Pharmacological and Therapeutic Properties of Punica granatum Phytochemicals: Possible Roles in Breast Cancer

Background: Pomgranate (Punica granatum) represents a high source of polyphenols with great bioavailability. The role of this fruit in the prevention and treatment of various malignant pathologies has been long time cited in both scientific and non-scientific literature, making thus important to identify its involvement in the pathophysiological processes. The treatment for breast cancer had focused on the inhibition of the mechanisms that governs the estrogen activity. These mechanisms are covered either by the antagonism of the estrogen receptor (ER) or by the inhibition of the estrogen synthesis. Our interest in identifying a bioactive compound rich in polyphenols, which induces both the antagonism of the estrogen receptor, and the inhibition of the estrogen synthesis, revealed us the pomegranate fruit and its derivatives: peel and seeds. Pomegranates’ chemical composition include many biological active substances such as flavonols, flavanols, anthocyanins, proanthocyanidins, ellagitannins and gallotannins. Materials and Methods: We performed a review of the scientific literature by using the following keywords: “pomegranate”, “breast cancer”, “Punica granatum”, “pomegranate polyphenols”. Our search was performed in the PubMed and Google Scholar databases, and it included only original research written in English from the last 20 years. None of the articles were excluded due to affiliation. A total number of 28 original papers, which mentioned the beneficial activity of pomegranate against breast cancer, were selected. Both clinical and preclinical studies were considered for this review. Results: Recent discoveries pointed out that polyphenols from Punica granatum possess strong anti-cancer activity, exhibited by a variety of mechanisms, such as anti-estrogenic, anti-proliferative, anti-angiogenetic, anti-inflammatory, and anti-metastatic. Pomegranate extracts induced cell cycle arrest in the G0/G1 phase, and induced cytotoxicity in a dose- and time-dependent manner. Moreover, several polyphenols extracted from pomegranate inhibited the invasion potential, migration and viability of breast cancer cells. The effects of pomegranate juice on serum estrogens and other sexual hormones levels were also investigated on two human cohorts. Conclusions: Punica granatum represents a promising area in oncology. The large availability and low cost, associated with the lack of side effects, made from this natural product a great strategy for the management of breast cancer. There are several mechanistic studies in mouse models and in breast cancer cell lines, suggesting the possible pathways through which polyphenols from pomegranate extracts act, but larger and better-controlled studies are necessary in the future. Only two small clinical trials were conducted on humans until now, but their results are contradictory and should be considered preliminary.     

Comparison of two methods for 14C analysis from essential oils using LSC

Natural essential oil sample obtained from basil (Ocinum basilicum), and ethanol sample obtained from wine were measured to determine ¹⁴C specific activity, using two different sample preparation methods, and liquid scintillation counting method. The paper describes the use of two preparation methods, direct measurement method and CO₂ absorption method, and the results obtained for this comparative study. Depending on carbon content of the sample and bubbling time, different correction factors of carbon mass trapped in liquid scintillation cocktail were established for CO₂ absorption method.

     

Occurence of an octanuclear motif of uranyl isophthalate with cation-cation interactions through edge-sharing connection mode

An uranyl isophthalate has been hydrothermally synthesized at 200 °C for 24 h, from a mixture of uranyl nitrate, isophthalic acid, and hydrazine in water. It was characterized by single-crystal analysis [triclinic, P ?1, a = 7.3934(3) ?, b = 13.3296(5) ?, c = 15.4432(5) ?, α = 111.865(2)°, β = 90.637(2)°, γ = 104.867(2)°, V = 1355.49(9) ?(3)] and different spectroscopic techniques (Raman, IR-ATR, UV-visible). The 3D structure of the phase (UO(2))(8)O(2)(OH)(4)(H(2)O)(4)(1,3-bdc)(4)·4H(2)O (1,3-bdc = 1,3-benzenedicarboxylate) reveals octanuclear units based on the association of 7-fold coordinated uranyl cations (pentagonal bipyramid) involving a rare case of cation-cation interaction together with edge-sharing polyhedral connection mode. UV-visible absorption spectroscopy confirmed that uranium was only involved in the structure as uranyl forms (excluding the presence of tetravalent or pentavalent uranium). Additionally, μ-Raman and IR-ATR experiments allowed assigning four uranyl contributions to the four types of uranyl entities in the structure, in agreement with the XRD analysis.     

A BPTTF-based self-assembled electron-donating triangle capable of C60 binding

A kinetically stable self-assembled redox-active triangle is isolated. The resulting electron-donating cavity, which incorporates three BPTTF units, exhibits a remarkable binding ability for electron-deficient C(60), supported by a favorable combination of structural and electronic features.     

Series of mixed uranyl-lanthanide (ce, nd) organic coordination polymers with aromatic polycarboxylates linkers

Three series of mixed uranyl-lanthanide (Ce or Nd) carboxylate coordination polymers have been successfully synthesized by means of a hydrothermal route using either conventional or microwave heating methods. These compounds have been prepared from mixtures of uranyl nitrate, lanthanide nitrate together with phthalic acid (1,2), pyromellitic acid (3,4), or mellitic acid (5,6) in aqueous solution. The X-ray diffraction (XRD) single-crystal revealed that the phthalate complex (UO(2))(4)O(2)Ln(H(2)O)(7)(1,2-bdc)(4)·NH(4)·xH(2)O (Ln = Ce(1), Nd(2); x = 1 for 1, x = 0 for 2), is based on the connection of tetranuclear uranyl-centered building blocks linked to discrete monomeric units LnO(2)(H(2)O)(7) via the organic species to generate infinite chains, intercalated by free ammonium cations. The pyromellitate phase (UO(2))(3)Ln(2)(H(2)O)(12)(btec)(3)·5H(2)O (Ce(3), Nd(4)) contains layers of monomeric uranyl-centered hexagonal and pentagonal bipyramids linked via the carboxylate arms of the organic molecules. The three-dimensionality of the structure is ensured by the connection of remaining free carboxylate groups with isolated monomeric units LnO(2)(H(2)O)(7). The network of the third series (UO(2))(2)(OH)Ln(H(2)O)(7)(mel)·5H(2)O (Ce(5), Nd(6)) is built up from dinuclear uranyl units forming layers through connection with the mellitate ligands, which are further linked to each other through discrete monomers LnO(3)(H(2)O)(6). The thermal decomposition of the various coordination complexes led to the formation of mixed uranium-lanthanide oxide, with the fluorite-type structure at 1500 °C (for 1, 2) or 1400 °C for 3-6. Expected U/Ln ratio from the crystal structures were observed for compounds 1-6.     

Binary adduct formation of desipramine with dicarboxylic acids

This paper presents the results obtained in a screening study for binary adduct formation of desipramine with three dicarboxylic acids—namely succinic, malonic and glutaric acids. Adduct formation is important because most tricyclic antidepressants show limited water solubility as free bases. Three binary adducts were prepared using a wet kneading method in non-homogenous media in presence of ethanol. Investigations of the solid state (ATR-FTIR, PXRD) and thermal analysis (TG/DTG/HF) were used for characterization of the prepared samples. The corroboration of data from employed instrumental techniques suggests that binary adducts in molar ratio 1:1 were obtained under the used experimental conditions.     

Synthesis, inclusion capabilities, and electrical properties of some asymmetrical cyclophanes

For the first time, we announce the synthesis of cyclo(bis-paraquat-p-phenylene-p-phenylene-carbonyl)tetrakis(hexafluorophosphate), named ‘CETOBOX’. This compound exists in three tautomeric forms. These forms were evidenced by NMR data (¹H NMR, TOCSY, COSY, and NOESY), UV-vis spectra coupled with pH measurements, and by synthesis. As the ‘CETOBOX’ gives ‘in situ’ only the corresponding monoylide, the synthesis of a new fluorescent indolizine cyclophane has been performed by a 3+2 cycloaddition. This cycloadduct, in an amidation reaction with 6-amino-β-cyclodextrin, furnishes the final two-cavity sensor with good yields. All structures of the new compounds presented herein have been established by NMR spectroscopy. Also, theoretical methods (MM3, AM1, AM1 (COSMO), and B88LYPDFT) have been used to determine the most stable conformer structures. For the fluorescent indolizine cycloadduct, we evaluated its inclusion capabilities and for the two-cavity sensor, we measured some of its electrical properties that make it suitable for use in VOCs detection and energy conversion.     

Mixed oxide growth on combinatorial aluminium–gadolinium alloys — a thermodynamic and first-principles approach

Metal surfaces covered with oxides have attracted considerable scientific attention in various applications. In particular, anodic films fabricated by cost-effective anodizing have been widely used in nano-structured engineering to provide various surface functionalities. However, understanding of alloy film stability, having individual elements with widely varying structures and morphologies, is very limited due to lack of thermodynamic information and effects of electrolyte chemistry. This requires many tedious efforts on a trial and error basis in selecting suitable electrolytes that can produce the protective film at high efficiency on alloys having mixed chemistries. It is, therefore, crucial to develop a combination of high throughput theoretical analysis and automated rapid localized electrochemical probing that provides a fast and simple solution for electrolyte choice and paves the way to the remarkable expansion of industrial applications of oxides. Herein, we demonstrate that combinatorial Al–Gd alloys covering 1.0 to 10.0 at.% Gd can be oxidized into ultra-thin anodic films of controlled thickness through a selection of electrolyte based on thermodynamics (phosphate buffer with a pH of 8.20). We propose that growth of anodic films on alloys at high efficiency is possible if Gibbs free energy minimization criteria would be systematically contemplate.

Graphical abstract

     

Asymptotic stability of a mathematical model of cell population

We consider a simplified system of a growing colony of cells described as a free boundary problem. The system consists of two hyperbolic equations of first order coupled to an ODE to describe the behavior of the boundary. The system for cell populations includes non-local terms of integral type in the coefficients. By introducing a comparison with solutions of an ODE's system, we show that there exists a unique homogeneous steady state which is globally asymptotically stable for a range of parameters under the assumption of radially symmetric initial data.