OBJECTIVES:This study investigates the spectrum of disorders of sexual development (DSD) cases documented in Duhok Governorate, Iraq, from 2012 to 2022. It further characterizes the molecular and clinical profiles of treated patients and evaluates their surgical outcomes. METHODS:Data were retrospectively collected from 52 DSD pediatric patients (0-18 years). Each patient underwent a comprehensive physical assessment and a diagnostic workup, including chromosomal analysis (karyotyping) and hormonal profiling. Endoscopic assessment was performed when further anatomical clarification was required. A multidisciplinary team evaluated each case to reach consensus on diagnosis, gender assignment, and management plans. Surgical interventions and non-surgical management, such as hormone replacement therapy, were provided as indicated. Postoperative follow-up protocols were implemented to monitor surgical outcomes. RESULTS:The prevalence of DSD was 28.7 per 10,000. Most cases (48.1 %) were diagnosed with congenital adrenal hyperplasia (CAH), followed by partial androgen insensitivity syndrome (PAIS, 23.1 %), complete androgen insensitivity syndrome (CAIS, 7.6 %), Persistent Müllerian Duct Syndrome (PMDS, 5.8 %), and Turner syndrome (1.9 %). The XX DSD group exhibited a higher proportion of CAH diagnoses, while the XY group had higher proportions of PAIS, CAIS, and PMDS. This difference was statistically significant (phi=0.715, p=0.003). CONCLUSIONS:This decade-long pediatric surgical experience in Duhok demonstrates that pediatricians and surgeons can accurately diagnose DSD categories, deliver care aligned with international standards, and achieve improved surgical outcomes. Future research should prioritize standardized psychosocial assessments and sustained investment to translate genomic advances into equitable, evidence-based care worldwide.
OBJECTIVES:Early prediction of gestational diabetes mellitus (GDM) is crucial. This study evaluated the combined predictive value of sex hormone-binding globulin (SHBG) and visceral adipose tissue-derived serine protease inhibitor (vaspin) in early pregnancy for GDM. METHODS:A retrospective case-control study was conducted involving 50 pregnant women diagnosed with GDM (GDM group) and 50 with normal glucose tolerance (control group) from January to December 2022 at Beijing Aerospace General Hospital. Fasting venous blood was collected at 8-13+6 weeks of gestation. Serum levels of SHBG and vaspin were measured by enzyme-linked immunosorbent assay (ELISA). Clinical data including age, body mass index (BMI), parity, family history of diabetes, gestational age, amniotic fluid index (AFI), mode of delivery, and neonatal birth weight were compared between groups. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive value of individual and combined biomarkers. RESULTS:Pre-pregnancy BMI, cesarean section rate, and neonatal birth weight were significantly higher in the GDM group. Serum SHBG levels were significantly lower (392.26 ± 46.34 vs. 454.49 ± 31.66 nmol/mL, p<0.001), and vaspin levels were significantly higher (3.04 ± 0.47 vs. 2.54 ± 0.36 ng/mL, p<0.001) in GDM. The combined model of SHBG and vaspin showed superior predictive performance (AUC=0.934, accuracy=91.0 %, sensitivity=87.2 %, specificity=94.9 %) compared to either biomarker alone. CONCLUSIONS:The combined measurement of serum SHBG and vaspin in early pregnancy suggests a potentially useful predictive performance for GDM. While limited by the relatively small sample size and the research-use-only nature of the vaspin assay, this dual-biomarker approach warrants further validation in larger studies before its clinical applicability can be fully established.
OBJECTIVES:Testosterone deficiency and metabolic dysfunction frequently coexist in aging men; however, whether metabolic impairment is associated with a progressive decline in testosterone across the metabolic spectrum remains unclear. METHODS:We analyzed 2,192 U.S. men aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES). Metabolic burden was assessed using the triglyceride-glucose (TyG) index. Survey-weighted linear regression models were used to evaluate the association between TyG and log-transformed total testosterone after adjustment for age, HDL cholesterol, diabetes, and smoking. Dose-response relationships were further examined using quartiles and restricted cubic spline analyses. RESULTS:Higher TyG levels were independently associated with lower testosterone concentrations. In fully adjusted models, each 1-unit increase in TyG was associated with an approximately 12 % decrease in testosterone (p<0.001). Compared with the lowest TyG quartile, men in the highest quartile had approximately 19 % lower testosterone levels. Spline analysis demonstrated a consistent inverse association without significant nonlinearity (p for nonlinearity=0.21), supporting a graded and continuous relationship across the metabolic spectrum. CONCLUSIONS:Higher metabolic burden was independently associated with lower total testosterone levels in middle-aged and older men. However, due to the cross-sectional design and absence of SHBG/free testosterone measurements, these findings should be interpreted cautiously and require confirmation in longitudinal studies.
OBJECTIVES:Type 2 Diabetes Mellitus (T2DM) is a global health challenge linked to microvascular complications like neuropathy and nephropathy. Metformin, first-line therapy, is associated with Vitamin B12 deficiency, potentially worsening neurological outcomes. This study assessed B12 supplementation's association with glycemic control, albuminuria, and peripheral neuropathy. METHODS:A cross-sectional study at Hindu Rao Hospital, New Delhi, included 151 T2DM patients (≥30 years) on B12 supplementation. Serum B12, HbA1c, and urinary albumin-creatinine ratio (ACR) were measured. Neuropathy was evaluated using the Diabetic Neuropathy Symptom (DNS) score. Analysis used SPSS v23; (p<0.05) was significant. RESULTS:Mean age was 50.79 ± 9.60 years (63.6 % female). Neuropathy prevalence (DNS≥1) was 76.8 %. Mean B12 was 452.25 ± 360.86 pg/mL. B12 levels differed significantly across glycemic groups (p<0.001), highest in HbA1c>8.5 %. Neuropathy associated with B12 levels (p=0.027) and oral hypoglycemic use (p=0.010). Logistic regression showed higher B12 paradoxically linked to neuropathy (AOR=1.003; (p=0.023)). No ACR difference (p=0.879). CONCLUSIONS:B12 shows complex ties to neuropathy and glycemic control in supplemented T2DM patients. Elevated serum levels may not indicate functional adequacy; monitoring functional markers like homocysteine or methylmalonic acid is recommended.
One of the most common treatments used for cancer is chemotherapy. Different drugs are used in chemotherapy depending on the type of cancer. In this regard, one of the most basic problems in chemotherapy is drug resistance, in which people undergoing treatment develop resistance to chemotherapy drugs over time. Therefore, the drug dose must be increased over time or the interval between treatments must be reduced, which leads to side effects and damage to normal cells and tissues. Various factors play a role in drug resistance, including ATP-binding cassette (ABC) transporters, which lead to drug resistance by transporting these drugs outside the cell. Also, various factors, including signaling pathways and heat shock proteins (HSP), can play an effective role in drug resistance by interfering with these pumps or other factors involved in drug resistance. A body of studies indicated that, one of the most important signaling pathways that involved in drug resistance is Notch pathway. This pathway plays a fundamental role in drug resistance in cancers by interfering with various mechanisms. Therefore, in this study, our goal is to investigate the role of Notch pathway mechanisms in drug resistance in different cancers.
Vitamin D3 supplementation is beneficial for various symptoms of aging and may stabilize hypothalamic-pituitary-adrenal (HPA) axis function. Systemic and local metabolic activation of vitamin D3 are essential for its acquisition of physiological activity and subsequent direct action. We reasonably believe that the direct effect of the active metabolite of vitamin D3 on the adrenal cortex is of secondary importance for glucocorticoid output, compared to the indirect, pituitary-mediated mechanism of its action. The initially decreased blood level of adrenocorticotropic hormone (ACTH), after the experimental application of vitamin D3, physiologically dominantly acts as a feed-forward mechanism that allows for subsequent increased secretion of stored corticosterone, from the lipid-droplets of adrenocortical zona fasciculata (ZF) cells. The observed absence of changes in mitochondrial dimensions and immunoexpression of 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme in ZF adrenocortical cells, indicating that glucocorticoid production is not intensified, devalues an alternative direct effect of the physiologically active form of vitamin D3 on the adrenal cortex. To verify our concept, specific (structural and expression) in vivo studies are needed, which investigate the effects of vitamin D3 application on the upper parts of the HPA axis. If it is confirmed that the dominant mechanism of action of supplemented vitamin D3 on glucocorticoid output is indirect (pituitary-mediated), and bearing in mind the pulsatile nature of ACTH-glucocorticoid secretion, the hourly and daily schedule of some therapeutic vitamin D3 administration could be more precisely adjusted.
OBJECTIVES:To assess the crosstalk between the serum levels of the metabolic hormones, NO-signaling components, and inflammation markers in patients with coronary artery disease (CAD) with 3-year follow-up. METHODS:A total of 218 included patients underwent coronary angiography and a phone survey with a 3-year follow-up, which included records of cardiovascular (CV) events. Gensini score was evaluated to quantify atherosclerosis. NO-synthases (NOS) were profiled by an Explorer antibody array (Full Moon Biosystems, USA). ELISA was used to assay NOS, endothelin-1, leptin, adiponectin, and cGAMP in the whole cohort. C-reactive protein (CRP), glucose, and insulin were measured according to a routine analysis. Serum NOx were measured spectrophotometrically under diet in a hospital setting. Spearman correlation analysis, ROC-analysis, and logistic regressions were used to evaluate the associations between analytes, Gensini score, and CV-events. RESULTS:Correlation analysis reveals a complex network in which leptin deficiency appears to be a central, unfavorable and independent factor linked to CV-events. A pathological cycle involved hormone levels, imbalanced NOS isoforms and endothelin, metabolic factors, and CRP as inflammation marker. The direct pro-atherogenic roles of glucose, insulin, and CRP, and the protective potential of adiponectin and NOx were revealed. CONCLUSIONS:Atherosclerosis was linked to a decrease in NOx. Elevated NOS isoforms may compensate for impaired NOS activity in atherosclerosis. Specific changes in the levels of NOS and NOx may be linked to the signaling pathways contributing to atherosclerosis and point to the correction of these changes using exogenous nitrate as dietary supplement.
Progestins are widely used for endometriosis with proven efficacy and favorable safety. Their microvascular effects, however, are not fully understood. We report a 35-year-old woman who developed recurrent hand erythema and significant nailfold videocapillaroscopy abnormalities after starting dienogest. This prompted a review of available evidence on the vascular impact of progestins, particularly dienogest. Current data indicate complex, dose-dependent effects on microcirculation. Dienogest appears to have a more favorable profile than other synthetic progestins, with limited impact on endothelial adhesion molecules and preservation of estrogen-induced vasodilation. Nonetheless, progestins can modulate endothelial proliferation, angiogenic factor expression, and vascular tone through genomic and non-genomic mechanisms. While generally safe, individual susceptibility to vascular effects may occur. Clinicians should be aware of potential microvascular manifestations during progestin therapy and consider capillaroscopy in patients presenting with relevant cutaneous changes.
OBJECTIVES:This study aimed to investigate the association between thyroid hormone disturbances, obesity-related parameters, and the expression profiles of Y-linked spermatogenic genes (AZFa, AZFb, and AZFc) in infertile men, and to determine whether endocrine and metabolic alterations predict AZF gene dysregulation. METHODS:A case-control study included 150 infertile men and 150 fertile controls. Anthropometric indices and hormonal, biochemical, and inflammatory markers were assessed. Relative expression levels of AZFa, AZFb, and AZFc genes were quantified using qRT-PCR and the 2ˆ-ΔΔCT method. Correlation analysis, LASSO regression, and ROC curve modeling were performed to identify predictors of AZF gene downregulation. RESULTS:Infertile men had significantly higher BMI, waist circumference, and thyroid-stimulating hormone (TSH) levels, with reduced triiodothyronine (T3) and thyroxine (T4) concentrations (p<0.001). AZFa, AZFb, and AZFc expression levels were significantly decreased and negatively correlated with TSH, BMI, and inflammatory cytokines. A combined model of TSH, BMI, and interleukin-6 demonstrated the highest diagnostic accuracy (AUC=0.88), with 86 % sensitivity and 80 % specificity. CONCLUSIONS:Thyroid dysfunction, obesity, and systemic inflammation synergistically downregulate AZF gene expression and impair spermatogenesis. Integrating endocrine, metabolic, inflammatory, and molecular markers may improve diagnostic precision and personalized management of male infertility.
OBJECTIVES:To investigate the association between p53 gene expression, prostate-specific antigen (PSA), and oxidative stress markers (sialic acid and vitamin C) in infertile men. METHODS:This case-control study involved 150 infertile men and 150 fertile controls from Kerala, India. Serum sialic acid, PSA, and vitamin C were measured by ELISA, and p53 expression was quantified by real-time PCR (2-ΔΔCt method). Non-parametric tests, correlation analyses, regression models, and ROC curves were used to assess associations, predictive value, and diagnostic performance. RESULTS:Infertile men showed significantly lower serum sialic acid and vitamin C levels and higher PSA concentrations and p53 gene expression than fertile controls (all p<0.05). p53 expression was significantly associated with PSA, sialic acid, and vitamin C in infertile men. Although no biomarker independently predicted infertility in logistic regression, robust linear regression identified vitamin C as a strong negative predictor and PSA as a positive predictor of p53 expression. ROC analysis revealed moderate discriminative ability for vitamin C, PSA, and sialic acid, while p53 expression alone showed limited diagnostic accuracy. CONCLUSIONS:The concurrent elevation of p53 expression, increased PSA levels, and antioxidant depletion in infertile men reflects activation of cancer-related cellular stress and genomic surveillance pathways rather than evidence of malignancy.
The current topic of sex reassignment is often under strong ideological influence and requires an impartial scientific approach. Considering the importance of corticosteroid status during male-to-female transition for numerous health aspects, here we focus on the 'transitional' functional histology of the hypothalamic-pituitary-adrenal (HPA) axis and corticosteroid output, from the perspective of our experimental experience and the available literature, both experimentally and clinically oriented. In a model of orchidectomized, estradiol-treated adult male rats we observed an increase in aldosterone secretion, as well as in corticosterone synthesis and secretion, but also a decrease in DHEA secretion, all of which were accompanied by expansive changes in adrenal tissue. Available experimental and clinical literature data support our findings. It is known that glucocorticoid excess increases the risk of metabolic complications, elevated blood aldosterone levels may underlie systemic hypertension, while reduced DHEA secretion is associated with various physical and mental issues. These health risks should be kept in mind before possibly starting the male-to-female transition through orchidectomy and estradiol administration.
OBJECTIVES:To evaluate the association of NOX1 gene expression with reproductive hormonal changes in hypothyroid infertile women and assess their diagnostic performance. METHODS:A case-control study was conducted among 150 infertile women with hypothyroidism and 150 healthy age-matched fertile controls. Hormonal (FSH, LH, prolactin) and molecular (NOX1 expression) parameters were measured using standardized assays including qRT-PCR. Group comparisons, Spearman's correlation analyses, scatterplot visualizations, and ROC curve evaluations were conducted to determine associations and diagnostic performance. RESULTS:Hypothyroid infertile women exhibited significantly elevated FSH (19.9 ± 7.5 mIU/mL), LH (20.0 ± 7.6 mIU/mL), prolactin (21.9 ± 8.4 ng/mL), and TSH (7.2 ± 1.8 µIU/mL), along with reduced T3 (0.82 ± 0.21 ng/mL) and T4 (5.1 ± 1.2 μg/dL) compared to controls (p<0.01). NOX1 expression was markedly higher in peripheral blood (1.9 ± 0.9 vs. 1.0 ± 0.2; p<0.01). Moderate positive correlations were observed between NOX1 and FSH (r=0.5638), LH (r=0.5787), and prolactin (r=0.5968), all statistically significant (p<0.01). ROC analysis showed good diagnostic accuracy for FSH (AUC 0.801), LH (AUC 0.732), and prolactin (AUC 0.748), while NOX1 demonstrated superior discriminative performance (AUC 0.835) with 100 % specificity and a positive predictive value of 100 %. CONCLUSIONS:Hypothyroidism-associated infertility is characterized by combined endocrine imbalance and heightened oxidative stress. The strong discriminative ability and hormonal correlations of NOX1 expression suggest its potential use as a molecular biomarker to support infertility risk detection in thyroid-compromised women, providing a basis for oxidative-stress-targeted therapeutic strategies.
OBJECTIVES:Osteoporosis is common among older adults, but the relationship between neuroendocrine factors - particularly catecholamines - and bone mineral density (BMD) is not well understood. This study examined associations between catecholamine levels and BMD in older adults. METHODS:Data from the 2017-2022 biomarkers wave of the Midlife in the United States (MIDUS 3) study were analyzed. Multiple linear regressions assessed associations between creatinine-adjusted urinary norepinephrine and epinephrine levels and BMD at the lumbar spine (L1-L4), right and left total femur, and one-third radius. Models adjusted for age, sex, body mass index (BMI), smoking history, diet, medications (thiazide diuretics, phosphate binders, beta blockers, and vitamin D analogues), and serum creatinine. RESULTS:Among 324 participants (41 % male; mean age 64.3±9.3 years), higher epinephrine levels were significantly associated with lower lumbar spine BMD (Beta=-0.122; 95 % CI: [-0.242 to -0.003], p=0.045), while norepinephrine showed no association (p=0.865). No significant relationships were observed at femoral or radial sites, though norepinephrine was marginally linked to lower one-third radius BMD (Beta=-0.087; 95 % CI: [-0.176 to 0.002], p=0.055). Male sex and higher BMI predicted greater BMD (p<0.05), whereas older age was linked to lower femoral and radial BMD (p<0.05). CONCLUSIONS:Elevated epinephrine levels are associated with reduced lumbar spine BMD in older adults, and elevated norepinephrine levels are associated with reduced distal radius BMD, suggesting catecholamines may influence bone metabolism in a site-specific manner relevant to osteoporosis pathophysiology.
INTRODUCTION:The measurement of HbA1c plays an important role in managing Diabetes mellitus [DM] types 1 and 2. It gives the patient a further insight on diabetes control. In addition to the daily blood sugar tests that show the real-time glucose levels, HbA1c gives an insight on the long-term glucose control. Hence the patient realizes that the higher the blood glucose levels over time, the more HbA1c is formed. The formulas to convert HbA1c into an estimated Average Glucose [eAG] are many, complex and may not be memorized by the patients and investigators alike. They may not give comparable results as well. That may create difficulties when they are utilized in diabetes researches. CONTENT:Hence the authors have analysed six established formulas and were able to derive three simplified formulas, to help patients and doctors alike easily convert their HbA1c to eAG. The authors tried several mathematical calculations and attempts over the simplest formulas [but with a com- parable result] in order to reach to the desired formulas. SUMMARY:The authors suggested 3 formulas that showed around 5 % deviation from the standard formulas results. OUTLOOK:The suggested formulas could convert HbA1c into an [eAG] more easily than the standard formulas and make the sugar measurement easier for the patients, health care providers and investigators as well. The suggested formulas would address a real-life need which is patient understanding and simplification of diabetes management favourably.
Objectives To report a rare case of ovotesticular disorder of sex development (OT-DSD) in a phenotypically male adolescent who presented with bilateral gynecomastia.Case presentation A 15-year-old phenotypically male child presented with progressive enlargement of bilateral breasts for the past 2 years. Clinical examination revealed Tanner stage 4 breast and pubic hair development, unilateral undescended testis, and normal external genitalia. Hormonal evaluation showed low testosterone and raised gonadotropins. Imaging revealed a hypoplastic uterus, fluid-filled vagina, and left-sided ovotestis. Karyotyping confirmed a 46, XX genotype. Clinical, hormonal, and imaging evaluations confirmed the diagnosis of OT-DSD. Because of the established male gender role in his community, he preserved his gender. The patient had liposuction and glandular removal of bilateral breast tissue, as well as left orchidopexy, before being discharged on testosterone replacement treatment.Conclusions Ovotesticular DSD is uncommon and may manifest in late adolescence with gynecomastia rather than ambiguous genitalia. Clinicians should consider OT-DSD in adolescents who presented with bilateral gynecomastia. Early diagnosis, karyotyping, and multidisciplinary management are crucial to optimize long-term outcomes.
INTRODUCTION:As a pivotal molecule in tissue development and homeostasis, WNT5A regulates various aspects of ovarian physiology, including folliculogenesis, oocyte maturation, and hormonal responses. CONTENT:This review summarizes current knowledge on the molecular mechanisms of WNT5A signaling, its role in ovarian health, and its pathological involvement in disorders such as polycystic ovary syndrome (PCOS) and ovarian cancer. We discuss how WNT5A may be a double-edged sword in ovarian diseases and explore its therapeutic potential. SUMMARY:In PCOS, WNT5A exacerbates the inflammatory environment and insulin resistance, disrupting normal folliculogenesis and leading to impaired ovarian function. Moreover, in ovarian cancer, WNT5A presents challenges for therapeutic targeting, as it can either inhibit or facilitate tumor progression depending on the context. OUTLOOK:Continued research into the peripheral and central regulatory mechanisms of WNT5A, along with its interactions with other signaling pathways, will be instrumental in unlocking its full therapeutic potential.
OBJECTIVES:The prevalence of metabolic diseases is increasing worldwide. The identification of novel biomarkers and peptides is one approach to diagnosing and treating such disorders. Spexin is a relatively new peptide hormone that plays a pivotal role in energy metabolism. The prominent role of spexin in obesity, non-alcoholic fatty liver disease, diabetes, and insulin resistance has been established. This mini-review summarizes recent findings on the physiological and potential therapeutic roles of spexin in metabolic disorders. METHODS:A targeted literature review of scientific sources was conducted using PubMed, Scopus, and Web of Science databases. The search focused on published experimental and clinical studies on the metabolic effects of spexin in the liver, adipose tissue, skeletal muscle, and pancreas. RESULTS:This peptide regulates energy homeostasis by affecting the metabolism of specific tissues. Spexin reduces hepatic fat accumulation by modulating lipogenesis and β-oxidation. In adipose tissue, spexin modulates adipocyte differentiation by enhancing lipolysis and inhibiting lipogenesis. In skeletal muscle, it is effective in increasing glucose uptake by upregulating glucose transporter 4. Spexin also affects insulin secretion and regulates β-cell function in the pancreas. CONCLUSIONS:Although studies on the physiological and therapeutic effects of spexin are ongoing, current evidence highlights its involvement in metabolic regulation. Further research is required to clarify the mechanisms and therapeutic potential of this pathway in metabolic diseases.
INTRODUCTION:The aim of this review was to review and summarize the current evidence regarding the expression and role of leptin and its receptor (LEPR) in colorectal cancer (CRC). This includes discussing their involvement in carcinogenesis, progression, and prognosis, as well as assessing their potential as biomarkers and therapeutic targets. CONTENT:We conducted a scoping literature review using several databases. We included studies in English or French that analyzed the expression of leptin and LEPR in the serum or tissue of CRC patients. Additionally, the GEPIA2 platform was employed to investigate the association between leptin and LEPR expression levels and overall survival, as well as their expression across pathological stages and microsatellite subtypes in CRC. SUMMARY:A total of 76 eligible studies published between 1994 and 2024 were included. Analyses through immunohistochemical methods, transcriptomics, and serum measurements indicated elevated expression of leptin and LEPR in CRC. However, findings regarding their prognostic value varied: some studies reported a link between high leptin and LEPR levels and poor prognosis, while others found no correlation or even suggested favorable outcomes. This variability in results can be attributed to differences in methodology, patient diversity, and genetic polymorphisms. OUTLOOK:The leptin-LEPR system seems to play a significant role in the development and progression of CRC, but its exact prognostic impact remains uncertain due to inconsistent findings. Further standardized and large-scale studies are necessary to clarify its clinical relevance. The leptin-LEPR axis shows promise as a biomarker and potential therapeutic target, particularly in the context of obesity-related CRC.
