The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in ...the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown.
Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen–glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.
•A first study to profile ischemic-responsive brain endothelial long non-coding RNAs•Total 217 lncRNAs were classified as ischemic-responsive endothelial lncRNAs.•The most highly altered lncRNAs were confirmed in brain microvessels after stroke.•Identified key transcription factors that regulate ischemic-responsive lncRNAs
Abstract Macrophages provide a crucial environment for Salmonella enterica serovar Typhi ( S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi ...interact remains limited. In this study, we delve into the dynamics of S . Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S . Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S . Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S . Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S . Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S . Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S . Typhi infection.
Many intracellular bacteria can establish chronic infection and persist in tissues within granulomas composed of macrophages. Granuloma macrophages exhibit heterogeneous polarization states, or ...phenotypes, that may be functionally distinct. Here, we elucidate a host-pathogen interaction that controls granuloma macrophage polarization and long-term pathogen persistence during Salmonella Typhimurium (STm) infection. We show that STm persists within splenic granulomas that are densely populated by CD11b+CD11c+Ly6C+ macrophages. STm preferentially persists in granuloma macrophages reprogrammed to an M2 state, in part through the activity of the effector SteE, which contributes to the establishment of persistent infection. We demonstrate that tumor necrosis factor (TNF) signaling limits M2 granuloma macrophage polarization, thereby restricting STm persistence. TNF neutralization shifts granuloma macrophages toward an M2 state and increases bacterial persistence, and these effects are partially dependent on SteE activity. Thus, manipulating granuloma macrophage polarization represents a strategy for intracellular bacteria to overcome host restriction during persistent infection.
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•M2-like granuloma macrophages are more permissive for Salmonella persistence•TNF signaling limits M2-like granuloma macrophages, thereby restricting Salmonella•Salmonella effector SteE promotes an M2 phenotype to overcome TNF-mediated restriction
Pham et al. show that granulomas in Salmonella-infected tissues are composed of macrophages that exhibit heterogenous polarization states, or phenotypes, and are functionally distinct. They elucidate a pathogen-driven virulence mechanism that controls granuloma macrophage polarization and long-term pathogen persistence during Salmonella infection.
The aim of this study was to test photodynamic therapy (PDT) as an alternative approach to biofilm disruption on dental hard tissue, We evaluated the effect of methylene blue and a 660 nm diode laser ...on the viability and architecture of Gram-positive and Gram-negative bacterial biofilms.
Ten human teeth were inoculated with bioluminescent Pseudomonas aeruginosa or Enterococcus faecalis to form 3 day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify and evaluate the bacterial viability, and scanning electron microscopic (SEM) imaging was used to assess architecture and morphology of bacterial biofilm before and after PDT employing methylene blue and 40 mW, 660 nm diode laser light delivered into the root canal via a 300 μm fiber for 240 sec, resulting in a total energy of 9.6 J. The data were statistically analyzed with analysis of variance (ANOVA) followed by Tukey test.
The bacterial reduction showed a dose dependence; as the light energy increased, the bioluminescence decreased in both planktonic suspension and in biofilms. The SEM analysis showed a significant reduction of biofilm on the surface. PDT promoted disruption of the biofilm and the number of adherent bacteria was reduced.
The photodynamic effect seems to disrupt the biofilm by acting both on bacterial cells and on the extracellular matrix.
Individuals foraging in groups can use two different tactics for obtaining food resources. Individuals can either search for food sources themselves (producing) or they can join food discoveries of ...others (scrounging). In this study we use a genetic algorithm in a spatially explicit producer-scrounger game to explore how individuals compromise between exploration (an important axis of animal personality) and scrounging and how characteristics of the environment affect this compromise. Agents varied in exploration and scrounging and a genetic algorithm searched for the optimal combination of exploration and scrounging. The foraging environments featured different levels of patch richness, predation and patch density. Our simulations show that under conditions of low patch densities slow exploring scroungers were favored whereas high patch density favored fast exploring individuals that either produced (at low patch richness) or scrounged (at high patch richness). In high predation environments fast exploring individuals were selected for but only at low to intermediate patch densities. Predation did not affect scrounging behavior. We did not find a divergence of exploration 'types' within a given environment, but there was a general association between exploration and scrounging across different environments: high rates of scrounging were observed over nearly the full spectrum of exploration values, whereas high rates of producing were only observed at high exploration values, suggesting that cases in which slow explorers start producing should be rare. Our results indicate that the spatial arrangement of food resources can affect the optimal social attraction rules between agents, the optimality of foraging tactic and the interaction between both.
A systematic review of literature analyzing fertility following uterine artery embolization (UAE) is presented. Twenty-one studies describing pregnancy and complications of pregnancy following UAE ...were included. Low-level evidence from these studies suggests that pregnancy rates following UAE are comparable to the age-adjusted rates in the general population. Although pregnancy complication rates were similar to those in patients with untreated fibroid tumors, a few studies have reported higher miscarriage rates following UAE. Further randomized controlled trials comparing UAE versus other fertility-preserving treatments are necessary to confirm these findings.
To analyze nationwide trends in abdominal aortic aneurysm (AAA) repair and the use of endovascular abdominal aortic aneurysm repair (EVAR) in the emergency setting.
Data were obtained from the ...Nationwide Inpatient Sample (NIS) using the International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM) codes for open and endovascular repairs from 2001-2009. Trends in outcome parameters and hospital charges were compared.
The number of emergency EVAR procedures increased from 382 in 2001 to 1,247 in 2009 (P < .001). During the study period, length of hospital stay associated with total number of EVAR procedures decreased from 3.8 days to 3.4 days (P < .05), and the in-hospital mortality decreased from 2.4% to 2% (P = .32). From 2001-2009, mean hospital charges associated with EVAR increased from $50,630 to $91,401 (74% increase), whereas charges associated with open repairs increased from $54,578 to $128,925 (136% increase). The proportion of patients needing rehabilitation or nursing home placement after EVAR increased from 5.8% to 7.7% (P < .01), and need for home health increased from 6.9% to 10.5% (P < .01).
There was a significant increase in the number of emergency EVAR procedures during the study period; however, the overall in-hospital mortality associated with EVAR remained unchanged, and the length of hospital stay showed a decreasing trend. The total hospital charges for EVAR were lower than the charges for open abdominal aneurysm repair throughout the study period; the difference in charges between the procedures showed a significant increasing trend with time.
Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear.
In this study, we isolated ...murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm(2) and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration.
We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.
Objectives
HIV infection is well known to cause impairment of the human immune system, and until recently was a leading cause of death. It has been shown that T lymphocytes are the main targets of ...HIV. The virus inactivates T lymphocytes by interfering with a wide range of cellular and molecular targets, leading to suppression of the immune system. The objective of this review is to investigate to what extent microRNAs (miRNAs) are involved in HIV pathogenesis.
Methods
The scientific literature (Pubmed and Google scholar) for the period 1988–2019 was searched.
Results
Mounting evidence has revealed that miRNAs are involved in viral replication and immune response, whether by direct targeting of viral transcripts or through indirect modulation of virus‐related host pathways. In addition, exosomes have been found to act as nanoscale carriers involved in HIV pathogenesis. These nanovehicles target their cargos (i.e. DNA, RNA, viral proteins and miRNAs) leading to alteration of the behaviour of recipient cells.
Conclusions
miRNAs and exosomes are important players in HIV pathogenesis. Additionally, there are potential diagnostic applications of miRNAs as biomarkers in HIV infection.
The unique properties of carbon nanotubes (CNTs) (such as their high surface to volume ratios, enhanced conductivity and strength, biocompatibility, ease of functionalization, optical properties, ...etc.) have led to their consideration to serve as novel drug and gene delivery carriers. CNTs are effectively taken up by many different cell types through several mechanisms. CNTs have acted as carriers of anticancer molecules (including docetaxel (DTX), doxorubicin (DOX), methotrexate (MTX), paclitaxel (PTX), and gemcitabine (GEM)), anti-inflammatory drugs, osteogenic dexamethasone (DEX) steroids, etc. In addition, the unique optical properties of CNTs have led to their use in a number of platforms for improved photo-therapy. Further, the easy surface functionalization of CNTs has prompted their use to deliver different genes, such as plasmid DNA (PDNA), micro-RNA (miRNA), and small interfering RNA (siRNA) as gene delivery vectors for various diseases such as cancers. However, despite all of these promises, the most important continuous concerns raised by scientists reside in CNT nanotoxicology and the environmental effects of CNTs, mostly because of their non-biodegradable state. Despite a lack of widespread FDA approval, CNTs have been studied for decades and plenty of in vivo and in vitro reports have been published, which are reviewed here. Lastly, this review covers the future research necessary for the field of CNT medicine to grow even further.
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