OPINION article Front. Artif. Intell., 19 April 2024Sec. Organoid Intelligence Volume 7 - 2024 | https://doi.org/10.3389/frai.2024.1385871

EDITORIAL article Front. Cardiovasc. Med., 31 May 2024Sec. Cardiovascular Metabolism Volume 11 - 2024 | https://doi.org/10.3389/fcvm.2024.1435850

OBJECTIVE: This study examines the role of MTHFR gene polymorphism (rs1801133) in women with lipedema (LIPPY) body composition parameters compared to a control group (CTRL).SUBJECTS AND METHODS: We carried out a study on a sample of 45 LIPPY and 50 women as a CTRL. Body composition parameters were examined by Dual-energy X-ray Absorptiometry (DXA). A genetic test was performed for the MTHFR polymorphism (rs1801133, 677C>T) using a saliva sample for LIPPY and CTRL groups. Mann-Whitney tests evaluated statistically significant differences between four groups (carriers and non-carriers of the MTHFR polymor-phism for LIPPY and CTRL groups) on anthro-pometric/body composition parameters to iden-tify patterns.RESULTS: LIPPY showed significantly higher (p<0.05) anthropometric parameters (weight, BMI, waist, abdominal, hip circumferences) and lower waist/hip ratio (p<0.05) compared to the CTRL group. The association between the poly-morphism alleles related to the rs1801133 MTH-FR gene and the body composition values LIP-PY carriers (+) showed an increase in fat tissue of legs and fat region of legs percentage, arm's fat mass (g), leg's fat mass (g), and leg's lean mass (g) (p<0.05) compared to CTRL (+). Lean/ fat arms and lean/fat legs were lower (p<0.05) in LIPPY (+) than in CTRL (+). In the LIPPY (+), the risk of developing the lipedema disease was 2.85 times higher (OR=2.85; p<0.05; 95% confi-dence interval = 0.842-8.625) with respect to LIP-PY (-) and CTRL.CONCLUSIONS: The presence or absence of MTHFR polymorphism offers predictive parameters that could better characterize women with lipedema based on the association between body composition and MTHFR presence.

The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.

- COVID-19 is a novel disease with a broad range of clinical patterns. Several patients show dysbiosis in the intestinal tract, with evidence of reduced beneficial bacteria, such as Bifidobacteria and Lactobacilli. It is well established that human gut microbiota dysbiosis is associated with several clinical conditions, including respiratory tract diseases due to the gut-lung axis. This narrative review discusses the role of nutrients in the relationship between the gut microbiota and the immune response in SARS-CoV-2 infection. In particular, we will focus on the benefits offered by vitamins and micronutrients on different aspects of COVID-19 disease while also discussing which diets seem to provide the most advantages.

OBJECTIVE Micronutrient deficiencies (MNDs) are common among patients with certain chronic inflammatory diseases. They are associated with a pro-inflammatory status and co-morbidities. However, no studies have specifically investigated MNDs in Spondyloarthritis (SpA). This paper aimed at analyzing the occurrence of anemia and deficiencies of ferritin (Fe), vitamin D [25(OH)D], vitamin B12 (B12), and folic acid (FA) in SpA patients. The interplay of MNDs with age, gender, and metabolic abnormalities was also explored. PATIENTS AND METHODS MNDs were evaluated in 220 SpA outpatients (137 females and 83 age-matched males) with psoriatic arthritis (PsA, n=110) and non-psoriatic SpA (n=110). Metabolic parameters were analyzed. Disease activity was assessed by either Disease Activity in PSoriatic Arthritis (DAPSA) or Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein (ASDAS-CRP) as appropriate, while the functional status was evaluated using Health Assessment Questionnaire modified for SpA (HAQ-S). RESULTS Anemia occurred in 13.6% of subjects of the study cohort and almost wholly in females (p=0.004). Females showed higher Fe deficiency (p=0.04) and lower Fe levels (p=0.0003) than males. Hemoglobin (Hb) resulted inversely related to age and CRP (p=0.01 and p=0.008) in male group. The 25(OH)D deficiency (≤20 ng/ml) was present in 23.2% of the cohort with a higher prevalence in males than females (p=0.02): moreover, 25(OH)D inversely correlated with disease duration (p=0.02) in males. The B12 deficiency (≤200 pmol/l) was rare (13.2%), while FA ≤4 ng/ml was frequent (22%) and associated with B12 deficiency in 31% of cases. SpA patients in moderate/high disease activity had higher Body Mass Index (BMI) (p=0.04) and HAQ-S (p<0.0001), as well as lower Hb (p=0.02), and Fe (p=0.03) than patients in remission/low disease activity (LDA). In patients with extra-articular manifestations, female sex was prevalent (F:M=2) and B12 levels were lower than in patients without (p=0.005). Interestingly, 25(OH)D was lower (p=0.04) and both BMI and HAQ-S (p=0.036 and p=0.01) were higher in patients without extra-articular involvement than patients with. CONCLUSIONS Our findings documented a relevant prevalence of MNDs in SpA patients, and its strict interplay with gender and metabolic abnormalities by highlighting the role of MNDs in inflammatory-dependent dysmetabolism in SpA.

The large, randomized, double-blind, placebo-controlled trial VITAL (Vitamin D and omega 3 trial) recently confirmed that vitamin D and omega-3 polyunsaturated fatty acid (PUFA) co-supplementation (VIDOM) can reduce the incidence of autoimmune diseases. Based on these relevant results, this commentary summarizes the molecular mechanisms behind the anti-inflammatory and immunomodulatory properties of vitamin D and omega-3 PUFAs. We also describe the potential bidirectional interplay between vitamin D metabolism and omega-3 PUFA metabolism that underlies the rationale for VIDOM co-supplementation and that may contribute to enhance the anti-inflammatory and immunomodulatory actions of vitamin D and omega-3 PUFAs when these compounds are administered in combination.

Elderly population is increasing rapidly together with the incidence of cardiovascular diseases (CVDs) and cardiovascular (CV) mortality. The evaluation of total CV risk is necessary for prevention of CV events, but the most used assessment tools do not include the elderly population. Among CV risk factors, hypercholesterolemia increases with the age, but the results about the association between total cholesterol (TC) levels and mortality in the elderly population are controversial. Statins are the first-choice drug for lipid-lowering therapy in the elderly due to their efficacy and safety. In primary prevention there are no recommendations to the use of statins in older adults because they do not reduce the risk of CV and all-cause mortality. On the contrary, statin treatment is recommend both in older than in younger people in secondary prevention because of the reduction of CV and all-causes mortality. High-intensity statins are more effective in the elderly population, but these dosages are associated to an increased incidence of adverse reactions, especially liver dysfunction. Finally, the degree of clinical frailty is inversely related to total cholesterol in the elderly and, accordingly, lower cholesterol levels are associated to higher mortality in this population. There are no studies that specifically evaluated the benefit of lipid-lowering therapy in severely frail older adults and a narrative-based approach, instead of an evidence-based one, has been used to choose the better treatment plan.

Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis. Furthermore, the protective effect of sir-2.3 knock-out is enhanced by block of glycolysis and eliminated by a null mutation in daf-16/FOXO transcription factor, supporting the involvement of the insulin/IGF pathway. However, data in Caenorhabditis elegans cell culture suggest that the effects of sir-2.3 knock-out act downstream of the DAF-2/IGF-1 receptor. Analysis of ROS in sir-2.3 knock-out reveals that ROS become elevated in this mutant under ischemic conditions in dietary deprivation (DD), but to a lesser extent than in wild type, suggesting more robust activation of a ROS scavenging system in this mutant in the absence of food. This work suggests a deleterious role of SIRT4 during ischemic processes in mammals that must be further investigated and reveals a novel pathway that can be targeted for the design of therapies aimed at protecting neurons from death in ischemic conditions.

Elderly people are characterized by a high prevalence of falls and sarcopenia. However, the relationship among Tinetti mobility test (TMT) score, a powerful tool to detect elderly people at risk of falls, and sarcopenia is still not thoroughly investigated. Thus, to determine the relationship between TMT score and muscle mass and strength, 337 elderly participants (mean age 77.1 ± 6.9 years) admitted to comprehensive geriatric assessment were enrolled. TMT score, muscle mass by bioimpedentiometer, and muscle strength by grip strength were evaluated. Muscle mass progressively decreased as TMT score decreased (from 15.3 ± 3.7 to 8.8 ± 1.8 kg/m2; p for trend <0.001). Similarly, muscle strength decreased progressively as Tinetti score decreased (from 34.7 ± 8.0 to 23.7 ± 8.7 kg; p for trend 0.001). Linear regression analysis demonstrated that TMT score is linearly related with muscle mass (y = 4.5x + 0.4, r = 0.61; p < 0.01) and strength (y = 14.0x + 0.8, r = 0.53; p < 0.01). Multivariate analysis confirms the strong relationship between the TMT score and muscle mass (r = 0.48, p = 0.024) and strength (r = 0.39, p = 0.046). The present study indicates that TMT score is significantly related to muscle mass and strength in non-institutionalized elderly participants. This evidence suggests that TMT score, together with evaluation of muscle mass and strength, may identify sarcopenic elderly participants at high risk of falls.

The slow and continuous loss of muscle mass that progresses with aging is defined as "sarcopenia". Sarcopenia represents an important public health problem, being closely linked to a condition of frailty and, therefore, of disability. According to the European Working Group on Sarcopenia in Older People, the diagnosis of sarcopenia requires the presence of low muscle mass, along with either low grip strength or low physical performance. However, age-related changes in skeletal muscle can be largely attributed to the complex interactions among factors including alterations of the neuromuscular junction, endocrine system, growth factors, and muscle proteins turnover, behavior-related and disease-related factors. Accordingly, the identification of a single biomarker of sarcopenia is unreliable, due to its "multifactorial" pathogenesis with the involvement of a multitude of pathways. Thus, in order to characterize pathophysiological mechanisms and to make a correct assessment of elderly patient with sarcopenia, a panel of biomarkers of all pathways involved should be assessed.

Senescence is a phenomenon characterized by a progressive decline of body homeostasis. Premature senescence acts when the cellular system is not able to adequately respond to noxious stimuli by synthesis of stressor molecules. Among those, serum-and-glucocorticoidinducible kinase-1 (SGK-1) dramatically increases under typical physiopathological conditions, such as glucocorticoid or mineralcorticoids exposure, inflammation, hyperglycemia, and ischemia. SGK-1 has been implicated in mechanism regulating oxidative stress, apoptosis, and DNA damage, which are all leading to a state of accelerating aging. Moreover, SGK-1-sensitive ion channels participate in the regulation of renal Na(+)/K(+) regulation, blood pressure, gastric acid secretion, cardiac action potential, and neuroexcitability. Recently, we demonstrated in endothelial cells as an increase in SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated nitric oxide production after hyperglycemia. Moreover, we showed as SGK-1 delays the onset of senescence by increasing telomerase activity, significantly decreasing reactive oxygen species (ROS) production, and by directly interacting with hTERT. Therefore, SGK-1 may represent a specific target to further develop novel therapeutic options against chronic diseases such as diabetes typical of aging. SGK-1 has been also associated with cancer, neurodegenerative diseases, and cardiovascular disease, among other age-related diseases. However, to date, the data available on SGK-1 and aging, are sparse, controversial, and only from C. elegans experimental models. In this review we sought to discuss the possible implication of SGK-1 in mechanisms regulating senescence and age-related diseases. Moreover, we aimed to discuss and identify the possible role of SGK-1 as possible molecular target to counteract and prevent aging.