor response with relapse and disease progression is associated to acquisition of resistance through different mechanisms, including dysregulation of c‐MYC proto‐oncogene. Gold nanoparticles (AuNPs) are shown to allow improved efficacy in gene silencing approaches toward cancer therapy. Herein, the silencing potential of AuNPs functionalized with antisense oligonucleotides selectively targeting the e14a2 BCR‐ABL1 or the c‐MYC, alone and combination is evaluated. It is demonstrated efficient silencing of gene expression that translated to a downregulation of protein levels in IM resistant CML cells (K562‐IM). This combination allowed for increased death of the malignant cells. These Au‐nanoconjugates may be useful to tackle IM‐resistance mechanisms, providing an additional tool for future combinatory schemes to fight CML with imatinib resistance. [ABSTRACT FROM AUTHOR]

Eight new amorphous organic salts of folic acid (FA) were prepared by mechanochemistry. FA can prevent cardiovascular and neurological diseases. Mechanochemistry overcomes serious FA solubility issues avoiding the use of toxic solvents. Due to low FA solubility, therapeutic effects in supplements and drugs are not achieved. Current strategies to improve FA solubility include its derivatization by using complex synthetic procedures. Herein, a simple and green procedure, avoiding structural modifications, was designed using mechanochemistry. Biocompatible amine‐derivative coformers were strategically combined with FA to obtain salts with good physicochemical properties. New 1 : 1 and 1 : 2 amorphous FA salts offer 10 to 10,000 times better aqueous solubility and 10 to 100 times better octanol‐water partition coefficient values (Koctanol/water) than FA alone. Koctanol/water is considered as a surrogate of cell permeability. No toxic effects in normal human primary dermal fibroblasts were detected for the prepared FA salts. Our findings suggest that 1 : 2 FA salts of choline hydroxide and derivatives could be good candidates for future pharmaceutical/nutraceutical applications. [ABSTRACT FROM AUTHOR]

Preterm birth is a major clinical and public health challenge, with a prevalence of 11% worldwide. It is the leading cause of death in children younger than 5 years old and represents 70% of neonatal deaths and 75% of neonatal morbidity. Despite the clinical and public health significance, this condition's etiology is still unclear, and most of the cases are spontaneous. There are several known preterm birth risk factors, including inflammatory diseases and the genetic background, although the underlying molecular mechanisms are far from understood. The present review highlights the research advances on the association between inflammatory‐related genes and the increased risk for preterm delivery. The most associated genetic variants are the TNFα rs1800629, the IL1α rs17561, and the IL1RN rs2234663. Moreover, many of the genes discussed in this review are also implicated in pathologies involving inflammatory or autoimmune systems, such as periodontal disease, bowel inflammatory disease, and autoimmune rheumatic diseases. This review presents evidence suggesting a common genetic background to preterm birth, autoimmune and inflammatory diseases susceptibility. [ABSTRACT FROM AUTHOR]

POXylated polyurea dendrimer nanoparticles (PUREG4OOx48) are loaded with sildenafil (SDF) by a supercritical carbon dioxide–assisted (scCO2) impregnation. Further supercritical CO2‐assisted spray drying (SASD) leads to hybrid nano‐in‐micro dry powder formulations that are investigated aiming at efficient pulmonary delivery of SDF in pulmonary arterial hypertension treatment. This is the first report of the production of poly(D,L‐lactide‐co‐glycolide)‐cholesterol (PLGA‐Chol) microparticles processed by SASD. The optimized formulation of nano‐in‐microparticles is composed of PLGA, Chol, and PUREG4OOx48, loaded with SDF solutions in a 77:23 ratio (PLGA‐Chol:dendrimer, w/w). The dry powders are fully characterized and found to be highly biodegradable and biocompatible, and the SDF release profile evaluates under different pH values. The median mass average diameter (MMAD) of the nano‐in‐micro systems varies between 2.57 and 5 µm and the fine particle fraction (FPF) between 36% and 29% for PUREG4OMeOx48[PLGA‐Chol] and PUREG4OEtOx48[PLGA‐Chol], respectively. The data validate the potential use of these new formulations in inhalation therapy. In vitro studies are also carried out in order to evaluate the effect of the free drug in cell viability and formulations cytotoxicity. [ABSTRACT FROM AUTHOR]

Abstract: A series of 4‐ethynylaniline gold(I) complexes containing monophosphane (1,3,5‐triaza‐7‐phosphaadamantane (pta; 2), 3,7‐diacetyl‐1,3,7‐triaza‐5‐phosphabicyclo[3.3.1]nonane (3), and PR3, with R=naphthyl (4), phenyl (5), and ethyl (6)) and diphosphane (bis(diphenylphosphino)acetylene (dppa; 7), trans‐1,2‐bis(diphenylphosphino)ethene (dppet; 8), 1,2‐bis(diphenylphosphino)ethane (dppe; 9), and 1,3‐bis(diphenylphosphino)propane (dppp; 10)) ligands have been synthesized and their efficiency against tumor cells evaluated. The cytotoxicity of complexes 2–10 was evaluated in human colorectal (HCT116) and ovarian (A2780) carcinoma as well as in normal human fibroblasts. All the complexes showed a higher antiproliferative effect in A2780 cells, with the cytotoxicity decreasing in the following order 5>6=9=10>8>2>4>7>3. Complex 4 stands out for its very high selectivity towards ovarian carcinoma cells (IC50=2.3 μ m) compared with colorectal carcinoma and normal human fibroblasts (IC50>100 μ m), which makes this complex very attractive for ovarian cancer therapy. Its cytotoxicity in these cells correlates with the induction of the apoptotic process and an increase of intracellular reactive oxygen species (ROS). The effects of the nuclearity, rigidity, and solubility of these complexes on their biological activity were also analyzed. X‐ray crystal structure determination allowed the identification of short N−H⋅⋅⋅π contacts as the main driving forces for the three‐dimensional packing in these molecules. [ABSTRACT FROM AUTHOR]

POxylated polyurea dendrimer (PUREG4OOx48)‐based nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX) and micronized with chitosan (CHT) by using supercritical CO2‐assisted spray drying (SASD). Respirable, biocompatible, and biodegradable dry powder formulations (DPFs) were produced to effectively transport and deliver the chemotherapeutics with a controlled rate to the deep lung. In vitro studies performed with the use of the lung adenocarcinoma cell line showed that DOX@PUREG4OOx48 nanoparticles were much more cytotoxic than the free drug. Additionally, the DPFs did not show higher cytotoxicity than the respective nanoparticles, and DOX‐DPFs showed a higher chemotherapeutic effect than PTX formulations in adenocarcinoma cells. Inhalation chemotherapeutics: Micronized POxylated polyurea dendrimers loaded with anticancer agents (paclitaxel or doxorubicin) are fabricated by using green methodologies. These drug‐delivery systems reveal enhanced drug accumulation into neoplastic cells and allow a reduction in drug dosages and undesired side effects. [ABSTRACT FROM AUTHOR]

A new and never before reported hetero-arylidene-9(10H)-anthrone structure (4) was unexpectedly isolated on reaction of 1,2-dimethyl-3-ethylimidazolium iodide (2) and 9-anthracenecarboxaldehyde (3) under basic conditions. Its structure was unequivocally confirmed by X-ray crystallography. No cytotoxicity in human healthy fibroblasts and in two different cancer cell lines was observed, indicating its applicability in biological systems. Compound 4 interacts with CT-DNA by intercalation between the adjacent base pairs of DNA with a high binding affinity [Kb = 2.0 (±0.20) x 105 M-1], which is 10 x higher than that described for doxorubicin [Kb = 3.2 (±0.23) x 104 M-1]. Furthermore, compound 4 quenches the fluorescence emission of a GelRed--CT-DNA system with a quenching constant (KSV) of 3.3 (±0.3) x 10³ M-1 calculated by the Stern--Volmer equation. [ABSTRACT FROM AUTHOR]

[CoCl(μ-Cl)(HpzPh)3]2 ( 1) and [CoCl2(HpzPh)4] ( 2) were obtained by reaction of CoCl2 with HC(pzPh)3 and HpzPh, respectively (HpzPh=3-phenylpyrazole). The compounds were isolated as air-stable solids and fully characterized by IR and far-IR spectroscopy, MS(ESI+/−), elemental analysis, cyclic voltammetry (CV), controlled potential electrolysis, and single-crystal X-ray diffraction. Electrochemical studies showed that 1 and 2 undergo single-electron irreversible CoII→CoIII oxidations and CoII→CoI reductions at potentials measured by CV, which also allowed, in the case of dinuclear complex 1, the detection of electronic communication between the Co centers through the chloride bridging ligands. The electrochemical behavior of models of 1 and 2 were also investigated by density functional theory (DFT) methods, which indicated that the vertical oxidation of 1 and 2 (that before structural relaxation) affects mostly the chloride and pyrazolyl ligands, whereas adiabatic oxidation (that after the geometry relaxation) and reduction are mostly metal centered. Compounds 1 and 2 and, for comparative purposes, other related scorpionate and pyrazole cobalt complexes, exhibit catalytic activity for the peroxidative oxidation of cyclohexane to cyclohexanol and cyclohexanone under mild conditions (room temperature, aqueous H2O2). In situ X-ray absorption spectroscopy studies indicated that the species derived from complexes 1 and 2 during the oxidation of cyclohexane (i.e., Ox- 1 and Ox- 2, respectively) are analogous and contain a CoIII site. Complex 2 showed low in vitro cytotoxicity toward the HCT116 colorectal carcinoma and MCF7 breast adenocarcinoma cell lines. [ABSTRACT FROM AUTHOR]

The compounds [mPTA][CoCl4] ( 1, mPTA = N-methyl-1,3,5-triaza-7-phosphaadamantane cation), [CoCl(H2O)(DION)2][BF4] ( 2, DION = 1,10-phenanthroline-5,6-dione), [Zn(DION)2]Cl2 ( 3) and [ZnCl(κ O-PTA=O)(DION)][BF4] ( 4) were synthesized by reaction of CoCl2 with [mPTA]I or DION and ZnCl2 with DION or 1,3,5-triaza-7-phosphaadamantane-7-oxide (PTA=O) and DION, respectively. All complexes are water soluble and have been characterized by IR, far-IR, 1H, 13C and 31P{1H} NMR spectroscopy, ESI-MS, elemental analyses and single-crystal X-ray diffraction structural analysis (for 1). They were screened against the human tumour cell lines HCT116, HepG2 and MCF7. Complexes 2 and 3 exhibit the highest in vitro cytotoxicity and show lower cytotoxic activities in normal human fibroblast cell line than in HCT116 tumour cell line, which demonstrates their slight specificity for this type of tumour cell. [ABSTRACT FROM AUTHOR]

Nano-in-Micro Sildenafil Dry Powder Formulations for the Treatment of Pulmonary Arterial Hypertension Disorders: The Synergic Effect of POxylated Polyurea Dendrimers, PLGA, and Cholesterol B 2020 b , I 37 i , 1900447 In the originally published manuscript, the author Márcia T. Tavares was omitted. The author is hereby added in the author byline and is associated with the first affiliation. [Extracted from the article]

Abstract: Invited for the cover of this issue are the groups of Laura Rodríguez, Alexandra R. Fernandes, João Carlos Lima, Pedro V. Baptista, and Kari Rissanen at the Universitat de Barcelona, Universidade Nova de Lisboa, and University of Jyväskylä. The image depicts the direct effect of the phosphine on the different biological activity of Au(I) complexes. Read the full text of the article at 10.1002/chem.201802547. [ABSTRACT FROM AUTHOR]

The Cover Feature shows engineered nano‐in‐microparticles specially designed for inhalation chemotherapy. The dry powder formulations, produced by supercritical CO2‐assisted co‐atomization of chitosan and polyurea dendrimers, deliver anticancer drugs to the deep lung. More information can be found in the Full Paper by R. B. Restani et al. on page 772 in Issue 10, 2018 (DOI: 10.1002/open.201800093). [ABSTRACT FROM AUTHOR]