Countering circumvention of restrictive measures: The EU response

Restrictive measures are always complemented by an “anti-circumvention clause” which prohibits participation in activities the object or effect of which is to circumvent EU provisions. This clause plays a key role in ensuring the effectiveness of sanctions and, ultimately, the objectives of EU external action. This article intends to shed light on the obligations arising from the anti-circumvention clause, with a specific focus on financial restrictive measures against designated individuals (which essentially entail asset freeze measures against them). First, the scope of the anti-circumvention clause under EU law is defined. Second, the actors involved in uncovering and countering circumvention practices within the territory of the Union are presented, illustrating the central role of the Member States in coordinating national and supranational efforts to ensure compliance with EU restrictive measures, through constant dialogue and cooperation with financial operators and the European Commission. Third, one specific circumvention strategy is explored, namely circumvention through family members. More precisely, the article investigates whether there is a presumption of circumvention when family members are involved. To this end, it considers the case law of the ECJ on the legality of family members’ designations under EU sanctions. Throughout the analysis, the article emphasizes how the exceptional circumstances in relation to the war in Ukraine have progressively changed the design of EU restrictive measures as well as the commitment of the Union to tackle circumvention. In this context, the unprecedented emphasis on circumvention is complemented by the Union’s unprecedented desire to resort to criminal enforcement. Accordingly, the effectiveness of EU restrictive measures has become a call for effective criminal enforcement. The article, however, argues that this may not be the most appropriate choice

Metabolic Syndrome and Inflammatory Cytokines in Psoriasis.

Obesity negatively affects the pathological states of chronic inflammation, such as Psoriasis and Psoriatic Arthritis. The inflammatory cytokines released by the adipose tissue determine, in addition to inflammation, a condition of insulin resistance, which is also a comorbidity of psoriasis. The state of chronic inflammation unites both psoriasis and obesity. The first is an autoimmune skin disease, where very thick skin layers are evident due to an abnormal proliferation of keratinocytes; obesity, on the other hand, represents one of the possible comorbidities of psoriasis the simultaneous presence in the same subject of two or more diseases

Target Therapy in Cancer Treatment: mPGES-1 and PARP

Target therapy is an approach focusing on specific protein or signaling pathways. This therapy is directly aimed to a molecular target such as a receptor, growth factor or enzyme in cancer cells. These targets are used by the tumor cells themselves to obtain uncontrolled proliferation, resistance to traditional therapies and to increase the number of blood vessels in the tissue of origin (neoangiogenesis). A purpose of target therapy may be to counteract the growth and proliferation of cancer cells through the use of drugs or monoclonal antibodies capable of inhibiting the receptor for the epidermal growth factor (EGFR), that is crucial in the process of neo-angiogenesis, protein kinases (PKs), as regulators of cell growth signals and human epidermal growth factor type 2 (HER2), which is essential in stimulating growth and proliferation of cancer cells. Among anticancer drugs, Bevacizumab, a humanised monoclonal antibody produced by recombinant DNA technique, is used for the first-line treatment of metastatic breast cancer, as it inhibits EGFR and the vascular endothelial cell growth factor (VEGF). Abemaciclib, a protein kinase inhibitor drug, is also used for the treatment of the same cancer. In 20-30% of primary breast tumors, the excessive expression of HER2 is observed; thus, HER2 inhibitors may represent another plausible therapy. A potent HER2 inhibitor is the recombinant humanized igG1 monoclonal antibody Trastuzumab, which was first tested in 1992 and is currently used for the treatment of HER2 positive breast cancer. Unfortunately, despite the numerous advances in finding new therapies, patients treated with these drugs often suffer from severe undesirable side effects. Therefore, the search for new therapeutic targets may be desirable. In this paper we analyse particularly two targets studied quite recently: the microsomal prostaglandin E2 synthase type 1 (mPGES-1) and poly (ADP-ribose) polymerase (PARP) proteins

NUTRACEUTICAL FUNCTIONS OF GREEN TEA

Today, the diffusion of neoplastic diseases is a widespread phenomenon. Thus, it is always necessary to identify new molecules able to fight them. In this paper, we will deal with the interesting antineoplastic properties of green tea. We will describe the different and plausible anticancer mechanisms of epigallocatechin gallate (EGCG), the major polyphenol found in green tea, and in particular the biochemical and computational discovery of a new target for the treatment of this disease will be discussed. The bio-active substances present in tea are essentially represented by methylxanthines, as well as by the antioxidant phenolic fraction (flavonoids). Among the other active substances contained in lower concentrations there are vitamins (B, C and K), amino acids (L-theanine) and minerals (aluminium and manganese). Tea extracts, particularly EGCG, could represent the starting point for the potential emergence of new drugs for the treatment of neoplastic diseases. Other activities of tea, as the involvement in neurodegenerative diseases prevention, as well as the antioxidant, antibacterial, antifungal and antiviral effects, will be also briefly described

NUTRACEUTICAL FUNCTIONS OF GREEN TEA

Today, the diffusion of neoplastic diseases is a widespread phenomenon. Thus, it is always necessary to identify new molecules able to fight them. In this paper, we will deal with the interesting antineoplastic properties of green tea. We will describe the different and plausible anticancer mechanisms of epigallocatechin gallate (EGCG), the major polyphenol found in green tea, and in particular the biochemical and computational discovery of a new target for the treatment of this disease will be discussed. The bio-active substances present in tea are essentially represented by methylxanthines, as well as by the antioxidant phenolic fraction (flavonoids). Among the other active substances contained in lower concentrations there are vitamins (B, C and K), amino acids (L-theanine) and minerals (aluminium and manganese). Tea extracts, particularly EGCG, could represent the starting point for the potential emergence of new drugs for the treatment of neoplastic diseases. Other activities of tea, as the involvement in neurodegenerative diseases prevention, as well as the antioxidant, antibacterial, antifungal and antiviral effects, will be also briefly described

Vitamin D in the Prevention, Development and Therapy of Oncological Diseases.

Vitamin D, traditionally known as a fat-soluble essential vitamin, is a precursor of a powerful steroid hormone that regulates a broad spectrum of physiological processes. In addition to its fundamental role in bone metabolism, epidemiological, preclinical and cellular researches in recent decades have revealed that vitamin D can play a considerable role in the prevention of some pathologies, including extra-skeletal ones, such as neoplasms. Vitamin D, as a prohormone, undergoes first hepatic and subsequently renal metabolism to produce a biologically active metabolite, calcitriol or 1α,25-dihydroxyvitamin D or (1,25 (OH)2D), which binds the vitamin D receptor by regulating the expression of several genes involved in bone metabolism and other biological functions. Furthermore, recent studies have revealed that vitamin D can be also metabolized and activated through a non-canonical metabolic pathway catalyzed by CYP11A1, the gene encoding the cholesterol side chain cleavage enzyme or P450scc. The metabolites of vitamin D deriving from the CYP11A1 enzyme have shown antiproliferative and anti-inflammatory activities and are able to promote the differentiation process on neoplastic cells in comparable way or better than calcitriol, thus contributing to its tumor preventive effect. Clinical data have demonstrated that vitamin D has anticancer activity against prostate, colon, and breast cancers. Several molecular mechanisms of vitamin D involved in tumor etiopathogenesis have been proposed that have not yet been fully clarified. Vitamin D may play a key role in preventing the early stage of the neoplastic process by exerting anti-inflammatory, antioxidant defenses and inducing enzymes responsible for repairing DNA damage and could also be involved in mechanisms of inhibition of cell proliferation, induction of cell differentiation, and cell death. In addition, some studies indicate various mechanisms through which vitamin D can quantitatively and qualitatively influence the intestinal microbiota, strongly linked to chronic inflammatory bowel diseases and the development of colon cancer. However, the metabolism and functions of vitamin D are dysregulated in some neoplasms which therefore develop resistance to the antiproliferative effect of vitamin D, and this promotes tumor development and progression. In this review, studies regarding vitamin D in relation to its activity in cancer have been summarized, as long as the metabolic pathways described for vitamin D

CGRP Antagonism and Ketogenic Diet in the Treatment of Migraine

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy

Natural Products for the Prevention, Treatment and Progression of Breast Cancer

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy

Genetic investigations on 8 patients affected by ring 20 chromosome syndrome

<p>Abstract</p> <p>Background</p> <p>Mosaic Chromosome 20 ring [r(20)] is a chromosomal disorder associated with a rare syndrome characterized by a typical seizure phenotype, a particular electroclinical pattern, cognitive impairment, behavioural problems and absence of a consistent pattern of dysmorphology. The pathogenic mechanism underlying seizures disorders in r(20) syndrome is still unknown. We performed a detailed clinical and genetic study on 8 patients with r(20) chromosome, aimed at detecting the genetic mechanism underlying r(20) syndrome.</p> <p>Methods</p> <p>We submitted 8 subjects with a previous diagnosis of ring 20 chromosome mosaicism to a clinical re-evaluation, followed by cytogenetic, FISH, array-CGH and molecular analyses. The genetic study was also extended to their available parents.</p> <p>Results</p> <p>FISH and array-CGH experiments indicate that cryptic deletions on chromosome 20 are not the cause of the r(20) chromosome associated disease. Moreover, no evidence of chromosome 20 uniparental disomy was found. Analysis of FISH signals given by variant in size alphoid tandem repeats probes on the normal chromosome 20 and the r(20) chromosome in the mosaic carriers suggests that the r(20) chromosome is the same chromosome not circularized in the "normal" cell line.</p> <p>Conclusions</p> <p>Higher percentages of r(20) chromosome cells were observed to be related with precocious age at seizure onset and with resistance to antiepileptic drug treatment. Behavioural problems also seem to be associated with higher percentages of r(20) chromosome cells. Our results suggest that an epigenetic mechanism perturbing the expression of genes close to the telomeric regions, rather than deletion of genes located at the distal 20p and/or 20q regions, may underlie the manifestation of r(20) syndrome.</p