Typical Biomarkers Research Articles

Antimitochondrial Antibodies: from Bench to Bedside.

Anti-mitochondrial antibodies (AMA) are directed against the E2 subunits of the 2-oxo acid dehydrogenase complexes (PDC-E2) and are the typical biomarkers of primary biliary cholangitis (PBC), being present in 90–95% of patients, with increasing sensitivity at increasing titers. Albeit being highly specific for PBC diagnosis, AMA can be detected in less than 1% of healthy subjects, and thus the management subjects with no sign or symptom of liver disease is still a challenge and data concerning clinical risk of developing PBC in this subgroup of patients are controversial. Moreover, AMA can also be detected in patients affected by overlap syndrome, as well as hepatic diseases (i.e., NASH and viral hepatitis), while the association with autoimmune diseases, in particular Sjögren’s syndrome, systemic sclerosis, and systemic lupus erythematosus, is well established. Furthermore, new associations are being identified with inflammatory myositis and heart disease. AMA are directed towards the pyruvate dehydrogenase multi enzyme complex (PDC-E2) subunit, which represents an epithelial specific autoantigen for PBC. This review focuses on the main characteristics of AMA, their association with autoimmune diseases and liver diseases.

Chemometric Classification of Oil Families in the Laizhouwan Depression, Bohai Bay Basin, Eastern China.

A suite of oil-sand bitumen and crude oil samples, collected from the Laizhouwan depression, Bohai Bay basin, were geochemically investigated for molecular compositions. Three oil families (A, B, and C) were classified by hierarchical cluster analysis (HCA) and principal component analysis on nine typical biomarker ratios. Typically, family A oils are characterized by relatively low values of gammacerane/C31 homohopane 22R (G/H31, 0.13–0.76) and C35/C34 homohopane (H35/H34, 0.39–0.78), suggesting a source from freshwater depositional environments. In contrast, family C oils show a relatively high G/H31 (2.49–5.41) and H35/H34 (1.43–2.45) ratios, indicating a source from hypersaline water depositional environments. Family B oils display ratios of G/H31 and H35/H34 in-between the range of families A and C, suggesting mixed origin. In addition, family A oils can be further classified into four subfamilies (A1, A2, A3, and A4) and family B oils into two subfamilies (B1 and B2) by HCA. The A1 oils characterized by a high C24 tetracyclic terpane/C26 tricyclic terpane (TeT24/TT26) ratio (1.02–1.39) are mainly distributed in the northeast, B1 oils characterized by relatively low TeT24/TT26 ratio are in the west, and A2, A3, and A4 oils with an intermediate TeT24/TT26 ratio are in the center of the depression. Oils in well L16-1-2 in the southern depression, however, show vertical variations with family C oils in the deeper reservoirs, subfamily B2 oils in the shallower reservoirs, and subfamily A4 oils in the middle-depth reservoirs. Based on the biomarker compositions, at least three oil charges were indicated: family C oils are likely sourced from the Es4 rock in the southern sag, B2 oils may be a mixture of family C with family A oils, and A4 oils without biodegradation influence may be the latest charge derived from the Es3 source rock in the northern sag. The oil families and/or subfamilies with typical genetic affinities, as well as the regular occurrence in different blocks, may indicate two major petroleum systems or multiple subsidiary oil systems existing in the Laizhouwan depression.

Risk assessments and health impacts of heavy metal pollution

<p indent="0mm">Heavy metal pollution is a serious global environmental issue, posing huge risks to food security and human health. As a typical biomarker of heavy metals, soil nematodes develop complex defenses in response to heavy metal exposures. Meanwhile, their gut microbiomes assist host resistance to heavy metals. Here we review the pollution status and assessment methods of heavy metals at home and abroad and summarize their effects on the behavior, physiology, and biochemistry of soil nematodes. Additionally, defense mechanisms of organisms against heavy metals are reviewed, including barrier functions of the cell wall and membrane, changes in active substances, metallothionein overexpression, and noncoding RNA regulation. We propose that the diversity and composition of the nematode gut microbiome can be used as a new indicator of heavy metal toxicity. Furthermore, long-term heavy metal exposure could lead to adaptive evolution, such as the emergence and enrichment of heavy metal hyperaccumulation, resistance, and detoxification genes. Additionally, we can map genetic changes, such as resistance mutations in genes and synergies of resistance, by quantifying the genome-level response of genetic variation under environmental stresses. Finally, we provide a prospect on the ecotoxicology of heavy metals and indicate that future research should focus on the current ecological environment and human health, explore the ecological role of soil fauna gut microbiome, and further understand the potential mechanism of occurrence and development of heavy metal toxicity and biological detoxification.

Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.

Primary immune regulatory disorders (PIRD) are associated with autoimmunity, autoinflammation and/or dysregulation of lymphocyte homeostasis. Autoimmune lymphoproliferative syndrome (ALPS) is a PIRD due to an apoptotic defect in Fas-FasL pathway and characterized by benign and chronic lymphoproliferation, autoimmunity and increased risk of lymphoma. Clinical manifestations and typical laboratory biomarkers of ALPS have also been found in patients with a gene defect out of the Fas-FasL pathway (ALPS-like disorders). Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), we identified more than 600 patients suffering from 24 distinct genetic defects described in the literature with an autoimmune lymphoproliferative phenotype (ALPS-like syndromes) corresponding to phenocopies of primary immunodeficiency (PID) (NRAS, KRAS), susceptibility to EBV (MAGT1, PRKCD, XIAP, SH2D1A, RASGRP1, TNFRSF9), antibody deficiency (PIK3CD gain of function (GOF), PIK3R1 loss of function (LOF), CARD11 GOF), regulatory T-cells defects (CTLA4, LRBA, STAT3 GOF, IL2RA, IL2RB, DEF6), combined immunodeficiencies (ITK, STK4), defects in intrinsic and innate immunity and predisposition to infection (STAT1 GOF, IL12RB1) and autoimmunity/autoinflammation (ADA2, TNFAIP3,TPP2, TET2). CTLA4 and LRBA patients correspond around to 50% of total ALPS-like cases. However, only 100% of CTLA4, PRKCD, TET2 and NRAS/KRAS reported patients had an ALPS-like presentation, while the autoimmunity and lymphoproliferation combination resulted rare in other genetic defects. Recurrent infections, skin lesions, enteropathy and malignancy are the most common clinical manifestations. Some approaches available for the immunological study and identification of ALPS-like patients through flow cytometry and ALPS biomarkers are provided in this work. Protein expression assays for NKG2D, XIAP, SAP, CTLA4 and LRBA deficiencies and functional studies of AKT, STAT1 and STAT3 phosphorylation, are showed as useful tests. Patients suspected to suffer from one of these disorders require rapid and correct diagnosis allowing initiation of tailored specific therapeutic strategies and monitoring thereby improving the prognosis and their quality of life.

Ecological Risks Due to Immunotoxicological Effects on Aquatic Organisms.

The immunotoxic effects of some anthropogenic pollutants on aquatic organisms are among the causes of concern over the presence of these pollutants in the marine environment. The immune system is part of an organism’s biological defense necessarily for homeostasis. Thus, the immunotoxicological impacts on aquatic organisms are important to understand the effects of pollutant chemicals in the aquatic ecosystem. When aquatic organisms are exposed to pollutant chemicals with immunotoxicity, it results in poor health. In addition, aquatic organisms are exposed to pathogenic bacteria, viruses, parasites, and fungi. Exposure to pollutant chemicals has reportedly caused aquatic organisms to show various immunotoxic symptoms such as histological changes of lymphoid tissue, changes of immune functionality and the distribution of immune cells, and changes in the resistance of organisms to infection by pathogens. Alterations of immune systems by contaminants can therefore lead to the deaths of individual organisms, increase the general risk of infections by pathogens, and probably decrease the populations of some species. This review introduced the immunotoxicological impact of pollutant chemicals in aquatic organisms, including invertebrates, fish, amphibians, and marine mammals; described typical biomarkers used in aquatic immunotoxicological studies; and then, discussed the current issues on ecological risk assessment and how to address ecological risk assessment through immunotoxicology. Moreover, the usefulness of the population growth rate to estimate the immunotoxicological impact of pollution chemicals was proposed.

Ultrastable Tb-Organic Framework as a Selective Sensor of Phenylglyoxylic Acid in Urine.

Industrial pollution and harmful chemicals seriously affect environment and human health. Styrene is a common air toxicant with widespread exposure sources, including smoking, automobile exhaust, and plastic pollutants. Phenylglyoxylic acid (PGA) is a typical biomarker for exposed styrene. Therefore, it is crucial to quickly identify and quantitatively detect PGA. Herein, an ultrastable terbium metal-organic framework (Tb-MOF 1) was developed, and the luminescence film (1/PLA) consisting of polylactic acid (PLA) and 1 was fabricated as a sensor for rapid detection of PGA. The sensor possesses the advantages of efficient detection [limit of detection (LOD) is 1.05 × 10-4 mg/mL] and rapid response speed (less than 10 s) for PGA in urine. Furthermore, this sensor exhibits high stability, outstanding anti-interference ability, and excellent recyclability. Based on this film technology, a paper-based probe was then developed for portable and convenient detection. The probe could easily distinguish different concentrations of PGA under the naked eye toward practical sensing applications. Meanwhile, photoinduced electron transfer was demonstrated to be responsible for the luminescence sensing. Hence, this study indicates that Tb-MOF is a promising material to detect PGA for evaluating the effect of styrene on the body.

Physiological Responses of Wheat Seedlings to Soil Waterlogging Applied after Treatment with Selective Herbicide.

Waterlogging impairs crop development and considerably affects plant productivity worldwide. Wheat is sensitive to waterlogging. Serrate® (Syngenta) is a selective herbicide controlling annual grass and broadleaf weeds for use in wheat. To extend the existing information about the physiological effects of selective herbicides (Serrate® in particular) and subsequent waterlogging in wheat, we monitored phenotype alterations and examined key enzymatic and non-enzymatic antioxidant defense systems together with typical oxidative stress biomarkers. Seventeen-day-old wheat (Triticum asetivum L., cv. Sadovo-1) plants were sprayed with Serrate®; 72 h later, waterlogging was applied for 7 days, and then seedlings were left to recover for 96 h. The herbicide did not alter plant phenotype and increased antioxidant defense, along with H2O2 content, confirming the wheat’s tolerance to Serrate®. Evident yellowing and wilting of the leaves were observed at 96 h of recovery in waterlogged wheat, which were stronger in plants subjected to Serrate® + waterlogging. Waterlogging alone and herbicide + waterlogging gradually enhanced the content of stress markers (malondialdehyde, proline, and H2O2), non-enzymatic antioxidants (low-molecular thiols and total phenolics), and the activity of superoxide dismutase, guaiacol peroxidase, and glutathione reductase. The effects of herbicide + waterlogging were stronger than those of waterlogging alone even during recovery, suggesting that Serrate® interacted synergistically with the subsequently applied flooding.

Benchtop Isolation and Characterisation of Small Extracellular Vesicles from Human Mesenchymal Stem Cells.

The objective of this study is to develop a simple protocol to isolate and characterise small extracellular vesicles (sEVs) from human umbilical cord-derived MSCs (hUC-MSCs). hUC-MSCs were characterised through analysis of morphology, immunophenotyping and multidifferentiation ability. SEVs were successfully isolated by ultrafiltration from the conditioned medium of hUC-MSCs. The sEVs' size distribution, intensity within a specific surface marker population were measured with zetasizer or nanoparticle tracking analysis. The expression of surface and internal markers of sEVs was also assessed by western blotting. Morphology of hUC-MSCs displayed as spindle-shaped, fibroblast-like adherent cells. Phenotypic analysis by flow cytometry revealed that hUC-MSCs expressed MSC surface marker, including CD90, CD73, CD105, CD44 and exhibited the capacity for osteogenic, adipogenic and chondrogenic differentiation. Populations of sEVs with CD9, CD63 and CD81 positive were detected with size distribution in the diameter of 63.2 to 162.5nm. Typical sEVs biomarkers such as CD9, CD63, CD81, HSP70 and TSG101 were also detected with western blotting. Our study showed that sEVs from hUC-MSCs conditioned medium were successfully isolated and characterised. Downstream application of hUC-MSCs-sEVs will be further explored.

Identification of biomarkers specific to five different nicotine product user groups: Study protocol of a controlled clinical trial

BackgroundAssessing biomarker profiles in various body fluids is of large value to discern between the sole use of nicotine products. In particular, the assessment of the product compliance is required for long-term clinical studies. The objective of this study was the identification of biomarkers and biomarker patterns in body fluids, to distinguish between combustibles, heated tobacco products, electronic cigarettes, oral tobacco and oral/dermal nicotine products used for nicotine replacement therapy (NRT), as well as a control group of non-users. MethodsA controlled, single-center study was conducted with 60 healthy subjects, divided into 6 groups (5 nicotine product user groups and one non-user group) based on their sole use of the products of choice. The subjects were confined for 76 h, during which, free and uncontrolled use of the products was provided. Sample collections were performed according to the study time schedule provided in Table 2. The primary outcome will be validated through analysis of the collected biospecimens (urine, blood, saliva, exhaled breath and exhaled breath condensate) by means of untargeted omics approaches (i.e. exposomics, breathomics and adductomics). Secondary outcome will include established biomarker quantification methods to allow for the identification of typical biomarker patterns. Statistical analysis tools will be used to specifically discriminate different product use categories. Results/ConclusionsThe clinical trial was successfully completed in May 2020, resulting in sample management and preparations for the quantitative and qualitative analyses. This work will serve as a solid basis to discern between biomarker profiles of different nicotine product user groups. The knowledge collected during this research will be required to develop prototype diagnostic tools that can reliably assess the differences and evaluate possible health risks of various nicotine products.

Entropy-driven strand displacement reaction for ultrasensitive detection of circulating tumor DNA based on upconversion and Fe3O4 nanocrystals

Early detection of cancer biomarkers applied in real-time disease diagnosis and therapies can increase the survival rate of patients. Circulating tumor DNA (ctDNA) as a typical cancer biomarker plays a great role in the process of tumor disease monitoring, especially in early diagnosis. Unfortunately, most ctDNA detection systems have not been widely used due to their low sensitivity, poor specificity, and high cost. Herein, we developed an alternative ctDNA detection system to present the levels of ctDNA by recording the fluorescence signals of the system containing upconversion nanoparticles (UCNPs), Fe3O4, and entropy-driven strand displacement reaction. The method has a practical sensitivity with a wide linear range from 100 amol L−1 to 1 nmol L−1 and a low detection limit of 1.6 amol L−1. Furthermore, the system demonstrates a practical application in mouse blood serum samples and meets the requirements for rapid, sensitive, specific, and economical diagnosis of cancers. Thus, this ctDNA detection system may have great potential for ctDNA detection and clinical diagnosis.

Effects of continuous and intermittent cadmium exposure on HPGL axis, GH/IGF axis and circadian rhythm signaling and their consequences on reproduction in female zebrafish: Biomarkers independent of exposure regimes

Typical biomarkers of cadmium (Cd) pollution have well been confirmed in fish from continuous exposure pattern. However, in a natural environment, fish may be exposed to Cd intermittently. In this study, juvenile female zebrafish were exposed for 48 days to 10 μg/L Cd continuously, 20 μg/L for 1 day in every 2 days or 30 μg/L for 1 day in every 3 days. The toxic effects were evaluated using 8 various physiological and biochemical endpoints like specific growth rate (SGR), 17β-estradiol (E2) and vitellogenin (VTG) concentrations in plasma, reproductive parameters (gonadosomatic index (GSI), egg-laying amount, spawning percentage, and hatching and mortality rate of embryos). Transcription of 59 genes related to hypothalamic-pituitary-gonadal-liver (HPGL) axis, circadian rhythm signaling and insulin-like growth factor (IGF) system was examined. SGR, spawning percentage, E2 and VTG levels declined in fish exposed to 10 and 20 μg/L Cd but remained relatively stable in fish exposed to 30 μg/L Cd. Exposure to 10, 20 and 30 μg/L Cd significantly reduced GSI, hatching rate and mortality rate. Similarly, mRNA expression of 27 genes were sensitive to both continuous and intermittent Cd exposure. Among these genes, expression levels of 10 genes had more than 5-fold increase or decrease, including mRNA levels of vtg1, vtg2, vtg3, esr1, igf2a, igf2b, igfbp5b, nr1d1, gnrh3 and gnrhr4. The most sensitive molecular biomarker was vtg3 expression with 1500–3100 fold increase in the liver. The present study, for the first time, provides effective candidate biomarkers for Cd, which are independent of exposure regimes.

Phytochemical constituents and chemotaxonomic study of Polygonatum prattii Baker

Fifteen compounds were obtained from Polygonatum prattii Baker, which could be divided into four steroids, nine flavonoids, one lignanoid and one acidamide. The chemotaxonomic significance of P. prattii and the some other species among Asparagaceae was also discussed. As a result, Polygonatum may have close relationships with Liriope, Disporopsis, Ophiopogon and Aspidistra. Additionally, homoisoflavanones and steroids can be recognized as typical biomarkers for the above genus.

An ultrasensitive disposable sandwich-configuration electrochemical immunosensor based on OMC@AuNPs composites and AuPt-MB for alpha-fetoprotein detection

Early finding and diagnosis are critical for prevention and treatment of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a typical biomarker of HCC. Since AFP level can reflect the severity of HCC, it is essential to ensure the accurate detection of AFP. In this study, through a combination of the advantages exhibited by ordered mesoporous carbon (OMC)@gold nanoparticles (AuNPs) composites and AuPt-methylene blue (AuPt-MB), a disposable ultrasensitive sandwich-configuration electrochemical immunosensor for determination of AFP was designed. Characterized by excellent conductivity, highly ordered pore distribution and great surface area, OMC can be effective in promoting electron transfer and loading a large number of AuNPs. In the meantime, AuNPs can also immobilize AFP-Ab1 through Au-N bonds. As a new redox-active species, rod-like AuPt-MB demonstrates high conductivity, uniform morphology and excellent biocompatibility, which makes it capable not only to fix AFP-Ab2, but also to release electrochemical signals. A wide linearity of 10 fg mL−1-100 ng mL−1 and a low detection limit of 3.33 fg mL−1 (S/N = 3) were obtained. Moreover, the proposed immunosensor exhibited acceptable selectivity, high stability and reproducibility. The excellent performance in detecting serum samples endows the proposed immunosensor with broad prospects of extensive application in the detection of disease biomarkers.

Facile hydrothermal synthesis of Ti3C2Tx-TiO2 nanocomposites for gaseous volatile organic compounds detection at room temperature

The gaseous volatile organic compounds (VOCs) sensors with high-selectivity and low-power consumption have been expected for practical applications in environmental monitoring and disease diagnosis. Herein, we demonstrate a room-temperature VOCs gas sensor with enhanced performance based on Ti3C2Tx-TiO2 nanocomposites. The Ti3C2Tx-TiO2 nanocomposites with regular morphology are successfully synthesized via a facile one-step hydrothermal synthesis strategy by using Ti3C2Tx itself as titanium source. Attributed to the formation of interfacial heterojunctions and the modulation of carrier density, the Ti3C2Tx-TiO2 sensor exhibits about 1.5–12.6 times enhanced responses for the detection of various VOCs at room temperature than pure MXene sensor. Moreover, the nanocomposite sensor has better response to hexanal, both an air pollutant and a typical lung cancer biomarker. The gas response of the Ti3C2Tx-TiO2 sensor towards 10 ppm hexanal is about 3.4%. The hexanal gas sensing results display that the nanocomposite sensor maintains a high signal-to-noise ratio and the lower detection limit to hexanal gas is as low as 217 ppb. Due to the low power consumption and easy fabrication process, the Ti3C2Tx-TiO2 nanocomposite sensor is promising for application in IoT environmental monitoring as well as real-time health monitoring.

Application of two-dimensional gas chromatography/time-of-flight mass spectrometry (GC × GC-TOFMS) for the thorough study of hydrocarbons in lignite pyrolysates

Two-dimensional gas chromatography/time-of-flight mass spectrometry (GC × GC-TOFMS) was applied to analyze the complex molecular compositions of hydrocarbons in the four tars produced from the slow pyrolysis of a low-maturity lignite without and with the post cracking of volatile matter. The liquid (EL-tar) extracted from the lignite with the mixture solvent of acetone and dichloromethane was analyzed by way of contrast. Up to 866 hydrocarbons were identified in a lignite pyrolysis tar, in contrast to only 64 hydrocarbons found in EL-tar. It was revealed that the lignite was enriched with fatty acids and isoprene moieties, most of which were tightly incorporated in the macrostructures. The pyrolysis with the post cracking at 500 °C allowed the lignite to liberate a wide variety of biomarker hydrocarbons, which comprised a significant part of open-chain and cyclic aliphatic hydrocarbons. GC × GC-TOFMS was capable of distinguishing between various isomers of terpenoid hydrocarbons and a large array of homologues of cyclopentane/cyclopentene and cyclohexane/cyclohexene. The work has discussed the possible origins of typical biomarker hydrocarbons for the lignite studied, and also provided an insight on the variations of hydrocarbon compounds with the volatile matter cracking at different temperatures.

Hydrothermal synthesis of flower-like Cr2O3-doped In2O3 nanorods clusters for ultra-low isoprene detection

Isoprene is a typical biomarker for nonalcoholic fatty liver disease (NAFLD) and can be used for early screening in breath diagnosis. In this study, a simple hydrothermal synthesis of flower-like Cr2O3-doped In2O3 nanorods clusters materials for ultra-low isoprene detection was reported. This special flower-like nanorods clusters structure has the large specific surface area and the Cr2O3 doping improves in the distribution of different oxygen components, crystallite size, and carrier concentration, which synthetically contributes to the enhanced isoprene sensing performance. The results show that among all the sensors, the 1 wt% Cr2O3-doped In2O3 sensor exhibits reliable ppb-level detection ability with a concentration less than 5 ppb. Meanwhile, the sensor shows good long-term stability for 4 weeks and considerable selectivity over other common breathing gases (benzene, acetone, octane, pentane, ethanol, ammonia, and nitrogen dioxide). Furthermore, the sensor has good humidity resistance under different ambient humidity (0–92% RH). Thus, we believe the sensor based on the flower-like Cr2O3-doped In2O3 nanorods clusters has a potential application value for the detection of trace isoprene in breath analysis.

Glucodensities: A new representation of glucose profiles using distributional data analysis.

Biosensor data have the potential to improve disease control and detection. However, the analysis of these data under free-living conditions is not feasible with current statistical techniques. To address this challenge, we introduce a new functional representation of biosensor data, termed the glucodensity, together with a data analysis framework based on distances between them. The new data analysis procedure is illustrated through an application in diabetes with continuous-time glucose monitoring (CGM) data. In this domain, we show marked improvement with respect to state-of-the-art analysis methods. In particular, our findings demonstrate that (i) the glucodensity possesses an extraordinary clinical sensitivity to capture the typical biomarkers used in the standard clinical practice in diabetes; (ii) previous biomarkers cannot accurately predict glucodensity, so that the latter is a richer source of information and; (iii) the glucodensity is a natural generalization of the time in range metric, this being the gold standard in the handling of CGM data. Furthermore, the new method overcomes many of the drawbacks of time in range metrics and provides more in-depth insight into assessing glucose metabolism.

Sini Decoction Ameliorates Colorectal Cancer and Modulates the Composition of Gut Microbiota in Mice.

Sini Decoction (SND), as a classic prescription of Traditional Chinese Medicine (TCM), has been proved to be clinically useful in cardiomyopathy and inflammatory bowel diseases. However, the role and mechanism of SND in colitis-associated cancer remains unclear. This study aims to evaluate the effect of SND on colorectal cancer(CRC) symptoms and further explore the changes of gut microbes mediated by SND extract in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mice through 16 S rRNA sequencing. Our results indicated that treatment with SND extract could ameliorate the tumors' malignant degree by decreasing tumor number and size. Also, the expression levels of Cyclooxygenase 2 and Mucin-2, which are typical CRC biomarkers, were reduced compared to the CRC group. In the meantime, SND extract can upregulate CD8+ T lymphocytes' expression and Occludin in the colonic mucosal layer. Besides, SND inhibited the expression of CD4+ T cells and inflammatory cytokines in CRC tissue. According to bioinformatics analysis, SND extract was also suggested could modulate the gut microbial community. After the SND treatment, compared with the CRC mice model, the number of pathogenic bacteria showed a significant reduction, including Bacteroides fragilis and Sulphate-reducing bacteria; and SND increased the relative contents of the beneficial bacteria, including Lactobacillus, Bacillus coagulans, Akkermansia muciniphila, and Bifidobacterium. In summary, SND can effectively intervene in colorectal cancer development by regulating intestinal immunity, protecting the colonic mucosal barrier, and SND can change the intestinal microbiota composition in mice.

Identification of Serum Circulating MicroRNAs as Novel Diagnostic Biomarkers of Gastric Cancer.

Gastric cancer (GC) is one of the leading causes of cancer-associated deaths worldwide. Due to the lack of typical symptoms and effective biomarkers for non-invasive screening, most patients develop advanced-stage GC by the time of diagnosis. Circulating microRNA (miRNA)-based panels have been reported as a promising tool for the screening of certain types of cancers. In this study, we performed differential expression analysis of miRNA profiles of plasma samples obtained from gastric cancer and non-cancer patients using two independent Gene Expression Omnibus (GEO) datasets: GSE113486 and GSE124158. We identified three miRNAs, hsa-miR-320a, hsa-miR-1260b, and hsa-miR-6515-5p, to distinguish gastric cancer cases from non-cancer controls. The three miRNAs showed an area under the curve (AUC) over 0.95 with high specificity (>93.0%) and sensitivity (>85.0%) in both the discovery datasets. In addition, we further validated these three miRNAs in two external datasets: GSE106817 [sensitivity: hsa-miR-320a (99.1%), hsa-miR-1260b (97.4%), and hsa-miR-6515-5p (92.2%); specificity: hsa-miR-320a (88.8%), hsa-miR-1260b (89.6%), and hsa-miR-6515-5p (88.7%); and AUC: hsa-miR-320a (96.3%), hsa-miR-1260b (97.4%), and hsa-miR-6515-5p (94.6%)] and GSE112264 [sensitivity: hsa-miR-320a (100.0%), hsa-miR-1260b (98.0%), and hsa-miR-6515.5p (98.0%); specificity: hsa-miR-320a (100.0%), hsa-miR-1260b (100.0%), and hsa-miR-6515.5p (92.7%); and AUC: hsa-miR-320a (1.000), hsa-miR-1260b (1.000), and hsa-miR-6515-5p (0.988)]. On the basis of these findings, the three miRNAs can be used as potential biomarkers for gastric cancer screening, which can provide patients with a higher chance of curative resection and longer survival.

Involvement of CD26 in Differentiation and Functions of Th1 and Th17 Subpopulations of T Lymphocytes.

CD26, acting as a costimulator of T cell activation, plays an important role in the immune system. However, the role of CD26 in the differentiation of T cell subsets, especially of new paradigms of T cells, such as Th17 and Tregs, is not fully clarified. In the present study, the role of CD26 in T cell differentiation was investigated in vitro. CD26 expression was analyzed in the different subsets of human peripheral blood T lymphocytes after solid-phase immobilized specific anti-CD3 mAb stimulation. Here, the percentage of CD4+ cells significantly increased and most of these cells were coexpressed with CD26, suggesting a close correlation of CD26 expression with the proliferation of CD4+ cells. Subsequently, after immobilized anti-CD3 mAb stimulation, CD26 high-expressing cells (CD26high) were separated from CD26 low-expressing cells (CD26low) by magnetic cell sorting. We found that the percentages of cells secreting Th1 typical cytokines (IL-2, IFN-γ) and Th17 typical cytokines (IL-6, IL-17, and IL-22) or expressing Th17 typical biomarkers (IL-23R, CD161, and CD196) in the CD26high group were markedly higher than in those in the CD26low group. In addition, a coexpression of CD26 with IL-2, IFN-γ, IL-17, IL-22, and IL-23R in lymphocytes was demonstrated by fluorescence microscopy. These results provide direct evidence that the high expression of CD26 is accompanied by the differentiation of T lymphocytes into Th1 and Th17, indicating that CD26 plays a crucial role in regulating the immune response.