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BioImpacts : BI 2024Cell culture-based technologies are widely utilized in various domains such as drug evaluation, toxicity assessment, vaccine and biopharmaceutical development,... (Review)
Review
Cell culture-based technologies are widely utilized in various domains such as drug evaluation, toxicity assessment, vaccine and biopharmaceutical development, reproductive technology, and regenerative medicine. It has been demonstrated that pre-adsorption of extracellular matrix (ECM) proteins including collagen, laminin and fibronectin provide more degrees of support for cell adhesion. The purpose of cell imprinting is to imitate the natural topography of cell membranes by gels or polymers to create a reliable environment for the regulation of cell function. The results of recent studies show that cell imprinting is a tool to guide the behavior of cultured cells by controlling their adhesive interactions with surfaces. Therefore, in this review we aim to compare different cell cultures with the imprinting method and discuss different cell imprinting applications in regenerative medicine, personalized medicine, disease modeling, and cell therapy.
PubMed: 38938752
DOI: 10.34172/bi.2023.29945 -
Biomedical Reports Aug 2024Despite proton pump inhibitors (PPIs) being generally safe, there are questions about their potential long-term complications. The present study aimed to investigate the...
Despite proton pump inhibitors (PPIs) being generally safe, there are questions about their potential long-term complications. The present study aimed to investigate the association between PPI therapy and the incidence of hepatic steatosis and liver fibrosis in the outpatient population of the United States. The present study included 7,395 individuals aged ≥20 years who underwent hepatic vibration-controlled transient elastography (VCTE) examination. The data were obtained from the January 2017 to March 2020 pre-pandemic National Health and Nutrition Examination Survey. Among the 7,395 adults who were included (mean age, 50.59 years; 3,656 male), 9.8% were prescribed PPIs. Following multivariable adjustment, the use of PPIs was significantly associated with hepatic steatosis [odds ratio (OR), 1.25; 95% confidence interval (CI), 1.02-1.53]. Prolonged use of PPIs was found to increase the risk of developing hepatic steatosis over time (P=0.006). Sensitivity analyses using different definitions of hepatic steatosis, such as a controlled attenuation parameter ≥285 dB/m (OR, 1.19; CI, 1.01-1.40), non-alcoholic fatty liver disease (OR, 1.50; 95% CI, 1.16-1.93) and metabolic dysfunction-associated steatotic liver disease (OR, 1.26; 95% CI, 1.05-1.52), consistently demonstrated an association between PPI prescription and hepatic steatosis. The administration of PPI therapy was linked with hepatic steatosis in US adults, although no significant association was observed with liver stiffness, as determined by VCTE.
PubMed: 38938738
DOI: 10.3892/br.2024.1804 -
Polish Journal of Radiology 2024Elbow arthroplasty is increasing in popularity and can be used to treat many conditions, such as trauma, primary and secondary osteoarthritis, inflammatory arthritis,... (Review)
Review
Elbow arthroplasty is increasing in popularity and can be used to treat many conditions, such as trauma, primary and secondary osteoarthritis, inflammatory arthritis, and osteonecrosis. Total elbow arthroplasty (TEA) is reserved for patients with severe symptoms refractory to more conservative management. In addition to TEA, hemi-arthroplasty, interposition arthroplasty, and resection arthroplasty also play roles in the management of elbow pain. There are specific indications for each type of arthroplasty. Postoperative complications may occur with elbow arthroplasties and may be surgery or hardware related. Imaging is important in both pre-operative planning as well as in post-surgical follow-up. This article reviews the different types of elbow arthroplasties, their indications, their normal postoperative imaging appearances, and imaging findings of potential complications.
PubMed: 38938657
DOI: 10.5114/pjr/186592 -
Frontiers in Immunology 2024The disruption of the circadian clock is associated with inflammatory and immunological disorders. BMAL2, a critical circadian protein, forms a dimer with CLOCK,...
BACKGROUND
The disruption of the circadian clock is associated with inflammatory and immunological disorders. BMAL2, a critical circadian protein, forms a dimer with CLOCK, activating transcription. Extracellular cold-inducible RNA-binding protein (eCIRP), released during sepsis, can induce macrophage endotoxin tolerance. We hypothesized that eCIRP induces BMAL2 expression and promotes macrophage endotoxin tolerance through triggering receptor expressed on myeloid cells-1 (TREM-1).
METHODS
C57BL/6 wild-type (WT) male mice were subjected to sepsis by cecal ligation and puncture (CLP). Serum levels of eCIRP 20 h post-CLP were assessed by ELISA. Peritoneal macrophages (PerM) were treated with recombinant mouse (rm) CIRP (eCIRP) at various doses for 24 h. The cells were then stimulated with LPS for 5 h. The levels of TNF-α and IL-6 in the culture supernatants were assessed by ELISA. PerM were treated with eCIRP for 24 h, and the expression of PD-L1, IL-10, STAT3, TREM-1 and circadian genes such as BMAL2, CRY1, and PER2 was assessed by qPCR. Effect of TREM-1 on eCIRP-induced PerM endotoxin tolerance and PD-L1, IL-10, and STAT3 expression was determined by qPCR using PerM from TREM-1 mice. Circadian gene expression profiles in eCIRP-treated macrophages were determined by PCR array and confirmed by qPCR. Induction of BMAL2 activation in bone marrow-derived macrophages was performed by transfection of BMAL2 CRISPR activation plasmid. The interaction of BMAL2 in the PD-L1 promoter was determined by computational modeling and confirmed by the BIAcore assay.
RESULTS
Serum levels of eCIRP were increased in septic mice compared to sham mice. Macrophages pre-treated with eCIRP exhibited reduced TNFα and IL-6 release upon LPS challenge, indicating macrophage endotoxin tolerance. Additionally, eCIRP increased the expression of PD-L1, IL-10, and STAT3, markers of immune tolerance. Interestingly, TREM-1 deficiency reversed eCIRP-induced macrophage endotoxin tolerance and significantly decreased PD-L1, IL-10, and STAT3 expression. PCR array screening of circadian clock genes in peritoneal macrophages treated with eCIRP revealed the elevated expression of BMAL2, CRY1, and PER2. In eCIRP-treated macrophages, TREM-1 deficiency prevented the upregulation of these circadian genes. In macrophages, inducible BMAL2 expression correlated with increased PD-L1 expression. In septic human patients, blood monocytes exhibited increased expression of BMAL2 and PD-L1 in comparison to healthy subjects. Computational modeling and BIAcore assay identified a putative binding region of BMAL2 in the PD-L1 promoter, suggesting BMAL2 positively regulates PD-L1 expression in macrophages.
CONCLUSION
eCIRP upregulates BMAL2 expression via TREM-1, leading to macrophage endotoxin tolerance in sepsis. Targeting eCIRP to maintain circadian rhythm may correct endotoxin tolerance and enhance host resistance to bacterial infection.
Topics: Animals; Mice; Sepsis; Male; Mice, Inbred C57BL; RNA-Binding Proteins; Endotoxins; Immune Tolerance; Macrophages, Peritoneal; Triggering Receptor Expressed on Myeloid Cells-1; Mice, Knockout; Macrophages; ARNTL Transcription Factors; Lipopolysaccharides; Disease Models, Animal
PubMed: 38938563
DOI: 10.3389/fimmu.2024.1426682 -
European Heart Journal. Case Reports Jun 2024The surface of the aorta generally does not show motion unless mobile atheroma, thrombi, vegetations, or intimal flaps are present. We previously described unusual...
BACKGROUND
The surface of the aorta generally does not show motion unless mobile atheroma, thrombi, vegetations, or intimal flaps are present. We previously described unusual mobile filamentous structures in the carotid artery. Here, we describe similar findings in the aorta and their possible cause.
CASE SUMMARY
An 88-year-old female with progressive exertional dyspnoea and severe aortic stenosis had a successful transcatheter aortic valve replacement (TAVR). A filamentous structure was noted on the focused pre-operative 2D transoesophageal echocardiography in the proximal descending aorta and post-TAVR as long strand-like structures attached to the thickened intimal wall with a planar component on 3D imaging. These findings were not associated with symptoms or clinical sequelae on short- and long-term follow-up.
DISCUSSION
The mobile structures that we describe are atypical for atheroma, thrombi, vegetations, and dissections in terms of their form and clinical presentation. 2D imaging showed that the filaments had focal thickening and emerged from the aortic surface. These findings suggest a relationship with the intima, perhaps from atherogenesis or injury with disruption or lifting of the intimal surface. No clinical sequelae were detected that may also relate to their position in the descending aorta and not the arch.
PubMed: 38938470
DOI: 10.1093/ehjcr/ytae263 -
Frontiers in Medicine 2024Professional identity formation (PIF) is an ongoing, self-reflective process involving habits of thinking, feeling and acting like a physician and is an integral...
INTRODUCTION
Professional identity formation (PIF) is an ongoing, self-reflective process involving habits of thinking, feeling and acting like a physician and is an integral component of medical education. While qualitative work has suggested that PIF is informed by professionalism, resilience, and leadership, there is a dearth of quantitative work in this area. Multiple methods build rigor and the present study aimed to quantitatively assess the relative psychometric contributions of professionalism, resilience, and leadership constructs to informing PIF, using a latent factor analysis approach.
METHODS
We analyzed data from the PILLAR study, which is an online cross-sectional assessment of a pre-clinical cohort of medical students in the RCSI University of Medicine and Health Sciences, Dublin, using established and validated quantitative measures in each area of interest: PIF, professionalism, leadership and resilience. A total of 76 items, combining four validated scales, along with a selection of demographic questions, were used. The hypothesis that PIF is informed by, and correlates with, professionalism, resilience and leadership was examined by conducting a confirmatory factor analysis of a proposed three-factor higher-order model. Model estimation used Maximum Likelihood Method (MLM) with geomin rotation. The hypothesized (measurement) model was examined against an alternative (saturated) model, as well as a three-factor model.
RESULTS
Latent variable analysis from 1,311 students demonstrated that a three-factor higher-order model best fit the data; suggesting PIF is informed by professionalism, resilience, and leadership, and that these constructs are statistically distinct and account for differential aspects of PIF. This higher-order model of PIF outperformed both the saturated model and the three-factor model. The analysis of which component may be the most or least influential was inconclusive, and the overall model was not influenced by year of training.
DISCUSSION
Building upon existing conceptual contentions, our study is the first to quantitatively support the contribution of professionalism, resilience, and leadership to the development of professional identity, and to delineate the inter-relationships between PIF and these constructs. This information can be used by medical educators when designing curricula and educational strategies intended to enhance PIF. Future work should seek to assess the influence of these constructs longitudinally.
PubMed: 38938377
DOI: 10.3389/fmed.2024.1385489 -
Journal of Extracellular Biology Sep 2023Extracellular vesicles (EVs) are nanoscale particles that facilitate intercellular communication. They are regarded as a promising natural drug delivery system for...
Extracellular vesicles (EVs) are nanoscale particles that facilitate intercellular communication. They are regarded as a promising natural drug delivery system for transporting and delivering bioactive macromolecules to target cells. Recently, researchers have engineered EVs with FKBP12/FRB heterodimerization domains that interact with rapamycin to load and deliver exogenous proteins for both and applications. In this study, we examined the tissue distribution of EVs using near-infrared fluorescent imaging. We evaluated the effectiveness of EV-mediated delivery of Cre recombinase specifically to hepatocytes in the livers of Ai9 Cre-loxP reporter mice. Intravenous injection resulted in more efficient Cre protein delivery to the liver than intraperitoneal injections. Depleting liver-resident macrophages with clodronate-encapsulated liposome pre-treatment did not enhance EV-mediated Cre delivery to hepatocytes. Moreover, we demonstrated that multiple intravenous injections of Cre-EVs facilitated functional Cre delivery to hepatocytes. To the best of our knowledge, this is the first study to simultaneously investigate the tissue distribution of FKBP12/FRB-engineered EVs and their subsequent intracellular protein delivery in Ai9 Cre-loxP reporter mice. These insights can inform preclinical research and contribute to developing next-generation EV-based platforms for delivering therapeutic proteins or genome editing technologies targeting the liver.
PubMed: 38938374
DOI: 10.1002/jex2.97 -
JACC. Advances Oct 2023The use of mobile health (mHealth, wireless communication devices, and/or software technologies) in health care delivery has increased rapidly in recent years. Their...
BACKGROUND
The use of mobile health (mHealth, wireless communication devices, and/or software technologies) in health care delivery has increased rapidly in recent years. Their integration into disease management programs (DMPs) has tremendous potential to improve outcomes for patients with coronary artery disease (CAD), yet a more robust evaluation of the evidence is required.
OBJECTIVES
The purpose of this study was to undertake a systematic review and meta-analysis of mHealth-enabled DMPs to determine their effectiveness in reducing readmissions and mortality in patients with CAD.
METHODS
We systematically searched English language studies from January 1, 2007, to August 3, 2021, in multiple databases. Studies comparing mHealth-enabled DMPs with standard DMPs without mHealth were included if they had a minimum 30-day follow-up for at least one of all-cause or cardiovascular-related mortality, readmissions, or major adverse cardiovascular events.
RESULTS
Of the 3,411 references from our search, 155 full-text studies were assessed for eligibility, and data were extracted from 18 publications. Pooled findings for all-cause readmissions (10 studies, n = 1,514) and cardiac-related readmissions (9 studies, n = 1,009) indicated that mHealth-enabled DMPs reduced all-cause (RR: 0.68; 95% CI: 0.50-0.91) and cardiac-related hospitalizations (RR: 0.55; 95% CI: 0.44-0.68) and emergency department visits (RR: 0.37; 95% CI: 0.26-0.54) compared to DMPs without mHealth. There was no significant reduction for mortality outcomes (RR: 1.72; 95% CI: 0.64-4.64) or major adverse cardiovascular events (RR: 0.68; 95% CI: 0.40-1.15).
CONCLUSIONS
DMPs integrated with mHealth should be considered an effective intervention for better outcomes in patients with CAD.
PubMed: 38938339
DOI: 10.1016/j.jacadv.2023.100591 -
Immunity, Inflammation and Disease Jun 2024The COVID-19 pandemic has taken many forms and continues to evolve, now around the Omicron wave, raising concerns over the globe. With COVID-19 being declared no longer... (Review)
Review
New variants of COVID-19 (XBB.1.5 and XBB.1.16, the "Arcturus"): A review of highly questioned concerns, a brief comparison between different peaks in the COVID-19 pandemic, with a focused systematic review on expert recommendations for prevention, vaccination, and treatment measures in the general...
INTRODUCTION
The COVID-19 pandemic has taken many forms and continues to evolve, now around the Omicron wave, raising concerns over the globe. With COVID-19 being declared no longer a "public health emergency of international concern (PHEIC)," the COVID pandemic is still far from over, as new Omicron subvariants of interest and concern have risen since January of 2023. Mainly with the XBB.1.5 and XBB.1.16 subvariants, the pandemic is still very much "alive" and "breathing."
METHODS
This review consists of five highly concerning questions about the current state of the COVID Omicron peak. We searched four main online databases to answer the first four questions. For the last one, we performed a systematic review of the literature, with keywords "Omicron," "Guidelines," and "Recommendations."
RESULTS
A total of 31 articles were included. The main symptoms of the current Omicron wave include a characteristically high fever, coughing, conjunctivitis (with itching eyes), sore throat, runny nose, congestion, fatigue, body ache, and headache. The median incubation period of the symptoms is shorter than the previous peaks. Vaccination against COVID can still be considered effective for the new subvariants.
CONCLUSION
Guidelines recommend continuation of personal protective measures, third and fourth dose boosters, along with administration of bivalent messenger RNA vaccine boosters. The consensus antiviral treatment is combination therapy using Nirmatrelvir and Ritonavir, and the consensus for pre-exposure prophylaxis is Tixagevimab and Cilgavimab combination. We hope the present paper raises awareness for the continuing presence of COVID and ways to lower the risks, especially for at-risk groups.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Vaccination; Pandemics; Antiviral Agents; COVID-19 Drug Treatment
PubMed: 38938013
DOI: 10.1002/iid3.1323 -
BMC Biology Jun 2024The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable...
BACKGROUND
The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse.
RESULTS
We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes.
CONCLUSIONS
Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.
Topics: Animals; DNA Transposable Elements; Single-Cell Analysis; Mice; Hematopoiesis; Humans; Hematopoietic Stem Cells; Endothelial Cells
PubMed: 38937802
DOI: 10.1186/s12915-024-01939-5