Endocrine Regulations Feed

Efficacy of whole-body vibration on hormonal responses in individuals with hormonal disorders: A systematic review and meta-analysis

Sat, 19 Sep 2026 00:00:00 GMT

Objective. This systematic review aims to examine the current literature on the effects of whole-body vibration on hormonal levels in individuals with hormonal disorders.Methods. A systematic search was performed on six electronic databases to retrieve studies examining the effects of whole-body vibration on hormonal levels in individuals with hormonal disorders. The retrieved studies were assessed against predetermined eligibility criteria in two stages: title and abstract filtration and full-text filtration. The quality of the studies included was assessed using the physiotherapy evidence based (PEDro) scale and their data were summarized in a data extraction sheet. A pooled statistical analysis was conducted in studies that showed homogeneity.Results. The included studies assessed hormonal level in individuals with hormonal disorders across various pathological conditions including fibromyalgia, multiple sclerosis, obese hypothyroid females, diabetes mellitus, and individuals with renal diseases. The effect of whole-body vibration was statistically significant on thyroid hormones, prolactin, cortisol, and irisin, while other studies showed no effect for whole-body vibration on insulin, gonadal hormones, ghrelin and leptin, adiponectin, parathyroid hormone, and insulin-like growth factor 1 in women with fibromyalgia.Conclusion. The whole-body vibration training may have an action in endocrine system as observed by the alteration of plasma concentration of thyroid hormones, prolactin, cortisol and irisin. It is possible that long-term, repeated mechanical vibration could directly or indirectly affect the levels of other hormones.

Estrogens hypersensitivity syndrome in endometriosis

Sat, 19 Sep 2026 00:00:00 GMT

Objectives. The aim of the study was to develop a diagnostic method for estrogen hypersensitivity syndrome in proliferative benign diseases of the female reproductive system. Using the example of endometriosis, changes in the activity of the chaperone protein Hsp90α were determined as a diagnostic biomarker.Methods. The study included 60 women aged 30 to 50 years, thirty of whom had a laparoscopically confirmed diagnosis of endometriosis and 30 were included in the control group. After blood sampling to determine the baseline levels of Hsp90α, the patients were prescribed a single oral dose of estradiol valerate 2 mg tablet. The plasma Hsp90α levels were remeasured 6 h later.Results. No significant change (p>0.05) in baseline Hsp90α concentrations was found between the group of patients with endometriosis and the control group. Six hours after estradiol valerate administration, a significant difference (p<0.001) in Hsp90α levels was observed between the group of patients with endometriosis and the control group. The increase in Hsp90α concentration following the test-load was also more pronounced in women with confirmed endometriosis compared to controls (27.29±15.62 ng/ml and 3.16±4.36 ng/ml, respectively) (p<0.001). ROC analysis indicated that the absolute increase in Hsp90α level of more than 8.6 ng/ml in patients with endometriosis has a sensitivity of 0.93 and a specificity of 0.97 (compared to the control group). This change in relative concentration corresponded to an increase of over 28.7%.Conclusion. The increase in Hsp90α plasma level of more than 30% within 6 h after the test-load is a specific criterion for estrogen hypersensitivity syndrome in endometriosis. Further investigation including other nosological forms (myoma, adenomyosis, endometrial hyperplasia) is required.

Prescription pattern of oral hydrocortisone by Indian healthcare professionals: An online questionnaire-based survey

Sat, 19 Sep 2026 00:00:00 GMT

Objective. Adrenal insufficiency is predominantly managed by glucocorticoids, from which hydrocortisone is most frequently prescribed. However, limited data are available on prescription patterns among Indian healthcare professionals (HCPs). This study assessed the prescription practices of hydrocortisone among Indian HCPs and evaluated their awareness of tapering protocols and necessity for modified-release formulations of hydrocortisone.Methods. This online questionnaire-based survey involved 300 HCPs across India who prescribe oral hydrocortisone for various endocrinological and non-endocrinological indications. Google Forms were used and survey was carried out over a period of two months. Only fully accomplished responses were included in the analysis and the response rate was calculated.Results. The survey response rate was 84.27%. Among HCPs, 94.7% prescribed oral hydrocortisone with 47.5% using it often and 28.9% very often. Prescription frequency varied from 29.9% (prescribed once weekly) to 25.7% (two or more times weekly). Awareness of approved indications was high (96.8%). Tapering protocols were widely practiced (95.4%) often or very often by 82.7% HCPs. Hydrocortisone was mainly prescribed for primary adrenal insufficiency (77.5%), secondary adrenal insufficiency (63.0%), and congenital adrenal hyperplasia (55.6%). Frequent adverse events included hyperglycemia (43.3%) and weight gain (43.0%). Most HCPs (89.8%) felt need for sustained-release hydrocortisone, particularly for primary adrenal insufficiency (81.7%). Alternatives of hydrocortisone mainly included prednisolone (65.8%), prednisone (37.3%), and dexamethasone (21.8%).Conclusion. Indian HCPs frequently prescribe oral hydrocortisone and are well-versed in tapering protocols. However, frequent adverse events and unmet needs emphasize strong demand for modified-release formulations, particularly for management of adrenal insufficiency.

Clinical course and management of adrenal endocrine hypertension: A single-center experience

Sat, 19 Sep 2026 00:00:00 GMT

Objectives. Endocrine etiologies of secondary hypertension (HTN) are frequent and increasingly diagnosed according to the learned societies. Adrenal causes as primary aldosteronism (PA), pheochromocytomas (PHEO), and ACTH-independent Cushing’s syndrome (CS) are widely described separately regarding their clinical, biochemical, and morphological aspects and only a few studies have developed the particular aspect of associated HTN. For this reason, we conducted a retrospective observational descriptive study at a tertiary referral center.Subjects. Fifty-five subjects were included (PA: 52.8%, PHEO: 29.1%, and CS: 18.1%). We found a slight female preponderance (60%). The average age of participants was 47.0±14.9 years. First-degree family history of HTN was described in up to two thirds of cases. Regarding HTN characteristics, subjects with PA presented significantly younger age at diagnosis and had more severe and resistant profile and required higher number of antihypertensive drugs. HTN-mediated organ damage (HMOD) was mainly cardiovascular and ocular. Patients with PHEO were significantly older at diagnosis and had more severe and paroxysmal HTN. Patients with CS had less severe HTN and less HMOD. Specific treatments were indicated in all cases aiming complete remission of HTN. Subjects with PA were treated medically with mineralocorticoid receptor antagonists in 72.4% of cases and HTN remission was achieved in only 21.8% after surgical treatment. All subjects with PHEO were operated with adrenalectomy and the remission was observed in 37.5% of cases, while patients with CS were surgically managed in 50% of cases with 40% of HTN remission.Conclusions. Diagnosis and management of adrenal endocrine HTN diseases are challenging for healthcare professionals and early screening is crucial for prevention of cardiovascular morbidity.

Predictors of genetic polymorphisms in patients with arterial hypertension and ischemic heart disease

Sat, 19 Sep 2026 00:00:00 GMT

Objective. This study was aimed to develop a mathematical model for predicting the presence of pathological alleles of the angiotensin II receptor type 1 (AGTR1) (C1166C) and endothelial nitric oxide synthase (eNOS) (T786C) genes in patients with arterial hypertension using readily available clinical and demographic parameters without the need for laboratory genetic analysis.Methods. The study included 86 patients with arterial hypertension, 45 of whom had also clinical signs of ischemic heart disease and 30 healthy controls. Clinical and demographic data, including age, sex, body mass index (BMI), smoking and alcohol habits, and systolic and diastolic blood pressure, were collected. A predictive model of genetic polymorphism was constructed using a multivariate regression analysis in Statistica 10.0. Model quality was assessed via residual analysis (histogram, normal probability plot, scatter plot), ANOVA, and the Nagelkerke coefficient of determination (R²).Results. Eight significant predictors of pathological gene variants were identified: age, sex, disease duration, BMI, smoking, alcohol consumption, systolic blood pressure, and diastolic blood pressure. The regression model explained 98.42% of the variance in gene polymorphism (R²=0.9842). Residuals were normally distributed and randomly scattered confirming the model adequacy. ANOVA analysis demonstrated high statistical significance (p<0.001) indicating that the model performed significantly better than predictions based on the mean values. The model allows inference of the probable presence of C alleles in AGTR1 and eNOS genes using simple clinical information.Conclusions. The proposed mathematical model demonstrates high predictive capability and statistical stability providing a cost-effective tool for preliminary genetic screening in patients with hypertension. It enables identification of individuals at risk for carrying pathological gene variants and supports the implementation of a personalized approach in clinical practice. Further validation on independent datasets is recommended.

Divergent transcriptional responses to pancreatic transcription factors are dictated by the cellular context

Mon, 31 Aug 2026 00:00:00 GMT

Objective. The outcome of directed differentiation for cell-based therapies is profoundly influenced by the starting cell’s intrinsic state, or cellular context. How pluripotent versus lineage-primed cells interpret the same developmental cues remains unclear. To address this, we performed a comparative transcriptomic analysis using two mouse cell lines engineered for episomal expression: a pluripotent embryonic stem cell line (PLT-ES) and a multipotent pancreatic stem cell line (PLT-PPPD).Methods. We introduced a core set of pancreatic transcription factors – PMN: Pdx1 (pancreatic and duodenal homeobox 1), MafA (MAF BZIP transcription factor A), and NeuroD1 (neurogenic differentiation 1) – into both cell types and analyzed global gene expression and insulin promoter activity.Results. The two cell types exhibited strikingly divergent fates. In lineage-primed PLT-PPPD cells, PMN expression induced a mixed pancreatic/hepatic phenotype. In stark contrast, PMN expression in pluripotent PLT-ES cells failed to initiate an endodermal program, instead robustly driving differentiation towards mesodermal lineages. Intriguingly, reporter assays revealed that the PMN factors could activate the insulin promoter in both PLT-ES and PLT-PPPD cells, regardless of the overall differentiation outcome.Conclusions. Our findings demonstrate that cellular context is a paramount determinant of cell fate. The activation of a single promoter is insufficient to orchestrate a complete differentiation program. While pancreatic stem cells exhibit plasticity within the endodermal lineage, pluripotent cells are misdirected towards entirely different germ layers if not appropriately primed. This study underscores the critical importance of using lineage-committed cells for predictable therapeutic outcomes.

ERN1 inhibition modifies hypoxic regulation of EGLN1 expression in U87MG glioblastoma cells

Mon, 31 Aug 2026 00:00:00 GMT

Objective. Glioblastomas are the most common and highly aggressive malignant brain tumors that are difficult to treat. Hypoxia is a significant factor in glioblastoma growth. Previous studies have shown that the inhibition of ERN1 (endoplasmic reticulum to nucleus signaling 1) significantly suppresses the glioblastoma cell proliferation and modifies the hypoxic regulation. The present study aimed to investigate the impact of hypoxia on the expression of endoplasmic reticulum stress-dependent genes including EGLN1 in U87MG glioblastoma cells in relation to ERN1 inhibition to reveal a possible role of the ERN1 signaling pathway in the hypoxic regulation of these genes’ expression.Methods. The control U87MG glioblastoma cells (transfected by an empty vector) and ERN1 knockdown cells with inhibited ERN1 endoribonuclease and protein kinase (dnERN1) were used. Hypoxia was induced at normoxic conditions with dimethyloxalylglycine (0.5 mM for 4 h). RNA was extracted and reverse transcribed. The expression levels of EGLN1, HSPA5, DDIT4, PA2G4, XIAP, and MTOR genes were studied by real-time qPCR and normalized to ACTB mRNA.Results. It was established that hypoxia increases the expression level of EGLN1, HSPA5, DDIT4, and XIAP in glioblastoma cells with native ERN1. However, the expression levels of two other stress-dependent genes (PA2G4 and MTOR) were reduced in these glioblastoma cells under hypoxia. Furthermore, inhibition of ERN1 enzymatic activity attenuated the effects of hypoxia on the expression of most of the genes studied in glioblastoma cells, while XIAP gene expression was dramatically increased.Conclusion. The results of this study showed that hypoxia differentially affects the expression of genes related to endoplasmic reticulum stress in glioblastoma cells and is dependent on ERN1 activity. This reflected the ERN1-mediated reprogramming of hypoxic regulation of gene expression.

Unmasking silent atherosclerosis in type 2 diabetes: the emerging role of adipocyte fatty acid-binding protein

Mon, 31 Aug 2026 00:00:00 GMT

Objectives. Atherosclerosis contributes to higher mortality and morbidity in people with diabetes. Preventing future complications largely depends on the early detection of imminent atherosclerosis. This study aimed to explore the relationship between the subclinical atherosclerosis measured by carotid intima-media thickness (CIMT), ankle-brachial index (ABI), and circulating levels of adipocyte fatty acid-binding protein (AFABP) in individuals with type 2 diabetes mellitus (T2DM).Methods. A total of 80 participants evenly divided into two groups: 40 newly diagnosed patients with T2DM and 40 healthy controls. Patients with T2DM had no prior history or clinical signs of macrovascular complications, such as coronary artery disease, cerebrovascular stroke or peripheral artery disease. Serum total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were measured. Plasma AFABP levels were determined using a human enzyme-linked immunosorbent assay (ELISA) kit. ABI was assessed using a sphygmomanometer with a cuff that fits the limb’s circumference and a portable Doppler device. Doppler ultrasound of the carotid artery was used to measure CIMT.Results. In patients with T2DM, circulating AFABP levels were significantly higher than those in healthy subjects (p=0.007). Multivariate regression analysis indicated that AFABP is the only independent factor influencing the maximum CIMT (β=0.004, 95% CI: 0.001–0.007, p=0.017).Conclusion. Plasma AFABP level could serve as a biomarker for early diagnosis of atherosclerosis in patients with T2DM.

Tributyltin chloride and triphenyltin chloride inhibit steroid hormone secretion by mouse Leydig cells TM3 and human adrenocortical cells H295R

Sun, 05 Jul 2026 00:00:00 GMT

Objective. To find a possible balance between toxicity and potential anticancer activity of novel triorganotin compounds, retinoid X receptor (RXR) agonists, investigation the relationship between the structure, physicochemical properties, and biological activity of these compounds in non-tumorigenic and tumorigenic cells is required. This study aimed to investigate the effects of selected triorganotin compounds, tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPTCl), on viability and steroidogenic function of non-tumorigenic mouse Leydig cell line TM3 and human adrenocortical carcinoma cell line H295R.Methods. Gene and protein expression of RXR subtypes (RXRα, RXRβ, RXRγ) in TM3 Leydig cells was identified by qualitative PCR and immunofluorescence. The potency of TBT-Cl and TPTCl to induce mRNA expression of RXR subtypes in TM3 cells was analyzed by semi-quantitative real-time PCR. After exposure of TM3 and H295R cells to different concentration of TBT-Cl and TPT-Cl (0.1 nM–1 µM) for different time periods (24, 48, 72 h), cell viability was evaluated by detection of mitochondrial activity (MTT assay) and membrane integrity (LDH assay), and steroid hormone (testosterone, cortisol) levels in culture media were measured by radioimmunoassay.Results. Qualitative PCR and immunofluorescence examination revealed that all RXR subtypes, RXRα, RXRβ, RXRγ, are expressed in TM3 Leydig cells. TBT-Cl (500 nM) activated the expression of RXRα and RXRβ and at a concentration of 100 nM, RXRγ expression. TPT-Cl (10 and 100 nM) activated the expression of all three RXR subtypes and at a concentration of 500 nM, reduced RXRα expression similar to 9cRA (100 nM). Both compounds, TBT-Cl and TPT-Cl, induced a dose- and time-dependent significant decrease in the viability of TM3 Leydig cells and, in addition, TBT-Cl (500 nM and 1 µM) significantly inhibited androstenedione-induced testosterone secretion by these cells. Similarly, both tested triorganotin compounds (1 µM) significantly decreased viability of adrenocortical H295R cells and basal as well as forskolin-stimulated testosterone and cortisol secretions by these cells.Conclusion. TBT-Cl and TPT-Cl compromised cell viability and induced important functional alteration in Leydig cells probably through RXR activation with potential implications for male reproductive function. Endocrine-disrupting properties of TBT-Cl and TPT-Cl were demonstrated in adrenocortical H295R cells.

Beyond canonical GPCR: emerging roles of seven transmembrane proteins in metabolic control – insights from GPR180: A review

Sun, 05 Jul 2026 00:00:00 GMT

G protein–coupled receptors (GPCRs) are traditionally defined by their seven-transmembrane (7TM) domain architecture and ability to activate heterotrimeric G proteins. However, accumulating evidence challenges this structure-centric view, revealing a growing class of 7TM proteins that operate through non-canonical mechanisms. GPR180, initially annotated as an orphan GPCR based on predicted 7TM structure, has emerged as a paradigmatic example of this divergence. It lacks demonstrable G protein coupling and instead regulates metabolic function through atypical signalling pathways that influence mitochondrial bioenergetics, lipid handling, and cellular phenotype across multiple metabolic tissues. In adipose tissue, GPR180 controls adipocyte metabolic capacity and thermogenic programming, whereas in the liver, it modulates lipid homeostasis. Importantly, experimental topology analyses reveal inverted membrane orientation, distinguishing GPR180 from bona fide GPCRs despite shared 7TM architecture. Recent structural and functional analyses place GPR180 within the GOST (GOLD-domain 7TM) protein family; here, we propose a metabolically specialized GOST subclass, defined by regulation of mitochondrial bioenergetics and metabolic cell identity rather than classical G protein signalling. Together, these findings argue that GPR180 does not operate as a classical GPCR and highlight the need for functional criteria that extend beyond 7TM architecture when defining receptor identity. More broadly, GPR180 exemplifies how atypical 7TM proteins integrate metabolic state and cellular context to shape signalling output, providing a conceptual framework to systematically identify additional GOST family members with organelle-centred, non-canonical metabolic functions.

Cardiac myocyte contractility, calcium dynamics, and morphology in Zucker diabetic fatty female and male rats – lacking data in this model of obesity and diabetes: A review

Sun, 05 Jul 2026 00:00:00 GMT

Diabetes mellitus (DM) represents an increasing global health burden with type 2 diabetes mellitus (T2DM) accounting for most cases. T2DM is associated with microvascular and macrovascular complications including myocardial ischemia and contributes to the development of a distinct form of cardiac dysfunction referred to as diabetic cardiomyopathy (DCM). Importantly, DCM contributes to 50–80% of mortality in patients with diabetes independent of other vascular comorbidities and is characterized by structural and functional alterations of the myocardium. Notably, these outcomes exhibit sex-specific differences in patients with T2DM. Despite this, most preclinical rodent studies fail to incorporate female subjects. This is truly the case of the Zucker diabetic fatty (ZDF) rat model, where the left ventricular contractile and morphological properties have been investigated almost exclusively in males. This review aims to: a) synthesize existing data on myocyte shortening and morphology in ZDF male and female rats; b) identify critical gaps in current knowledge and define priorities for future experiments; and c) emphasize the urgent need for longitudinal studies assessing cardiomyocyte contractility and structural remodeling in both sexes. Cardiac myocyte contractility and calcium dynamics data are entirely lacking in ZDF female rats, while findings in males remain limited and, in some cases, inconsistent. For morphological and ultrastructural alterations in cardiac myocytes information is scarce for both ZDF males and females. Overall, this review highlights the need for comprehensive longitudinal investigations spanning the early and advanced stages of DCM including progression to heart failure in both male and female ZDF rats.

Milder Form of Vici Syndrome Due to Novel Missense Variant in Epg5 Gene Affecting Splicing: A Case Report

Sun, 05 Jul 2026 00:00:00 GMT

Objective. Vici syndrome is a rare neurodevelopmental disorder with multisystem involvement, caused by mutations in the EPG5 gene encoding a protein involved in autophagy. It includes dysgenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, and immuno-deficiency. Here we report a case of a 9-year-old boy of Roma ethnicity with a milder form of Vici syndrome and a novel variant in the EPG5 gene.Methods. DNA and RNA were extracted from the whole blood. Whole exome sequencing was performed and analysed with an in-house bioinformatics pipeline. A mini-gene assay was performed for EPG5 exon 23 with or without the tested variant.Results. The patient was born prematurely and presented with hypotonia, severe hypotrophy and growth retardation, developmental delay, congenital heart defects, mild brain atrophy, and a thin corpus callosum. Whole exome analysis identified a novel variant c.4205G>A, p.(Arg1402Lys) in the EPG5 gene, suggesting the diagnosis of Vici syndrome. Further examination of symptoms commonly associated with Vici syndrome confirmed hypopigmented skin areas and immunodeficiency. No seizures, cataracts, or cardiomyopathy were observed. As the variant is located at the last base of exon 23, we sequenced the patient’s EPG5 mRNA and detected aberrant transcripts in addition to correctly spliced ones. The mini-gene assay confirmed decreased inclusion of the mutated exon compared with the wild-type (40% vs. 72%, respectively).Conclusion. Novel variant EPG5:c.4205G>A, p.(Arg1402Lys) causes aberrant splicing only in a small proportion of transcripts; therefore, the milder presentation of Vici syndrome in our patient is probably due to the residual presence of EPG5 protein.

Tissue-specific steroid hormone-regulated secretion of proteins in Drosophila melanogaster salivary glands – molecular and genetic aspects: A review

Sun, 05 Jul 2026 00:00:00 GMT

Larval salivary glands (SGs) of Drosophila melanogaster (further Drosophila) are classical and well-known system, in which steroid hormone ecdysone controlling metamorphosis activates sequence of genes or transcriptional cascade that leads to formation distinct groups of puffs in polytene chromosomes and shortly prior to pupariation to release of unique glue that affix freshly formed puparium to the substrate. Although this system was studied since 1950s and most intensely during 1970s and 1980s, there are still several less known and unappreciated aspects, which deserve special attention. Some functional links between visible puffing and other active genes that do not form puffs are still missing. Production and formation of large secretory granules that are supposed to contain so-called Sgs-material that is secreted upon sturdy increase in ecdysone pulse require plethora of additional and supportive activities of SG cells that were not previously considered to be under direct hormonal control or considered at all. Although some of these physiological processes may appear to be hormone-independent and takes place because all necessary components of particular machinery are already present, there are several other processes that need be coordinated with early, mid or later phase of the ecdysone response and therefore they deserve special attention to fill the gaps. After detailed description of well studies model of Sgs-genes and their hormonal regulation, we tried to integrate this knowledge to a broader context of more advanced and current studies in Drosophila organism or cell lines using whole-genomic approach provided that functional and physiological information is conceptually included. After general introduction to the system, this review is committed to sketch functional and logical connections to processes that are conditionally required to fulfill SG organ-specific function but so far were out of the major research focus.

Endocannabinoid signalling in the regulation of hypothalamic-pituitary neuroendocrine circuits: A review

Sat, 27 Jun 2026 00:00:00 GMT

The endocannabinoid system (ECS), comprising cannabinoid receptors, endogenous lipid ligands, and enzymes that regulate their synthesis and degradation, has emerged as an important modulator of neuroendocrine regulation. This review summarises current evidence on the role of endocannabinoid signalling in hypothalamic-pituitary neuroendocrine circuits, with particular focus on the hypothalamic-pituitary-adrenocortical, gonadal, thyroid, and somatotropic axes, as well as prolactin and posterior pituitary hormones regulation. Available data indicate that endocannabinoid signalling predominantly influences neuroendocrine function by modulating synaptic transmission within hypothalamic circuits. Acting mainly as retrograde messengers at presynaptic CB1 receptors, endocannabinoids regulate excitatory and inhibitory inputs to neurosecretory neurons and thus shape endocrine output in a context-dependent manner. Among the systems discussed, the hypothalamic-pituitary-adrenocortical axis is the best characterised, with relatively well-defined links between glucocorticoid feedback and rapid endocannabinoid-mediated suppression of synaptic input to corticotropin-releasing hormone neurons. In other neuroendocrine systems, evidence supports a predominantly modulatory, often inhibitory, role for endocannabinoid signalling, although the underlying cellular processes remain less well-defined and are largely based on preclinical studies. Interactions with glucocorticoids, gonadal steroids and neuropeptidergic pathways further underscore the integrative nature of ECS signalling. Overall, the ECS should be viewed not as a primary endocrine driver, but as a dynamic regulatory network that fine-tunes the translation of neural activity into hormonal responses.

Early life adversity influences brain development through neuroendocrine, immune, and microbiota-related mechanisms: A review

Sat, 27 Jun 2026 00:00:00 GMT

The early life experiences have an important impact on the development of the brain and behavior and early life adversities (ELA) may affect several biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter and immune signaling systems, and microbiota composition. Dysregulation of these systems may result in an altered stress reactivity in both early life and the adulthood periods leading to maladaptive responses to the environmental stimuli. The activation of certain neuropeptides, including oxytocin, stimulation of the HPA axis, and increased glucocorticoid levels, may also play an important role in the early adaptive processes. In terms of brain maturation, ELA can directly or indirectly elicit structural changes in neurite growth, neurogenesis, neuronal connectivities, and signaling processes, which may contribute to the production of the long-term behavioral changes associated with an increased risk of the neuropsychiatric disorders’ development in later periods of the life. In this review, we summarize the effect of ELA on the HPA axis function, stress-related hormonal balance, immune responses, and the gut microbiome indicating how these changes may affect the brain function and behavior in the early stages of the life and adulthood. We also provide insight into animal studies revealing the responses of corticotropin-releasing hormone, urocortins, and corticosterone in various neural circuits in response to ELA evoked by maternal separation and limited bedding paradigms.

Current perspectives on the pathogenesis of multiple sclerosis: A minireview

Sat, 27 Jun 2026 00:00:00 GMT

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system characterized by inflammation, reactive gliosis, and progressive neuroaxonal damage resulting in heterogeneous clinical and histopathological manifestations. As MS often leads to disability at a young age, it represents a substantial socio-economic burden in developed countries. The etiopathogenesis of MS is multifactorial and incompletely understood, involving genetic, immunologic, and environmental factors. Recent research highlights immune responses to Epstein-Barr virus, blood-brain barrier disruption, microbiome-gut-brain axis alterations, oxidative damage, and mitochondrial dysfunction. Studying patients with newly diagnosed MS without significant comorbidities provides insight into early disease mechanisms before disability development or long-term treatment effects. This mini-review focuses on early vascular and metabolic alterations that may contribute to MS, including lipoprotein subfractions as markers of incipient atherosclerosis, endothelial dysfunction as an initiating vascular event, and autonomic nervous system imbalance during disease progression. It also addresses insulin sensitivity as a key metabolic factor alongside chronic inflammation and oxidative damage as interconnected mechanisms driving tissue injury. Metabolic changes reflecting neuronal impairment, mitochondrial dysfunction, and astroglial activation are detectable in both lesional and normal-appearing white matter in early stages. Reduced antioxidant capacity supports a role of oxidative damage in MS pathogenesis. Accelerated vascular aging, independent of traditional cardiovascular risk factors, may progress from endothelial dysfunction to structural atherosclerotic changes. Subtle alterations in lipoprotein profiles further suggest an increased risk of atherosclerosis, potentially influenced by inflammatory activity and oxidative damage, with possible sex-specific differences. Autonomic dysfunction appears to develop secondary to disease progression rather than as a primary driver of pathogenesis.

ERN1-dependent regulation of BAG cochaperone 1 expression and the sensitivity to glutamine deprivation in U87MG glioblastoma cells

Tue, 24 Mar 2026 00:00:00 GMT

Objective. The BAG cochaperone 1 (BAG1) binds to oncogene BCL2 and markedly enhances its anti-apoptotic effects. This cochaperone represents a link between growth factor receptors and anti-apoptotic mechanisms mediated by endoplasmic reticulum stress. BAG1 interacts with the glucocorticoid receptor and modulates its transcription activity. As a cochaperone for several HSP70 proteins, it participates in control of protein folding. The present study aims to investigate the regulation of the BAG1 mRNA expression in U87MG glioblastoma cells by hypoxia and glucose or glutamine deprivation, depending on the inhibition of ERN1 (endoplasmic reticulum to nucleus signaling 1) with the intent to reveal the role of ERN1 signaling in the regulation of this gene expression and function in oncogenesis.Methods. The U87MG glioblastoma cells (transfected by an empty vector; control) and cells with inhibited ERN1 endoribonuclease and protein kinase (dnERN1) or only ERN1 endoribonuclease (dnrERN1) were used. Silencing of ERN1 and XBP1 mRNAs for suppression of ERN1 function was also used. A hypoxic condition was created by dimethyloxalylglycine (4 h). DMEM medium without glucose or glutamine was used for glucose and glutamine deprivation (16 h). The expression level of the BAG1 mRNA was studied by real-time qPCR and normalized to the beta-actin mRNA.Results. Inhibition of the endoribonuclease activity of ERN1 significantly decreased BAG1 mRNA expression. However, a lesser suppression of this mRNA expression was observed in dnERN1 cells (with inhibited ERN1 endoribonuclease and protein kinase) indicating the involvement of protein kinase in controlling BAG1 expression. The silencing of ERN1 and XBP1 mRNAs also reduced the expression of BAG1 mRNA demonstrating the involvement of XBP1s in this regulation. The expression of the BAG1 gene was resistant to glutamine deprivation and upregulated in response to glucose deprivation in control glioblastoma cells. However, the inhibition of ERN1 increased the sensitivity of BAG1 gene expression to both glucose and glutamine deprivation. Furthermore, the expression of the BAG1 gene was increased under hypoxia in control U87MG cells; however, a greater induction was observed in dnERN1 cells.Conclusion. The results of this study demonstrated that ERN1 inhibition reduces BAG1 mRNA expression through the endoribonuclease activity of ERN1 and that protein kinase activity counteracts endoribonuclease in regulating the expression of BAG1 mRNA. Moreover, ERN1 inhibition also enhances the sensitivity of BAG1 mRNA expression to nutrient supply and hypoxia resulting in reduced resistance of glioblastoma cells.

One genotype with a myriad of phenotypes: A family with multiple endocrine neoplasia

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Multiple endocrine neoplasia type 1 (MEN1) is a very rare genetic disorder characterized by an autosomal dominant inheritance. We aim through this case series to delineate the wide spectrum of its clinical features.Methods. In the present study, we report the clinical and genetic findings of four siblings affected by this disorder. DNA was extracted from patients’ blood leukocytes using a phenol-chloroform method and assessed for purity with a NanoDrop spectrophotometer. Ten exons of the MEN1 gene were amplified by PCR, verified by gel electrophoresis, and sequenced using Big Dye Terminator chemistry followed by capillary electrophoresis. The sequences were than analyzed with CHROMAS and compared to reference sequences. As for the variant, interpretation and pathogenicity were assessed using Ensembl, ClinVar, dbSNP, gnomAD, Alamut Visual, and VARSOME.Results. We highlight the wide range of phenotypes encompassing primary hyperparathyroidism, macroprolactinoma, lipomas, papillary thyroid carcinoma, ectopic thyroid, multinodular goiter, and bilateral adrenal nodules observed in this family contrasting with the same pathogenic frameshift mutation. We also pinpoint to a second mutation detected in two of the siblings while discussing its pathogenicity. Finally, we provide an overview of the clinical manifestations of MEN1 and its genetic background.Conclusion. This research sets the stage to further investigate the molecular mechanisms underlying the novel nonsense mutation. Additionally, it incites other research to explore the frequency of this mutation in other populations and finally to conduct functional studies.

Circulating CXCL1 in newly diagnosed type 2 diabetes: context-dependent association with inflammatory load and metabolic indices

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) share a chronic low-grade inflammatory milieu driven by adiposity. C-X-C motif chemokine ligand 1 (CXCL1) has been linked to insulin resistance and endothelial dysfunction, but its diagnostic relevance remains unclear.Methods. Our study employed a cross-sectional design and enrolled 104 adults: 52 newly diagnosed treatment-naive T2DM patients and 52 normoglycemic controls matched for age and sex. Serum CXCL1, high-sensitivity C-reactive protein (hs-CRP), and metabolic parameters were measured. Logistic regression models to discriminate MS and T2DM status were constructed (base model: age, sex, BMI) and then expanded by adding hs-CRP, CXCL1, or both. Model performance was assessed for discrimination (AUC), calibration (Integrated Calibration Index [ICI], Expected Calibration Error [ECE]), and clinical utility (decision curve analysis, DCA) in accordance with TRIPOD 2024.Results. CXCL1 correlated with BMI (r=0.33, q=0.004) and hs-CRP (r=0.29, q=0.021), but not glycemic indices. For MS, CXCL1 marginally improved the base model (ΔAUC=+0.003, p=0.81); for T2DM, ΔAUC=+0.007 (p=0.60). hs-CRP performed better (AUC=0.744 for T2DM; 0.743 for MS) and the combined panel achieved the highest discrimination (AUC=0.769 and 0.745, respectively).Conclusions. CXCL1 reflects adiposity-related inflammation but provides only minimal incremental discrimination for metabolic syndrome and T2DM beyond conventional markers such as age, sex, BMI, and hs-CRP. The combined hs-CRP+CXCL1 panel achieved the best overall statistical performance, although its clinical utility remains limited. These findings emphasize the need for integrated multi-marker approaches rather than single-biomarker screening in metabolic risk assessment.

Prevalence and predictors of poor glycemic control in patients with type 2 diabetes mellitus attending Alexandria Main University Hospital

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Despite the advances in diabetes management, there is still a high prevalence of poor glycemic control worldwide. This study aimed to determine the prevalence and predictors of poor glycemic control among patients with type 2 diabetes mellitus (T2DM) attending the outpatient clinic at Alexandria Main University Hospital (AMUH) Egypt.Methods. This cross-sectional study was conducted on 290 patients with T2DM. Data were collected on sociodemographic factors, medical history, comorbidities, lifestyle behaviors, medication adherence, and biochemical measures. Statistical analyses including correlation and regression models were used to explore the relationships between various factors and glycemic control.Results. The study revealed that 82.8% of participants had uncontrolled diabetes. Poor glycemic control was significantly associated with older age, lower education, rural residence, unemployment, and lower income. Additionally, patients with uncontrolled diabetes had higher rates of hypertension, dyslipidemia, ischemic heart disease, and diabetic peripheral neuropathy. Better physical activity and dietary adherence were linked to improved glycemic control, while medication adherence was significantly lower in the uncontrolled group. Among the significant predictors, physical activity (ORs=116.6–575.8) was the strongest predictor of improved diabetes control. Moreover, medication adherence (OR=4.098) and higher education (OR=8.354) were strongly associated with better diabetes control.Conclusions. Socioeconomic factors, lifestyle behaviors, and medication adherence are key predictors of glycemic control in T2DM patients. Physical activity, medication adherence, and higher education were the strongest predictors of better glycemic control. Addressing these factors through targeted interventions, particularly in rural areas, is crucial for improving diabetes management and reducing the related complications.