https://academicworks.medicine.hofstra.edu/cgi/viewcontent.cgi?article=1534&context=articles

HMGB1 in Health and Disease

Cell death was once viewed as unregulated. It is now clear that at least a portion of cell death is a regulated cell suicide process. This type of death can exhibit multiple morphologies. One of these, apoptosis, has long been recognized to be actively mediated, and many of its underlying mechanisms have been elucidated. Moreover, necrosis, the traditional example of unregulated cell death, is also regulated in some instances. Autophagy is usually a survival mechanism but can occur in association with cell death. Little is known, however, about how autophagic cells die. Apoptosis, necrosis, and autophagy occur in cardiac myocytes during myocardial infarction, ischemia/reperfusion, and heart failure. Pharmacological and genetic inhibition of apoptosis and necrosis lessens infarct size and improves cardiac function in these disorders. The roles of autophagy in ischemia/reperfusion and heart failure are unresolved. A better understanding of these processes and their interrelationships may allow for the development of novel therapies for the major heart syndromes.

Cell Death in the Pathogenesis of Heart Disease: Mechanisms and Significance

Under normal physiological conditions, cellular homeostasis is partly regulated by a balance of pro- and anti-phagocytic signals. CD47, which prevents cancer cell phagocytosis by the innate immune system, is highly expressed on several human cancers including acute myeloid leukemia, non-Hodgkin's lymphoma, and bladder cancer. Blocking CD47 with a monoclonal antibody results in phagocytosis of cancer cells and leads to in vivo tumor elimination, yet normal cells remain mostly unaffected. Thus, we postulated that cancer cells must also display a potent pro-phagocytic signal. Here, we identified calreticulin as a pro-phagocytic signal that was highly expressed on the surface of several human cancers, but was minimally expressed on most normal cells. Increased CD47 expression correlated with high amounts of calreticulin on cancer cells and was necessary for protection from calreticulin-mediated phagocytosis. Blocking the interaction of target cell calreticulin with its receptor, low-density lipoprotein receptor-related protein, on phagocytic cells prevented anti-CD47 antibody-mediated phagocytosis. Furthermore, increased calreticulin expression was an adverse prognostic factor in diverse tumors including neuroblastoma, bladder cancer, and non-Hodgkin's lymphoma. These findings identify calreticulin as the dominant pro-phagocytic signal on several human cancers, provide an explanation for the selective targeting of tumor cells by anti-CD47 antibody, and highlight the balance between pro- and anti-phagocytic signals in the immune evasion of cancer.

/pdf/calreticulin-is-the-dominant-pro-phagocytic-signal-on-3m50twx7e5.pdf

Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47

A complex and multilayered immune defence system protects the host against harmful agents and maintains tissue homeostasis. Cigarette smoke exposure markedly impacts the immune system, compromising the host's ability to mount appropriate immune and inflammatory responses and contributing to smoking-related pathologies. These adverse effects on the immune system not only occur in active smokers, but also in those exposed to smoke passively in contaminated environments, and may persist for decades after exposure has ended.

How cigarette smoke skews immune responses to promote infection, lung disease and cancer

High-mobility group box 1 and cancer.

Phagocytosis of apoptotic cells, also called efferocytosis, is an essential feature of immune responses and critical to resolution of inflammation. Impaired efferocytosis is associated with an unfavorable outcome from inflammatory diseases, including acute lung injury and pulmonary manifestations of cystic fibrosis. High mobility group protein-1 (HMGB1), a nuclear nonhistone DNA-binding protein, has recently been found to be secreted by immune cells upon stimulation with LPS and cytokines. Plasma and tissue levels of HMGB1 are elevated for prolonged periods in chronic and acute inflammatory conditions, including sepsis, rheumatoid arthritis, acute lung injury, burns, and hemorrhage. In this study, we found that HMGB1 inhibits phagocytosis of apoptotic neutrophils by macrophages in vivo and in vitro. Phosphatidylserine (PS) is directly involved in the inhibition of phagocytosis by HMGB1, as blockade of HMGB1 by PS eliminates the effects of HMGB1 on efferocytosis. Confocal and fluorescence resonance energy transfer demonstrate that HMGB1 interacts with PS on the neutrophil surface. However, HMGB1 does not inhibit PS-independent phagocytosis of viable neutrophils. Bronchoalveolar lavage fluid from Scnn + mice, a murine model of cystic fibrosis lung disease which contains elevated concentrations of HMGB1, inhibits neutrophil efferocytosis. Anti-HMGB1 Abs reverse the inhibitory effect of Scnn + bronchoalveolar lavage on efferocytosis, showing that this effect is due to HMGB1. These findings demonstrate that HMGB1 can modulate phagocytosis of apoptotic neutrophils and suggest an alternative mechanism by which HMGB1 is involved in enhancing inflammatory responses.

High Mobility Group Protein-1 Inhibits Phagocytosis of Apoptotic Neutrophils through Binding to Phosphatidylserine

Phagocytosis of apoptotic cells, also called efferocytosis, is an essential feature of immune responses and critical for the resolution of inflammation. Plasma and tissue levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, are elevated in inflammatory conditions, including sepsis and acute lung injury, in which activated neutrophils accumulate in tissues and contribute to organ dysfunction. In this study, we explored the potential involvement of PAI-1 in modulating neutrophil efferocytosis. We found enhanced phagocytosis of viable PAI-1 deficient (PAI-1(-/-)) and of wild-type neutrophils treated with anti-PAI-1 antibodies. PAI-1 levels were decreased on the surface of apoptotic neutrophils and the enhanced phagocytosis of apoptotic wild-type neutrophils or of viable PAI-1(-/-) neutrophils was diminished by preincubation with PAI-1. The increased phagocytosis associated with PAI-1 deficiency or blockade depended on both the lipoprotein receptor-related protein (LRP) and its ligand, calreticulin (CRT), because the LRP-mediated increase in phagocytosis of viable neutrophils induced by blockade of CD 47 was abrogated by PAI-1. CRT levels are increased on viable PAI-1(-/-) neutrophils. While CRT colocalizes with PAI-1 on viable neutrophils, markedly diminished colocalization of PAI-1 and CRT was present on apoptotic neutrophils. Our data therefore indicate that PAI-1 serves as a novel "don't eat me" signal for viable and apoptotic neutrophils.

https://www.pnas.org/content/pnas/105/33/11784.full.pdf

PAI-1 inhibits neutrophil efferocytosis

As natural lightning strikes on a transmission tower, lightning current will flow along grounding lines into the adjacent tower grounding grid. As lightning current is dispersed from the tower grounding grid into the soil, a lightning overvoltage may be produced on adjacent pipelines. In this paper, the lightning current shunt characteristics in multi-tower scenarios are calculated by simulation method under different soil resistivity conditions. Then, based on the lightning current shunt characteristics, the current dispersion process among multi-tower grounding grids and the pipeline is analyzed with different soil resistivities, gap distances, and lightning current amplitudes. Finally, the protective effect of “drain wire” and “forced commutation” on pipeline overvoltage are compared. Simulation results showed that with increasing soil resistivity, tower grounding resistance was increased and tower shunt coefficient decreased. Considering lightning current through the multi-tower grounding grids, pipeline overvoltage is much larger than that of a single tower. Pipeline overvoltage is increased with soil resistivity and lightning current amplitude, while it is decreased with “pipeline-line” distance. Both “drain wire” method and “forced commutation” method can effectively reduce pipeline potential.

/pdf/research-on-lightning-overvoltage-of-oil-gas-pipeline-caused-v02il8eg.pdf

Research on Lightning Overvoltage of Oil-Gas Pipeline Caused by Lightning Strikes on Adjacent Electrical Transmission Line

Brain-computer interface (BCI) based on lower-limb motor imagery (LMI) enables hemiplegic patients to stand and walk independently. However, LMI ability is usually poor for BCI-illiterate (e.g., some stroke patients), limiting BCI performance. This study proposed a novel LMI-BCI paradigm with kinesthetic illusion(KI) induced by vibratory stimulation on Achilles tendon to enhance LMI ability. Sixteen healthy subjects were recruited to carry out two research contents: (1) To verify the feasibility of induced KI by vibrating Achilles tendon and analyze the EEG features produced by KI, research 1 compared the subjective feeling and brain activity of participants during rest task with and without vibratory stimulation (V-rest, rest). (2) Research 2 compared the LMI-BCI performance with and without KI (KI-LMI, no-LMI) to explore whether KI enhances LMI ability. The analysis methods of both experiments included classification accuracy (V-rest vs. rest, no-LMI vs. rest, KI-LMI vs. rest, KI-LMI vs. V-rest), time-domain features, oral questionnaire, statistic analysis and brain functional connectivity analysis. Research 1 verified that induced KI by vibrating Achilles tendon might be feasible, and provided a theoretical basis for applying KI to LMI-BCI paradigm, evidenced by oral questionnaire (Q1) and the independent effect of vibratory stimulation during rest task. The results of research 2 that KI enhanced mesial cortex activation and induced more intensive EEG features, evidenced by ERD power, topographical distribution, oral questionnaire (Q2 and Q3), and brain functional connectivity map. Additionally, the KI increased the offline accuracy of no-LMI/rest task by 6.88 to 82.19% (p < 0.001). The simulated online accuracy was also improved for most subjects (average accuracy for all subjects: 77.23% > 75.31%, and average F1_score for all subjects: 76.4% > 74.3%). The LMI-BCI paradigm of this study provides a novel approach to enhance LMI ability and accelerates the practical applications of the LMI-BCI system.

/pdf/enhanced-lower-limb-motor-imagery-by-kinesthetic-illusion-1q8np26r.pdf

Enhanced lower-limb motor imagery by kinesthetic illusion

INTRODUCTION
Patients undergoing total aortic arch replacement (TAAR) usually require blood products perioperatively. This cohort study aimed to investigate the impact of a comprehensive blood conservation program on the major complications in these patients.


METHODS
Patients with traditional or comprehensive blood management intraoperatively from January 2017 to December 2018 were included. We compared the rates of major complications (cerebral vascular accident, acute kidney injury, or mortality) between the two groups after propensity score matching (PSM). The association between blood management and outcomes was assessed by logistic regression. Restricted cubic splines (RCS) were built to evaluate the impact of fresh frozen plasma (FFP) on complications. Patients were stratified by the ratio of FFP/RBC (red blood cell) to investigate the effect of the ratio on complications.


RESULTS
After 1:1 PSM, 200 patients were selected. 35% (35/100) of patients suffered major complications in the traditional group, while it decreased to 22% (22/100) in the comprehensive management group (OR = 0.524, p = 0.043). Multivariable logistic regression showed that FFP was a risk factor (OR = 1.186, p = 0.014). RCS results indicated that with the increase of FFP, the risk of complications gradually increases. The cut-off value was 402 mL. Patients in the group of ratio = 0 ∼ 0.5 had a higher chance than those without transfusion (OR = 7.487, p < 0.001).


CONCLUSIONS
Comprehensive blood conservation program in patients undergoing TAAR is safe and can reduce the incidence of major complications, which are associated with FFP volume and the ratio of FFP/RBC.

The impact of comprehensive blood conservation program on major complications after total aortic arch replacement.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Jing Wang

Author Tools

Chat about Author