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Article ; Online: Role of CD20+ T cells in cancer, autoimmunity and obesity.

Pinho, Aryane Cruz Oliveira / Laranjeira, Paula / Carvalho, Eugenia

2024 Volume 260, Issue 3

Abstract: Despite the known link between obesity and insulin resistance (IR) to chronic low-grade inflammation, new markers capable of early IR detection are needed. Immune cells are components of adipose tissue's (AT) stromal vascular fraction (SVF) that regulate ...

Abstract	Despite the known link between obesity and insulin resistance (IR) to chronic low-grade inflammation, new markers capable of early IR detection are needed. Immune cells are components of adipose tissue's (AT) stromal vascular fraction (SVF) that regulate AT homeostasis. The altered phenotype and function of AT-infiltrating immune cells may contribute to the development and maintenance of local AT inflammation observed under obesity-induced IR conditions. Impaired AT-specific immunometabolic function may influence the whole organism. Therefore, AT-infiltrating immune cells may be important players in the development of obesity-related metabolic complications, such as type 2 diabetes mellitus (T2DM). B and T cells, particularly CD20+ T cells, play important roles in human pathology, such as autoimmune disease and cancer. However, the question remains as to whether CD20+ T cells have an important contribution to the development of obesity-related IR. While circulating CD20+ T cells are mostly of the central memory phenotype (i.e. antigen-experienced T cells with the ability to home to secondary lymphoid organs), tissues-infiltrated CD20+ T cells are predominantly of the effector memory phenotype (i.e. antigen-experienced T cells that preferentially infiltrate peripheral tissues). The latter produce pro-inflammatory cytokines, such as IFN-γ and IL-17, which play a role in obesity-related IR development. This review describes the CD20 molecule and its presence in both B and T cells, shedding light on its ontogeny and function, in health and disease, with emphasis on AT. The link between CD20+ T cell dysregulation, obesity, and IR development supports the role of CD20+ T cells as markers of adipose tissue dysmetabolism.
MeSH term(s)	Humans ; Autoimmunity ; Diabetes Mellitus, Type 2/metabolism ; Adipose Tissue/metabolism ; Obesity/metabolism ; T-Lymphocytes/metabolism ; Inflammation/metabolism ; Neoplasms/complications ; Neoplasms/metabolism ; Neoplasms/pathology ; Insulin Resistance/genetics
Language	English
Publishing date	2024-02-12
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3028-4
ISSN	1479-6805 ; 0022-0795
ISSN (online)	1479-6805
ISSN	0022-0795
DOI	10.1530/JOE-23-0242
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Article ; Online: Heme Oxygenase-1 as Therapeutic Target for Diabetic Foot Ulcers.

Leal, Ermelindo Carreira / Carvalho, Eugenia

International journal of molecular sciences

2022 Volume 23, Issue 19

Abstract: A diabetic foot ulcer (DFU) is one of the major complications of diabetes. Wound healing under diabetic conditions is often impaired. This is in part due to the excessive oxidative stress, prolonged inflammation, immune cell dysfunction, delayed re- ... ...

Abstract	A diabetic foot ulcer (DFU) is one of the major complications of diabetes. Wound healing under diabetic conditions is often impaired. This is in part due to the excessive oxidative stress, prolonged inflammation, immune cell dysfunction, delayed re-epithelialization, and decreased angiogenesis present at the wound site. As a result of these multifactorial impaired healing pathways, it has been difficult to develop effective therapeutic strategies for DFU. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation generating carbon monoxide (CO), biliverdin (BV) which is converted into bilirubin (BR), and iron. HO-1 is a potent antioxidant. It can act as an anti-inflammatory, proliferative, angiogenic and cytoprotective enzyme. Due to its biological functions, HO-1 plays a very important role in wound healing, in part mediated through the biologically active end products generated by its enzymatic activity, particularly CO, BV, and BR. Therapeutic strategies involving the activation of HO-1, or the topical application of its biologically active end products are important in diabetic wound healing. Therefore, HO-1 is an attractive therapeutic target for DFU treatment. This review will provide an overview and discussion of the importance of HO-1 as a therapeutic target for diabetic wound healing.
MeSH term(s)	Anti-Inflammatory Agents ; Antioxidants ; Biliverdine/metabolism ; Biliverdine/therapeutic use ; Carbon Monoxide/metabolism ; Diabetes Mellitus ; Diabetic Foot/drug therapy ; Heme/metabolism ; Heme Oxygenase (Decyclizing)/metabolism ; Heme Oxygenase-1/metabolism ; Humans ; Iron/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Heme (42VZT0U6YR) ; Carbon Monoxide (7U1EE4V452) ; Iron (E1UOL152H7) ; Heme Oxygenase (Decyclizing) (EC 1.14.14.18) ; Heme Oxygenase-1 (EC 1.14.14.18) ; Biliverdine (O9MIA842K9)
Language	English
Publishing date	2022-10-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231912043
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Article: Green Antimicrobials as Therapeutic Agents for Diabetic Foot Ulcers.

Teixeira, Ines D / Carvalho, Eugenia / Leal, Ermelindo C

Antibiotics (Basel, Switzerland)

2023 Volume 12, Issue 3

Abstract: Diabetic foot ulcers (DFU) are one of the most serious and devastating complications of diabetes and account for a significant decrease in quality of life and costly healthcare expenses worldwide. This condition affects around 15% of diabetic patients ... ...

Abstract	Diabetic foot ulcers (DFU) are one of the most serious and devastating complications of diabetes and account for a significant decrease in quality of life and costly healthcare expenses worldwide. This condition affects around 15% of diabetic patients and is one of the leading causes of lower limb amputations. DFUs generally present poor clinical outcomes, mainly due to the impaired healing process and the elevated risk of microbial infections which leads to tissue damage. Nowadays, antimicrobial resistance poses a rising threat to global health, thus hampering DFU treatment and care. Faced with this reality, it is pivotal to find greener and less environmentally impactful alternatives for fighting these resistant microbes. Antimicrobial peptides are small molecules that play a crucial role in the innate immune system of the host and can be found in nature. Some of these molecules have shown broad-spectrum antimicrobial properties and wound-healing activity, making them good potential therapeutic compounds to treat DFUs. This review aims to describe antimicrobial peptides derived from green, eco-friendly processes that can be used as potential therapeutic compounds to treat DFUs, thereby granting a better quality of life to patients and their families while protecting our fundamental bio-resources.
Language	English
Publishing date	2023-02-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics12030467
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Article ; Online: Adipose-related microRNAs as modulators of the cardiovascular system: the role of epicardial adipose tissue.

Santos, Diana / Carvalho, Eugenia

The Journal of physiology

2021 Volume 600, Issue 5, Page(s) 1171–1187

Abstract: Adipose tissue expansion and subsequent metabolic dysfunction has been considered one of the major risk factors for development of cardiometabolic disease. Epicardial adipose tissue (EAT) in particular is a unique subtype of visceral adipose tissue ... ...

Abstract	Adipose tissue expansion and subsequent metabolic dysfunction has been considered one of the major risk factors for development of cardiometabolic disease. Epicardial adipose tissue (EAT) in particular is a unique subtype of visceral adipose tissue located on the surface of the heart, around the coronary arteries. Due to its proximity, EAT can modulate the local metabolic and immune function of cardiomyocytes and coronary arteries. Several microRNAs have been described as key players in both cardiac and vascular function that when dysregulated will contribute to dysfunction. Here we review the influence of obesity in the crosstalk between specific adipose tissue types, in particular the EAT-secreted microRNAs, as key modulators of cardiac disease progression, not only as early biomarkers but also as therapeutic targets for cardiometabolic disease.
MeSH term(s)	Adipose Tissue/metabolism ; Cardiovascular Diseases ; Coronary Artery Disease/metabolism ; Humans ; Intra-Abdominal Fat/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Pericardium/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-09-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP280917
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Article ; Online: The role of CD20

Pinho, Aryane Cruz Oliveira / Barbosa, Pedro / Pereira, Maria João / Paiva, Artur / Carvalho, Eugenia / Laranjeira, Paula

Cytometry. Part B, Clinical cytometry

2024

Abstract: ... ...

Abstract	CD20
Language	English
Publishing date	2024-05-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2099657-3
ISSN	1552-4957 ; 1552-4949 ; 0196-4763
ISSN (online)	1552-4957
ISSN	1552-4949 ; 0196-4763
DOI	10.1002/cyto.b.22178
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Article ; Online: Innovative Functional Biomaterials as Therapeutic Wound Dressings for Chronic Diabetic Foot Ulcers.

Da Silva, Jessica / Leal, Ermelindo C / Carvalho, Eugénia / Silva, Eduardo A

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: The imbalance of local and systemic factors in individuals with diabetes mellitus (DM) delays, or even interrupts, the highly complex and dynamic process of wound healing, leading to diabetic foot ulceration (DFU) in 15 to 25% of cases. DFU is the ... ...

Abstract	The imbalance of local and systemic factors in individuals with diabetes mellitus (DM) delays, or even interrupts, the highly complex and dynamic process of wound healing, leading to diabetic foot ulceration (DFU) in 15 to 25% of cases. DFU is the leading cause of non-traumatic amputations worldwide, posing a huge threat to the well-being of individuals with DM and the healthcare system. Moreover, despite all the latest efforts, the efficient management of DFUs still remains a clinical challenge, with limited success rates in treating severe infections. Biomaterial-based wound dressings have emerged as a therapeutic strategy with rising potential to handle the tricky macro and micro wound environments of individuals with DM. Indeed, biomaterials have long been related to unique versatility, biocompatibility, biodegradability, hydrophilicity, and wound healing properties, features that make them ideal candidates for therapeutic applications. Furthermore, biomaterials may be used as a local depot of biomolecules with anti-inflammatory, pro-angiogenic, and antimicrobial properties, further promoting adequate wound healing. Accordingly, this review aims to unravel the multiple functional properties of biomaterials as promising wound dressings for chronic wound healing, and to examine how these are currently being evaluated in research and clinical settings as cutting-edge wound dressings for DFU management.
MeSH term(s)	Humans ; Diabetic Foot/drug therapy ; Biocompatible Materials/therapeutic use ; Bandages ; Wound Healing ; Anti-Infective Agents/therapeutic use ; Diabetes Mellitus
Chemical Substances	Biocompatible Materials ; Anti-Infective Agents
Language	English
Publishing date	2023-06-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24129900
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Article: The Role of Nutraceutical Containing Polyphenols in Diabetes Prevention.

Fernandes, Iva / Oliveira, Joana / Pinho, Aryane / Carvalho, Eugenia

Metabolites

2022 Volume 12, Issue 2

Abstract: Research in pharmacological therapy has led to the availability of many antidiabetic agents. New recommendations for precision medicine and particularly precision nutrition may greatly contribute to the control and especially to the prevention of ... ...

Abstract	Research in pharmacological therapy has led to the availability of many antidiabetic agents. New recommendations for precision medicine and particularly precision nutrition may greatly contribute to the control and especially to the prevention of diabetes. This scenario greatly encourages the search for novel non-pharmaceutical molecules. In line with this, the daily and long-term consumption of diets rich in phenolic compounds, together with a healthy lifestyle, may have a protective role against the development of type 2 diabetes. In the framework of the described studies, there is clear evidence that the bio accessibility, bioavailability, and the gut microbiota are indeed affected by: the way phenolic compounds are consumed (acutely or chronically; as pure compounds, extracts, or in-side a whole meal) and the amount and the type of phenolic compounds (ex-tractable or non-extractable/macromolecular antioxidants, including non-bioavailable polyphenols and plant matrix complexed structures). In this review, we report possible effects of important, commonly consumed, phenolic-based nutraceuticals in pre-clinical and clinical diabetes studies. We highlight their mechanisms of action and their potential effects in health promotion. Translation of this nutraceutical-based approach still requires more and larger clinical trials for better elucidation of the mechanism of action toward clinical applications.
Language	English
Publishing date	2022-02-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo12020184
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Article ; Online: Effectiveness of Two Stress Reduction Interventions in Patients with Chronic Diabetic Foot Ulcers (PSY-DFU): Protocol for a Longitudinal RCT with a Nested Qualitative Study Involving Family Caregivers.

Pereira, M Graça / Vilaça, Margarida / Carvalho, Eugenia

International journal of environmental research and public health

2022 Volume 19, Issue 14

Abstract: Diabetic foot ulcer (DFU) is the leading cause of lower-limb amputations, with a significant impact on patients, families, and society. Since DFU medical treatments represent a major socioeconomic burden, cost-effective interventions are needed. This ... ...

Abstract	Diabetic foot ulcer (DFU) is the leading cause of lower-limb amputations, with a significant impact on patients, families, and society. Since DFU medical treatments represent a major socioeconomic burden, cost-effective interventions are needed. This trial aims to assess the effectiveness of a muscle relaxation intervention compared to a hypnosis intervention versus active and passive control groups on DFU healing, physiological indicators of healing prognosis, and quality of life (QoL) in clinically distressed patients with a chronic DFU. A multicenter, randomized controlled trial with three assessment moments (baseline, two months post-intervention, and four months follow-up) will be conducted. Approximately 170 patients will be randomized and allocated to either treatment or control groups. Primary outcomes will be DFU healing, physiological indicators of healing prognosis, and QoL. Secondary outcomes will include perceived stress, psychological morbidity, and DFU representations. The efficacy of sessions on DFU healing will be qualitatively assessed in 12 patients allocated to the treatment and active control groups, as well as their family caregivers. This study will provide evidence regarding the effectiveness of two psychological interventions for the DFU healing process and the QoL of patients, with direct clinical relevance regarding DFU treatment and recurrence.
MeSH term(s)	Amputation, Surgical ; Caregivers ; Diabetes Mellitus ; Diabetic Foot/therapy ; Humans ; Multicenter Studies as Topic ; Quality of Life ; Randomized Controlled Trials as Topic ; Wound Healing
Language	English
Publishing date	2022-07-13
Publishing country	Switzerland
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19148556
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Article ; Online: Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers.

Da Silva, Jessica / Leal, Ermelindo C / Carvalho, Eugénia

Biomolecules

2021 Volume 11, Issue 12

Abstract: Diabetic foot ulcer (DFU) is a devastating complication, affecting around 15% of diabetic patients and representing a leading cause of non-traumatic amputations. Notably, the risk of mixed bacterial-fungal infection is elevated and highly associated with ...

Abstract	Diabetic foot ulcer (DFU) is a devastating complication, affecting around 15% of diabetic patients and representing a leading cause of non-traumatic amputations. Notably, the risk of mixed bacterial-fungal infection is elevated and highly associated with wound necrosis and poor clinical outcomes. However, it is often underestimated in the literature. Therefore, polymicrobial infection control must be considered for effective management of DFU. It is noteworthy that antimicrobial resistance is constantly rising overtime, therefore increasing the need for new alternatives to antibiotics and antifungals. Antimicrobial peptides (AMPs) are endogenous peptides that are naturally abundant in several organisms, such as bacteria, amphibians and mammals, particularly in the skin. These molecules have shown broad-spectrum antimicrobial activity and some of them even have wound-healing activity, establishing themselves as ideal candidates for treating multi-kingdom infected wounds. Furthermore, the role of AMPs with antifungal activity in wound management is poorly described and deserves further investigation in association with antibacterial agents, such as antibiotics and AMPs with antibacterial activity, or alternatively the application of broad-spectrum antimicrobial agents that target both aerobic and anaerobic bacteria, as well as fungi. Accordingly, the aim of this review is to unravel the molecular mechanisms by which AMPs achieve their dual antimicrobial and wound-healing properties, and to discuss how these are currently being applied as promising therapies against polymicrobial-infected chronic wounds such as DFUs.
MeSH term(s)	Antimicrobial Peptides/pharmacology ; Antimicrobial Peptides/therapeutic use ; Bacteria/drug effects ; Bacteria/growth & development ; Biological Factors/pharmacology ; Biological Factors/therapeutic use ; Diabetic Foot/drug therapy ; Diabetic Foot/microbiology ; Drug Resistance, Bacterial/drug effects ; Drug Resistance, Fungal/drug effects ; Fungi/drug effects ; Fungi/growth & development ; Humans ; Wound Infection/drug therapy ; Wound Infection/microbiology
Chemical Substances	Antimicrobial Peptides ; Biological Factors
Language	English
Publishing date	2021-12-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11121894
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Article ; Online: Real-time OXPHOS capacity analysis in wounded skin from diabetic mice: A pilot study.

Pinho, Aryane Cruz Oliveira / Santos, Diana / Oliveira, Paulo J / Leal, Ermelindo Carreira / Carvalho, Eugenia

European journal of clinical investigation

2023 Volume 54, Issue 3, Page(s) e14128

Abstract: Introduction: Diabetes mellitus (DM) impairs wound healing. The aim was to determine whether DM influences mitochondrial respiration in wounded skin (WS) and non-wounded skin (NWS), in a pre-clinical wound healing model of streptozotocin (STZ)-induced ... ...

Abstract	Introduction: Diabetes mellitus (DM) impairs wound healing. The aim was to determine whether DM influences mitochondrial respiration in wounded skin (WS) and non-wounded skin (NWS), in a pre-clinical wound healing model of streptozotocin (STZ)-induced diabetes. Methods: Six weeks after diabetes induction, two wounds were created in the back of C57BL/J6 mice. Using high-resolution respirometry (HRR), oxygen flux was measured, in WS and NWS, using two substrate-uncoupler-inhibitor titration protocols, at baseline (day 0), day 3 and 10 post-wounding, in STZ-DM and non-diabetic (NDM) mice. Flux control ratios for the oxidative phosphorylation (OXPHOS) capacity were calculated. Results: A significant increase in mitochondrial respiration was observed in STZ-DM skin compared to control skin at baseline. The OXPHOS capacity was decreased in WS under diabetes at day 3 post-wounding (inflammation phase). However, at day 10 post-wounding (remodeling phase), the OXPHOS capacity was higher in WS from STZ-DM compared to NDM mice, and compared to NWS from STZ-DM mice. A significant relative contribution of pyruvate, malate and glutamate (PMG) oxidation to the OXPHOS capacity was observed in WS compared to NWS from STZ-DM mice, at day 10, while the relative contribution of fatty acid oxidation to the OXPHOS capacity was higher in NWS. The OXPHOS capacity is altered in WS from STZ-DM compared to NDM mice across the healing process, and so is the substrate contribution in WS and NWS from STZ-DM mice, at each time point. Conclusion: HRR may be a sensitive tool to evaluate the underlying mechanisms of tissue repair during wound healing.
MeSH term(s)	Mice ; Animals ; Oxidative Phosphorylation ; Diabetes Mellitus, Experimental/metabolism ; Pilot Projects ; Mice, Inbred C57BL ; Skin/metabolism
Language	English
Publishing date	2023-11-17
Publishing country	England
Document type	Journal Article
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.14128
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