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

Urine Proteome Analysis May Allow Noninvasive Differential Diagnosis of Diabetic Nephropathy

AbstractObjective: Chronic renal insufficiency and/or proteinuria in type 2 diabetes may stem from chronic renal diseases (CKD) other than classic diabetic nephropathy (DN) in over one third of cases. We interrogated urine proteomic profiles generated by SELDI-TOF/MS with the aim to isolate a set of biomarkers able to reliably identify biopsy-proven DN and to establish a stringent correlation with the different patterns of renal injury. Research design and methods: Ten mug urine proteins from 190 subjects [20 healthy subjects (HS), 20 normoalbuminuric (NAD) and 18 microalbuminuric (MICRO) diabetic patients, and 132 patients with biopsy-proven nephropathy (65 DN, 10 diabetics with non-diabetic CKD (nd-CKD) and 57 non-diabetic patients with CKD)] were run by CM10 ProteinChip array and analysed by supervised learning methods (CART analysis). Results: The classification model correctly identified 75% NAD, 87.5% MICRO and 87.5% DN when applied to a blinded testing set. Most importantly, it was able to reliably differentiate DN from nd-CKD in both diabetic and non-diabetic patients. Among the best predictors of the classification model, we identified and validated 2 proteins, ubiquitin and ss2-microglobulin. Conclusions: Our data suggest the presence of a specific urine proteomic signature able to reliably identify type 2 diabetic patients with diabetic glomerulosclerosis

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

Urinary myeloid IgA Fc alpha receptor (CD89) and transglutaminase-2 as new biomarkers for active IgA nephropathy and henoch-Schönlein purpura nephritis

Background: IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) are glomerular diseases that share a common and central pathogenic mechanism. The formation of immune complexes containing IgA1, myeloid IgA Fc alpha receptor (FcαRI/CD89) and transglutaminase-2 (TG2) is observed in both conditions. Therefore, urinary CD89 and TG2 could be potential biomarkers to identify active IgAN/HSPN. Methods: In this multicenter study, 160 patients with IgAN or HSPN were enrolled. Urinary concentrations of CD89 and TG2, as well as some other biochemical parameters, were measured. Results: Urinary CD89 and TG2 were lower in patients with active IgAN/HSPN compared to IgAN/HSPN patients in complete remission (P &lt; 0.001). The CD89xTG2 formula had a high ability to discriminate active from inactive IgAN/HSPN in both situations. : CD89xTG2/proteinuria ratio (AUC: 0.84, P &lt; 0.001, sensitivity: 76%, specificity: 74%) and CD89xTG2/urinary creatinine ratio (AUC: 0.82, P &lt; 0.001, sensitivity: 75%, specificity: 74%). Significant correlations between urinary CD89 and TG2 (r = 0.711, P &lt; 0.001), proteinuria and urinary CD89 (r = -0.585, P &lt; 0.001), and proteinuria and urinary TG2 (r = -0.620, P &lt; 0.001) were observed. Conclusions: Determination of CD89 and TG2 in urine samples can be useful to identify patients with active IgAN/HSPN

Oral dysbiosis in pancreatic cancer and liver cirrhosis: A review of the literature

The human body is naturally colonized by a huge number of different commensal microbial species, in a relatively stable equilibrium. When this microbial community undergoes dysbiosis at any part of the body, it interacts with the innate immune system and results in a poor health status, locally or systemically. Research studies show that bacteria are capable of significantly influencing specific cells of the immune system, resulting in many diseases, including a neoplastic response. Amongst the multiple different types of diseases, pancreatic cancer and liver cirrhosis were significantly considered in this paper, as they are major fatal diseases. Recently, these two diseases were shown to be associated with increased or decreased numbers of certain oral bacterial species. These findings open the way for a broader perception and more specific investigative studies, to better understand the possible future treatment and prevention. This review aims to describe the correlation between oral dysbiosis and both pancreatic cancer and liver cirrhotic diseases, as well as demonstrating the possible diagnostic and treatment modalities, relying on the oral microbiota, itself, as prospective, simple, applicable non-invasive approaches to patients, by focusing on the state of the art. PubMed was electronically searched, using the following key words: "oral microbiota" and "pancreatic cancer" (PC), "liver cirrhosis", "systemic involvement", and "inflammatory mediators". Oral dysbiosis is a common problem related to poor oral or systemic health conditions. Oral pathogens can disseminate to distant body organs via the local, oral blood circulation, or pass through the gastrointestinal tract and enter into the systemic circulation. Once oral pathogens reach an organ, they modify the immune response and stimulate the release of the inflammatory mediators, this results in a disease. Recent studies have reported a correlation between oral dysbiosis and the increased risk of pancreatic and liver diseases and provided evidence of the presence of oral pathogens in diseased organs. The profound impact that microbial communities have on human health, provides a wide domain towards precisely investigating and clearly understanding the mechanism of many diseases, including cancer. Oral microbiota is an essential contributor to health status and imbalance in this community was correlated to oral and systemic diseases. The presence of elevated numbers of certain oral bacteria, particularly P. gingivalis, as well as elevated levels of blood serum antibodies, against this bacterial species, was associated with a higher risk of pancreatic cancer and liver cirrhosis incidence. Attempts are increasingly directed towards investigating the composition of oral microbiome as a simple diagnostic approach in multiple diseases, including pancreatic and liver pathosis. Moreover, treatment efforts are concerned in the recruitment of microbiota, for remedial purposes of the aforementioned and other different diseases. Further investigation is required to confirm and clarify the role of oral microbiota in enhancing pancreatic and liver diseases. Improving the treatment modalities requires an exertion of more effort, especially, concerning the microbiome engineering and oral microbiota transplantation

Functional implications of bound phenolic compounds and phenolics–food interaction: A review

Sizeable scientific evidence indicates the health benefits related to phenolic compounds and dietary fiber. Various phenolic compounds-rich foods or ingredients are also rich in dietary fiber, and these two health components may interrelate via noncovalent (reversible) and covalent (mostly irreversible) interactions. Notwithstanding, these interactions are responsible for the carrier effect ascribed to fiber toward the digestive system and can modulate the bioaccessibility of phenolics, thus shaping health-promoting effects in vivo. On this basis, the present review focuses on the nature, occurrence, and implications of the interactions between phenolics and food components. Covalent and noncovalent interactions are presented, their occurrence discussed, and the effect of food processing introduced. Once reaching the large intestine, fiber-bound phenolics undergo an intense transformation by the microbial community therein, encompassing reactions such as deglycosylation, dehydroxylation, α- and β-oxidation, dehydrogenation, demethylation, decarboxylation, C-ring fission, and cleavage to lower molecular weight phenolics. Comparatively less information is still available on the consequences on gut microbiota. So far, the very most of the information on the ability of bound phenolics to modulate gut microbiota relates to in vitro models and single strains in culture medium. Despite offering promising information, such models provide limited information about the effect on gut microbes, and future research is deemed in this field