Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.     

Obesity and Male Reproduction: Do Sirtuins Play a Role?

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.     

Myo-Inositol Limits Kainic Acid-Induced Epileptogenesis in Rats

Epilepsy is a severe neurological disease characterized by spontaneous recurrent seizures (SRS). A complex pathophysiological process referred to as epileptogenesis transforms a normal brain into an epileptic one. Prevention of epileptogenesis is a subject of intensive research. Currently, there are no clinically approved drugs that can act as preventive medication. Our previous studies have revealed highly promising antiepileptogenic properties of a compound–myo-inositol (MI) and the present research broadens previous results and demonstrates the long-term disease-modifying effect of this drug, as well as the amelioration of cognitive comorbidities. For the first time, we show that long-term treatment with MI: (i) decreases the frequency and duration of electrographic SRS in the hippocampus; (ii) has an ameliorating effect on spatial learning and memory deficit associated with epileptogenesis, and (iii) attenuates cell loss in the hippocampus. MI treatment also alters the expression of the glial fibrillary acidic protein, LRRC8A subunit of volume-regulated anion channels, and protein tyrosine phosphatase receptor type R, all expected to counteract the epileptogenesis. All these effects are still present even 4 weeks after MI treatment ceased. This suggests that MI may exert multiple actions on various epileptogenesis-associated changes in the brain and, therefore, could be considered as a candidate target for prevention of epileptogenesis.     

Azacrown Ethers with Naphthyl Branches. Fluorescence Properties,Protonation and Metal Coordination

Starting from 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane, we have prepared two compounds by replacing the amine hydrogens with naphthyl or 3,5-bis(2′-oxymethylnaphthyl)benzyl units. The absorption and emission spectra of compounds 2 (N,N′-bis(2-naphthylmethyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane) and 3 (N,N′-bis[3,5-bis(2′-oxymethylnaphthyl)benzyl]-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane) have been studied in CH₃CN:CH₂Cl₂ 1:1 (v/v) solution. For comparison purposes, the spectroscopic properties of N-methyl(2-methylnaphthalene)ethylamine (1) have also been investigated. For each compound, the absorption spectra are qualitatively very similar to that of naphthalene, with molar absorption coefficients as expected for the presence of one (1), two (2), and four (3) naphthyl chromophoric groups. The fluorescence spectra, however, are quite different from that of naphthalene. The naphthalene-type fluorescence (λ_max = 337 nm) is strongly quenched, particularly for compounds 1 and 2 which also exhibit a broad emission band in the visible region (λ_max ≈ 480 nm) assigned to a low lying charge-transfer excited state. In the case of compound 3, a quenched naphthalene-type band is accompanied by weak exciplex and excimer emissions. Upon titration with CF₃SO₃H, the charge transfer bands of 1 and 2 and the exciplex emission of 3 disappear and the naphthalene-type bands regain intensity. Titration plots show that in compounds 2 and 3 the protonation of the two nitrogens occurs stoichiometrically in two distinct steps. Titration with Zn²⁺ gives rise to 2.Zn²⁺ and 3.Zn²⁺ complexes. This article is dedicated to Professor Dedier Astruc.     

Crystalline structures of intercalate molecular complexes of syndiotactic polystyrene with two fluorescent guests: 1,3,5-Trimethyl-benzene and 1,4-dimethyl-naphthalene

The crystal structures of two molecular complex phases of syndiotactic polystyrene (s-PS) with 1,3,5-trimethyl-benzene (TMB) and 1,4-dimethyl-naphthalene (DMN) have been described. These structures present a monoclinic unit cell in which the s(2/1)2 polymer helices and guest molecules are packed according the space group P2₁/a and unit cell constants: a=17.3 Å, b=15.4 Å, c=7.8 Å and γ=95.7° for s-PS/TMB and a=17.4 Å, b=17.2 Å, c=7.8 Å and γ=116.4° for s-PS/DMN. Both structures can be described as intercalates, since they present ac layers of polymer helices alternated to layers of contiguous guest molecules and a guest/monomeric-unit molar ratio of 1/2, as recently observed only for s-PS/norbornadiene molecular complex. On the basis of a comparison between crystalline structures and X-ray diffraction data of several s-PS molecular complexes, a simple criterion to anticipate their clathrate or intercalate nature has been suggested.     

模拟嵌入式FRP条增强钢筋混凝土梁抗剪的三维力学模型

嵌入式FRP增强钢筋混凝土梁抗剪是进行结构修复的新技术,由于嵌入式FRP所具有的一些优势,使其成为较好的外贴加固技术,越来越受到重视。嵌入式FRP主要优势在于材料开发、对结构完整性的保护以及相对较快的适用性。由于FRP条复杂的几何尺寸,粘结后的非线性力学性能,混凝土受拉性能的离散性,使得嵌入式FRP条加固的性能十分复杂,一般通过试验来获得其性能。为更好地掌握表面嵌贴FRP带的性能,提出三维力学模型,用于模拟在相似加载过程中,嵌入式FRP条体系对钢筋混凝土梁抗剪强度的贡献。模型很好地解释了试验结果,并在模型中考虑了粘结滑移力和混凝土破坏之间的相互作用以及相邻FRP条之间的相互作用等复杂现象。     

Dietary krill oil increases docosahexaenoic acid and reduces 2-arachidonoylglycerol but not N-acylethanolamine levels in the brain of obese Zucker rats

Evidence suggests that dietary long chain polyunsaturated fatty acids (LCPUFAs), and particularly those belonging to the n-3 family, may influence the brain fatty acid profile and, thereby, the biosynthesis of endocannabinoids in rodents. However, the doses used are usually quite high and not comparable with human intake. Recently, we have shown that relatively low doses of dietary n-3 LCPUFAs (4 weeks), in the form of either fish or krill oil, balanced for EPA and DHA content, and against a control diet with no EPA and DHA and similar contents of oleic, linoleic and α-linolenic acids, lower the concentrations of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in the visceral adipose tissue, and of AEA in the liver and heart, of obese Zucker rats. This, in turn, is associated with lower levels of arachidonic acid in membrane phospholipids and with amelioration of some metabolic syndrome parameters. We investigated here whether in Zucker rats, under the same conditions, fish and krill oil are also able to influence LCPUFA and endocannabinoid profiles in brain. Only krill oil was able to increase significantly DHA levels in brain phospholipids, with no changes in arachidonic acid. DHA increase was associated with lower levels of 2-AG in the brain, whereas AEA and its congeners, N-palmitoylethanolamine and N-oleoylethanolamine, were unchanged. We conclude that, despite the strong impact of dietary n-3 fatty acid on endocannabinoid levels previously observed in peripheral tissues, in the brain only 2-AG is affected by dietary krill oil, suggesting that the beneficial effect of the latter on the metabolic syndrome is mostly exerted by modifying peripheral endocannabinoids. Nevertheless, possible effects of dietary krill oil in the brain through modification of 2-AG levels deserve further investigation.     

Profiling selected phytochemicals and nutrients in different tissues of the multipurpose tree Moringa oleifera L., grown in Ghana

The purpose of this new study was to determine the types and levels of major phytochemicals (non-nutrients) and nutrients in the different tissues from vegetative and flowering Moringa oleifera L. an important multipurpose crop. Rhamnose and acetyl-rhamnose-substituted glucosinolates were found in all of the M. oleifera tissues with different profiles depending on the tissue. In addition the tissues of M. oleifera had a relatively complex flavonoid profile consisting of glucosides, rutinosides, malonylglucosides and traces of acetylglucosides of kaempferol, quercetin and isorhamnetin. Fatty acid profiling of the different tissues showed that leaves were rich in palmitic (16:0) and linolenic (18:3) acid whereas seeds were predominated by oleic acid (18:1). Roots were rich in palmitic and oleic acid, whereas stems and twigs predominately contained palmitic acid. Potassium, magnesium and calcium were the predominant minerals in all of the tissues. Low levels of selenium were detected only in whole seeds.