Endocrine System Research Articles

STU3Net: An Improved U‐Net With Swin Transformer Fusion for Thyroid Nodule Segmentation

ABSTRACTThyroid nodules are a common endocrine system disorder for which accurate ultrasound image segmentation is important for evaluation and diagnosis, as well as a critical step in computer‐aided diagnostic systems. However, the accuracy and consistency of segmentation remains a challenging task due to the presence of scattering noise, low contrast and resolution in ultrasound images. Therefore, we propose a deep learning‐based CAD (computer‐aided diagnosis) method, STU3Net in this paper, aiming at automatic segmentation of thyroid nodules. The method employs a modified Swin Transformer combined with a CNN encoder, which is capable of extracting morphological features and edge details of thyroid nodules in ultrasound images. In decoding through the features for image reconstruction, we introduce a modified three‐layer U‐Net network with cross‐layer connectivity to further enhance image reduction. This cross‐layer connectivity enhances the network's capture and representation of the contained image feature information by creating skip connections between different layers and merging the detailed information of the shallow network with the abstract information of the deeper network. Through comparison experiments with current mainstream deep learning methods on the TN3K and BUSI datasets, we validate the superiority of the STU3Net method in thyroid nodule segmentation performance. The experimental results show that STU3Net outperforms most of the mainstream models on the TN3K dataset, with Dice and IoU reaching 0.8368 and 0.7416, respectively, which are significantly better than other methods. The method demonstrates excellent performance on these datasets and provides radiologists with an effective auxiliary tool to accurately detect thyroid nodules in ultrasound images.

Health Risk Assessment of Ambient Volatile Organic Compounds in a Border City in Canada

This study characterizes cancer and non-cancer risks due to inhalation exposure to volatile organic compounds (VOCs) in a border city of Windsor in southern Ontario, Canada, using hourly ambient concentrations collected from 17 November 2021 to 17 March 2023. The total incremental lifetime cancer risk (CR) due to benzene and ethylbenzene is 4.33 × 10−6, which is in the acceptable risk range of 1 × 10−6 to 1 × 10−4 used by the USEPA. The CR was higher in winter (5.20 × 10−6), followed by fall (4.32 × 10−6), spring (3.86 × 10−6), and summer (2.96 × 10−6), all in the acceptable range. The total chronic non-cancer risk (Hazard Quotient, HQ) of inhalation exposure to 16 VOCs was 0.0488, with a higher value in fall (0.0571), followed by winter (0.0464), and lower in spring (0.0454) and summer (0.0451), all in the safe level of below HQ = 1 used by the USEPA. The hazard index (HI) by organs was higher for the nervous system (0.0213), followed by the hematologic system and immune system (0.0165 each), but much lower for the other five target organs, i.e., the liver/kidney (1.52 × 10−4), developmental system (3.38 × 10−4), endocrine system and urinary system (2.82 × 10−4 each), and respiratory system (9.70 × 10−5). Similar hour-of-day trends were observed in the total CR, total HQ, and HI by organs with higher values in the early morning hours of 5:00–8:00 and lower values during 12:00 to 15:00. Benzene was the major contributor to both total CR (89%) and total HQ (34%) due to its high toxicity and high concentrations. Benzene, toluene, ethylbenzene, and xylenes (BTEX) contributed 100% of the total CR and 51% of the total HQ. Further, BTEX is the sole contributor to the HI for the hematologic system and immune system and the major contributor to the HI for the nervous system (39%) and developmental system (55%). Higher cancer and non-cancer risks were associated with the airmass from the east, southeast, and southwest of Windsor.

Effects of tauroursodeoxycholate on arsenic-induced hepatic injury in mice: A comparative transcriptomic analysis

BackgroundProlonged exposure to excessive arsenic (As) and its compounds can cause damage to multiple systems, including respiratory, cardiovascular, immune, nervous, and endocrine systems. Manifestations include changes in skin pigmentation, excessive keratosis on palms and soles, gastrointestinal symptoms, and anemia. The liver as an important detoxification organ of the body, is a significant target organ for arsenic toxicity, and liver diseases are common. So far, the molecular mechanism has not been fully elucidated. Evidence suggests that taurodeoxycholic acid (TUDCA) has a protective role in arsenic-induced liver injury. This study aims to reveal potential target genes at the transcriptional level following TUDCA intervention, providing insights for the intervention of arsenic-induced liver injury. MethodsThe TUDCA intervention model of arsenic liver injury in C57BL/6 N mice was established. The experiment was divided into two phases and lasted for 24 weeks. The phase I trial (12 weeks) was divided into control, low, middle and high groups according to the dose of As. The phaseⅡtrial (12 weeks) was administered in combination with 10 mg/L sodium arsenite (the first stage high arsenic group) and TUDCA, so subsequent groups was named with H indicating high arsenic. Divide into four groups: control group(C), TUDCA solvent control group(H-Vehicle), TUDCA combined with As group(H-TUDCA), arsenic group (As). As was ingested through free water and TUDCA was administered to mice by gavage at a dose of 0.1 mL/10 g.b.w (100 mg/kg) once a day for 12 weeks. The differential expression gene (DEG) profile was obtained from the second batch of mouse liver tissues by RNA sequencing technology. Comparative transcriptomic analysis methods were used to identify co-varying DEGs between arsenic induction and TUDCA intervention, along with their associated pathways. QRT-PCR was utilized for validation. ResultsTranscriptome results showed that 487 DEGs were identified after arsenic induction. TUDCA intervention identified 231 DEGs (p-values < 0.05 and | log2(fold change) | > 1). The comparison of "AS vs C" and "H_TUDCA vs AS" identified 65 covariant DEGs, and further screened the TUDCA pathways and related genes among these genes，six pathways and 11 genes (Ccl21a, Ccr7, Mdm2, Slc2a4, Akr1b7, Pnpla3, Dusp8, Hspa1a, Cyp7a1, Cybrd1, Trpm6) were obtained. Next, we screened for covariant DEGs among the top 50 potential hub genes in arsenic-induced DEGS, and obtained 7 (Hbb-bs, Hspa1a, Mdm2, Slc2a4, Ptk6, Egr1, and Dusp8). Finally, the intersection of Hub gene and pathway gene was selected as the target genes Dusp8, Hspa1a, Mdm2 and Slc2a4. The sequencing results showed that the mRNA expressions of Dusp8, Hspa1a and Mdm2 were significantly increased after arsenic induction, while the expression of Slc2a4 was significantly decreased (P<0.05). Conversely, TUDCA intervention reversed these DEGs changes, consistent with QRT-PCR validation results. ConclusionThis study contributes to understanding the potential health effects of arsenic-induced liver injury, identifying new potential targets, and providing references for TUDCA intervention.

Age Specifics of Homeostasis Response to Cold Stress in Wistar Rats: Endurance Improvement or Disorganization?

Cold exposure, especially in combination with exercise, is a common procedure to fortify the body. However, its effects in old age are poorly understood. Using the homeostasis stability coefficient as an indicator, the body response to a 20-min swim in cold water was for the first time studied comprehensively in old and young Wistar rats. Effects on the hormonal, hematological, and morphofunctional systems of the liver and thymus were assessed. Unfavorable age-related changes in the stability of homeostasis were observed in old rats. The changes complicated the recovery after cold stress and required the involvement of a greater number of homeostatic mechanisms than in young rats. The liver was found to be the most vulnerable to cold stress. It was concluded that fortifying the body by cold exposure is possible to use in old age, but with due regard to age-related restrictions.

Straw Tar Epoxy Resin for Carbon Fiber-Reinforced Plastic: A Review.

The massive consumption of fossil fuels has led to the serious accumulation of carbon dioxide gas in the atmosphere and global warming. Bioconversion technologies that utilize biomass resources to produce chemical products are becoming widely accepted and highly recognized. The world is heavily dependent on petroleum-based products, which may raise serious concerns about future environmental security. Most commercially available epoxy resins (EPs) are synthesized by the condensation of bisphenol A (BPA), which not only affects the human endocrine system and metabolism, but is also costly to produce and environmentally polluting. In some cases, straw tar-based epoxy resins have been recognized as potential alternatives to bisphenol A-based epoxy resins, and are receiving increasing attention due to their important role in overcoming the above problems. Using straw tar and lignin as the main raw materials, phenol derivatives were extracted from the middle tar instead of bisphenol A. Bio-based epoxy resins were prepared by replacing epichlorohydrin with epoxylated lignin to press carbon fiber sheets, which is a kind of bio-based fine chemical product. This paper reviews the research progress of bio-based materials such as lignin modification, straw pyrolysis, lignin epoxidation, phenol derivative extraction, and synthesis of epoxy resin. It improves the performance of carbon fiber-reinforced plastic (CFRP) while taking into account the ecological and environmental protection, so that the epoxy resin is developed in the direction of non-toxic, harmless and high-performance characteristics, and it also provides a new idea for the development of bio-based carbon fibers.

Health comorbidities in children with down syndrome (DS) at Dr. Sardjito General Hospital, Yogyakarta

Down syndrome (DS) is a disease caused by trisomy of chromosome 21. The phenotype in DS leads to manifestations in several organ systems. This study aimed to identify the pattern of comorbidities in DS patients. It was a single-center, cross-sectional study at Dr. Sardjito General Hospital, Yogyakarta. Medical records of pediatric patients with DS from a period of January 2022 to May 2023 were included. Descriptive analysis was performed to demonstrate demographic and clinical characteristics. A total of 355 pediatric patients with DS were found at Dr. Sardjito General Hospital and the majority were male (196 children or 55.2%). As much as 339 children (95.49%) had comorbidities. The highest comorbidity was congenital heart disease (230 patients or 67.84%) in specifics were atrial septal defect (41 patients or 12.39%), atrioventricular septal defect (29 patients or 8.17%), and patent ductus arteriosus (28 patients or 7.88%). The second highest comorbidity was endocrine system disorders (102 patients or 30.09%), with 100 patients (28.16%) children suffering hypothyroidism. The number of children who had one comorbidity was 248 patients (69.86%), 74 patients (20.48%) had two comorbidities, and 17 patients (4.79%) had three or more comorbidities. The highest co-prevalence of the two comorbidities was congenital heart disease and endocrine system disorders (36 patients or 10.14%). The highest co-prevalence of 3 or more comorbidities was a combination of congenital heart disease, visual impairment, and hearing impairment (6 patients or 1.69%). In conclusion, 95.49% of children with DS have comorbidities. The most common comorbidity was heart defects. About 25.63% of patients had more than one comorbidity. Children with DS who have comorbidities require more attention to prevent complications and to reduce morbidity.

Serum thyroid autoantibodies in malignant thyroid nodules

Background: Thyroid cancer is one of the most common malignant tumours of the endocrine system. Thyroid autoantibodies were reported to be associated with malignant thyroid nodules. This study aimed to assess the diagnostic accuracy of serum thyroid autoantibody levels for malignant thyroid nodules. Methods: From March 2023 to January 2024, we recruited 104 consecutive patients with thyroid nodules confirmed by ultrasonography in three departments of Bangabandhu Sheikh Mujib Medical University. Out of these, 52 were diagnosed with malignant thyroid nodules using fine needle aspiration cytology, while the remaining 52 had benign thyroid nodules. Serum thyroid autoantibodies were measured using the immunoassay technique. Results: The mean levels of serum thyroid peroxidase antibody (TPOAb) were significantly higher (P&lt;0.001) in the malignant group compared to the benign group (36.1 versus 24.0 IU/mL). The mean levels of serum thyroglobulin antibodies (TgAb) were also significantly higher (P&lt;0.001) in the malignant group (39.8 IU/mL versus 29.1 IU/mL). Elevated TPOAb (&gt;40 IU/mL) and TgAb (&gt;35 IU/mL) showed reasonable accuracy (60% to 65%) in detecting malignancy of thyroid nodules. Conclusions: Thyroid malignancy is positively associated with TgAb and TPOAb. Therefore, thyroid autoantibodies could be considered for screening malignancy in thyroid nodules.

Potential of Curcumin in Curcuma Longa as an Alternative Therapy for PCOS: A Literature Review

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine hormone disorder in women of childbearing age with a global incidence of 8-13%. The use of medical drugs in the long term can cause serious side effects so that the utilization of curcumin contained in Curcuma longa can be an alternative therapy consideration for PCOS. This paper will discuss the potential and benefits of curcumin content as an alternative therapy for PCOS. The method used, namely by reviewing the literature in national and international journals that are in accordance with the objectives of the review. The results of the literature review show that curcumin has effectiveness in treating PCOS through various mechanisms of action accompanied by minimal side effects. Alternative therapy of PCOS by taking curcumin needs to consider the dose, duration of use, and further research with larger subjects in assessing its effectiveness and side effects. However, it is suspected that nanocurcumin formulations have higher bioavailability and solubility than free curcumin, giving it even greater potential in the treatment of PCOS in the future. In conclusion, curcumin has the potential as an alternative therapy for PCOS that requires further research to achieve the optimization of PCOS treatment in the future.

FN1, a reliable prognostic biomarker for thyroid cancer, is associated with tumor immunity and an unfavorable prognosis.

Thyroid cancer (THCA) is a malignant tumor that affects the endocrine system. At present, an effective treatment for THCA remains elusive, particularly for medullary carcinoma and undifferentiated carcinoma, due to the lack of suitable medications and prognostic markers. Patient RNA-sequencing and clinical data were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Protein-protein interaction analyses were performed for differentially expressed genes related to THCA. Moreover, the associations between fibronectin 1 (FN1), clinical data, immune checkpoint genes and immune cell infiltration was assessed. The potential functional role of the FN1 gene was evaluated through gene set enrichment analysis. Immunohistochemistry was used to assess FN1 expression in 103 cases of THCA, comprising 32 with papillary carcinoma, 30 with follicular carcinoma, 35 with medullary carcinoma and 6 with undifferentiated carcinoma. Finally, 11 co-expression modules were constructed and the expression of five identified hub genes (FN1, mucin-1, keratin 19, intracellular adhesion molecule 1 and neural cell adhesion molecule) were evaluated. The results demonstrated that higher FN1 gene expression levels were strongly associated with a higher pathologic stage and tumor stage, and were significantly associated with immune cell infiltration in THCA. Significant increases in FN1 protein expression levels were noted among patients diagnosed with four types of THCA, comprising papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Patients diagnosed with medullary carcinoma and undifferentiated carcinoma, and with low FN1 expression levels, exhibited a significant survival advantage compared with those with high FN1 expression levels. In conclusion, the present study identified five hub genes involved in the onset and progression of THCA. Furthermore, FN1 could serve as a candidate biomarker and a therapeutic target for THCA and may be a key gene mediating THCA immune infiltration.

Chronic pelvic pain syndrome in women of reproductive age: An observational cohort clinical ultrasound study

Background. The annual number of new cases of chronic pelvic pain syndrome in women of reproductive age is increasing worldwide. The high prevalence of this condition among the able-bodied female population leads to higher state expenditures on the treatment of this category of patients. New methods of diagnosis and early prophylaxis contribute to reducing economic burden associated with chronic pelvic pain syndrome in women and improving health of the female population as a fundamental demographic factor.Objectives. To determine somatic, obstetric-gynecological, anatomical, and psycho-emotional predictors of chronic pelvic pain syndrome.Methods. An observational cohort clinical and ultrasound study involved 60 patients of reproductive age. The study was conducted on the basis of the clinic for women, Voronezh City Outpatient Clinic No. 1 — clinical base of the Department of Obstetrics and Gynecology No. 2, Voronezh State Medical University named after N. N. Burdenko, Russia. According to clinical and laboratory data, the participants were divided into 2 groups. Group 1 (n = 30) included women of reproductive age without clinical manifestations of chronic pelvic pain syndrome; Group 2 (n = 30) enrolled women of reproductive age clinically diagnosed with chronic pelvic pain.Results. The mean age of the study participants in the main group comprised 27.4 ± 6.30 and 26.3 ± 7.25 years in the control group, p &gt; 0.05. Diseases of gastrointestinal tract, endocrine, cardiovascular, musculoskeletal and urinary systems, as well as neurocirculatory and vegetative disorders prevailed in the structure of somatic pathology in the main group, p &lt; 0.001. Analysis of obstetric and gynecologic anamnesis revealed no statistically significant differences in the incidence of gynecologic pathology in the study groups. However, according to the detailed analysis of the delivery history of the participants, 23 patients of the main group (76 %) and 3 patients (6.6 %) of the control group underwent episiotomy during labor, p &lt; 0.001. The evaluation of the comparison groups in terms of pain component in myofascial syndrome involved the pain rating index, number of selected descriptors, sensory index of the selected descriptors, emotional index of the selected descriptors, and pain intensity. Statistically significant differences were revealed for all of the above indicators, thereby confirming a reliable picture of pathopsychological changes in the compared groups of women. The analysis of the ultrasound parameters of topographic and anatomical relationships demonstrated the relevant change in the following parameters: urethral length, diameter of the external urethral sphincter, angle between the external urethra and the body of the bladder, direct and transverse dimensions of the levator hiatus in the studied groups under the muscle tension.Conclusion. An issue of early diagnosis and prophylaxis of chronic pelvic pain syndrome in women of reproductive age remains urgent and requires interdisciplinary participation of medical specialists. The development of new approaches to ultrasound evaluation of pelvic floor will increase the effectiveness of therapeutic and prophylactic measures and reduce the economic burden of this nosology in the morbidity structure of the able-bodied female population.

Healthcare utilisation and associated costs for methadone versus buprenorphine recipients: Examination of interlinked primary and secondary care electronic health records in England.

More evidence for patterns of healthcare utilisation and associated costs among people receiving opioid agonist therapy (OAT) is needed. We investigated primary and secondary healthcare usage and costs among methadone and buprenorphine recipients in England. We conducted a cohort study using the Clinical Practice Research Datalink GOLD and Aurum databases of patients who were prescribed OAT between 1 January 2007 and 31 July 2019. The cohort was linked to Hospital Episode Statistics admitted patient care, outpatient and emergency department data, neighbourhood- and practice-level Index of Multiple Deprivation quintiles and mortality records. Negative binomial regression models were applied to estimate weighted rate ratios (wRR) of healthcare utilisation. Total and mean costs were calculated using Unit Costs of Health and Social Care and the National Healthcare Service Payment by Results National Tariffs. Among 12,639 patients observed over 39,016 person-years, we found higher rate of hospital admissions (wRR 1.18; 1.08-1.28) among methadone compared with buprenorphine recipients. The commonest hospital discharge diagnoses among methadone patients were infectious diseases (19.2%), mental and behavioural disorders (17.0%) and drug-related poisoning (16.5%); the three commonest among buprenorphine patients were mental and behavioural diseases (21.5%), endocrine (13.8%) and genitourinary system diseases (13.1%). Methadone patients had similar mean costs compared with buprenorphine patients (cost difference: £539.01; 432.11-1006.69). Differences in healthcare utilisation frequency for methadone versus buprenorphine recipients were observed. The differences in associated costs were mainly driven by hospital admissions. These findings offer valuable insights for optimising care strategies and resource allocation for OAT recipients.

Prophylactic effects of Tibetan goat kefir on depression-like behaviors in chronic unpredictable stress model through the gut-brain axis.

Depression is a common psychological disorder, and traditional therapeutic drugs often result in side effects such as emesis, dry mouth, headache, dysentery and constipation. Probiotics and goat milk have garnered widespread attention for their ability to modulate immune function and regulate the endocrine system, and for their anti-inflammatory effects. In this work, the effects of Tibetan goat kefir on the behavior, immune status, neuroendocrine response and gut microbiological composition of chronic unpredictable mild stress (CUMS) mouse models were evaluated. The results indicated that Tibetan kefir goat milk significantly alleviated behavioral despair in mice. Furthermore, the results demonstrated that Tibetan kefir goat milk mitigated the inflammatory response in the mice and moderated the hyperactivity of the hypothalamic-pituitary-adrenal axis and the expression of brain-derived neurotrophic factor. Meanwhile, chronic stress-induced gut microbial abnormalities were restored. In addition, the correlation between gut microbiota and nervous system was evaluated. These results explained the potential mechanism of Tibetan kefir in the antidepressant effect on the CUMS model and enriched diets for depressed patients. © 2024 Society of Chemical Industry.

The Impact of Adenomyosis on Pregnancy.

Adenomyosis is characterized by ectopic proliferation of endometrial tissue within the myometrium. Histologically, this condition is marked by the presence of islands of benign endometrial glands surrounded by stromal cells. The myometrium appears thinner, and cross-sectional analysis often reveals signs of recent or chronic hemorrhage. The ectopic endometrial tissue may respond to ovarian hormonal stimulation, exhibiting proliferative or secretory changes during the menstrual cycle, potentially leading to bleeding, uterine swelling, and pain. Adenomyosis can appear as either a diffuse or focal condition. It is crucial to understand that adenomyosis involves the infiltration of the endometrium into the myometrium, rather than its displacement. The surgical management of adenomyosis is contingent upon its anatomical extent. The high incidence of the disease and the myths that develop around it increase the need to study its characteristics and its association with pregnancy and potential obstetric complications. These complications often require quick decisions, appropriate diagnosis, and proper counseling. Therefore, knowing the possible risks associated with adenomyosis is key to decision making. Pregnancy has a positive effect on adenomyosis and its painful symptoms. This improvement is not only due to the inhibition of ovulation, which inhibits the bleeding of adenomyotic tissue, but also to the metabolic, hormonal, immunological, and angiogenic changes associated with pregnancy. Adenomyosis affects pregnancy through disturbances of the endocrine system and the body's immune response at both local and systemic levels. It leads to bleeding from the adenomyotic tissue, molecular and functional abnormalities of the ectopic endometrium, abnormal placentation, and destruction of the adenomyotic tissue due to changes in the hormonal environment that characterizes pregnancy. Some of the obstetric complications that occur in women with adenomyosis in pregnancy include miscarriage, preterm delivery, placenta previa, low birth weight for gestational age, obstetric hemorrhage, and the need for cesarean section. These complications are an understudied field and remain unknown to the majority of obstetricians. These pathological conditions pose challenges to both the typical progression of pregnancy and the smooth conduct of labor in affected women. Further multicenter studies are imperative to validate the most suitable method for concluding labor following surgical intervention for adenomyosis.

The Effects of Prolonged Indoor Inhalation of Nature-Derived Odors on Menopausal Women.

This study aimed to investigate the effects of prolonged inhalation of nature-derived odors indoors on humans. Twenty-six women participated in this study. Heart rate variability, heart rate, blood pressure, pulse rate, estradiol, testosterone, and cortisol were used as indicators of autonomic nervous system and endocrine system activities. Profile of mood state, state-trait anxiety inventory, menopause rating scale and general sleep disturbance scale were used as psychological indicators. The order was as follows: After the participants relaxed in a chair for 5 min, their heart rate variability and heart rate were measured for 3 min with their eyes closed. Subsequently, blood pressure and pulse rate were measured, salivary samples were collected for estradiol, testosterone, and cortisol analyses, and a subjective assessment was conducted. The participants received a diffuser containing fir essential oil and were instructed on its usage and precautions. Subsequently, they returned home and inhaled the fir oil for a week. After 7 days, participants revisited the laboratory for posttest measurements, conducted at the same time as the pretest. Prolonged inhalation of the fir essential oil resulted in increased estradiol concentration, decreased systolic and diastolic blood pressure, relief of menopausal symptoms, reduced anxiety levels, improved sleep quality and mood states. Prolonged inhalation of the fir essential oil induced physiological and psychological relaxation on menopausal women.

RNAseq analysis of whole zebrafish (Danio rerio) larvae revealed the main cellular biological effects of geosmin and microcystin exposure at environmentally relevant concentrations

Cyanobacterial blooms are common events that releases secondary metabolites into water posing considerable threats to the environment, wildlife, and public health. Some of these metabolites, such as microcystin, have been extensively studied and associated with harmful effects in mammals and aquatic organisms, while the biological effects of others, like geosmin, remain much less investigated. Enhancing our understanding of cyanotoxins effects on organisms is especially relevant facing the complex scenarios projected due to global warming. The aim of this study was to assess the transcriptional modulation in whole zebrafish (Danio rerio) larvae (n = 9) in response to a 7-days immersion exposure to 3 μg L−1 MCLR or 5 μg L−1 geosmin. No mortality or differences in length gain were observed in zebrafish larvae exposed to environmentally realistic doses of both cyanotoxins. The exposure to MCLR and to geosmin caused the differential expression of 164 and 172 genes respectively, being 23 upregulated by MCLR and 98 upregulated by geosmin. Among the upregulated genes, 16 were shared, while 42 were shared among the downregulated genes. Over-representation analysis identified three enriched GO terms only among the genes upregulated by geosmin: organic hydroxy compound metabolic process (1901615), small molecule biosynthetic process (0044283), and lipid metabolic process (0006629). In fact, the expression of 12 of the 13 genes directly involved in the synthesis of cholesterol from acetyl-CoA was upregulated by geosmin. A chronic upregulation of cholesterol biosynthetic pathway is linked to several diseases and metabolic disorders, including alterations in sex-related hormones. Moreover, our results indicate that geosmin and MCLR acts through different mechanisms. Geosmin does not appear to provoke short-term adverse effects as MCLR but could disrupt the endocrine system by altering the lipid and steroid metabolism.

Navigating Complexity in Postural Orthostatic Tachycardia Syndrome.

Postural Orthostatic Tachycardia Syndrome (POTS) affects up to 1% of the US population, predominantly women, and is characterized by a complex, elusive etiology and heterogeneous phenotypes. This review delves into the intricate physiology and etiology of POTS, decoding the roles of the sinoatrial node, the autonomic nervous system, fluid dynamics, and the interplay between the immune and endocrine systems. It further examines key contributing factors such as dysautonomia, thoracic hypovolemia, autonomic neuropathies, sympathetic denervation, autoimmune responses, and associations with conditions such as small-fiber neuropathy and mast cell activation syndrome. Given the numerous mysteries surrounding POTS, we also cautiously bring attention to sinoatrial node and myocardial function, particularly in how the heart responds to stress despite exhibiting a normal cardiac phenotype at rest. The potential of genomic research in elucidating the underlying mechanisms of POTS is emphasized, suggesting this as a valuable approach that is likely to improve our understanding of the genetic underpinnings of POTS. The review introduces a tentative classification system for the etiological factors in POTS, which seeks to capture the condition's diverse aspects by categorizing various etiological factors and acknowledging co-occurring conditions. This classification, while aiming to enhance understanding and optimize treatment targets, is presented as a preliminary model needing further study and refinement. This review underscores the ongoing need for research to unravel the complexities of POTS and to develop targeted therapies that can improve patient outcomes.

Fluoride-Induced Alterations in the Pancreas of Mammals: A Meta-analysis.

This review explores the diverse effects of fluoride on pancreatic function, encompassing both in vitro and in vivo studies. Fluoride exposure induces notable alterations at the cellular and molecular levels, affecting pancreatic morphology, histology, and enzymatic activity. In vitro studies demonstrate significant inhibition of pancreatic α-amylase activity and apoptosis in pancreatic beta cells. In vivo investigations reveal structural abnormalities in pancreatic cells, including mitochondrial damage, vacuolation, and nuclear damage. Moreover, fluoride exposure disrupts antioxidant enzyme activity, exacerbating oxidative stress and lipid peroxidation. Changes in digestive enzyme activity, such as the inhibition of pancreatic lipase and α-amylase, further contribute to pancreatic dysfunction. Additionally, alterations in hormone secretion, notably insulin levels and disturbed glucose homeostasis, highlight the complex effects of fluoride on the pancreatic endocrine system. These findings underscore fluoride-induced pancreatic toxicity and highlight the need for a comprehensive understanding and mitigation strategies to safeguard pancreatic health.

Expanding the Repertoire of ceDAF-12 Ligands for Modulation of the Steroid Endocrine System in C. Elegans.

Steroid hormones are essential for the biological processes of eukaryotic organisms. The steroid endocrine system of C. elegans, which includes dafachronic acids (DA) and the nuclear receptor ceDAF-12, provides a simple model for exploring the role of steroid hormone signaling pathways in animals. In this study, we show for the first time the feasibility of designing synthetic steroids that can modulate different physiological processes, such as development, reproduction and ageing, in relation to ceDAF-12. Our results not only confirm the conclusions derived from genetic studies linking these processes but also provide new chemical tools to selectively manipulate them, as we found that different compounds produce different phenotypic results. The structures of these compounds are much more diverse than those of endogenous hormones and analogues previously described by other researchers, allowing further development of the chemical modulation of the steroid endocrine system in C. elegans and related nematodes.

Precision Psychiatry Approach to Treat Depression and Anxiety Targeting the Stress Hormone System - V1b-antagonists as a Case in Point.

The future of depression pharmacotherapy lies in a precision medicine approach that recognizes that depression is a disease where different causalities drive symptoms. That approach calls for a departure from current diagnostic categories, which are broad enough to allow adherence to the "one-size-fits-all" paradigm, which is complementary to the routine use of "broad-spectrum" mono-amine antidepressants. Similar to oncology, narrowing the overinclusive diagnostic window by implementing laboratory tests, which guide specifically targeted treatments, will be a major step forward in overcoming the present drug discovery crisis.A substantial subgroup of patients presents with signs and symptoms of hypothalamic-pituitary-adrenocortical (HPA) overactivity. Therefore, this stress hormone system was considered to offer worthwhile targets. Some promising results emerged, but in sum, the results achieved by targeting corticosteroid receptors were mixed.More specific are non-peptidergic drugs that block stress-responsive neuropeptides, corticotropin-releasing hormone (CRH), and arginine vasopressin (AVP) in the brain by antagonizing their cognate CRHR1-and V1b-receptors. If a patient's depressive symptomatology is driven by overactive V1b-signaling then a V1b-receptor antagonist should be first-line treatment. To identify the patient having this V1b-receptor overactivity, a neuroendocrine test, the so-called dex/CRH-test, was developed, which indicates central AVP release but is too complicated to be routinely used. Therefore, this test was transformed into a gene-based "near-patient" test that allows immediate identification if a depressed patient's symptomatology is driven by overactive V1b-receptor signaling. We believe that this precision medicine approach will be the next major innovation in the pharmacotherapy of depression.

New insights about the toxicity of 2,4-D: Gene expression analysis reveals modulation on several subcellular responses in Chironomus riparius

Herbicides are the main class of pesticides applied in crops and are capable of polluting the surrounding freshwater system; thus, understanding their impact on non-target species, whose mechanism of action is not described, helps to elucidate the real risks of these pollutants to the environment. 2,4-dichlorophenoxyacetic acid (2,4-D) is frequently detected in water and, due to its persistence, poses a risk to wildlife. In this way, the present work aimed to describe the implication of exposure to concentrations of 2,4-D already reported in aquatic environments in several physiological mechanisms of C. riparius at molecular and biochemical levels. To achieve this, bioassays were conducted with fourth instar larvae exposed to three concentrations of 2,4-D (0.1, 1.0, and 7.5 μg L−1). Larvae were collected after 24 and 96 h of exposure, and the expression of 42 genes, related to six subcellular mechanisms, was assessed by Real-Time PCR (RT-PCR). Besides, the activity of the enzymes catalase (CAT), glutathione S-transferase (GST), and acetylcholinesterase (AChE) was determined. The main metabolic route altered after exposure to 2,4-D was the endocrine system (mainly related to 20-hydroxyecdysone and juvenile hormone), confirming its endocrine disruptor potential. Four of the eleven stress response genes studied were down-regulated, and later exposure modulated DNA-repair genes suggesting genotoxic capacity. Moreover, only one gene from each detoxification phase was modulated at short exposure to 1.0 μg L−1. The molecular responses were not dose-dependent, and some early responses were not preserved after 96 h, indicating a transient response to the herbicide. Exposure to 2,4-D did not alter the activity of CAT, GST, and AChE enzymes. The responses described in this study reveal new mechanistic pathways of toxicity for 2,4-D in non-target organisms and highlight potential ecological consequences for chironomids in aquatic systems at the edges of agricultural fields.