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17 pages, 12147 KiB

Open AccessEditor’s ChoiceArticle

Unlocking the Memory Component of Alzheimer’s Disease: Biological Processes and Pathways across Brain Regions

by Nikolas Dovrolis, Maria Nikou, Alexandra Gkrouzoudi, Nikolaos Dimitriadis and Ioanna Maroulakou

Biomolecules 2022, 12(2), 263; https://doi.org/10.3390/biom12020263 - 06 Feb 2022

Cited by 1 | Viewed by 2549

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive loss of memory and a general cognitive decline leading to dementia. AD is characterized by changes in the behavior of the genome and can be traced across multiple brain regions and cell [...] Read more.

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive loss of memory and a general cognitive decline leading to dementia. AD is characterized by changes in the behavior of the genome and can be traced across multiple brain regions and cell types. It is mainly associated with β-amyloid deposits and tau protein misfolding, leading to neurofibrillary tangles. In recent years, however, research has shown that there is a high complexity of mechanisms involved in AD neurophysiology and functional decline enabling its diverse presentation and allowing more questions to arise. In this study, we present a computational approach to facilitate brain region-specific analysis of genes and biological processes involved in the memory process in AD. Utilizing current genetic knowledge we provide a gene set of 265 memory-associated genes in AD, combinations of which can be found co-expressed in 11 different brain regions along with their functional role. The identified genes participate in a spectrum of biological processes ranging from structural and neuronal communication to epigenetic alterations and immune system responses. These findings provide new insights into the molecular background of AD and can be used to bridge the genotype–phenotype gap and allow for new therapeutic hypotheses. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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14 pages, 1209 KiB

Open AccessArticle

Data Mining of Molecular Simulations Suggest Key Amino Acid Residues for Aggregation, Signaling and Drug Action

by Vaibhav Gurunathan, John Hamre III, Dmitri K. Klimov and Mohsin Saleet Jafri

Biomolecules 2021, 11(10), 1541; https://doi.org/10.3390/biom11101541 - 19 Oct 2021

Cited by 1 | Viewed by 2390

Abstract

Alzheimer’s disease, the most common form of dementia, currently has no cure. There are only temporary treatments that reduce symptoms and the progression of the disease. Alzheimer’s disease is characterized by the prevalence of plaques of aggregated amyloid β (Aβ) peptide. Recent treatments [...] Read more.

Alzheimer’s disease, the most common form of dementia, currently has no cure. There are only temporary treatments that reduce symptoms and the progression of the disease. Alzheimer’s disease is characterized by the prevalence of plaques of aggregated amyloid β (Aβ) peptide. Recent treatments to prevent plaque formation have provided little to relieve disease symptoms. Although there have been numerous molecular simulation studies on the mechanisms of Aβ aggregation, the signaling role has been less studied. In this study, a total of over 38,000 simulated structures, generated from molecular dynamics (MD) simulations, exploring different conformations of the Aβ42 mutants and wild-type peptides were used to examine the relationship between Aβ torsion angles and disease measures. Unique methods characterized the data set and pinpointed residues that were associated in aggregation and others associated with signaling. Machine learning techniques were applied to characterize the molecular simulation data and classify how much each residue influenced the predicted variant of Alzheimer’s Disease. Orange3 data mining software provided the ability to use these techniques to generate tables and rank the data. The test and score module coupled with the confusion matrix module analyzed data with calculations of specificity and sensitivity. These methods evaluating frequency and rank allowed us to analyze and predict important residues associated with different phenotypic measures. This research has the potential to help understand which specific residues of Aβ should be targeted for drug development. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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Review

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25 pages, 1139 KiB

Open AccessReview

Oxytocin: A Multi-Functional Biomolecule with Potential Actions in Dysfunctional Conditions; From Animal Studies and Beyond

by Anastasia S. Tsingotjidou

Biomolecules 2022, 12(11), 1603; https://doi.org/10.3390/biom12111603 - 31 Oct 2022

Cited by 6 | Viewed by 5330

Abstract

Oxytocin is a hormone secreted from definite neuroendocrine neurons located in specific nuclei in the hypothalamus (mainly from paraventricular and supraoptic nuclei), and its main known function is the contraction of uterine and/or mammary gland cells responsible for parturition and breastfeeding. Among the [...] Read more.

Oxytocin is a hormone secreted from definite neuroendocrine neurons located in specific nuclei in the hypothalamus (mainly from paraventricular and supraoptic nuclei), and its main known function is the contraction of uterine and/or mammary gland cells responsible for parturition and breastfeeding. Among the actions of the peripherally secreted oxytocin is the prevention of different degenerative disorders. These actions have been proven in cell culture and in animal models or have been tested in humans based on hypotheses from previous studies. This review presents the knowledge gained from the previous studies, displays the results from oxytocin intervention and/or treatment and proposes that the well described actions of oxytocin might be connected to other numerous, diverse actions of the biomolecule. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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9 pages, 318 KiB

Open AccessReview

Evaluation of Adipose Cell-Based Therapies for the Treatment of Thumb Carpometacarpal Joint Osteoarthritis

by Eleni Karagergou, Theodora Ligomenou, Byron Chalidis, Dimitrios Kitridis, Sophia Papadopoulou and Panagiotis Givissis

Biomolecules 2022, 12(3), 473; https://doi.org/10.3390/biom12030473 - 20 Mar 2022

Cited by 4 | Viewed by 4056

Abstract

Adipose tissue and its regenerative products which are isolated with enzymatic or mechanical processing of the harvested fat have been studied in a wide range of degenerative diseases, including osteoarthritis of the knee and hip. Intra-articular injection of these products can provide symptomatic [...] Read more.

Adipose tissue and its regenerative products which are isolated with enzymatic or mechanical processing of the harvested fat have been studied in a wide range of degenerative diseases, including osteoarthritis of the knee and hip. Intra-articular injection of these products can provide symptomatic relief of pain and postpone surgery. However, their use in the treatment of thumb carpometacarpal joint (CMCJ) osteoarthritis is limited and just a few studies have been published on that topic. For this reason, a review of the literature was performed by a thorough search of eight terms using the Pubmed database. In total, seven human studies met the selection criteria, including case-control studies, case-series and one case report. In all studies, intra-articular injection of autologous fat in osteoarthritic thumb CMCJ provided reduction in pain and improvement in hand function. Grip and pinch strength showed variable results, from no change to significant improvement. Fat-processing techniques were based on centrifugation and mechanical homogenization but biological characterization of the injected cells was not performed in any study. Although the results are encouraging, a uniformly standardized method of fat processing and the conduction of randomized controlled trials in the future could better evaluate the effectiveness of this procedure for thumb CMCJ osteoarthritis. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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39 pages, 1459 KiB

Open AccessReview

A Review of In Vivo and Clinical Studies Applying Scaffolds and Cell Sheet Technology for Periodontal Ligament Regeneration

by Maria Bousnaki, Anastasia Beketova and Eleana Kontonasaki

Biomolecules 2022, 12(3), 435; https://doi.org/10.3390/biom12030435 - 11 Mar 2022

Cited by 16 | Viewed by 6434

Abstract

Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies [...] Read more.

Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies and clinical trials. Most of those developments include the use of polymeric materials with different patterning and surface nanotopography and printing of complex and sophisticated multiphasic composite scaffolds with different compartments to accomodate for the different periodontal tissues’ architecture. Despite the increased effort in producing these scaffolds and their undoubtable efficiency to guide and support tissue regeneration, appropriate source of cells is also needed to provide new tissue formation and various biological and mechanochemical cues from the Extraccellular Matrix (ECM) to provide biophysical stimuli for cell growth and differentiation. Cell sheet engineering is a novel promising technique that allows obtaining cells in a sheet format while preserving ECM components. The right combination of those factors has not been discovered yet and efforts are still needed to ameliorate regenerative outcomes towards the functional organisation of the developed tissues. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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22 pages, 760 KiB

Open AccessFeature PaperReview

Biomolecules Orchestrating Cardiovascular Calcification

by Yin Tintut, Henry M. Honda and Linda L. Demer

Biomolecules 2021, 11(10), 1482; https://doi.org/10.3390/biom11101482 - 07 Oct 2021

Cited by 9 | Viewed by 3130

Abstract

Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic [...] Read more.

Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli. Although calcium deposits in the vessel wall introduce rupture stress at their edges facing applied tensile stress, they simultaneously reduce rupture stress at the orthogonal edges, leaving the net risk of plaque rupture and consequent cardiac events depending on local material strength. A clinically important consequence of the shared mechanisms between the vascular and bone tissues is that therapeutic agents designed to inhibit vascular calcification may adversely affect skeletal mineralization and vice versa. Thus, it is essential to consider both systems when developing therapeutic strategies. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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18 pages, 305 KiB

Open AccessReview

The Combined Use of Platelet-Rich Plasma and Adipose-Derived Mesenchymal Stem Cells Promotes Healing. A Review of Experimental Models and Future Perspectives

by Dimitris Tatsis, Varvara Vasalou, Efstathios Kotidis, Elissavet Anestiadou, Ioannis Grivas, Angeliki Cheva, Georgios Koliakos, Gregory Venetis, Manousos-George Pramateftakis, Nikolaos Ouzounidis and Stamatis Angelopoulos

Biomolecules 2021, 11(10), 1403; https://doi.org/10.3390/biom11101403 - 24 Sep 2021

Cited by 6 | Viewed by 3757

Abstract

Wound healing and tissue regeneration are a field of clinical medicine presenting high research interest, since various local and systematic factors can inhibit these processes and lead to an inferior result. New methods of healing enhancement constantly arise, which, however, require experimental validation [...] Read more.

Wound healing and tissue regeneration are a field of clinical medicine presenting high research interest, since various local and systematic factors can inhibit these processes and lead to an inferior result. New methods of healing enhancement constantly arise, which, however, require experimental validation before their establishment in everyday practice. Platelet-rich plasma (PRP) is a well-known autologous factor that promotes tissue healing in various surgical defects. PRP derives from the centrifugation of peripheral blood and has a high concentration of growth factors that promote healing. Recently, the use of adipose-derived mesenchymal stem cells (ADMSCs) has been thoroughly investigated as a form of wound healing enhancement. ADMSCs are autologous stem cells deriving from fat tissue, with a capability of differentiation in specific cells, depending on the micro-environment that they are exposed to. The aim of the present comprehensive review is to record the experimental studies that have been published and investigate the synergistic use of PRP and ADMSC in animal models. The technical aspects of experimentations, as well as the major results of each study, are discussed. In addition, the limited clinical studies including humans are also reported. Future perspectives are discussed, along with the limitations of current studies on the long-term follow up needed on efficacy and safety. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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8 pages, 2970 KiB

Open AccessSystematic Review

Biomolecules Related to Rotator Cuff Pain: A Scoping Review

by Nikolaos Platon Sachinis, Christos K. Yiannakopoulos, Byron Chalidis, Dimitrios Kitridis and Panagiotis Givissis

Biomolecules 2022, 12(8), 1016; https://doi.org/10.3390/biom12081016 - 22 Jul 2022

Cited by 4 | Viewed by 2645

Abstract

The pathophysiology of pain in patients suffering from rotator cuff (RC) tendinopathy or tears has been examined in various ways. Several molecules from tissue samples taken from the subacromial bursa, supraspinatus tendon, glenohumeral joint fluid, and synovium as well as from peripheral blood [...] Read more.

The pathophysiology of pain in patients suffering from rotator cuff (RC) tendinopathy or tears has been examined in various ways. Several molecules from tissue samples taken from the subacromial bursa, supraspinatus tendon, glenohumeral joint fluid, and synovium as well as from peripheral blood have been investigated. This article explores these studies, the assessed biomarkers, and groups their results according to the status of tendon integrity (tendinopathy or tear). Through a structured PubMed database search, 9 out of 658 articles were reviewed. Interleukins, mostly IL-1b and its antagonist, IL-1ra, matrix Metalloproteinases (MMPs), the vascular endothelial growth factor (VEGF) and TNF-a are biomarkers directly searched for correlation to pain level. Most studies agree that IL-1b is directly positively correlated to the degree of pain in patients with RC tendinopathy, especially when the examined sample is taken from the subacromial bursa. VEGF, and TNF-a have been related to shoulder pain preoperatively and TNF-a has also been linked with sleep disturbance. Further studies pointing to more biomarkers taken from the subacromial bursa or tendon directly relating to pain degree are warranted. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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18 pages, 1810 KiB

Open AccessSystematic Review

Biomolecule-Mediated Therapeutics of the Dentin–Pulp Complex: A Systematic Review

by Foteini Machla, Ioannis Angelopoulos, Matthias Epple, Maria Chatzinikolaidou and Athina Bakopoulou

Biomolecules 2022, 12(2), 285; https://doi.org/10.3390/biom12020285 - 09 Feb 2022

Cited by 7 | Viewed by 2513

Abstract

The aim of this systematic review was to evaluate the application of potential therapeutic signaling molecules on complete dentin-pulp complex and pulp tissue regeneration in orthotopic and ectopic animal studies. A search strategy was performed according to the Preferred Reporting Items for Systematic [...] Read more.

The aim of this systematic review was to evaluate the application of potential therapeutic signaling molecules on complete dentin-pulp complex and pulp tissue regeneration in orthotopic and ectopic animal studies. A search strategy was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in the MEDLINE/PubMed database. Animal studies evaluating the application of signaling molecules to pulpectomized teeth for pulp tissue or dentin-pulp complex regeneration were included. From 2530 identified records, 18 fulfilled the eligibility criteria and were subjected to detailed qualitative analysis. Among the applied molecules, basic fibroblast growth factor, vascular endothelial growth factor, bone morphogenetic factor-7, nerve growth factor, and platelet-derived growth factor were the most frequently studied. The clinical, radiographical and histological outcome measures included healing of periapical lesions, root development, and apical closure, cellular recolonization of the pulp space, ingrowth of pulp-like connective tissue (vascularization and innervation), mineralized dentin-like tissue formation along the internal dentin walls, and odontoblast-like cells in contact with the internal dentin walls. The results indicate that signaling molecules play an important role in dentin/pulp regeneration. However, further studies are needed to determine a more specific subset combination of molecules to achieve greater efficiency towards the desired tissue engineering applications. Full article

(This article belongs to the Special Issue Core of Biomolecules Affecting Degenerative Disorders)

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