Metabolomics in Team-Sport Athletes: Current Knowledge, Challenges, and Future Perspectives

Metabolomics is a promising tool for studying exercise physiology and exercise-associated metabolism. It has recently been defined with the term "sportomics" due to metabolomics' capability to characterize several metabolites in several biological samples simultaneously. This narrative review on exercise metabolomics provides an initial and brief overview of the different metabolomics technologies, sample collection, and further processing steps employed for sport. It also discusses the data analysis and its biological interpretation. Thus, we do not cover sample collection, preparation, and analysis paragraphs in detail here but outline a general outlook to help the reader to understand the metabolomics studies conducted in team-sports athletes, alongside endeavoring to recognize existing or emergent trends and deal with upcoming directions in the field of exercise metabolomics in a team-sports setting

Investigation of TNBC in vitro Antiproliferative Effects of Versatile Pirrolo[1,2-a]quinoxaline Compounds

he triple-negative breast cancer (TNBC) is characterized by a more aggressive nature and poorer prognosis, nowadays none pharmaceutical approach is still available. For this reason, the research of new active compounds and attractive targets represents an interesting field. In this context MDA- MB-231 cell line was selected to evaluate the antiproliferative effects of new [1,2-a]-pyrroloquinoxaline derivatives. The MTT assay revealed that the amine forms of synthesized molecules were more active compared to iminic ones at 72 h of incubation. The antiproliferative effect of the most promising compounds highlighted the formation of autophagic vacuoles

Strength training in elderly: An useful tool against sarcopenia

The loss of muscle mass and strength in elderly population (especially after the age of 65–70) represents a public health problem. Due to the high prevalence of frailty in older adults, cardiovascular or low-intensity exercise is implemented as first choice option. Although beneficial these training schemes are not as effective as strength-based resistance training for increasing muscle strength and hypertrophy. In fact, when performed progressively and under professional supervision, strength-based training has been proposed as an important and valid methodology to reduce sarcopenia-related problems. In this mini-review, we not only summarize the benefits of weight resistance training but also highlight practical recommendations and other non-conventional methods (e.g., suspension training) as part of an integral anti-sarcopenia strategy. Future directions including cluster set configurations and high-speed resistance training are also outlined

Spotted fever from Rickettsia typhi in an older woman: a case report from a geographic area where it would not be expected

Summary We describe the case of a 75-year-old woman presenting with spotted fever followed by acute renal failure and septic shock. The infection was caused by Rickettsia typhi , not reported in Calabria district (southern Italy) since World War II. The diagnosis of murine typhus was made 3 days after admission and was based solely on clinical criteria when her worsening condition required a prompt move to the intensive care unit. Therapy with tigecycline was then started immediately and the patient improved dramatically. The diagnosis of murine typhus was confirmed 10 days after admission by immunofluorescence assay. Our case is an example of how the diagnosis of murine typhus is challenging. However, in the case of a disease lacking specific symptoms, clinicians should never forget that, even in geographic areas considered free of flea-borne diseases, the components of the enzootic cycle are present and the diagnosis should never be underestimated

Estradiol via estrogen receptor beta influences ROS levels through the transcriptional regulation of SIRT3 in human seminoma TCam-2 cells

Human testis, gonocytes, and adult germ cells mainly express estrogen receptor beta, and estrogen receptor beta loss is associated with advanced tumor stage; however, the molecular mechanisms of estrogen receptor beta–protective effects are still to be defined. Herein, we provide evidence that in human seminoma TCam-2 cells, E2 through estrogen receptor beta upregulates the mitochondrial deacetylase sirtuin-3 at protein and messenger RNA levels. Specifically, E2 increases sirtuin-3 expression through a transcriptional mechanism due to the occupancy of sirtuin-3 promoter by estrogen receptor beta, together with the transcription factor Sp1 as evidenced by Chip reChIp assay. This complex binds to a GC cluster located between −128 bp/+1 bp and is fundamental for E2 effects, as demonstrated by Sp1 small interfering RNA studies. Beside, after 24 h, E2 stimulus significantly increased activities of superoxide dismutase and catalase to scavenge reactive oxygen species produced by 30 min of E2 stimulus. In summar..

Metabolic remodeling of the tumor microenvironment: migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth.

Migration stimulating factor (MSF) is a genetically truncated N-terminal isoform of fibronectin that is highly expressed during mammalian development in fetal fibroblasts, and during tumor formation in human cancer-associated myofibroblasts. However, its potential functional role in regulating tumor metabolism remains unexplored. Here, we generated an immortalized fibroblast cell line that recombinantly overexpresses MSF and studied their properties relative to vector-alone control fibroblasts. Our results indicate that overexpression of MSF is sufficient to confer myofibroblastic differentiation, likely via increased TGF-b signaling. In addition, MSF activates the inflammation-associated transcription factor NFκB, resulting in the onset of autophagy/mitophagy, thereby driving glycolytic metabolism (L-lactate production) in the tumor microenvironment. Consistent with the idea that glycolytic fibroblasts fuel tumor growth (via L-lactate, a high-energy mitochondrial fuel), MSF fibroblasts significantly increased tumor growth, by up to 4-fold. Mechanistic dissection of the MSF signaling pathway indicated that Cdc42 lies downstream of MSF and fibroblast activation. In accordance with this notion, Cdc42 overexpression in immortalized fibroblasts was sufficient to drive myofibroblast differentiation, to provoke a shift towards glycolytic metabolism and to promote tumor growth by up to 2-fold. In conclusion, the MSF/Cdc42/NFκB signaling cascade may be a critical druggable target in preventing Warburg-like cancer metabolism in tumor-associated fibroblasts. Thus, MSF functions in the metabolic remodeling of the tumor microenvironment by metabolically reprogramming cancer-associated fibroblasts toward glycolytic metabolism

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Pharmacophore-guided repurposing of fibrates and retinoids as GPR40 allosteric ligands with activity on insulin release

A classical drug repurposing approach was applied to find new putative GPR40 allosteric binders. A twostep computational protocol was set up, based on an initial pharmacophoric-based virtual screening of the DrugBank database of known drugs, followed by docking simulations to confirm the interactions between the prioritised compounds and GPR40. The best-ranked entries showed binding poses comparable to that of TAK-875, a known allosteric agonist of GPR40. Three of them (tazarotenic acid, bezafibrate, and efaproxiral) affect insulin secretion in pancreatic INS-1 832/13 b-cells with EC50 in the nanomolar concentration (5.73, 14.2, and 13.5 nM, respectively). Given the involvement of GPR40 in type 2 diabetes, the new GPR40 modulators represent a promising tool for therapeutic intervention towards this disease. The ability to affect GPR40 was further assessed in human breast cancer MCF-7 cells in which this receptor positively regulates growth activities (EC50 values were 5.6, 21, and 14 nM, respectively). © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group