What Is the Role of Nutraceutical Products in Cancer Patients? A Systematic Review of Randomized Clinical Trials.

Chemotherapy represents the main pharmacological cancer treatment. Recently, positive effects emerged with the combination of anticancer therapy and nutraceutical products. The aim of this systematic review is to collect and synthesize the available scientific evidence regarding the potential effects of nutraceuticals on cancer cells. A systematic literature search of randomized clinical trials of nutraceutical products in patients with cancer published up to 15 December 2022 was conducted using three data sources: Embase, PubMed, and Web of Science. The effect of high-dose isoflavone supplements on prostate cancer resulted in stabilization or reduction of PSA concentrations in 50% of isoflavone group patients six months after treatment. High doses of vitamin D supplementation plus chemotherapy in patients with advanced or metastatic colorectal cancer showed a median PFS of 13.0 months (95% CI, 10.1-14.7 months) for 49 patients. The effect of vitamin D supplementation on markers of inflammatory level and antioxidant capacity in women with breast cancer showed a significant increase in serum vitamin D concentration (28 ± 2.6 to 39 ± 3.5; p = 0.004) after 8 weeks of treatment. In conclusion, nutraceutical supplements represent a potentially growing sector and can be utilized in medical treatment or nutrition to provide integrated medical care.

On the Policy of the Italian Government in the Discovery, Development, and Access to Medicines.

This commentary outlines how discovery, development, and access to medicines are regulated and promoted in Italy by the government through the Ministry of University and Research, the Ministry of Health, and the Italian Medicines Agency. We describe and comment on the existing research programs stimulating preclinical, translational, and clinical research and how access to medicines and their pricing is regulated by Italy's National Health Service both at the national and regional levels. Finally, we describe the current scenario of industrial research and medicines manufacturing. The resulting picture shows a country in which high-level competitive research on medicines is promoted alongside an excellent national health system working toward fairness of access to health care services for all citizens and fiscal solidarity as a fundamental form of system financing. Critical challenges still exist, including the relative scarcity of public funding for research and the non-uniform access to the benefits of the National Health Service across Italian regions.

Prevention of food and airway allergy: consensus of the Italian Society of Preventive and Social Paediatrics, the Italian Society of Paediatric Allergy and Immunology, and Italian Society of Pediatrics.

BACKGROUND: Allergic sensitization in children and allergic diseases arising therefrom are increasing for decades. Several interventions, functional foods, pro- and prebiotics, vitamins are proposed for the prevention of allergies and they can't be uncritically adopted. OBJECTIVE: This Consensus document was developed by the Italian Society of Preventive and Social Paediatrics and the Italian Society of Paediatric Allergy and Immunology. The aim is to provide updated recommendations regarding allergy prevention in children. METHODS: The document has been issued by a multidisciplinary expert panel and it is intended to be mainly directed to primary care paediatricians. It includes 19 questions which have been preliminarily considered relevant by the panel. Relatively to each question, a literature search has been performed, according to the Italian National Guideline Program. Methodology, and a brief summary of the available literature data, has been provided. Many topics have been analyzed including the role of mother's diet restriction, use of breast/formula/hydrolyzed milk; timing of introduction of complementary foods, role (if any) of probiotics, prebiotics, vitamins, exposure to dust mites, animals and to tobacco smoke. RESULTS: Some preventive interventions have a strong level of recommendation. (e.g., the dehumidifier to reduce exposure to mite allergens). With regard to other types of intervention, such as the use of partially and extensively hydrolyzed formulas, the document underlines the lack of evidence of effectiveness. No preventive effect of dietary supplementation with polyunsaturated fatty acids, vitamins or minerals has been demonstrated. There is no preventive effect of probiotics on asthma, rhinitis and allergic diseases. It has demonstrated a modest effect, but steady, in the prevention of atopic dermatitis. CONCLUSIONS: The recommendations of the Consensus are based on a careful analysis of the evidence available. The lack of evidence of efficacy does not necessarily imply that some interventions may not be effective, but currently they can't be recommended.

Type III or allosteric kinase inhibitors for the treatment of non-small cell lung cancer.

INTRODUCTION: In recent times, there has been much interest in the development of pharmacological kinase inhibitors that treat NSCLC. Furthermore, treatment options have been guided by the development of a wide panel of synthetic small molecule kinase inhibitors. Most of the molecules developed belong to the type I class of inhibitors that target the ATP-binding site in its active conformation. The high sequence similarity in the ATP-binding site among members of the kinase families often results in low selectivity and additional toxicities. Also, second mutations in the ATP-binding site, such as threonine to methionine at position 790, have been described as a mechanism of resistance to ATP-competitive kinase inhibitors. For these reasons, alternative drug development approaches targeting sites other than the ATP cleft are being pursued. The class III or allosteric inhibitors, which bind outside the ATP-binding site, have been shown to negatively modulate kinase activity. AREAS COVERED: In this review, the authors discuss the most well-characterised allosteric inhibitors that have reached clinical development in NSCLC. EXPERT OPINION: Great progress has made in developing inhibitors with entirely new modes of action. That being said, it is important to highlight that despite their apparent simplicity, biochemical assays will remain at the core of drug discovery activities to better explore these new opportunities.

Metabolic syndrome and cancer: holistic or reductionist?

Metabolic syndrome has become a major public health problem worldwide and represents a common clinical condition in countries with a high incidence of obesity and western dietary patterns. Metabolic syndrome associates with common cancers at many sites, including liver, colorectal, and bladder cancers in men, and endometrial, pancreatic, breast post-menopausal, and colorectal cancers in women. However, the role played by each single component of the syndrome on cancer risk is still unclear. For endometrial cancer, obesity and/or high circumference waist explain all the risk associated with the full metabolic syndrome, while for post-menopausal breast cancer, the risk conveyed by metabolic syndrome appears to be greater than its parts, as no single component explains the full risk associated with the syndrome. Future research should cover other avenues in order to elucidate the complexity of biological processes linking metabolic syndrome and cancer.

Intraperitoneal oxygen/ozone treatment decreases the formation of experimental postsurgical peritoneal adhesions and the levels/activity of the local ubiquitin-proteasome system.

We have investigated whether an oxygen/ozone (95%O2/5%O3) mixture would have potential against the formation of experimental postsurgical peritoneal adhesions. In two groups of rats, one control intraperitoneally injected with 3 mL/rat of O2 and one intraperitoneally injected with oxygen/ozone mixture (3 mL/rat equivalent to 300 µg/kg ozone), we induced a midline laparotomy and an enterotomy at the level of the ileum to encourage the formation of peritoneal adhesions. Samples were taken from the parietal peritoneal tissue to assess the formation of adhesions 0 and 10 days after the surgical procedure and to assess the levels of ubiquitin and 20S proteasome. We found decreased formation of postsurgical peritoneal adhesions after treatment of the rats with 300 µg/kg ozone associated with a decreased levels of ubiquitin and 20S proteasome subunit within the adhered tissue. Oxygen/ozone mixture is potentially useful for approaching the post-surgical peritoneal adhesions, and the UPS system is involved in this.

Hyperbaric oxygen therapy reduces the toll-like receptor signaling pathway in multiple organ failures.

PURPOSE: Zymosan-induced generalized inflammation is the only experimental model that reproduces characteristics of human multiple organ dysfunction syndrome (MODS). Toll-like receptors (TLRs) are key components in innate immune responses and their signaling pathway is known to activate target genes such as nuclear factor-κB (NF-κB) and cytokines that are involved in inflammation and immune responses. We previously reported that hyperbaric oxygen (HBO) therapy is effective in the treatment of severe zymosan-induced inflammation in MODS. The aim of this study was to investigate the effect of HBO exposure on TLR2 and TLR4 signal transduction and organ dysfunction during MODS induced by zymosan in the rat. METHODS: Male Wistar rats were randomized into four groups and treated as follows: (1) saline solution (control); (2) zymosan; (3) HBO 4 and 11 h after zymosan injection; (4) HBO 4 and 11 h after saline solution injection. Zymosan-induced damage of the lungs, liver, and small intestine was evaluated using histology and biochemistry. The activation of the TLR signaling pathway was measured with Western blot, reverse transcriptase polymerase chain reaction analysis (RT-PCR), and immunohistochemistry. RESULTS: Zymosan induced a severe inflammatory response characterized by the activation of the TLR signaling pathway and by an organ dysfunction. HBO exposure significantly reduced the development of lung, liver, and intestine injury in our experimental model. It also significantly reduced the zymosan-induced expression of TLR2 and TLR4, NF-κB activation, and cytokine production. CONCLUSIONS: Taken together, these results suggest that, by interfering with the TLR pathway, HBO treatment may exert a protective effect against tissue injury caused by zymosan-induced generalized inflammation.

Hyperbaric oxygen therapy prevents coagulation disorders in an experimental model of multiple organ failure syndrome.

OBJECTIVE: To evaluate the effects of hyperbaric oxygen (HBO) therapy on the coagulation cascade using an experimental model of multiple organ failure syndrome (MOFS). DESIGN: MOFS was induced by zymosan (500mg/kg i.p.) in rats. HBO therapy (2ATA) was administered in a cylindrical steel chamber 4 and 11h after zymosan administration. In a separate set of experiments animals were monitored for 72h, and systemic toxicity was scored. INTERVENTION: Eighteen hours after zymosan administration, rats were killed and blood samples were used for analysis of hemocoagulative parameters, hemodynamics, and arterial blood gas. MAIN RESULTS: Zymosan administration caused MOFS by affecting the coagulation cascade, as shown by a significant increase in plasma levels of fibrinogen, tissue plasminogen activator, inhibitor of tissue plasminogen activator of type 1, and plasma levels of fibrin degradation products vs. control rats. Zymosan-induced MOFS was also characterized by a significant increase in von Willebrand antigen plasma levels vs. controls. Moreover, zymosan administration induced a significant fall in mean arterial blood pressure and alteration in blood gas values. HBO therapy significantly reduced the derangements of coagulation cascade, the fall in mean blood pressure and alteration in blood gas induced by zymosan administration. CONCLUSIONS: The hypercoagulability induced by zymosan could be responsible for organ failure and death. Our data demonstrate that HBO therapy significantly prevents the alteration in the coagulation cascade and arterial blood gas in an experimental model of MOFS.

New 1,3,4-thiadiazole derivatives endowed with analgesic and anti-inflammatory activities.

Two series of N-[5-oxo-4-(arylsulfonyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl]-amides were synthesized and tested in vivo for their analgesic and anti-inflammatory activities. All the new compounds possess good antalgic action in the acetic acid writhing test and some terms of the series showed also fair anti-inflammatory activity in the carrageenan rat paw edema test. Ulcerogenic and irritative action on the gastrointestinal mucose, in comparison with indomethacin is low.