Endocrines

Diet has an impact on male reproductive potential, but few studies have focused on the specific impact of food groups or dietary patterns on fertility. Male reproductive health, as indicated by improved semen parameters and increased chances of conceiving, is associated with the Mediterranean diet, while the Western diet is considered a risk factor for male infertility. The potential mechanisms that may explain the impact of these diets on semen quality are still largely unknown. However, numerous studies suggest that nutritional interventions are crucial for the preservation and improvement of male fertility. This review aims to summarize the most recent evidence on the influence of components of the Mediterranean diet on sperm parameters. Unlike other risk factors, dietary modulation represents a great opportunity for improving overall health and can also be an important tool in recommendations for male reproductive health. Full article

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

The increased frequency of type 2 diabetes worldwide has led to a concomitant increase in pregnancies complicated by type 2 diabetes for the past 20 years. This is mainly due to two factors: the earlier age of diabetes onset and the advanced age of pregnancy occurrence. Patients with type 2 diabetes in pregnancy show a high frequency of maternal and fetal complications, posing a series of problems in the follow-up of these women. In this narrative review, changes in epidemiology, maternal and fetal complications, and evidence of critical unmet needs before and during pregnancy complicated by type 2 diabetes are reported and discussed to review the possible approaches. Full article

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

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

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

Given the demanding daily regimen for type 1 diabetes (T1D) and emphasis on personal responsibility for self-management, people with T1D can experience self-criticism and diabetes distress. How an individual responds to and copes with diabetes-related feedback may influence self-care, health outcomes, and overall well-being. Self-compassion in the context of diabetes has limited but promising research on its ability to alleviate distress in people with T1D. This narrative review captures relevant, existing literature on self-compassion, compassion-based interventions, and T1D and describes four topic areas where diabetes-specific self-compassion and compassion-based interventions may be particularly relevant: (1) diabetes technology use; (2) relationship with eating and body image; (3) social interactions; and (4) healthcare interactions. Compassion-based interventions have the potential to enhance positive coping skills and to alleviate diabetes distress; more research is needed to understand the role of diabetes-specific self-compassion and to develop high-quality evidence-based interventions. Full article

Longitudinal growth and puberty are the result of a complex interaction of genetic, hormonal, nutritional, and environmental factors. Acne vulgaris is a chronic disease of the pilosebaceous unit that affects 85% of adolescents worldwide. Isotretinoin is a synthetic vitamin A derivative drug effective and is widely employed for the treatment of moderate and severe acne vulgaris. Premature epiphyseal closure has been reported in patients with neuroblastoma treated with high doses of isotretinoin as well as in patients with acne receiving lower doses. Although the mechanisms for these effects are not clear, it has been suggested that isotretinoin may have a negative impact on the GH-IGF-I axis, leading to a reduction in IGF-I and IGFBP3 serum levels. Although many of the isotretinoin adverse effects in pediatric patients are transient, premature epiphyseal closure and bone abnormalities can lead to transient abnormalities and permanent deformities with a negative impact on longitudinal growth and final height. The aim of this study was to review the potential effects of oral isotretinoin on the growth plate and growth during childhood and adolescence. Full article

Sex hormones and their receptors play a crucial role in human sexual dimorphism and have been traditionally associated with hormone-dependent cancers like breast, prostate, and endometrial cancer. However, recent research has broadened our understanding by revealing connections with other types of cancers, such as lung cancer, where the androgen receptor has been found to be particularly significant. This review aims to explore the molecular mechanisms of androgen action in lung cancer pathogenesis and progression, highlighting the potential of inhibiting the androgen receptor signaling pathway as a therapeutic strategy for lung cancer treatment. Full article

Insulin resistance (IR) is considered cardinal to the pathophysiology of metabolic syndrome (MetS). Previously, several simple indexes of IR calculated from biochemical and anthropometric variables have been proposed. However, these indexes are population-dependent; therefore, further studies on a global scale are necessary. The present study assessed the diagnostic accuracy of eight IR indicators, namely, METS-IR, TG-HDL-c, TyG, TyG-BMI, TyG-NC, TyG-NHtR, TyG-WC, and TyG-WHtR, in indicating MetS among a Brazilian population. For this, 268 patients (152 men and 116 women, 53–59 years of age) were included in the study, out of which 111 were diagnosed with MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). All indexes achieved significant accuracy, with TyG-WC (0.849 (0.800–0.889)), TyG (0.837 (0.787–0.879)), and TG-HDL-c (0.817 (0.765–0.861)) having the highest area under the curve (AUC). Further, the most heightened diagnostic sensitivities were observed for TG-HDL-c (90.99%), TyG-WC (89.19%), and TyG-NC (84.68%), whereas the highest diagnostic specificities were noted for TyG (73.89%), TyG-WHtR (72.61%), and TyG-WC (66.88%). Thus, TyG-WC, TyG, and TG-HDL-c reached the greatest AUC values in our analyses, making them useful diagnostic indicators of MetS, and crucial for patients’ clinical management. Full article

Estradiol promotes neuronal growth, transmission, survival, myelinization, plasticity, synaptogenesis, and dendritic branching and it improves cognitive function. Alzheimer’s disease (AD) is characterized by amyloid plaques, neurofibrillary tangles, and the loss of neuronal connection in the brain. Genomic analysis has concluded that hypoestrogenism influences the APOE gene and increases the risk of AD. Premature ovarian insufficiency (POI) is defined as oligo/amenorrhea in women below 40 years of age, low estradiol, and high-gonadotropin levels. Early symptoms and signs of POI must be detected in time in order to prevent subsequent complications, such as Alzheimer’s disease. Meta-analysis has shown favorable effects of estrogen in preventing Alzheimer’s. We measured some of the typical markers of AD in women with POI such as interleukin 6 (IL-6), interleukin 8 (IL-8), tissue necrosis factor α (TNFα), TAU1, TREM2, and amyloid precursor proteins (APP). While FSH, LH, and IL-8 were significantly higher in POI group, compared to controls, testosterone and DHEAS were lower. A significant decrease in IL-6 was found in the POI group during a 6-month therapy, as well as an increase in amyloid precursor proteins. CONCLUSION: Neurological complications of POI, such as declining short-term memory, cognitive function, and dementia, have to be promptly stopped by initiating estro-progestogen therapy in POI. A long-term continuation of the therapy would be strongly advised. Full article

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

Parathyroid carcinoma (PC) is a very rare endocrine cancer with aggressive behavior, a high metastatic potential, and a poor prognosis. Surgical resection of affected gland(s) and other involved structures is the elective therapy. Pre-operative and intra-operative differential diagnosis with benign parathyroid adenoma remains a challenge. The lack of a clear pre-operative diagnosis does not allow one, in many cases, to choose the correct surgical approach to malignant PC, increasing persistence, the recurrence rate, and the risk of metastases. An initial wrong diagnosis of parathyroid adenoma, with a minimally invasive parathyroidectomy, is associated with over 50% occurrence of metastases after surgery. Genetic testing could help in identifying patients at risk of congenital PC (i.e., CDC73 gene) and in driving the choice of neck surgery extension. Targeted effective treatments, other than surgery, for advanced and metastatic PC are needed. The pathogenesis of malignant parathyroid carcinogenesis is still largely unknown. In the last few years, advanced molecular techniques allowed researchers to identify various genetic abnormalities and epigenetic features characterizing PC, which could be crucial for selecting molecular targets and developing novel targeted therapeutic agents. We reviewed current findings in PC genetics, epigenetics, and proteomics and state-of-the-art therapies. Full article

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

Introduction: The Krebs cycle is an important set of reactions that synthesize different molecules and substances that affect various organs. The objective of this paper was to compare the effects of Krebs cycle intermediates on the endocrine system and the immune system. Methods and Materials: The articles used in this paper were obtained from a systematic search of PsycINFO, PubMed, Web of Science, CINAHL, and primary databases. The search terms were “Krebs cycle,” “intermediates,” “endocrine system,” “tricarboxylic acid,” “citric acid cycle,” and “immune system,” and Boolean operators (AND/OR) were used to combine terms. Results: A review of the selected studies showed that Krebs cycle intermediates influence how the endocrine system regulates and controls body processes, including energy uptake. Moreover, these intermediates have both direct and indirect effects on immune function, memory, and activation. Discussion: An understanding of the effects of Krebs cycle intermediates on endocrine and immune processes will provide valuable insights for the development of new therapies. Additionally, this knowledge is a basis for exploring the pathogenesis of the complications related to endocrine system function and for evaluating the immune system response to pathogens. Conclusions: The evidence gathered in this review shows that Krebs cycle intermediates have significant effects on immune and endocrine processes. However, further human and in vivo studies are required to generate additional evidence for the underlying pathways and to identify the potential strategies for targeting these mechanisms to manage specific disorders. Full article

Background: Several studies have evaluated the role of IGF-1 in the diagnosis of growth hormone deficiency (GHD). According to a recent study, an IGF-1 concentration of a −1.5 standard deviation score (SDS) appeared to be the best cut-off for distinguishing between children with GHD and normal children. This value should always be interpreted in conjunction with other clinical and biochemical parameters for the diagnosis of GHD, since both stimulation tests and IGF-1 assays have poor diagnostic accuracy by themselves. Our study was designed to evaluate the adult height (AH) in children with short stature and baseline IGF-1 concentration ≤ −1.5 SDS. Design: This retrospective analysis included 52 children and adolescents evaluated over the last 30 years for short stature and/or deceleration of the growth rate who underwent diagnostic procedures to evaluate a possible GHD. Only the patients who had baseline IGF-1 values $\le$−1.5 SDS at the time of the first test were included in the study. Patients with genetic/organic GHD or underlying diseases were not included. Method: The case group consisted of 24 patients (13 boys and 11 girls) with non-permanent, idiopathic, and isolated GHD (peak GH < 10 μg/L after two provocative tests with arginine (Arg), insulin tolerance test (ITT), and clonidine (Clo), or <20 μg/L after GHRH + Arginine (GHRH+Arg); normal MRI; normal GH; and/or normal IGF-1 concentrations at near-AH). These patients were treated with GH (25–35 μg/kg/die) until near-AH. The control group consisted of 28 patients (23 boys and 5 girls) with idiopathic short stature (ISS, normal peak GH after provocative testing, no evidence of other causes for their shortness). Both groups had basal IGF-1 ≤−1.5 SDS. Results: AH and height gain in both groups were comparable. In the group of cases, mean IGF-1 SDS at the time of diagnosis was significantly lower than the levels found at the time of retesting. Conclusions: In this study, both treated patients with idiopathic GHD and untreated patients with ISS reached similar near-AHs (within target height) and showed similar increases in SDS for their height. Thus, the efficacy of treatment with rhGH in these patients may be questionable. This could be due to the fact that children with ISS are frequently misdiagnosed with GHD. Full article

X-linked hypophosphatemia (XLH) is characterized by mutations in the PHEX gene, leading to elevated serum levels of FGF23, decreased production of 1,25 dihydroxyvitamin D₃ (1,25D), and hypophosphatemia. Those affected with XLH manifest impaired growth and skeletal and dentoalveolar mineralization as well as increased mineralization of the tendon–bone attachment site (enthesopathy), all of which lead to decreased quality of life. Many molecular and murine studies have detailed the role of mineral ions and hormones in regulating complications of XLH, including how they modulate growth and growth plate maturation, bone mineralization and structure, osteocyte-mediated mineral matrix resorption and canalicular organization, and enthesopathy development. While these studies have provided insight into the molecular underpinnings of these skeletal processes, current therapies available for XLH do not fully prevent or treat these complications. Therefore, further investigations are needed to determine the molecular pathophysiology underlying the complications of XLH. Full article

Adult-onset primary hypothyroidism is commonly caused by iatrogenic or autoimmune mechanisms; whether other factors might also contribute to adult hypothyroidism is unclear. Cellular Retinoic-Acid-Binding Protein 1 (CRABP1) is a mediator for Non-canonical signalling of all-trans retinoic acid (atRA). CRABP1 Knockout (CKO) mice develop and reproduce normally but begin to exhibit primary hypothyroidism in adults (~3 months old) including increased body weight, decreased body temperature, reduced plasma levels of triiodothyronine and thyroxine, and elevated levels of thyroid-stimulating hormone. Histopathological and gene expression studies reveal significant thyroid gland morphological abnormalities and altered expression of genes involved in thyroid hormone synthesis, transport, and metabolism in the CKO thyroid gland at ~6 months old. These significantly affected genes in CKO mice are also found to be genetically altered in human patients with hypothyroidism which could result in a loss of function, supporting the clinical relevance of CKO mice in humans with hypothyroidism. This study identifies, for the first time, an important role for CRABP1 in maintaining the health of the thyroid gland in adults and reports that CKO mice may provide an experimental animal model for studying the mechanisms underlying the development of adult hypothyroidism in humans. Full article

X-linked hypophosphatemia (XLH) is a rare type of hereditary hypophosphatemic rickets. Patients with XLH have various symptoms that lower their QOL as defined by HAQ, RAPID3, SF36-PCS, and SF36-MCS in adult patients and SF-10 and PDCOI in pediatric patients. Early diagnosis and treatment are needed to reduce the burden, but the condition is often diagnosed late in childhood. The present review aims to summarize the symptoms, radiological and biological characteristics, and long-term prognosis of pediatric XLH. Typical symptoms of XLH are lower leg deformities (age six months or later), growth impairment (first year of life or later), and delayed gross motor development with progressive lower limb deformities (second year of life or later). Other symptoms include dental abscess, bone pain, hearing impairment, and Chiari type 1 malformation. Critical, radiological findings of rickets are metaphyseal widening, cupping, and fraying, which tend to occur in the load-bearing bones. The Rickets Severity Score, validated for XLH, is useful for assessing the severity of rickets. The biochemical features of XLH include elevated FGF23, hypophosphatemia, low 1,25(OH)2D, and elevated urine phosphate. Renal phosphate wasting can be assessed using the tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR), which yields low values in patients with XLH. XLH should be diagnosed early because the multisystem symptoms often worsen over time. The present review aims to help physicians diagnose XLH at an early stage. Full article