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Microbial exopolysaccharides (EPSs) are receiving growing interest today, owing to their diversity in chemical structure and source, multiple functions, and immense potential applications in many food and non-food industries. Their health-promoting benefits for humans deserve particular attention because of their various biological activities and physiological functions. The aim of this paper is to provide a comprehensive review of microbial EPSs, covering (1) their chemical and biochemical diversity, including composition, biosynthesis, and bacterial sources belonging mainly to lactic acid bacteria (LAB) or probiotics; (2) their technological and analytical aspects, especially their production mode and characterization; (3) their biological and physiological aspects based on their activities and functions; and (4) their current and future uses in medical and pharmaceutical fields, particularly for their prebiotic, anticancer, and immunobiotic properties, as well as their applications in other industrial and agricultural sectors. Full article

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EPS chemical structure examples. Full article ">Figure 2
Biosynthesis of polysaccharides in microorganisms. Wzx/Wzy-dependent pathway: Responsible for synthesizing lipopolysaccharide O-antigen polysaccharides in Gram-negative bacteria, as well as capsular polysaccharides (CPSs) and EPSs in both Gram-negative and Gram-positive bacteria. ATP-binding ABC transporter pathway: Facilitates the synthesis of CPS specifically in Gram-negative bacteria. Synthase-dependent pathway: Involved in the synthesis of both CPSs and EPSs in Gram-negative and Gram-positive bacteria. Extracellular synthesis via a single glycosyltransferase: Responsible for the synthesis of EPSs that fall under the category of HoPS. Full article ">Figure 3
Outline of biosynthesis of HePS. The abbreviations are TDP: thymidine diphosphate; UDP: uridine diphosphate; GDP: guanosine diphosphate; Man-1-P: mannose-1-phosphate; Glc: glucose; Gal: galactose; Man: mannose. Full article ">Figure 4
Workflow of EPS production. Full article ">Figure 5
Physiological functions of EPS. Full article ">

16 pages, 1043 KiB

Open AccessReview

Research Progress on Dendritic Cells in Hepatocellular Carcinoma Immune Microenvironments

by Wenya Li, Guojie Chen, Hailin Peng, Qingfang Zhang, Dengyun Nie, Ting Guo, Yinxing Zhu, Yuhan Zhang and Mei Lin

Biomolecules 2024, 14(9), 1161; https://doi.org/10.3390/biom14091161 - 16 Sep 2024

Abstract

Dendritic cells (DCs) are antigen-presenting cells that play a crucial role in initiating immune responses by cross-presenting relevant antigens to initial T cells. The activation of DCs is a crucial step in inducing anti-tumor immunity. Upon recognition and uptake of tumor antigens, activated DCs present these antigens to naive T cells, thereby stimulating T cell-mediated immune responses and enhancing their ability to attack tumors. It is particularly noted that DCs are able to cross-present foreign antigens to major histocompatibility complex class I (MHC-I) molecules, prompting CD8⁺ T cells to proliferate and differentiate into cytotoxic T cells. In the malignant progression of hepatocellular carcinoma (HCC), the inactivation of DCs plays an important role, and the activation of DCs is particularly important in anti-HCC immunotherapy. In this review, we summarize the mechanisms of DC activation in HCC, the involved regulatory factors and strategies to activate DCs in HCC immunotherapy. It provides a basis for the study of HCC immunotherapy through DC activation. Full article

28 pages, 601 KiB

Open AccessReview

Exploring the Connection between Social Housing and Employment: A Scoping Review

by Julia Jansen-van Vuuren, Hibo Rijal, Nicole Bobbette, Rosemary Lysaght, Terry Krupa and Daniella Aguilar

Int. J. Environ. Res. Public Health 2024, 21(9), 1217; https://doi.org/10.3390/ijerph21091217 - 16 Sep 2024

Abstract

Adequate housing is a social determinant of health and well-being, providing stability from which people can engage in important life activities, including self-care and productivity. Social housing is a system-level intervention that aims to provide affordable housing to people vulnerable to experiencing social and economic marginalisation. Given the importance of employment to social-economic status and overall health and well-being, we sought to better understand the available knowledge and research related to employment and living in a social housing environment. We used scoping review methodology to explore peer-reviewed research published between 2012–2022 regarding social housing and employment, identifying 29 relevant articles. Using the Psychology of Working Theory and neighbourhood effects as interpretive theoretical frameworks, we analysed the extracted data. Overall, the results affirmed that social housing residents have low employment rates conceptualised as related to the complex interplay of a range of personal and environmental factors. Most published literature was quantitative and originated from the United States. Policy and research implications are discussed, including the need for more multifaceted, person-centred interventions that support employment and ultimately promote health and quality of life for social housing residents. Full article

25 pages, 8440 KiB

Open AccessReview

Targeted Drug Delivery Strategies for the Treatment of Hepatocellular Carcinoma

by Yonghui Liu, Yanan Wu, Zijian Li, Dong Wan and Jie Pan

Molecules 2024, 29(18), 4405; https://doi.org/10.3390/molecules29184405 - 16 Sep 2024

Abstract

Hepatocellular carcinoma (HCC) ranks among the most prevalent malignant tumors, exhibiting a high incidence rate that presents a substantial threat to human health. The use of sorafenib and lenvatinib, commonly employed as single-agent targeted inhibitors, complicates the treatment process due to the absence of definitive targeting. Nevertheless, the advent of nanotechnology has injected new optimism into the domain of liver cancer therapy. Nanocarriers equipped with active targeting or passive targeting mechanisms have demonstrated the capability to deliver drugs to tumor cells with high efficiency. This approach not only facilitates precise delivery to the affected site but also enables targeted drug release, thereby enhancing therapeutic efficacy. As medical technology progresses, there is an increasing call for innovative treatment modalities, including novel chemotherapeutic agents, gene therapy, phototherapy, immunotherapy, and combinatorial treatments for HCC. These emerging therapies are anticipated to yield improved clinical outcomes for patients, while minimizing systemic toxicity and adverse effects. Consequently, the application of nanotechnology is poised to significantly improve HCC treatment. This review focused on targeted strategies for HCC and the application of nanotechnology in this area. Full article

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21 pages, 2282 KiB

Open AccessReview

Effects and Mechanisms of Polyunsaturated Fatty Acids on Age-Related Musculoskeletal Diseases: Sarcopenia, Osteoporosis, and Osteoarthritis—A Narrative Review

by Haoqi Chen, Ruogu Xiong, Jin Cheng, Jialu Ye, Yingzhen Qiu, Siyu Huang, Mengchu Li, Zhaoyan Liu, Jinzhu Pang, Xuguang Zhang, Shanshan Guo, Huabin Li and Huilian Zhu

Nutrients 2024, 16(18), 3130; https://doi.org/10.3390/nu16183130 - 16 Sep 2024

Abstract

Background: The process of the globally aging population has been accelerating, leading to an increasing social burden. As people age, the musculoskeletal system will gradually go through a series of degenerative and loss of function and eventually develop age-related musculoskeletal diseases, like sarcopenia, osteoporosis, and osteoarthritis. On the other hand, several studies have shown that polyunsaturated fatty acids (PUFAs) possess various important physiological functions on the health of muscles, bones, and joints. Objective: This narrative review paper provides a summary of the literature about the effects and mechanisms of PUFAs on age-related musculoskeletal diseases for the prevention and management of these diseases. Methods: Web of Science, PubMed, Science Direct, and Scopus databases have been searched to select the relevant literature on epidemiological, cellular, and animal experiments and clinical evidence in recent decades with keywords “polyunsaturated fatty acids”, “PUFAs”, “omega-3”, ”omega-6”, ”musculoskeletal diseases”, “sarcopenia”, “osteoporosis”, “osteoarthritis”, and so on. Results: PUFAs could prevent and treat age-related musculoskeletal diseases (sarcopenia, osteoporosis, and osteoarthritis) by reducing oxidative stress and inflammation and controlling the growth, differentiation, apoptosis, and autophagy of cells. This review paper provides comprehensive evidence of PUFAs on age-related musculoskeletal diseases, which will be helpful for exploitation into functional foods and drugs for their prevention and treatment. Conclusions: PUFAs could play an important role in the prevention and treatment of sarcopenia, osteoporosis, and osteoarthritis. Full article

(This article belongs to the Section Lipids)

30 pages, 2168 KiB

Open AccessReview

Cartilage Repair: Promise of Adhesive Orthopedic Hydrogels

by Peyman Karami, Alexis Laurent, Virginie Philippe, Lee Ann Applegate, Dominique P. Pioletti and Robin Martin

Int. J. Mol. Sci. 2024, 25(18), 9984; https://doi.org/10.3390/ijms25189984 (registering DOI) - 16 Sep 2024

Abstract

Cartilage repair remains a major challenge in human orthopedic medicine, necessitating the application of innovative strategies to overcome existing technical and clinical limitations. Adhesive hydrogels have emerged as promising candidates for cartilage repair promotion and tissue engineering, offering key advantages such as enhanced tissue integration and therapeutic potential. This comprehensive review navigates the landscape of adhesive hydrogels in cartilage repair, discussing identified challenges, shortcomings of current treatment options, and unique advantages of adhesive hydrogel products and scaffolds. While emphasizing the critical need for in situ lateral integration with surrounding tissues, we dissect current limitations and outline future perspectives for hydrogel scaffolds in cartilage repair. Moreover, we examine the clinical translation pathway and regulatory considerations specific to adhesive hydrogels. Overall, this review synthesizes the existing insights and knowledge gaps and highlights directions for future research regarding adhesive hydrogel-based devices in advancing cartilage tissue engineering. Full article

(This article belongs to the Special Issue Focus on Cartilage Biology)

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14 pages, 1317 KiB

Open AccessReview

Enhancing Capacity to Comply with Sustainability Standards in the Milk Value Chain in East Africa: Challenges, Prospects, and Policy Implications

by Fredy Timothy Mlyavidoga Kilima, George Mutani Msalya and Amos Omore

Sustainability 2024, 16(18), 8100; https://doi.org/10.3390/su16188100 (registering DOI) - 16 Sep 2024

Abstract

This paper addresses the need to contextualize sustainability standards and supply chain management in dairy value chains in East Africa, where milk perishability and limited cold storage significantly impact the industry. The study highlights the importance of localizing these standards, given the greater dependence on local supply chains following the COVID-19 pandemic. Drawing on milk standards literature and various interventions aimed at promoting systemic change, this review analyses the capacity of marginalized stakeholders in East Africa’s dairy value chains to meet sustainability standards, focusing particularly on the social dimensions of these standards. The findings indicate that compliance with sustainability and safety standards is predominantly restricted to formal dairy networks, which process less than 20 percent of milk produced in the region. Most milk sales occur through informal or unorganized markets, which face significant barriers to meeting international sustainability benchmarks. The review advocates for the alignment of international sustainability standards with the unique conditions of the informal markets dominating East Africa’s dairy sector. It suggests enhancing stakeholder capabilities and addressing regulatory barriers as necessary steps for improving compliance with these standards. The co-operative model is highlighted as a promising approach to integrating farmers and marginalized value chain actors into the formal sector, thereby facilitating incremental adoption of sustainability standards. The paper identifies strategic entry points for organizing and upgrading the supply chain, including capacity building, certification, and catalyzing farmer groups to compliance and productivity. Full article

(This article belongs to the Special Issue Sustainable Logistics and Supply Chain Management in the Post-COVID-19 Era: Future Challenges and Challenging Futures)

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Illustration of interrelations relevant to sustainability pillars around the dairy farming system. Full article ">Figure 2
Sustainable dairy value chain development framework. Source: adapted from [<a href="#B29-sustainability-16-08100" class="html-bibr">29</a>]. Full article ">Figure A1
Schematic representation of the quality assurance scheme. Source: [<a href="#B36-sustainability-16-08100" class="html-bibr">36</a>]. Full article ">

21 pages, 601 KiB

Open AccessReview

Current Insights into Molecular Mechanisms and Potential Biomarkers for Treating Radiation-Induced Liver Damage

by Biki Saha, Sneha Pallatt, Antara Banerjee, Abhijit G. Banerjee, Rupak Pathak and Surajit Pathak

Cells 2024, 13(18), 1560; https://doi.org/10.3390/cells13181560 - 16 Sep 2024

Abstract

Highly conformal delivery of radiation therapy (RT) has revolutionized the treatment landscape for primary and metastatic liver cancers, yet concerns persist regarding radiation-induced liver disease (RILD). Despite advancements, RILD remains a major dose-limiting factor due to the potential damage to normal liver tissues by therapeutic radiation. The toxicity to normal liver tissues is associated with a multitude of physiological and pathological consequences. RILD unfolds as multifaceted processes, intricately linking various responses, such as DNA damage, oxidative stress, inflammation, cellular senescence, fibrosis, and immune reactions, through multiple signaling pathways. The DNA damage caused by ionizing radiation (IR) is a major contributor to the pathogenesis of RILD. Moreover, current treatment options for RILD are limited, with no established biomarker for early detection. RILD diagnosis often occurs at advanced stages, highlighting the critical need for early biomarkers to adjust treatment strategies and prevent liver failure. This review provides an outline of the diverse molecular and cellular mechanisms responsible for the development of RILD and points out all of the available biomarkers for early detection with the aim of helping clinicians decide on advance treatment strategies from a single literature recourse. Full article

(This article belongs to the Section Cellular Pathology)

30 pages, 720 KiB

Open AccessReview

Inclusive Crisis Communication in a Pandemic Context: A Rapid Review

by Karin Hannes, Pieter Thyssen, Theresa Bengough, Shoba Dawson, Kristel Paque, Sarah Talboom, Krizia Tuand, Thomas Vandendriessche, Wessel van de Veerdonk, Daniëlle Wopereis and Anne-Mieke Vandamme

Int. J. Environ. Res. Public Health 2024, 21(9), 1216; https://doi.org/10.3390/ijerph21091216 - 16 Sep 2024

Abstract

Background: Crisis communication might not reach non-native speakers or persons with low literacy levels, a low socio-economic status, and/or an auditory or visual impairments as easily as it would reach other citizens. The aim of this rapid review was to synthesize the evidence on strategies used to improve inclusive pandemic-related crisis communication in terms of form, channel, and outreach. Methods: After a comprehensive search and a rigorous screening and quality assessment exercise, twelve comparative studies were selected for inclusion in this review. Data were analyzed and represented by means of a structured reporting of available effects using narrative tables. Results: The findings indicate that a higher message frequency (on any channel) may lead to a lower recall rate, audio–visual productions and tailored messages prove to be valuable under certain conditions, and primary healthcare practitioners appear to be the most trusted source of information for most groups of citizens. Trust levels were higher for citizens who were notified in advance of potential exceptions to the rule in the effect of preventive and curative measures promoted. Conclusions: This review contributes to combatting information inequality by providing evidence on how to remove the sensorial, linguistic, cultural, and textual barriers experienced by minorities and other underserved target audiences in COVID-19-related governmental crisis communication in response to the societal, health-related costs of ineffective communication outreach. Full article

(This article belongs to the Special Issue Health Literacy and Communicable Diseases)

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Outline of included and excluded studies. Full article ">

27 pages, 1112 KiB

Open AccessReview

Fighting Pancreatic Cancer with a Vaccine-Based Winning Combination: Hope or Reality?

by Silvia Brugiapaglia, Ferdinando Spagnolo, Simona Intonti, Francesco Novelli and Claudia Curcio

Cells 2024, 13(18), 1558; https://doi.org/10.3390/cells13181558 - 16 Sep 2024

Abstract

Pancreatic adenocarcinoma (PDA) represents the fourth leading cause of cancer-related mortality in the USA. Only 20% of patients present surgically resectable and potentially curable tumors at diagnosis, while 80% are destined for poor survival and palliative chemotherapy. Accordingly, the advancement of innovative and effective therapeutic strategies represents a pivotal medical imperative. It has been demonstrated that targeting the immune system represents an effective approach against several solid tumors. The immunotherapy approach encompasses a range of strategies, including the administration of antibodies targeting checkpoint molecules (immune checkpoint inhibitors, ICIs) to disrupt tumor suppression mechanisms and active immunization approaches that aim to stimulate the host’s immune system. While vaccines have proved effective against infectious agents, vaccines for cancer remain an unfulfilled promise. Vaccine-based therapy targeting tumor antigens has the potential to be a highly effective strategy for initiating and maintaining T cell recognition, enhancing the immune response, and ultimately promoting cancer treatment success. In this review, we examined the most recent clinical trials that employed diverse vaccine types to stimulate PDA patients’ immune systems, either independently or in combination with chemotherapy, radiotherapy, ICIs, and monoclonal antibodies with the aim of ameliorating PDA patients’ quality of life and extend their survival. Full article

11 pages, 1187 KiB

Open AccessReview

Carbon Monoxide: A Pleiotropic Redox Regulator of Life and Death

by Andrey Y. Abramov, Isabella Myers and Plamena R. Angelova

Antioxidants 2024, 13(9), 1121; https://doi.org/10.3390/antiox13091121 - 16 Sep 2024

Abstract

Despite recent technological progress, carbon monoxide poisoning is still one of the leading causes of domestic and industrial morbidity and mortality. The brain is particularly vulnerable to CO toxicity, and thus the majority of survivors develop delayed movement and cognitive complications. CO binds to haemoglobin in erythrocytes, preventing oxygen delivery to tissues, and additionally inhibits mitochondrial respiration. This renders the effect of CO to be closely related to hypoxia reperfusion injury. Oxygen deprivation, as well as CO poisoning and re-oxygenation, are shown to be able to activate the production of reactive oxygen species and to induce oxidative stress. Here, we review the role of reactive oxygen species production and oxidative stress in the mechanism of neuronal cell death induced by carbon monoxide and re-oxygenation. We discuss possible protective mechanisms used by brain cells with a specific focus on the inhibition of CO-induced ROS production and oxidative stress. Full article

(This article belongs to the Special Issue The Role of Mitochondrial Redox Regulations in Inflammation and Disease)

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The role of carbon monoxide in physiology and pathology. Left: at physiological conditions of the cell, CO is produced in the HO-1 and enables cell detoxification and signalling processes. Right: at pathologically acute high doses of CO-NOX, XO and mitochondria produce ROS with higher rates, which leads to lipid peroxidation and mPTP opening and, ultimately, to cell death. CO—carbon monoxide; ROS—reactive oxygen species; NOX—NADPH oxidases; HO-1—heme oxygenase; Nrf-2—nuclear factor erythroid 2-related factor 2; XO—xanthine oxidase; MAO—monoamine oxidase; NADPH—reduced nicotinamide adenine dinucleotide phosphate, NADP+—oxidised nicotinamide adenine dinucleotide phosphate; ATP—adenosine 3-phosphate; mPTP—mitochondrial permeability transition pore; MDA—malone dialdehyde; 8-OHdG-8-hydroxy-2′-deoxyguanosine; SOD—superoxide dismutase; CAT—catalase; GPx—glutathione peroxidase. Full article ">

26 pages, 6574 KiB

Open AccessReview

Research Progress in Microporous Materials for Selective Adsorption and Separation of Methane from Low-Grade Gas

by Dongrui Su, Panpan Chen, Cunlei Li, Yongfei Yan, Ranlei Zhao, Qingyou Yue and Yupeng Qiao

Molecules 2024, 29(18), 4404; https://doi.org/10.3390/molecules29184404 - 16 Sep 2024

Abstract

Given that methane (CH₄) and nitrogen (N₂) have similar properties, achieving high-purity enrichment of CH₄ from nitrogen-rich low-grade gas is extremely challenging and is of great significance for sustainable development in energy and the environment. This paper reviews the research progress on carbon-based materials, zeolites, and MOFs as adsorbent materials for CH₄/N₂ separation. It focuses on the relationship between the composition, pore size, surface chemistry of the adsorbents, CH₄/N₂ selectivity, and CH₄ adsorption capacity. The paper also highlights that controlling pore size and atomic-scale composition and optimizing these features for the best match are key directions for the development of new adsorbents. Additionally, it points out that MOFs, which combine the advantages of carbon-based adsorbents and zeolites, are likely to become the most promising adsorbent materials for efficient CH₄/N₂ separation. Full article

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39 pages, 2751 KiB

Open AccessSystematic Review

Sustainable and Naturally Derived Wet Spun Fibers: A Systematic Literature Review

by Cristiana Pereira, Tânia V. Pinto, Raquel M. Santos and Nuno Correia

Fibers 2024, 12(9), 75; https://doi.org/10.3390/fib12090075 - 16 Sep 2024

Abstract

Increasing economic and environmental concerns arising from the extensive exploration and dependence on fossil fuel-based materials have encouraged the search for eco-friendly alternatives. Fibers based on biomass-derived materials have been attracting growing interest. Among other features, the mechanical performance of bio-based fibers needs to be improved to effectively compete with their counterparts and emerge as viable substitutes. This review presents scientific advancements in the development of naturally derived fibers, and strategies for their production with tailored mechanical properties. The potential of natural precursor-based fibers for their conversion into high-performance carbon fibers is also emphasized. Studies reporting the mechanical properties of bio-based fibers developed by wet spinning are identified, analyzed, and discussed. These studies show that cellulose is the most studied material, while Ioncell technology is identified as the most suitable method for producing cellulose-based fibers with the highest tensile strength. Studies have also demonstrated that silk fibroin exhibits tensile strength and elongation at break ranging from 300 to 600 MPa and 30 to 50%. Although several novel processes have been explored, there are still challenges that need to be addressed for bio-based fibers to become feasible options, and to boost their usage across industries. Full article

(This article belongs to the Collection Review Papers of Fibers)

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General schematic representation of both (a) wet spinning and (b) dry-jet wet spinning processes: (1) spinning dope container, (2) spinneret/nozzle, (3) coagulation bath, (4) washing/stretching bath, and (5) rotating spool. Full article ">Figure 2
PRISMA flow chart. Adapted from Ref. [<a href="#B13-fibers-12-00075" class="html-bibr">13</a>]. Full article ">Figure 3
Graphical illustration of the screening process and selected manuscripts. (a) General overview of the screening process (abstract/title and full text analysis). Graphical illustration of the included records per (b) polymer, (c) year of publication, (d) per polymer between 2018 and 2023, and (e) spinning process. Full article ">Figure 4
Schematic representation of cellulose structure composed by β-D-anhydroglucopyranose monomeric units linked by β-(1<tt>→</tt>4)-glycosidic bonds, with cellobiose as the repeating stereoregular unit. Full article ">Figure 5
Schematic representation of silk fibroin protein structure, with amino acid composition consisting of glycine (Gly), alanine (Ala), and serine (Ser). Full article ">Figure 6
Schematic representation of extraction of alginate from algal material. Adapted from Ref. [<a href="#B109-fibers-12-00075" class="html-bibr">109</a>]. Full article ">Figure 7
Schematic representation of alginate structure, with the chair conformation of GG block, MM block, and GM block. Adapted from Ref. [<a href="#B109-fibers-12-00075" class="html-bibr">109</a>]. Full article ">Figure 8
Schematic representation of chitin and chitosan structures. Full article ">

30 pages, 4353 KiB

Open AccessReview

Is Seeing Believing? A Practitioner’s Perspective on High-Dimensional Statistical Inference in Cancer Genomics Studies

by Kun Fan, Srijana Subedi, Gongshun Yang, Xi Lu, Jie Ren and Cen Wu

Entropy 2024, 26(9), 794; https://doi.org/10.3390/e26090794 - 16 Sep 2024

Abstract

Variable selection methods have been extensively developed for and applied to cancer genomics data to identify important omics features associated with complex disease traits, including cancer outcomes. However, the reliability and reproducibility of the findings are in question if valid inferential procedures are not available to quantify the uncertainty of the findings. In this article, we provide a gentle but systematic review of high-dimensional frequentist and Bayesian inferential tools under sparse models which can yield uncertainty quantification measures, including confidence (or Bayesian credible) intervals, p values and false discovery rates (FDR). Connections in high-dimensional inferences between the two realms have been fully exploited under the “unpenalized loss function + penalty term” formulation for regularization methods and the “likelihood function × shrinkage prior” framework for regularized Bayesian analysis. In particular, we advocate for robust Bayesian variable selection in cancer genomics studies due to its ability to accommodate disease heterogeneity in the form of heavy-tailed errors and structured sparsity while providing valid statistical inference. The numerical results show that robust Bayesian analysis incorporating exact sparsity has yielded not only superior estimation and identification results but also valid Bayesian credible intervals under nominal coverage probabilities compared with alternative methods, especially in the presence of heavy-tailed model errors and outliers. Full article

(This article belongs to the Special Issue Bayesian Learning and Its Applications in Genomics)

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A brief history of frequentist and Bayesian variable selection methods. Full article ">Figure 2
Confidence and credible intervals and their coverage probabilities under a 95% nominal level for the first 10 predictors, where the first 3 are true nonzero coefficients. Data were simulated under AR(1) correlation <math display="inline"><semantics> <mrow> <mo>(</mo> <mi>n</mi> <mo>,</mo> <mi>p</mi> <mo>)</mo> <mo>=</mo> <mo>(</mo> <mn>100</mn> <mo>,</mo> <mn>501</mn> <mo>)</mo> </mrow> </semantics></math> and N(0,1) error across 1000 replicates. Full article ">Figure 3
Confidence and credible intervals and their coverage probabilities under a 95% nominal level for the first 10 predictors, where the first 3 are true nonzero coefficients. Data were simulated under AR(1) correlation <math display="inline"><semantics> <mrow> <mo>(</mo> <mi>n</mi> <mo>,</mo> <mi>p</mi> <mo>)</mo> <mo>=</mo> <mo>(</mo> <mn>100</mn> <mo>,</mo> <mn>501</mn> <mo>)</mo> </mrow> </semantics></math> and t(2) error across 1000 replicates. Full article ">Figure A1
Confidence and credible intervals and their coverage probabilities under a 95% nominal level for the first 10 predictors, where the first 3 are true nonzero coefficients. Data are simulated under independent covariance <math display="inline"><semantics> <mrow> <mo>(</mo> <mi>n</mi> <mo>,</mo> <mi>p</mi> <mo>)</mo> <mo>=</mo> <mo>(</mo> <mn>100</mn> <mo>,</mo> <mn>501</mn> <mo>)</mo> </mrow> </semantics></math> and N(0,1) error across 1000 replicates. Full article ">Figure A2
Confidence and credible intervals and their coverage probabilities under a 95% nominal level for the first 10 predictors, where the first 3 are true nonzero coefficients. Data are simulated under independent covariance <math display="inline"><semantics> <mrow> <mo>(</mo> <mi>n</mi> <mo>,</mo> <mi>p</mi> <mo>)</mo> <mo>=</mo> <mo>(</mo> <mn>100</mn> <mo>,</mo> <mn>501</mn> <mo>)</mo> </mrow> </semantics></math> and t(2) error across 1000 replicates. Full article ">

21 pages, 1064 KiB

Open AccessReview

The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists in the Management of Obesity-Related Heart Failure with Preserved Ejection Fraction: Benefits beyond What Scales Can Measure?

by Paschalis Karakasis, Nikolaos Fragakis, Dimitrios Patoulias, Panagiotis Theofilis, Marios Sagris, Theocharis Koufakis, Panayotis K. Vlachakis, Imran Rashid Rangraze, Mohamed El Tanani, Konstantinos Tsioufis and Manfredi Rizzo

Biomedicines 2024, 12(9), 2112; https://doi.org/10.3390/biomedicines12092112 - 16 Sep 2024

Abstract

Obesity is a significant predisposing factor for heart failure with preserved ejection fraction (HFpEF). Although a substantial proportion of individuals with HFpEF also have obesity, those with obesity are under-represented in clinical trials for heart failure. In turn, current guidelines provided limited recommendations for the medical management of this patient population. Both obesity and diabetes induce a pro-inflammatory state that can contribute to endothelial dysfunction and coronary microvascular impairment, finally resulting in HFpEF. Additionally, obesity leads to increased epicardial and chest wall adiposity, which enhances ventricular interdependence. This condition is further aggravated by plasma and blood volume expansion and excessive vasoconstriction, ultimately worsening HFpEF. Despite the well-documented benefits of GLP-1 receptor agonists in subjects with diabetes, obesity, or both, their role in obesity-related HFpEF remains unclear. In light of the recently published literature, this review aims to investigate the potential mechanisms and synthesize the available clinical evidence regarding the role of GLP-1 receptor agonists in patients with obesity-related HFpEF. Full article

(This article belongs to the Collection Feature Papers in Obesity, Type 2 Diabetes and Metabolic Syndrome)

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The pathophysiological mechanisms underlying obesity-related alterations in cardiac structure and function involve a complex interplay of inflammatory processes and cardiovascular remodeling. Obesity triggers a transformation of adipose tissue into a pro-inflammatory state, which can adversely affect the vasculature and various visceral organs. In heart failure with preserved ejection fraction (HFpEF) patients, coronary microvascular endothelial dysfunction is evidenced by elevated expression of endothelial adhesion molecules, such as vascular cell adhesion molecule (VCAM) and E-selectin, observed in myocardial biopsy specimens. Additionally, pro-inflammatory cytokines stimulate the endothelial generation of reactive oxygen species (ROS) through the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, leading to increased nitrosative and oxidative stress within the myocardium of HFpEF patients. Obesity, along with increased visceral adiposity, is further associated with significant abnormalities in cardiac structure and function, including increased left ventricular (LV) mass, enhanced LV concentric hypertrophy, and more severe LV diastolic dysfunction. The presence of excess adipose tissue also correlates with plasma volume expansion and impaired LV relaxation, likely driven by systemic inflammation. These pathophysiological changes may contribute to reduced ventricular compliance, elevated LV filling pressures, and the characteristic clinical manifestations of HFpEF. Abbreviations: LV, left ventricular; RV, right ventricular; RAAS, renin-angiotensin-aldosterone system; SNS, sympathetic nervous system; NO, nitric oxide; HFpEF, heart failure with preserved ejection fraction. Full article ">Figure 2
The pleiotropic effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and their potential role in management of obesity-related heart failure with preserved ejection fraction (HFpEF). Full article ">Figure 3
In the context of cardiometabolic heart failure with preserved ejection fraction (HFpEF), significant energetic alterations occur. Under normal physiological conditions, the heart primarily relies on fatty acids (approximately 70%) for adenosine triphosphate (ATP) production, supplemented by glucose, branched-chain amino acids, ketone bodies, and lactate. The healthy heart exhibits metabolic flexibility, enabling it to switch between these energy substrates based on nutrient availability. However, in the setting of obesity-associated HFpEF, an excess influx of fatty acids disturbs the balance among these energy substrates, detrimentally affecting cardiac energy homeostasis—for instance, by inhibiting glucose oxidation (as illustrated in the right portion of the figure). This disruption in the physiological substrate oxidation pattern leads to an imbalance in the redox state and alters metabolite availability, which, in turn, modulates cellular signaling pathways through post-translational modifications (PTMs). This imbalance also increases oxidative and nitrosative stress (e.g., reactive nitrogen/oxygen species (R/NOS) production), fostering a state of cardiac hypoxia or pseudohypoxia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to favor glucose oxidation, thereby restoring metabolic flexibility and providing protection against cardiac pseudohypoxia.Abbreviations: ATP, adenosine triphosphate; HIF, hypoxia-inducible factor; GLP-1, glucagon-like peptide-1; NAD+/NADH, Nicotinamide-adenine dinucleotide PDH, pyruvate dehydrogenase; PTMs, post-translational modifications; TCA, tricarboxylic acid; ROS, reactive oxygen species. Full article ">

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