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18 pages, 699 KiB  
Review
Telomere Length and Telomerase Activity as Potential Biomarkers for Gastrointestinal Cancer
by Christina Loukopoulou, Taxiarchis Nikolouzakis, Ioannis Koliarakis, Elena Vakonaki and John Tsiaoussis
Cancers 2024, 16(19), 3370; https://doi.org/10.3390/cancers16193370 - 1 Oct 2024
Viewed by 232
Abstract
Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new [...] Read more.
Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers. Full article
(This article belongs to the Section Cancer Biomarkers)
18 pages, 338 KiB  
Systematic Review
Postpartum Interventions to Increase Maternal Vaccination Uptake: Is It Worth It?
by Eleni Konstantinou, Sofia Benou, Eleftheria Hatzidaki, Aggeliki Vervenioti, Gabriel Dimitriou, Vassiliki Papaevangelou, Christine E. Jones and Despoina Gkentzi
Vaccines 2024, 12(10), 1130; https://doi.org/10.3390/vaccines12101130 - 1 Oct 2024
Viewed by 282
Abstract
Background/Objectives: Vaccination of pregnant and postpartum women for pertussis, influenza and COVID-19 not only protects themselves but also offspring. Despite the benefits of this approach, vaccination uptake remains suboptimal in pregnancy. Where the opportunity to be vaccinated in pregnancy is missed, the offer [...] Read more.
Background/Objectives: Vaccination of pregnant and postpartum women for pertussis, influenza and COVID-19 not only protects themselves but also offspring. Despite the benefits of this approach, vaccination uptake remains suboptimal in pregnancy. Where the opportunity to be vaccinated in pregnancy is missed, the offer of vaccination in the post-partum period may be an alternative strategy. The aim of this systematic review is to assess the impact of interventions to increase vaccination uptake in the postpartum period on vaccination uptake. Methods: A literature search was performed in MEDLINE, including interventional studies promoting vaccination uptake in postpartum women published between 2009 and 2024. The search was conducted according to PRISMA guidelines and registered with PROSPERO. Results: We finally included 16 studies in the review, and the primary outcome was vaccination uptake in the postpartum period. The most significant factors for increasing uptake were recommendation from healthcare providers, type of interventions used, and delivery of vaccines in the maternity wards or the community. Conclusions: In conclusion, maternal vaccination rates in the postpartum period may increase with targeted education by healthcare professionals and positive reinforcement. The interventions described in these studies could be applied in the healthcare systems worldwide. Full article
(This article belongs to the Special Issue Impact of Immunization Safety Monitoring on Vaccine Coverage)
24 pages, 16220 KiB  
Article
Comprehensive Evaluation of the Massively Parallel Direct Simulation Monte Carlo Kernel “Stochastic Parallel Rarefied-Gas Time-Accurate Analyzer” in Rarefied Hypersonic Flows—Part A: Fundamentals
by Angelos Klothakis and Ioannis K. Nikolos
Computation 2024, 12(10), 198; https://doi.org/10.3390/computation12100198 - 1 Oct 2024
Viewed by 288
Abstract
The Direct Simulation Monte Carlo (DSMC) method, introduced by Graeme Bird over five decades ago, has become a crucial statistical particle-based technique for simulating low-density gas flows. Its widespread acceptance stems from rigorous validation against experimental data. This study focuses on four validation [...] Read more.
The Direct Simulation Monte Carlo (DSMC) method, introduced by Graeme Bird over five decades ago, has become a crucial statistical particle-based technique for simulating low-density gas flows. Its widespread acceptance stems from rigorous validation against experimental data. This study focuses on four validation test cases known for their complex shock–boundary and shock–shock interactions: (a) a flat plate in hypersonic flow, (b) a Mach 20.2 flow over a 70-degree interplanetary probe, (c) a hypersonic flow around a flared cylinder, and (d) a hypersonic flow around a biconic. Part A of this paper covers the first two cases, while Part B will discuss the remaining cases. These scenarios have been extensively used by researchers to validate prominent parallel DSMC solvers, due to the challenging nature of the flow features involved. The validation requires meticulous selection of simulation parameters, including particle count, grid density, and time steps. This work evaluates the SPARTA (Stochastic Parallel Rarefied-gas Time-Accurate Analyzer) kernel’s accuracy against these test cases, highlighting its parallel processing capability via domain decomposition and MPI communication. This method promises substantial improvements in computational efficiency and accuracy for complex hypersonic vehicle simulations. Full article
(This article belongs to the Special Issue Post-Modern Computational Fluid Dynamics)
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12 pages, 860 KiB  
Article
Secondary Metabolites and Their Biological Evaluation from the Aerial Parts of Staehelina uniflosculosa Sibth. & Sm. (Asteraceae)
by Maria Lazanaki, George Tsikalas, Olga S. Tsiftsoglou, Haralambos Katerinopoulos, Dimitra Hadjipavlou-Litina and Diamanto Lazari
Int. J. Mol. Sci. 2024, 25(19), 10586; https://doi.org/10.3390/ijms251910586 - 1 Oct 2024
Viewed by 196
Abstract
Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6 [...] Read more.
Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide (7), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide (8), 1β-hydroxy-arbusculin A (9), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate (10) and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate (11); one lignan, pinoresinol (12); one norisoprenoid, loliolide (13); six flavonoids (four genins and two glycosides), hispidulin (14), nepetin (15), jaceosidin (16), eriodictyol (17), eriodictyol-3′-O-β-D-glucoside (18) and eriodictyol-7-O-β-D-glucuronide (19); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid (20), arbutin (21) and nebrodenside A (22). From the isolated compounds, only nepetin (15) has been reported previously from the Staehelina genus and, to the best of our knowledge, it is the first time that compound (18) has been identified in Asteraceae. A number of these substances were tested for (a) inhibition of lipoxygenase and acetylocholinesterase, (b) their antioxidant activity using the DPPH (1,1-Diphenyl-2-picrylhydrazyl) method or/and (c) inhibition of lipid peroxidation. The tested components exhibited low antioxidant activity with the exception of 5 and 22, while the effectiveness of these compounds in the inhibition of acetylocholinesterase is limited. Furthermore, Molinspiration, an online computer tool, was used to determine the bioactivity ratings of the isolated secondary metabolites. The compounds’ bioactivity ratings for potential therapeutic targets were very promising. Full article
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15 pages, 13710 KiB  
Article
Decoding Socio-Economic Demographic Trends: The Power of Spatial Econometrics and Geographic Analysis
by Evgenia Anastasiou
Urban Sci. 2024, 8(4), 163; https://doi.org/10.3390/urbansci8040163 - 30 Sep 2024
Viewed by 256
Abstract
Greece is experiencing a steady population decline caused by the declining migratory and natural balance. This research investigates the spatial impact of socio-economic and demographic factors on the natural population balance in Greece for the spatial zoning of municipal administrative units. Using geographically [...] Read more.
Greece is experiencing a steady population decline caused by the declining migratory and natural balance. This research investigates the spatial impact of socio-economic and demographic factors on the natural population balance in Greece for the spatial zoning of municipal administrative units. Using geographically weighted regression (GWR) on data from the 2011 Greek census, the research explores the local impacts of factors like housing repair permits, vacant housing, employment rates, population inflows, distance from regional centers, aging, gender ratios, and education levels. An initial ordinary least squares (OLS) regression was conducted, revealing significant spatial variation and emphasizing the necessity of spatial econometric methods. The GWR model proved to be more effective in accounting for the variance in the data, removing spatial autocorrelation and revealing high local variation. Results show the high negative impact of the aging index in Western Greece and the Ionian islands, the counterintuitive positive effect of the gender ratio in urban areas, and the positive influence of population inflows in high-migration regions like Northern Greece and Crete. The results of this study underline the need to utilize spatial econometric methods for a precise and detailed understanding of demographic trends and provide valuable insights for localized strategies to address demographic challenges. Full article
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11 pages, 802 KiB  
Article
Presence of Ochratoxin a Residues in Blood Serum of Slaughtered Pigs in Greece
by Mikela Vlachou, Andreana Pexara, Nikolaos Solomakos, Alexander Govaris, Dimitrios Palaiogiannis, Vassilis Athanasiadis and Stavros I. Lalas
Toxins 2024, 16(10), 421; https://doi.org/10.3390/toxins16100421 - 30 Sep 2024
Viewed by 274
Abstract
This study aimed to assess the presence of ochratoxin A (OTA) residues in the blood serum of slaughtered pigs in Greece. Samples were obtained from 1695 healthy slaughtered pigs originating from 113 different farms located in 21 geographic regional units in 8 different [...] Read more.
This study aimed to assess the presence of ochratoxin A (OTA) residues in the blood serum of slaughtered pigs in Greece. Samples were obtained from 1695 healthy slaughtered pigs originating from 113 different farms located in 21 geographic regional units in 8 different geographic regions of Greece and were analyzed using an immunosorbent assay (ELISA) and high-performance liquid chromatography with fluorescence detector (HPLC-FD). OTA contamination assessment showed that 782 (46.1%) and 1233 (72.7%) samples were OTA-positive, with a concentration range of 0.20–5.38 μg/L and 0.15–5.96 µg/L according to ELISA and HPLC-FD analysis, respectively. Also, 88 (77.9%) and 108 (95.6%) of farms were found to be OTA-positive by ELISA and HPLC-FD analysis, respectively. The highest OTA serum positivity rate (>98%) and toxin level (5.96 µg/L) determined by HPLC-FD were observed in the Thessaly region, whereas a high prevalence of up to 100% (range 75–100%) was found on farms in the Crete Island region. The detection of OTA in the serum of slaughtered pigs in different regions in Greece poses a risk for animal and human health and highlights the need for constant OTA monitoring in the swine industry and pork meat production facilities. Full article
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12 pages, 1084 KiB  
Review
Artificial Intelligence in Infectious Disease Clinical Practice: An Overview of Gaps, Opportunities, and Limitations
by Andreas Sarantopoulos, Christina Mastori Kourmpani, Atshaya Lily Yokarasa, Chiedza Makamanzi, Polyna Antoniou, Nikolaos Spernovasilis and Constantinos Tsioutis
Trop. Med. Infect. Dis. 2024, 9(10), 228; https://doi.org/10.3390/tropicalmed9100228 - 30 Sep 2024
Viewed by 749
Abstract
The integration of artificial intelligence (AI) in clinical medicine marks a revolutionary shift, enhancing diagnostic accuracy, therapeutic efficacy, and overall healthcare delivery. This review explores the current uses, benefits, limitations, and future applications of AI in infectious diseases, highlighting its specific applications in [...] Read more.
The integration of artificial intelligence (AI) in clinical medicine marks a revolutionary shift, enhancing diagnostic accuracy, therapeutic efficacy, and overall healthcare delivery. This review explores the current uses, benefits, limitations, and future applications of AI in infectious diseases, highlighting its specific applications in diagnostics, clinical decision making, and personalized medicine. The transformative potential of AI in infectious diseases is emphasized, addressing gaps in rapid and accurate disease diagnosis, surveillance, outbreak detection and management, and treatment optimization. Despite these advancements, significant limitations and challenges exist, including data privacy concerns, potential biases, and ethical dilemmas. The article underscores the need for stringent regulatory frameworks and inclusive databases to ensure equitable, ethical, and effective AI utilization in the field of clinical and laboratory infectious diseases. Full article
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18 pages, 2958 KiB  
Article
Population Dynamics of Potential Insect Vectors of Xylella fastidiosa (Xanthomanadales: Xanthomonadaceae) and Other Auchenorrhyncha in Olive and Citrus Groves of Crete, Greece
by Ioannis E. Koufakis, Argyro P. Kalaitzaki, Maria L. Pappas, Antonios E. Tsagkarakis, Despina K. Tzobanoglou and George D. Broufas
Agronomy 2024, 14(10), 2243; https://doi.org/10.3390/agronomy14102243 - 28 Sep 2024
Viewed by 514
Abstract
This study investigated the phenology and population dynamics of potential insect vectors of Xylella fastidiosa Wells et al. and other Auchenorrhyncha species in olive and citrus groves of Chania province, Crete, Greece. Although X. fastidiosa has not been reported in Greece, its introduction [...] Read more.
This study investigated the phenology and population dynamics of potential insect vectors of Xylella fastidiosa Wells et al. and other Auchenorrhyncha species in olive and citrus groves of Chania province, Crete, Greece. Although X. fastidiosa has not been reported in Greece, its introduction could cause serious diseases in many crops, including olives and citrus. Olive groves of Olea europaea L. ‘Koroneiki’ were sampled systematically using sweep net and Malaise traps over 24 months. One citrus grove was sampled for one year using a Malaise trap. Sweep net samples were taken from the herbaceous cover, tree canopy, and field borders of olive groves. Auchenorrhyncha were more abundant on the herbaceous cover compared to the canopy and field margins. Aphrophoridae species were mostly found on the herbaceous cover and in low numbers during fall (October–December) and spring (April–May). Cicadellidae species, such as Euscelis spp., were frequently found on the herbaceous cover of both olive and citrus groves. One Aphrophoridae and several Cicadellidae species were recorded in the citrus grove. Altitude was found to influence the population abundance of some Auchenorrhyncha species in olive groves. These results provide information for effective integrated management of insect vectors and their vector-borne pathogens. Full article
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14 pages, 5955 KiB  
Communication
A Holistic Irrigation Advisory Policy Scheme by the Hellenic Agricultural Organization: An Example of a Successful Implementation in Crete, Greece
by Nektarios N. Kourgialas
Water 2024, 16(19), 2769; https://doi.org/10.3390/w16192769 - 28 Sep 2024
Viewed by 412
Abstract
The aim of this communication article is to present a successful irrigation advisory scheme on the island of Crete (Greece) provided by the Hellenic Agricultural Organization (ELGO DIMITRA), which is well adapted to the different needs of farmers and water management agencies. The [...] Read more.
The aim of this communication article is to present a successful irrigation advisory scheme on the island of Crete (Greece) provided by the Hellenic Agricultural Organization (ELGO DIMITRA), which is well adapted to the different needs of farmers and water management agencies. The motivation to create this advisory scheme stems from the need to save water resources while ensuring optimal production in a region like Crete where droughts seem to occur more and more frequently in recent years. This scheme/approach has three different levels of implementation (components) depending on the spatial level and end-users’ needs. The first level concerns the weekly irrigation bulletins in the main agricultural areas of the island with the aim of informing farmers and local water managers about crop irrigation needs. The second level concerns an innovative digital web-based platform for the precise determination of the irrigation needs of Crete’s crops at a parcel level as well as optimal adaptation strategies in the context of climate change. In this platform, important features such as real-time meteorological information, spatial data on the cultivation type of parcels, validated algorithms for calculating crop irrigation needs, an accurate soil texture map derived from satellite images, and appropriate agronomic practices to conserve water based on cultivation and the geomorphology of a farm are considered. The third level of the proposed management approach includes an open-source Internet of Things (IoT) intelligent irrigation system for optimal individual parcel irrigation scheduling. This IoT system includes soil moisture and atmospheric sensors installed on the field, as well as the corresponding laboratory soil hydraulic characterization service. This third-level advisory approach provides farmers with specialized information on the automated irrigation system and optimization of irrigation water use. All the above irrigation advisory approaches have been implemented and evaluated by end-users with a very high degree of satisfaction in terms of effectiveness and usability. Full article
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10 pages, 235 KiB  
Article
Association between Inflammatory Markers and Psychometric Scores in Patients with Hidradenitis Suppurativa
by Aikaterini I. Liakou, Nikolaos Rotsiamis, Andreas G. Tsantes, Eleni Routsi, Natalia Rompoti, Petros Ioannou, Alexandra Mpakosi, Lydia Tsamtsouri, Efthymia Agiasofitou, Ourania Kotsafti, Stefanos Bonovas, Alexander Katoulis, Evangelia Papadavid and Dimitris Rigopoulos
J. Clin. Med. 2024, 13(19), 5795; https://doi.org/10.3390/jcm13195795 - 28 Sep 2024
Viewed by 313
Abstract
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with a significant impact on the quality of life of affected patients. This study aimed to correlate serum inflammatory markers with specific tools assessing quality of life, emotional well-being, and loneliness, such [...] Read more.
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with a significant impact on the quality of life of affected patients. This study aimed to correlate serum inflammatory markers with specific tools assessing quality of life, emotional well-being, and loneliness, such as the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), and the UCLA Loneliness Scale. Methods: A pilot observational study including 37 patients with HS was conducted. Inflammatory serum markers, including C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR), were evaluated at baseline, 3 months, and 6 months later. Psychometric scores were also evaluated at the same study intervals. Results: DLQI was correlated with ESR at baseline (Spearman’s rho = 0.35, p = 0.03), indicating that poorer quality of life is associated with changes in this serum marker. Disease activity, as reflected by inflammatory markers, was associated with significant psychological burden. Specifically, a worse DLQI score was associated with higher ESR (estimate β = 0.14, 95% confidence interval [CI]: 0.05–0.22; p = 0.001) and higher CRP level (estimate β = 0.25, 95% CI: 0.02–0.48; p = 0.02). Similarly, a worse UCLA score was associated with higher ESR (estimate β = 0.11, 95% CI: 0.02–0.20, p = 0.01). Conclusions: Our study results underline the close relation between systemic inflammatory markers and clinical severity together with psychological burden in HS patients, as indicated by the significant association that was revealed between ESR/CRP and poorer psychometric scores. However, further research is warranted to validate these findings. Full article
(This article belongs to the Special Issue Recent Advances in Acne, Rosacea and Hidradenitis Suppurativa)
10 pages, 5017 KiB  
Case Report
Unexpected Cytological Detection of Leishmania infantum within the Secretion of a Canine Mammary Carcinoma
by Katrin Törner, Heike Aupperle-Lellbach, Elisabeth Müller, Torsten J. Naucke and Ingo Schäfer
Animals 2024, 14(19), 2794; https://doi.org/10.3390/ani14192794 - 27 Sep 2024
Viewed by 464
Abstract
Mammary tumors are one of the most common neoplasms in female dogs, and cytology represents a non-invasive diagnostic method. The protozoal pathogen Leishmania spp. was previously demonstrated in canine mammary glands. An eight-year-old, female-spayed Doberman was imported from Crete, Greece, three years before [...] Read more.
Mammary tumors are one of the most common neoplasms in female dogs, and cytology represents a non-invasive diagnostic method. The protozoal pathogen Leishmania spp. was previously demonstrated in canine mammary glands. An eight-year-old, female-spayed Doberman was imported from Crete, Greece, three years before the first presentation. The dog was presented due to a mammary tumor two years after adoption. The clinical examination revealed fever and weight loss. Smears of the mammary secretion were investigated cytologically. Multiple atypical epithelial cells with moderate to marked criteria of malignancy were detected. Furthermore, amastigotes were visible intra- and extracellularly. The diagnosis of L. infantum infection was based on a positive PCR out of the cytological smear, and a positive serology. Mammary carcinoma and granulomatous inflammation with amastigotes were confirmed by histopathology. We aimed to provide a complete report of cytological, histopathological, hematological, and biochemistry findings in a dog with L. infantum in the mammary glands with focus on trans-mammary pathogen transmission as a potential alternative way of spreading Leishmania infections. Canine leishmaniasis should be a potential differential diagnosis in dogs with lesions and/or inflammation in the mammary glands and a history of presence in areas endemic for L. infantum, especially the Mediterranean in Europe. Full article
(This article belongs to the Section Companion Animals)
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18 pages, 7146 KiB  
Article
Non-Invasive Optoacoustic Imaging for In-Depth Cultural Heritage Diagnostics
by George J. Tserevelakis, Eleanna Pirgianaki, Kristalia Melessanaki, Giannis Zacharakis and Costas Fotakis
Photonics 2024, 11(10), 902; https://doi.org/10.3390/photonics11100902 - 25 Sep 2024
Viewed by 454
Abstract
The complex composition of cultural heritage (CH) items presents significant challenges in assessing their condition and predicting potential risks of material degradation. Typically employed diagnostic optical methods are inevitably limited by light scattering, thus restricting in-depth investigations of objects with complex structural and [...] Read more.
The complex composition of cultural heritage (CH) items presents significant challenges in assessing their condition and predicting potential risks of material degradation. Typically employed diagnostic optical methods are inevitably limited by light scattering, thus restricting in-depth investigations of objects with complex structural and optical properties. To address this issue, we introduce a novel reflection-mode optoacoustic (OA) diagnostic system for non-contact and non-invasive measurements of CH, placing emphasis on the detection of ageing-related modifications in artistic media such as paints. In this direction, the sensitivity of OA measurements was proven to be up to two orders of magnitude higher than conventional absorption spectroscopy assessments. Furthermore, we have evaluated the in-depth imaging capabilities of the developed OA system, demonstrating that it can offer superior contrast levels of sketches beneath opaque paint layers compared to standard near-infrared diagnostic techniques. The current OA imaging technology may advance state-of-the-art diagnostic capabilities in CH preservation by delivering unprecedented depth-to-resolution ratios combined with exceptional optical absorption sensitivity in a non-invasive manner. These features are crucial for the early detection of material degradation and the comprehensive analysis of CH objects, facilitating the development of optimal conservation strategies to prolong their lifespan and preserve their aesthetic value. Full article
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26 pages, 399 KiB  
Review
Pharmacological Treatments of Negative Symptoms in Schizophrenia—An Update
by Evangelia Maria Tsapakis, Michael Treiber, Calypso Mitkani, Zoe Drakaki, Anastasios Cholevas, Cleanthe Spanaki and Konstantinos N. Fountoulakis
J. Clin. Med. 2024, 13(18), 5637; https://doi.org/10.3390/jcm13185637 - 23 Sep 2024
Viewed by 642
Abstract
Schizophrenia is a chronic psychotic disorder comprising positive symptoms, negative symptoms, and cognitive deficits. Negative symptoms are associated with stigma, worse functional outcomes, and a significant deterioration in quality of life. Clinical diagnosis is challenging despite its significance, and current treatments offer little [...] Read more.
Schizophrenia is a chronic psychotic disorder comprising positive symptoms, negative symptoms, and cognitive deficits. Negative symptoms are associated with stigma, worse functional outcomes, and a significant deterioration in quality of life. Clinical diagnosis is challenging despite its significance, and current treatments offer little improvement in the burden of negative symptoms. This article reviews current pharmacological strategies for treating negative symptoms. Dopaminergic, glutamatergic, serotonergic, noradrenergic, cholinergic, anti-inflammatory compounds, hormones, and psychostimulants are explored. Finally, we review pharmacological global treatment guidelines for negative symptoms. In general, switching to a second-generation antipsychotic seems to be most often recommended for patients with schizophrenia on first-generation antipsychotics, and an add-on antidepressant is considered when depression is also present. However, the treatment of negative symptoms remains an unmet need. Future, larger clinical studies and meta-analyses are needed to establish effective pharmacological agents for the effective treatment of negative symptoms. Full article
(This article belongs to the Section Mental Health)
49 pages, 5746 KiB  
Review
Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease
by Aikaterini Berdiaki, Monica Neagu, Petros Tzanakakis, Ioanna Spyridaki, Serge Pérez and Dragana Nikitovic
Biomolecules 2024, 14(9), 1186; https://doi.org/10.3390/biom14091186 - 20 Sep 2024
Viewed by 1261
Abstract
Glycosaminoglycans (GAGs) and proteoglycans (PGs) are essential components of the extracellular matrix (ECM) with pivotal roles in cellular mechanosensing pathways. GAGs, such as heparan sulfate (HS) and chondroitin sulfate (CS), interact with various cell surface receptors, including integrins and receptor tyrosine kinases, to [...] Read more.
Glycosaminoglycans (GAGs) and proteoglycans (PGs) are essential components of the extracellular matrix (ECM) with pivotal roles in cellular mechanosensing pathways. GAGs, such as heparan sulfate (HS) and chondroitin sulfate (CS), interact with various cell surface receptors, including integrins and receptor tyrosine kinases, to modulate cellular responses to mechanical stimuli. PGs, comprising a core protein with covalently attached GAG chains, serve as dynamic regulators of tissue mechanics and cell behavior, thereby playing a crucial role in maintaining tissue homeostasis. Dysregulation of GAG/PG-mediated mechanosensing pathways is implicated in numerous pathological conditions, including cancer and inflammation. Understanding the intricate mechanisms by which GAGs and PGs modulate cellular responses to mechanical forces holds promise for developing novel therapeutic strategies targeting mechanotransduction pathways in disease. This comprehensive overview underscores the importance of GAGs and PGs as key mediators of mechanosensing in maintaining tissue homeostasis and their potential as therapeutic targets for mitigating mechano-driven pathologies, focusing on cancer and inflammation. Full article
(This article belongs to the Section Cellular Biochemistry)
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37 pages, 3636 KiB  
Review
Relationship of Signaling Pathways between RKIP Expression and the Inhibition of EMT-Inducing Transcription Factors SNAIL1/2, TWIST1/2 and ZEB1/2
by Andrew Bustamante, Stavroula Baritaki, Apostolos Zaravinos and Benjamin Bonavida
Cancers 2024, 16(18), 3180; https://doi.org/10.3390/cancers16183180 - 17 Sep 2024
Viewed by 791
Abstract
Untreated primary carcinomas often lead to progression, invasion and metastasis, a process that involves the epithelial-to-mesenchymal transition (EMT). Several transcription factors (TFs) mediate the development of EMT, including SNAIL1/SNAIL2, TWIST1/TWIST2 and ZEB1/ZEB2, which are overexpressed in various carcinomas along with the under expression [...] Read more.
Untreated primary carcinomas often lead to progression, invasion and metastasis, a process that involves the epithelial-to-mesenchymal transition (EMT). Several transcription factors (TFs) mediate the development of EMT, including SNAIL1/SNAIL2, TWIST1/TWIST2 and ZEB1/ZEB2, which are overexpressed in various carcinomas along with the under expression of the metastasis suppressor Raf Kinase Inhibitor Protein (RKIP). Overexpression of RKIP inhibits EMT and the above associated TFs. We, therefore, hypothesized that there are inhibitory cross-talk signaling pathways between RKIP and these TFs. Accordingly, we analyzed the various properties and biomarkers associated with the epithelial and mesenchymal tissues and the various molecular signaling pathways that trigger the EMT phenotype such as the TGF-β, the RTK and the Wnt pathways. We also presented the various functions and the transcriptional, post-transcriptional and epigenetic regulations for the expression of each of the EMT TFs. Likewise, we describe the transcriptional, post-transcriptional and epigenetic regulations of RKIP expression. Various signaling pathways mediated by RKIP, including the Raf/MEK/ERK pathway, inhibit the TFs associated with EMT and the stabilization of epithelial E-Cadherin expression. The inverse relationship between RKIP and the TF expressions and the cross-talks were further analyzed by bioinformatic analysis. High mRNA levels of RKIP correlated negatively with those of SNAIL1, SNAIL2, TWIST1, TWIST2, ZEB1, and ZEB2 in several but not all carcinomas. However, in these carcinomas, high levels of RKIP were associated with good prognosis, whereas high levels of the above transcription factors were associated with poor prognosis. Based on the inverse relationship between RKIP and EMT TFs, it is postulated that the expression level of RKIP in various carcinomas is clinically relevant as both a prognostic and diagnostic biomarker. In addition, targeting RKIP induction by agonists, gene therapy and immunotherapy will result not only in the inhibition of EMT and metastases in carcinomas, but also in the inhibition of tumor growth and reversal of resistance to various therapeutic strategies. However, such targeting strategies must be better investigated as a result of tumor heterogeneities and inherent resistance and should be better adapted as personalized medicine. Full article
(This article belongs to the Section Tumor Microenvironment)
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