The design of bright NIR‐II luminescent nanomaterials that enable efficient labelling of proteins without disturbing their physiological properties in vivo is challenging. We developed an efficient ...strategy to synthesize bright NIR‐II gold nanoclusters (Au NCs) protected by biocompatible cyclodextrin (CD). Leveraging the ultrasmall size of Au NCs (<2 nm) and strong macrocycle‐based host–guest chemistry, the as‐synthesized CD‐Au NCs can readily label proteins/antibodies. Moreover, the labelled proteins/antibodies enable highly efficient in vivo tracking during blood circulation, without disturbing their biodistribution and tumor targeting ability, thus leading to a sensitive tumor‐targeted imaging. CD‐Au NCs are stable in the harsh biological environment and show good biocompatibility and high renal clearance efficiency. Therefore, the NIR‐II biolabels developed in this study provide a promising platform to monitor the physiological behavior of biomolecules in living organisms.
Bright NIR‐II Au nanoclusters (NCs) were rationally synthesized by using biocompatible cyclodextrin (CD) as the ligands. The renal‐clearable CD‐Au NCs can readily label proteins/antibodies via strong macrocycle‐based host–guest chemistry and enable highly efficient in vivo tracking during blood circulation, without disturbing their biodistribution and tumor targeting ability, thus leading to a sensitive tumor‐targeted NIR‐II visualization.
The recent development of non-invasive imaging techniques has enabled the visualization of molecular events underlying cellular processes in live cells. Although microscopic objects can be readily ...manipulated at the cellular level, additional physiological insight is likely to be gained by manipulation of cells in vivo, which has not been achieved so far. Here we use infrared optical tweezers to trap and manipulate red blood cells within subdermal capillaries in living mice. We realize a non-contact micro-operation that results in the clearing of a blocked microvessel. Furthermore, we estimate the optical trap stiffness in the capillary. Our work expands the application of optical tweezers to the study of live cell dynamics in animals.
Abstract
The modulation of intracellular reactive oxygen species (ROS) levels is crucial for cellular homeostasis and determination of cellular fate. A sublethal level of ROS sustains cell ...proliferation, differentiation and promotes tumor metastasis, while a drastic ROS burst directly induces apoptosis. Herein, surface-oxidized arsenene nanosheets (As/As
x
O
y
NSs) with type II heterojunction are fabricated with efficient ·O
2
−
and
1
O
2
production and glutathione consumption through prolonging the lifetime of photo-excited electron-hole pairs. Moreover, the portion of As
x
O
y
with oxygen vacancies not only catalyzes a Fenton-like reaction, generating ·OH and O
2
from H
2
O
2
, but also inactivates main anti-oxidants to cut off the “retreat routes” of ROS. After polydopamine (PDA) and cancer cell membrane (M) coating, the engineered As/As
x
O
y
@PDA@M NSs serve as an intelligent theranostic platform with active tumor targeting and long-term blood circulation. Given its narrow-band-gap-enabled in vivo fluorescence imaging properties, As/As
x
O
y
@PDA@M NSs could be applied as an imaging-guided non-invasive and real-time nanomedicine for cancer therapy.
Circular RNA (circ-RNA) and exosomes have recently been shown to play important roles in different tumors. However, the functions and regulatory mechanisms of exosomal circ-RNA in pancreatic ductal ...adenocarcinoma (PDAC) tumor progression remain unclear. Here, we identified a circular RNA (circ-PDE8A) from liver-metastatic PDAC cells by microarray analysis, detected its expression levels in clinical tissues and found that high circ-PDE8A expression was correlated with lymphatic invasion, TNM stage and a poor survival rate of PDAC patients. Further study revealed that circ-PDE8A promotes the invasive growth of PDAC cells via upregulating MET. Circ-PDE8A acts as a ceRNA for miR-338 to regulate MACC1 and stimulates invasive growth via the MACC/MET/ERK or AKT pathways. We further imaged the exosome communication between tumor cells and identified the tumor secreted exosomes in blood circulation. Finally, we analyzed the circ-PDE8A expression in plasma exosomes of PDAC patients and found that exosomal circ-PDE8A was associated with progression and prognosis in PDAC patients. Thus, circ-PDE8A may play an important role in tumor invasion, and exosomal circ-PDE8A may be a useful marker of PDAC diagnosis or progression.
•High level of circ-PDE8A is associated with tumor progression and prognosis.•Circ-PDE8A promotes the invasive growth via miR-338/MACC1/MET pathway.•Tumor released exosomes could enter into blood circulation and be detected.•Plasma exosomal circ-PDE8A is correlated to tumor invasion of PDAC patients.
Alzheimer disease is more than a pure proteopathy. Chronic neuroinflammation stands out during the pathogenesis of the disease and in turn modulates disease progression. The central nervous system ...(CNS) is separated from the blood circulation by the blood-brain barrier. In Alzheimer disease, neuroinflammation heavily relies on innate immune responses that are primarily mediated by CNS-resident microglia. APOE (which encodes apolipoprotein E) is the strongest genetic risk factor for Alzheimer disease, and APOE was recently shown to affect the disease in part through its immunomodulatory function. This function of APOE is likely linked to triggering receptor expressed on myeloid cells 2 (TREM2), which is expressed by microglia in the CNS. Here, we review the rapidly growing literature on the role of disease-associated microglia, TREM2 and APOE in the pathogenesis of Alzheimer disease and present an integrated view of innate immune function in Alzheimer disease.
The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system limits the activity of many nanoparticle formulations. Here, we show that inducing a slight and ...transient depletion of erythrocytes in mice (~5% decrease in haematocrit) by administrating a low dose (1.25 mg kg
) of allogeneic anti-erythrocyte antibodies increases the circulation half-life of a range of short-circulating and long-circulating nanoparticle formulations by up to 32-fold. Treatment of the animals with anti-erythrocyte antibodies significantly improved the targeting of CD4
cells in vivo with fluorescent anti-CD4-antibody-conjugated nanoparticles, the magnetically guided delivery of ferrofluid nanoparticles to subcutaneous tumour allografts and xenografts, and the treatment of subcutaneous tumour allografts with magnetically guided liposomes loaded with doxorubicin and magnetite or with clinically approved 'stealthy' doxorubicin liposomes. The transient and partial blocking of the mononuclear phagocyte system may enhance the performance of a wide variety of nanoparticle drugs.
One-dimensional (1-D) nanomaterials possess unique shape-dependent phyicochemical properties and are increasingly recognized as promising materials for nanotechnology. 1-D nanomaterials can be ...classified according to their shape, such as nanorods, nanotubes, nanowires, self-assembled nanochains,
etc.
, and have been applied in electronics, photonics, and catalysis. The biological characteristics of 1-D nanomaterials, including high drug loading efficiency, prolonged blood circulation, the ability to capture cancer cells, unique cellular uptake mechanisms, efficient photothermal conversion, and material tunability, have aided in extending their potential to biomedical applications, particularly in cancer therapy and diagnosis. This review highlights a novel perspective on emerging 1-D nanomaterials for cancer therapy and diagnosis by introducing the definition of 1-D nanomaterials, their shape-dependent physicochemical properties, biomedical applications, and recent advances in cancer therapy and diagnosis. This review also proposes unexplored potential nanomaterial types and therapeutic applications for 1-D nanomaterials. In particular, the most significant and exciting advances in recent years, including ultrasound-enabled sonodynamic therapy, magnetic field-based therapy, and bioresponsive 1-D nanomaterials for intracellular self-assembly
in situ
, are discussed along with novel therapeutic concepts, such as piezoelectric 1-D nanomaterials, nanozyme-based nanomedicine, and others.
This review summarizes a novel perspective on emerging 1-D nanomaterials for cancer therapy and diagnosis, highlighting the unique shape-dependent properties, recent advancements, and unexplored nanomaterial types and therapeutic applications.
Circulating tumor cells (CTCs) are cancer cells that circulate in the blood stream after being naturally shed from original or metastatic tumors, and can lead to a new fatal metastasis. CTCs have ...become a hotspot research field during the last decade. Detection of CTCs, as a liquid biopsy of tumors, can be used for early diagnosis of cancers, earlier evaluation of cancer recurrence and chemotherapeutic efficacy, and choice of individual sensitive anti-cancer drugs. Therefore, CTC detection is a crucial tool to fight against cancer. Herein, we classify the currently reported CTC detection technologies, introduce some representative samples for each technology, conclude the advantages and limitations, and give a future perspective including the challenges and opportunities of CTC detection.
Background
Out‐of‐hospital cardiac arrest (OHCA) is a major cause of death worldwide. Cardiac arrest can be subdivided into asphyxial and non asphyxial etiologies. An asphyxia arrest is caused by ...lack of oxygen in the blood and occurs in drowning and choking victims and in other circumstances. A non asphyxial arrest is usually a loss of functioning cardiac electrical activity. Cardiopulmonary resuscitation (CPR) is a well‐established treatment for cardiac arrest. Conventional CPR includes both chest compressions and ‘rescue breathing’ such as mouth‐to‐mouth breathing. Rescue breathing is delivered between chest compressions using a fixed ratio, such as two breaths to 30 compressions or can be delivered asynchronously without interrupting chest compression. Studies show that applying continuous chest compressions is critical for survival and interrupting them for rescue breathing might increase risk of death. Continuous chest compression CPR may be performed with or without rescue breathing.
Objectives
To assess the effects of continuous chest compression CPR (with or without rescue breathing) versus conventional CPR plus rescue breathing (interrupted chest compression with pauses for breaths) of non‐asphyxial OHCA.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1 2017); MEDLINE (Ovid) (from 1985 to February 2017); Embase (1985 to February 2017); Web of Science (1985 to February 2017). We searched ongoing trials databases including controlledtrials.com and clinicaltrials.gov. We did not impose any language or publication restrictions.
Selection criteria
We included randomized and quasi‐randomized studies in adults and children suffering non‐asphyxial OHCA due to any cause. Studies compared the effects of continuous chest compression CPR (with or without rescue breathing) with interrupted CPR plus rescue breathing provided by rescuers (bystanders or professional CPR providers).
Data collection and analysis
Two authors extracted the data and summarized the effects as risk ratios (RRs), adjusted risk differences (ARDs) or mean differences (MDs). We assessed the quality of evidence using GRADE.
Main results
We included three randomized controlled trials (RCTs) and one cluster‐RCT (with a total of 26,742 participants analysed). We identified one ongoing study. While predominantly adult patients, one study included children.
Untrained bystander‐administered CPR
Three studies assessed CPR provided by untrained bystanders in urban areas of the USA, Sweden and the UK. Bystanders administered CPR under telephone instruction from emergency services. There was an unclear risk of selection bias in two trials and low risk of detection, attrition, and reporting bias in all three trials. Survival outcomes were unlikely to be affected by the unblinded design of the studies.
We found high‐quality evidence that continuous chest compression CPR without rescue breathing improved participants’ survival to hospital discharge compared with interrupted chest compression with pauses for rescue breathing (ratio 15:2) by 2.4% (14% versus 11.6%; RR 1.21, 95% confidence interval (CI) 1.01 to 1.46; 3 studies, 3031 participants).
One trial reported survival to hospital admission, but the number of participants was too low to be certain about the effects of the different treatment strategies on survival to admission(RR 1.18, 95% CI 0.94 to 1.48; 1 study, 520 participants; moderate‐quality evidence).
There were no data available for survival at one year, quality of life, return of spontaneous circulation or adverse effects.
There was insufficient evidence to determine the effect of the different strategies on neurological outcomes at hospital discharge (RR 1.25, 95% CI 0.94 to 1.66; 1 study, 1286 participants; moderate‐quality evidence). The proportion of participants categorized as having good or moderate cerebral performance was 11% following treatment with interrupted chest compression plus rescue breathing compared with 10% to 18% for those treated with continuous chest compression CPR without rescue breathing.
CPR administered by a trained professional
In one trial that assessed OHCA CPR administered by emergency medical service professionals (EMS) 23,711 participants received either continuous chest compression CPR (100/minute) with asynchronous rescue breathing (10/minute) or interrupted chest compression with pauses for rescue breathing (ratio 30:2). The study was at low risk of bias overall.
After OHCA, risk of survival to hospital discharge is probably slightly lower for continuous chest compression CPR with asynchronous rescue breathing compared with interrupted chest compression plus rescue breathing (9.0% versus 9.7%) with an adjusted risk difference (ARD) of ‐0.7%; 95% CI (‐1.5% to 0.1%); moderate‐quality evidence.
There is high‐quality evidence that survival to hospital admission is 1.3% lower with continuous chest compression CPR with asynchronous rescue breathing compared with interrupted chest compression plus rescue breathing (24.6% versus 25.9%; ARD ‐1.3% 95% CI (‐2.4% to ‐0.2%)).
Survival at one year and quality of life were not reported.
Return of spontaneous circulation is likely to be slightly lower in people treated with continuous chest compression CPR plus asynchronous rescue breathing (24.2% versus 25.3%; ‐1.1% (95% CI ‐2.4 to 0.1)), high‐quality evidence.
There is high‐quality evidence of little or no difference in neurological outcome at discharge between these two interventions (7.0% versus 7.7%; ARD ‐0.6% (95% CI ‐1.4 to 0.1).
Rates of adverse events were 54.4% in those treated with continuous chest compressions plus asynchronous rescue breathing versus 55.4% in people treated with interrupted chest compression plus rescue breathing compared with the ARD being ‐1% (‐2.3 to 0.4), moderate‐quality evidence).
Authors' conclusions
Following OHCA, we have found that bystander‐administered chest compression‐only CPR, supported by telephone instruction, increases the proportion of people who survive to hospital discharge compared with conventional interrupted chest compression CPR plus rescue breathing. Some uncertainty remains about how well neurological function is preserved in this population and there is no information available regarding adverse effects.
When CPR was performed by EMS providers, continuous chest compressions plus asynchronous rescue breathing did not result in higher rates for survival to hospital discharge compared to interrupted chest compression plus rescue breathing. The results indicate slightly lower rates of survival to admission or discharge, favourable neurological outcome and return of spontaneous circulation observed following continuous chest compression. Adverse effects are probably slightly lower with continuous chest compression.
Increased availability of automated external defibrillators (AEDs), and AED use in CPR need to be examined, and also whether continuous chest compression CPR is appropriate for paediatric cardiac arrest.
DNA methylation represents an annotation system for marking the genetic text, thus providing instruction as to how and when to read the information and control transcription. Unlike sequence ...information, which is inherited, methylation patterns are established in a programmed process that continues throughout development, thus setting up stable gene expression profiles. This DNA methylation paradigm is a key player in medicine. Some changes in methylation closely correlate with age providing a marker for biological ageing, and these same sites could also play a part in cancer. The genome continues to undergo programmed variation in methylation after birth in response to environmental inputs, serving as a memory device that could affect ageing and predisposition to various metabolic, autoimmune, and neurological diseases. Taking advantage of tissue-specific differences, methylation can be used to detect cell death and thereby monitor many common diseases with a simple cell-free circulating-DNA blood test.
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