Liquid biopsy in the assessment of microRNAs in oral squamous cell carcinoma: a systematic review

Background: The identification of non-invasive biomarkers from biological fluids collected by liquid biopsy provides new horizons for individualized therapeutic strategies and improves clinical decision-making in OSCC patients. Circulating microRNAs have emerged as biomarkers that may reflect not only the existence of cancer, but also the dynamic, malignant potential, and drug resistance of tumors. The aim of the systematic review is to evaluate and summarize the results of the published studies regarding the use of microRNAs as biomarkers for OSCC. Material and methods: A literature search was conducted on PubMed, Scopus, Web of Science, and Cochrane databases till November 2020. A total of 34 studies met the inclusion criteria and were therefore subjected to quality assessment. Each study was subjected to data extraction including; patient characteristics, type of fluid sample (whole blood, plasma, serum, or saliva), molecular analysis method, specific dysregulated microRNA, and microRNA expression pattern. Results: The analysis showed that 57 microRNAs of liquid biopsy samples of four different fluids (whole blood, serum, plasma, and saliva) were analyzed. The prognostic and therapeutic significance of these microRNAs were suggested by several studies; where 41 microRNAs were upregulated while 16 were downregulated. Conclusions: Scientific evidence supports the interest in the use of microRNAs in the diagnosis and prognosis in OSCC patients; however, further studies in a larger cohort of patients are mandatory to introduce liquid biopsy in the routine clinical practice for the OSCC management. Key words:Biomarkers, liquid biopsy, microRNA, oral squamous cell carcinoma, systematic review.Background: The identification of non-invasive biomarkers from biological fluids collected by liquid biopsy provides new horizons for individualized therapeutic strategies and improves clinical decision-making in OSCC patients. Circulating microRNAs have emerged as biomarkers that may reflect not only the existence of cancer, but also the dynamic, malignant potential, and drug resistance of tumors. The aim of the systematic review is to evaluate and summarize the results of the published studies regarding the use of microRNAs as biomarkers for OSCC. Material and methods: A literature search was conducted on PubMed, Scopus, Web of Science, and Cochrane databases till November 2020. A total of 34 studies met the inclusion criteria and were therefore subjected to quality assessment. Each study was subjected to data extraction including; patient characteristics, type of fluid sample (whole blood, plasma, serum, or saliva), molecular analysis method, specific dysregulated microRNA, and microRNA expression pattern. Results: The analysis showed that 57 microRNAs of liquid biopsy samples of four different fluids (whole blood, serum, plasma, and saliva) were analyzed. The prognostic and therapeutic significance of these microRNAs were suggested by several studies; where 41 microRNAs were upregulated while 16 were downregulated. Conclusions: Scientific evidence supports the interest in the use of microRNAs in the diagnosis and prognosis in OSCC patients; however, further studies in a larger cohort of patients are mandatory to introduce liquid biopsy in the routine clinical practice for the OSCC management. Key words:Biomarkers, liquid biopsy, microRNA, oral squamous cell carcinoma, systematic review

Phytochemical profiling, antibacterial and antioxidant properties of Crocus sativus flower: A comparison between tepals and stigmas

Several studies have demonstrated that stigmas of Crocus sativus contain several bioactive compounds with potential health-promoting properties. However, during the processing of stigmas, large amounts of floral bio-residues are normally discarded as by-products. In this study, using untargeted metabolomics, the comprehensive phytochemical composition of C. sativus stigma and tepals was investigated. Moreover, the antibacterial and anti-biofilm properties of the extracts of C. sativus stigmas and tepals were compared. The study was carried out using two methicillin-resistant staphylococcal reference strains (i.e., Staphylococcus aureus ATCC 43300 and Staphylococcus epidermidis ATCC 35984), representing important Gram-positive biofilm-forming human pathogens. The antibacterial properties were correlated with total polyphenol content, total terpenoid content, and in vitro antioxidant properties of tepals and stigmas. The results demonstrated that stigma and tepal extracts, at the sub-toxic concentrations, were able to interfere with biofilm formation by ATCC 43300 and ATCC 35984. Besides, the higher antibacterial activity of tepals than stigmas was associated with higher levels of phycompounds. Therefore, our results demonstrated that C. sativus stigmas and bio-residues, such as tepals, are potential antioxidant sources and good candidates as antibacterial agents to prevent biofilm formation. Taken together, these findings showed that C. sativus could be used as functional ingredient by the food and pharmaceutical industries

Beyond the Visible and Below the Peel: How UV-B Radiation Influences the Phenolic Profile in the Pulp of Peach Fruit. A Biochemical and Molecular Study

In the last decades, UV-B radiation has attracted attention due to its potential to increase nutraceutical values of fruit and vegetables, especially by inducing the accumulation of phenolics in a structure-dependent way. However, most current studies have investigated the UV-B-driven changes only in the peel or focusing on individual phenolic classes. Adopting an \u201c-omics\u201d approach, this work aimed to deepen the knowledge about the effects of UV-B radiation on the phenolic profile in the pulp of peach fruit. Based on these considerations, melting flesh yellow peaches (Prunus persica L., cv. Fairtime) were subjected to either a 10- or 60-min UV-B treatment (1.39 and 8.33 kJ m\u20132, respectively), and sampled at different time points from the exposure. A UHPLC-ESI/QTOF-MS analysis coupled with a phenolics-specific database for the annotation of compounds and a multivariate discriminant analysis revealed a marked effect of UV-B radiation on the phenolic profiles of peach pulp. Particularly, a general, transient increase was observed after 24 h from the irradiation, especially for flavanols, flavonols, and flavones. Such behavior diverges from what was observed in the peel, where an overall increase of phenolics was observed after 36 h from the irradiation. Concerning the flavonols in the pulp, UV-B exposure stimulated a specific accumulation of isorhamnetin and kaempferol derivatives, with variations imposed by the different sugar moiety bound. Anthocyanins, which were the second most abundant flavonoid group after flavonols, displayed a general decrease after 36 h that was not attributable to specific molecules. The UV-B treatments also increased the glycoside/aglycone ratio of flavonols and anthocyanins after 24 h, by increasing the glycoside concentration of both, flavonols and anthocyanins, and decreasing the aglycone concentration of anthocyanins. In support of the biochemical results, targeted gene expression analysis by RT-qPCR revealed an UV-B-induced activation of many genes involved in the flavonoid pathway, e.g., CHS, F3H, F3\u2032H, DFR, as well as some MYB transcription factors and few genes involved in the UV-B perception. Generally, all the flavonoid-related and MYB genes showed a transient UV-B dose-dependent activation after 6 h from the irradiation, similarly to what was observed in the peel

Is the pain just physical? The role of psychological distress, quality of life, and autistic traits in ehlers–danlos syndrome, an internet-based survey in italy

Background: Ehlers–Danlos syndromes (EDS) have been associated with psychological distress, comorbid psychiatric disorders, and worsening in quality of life (QoL). Among the neurodevelopmental disorders, autism spectrum disorders (ASD) have shown the highest rates of co-occurrence with EDS. The reasons for these associations are unknown and a possible role of pain in increasing the risk of psychiatric disorders in EDS has been suggested. However, a detailed picture of an Italian EDS sample is still lacking. Methods: We conducted a web-based survey in a third level center for the diagnosis of EDS in northern Italy, to investigate psychological distress, QoL, and the presence of autistic traits. Furthermore, we correlated the psychometric data with some clinical variables. Results: We observed a high rate of psychological distress with 91% of the responders at high risk of common mental disorders, low QoL, and high prevalence of autistic traits in EDS patients. Specifically, patients lacking a specific genetic test, diagnosed as suspects of EDS appeared to be at greater risk and reported worse psychological QoL. Pain was significantly associated with both psychological distress and worse QoL. Conclusions: Our findings support the need of further research and of a multi-disciplinary approach to EDS including psychological and psychiatric liaison

Volatile compounds, gamma-glutamyl-peptides and free amino acids as biomarkers of long-ripened protected designation of origin Coppa Piacentina

Coppa Piacentina is an Italian protected designation of origin (PDO) dry-cured product obtained from the muscle of pork neck and ripened for at least six months. Metabolomics- and volatilomics-based strategies, combined with a chemical characterization of free amino acids were applied to identify biomarkers of long-ripened Coppa Piacentina PDO. Long ripening induced a significantly increase of total free amino acids, mainly represented by glutamic acid, involved in the umami taste perception. Untargeted metabolomics, performed using UHPLC-HRMS, allowed to identify 32 putative gamma-glutamyl-peptides, known as main contributors to the kokumi taste. Unsupervised and supervised multivariate statistics observed a clear modification of these peptides over the ripening, with gamma-glutamyl-peptides which significantly increased in long-ripened samples. A volatilomics-based strategy, conducted with GCxGC-MS, was then performed, and 93 different compounds were identified, with aldehyde and ketones deriving from the lipid auto-oxidation which increased according to ripening

Unusual association of NDM-1 with KPC-2 and armA among Brazilian Enterobacteriaceae isolates

We report the microbiological characterization of four New Delhi metallo-beta-lactamase-1 (bla(NDM-1))-producing Enterobacteriaceae isolated in Rio de Janeiro, Brazil. bla(NDM-1) was located on a conjugative plasmid and was associated with Klebsiella pneumoniae carbapenemase-2 (bla(KPC-2)) or aminoglycoside-resistance methylase ( armA), a 16S rRNA methylase not previously reported in Brazil, in two distinct strains of Enterobacter cloacae. Our results suggested that the introduction of bla(NDM-1) in Brazil has been accompanied by rapid spread, since our isolates showed no genetic relationship.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Med, Lab Especial Microbiol Clin, São Paulo, SP, BrazilDASA, Lab Diagnost Amer, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Med, Lab Especial Microbiol Clin, São Paulo, SP, BrazilWeb of Scienc

Suicide risk in medically ill inpatients referred to consultation-liaison psychiatric services: A multicenter study

Background: The aim of this multicenter study was to investigate the suicide risk in medically ill patients admitted to six Italian hospitals for whom a consultation-liaison intervention was requested. Methods: Participants completed socio-demographic and clinical report forms and the Brief Illness Perception Questionnaire. Suicidality was assessed using the P4 screener that investigates the presence of Past suicide attempts, Plans to commit a suicide, Probability of completing suicide, and Preventive factors. Participants were categorized as being at no, low or high suicide risk. Univariate and multivariable associations of categorical and continuous variables with suicide risk were investigated using multinomial logistic regression. Results: Of the 641 inpatients, with mean age 60 years (SD = 16.9) and 49.2 % male, 13.2 % were at high suicidal risk (HR), 7.6 % low risk (LR) and 79.2 % no risk. Contacts with psychiatrists in the previous six months were associated with LR and HR (OR = 2.159 and 2.634, respectively), ongoing benzodiazepine use was associated with a threefold likelihood of LR (OR = 3.005), and the experienced intensity of illness symptoms was associated with LR and HR (OR = 1.257 and OR = 1.248, respectively). CL psychiatrists prescribed appropriate psychotropic drugs and activated liaison interventions and psychological support for the level of suicidal risk. Limitations: The use of self-report measures bears the risk of recall bias. Conclusions: Our findings based on psychiatric consultations in the general hospital underscore the need to include suicide risk in the routine assessment of inpatients referred to CL psychiatric services and to plan an appropriate management of suicidal risk after discharge

Combination with tomatidine improves the potency of posaconazole against Trypanosoma cruzi

Azoles such as posaconazole (Posa) are highly potent against Trypanosoma cruzi. However, when tested in chronic Chagas disease patients, a high rate of relapse after Posa treatment was observed. It appears that inhibition of T. cruzi cytochrome CYP51, the target of azoles, does not deliver sterile cure in monotherapy. Looking for suitable combination partners of azoles, we have selected a set of inhibitors of sterol and sphingolipid biosynthetic enzymes. A small-scale phenotypic screening was conducted in vitro against the proliferative forms of T. cruzi, extracellular epimastigotes and intracellular amastigotes. Against the intracellular, clinically relevant forms, four out of 15 tested compounds presented higher or equal activity as benznidazole (Bz), with EC50 values </=2.2 muM. Ro48-8071, an inhibitor of lanosterol synthase (ERG7), and the steroidal alkaloid tomatidine (TH), an inhibitor of C-24 sterol methyltransferase (ERG6), exhibited the highest potency and selectivity indices (SI = 12 and 115, respectively). Both were directed to combinatory assays using fixed-ratio protocols with Posa, Bz, and fexinidazole. The combination of TH with Posa displayed a synergistic profile against amastigotes, with a mean SigmaFICI value of 0.2. In vivo assays using an acute mouse model of T. cruzi infection demonstrated lack of antiparasitic activity of TH alone in doses ranging from 0.5 to 5 mg/kg. As observed in vitro, the best combo proportion in vivo was the ratio 3 TH:1 Posa. The combination of Posa at 1.25 mpk plus TH at 3.75 mpk displayed suppression of peak parasitemia of 80% and a survival rate of 60% in the acute infection model, as compared to 20% survival for Posa at 1.25 mpk alone and 40% for Posa at 10 mpk alone. These initial results indicate a potential for the combination of posaconazole with tomatidine against T. cruzi

A response surface methodology approach to improve nitrogen use efficiency in maize by an optimal mycorrhiza-to-Bacillus co-inoculation rate

Co-inoculation of arbuscular mycorrhizal fungi (AMF) and bacteria can synergically and potentially increase nitrogen use efficiency (NUE) in plants, thus, reducing nitrogen (N) fertilizers use and their environmental impact. However, limited research is available on AMF-bacteria interaction, and the definition of synergisms or antagonistic effects is unexplored. In this study, we adopted a response surface methodology (RSM) to assess the optimal combination of AMF (Rhizoglomus irregulare and Funneliformis mosseae) and Bacillus megaterium (a PGPR—plant growth promoting rhizobacteria) formulations to maximize agronomical and chemical parameters linked to N utilization in maize (Zea mays L.). The fitted mathematical models, and also 3D response surface and contour plots, allowed us to determine the optimal AMF and bacterial doses, which are approximately accorded to 2.1 kg ha–1 of both formulations. These levels provided the maximum values of SPAD, aspartate, and glutamate. On the contrary, agronomic parameters were not affected, except for the nitrogen harvest index (NHI), which was slightly affected (p-value of &lt; 0.10) and indicated a higher N accumulation in grain following inoculation with 4.1 and 0.1 kg ha–1 of AMF and B. megaterium, respectively. Nonetheless, the identification of the saddle points for asparagine and the tendency to differently allocate N when AMF or PGPR were used alone, pointed out the complexity of microorganism interaction and suggests the need for further investigations aimed at unraveling the mechanisms underlying this symbiosis