RIscoper 2.0: A deep learning tool to extract RNA biomedical relation sentences from literature.

RNA plays an extensive role in a multi-dimensional regulatory system, and its biomedical relationships are scattered across numerous biological studies. However, text mining works dedicated to the extraction of RNA biomedical relations remain limited. In this study, we established a comprehensive and reliable corpus of RNA biomedical relations, recruiting over 30,000 sentences manually curated from more than 15,000 biomedical literature. We also updated RIscoper 2.0, a BERT-based deep learning tool to extract RNA biomedical relation sentences from literature. Benefiting from approximately 100,000 annotated named entities, we integrated the text classification and named entity recognition tasks in this tool. Additionally, RIscoper 2.0 outperformed the original tool in both tasks and can discover new RNA biomedical relations. Additionally, we provided a user-friendly online search tool that enables rapid scanning of RNA biomedical relationships using local and online resources. Both the online tools and data resources of RIscoper 2.0 are available at http://www.rnainter.org/riscoper.

Outstanding Energy-Storage Density Together with Efficiency of above 90% via Local Structure Design.

Dielectric ceramic capacitors with high recoverable energy density (Wrec) and efficiency (η) are of great significance in advanced electronic devices. However, it remains a challenge to achieve high Wrec and η parameters simultaneously. Herein, based on density functional theory calculations and local structure analysis, the feasibility of developing the aforementioned capacitors is demonstrated by considering Bi0.25Na0.25Ba0.5TiO3 (BNT-50BT) as a matrix material with large local polarization and structural distortion. Remarkable Wrec and η of 16.21 J/cm3 and 90.5% have been achieved in Bi0.25Na0.25Ba0.5Ti0.92Hf0.08O3 via simple chemical modification, which is the highest Wrec value among reported bulk ceramics with η greater than 90%. The examination results of local structures at lattice and atomic scales indicate that the disorderly polarization distribution and small nanoregion (∼3 nm) lead to low hysteresis and high efficiency. In turn, the drastic increase in local polarization activated via the ultrahigh electric field (80 kV/mm) leads to large polarization and superior energy storage density. Therefore, this study emphasizes that chemical design should be established on a clear understanding of the performance-related local structure to enable a targeted regulation of high-performance systems.

Biomimetic graphene oxide quantum dots nanoparticles targeted photothermal-chemotherapy for gastric cancer.

Direct use of chemotherapy drugs in the treatment of gastric cancer often leads to systemic side effects and unsatisfied therapeutic efficacy due to the lack of tumour-targeting ability. The excellent properties of nanoparticles make them good tools to provide more options for the targeted delivery of chemotherapeutic drugs. Herein, we developed a novel nanomedicine (GOQD-ICG-CS-6@HM nanoparticles, GIC@HM NPs), which employed graphene oxide quantum dots (GOQDs) to co-load photosensitizer indocyanine green (ICG) and chemotherapeutic drug gamabufotalin (CS-6) as the core and wrapped with the hybrid membrane (erythrocyte membrane and gastric cancer cell membrane, HM) on its surface. This nanomedicine possesses the functions of photothermal therapy and chemotherapy, making it a good choice for the treatment of gastric cancer. The results showed that the bionic-coated hybrid membrane not only improves the biocompatibility of the nanomedicine, and prolong its circulating half-life, but also delivers the drug to the tumour site precisely and improves the efficiency of drug utilisation. In vitro and in vivo studies further showed that GIC@HM NPs exhibited combinational effects on tumour therapy while displaying no obvious side effects on normal tissue. To sum up, the newly developed GIC@HM NPs provide a safer, more efficient, and more precise method for gastric cancer treatment.

Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer.

PURPOSE: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. Saliva is an important source for discovering biomarkers and contains an abundance of biological information. The purpose of this study was to determine whether galactosylation levels of salivary proteins are associated with LC. EXPERIMENTAL DESIGN: First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. Pooled samples from each group were subsequently validated by the lectin blotting technique. Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. RESULTS: The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV. Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). CONCLUSIONS AND CLINICAL RELEVANCE: These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva.

Emerging Roles of the Unique Molecular Chaperone Cosmc in the Regulation of Health and Disease.

The core-1 ß1-3galactosyltransferase-specific chaperone 1 (Cosmc) is a unique molecular chaperone of core-1 ß1-3galactosyltransferase(C1GALT1), which typically functions inside the endoplasmic reticulum (ER). Cosmc helps C1GALT1 to fold correctly and maintain activity. It also participates in the synthesis of the T antigen, O-glycan, together with C1GALT1. Cosmc is a multifaceted molecule with a wide range of roles and functions. It involves platelet production and the regulation of immune cell function. Besides that, the loss of function of Cosmc also facilitates the development of several diseases, such as inflammation diseases, immune-mediated diseases, and cancer. It suggests that Cosmc is a critical control point in diseases and that it should be regarded as a potential target for oncotherapy. It is essential to fully comprehend Cosmc's roles, as they may provide critical information about its involvement in disease development and pathogenesis. In this review, we summarize the recent progress in understanding the role of Cosmc in normal development and diseases.

Role of salivary glycopatterns for oral microbiota associated with gastric cancer.

Microbiota in the oral cavity plays an important role in maintaining human health. Our previous studies have revealed significant alterations of salivary glycopatterns in gastric cancer (GC) patients, but it is unclear whether these altered salivary glycopatterns can cause the dysbiosis of oral microbiota. In this study, the oral microbiome of healthy volunteers (HVs) and GC patients were detected. The neoglycoproteins were then synthesized according to the altered glycopatterns in GC patients and used to explore the effects of specific salivary glycopattern against oral microbiota. The results showed that five species were significantly increased (p < 0.05) while two species were significantly decreased (p < 0.01) in the saliva of GC patients compared with that of HVs. And the fucose-neoglycoproteins (30-100 µg/mL) could reduce the adhesion and toxicity of Aggregatibacter segnis (A. segnis) to oral cells (HOEC and CAL-27), change the glycan structures of lipopolysaccharide on the surface of A. segnis, and enhance the capacity of A. segnis to trigger innate immune responses. This study revealed that the changes of salivary protein glycopatterns in GC patients might contribute to the dysbiosis of oral microbiota, and had important implications in developing new carbohydrate drugs to maintain a balanced microbiota in the oral.

Update on the role of C1GALT1 in cancer.

Cancer remains one of the most difficult diseases to treat. In the quest for early diagnoses to improve patient survival and prognosis, targeted therapies have become a hot research topic in recent years. Glycosylation is the most common posttranslational modification in mammalian cells. Core 1ß1,3-galactosyltransferase (C1GALT1) is a key glycosyltransferase in the glycosylation process and is the key enzyme in the formation of the core 1 structure on which most complex and branched O-glycans are formed. A recent study reported that C1GALT1 was aberrantly expressed in tumors. In cancer cells, C1GALT1 is regulated by different factors. In the present review, the expression of C1GALT1 in different tumors and its possible molecular mechanisms of action are described and the role of C1GALT1 in cancer development is discussed.

Risk Factors of Lymph Node Metastasis and Its Prognostic Significance in Early Gastric Cancer: A Multicenter Study.

BACKGROUND: Early gastric cancer (EGC) is invasive gastric cancer that invades no deeper than the submucosa, regardless of lymph node metastasis (LNM). It is mainly treated by surgery. Recently, the resection range of EGC has been minimized, but cancer recurrence and overall survival in some patients should be given high status. LNM is an important indicator of prognosis and treatment in gastric cancer. The law of the number and location of metastatic lymph nodes in EGC is not yet clear. Therefore, we aimed to identify the risk factors of LNM in radically resected EGC and guide treatment. METHODS: The clinicopathological factors of 611 patients with EGC were retrospectively analyzed in six hospitals between January 2010 and December 2016. The relationship between clinicopathological factors and LNM, as well as their prognostic significance, were analyzed by univariate and multivariate analyses. RESULTS: The rate of LNM was 20.0% in the 611 EGC patients. The depth of invasion, differentiation type, tumor diameter, morphological ulceration, and lymphovascular invasion were independent risk factors for LNM (P<0.05) by logistic regression analysis. Tumor location in the proximal third of the stomach and morphological ulceration were significant factors for group 2 LNM. Moreover, the 5-year survival rate was 94.9% for patients with no positive nodes, 88.5% for patients with 1-2 positive nodes, 64.3% for patients with 3-6 positive nodes, and 41.8% for patients with >6 metastatic nodes. Interestingly, the 7-year risk of relapse diminished for patients with no LNM or retrieved no less than 15 lymph nodes. CONCLUSIONS: Fifteen lymph node dissection and D2 radical operation are the surgical options in case of high risk factors for LNM. Extended lymph node dissection (D2+) is recommended for morphological ulceration or disease located in the proximal third of the stomach due to their high rate of group 2 LNM. Furthermore, LNM is a significant prognostic factor of EGC. Moreover, lymph nodes can also play a significant role in the chemotherapeutic and radiotherapy approach for non-surgical patients with EGC.

The effect of Helicobacter pylori eradication on prognosis of postoperative early gastric cancer: a multicenter study.

OBJECTIVE: To investigate the effect of Helicobacter pylori (H. pylori) eradication on the prognosis of postoperative early gastric cancer (EGC). METHODS: This is a retrospective study based on data from 6 hospitals. We identified 429 patients with EGC who underwent curative gastrectomy from January 2010 to December 2016. All of the patients were tested for H. pylori. Patients were divided into two groups, the successful H. pylori eradication group (group A, 268 patients) and the non-H. pylori eradication group (group B, 161 patients), for calculating the disease-free survival (DFS) and overall survival (OS) of each group. RESULT: Positive node metastasis (hazard ratio (HR), 3.13; 95% confidence interval (CI), 1.84-5.32; P < 0.001), undifferentiated type (HR, 2.54; 95% CI, 1.51-4.28; P < 0.001), and non-H. pylori eradication (HR, 1.73; 95% CI, 1.08-2.77; P = 0.023) were statistically significantly independent risk factors of recurrence. Patient's age ≥60 years old (HR, 3.32; 95% CI, 2.00-5.53; P < 0.001), positive node metastasis (HR, 3.71; 95% CI, 2.25-6.12; P < 0.001), undifferentiated type (HR, 3.06; 95% CI, 1.79-5.23; P < 0.001), and non-H. pylori eradication (HR, 1.83; 95% CI, 1.11-3.02; P = 0.018) were statistically significantly independent risk factors of overall survival. CONCLUSION: H. pylori eradication treatment could prevent the recurrence of postoperative EGC to prolong the overall survival of patients with EGC.

Glutamine Regulates Cell Growth and Casein Synthesis through the CYTHs/ARFGAP1-Arf1-mTORC1 Pathway in Bovine Mammary Epithelial Cells.

In the dairy industry, glutamine (Gln) is often used as a feed additive to increase milk yield and quality; however, the molecular regulation underneath needs further clarification. Here, with bovine mammary epithelial cells (BMECs), the effects and mechanisms of Gln on cell growth and casein synthesis were assessed. When Gln was added or depleted from BMECs, both cell growth and ß-casein (CSN2) expression were increased or decreased, respectively. Overexpressing or inhibiting the mechanistic target of rapamycin (mTOR) revealed that Gln regulated cell growth and CSN2 synthesis through the mTORC1 pathway. A similar intervention of ADP-ribosylation factor 1 (Arf1) uncovered that Gln activated the mTORC1 pathway through Arf1. We next observed that both guanine nucleotide exchange factors, Cytohesin-1/2/3 (CYTH1/2/3, CYTHs) and ADP-ribosylation factor GTPase activating protein 1 (ARFGAP1), interacted with Arf1. Inhibiting CYTHs or ARFGAP1 showed that Gln supplement or depletion activated or inactivated Arf1 through CYTHs or ARFGAP1, respectively. Collectively, this study demonstrated that Gln positively regulated cell growth and casein synthesis in BMECs, which works through the CYTHs/ARFGAP1-Arf1-mTORC1 pathway. These results greatly enhanced current understanding regarding the regulation of the mTOR pathway and provided new insights for the processes of cell growth and casein synthesis by amino acids, particularly Gln.

Safety assessment of multiple repeated percutaneous punctures for the collection of cerebrospinal fluid in rats.

The objective of this study was to examine the safety of multiple repeated percutaneous punctures of cisterna magna for collecting cerebrospinal fluid (CSF) and preliminarily determine the optimal time interval and volume at each collection. Sixty Wistar rats were randomly assigned to six groups: 10 d-0 µL, 10 d-100 µL (100 µL CSF collected at an interval of 10 days), 10 d-150 µL, 15 d-0 µL, 15 d-100 µL, and 15 d-150 µL. CSF was collected by percutaneous puncture of the cisterna magna at four time-points. Simultaneously, locomotor activity, cisterna magna pressure, and acetylcholine levels in the CSF were monitored. Compared with the 10 d-0 µL group, the escape latency by Morris water maze was significantly prolonged in the 10 d-100 µL and 10 d-150 µL groups (P<0.05). Compared with the 15 d-0 µL group, the indices of 15 d-100 µL and 15 d-150 µL groups had no significant differences. When compared with that at the first training, the exception of the 10 d-150 µL and 15 d-150 µL groups, significant differences in escape latency were found at the 6th attempt (P<0.05). Compared with baseline readings for each group, the cisterna magna pressure in the 10 d-150 µL group began to decrease significantly from the third measurement (P<0.05). The optimal time interval during four CSF collections (100 µL per collection) via cisterna magna percutaneous puncture was determined to be 15 days. The procedure did not significantly affect learning processes, performance, or other related indices.

Safety assessment of multiple repeated percutaneous punctures for the collection of cerebrospinal fluid in rats

The objective of this study was to examine the safety of multiple repeated percutaneous punctures of cisterna magna for collecting cerebrospinal fluid (CSF) and preliminarily determine the optimal time interval and volume at each collection. Sixty Wistar rats were randomly assigned to six groups: 10 d-0 μL, 10 d-100 μL (100 μL CSF collected at an interval of 10 days), 10 d-150 μL, 15 d-0 μL, 15 d-100 μL, and 15 d-150 μL. CSF was collected by percutaneous puncture of the cisterna magna at four time-points. Simultaneously, locomotor activity, cisterna magna pressure, and acetylcholine levels in the CSF were monitored. Compared with the 10 d-0 μL group, the escape latency by Morris water maze was significantly prolonged in the 10 d-100 μL and 10 d-150 μL groups (P<0.05). Compared with the 15 d-0 μL group, the indices of 15 d-100 μL and 15 d-150 μL groups had no significant differences. When compared with that at the first training, the exception of the 10 d-150 μL and 15 d-150 μL groups, significant differences in escape latency were found at the 6th attempt (P<0.05). Compared with baseline readings for each group, the cisterna magna pressure in the 10 d-150 μL group began to decrease significantly from the third measurement (P<0.05). The optimal time interval during four CSF collections (100 μL per collection) via cisterna magna percutaneous puncture was determined to be 15 days. The procedure did not significantly affect learning processes, performance, or other related indices.

PD-L1 and miR-34a are Prognostic Factors for Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP.

INTRODUCTION: Primary gastric diffuse large B-cell lymphoma (GDLBCL) is a heterogeneous disease in clinicopathological features and prognosis. Programmed death ligand-1 (PD-L1) and microRNA-34a (miR-34a) play crucial roles in GDLBCL progress. The purpose of this research is to explore the clinical significance of PD-L1 and miR-34a expression in GDLBCL. PATIENTS AND METHODS: The expressions of PD-L1 and miR-34a were examined by IHC and qRT-PCR in 109 patients who were diagnosed with GDLBCL and were treated with rituximab plus cyclophosphamide, doxorubicin, prednisone vincristine and prednisone chemotherapy (R-CHOP) from January 2010 to December 2018. RESULTS: PD-L1 level was significantly higher in tumor tissues than adjacent non-tumor tissues (60.5%, P<0.001), while the miR-34a level was just reversed (50.5%, P<0.001), which was negatively correlated (r=-0.524, P<0.001). Notably, PD-L1-positive and miR-34a-negative expressions were significantly correlated with the advanced Lugano stage of IIE-IV stage (P<0.001 and P<0.01), elevated serumal LDH levels (P<0.001 and P<0.05), B symptoms present (P<0.001 and P<0.001), non-GCB subtype (P<0.001 and P<0.001) and negative Bcl-2 expression (P<0.05 and P<0.001). PD-L1 high and miR-34a low expression groups had more patients with IPI scores of 2 or greater (P<0.001 and P<0.05) and poor R-IPI (P<0.01 and P<0.01). The complete response rate was upregulated in patients with negative PD-L1 and positive miR-34a expression after R-CHOP treatment. DISCUSSION: PD-L1 expression and miR-34a expression were significantly associated with clinicopathological characteristics and survival prognosis; they may serve as novel prognostic markers in GDLBCL patients who were treated with R-CHOP. Immunotherapies targeting PD-L1 and miR-34a pathway may have therapeutic potential in GDLBCL.

A RBC membrane-camouflaged biomimetic nanoplatform for enhanced chemo-photothermal therapy of cervical cancer.

Due to the untargeted release of chemical drugs, the efficacy of chemotherapy is often compromised along with serious side effects on patients. Recently, the development of targeted delivery systems using nanomaterials as carriers has provided more alternatives for chemical drug transportation. In this study, we developed a novel targeted nanocomplex of GOQD-ICG-DOX@RBCM-FA NPs (GID@RF NPs). First, PEG modified graphene oxide quantum dots (GOQDs) were used to co-load the photosensitizer of indocyanine green (ICG) and DOX, to form GOQD-ICG-DOX NPs (GID NPs). Then, the red blood cell membrane (RBCM) was applied for GID NP camouflage to avoid immune clearance. Finally, folic acid was used to endow the targeting ability of GID@RF NPs. MTT assay showed that the survival rate of HeLa cells reduced by 71% after treatment with GID@RF NPs and laser irradiation. Meanwhile, membrane camouflage significantly prolonged the blood circulation time and enhanced the immune evading ability of GID NPs. Moreover, the drug accumulation at tumor sites was significantly improved through the strong interaction between FA and FA receptor highly expressed on the tumor cells. In vivo assay demonstrated the strongest tumor growth inhibition ability of the combinational chemo/photothermal therapy. H&E analysis indicated no significant abnormalities in the major organs of mice undergoing GID@RF NPs treatment. The level of blood and biochemical parameters remained stable as compared to the control. In summary, this combinational therapy system provides a safe, rapid and effective alternative for the treatment of cervical cancer in the future.

Comparative Pharmacokinetic Studies of Four Ginsenosides in Rat Plasma by UPLC-MS/MS after Oral Administration of Panax quinquefolius-Acorus gramineus and Panax quinquefolius Extracts.

Panax quinquefolius (PQ) and Acorus gramineus (AG) are drug target pairs in traditional Chinese medicine (TCM), which are used to treat age-related diseases. In the present study, we simultaneously determined the contents of four main bioactive ginsenosides (Rb1, Rb2, Rd, and Re) in rat plasma using an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Plasma specimens were purified by using the solid-phase extraction procedure, and separation was performed on Waters ACQUITY UPLC BEH C18 (100 mm × 2.1 mm, 1.7 µm) in multiple reaction monitoring (MRM) mode and negative electrospray ionization (ESI) mode. The established UPLC-MS/MS method showed good linear correlation (r ≥ 0.9978), stability (-11.93 to 12.11%), precision (RSD < 14.63%), and recovery (76.43%-95.20%). The lower limit of quantification was 3.6 ng/mL for Rb1, 1.6 ng/mL for Rb2, 1.2 ng/mL for Rd, and 2.5 ng/mL for Re. This validated method was successfully employed to investigate the pharmacokinetics of the four ginsenosides in rat plasma after oral administration of PQ-AG and PQ extracts. The results revealed the pharmacokinetic profiles of PQ-AG drug pair and clarified that AG played a critical role in stimulating the absorption of active ginsenosides in PQ. Collectively, our findings provided valid and reliable evidence for the rational use of PQ-AG in clinical practice.

Integrated Glycome Strategy for Characterization of Aberrant LacNAc Contained N-Glycans Associated With Gastric Carcinoma.

Aberrant glycosylation is not only a feature of malignant cell transformation, but also plays an important role in metastasis. In the present study, an integrated strategy combining the lectin microarrays and lectin cytochemistry was employed to investigate and verify the altered glycopatterns in gastric cancer (GC) cell lines as well as resected tumor specimens from matched tissue sets of 46 GC patients. Subsequently, lectin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS were employed to further acquire precise structural information of the altered glycans. According to the results, the glycopatterns recognized by 10 (e.g., ACA, MAL-I, and ConA) and 3 lectins (PNA, MAL-I, and VVA) showed significantly variations in GC cells and tissue compared to their corresponding controls, respectively. Notably, the relative abundance of Galß-1,4GlcNAc (LacNAc) recognized by MAL-I exhibited a significant increase in GC cells (p < 0.001) and tissue from patients at stage II and III (p < 0.05), and a significant increase in lymph node positive tumor cases, compared with lymph node negative tumor cases (p < 0.05). More LacNAc contained N-glycans were characterized in tumor sample with advanced stage compared to corresponding control. Moreover, there were 10 neo-LacNAc-contained N-glycans (e.g., m/z 1625.605, 1803.652, and 1914.671) only presented in GC tissue with advanced stage. Among these, six N-glycans were modified with sialic acid or fucose based on LacNAc to form sialylated N-glycans or lewis antigens, respectively. Our results revealed that the aberrant expression of LacNAc is a characteristic of GC, and LacNAc may serve as a scaffold to be further modified with sialic acid or fucose. Our findings provided useful information for us to understand the development of GC.

Voxel-based morphology analysis of STZ-induced type 1 diabetes mellitus rats with and without cognitive impairment.

Incidence of diabetes has increased dramatically. Consequently, diabetes-induced cognitive impairment has attracted increasing attention. This study aimed to explore the changes in brain structure in the diabetic rats with and without cognitive impairment. Morris water maze method was used for screening the diabetic rats with/without cognitive impairment. These diabetic rats and controls were imaged using magnetic resonance imaging that segmented into gray and white matter, which was further analyzed using voxel-based morphology (VBM) and regions of interest (ROI) based image retrieval. The ROI results showed that the whole brain volume decreased in diabetic rats with/without cognitive impairment as compared to the control (P < 0.05). The VBM results showed differences in the caudate putamen and prefrontal cortex in the diabetic rats with/without cognitive impairment. The change in the brain of rats with cognitive impairment occurred primarily in the area associated with cognition, such as caudate putamen and hippocampus, and the bi-directional change occurred in the different area of hippocampus. The current results provided important imaging information for early diagnosis and timely treatment of diabetic cognitive impairment.

Identification of N- and O-linked glycans recognized by AAL in saliva of patients with atrophic gastritis and gastric cancer.

BACKGROUND AND AIM: Gastric cancer (GC) is a common and fatal malignancy with a worldwide occurrence. There still lacks effective biomarkers for precisely evaluating GC. Saliva is a biological fluid with enormous diagnostic potentials which emerged many advantages. We aimed to discover the novel biomarkers for accurately distinguishing early GC based on saliva glycopatterns. METHODS: We used Aleuria Aurantia Lectin (AAL)-magnetic particle conjugates to isolate fucosylated glycoproteins in the pooled saliva of healthy volunteers (HV, n= 51) and patients with atrophic gastritis (AG, n= 51) or GC (n= 51), following to release the N- and O-linked glycans from the isolated proteins with PNGase F and NaClO, and further identified the released glycans by MALDI-TOF/TOF-MS, respectively. RESULTS: A total of 9/9, 8/11, and 9/9 fucosylated N-/O-linked glycans were annotated in the isolated salivary proteins from HV, AG, and GC, respectively. Among these, six fucosylated N-linked glycansand four O-linked glycans exhibited significantly increased expression levels in GC, while five fucosylated N-linked glycans and ten fucosylated O-linked glycans exhibited significantly decreased expression levels in GC. The proportion of fucosylated N-linked glycans was decreased in GC (41.66%) compared with AG (43.63%) and HV (52.57%), as well as the fucosylated O-linked glycans was apparently decreased in GC (19.58%) compared with AG (25.43%) and HV (55.54%). CONCLUSIONS: This study could provide pivotal information to distinguish among HV, AG, and GC, and facilitate the discovery of biomarkers for GC diagnosis based on precise alterations of N- and O-linked glycans in saliva.

MiRNA-545 negatively regulates the oncogenic activity of EMS1 in gastric cancer.

Gastric cancer (GC) is a common malignant tumor of the digestive system. In addition, GC metastasis is an extremely complicated process. In this article, high expression levels of EMS1 mRNA and protein were found to be positively correlated with an enhanced malignant potential of GC cells and a poor clinical prognosis of GC patients. Interestingly, the expression levels of EMS1 mRNA and protein in GC cells were inhibited by microRNA-545 (miR-545), which was identified by a bioinformatics analysis. The expression level of miR-545 in carcinoma tissues was significantly lower than that in para-carcinoma tissues. The proliferation and epithelial-mesenchymal transition (EMT) of GC cells were suppressed by exogenous oligonucleotides of miR-545 mimics. In addition, the expression levels of EMT-associated markers were altered with the expression of miR-545. Notably, the growth rates of tumors in nude mice were seriously restrained by an intratumoral injection of oligonucleotides of the miR-545 mimics. These results suggest a negative regulatory role of miR-545 on the oncogenic activity of EMS1. In addition, EMS1 and miR-545 may be potential biomarkers for GC diagnosis. Synthesized oligonucleotides of miR-545 mimics may be developed as important gene medicines for GC therapy in the future.

Study of the NLRP3 inflammasome component genes and downstream cytokines in patients with type 2 diabetes mellitus with carotid atherosclerosis.

BACKGROUND: A role for the NLRP3 inflammasome has been reported in various diseases, such as diabetes mellitus, atherosclerosis (AS), nephropathy, rheumatism, and others, although limited information is available concerning the role of the NLRP3 inflammasome, interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in patients with type 2 diabetes mellitus (T2DM) and carotid atherosclerosis (CAS). Therefore, this cross-sectional study investigated these inflammatory components in patients with T2DM complicated with carotid atherosclerosis (T2DM + CAS). METHODS: A total of 107 inpatients or outpatients were included,including 81 T2DM + CAS patients and 26 T2DM patients. Patients with T2DM or T2DM + CAS were recruited to compare the expression levels of NLRP3 pathway genes (NLRP3, ASC and caspase-1 mRNA) and the serum IL-1ß and IL-18 concentrations. In the T2DM + CAS group, patients with thickened intima media thickness (IMT) and those with plaques were compared, and the correlation of the 5 variables with Crouse scores were analyzed. RESULTS: The expression of NLRP3 pathway genes except caspase-1 was significantly higher in patients with T2DM and CAS compared to T2DM patients. Serum IL-1ß and IL-18 concentrations shows no difference between the T2DM + CAS and T2DM group. In the T2DM + CAS group, the expression levels of the three inflammasome genes and IL-18 were increased in patients with thickened IMT compared to those with the plaque. All of the above factors negatively correlated with Crouse scores. CONCLUSION: NLRP3 inflammasome pathway activity is significantly increased in patients with AS and T2DM at the early stage of plaque formation.