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Extracellular Vesicle Jun 2024Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular milieu from various cell types including host cells and pathogens that infect...
Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular milieu from various cell types including host cells and pathogens that infect them. As carriers of nucleic acids, proteins, lipids, metabolites, and virulence factors, EVs act as delivery vehicles for intercellular communication and quorum sensing. Innate immune cells have the capacity to intercept, internalize, and interpret 'messages' contained within these EVs. This review categorizes the ability of EVs secreted by bacterial, parasitic, and fungal pathogens to trigger both pro- and anti-inflammatory innate immune responses in the host. Understanding molecular pathways and inflammatory responses activated in innate immune cells upon pathogen-derived EV stimulation is critical to gain insight into potential therapeutics and combat these infectious diseases.
PubMed: 38939756
DOI: 10.1016/j.vesic.2024.100043 -
Cell culture-derived extracellular vesicles: Considerations for reporting cell culturing parameters.Journal of Extracellular Biology Oct 2023Cell culture-conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. Cell culturing...
Cell culture-conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. Cell culturing parameters affect the biochemical composition, release and possibly the function of CCM-derived EVs (CCM-EV). The CCM-EV task force of the Rigor and Standardization Subcommittee of the International Society for Extracellular Vesicles aims to identify relevant cell culturing parameters, describe their effects based on current knowledge, recommend reporting parameters and identify outstanding questions. While some recommendations are valid for all cell types, cell-specific recommendations may need to be established for non-mammalian sources, such as bacteria, yeast and plant cells. Current progress towards these goals is summarized in this perspective paper, along with a checklist to facilitate transparent reporting of cell culturing parameters to improve the reproducibility of CCM-EV research.
PubMed: 38939735
DOI: 10.1002/jex2.115 -
Journal of Extracellular Biology Oct 2023Parasites are responsible for the most neglected tropical diseases, affecting over a billion people worldwide (WHO, 2015) and accounting for billions of cases a year and...
Parasites are responsible for the most neglected tropical diseases, affecting over a billion people worldwide (WHO, 2015) and accounting for billions of cases a year and responsible for several millions of deaths. Research on extracellular vesicles (EVs) has increased in recent years and demonstrated that EVs shed by pathogenic parasites interact with host cells playing an important role in the parasite's survival, such as facilitation of infection, immunomodulation, parasite adaptation to the host environment and the transfer of drug resistance factors. Thus, EVs released by parasites mediate parasite-parasite and parasite-host intercellular communication. In addition, they are being explored as biomarkers of asymptomatic infections and disease prognosis after drug treatment. However, most current protocols used for the isolation, size determination, quantification and characterization of molecular cargo of EVs lack greater rigor, standardization, and adequate quality controls to certify the enrichment or purity of the ensuing bioproducts. We are now initiating major guidelines based on the evolution of collective knowledge in recent years. The main points covered in this position paper are methods for the isolation and molecular characterization of EVs obtained from parasite-infected cell cultures, experimental animals, and patients. The guideline also includes a discussion of suggested protocols and functional assays in host cells.
PubMed: 38939734
DOI: 10.1002/jex2.117 -
JACC. Advances Feb 2024Vitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in...
BACKGROUND
Vitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function.
OBJECTIVES
The authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity.
METHODS
A total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes.
RESULTS
VDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort.
CONCLUSIONS
VDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.
PubMed: 38939377
DOI: 10.1016/j.jacadv.2023.100804 -
Biochemistry Research International 2024Eg5 is a protein encoded by KIF11 gene and is primarily involved in correct mitotic cell division. It is also involved in nonmitotic processes such as polypeptide... (Review)
Review
Eg5 is a protein encoded by KIF11 gene and is primarily involved in correct mitotic cell division. It is also involved in nonmitotic processes such as polypeptide synthesis, protein transport, and angiogenesis. The scientific literature sheds light on the ubiquitous functions of KIF11 and its involvement in the onset and progression of different pathologies. This review focuses attention on two main points: (1) the correlation between Eg5 and cancer and (2) the involvement of Eg5 in noncancerous conditions. Regarding the first point, several tumors revealed an overexpression of this kinesin, thus pushing to look for new Eg5 inhibitors for clinical practice. In addition, the evaluation of Eg5 expression represents a crucial step, as its overexpression could predict a poor prognosis for cancer patients. Referring to the second point, in specific pathological conditions, the reduced activity of Eg5 can be one of the causes of pathological onset. This is the case of Alzheimer's disease (AD), in which A and Tau work as Eg5 inhibitors, or in acquired immune deficiency syndrome (AIDS), in which Tat-mediated Eg5 determines the loss of CD T-lymphocytes. Reduced Eg5 activity, due to mutations of KIF11 gene, is also responsible for pathological conditions such as microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability (MCLRI) and familial exudative vitreous retinopathy (FEVR). In conclusion, this review highlights the double impact that overexpression or loss of function of Eg5 could have in the onset and progression of different pathological situations. This emphasizes, on one hand, a possible role of Eg5 as a potential biomarker and new target in cancer and, on the other hand, the promotion of Eg5 expression/activity as a new therapeutic strategy in different noncancerous diseases.
PubMed: 38939361
DOI: 10.1155/2024/3649912 -
Frontiers in Oncology 2024Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that...
INTRODUCTION
Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence.
METHODS
We performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors.
RESULTS
Our data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors.
DISCUSSION
Our analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity.
PubMed: 38939336
DOI: 10.3389/fonc.2024.1272432 -
Cureus May 2024Vasopressin infusion is commonly used in intensive care settings during states of advanced vasodilatory shock for its vasoconstrictive properties. Vasopressin also acts...
Vasopressin infusion is commonly used in intensive care settings during states of advanced vasodilatory shock for its vasoconstrictive properties. Vasopressin also acts on renal tubular cell receptors in the collecting ducts of kidneys to allow for water reabsorption. The sudden discontinuation of vasopressin infusion can lead to the development of transient diabetes insipidus (DI) with classic findings of polyuria, dilute urine, and hypernatremia. We report the case of a 59-year-old male who underwent an emergent bedside cricothyrotomy procedure secondary to papillary carcinoma of the thyroid and subsequently developed septic shock requiring initiation of vasopressin infusion for hemodynamic support. He remained on vasopressin for five days before the infusion was discontinued after clinical improvement. Within 12 hours of vasopressin discontinuation, the patient developed polyuria (> 3 L/day urine output) with volumes as high as 1 L per hour. His serum sodium levels increased more than 10 mmol/L from 137 to 149 mmol/L. This case is unique from prior reports, as our patient was without any neurological or neurosurgical comorbidities that would predispose him to an organic central cause of DI. Furthermore, the patient's large-volume diuresis and serum abnormalities spontaneously self-improved within 24 hours without significant medical intervention. In conclusion, this case adds to a growing number of reports of transient DI following vasopressin withdrawal, demonstrating the need to formally recognize this occurrence as a potential consequence of vasopressin use in intensive care settings.
PubMed: 38939271
DOI: 10.7759/cureus.61253 -
Chemical Science Jun 2024Exploration of porous adsorbents with high CO/N selectivity is of great significance for reducing CO content in the atmosphere. In this study, a series of isoreticular...
Exploration of porous adsorbents with high CO/N selectivity is of great significance for reducing CO content in the atmosphere. In this study, a series of isoreticular ultramicroporous fluorinated metal-organic frameworks (MOFs) were prepared to explore the benefits of fluorinated ultramicropores in improving CO/N selectivity. Gas adsorption measurements revealed that the increase in the number of fluorine atoms in a ligand molecule leads to the increased CO uptakes and CO/N selectivity. Theoretical calculations indicate that the interaction between the fluorine atoms and adsorbed CO molecules enhances the CO-philicity, offering useful insight into the improvement of CO/N selectivity in isoreticular frameworks.
PubMed: 38939130
DOI: 10.1039/d4sc01525h -
Journal of Extracellular Biology Jul 2023High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung...
High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility.
PubMed: 38939072
DOI: 10.1002/jex2.98 -
Frontiers in Cellular and Infection... 2024[This corrects the article DOI: 10.3389/fcimb.2023.1165295.].
[This corrects the article DOI: 10.3389/fcimb.2023.1165295.].
PubMed: 38938881
DOI: 10.3389/fcimb.2024.1419131