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PloS One 2024Glioblastoma, the most aggressive form of brain cancer, poses a significant global health challenge with a considerable mortality rate. With the predicted increase in...
Host-defence caerin 1.1 and 1.9 peptides suppress glioblastoma U87 and U118 cell proliferation through the modulation of mitochondrial respiration and induce the downregulation of CHI3L1.
Glioblastoma, the most aggressive form of brain cancer, poses a significant global health challenge with a considerable mortality rate. With the predicted increase in glioblastoma incidence, there is an urgent need for more effective treatment strategies. In this study, we explore the potential of caerin 1.1 and 1.9, host defence peptides derived from an Australian tree frog, in inhibiting glioblastoma U87 and U118 cell growth. Our findings demonstrate the inhibitory impact of caerin 1.1 and 1.9 on cell growth through CCK8 assays. Additionally, these peptides effectively curtail the migration of glioblastoma cells in a cell scratch assay, exhibiting varying inhibitory effects among different cell lines. Notably, the peptides hinder the G0/S phase replication in both U87 and U118 cells, pointing to their impact on the cell cycle. Furthermore, caerin 1.1 and 1.9 show the ability to enter the cytoplasm of glioblastoma cells, influencing the morphology of mitochondria. Proteomics experiments reveal intriguing insights, with a decrease in CHI3L1 expression and an increase in PZP and JUNB expression after peptide treatment. These proteins play roles in cell energy metabolism and inflammatory response, suggesting a multifaceted impact on glioblastoma cells. In conclusion, our study underscores the substantial anticancer potential of caerin 1.1 and 1.9 against glioblastoma cells. These findings propose the peptides as promising candidates for further exploration in the realm of glioblastoma management, offering new avenues for developing effective treatment strategies.
Topics: Glioblastoma; Humans; Cell Proliferation; Mitochondria; Cell Line, Tumor; Down-Regulation; Cell Respiration; Animals; Brain Neoplasms; Antimicrobial Cationic Peptides; Cell Movement
PubMed: 38848430
DOI: 10.1371/journal.pone.0304149 -
PloS One 2024Craniopharyngiomas are rare tumors of the central nervous system that typically present with symptoms such as headache and visual impairment, and those reflecting...
Craniopharyngiomas are rare tumors of the central nervous system that typically present with symptoms such as headache and visual impairment, and those reflecting endocrine abnormalities, which seriously affect the quality of life of patients. Patients with craniopharyngiomas are at higher cardiometabolic risk, defined as conditions favoring the development of type 2 diabetes and cardiovascular disease. However, the underlying common pathogenic mechanisms of craniopharyngiomas and type 2 diabetes are not clear. Especially due to the difficulty of conducting in vitro or in vivo experiments on craniopharyngioma, we thought the common pathway analysis between craniopharyngioma and type 2 diabetes based on bioinformatics is a powerful and feasible method. In the present study, using public datasets (GSE94349, GSE68015, GSE38642 and GSE41762) obtained from the GEO database, the gene expression associated with adamantinomatous craniopharyngioma, a subtype of craniopharyngioma, and type 2 diabetes were analyzed using a bioinformatic approach. We found 11 hub genes using a protein-protein interaction network analysis. Of these, seven (DKK1, MMP12, KRT14, PLAU, WNT5B, IKBKB, and FGF19) were also identified by least absolute shrinkage and selection operator analysis. Finally, single-gene validation and receptor operating characteristic analysis revealed that four of these genes (MMP12, PLAU, KRT14, and DKK1) may be involved in the common pathogenetic mechanism of adamantinomatous craniopharyngioma and type 2 diabetes. In addition, we have characterized the differences in immune cell infiltration that characterize these two diseases, providing a reference for further research.
Topics: Humans; Craniopharyngioma; Diabetes Mellitus, Type 2; Computational Biology; Pituitary Neoplasms; Protein Interaction Maps; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Gene Expression Profiling; Biomarkers
PubMed: 38848397
DOI: 10.1371/journal.pone.0304404 -
Endocrinology, Diabetes & Metabolism Jul 2024During the process of transition from paediatric to adult health care, counselling concerning fertility is an important issue and is based mainly on serum markers of...
OBJECTIVE
During the process of transition from paediatric to adult health care, counselling concerning fertility is an important issue and is based mainly on serum markers of gonadal function. Here, we analysed these markers in adolescents with various underlying endocrine diseases at the time of transition.
METHODS
After reaching near adult height and late puberty (girls: bone age [BA] ≥14 years, and boys: BA ≥16 years), we assessed stages of puberty according to Tanner and measured testes or ovarian volumes and serum markers of gonadal function (anti-Mullerian hormone [AMH], inhibin B, 17β-estradiol, testosterone).
RESULTS
One hundred and ten patients (56 females and 54 males) were included from May 2010 to March 2016 with multiple pituitary hormone deficiency (MPHD; n = 17), growth hormone deficiency (GHD; n = 35), Turner syndrome (TS; n = 27), short stature after being born small for gestational age (SGA; n = 20) and Klinefelter syndrome (KS; n = 11). Female and male adolescents exhibited mature secondary sexual characteristics. The levels of serum inhibin B and AMH were lower in TS and female MPHD than in GHD and SGA, each independently (p < 0.05). The levels of serum AMH were higher whereas serum inhibin B were lower in male MPHD and KS (p < 0.05). Ovary volumes were significantly smaller in patients with TS, and testicular volumes were smaller in patients with KS.
CONCLUSIONS
After current established treatments with sex steroids, the development of secondary sexual characteristics was mature. However, impaired markers of fertility have been identified in patients with TS, KS and MPHD, reflecting gonadal dysgenesis in TS and KS, but gonadal immaturity in MPHD as gonadal gonadotropin stimulation is lacking throughout development. Consequently, in patients with MPHD, these markers cannot reliably predict individual fertility, which warrants consideration and incorporation in future treatment concepts.
Topics: Humans; Adolescent; Female; Male; Biomarkers; Anti-Mullerian Hormone; Transition to Adult Care; Fertility; Inhibins; Adult; Young Adult; Endocrine System Diseases; Testosterone; Turner Syndrome; Chronic Disease; Estradiol; Puberty; Klinefelter Syndrome
PubMed: 38845445
DOI: 10.1002/edm2.493 -
Acta Neurochirurgica Jun 2024An ACTH-secreting pituitary adenoma is the most common cause of excessive endogenous glucocorticoid production resulting in Cushing's Syndrome. A multidisciplinary...
BACKGROUND
An ACTH-secreting pituitary adenoma is the most common cause of excessive endogenous glucocorticoid production resulting in Cushing's Syndrome. A multidisciplinary approach is paramount. Selective adenomectomy is the treatment of choice.
METHOD
Endoscopic transnasal transsphenoidal approach to the tumour, along with techniques for resection, are demonstrated.
CONCLUSION
Endoscopic transsphenoidal approaches with its magnified view of the pituitary gland allows precise microsurgical dissection during selective adenomectomy. This technique increases the possibility of proving a gross total resection, leading to clinical and biochemical cure in these patients.
Topics: Humans; Adenoma; Pituitary ACTH Hypersecretion; Endoscopy; ACTH-Secreting Pituitary Adenoma; Pituitary Neoplasms; Neuroendoscopy; Treatment Outcome; Neurosurgical Procedures; Female; Sphenoid Bone
PubMed: 38842720
DOI: 10.1007/s00701-024-06078-y -
EClinicalMedicine Jul 2024Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This "mixed" entity is poorly characterized. We here...
BACKGROUND
Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This "mixed" entity is poorly characterized. We here investigated the clinical phenotype, outcome, and prognostic factors of a large cohort of patients with mixed ECD-LCH.
METHODS
This retrospective study was performed at two referral centers in France and Italy (Pitié-Salpêtrière Hospital, Paris; Meyer Children's Hospital, Florence). We included children and adults with ECD diagnosed in 2000-2022 who had biopsy-proven LCH, available data on clinical presentation, treatment and outcome, and a minimum follow-up of one year. Outcomes included differences in clinical presentation and survival between mixed ECD-LCH and isolated ECD; we also investigated response to treatments and predictors of survival in the mixed cohort. Survival was analyzed using the Kaplan-Maier method and differences in survival with the long-rank test. Cox regression models were used to evaluate the potential impact of age and gender on survival and to identify predictors of non-response and survival.
FINDINGS
Out of a cohort of 502 ECD patients, 69 (14%) had mixed ECD-LCH. Compared to isolated ECD, mixed ECD-LCH occurred more frequently in females (51 26%, < 0.001) and in patients with multisystem disease (≥4 sites). Mixed ECD-LCH more frequently involved long bones (91 79%, = 0.014), central nervous system (51 34%, = 0.007), facial/orbit (52 38%, = 0.031), lungs (43 28%, = 0.009), hypothalamic/pituitary axis (51 26%, < 0.001), skin (61 29%, < 0.001), and lymph nodes (15 7%, = 0.028); the mutation was also more frequent in mixed ECD-LCH (81 59%, < 0.001). Targeted treatments (BRAF and/or MEK inhibitors) induced response more frequently than conventional therapies (interferon-α, chemotherapy), either as first-line (77 29%, < 0.001) or as any line (75 24%, < 0.001). After a median follow-up of 71 months, 24 patients (35%) died. Survival probability was comparable between ECD alone and mixed ECD-LCH (log-rank = 0.948). At multivariable analysis, age at diagnosis (HR 1.052, 95% CI 1.008-1.096), associated hematologic conditions (HR 3.030, 95% CI 1.040-8.827), and treatment failure (HR 9.736, 95% CI 2.919-32.481) were associated with an increased risk of death, while lytic bone lesions with a lower risk (HR 0.116, 95% CI 0.031-0.432).
INTERPRETATION
Mixed ECD-LCH is a multisystem disease driven by the mutation and targeted treatments are effective. Age at diagnosis, bone lesion patterns, associated hematologic conditions, and treatment failure are the main predictors of death in mixed ECD-LCH.
FUNDING
None.
PubMed: 38841707
DOI: 10.1016/j.eclinm.2024.102658 -
BMC Endocrine Disorders Jun 2024Thyroid disorders have been reported in hypercortisolism patients. Endogenous Cushing's syndrome (CS) potentially complicates its metabolic sequelae. We investigated... (Meta-Analysis)
Meta-Analysis
PURPOSE
Thyroid disorders have been reported in hypercortisolism patients. Endogenous Cushing's syndrome (CS) potentially complicates its metabolic sequelae. We investigated thyroid function in CS patients to determine this relationship.
METHODS
In this cross-sectional study, we screened CS patients from 2016 to 2019 at our hospital. Patient demographic, medical history, and laboratory data were collected. Additionally, we performed a meta-analysis to demonstrate the prevalence of thyroid dysfunction in patients with CS.
RESULTS
Among 129 CS patients, 48.6% had triiodothyronine (TT3), 27.9% had thyroxine (TT4), 24.6% had free T3 (FT3), 27.7% had free T4 (FT4), and 6.2% had thyroid-stimulating hormone (TSH) levels below the reference values. Those with clinical CS showed more pronounced thyroid suppression than did those with subclinical CS. Cortisol levels were markedly greater in patients with pituitary hypothyroidism (P < 0.001). Serum cortisol levels throughout the day and post low-dose dexamethasone-suppression test (LDDST) results correlated with thyroid hormone levels, particularly in ACTH-independent CS. Correlations varied by thyroid status; FT3 and TSH were linked to cortisol in euthyroid individuals but not in those with low T3 or central hypothyroidism. TSH levels notably halved from the lowest to highest cortisol tertile post-LDDST. Finally, meta-analysis showed 22.7% (95% CI 12.6%-32.9%) central hypothyroidism in 528 CS patients of nine studies.
CONCLUSION
Thyroid hormone levels are significantly correlated with cortisol levels and are impaired in patients with CS. However, the physiological adaptation and pathological conditions need further study.
Topics: Humans; Cushing Syndrome; Cross-Sectional Studies; Male; Female; Thyroid Function Tests; Adult; Middle Aged; Thyroid Gland; Thyroid Diseases; Thyrotropin; Hydrocortisone; Thyroid Hormones; Thyroxine; Prognosis
PubMed: 38840128
DOI: 10.1186/s12902-024-01614-4 -
Endocrinology, Diabetes & Metabolism... Apr 2024We report a case of a 59-year-old woman with Cushing's disease who developed hyperthyroidism following treatment of hypercortisolaemia. The patient with a history of...
SUMMARY
We report a case of a 59-year-old woman with Cushing's disease who developed hyperthyroidism following treatment of hypercortisolaemia. The patient with a history of recurrent hospitalisations caused by multi-sited soft tissue abscesses was admitted with sepsis. Both her medical history and physical examination suggested Cushing's syndrome. The initial hormonal diagnostic process, conducted after sepsis treatment, brought forth conflicting results. However, hormonal assessment repeated 3 months later indicated pituitary hypercortisolaemia, which was confirmed through bilateral inferior petrosal sinus sampling and was successfully treated with transsphenoidal pituitary surgery. Three months after the surgery, the patient was readmitted to our epartment with symptoms of hyperthyroidism, which was confirmed by laboratory tests. Thyroid scintiscans indicated Graves' disease. However, the absence of anti-thyroid stimulating hormone antibodies suggested other etiologies of hyperthyroidism. Eventually, the patient underwent radioiodine therapy. Currently, her condition is improving and she has had no recurrence of abscesses, severe infections, or hyperthyroidism. In conclusion, while clinical manifestation of hypercortisolaemia might be non-specific, its treatment may trigger the development of autoimmune diseases.
LEARNING POINTS
The presence of recurrent severe infections should prompt physicians to consider the possibility of hypercortisolaemia. Chronic hypercortisolism is debilitating and can lead to significant disability. Dexamethasone suppression testing in patients with active or recent severe inflammatory or infectious illnesses may produce misleading or confusing results. Clinicians should be aware of the potential development of autoimmune diseases following successful treatment of hypercortisolaemia.
PubMed: 38838715
DOI: 10.1530/EDM-23-0040 -
Frontiers in Endocrinology 2024Individuals with hypopituitarism (HPs) have an increased risk of developing non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) due to growth...
OBJECTIVE
Individuals with hypopituitarism (HPs) have an increased risk of developing non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) due to growth hormone deficiency (GHD). We aimed to investigate the possible mechanisms underlying the relationship between GHD and NAFLD using proteomic and metabolomic insights.
METHODS
Serum metabolic alternations were assessed in male HPs using untargeted metabolomics. A rat model of HP was established through hypophysectomy, followed by recombinant human growth hormone (rhGH) intervention. The mechanisms underlying GHD-mediated NAFLD were elucidated through the application of label-free proteomics and phosphorylation proteomics.
RESULTS
Metabolomic analysis revealed that biomarkers of mitochondrial dysfunction and oxidative stress, such as alanine, lactate, and creatine, were significantly elevated in HPs compared to age-matched controls. In rats, hypophysectomy led to marked hepatic steatosis, lipid peroxidation, and reduced glutathione (GSH), which were subsequently modulated by rhGH replacement. Proteomic analysis identified cytochrome P450s, mitochondrial translation elongation, and PPARA activating genes as the major distinguishing pathways in hypophysectomized rats. The processes of fatty acid transport, synthesis, oxidation, and NADP metabolism were tightly described. An enhanced regulation of peroxisome β-oxidation and ω-oxidation, together with a decreased NADPH regeneration, may exacerbate oxidative stress. Phosphoproteome data showed downregulation of JAK2-STAT5B and upregulation of mTOR signaling pathway.
CONCLUSIONS
This study identified proteo-metabolomic signatures associated with the development of NAFLD in pituitary GHD. Evidence was found of oxidative stress imbalance resulting from abnormal fatty acid oxidation and NADPH regeneration, highlighting the role of GH deficiency in the development of NAFLD.
Topics: Animals; Male; Oxidative Stress; Non-alcoholic Fatty Liver Disease; Rats; Proteomics; Metabolomics; Hypopituitarism; Rats, Sprague-Dawley; Human Growth Hormone; Humans
PubMed: 38836220
DOI: 10.3389/fendo.2024.1371444 -
Chinese Neurosurgical Journal Jun 2024This study aimed to investigate clinical features and treatment strategies for intracranial aneurysm (IA) associated with pituitary adenoma (PA).
BACKGROUND
This study aimed to investigate clinical features and treatment strategies for intracranial aneurysm (IA) associated with pituitary adenoma (PA).
METHODS
We enrolled patients with lesions in the sellar region and age-matched general population who were confirmed with IA from two hospitals. Four types of treatment strategies were performed, which included Type I (both IA and PA were treated with surgery), Type II (IA was treated with surgery and PA was performed by non-surgical treatment), Type III (PA was performed with surgery and observation was available for IA) and Type IV (both IA and PA were performed with non-surgical treatment).
RESULTS
The incidence of IA was 2.2% in the general population, 6.1% in patients with PA, 4.3% in patients with Rathke cleft cyst, 2.8% in patients with meningioma and none were found with IA in patients with craniopharyngioma. Age over 50 years (OR, 2.69; 95% CI, 1.20-6.04; P = 0.016), female (OR, 3.83, P = 0.003), and invasive tumor (OR, 3.26, P = 0.003) were associated with a higher incidence of IA in patients with PA. During the mean follow-up of 49.2 months, no patients experienced stroke, and recurrence of aneurysms and aneurysms treated with observation were stable. Of four patients with recurrence of PA, three patients were treated for type I and one patient for type III.
CONCLUSIONS
Preoperative evaluation for aneurysm screening is necessary due to the high incidence of IA in PA patients. Our current treatment strategies may provide a benefit for these patients.
PubMed: 38835088
DOI: 10.1186/s41016-024-00370-7 -
Poultry Science May 2024Dietary energy density influences feed intake (FI) and development of layer-type pullets. A total of 384 nine-wk-old Hy-Line Brown pullets were randomly assigned to one...
Dietary energy density influences feed intake (FI) and development of layer-type pullets. A total of 384 nine-wk-old Hy-Line Brown pullets were randomly assigned to one of 3 dietary treatments: fed a diet with 2,600, 2,750, and 2,900 Kcal metabolizable energy/kg (ME/kg) from 10 to 21 wk of age. The results showed that the 2,900 and 2,600 ME groups had lower feed and ME intake (P < 0.01) from 10 to 21 wk of age. The 2,600 ME pullets had heavier body weight (BW) and longer shank length (P < 0.05) at 21 wk of age than the 2,750 ME group. The eggshell percentage was increased by the 2,600 and 2,900 kcal/kg treatments (P = 0.002). Serum concentration of 17-β-estradiol (E), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) decreased at 70 wk of age (P < 0.05). Pullet diet and its interaction with age had a significant influence (P < 0.001) on the expression of gonadotropin-releasing hormone 1 (GnRH-1) and gonadotropin-inhibitory hormone (GnIH) in the hypothalamus and of gonadotropin releasing hormone 1 receptor (GnRH-1R) and gonadotropin-inhibitory hormone receptor (GnIHR) in the pituitary. In the hypothalamus, GnRH-1 expression increased from 9 to 40 wk of age and then decreased; however, GnIH expression was highest at 70 wk of age. Follicle-stimulating hormone receptor (FSHR) expression increased (P < 0.001) at wk 40 and decreased at wk 70 compared to wk 21 at various follicular stages. In conclusion, the energy level of pullet diet had no unfavorable influence on feed intake, laying rate, egg mass, and FCR, whereas change egg weight and mortality during the laying period from 21 to 70 wk of age. during the laying period. These results suggest that pullet dietary energy can activate the expression of genes related to reproduction in the hypothalamus, whereas it plays a minor role in the regulation of genes in the pituitary and ovary. Age-induced gene expression in the hypothalamus-pituitary-gonadal (HPG) axis is associated with laying performance in hens.
PubMed: 38833747
DOI: 10.1016/j.psj.2024.103873