scholarly journals Apolipoprotein Signature of HDL and LDL from Atherosclerotic Patients in Relation with Carotid Plaque Typology: A Preliminary Report

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1156
Author(s):  
Francesco Finamore ◽  
Gabriele Nieddu ◽  
Silvia Rocchiccioli ◽  
Rita Spirito ◽  
Anna Guarino ◽  
...  
Keyword(s):  
Differential Expression Analysis ◽  
Shotgun Proteomics ◽  
Plaque Formation ◽  
Low Density Lipoproteins ◽  
Protein Species ◽  
The Past ◽  
Pathological Conditions ◽  
Composition And Structure ◽  
Associated Proteins ◽  
Plasma Fractions

In the past years, it has become increasingly clear that the protein cargo of the different lipoprotein classes is largely responsible for carrying out their various functions, also in relation to pathological conditions, including atherosclerosis. Accordingly, detailed information about their apolipoprotein composition and structure may contribute to the revelation of their role in atherogenesis and the understanding of the mechanisms that lead to atherosclerotic degeneration and toward vulnerable plaque formation. With this aim, shotgun proteomics was applied to identify the apolipoprotein signatures of both high-density and low-density lipoproteins (HDL and LDL) plasma fractions purified from healthy volunteers and atherosclerotic patients with different plaque typologies who underwent carotid endarterectomy. By this approach, two proteins with potential implications in inflammatory, immune, and hemostatic pathways, namely, integrin beta-2 (P05107) and secretoglobin family 3A member 2 (Q96PL1), have been confirmed to belong to the HDL proteome. Similarly, the list of LDL-associated proteins has been enriched with 21 proteins involved in complement and coagulation cascades and the acute-phase response, which potentially double the protein species of LDL cargo. Moreover, differential expression analysis has shown protein signatures specific for patients with “hard” or “soft” plaques.

scholarly journals Heterogeneity of SARS-CoV-2 virus produced in cell culture revealed by shotgun proteomics and supported by genome sequencing

2021 ◽  
Author(s):  
Fabrice Gallais ◽  
Olivier Pible ◽  
Jean-Charles Gaillard ◽  
Stéphanie Debroas ◽  
Hélène Batina ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Cell Culture ◽  
Shotgun Proteomics ◽  
Rapid Analysis ◽  
Diagnostic Tools ◽  
Tandem Mass ◽  
The Past ◽  
Viral Particles ◽  
Depth Analysis ◽  
The Subject

AbstractCOVID-19 is the most disturbing pandemic of the past hundred years. Its causative agent, the SARS-CoV-2 virus, has been the subject of an unprecedented investigation to characterize its molecular structure and intimate functioning. While markers for its detection have been proposed and several diagnostic methodologies developed, its propensity to evolve and evade diagnostic tools and the immune response is of great concern. The recent spread of new variants with increased infectivity requires even more attention. Here, we document how shotgun proteomics can be useful for rapidly monitoring the evolution of the SARS-CoV-2 virus. We evaluated the heterogeneity of purified SARS-CoV-2 virus obtained after culturing in the Vero E6 cell line. We found that cell culture induces significant changes that are translated at the protein level, such changes being detectable by tandem mass spectrometry. Production of viral particles requires careful quality control which can be easily performed by shotgun proteomics. Although considered relatively stable so far, the SARS-CoV-2 genome turns out to be prone to frequent variations. Therefore, the sequencing of SARS-CoV-2 variants from patients reporting only the consensus genome after its amplification would deserve more attention and could benefit from more in-depth analysis of low level but crystal-clear signals, as well as complementary and rapid analysis by shotgun proteomics. Graphical abstract

scholarly journals Proteomics in Diagnosis of Prostate Cancer/ Протеомика Во Дијагноза На Простатниот Карцином

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 5-36 ◽  
Author(s):  
Katarina Davalieva ◽  
Momir Polenakovic
Keyword(s):  
Prostate Cancer ◽  
Tumor Tissue ◽  
Biomarker Discovery ◽  
Molecular Level ◽  
Specific Antigen ◽  
Shotgun Proteomics ◽  
Comparative Proteomics ◽  
Label Free ◽  
The Past ◽  
Proteomics Research

Abstract Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. The introduction of prostate specific antigen (PSA) has greatly increased the number of men diagnosed with PCa but at the same time, as a result of the low specificity, led to overdiagnosis, resulting to unnecessary biopsies and high medical cost treatments. The primary goal in PCa research today is to find a biomarker or biomarker set for clear and effecttive diagnosis of PCa as well as for distinction between aggressive and indolent cancers. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, MALDI MS profiling, shotgun proteomics with label-based (ICAT, iTRAQ) and label-free (SWATH) quantification, MudPIT, CE-MS have been applied to the study of PCa in the past 15 years. Various biological samples, including tumor tissue, serum, plasma, urine, seminal plasma, prostatic secretions and prostatic-derived exosomes were analyzed with the aim of identifying diagnostic and prognostic biomarkers and developing a deeper understanding of the disease at the molecular level. This review is focused on the overall analysis of expression proteomics studies in the PCa field investigating all types of human samples in the search for diagnostics biomarkers. Emphasis is given on proteomics platforms used in biomarker discovery and characterization, explored sources for PCa biomarkers, proposed candidate biomarkers by comparative proteomics studies and the possible future clinical application of those candidate biomarkers in PCa screening and diagnosis. In addition, we review the specificity of the putative markers and existing challenges in the proteomics research of PCa.

scholarly journals A Change in Bile Flow: Looking Beyond Transporter Inhibition in the Development of Drug-induced Cholestasis

2019 ◽  
Vol 20 (8) ◽  
pp. 621-632 ◽  
Author(s):  
Brandy Garzel ◽  
Lei Zhang ◽  
Shiew-Mei Huang ◽  
Hongbing Wang
Keyword(s):  
Bile Flow ◽  
Bile Salt Export Pump ◽  
Drug Induced ◽  
Biliary Clearance ◽  
Drug Induced Liver Injury ◽  
The Past ◽  
3D Cell Cultures ◽  
Associated Proteins ◽  
Hepatic Transporters

Background:Drug-induced Liver Injury (DILI) has received increasing attention over the past decades, as it represents the leading cause of drug failure and attrition. One of the most prevalent and severe forms of DILI involves the toxic accumulation of bile acids in the liver, known as Drug-induced Cholestasis (DIC). Traditionally, DIC is studied by exploring the inhibition of hepatic transporters such as Bile Salt Export Pump (BSEP) and multidrug resistance-associated proteins, predominantly through vesicular transport assays. Although this approach has identified numerous drugs that alter bile flow, many DIC drugs do not demonstrate prototypical transporter inhibition, but rather are associated with alternative mechanisms.Methods:We undertook a focused literature search on DIC and biliary transporters and analyzed peer-reviewed publications over the past two decades or so.Results:We have summarized the current perception regarding DIC, biliary transporters, and transcriptional regulation of bile acid homeostasis. A growing body of literature aimed to identify alternative mechanisms in the development of DIC has been evaluated. This review also highlights current in vitro approaches used for prediction of DIC.Conclusion:Efforts have continued to focus on BSEP, as it is the primary route for hepatic biliary clearance. In addition to inhibition, drug-induced BSEP repression or the combination of these two has emerged as important alternative mechanisms leading to DIC. Furthermore, there has been an evolution in the approaches to studying DIC including 3D cell cultures and computational modeling.

To the heart block clinic

1926 ◽  
Vol 22 (1) ◽  
pp. 23-33
Author(s):  
A. F. Samoylov ◽  
M. N. Cheboksarov
Keyword(s):  
Medical Journal ◽  
Heart Block ◽  
The Past ◽  
Pathological Conditions ◽  
Rare Combination

Over the past five years, we have observed four cases of complete transverse heart block at the Faculty Therapeutic Clinic. One of these cases has already been described by Dr. Rufimsky on the pages of Kazan Medical Journal (1921, No. 2), and two new cases where transverse dissociation of the heart was found in patients in a rare combination with other pathological conditions from this body, we consider it interesting to describe in this article.

scholarly journals Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1184
Author(s):  
Alam Zeb ◽  
Isra Rana ◽  
Ho-Ik Choi ◽  
Cheol-Ho Lee ◽  
Seong-Woong Baek ◽  
...  
Keyword(s):  
Viable Option ◽  
Commercial Success ◽  
Drug Products ◽  
The Past ◽  
Small Molecule Drug ◽  
Parenteral Delivery ◽  
Pathological Conditions ◽  
Efficient Delivery ◽  
Intracellular Targets ◽  
Plasma Half Life

During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions.

scholarly journals The Role of Phosphatases in Nuclear Envelope Disassembly and Reassembly and Their Relevance to Pathologies

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 687 ◽  
Author(s):  
Florentin Huguet ◽  
Shane Flynn ◽  
Paola Vagnarelli
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Nuclear Envelope ◽  
Current Understanding ◽  
The Past ◽  
Pathological Conditions ◽  
Regulation Of Cell Cycle

The role of kinases in the regulation of cell cycle transitions is very well established, however, over the past decade, studies have identified the ever-growing importance of phosphatases in these processes. It is well-known that an intact or otherwise non-deformed nuclear envelope (NE) is essential for maintaining healthy cells and any deviation from this can result in pathological conditions. This review aims at assessing the current understanding of how phosphatases contribute to the remodelling of the nuclear envelope during its disassembling and reformation after cell division and how errors in this process may lead to the development of diseases.

Spontaneous Rupture of Spleen in a Patient with Splenic Metastasis of Melanoma. A Case Report

1992 ◽  
Vol 78 (1) ◽  
pp. 47-48 ◽  
Author(s):  
Thomas M. Buzbee ◽  
Sewa S. Legha
Keyword(s):  
Case Report ◽  
Metastatic Melanoma ◽  
Splenic Rupture ◽  
Splenic Metastasis ◽  
Spontaneous Splenic Rupture ◽  
The Past ◽  
Pathological Conditions ◽  
High Incidence ◽  
Previous Trauma ◽  
Splenic Metastases

We report a case of spontaneous splenic rupture in a patient with metastatic melanoma. Spontaneous splenic rupture without previous trauma has been observed in various pathological conditions such as infectious mononucleosis, malaria, typhoid fever and, rarely, neoplasms affecting the spleen. There have been several reported cases of splenic rupture in leukemias. Despite the high incidence of splenic metastases in metastatic melanoma, there have been only 3 cases of spontaneous splenic rupture reported in the past.

What is Known About Caries in Relation to Restorations as a Reason for Replacement? a Review

1995 ◽  
Vol 9 (4) ◽  
pp. 394-402 ◽  
Author(s):  
L. Ozer ◽  
A. Thylstrup
Keyword(s):  
Risk Factor ◽  
Dental Caries ◽  
Plaque Formation ◽  
The Other ◽  
Professional Behavior ◽  
Critical Approach ◽  
Secondary Caries ◽  
Local Conditions ◽  
The Past ◽  
Dental Restorations

In the past 20 years, a great many studies have identified secondary caries to be the most common reason for the replacement of restorations. This review raises the question whether clinicians use 'secondary caries' as a catch-all into which they put a variety of reasons for replacement, or whether they do have professionally based reasons for focusing on caries adjacent to restorations. There is no consensus among researchers concerning the nature of secondary caries, but it is possible to identify two major-and conflicting-trends : One adheres to a critical approach concerning the frequency of replacements and recommends a much more conservative evaluation of existing fillings. In contrast, the other trend focuses on the clinical undetectable microleakage as the major risk factor for the initiation and uncontrolled dentinal spread of secondary caries. Since the latter trend offers a reasonable explanation for the clinicians' concern about invisible 'secondary caries', and hence reinforces the tendency to replacement, it is relevant to reconsider the conventional concept that microleakage leads to the initiation of secondary caries. Available data indicate that visible gaps and marginal discrepancies are poorly related to secondary caries, and that secondary caries is a localized phenomenon caused by localized conditions for the evolution of cariogenic plaque. Consequently, secondary caries is not a universal attack along the entire interface between tooth and restoration, but rather a new lesion or a re-beginning of caries on the surface due to local conditions for plaque formation with cariogenic potential. It is concluded that reinforcement of a new and more appropriate professional behavior should be based on diffusion of existing knowledge of dental caries as a disease rather than on simplified criteria for the placement and replacement of dental restorations.

scholarly journals Mechanisms of ventricular arrhythmias elicited by coexistence of multiple electrophysiological remodeling in ischemia: a simulation study

2021 ◽  
Author(s):  
Cuiping Liang ◽  
Qince Li ◽  
Kuanquan Wang ◽  
Yimei Du ◽  
Wei Wang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ventricular Arrhythmias ◽  
Pathological Condition ◽  
Excitation Threshold ◽  
Coronary Syndrome ◽  
Refractory Periods ◽  
The Past ◽  
Pathological Conditions ◽  
Three Stages ◽  
Tissue Models

Myocardial ischemia, injury and infarction (MI) are the three stages of acute coronary syndrome (ACS). In the past two decades, a great number of studies focused on myocardial ischemia and MI individually, and showed that the occurrence of reentrant arrhythmias is often associated with myocardial ischemia or MI. However, arrhythmogenic mechanisms in the tissue with various degrees of remodeling in the ischemic heart have not been fully understood. In this study, biophysical detailed single-cell models of ischemia 1a, 1b, and MI were developed to mimic the electrophysiological remodeling at different stages of ACS. 2D tissue models with different distributions of ischemia and MI were constructed to investigate the mechanisms of initiation of reentrant waves during the progression of ischemia. Simulation results in 2D tissues showed that the vulnerable window (VW) in the tissue with multiple pathological conditions were determined by the VWs in the tissues with a single pathological condition. In different pathological conditions, action potential duration (APD) and the conduction velocity (CV) change differently. In the tissue with multiple pathological conditions, when the borders of different pathological conditions were perpendicular to the excitation wavefront, reentrant waves were mainly induced by the spatial heterogeneity of refractory periods due to the interaction of APD and CV along the wavefront. When the borders were parallel to the wavefront, the increased excitation threshold of MI region as well as the impaired excitability of ischemia region were the primary reason for the generation of reentry. Finally, the reentrant wave was observed in a 3D model with a scar reconstructed from MRI images of a MI patient. These comprehensive findings provide novel insights for understanding the arrhythmic risk during the progression of myocardial ischemia and highlight the importance of the multiple pathological stage in designing medical therapies for arrhythmia in ischemia.

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