Plasmatic Exosome Number and Size Distinguish Prostate Cancer Patients From Healthy Individuals: A Prospective Clinical Study
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ABSTRACT:
SUBMITTER: Logozzi M
PROVIDER: S-EPMC8564386 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prostate Specific Antigen (PSA) fails to discriminate between benign prostatic hyperplasia (BPH) and Prostate Cancer (PCa), resulting in large numbers of unnecessary biopsies and missed cancer diagnoses. Nanovesicles called exosomes are directly detectable in patient plasma and here we explore the potential use of plasmatic exosomes expressing PSA (Exo-PSA) in distinguishing healthy individuals, BPH, and PCa. Exosomes were obtained from plasma samples of 80 PCa, 80 BPH, and 80 healthy donors (CTR). Nanoparticle Tracking Analysis (NTA), immunocapture-based ELISA (IC-ELISA), and nanoscale flow-cytometry (NSFC), were exploited to detect and characterize plasmatic exosomes. Statistical analysis showed that plasmatic exosomes expressing both CD81 and PSA were significantly higher in PCa as compared to both BPH and CTR, reaching 100% specificity and sensitivity in distinguishing PCa patients from healthy individuals. IC-ELISA, NSFC, and Exo-PSA consensus score (EXOMIX) showed 98% to 100% specificity and sensitivity for BPH-PCa discrimination. This study outperforms the conventional PSA test with a minimally invasive widely exploitable approach.
| S-EPMC6826376 | biostudies-literature
Project description:Objective: The intestinal microbiome is associated with various autoimmune diseases. Regional difference is the main influencing factor of intestinal microbial difference. This study aimed to identify the differences in fecal microbiome between autoimmune hepatitis (AIH) patients and healthy controls (HCs) in Central China, and to validate the efficacy of fecal microbiome as a diagnostic tool for AIH. Design: We collected 115 fecal samples from AIH patients (N = 37) and HCs (N = 78) in Central China and performed gene sequencing. Fecal microbiomes were characterized and microbial markers for AIH were identified. Results: Fecal microbial diversity showed a downward trend in AIH compared with HCs. Fecal microbial communities significantly differed between both groups. At the phylum level, Verrucomicrobia abundance was significantly increased, while Lentisphaerae and Synergistetes were significantly decreased in the AIH patients vs. the HCs. Compared to the HCs, 15 genera, including Veillonella, Faecalibacterium, and Akkermansia, were enriched, while 19 genera, such as Pseudobutyrivibrio, Lachnospira, and Ruminococcaceae, were decreased in the AIH patients. Ten genera, including Veillonella, Faecalibacterium, and Akkermansia, predominated in the AIH patients. Five microbial biomarkers were deemed optimal diagnostic tools for AIH. The probability of disease was significantly increased in AIH group vs. HCs, achieving 83.25% value of area under the curve. Conclusion: We present the characteristics of AIH patients in Central China for the first time. Five microbial biomarkers, including Lachnospiraceae, Veillonella, Bacteroides, Roseburia, and Ruminococcaceae, achieved a high potential distinguishing AIH patients from HCs.
| S-EPMC7416601 | biostudies-literature
Project description:Circular RNAs (circRNAs) have recently emerged as a new class of RNAs, highly enriched in the brain and very stable within cells, exosomes and body fluids. In this study, we aimed to screen the exosome derived circRNAs in glioblastoma multiforme (GBM) and investigate whether these circRNAs could predict GBM as potential biomarkers. The exosome was extracted from the plasma of GBM patients and healthy volunteers and validated by immunoblotting. The circRNA microarray was employed with three samples in each group to screen the dysregulated circRNAs isolated from the exosome. Five circRNAs were first selected as candidates with the upregulated level in exosome isolated from the plasma of GBM. Further validation found that only hsa_circ_0055202, hsa_circ_0074920 and hsa_circ_0043722 were consistent with training set. The Receiver operating characteristic (ROC) curve also revealed a high diagnostic ability an area under ROC curve value (AUC) for single circRNA and combined. The AUC for hsa_circ_0055202, hsa_circ_0074920, hsa_circ_0043722 and the combined was 0.810, 0.670, 0.938 and 0.988 in training set. For the validation set, the AUC was 0.850, 0.625, 0.750 and 0.925. The three circRNAs were further investigated with stable expression in human plasma samples. In conclusion, the exosome derived hsa_circ_0055202, hsa_circ_0074920 and hsa_circ_0043722 might be the potential biomarker for predicting the GBM.
| S-EPMC8386567 | biostudies-literature
Project description:The association between depressive disorders and measures reflecting myelin content is underexplored, despite growing evidence of associations with white matter tract integrity. We characterized the T1w/T2w ratio using the Glasser atlas in 39 UD and 47 HC participants (ages = 19-44, 75% female). A logistic elastic net regularized regression with nested cross-validation and a subsequent linear discriminant analysis conducted on held-out samples were used to select brain regions and classify patients vs. healthy controls (HC). True-label model performance was compared against permuted-label model performance. The T1w/T2w ratio distinguished patients from HC with 68% accuracy (p < 0.001; sensitivity = 63.8%, specificity = 71.5%). Brain regions contributing to this classification performance were located in the orbitofrontal cortex, anterior cingulate, extended visual, and auditory cortices, and showed statistically significant differences in the T1w/T2w ratio for patients vs. HC. As the T1w/T2w ratio is thought to characterize cortical myelin, patterns of cortical myelin in these regions may be a biomarker distinguishing individuals with depressive disorders from HC.
| S-EPMC8406024 | biostudies-literature
Project description:Rationale. Obesity is a risk factor for atherothrombosis and various cancers. However, the mechanisms are not completely uncovered. Objectives. We aimed to verify whether the microparticles (MPs) released from thrombin-activated platelets differed in obese and nonobese women for number, size, and proteomics cargo and the capacity to modulate in vitro the expression of genes related to the epithelial to mesenchymal transition (EMT) and the endothelial to mesenchymal transition (EndMT), and COX-2, a pro-angiogenic pathway. Methods and Results. MPs were obtained from thrombin activated platelets of four obese women and their matched, lean controls . MPs were analyzed by cytofluorimeter and protein content by liquid chromatography-mass spectrometry. Obese MPs were not different in number but were characterized by increased heterogeneity in size. In obese individuals, MPs containing mitochondria (mitoMPs) expressed lower CD41 levels and increased phosphatidylserine associated with enhanced Factor V representing a signature of a prothrombotic state. Proteomics analysis identified 44 proteins downregulated and 3 upregulated in obese versus nonobese MPs . A reduction in the proteins involved in mitophagy and antioxidant defenses, and of the -granular membrane was detected in the MPs of obese individuals. MPs released from platelets of obese individuals were more prone to induce the expression of marker genes of EMT and EndMT when incubated with HT29 cells and human cardiac microvascular endothelial cells(HCMEC), respectively. A protein, highly enhanced in obese MPs, was the pro-platelet basic protein with pro-inflammatory and tumorigenic actions. MPs from obese, but not nonobese, women induced COX-2 in HCMEC. Conclusions. Platelet-derived MPs of obese women showed higher heterogeneity in size and contained different levels of proteins relevant to thrombosis and tumorigenesis. Obese MPs presented enhanced capacity to induce changes in the expression of EMT and EndMT markers and COX-2. These effects might contribute to the increased risk for the development of thrombosis and multiple malignancies in obesity.
2019-02-19 | PXD011563 | Pride
Project description:Importance:An aging population experiences an increase in age-related problems, such as presbyphonia. The causes of pathologic presbyphonia are incompletely understood. Objective:To determine what distinguishes pathologic presbyphonia from presbylaryngis. Design, Setting, and Participants:This was a cohort study at an outpatient otolaryngology subspecialty clinic of a tertiary academic referral center. Participants were consecutive consenting adults older than 74 years without laryngeal pathologic abnormalities who visited the clinic as participants or companions. Patient questionnaires, otolaryngologic, video stroboscopic, and voice examinations were compiled. Patients were divided into groups based on whether they endorsed a voice complaint. Three blinded authors graded stroboscopic examinations for findings consistent with presbylaryngis (vocal fold bowing, vocal process prominence, glottic insufficiency). Main Outcomes and Measures:Voice Handicap Index-10, Reflux Symptom Index, Cough Severity Index, Dyspnea Index, Singing Voice Handicap Index-10 , Eating Assessment Tool -10, Voice-Related Quality of Life (VRQOL), and Short-Form Health Survey; face-sheet addressing social situation, work, marital status, education, voice use, transportation; acoustic and aerodynamic measures; and a full otolaryngologic examination, including videostroboscopic imaging. Results:A total of 31 participants with dysphonia (21 were female; their mean age was 83 years [range, 75-97 years]) and 26 control participants (16 were female; their mean age was 81 years [range, 75-103 years]) completed the study. Presbylaryngis was visible in 27 patients with dysphonia (87%) and 22 controls (85%). VHI-10 and VRQOL scores were worse in patients with pathologic presbyphonia (median [range] VHI-10 scores, 15 (0-40) vs 0 (0-16) and median VRQOL score, 19 [0-43] vs 10 [10-23]). All other survey results were indistinguishable, and no social differences were elucidated. Acoustic measures revealed that both groups averaged lower than normal speaking fundamental frequency (mean [SD], 150.01 [36.23] vs 150.85 [38.00]). Jitter was 3.44% (95% CI, 2.46%-4.61%) for pathologic presbyphonia and 1.74% (95% CI, 1.35%-2.14%) for controls (d = 0.75). Shimmer means (95% CI) were 7.8 2 (6.08-10.06) for the pathologic presbyphonia group and 4.84 (3.94-5.72) for controls (d = 0.69). Aerodynamic measures revealed an odds ratio of 3.03 (95% CI, 0.83-11.04) for patients with a maximum phonation time of less than 12 seconds who had complaints about dysphonia. Conclusions and Relevance:Presbylaryngis is present in most ambulatory people older than 74 years. Some will endorse pathologic presbyphonia that has a negative effect on their voice and quality of life. Pathologic presbyphonia seems to be influenced by respiratory capacity and sex. Further study is required to isolate other social, physiologic, and general health characteristics that contribute to pathologic presbyphonia.
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Project description:Bladder outlet obstruction (BOO) in large and small prostates is managed in a similar manner despite considerably different pathophysiology, which can result in higher failure rates. We investigate the clinical and urodynamic features and study the outcome of patients with benign prostate hyperplasia (BPH) according to their prostate size.We prospectively analyzed 100 BPH patients undergoing urodynamic study between January 2015 and August 2016 and divided them into two groups according to their prostate size: small (≤30 mL) and large prostate (>30 mL) groups. We compared the groups regarding age, International Prostate Symptom Score, maximal flow rate (Qmax), postvoided residual, serum prostate-specific antigen (PSA), prostate volume measured by ultrasonography (USG), and urodynamic findings.For testing the hypothesis, we used the Chi-square test, Student's t-test, and one-way analysis of variance when comparing between groups and conducted the logistic regression analysis for determining predictive factors of BOO.Although the total prostate volume significantly correlated with the PSA, patients with a small prostate had lower Qmax (5.27 ± 4.8 mL/s vs. 6.14 ± 6.66 mL/s; P = 0.74), higher incidence of abnormal baldder capacity (39.9% vs. 31.25%), lower voiding efficiency (39.3 ± 40.5% vs. 40.57 ± 32.11%), low compliance (44.4% vs. 31.3%), higher incidence of indeterminate detrusor contractions (38.9% vs. 37.5%), lower incidence of detrusor underactivity (33.3% vs. 28.1%), lower BOO index (40.9 ± 43.2 vs. 49.10 ± 44.48), lower bladder contractility index (77.8 ± 48.84 vs. 92.09 ± 52.79), and lower PdetQmax (51.44 ± 42.23 vs. 61.38 ± 42.01 cmH2O). Small prostates had higher failed voiding trials postsurgery.BOO patients with a small prostate showed poor urodynamic parameters and reported higher postoperative complications.
| S-EPMC5532887 | biostudies-other
Project description:Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota.
| S-EPMC4757479 | biostudies-literature
Project description:Estimating effective population size (N e) is important for theoretical and practical applications in evolutionary biology and conservation. Nevertheless, estimates of N e in organisms with complex life-history traits remain scarce because of the challenges associated with estimation methods. Partially clonal plants capable of both vegetative (clonal) growth and sexual reproduction are a common group of organisms for which the discrepancy between the apparent number of individuals (ramets) and the number of genetic individuals (genets) can be striking, and it is unclear how this discrepancy relates to N e. In this study, we analysed two populations of the orchid Cypripedium calceolus to understand how the rate of clonal versus sexual reproduction affected N e. We genotyped >1000 ramets at microsatellite and SNP loci, and estimated contemporary N e with the linkage disequilibrium method, starting from the theoretical expectation that variance in reproductive success among individuals caused by clonal reproduction and by constraints on sexual reproduction would lower N e. We considered factors potentially affecting our estimates, including different marker types and sampling strategies, and the influence of pseudoreplication in genomic data sets on N e confidence intervals. The magnitude of N e/N ramets and N e/N genets ratios we provide may be used as reference points for other species with similar life-history traits. Our findings demonstrate that N e in partially clonal plants cannot be predicted based on the number of genets generated by sexual reproduction, because demographic changes over time can strongly influence N e. This is especially relevant in species of conservation concern in which population declines may not be detected by only ascertaining the number of genets.
| S-EPMC10033856 | biostudies-literature
Project description:Six percent of American adults say they are "in recovery" from an alcohol or drug problem yet only a scant emergent literature has begun to ask how they define "recovery" or explored whether there is heterogeneity among their definitions.Secondary analysis of the "What is Recovery?" online survey employed latent class analysis (LCA) to identify typologies of study participants based on their actual endorsement of 39 recovery elements and to compare the composition of these typologies in terms of distinguishing personal characteristics.A five-class solution provided the best fit and conceptual representation for the recovery definitions. Classes were labeled 12-step traditionalist (n=4912); 12-step enthusiast (n=2014); secular (n=980); self-reliant (n=1040); and atypical (n=382) based on patterns of endorsement of the recovery elements. Abstinence, spiritual, and social interaction elements differentiated the classes most (as did age and recovery duration but to a lesser extent). Although levels and patterns of endorsement to the elements varied by class, a rank-ordering of the top 10 elements indicated that four elements were endorsed by all five classes: being honest with myself, handling negative feelings without using, being able to enjoy life, and process of growth and development.The results of the LCA demonstrate the diversity of meanings, and varying degrees of identification with, specific elements of recovery. As others have found, multiple constituents are invested in how recovery is defined and this has ramifications for professional, personal, and cultural processes related to how strategies to promote recovery are implemented.
| S-EPMC4330112 | biostudies-literature