Delicate interplay between the D0D?0, ρ0J/ψ, and ωJ/ψ channels in the X(3872) resonance

The nature of the X(3872) enhancement is analyzed in the framework of the Resonance-Spectrum Expansion, by studying it as a regular J ^PC =1⁺⁺ charmonium state, though strongly influenced and shifted by open-charm decay channels. The observed but Okubo–Zweig–Iizuka-forbidden ρ ⁰ J/ψ and ωJ/ψ channels are coupled as well, but effectively smeared out by using complex ρ ⁰ and ω masses, in order to account for their physical widths, followed by a rigorous algebraic procedure to restore unitarity. A very delicate interplay between the D ⁰ D ^∗0, ρ ⁰ J/ψ, and ωJ/ψ channels is observed. The data clearly suggest that the X(3872) is a very narrow axial-vector c[`(c)]c\bar{c} resonance, with a pole at or slightly below the D ⁰ D ^∗0 threshold.     

Portuguese Propolis Antitumoral Activity in Melanoma Involves ROS Production and Induction of Apoptosis

Melanoma is the most aggressive and life-threatening skin cancer type. The melanoma genome is the most frequently mutated, with the BRAF mutation present in 40–60% of melanoma cases. BRAF-mutated melanomas are characterized by a higher aggressiveness and progression. Adjuvant targeted treatments, such as BRAF and MEK inhibitors, are added to surgical excision in BRAF-mutated metastatic melanomas to maximize treatment effectiveness. However, resistance remains the major therapeutic problem. Interest in natural products, like propolis, for therapeutic applications, has increased in the last years. Propolis healing proprieties offer great potential for the development of novel cancer drugs. As the activity of Portuguese propolis has never been studied in melanoma, we evaluated the antitumoral activity of propolis from Gerês (G18.EE) and its fractions (n-hexane, ethyl acetate (EtOAc), and n-butanol) in A375 and WM9 melanoma cell lines. Results from DPPH•/ABTS• radical scavenging assays indicated that the samples had relevant antioxidant activity, however, this was not confirmed in the cell models. G18.EE and its fractions decreased cell viability (SRB assay) and promoted ROS production (DHE/Mitotracker probes by flow cytometry), leading to activation of apoptotic signaling (expression of apoptosis markers). Our results suggest that the n-BuOH fraction has the potential to be explored in the pharmacological therapy of melanoma.     

Midkine Interaction with Chondroitin Sulfate Model Synthetic Tetrasaccharides and Their Mimetics: The Role of Aromatic Interactions

Midkine (MK) is a neurotrophic factor that participates in the embryonic central nervous system (CNS) development and neural stem cell regulation, interacting with sulfated glycosaminoglycans (GAGs). Chondroitin sulfate (CS) is the natural ligand in the CNS. In this work, we describe the interactions between a library of synthetic models of CS-types and mimics. We did a structural study of this library by NMR and MD (Molecular Dynamics), concluding that the basic shape is controlled by similar geometry of the glycosidic linkages. Their 3D structures are a helix with four residues per turn, almost linear. We have studied the tetrasaccharide-midkine complexes by ligand observed NMR techniques and concluded that the shape of the ligands does not change upon binding. The ligand orientation into the complex is very variable. It is placed inside the central cavity of MK formed by the two structured beta-sheets domains linked by an intrinsically disordered region (IDR). Docking analysis confirmed the participation of aromatics residues from MK completed with electrostatic interactions. Finally, we test the biological activity by increasing the MK expression using CS tetrasaccharides and their capacity in enhancing the growth stimulation effect of MK in NIH3T3 cells.     

Brønsted Acid-Catalysed Dehydrative Substitution Reactions of Alcohols

The direct, catalytic dehydrative substitution of alcohols is a challenging, yet highly desirable process in the development of more sustainable approaches to organic chemistry. This review outlines recent advances in Brønsted acid-catalysed dehydrative substitution reactions for C−C, C−O, C−N and C−S bond formation. The wide range of processes that are now accessible using simple alcohols as the formal electrophile are highlighted, while current limitations and therefore possible future directions for research are also discussed.     

Low Pre-Transplant Caveolin-1 Serum Concentrations Are Associated with Acute Cellular Tubulointerstitial Rejection in Kidney Transplantation

Acute and chronic transplant rejections due to alloreactivity are essential contributors to graft loss. However, the strength of alloreactivity is biased by non-immunological factors such as ischemia reperfusion injury (IRI). Accordingly, protection from IRI could be favorable in terms of limiting graft rejection. Caveolin-1 (Cav-1) is part of the cell membrane and an important regulator of intracellular signaling. Cav-1 has been demonstrated to limit IRI and to promote the survival of a variety of cell types including renal cells under stress conditions. Accordingly, Cav-1 could also play a role in limiting anti-graft immune responses. Here, we evaluated a possible association between pre-transplant serum concentrations of Cav-1 and the occurrence of rejection during follow-up in a pilot study. Therefore, Cav-1-serum concentrations were analyzed in 91 patients at the time of kidney transplantation and compared to the incidence of acute and chronic rejection. Higher Cav-1 levels were associated with lower occurrence of acute cellular tubulointerstitial rejection episodes.     

Selective Cytotoxicity of Portuguese Propolis Ethyl Acetate Fraction towards Renal Cancer Cells

Renal cell carcinoma is the most lethal cancer of the urological system due to late diagnosis and treatment resistance. Propolis, a beehive product, is a valuable natural source of compounds with bioactivities and may be a beneficial addition to current anticancer treatments. A Portuguese propolis sample, its fractions (n-hexane, ethyl acetate, n-butanol and water) and three subfractions (P1–P3), were tested for their toxicity on A498, 786-O and Caki-2 renal cell carcinoma cell lines and the non-neoplastic HK2 kidney cells. The ethyl acetate fraction showed the strongest toxicity against A498 (IC₅₀ = 0.162 µg mL⁻¹) and 786-O (IC₅₀ = 0.271 µg mL⁻¹) cells. With similar toxicity against 786-O, P1 (IC₅₀ = 3.8 µg mL⁻¹) and P3 (IC₅₀ = 3.1 µg mL⁻¹) exhibited greater effect when combined (IC₅₀ = 2.5 µg mL⁻¹). Results support the potential of propolis and its constituents as promising coadjuvants in renal cell carcinoma treatment.     

The Conformations of Isolated Gallic Acid: A Laser-Ablation Rotational Study

The rotational spectrum of laser-ablated gallic acid has been recorded using CP-FTMW spectroscopy. Two rotamers have been detected, and their rotational spectra have been assigned and analyzed to obtain the molecular spectroscopic parameters. The observed rotamers have been unambiguously identified in the light of theoretical computations, based on the comparison of the experimental line intensities and rotational parameters with the rotational constants and electric dipole moments predicted from theoretical calculations. The values of the planar inertial moments confirm that the observed conformers are planar, and their relative stability and population have been determined from relative intensity measurements. The B3LYP-D3/6-311++G(2d,p) level has been shown to be the best method among a series of levels normally used to predict the rotational parameters in rotational spectroscopy. In the observed conformers, the three adjacent OH groups are arranged in a sequential form, and the only difference between them lies in the orientation of the COOH group. Although weak attractive OH···O interactions seem to exist, the analysis of the electron density topology does not show the existence of any critical point corresponding to these interactions.     

Stereocontrolled synthesis of (S)-9-cis-4-oxo-13,14-dihydroretinoic acid

(S)-9-cis-4-Oxo-13,14-dihydroretinoic acid (S)-1, a new major endogenous vitamin A metabolite that activates retinoic acid receptor signaling both in vitro and in vivo, has been synthesized stereoselectively by Horner–Wadsworth–Emmons condensation and Stille cross-coupling as bond forming reactions.     

Determination of memantine in plasma and vitreous humour by HPLC with precolumn derivatization and fluorescence detection

A new HPLC procedure with precolumn derivatization and rimantadine as the internal standard for determining memantine, a candidate agent for the treatment of glaucoma in plasma and vitreous humour, has been developed and validated. Precolumn derivatization was performed with 9-fluorenylmethyl-chloroformate-chloride (FMOC-Cl) as the derivatization reagent and followed by a liquid-liquid extraction with n-hexane. Optimal conditions for derivatization were an FMOC-Cl concentration of 1.5 mM, a reaction time of 20 min, the temperature at 30°C, the borate buffer pH 8.5, and a borate buffer-acetonitrile ratio of 1:1. The derivatives were analyzed by isocratic HPLC with the fluorescence detector λex 260 nm λem 315 nm on a Novapack C(18) reversed-phase column with a mobile phase of acetonitrile-water (73:27, v/v), 40°C, and a flow rate of 1.2 mL/min. The linear range was 10-1000 ng/mL with a quantification limit of ～ 10 ng/mL for both types of samples. This analytical method may be suitable for using in ocular availability studies.     

Diels-Alder reactions of 3-(1H-tetrazol-5-yl)-nitrosoalkenes: synthesis of functionalized 5-(substituted)-1H-tetrazoles

A general route to 1,2-oxazines and open chain oximes bearing a 1H-tetrazolyl substituent via Diels-Alder reaction of 3-(tetrazol-5-yl)-nitrosoalkenes is reported. It was also demonstrated that reduction of these adducts followed by deprotection of the tetrazolyl group give 5-(1-aminoalkyl)-1H-tetrazoles, α-amino acid analogues.