Fish and human health: an umbrella review of observational studies.

Fish represents one of the most important dietary sources of omega-3 polyunsaturated fatty acids, which are known to be associated with various health benefits. This study aimed to systematically review existing meta-analyses of observational studies exploring the association between fish intake and various health outcomes. A systematic search of electronic databases was conducted to retrieve a total of 63 studies. Evidence was deemed as possible for the association between higher fish intake and decreased risk of the acute coronary syndrome, liver cancer, and depression, and limited for other outcomes (including age-related macular degeneration, Alzheimer's disease, heart failure, all-cause and coronary heart disease mortality, total and ischaemic stroke) due to heterogeneity between results and potential otherwise inexplicable confounding factors. In conclusion, results from epidemiological studies support the mechanistic effects associated with omega-3 fatty acids from high fish consumption, but evidence needs to be further corroborated with more reliable results.

Total, red and processed meat consumption and human health: an umbrella review of observational studies.

Meat consumption has represented an important evolutionary step for humans. However, modern patterns of consumption, including excess intake, type of meat and cooking method have been the focus of attention as a potential cause of rise in non-communicable diseases. The aim of this study was to investigate the association between total, red and processed meat with health outcomes and to assess the level of evidence by performing a systematic search of meta-analyses of prospective cohort studies. Convincing evidence of the association between increased risk of (i) colorectal adenoma, lung cancer, CHD and stroke, (ii) colorectal adenoma, ovarian, prostate, renal and stomach cancers, CHD and stroke and (iii) colon and bladder cancer was found for excess intake of total, red and processed meat, respectively. Possible negative associations with other health outcomes have been reported. Excess meat consumption may be detrimental to health, with a major impact on cardiometabolic and cancer risk.

Corrigendum: Results of the ECHO (Eating habits CHanges in Oncologic patients) Survey: An Italian Cross-Sectional Multicentric Study to Explore Dietary Changes and Dietary Supplement Use, in Breast Cancer Survivors.

[This corrects the article DOI: 10.3389/fonc.2021.705927.].

Results of the ECHO (Eating habits CHanges in Oncologic patients) Survey: An Italian Cross-Sectional Multicentric Study to Explore Dietary Changes and Dietary Supplement Use, in Breast Cancer Survivors.

The role of a healthy diet in cancer prevention is well recognized. Recent data indicate that following the same advices can also improve cancer survivors' quality of life. Breast cancer (BC) patients are commonly concerned about diet and nutrition and frequently express the need to obtain health-related information and the will to change their diet and lifestyle. Hence, be aware of survivors' dietary changes and information needs is crucial for healthcare professionals to guide them toward optimal lifestyle choices. In order to investigate eating habits changes in a BC survivors' population, we conceived the cross-sectional multicentric study ECHO (Eating habits CHanges in Oncologic patients) Survey. Data were collected from 684 patients, diagnosed with invasive breast cancer, in order to investigate their changes in food consumption, use of supplements, or the beginning of a specific diet, after BC diagnosis. We also examined the sources of information used and if any modification in their diets was reported to the oncologist. We primarily observed that patients increased their consumption of vegetables, pulses, nuts, fruits, wholemeal bread/pasta, grains and fish; while decreasing red and processed meat, refined bread/pasta, baked good and animal fat consumption. Survivors also reported the use of dietary supplements, mainly vitamins, aimed at counteracting therapies' side effects. Changes in nutritional habits were often adopted without asking or informing the oncologist. Despite BC survivors made some positive changes in their nutritional habits, those modifications were mostly pursued by less than half of them, while the majority of patients consumed nutritional supplements after diagnosis. These results, as well as the failure to communicate with the physicians, reinforce the need to both improve the patient-healthcare professional relationship and to develop tailored nutrition counselling and intervention programs for cancer survivors.

Nut and legume consumption and human health: an umbrella review of observational studies.

Consumption of nuts and legumes has been associated with several health benefits. The aim of this study was to systematically review existing meta-analyses of observational studies on nut and legume intake and non-communicable diseases, and assess the level of evidence. Out of the six meta-analyses focussed on legume and 15 on nut intake, a possible association with decreased risk of colorectal adenoma and coronary heart disease was found for higher legume consumption, and a decreased risk of cardiovascular and cancer mortality, colon cancer, hypertension and ischaemic stroke for higher nut consumption. The association between legume consumption and cardiovascular diseases (CVDs), as well as nut consumption and risk of cancer, CVD incidence and all-cause mortality, was deemed as "limited" due to heterogeneity between results and/or potential confounding factors. General benefit towards better health can be observed for nut and legume consumption. Further studies are needed to better elucidate potential confounding factors.

Whole grain consumption and human health: an umbrella review of observational studies.

Whole grains have been associated with a number of health benefits. We systematically reviewed existing meta-analyses of observational studies and evaluated the level of evidence for their putative effects based on pre-selected criteria. Of the 23 included studies, we found convincing evidence of an inverse association between whole grain consumption and risk of type-2 diabetes and colorectal cancer; possible evidence of decreased risk of colon cancer and cardiovascular mortality with increased whole grain intake, as well as increased risk of prostate cancer. Limited or insufficient evidence was available for all other outcomes investigated. Overall findings are encouraging for a positive effect of whole grain consumption on certain diseases, especially highly prevalent metabolic diseases, however, uncertainty of some negative associations deserves further attention.

Egg consumption and human health: an umbrella review of observational studies.

Egg consumption has been an area of controversy regarding its impact on human health largely due to the content in cholesterol and its potential role in cardio-metabolic outcomes. This study aimed to summarise the level of evidence of egg consumption on various health outcomes. A systematic search for meta-analyses was performed: study design, dose-response relationship, heterogeneity and agreement of results over time, and identification of potential confounding factors were considered to assess the level of evidence. Results from this umbrella review showed a substantial no association between egg consumption and a number of health outcomes, including cancer, cardiovascular and metabolic disorders. In contrast, evidence of possible beneficial effects toward stroke risk has been found. In conclusions, egg may be part of a healthy diet; however, additional studies exploring confounding factors are needed to ascertain the potential detrimental effects.

Dairy foods and health: an umbrella review of observational studies.

Evidence on consumption of dairy foods and human health is contradictory. This study aimed to summarize the level of evidence of dairy consumption on various health outcomes. A systematic search for meta-analyses was performed: study design, dose-response relationship, heterogeneity and agreement of results over time, and identification of potential confounding factors were considered to assess the level of evidence. Convincing and probable evidence of decreased risk of colorectal cancer, hypertension and cardiovascular disease, elevated blood pressure and fatal stroke, respectively, was found for total dairy consumption; possible decreased risk of breast cancer, metabolic syndrome, stroke and type-2 diabetes, and increased risk of prostate cancer and Parkinson's disease was also found. Similar, yet not entirely consistent evidence for individual dairy products was reported. Among potential confounding factors, geographical localisation and fat content of dairy have been detected. In conclusions, dairy may be part of a healthy diet; however, additional studies exploring confounding factors are needed to ascertain the potential detrimental effects.

Fruit and vegetable consumption and health outcomes: an umbrella review of observational studies.

The aim of this study was to provide a comprehensive evaluation of current evidence on fruit and vegetable consumption and health outcomes. A systematic search for quantitative syntheses was performed. Several criteria, including study design, dose-response relationship, heterogeneity and agreement of results over time, and identification of potential confounding factors, were used to assess the level of evidence. The strongest (probable) evidence was found for cardiovascular disease protection; possible evidence for decreased risk of colon cancer, depression and pancreatic diseases was found for fruit intake; and colon and rectal cancer, hip fracture, stroke, depression and pancreatic diseases was found for vegetable intake. Suggestive and rather limited associations with other outcomes have been found. Evidence of potential confounding by sex and geographical localisation has been reported. Despite findings are consistent enough for hypothesising causation (at least for cardiovascular-related outcomes), further studies are needed to clarify the role of potential confounding factors.

Lifestyle, nutrition and breast cancer: facts and presumptions for consideration.

Breast cancer is the most common cancer in women worldwide, and the high incidence of this cancer coupled with improvements in initial treatments has led to an ever-increasing number of breast cancer survivors. Among the prospective epidemiological studies on diet and breast cancer incidence and recurrence, to date, there is no association that is strong, reproducible and statistically significant, with the exception of alcohol intake, overweight, and weight gain. Nevertheless, many beliefs about food and breast cancer persist in the absence of supporting scientific evidence. After a comprehensive review regarding the role of lifestyle on breast cancer outcomes and a thorough study of the dissemination field including mass media, clinical institutions, and academic figures, we briefly reported the most common presumptions and also facts from the literature regarding lifestyle, nutrition, and breast cancer. The randomised controlled trial is the best study-design that could provide direct evidence of a causal relationship; however, there are methodological difficulties in applying and maintaining a lifestyle intervention for a sufficient period; consequently, there is a lack of this type of study in the literature. Instead, it is possible to obtain indirect evidence from observational prospective studies. In this article, it becomes clear that for now the best advice for women's health is to follow the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) recommendations on diet, nutrition, physical activity, and weight management for cancer prevention, because they are associated with a lower risk of developing most types of cancer, including breast cancer. Despite current awareness of the role of nutrition in cancer outcomes, there is inadequate translation from research findings into clinical practice. We suggest the establishment of a multidisciplinary research consortium to demonstrate the real power of lifestyle interventions.

Fruitful adrenergic α(2C)-agonism/α(2A)-antagonism combination to prevent and contrast morphine tolerance and dependence.

The functional in vitro study of the enantiomers of imidazolines 4-7 highlighted the role played by the nature of the ortho phenyl substituent in determining the preferred α(2C)-AR configuration. Indeed, the (S) enantiomers of 4-6 or (R) enantiomer of 7 behave as eutomers and activate this subtype as full agonists; the corresponding distomers are partial agonists. Because in clinical pain management with opioids α(2C)-AR agonists, devoid of the α(2A)-AR-mediated side effects, may represent an improvement over current therapies with clonidine like drugs, 4 and its enantiomers, showing α(2C)-agonism/α(2A)-antagonism, have been studied in vivo. The data suggest that partial α(2C)-activation is compatible with effective enhancement of morphine analgesia and reduction both of morphine tolerance acquisition and morphine dependence acquisition and expression. On the contrary, full α(2C)-activation appears advantageous in reducing morphine tolerance expression. Interestingly, the biological profile displayed by 4 (allyphenyline) and its eutomer (S)-(+)-4 has been found to be very unusual.

Might adrenergic alpha2C-agonists/alpha2A-antagonists become novel therapeutic tools for pain treatment with morphine?

The imidazoline nucleus linked in position 2 via an oxyethylene bridge to a phenyl ring carrying an ortho substituent of moderate steric bulk provided alpha(2)-adrenergic (AR) ligands endowed with significant alpha(2C)-agonism/alpha(2A)-antagonism. Similar behavior was displayed by cirazoline (12). For their positive morphine analgesia modulation (due to alpha(2C)-AR stimulation) and sedation overcoming (due to alpha(2A)-AR antagonism), 8 and 11 might be useful as adjuvant agents in the management of pain with morphine.

Probiotic properties of Lactobacillus rhamnosus and Lactobacillus paracasei isolated from human faeces.

BACKGROUND: The possibility of using microbes to maintain health, and to prevent or treat disease is a topic as old as microbiology. The research of novel probiotic strains is important in order to satisfy the increasing request of the market and to obtain functional products in which the probiotic cultures are more active and with better probiotic characteristics than those already present on the market. AIM OF THE STUDY: In this study, the probiotic potential of Lactobacillus strains isolated from Italian elderly human faeces was investigated. METHODS: The Lactobacillus strains were identified and examined for resistance to gastric acidity and bile toxicity, adhesion to HT-29 cells, antimicrobial activities, antibiotic susceptibility and plasmid profile. Survival of the strains through human intestine was examined in a 3 months human feeding trial. RESULTS: Two strains, Lactobacillus rhamnosus IMC 501 and Lactobacillus paracasei IMC 502, tolerated well low pH and bile acids. In antimicrobial activity assays, both strains showed inhibitory properties towards selected potential harmful microorganisms, particularly against Candida albicans. The two selected strains expressed high in vitro adherence to HT-29 cells increasing this characteristic when they are used in combination and they were resistant to vamcomycin, colistin sulphate, gentamicin, oxolinic acid and kanamycin. Moreover, the two strains could be recovered from stools of volunteers after the feeding trials. CONCLUSIONS: Lactobacillus rhamnosus IMC 501 and L. paracasei IMC 502 present favourable strain-specific properties for their utilisation as probiotics in functional foods and the high adhesion ability of the L. rhamnosus IMC 501 and L. paracasei IMC 502 used in combination, confirmed by both in vitro and in vivo study, indicate that the two bacterial strains could be used as health-promoting bacteria.

Novel ligands rationally designed for characterizing I2-imidazoline binding sites nature and functions.

The study of two series of 2-aryl-ethylen-imidazolines 3-7 and 8-12 inspired by I2-IBS ligands phenyzoline (1) and diphenyzoline (2), respectively, confirmed the interesting "positive" or "negative" morphine analgesia modulation displayed by their corresponding leads and demonstrated that these effects might be correlated with morphine tolerance and dependence, respectively. By comparative examination of rationally designed compounds, some analogies between binding site cavity of I2-IBS proteins and alpha 2C-adrenoreceptor emerged.

Alpha2-adrenoreceptors profile modulation. 4. From antagonist to agonist behavior.

The goal of the present study was to modulate the receptor interaction properties of known alpha 2-adrenoreceptor (AR) antagonists to obtain novel alpha 2-AR agonists with desirable subtype selectivity. Therefore, a phenyl group or one of its bioisosteres or aliphatic moieties with similar steric hindrance were introduced into the aromatic ring of the antagonist lead basic structure. The functional properties of the novel compounds allowed our previous observations to be confirmed. The high efficacy of 7, 12, and 13 as alpha 2-AR agonists and the significant alpha 2C-AR subtype selective activation displayed by 11 and 15 demonstrated that favorable interactions to induce alpha 2-AR activation were formed between the pendant groups of the ligands and the aromatic cluster present in transmembrane domain 6 of the binding site cavity of the receptors.

Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist.

To assess the stereochemical requirements for efficient alpha2C-adrenoreceptor activation, the enantiomeric forms of m-nitrobiphenyline [(+/-)-5] were prepared and tested on cells expressing the human alpha2-adrenoreceptor subtypes. The importance of chirality was confirmed, since the enantiomer (R)-(+)-5 was much more efficient than (S)-(-)-5 in producing alpha2C-activation. Surprising reversal of enantioselectivity was observed with respect to structurally similar biphenyline [(+/-)-1] whose (S)-(-)-form proved the preferred alpha2C-configuration.

Involvement of I2-imidazoline binding sites in positive and negative morphine analgesia modulatory effects.

Some studies, suggesting the involvement of I(2)-imidazoline binding sites (I(2)-IBS) in morphine analgesia modulation, prompted us to examine on mice antinociceptive assays the effect produced by 1 (phenyzoline), that in view of its high I(2)-IBS affinity and high I(2)-IBS selectivity with regard to I(1)-IBS, alpha(2)-adrenoreceptors and mu-opioid receptors might be considered the first interesting I(2)-IBS ligand. The study was also applied to its ortho phenyl derivative 2 (diphenyzoline), designed and prepared in order to produce a possible modification of the biological profile of 1. Diphenyzoline (2) retains a significant I(2)-IBS selectivity with regard to I(1)-IBS, alpha(2)-adrenoreceptors and mu-opioid receptors. Moreover, by the functional assays 1 and 2 proved inactive at all alpha(2)-adrenoreceptors subtypes up to 10(-3) M. As expected, phenyzoline and diphenyzoline, which are structurally related, highlighted an interesting "positive" or "negative", respectively, morphine analgesia modulatory effect. In fact, 1 (s.c. 10 mg/kg) enhanced morphine analgesia (60% and 40% in mouse tail-flick and mouse hot-plate, respectively), while 2 (s.c. 10 mg/kg) decreased it (-41% and -20%, respectively). The ability to decrease morphine analgesia had never been observed before in I(2)-IBS ligands. These effects were not affected by i.p. treatment of animals with yohimbine (a selective alpha(2)-adrenoreceptor antagonist, 0.625 mg/kg) or efaroxan (an I(1)-IBS/alpha(2)-adrenoreceptor antagonist, 1.0 mg/kg). In contrast, they were completely reversed by i.p. treatment of animals with idazoxan (an I(2)-IBS/alpha(2)-adrenoreceptor antagonist, 2 mg/kg). Moreover, compound 2, in mouse tail-flick test, was able to potentiate by 23% the naloxone-induced decrease of morphine analgesia. Therefore, the results of this study indicate the crucial involvement of I(2)-IBS in the morphine analgesia modulatory effects of 1 and 2.

Endocannabinoid system in Xenopus laevis development: CB1 receptor dynamics.

This study investigates for the first time the dynamics of endocannabinoid system appearance during low vertebrate Xenopus laevis development. We observed that the CB1 gene started to be expressed during the organogenesis period (+/- 1 dpf, st. 28) and expression persisted throughout the three further stages analyzed. Attention was focused on the localization of the CB1 messenger that was found both at the central level (in romboencephalon and in olfactory placods) and at the peripheral level (in the gastrointestinal tract) at +/- 3 dpf (st. 41), +/- 4 dpf (st. 46) and +/- 12 dpf (st. 49). We also considered the synthesis of CB1 protein that occurred from st. 41 onwards and, from this stage, we tested the receptor functionality in response to anandamide using cytosensor microphysiometry. CB1 functionality increased with development at both central and peripheral level. These data provide sufficient evidence to encourage further analysis on endocannabinoid physiological roles during embryonic and larval X. laevis growth.

alpha 2-adrenoreceptors profile modulation. 2. Biphenyline analogues as tools for selective activation of the alpha 2C-subtype.

A series of derivatives structurally related to biphenyline (3) was designed with the aim to modulate selectivity toward the alpha(2)-AR subtypes. The results obtained demonstrated that the presence of a correctly oriented function with positive electronic effect (+sigma) in portion X of the ligands is an important factor for significant alpha(2C)-subtype selectivity (imidazolines 5, 13, 16, and 19). Homology modeling and docking studies support experimental data and highlight the crucial role for the hydrogen bond between the pyridine nitrogen in position 3 of 5 and the NH-indole ring of Trp6.48, which is favorably oriented in the alpha(2C)-subtype, only.

Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine.

A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (1), was synthesized and tested to evaluate their affinity and selectivity for M(1), M(2), M(3) and M(4) receptor subtypes. The conformational constraint of 1 in a bicyclic structure, and the variation in distance and stereochemistry of the active functions allowed us to modulate the selectivity of interaction with the M(1)-M(3) receptor subtypes. The most interesting compound was (cis,trans)-2-(2,2-diphenylethyl)-5-methyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole oxalate (6), which is equipotent with Pirenzepine on rabbit vas deferens (M(1)-putative) but shows a better selectivity profile.