scholarly journals Application of Proteomics in Cancer: Recent Trends and Approaches for Biomarkers Discovery

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Woo Kwon ◽  
Han-Seul Jo ◽  
Sungwon Bae ◽  
Youngsuk Seo ◽  
Parkyong Song ◽  
...  
Keyword(s):  
Translational Research ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Global Trends ◽  
Cancer Proteomics ◽  
Important Field ◽  
Recent Trends ◽  
Tumor Growth And Metastasis ◽  
Identity Expression

Proteomics has become an important field in molecular sciences, as it provides valuable information on the identity, expression levels, and modification of proteins. For example, cancer proteomics unraveled key information in mechanistic studies on tumor growth and metastasis, which has contributed to the identification of clinically applicable biomarkers as well as therapeutic targets. Several cancer proteome databases have been established and are being shared worldwide. Importantly, the integration of proteomics studies with other omics is providing extensive data related to molecular mechanisms and target modulators. These data may be analyzed and processed through bioinformatic pipelines to obtain useful information. The purpose of this review is to provide an overview of cancer proteomics and recent advances in proteomic techniques. In particular, we aim to offer insights into current proteomics studies of brain cancer, in which proteomic applications are in a relatively early stage. This review covers applications of proteomics from the discovery of biomarkers to the characterization of molecular mechanisms through advances in technology. Moreover, it addresses global trends in proteomics approaches for translational research. As a core method in translational research, the continued development of this field is expected to provide valuable information at a scale beyond that previously seen.

scholarly journals Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints

2021 ◽  
Vol 8 ◽  
Author(s):  
Janne W. Bolt ◽  
Chaja M. J. van Ansenwoude ◽  
Ihsan Hammoura ◽  
Marleen G. van de Sande ◽  
Lisa G. M. van Baarsen
Keyword(s):  
Psoriatic Arthritis ◽  
Translational Research ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Treatment Strategies ◽  
Continuous Treatment ◽  
Adaptive Immune Cells ◽  
Novel Treatment Strategies

Patients with psoriatic arthritis (PsA) are suffering from a decreased quality of life despite currently available treatments. In the latest years, novel therapies targeting the IL-17/IL-23 and TNF pathways improved clinical outcome. Despite this, remission of disease is not achieved in a considerable group of patients, continuous treatment is very often required to reach clinical remission, and prevention of PsA in patients with psoriasis (PsO) is currently impossible. A better understanding of PsA pathogenesis is required to develop novel treatment strategies that target inflammation and destruction more effectively and at an early stage of the disease, or even before clinically manifest disease. The skin is considered as one of the sites of onset of immune activation, triggering the inflammatory cascade in PsA. PsO develops into PsA in 30% of the PsO patients. Influenced by environmental and genetic factors, the inflammatory process in the skin, entheses, and/or gut may evolve into synovial tissue inflammation, characterized by influx of immune cells. The exact role of the innate and adaptive immune cells in disease pathogenesis is not completely known. The involvement of activated IL-17A+ T cells could implicate early immunomodulatory events generated in lymphoid organs thereby shaping the pathogenic inflammatory response leading to disease. In this perspective article, we provide the reader with an overview of the current literature regarding the immunological changes observed during the earliest stages of PsA. Moreover, we will postulate future areas of translational research aimed at increasing our knowledge on the molecular mechanisms driving disease development, which will aid the identification of novel potential therapeutic targets to limit the progression of PsA.

Nonwovens: Global Trends in World Economy, European Foreign Trade, and Selected Case Studies from Poland and Asian Brics Countries

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Zofia Wysokińska ◽  
Tomasz Czajkowski ◽  
Katarzyna Grabowska
Keyword(s):  
Case Studies ◽  
World Economy ◽  
World Market ◽  
Global Trends ◽  
Textile Materials ◽  
Brics Countries ◽  
Recent Trends ◽  
Almost All ◽  
Special Case

AbstractNonwovens are one of the most versatile textile materials and have become increasingly popular in almost all sectors of the economy due to their low manufacturing costs and unique properties. In the next few years, the world market of nonwovens is predicted to grow by 7%–8% annually (International Nonwovens & Disposables Association [INDA], European Disposables and Nonwovens Association [EDANA], and Markets and Markets). This article aims to analyze the most recent trends in the global export and import of nonwovens, to present two case studies of Polish companies that produce them, and to present one special case study of the market of nonwoven geotextiles in China and India, which are the Asian transition economies among the BRICS countries (Brazil, Russia, India, China, and South Africa).

Cancer Proteomics: New Horizons and Insights into Therapeutic Applications

2020 ◽  
Vol 17 ◽  
Author(s):  
Perumal Subramaniana ◽  
Jaime Jacqueline Jayapalan ◽  
Puteri Shafinaz Abdul-Rahmanb
Keyword(s):  
Molecular Mechanisms ◽  
Rapid Development ◽  
New Horizons ◽  
Cancer Management ◽  
Proteomic Approach ◽  
Cancer Proteomics ◽  
Therapeutic Outcomes ◽  
A Genome ◽  
Highly Sensitive ◽  
Dimensional Electrophoresis

A proteome is an efficient rendition of a genome, unswervingly controlling various cancer processes. Molecular mechanisms of several cancer processes have been unraveled by proteomic approach. Thus far, numerous tumors of diverse status have been investigated by two-dimensional electrophoresis. Numerous biomarkers have been recognized and precise categorization of apparent lesions has led to the timely detection of various cancers in persons at peril. Currently used pioneering approaches and technologies in proteomics have led to highly sensitive assays of cancer biomarkers and improved the early diagnosis of various cancers. The discovery of novel and definite biomarker signatures further widened our perceptive of the disease and novel potent drugs for efficient and aimed therapeutic outcomes in persistent cancers have emerged. However, a major limitation, even today, of proteomics is resolving and quantifying the proteins of low abundance. Despite the rapid development of proteomic technologies and their applications in cancer management, annulling the shortcomings of present proteomic technologies and development of better methods are still desirable. The main objectives of this review are to discuss the developing aspects, merits and demerits of pharmacoproteomics, redox proteomics, novel approaches and therapies being used for various types of cancer based on proteome studies.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

scholarly journals Genetic mapping and transcriptomic characterization of a new fuzzless-tufted cottonseed mutant

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qian-Hao Zhu ◽  
Warwick Stiller ◽  
Philippe Moncuquet ◽  
Stuart Gordon ◽  
Yuman Yuan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Agronomic Traits ◽  
Gene Families ◽  
Mutant Phenotype ◽  
Wild Type ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Flanking Region ◽  
Comparative Transcriptomic Analysis

Abstract Fiber mutants are unique and valuable resources for understanding the genetic and molecular mechanisms controlling initiation and development of cotton fibers that are extremely elongated single epidermal cells protruding from the seed coat of cottonseeds. In this study, we reported a new fuzzless-tufted cotton mutant (Gossypium hirsutum) and showed that fuzzless-tufted near-isogenic lines (NILs) had similar agronomic traits and a higher ginning efficiency compared to their recurrent parents with normal fuzzy seeds. Genetic analysis revealed that the mutant phenotype is determined by a single incomplete dominant locus, designated N5. The mutation was fine mapped to an approximately 250-kb interval containing 33 annotated genes using a combination of bulked segregant sequencing, SNP chip genotyping, and fine mapping. Comparative transcriptomic analysis using 0–6 days post-anthesis (dpa) ovules from NILs segregating for the phenotypes of fuzzless-tufted (mutant) and normal fuzzy cottonseeds (wild-type) uncovered candidate genes responsible for the mutant phenotype. It also revealed that the flanking region of the N5 locus is enriched with differentially expressed genes (DEGs) between the mutant and wild-type. Several of those DEGs are members of the gene families with demonstrated roles in cell initiation and elongation, such as calcium-dependent protein kinase and expansin. The transcriptome landscape of the mutant was significantly reprogrammed in the 6 dpa ovules and, to a less extent, in the 0 dpa ovules, but not in the 2 and 4 dpa ovules. At both 0 and 6 dpa, the reprogrammed mutant transcriptome was mainly associated with cell wall modifications and transmembrane transportation, while transcription factor activity was significantly altered in the 6 dpa mutant ovules. These results imply a similar molecular basis for initiation of lint and fuzz fibers despite certain differences.

scholarly journals Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7406
Author(s):  
Ana Amor López ◽  
Marina S. Mazariegos ◽  
Alessandra Capuano ◽  
Pilar Ximénez-Embún ◽  
Marta Hergueta-Redondo ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cell Viability ◽  
Extracellular Vesicles ◽  
Primary Tumor ◽  
Molecular Mechanisms ◽  
Primary Tumor Growth ◽  
Node Metastasis ◽  
Metastatic Cells ◽  
Tumor Growth And Metastasis

Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.

scholarly journals A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

2021 ◽  
Vol 22 (14) ◽  
pp. 7390
Author(s):  
Nicole Wesch ◽  
Frank Löhr ◽  
Natalia Rogova ◽  
Volker Dötsch ◽  
Vladimir V. Rogov
Keyword(s):  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Effective Interaction ◽  
Regulatory Region ◽  
Titration Calorimetry ◽  
Enzymatic Reactions ◽  
Cellular Processes ◽  
Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

scholarly journals High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Betty Ha ◽  
Kevin P. Larsen ◽  
Jingji Zhang ◽  
Ziao Fu ◽  
Elizabeth Montabana ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Viral Entry ◽  
Reverse Transcription ◽  
Molecular Mechanisms ◽  
Dissociation Kinetics ◽  
Structural Mechanism ◽  
Medium Resolution ◽  
Kinetics Of ◽  
Hiv 1

AbstractReverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon viral entry, HIV-1 reverse transcriptase (RT) initiates from a host tRNALys3 primer bound to the vRNA genome and is the target of key antivirals, such as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Initiation proceeds slowly with discrete pausing events along the vRNA template. Despite prior medium-resolution structural characterization of reverse transcriptase initiation complexes (RTICs), higher-resolution structures of the RTIC are needed to understand the molecular mechanisms that underlie initiation. Here we report cryo-EM structures of the core RTIC, RTIC–nevirapine, and RTIC–efavirenz complexes at 2.8, 3.1, and 2.9 Å, respectively. In combination with biochemical studies, these data suggest a basis for rapid dissociation kinetics of RT from the vRNA–tRNALys3 initiation complex and reveal a specific structural mechanism of nucleic acid conformational stabilization during initiation. Finally, our results show that NNRTIs inhibit the RTIC and exacerbate discrete pausing during early reverse transcription.

scholarly journals Hemolysis in the spleen drives erythrocyte turnover

Blood ◽  
2020 ◽  
Author(s):  
Thomas robert leon Klei ◽  
Jill Jasmine Dalimot ◽  
Benjamin Nota ◽  
Martijn Veldthuis ◽  
Erik Mul ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Matrix Proteins ◽  
Human Spleen ◽  
Erythrocyte Adhesion ◽  
Subsequent Degradation ◽  
Macrophage Subpopulations ◽  
Senescent Erythrocytes ◽  
Red Pulp

Red pulp macrophages of the spleen mediate turnover of billions of senescent erythrocytes per day. However, the molecular mechanisms involved in sequestration of senescent erythrocytes, their recognition and their subsequent degradation by red pulp macrophages remain unclear. In this study we provide evidence that the splenic environment is of substantial importance in facilitating erythrocyte turnover through induction of hemolysis. Upon isolating human spleen red pulp macrophages we noted a substantial lack of macrophages that were in the process of phagocytosing intact erythrocytes. Detailed characterization of erythrocyte and macrophage subpopulations from human spleen tissue led to the identification of erythrocytes that are devoid of hemoglobin, so-called erythrocyte ghosts. By in vivo imaging and transfusion experiments we further confirmed that senescent erythrocytes that are retained in the spleen are subject to hemolysis. Additionally, we show that erythrocyte adhesion molecules, which are specifically activated on aged erythrocytes, cause senescent erythrocytes to interact with extracellular matrix proteins that are exposed within the splenic architecture. Such adhesion molecule-driven retention of senescent erythrocytes, under low shear conditions, was found to result in steady shrinkage of the cell and ultimately resulted in hemolysis. In contrast to intact senescent erythrocytes, the remnant erythrocyte ghost shells were prone to recognition and breakdown by red pulp macrophages. These data identify hemolysis as a key event in the turnover of senescent erythrocytes, which alters our current understanding of how erythrocyte degradation is regulated.

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