Adverse effect of immune checkpoint inhibitors in the endocrine system.

Chlorpyrifos promotes chondrocyte pyroptosis to induce articular cartilage degeneration via activating NF-κB signaling.

Minimising exposure to endocrine disruptors (EDs) is a priority within the European Union's political agenda. These chemical substances interfere with the endocrine system, leading to adverse effects on human health and the environment. Despite extensive research, significant uncertainties remain regarding safe levels of exposure to EDs. This paper highlights the need for cautious risk assessment due to substantial knowledge gaps, limitations in testing and unresolved questions about thresholds, non-monotonic dose-responses and low-dose effects. On this basis, we recommend a precautionary approach to risk assessment of EDs and in general support initiatives to reduce exposure by phasing out use and production. In cases where EDs are found in for instance food and drinking water, we propose the use of an additional uncertainty factor of 10 (as default) for the nature of ED effects to ensure more protective risk assessments. Our recommendations aim to contribute to the ongoing discussion on how to effectively manage the risks associated with endocrine disruptors. • There is a growing need for risk assessment of endocrine disruptors (EDs) • Significant uncertainties remain in deriving safe levels of exposure to EDs • Uncertainties include major knowledge gaps, testing limitations, questions around thresholds, and potential for non-monotonic and low-dose effects • Applying an additional uncertainty factor of 10 for ED effects is recommended as a pragmatic precautionary approach

Chronic exposure to chlorpyrifos disturbs the locomotor behavior, vocal traits, and brain transcriptional profile of Japanese medaka (Oryzias latipes).

Microplastics (MPs) have emerged as an important environmental challenge and can threaten human health. These particles can enter the human body through food consumption, breathing and even skin absorption and cause disruption in the functioning of various organs. In addition, MPs also have an effect on reproduction and can have a negative effect on various stages of reproduction, including gametogenesis and fertilization to embryo formation, and as a result, aggravate infertility problems. This research has investigated the effects of MPs on the male reproductive system, focusing on cellular and molecular processes and approaches to deal with this issue. This review conducted a comprehensive literature search across multiple scientific databases. Searches were performed in Google Scholar, Scopus, PubMed, and Web of Science to identify relevant publications. The search terms used included a combination of MPs, male infertility, sperm, toxicity, and related keywords. The final set of selected articles provides a comprehensive overview of the effects of MPs on cellular and molecular processes in the male reproductive system. In men, MPs can affect the structure and function of the testis and induce the aging process and the inflammatory signaling pathway, oxidative stress, and testicular malignancy. Also, these particles affect the process of spermatogenesis and disrupt sperm parameters. MPs activate different cell signaling pathways and have effects including reducing ATP production, reducing sperm DNA integrity, impairing sperm function and reducing sperm survival. On the other hand, MPs may have destructive effects on the production and balance of male hormones through interaction with the endocrine system. It is evident that proactive measures need to be implemented to address this issue and enhance reproductive health parameters.

The thyroid hormone (TH) system of humans, aquatic and terrestrial life forms is a major target for endocrine disrupting chemicals (EDC) during development and adult life. EDC adversely interfere with TH biosynthesis in vascularized thyroid follicles, secretion and distribution to target organs. EDC exposure may affect TH transmembrane transport, intracellular (in-)activation by deiodinases and conjugation reactions as well as T3 binding to intracellular T3 receptors in target cells. Predominant EDC interferences occur with TH distribution in the circulation and with cellular reactions controlling local availability of the active hormone T3 at the pre-receptor level. Developmental EDC interference may irreversible alter setpoints of the feedback regulation of the hypothalamus-pituitary-thyroid axis, TH-dependent brain development, and metabolic functions in adults. The worldwide still prevailing inadequate iodide status, especially during pregnancy and lactation, might exacerbate adverse effects of an increasing spectrum of identified and suspected EDC and their mixtures on human and environmental health. • EDC interfere with TH binding to distributor proteins in the blood, with cellular THTMTs, intracellular DIOs and conjugating enzymes, hereby disturbing pre-receptor control of T3 ligand availability for TRs. • NIS and TPO are main targets of EDC interference with thyroidal TH biosynthesis. • Adversity of EDC actions appears to be increased under conditions of the still prevailing maternal iodide deficiency, especially during pregnancy and lactation.

Clinical-genetic features of the TBCE-related spectrum disorders: A focus on the childhood-onset neurodegenerative phenotype.

Di-tert-Butylphenol (2,4-DTBP) and its analogs disrupt thyroid hormone signaling via activation of retinoid X receptor α.

Immunotherapy and ferroptosis regulation in thyroid cancer: Novel strategies and future perspectives.

Estrone exposure-induced feminization in male Siniperca chuatsi: A multidimensional study on sex reversal, liver damage, and changes in gene expression.

The enrichment of endocrine-disrupting bisphenols by hydroxyl‑functionalized covalent organic framework prior to detection by HPLC-MS.

Recent advances in biomedical research have facilitated the exploration of biomimetic materials and their potential for diagnosing and treating diseases. This review synthesizes reports of recent research into biomimetic materials and provides a focused analysis of their therapeutic and diagnostic efficacy across multiple physiological systems, including the locomotor, digestive, respiratory, urinary, endocrine, nervous, integumentary, hematopoietic, and circulatory systems. These findings highlight the transformative potential of these materials in the management of systemic diseases. They also reveal the challenges associated with material optimization, clinical translation, and future research. These challenges highlight the unresolved hurdles and largely untapped opportunities.

Renal tubular disease causes loss of electrolytes and other molecules. One of these electrolytes is inorganic sulfate, which is reabsorbed by dedicated transporters, including NaS1, encoded by the SLC13A1 gene. Still, inorganic sulfate is rarely measured in clinical practice, although it is essential for the development and functioning of several organ systems. The importance of adequate sulfate stores is emphasized by genetic disorders impairing sulfate metabolism in the brain, bone, and the endocrine system, causing severe neurodevelopmental disorders, skeletal dysplasia, and hormonal imbalance. Low availability due to renal loss of inorganic sulfate has also been linked to these disorders. We aimed to assess the prevalence of renal inorganic sulfate wasting in renal tubular diseases in a small cohort as an exploratory study. Inorganic sulfate was measured in serum and urine of patients with proximal renal tubular disorders using remnant material obtained during routine check-ups. Fractional excretion of inorganic sulfate was calculated alongside plasma inorganic sulfate concentrations and cystatin C-based eGFR. Fourteen patients were included, in whom 1 to 4 paired measurements of urine and plasma inorganic sulfate were available. Five patients had decreased plasma sulfate on at least one occasion; 13 patients had increased fractional excretion in at least one measurement. In patients with cystinosis, during cysteamine treatment plasma inorganic sulfate levels were often normal despite increased fractional excretion. Increased inorganic sulfate loss is prevalent in children with proximal tubular defects and sulfate stores can be repleted by oral drugs like cysteamine.

Pharmaceuticals are fast becoming a major source of environmental pollution. Many pharmaceuticals are endocrine disruptors and can thus interfere with the endocrine system of exposed organisms, leading to a suite of behavioural and physiological alterations. While numerous studies have shown that exposure to pharmaceutical contaminants can disrupt the reproductive ecology of oviparous fishes, far less attention has been given to understanding the impacts on viviparous fishes, despite their ecological and evolutionary importance. Here, we investigated the impacts of the pharmaceutical contaminant 17ɑ-ethinylestradiol (EE2) on the reproductive biology of a marine livebearer, the Southern crested weedfish (Cristiceps australis). Adult weedfish were exposed to one of three nominal concentrations of EE2 (0, 30, and 300 ng/L) for 14 days. We then assessed the impacts of exposure on morphology of both sexes, and female gametogenesis. In doing so, we found no differences in the body length, weight, or condition of fish between treatment groups. We additionally found no differences in gonadosomatic index (GSI) or gametogenesis between exposed and unexposed females. In contrast to reports in other taxa, our findings suggest that short-term exposure to EE2 does not produce detectable effects on weedfish growth and reproduction. However, the extent to which exposure duration influences these responses is unknown. Ultimately, these results emphasise the importance of assessing the effects of EE2 on a diverse range of organisms if we are to gain a more comprehensive understanding of its ecological impacts.

The effect of social isolation on rat behavior and expression of genes related to neuroinflammation depends on sex.

Linear growth stunting increases a child's risk for mortality and lifelong morbidities. Understanding and preventing the causes of childhood stunting is a global health priority. The leading contributors to stunting are undernutrition and infection. Schistosomiasis, a neglected tropical disease, has long been associated with childhood stunting, but there are limited reviews summarizing the evidence. This narrative review examines cross-sectional associations between infection and linear growth, longitudinal impacts of schistosomiasis treatment on growth and the influence of schistosomiasis on the endocrine system, specifically the growth hormone (GH) and insulin-like growth factor 1 (IGF-1) axis. After reviewing more than 60 years of research, there is evidence for an association between schistosomiasis infection and linear growth measures but mixed results relating to stunting, a categorical outcome based on low height-for-age measures. This may be due to limitations in study design or the length of time required to induce stunting. The reports also support the theory that schistosomiasis disrupts the GH/IGF-1 axis, resulting in reduced IGF-1 and impaired linear growth. These findings reinforce the need for early treatment interventions for children living in schistosomiasis-endemic regions and encourage research to include stunting risk factors and endocrine measures in future schistosomiasis study designs. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.

Endocrine Modulation of Self- and Other-Models: A Cross-Species Framework for Dyadic Social Interaction.

Evolutionary shifts in plant adaptations mediated by phytohormones.

Male reproductive health has declined over recent decades, characterized by rising rates of reproductive birth defects, reduced semen quality, and an increased risk of testicular cancer. This global trend has been linked to exposure to endocrine-disrupting chemicals (EDCs), which can interfere with the endocrine system including disrupting steroidogenesis, the process by which steroid hormones are synthesized. Steroid hormones, not least testosterone, are essential for male sex differentiation, masculinization, and spermatogenesis. During human fetal development, Leydig and Sertoli cells of the testis together produce androgens, whereas in adults, Leydig cells can synthesize testosterone alone. EDCs can disrupt this process through various mechanisms. Advances in in vitro models of the steroidogenic system, particularly three-dimensional (3D) cell cultures, have provided a more accurate representation of the in vivo environment, enabling more realistic responses to external stimuli. These models offer a powerful tool for studying the effects of EDCs on steroidogenesis and will deepen our understanding of the mechanisms underlying endocrine disruption, knowledge that is important in developing new strategies for chemical safety assessment. This review provides a comprehensive analysis of the steroidogenic system, with a focus on key enzymes involved. The current regulatory test strategies to reduce the impact of EDCs on male fertility is discussed. Furthermore, 3D testis models are compared, highlighting their strengths and limitations for testing effects on testis steroidogenesis. Emphasis is placed on the urgent need for innovative, practical, and cost-effective alternatives to traditional in vivo testing to improve chemical risk assessments.

The regulation of electrical excitability of anterior pituitary corticotrophs is critical for an appropriate response of the hypothalamic-pituitary-adrenal (HPA) axis in the face of diverse physiological challenges in health and disease. However ion channels that control corticotroph excitability remain poorly characterised. Members of the mammalian ether-à-go-go (EAG) channel family are voltage-gated potassium channels with diverse functions in the endocrine, cardiovascular and nervous systems. Expression of Kcnh2 mRNA, which encodes for the Eag-related potassium channel Erg1, is enriched in the anterior pituitary although its functional role is poorly understood in native anterior pituitary cells. We reveal that Kcnh2 is the major Eag-channel family member mRNA expressed in male and female murine corticotrophs. Patch clamp electrophysiological analysis revealed corticotrophs exhibit robust Erg-like currents that are inhibited by the selective Erg-inhibitor E4031 but are not regulated by the major hypothalamic secretagogues, corticotrophin releasing hormone (CRH) or arginine vasopressin (AVP), that increase corticotroph excitability. Pharmacological inhibition of Erg currents had no effect on spontaneous electrical excitability in corticotrophs. Rather, paradoxically, Erg currents were important for supporting CRH-induced bursting, similar to the role of large-conductance calcium- and voltage-activated potassium (BK) channels, providing a level of redundancy to control bursting. Indeed mathematical modelling revealed that in the absence of BK channels CRH-induced bursting can be supported in thepresence of Erg current. We thus reveal a novel role for Erg-like channels in controlling CRH-induced bursting in murine anterior pituitary corticotrophs that is likely to be an important determinant of HPA axis regulation in health and disease. KEY POINTS: Voltage-gated ether-à-go-go-related (Erg) potassium channels are key determinants of cellular excitability; however their functional role in native anterior pituitary cells remains poorly understood. Male and female murine corticotrophs predominantly express Kcnh2 (Erg1) mRNA, and electrophysiological recordings reveal functional Erg-like potassium currents sensitive to the Erg inhibitor E4031. Erg currents do not control the basal electrical excitability of corticotrophs. We reveal a novel role for Erg currents in supporting electrical bursting in corticotrophs induced by the hypothalamic secretagogue, corticotrophin releasing hormone (CRH). Bursting in corticotrophs can be supported by both Erg and BK channels revealing a level of redundancy to the CRH response that will be critical for understanding the role of Erg channels in control of the stress axis in health and disease.