Immunobiology of solid cancers: cellular and molecular pathways as potential diagnostic and therapeutic targets

In the last four decades, tumor immunology has shed light on identity and functions of cells and molecules involved in tumor rejection through the involvement of the immune system [1]. Several groups of immune cells have been demonstrated to be able to contrast tumor occurrence and tumor progression by killing immunogenic tumor cells, a phenomenon recognized under the definition of “immunosurveillance” [2]. Unfortunately, cancer may evade immunosurveillance and progress through the modifications of its own antigens, which can reduce tumor immunogenicity and/or increase its immunosuppressive action [3]. After years of investigations, harnessing the immune system to attack cancer has recently led scientists to gather enough clinical data to show what a powerful sword immunotherapy can be

Is a combination of melatonin and amino acids useful to sarcopenic elderly patients? A randomized trial

This study evaluated the effectiveness of a 4-week intervention of melatonin and essential aminoacid supplementation on body composition, protein metabolism, strength and inflammation in 159 elderly sarcopenic patients (42/117, men/women), assigned to four groups: isocaloric placebo (P, n = 44), melatonin (M, 1 mg/daily, n = 42), essential amino acids (eAA 4 g/daily, n = 40) or eAA plus melatonin (eAAM, 4 g eAA and 1 mg melatonin/daily, n = 30). Data from body composition (dual X-ray absortiometry (DXA)), strength (handgrip test) and biochemical parameters for the assessment of protein metabolism (albumin) and inflammation (CRP) were collected at baseline and after the 4-week intervention. Compared with P and M, supplementation with eAA plus M increased total fat-free mass (vs. P: +2190 g; p < 0.01; vs. M: +2107 g; p < 0.05). M alone lowered albumin levels (vs. P: -0.39 g; p < 0.01; vs. eAA: -0.47 g; p < 0.01). This data on albumin was confirmed by within-group analysis (M -0.44g; p < 0.001; eAAM: -0.34 p < 0.05). M and eAA seemed to lower the percentage of gynoid fat (p < 0.05) and android fat (p < 0.01). No significant changes in inflammation or strength were reported. A 4-week intervention with eAA plus M together may be effective in enhancing fat-free-mass compared to M and P but not versus eAA. M alone demonstrates a negative effect on albumin level

Pivotal role of boron supplementation on bone health: A narrative review

Background: Boron is a trace element that plays an important role in numerous biological functions, including calcium metabolism, growth and maintenance of bone tissue. However, there are still no precise indications regarding a possible role of boron supplementation, and its amount of supplementation, to maintain bone health. So the aim of this narrative review was to consider the state of the art on the effectiveness of boron supplementation (alone or with other micronutrients) on growth and maintenance of bone in humans through control of calcium, vitamin D and sex steroid hormone metabolism in order to suggest a daily dosage of boron supplementation. Main findings: This review included 11 eligible studies: 7 regarding the supplementation with boron alone and 4 regarding supplementation with boron and other nutrients. Despite the number of studies considered being low, the number of subjects studied is high (594) and the results are interesting. Conclusions: The studies considered in this narrative review have evaluated the positive effectiveness on bone, in humans, through control of calcium, vitamin D and sex steroid hormone metabolism, considering a dietary supplementation of 3 mg/day of boron (alone or with other nutrients); this supplementation is demonstrably useful to support bone health (in order to prevent and maintain adequate bone mineral density), also considering the daily dose of 3 mg is much lower than the Upper Level indicated by EFSA in the daily dose of 10 mg

Polycystic ovary syndrome management: a review of the possible amazing role of berberine

Purpose: The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment. Methods: The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management. Results: This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates. Conclusions: Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy

MKRN3 and KISS1R mutations in precocious and early puberty

Background Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of KISSR1 (previously named GPR54) and MKRN3 genes on pubertal timing. Methods We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8 years of age, and in 6 girls affected by early puberty (EP) between 8 and 10 years of age. Results Direct sequencing of the KISS1R (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the GPR54 gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of MKRN3 in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3/13 CPP patients and 3/6 EP patients) we found the synonymous variant c.663C &gt; T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient. Conclusion In conclusion, we identified sequence variations of the KISS1R and MKRN3 genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP

Current opinion on dietary advice in order to preserve fat-free mass during a low-calorie diet

Objectives: The loss of fat-free mass (FFM) that occurs during weight loss secondary to low-calorie diet can lead to numerous and deleterious consequences. We performed a review to evaluate the state of the art on metabolic and nutritional correlates of loss of fat free mass during low calorie diet and treatment for maintaining fat free mass. Methods: This review included 44 eligible studies. There are various diet strategies to maintain FFM during a low-calorie diet, including adoption of a very low carbohydrate ketogenic diet (VLCKD) and taking an adequate amount of specific nutrients (vitamin D, leucine, whey protein). Results: Regarding the numerous and various low-calorie diet proposals for achieving weight loss, the comparison of VLCKD with prudent low-calorie diet found that FFM was practically unaffected by VLCKD. There are numerous possible mechanisms for this, involving insulin and the insulin-like growth factor-1–growth hormone axis, which acts by stimulating protein synthesis. Conclusions: Considering protein and amino acids intake, an adequate daily intake of leucine (4 g/d) and whey protein (20 g/d) is recommended. Regarding vitamin D, if the blood vitamin D has low values (<30 ng/mL), it is mandatory that adequate supplementation is provided, specifically calcifediol, because in the obese patient this form is recommended to avoid seizure in the adipose tissue; 3 to 4 drops/d or 20 to 30 drops/wk of calcifediol are generally adequate to restore normal 25(OH)D plasma levels in obese patients

Micronutrients dietary supplementation advices for celiac patients on long-term gluten-free diet with good compliance: A review

Background and objective: Often micronutrient deficiencies cannot be detected when patient is already following a long-term gluten-free diet with good compliance (LTGFDWGC). The aim of this narrative review is to evaluate the most recent literature that considers blood micronutrient deficiencies in LTGFDWGC subjects, in order to prepare dietary supplementation advice (DSA). Materials and methods: A research strategy was planned on PubMed by defining the following keywords: celiac disease, vitamin B12, iron, folic acid, and vitamin D. Results: This review included 73 studies. The few studies on micronutrient circulating levels in long-term gluten-free diet (LTGFD) patients over 2 years with good compliance demonstrated that deficiency was detected in up to: 30% of subjects for vitamin B12 (DSA: 1000 mcg/day until level is normal, then 500 mcg), 40% for iron (325 mg/day), 20% for folic acid (1 mg/day for 3 months, followed by 400–800 mcg/day), 25% for vitamin D (1000 UI/day or more-based serum level or 50,000 UI/week if level is <20 ng/mL), 40% for zinc (25–40 mg/day), 3.6% of children for calcium (1000–1500 mg/day), 20% for magnesium (200–300 mg/day); no data is available in adults for magnesium. Conclusions: If integration with diet is not enough, starting with supplements may be the correct way, after evaluating the initial blood level to determine the right dosage of supplementation

Novel insights on intake of fish and prevention of sarcopenia: All reasons for an adequate consumption

Sarcopenia is defined as a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength and it is diagnosed by measurements of muscle mass, muscle strength, and physical performance. Sarcopenia affects quality of life and is associated with several adverse health effects. Muscle decline is aggravated by a sedentary lifestyle and can be prevented through proper nutrition, together with adequate physical activity. Fish contains biologically active compounds, such as omega-3 polyunsaturated fatty acids, proteins, vitamin D, magnesium, and carnitine, which are able to intervene positively on muscle metabolism. This narrative literature review was performed to evaluate evidence regarding the actual benefit of fish consumption in the prevention of sarcopenia and the positive action on the muscle mass of the biological compounds present in fish. The results demonstrated that fish consumption has a protective and anti-inflammatory function on skeletal muscle and that its biologically active compounds help to maintain good muscle performance, preventing sarcopenia. Considering the nutritional and health benefits, elderly with sarcopenia should consume at least three servings per week of fish in order to have a minimum intake of 4–4.59 g daily of omega 3, and reaching the 50% RDA in Vitamin E and D. High biological value of proteins in 150 g of fish and its high available magnesium (20% of RDA in 150 g of fish) are an added value that could suggest fish as a “functional food” in order to prevent and treat sarcopenia

Variable stiffness control for oscillation damping

In this paper a model-free approach for damping control of Variable Stiffness Actuators is proposed. The idea is to take advantage of the possibility to change the stiffness of the actuators in controlling the damping. The problem of minimizing the terminal energy for a one degree of freedom spring-mass model with controlled stiffness is first considered. The optimal bang-bang control law uses a maximum stiffness when the link gets away from the desired position, i.e. the link velocity is decreasing, and a minimum one when the link is going towards it, i.e. the link velocity is increasing. Based on Lyapunov stability theorems the obtained law has been proved to be stable for a multi-DoF system. Finally, the proposed control law has been tested and validated through experimental tests