Enhancing the Retention and Oxidative Stability of Volatile Flavors: A Novel Approach Utilizing O/W Pickering Emulsions Based on Agri-Food Byproducts and Spray-Drying.

Spray-drying is a commonly used method for producing powdered flavors, but the high temperatures involved often result in the loss of volatile molecules. To address this issue, our study focused on a novel approach: developing O/W Pickering emulsions with agri-food byproducts to encapsulate and protect D-limonene during spray-drying and storage. Emulsions formulated with lupin hull, lupin-byproduct (a water-insoluble protein-fiber byproduct derived from the production of lupin protein isolate), and camelina press-cake were subjected to spray-drying at 160 °C. The results revealed that these emulsions exhibited good stability against creaming. The characteristics of the dry emulsions (powders) were influenced by the concentration of byproducts. Quantitative analysis revealed that Pickering emulsions enhanced the retention of D-limonene during spray-drying, with the highest retention achieved using 3% lupin hull and 1% camelina press-cake. Notably, lupin-stabilized emulsions yielded powders with enhanced oxidative stability compared to those stabilized with camelina press-cake. Our findings highlight the potential of food-grade Pickering emulsions to improve the stability of volatile flavors during both processing and storage.

Podophyllic Aldehyde, a Podophyllotoxin Derivate, Elicits Different Cell Cycle Profiles Depending on the Tumor Cell Line: A Systematic Proteomic Analysis.

When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of special importance to investigate chemomodulation to further explore antitumoral pharmacological activities. In this work, the compound podophyllic aldehyde, a cyclolignan derived from the chemomodulation of the natural product podophyllotoxin, has been evaluated for its viability, influence on the cell cycle, and effects on intracellular signaling. We used functional proteomics characterization for the evaluation. Compared with the FDA-approved drug etoposide (another podophyllotoxin derivative), we found interesting results regarding the cytotoxicity of podophyllic aldehyde. In addition, we were able to observe the effect of mitotic arrest in the treated cells. The use of podophyllic aldehyde resulted in increased cytotoxicity in solid tumor cell lines, compared to etoposide, and blocked the cycle more successfully than etoposide. High-throughput analysis of the deregulated proteins revealed a selective antimitotic mechanism of action of podophyllic aldehyde in the HT-29 cell line, in contrast with other solid and hematological tumor lines. Also, the apoptotic profile of podophyllic aldehyde was deciphered. The cell death mechanism is activated independently of the cell cycle profile. The results of these targeted analyses have also shown a significant response to the signaling of kinases, key proteins involved in signaling cascades for cell proliferation or metastasis. Thanks to this comprehensive analysis of podophyllic aldehyde, remarkable cytotoxic, antimitotic, and other antitumoral features have been discovered that will repurpose this compound for further chemical transformations and antitumoral analysis.

Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.

Functional proteomics based on protein microarray technology for biomedical research.

This chapter traces a route through Proteomics from its origins to the present day. The different proteomics applications are discussed with a focus on microarray technology. Analytical microarrays, functional microarrays and reverse phase microarrays and their different applications are discussed. Several studies are mentioned where the great versatility of this approach is shown. Finally, the advantages and future challenges of microarray technology are outlined.

Non-apoptotic FAS signaling controls mTOR activation and extrafollicular maturation in human B cells.

Defective FAS (CD95/Apo-1/TNFRSF6) signaling causes autoimmune lymphoproliferative syndrome (ALPS). Hypergammaglobulinemia is a common feature in ALPS with FAS mutations (ALPS-FAS), but paradoxically, fewer conventional memory cells differentiate from FAS-expressing germinal center (GC) B cells. Resistance to FAS-induced apoptosis does not explain this phenotype. We tested the hypothesis that defective non-apoptotic FAS signaling may contribute to impaired B cell differentiation in ALPS. We analyzed secondary lymphoid organs of patients with ALPS-FAS and found low numbers of memory B cells, fewer GC B cells, and an expanded extrafollicular (EF) B cell response. Enhanced mTOR activity has been shown to favor EF versus GC fate decision, and we found enhanced PI3K/mTOR and BCR signaling in ALPS-FAS splenic B cells. Modeling initial T-dependent B cell activation with CD40L in vitro, we showed that FAS competent cells with transient FAS ligation showed specifically decreased mTOR axis activation without apoptosis. Mechanistically, transient FAS engagement with involvement of caspase-8 induced nuclear exclusion of PTEN, leading to mTOR inhibition. In addition, FASL-dependent PTEN nuclear exclusion and mTOR modulation were defective in patients with ALPS-FAS. In the early phase of activation, FAS stimulation promoted expression of genes related to GC initiation at the expense of processes related to the EF response. Hence, our data suggest that non-apoptotic FAS signaling acts as molecular switch between EF versus GC fate decisions via regulation of the mTOR axis and transcription. The defect of this modulatory circuit may explain the observed hypergammaglobulinemia and low memory B cell numbers in ALPS.

Local niches explain coexistence in environmentally-distinct contact zones between Western Mediterranean vipers.

Species' ecological niches are frequently analysed to gain insights into how anthropogenic changes affect biodiversity. Coping with these changes often involves shifts in niche expression, which can disrupt local biotic interactions. Secondary contact zones, where competition and ecological segregation commonly occur, are ideal for studying the ecological factors influencing species' niches. In this study, we investigated the effect of climate and landscape factors on the ecological niches of two viper species, Vipera aspis and Vipera latastei, across three contact zones in northern Iberia, characterized by varying levels of landscape alteration. Using niche overlap tests, ecological niche models and spatial analyses we observed local variation in the expression of the species' niches across the three contact zones, resulting from the different abiotic and biotic conditions of each area. Rather than spatial niche segregation, we observed high niche overlap, suggesting niche convergence. A pattern of asymmetrical niche variation was identified in all contact zones, driven by species' climatic tolerances and the environmental conditions of each area. V. aspis generally exhibited a wider niche, except in the southernmost zone where the pure Mediterranean climate favored V. latastei. Human-induced landscape changes intensified niche asymmetry, by favoring the most generalist V. aspis over the specialist V. latastei, increasing habitat overlap, and likely competition. This study presents a comprehensive analysis of niche expression at range margins, anticipating a heightened impact of landscape changes in V. latastei. The methodological framework implemented here, and our findings, hold significant relevance for biodiversity management and conservation in human-impacted areas.

Health-care policies during the COVID-19 pandemic in Mexico: A continuous case of heterogeneous, reactive, and unequal response.

Background: The pandemic in Mexico underlined pre-existing health-care system inequalities. Within the first six months of the COVID-19 pandemic, 154 health policies across health institutions were found to be uncoordinated and heterogeneous, leading to health inequalities in access and potential health outcomes. Data & methods: Using a rapid qualitative research methodology, data was collected using purposive sampling of institutional policies published for public access on the official websites of the four public health institutions in Mexico from June 16th, 2020 to October 30th, 2021. This policy review used archival analysis to understand the differences in health-care policies during the COVID-19 pandemic in Mexico. These policies were classified under the RREAL framework and as a continuation of our first publication. Results: During this study, categories of public health response and vaccination dominated the policies enacted. The SSA was the main author of publications. There seems to be a more unified policy response. However, health inequalities persist. Conclusions: The Mexican government continued to be reactive to the increase in cases or the arrival of new variants, rather than preventative. Research and development of policies need to work together in soaring cases like COVID-19 to work more effectively against the economic and epidemiological burden of a pandemic. It is suggested that this "vaccination" should be included in the RREAL classification. Other sectors (i.e. the ministry of foreign affairs) should be considered relevant players in the future management of a pandemic.

Treatment with SGLT2 Inhibitors in Patients with Diabetes Mellitus and Extensive Coronary Artery Disease: Mortality and Cardiovascular Outcomes.

INTRODUCTION: Sodium-glucose type 2 cotransporter inhibitors (SGLT2-I) have shown solid benefits in reducing cardiovascular mortality and admissions for heart failure in patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, no specific studies exist in patients with high-risk coronary artery disease (CAD). METHODS: Single-center, retrospective, observational study including patients with T2DM and a new diagnosis of extensive CAD (defined as left main disease or three main coronary vessel disease). Patients were recruited from 2015 until 2020, with a follow-up of at least 12 months. The primary outcome was to compare all-cause mortality in patients treated with or without SGLT2-I at discharge and adjusted by inverse probability of treatment weighting (IPTW) propensity score. RESULTS: A total of 420 patients were included: 104 (24.7%) were treated with SGLT2-I and 316 (75.3%) were not (non-SGLT2-I group). The presentation was acute coronary syndrome in 44.3%. The mean age was 71.2 ± 10.5 years. The mean left ventricular ejection fraction was 51.5 ± 12.5%, and the mean estimated glomerular filtration rate was 73.9 ± 22 ml/min. After a mean follow-up of 3 ± 1.6 years, all-cause mortality was 16.4%, and cardiovascular mortality was 9.5%. After IPTW, the risk of all-cause death was lower in the SGLT2-I group with a hazard ratio of 0.32 (95% confidence interval 0.12-0.81), p = 0.016. With regard to secondary outcomes, patients in the SGLT2-I group were associated with less renal function deterioration but an increase in unplanned revascularizations. CONCLUSIONS: In patients with T2DM and extensive CAD, treatment with SGLT2-I after discharge was associated with a reduced risk of all-cause death.

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

Enhancement of Tumor Cell Immunogenicity and Antitumor Properties Derived from Platinum-Conjugated Iron Nanoparticles.

From chemistry design to clinical application, several approaches have been developed to overcome platinum drawbacks in antitumoral therapies. An in-depth understanding of intracellular signaling may hold the key to the relationship of both conventional drugs and nanoparticles. Within these strategies, first, nanotechnology has become an essential tool in oncotherapy, improving biopharmaceutical properties and providing new immunomodulatory profiles to conventional drugs mediated by activation of endoplasmic reticulum (ER) stress. Secondly, functional proteomics techniques based on microarrays have proven to be a successful method for high throughput screening of proteins and profiling of biomolecule mechanisms of action. Here, we conducted a systematic characterization of the antitumor profile of a platinum compound conjugated with iron oxide nanoparticles (IONPs). As a result of the nano-conjugation, cytotoxic and proteomics profiles revealed a significant improvement in the antitumor properties of the starting material, providing selectivity in certain tumor cell lines tested. Moreover, cell death patterns associated with immunogenic cell death (ICD) response have also been identified when ER signaling pathways have been triggered. The evaluation in several tumor cell lines and the analysis by functional proteomics techniques have shown novel perspectives on the design of new cisplatin-derived conjugates, the high value of IONPs as drug delivery systems and ICD as a rewarding approach for targeted oncotherapy and onco-immunotherapies.

Herbivory Damage Increased VOCs in Wild Relatives of Murtilla Plants Compared to Their First Offspring.

Murtilla (Ugni molinae) is a shrub native to Chile that has undergone an incipient domestication process aimed at increasing its productivity. The reduction in intrinsic chemical defenses due to the domestication process has resulted in a decrease in the plant's ability to defend itself against mechanical or insect damage. In response to this damage, plants release volatile organic compounds (VOCs) as a means of defense. To understand how domestication has impacted the production of VOCs in the first offspring of murtilla, we hypothesized that their levels would be reduced due to the induction of mechanical and herbivore damage. To test this hypothesis, we collected VOCs from four offspring ecotypes and three wild relatives of murtilla. We induced mechanical and herbivore damage in the plants and then enclosed them in a glass chamber, where we captured the VOCs. We identified 12 compounds using GC-MS. Our results showed that wild relative ecotypes had a higher VOC release rate of 624.6 µg/cm2/day. Herbivore damage was the treatment that produced the highest release of VOCs, with 439.3 µg/cm2/day in wild relatives. These findings suggest that herbivory triggers defenses through the emission of VOCs, and that domestication has influenced the production of these compounds in murtilla. Overall, this study contributes to bridging the gap in the incipient domestication history of murtilla and highlights the importance of considering the impact of domestication on a plant's chemical defenses.

A Longitudinal Study of Individual Radiation Responses in Pediatric Patients Treated with Proton and Photon Radiotherapy, and Interventional Cardiology: Rationale and Research Protocol of the HARMONIC Project.

The Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy (photon and proton) in Pediatrics (HARMONIC) is a five-year project funded by the European Commission that aimed to improve the understanding of the long-term ionizing radiation (IR) risks for pediatric patients. In this paper, we provide a detailed overview of the rationale, design, and methods for the biological aspect of the project with objectives to provide a mechanistic understanding of the molecular pathways involved in the IR response and to identify potential predictive biomarkers of individual response involved in long-term health risks. Biological samples will be collected at three time points: before the first exposure, at the end of the exposure, and one year after the exposure. The average whole-body dose, the dose to the target organ, and the dose to some important out-of-field organs will be estimated. State-of-the-art analytical methods will be used to assess the levels of a set of known biomarkers and also explore high-resolution approaches of proteomics and miRNA transcriptomes to provide an integrated assessment. By using bioinformatics and systems biology, biological pathways and novel pathways involved in the response to IR exposure will be deciphered.

Improving Properties of Podophyllic Aldehyde-Derived Cyclolignans: Design, Synthesis and Evaluation of Novel Lignohydroquinones, Dual-Selective Hybrids against Colorectal Cancer Cells.

New lignohydroquinone conjugates (L-HQs) were designed and synthesized using the hybridization strategy, and evaluated as cytotoxics against several cancer cell lines. The L-HQs were obtained from the natural product podophyllotoxin and some semisynthetic terpenylnaphthohydroquinones, prepared from natural terpenoids. Both entities of the conjugates were connected through different aliphatic or aromatic linkers. Among the evaluated hybrids, the L-HQ with the aromatic spacer clearly displayed the in vitro dual cytotoxic effect derived from each starting component, retaining the selectivity and showing a high cytotoxicity at short (24 h) and long (72 h) incubation times (4.12 and 0.0450 µM, respectively) against colorectal cancer cells. In addition, the cell cycle blockade observed by flow cytometry studies, molecular dynamics, and tubulin interaction studies demonstrated the interest of this kind of hybrids, which docked adequately into the colchicine binding site of tubulin despite their large size. These results prove the validity of the hybridization strategy and encourage further research on non-lactonic cyclolignans.

Streptococcus canis genomic epidemiology reveals the potential for zoonotic transfer.

Streptococcus canis, a multi-host pathogen commonly isolated from dogs and cats, has been occasionally reported in severe cases of human infection. To address the gap in knowledge on its virulence and host tropism, we investigated S. canis genomic epidemiology and report the results of this analysis for the first time. We analysed 59 S. canis whole genome sequences originating from a variety of host species, comprising 39 newly sequenced isolates from UK sources, along with all (n=20) publicly available genomes. Antimicrobial resistance (AMR) phenotype was determined for all 39 available isolates. Genomes were screened for determinants of resistance and virulence. We created a core SNP phylogeny and compared strain clustering to multi-locus sequence typing (MLST) and S. canis M-like protein (SCM) typing. We investigated the dataset for signals of host adaptation using phylogenetic analysis, accessory genome clustering and pan-genome-wide association study analysis. A total of 23 % (9/39) of isolates exhibited phenotypic resistance to lincosamides, macrolides and/or tetracyclines. This was complemented by the identification of AMR-encoding genes in all genomes: tetracycline (tetO 14 %, 8/59; and tetM 7 %, 4/59) and lincosamide/macrolide (ermB, 7 %, 4/59). AMR was more common in human (36 %, 4/11) compared to companion animal (18 %, 5/28) isolates. We identified 19 virulence gene homologues, 14 of which were present in all strains analysed. In an S. canis strain isolated from a dog with otitis externa we identified a homologue of S. pyogenes superantigen SMEZ. The MLST and SCM typing schemes were found to be incapable of accurately representing core SNP-based genomic diversity of the S. canis population. No evidence of host adaptation was detected, suggesting the potential for inter-species transmission, including zoonotic transfer.

Malignant syphilis as the presenting complaint of advanced HIV.

Malignant syphilis is an infrequent secondary manifestation in patients with human immunodeficiency virus (HIV), with polymorphous and disseminated skin lesions being related to severe immunosuppression. Lesions have intense inflammatory circinate, ulcer-crusted and nodular skin lesions of diffuse distribution throughout the body, that can be confused with vasculitis or cutaneous lymphomas. We report a patient recently diagnosed with HIV infection in the acquired immunodeficiency syndrome stage with malignant syphilis as the debut of HIV.

Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Studies of CLL antibody reactivity have shown differential targets to autoantigens and antimicrobial molecular motifs that support the current hypothesis of CLL pathogenesis. METHODS: In this study, we conducted a quantitative serum analysis of 7 immunoglobulins in CLL and monoclonal B-cell lymphocytosis (MBL) patients (bead-suspension protein arrays) and a serological profile (IgG and IgM) study of autoantibodies and antimicrobial antigens (protein microarrays). RESULTS: Significant differences in the IgA levels were observed according to disease progression and evolution as well as significant alterations in IgG1 according to IGHV mutational status. More representative IgG autoantibodies in the cohort were against nonmutagenic proteins and IgM autoantibodies were against vesicle proteins. Antimicrobial IgG and IgM were detected against microbes associated with respiratory tract infections. CONCLUSIONS: Quantitative differences in immunoglobulin serum levels could be potential biomarkers for disease progression. In the top 5 tumoral antigens, we detected autoantibodies (IgM and IgG) against proteins related to cell homeostasis and metabolism in the studied cohort. The top 5 microbial antigens were associated with respiratory and gastrointestinal infections; moreover, the subsets with better prognostics were characterized by a reactivation of Cytomegalovirus. The viral humoral response could be a potential prognosis biomarker for disease progression.

Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex disease whose polygenic component is mainly unidentified. We propose that levels of intermediate molecular phenotypes in the myocardium associated with histopathological damage could explain CDA susceptibility; so that variants of genes encoding these intermediate molecular phenotypes could identify patients susceptible to this complication. A genetically heterogeneous cohort of mice generated by backcrossing (N = 165) was treated with doxorubicin and docetaxel. Cardiac histopathological damage was measured by fibrosis and cardiomyocyte size by an Ariol slide scanner. We determine intramyocardial levels of intermediate molecular phenotypes of CDA associated with histopathological damage and quantitative trait loci (ipQTLs) linked to them. These ipQTLs seem to contribute to the missing heritability of CDA because they improve the heritability explained by QTL directly linked to CDA (cda-QTLs) through genetic models. Genes encoding these molecular subphenotypes were evaluated as genetic markers of CDA in three cancer patient cohorts (N = 517) whose cardiac damage was quantified by echocardiography or Cardiac Magnetic Resonance. Many SNPs associated with CDA were found using genetic models. LASSO multivariate regression identified two risk score models, one for pediatric cancer patients and the other for women with breast cancer. Molecular intermediate phenotypes associated with heart damage can identify genetic markers of CDA risk, thereby allowing a more personalized patient management. A similar strategy could be applied to identify genetic markers of other complex trait diseases.

Prevalence of acute oral mucosal damage secondary to the use of systemic antineoplastics: A systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to determine the prevalence of acute oral mucosal toxicities in non-irradiated patients treated with systemic antineoplastics agents. The secondary objective was to find out differences in its prevalence among the different types of systemic antineoplastics. STUDY DESIGN: A systematic review and meta-analysis was performed. Articles from 2010 to July 2022 were retrieved and included if patients were adults undergoing oral assessment after administration of commercially available systemic antineoplastics. Data was extracted and pooled proportions were estimated using random-effect model method (Der Simonian and Lair). RESULTS: Eighty-two articles were included in the study. The overall prevalence of acute oral mucosal damage across studies was 38.2% (95% CI: 33.1%-43.3%). The prevalence was 42.9% (95% CI: 32.8%-53%) in patients treated with chemotherapy alone, 38% (95% CI: 29.1%-47%) in patients treated with a combination of chemotherapy and targeted therapies, and 32.1% (95% CI: 26.8%-37.5%) in targeted therapies alone-treated patients. No statistically significant differences were found in the prevalence of oral mucosal toxicities between the different types of systemic antineoplastic treatments. CONCLUSIONS: Oral mucosal toxicity is a major side effect in non-irradiated cancer patients undergoing systemic antineoplastics.

Exploring High-Throughput Immunoassays for Biomarker Validation in Rheumatic Diseases in the Context of the Human Proteome Project.

Rheumatic diseases are high prevalence pathologies with different etiology and evolution and low sensitivity in clinical diagnosis. Therefore, it is necessary to develop an early diagnosis method which allows personalized treatment, depending on the specific pathology. The biology/disease initiative, at Human Proteome Project, is an integrative approach to identify relevant proteins in the human proteome associated with pathologies. A previously reported literature data mining analysis, which identified proteins related to osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PSA) was used to establish a systematic prioritization of potential biomarkers candidates for further evaluation by functional proteomics studies. The aim was to study the protein profile of serum samples from patients with rheumatic diseases such as OA, RA, and PSA. To achieve this goal, customized antibody microarrays (containing 151 antibodies targeting 121 specific proteins) were used to identify biomarkers related to early and specific diagnosis in a screening of 960 serum samples (nondepleted) (OA, n = 480; RA, n = 192; PSA, n = 288). This functional proteomics screening has allowed the determination of a panel (30 serum proteins) as potential biomarkers for these rheumatic diseases, displaying receiver operating characteristics curves with area under the curve values of 80-90%.

Translational research into frailty from bench to bedside: Salivary biomarkers for inflammaging.

Frailty is a complex physiological syndrome associated with adverse ageing and decreased physiological reserves. Frailty leads to cognitive and physical disability and is a significant cause of morbidity, mortality and economic costs. The underlying cause of frailty is multifaceted, including immunosenescence and inflammaging, changes in microbiota and metabolic dysfunction. Currently, salivary biomarkers are used as early predictors for some clinical diseases, contributing to the effective prevention and treatment of diseases, including frailty. Sample collection for salivary analysis is non-invasive and simple, which are paramount factors for testing in the vulnerable frail population. The aim of this review is to describe the current knowledge on the association between frailty and the inflammatory process and discuss methods to identify putative biomarkers in salivary fluids to predict this syndrome. This study describes the relationship between i.-inflammatory process and frailty; ii.-infectious, chronic, skeletal, metabolic and cognitive diseases with inflammation and frailty; iii.-inflammatory biomarkers and salivary fluids. There is a limited number of previous studies focusing on the analysis of inflammatory salivary biomarkers and frailty syndrome; hence, the study of salivary fluids as a source for biomarkers is an open area of research with the potential to address the increasing demands for frailty-associated biomarkers.