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Steroidogenesis of gonadal cells is tightly regulated by gonadotropins. However, certain polycyclic aromatic hydrocarbons, including Benzo[a]pyrene (BaP), induce reproductive toxicity. Several existing studies have considered higher than environmentally relevant concentrations of BaP on male and female steroidogenesis following long-term exposure. Also, the impact of short-term exposure to BaP on gonadotropin-stimulated cells is understudied. Therefore, we evaluated the effect of 1 nM and 1 µM BaP on luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e. the mouse tumor Leydig cell line mLTC1, and the human primary granulosa lutein cells (hGLC) post 8- and 24-h exposure. Cell signalling studies were performed by homogeneous time-resolved fluorescence (HTRF) assay, bioluminescence energy transfer (BRET) and Western blotting, while immunostainings and immunoassays were used for intracellular protein expression and steroidogenesis analyses, respectively. BaP decreased cAMP production in gonadotropin-stimulated mLTC1 interfering with Gαs activation. Therefore, decrease in gonadotropin-mediated CREB phosphorylation in mLTC1 treated with 1 μM BaP was observed, while StAR protein levels in gonadotropin-stimulated mLTC1 cells were unaffected by BaP. Further, BaP decreased LH- and hCG-mediated progesterone production in mLTC1. Contrastingly, BaP failed to mediate any change in cAMP, genes and proteins of steroidogenic machinery and steroidogenesis of gonadotropin-treated hGLC. Our results indicate that short-term exposure to BaP significantly impairs steroidogenic signalling in mLTC1 interfering with Gαs. These findings could have a significant impact on our understanding of the mechanism of reproductive toxicity by endocrine disruptors., (© 2024. The Author(s).)

Bisphenol A (BPA) is a ubiquitous, synthetic chemical proven to induce reproductive disorders in both men and women. The available studies investigated the effects of BPA on male and female steroidogenesis following long-term exposure to the compound at relatively high environmental concentrations. However, the impact of short-term exposure to BPA on reproduction is poorly studied. We evaluated if 8 and 24 h exposure to 1 nM and 1 µM BPA perturbs luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e., the mouse tumour Leydig cell line mLTC1, and human primary granulosa lutein cells (hGLC). Cell signalling studies were performed using a homogeneous time-resolved fluorescence (HTRF) assay and Western blotting, while gene expression analysis was carried out using real-time PCR. Immunostainings and an immunoassay were used for intracellular protein expression and steroidogenesis analyses, respectively. The presence of BPA leads to no significant changes in gonadotropin-induced cAMP accumulation, alongside phosphorylation of downstream molecules, such as ERK1/2, CREB and p38 MAPK, in both the cell models. BPA did not impact STARD1 , CYP11A1 and CYP19A1 gene expression in hGLC, nor Stard1 and Cyp17a1 expression in mLTC1 treated with LH/hCG. Additionally, the StAR protein expression was unchanged upon exposure to BPA. Progesterone and oestradiol levels in the culture medium, measured by hGLC, as well as the testosterone and progesterone levels in the culture medium, measured by mLTC1, did not change in the presence of BPA combined with LH/hCG. These data suggest that short-term exposure to environmental concentrations of BPA does not compromise the LH/hCG-induced steroidogenic potential of either human granulosa or mouse Leydig cells.

We report the synthesis and pH dependent emission spectral behaviour of four emissive iridium(III) complexes (Ir1-Ir4) with two isomeric pairs of bis-trifluoromethyl appended benzimidazole ligands. The imidazolyl hydrogen(N-H) has been replaced by phenyl groups (N-Ph) in two ligands to understand the impact of hydrogen bonding on the photophysical properties of the complexes and it indeed plays interesting role in the charge-transfer dynamics. The pH dependent electronic spectral change is observed for two of the complexes. The enhancement of emission intensity is observed at different wavelength for pH<7 and pH>7 for Ir1 and Ir3. The emission sensing of biogenic amines with pk a values ranging from 5.80-9.74 is reported along with cellular imaging. The complex Ir1 specifically localizes within lysosome (pH=4.5-5) and thus image this organelle with great precision. The detail electronic spectra and electrochemical behaviour were reported here along with TDDFT results., (© 2024 Wiley-VCH GmbH.)

Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma ofthe FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed. [ABSTRACT FROM AUTHOR]

We recently described a solid phase immunoradiometric assay (IRMA) for anti-thyroglobulin and anti-thyroid microsomal antibodies. In the present study a similar IRMA for gastric parietal cell antibodies (PCA) has been developed. Samples to be tested are incubated within wells of polyvinyl microtitre plates coated with solubilized gastric microsomal antigen. After removal of unbound material, PCA is detected by adding purified 125I-anti-human IgG antibody. A good correlation was found with the results of PCA assays obtained by indirect immunofluorescence. In contrast, negative PCA by IRMA were consistently obtained in sera containing high titres of several other organ specific and non-organ specific autoantibodies. PCA determinations by IRMA were than carried out in a series of normal controls and patients with autoimmune or non-autoimmune thyroid disorders. Positive results were obtained in three of 70 (4.3%) apparently normal subjects, in 16 of 87 (18.4%) patients with Hashimoto's thyroiditis, in 10 of 48 (20.8%) with idiopathic myxoedema. in 25 of 95 (25.6%) with Graves' disease and in five of 64 (7.8%) with other non-autoimmune thyroid disorders. Preliminary results showed that quantitative measurements of PCA by IRMA could be performed using a serum containing high levels of PCA as standard reference. In conclusion, PCA may be easily and specifically detected using the same IRMA procedure previously developed for anti-thyroid antibodies. We therefore suggest that the present IRMA may be proposed as a general technique for the detection of different organ specific autoantibodies. [ABSTRACT FROM AUTHOR]

Activating photosensitizers with long-wavelength excitation is an important parameter for effective photodynamic therapy due to the minimal toxicity of this light, its superior tissue penetration, and excellent spatial resolution. Unfortunately, most Ir(III) complexes suffer from limited absorption within the phototherapeutic window, rendering them ineffective against deep-seated and/or large tumors, which poses a significant barrier to their clinical application. To address this issue, several efforts have been recently made to shift the absorption of Ir(III) photosensitizers to the deep-red/near-infrared region by using different strategies: functionalization with organic fluorophores, including porphyrinoid compounds, and ligand design via π-extension and donor–acceptor interactions. In this Frontier, we highlight such new developments and the ongoing challenges in this field. [ABSTRACT FROM AUTHOR]

A highly regio-, enantio- and diastereo-selective strategy involving initial enantioselective conjugate addition to 4-nitro-5-styrylisoxazoles serves as a key step for the desymmetrization of 2,5-cyclohexadienones has been disclosed. We have designed a new class of 2,5-cyclohexadienones appended with 4-nitro-5-styrylisoxazoles to undergo organocatalytic asymmetric double or triple conjugate addition in a domino sequence depending on the substrate type leading to desymmetrization of the 2,5-cyclohexadienone core. The developed protocol allows the construction of a valuable hydrophenanthrene core or a unique bridged scaffold bearing multiple chiral centers with excellent enantio- (up to >99.5 : 0.5 er) and diastereo-control for diverse substrates. [ABSTRACT FROM AUTHOR]

Classified as endocrine disrupting chemicals (EDCs), perchlorate, nitrate, and thiocyanate have been implicated with obesity and reproductive disorders. This study used three cycles of the National Health and Nutrition Examination Survey (NHANES 2013–2018); 813 women of reproductive age were finally included. We used multivariable logistic regression to analyze the associations between the three anions and obesity and infertility. Subsequently, we performed mediation analysis to explore the potential mediating effect of obesity on infertility in association with anion exposure. Increased concentrations of perchlorate and nitrate showed inverse correlations with the risk of obesity (OR = 0.73, 95% CI: 0.55–0.96; OR = 0.59, 95% CI: 0.40–0.87). Perchlorate was negatively associated with infertility (OR = 0.68, 95% CI: 0.51–0.91), and obesity was a mediator in association between perchlorate and infertility. These findings suggest that women of reproductive age may be protected from obesity and infertility by exposure to perchlorate and nitrate, with obesity acting as a moderating factor in the observed association. This study provides a valuable understanding of the complex links between environmental contaminants, obesity, and reproductive health, and identifies potential strategies to reduce the risk of infertility and improve women's health. [ABSTRACT FROM AUTHOR]

Background: Few studies are reported on interventions that have been carried out in children and adolescents using diaphragmatic breathing (DB) together with methods like counseling, muscle relaxation, therapeutic exercise, and music therapy. Objective: The goal of the review is to evaluate the effectiveness of DB as complementary therapy in the stress of the pediatric population (6–18 years old). Methods: Detailed research was carried out in the current literature to find relevant studies published from 2010 to October 2024 in PubMed and Cochrane Library. Thirteen studies that fulfilled the inclusion criteria were included in the study. Nine studies involved obese and overweight pediatric populations and the other four involved pediatric patients. Results: The interventions comprised two 8-week studies in an obese pediatric population, seven studies in healthy children and adolescents with normal weight. The studies were based on DB, muscle relaxation, nutrition, counseling, music therapy, and slow breathing exercises. The participants in the intervention group improved in comparison to those in the control group in terms of stress and depression in most included studies, in terms of school performance in two studies, in terms of better family relationships in one study, and showed improvement in anthropometric indicators in two studies. In four studies that involved pediatric patients, stress and fear of medical procedures were reduced. Conclusions: DB can effectively contribute on its own or in combination with other therapeutic methods to improving physiological and psychological indicators in the pediatric population. It is useful to integrate stress management programs that include DB training as clinical practice in primary healthcare and in school schedules for elementary and high-school students. [ABSTRACT FROM AUTHOR]

Thyroid function plays a seminal role in the growth and development of children, and alterations in signaling pathways which interfere with the biosynthesis, transport, and metabolism of thyroid hormones might impact on the skin of such patients: this review explores the relationship between different thyroid disorders and dermatological manifestations with a particular focus on the pediatric population. Common cutaneous conditions associated with thyroid dysfunction may include chronic urticaria, vitiligo, and alopecia, which can be early harbingers of an underlying endocrine disruption. This review also highlights the growing cognizance of a "thyroid–skin axis", with thyroid hormones influencing many physiologic processes within the skin such as keratinocyte proliferation, hair growth, and epidermal differentiation. A precocious recognition of abnormal dermatological signs can be crucial in pediatric patients for a timely diagnosis before any development of complications and for personalized treatments of an underlying thyroid disorder, which can even be symptomless at an initial phase. Despite the lack of standardized guidelines for managing dermatologic manifestations occurring in thyroid diseases, a regular screening to identify endocrine dysfunction is recommended in those children who present chronic urticaria, vitiligo, or alopecia, though further research is needed to decipher mechanisms involved in the thyroid-skin partnership and develop more targeted management approaches. [ABSTRACT FROM AUTHOR]

Parallel measurements of circulating anti-thyroid microsomal (anti-M) antibodies by radioassay and haemagglutinatinn were performed on subjects with or without thyroid disorders. Three quarters (75.4%) of control subjects had undetectable antibody levels (< 10 u/ml) by radioassay and only 3.1% had concentrations of &ges; 75 u/ml. Abnormally elevated levels (&ges; 75 u/ml) were found in most of the patients with Hashimoto's thyroiditis (94.1%) or idiopathic myxoedema (86.7%), in the majority (75.0%) of those with Graves' disease and only in a minority of those with other thyroid disorders. The percentage of positive sera by haemagglutination was verisimilar in all groups to that of abnormal values observed in the radioassay. Direct comparison of parallel tests on a total of 631 sera revealed a highly significant correlation (r = 0.91, P < 0.001) between the two methods, but elevated antibody titres by haemaegglutination were found in some sera with negative radioassays. All these sera were from a single patient with thyroid carcinoma associated with Hashimoto's thyroiditis and had elevated levels of anti-thyroglobulin (anti-Tg) antibodies. Evidence that such discrepancies were due to anti-Tg antibodies reacting with microsomal-bound Tg was provided by the demonstration that the haemagglutination produced by these sera could be completely inhibited by the addition of Tg. A similar inhibition was observed with two rabbit antisera to human Tg, but not with sera from patients with thyroid autoimmune disorders containing high levels of anti-microsomal anti-bodies. [ABSTRACT FROM AUTHOR]

Objectives: To examine, by ultrasonography the prevalence of thyroid nodules in a cross sectional study of male medical workers occupationally exposed to chi radiation at the Pisa hospital, in comparison with controls matched for age and sex.Methods: 50 male medical workers exposed to radiation were randomly matched for age (+/- 2 years) with 100 male workers not occupationally exposed to ionising radiation who lived in a slightly iodine deficient area of Tuscany (Lunigiana) (control group 1), and with 100 male workers not exposed to radiation who lived in the same area (Pisa) (control group 2).Results: Of the occupationally exposed subjects, thyroid nodules were detected in 19/50 (38.0%). Among controls, thyroid nodules were detected in 19/100 subjects of control group 1 and in 13/100 of control group 2. Comparison of exposed and control groups, stratified into 30-39, 40-49, and 50-59 year old age subgroups, showed a higher significant relative risk for thyroid nodules in the exposed subjects.Conclusion: The results suggest that occupational exposure to radiation may be a risk factor for thyroid nodules. [ABSTRACT FROM AUTHOR]