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Metal(loid) salts were used to treat infectious diseases in the past due to their exceptional biocidal properties at low concentrations. However, the mechanism of their toxicity has yet to be fully elucidated. The production of reactive oxygen species (ROS) has been linked to the toxicity of soft metal(loid)s such as Ag(I), Au(III), As(III), Cd(II), Hg(II), and Te(IV). Nevertheless, few reports have described the direct, or ROS-independent, effects of some of these soft-metal(loid)s on bacteria, including the dismantling of iron-sulfur clusters [4Fe-4S] and the accumulation of porphyrin IX. Here, we used genome-wide genetic, proteomic, and biochemical approaches under anaerobic conditions to evaluate the direct mechanisms of toxicity of these metal(loid)s in Escherichia coli. We found that certain soft-metal(loid)s promote protein aggregation in a ROS-independent manner. This aggregation occurs during translation in the presence of Ag(I), Au(III), Hg(II), or Te(IV) and post-translationally in cells exposed to Cd(II) or As(III). We determined that aggregated proteins were involved in several essential biological processes that could lead to cell death. For instance, several enzymes involved in amino acid biosynthesis were aggregated after soft-metal(loid) exposure, disrupting intracellular amino acid concentration. We also propose a possible mechanism to explain how soft-metal(loid)s act as proteotoxic agents.

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Cancer is a process involving cell mutation, increased proliferation, invasion, and metastasis. Over the years, this condition has represented one of the most concerning health problems worldwide due to its significant morbidity and mortality. At present, the incidence of cancer continues to grow exponentially. Thus, it is imperative to open new avenues in cancer research to understand the molecular changes driving DNA transformation, cell-to-cell interaction derangements, and immune system surveillance decay. In this regard, evidence supports the relationship between chronic inflammation and cancer. In light of this, a group of bioactive lipids derived from polyunsaturated fatty acids (PUFAs) may have a position as novel anti-inflammatory molecules known as the specialized pro-resolving mediators (SPMs), a group of pro-resolutive inflammation agents that could improve the anti-tumor immunity. These molecules have the potential role of chemopreventive and therapeutic agents for various cancer types, and their effects have been documented in the scientific literature. Thus, this review objective centers around understanding the effect of SPMs on carcinogenesis and their potential therapeutic effect.

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Longevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.

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The gut microbiota (GM) has been the subject of intense research in recent years. Therefore, numerous factors affecting its composition have been thoroughly examined, and with them, their function and role in the individual's systems. The gut microbiota's taxonomical composition dramatically impacts older adults' health status. In this regard, it could either extend their life expectancy via the modulation of metabolic processes and the immune system or, in the case of dysbiosis, predispose them to age-related diseases, including bowel inflammatory and musculoskeletal diseases and metabolic and neurological disorders. In general, the microbiome of the elderly tends to present taxonomic and functional changes, which can function as a target to modulate the microbiota and improve the health of this population. The GM of centenarians is unique, with the faculty-promoting metabolic pathways capable of preventing and counteracting the different processes associated with age-related diseases. The molecular mechanisms by which the microbiota can exhibit anti-ageing properties are mainly based on anti-inflammatory and antioxidant actions. This review focuses on analysing the current knowledge of gut microbiota characteristics and modifiers, its relationship with ageing, and the GM-modulating approaches to increase life expectancy.

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Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.

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Background: Electrolytes, proteins, and other salivary molecules play an important role in tooth integrity and can serve as biomarkers associated with caries. Objective: To determine the concentration of potential biomarkers in children without caries (CF) and children with caries (CA). Methods: Unstimulated saliva was collected, and the biomarkers quantified in duplicate, using commercial Enzyme Linked Immunosorbent Assay (ELISA) kits to determine IgA, fibronectin, cathelicidin LL-37, and statherin levels, as well as colorimetric tests to detect formate and phosphate. Results: Significantly higher concentrations of statherin was detected in the CF group (Median: 94,734.6; IQR: 92,934.6-95,113.7) compared to the CA2 group (90,875.0; IQR: 83,580.2-94,633.4) (p = 0.03). Slightly higher median IgA (48,250.0; IQR: 31,461.9-67,418.8) and LL-37 levels (56.1; IQR 43.6-116.2) and a lower concentration of formate were detected in the CF group (0.02; IQR 0.0034-0.15) compared to the group with caries (IgA: 37,776.42; IQR: 33,383.9-44,128.5; LL-37: 46.3; IQR: 40.1011-67.7; formate: 0.10; IQR: 0.01-0.18), but these differences were not statistically significant. Conclusion: The fact that these compounds have been identified as good markers for caries among European adults highlights the difficulty of identifying universal biomarkers that are applicable to all ages or to different populations.

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that involves a pathological inflammatory response against articular cartilage in multiple joints throughout the body. It is a complex disorder associated with comorbidities such as depression, lymphoma, osteoporosis, and cardiovascular disease (CVD), which significantly deteriorate patients' quality of life and prognosis. This has ignited a large initiative to elucidate the physiopathology of RA, aiming to identify new therapeutic targets and approaches in its multidisciplinary management. Recently, various lipid bioactive products have been proposed to have an essential role in this process, including eicosanoids, specialized pro-resolving mediators, phospholipids/sphingolipids, and endocannabinoids. Dietary interventions using omega-3 polyunsaturated fatty acids or treatment with synthetic endocannabinoid agonists have been shown to significantly ameliorate RA symptoms. Indeed, the modulation of lipid metabolism may be crucial in the pathophysiology and treatment of autoimmune diseases.

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The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways' role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.

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Lifestyle modifications such as energy restriction and increased physical activity are highly effective in the management of obesity. However, adherence to these therapeutic approaches is poor. On the other hand, synthetic drugs used for obesity control are plagued by adverse effects. Despite these failures, adipose tissue is still an attractive therapeutic target for novel molecules, and thus, the characterisation of new and safer anti-obesity drugs is of significant interest. For this reason, in recent years, phenolic constituents of diverse plants have drawn much attention due to their health-promoting properties, opening new research lines related to brown adipose tissue activation and white adipose tissue (WAT) browning. The goal is to increase energy expenditure levels through thermogenic activity activation by multiple factors, like polyphenols. The suggested mechanisms by which polyphenols can modulate thermogenesis include Nor-epinephrine/Catechol-O-Methyl-Transferase (NE/COMT) inhibition, PPARγ co-activator alpha (PGC-1α)-dependent pathways activation, and mitochondrial biogenesis, among others. Although polyphenols such as quercetin, catechins, chrysin, luteolin, curcumin, resveratrol, gallic acid, and lignans have shown a positive effect on Non-Shivering Thermogenesis and WAT browning, most of them have only been active in murine models or in vitro systems, and their reproducibility in humans has to be proved. Probably in the future, an approach that includes these compounds as part of the nutritional regimen in conjunction with physical exercise, pharmacological and surgical therapy, would allow modulating a pathophysiological mechanism that is still elusive.

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Streptococcus dentisani has been identified as an oral cavity probiotic due to its beneficial characteristics. One of its beneficial features is the production of bacteriocins, which inhibit the growth of cariogenic bacteria, and another is its buffering capacity through the production of ammonium from arginine. The purpose of this study was to determine the presence of S. dentisani in the dental plaque of Colombian children and whether the presence of this bacterium is related to oral health and other conditions. Dental plaque and information on diet and oral hygiene habits were collected from children between 6 and 12 years of age from four Colombian cities, divided into caries-free children (International Caries Detection and Assessment System [ICDAS] 0, Decayed Missing Filled Teeth index [DMFT] 0), children with ICDAS 1 and 2, and children with ICDAS >3. Plaque DNA was extracted and quantified, and real-time polymerase chain reaction was performed using specific primers. This bacterium was identified in all samples, with a median of 0.46 cells/ng DNA (interquartile range [IQR] 0.13-1.02), without finding significant differences between the groups (P > 0.05). In caries-free children, a median of 0.45 cells/ng DNA (IQR 0.14-1.23) was found. In children with ICDAS 1 and 2, the median was 0.49 cells/ng DNA (IQR 0.11-0.97), and in children with ICDAS >3, the median was 0.35 cells/ng DNA (IQR 0.12-1.07). However, statistically significant differences were found in the origin of children (P < 0.01), the use of fluoride-containing products (P < 0.01), and the frequency of food intake (P < 0.05). In conclusion, the presence of S. dentisani was quantified in children from four Colombian cities, without finding significant differences in oral health status. Nevertheless, three conditions showed a possible relationship with S. dentisani.

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