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Luca Gallelli,1,2 Erika Cione,3 Tian Wang,4 Leiming Zhang4 1Department of Health Science, School of Medicine, Operative Unit of Clinical Pharmacology, Mater Domini University Hospital, Catanzaro, Italy; 2Research Center FAS@UMG, University Magna Graecia of Catanzaro, Catanzaro, Italy; 3Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018– 2022, University of Calabria, Rende, 87036, CS, Italy; 4Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, People’s Republic of ChinaCorrespondence: Luca GallelliDepartment of Health Science, School of Medicine, Operative Unit of Clinical Pharmacology, Mater Domini University Hospital, Catanzaro, ItalyTel +39 0961712322Email gallelli@unicz.itLeiming ZhangKey Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, People’s Republic of ChinaTel +86 5356706066Email zhangleiming2009@126.comAbstract: Saponins are a group of compounds used in clinical practice in the management of several diseases. Escin is a natural mixture of triterpene saponins which mainly consist of several isoforms, in which the α- and β-escin are predominant. β-escin is the major active compound that exerts a therapeutic effect by relieving tissue edema, promoting venous drainage, and reducing inflammation. In this review, we describe the features of its glucocorticoid-like activity that could explain its clinical effects. Using PubMed, Embase Cochrane library and reference lists for articles published until October 01, 2020, we documented that escin is likely able to exert its anti-inflammatory and anti-edematous effects through a glucocorticoid-like activity, but without the development of glucocorticoid-like adverse drug reactions.Keywords: escin, mechanism of action, glucocorticoid-like activity, clinical efficacy

Lipedema is a chronic disorder affecting women with a 10% incidence worldwide. It is often confused with obesity. This study was undertaken to study microRNAs in lipedema tissue assessed by direct hybridization using the robust n-counter flex DX CE-IVD platform. The mean age of the subjects participating in the study was 40.29 (±12.17). The mean body weight and BMI were 67.37 (±10.02) and 25.75 (±4.10), respectively. The lipedema stages included were I and II. The differential expressed human (hsa)-miRNAs were determined according to a log2 fold-change (LFC) of 0.5 and p value < 0.05. To these, increased expression of hsa-let-7g-5p was evident, as well as reduced levels of hsa-miR-371a-5p, -4454+7975, -365a+b-3p, -205-5p, -196a-5p, -4488, -2116-5p, -141-3p, -208a-3p, -302b-3p, 374a-5p, and -1297. Then, several bioinformatics tools were used to analyze microarray data focusing on validated target genes in silico. KEGG and Gene Ontology (GO) pathway enrichment analysis was conducted. Furthermore, the protein-protein interaction and co-expression network were analyzed using STRING and Cytoscape, respectively. The most upregulated miRNA mainly affected genes related to cell cycle, oocyte meiosis, and inflammatory bowel disease. The downregulated microRNAs were related to endocrine resistance, insulin resistance, hypersensitivity to AGE-RAGEs, and focal adhesion. Finally, we validated by RT-PCR the upregulated hsa-let-7g-5p and two down-regulated ones, hsa-miR-205-5p and hsa-miR-302b-3p, confirming microarray results. In addition, three mRNA target miRNAs were monitored, SMAD2, the target of the hsa-let-7g-5p, and ESR1 and VEGFA, the target of hsa-miR-205-5p and hsa-miR-302b-3p, respectively. Our results open a new direction for comprehending biochemical mechanisms related with the pathogenesis of lipedema, shedding light on this intricate pathophysiological condition that could bring to light possible biomarkers in the future.

Inflammation is expected in sports, especially when practiced at a high level. The human body is pushed toward its limit, and this is perceived as a "stressogenic agent". Athletes, especially elite ones, desire it because their bodies can react with super-compensation, i.e., improve muscle mass, strength, speed, resistance, and, therefore, athletic performance. Thus, the inflammatory stimuli should be there during training but also counteracted to have the body placed in the optimal conditions for reacting with super-compensation. In this sense, omega-3 fatty acids have been shown to have anti-inflammatory biochemical activity. In this review, we will present the biochemical mechanisms of action of omega-3 fatty acids through their mediators, specialized pro-resolving mediators, which have anti-inflammatory activity. A focus will be on studies on omega-3 fatty acid supplementation in sports, and we will provide indications for possible practical applications and future studies, which are undoubtedly necessary to clarify the omega-3 fatty acids used in sports practice.

Assessing respiratory frequency ( f R ) is practical in monitoring training progress in competitive athletes, especially during exercise. This study aimed to validate a new wearable chest strap (wCS) to estimate f R against ergospirometry as a criterion device in soccer players. A total of 26 elite professional soccer players (mean [standard deviation]: 23.6 [4.8] years; 180.6 [5.7] cm; 77.2 [5.4] kg) from three Italian Serie A League teams participated in this cross-sectional study. The sample included attackers, midfielders, and defenders. f R was assessed during a maximal cardiopulmonary exercise test (CPET) on a treadmill using (i) a breath-by-breath gas exchange analyzer (Vyntus ® CPX, Vyaire Medical) and (ii) a novel wCS with sensors designed to assess breath frequency following chest expansions. Pearson's correlation coefficient ( r ), adjusted coefficient of determination (aR 2 ), Bland-Altman plot analysis, and Lin's concordance correlation coefficient (ρ c ) were used for comparative analysis (correlation and concordance) among the methods. The repeated measures correlation coefficient (r rm ) was used to assess the strength of the linear association between the methods. The intraclass correlation coefficient (ICC) and the Finn coefficient (r F ) were used for inter-rater reliability. All statistical analyses were performed within the R statistical computing environment, with 95% confidence intervals (95% CIs) reported and statistical significance set at p < 0.05. A total of 16529 comparisons were performed after collecting the CPET data. The robust time series analysis with Hodges-Lehmann estimation showed no significant differences between both methods ( p > 0.05). Correlation among devices was statistically significant and very large ( r [95% CI]: 0.970 [0.970, 0.971], p < 0.01; aR 2 [95% CI]: 0.942 [0.942, 0.943], p < 0.01) with strong evidence supporting consistency of the new wCS (BF 10 > 100). In addition, a high concordance was found (ρ c [95% CI]: 0.970 [0.969, 0.971], bias correction factor: 0.999). Vyntus TM CPX, as a standard criterion, showed moderate agreement with wCS after Bland-Altman analysis (bias [95% lower to the upper limit of agreement]; % agree: 0.170 [-4.582 to 4.923] breaths·min -1 ; 69.9%). A strong association between measurements (r rm [95% CI]: 0.960 [0.959, 0.961]), a high absolute agreement between methods (ICC [95% CI]: 0.970 [0.970, 0.971]), and high inter-rater reliability (r F : 0.947) were found. With an RMSE = 2.42 breaths·min -1 , the new wCS seems to be an valid and reliable in-field method to evaluate f R compared to a breath-by-breath gas exchange analyzer. Notwithstanding, caution is advised if methods are used interchangeably while further external validation occurs.

Introduction: Neuropathic pain is defined as pain induced by a lesion or disease of the somatosensory nervous system. Pharmacological and non-pharmacological treatments are frequently employed. In the current clinical investigation, we assessed the effects of sex on the safety and effectiveness of medications used to treat neuropathic pain. Methods: We conducted a prospective analysis between 1 February 2021 and 20 April 2024, involving patients with neuropathic pain referred to the Ambulatory of Pain Medicine of "Renato Dulbecco" University Hospital in Catanzaro (Calabria, Italy). Patients over 18 years old with signs of neuropathic pain (Douleur Neuropathique en 4 questionnaire ≥ 4) were included. Exclusion criteria comprised patients with Alzheimer's disease; patients with nociplastic or nociceptive pain; and patients with neoplasms. Patients with fewer than two accesses to ambulatory care were excluded, as were those who did not sign the informed consent. Clinical data were collected from each enrolled patient and subsequently analyzed, considering clinical outcomes. Sex and gender differences in efficacy were estimated using multivariate linear modeling and propensity-score matching. Results: During the study, 531 patients were screened, and 174 were enrolled (33.5%, mean age 61.5 ± 13.1; 64 males and 110 females, mean age 60.6 ± 13.4 and 61.96 ± 13.0) in accordance with the inclusion and exclusion criteria. Only minor differences in treatment prescription were observed based on age, body mass index, and comorbidities. Smoking, sex, educational level, and body mass index did not induce a significant change in pain perception. Males required slightly higher, though not significantly, doses of drugs for pain control than females. The treatment was not significantly more effective for females than for males. Females did not exhibit a significantly lower number of adverse drug reactions compared to males. Conclusions: The current study found that there are no appreciable differences between the sexes when it comes to the treatment of neuropathic pain.

Objective: This meta-analysis with a systematic review was undertaken to assess the association between APOE allelic genotypes and the risk of Alzheimer's disease (AD) in the Italian population. Methods: The Web of Science, PubMed, and Scopus databases were searched until 15 November 2023. The odds ratio (OR) with a 95% confidence interval (CI) was calculated using fixed and random effect models, depending on the I 2 statistic value. The systematic review and meta-analysis were conducted in agreement with the PRISMA guideline and registered with PROSPERO (CRD42023492580). Results: Our meta-analysis based on 15 studies revealed a higher risk of AD among Italian individuals carrying the APOE ε4 allele (OR = 3.60, 95% CI [2.90-4.47], p < 0.0001). The association of AD genotype APOE ε2ε4 (OR = 1.36, 95% CI [0.76-2.41], p = 0.29) was not statistically significant, while APOE ε3ε4 (OR = 3.43, 95% CI [2.95-3.99], p < 0.0001) has a high risk of AD development; the risk is more notably in the APOE ε4ε4 genotype (OR = 7.08, 95% CI [4.22-11.86], p < 0.0001). The APOE ε2 allele has a protective effect ( APOE ε2 (OR = 0.47, 95% CI [0.29-0.74], p = 0.0013)), and similar results were achieved by APOE ε3 (OR  =  0.49, 95% CI [0.37-0.65], p < 0.0001). Subgroup analysis of three areas of Italy (southern, northern, and center) revealed that that APOE ε 4 allele was a risk factor with a higher OR in northern Italy (OR 4.22; 95% CI [3.46-5.16], p < 0.0001) compared to southern and center Italy (OR 3.02; 95% CI [2.28-4.01], p < 0.0001 and OR 3.97; 95% CI [1.37-11.56], p < 0.0001, respectively). As well, APOE ε4ε4 genotype carriers had a significantly higher OR in northern Italy (OR 9.69; 95% CI [4.94-18.99], p < 0.0001) compared to in southern and center Italy (OR 4.38; 95% CI [1.54-12.47], p < 0.0001 and OR 3.59; 95% CI [0.87-14.86], p < 0.0001, respectively). Conclusions : This systematic review with a meta-analysis of the Italian population on APOE alleles, genotyping, and AD incidence, highlights that individuals harboring APOE ε4 have a higher risk of developing AD compared to those with other alleles. It also supports the protective effect of the APOE ε2 allele against the progress of AD. The qualitative analysis on the complex genetic interactions influencing Alzheimer risk emphasizes the need for further research on genetic and environmental factors for effective prevention strategies.

Dietary microRNAs (miRs) represent a new area in food science. Although they have been found in many foods, including honey, more research is needed about their stability and fate during digestion. Hence, this study aimed to analyze the digestive stability of two selected miRs in honey. We extracted miR-92a-3p and miR-30c-5p from pasteurized and unpasteurized forms of polyfloral honey using two different methods and kits: a column-based manual method and a phenol-free semi-automated magnetic-bead-based method. The latter option was used for the subsequent analysis of samples according to the INFOGEST static in vitro digestion protocol. Also, the honey samples were examined for exosome-like particles using dynamic light scattering. Although the expression levels of both miRs were significantly lower following intestinal digestion, we found a difference in the resilience of the miRs to gastrointestinal conditions, with miR-30c-5p being relatively stable compared to miR-92a-3p following digestion, regardless of the honey's pasteurization treatment. Moreover, there was marked heterogeneity in the extracellular vesicle profile of the pasteurized sample. We identified the presence of two broadly conserved miRs in honey: miR-92a-3p and miR-30c-5p. Despite honey exhibiting high digestibility, miR-92a-3p was less resilient than miR-30c-5p, demonstrating considerable resistance under gastrointestinal conditions. Although further research is needed, the results obtained from this study may represent a starting point for utilizing honey as a source of exogenous miRNAs for preventive strategies and more "natural" treatments.

The growing interest in fermented dairy products is due to their health-promoting properties. The use of milk kefir grains as a starter culture made it possible to obtain a product with a better nutritional and biological profile depending on the type of milk. Cow, buffalo, camel, donkey, goat, and sheep milk kefirs were prepared, and the changes in sugar, protein, and phenol content, fatty acid composition, including conjugated linoleic acids (CLAs), as well as antioxidant activity, determined by ABTS and FRAP assays, were evaluated and compared. The protein content of cow, buffalo, donkey, and sheep milk increased after 24 h of fermentation. The fatty acid profile showed a better concentration of saturated and unsaturated lipids in all fermented milks, except buffalo milk. The highest content of beneficial fatty acids, such as oleic, linoleic, and C18:2 conjugated linoleic acid, was found in the cow and sheep samples. All samples showed a better antioxidant capacity, goat milk having the highest value, with no correlation to the total phenolic content, which was highest in the buffalo sample (260.40 ± 5.50 μg GAE/mL). These findings suggested that microorganisms living symbiotically in kefir grains utilize nutrients from different types of milk with varying efficiency.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports a role of the immune system, mainly played by alveolar macrophages (AMs), in key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore their involvement in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine the expressions of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, a bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group, suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insights for diagnosis or pharmacological treatment.

The DNA methylation levels of host cell genes increase with the severity of the cervical intraepithelial neoplasia (CIN) grade and are very high in cervical cancer. Our study aims to evaluate FAM19A4 and hsa-miR124-2 methylation in Atypical Squamous cells with high-grade squamous intraepithelial lesions (ASC-H) and in CIN1, defined as low-grade squamous intraepithelial lesions (LSILs) by the Bethesda classification, as possible early warning biomarkers for managing women with high-risk HPV infections (hrHPV). FAM19A4 and hsa-miR124-2 methylation tests were conducted on fifty-six cervical screening samples from a subset of women aged 30-64 years old. Specimens were collected into ThinPrep PreservCyt Solution. Their HrHPV genotype and cytology diagnosis were known. A Qiasure (Qiagen) was used for FAM19A4 and hsa-miR124-2 methylation testing on bisulfite-converted DNA, according to the manufacturer's specifications. The reported results were hypermethylation-positive or -negative. We found that FAM194A4 and hsa-miR124-2 methylation was detected in 75% of ASC-H cases with a persistent infection of hrHPV. A total of 60% of CIN1 lesions were found to be positive for methylation, and 83.3% were when the cytology was CIN2/3. In addition, as a novelty of this pilot study, we found that combined FAM19A4 and hsa-miR124-2 methylation positivity rates (both methylated) were associated with the HPV genotypes 16, 18, and 59 and covered 22 and 25% of ASC-H and CIN1 cases, respectively. The methylation of these two genes, in combination with HPV genotyping, can be used as an early warning biomarker in the management and follow-up of women with ASC-H and CIN1 to avoid their progression to cervical cancer.

Introduction: The process of bar creation involves improving the texture of the product to increase its palatability, which can be further induced by various physical or chemical changes during storage, such as sugar crystallization and molecular migrations in which Maillard's reaction occurs, forming the N-epsilon- (carboxymethyl) lysine (CML) adduct. In this study, we aimed to assess (the CML) adduct used in commercial bars today as meal substitutes or for athletic or sports purposes. The adduct CML is an advanced glycation end-product (AGEs) found in the human body (serum) and foods. It is the significant ligand for the Receptor for Advanced Glycation End Products (RAGE), resulting in chronic inflammation upon CML activation. Additionally, it aimed to assess the amount of AGEs-CML in various energy bars available on the Italian market., Method: CML OxiSelect ™ ELISA was used to assess the quantity of CML bars. The amount of AGE-CML was assessed in commercially available energy bars., Results: According to the ELISA analysis, CML concentrations per g protein in all the tested energy bars varied from 138,42 to 1387,54 μg/gr per bar and from 461,41 to 3970,46 μg/gr per 100 gr of product, which depends on the quantity of protein., Conclusion: The amount per gram of protein is relatively uniform (with a variation of about 10%), and when compared to other foods, it is positioned in a medium-low range., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Individuals with homozygous familial hypercholesterolemia (HoFH) have a severe clinical problem in their first decade of life, which is not usually present in heterozygous FH (HeFH) individuals. For this latter group of patients, FH diagnosis is mostly severely delayed with a significant increase in the risk of angina, myocardial infarction, peripheral artery disease, stroke, and cardiovascular and all-cause mortality., Methods: This study used various bioinformatics tools to analyze microarray data and identify critical miRNAs and their target genes associated with FH and its severity. Differentially expressed serum miRNAs from direct hybridization microarray data in three groups of subjects: healthy, HeFH, and HoFH. The differential expressed miRNAs were determined according to a log of fold-change (LFC) <-0.5 or >0.5 and of p < 0.05. Then, we assessed their target genes in silico . Gene ontology (GO) enrichment was applied by Cytoscape. The protein-protein interaction and co-expression network were analyzed by the STRING and GeneMANIA plugins of Cytoscape, respectively., Results: We identified increased expression of circulating hsa-miR-604, hsa-miR-652-5p, and hsa-miR-4451 as well as reduced expression of hsa-miR-3140-3p, hsa-miR-550a-5p, and hsa-miR-363-3p in both group of FH vs. healthy subjects. Higher levels of hsa-miR-1183, hsa-miR-1185-1-3p, hsa-miR-122-5p, hsa-miR-19a-3p, hsa-miR-345-3p, and hsa-miR-34c-5p were detected in HeFH in respect to HoFH when compared to healthy subjects. Most upregulated miRNAs mainly affected gene related to cardiac myofibrillogenesis, cholesterol synthesis, RNA editing for apolipoprotein B, and associated with LDL-cholesterol levels. In contrast, down-regulated miRNAs mainly affected gene related to plasma biomarker for coronary artery disease, lipids metabolism, cell adhesion and migration, genetic predictors of type 2 diabetes and cholesterol metabolism. The essential genes were primarily enriched in GO regarding biological regulation, intracellular nucleic acid binding, and the KEGG pathway of TGF-β signaling., Conclusions: The case-control nature of this study precluded the possibility of assessing the predictive role of the identified differentially expressed miRNAs for cardiovascular events. Therefore, the signature of miRNAs reflecting the pathogenesis of both HeFH and HoFH., (© 2024 The Authors.)

Background: Dietary nitrate (NO 3 ) has been shown to be useful as an ergogenic aid with potential applications in health and disease (e.g., blood pressure control). However, there is no consensus about the effects of dietary NO - ) has been shown to be useful as an ergogenic aid with potential applications in health and disease (e.g., blood pressure control). However, there is no consensus about the effects of dietary NO 3 - or beetroot (BR) juice supplementation on cognitive function., Objective: The aim of this study was to evaluate the effects of a single dose of a chewable BR-based supplement on cognitive performance., Methods: A double-blind randomized placebo-controlled two-period crossover clinical trial was carried out based on the extension of the CONSORT guidelines for randomized crossover trials. A total of 44 participants (24 F; 20 M; 32.7 [12.5] years; 66.3 [9.0] kg; 170 [9.2] cm; 22.8 [1.4] kg/m 2 ) were randomly allocated to receive first either four BR-based chewable tablets (BR-CT) containing 3 g of a Beta vulgaris extract (RedNite ® ) or four tablets of a placebo (maltodextrin). A 4-day washout period was used before crossover. Ninety minutes after ingestion of the treatments, a neuropsychological testing battery was administered in each period. The trial was registered at clinicaltrials.gov NCT05509075., Results: Significant improvements with moderate effect size were found on memory consolidation at the short and long term only after BR-CT supplementation via the Rey Auditory Verbal Learning Test immediate (+ 20.69%) and delayed (+ 12.34%) recalls. Likewise, enhancement on both frontal lobe functions (+ 2.57%) and cognitive flexibility (+ 11.16%) were detected after BR-CT. There was no significant change (p < 0.05) on verbal memory of short-term digits, working memory and information processing speed. Mixed results were found on mood and anxiety through the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory (STAI-Y1 and STAI-Y2); however, sequence and period effects were seen on STAI-Y2., Conclusions: The acute administration of a chewable BR-based supplement improves certain aspects of cognitive function in healthy females and males, particularly memory capacity and frontal skills., (© 2023. The Author(s).)

We analyzed the medical condition of 360 women affected by lipedema of the lower limbs in stages 1, 2, and 3. The data were assessed for the whole population and compared between different clinical stages, distinguishing between obese and non-obese patients. The most frequent clinical signs were pain when pinching the skin, subcutaneous nodules, and patellar fat pads. The most frequently painful site of the lower limbs was the medial lower third of the thigh. The pain score obtained on lower limb points increased progressively with the clinical stage. In all points evaluated, the thickness of the subcutaneous tissue increased with the clinical stage. Analyzing the data on the lower medial third of the leg and considering only patients with type 3 lipedema, the difference between stages was statistically significant after correction for age and BMI. We found higher levels of C-reactive protein at more severe clinical stages, and the difference was significant after correction for age and BMI between the stages. Overall, the prevalence of alterations of glucose metabolism was 34%, with a progressive increase in prevalence with the clinical stage. The most frequent comorbidities were vitamin D insufficiency, chronic venous disease, allergies, dyslipidemia, headache, and depression of mood. Interestingly, in comparison with the general population, we found higher prevalence of chronic autoimmune thyroiditis and polycystic ovary syndrome. Finally, the clinical stage and the involvement of the upper limbs or obesity suggest a worse clinical, anthropometric, and endocrine-metabolic profile.

Background: Protein supplements are important to maintain optimum health and physical performance, particularly in athletes and active individuals to repair and rebuild their skeletal muscles and connective tissues. Soy protein (SP) has gained popularity in recent years as an alternative to animal proteins., Objectives: This systematic review evaluates the evidence from randomised controlled clinical trials of the effects of SP supplementation in active individuals and athletes in terms of muscle adaptations, metabolic and antioxidant status, hormonal response and exercise performance. It also explores the differences in SP supplementation effects in comparison to whey protein., Methods: A systematic search was conducted in PubMed, Embase and Web of Science, as well as a manual search in Google Scholar and EBSCO, on 27 June 2023. Randomised controlled trials that evaluated the applications of SPs supplementation on sports and athletic-related outcomes that are linked with exercise performance, adaptations and biomarkers in athletes and physically active adolescents and young adults (14 to 39 years old) were included, otherwise, studies were excluded. The risk of bias was assessed according to Cochrane's revised risk of bias tool., Results: A total of 19 eligible original research articles were included that investigated the effect of SP supplementation on muscle adaptations (n = 9), metabolic and antioxidant status (n = 6), hormonal response (n = 6) and exercise performance (n = 6). Some studies investigated more than one effect. SP was found to provide identical increases in lean mass compared to whey in some studies. SP consumption promoted the reduction of exercise-induced metabolic/blood circulating biomarkers such as triglycerides, uric acid and lactate. Better antioxidant capacity against oxidative stress has been seen with respect to whey protein in long-term studies. Some studies reported testosterone and cortisol fluctuations related to SP; however, more research is required. All studies on SP and endurance performance suggested the potential beneficial effects of SP supplementation (10-53.3 g) on exercise performance by improving high-intensity and high-speed running performance, enhancing maximal cardiac output, delaying fatigue and improving isometric muscle strength, improving endurance in recreational cyclists, increasing running velocity and decreasing accumulated lactate levels; however, studies determining the efficacy of soy protein on VO 2 max provided conflicted results., Conclusion: It is possible to recommend SP to athletes and active individuals in place of conventional protein supplements by assessing their dosage and effectiveness in relation to different types of training. SP may enhance lean mass compared with other protein sources, enhance the antioxidant status, and reduce oxidative stress. SP supplementation had an inconsistent effect on testosterone and cortisol levels. SP supplementation may be beneficial, especially after muscle damage, high-intensity/high-speed or repeated bouts of strenuous exercise., (© 2023. The Author(s).)

β-carotene is a powerful antioxidant and dietary precursor of vitamin A whose role in maintaining mental health and cognitive performance, either alone or in combination with other dietary compounds, has been a topic of recent research. However, its effectiveness is still unclear. This systematic review, conducted according to the PRISMA guideline and assisted by the MySLR platform, addressed this issue. A total of 16 eligible original research articles were identified. Dietary intake or β-carotene serum levels were associated with improved measures of cognitive function in 7 out of 10 epidemiological studies included. In intervention studies, β-carotene consumption alone did not promote better cognitive function in the short term, but only in a long-term intervention with a mean duration of 18 years. However, all but one intervention study suggested the beneficial effects of β-carotene supplementation at doses ranging from 6 mg to 50 mg per day in combination with a multicomplex such as vitamin E, vitamin C, zinc, or selenium for a period of 16 weeks to 20 years. Despite the current limitations, the available evidence suggests a potential association between β-carotene dietary/supplementary intake and the maintenance of cognitive function. The β-carotene most probably does not act alone but in synergy with other micronutrients.

Injury in sports is an occurrence that prevents athletes from participating in training and competitions and has an incidence of 8.1 injuries/1000 h of practice. This translates into a cost and also into danger, especially if the event is repeated, for the health of the athlete; the injury certainly has a multifactorial causality. On the other hand, having instruments that can represent an alarm could be helpful for those involved in sports science. We used a specifically designed instrument, presented in a previous work, which shows excellent reliability and repeatability in measuring the strength of the knee flexors and extensors to test 107 players belonging to three different teams playing in the Italian Serie A. We took three measurements, beginning of the season, mid-season, and close to the end of the season. This retrospective study on 107 professional soccer players demonstrates that isometric force-related parameters of the knee extensors and flexors are associated with the risk of injury to lower limbs. Logistic regression evidenced a significant correlation between the parameter indicating the imbalance of the force between the flexors of the two limbs (p≤0.05, OR = 1.089) and the occurrence of injuries. Survival analyses (p≤0.001) evidenced a correlation between the population survival time and the injury incidence. We demonstrated that the analysis of the strength imbalance is correlated with injury occurrence, but it is well known that sports injuries are a multifactorial event; so, they cannot be predicted by only one parameter. However, the method proposed in this paper could represent a useful tool for sport scientists.

Food, a vital component of our daily life, is fundamental to our health and well-being, and the knowledge and practices relating to food have been passed down from countless generations of ancestors. Systems may be used to describe this extremely extensive and varied body of agricultural and gastronomic knowledge that has been gathered via evolutionary processes. The gut microbiota also underwent changes as the food system did, and these alterations had a variety of effects on human health. In recent decades, the gut microbiome has gained attention due to its health benefits as well as its pathological effects on human health. Many studies have shown that a person's gut microbiota partially determines the nutritional value of food and that diet, in turn, shapes both the microbiota and the microbiome. The current narrative review aims to explain how changes in the food system over time affect the makeup and evolution of the gut microbiota, advancing obesity, cardiovascular disease (CVD), and cancer. After a brief discussion of the food system's variety and the gut microbiota's functions, we concentrate on the relationship between the evolution of food system transformation and gut microbiota system transition linked to the increase of non-communicable diseases (NCDs). Finally, we also describe sustainable food system transformation strategies to ensure healthy microbiota composition recovery and maintain the host gut barrier and immune functions to reverse advancing NCDs.

Biological drugs are used to treat severe asthma with an improvement of clinical symptoms. Data on sex difference of these drugs in patients with severe asthma are sparse. This study aimed to assess the effects of sex-related differences on biological drugs in patients with severe asthma. In this observational, open-label, prospective, noncontrolled, single-center cohort pilot study, we enrolled adult patients aged >18 years diagnosed with severe asthma and not previously treated with biological drugs. The first clinical end point was the statistical difference (P < .05) in the efficacy of biological drugs evaluated using the asthma control test and spirometry between sexes. The first safety end point was the statistical difference (P < .05) in developing adverse drug reactions between sexes. We enrolled 74 patients with severe asthma (48 women and 26 men) with a mean age of 59.4 (standard deviation, 11.8) years. The mean forced expiratory volume in 1 second was 6.9 (standard deviation, 13.9) for women and 9.4 (standard deviation, 10.7) for men and improved significantly after the treatment (P < .01), with no significant differences in sex (P = .8). Similarly, the asthma control test improved 12 months after the beginning of the treatment without significant differences between men and women (P = .5). The most common drug used was omalizumab (45.9% of the patients; P < .01) without significant differences between sex (P > .05). We did not observe the development of adverse drug reactions during the study. In conclusion, in asthmatic patients, sex does not have a role in either the effectiveness or safety of biological drugs., (© 2022, The American College of Clinical Pharmacology.)

Atopy is an exaggerated IgE-mediated immune response to foreign antigens in which metabolic abnormalities of the leukotrienes (LTs) pathway play a crucial role. Recent studies have described sex as a key variable in LT biosynthesis, partly explaining why treatment with anti-LT drugs in atopic subjects leads to better control of symptoms in women. In addition, variability in LT production is often associated with single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase ( ALOX5 ) gene, which encodes the leukotriene-synthesizing enzyme machinery, 5-lipoxygenase ( 5-LO ). This study aimed to investigate whether two SNPs of ALOX5 are implicated in sex differences in allergic diseases in a prospective cohort of 150 age- and sex-matched atopic and healthy subjects. Rs2029253 and rs2115819 were genotyped using allele-specific RT-PCR, and serum levels of 5-LO and LTB4 were measured by ELISA. Both polymorphisms are significantly more common in women than in men, and their influences on LT production vary as a function of sex, leading to a decrease in men's and an increase in women's serum levels of 5-LO and LTB4 . These data represent a new resource for understanding sex-related differences in lung inflammatory diseases, partly explaining why women are more likely to develop allergic disorders than men.

Objectives: Nearly three years into the pandemic, SARS-CoV-2 infections are occurring in vaccinated and naturally infected populations. While humoral and cellular responses in COVID-19 are being characterized, novel immune biomarkers also being identified. Recently, an increase in angiotensin-converting enzyme 2 expressing (aka, ACE2 positive) circulating exosomes (ExoACE2) were identified in the plasma of COVID-19 patients (El-Shennawy et al.). In this pilot study, we describe a method to characterize the exosome-associated microRNA (exo-miRNA) signature in ACE2-positive and ACE2-negative exosomal populations (non-ExoACE2)., Methods: We performed a sorting protocol using the recombinant biotin-conjugated SARS CoV-2 spike protein containing the receptor binding domain (RBD) on plasma samples from six patients. Following purification, exo-miRNA were characterized for ACE2-positive and ACE2-negative exosome subpopulations by RT-PCR., Results: We identified differential expression of several miRNA. Specifically let-7g-5p and hsa-miR-4454+miR-7975 were upregulated, while hsa-miR-208a-3p and has-miR-323-3p were downregulated in ExoACE2 vs. non-ExoACE2., Conclusions: The SARS CoV-2 spike-protein guided exosome isolation permits isolation of ExoACE2 exosomes. Such purification facilitates detailed characterization of potential biomarkers (e.g. exo-miRNA) for COVID-19 patients. This method could be used for future studies to further the understanding mechanisms of host response against SARS CoV-2., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex biological fluid contains numerous immunologically active factors such as microorganisms, immunoglobulins, cytokines and microRNAs (miRNAs). Here, we set out to predict the function of the top 10 expressed miRNAs in human breast milk, focusing on their relevance in oral tolerance development and allergy prevention in the infant. The top expressed miRNAs in human breast milk were identified on basis of previous peer-reviewed studies gathered from a recent systematic review and an updated literature search. The miRNAs with the highest expression levels in each study were used to identify the 10 most common miRNAs or miRNA families across studies and these were selected for subsequent target prediction. The predictions were performed using TargetScan in combination with the Database for Annotation, Visualization and Integrated Discovery. The ten top expressed miRNAs were: let-7-5p family, miR-148a-3p, miR-30-5p family, miR-200a-3p + miR-141-3p, miR-22-3p, miR-181-5p family, miR-146b-5p, miR-378a-3p, miR-29-3p family, miR-200b/c-3p and miR-429-3p. The target prediction identified 3,588 potential target genes and 127 Kyoto Encyclopedia of Genes and Genomes pathways; several connected to the immune system, including TGF-b and T cell receptor signaling and T-helper cell differentiation. This review highlights the role of breast milk miRNAs and their potential contribution to infant immune maturation. Indeed, breast milk miRNAs seem to be involved in several pathways that influence oral tolerance development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahlberg, Al-Kaabawi, Thune, Simpson, Pedersen, Cione, Jenmalm and Tingö.)

Non-small cell lung cancer (NSCLC) is one of the deadliest diseases worldwide and represents an impending burden on the healthcare system. Despite increasing attention, the mechanisms underlying tumorigenesis in cancer-related diseases such as COPD remain unclear, making novel biomarkers necessary to improve lung cancer early diagnosis. MicroRNAs (miRNAs) are short non-coding RNA that interfere with several pathways and can act as oncogenes or tumor suppressors. This study aimed to compare miRNA lung expression between subjects with NSCLC and COPD and healthy controls to obtain the miRNA expression profile by analyzing shared pathways. Lung specimens were collected from a prospective cohort of 21 sex-matched subjects to determine the tissue miRNA expression of hsa-miR-34a-5p, 33a-5p, 149-3p, 197-3p, 199-5p, and 320a-3p by RT-PCR. In addition, an in silico prediction of miRNA target genes linked to cancer was performed. We found a specific trend for has-miR-149-3p, 197-3p, and 34a-5p in NSCLC, suggesting their possible role as an index of the tumor microenvironment. Moreover, we identified novel miRNA targets, such as the Cyclin-Dependent Kinase (CDK) family, linked to carcinogenesis by in silico analysis. In conclusion. this study identified lung miRNA signatures related to the tumorigenic microenvironment, suggesting their possible role in improving the evaluation of lung cancer onset.

Background: Assessing lower limb strength in the field is problematic, as the "gold standard assessment" with isokinetic strength is cumbersome, and the device is costly and not transportable and keeps the angle of the hip at around 90°. Methods : We evaluated isometric muscle strength in a standing position with the help of an exoskeleton that holds the subject and makes the test easily repeatable. Results: The optimal device angles for hip and knee were, respectively, 20° and 80° for flexor tests and 30° and 40° for extensor tests. Test-retest reliability was very high for the right knee extensor (ICC 0.96-0.98), left knee extensor (ICC 0.96-0.97), right knee flexor (ICC 0.91-0.96), and left knee flexor (ICC 0.96-0.97). Furthermore, the typical error in percent (T.E.%) ranged from 2.50 to 5.50%, and the change in the mean in percent ranged from 0.84 to 7.72%, making it possible to determine even a slight variation in force. Conclusions: this new method could represent a valid alternative for assessing strength, due to the high reliability and the favorable joint position, particularly in football.

Plants possess an arsenal of different classes of small RNAs (sRNAs) of variable size, which play a regulatory role in a multitude of physiological and pathological processes via transcriptional or post-transcriptional gene silencing. The hard challenges that agriculture will face in the next few decades, such as an increasing demand for agrifood production related to the global increase in population, have stimulated the development of innovative biotechnological approaches in agriculture. In this regard, the use of artificial sRNAs has already been exploited successfully for many purposes, including control of severe plant diseases, improvement of genetic and agronomic traits of cultivated species, and increasing the nutritional value of plant foodstuffs. This strategy relies on the application of synthetic sRNA molecules to induce specific physiological responses by triggering appropriate RNA silencing pathways. This review contextualizes the use of artificial sRNAs in consideration of the huge diversity of RNA silencing mechanisms in plants. Additionally, the discussion also examines microRNAs from edible plants and exosome-like vesicles, also known as plant-derived edible nanoparticles (ENPs), which themselves can act as micronutrients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It is now well established that lifestyle, particularly eating habits, modulates the synthesis and action of microRNAs (miRNAs). In particular, several nutritional schemes have proven effective in improving body composition, but molecular mechanisms still need to be fully understood. Within the complex physiological network of food intake regulation, it is essential to understand the changes in endocrine activity after the reduction of adipose tissue during a weight loss program. This could be the key to identifying the optimal endocrine profile in high responders, the assessment of musculoskeletal status, and long-term management. In this review, we summarize the state of the art regarding miRNAs as a function of weight loss and as a mechanistic regulator of the effectiveness of the nutritional program., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 20 to 25 nucleotides, present in all body fluids; they can be used as biomarkers, but much more than this as a therapy to replace missing protein or to downregulate excess or aberrant synthesis; here we report possible insight to future studies, needed in this exciting field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

One of the major organs in the body with multiple functions is the liver. It plays a central role in the transformation of macronutrients and clearance of chemicals and drugs. The serum biomarkers often used to indicate liver damage are not specifically for drug-induced liver injury (DILI) or liver injury caused by other xenobiotics, nor for viral infection. In this case, microRNAs (miRNAs) could play an exciting role as biomarkers of specific liver damage. In this review, we aimed to update the current literature on liver damage induced by drugs, as acute conditions and viral infections mediated by the hepatitis B virus (HBV) linked these two conditions to advanced research, with a focus on microRNAs as early biomarkers for liver damage. The undoubtable evidence that circulating miR-122 could be used as a human biomarker of DILI came from several studies in which a strong increase of it was linked with the status of liver function. In infancy, there is the possibility of an early miRNA detection for hepatitis B virus infection, but there are a lack of solid models for studying the HVB molecular mechanism of infection in detail, even if miRNAs do hold unrealized potential as biomarkers for early detection of hepatitis B virus infection mediated by HBV.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains a challenging clinical condition to manage. Here, we evaluate the efficacy and tolerability of a new treatment option (suppositories) containing pollen extract in combination with hyaluronic acid and vitamins in the management of patients with CP/CPPS., Methods: In this prospective, randomized, controlled, single-blinded, phase-III study we enrolled CP/CPPS patients between March and December 2019. Participants were randomized (1:1) to the following treatment groups: 1) pollen extract suppositories 1 daily for 10 days; or 2) ibuprofen 600 mg 1 tablet in the morning for 10 days. At the enrolment time and at the follow-up evaluations (3, 6 months), all patients completed baseline questionnaires ([National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] and Quality of Well-Being [QoL]) and underwent urological examination and microbiological evaluation. The primary endpoint was the quality-of-life assessment with Patients' Reported Outcomes (PROs)., Results: One hundred and eighty-seven patients were screened. Finally, one hundred and twenty-four patients (mean age 34.6±3.9 years) were randomly allocated to the new pollen extract treatment (N.=63) or ibuprofen (N.=61) groups. At the end of follow-up examinations 56/63 group 1 patients (88.8%) showed a significant reduction of the NIH-CPSI total score, compared with 17/61 (27.8%) in group 2 (P<0.0001). Group 1 patients also reported a higher improvement in terms of PROs, when compared with the control group and group 1 patients reported a significant reduction of leucocyte count at the Meares-Stamey Test (-12; -4; P<0.001). Only mild adverse events were reported in the two groups and adverse events were less frequent in the pollen extract suppositories group., Conclusions: The combination of pollen extract with hyaluronic acid and vitamins is more effective than ibuprofen in improving symptoms and Quality of Life in patients affected with CP/CPPS and has less side effects.

Background: Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Although the prostate-specific antigen (PSA) test is used in clinical practice for screening and/or early detection of PCa, it is not specific, thus resulting in high false-positive rates. MicroRNAs (miRs) provide an opportunity as biomarkers for diagnosis, prognosis, and recurrence of PCa. Because the size of the literature on it is increasing and often controversial, this study aims to consolidate the state-of-art of relevant published research. Methods: A Systematic Literature Review (SLR) approach was applied to analyze a set of 213 scientific publications through a text mining method that makes use of the Latent Dirichlet Allocation (LDA) algorithm. Results and Conclusions: The result of this activity, performed through the MySLR digital platform, allowed us to identify a set of three relevant topics characterizing the investigated research area. We analyzed and discussed all the papers clustered into them. We highlighted that several miRs are associated with PCa progression, and that their detection in patients' urine seems to be the more reliable and promising non-invasive tool for PCa diagnosis. Finally, we proposed some future research directions to help future scientists advance the field further.

High-intensity, low-frequency magnetic fields (MFs) have been widely used in the treatment of diseases and in drug delivery, even though they could induce structural changes in pharmacological molecules. Morphological changes in ketoprofen and KiOil were investigated through Fourier-transform infrared spectroscopy (FT-IR). Unsupervised principal component analysis was carried out for data clustering. Clinical validation on 22 patients with lower back pain was managed using diamagnetic therapy plus topical ketoprofen or KiOil. The Numerical Rating Scale (NRS) and Short-Form Health Survey 36 (SF-36) were used to evaluate clinical and functional response. Ketoprofen showed clear clustering among samples exposed to MF (4000−650 cm−1), and in the narrow frequency band (1675−1475 cm−1), results evidenced structural changes which involved other excipients than ketoprofen. KiOil has evidenced structural modifications in the subcomponents of the formulation. Clinical treatment with ketoprofen showed an average NRS of 7.77 ± 2.25 before and an average NRS of 2.45 ± 2.38 after MF treatment. There was a statistically significant reduction in NRS (p = 0.003) and in SF-36 (p < 0.005). Patients treated with KiOil showed an average NRS of 7.59 ± 2.49 before treatment and an average NRS of 1.90 ± 2.26 after treatment (p < 0.005). SF-36 showed statistical significance for all items except limitations due to emotional problems. A high-intensity pulsed magnetic field is an adjunct to topical treatment in patients with localized pain, and the effect of MF does not evidence significant effects on the molecules.

Background: Bronchial asthma is an inflammatory airway disease with an ever-increasing incidence. Therefore, innovative management strategies are urgently needed. MicroRNAs are small molecules that play a key role in lungs cellular functions and are involved in chronic inflammatory diseases, such as bronchial asthma. This study aims to compare microRNA serum expression between subjects with asthma, obesity, the most common co-morbidity in asthma, and healthy controls to obtain a specific expression profile specifically related to lung inflammation., Methods: We collected serum samples from a prospective cohort of 25 sex-matched subjects to determine circulating miRNAs through a quantitative RT-PCR. Moreover, we performed an in silico prediction of microRNA target genes linked to lung inflammation., Results: Asthmatic patients had a significant lower expression of hsa-miR-34a-5p, 181a-5p and 146a-5p compared to both obese and healthy ones suggesting microRNAs' specific involvement in the regulation of lungs inflammatory response. Indeed, using in silico analysis, we identified microRNAs novel target genes as GATA family, linked to the inflammatory-related pathway., Conclusions: This study identifies a novel circulating miRNAs expression profile with promising potentials for asthma clinical evaluations and management. Further and larger investigations will be needed to confirm the potential role of microRNA as a clinical marker of bronchial asthma and eventually of pharmacological treatment response.