Research

23 pages, 8756 KiB

Open AccessArticle

Insights into the Mechanism of Action of Helianthus annuus (Sunflower) Seed Essential Oil in the Management of Type-2 Diabetes Mellitus Using Network Pharmacology and Molecular Docking Approaches

by Athika Rampadarath, Fatai Oladunni Balogun and Saheed Sabiu

Endocrines 2023, 4(2), 327-349; https://doi.org/10.3390/endocrines4020026 - 02 May 2023

Cited by 3 | Viewed by 1907

Abstract

Type-2 diabetes mellitus (T2D) is one of the leading non-communicable diseases of global concern. Knowing the exact mechanism of action of available antidiabetic agents, particularly natural products, may assist in providing effective therapeutic solutions. The antidiabetic action of Helianthus annuus (sunflower) seed has [...] Read more.

Type-2 diabetes mellitus (T2D) is one of the leading non-communicable diseases of global concern. Knowing the exact mechanism of action of available antidiabetic agents, particularly natural products, may assist in providing effective therapeutic solutions. The antidiabetic action of Helianthus annuus (sunflower) seed has been established; however, the molecular mechanism of action, especially the essential oil, is lacking. The study explored network pharmacology and molecular docking studies to determine the active phytoconstituents, signaling pathways, and probable therapeutic targets to determine the antidiabetic potential of sunflower seed essential oil. Preliminary analysis established 23 target genes with 15 phytoconstituents involved in T2D which all passed Lipinski’s rule of five with no violation. Three pathways were proposed by KEGG analysis as therapeutic targets for T2D development with PPAR as the major route affecting PPARA, FABP4, PPARD, PPARG, and CPT2 genes. Molecular docking investigation confirmed the effectiveness of active SSEO compounds against the identified genes (targets) and established phylloquinone, linoleic acid, tricosylic acid, and lignoceric acid as the probable drug candidates that could offer laudable therapeutic effects in an effort towards T2D management. Thereby, we present an insight toward understanding the mechanism of the antidiabetic action of sunflower seeds via the stimulation of glucose to enhance insulin release. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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15 pages, 2551 KiB

Open AccessArticle

High-Intensity Interval Cycling and Running Yield a Similar Myokine and Osteokine Response in Young Adult Females

by Giti Borzooeian, Steven Kottaras, Rozalia Kouvelioti, Madison Bell, Wendy E. Ward, Evangelia Tsiani and Panagiota Klentrou

Endocrines 2023, 4(2), 312-326; https://doi.org/10.3390/endocrines4020025 - 01 May 2023

Cited by 1 | Viewed by 1575

Abstract

Background: The differential responses of the myokine irisin, in combination with changes in markers and regulators of bone remodeling to high-intensity interval exercise of high and low impact, were examined in 18 young adult females (22.5 ± 2.7 years). Methods: Participants performed two [...] Read more.

Background: The differential responses of the myokine irisin, in combination with changes in markers and regulators of bone remodeling to high-intensity interval exercise of high and low impact, were examined in 18 young adult females (22.5 ± 2.7 years). Methods: Participants performed two high-intensity interval exercise trials in random order: running on a treadmill and cycling on a cycle ergometer. Trials consisted of eight 1 min running or cycling intervals at ≥ 90% of maximal heart rate, separated by 1 min passive recovery intervals. Blood samples were collected at rest (pre-exercise) and 5 min, 1 h, and 24 h following each exercise trial. Irisin, osteocalcin, sclerostin, osteoprotegerin (OPG), receptor activator nuclear factor kappa-β ligand (RANKL), and parathyroid hormone (PTH) were analyzed in serum, with post-exercise concentrations being corrected for exercise-induced changes in plasma volume. Results: Irisin was elevated 24 h post-exercise compared to its resting values in both trials (20%, p < 0.05) and was higher after cycling compared to running (exercise mode effect, p < 0.05) with no interaction. Osteocalcin, sclerostin, PTH, and RANKL increased from pre- to 5 min post-exercise (18%, 37%, 83%, and 33%, respectively, p < 0.05), returning to baseline levels in 1 h, with no trial or interaction effects. OPG showed a time effect (p < 0.05), reflecting an overall increase at 5 min and 1 h post-exercise, which was not significant after the Bonferroni adjustment. Conclusions: In young adult females, high-intensity interval exercise induced an immediate response in markers and regulators of bone remodeling and a later response in irisin concentrations, which was independent of the gravitational impact. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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11 pages, 540 KiB

Open AccessArticle

The Impact of COVID-19 Regulations on Adherence to Recombinant Human Growth Hormone Therapy: Evidence from Real-World Data

by Paula van Dommelen, Rosa Maria Baños, Lilian Arnaud, Quentin Le Masne and Ekaterina Koledova

Endocrines 2023, 4(1), 194-204; https://doi.org/10.3390/endocrines4010017 - 09 Mar 2023

Viewed by 1309

Abstract

Worldwide regulations during COVID-19 positively and negatively impacted self-management in paediatric patients with chronic medical conditions. We investigated the impact of regulations on adherence to recombinant human growth hormone (r-hGH) therapy in paediatric patients with growth disorders, using real-world adherence data extracted March [...] Read more.

Worldwide regulations during COVID-19 positively and negatively impacted self-management in paediatric patients with chronic medical conditions. We investigated the impact of regulations on adherence to recombinant human growth hormone (r-hGH) therapy in paediatric patients with growth disorders, using real-world adherence data extracted March 2019–February 2020 (before COVID-19) and March 2020–February 2021 (during COVID-19) from the easypod™ connect ecosystem. Data from three measures of regulations were analysed: stringency index (SI), school closure and stay-at-home. The mean SI, and the proportion of days with required school closure or stay-at-home during COVID-19 were categorised as high versus medium/low based on the 75th percentile. Adherence was categorised as optimal (≥85%) versus suboptimal (<85%). Adherence data were available for 8915 patients before and 7606 patients during COVID-19. A high SI (mean ≥68) and a high proportion of required school closure (≥88%) resulted in an increase in the proportion of optimal adherence during COVID-19 versus pre-COVID-19 (p < 0.001). Stay-at-home requirements showed no statistically significant effect (p = 0.13). Stringent COVID-19 regulations resulted in improved adherence to r-hGH therapy in patients with growth disorders, supported by connected digital health technologies. Insights into patient behavior during this time are useful to understand potential influences and strategies to improve long-term adherence to r-hGH. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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Review

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14 pages, 1040 KiB

Open AccessReview

Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy

by Guy Leclercq

Endocrines 2024, 5(1), 102-115; https://doi.org/10.3390/endocrines5010007 - 06 Mar 2024

Viewed by 682

Abstract

The evolution of breast cancers results from the emergence of epithelial cell subpopulations containing variant Estrogen Receptor α which is able to bypass conventional treatments aimed at antagonizing the activity of this tumor-promoting receptor. The present investigation concerns a few estradiol derivates bearing [...] Read more.

The evolution of breast cancers results from the emergence of epithelial cell subpopulations containing variant Estrogen Receptor α which is able to bypass conventional treatments aimed at antagonizing the activity of this tumor-promoting receptor. The present investigation concerns a few estradiol derivates bearing substituents in position 11β that might not only contribute to the development of drugs to alleviate this unfortunate issue but that may be also helpful in identifying molecular aspects of resistance to this receptor in order to elaborate other therapeutic approaches. In this regard, AP-1 assisted and ERE-directed ERα transcriptions are demonstrated to be key factors in this area: AP-1 transcriptions are shown to antagonize ERE transcriptions, thereby limiting their tumor-promoting activity. This property results from a conformal change in the receptor, which is induced essentially by estrogenic ligands which, inserted into a cavity of ERα’s ligand-binding pocket, govern this regulatory mechanism. Flexible 11β side-chains favor this insertion, in contrast to their rigid counterparts, which counteract it; these properties give rise to strong estrogenic, SERM or SERD profiles. Suspected extracellular regulatory mechanisms resulting from these ligand-induced transcriptions are elaborated on in the present work in the context of breast cancer development. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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16 pages, 347 KiB

Open AccessReview

Focus on Thyroid Cancer in Elderly Patients

by Rosa Lauretta, Marta Bianchini, Marilda Mormando, Giulia Puliani and Marialuisa Appetecchia

Endocrines 2023, 4(4), 757-771; https://doi.org/10.3390/endocrines4040055 - 05 Dec 2023

Viewed by 1598

Abstract

Thyroid cancer is more aggressive in elderly patients due to biological causes related to age, histotype, and the advanced stage at diagnosis. In the elderly, both the diagnosis and treatment of thyroid cancer impact quality of life. This review aimed to collect and [...] Read more.

Thyroid cancer is more aggressive in elderly patients due to biological causes related to age, histotype, and the advanced stage at diagnosis. In the elderly, both the diagnosis and treatment of thyroid cancer impact quality of life. This review aimed to collect and discuss the different therapeutic approaches in elderly patients affected by thyroid cancer. Our analysis examined the therapeutic surgical approach according to age and how this affects the prognosis of patients with thyroid cancer, along with how iodine 131 therapy is tolerated and how effective it is. Furthermore, we investigated whether levothyroxine suppressive therapy is always necessary and safe in elderly patients with thyroid cancer and the safety and efficacy of systemic therapy in the elderly. We also intended to identify peculiar features of thyroid cancer in elderly subjects and to evaluate how the disease and its treatment affect their quality of life. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

14 pages, 969 KiB

Open AccessReview

Anti-Dyslipidemic and Anti-Diabetic Properties of Corosolic Acid: A Narrative Review

by Rossella Cannarella, Vincenzo Garofalo and Aldo E. Calogero

Endocrines 2023, 4(3), 616-629; https://doi.org/10.3390/endocrines4030044 - 01 Sep 2023

Viewed by 2410

Abstract

Corosolic acid (CA), a natural compound derived from the Banaba tree (Lagerstroemia speciosa), has attracted attention for its potential therapeutic properties in the management of metabolic diseases. This narrative review aims to summarize the current evidence on the anti-dyslipidemic, anti-diabetic, and [...] Read more.

Corosolic acid (CA), a natural compound derived from the Banaba tree (Lagerstroemia speciosa), has attracted attention for its potential therapeutic properties in the management of metabolic diseases. This narrative review aims to summarize the current evidence on the anti-dyslipidemic, anti-diabetic, and anti-inflammatory effects of CA and to understand the pharmacokinetics and molecular mechanisms through the analysis of preclinical and clinical studies. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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22 pages, 1430 KiB

Open AccessReview

Hormones and Signaling Pathways Involved in the Stimulation of Leydig Cell Steroidogenesis

by Karine de Mattos, Kenley Joule Pierre and Jacques J. Tremblay

Endocrines 2023, 4(3), 573-594; https://doi.org/10.3390/endocrines4030041 - 01 Aug 2023

Cited by 2 | Viewed by 2626

Abstract

Leydig cells, located in the testis interstitial space, are the primary source of testosterone in males. Testosterone plays critical roles in both reproductive and metabolic functions and therefore is essential for male health. Steroidogenesis must be properly regulated since dysregulated hormone production can [...] Read more.

Leydig cells, located in the testis interstitial space, are the primary source of testosterone in males. Testosterone plays critical roles in both reproductive and metabolic functions and therefore is essential for male health. Steroidogenesis must be properly regulated since dysregulated hormone production can lead to infertility and metabolic disorders. Leydig cell steroidogenesis relies on the coordinated interaction of various factors, such as hormones and signaling molecules. While luteinizing hormone (LH) is the main regulator of Leydig cell steroidogenesis, other molecules, including growth hormones (GH), prolactin, growth factors (insulin, IGF, FGF, EGF), and osteocalcin, have also been implicated in the stimulation of steroidogenesis. This review provides a comprehensive summary of the mechanisms and signaling pathways employed by LH and other molecules in the stimulation of Leydig cell steroidogenesis, providing valuable insights into the complex regulation of male reproductive and metabolic health. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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20 pages, 1742 KiB

Open AccessReview

Role of the Androgen Receptor in Gender-Related Cancers

by Emilia Sabbatino, Viviana Tutino, Fabrizio Licitra, Marzia Di Donato, Gabriella Castoria, Antimo Migliaccio and Pia Giovannelli

Endocrines 2023, 4(2), 407-426; https://doi.org/10.3390/endocrines4020031 - 01 Jun 2023

Viewed by 1827

Abstract

The androgen receptor (AR) is expressed in many cell types, and its related signaling is widely investigated in hormone-dependent cancers such as prostate and breast. The significance of the AR, however, has been detected even in other cancers, including gastric, bladder, kidney, lung, [...] Read more.

The androgen receptor (AR) is expressed in many cell types, and its related signaling is widely investigated in hormone-dependent cancers such as prostate and breast. The significance of the AR, however, has been detected even in other cancers, including gastric, bladder, kidney, lung, hepatic, and pancreatic, in which growth and spreading are not strictly or notoriously dependent on sex steroid hormone action. The incidence and mortality of these cancers are, however, somewhat related to gender and, specifically, are higher in men than in women, with the ratio reaching 3–4:1 for bladder cancer. This direct correlation between cancer incidence, mortality, and gender makes sex one of the most important risk factors for these cancers and has incited investigation about the role of sex steroid receptors and their activating hormones in gender-related cancers. In these cancers, the AR is often expressed and seems to play a pivotal role in different processes contributing to cancer onset and progression such as growth, spreading, and epithelial to mesenchymal transition (EMT). This manuscript will offer an overview of the role of the AR in many cancers of the respiratory and gastrointestinal systems wherein its role has been at least partially analyzed. Understanding the role of the AR in these tumors could help us to identify a new biomarker for early diagnostic guidance and to develop better therapeutic approaches by directly targeting the AR or its downstream signaling in individual cells of hormone-related cancers at different stages. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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16 pages, 6049 KiB

Open AccessReview

Chronic Stress-Related Osteosarcopenic Obesity: A Common Modern Syndrome Requiring Sustained Lifestyle Changes and Stress Management

by Nektaria Papadopoulou-Marketou, Anna Papageorgiou and George P. Chrousos

Endocrines 2023, 4(2), 378-393; https://doi.org/10.3390/endocrines4020029 - 15 May 2023

Cited by 1 | Viewed by 1760

Abstract

Through several pathological mechanisms, chronic stress contributes to the development of “osteosarcopenic obesity”, a clinical syndrome that includes impairments in the structure and function of a patient’s bones, skeletal muscles, and adipose tissue. This syndrome, which could be alternatively called “chronic stress and [...] Read more.

Through several pathological mechanisms, chronic stress contributes to the development of “osteosarcopenic obesity”, a clinical syndrome that includes impairments in the structure and function of a patient’s bones, skeletal muscles, and adipose tissue. This syndrome, which could be alternatively called “chronic stress and inflammation syndrome”, has its genesis in early life and, by the age of 50–60 years, affects up to two-thirds of Western populations. Chronic psycho-socioeconomic stress and lifestyle factors, such as a sedentary life, poor quality nutrition, irregular daily schedules, and inadequate sleep, which all act on a genetic and epigenetic predisposition background, play essential pathogenic roles in the development of this widespread syndrome. Key pathogenic mediators are those of the stress system and inflammatory reaction. Lifestyle changes, in combination with stress management, can prevent, arrest, or reverse this debilitating syndrome. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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16 pages, 1709 KiB

Open AccessReview

The Androgen Regulation of Matrix Metalloproteases in Prostate Cancer and Its Related Tumor Microenvironment

by Carmela Sorrentino, Rosa D’Angiolo, Giulia Gentile, Pia Giovannelli, Bruno Perillo, Antimo Migliaccio, Gabriella Castoria and Marzia Di Donato

Endocrines 2023, 4(2), 350-365; https://doi.org/10.3390/endocrines4020027 - 09 May 2023

Viewed by 1667

Abstract

Prostate cancer represents the most common type of cancer among males and the second leading cause of cancer death in men in Western society. In most cases (~70%), PC has a slow and symptom-free growth, whereas it is more aggressive in the remaining [...] Read more.

Prostate cancer represents the most common type of cancer among males and the second leading cause of cancer death in men in Western society. In most cases (~70%), PC has a slow and symptom-free growth, whereas it is more aggressive in the remaining patients. Current PC therapies prevalently target the proliferative function of the androgen receptor and may only be effective within short periods, beyond which the disease will progress to metastatic and castration-resistant phenotype. Preclinical and clinical studies are aimed at investigating the molecular basis for prostate cancer spreading. Although considerable efforts have been made to dissect the programs that foster prostate cancer spreading, few biomarkers predictive of metastatic phenotype have yet been identified and few therapeutic options are available for treatment of the metastatic disease. In the present paper, we will discuss innovative aspects of prostate cancer biology, which impinge on the role of cancer-associated fibroblasts and the released matrix metalloproteinases in the disease progression. Investigating these aspects might allow the discovery of clinically actionable biomarkers to target in the advanced stages of prostate cancer. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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14 pages, 2351 KiB

Open AccessReview

The Role of Ketone Bodies in Various Animal Models of Kidney Disease

by Haoxin Liu and Liang-Jun Yan

Endocrines 2023, 4(1), 236-249; https://doi.org/10.3390/endocrines4010019 - 16 Mar 2023

Cited by 1 | Viewed by 4820

Abstract

The kidney is a vital organ that carries out significant metabolic functions in our body. Due to the complexity of its role, the kidney is also susceptible to many disease conditions, such as acute kidney injury (AKI) and chronic kidney disease (CKD). Despite [...] Read more.

The kidney is a vital organ that carries out significant metabolic functions in our body. Due to the complexity of its role, the kidney is also susceptible to many disease conditions, such as acute kidney injury (AKI) and chronic kidney disease (CKD). Despite the prevalence and our increased understanding of the pathophysiology of both AKI and CKD as well as the transition of AKI to CKD, no well-established therapeutics have been applied clinically to these conditions, rendering an urgent need for a novel potential therapeutic target to be developed. In this article, we reviewed the function of ketone bodies in some common kidney conditions, such as drug-induced nephrotoxicity, ischemia and reperfusion injury, fibrosis development, diabetic kidney disease, kidney aging, hypertension, and CKD progression. All the selected studies reviewed were performed in animal models by primarily utilizing rodents, which also provide invaluable sources for future clinical applications. Ketone bodies have shown significant renal protective properties via attenuation of oxidative stress, increased expression of anti-inflammatory proteins, gene regulation, and a reduction of apoptosis of renal cells. A physiological level of ketone bodies could be achieved by fasting, a ketogenic diet, and an exogenous ketone supplement. Finally, the limitations of the long-term ketogenic diet were also discussed. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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Other

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11 pages, 451 KiB

Open AccessPerspective

Insulin Resistance and Glucose Metabolism during Infection

by Borros Arneth

Endocrines 2023, 4(4), 685-695; https://doi.org/10.3390/endocrines4040049 - 07 Oct 2023

Viewed by 1295

Abstract

Specific critical functions of endocrine and immune cells ensure that an individual remains healthy and free from infection. This study aimed to explore immune–endocrine associations involved in disease. Methods: The PsycINFO, PubMed, Web of Science, and CINAHL databases were searched for relevant articles [...] Read more.

Specific critical functions of endocrine and immune cells ensure that an individual remains healthy and free from infection. This study aimed to explore immune–endocrine associations involved in disease. Methods: The PsycINFO, PubMed, Web of Science, and CINAHL databases were searched for relevant articles using the following search terms and phrases: “hormones”, “hormonal responses”, “immune system”, “endocrine system”, “infection”, “immune cells”, “endocrine cells”, “infection”, “immune”, “endocrine”, and “interactions”. The search was limited to articles published between 2009 and 2023. Results: A review of ninety-three studies showed that metabolic activity levels in the body as well as energy consumption patterns are affected by feedback loops that connect the endocrine and immune systems. The associations between endocrine cells and immune cells are complex and involve a wide range of hormones, molecules, and receptors related to antipathogen responses and metabolic regulation. Conclusions: During infection, endocrine cells and immune cells interact via feedback loops to ensure optimal energy utilization and a timely response to pathogens. Therefore, the endocrine system helps to regulate systemic metabolism while controlling the outcomes of regulatory elements of the immune system. Full article

(This article belongs to the Special Issue Feature Papers in Endocrines 2023)

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