Miracle-dz/UniFAR-FTUs huggingface dataset:
Roles for Exosome in Various Kidney Diseases and Disorders

Exosome is a nanoscale vesicle with a size range of 30–100 nm. It is secreted from cell to extracellular space by exocytosis after fusion of multivesicular body (MVB) (formed by endocytic vesicles) with plasma membrane. Exosome plays several important roles in cellular homeostasis and intercellular communications. During the last two decades, exosome has acquired a wide attention to explore its additional roles in various aspects of cell biology and function in several organ systems. For the kidney, several lines of evidence have demonstrated 1that exosome is involved in the renal physiology and pathogenic mechanisms of various kidney diseases/disorders. This article summarizes roles of the exosome as the potential source of biomarkers, pathogenic molecules, and therapeutic biologics that have been extensively investigated in many kidney diseases/disorders, including lupus nephritis (LN), other glomerular diseases, acute kidney injury (AKI), diabetic nephropathy (DN), as well as in the process of renal fibrosis and chronic kidney disease (CKD) progression, in addition to polycystic kidney disease (PKD), kidney transplantation, and renal cell carcinoma (RCC). Moreover, the most recent evidence has shown its emerging role in kidney stone disease (or nephrolithiasis), involving inflammasome activation and inflammatory cascade frequently found in kidney stone pathogenesis.
Critical Role of microRNA-21 in the Pathogenesis of Liver Diseases

MicroRNAs are small non-coding RNAs that range in length from 18 to 24 nucleotides. As one of the most extensively studied microRNAs, microRNA-21 (miR-21) is highly expressed in many mammalian cell types. It regulates multiple biological functions such as proliferation, differentiation, migration, and apoptosis. In this review, we summarized the mechanism of miR-21 in the pathogenesis of various liver diseases. While it is clear that miR-21 plays an important role in different types of liver diseases, its use as a diagnostic marker for specific liver disease or its therapeutic implication are not ready for prime time due to significant variability and heterogeneity in the expression of miR-21 in different types of liver diseases depending on the studies. Additional studies to further define miR-21 functions and its mechanism in association with each type of chronic liver diseases are needed before we can translate the bedside observations into clinical settings.
Increased Hypothalamic Projections to the Lateral Hypothalamus and Responses to Leptin in Rat Neonates From High Fat Fed Mothers

The lateral hypothalamus (LHA) is a central hub in the regulation of food intake and metabolism, as it integrates homeostatic and hedonic circuits. During early development, maturing input to and output from the LHA might be particularly sensitive to environmental dietary changes. We examined the effects of a maternal high fat diet (HFD, 60% Kcal in fat) on the density of hypothalamic projections to the orexin (ORX-A) field of the LHA in 10 day-old (PND10) rat pups using retrograde labeling with fluorescent microspheres. We also compared responsiveness of phenotypically identified LHA neurons to leptin administration (3 mg/kg, bw) between pups from control (CD) or high fat (HFD) fed mothers on PND10 and 15-16, at the onset of independent feeding. HFD pups exhibited a higher density of LHA projections (p = 0.05) from the ventromedial hypothalamus (VMH) compared to CD pups and these originated from both SF-1 and BDNF-positive neurons in the VMH. Increased circulating leptin levels in HFD pups, particularly on PND15-16 was consistent with enhanced pSTAT3 responses to leptin in the orexin (ORX-A) field of the LHA, with some of the activated neurons expressing a GABA, but not CART phenotype. ORX-A neurons colocalizing with pERK were significantly higher in PND15-16 HFD pups compared to CD pups, and leptin-induced increase in pERK signaling was only observed in CD pups. There was no significant effect of leptin on pERK in HFD pups. These results suggest that perinatal maternal high fat feeding increases hypothalamic projections to the ORX-A field of the LHA, increases basal activation of ORX-A neurons and direct responsiveness of LHA neurons to leptin. Since these various LHA neuronal populations project quite heavily to Dopamine (DA) neurons in the ventral tegmental area, they might participate in the early dietary programming of mesocorticolimbic reward circuits and food intake.
Polarization of Macrophages in Epidural Inflammation Induced by Canine Intervertebral Disc Herniation

Introduction: Canine interverterbral disc (IVD), although physiologically acellular, displays an inflammatory cell population consisting almost exclusively of macrophages (Mϕ) when acutely herniated. Mϕ encompass a heterogenous cell population, roughly divided into classically (M1) or alternatively activated (M2)Mϕ. Polarization into M1 Mϕ leads to strong antimicrobial activity and pro-inflammatory response. In contrast, M2Mϕ exibit anti-inflammatory function and regulate wound healing. The purpose of this study was to characterize the phenotype of the Mϕ population present in naturally occurring IVD herniation. Materials and Methods: IVD material of dogs with IVD disease was collected during standard decompressive surgery. A negative control consisting of IVD material of dogs without IVD degeneration and a positive control consisting of canine liver and lymph node samples were also included. All samples were embedded in OCT and shock frozen. Eight micrometer cryostat sections were prepared, air dried and immunostained without prefixation or permeabilization. CD14 was used as marker Mϕ, MHCII for M1Mϕ and CD206 for M2Mϕ. Results: Fifteen samples of dogs with IVD herniation, 10 negative, and 5 positive control samples were obtained. No positive cell was found in the negative control group. The positive control group displayed several MHCII and CD206 positive cells, all of them being simultaneously positive to CD14. All herniated samples displayed a mixed population of M1Mϕ and M2Mϕ, and some sparse Mϕ displaying markers for both M1 and M2Mϕ simultaneously. Conclusion: The mixed phenotype encountered shows the plasticity and dynamism of Mϕ and evidences the chronic component of IVD disease despite its acute clinical presentation.
Uncovering Signatures of DNA Methylation in Ancient Plant Remains From Patterns of Post-mortem DNA Damage

The ultra-short DNA molecules still preserved in archeological remains can provide invaluable genetic information about past individuals, species, and communities within the half to 1-million-year time range. The sequence data are, however, generally affected by post-mortem DNA damage and include specific patterns of nucleotide mis-incorporations, which can help data authentication. Recent work in ancient mammals has shown that such patterns can also help assess past levels of DNA methylation in CpG contexts. Despite pioneering work in barley and sorghum, ancient epigenetic marks have received limited attention in plants and it remains unknown whether ancient epigenetic signatures can be retrieved in any of the three main sequence contexts (CG, CHG, and CHH). To address this question, we extended a statistical methylation score originally proposed to trace cytosine methylation in mammal sequence data to accommodate the three methylation contexts common in plants. We applied this score to a range of tissues (wood, cobs, and grains) and species (oak, maize, and barley), spanning both desiccated and waterlogged archeological samples. Ancient sequence data obtained for USER-treated DNA extracts yielded methylation scores on par with DNA methylation levels of modern organellar and nuclear genomes. At the quantitative level, scores were (1) positively correlated to post-mortem cytosine deamination, and (2) replicated relative contributions of CG, CHG, and CHH contexts to DNA methylation assessed by bisulfite DNA sequencing of modern plant tissues. This demonstrates that genuine DNA methylation signatures can be characterized in ancient plant remains, which opens new avenues for investigating the plant evolutionary response to farming, pollution, epidemics, and changing environmental conditions.
PVT1 Long Non-coding RNA in Gastrointestinal Cancer

Whole genome and transcriptome sequencing technologies have led to the identification of many long non-coding RNAs (lncRNAs) and stimulated the research of their role in health and disease. LncRNAs participate in the regulation of critical signaling pathways including cell growth, motility, apoptosis, and differentiation; and their expression has been found dysregulated in human tumors. Thus, lncRNAs have emerged as new players in the initiation, maintenance and progression of tumorigenesis. PVT1 (plasmacytoma variant translocation 1) lncRNA is located on chromosomal 8q24.21, a large locus frequently amplified in human cancers and predictive of increased cancer risk in genome-wide association studies (GWAS). Combined, colorectal and gastric adenocarcinomas are the most frequent tumor malignancies and also the leading cause of cancer-related deaths worldwide. PVT1 expression is elevated in gastrointestinal tumors and correlates with poor patient prognosis. In this review, we discuss the mechanisms of action underlying PVT1 oncogenic role in colorectal and gastric cancer such as MYC upregulation, miRNA production, competitive endogenous RNA (ceRNA) function, protein stabilization, and epigenetic regulation. We also illustrate the potential role of PVT1 as prognostic biomarker and its relationship with resistance to current chemotherapeutic treatments.
Association of Novel Streptococcus sanguinis Virulence Factors With Pathogenesis in a Native Valve Infective Endocarditis Model

Streptococcus sanguinis (S. sanguinis) is an abundant oral commensal which can cause disseminated human infection if it gains access to the bloodstream. The most important among these diseases is infective endocarditis (IE). While virulence phenotypes of S. sanguinis have been correlated to disease severity, genetic factors mediating these phenotypes, and contributing to pathogenesis are largely uncharacterized. In this report, we investigate the roles of 128 genes in virulence-related phenotypes of S. sanguinis and characterize the pathogenic potential of two selected mutants in a left-sided, native valve IE rabbit model. Assays determining the ability of our mutant strains to produce a biofilm, bind to and aggregate platelets, and adhere to or invade endothelial cells identified sixteen genes with novel association to these phenotypes. These results suggest the presence of many uncharacterized genes involved in IE pathogenesis which may be relevant for disease progression. Two mutants identified by the above screening process – SSA_1099, encoding an RTX-like protein, and mur2, encoding a peptidoglycan hydrolase – were subsequently evaluated in vivo. Wild type (WT) S. sanguinis reliably induced cardiac vegetations, while the SSA_1099 and mur2 mutants produced either no vegetation or vegetations of small size. Splenomegaly was reduced in both mutant strains compared to WT, while pathology of other distal organs was indistinguishable. Histopathology analyses suggest the cardiac lesions and vegetations in this model resemble those observed in humans. These data indicate that SSA_1099 and mur2 encode virulence factors in S. sanguinis which are integral to pathogenesis of IE.
Management of Pharyngeal Gonorrhea Is Crucial To Prevent the Emergence and Spread of Antibiotic-Resistant Neisseria gonorrhoeae

We read with great interest the paper recently published by Unemo et al. that reported a second strain (F89) of Neisseria gonorrhoeae with a high level of ceftriaxone resistance, for which the ceftriaxone MIC was 1 μg/ml, that was isolated in France in 2010 ([10][1]). The first high-level
Hypertension and the Risk of Dementia

Hypertension, particularly midlife high blood pressure, has been related to a higher risk of cognitive decline and dementia, including Alzheimer disease. However, these associations are complex and not fully elucidated. Cerebral small vessel disease emerges as one of the most important causes. Several observational studies have shown the potential beneficial role of antihypertensive treatment in preventing cognitive decline. However, randomized clinical trials (RCTs) have shown controversial results without proving nor disproving the association. On the other hand, in very elderly or frail people some studies have observed a relationship between low blood pressure and worse cognitive function. The optimal systolic and diastolic blood pressure values for protecting cognitive function, especially in elderly people, are not known.
Comparison of the ERP-Based BCI Performance Among Chromatic (RGB) Semitransparent Face Patterns

Objective Previous studies have shown that combing with color properties may be used as part of the display presented to BCI users in order to improve performance. Build on this, we explored the effects of combinations of face stimuli with three primary colors (RGB) on BCI performance which is assessed by classification accuracy and information transfer rate (ITR). Furthermore, we analyzed the waveforms of three patterns. Methods We compared three patterns in which semitransparent face is overlaid three primary colors as stimuli: red semitransparent face (RSF), green semitransparent face (GSF), and blue semitransparent face (BSF). Bayesian linear discriminant analysis (BLDA) was used to construct the individual classifier model. In addition, a Repeated-measures ANOVA (RM-ANOVA) and Bonferroni correction were chosen for statistical analysis. Results The results indicated that the RSF pattern achieved the highest online averaged accuracy with 93.89%, followed by the GSF pattern with 87.78%, while the lowest performance was caused by the BSF pattern with an accuracy of 81.39%. Furthermore, significant differences in classification accuracy and ITR were found between RSF and GSF (p < 0.05) and between RSF and BSF patterns (p < 0.05). Conclusion The semitransparent faces colored red (RSF) pattern yielded the best performance of the three patterns. The proposed patterns based on ERP-BCI system have a clinically significant impact by increasing communication speed and accuracy of the P300-speller for patients with severe motor impairment.
Altered Amplitude of Low-Frequency Fluctuations and Functional Connectivity in Excessive Daytime Sleepiness in Parkinson Disease

Object Excessive daytime sleepiness (EDS) is common in Parkinson disease (PD), but the neural basis of EDS in PD is unclear. We aim to analyze the neural activity changes in PD-related EDS. Methods In the present study, 38 PD patients and 19 healthy controls underwent clinical assessments and resting state functional magnetic resonance imaging (MRI) at 3T. Patients were further classified into PD patients with EDS (n = 17) and PD patients without EDS (n = 21), according to the Epworth Sleepiness Scale (ESS) cutoff score with greater than 10 or less than 3. We evaluated all patients using PD-related motor and non-motor clinical scales. An analysis of covariance and post hoc two-sample t-tests were performed to examine between-groups differences of the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC). Results We found that, all PD-EDS subjects in our study were male. Compared with the control subjects, PD patients with EDS had decreased ALFF in the Pons and increased ALFF in the Frontal_Mid_Orb_L (p < 0.01, corrected). Moreover, PD patients with EDS showed decreased ALFF in the left posterior cingulate cortex (PCC) relative to PD without EDS, which was negatively correlated with the ESS score (p < 0.001). After that, the FC analysis with the left PCC region of interest showed reduced FC of the right PCC and right precuneus in PD with EDS compared with PD without EDS (p < 0.01, corrected). Conclusion We hypothesized the wake-promoting pathways and the default mode network dysfunction underlying the EDS in male PD patients.
Acute Exacerbation of Interstitial Lung Disease in Adult Patients With Idiopathic Inflammatory Myopathies: A Retrospective Case-Control Study

Objective: This study aimed at clarifying the prevalence, risk factors, outcome, and outcome-related factors of acute exacerbation of interstitial lung disease (AE-ILD) in patients with idiopathic inflammatory myopathy (IIM). Methods: Data of IIM patients who were admitted to the First Affiliated Hospital of Zhejiang University (FAHZJU) from September 2007 to September 2019 were retrospectively collected. And the IIM patients with AE-ILD formed the case group. In addition, age and sex matched IIM patients without AE-ILD were randomly selected to constitute the control group. A 1:2 case-control study and intragroup analysis were performed to identify risk factors for development of AE-ILD in IIM patients and unfavorable short-term outcome in AE-ILD patients through comparison, univariate and multivariate logistic regression analysis. Results: AE-ILD occurred in 64 out of 665 IIM patients (9.6%) with a short-term mortality rate of 39.1%. And the 64 IIM patients with AE-ILD formed the case group. Besides, 128 age and sex matched IIM patients without AE-ILD were randomly selected to constitute the control group. The retrospective case-control study revealed that elevated on-admission disease activity (P < 0.001), lower percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.013) and diagnosis of clinically amyopathic dermatomyositis (CADM, P = 0.007) were risk factors for development of AE-ILD in IIM patients. The following intragroup analysis indicated that elevated on-admission disease activity (P = 0.008) and bacterial infection (P = 0.003) were significantly correlated with the unfavorable short-term outcome of patients complicated with AE-ILD. In addition, combined use of steroid and disease modifying antirheumatic drugs (DMARDs, P = 0.006) was found to significantly reduce the short-term mortality in IIM patients with AE-ILD. Conclusion: AE-ILD is a less frequent but fatal complication in IIM patients with elevated on-admission disease activity, lower DLCO% and diagnosis of CADM working as risk factors, indicating the potential roles of autoimmune abnormality and hypoxia in development of AE-ILD. Elevated on-admission disease activity and bacterial infection could predict unfavorable short-term outcome of IIM patients with AE-ILD. A therapeutic regimen of steroid and DMARDs was found to reduce short-term death in these patients.
Deep Eutectic Solvents as Media for the Prebiotic DNA-Templated Synthesis of Peptides

Translation of genetic information into peptide products is one of the fundamental processes of biology. How this occurred prebiotically, in the absence of enzyme catalysts, is an intriguing question. Nucleic acid-templated synthesis (NATS) promotes reactions by bringing building blocks tethered to complementary DNA strands into close proximity and has been shown to enable peptide synthesis without enzymes—it could therefore serve as a model for prebiotic translation of information stored in nucleic acid sequences into functional peptides. The decomposition of highly reactive DNA adapters has so far limited the effectiveness of NATS, but these studies have been performed exclusively in aqueous solution. Deep eutectic solvents (DESs) have been proposed as a feasible solvent for prebiotic replication of nucleic acids, and here are studied as media for prebiotic translation using NATS as a model. DESs are shown to enhance the stability of DNA-conjugated activated esters, the precursors of peptides. However, this enhanced stability was coupled with decreased amine reactivity that hampered the formation of peptide bonds in DESs. These properties are exploited to demonstrate the storage of DNA-conjugated activated esters in a DES followed by transfer into aqueous buffer to activate the NATS of peptides “on demand. ” These findings, together with the reported functions of DESs in prebiotic processes, shed light on how DESs could have facilitated the non-enzymatic translation of genetic information into functional peptides on the early Earth.
Two Novel Loci of RELN Associated With Antipsychotics Response in Chinese Han Population

Background There are great individual differences in the drug responses; however, there are few prognostic drug response biomarkers available. RELN is one of the more extensively examined schizophrenia candidate genes. The purpose of this study was to determine whether RELN can affect antipsychotics response in the Chinese population. This may lead to the discovery of relevant novel drug response markers. Methods The unrelated 260 Chinese Han inpatients with schizophrenia were enrolled in the present study. The enrolled subjects have been prescribed antipsychotic medication during the study. A total of 15 SNPs of RELN were genotyped by MassARRAY® platform. The association of the RELN gene with therapeutic response to antipsychotics was analyzed based on sex and age at onset. Results Two novel SNPs of RELN were found to be associated with antipsychotic treatment response (rs155333, p = 0.010 and rs6465938, p = 0.049) at nominal significance threshold, but not after multiple correction. Our study also revealed highly significant association of a haplotype consisting of three SNPs (rs362814-rs362626-rs2237628) with antipsychotic treatment response. Even after permutation, the p-value indicated significant association (rs362814-rs362626-rs2237628: ACT, χ2 = 6.353, p = 0.0117, permuted p = 0.04). Furthermore, a novel SNP, rs2535764, was found to be associated with antipsychotic response under overdominant genetic model at a marginal significant level of 0.046 (C/T vs. C/C + T/T: p = 0.046, AIC = 314.7, BIC = 321.6). Conclusion Our data indicated that RELN can affect antipsychotic treatment outcomes in the Chinese population. SNPs of RELN could be used as predictive biomarkers for future personalized medicine of antipsychotic drug treatment. However, none of the three novel SNPs (rs155333, rs6465938, and rs2535764) remained significant after Bonferroni correction. Therefore, validation is needed in larger pharmacogenetic studies.
Development and Diversity of Bacterial Biofilms in Response to Internal Tides, a Case Study off the Coast of Kuwait

Information pertaining to changes in abundance and composition of microbial communities on offshore platforms in relation to changes in environmental conditions due to internal tides are scarce. In this study, artificial substrata were deployed at two locations on a gently sloping seabed off the coast of Kuwait. The abiotic factors at the two sites were recorded spatially and temporally using time-series measurements and continuous turbulence profiling for 13 days. Results showed variations in water density between the upper and deeper waters with the pycnocline undulating between 6 and 15 m depth at both locations. In the water layer beneath the pycnocline, significant current shear due to the internal tides led to higher turbidity coupled with lower dissolved oxygen (DO) and chlorophyll a concentration. The microbiological data showed a significant decrease in the biofilm total biomass, bacterial counts and phototrophic biomass with increase in depth at both locations. The 16S rRNA amplicon sequence analysis revealed that biofouling bacterial communities were affected by depth with Alphaproteobacteria and Bacteroidetes members dominating the upper and deeper waters at both locations. The non-metric multidimensional scaling (NMDS) based-ordination analysis revealed that biofouling bacterial communities at 3 m were different than at 15 m, with a percentage of shared operational taxonomic units (OTUs) ≤64% between locations and depths. The power of the employed system is demonstrated in the results that shed light on the significance of prevailing environmental conditions associated with internal tides in shaping the biofilm community in subtropical offshore water systems.