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Journal of Translational Medicine May 2024Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested...
BACKGROUND
Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements.
METHODS
Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed.
RESULTS
GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level.
CONCLUSIONS
This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option.
Topics: Humans; Male; Female; Osteoarthritis; Middle Aged; Heart Rate; Aged; Sympathetic Nervous System; Hydrocortisone; Pain
PubMed: 38755685
DOI: 10.1186/s12967-024-05258-9 -
The Journal of Clinical Endocrinology... May 2024Hierarchical clustering (HC) identifies subtypes of polycystic ovary syndrome (PCOS).
CONTEXT
Hierarchical clustering (HC) identifies subtypes of polycystic ovary syndrome (PCOS).
OBJECTIVE
This work aimed to identify clinically significant subtypes in a PCOS cohort diagnosed with the Rotterdam criteria and to further characterize the distinct subtypes.
METHODS
Clustering was performed using the variables body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), testosterone, insulin, and glucose. Subtype characterization was performed by analyzing the variables estradiol, androstenedione, dehydroepiandrosterone, cortisol, anti-Müllerian hormone (AMH), total follicle count (TFC), lipid profile, and blood pressure. Study participants were girls and women who attended our university hospital for reproductive endocrinology screening between February 1993 and February 2021. In total, 2502 female participants of European ancestry, aged 13 to 45 years with PCOS (according to the Rotterdam criteria), were included. A subset of these (n = 1067) fulfilled the National Institutes of Health criteria (ovulatory dysfunction and hyperandrogenism). Main outcome measures included the identification of distinct PCOS subtypes using cluster analysis. Additional clinical variables associated with these subtypes were assessed.
RESULTS
Metabolic, reproductive, and background PCOS subtypes were identified. In addition to high LH and SHBG levels, the reproductive subtype had the highest TFC and levels of AMH (all P < .001). In addition to high BMI and insulin levels, the metabolic subtype had higher low-density lipoprotein levels and higher systolic and diastolic blood pressure (all P < .001). The background subtype had lower androstenedione levels and features of the other 2 subtypes.
CONCLUSION
Reproductive and metabolic traits not used for subtyping differed significantly in the subtypes. These findings suggest that the subtypes capture distinct PCOS causal pathways.
PubMed: 38753423
DOI: 10.1210/clinem/dgae298 -
Human Cell Jul 2024Human ATP-binding cassette transporter C11 (ABCC11) is a membrane protein exhibiting ATP-dependent transport activity for a variety of lipophilic anions including...
Human ATP-binding cassette transporter C11 (ABCC11) is a membrane protein exhibiting ATP-dependent transport activity for a variety of lipophilic anions including endogenous substances and xenobiotics such as anti-cancer agents. Accumulating evidence indicates that ABCC11 wild type is responsible for the high-secretion phenotypes in human apocrine glands including wet type of earwax and the risk of axillary osmidrosis. Also, a less-functional variant of ABCC11 was reportedly associated with a risk for drug-induced toxicity in humans. Thus, functional change in ABCC11 may affect individual's constitution and drug toxicity, which led us to reason that functional validation of genetic variations in ABCC11 should be of importance. Therefore, in addition to p.G180R (a well-characterized non-functional variant of ABCC11), we studied cellular expression and function of 10 variants of ABCC11. In this study, ABCC11 function was evaluated as an ATP-dependent transport of radio labeled-dehydroepiandrosterone sulfate using ABCC11-expressing plasma membrane vesicles. Except for p.G180R, other 10 variants were maturated as an N-linked glycoprotein and expressed on the plasma membrane. We found that six variants impaired the net cellular function of ABCC11. Among them, p.R630W was most influential. Including this identification of a significantly-dysfunctional variant, our findings will extend our understanding of genetic variations and biochemical features of ABCC11 protein.
Topics: Humans; ATP-Binding Cassette Transporters; Sweat Gland Diseases; Genetic Variation; Risk Factors; Apocrine Glands; Cell Membrane; Gene Expression; Biological Transport; Adenosine Triphosphate
PubMed: 38750405
DOI: 10.1007/s13577-024-01074-x -
Frontiers in Endocrinology 2024The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically.
CONTEXT
The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically.
OBJECTIVE
To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population.
DESIGN
Retrospective cohort study.
METHODS
We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion.
RESULTS
UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery.
CONCLUSIONS
UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.
Topics: Humans; Hyperaldosteronism; Male; Female; Middle Aged; Hydrocortisone; Retrospective Studies; Adult; Aldosterone; Adrenalectomy; China; Treatment Outcome; Adrenocorticotropic Hormone; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Follow-Up Studies; Prognosis
PubMed: 38745957
DOI: 10.3389/fendo.2024.1369582 -
Alternative Therapies in Health and... May 2024To investigate and analyze the influencing factors of simple early breast development in girls, to discover the dangers and triggers of PT conversion to ICPP, and the...
Analysis of Influencing Factors and Strategies for Premature Breast Development in Female Children based on Logistic Regression Analysis: A Randomized Double-blind Controlled Clinical Trial.
OBJECTIVE
To investigate and analyze the influencing factors of simple early breast development in girls, to discover the dangers and triggers of PT conversion to ICPP, and the time point of transformation in order to detect and prevent the occurrence of transformation in advance and reduce the incidence of idiopathic central precocious puberty. Ensure children's physical and mental health and normal growth and development.
METHODS
A total of 50 children with PT admitted to our hospital from April 2019 to December 2020 were included in the study group, and 50 children with physical examination during the same period were selected as the control group. All children were tested for vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., and IGFBp-3 at 3, 6, 9 and 12 months after the diagnosis of PT.
RESULTS
Vitamin D levels decreased in the child, indicating that vitamin D deficiency was closely related to the age of breast development in ICPP girls and may be related to serum P-FSH, P-LH and E2 levels. Increased levels of IGFBp-3 indicate that these indicators are involved in the onset of ICPP. Children have a higher BMI, watch idol dramas or play mobile games longer, often eat snacks containing preservatives, have a fishy diet, are more irritable and sensitive, and dry stools are also risk factors affecting the early development of simple breasts in girls.
CONCLUSION
The influencing factors leading to simple, early breast development in girls include vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., IGFBp-3, and should be combined with the progression of breast Tanner staging (complete regression, recurrent, and persistent), height growth rate, bone age, Uterine and ovarian B ultrasound, sex hormones, etc., warn of the conversion of PT to ICPP, and ensure children's physical and mental health and normal growth and development.
PubMed: 38743888
DOI: No ID Found -
International Journal of Occupational... May 2024The incidence of occupational traumatic injuries caused by human error has been reported to occur at 11:00 and 8-9 h after commencing work. Impaired attention is...
The incidence of occupational traumatic injuries caused by human error has been reported to occur at 11:00 and 8-9 h after commencing work. Impaired attention is closely related to the incidence of these accidents. Therefore, this study aimed to clarify the changes in blood glucose, fatigue and stress response hormone levels over time among workers in a secondary industry. The blood glucose and subjective fatigue levels of 26 male secondary-industry workers were measured on workdays. In addition, the cortisol and dehydroepiandrosterone levels in saliva were measured on one workday and one holiday. Blood glucose levels at 11:00 and 17:30 on the workday were significantly lower than those at 09:30. Moreover, hypoglycemia was observed in some participants. A significant increase in subjective fatigue levels was observed during the workday. However, no significant differences in salivary cortisol levels were observed between the workday and the holiday at any time point. Blood glucose levels decreased and subjective fatigue levels increased at the time points that occupational accidents were reported to occur most frequently during work. These factors may contribute to human errors due to impaired attentional function.
PubMed: 38741548
DOI: 10.1080/10803548.2024.2347742 -
Comprehensive Psychoneuroendocrinology Aug 2024Suicidal ideation, an important risk factor for suicide attempts, has an unclear neurobiological basis and is potentially linked to the dysregulation of the...
Higher levels of plasma Adrenocorticotropic hormone (ACTH) are associated with lower suicidal ideation in depressed patients compared to controls and suicide attempters, independently from depression severity.
INTRODUCTION
Suicidal ideation, an important risk factor for suicide attempts, has an unclear neurobiological basis and is potentially linked to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and immune-inflammatory systems. While inflammatory markers have been associated with suicide attempts and, to a lower extent suicidal ideation, the data on the role of a stress-response system is less robust, with most studies carried out with cortisol showing inconsistent results. The present study extends on the previous studies implicating stress-response and immune-inflammatory systems in suicidal thoughts and behaviours, focusing on the associations of several stress-response (adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA)) and immune-inflammatory (C-reactive protein (CRP),interle ukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha)) with suicidal ideation severity in recent suicide attempters, patients with major depressive disorder, and non-psychiatric controls.
METHODS
This observational study included 156 adults from three Vilnius hospitals, recruited into one of the three groups in equal parts: recent suicide attempters, patients with major depressive disorder in current depressive episode, and non-psychiatric controls. Measures included the Hamilton Depression Rating Scale (HDRS-17) and the Beck Scale for Suicide Ideation/Suicide Severity Index (BSS/SSI), alongside sociodemographic data, alcohol, tobacco use, and morning blood samples, measuring plasma ACTH, cortisol, DHEA, CRP, and IL-6. Data were analysed with non-parametric tests, Kendall's tau correlation, and multivariate linear regression adjusted for confounders.
RESULTS
We found a negative correlation between the plasma ACTH levels and suicidal ideation severity (tau = -0.130, p = 0.033), which was driven by the patients with major depressive disorder (tau = -0.237, p = 0.031). Suicidal ideation severity was also negatively correlated with TNF-alpha (tau = -0.231; p < 0.001), positively correlated with IL-6 (tau = 0.154, p = 0.015), and CRP levels (tau = 0.153, p = 0.015), but no differences were observed in group-stratified analyses. The association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder remained robust to adjustment for major confounders (adjusted for age, sex, education years, body mass index, smoking status, plasma CRP and PEth concentration (measuring chronic alcohol exposure), and antidepressant use) in the linear regression model (t = -2.71, p = 0.011), as well as additionally adjusting for depression severity (t = -2.99, p = 0.006).
DISCUSSION
The present study shows an association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder, robust to adjustment for antidepressant use and depression severity. This finding highlights the potential role of ACTH, in elucidating the effects of stress and mental health disorders. Our findings underscore the importance of the HPA axis in the diagnosis and treatment of suicidal ideation in major depressive disorder and invite further research on interventions targeting this pathway.
PubMed: 38737407
DOI: 10.1016/j.cpnec.2024.100235 -
Revista Internacional de Andrologia Mar 2024Dopamine and prolactin are the key mediators involved in sexual function in both males and females, but the role of dopamine in female sexual dysfunction (FSD) is still...
Dopamine and prolactin are the key mediators involved in sexual function in both males and females, but the role of dopamine in female sexual dysfunction (FSD) is still unclear. The aim was to investigate the possible role of dopamine and their relationship with sex steroid hormones (estrogen, progesterone and dehydroepiandrosterone; DHEA) and prolactin levels in Egyptian women suffering from sexual dysfunction. This study included 84 women having sexual dysfunction (FSD group) and 84 normal sexual function (control group). All women were subjected to the questionnaire to assess their demographic and gynecological data as well as female sexual function index (FSFI). Blood samples were collected from all women for measuring serum estradiol, progesterone, DHEA, prolactin and dopamine levels. FSD patients had significantly higher serum progesterone and DHEA and prolactin levels; while significantly lower dopamine and estradiol levels versus controls ( < 0.001). In all women, dopamine level appeared as a predictor of FSD at cut-off point ≤8.8 ng/mL with sensitivity (75%), specificity (92%) and accuracy (83%) ( < 0.001). The low levels of dopamine were associated with significantly higher prevalence in patients with low estradiol ( < 0.001) and high progesterone ( < 0.001), DHEA ( < 0.001) and prolactin ( = 0.004). Also, dopamine was significantly positive correlation with arousal score ( = 0.16, = 0.04), and negative correlation with age ( = -0.31, < 0.001), pain score ( = -0.19, = 0.01), DHEA ( = -0.45, < 0.001) and prolactin ( = -0.28, < 0.001). Low serum dopamine level is a potential diagnostic biomarker in women's sexual dysfunction and their association with high prolactin and sex steroid hormones dysfunction.
Topics: Humans; Female; Dopamine; Biomarkers; Adult; Sexual Dysfunction, Physiological; Prolactin; Progesterone; Estradiol; Case-Control Studies; Egypt; Sensitivity and Specificity; Surveys and Questionnaires; Young Adult; Middle Aged; Dehydroepiandrosterone; Gonadal Steroid Hormones
PubMed: 38735872
DOI: 10.22514/j.androl.2024.002 -
Gene Aug 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs...
Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50-70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a blue-green alga that may increase insulin sensitivity. Therefore, our study aims to evaluate SP as an alternative treatment to Met for improving glucose homeostasis by assessing the expression of 11 crucial genes involved in the insulin signaling pathway. After induction of the PCOS model using dehydroepiandrosterone (DHEA) (60 mg/kg bwt) for 30 consecutive days, rats were allocated into six groups. Relative liver weight, glutamic pyruvic transaminase (GPT) serum levels, glutamic-oxaloacetic transaminase (GOT), and insulin were determined. Furthermore, the gene expression of Ins1, Irs1, Pik3ca, Prkcz, Foxo1, Srebf1, Ppargc1a, Pklr, Gk, G6pc, and Pepck in the rat's liver tissue was determined using qRT-PCR. Treatment of the PCOS control group with Met or SP revealed a decrease in all these parameters compared with the PCOS model. Additionally, we found a statistically significant difference in the expression of both the Gk and Prkcz genes. To summarize our study results, SP or Met supplementation to PCOS rats had almost the same effect on assessed relative liver weight, GOT, GPT, and insulin levels compared with PCOS control rats. If further studies confirm and detect more impact of SP on IR in PCOS, SP could be used instead of Met since the latter causes many side effects.
Topics: Animals; Polycystic Ovary Syndrome; Female; Metformin; Rats; Signal Transduction; Spirulina; Insulin; Disease Models, Animal; Insulin Resistance; Liver; Rats, Wistar; Hypoglycemic Agents; Gene Expression Regulation
PubMed: 38735598
DOI: 10.1016/j.gene.2024.148524 -
Journal of Ovarian Research May 2024Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such as insulin resistance and obesity, which often lead to the development of type II diabetes and cardiovascular disease with serious consequences. Current treatment of PCOS with symptomatic treatments such as hormone replacement, which has many side effects. Research on its origin and pathogenesis is urgently needed. Although improving the metabolic status of the body can alleviate reproductive function in some patients, there is still a subset of patients with metabolically normal PCOS that lacks therapeutic tools to address ovarian etiology.
METHODS
The effect of IL-22 on PCOS ovarian function was verified in a non-metabolic PCOS mouse model induced by dehydroepiandrosterone (DHEA) and rosiglitazone, as well as granulosa cell -specific STAT3 knockout (FshrStat3) mice (10 groups totally and n = 5 per group). Mice were maintained under controlled temperature and lighting conditions with free access to food and water in a specific pathogen-free (SPF) facility. Secondary follicles separated from FshrStat3 mice were cultured in vitro with DHEA to mimic the hyperandrogenic environment in PCOS ovaries (4 groups and n = 7 per group) and then were treated with IL-22 to investigate the specific role of IL-22 on ovarian function.
RESULTS
We developed a non-metabolic mice model with rosiglitazone superimposed on DHEA. This model has normal metabolic function as evidenced by normal glucose tolerance without insulin resistance and PCOS-like ovarian function as evidenced by irregular estrous cycle, polycystic ovarian morphology (PCOM), abnormalities in sex hormone level. Supplementation with IL-22 improved these ovarian functions in non-metabolic PCOS mice. Application of DHEA in an in vitro follicular culture system to simulate PCOS follicular developmental block and ovulation impairment. Follicles from FshrStat3 did not show improvement in POCS follicle development with the addition of IL-22. In DHEA-induced PCOS mice, selective ablation of STAT3 in granulosa cells significantly reversed the ameliorative effect of IL-22 on ovarian function.
CONCLUSION
IL-22 can improve non-metabolic PCOS mice ovarian function. Granulosa cells deficient in STAT3 reverses the role of IL-22 in alleviating ovary dysfunction in non-metabolic PCOS mice.
Topics: Female; Animals; Polycystic Ovary Syndrome; Interleukin-22; Mice; Interleukins; Ovary; Disease Models, Animal; Dehydroepiandrosterone; STAT3 Transcription Factor; Rosiglitazone; Granulosa Cells; Mice, Knockout
PubMed: 38734641
DOI: 10.1186/s13048-024-01428-x