The roles of long non-coding RNAs in Alzheimer's disease diagnosis, treatment, and their involvement in Alzheimer's disease immune responses.

Alzheimer's disease (AD) is the most frequent type of dementia, presenting a substantial danger to the health and well-being of the aged population. It has arisen as a significant public health problem with considerable socioeconomic repercussions. Unfortunately, no effective treatments or diagnostic tools are available for Alzheimer's disease. Despite substantial studies on the pathophysiology of Alzheimer's, the molecular pathways underpinning its development remain poorly understood. Long non-coding RNAs (lncRNAs) vary in size from 200 nucleotides to over 100 kilobytes and have been found to play critical roles in various vital biological processes that play critical in developing Alzheimer's disease. This review intends to examine the functions of long non-coding RNAs in diagnosing and treating Alzheimer's disease and their participation in immunological responses associated with AD.

The Involvement of Long Non-Coding RNAs in Glioma: From Early Detection to Immunotherapy.

Glioma is a brain tumor that arises in the central nervous system and is categorized according to histology and molecular genetic characteristics. Long non-coding RNAs (lncRNAs) are RNAs longer than 200 nucleotides in length. They have been reported to influence significant events such as carcinogenesis, progression, and increased treatment resistance on glioma cells. Long non-coding RNAs promote cell proliferation, migration, epithelial-to-mesenchymal transition and invasion in glioma cells. Various significant advancements in transcriptomic profiling studies have enabled the identification of immune-related long non-coding RNAs as immune cell-specific gene expression regulators that mediates both stimulatory and suppressive immune responses, implying lncRNAs as potential candidates for improving immunotherapy efficacy against tumors and due to the lack of different diagnostic and treatments for glioma, lncRNAs are potential candidates to be used as future diagnostic, prognostic biomarker and treatment tools for glioma. This review's primary purpose is to concentrate on the role of long non-coding RNAs in early glioma identification, treatment, and immunotherapy.

The Roles of Exosomes as Future Therapeutic Agents and Diagnostic Tools for Glioma.

Glioma is a common type of tumor originating in the brain. Glioma develops in the gluey supporting cells (glial cells) that surround and support nerve cells. Exosomes are extracellular vesicles that contain microRNAs, messenger RNA, and proteins. Exosomes are the most prominent mediators of intercellular communication, regulating, instructing, and re-educating their surrounding milieu targeting different organs. As exosomes' diameter is in the nano range, the ability to cross the blood-brain barrier, a crucial obstacle in developing therapeutics against brain diseases, including glioma, makes the exosomes a potential candidate for delivering therapeutic agents for targeting malignant glioma. This review communicates the current knowledge of exosomes' significant roles that make them crucial future therapeutic agents and diagnostic tools for glioma.

Characterization of a bacterial strain Lactobacillus paracasei LP10266 recovered from an endocarditis patient in Shandong, China.

BACKGROUND: Lactobacilli are often recognized as beneficial partners in human microbial environments. However, lactobacilli also cause diseases in human, e.g. infective endocarditis (IE), septicaemia, rheumatic vascular disease, and dental caries. Therefore, the identification of potential pathogenic traits associated with lactobacilli will facilitate the prevention and treatment of the diseases caused by lactobacilli. Herein, we investigated the genomic traits and pathogenic potential of a novel bacterial strain Lactobacillus paracasei LP10266 which has caused a case of IE. We isolated L. paracasei LP10266 from an IE patient's blood to perform high-throughput sequencing and compared the genome of strain LP10266 with those of closely related lactobacilli to determine genes associated with its infectivity. We performed the antimicrobial susceptibility testing on strain LP10266. We assessed its virulence by mouse lethality and serum bactericidal assays as well as its serum complement- and platelet-activating ability. The biofilm formation and adherence of strain LP10266 were also studied. RESULTS: Phylogenetic analysis revealed that strain LP10266 was allied with L. casei and L. paracasei. Genomic studies revealed two spaCBA pilus clusters and one novel exopolysaccharides (EPS) cluster in strain LP10266, which was sensitive to ampicillin, penicillin, levofloxacin, and imipenem, but resistant to cefuroxime, cefazolin, cefotaxime, meropenem, and vancomycin. Strain LP10266 was nonfatal and sensitive to serum, capable of activating complement 3a and terminal complement complex C5b-9 (TCC). Strain LP10266 could not induce platelet aggregation but displayed a stronger biofilm formation ability and adherence to human vascular endothelial cells (HUVECs) compared to the standard control strain L. paracasei ATCC25302. CONCLUSION: The genome of a novel bacterial strain L. paracasei LP10266 was sequenced. Our results based on various types of assays consistently revealed that L. paracasei LP10266 was a potential pathogen to patients with a history of cardiac disease and inguinal hernia repair. Strain LP10266 showed strong biofilm formation ability and adherence, enhancing the awareness of L. paracasei infections.

Aberrant hypermethylation induced downregulation of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 correlate with tumorigenesis of glioma.

AIMS: The expression of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 were found to be downregulated in glioma by RNA sequencing; however, the function and mechanism of both two genes in the development of glioma have not been studied. MATERIALS AND METHODS: QRT-PCR and western blot were used to determine the transcriptional and translational levels of moleculars. MSP and BSP assays were used to evaluate the methylation status of promoter CpG island. MTT, EdU, flow cytometry, and transwell assays were used to reveal biological effects. The in vivo mice model was used to validate the role of target genes in tumorigenesis. KEY FINDINGS: The mRNA and protein expression of STXBP5 was significantly downregulated in glioma tissues and positively correlated with prognosis. STXBP5-AS1 was downregulated in glioma cells and tissues, and associated with tumor size and clinical stages. Both of two genes were significantly restored in cells treatment with 5-Aza. The promoter CpG island of STXBP5/STXBP5-AS1 was hypermethylated in glioma cells, but partially methylated in NHA cells. We found that promoter methylation frequency was significantly higher in glioma tissues. Functionally, overexpression of STXBP5 and STXBP5-AS1 inhibited cell proliferation, migration, and invasion and promoted apoptosis in vitro, whereas depletion of STXBP5 and STXBP5-AS1 showed opposite effects. Both the mRNA and protein expression of STXBP5 were positively regulated by STXBP5-AS1. Ectopic expression of STXBP5 and STXBP5-AS1 suppressed tumor formation in vivo. SIGNIFICANCE: Our findings suggested that epigenetically silenced STXBP5-AS1 and STXBP5 might act as novel tumor suppressors of glioma.

Expression of microRNA-184 in glioma.

The aim of the present study was to examine the expression of microRNA (miRNA)-184 in gliomas with different pathological grades, and its effect on survival prognosis. For the present study, 40 participants were selected with different pathological grades of glioma tissues with grade I (n=10), grade II (n=8), grade III (n=16), and grade IV (n=6). In addition, 10 cases of normal brain tissue (obtained by decompression because of traumatic brain injury) were selected. RT-PCR and immunohistochemical techniques were used to detect the expression level and intensity of miRNA-184 in different grades of glioma tissues. The length of survival of miRNA-184-positive patients was analyzed. miRNA-184 mRNA expression was found in normal tissues and tumor tissues, and the expression in tumor tissues was significant (P<0.05). Statistically significant differences of miRNA-184 expression were observed among different grades (P<0.05). miRNA-184 expression increased with the increase of grade level. The differences in expression across grade levels was statistically significant (P<0.05). A positive expression was not related to the pathological types of glioma cells. The median survival time of patients with miRNA-184-positive expression was significantly shorter than that of the negative expression group (P<0.05). miRNA-184 is highly expressed in gliomas, which is positively correlated with pathological grade, and is not correlated with pathological type, and negatively correlated with survival time. Thus, miRNA-184 is a potentially important molecular marker for glioma.

Circulating Long RNAs in Serum Extracellular Vesicles: Their Characterization and Potential Application as Biomarkers for Diagnosis of Colorectal Cancer.

BACKGROUND: Long noncoding RNA (lncRNA) and mRNAs are long RNAs (≥200 nucleotides) compared with miRNAs. In blood, long RNAs may be protected by serum extracellular vesicles, such as apoptotic bodies (AB), microvesicles (MV), and exosomes (EXO). They are potential biomarkers for identifying cancer. METHODS: Sera from 76 preoperative colorectal cancer patients, 76 age- and sex-matched healthy subjects, and 20 colorectal adenoma patients without colorectal cancer were collected. We investigated the distribution of long RNAs into the three vesicles. Seventy-nine cancer-related long RNAs were chosen and detected using qPCR. RESULTS: The quantity of long RNA has varying distribution among three subtypes of extracellular vesicles in serum. Most mRNA and lncRNA genes had higher quantity in EXOs than that in ABs and MVs, whereas MVs contain lowest quantity. We investigated 79 long RNAs chosen from The Cancer Genome Atlas and the LncRNADisease database in the sera of healthy patients, and those with colorectal cancer. In the training and test sets, the AUCs were 0.936 and 0.877, respectively. The AUC of total serum RNA was lower (0.857) than that of exosomal RNA in the same samples (0.936). CONCLUSION: The present study shows that exosomal mRNAs and lncRNAs in serum could be used as biomarkers to detect colorectal cancer. IMPACT: Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured long RNAs. The combination of two mRNAs, KRTAP5-4 and MAGEA3, and one lncRNA, BCAR4, could be potential candidates to detect colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1158-66. ©2016 AACR.

[Study on the association of thrombin activatable fibrinolysis inhibitor and the Thr325Ile and Thr147Ala polymorphisms of its encoding gene CPB2 in patients with coronary heart disease].

OBJECTIVE: To investigate the association of thrombin activatable fibrinolysis inhibitor (TAFI) and its encoding gene CPB2 polymorphism in patients with coronary heart disease (CHD). METHODS: The CPB2 gene polymorphisms of Thr325Ile and Thr147Ala were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients of acute myocardial infarction (n=100), acute angina pectoris (n=110) and a control group (n=190). The antigen (Ag) and activity (Act) of the TAFI were determined by sandwich enzyme link immunosorbent assay specific for human TAFI and chromogenic assay for activated human TAFI in plasma, respectively. The relationship between Thr325Ile and Thr147Ala gene polymorphism and TAFI Ag and Act were also analyzed. RESULTS: Plasma TAFI Act and TAFI Ag in acute myocardial infarction group and acute angina pectoris group (CHD patients group) were both significantly higher than those of the control group. The genotype frequencies of Thr325Ile (C1040T) and Thr147Ala (G505A) were as the following: C1040C (Thr325Thr) 67 (31.9%) and 64 (33.6%); C1040T (Thr325Ile) 109 (51.9%) and 92 (48.4%); T1040T (Ile325Ile) 34 (16.2%) and 34(17.8%); G505G (Ala147 Ala) 75 (35.7%) and 72 (37.8%); G505A(Thr147Ala) 112 (53.3%) and 96 (50.5%); A505A(Thr147Thr)23 (10.9%) and 22 (11.7%), in the CHD patients and control respectively. Chi-square analysis showed no significant difference in the Thr325Ile and Thr147Ala polymorphism distributions (P > 0.05). In addition, at the 325 position, the TAFI antigen of the Thr325Thr was higher than that of the other genotypes (Thr325Ile and Ile325Ile, P < 0.05). There was no statistical significance between the TAFI antigen of the Thr325Ile and Ile325Ile (P > 0.05). No significant correlation was found between the TAFI Act and the Thr325Ile polymorphism. At the position 147, significant correlation between the polymorphism of the Thr147Ala and TAFI Ag and Act was not found. CONCLUSION: TAFI plays an important role in anti-fibrinolysis. It might be a risk factor for acute myocardial infarction and acute angina pectoris. The Thr325Ile polymorphism had obvious effect on TAFI antigen levels, but the Thr325Ile and Thr147Ala polymorphism had no association with coronary heart disease.