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Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal. They play a critical role in cell therapy due to their powerful immunomodulatory and regenerative effects. Recent studies suggest that one of the key therapeutic mechanisms of MSCs seems to derive from their paracrine product, called extracellular vesicles (EVs). The EVs contain much DNA, messenger RNA (mRNA), microRNA, and protein components, which can exert intracellular communication to target cells. In clinical applications, the MSC-EVs have been widely used in tissue repair and immune disorder diseases. However, there are serval issues need to be considered such as how to accomplish the large-scale production of EVs and how to verify the exact mechanism of EVs. In this review, we summarize the current progress of MSC-EVs and discuss the challenges and future of MSC-EVs. [ABSTRACT FROM AUTHOR]

Abstract Background The histopathological and molecular heterogeneity of normal tissue adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue (NTAB), and the availability of limited specimens make deciphering the mechanisms of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers that could be reliably used to define a transforming fingerprint using RNA in situ hybridization. Methods We evaluated 15 tumor-related RNA in situ hybridization biomarkers using tumor microarray and samples of seven tumor-adjacent normal tissues from 314 patients. Biomarkers were determined using comprehensive statistical methods (significance of support vector machine-based artificial intelligence and area under curve scoring of classification distribution). Results TP53 was found to be a most reliable index (P -7; area under curve >87%) for distinguishing NTAC from NTAB, according to the results of a significance panel (BCL10, BECN1, BRCA2, FITH, PTCH11 and TP53). Conclusions The genetic alterations in TP53 between NTAC and NTAB may provide new insight into the field of cancerization and tumor transformation.

Background: Suppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, its role in the progression of breast cancer remains vague. Methods: Online database analysis was determined by Oncomine and Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4). Tumor biology behaviors were measured by MTT assay, wound healing model, Transwell and Flow cytometry assays. Methylation-specific PCR (MSP) was employed to detect promoter methylation. Results: Low level of ST5 was observed in breast cancer specimens, particularly in recurrent, invasive breast cancer cases compared to para-carcinoma tissue or non-invasive breast cancer. The downregulation of ST5 was also proved in MDA-MB-231 and SKBR3 cell lines with a high invasive capability as compared to MCF-7 cell with a low invasive capability. ST5 was negatively associated with pathological stages of breast cancer. ST5-downregulation promoted, while ST5-upregulation inhibited the progression of cell proliferation, cell cycle and migration of MDA-MB-231 cells. Additionally, ST5 knockdown inhibited, whereas ST5 overexpression promoted apoptosis of MDA-MB-231 cells. However, ST5 modification, either upregulation or downregulation, had no significant impact on tumor behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated ERK1/2 and JNK, and subsequently the expression of c-Myc. PD98059-mediated ERK1/2 inhibition abolished the stimulatory effects of ST5-depletion on ERK1/2/JNK/c-Myc signaling axis, and ST5 depletion-mediated cell over-proliferation and migration. Of note, ST5 reduction in invasive breast cancer cells should implicate in the hypermethylation of ST5 promoter region. Conclusion: Our findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Gut microbiome maintains local gut integrity and systemic host homeostasis, where optimal control of intestinal lipopolysaccharides (LPS) activity may play an important role. LPS mainly produced from gut microbiota are a group of lipid-polysaccharide chemical complexes existing in the outer membrane of Gram-negative bacteria. Traditionally, LPS mostly produced from Proteobacteria are well known for their ability in inducing strong inflammatory responses (proinflammatory LPS, abbreviated as P-LPS), leading to septic shock or even death in animals and humans. Although the basic structures and chemical properties of P-LPS derived from different bacterial species generally show similarity, subtle and differential immune activation activities are observed. On the other hand, frequently ignored, a group of LPS molecules mainly produced by certain microbiota bacteria such as Bacteroidetes show blunt or even antagonistic activity in initiating pro-inflammatory responses (anti-inflammatory LPS, abbreviated as A-LPS). In this review, besides the immune activation properties of P-LPS, we also focus on the description of anti-inflammatory effects of A-LPS, and their potential antagonistic mechanism. We address the possibility of using native or engineered A-LPS for immune modulation in prevention or even treatment of P-LPS induced chronic inflammation related diseases. Understanding the exquisite interactive relationship between structure-activity correlation of P- and A-LPS not only contributes to molecular understanding of immunomodulation and homeostasis, but also re-animates the development of novel LPS-based pharmacological strategy for prevention and therapy of chronic inflammation related diseases. [ABSTRACT FROM AUTHOR]

Background: Leukoaraiosis (LA) is shown as white matter hyperintensities on T2-weighted magnetic resonance imaging brain scans. Together with candidate gene association studies (CGAS), multiple genome-wide association studies (GWAS) have reported large numbers of single nucleotide polymorphisms (SNPs) to be associated with LA in European populations. To date, no replication studies have been reported in independent Chinese samples. Methods: Here, we performed a candidate gene association study comprising 220 Chinese subjects with LA and 50 controls. Thirty-nine polymorphisms on 32 risk genes were selected from previous studies, and they were genotyped through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Genetic association analysis was firstly performed in all subjects with LA. Then, the same analysis was conducted in the six random sampling cohorts of 50 LA patients, respectively. Data analyses on the associations of SNPs with LA risk were evaluated through Pearson's χ2 and multivariate logistic regression tests. Results: We found that eight polymorphisms in six genes (PMF1 , ICAM1 , TRIM65 , AGT , FBF1 , and ACOX1) were significantly associated with LA in the genetic association tests. Except for those eight gene variants, 24 other polymorphisms were not found to be significantly associated with LA in general genetic model, dominant model, recessive model, or multiplicative model. Among those eight polymorphisms, rs2984613 in PMF1 showed significant association with LA in the cohort of 220 LA subjects, and such significant association remained in both general genetic model (OR: 0.262, 95% CI: 0.091–0.752, p adj = 0.030) and recessive model (OR: 0.323, 95% CI: 0.119–0.881, p adj = 0.038) when controlling for clinical variables. Seven other significant variants (rs5498 in ICAM1 , rs699 in AGT , rs2305913 in FBF1 , rs1135640 in ACOX1 , and rs3760128, rs7214628, and rs7222757 in TRIM65) were identified in those six random sampling tests that were conducted in the adjusted cohorts of 50 LA patients. In addition, except for rs699 which showed detrimental effect and represented a risk variant for LA, seven other polymorphisms seemed to exert protective effects on LA and to reduce the risk of LA. It is necessary to confirm these associations in an independent cohort. Conclusions: This first replication study on multiple genes in an independent Chinese population did not replicate any risk polymorphisms for LA other than rs 699 in AGT but revealed the significantly negative associations of PMF1 , ICAM1 , TRIM65 , FBF1 , and ACOX1 polymorphisms with LA. It not only supported the strong ethnic differences in the genetics of LA but also indicated that those six identified genes may be involved in Chinese white matter lesions. Larger scales of CGAS and GWAS are necessary to confirm and decipher those ethnic-Han specific risk genes for LA in China. [ABSTRACT FROM AUTHOR]

Idiopathic normal pressure hydrocephalus (INPH) with comorbid vascular dementia (VD) often have poor response to ventriculo-peritoneal (V-P) shunt. Here, three patients over the age of 60 came to the hospital with the similar clinical symptoms, Evan index over 0.3, mini-mental state examination (MMSE) score <27, and cerebrospinal fluid (CSF) pressure under 200 mmH2O. They accepted conventional brain imaging scanning, followed by magnetic resonance-susceptibility weighted imaging (MR-SWI) scanning. We found that MR-SWI could distinguish INPH from leukoaraiosis (LA) and cerebral amyloid angiopathy (CAA), through cerebral microbleed (CMB) images, sharply. We highly recommended incorporation of MR-SWI into INPH international guidance as a routine pre-operative diagnostic method preceding V-P shunt treatment. [ABSTRACT FROM AUTHOR]

Background: Vitamin D3 has been known to have an anticancer effect, but the mechanisms underlying this is poorly explored. The present study aimed to investigate the antitumor role of vitamin D3 on gastric cancer and mechanisms. Methods: The Roche Elecsys platform was applied in retrospective studies to detect the role of 25-hydroxylvitamin D3 in adenocarcinoma and colony formation assay was conducted to verify the effect of 1, 25-dihydroxyvitamin D3 on the proliferation of gastric cancer cells. After the identification of hypermethylation of BMP3 CpG islands by bisulfite genomic sequencing (BGS), we further investigated the relationship of BMP3 expression and gastric carcinogenesis by Western blot analysis and gel electrophoresis mobility shift assay (EMSA). Results: Here we show that low concentration of 1, 25-dihydroxyvitamin D3 links to cancerization and significantly inhibits proliferation of undifferentiated gastric cancer cell lines SGC-7901 and BGC-823. BMP3 promoter hypermethylation was highly correlated with gastric tumor. Moreover, BMP3 expression was regulated by its promoter methylation in gastric cells. The further exploration of the relationship between 1, 25-dihydroxyvitamin D3 and BMP3 by EMSA results that 1, 25-dihydroxyvitamin D3 stimulates BMP3 expression by the inhibition of BMP3 promoter methylation in gastric tumor cells. Conclusion: In combination with the data from clinical research, bioinformatics analysis and experimental verification, we propose that 1, 25-hydroxylvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation. [ABSTRACT FROM AUTHOR]

Liquid biopsy with circulating tumor DNA (ctDNA) profiling by next-generation sequencing holds great promise to revolutionize clinical oncology. It relies on the basis that ctDNA represents the real-time status of the tumor genome which contains information of genetic alterations. Compared to tissue biopsy, liquid biopsy possesses great advantages such as a less demanding procedure, minimal invasion, ease of frequent sampling, and less sampling bias. Next-generation sequencing (NGS) methods have come to a point that both the cost and performance are suitable for clinical diagnosis. Thus, profiling ctDNA by NGS technologies is becoming more and more popular since it can be applied in the whole process of cancer diagnosis and management. Further developments of liquid biopsy ctDNA testing will be beneficial for cancer patients, paving the way for precision medicine. In conclusion, profiling ctDNA with NGS for cancer diagnosis is both biologically sound and technically convenient. [ABSTRACT FROM AUTHOR]

In this study, the authors show a method of enhancing the deoxyribonucleic acid (DNA) hybridization efficiency by exploiting the photovoltaic effect. The arrayed microchip is fabricated in a semiconductor wafer coated with metal thin films to immobilize the probe DNA. Hybridization between immobilized probe DNAs and fluorescent-labeled target DNA is performed under illumination by a laser. The photovoltaic effect induces positive charges on the surface of the microchip to attract negatively charged target DNAs toward the hybridization sites, increasing the hybridization rate by up to two orders of magnitude. The experimental results reveal that the method represents a cutting-edge solution to the problem of the time consuming microchip process. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify mRNA targets of dysregulated miRNAs through the integrated analysis of miRNA and mRNA expression profiling in men with normal versus impaired spermatogenesis. The expression of mRNAs and miRNAs in testicular tissues obtained from males with non-obstructive azoospermia (NOA, n = 4) or obstructive azoospermia (OA, n = 3) with normal spermatogenesis was analyzed using microarray technology. Some of the most interesting results were validated by real time PCR using samples from the same cohort. Ninety-three miRNAs and 4172 mRNAs were differentially expressed in the NOA and normozoospermic OA patients. In addition to confirming that significantly dysregulated genes and miRNAs play pivotal roles in NOA, promising correlation signatures of these miRNA/mRNA pairs were discovered in this study. The functional classification of the miRNA/mRNA pairs revealed that differentially expressed genes were most frequently associated with spermatogenesis, the cell meiosis, the cell cycle, and the development of secondary male sexual characteristics. This is the first systematic profiling of both mRNA and miRNA in testicular tissues of patients with NOA and OA. Our results indicate that the phenotypic status of NOA is characterized by the dysfunction of normal spermatogenesis when compared with OA or normozoospermic males. [ABSTRACT FROM AUTHOR]

Presents information on the biological roles of inorganic polyphospate (polyP). Materials and methods used; Definition of inorganic polyphosphates (polyP); Information on the extraction of polyP with Glassmilk.

Leukoaraiosis (LA) manifests as cerebral white matter hyperintensities on T2-weighted magnetic resonance imaging scans and corresponds to white matter lesions or abnormalities in brain tissue. Clinically, it is generally detected in the early 40s and is highly prevalent globally in individuals aged >60 years. From the imaging perspective, LA can present as several heterogeneous forms, including punctate and patchy lesions in deep or subcortical white matter; lesions with periventricular caps, a pencil-thin lining, and smooth halo; as well as irregular lesions, which are not always benign. Given its potential of having deleterious effects on normal brain function and the resulting increase in public health burden, considerable effort has been focused on investigating the associations between various risk factors and LA risk, and developing its associated clinical interventions. However, study results have been inconsistent, most likely due to potential differences in study designs, neuroimaging methods, and sample sizes as well as the inherent neuroimaging heterogeneity and multi-factorial nature of LA. In this article, we provided an overview of LA and summarized the current knowledge regarding its epidemiology, neuroimaging classification, pathological characteristics, risk factors, and potential intervention strategies.

White matter lesions known as leukoaraiosis (LA) are cerebral white matter hyperintensities observed in elderly individuals. Currently, no reliable molecular biomarkers are available for monitoring their progression over time. To identify biomarkers for the onset and progression of LA, we analyzed whole blood-based, microRNA expression profiles of leukoaraiosis, validated those exhibiting significant microRNA changes in clinical subjects by means of quantitative real-time polymerase chain reactions and determined the function of miRNA in cell lines by means of microRNA mimic transfection assays. A total of seven microRNAs were found to be significantly down-regulated in leukoaraiosis. Among the microRNAs, hsa-miR-1972 was downregulated during the early onset phase of leukoaraiosis, as confirmed in independent patients, and it was found to target leukoaraiosis-dependent BAIAP3, decreasing its expression in 293T cell lines. Functional enrichment analysis revealed that significantly dysregulated miRNAs-mRNAs changes associated with the onset of leukoaraiosis were involved in neurogenesis, neuronal development, and differentiation. Taken together, the study identified a set of candidate microRNA biomarkers that may usefully monitor the onset and progression of leukoaraiosis. Given the enrichment of leukoaraiosis-associated microRNAs and mRNAs in neuron part and membrane system, BAIAP3 could potentially represent a novel target of hsa-miR-1972 in leukoaraiosis through which microRNAs are involved in the pathogenesis of white matter lesions.

Background: Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking., Methods: We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1 year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied., Results: A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1., Conclusion: These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)